bluuebunny/crossref_metadata_2025 huggingface dataset:
Statistical properties of sites visited by independent random walks
Authors: Ben-Naim E , Krapivsky P L
Published: November 2022

The set of visited sites and the number of visited sites are two basic properties of the random walk trajectory. We consider two independent random walks on hyper-cubic lattices and study ordering probabilities associated with these characteristics. The first is the probability that during the time interval (0, t), the number of sites visited by a walker never exceeds that of another walker. The second is the probability that the sites visited by a walker remain a subset of the sites visited by another walker. Using numerical simulations, we investigate the leading asymptotic behaviors of the ordering probabilities in spatial dimensions d = 1, 2, 3, 4. We also study the time evolution of the number of ties between the number of visited sites. We show analytically that the average number of ties increases as a
1 ln t with a
1 = 0.970 508 in one dimension and as (ln t)2 in two dimensions.
Extreme value statistics of positive recurrent centrally biased random walks
Authors: Artuso Roberto , Onofri Manuele , Pozzoli Gaia , Radice Mattia
Published: November 2022

We consider the extreme value statistics of centrally-biased random walks with asymptotically-zero drift in the ergodic regime. We fully characterize the asymptotic distribution of the maximum for this class of Markov chains lacking translational invariance, with a particular emphasis on the relation between the time scaling of the expected value of the maximum and the stationary distribution of the process.
Effects of tongue hair flexural deformation on viscous fluid transport by bees
Authors: Wang Bo , Yang Jinzhao , Zhang Jie , Ke Zetao , Zhang Huafang , Yang Yunqiang , Wu Jianing
Published: November 2022

A bee’s tongue is coated in dynamic hairs that gradually unfold to entrain the viscid nectar, during which hairs inevitably deflect as a result of fluid drag. The hair deflection induced decline in nectar capture rate may be a coupled elastoviscous problem and remains poorly understood. Here we employed geometric beam theory coupled with the effective viscous force to derive a dynamic model for a rotary tongue hair deflection in a viscous fluid. Considering deflection of the tongue hair, we rationalized the nectar capture rate by taking Bombus
terrestris as a model system. When the nectar concentration increases from 20% to 70%, the nectar capture rate declines by 87%, indicating that hair erection is more severely impeded in thicker nectar. Based on this model, we predicted an optimal hair length with which the bee can reach the maximum nectar capture rate. This work may provide a new theoretical framework for quantifying viscous liquid transport by hairy surfaces and shed light on design methodologies for fluid transport devices using hairy beds.
Cytocompatibility of MG-63 osteosarcoma cells on chitosan/hydroxyapatite/lignin hybrid composite scaffold in vitro
Authors: Kandil Heba , Ekram Basma , Abo-Zeid Mona A M
Published: November 2022

This study aims at fabricating promising cytocompatible hybrid biocomposite scaffolds from chitosan (CS), hydroxyapatite (HAP) and lignin (L) for bone tissue engineering by using freeze-drying technique. Different ratios of HAP to L (50:0, 37.5:12.5, 25:25 and 12.5:37.5) were taken to determine the optimum ratio for obtaining a composite with superior properties. The mechanical and biological properties of the resulting composites were investigated. The mechanical results showed that the prepared composite with a ratio of 25:25 of HAP/L exhibited a remarkable enhancement in the mechanical properties compared to the others. Additionally, it was found from the in vitro results that the addition of L enhanced the water uptake value of the resulting scaffolds indicating their increased hydrophilicity. As a result, a significant increase in the attachment and proliferation of MG-63 cell line (osteoblast like cells) was observed in composite scaffolds with L over the scaffold without L (CS/HAP). From these results, it could be suggested that the prepared composite scaffold with 25:25 of HAP/L is very promising biomaterials in bone tissue-engineering as it exhibited a better mechanical and biological properties than the other prepared composites.
Present global warming: a justifiable and stable metric for evaluating short-lived climate pollutants
Authors: Pomerantz Andrew E , Kleinberg Robert L
Published: November 2022

The impacts of short-lived climate pollutants (SLCPs) such as methane are typically described using metrics that compare their climate impacts to carbon dioxide’s climate impact. The metrics consider a climate pollutant’s atmospheric heat-trapping effectiveness and atmospheric lifetime. Here we introduce an alternative metric called the Present Global Warming (PGW), which uses economic exponential discount modelling to characterize short-term and long-term effects simultaneously, resulting in a justifiable, familiar, and stable metric for evaluating SLCPs. We recommend quantifying the climate impacts of methane emissions using 2.5% annual discounting—consistent with the discount rates recently proposed in academic work and traditionally used in climate policy—corresponding to methane PGW2.5% = 50. In this context, one ton of emitted methane has the same climate impact as 50 tons of emitted carbon dioxide.
Eigenmodes of aberrated systems: the tilted lens
Authors: Buono Wagner Tavares , Peters Cade , Tau Jacuquline , Nape Isaac , Forbes Andrew
Published: November 2022

When light propagates through aberrated optical systems, the resulting degradation in amplitude and phase has deleterious effects, for example, on resolution in imaging, spot sizes in focussing, and the beam quality factor of the output beam. Traditionally, this is either pre- or post-corrected by adaptive optics or phase conjugation. Here, we consider the medium as a complex channel and determine the corresponding eigenmodes which are impervious of the channel perturbation. We employ a quantum-inspired approach and apply it to the tilted lens as our example channel, a highly astigmatic system that is routinely used as a measure of orbital angular momentum. We find the eigenmodes analytically, show their robustness in a practical experiment, and outline how this approach may be extended to arbitrary astigmatic systems.
Coherent control of evanescent waves via beam shaping
Authors: Savino Nicholas J , Leamer Jacob M , Zhang Wenlei , Saripalli Ravi K , Glasser Ryan T , Bondar Denys I
Published: November 2022

Evanescent waves are central to many technologies such as near-field imaging that beats the diffraction limit and plasmonic devices. Frustrated total internal reflection (FTIR) is an experimental method commonly used to study evanescent waves. In this paper, we shape the incident beam of the FTIR process with a Mach–Zehnder interferometer and measure light transmittance while varying the path length difference and interferometric visibility. Our results show that the transmittance varies with the path length difference and, thus, the intensity distribution of the shaped beam. Experiment and finite element method simulation produce results that agree. We also show, through simulations, that the transmittance can be controlled via other methods of beam shaping. Our work provides a proof-of-concept demonstration of the coherent control of the FTIR process, which could lead to advancements in numerous applications of evanescent waves and FTIR.
Fusion power supply advances by the J-TEXT engineering team
Authors: ZHANG Ming , ZHANG Hongqi , WANG Rumeng , XIE Xiaohan , WANG Wenshan , JIANG Yixing , LI Zhiheng , ZHANG Peilong , WANG Liye , MA Shaoxiang , YANG Yong , ZHENG Wei , RAO Bo
Published: November 2022

To meet the stringent requirements of the fusion power supply for large-scale fusion devices, the J-TEXT engineering team has carried out key technology research and applications in several important directions of fusion power supply. This article presents the advances made by the J-TEXT engineering team in recent years in the following areas: (1) a high-voltage power supply for an auxiliary heating system; (2) a breakdown protection device for an auxiliary heating power supply; (3) magnetic field compatibility; (4) a high-voltage pulsed power supply for a field-reversed configuration; (5) a large physics experimental facility control system. The research backgrounds, technical progress, test results, applications, summaries and prospects are described in detail in each part. These innovative research results and valuable engineering experience can promote the progress of fusion power supply technology, and also lay a foundation for the development of power supplies with higher parameters in the future.
Linear 𝑞-difference, difference and differential operators preserving some 𝒜-entire functions
Authors: Huang Jiaxing , Ng Tuen-Wai
Published: November 2022

We apply Rossi’s half-plane version of Borel’s theorem to study the zero distribution of linear combinations ofA\mathcal {A}-entire functions (Theorem 1.2). This provides a unified way to study linearqq-difference, difference and differential operators (with entire coefficients) preserving subsets ofA\mathcal {A}-entire functions, and hence obtain several analogous results for the Hermite-Poulain theorem to linear finite (qq-)difference operators with polynomial coefficients. The method also produces a result on the existence of infinitely many non-real zeros of some differential polynomials of functions in certain sub-classes ofA\mathcal {A}-entire functions.
Homotopy relative Rota-Baxter lie algebras, triangular 𝐿_{∞}-bialgebras and higher derived brackets
Authors: Lazarev Andrey , Sheng Yunhe , Tang Rong
Published: November 2022

We describe

L
∞

L_\infty

-algebras governing triangular

L
∞

L_\infty

-bialgebras and homotopy relative Rota-Baxter Lie algebras and establish a map between them. Our formulas are based on a functorial approach to Voronov’s higher derived brackets construction which is of independent interest.
Loss-of-function approach using mouse retinal explants showed pivotal roles of Nmnat2 in early and middle stages of retinal development
Authors: Kuribayashi Hiroshi , Katahira Miku , Aihara Makoto , Suzuki Yutaka , Watanabe Sumiko
Published: November 2022

Nicotinamide mononucleotide adenylyltransferase (Nmnat) is a group of enzymes consisting of three members (Nmnat1-3). shRNA-based loss-of-function analysis of Nmnat2 during mouse retinal development was done. Nmnat2 has multiple developmental stage–dependent roles during mouse retinal development, which were clearly different from those of Nmnat1.
Subjective Report, Objective Neurocognitive Performance, and “Invisible Symptoms” in Multiple Sclerosis
Authors: Thomas Garrett A , Riegler Kaitlin E , Bradson Megan L , O’Shea Dede U , Arnett Peter A
Published: November 2022

Background

Self- and informant-report measures are often useful in predicting objective cognitive performance; however, the relationship between these reports and mood, anxiety, and fatigue requires further examination. Additionally, it remains unclear as to how these factors might be associated with objective neurocognitive performance.

Methods

Eighty-six persons with multiple sclerosis (PwMS; F = 65, M = 21) completed a comprehensive neuropsychological battery that included objective neurocognitive measures, subjective reports of neurocognitive function with the Multiple Sclerosis Neuropsychological Screening Questionnaire (MSNQ) Self-Report (MSNQ-S) and Informant-Report (MSNQ-I), and self-report measures of anxiety, depression, and fatigue. Hierarchical linear regressions were conducted with depression, anxiety, the interaction between depression and anxiety, cognitive fatigue, and physical fatigue as predictors. Outcome variables included the MSNQ-S, MSNQ-I, each of five neurocognitive composites, and global intraindividual variability (IIV).

Results

Although greater cognitive fatigue was associated with greater reported cognitive dysfunction, it was not associated with objective neurocognitive impairment. Greater depression predicted poorer performance on measures of processing speed and verbal memory, though the effects became non-significant once accounting for anxiety. The interaction between depression and anxiety predicted greater neurocognitive IIV; those with high levels of depression and anxiety demonstrated greater dispersion of scores.

Conclusions

Cognitive fatigue may skew one’s perception of their cognition, though it is not associated with objective impairment. However, co-occurring depression and anxiety were associated with greater variability which is a marker of poorer neurocognitive integrity. Our findings highlight the importance of accounting for depression, anxiety, and cognitive fatigue in PwMS, given that they are all potentially modifiable factors.
PEMT: a patent enrichment tool for drug discovery
Authors: Gadiya Yojana , Zaliani Andrea , Gribbon Philip , Hofmann-Apitius Martin
Published: November 2022

Motivation

Drug discovery practitioners in industry and academia use semantic tools to extract information from online scientific literature to generate new insights into targets, therapeutics and diseases. However, due to complexities in access and analysis, patent-based literature is often overlooked as a source of information. As drug discovery is a highly competitive field, naturally, tools that tap into patent literature can provide any actor in the field an advantage in terms of better informed decision-making. Hence, we aim to facilitate access to patent literature through the creation of an automatic tool for extracting information from patents described in existing public resources.

Results

Here, we present PEMT, a novel patent enrichment tool, that takes advantage of public databases like ChEMBL and SureChEMBL to extract relevant patent information linked to chemical structures and/or gene names described through FAIR principles and metadata annotations. PEMT aims at supporting drug discovery and research by establishing a patent landscape around genes of interest. The pharmaceutical focus of the tool is mainly due to the subselection of International Patent Classification codes, but in principle, it can be used for other patent fields, provided that a link between a concept and chemical structure is investigated. Finally, we demonstrate a use-case in rare diseases by generating a gene-patent list based on the epidemiological prevalence of these diseases and exploring their underlying patent landscapes.

Availability and implementation

PEMT is an open-source Python tool and its source code and PyPi package are available at https://github.com/Fraunhofer-ITMP/PEMT and https://pypi.org/project/PEMT/, respectively.

Supplementary information

Supplementary data are available at Bioinformatics online.
Marginal proportional hazards models for multivariate interval-censored data
Authors: Xu Yangjianchen , Zeng Donglin , Lin D Y
Published: November 2022

Multivariate interval-censored data arise when there are multiple types of events or clusters of study subjects, such that the event times are potentially correlated and when each event is only known to occur over a particular time interval. We formulate the effects of potentially time-varying covariates on the multivariate event times through marginal proportional hazards models while leaving the dependence structures of the related event times unspecified. We construct the nonparametric pseudolikelihood under the working assumption that all event times are independent, and we provide a simple and stable EM-type algorithm. The resulting nonparametric maximum pseudolikelihood estimators for the regression parameters are shown to be consistent and asymptotically normal, with a limiting covariance matrix that can be consistently estimated by a sandwich estimator under arbitrary dependence structures for the related event times. We evaluate the performance of the proposed methods through extensive simulation studies and present an application to data from the Atherosclerosis Risk in Communities Study.
Benchmarking of robotic and laparoscopic spleen-preserving distal pancreatectomy by using two different methods
Authors: van Ramshorst Tess M E , Giani Alessandro , Mazzola Michele , Dokmak Safi , Ftériche Fadhel Samir , Esposito Alessandro , de Pastena Matteo , Lof Sanne , Edwin Bjørn , Sahakyan Mushegh , Boggi Ugo , Kauffman Emanuele Federico , Fabre Jean Michel , Souche Regis Francois , Zerbi Alessandro , Butturini Giovanni , Molenaar Quintus , Al-Sarireh Bilal , Marino Marco V , Keck Tobias , White Steven A , Casadei Riccardo , Burdio Fernando , Björnsson Bergthor , Soonawalla Zahir , Koerkamp Bas Groot , Fusai Giuseppe Kito , Pessaux Patrick , Jah Asif , Pietrabissa Andrea , Hackert Thilo , D’Hondt Mathieu , Pando Elizabeth , Besselink Marc G , Ferrari Giovanni , Hilal Mohammad Abu ,   for the European Consortium on Minimally Invasive Pancreatic Surgery
Published: November 2022

Background

Benchmarking is an important tool for quality comparison and improvement. However, no benchmark values are available for minimally invasive spleen-preserving distal pancreatectomy, either laparoscopically or robotically assisted. The aim of this study was to establish benchmarks for these techniques using two different methods.

Methods

Data from patients undergoing laparoscopically or robotically assisted spleen-preserving distal pancreatectomy were extracted from a multicentre database (2006–2019). Benchmarks for 10 outcomes were calculated using the Achievable Benchmark of Care (ABC) and best-patient-in-best-centre methods.

Results

Overall, 951 laparoscopically assisted (77.3 per cent) and 279 robotically assisted (22.7 per cent) procedures were included. Using the ABC method, the benchmarks for laparoscopically assisted and robotically assisted spleen-preserving distal pancreatectomy respectively were: 150 and 207 min for duration of operation, 55 and 100 ml for blood loss, 3.5 and 1.7 per cent for conversion, 0 and 1.7 per cent for failure to preserve the spleen, 27.3 and 34.0 per cent for overall morbidity, 5.1 and 3.3 per cent for major morbidity, 3.6 and 7.1 per cent for pancreatic fistula grade B/C, 5 and 6 days for duration of hospital stay, 2.9 and 5.4 per cent for readmissions, and 0 and 0 per cent for 90-day mortality. Best-patient-in-best-centre methodology revealed milder benchmark cut-offs for laparoscopically and robotically assisted procedures, with operating times of 254 and 262.5 min, blood loss of 150 and 195 ml, conversion rates of 5.8 and 8.2 per cent, rates of failure to salvage spleen of 29.9 and 27.3 per cent, overall morbidity rates of 62.7 and 55.7 per cent, major morbidity rates of 20.4 and 14 per cent, POPF B/C rates of 23.8 and 24.2 per cent, duration of hospital stay of 8 and 8 days, readmission rates of 20 and 15.1 per cent, and 90-day mortality rates of 0 and 0 per cent respectively.

Conclusion

Two benchmark methods for minimally invasive distal pancreatectomy produced different values, and should be interpreted and applied differently.
Navigating parenthood in the surgical profession: mixed-methods study
Authors: Vasey Carolyn E , Watson Eleanor G R , Commons Robert J , Liang Rhea , Nestel Debra
Published: November 2022

Background

Significant barriers exist to surgeons being good parents and parents being good surgeons, and these barriers are heightened for women. Considering the gender balance now present in postgraduate medical schools, it is critical that these barriers are overcome if surgery is to attract and retain applicants. This study aimed to investigate patterns of parenthood in surgery, explore associated attitudes and experiences, and identify barriers and solutions within an Australian and New Zealand context.

Methods

Surgeons and trainees were invited to participate in a survey and focus groups. Quantitative results were described, and textual responses and focus group transcriptions were analysed thematically.

Results

There were 261 survey respondents (62.8 per cent women, 37.2 per cent men) and six focus groups (34 participants). Of the survey respondents, 79.6 per cent of women and 86.5 per cent of men had children. Women were more likely to time childbirth around training or work, and most respondents without children attributed this to their career. Tensions between parenthood and surgery engendered guilt for surgeon-parents. Parenthood was often the ‘elephant in the room’ in training and employment discussions. Breaking the silence around parenthood and surgery made it more acceptable, normalising positive behaviour changes. The major barrier to parenthood and surgery was the lack of flexible training opportunities. Participants called for top-down establishment of mandated, stand-alone, permanent part-time training positions.

Conclusion

Many barriers to parenthood in surgery are created by rigid workplace and professional structures that are reflective of male-dominated historical norms. A willingness to be flexible, innovative and rethink models of training and employment is central to change.
Does Chinese Social Work Students’ Career Intention Match Their Professional Identity? The Role of Background Factors
Authors: Liu Tingting , Yi Songguo , Zhu Yuhong
Published: November 2022

Professional identity is essential for the career choice of social work. Exploring social work students’ perceptions of professional identity and career intention is necessary to understand the phenomenon of major-to-occupation mismatch in China. The present study involved a national sample of 2,018 social work undergraduates and postgraduates to investigate whether students displayed matching levels of professional identity and career intention and the association with their personal and educational background. To differentiate between social work as a discipline and an occupation, the concept of professional identity was split into two variables: disciplinary and occupational identity. Three groups of students were identified and labelled as having matching perceptions (49.8/44.1 per cent), lower disciplinary/occupational identity and higher career intention (7.8/5.6 per cent) and higher disciplinary/occupational identity and lower career intention (42.5/50.3 per cent), respectively. Multinomial logistic regression analyses revealed that students’ residential area, family economic status, degree programme, grade of study, university category and university location were significantly associated with whether they reported matching levels of professional identity and career intention. The findings can be explained by the imbalanced development of social work education and practice in China, implying the necessity of promoting social work employment benefits and cooperation between academic institutions and service organisations.
MCAM+ brain endothelial cells contribute to neuroinflammation by recruiting pathogenic CD4+ T lymphocytes
Authors: Charabati Marc , Zandee Stephanie , Fournier Antoine P , Tastet Olivier , Thai Karine , Zaminpeyma Roxaneh , Lécuyer Marc-André , Bourbonnière Lyne , Larouche Sandra , Klement Wendy , Grasmuck Camille , Tea Fiona , Zierfuss Bettina , Filali-Mouhim Ali , Moumdjian Robert , Bouthillier Alain , Cayrol Romain , Peelen Evelyn , Arbour Nathalie , Larochelle Catherine , Prat Alexandre
Published: November 2022

The trafficking of autoreactive leucocytes across the blood–brain barrier endothelium is a hallmark of multiple sclerosis pathogenesis. Although the blood–brain barrier endothelium represents one of the main CNS borders to interact with the infiltrating leucocytes, its exact contribution to neuroinflammation remains understudied. Here, we show that Mcam identifies inflammatory brain endothelial cells with pro-migratory transcriptomic signature during experimental autoimmune encephalomyelitis. In addition, MCAM was preferentially upregulated on blood–brain barrier endothelial cells in multiple sclerosis lesions in situ and at experimental autoimmune encephalomyelitis disease onset by molecular MRI. In vitro and in vivo, we demonstrate that MCAM on blood–brain barrier endothelial cells contributes to experimental autoimmune encephalomyelitis development by promoting the cellular trafficking of TH1 and TH17 lymphocytes across the blood–brain barrier. Last, we showcase ST14 as an immune ligand to brain endothelial MCAM, enriched on CD4+ T lymphocytes that cross the blood–brain barrier in vitro, in vivo and in multiple sclerosis lesions as detected by flow cytometry on rapid autopsy derived brain tissue from multiple sclerosis patients. Collectively, our findings reveal that MCAM is at the centre of a pathological pathway used by brain endothelial cells to recruit pathogenic CD4+ T lymphocyte from circulation early during neuroinflammation. The therapeutic targeting of this mechanism is a promising avenue to treat multiple sclerosis.
Running up that pill for amyotrophic lateral sclerosis
Authors: Smeyers Julie , Mordes Daniel A
Published: November 2022

This scientific commentary refers to ‘Maiden voyage: induced pluripotent stem cell-based drug screening for amyotrophic lateral sclerosis’ by Ito et al. (https://doi.org/10.1093/brain/awac306).
Default mode network scaffolds immature frontoparietal network in cognitive development
Authors: Chen Menglu , He Ying , Hao Lei , Xu Jiahua , Tian Ting , Peng Siya , Zhao Gai , Lu Jing , Zhao Yuyao , Zhao Hui , Jiang Min , Gao Jia-Hong , Tan Shuping , He Yong , Liu Chao , Tao Sha , Uddin Lucina Q , Dong Qi , Qin Shaozheng
Published: November 2022

The default mode network (DMN) is a workspace for convergence of internal and external information. The frontal parietal network (FPN) is indispensable to executive functioning. Yet, how they interplay to support cognitive development remains elusive. Using longitudinal developmental fMRI with an n-back paradigm, we show a heterogeneity of maturational changes in multivoxel activity and network connectivity among DMN and FPN nodes in 528 children and 103 young adults. Compared with adults, children exhibited prominent longitudinal improvement but still inferior behavioral performance, which paired with less pronounced DMN deactivation and weaker FPN activation in children, but stronger DMN coupling with FPN regions. Children’s DMN reached an adult-like level earlier than FPN at both multivoxel activity pattern and intranetwork connectivity levels. Intrinsic DMN-FPN internetwork coupling in children mediated the relationship between age and working memory-related functional coupling of these networks, with posterior cingulate cortex (PCC)-dorsolateral prefrontal cortex (DLPFC) coupling emerging as most prominent pathway. Coupling of PCC-DLPFC may further work together with task-invoked activity in PCC to account for longitudinal improvement in behavioral performance in children. Our findings suggest that the DMN provides a scaffolding effect in support of an immature FPN that is critical for the development of executive functions in children.
Identifying vulnerable brain networks associated with Alzheimer’s disease risk
Authors: Mahzarnia Ali , Stout Jacques A , Anderson Robert J , Moon Hae Sol , Yar Han Zay , Beck Kate , Browndyke Jeffrey N , Dunson David B , Johnson Kim G , O’Brien Richard J , Badea Alexandra
Published: November 2022

The selective vulnerability of brain networks in individuals at risk for Alzheimer’s disease (AD) may help differentiate pathological from normal aging at asymptomatic stages, allowing the implementation of more effective interventions. We used a sample of 72 people across the age span, enriched for the APOE4 genotype to reveal vulnerable networks associated with a composite AD risk factor including age, genotype, and sex. Sparse canonical correlation analysis (CCA) revealed a high weight associated with genotype, and subgraphs involving the cuneus, temporal, cingulate cortices, and cerebellum. Adding cognitive metrics to the risk factor revealed the highest cumulative degree of connectivity for the pericalcarine cortex, insula, banks of the superior sulcus, and the cerebellum. To enable scaling up our approach, we extended tensor network principal component analysis, introducing CCA components. We developed sparse regression predictive models with errors of 17% for genotype, 24% for family risk factor for AD, and 5 years for age. Age prediction in groups including cognitively impaired subjects revealed regions not found using only normal subjects, i.e. middle and transverse temporal, paracentral and superior banks of temporal sulcus, as well as the amygdala and parahippocampal gyrus. These modeling approaches represent stepping stones towards single subject prediction.
Comparison of Single Molecule, Real-Time Sequencing and Nanopore Sequencing for Analysis of the Size, End-Motif, and Tissue-of-Origin of Long Cell-Free DNA in Plasma
Authors: Yu Stephanie C Y , Deng Jiaen , Qiao Rong , Cheng Suk Hang , Peng Wenlei , Lau So Ling , Choy L Y Lois , Leung Tak Y , Wong John , Wong Vincent Wai-Sun , Wong Grace L H , Jiang Peiyong , Chiu Rossa W K , Chan K C Allen , Lo Y M Dennis
Published: November 2022

Background

Recent studies using single molecule, real-time (SMRT) sequencing revealed a substantial population of analyzable long cell-free DNA (cfDNA) in plasma. Potential clinical utilities of such long cfDNA in pregnancy and cancer have been demonstrated. However, the performance of different long-read sequencing platforms for the analysis of long cfDNA remains unknown.

Methods

Size biases of SMRT sequencing by Pacific Biosciences (PacBio) and nanopore sequencing by Oxford Nanopore Technologies (ONT) were evaluated using artificial mixtures of sonicated human and mouse DNA of different sizes. cfDNA from plasma samples of pregnant women at different trimesters, hepatitis B carriers, and patients with hepatocellular carcinoma were sequenced with the 2 platforms.

Results

Both platforms showed biases to sequence longer (1500 bp vs 200 bp) DNA fragments, with PacBio showing a stronger bias (5-fold overrepresentation of long fragments vs 2-fold in ONT). Percentages of cfDNA fragments 500 bp were around 6-fold higher in PacBio compared with ONT. End motif profiles of cfDNA from PacBio and ONT were similar, yet exhibited platform-dependent patterns. Tissue-of-origin analysis based on single-molecule methylation patterns showed comparable performance on both platforms.

Conclusions

SMRT sequencing generated data with higher percentages of long cfDNA compared with nanopore sequencing. Yet, a higher number of long cfDNA fragments eligible for the tissue-of-origin analysis could be obtained from nanopore sequencing due to its much higher throughput. When analyzing the size and end motif of cfDNA, one should be aware of the analytical characteristics and possible biases of the sequencing platforms being used.
Increased Primary Bile Acids with Ileocolonic Resection Impact Ileal Inflammation and Gut Microbiota in Inflammatory Bowel Disease
Authors: Battat Robert , Scherl Ellen J , Lukin Dana , Charilaou Paris , Mahtani Prerna , Gerber Juliette , Gandara Jorge A ,   JRI IBD Live Cell Bank Consortium, Longman Randy , Sonnenberg Gregory , Scherl Ellen , Sockolow Robbyn , Lukin Dana , Battat Robert , Ciecierega Thomas , Solomon Aliza , Barfield Elaine , Chien Kimberley , Ferreira Johanna , Williams Jasmin , Khan Shaira , Chong Peik Sean , Mozumder Samah , Chou Lance , Zhou Wenqing , Ahmed Anees , Zhong Connie , Joseph Ann , Gladstone Joseph , Jensen Samantha , Dündar Friederike , Zumbo Paul , Betel Doron , Guo Chun-Jun , Longman Randy S
Published: November 2022

Background

Most Crohn’s disease [CD] patients require surgery. Ileitis recurs after most ileocolectomies and is a critical determinant for outcomes. The impacts of ileocolectomy-induced bile acid [BA] perturbations on intestinal microbiota and inflammation are unknown. We characterized the relationships between ileocolectomy, stool BAs, microbiota and intestinal inflammation in inflammatory bowel disease [IBD].

Methods

Validated IBD clinical and endoscopic assessments were prospectively collected. Stool primary and secondary BA concentrations were compared based on ileocolectomy and ileitis status. Primary BA thresholds for ileitis were evaluated. Metagenomic sequencing was use to profile microbial composition and function. Relationships between ileocolectomy, BAs and microbiota were assessed.

Results

In 166 patients, elevated primary and secondary BAs existed with ileocolectomy. With ileitis, only primary BAs [795 vs 398 nmol/g, p = 0.009] were higher compared to without ileitis. The optimal primary BA threshold [≥228 nmol/g] identified ileitis on multivariable analysis [odds ratio = 2.3, p = 0.04]. Microbial diversity, Faecalibacterium prausnitzii and O-acetylhomoserine aminocarboxypropyltransferase [MetY] were decreased with elevated primary BAs. Amongst ileocolectomy patients, only those with elevated primary BAs had diversity, F. prausnitzii and MetY reductions. Those with both ileocolectomy and intermediate [p = 0.002] or high [≥228 nmol/g, p = 9.1e-11]] primary BA concentrations had reduced F. prausnitzii compared to without ileocolectomy. Those with ileocolectomy and low [<29.2 nmol/g] primary BA concentrations had similar F. prausnitzii to those without ileocolectomy [p = 0.13]. MetY was reduced with ileitis [p = 0.02].

Conclusions

Elevated primary BAs were associated with ileitis, and reduced microbial diversity, F. prausnitzii abundance and enzymatic abundance of MetY [acetate and l-methionine-producing enzyme expressed by F. prausnitzii], and were the only factors associated with these findings after ileocolectomy.
Foot, ankle, and leg problems in Australian primary care: consultation patterns, management practices, and costs
Authors: Menz Hylton B , Williams Cylie M , Lazzarini Peter A , Gordon Julie , Harrison Christopher
Published: November 2022

Objective

To explore consultation patterns, management practices, and costs of foot, ankle, and leg problems in Australian primary care.

Study design

We analyzed data from the Bettering the Evaluation and Care of Health program, April 2000 to March 2016. Foot, ankle, and leg problems were identified using the International Classification of Primary Care, Version 2 PLUS terminology. Data were summarized using descriptive statistics examining general practitioner (GP) and patient characteristics associated with a foot, ankle, or leg problem being managed. Cost to government was estimated by extracting fees for GP consultations, diagnostic imaging, and pathology services from the Medicare Benefits Schedule (MBS) database. Costs for prescription-only medicines were extracted from the Pharmaceutical Benefits Schedule and for nonprescribed medications, large banner discount pharmacy prices were used.

Results

GPs recorded 1,568,100 patient encounters, at which 50,877 foot, ankle, or leg problems were managed at a rate of 3.24 (95% confidence intervals [CIs] 3.21–3.28) per 100 encounters. The management rate of foot, ankle, or leg problems was higher for certain patient characteristics (older, having a health care card, socioeconomically disadvantaged, non-Indigenous, and being English speaking) and GP characteristics (male sex, older age, and Australian graduate). The most frequently used management practice was the use of medications. The average cost (Australian dollars) per encounter was A$52, with the total annual cost estimated at A$256m.

Conclusions

Foot, ankle, and leg problems are frequently managed by GPs, and the costs associated with their management represent a substantial economic impact in Australian primary care.
The impact of conformational sampling on first-principles calculations of vicinal COCH J-couplings in carbohydrates
Authors: Reeves Hannah L , Wang Lee-Ping
Published: November 2022

Dihedral angles in organic molecules and biomolecules are vital structural parameters that can be indirectly probed by nuclear magnetic resonance (NMR) measurements of vicinal J-couplings. The empirical relations that map the measured couplings to dihedral angles are typically determined by fitting using static structural models, but this neglects the effects of thermal fluctuations at the finite temperature conditions under which NMR measurements are often taken. In this study, we calculate ensemble-averaged J-couplings for several structurally rigid carbohydrate derivatives using first-principles molecular dynamics simulations to sample the thermally accessible conformations around the minimum energy structure. Our results show that including thermal fluctuation effects significantly shifts the predicted couplings relative to single-point calculations at the energy minima, leading to improved agreement with experiments. This provides evidence that accounting for conformational sampling in first-principles calculations can improve the accuracy of NMR-based structure determination for structurally complex carbohydrates.
Virtual sovereignty? Private internet capital, digital platforms and infrastructural power in the United States
Authors: Kelton Maryanne , Sullivan Michael , Rogers Zac , Bienvenue Emily , Troath Sian
Published: November 2022

Infrastructural power in the United States, which is the capacity to extract and deploy social resources and initiate and harness technological innovation, is increasingly generated by private internet capital and exercised by digital platforms. In this article we argue that while these private actors do not possess legitimacy, this is a form of ‘virtual sovereignty’ which complicates the capacity of the US state to exercise infrastructural power. Though internet software was designed largely by US corporations, commercial users operate increasingly in deterritorialized global spaces, where citizen consent and the interests of the US state are not business priorities. Moreover, much of the internet's hardware is financed by private internet capital within global wealth chains and digital spaces populated by US and non-US corporations. We argue that digital platforms acquire infrastructural power through the accumulation and commercialization of big data, from which they curate individual thinking and behaviour. We point to the targeting of US liberal democratic resilience by hostile, domestic and foreign actors weaponizing social media, and the potential ramifications of the exercise of virtual sovereignty for the return of great power rivalry in international relations. The article concludes that private internet capital's command of vast socio-economic resources reinforces the digital platforms' leadership in technological innovation and challenges the sovereign state's monopoly over national security.
Russia, Ukraine and state survival through neutrality
Authors: Allison Roy
Published: November 2022

During the Cold War neutrality and a ‘non-bloc’ status were used by certain European states to escape great power rivalries. But these foreign and security policy strategies declined in significance and have received little scholarly attention since the early 1990s. This article argues that in a period of renewed confrontation between Russia and western powers, significant insights may be derived from a critical review of the past experiences of neutral and non-bloc states. These help scholars and practitioners assess the contemporary options of states in vulnerable locations which choose or are compelled to survive outside alliances. This article probes the critical case of Ukraine as a sovereign but potentially neutral state. Relevant criteria for neutrality are drawn from short interpretive case-studies of Austria and Finland during the Cold War, as well as Moldova and Finland in post-Cold War years. Soviet and Russian policy prioritized the strategic denial of these states to NATO, while forms of armed neutrality helped sustain conventional deterrence against Russian coercion. If Moscow reigns in its ambitions for the political subjugation of Ukraine and accepts its statehood, such thinking may form part of an eventual security policy settlement beyond the current war.
Impact of Biologic Agents on the Immune Response Induced by the Additional Dose of SARS-CoV-2 Vaccine in Inflammatory Bowel Disease Patients
Authors: Ramos Laura , Hernández-Porto Miriam , Carrillo-Palau Marta , Alonso-Abreu Inmaculada , Reygosa Cristina , Hernandez-Guerra Manuel
Published: November 2022

Lay Summary

The immusne response to the vaccine against SARS-CoV-2 is altered in patients with inflammatory bowel disease using biological agents, and so we should ensure effective immunization in these patients by prioritizing those receiving anti-tumor necrosis factor agents in the indication of new doses or booster doses of the vaccine.
Revisiting due diligence in cyberspace: crafting international law’s arsenal against transboundary Botnets
Authors: Shrivastava Abhijeet , Lakra Rudraksh
Published: November 2022

The emergence of cyberspace has been followed by increasingly unpredictable threats to cybersecurity, including Botnets, which have been frequently exploited in cyber-criminal activities affecting dozens or hundreds of States at once. In existing scholarship, many reasons have informed growing support for the promise of ‘due diligence’ obligations in regulating transboundary cyber operations. We affirm this position through a study of the specific context of Botnets, although bringing much-needed caution and complexity to the discourse. We offer a comprehensive account of the standard of conduct expected of States in detecting, mitigating and preventing Botnet-linked harms under due diligence; as well as to pursue cyber capacity building toward discharging these obligations. In so doing, we problematize and elaborate on the nature of due diligence as an obligation of conduct, therefore accounting for differential State capacities against Botnet-linked harms. The paper involves attempts to unpack a coherent conception of due diligence, appreciating the spectrum of obligations that it demands, and demonstrating these nuances through an appraisal of good practices adopted by States and private actors against Botnets. Consequently, we provide a unique holistic account of how States and their law enforcement could practically understand the conduct expected of them when faced with transboundary Botnets on a case-to-case basis. In the end, while underscoring potential dilemmas within this legal regime that may be faced by target States, as also its unresolved questions, we submit that due diligence is indeed the most appropriate candidate to act as a legal arsenal against transboundary Botnets.
Isoparametric Polynomials and Sums of Squares
Authors: Ge Jianquan , Tang Zizhou
Published: November 2022

Hilbert’s 17th problem asks whether every nonnegative polynomial can be a sum of squares of rational functions. It has been answered affirmatively by Artin. However, the question as to whether a given nonnegative polynomial is a sum of squares of polynomials is still a central question in real algebraic geometry. In this paper, we solve this question completely for the nonnegative polynomials associated with isoparametric polynomials, initiated by E. Cartan, which define the focal submanifolds of the corresponding isoparametric hypersurfaces.

Dedicated to Professor Chia-Kuei Peng on his 80th birthday
Genome-Wide Association Studies Identify an Association of Transferrin Binding Protein B Variation and Invasive Serogroup Y Meningococcal Disease in Older Adults
Authors: Maynard-Smith Laura , Derrick Jeremy P , Borrow Ray , Lucidarme Jay , Maiden Martin C J , Heyderman Robert S , Harrison Odile B
Published: November 2022

Background

Neisseria meningitidis serogroup Y, especially ST-23 clonal complex (Y:cc23), represents a larger proportion of invasive meningococcal disease (IMD) in older adults compared to younger individuals. This study explored the meningococcal genetic variation underlying this association.

Methods

Maximum-likelihood phylogenies and the pangenome were analyzed using whole-genome sequence (WGS) data from 200 Y:cc23 isolates in the Neisseria PubMLST database. Genome-wide association studies (GWAS) were performed on WGS data from 250 Y:cc23 isolates from individuals with IMD aged ≥65 years versus < 65 years.

Results

Y:cc23 meningococcal variants did not cluster by age group or disease phenotype in phylogenetic analyses. Pangenome comparisons found no differences in presence or absence of genes in IMD isolates from the different age groups. GWAS identified differences in nucleotide polymorphisms within the transferrin-binding protein B (tbpB) gene in isolates from individuals ≥65 years of age. TbpB structure modelling suggests these may impact binding of human transferrin.

Conclusions

These data suggest differential iron scavenging capacity amongst Y:cc23 meningococci isolated from older compared to younger patients. Iron acquisition is essential for many bacterial pathogens including the meningococcus. These polymorphisms may facilitate colonization, thereby increasing the risk of disease in vulnerable older people with altered nasopharyngeal microbiomes and nutritional status.
Serologic Response to Human Papillomavirus Genotypes Among Unvaccinated Women: Findings From the HITCH Cohort Study
Authors: Morais Samantha , Wissing Michel D , Khosrow-Khavar Farzin , Burchell Ann N , Tellier Pierre-Paul , Coutlée François , Waterboer Tim , El-Zein Mariam , Franco Eduardo L
Published: November 2022

Background

Humoral immune responses may be critical for preventing, controlling, and/or eliminating human papillomavirus (HPV) infection. We analyzed humoral response to natural HPV infection considering phylogenetic relatedness among unvaccinated women.

Methods

We included 399 young women attending university/college in Montreal, Canada who were participants of the HITCH cohort. Participants provided blood samples at baseline and 5 follow-up visits. Antibody response to bacterially expressed L1 and E6 glutathione S-transferase (GST) fusion proteins, and virus-like particles (VLP-L1) of Alphapapillomavirus types were measured using multiplex serology. We assessed correlations and associations between HPV types at baseline using Pearson correlation coefficients (r) and univariable linear regressions.

Results

At baseline, > 40% were seropositive for GST-L1 antibodies of at least 1 HPV type. Strong correlations between GST-L1 were observed for α9 HPV types: 58–52 (r = 0.86), 58–33 (r = 0.75), 33–52 (r = 0.72), and between GST-E6: 52–11 (r = 0.84), 52–18 (r = 0.79), 58–33 (r = 0.78), 35–11 (r = 0.76). HPV16 VLP-L1 moderately explained variability in HPV16 GST-L1 (regression coefficient [b] = 0.38, R2 = 43.1%), and HPV45 GST-L1 in HPV18 GST-L1 (b = 0.68, R2 = 42.8%). GST-E6 antibodies accounted for a low to moderate proportion of variability in HPV16 and HPV18 GST-E6 (R2 = 6.4%–62.2%).

Conclusions

Associations between naturally induced HPV-specific antibodies depend on phylogenetic relatedness.