bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnosis and treatment of von Willebrand disease in 2024 and beyond
Authors: James Paula , Leebeek Frank , Casari Caterina , Lillicrap David
Published: March 2024

Manuscript background and aim

The diagnosis and clinical care of patients with von Willebrand disease (VWD) has continued to evolve since the characterization of the von Willebrand factor (VWF) gene in 1985. This condition is almost certainly the most common inherited bleeding disorder, and the major symptomatic burden of the disease is experienced by females during their reproductive years. Diagnosis relies on the identification of a personal and family history of excessive mucocutaneous bleeding, and laboratory features consistent with quantitative and/or qualitative abnormalities of VWF. This review focuses on three aspects of VWD management, with current updates and a look into the future.

Manuscript themes

First, we will address the role of genetics in the diagnosis and possible therapies for VWD. With current technologies, VWD genetic diagnosis is usually confined to the confirmation of type 2 subtypes of the disease and type 3 VWD analysis for family planning. While type 3 VWD is a potential candidate for the application of gene therapy, no treatments are currently close to entering the clinic. Second, the peri‐procedural management of patients with VWD remains an important element of care. The choice of product, its dose and schedule all require careful consideration depending upon the type and disruptive nature of the planned procedure. Lastly, in addition to gene therapy, several other novel therapeutic interventions are also being developed for bleeding and prophylaxis in VWD. These include a VWF aptamer interfering with VWF clearance and bioengineered forms of VWF.
Phylogeography of the Iberian endemic butterfly Erebia palarica Chapman, 1905 (Lepidoptera: Nymphalidae): An integrative approach
Authors: Torrado‐Blanco Laura , Eberle Jonas , Romo Helena , Mortera Hugo , Vila Marta
Published: March 2024

Montane biodiversity is particularly vulnerable to rapid oscillations in environmental conditions. Recent modelling showed that only three of the 19 butterfly species of Erebia (Nymphalidae, Satyrinae) currently present in Iberia would persist in a worst‐case scenario for 2070. One of them is Erebia palarica, endemic to Northwest Spain. We combined genetics, morphometrics and ecological niche modelling to reconstruct its evolutionary history.

First, sequences of the cytochrome oxidase I (COI) mitochondrial gene obtained from 305 specimens revealed a double star‐like network that suggests a demographic expansion from two ancestral populations. This finding is congruent with the larger and disjunct putative distribution revealed by climatic modelling during the Last Glacial Maximum.

Second, genotyping of 262 samples with seven microsatellite markers produced a large cluster at the centre‐East of the Cantabrian range, mostly affected by isolation by distance, and revealed different levels of structure in the western localities.

Lastly, we reviewed the intraspecific taxonomy of the species. The westernmost site (Queixa) stands as a clearly separated unit according to genetic and morphometric analyses, which further supports its vague former description as subspecies E. p. castroviejoi.

Altogether, the case of E. palarica exemplifies the complexity that narrow endemics can show and highlights that understanding the evolutionary history of species is crucial for designing adequate conservation strategies.
Phase purifying and dielectric improvement in Zn2SiO4 ceramics via simply controlling the particle size of SiO2
Authors: Xing Zhuo , Song Julong , Pan Hong
Published: March 2024

The zinc orthosilicate, Zn2SiO4 ceramics, exhibit great potential as microwave dielectric materials due to their low dielectric constant and ultrahigh quality factor. The solid‐state synthesis of Zn2SiO4 ceramics often results in the presence of a secondary phase of ZnO, however, leading to significantly lower Q×f values. Cold‐isostatic‐pressing (CIP) and nonstoichiometry have been proven effective in purifying the Zn2SiO4 but need elaborate process and composition manipulation. In this work, it was found that the particle size of SiO2 plays a crucial role in purifying the Zn2SiO4 phase. Specially, nano‐sized SiO2 particles (15 and 30 nm) led to the formation of a ZnO secondary phase in synthesized Zn2SiO4 ceramics, while micro‐sized (2 and 10 µm) resulted in pure‐phase Zn2SiO4 with excellent microwave properties. Notably, when prepared with 10 µm SiO2 and sintered at 1 340°C, the resulting Zn2SiO4 exhibited outstanding microwave performances with a Q×f value of 122 570 GHz, a temperature coefficient of frequency τf of −51.9 ppm/°C, and a dielectric constant (εr) of 6.5. These findings highlight the importance of controlling particle size during synthesis to achieve desired material properties such as purity and excellent microwave performances.
How orientation training socializes newcomers: The mediating role of learning in reducing turnover and boosting performance among new salespersons
Authors: Xie Di , Zong Zhaobiao
Published: March 2024

Orientation training plays a crucial role in the process of newcomer socialization by equipping employees with the knowledge, abilities, and skills necessary for success in a new work setting. However, relatively few studies have investigated orientation training from a socialization perspective and addressed its underlying mechanisms. To address this issue, we developed a model to elucidate the socialization process of newly hired salespersons undergoing skill‐based orientation training. The model includes training reactions, two learning outcomes (learning engagement and skill acquisition), as well as two distal socialization outcomes (retention status and annual sales performance). Using a one‐year multiperiod design, we conducted a multilevel analysis on data of 1184 new salesperson records nested in 37 off‐site classes, which was obtained from a US pharmaceutical company operating in China. The results revealed that newcomers' reactions to orientation training were positively associated with their learning engagement and skill acquisition, which in turn resulted in a higher newcomer retention ratio. Furthermore, skill acquisition was found to be a significant mediator between training reactions and newcomers' annual sales performance. By combining self‐report, trainer‐report and objective indicators, this study provides a new and compelling evidence on how orientation training accelerates newcomer socialization success.
Differing industrial relations: The public and the private sector in Germany
Authors: Schmidt Werner , Müller Andrea
Published: March 2024

This article argues that industrial relations (IR) in the German public sector are not just a replica of private sector IR. It suggests that neither the structures, nor the outcomes can be sufficiently explained by derivation from private sector IR processes. Primarily, the specifics and developments of the public sector explain public sector IR. It is of fundamental importance whether trade unions operate in a profit‐driven market environment or a publicly financed environment that is under public control. Differences between the public and the private sector result not least in the distinct relevance and meanings of trade union power resources. This influences the ways in which industrial action in the private and the public sector works and is relevant for trade union strategies.
Identification of a new gregarine parasite associated with mass mortality events of freshwater pearl mussels (Margaritifera margaritifera) in Sweden
Authors: Alfjorden Anders , Onut‐Brännström Ioana , Wengström Niklas , Kristmundsson Arni , Jamy Mahwash , Persson B. David , Burki Fabien
Published: March 2024

Freshwater bivalves play key ecological roles in lakes and rivers, largely contributing to healthy ecosystems. The freshwater pearl mussel, Margaritifera margaritifera, is found in Europe and on the East coast of North America. Once common in oxygenated streams, M. margaritifera is rapidly declining and consequently assessed as a threatened species worldwide. Deterioration of water quality has been considered the main factor for the mass mortality events affecting this species. Yet, the role of parasitic infections has not been investigated. Here, we report the discovery of three novel protist lineages found in Swedish populations of M. margaritifera belonging to one of the terrestrial groups of gregarines (Eugregarinorida, Apicomplexa). These lineages are closely related–but clearly separated–from the tadpole parasite Nematopsis temporariae. In one lineage, which is specifically associated with mortality events of M. margaritifera, we found cysts containing single vermiform zoites in the gills and other organs of diseased individuals using microscopy and in situ hybridization. This represents the first report of a parasitic infection in M. margaritifera that may be linked to the decline of this mussel species. We propose a tentative life cycle with the distribution of different developmental stages and potential exit from the host into the environment.
The OsWRKY72–OsAAT30/OsGSTU26 module mediates reactive oxygen species scavenging to drive heterosis for salt tolerance in hybrid rice
Authors: Liu Citao , Mao Bigang , Zhang Yanxia , tian Lei , Ma Biao , Chen Zhuo , Wei Zhongwei , Li Aifu , Shao Ye , Cheng Gongye , Li Lingling , Li Wenyu , Zhang Di , Ding Xiaoping , Peng Jiangxiang , Peng Yulin , He Jiwai , Ye Nenghui , Yuan Dingyang , Chu Chengcai , Duan Meijuan
Published: March 2024

Hybrid rice (Oryza sativa) generally outperforms its inbred parents in yield and stress tolerance, a phenomenon termed heterosis, but the underlying mechanism is not completely understood. Here, we combined transcriptome, proteome, physiological, and heterosis analyses to examine the salt response of super hybrid rice Chaoyou1000 (CY1000). In addition to surpassing the mean values for its two parents (mid‐parent heterosis), CY1000 exhibited a higher reactive oxygen species scavenging ability than both its parents (over‐parent heterosis or heterobeltiosis). Nonadditive expression and allele‐specific gene expression assays showed that the glutathione S‐transferase gene OsGSTU26 and the amino acid transporter gene OsAAT30 may have major roles in heterosis for salt tolerance, acting in an overdominant fashion in CY1000. Furthermore, we identified OsWRKY72 as a common transcription factor that binds and regulates OsGSTU26 and OsAAT30. The salt‐sensitive phenotypes were associated with the OsWRKY72paternal genotype or the OsAAT30maternal genotype in core rice germplasm varieties. OsWRKY72paternal specifically repressed the expression of OsGSTU26 under salt stress, leading to salinity sensitivity, while OsWRKY72maternal specifically repressed OsAAT30, resulting in salinity tolerance. These results suggest that the OsWRKY72–OsAAT30/OsGSTU26 module may play an important role in heterosis for salt tolerance in an overdominant fashion in CY1000 hybrid rice, providing valuable clues to elucidate the mechanism of heterosis for salinity tolerance in hybrid rice.
Potassium transporter OsHAK9 regulates seed germination under salt stress by preventing gibberellin degradation through mediating OsGA2ox7 in rice
Authors: Zeng Peng , Xie Ting , Shen Jiaxin , Liang Taokai , Yin Lu , Liu Kexin , He Ying , Chen Mingming , Tang Haijuan , Chen Sunlu , Shabala Sergey , Zhang Hongsheng , Cheng Jinping
Published: March 2024

Soil salinity has a major impact on rice seed germination, severely limiting rice production. Herein, a rice germination defective mutant under salt stress (gdss) was identified by using chemical mutagenesis. The GDSS gene was detected via MutMap and shown to encode potassium transporter OsHAK9. Phenotypic analysis of complementation and mutant lines demonstrated that OsHAK9 was an essential regulator responsible for seed germination under salt stress. OsHAK9 is highly expressed in germinating seed embryos. Ion contents and non‐invasive micro‐test technology results showed that OsHAK9 restricted K+ efflux in salt‐exposed germinating seeds for the balance of K+/Na+. Disruption of OsHAK9 significantly reduced gibberellin 4 (GA4) levels, and the germination defective phenotype of oshak9a was partly rescued by exogenous GA3 treatment under salt stress. RNA sequencing (RNA‐seq) and real‐time quantitative polymerase chain reaction analysis demonstrated that the disruption of OsHAK9 improved the GA‐deactivated gene OsGA2ox7 expression in germinating seeds under salt stress, and the expression of OsGA2ox7 was significantly inhibited by salt stress. Null mutants of OsGA2ox7 created using clustered, regularly interspaced, short palindromic repeat (CRISPR)/CRISPR‐associated nuclease 9 approach displayed a dramatically increased seed germination ability under salt stress. Overall, our results highlight that OsHAK9 regulates seed germination performance under salt stress involving preventing GA degradation by mediating OsGA2ox7, which provides a novel clue about the relationship between GA and OsHAKs in rice.
Flexural properties and fatigue limit of 3D‐printed and milled resin‐based materials
Authors: Sartori Neimar , Sanchez Said Arturo , Oliveira Dayane , Hosney Sherif , Zoidis Panagiotis , Martin William , Gonzaga Luiz , Rocha Mateus G.
Published: March 2024

Purpose

The purpose of this study was to evaluate the flexural strength (FS), flexural modulus (FM), and fatigue limit (FL) of 3D‐printed resin‐based polymers and composites and compare them to 3D‐printed composites.

Materials and Methods

A bar‐shaped specimen (25 × 2 × 2 mm) was CAD designed according to ISO 4049:2019, and 60 duplicates of the 3D model were nested at a 45‐degree angle with the printing platform and 3D‐printed with three materials: denture teeth resin (Denture Teeth, Formlabs), temporary crown and bridge resin (Temporary CB, Formlabs), and composite (Flexcera Smile Ultra+, Desktop Health). The 3D model was also imported into a dental CAM software, duplicated 60 times, nested, and milled from a 3D‐milled composite puck (Ivotion Denture Teeth, Ivoclar). All specimens were post‐processed following the manufacturer's recommendation. The specimens were then subjected to a three‐point bending test until failure using a Universal Testing Machine at a crosshead speed of 0.75 mm/min, and FS and FM were calculated. The remaining thirty specimens were tested for Fatigue Limit using the staircase approach starting at 50% FS maximum up to 1.2 M cycles at 10 Hz. The data were analyzed using one‐way ANOVA and the Weibull distribution (α = 0.05).

Results

The results showed that Ivotion and Flexcera had higher FS (110.3 ± 7.1 MPa and 107.6 ± 6.4 MPa, respectively) and FM (3.3 ± 0.1 GPa and 3.0 ± 0.2 GPa, respectively) compared to the 3D‐printed Denture Teeth (FS = 66.4 ± 18.5 MPa and FM = 1.8 ± 0.1 GPa) and Temporary CB (FS = 79.6 ± 12.1 MPa and FM = 2.7 ± 0.4 GPa). Weibull analysis showed that the Ivotion and Flexcera had a more uniform and narrower spatial distribution of defects (m: 27.98 and 29.19) than the printed materials, which had m values of 8.17 and 4.11 for Temporary CB and Denture Teeth, respectively. Although no differences were found in the static properties (FS and FM) between Ivotion and Flexcera, Ivotion presented a higher endurance limit than Flexcera (51.43 vs. 40.95 MPa). The Temporary CB presented 21.08 MPa and Denture Teeth presented 17.80 MPa of endurance limit.

Conclusions

3D‐milled (Ivotion Denture Teeth) and 3D‐printed (Flexcera Smile Ultra+) composites outperformed 3D‐printed resins (Formlabs Denture Teeth and Temporary Crown & Bridge) in terms of flexural properties and fatigue resistance. 3D‐milled (Ivotion) and 3D‐printed (Flexcera) composites exhibited similar flexural properties, but 3D‐milled composites showed a 25% higher fatigue endurance limit, suggesting improved clinical longevity.
Effects of an ice roller on chronic kidney disease‐associated pruritus in patients receiving haemodialysis
Authors: Lin Jong‐Ni , Chen Chiu‐Feng , Huang Chih‐Yuan , Lai Feng‐Min , Wang Chi‐Jane
Published: March 2024

Background

Chronic kidney disease‐associated pruritus is a distressing symptom and has a far‐reaching impact on patients' sleep and quality of life for most patients receiving haemodialysis. Traditional therapies have limited effectiveness.

Objectives

This study aimed to invent a self‐operated ice roller and evaluate its efficacy in relieving pruritus, sleep quality, and quality of life.

Design

This study was experimental with a two‐arm parallel group design.

Participants

A convenient sampling method was used to recruit 60 patients receiving haemodialysis who reported pruritus (5D‐Itch Scale score >5) lasting over 4 weeks in Taiwan. The participants were randomly assigned to one of two groups: the intervention group used an ice roller for 7 days, while the control group received no anti‐pruritus treatment.

Measurements

This study was experimental with a two‐arm parallel group design. The measurement instruments included the 5D‐Itch Scale, Pittsburgh Sleep Quality Index and WHOQOL‐BREF‐Taiwan Version. The analysis of covariance, chi‐square, Independent t tests, and partial Eta2 (η2p) were used to analyse the data.

Results

The participants' mean age was 62.77 years. Application of the ice roller significantly decreased overall pruritus (p < .05; η2p = .09) and distribution of pruritus‐associated bodily parts (p = .03; η2p = .08). There were no statistically significant differences in sleep quality and related indicators between the experimental and control groups at the study endpoint. Regarding quality of life, only the social relationship domain significantly differed between the two groups (p = .02; η2p = .08).

Conclusions

The ice roller can decrease pruritus and its distribution in patients receiving haemodialysis, serving as an adjunct therapy alongside conventional anti‐pruritus treatments.
Ecological characteristics explain neutral genetic variation of three coastal sparrow species
Authors: Maxwell Logan M. , Clark Jonathan D. , Walsh Jennifer , Conway Meaghan , Olsen Brian J. , Kovach Adrienne I.
Published: March 2024

Eco‐phylogeographic approaches to comparative population genetic analyses allow for the inclusion of intrinsic influences as drivers of intraspecific genetic structure. This insight into microevolutionary processes, including changes within a species or lineage, provides better mechanistic understanding of species‐specific interactions and enables predictions of evolutionary responses to environmental change. In this study, we used single nucleotide polymorphisms (SNPs) identified from reduced representation sequencing to compare neutral population structure, isolation by distance (IBD), genetic diversity and effective population size (Ne) across three closely related and co‐distributed saltmarsh sparrow species differing along a specialization gradient—Nelson's (Ammospiza nelsoni subvirgata), saltmarsh (A. caudacuta) and seaside sparrows (A. maritima maritima). Using an eco‐phylogeographic lens within a conservation management context, we tested predictions about species' degree of evolutionary history and ecological specialization to tidal marshes, habitat, current distribution and population status on population genetic metrics. Population structure differed among the species consistent with their current distribution and habitat factors, rather than degree of ecological specialization: seaside sparrows were panmictic, saltmarsh sparrows showed hierarchical structure and Nelson's sparrows were differentiated into multiple, genetically distinct populations. Neutral population genetic theory and demographic/evolutionary history predicted patterns of genetic diversity and Ne rather than degree of ecological specialization. Patterns of population variation and evolutionary distinctiveness (Shapely metric) suggest different conservation measures for long‐term persistence and evolutionary potential in each species. Our findings contribute to a broader understanding of the complex factors influencing genetic variation, beyond specialist‐generalist status and support the role of an eco‐phylogeographic approach in population and conservation genetics.
Between cyber retaliation and escalation: Explaining the variations in state compliance with the principle of proportionality
Authors: Katagiri Nori
Published: March 2024

I examine how the proportionality principle shapes state responses to a cyberattack. I do so by investigating variation in the effects of the principle of proportionality on the state response. The variation accounts for four types of state response. First, if states respond to a first strike in a proportionate manner, they are in compliance with the principle, and attackers are likely to take it as an indication of willingness to honor the principle. Second, states may react to attackers with an excessive response in violation of the principle, which would force attackers to react as or more harshly. Third, states may accidentally make a proportionate response when they in fact seek to impose excessive harm on attackers. Finally, states may generate an excessive response by error when they in fact seek to comply with the principle.

Related Articles

Glen, Carol. 2021. “Norm Entrepreneurship in Global Cybersecurity.” Politics & Policy 49(5): 1121–45. https://doi.org/10.1111/polp.12430.

Glen, Carol M. 2014. “Internet Governance: Territorializing Cyberspace?” Politics & Policy 42(5): 635–57. http://onlinelibrary.wiley.com/doi/10.1111/polp.12093/full.

Zeng, Jinghan, Tim Stevens, and Yaru Chen. 2017. “China's Solution to Global Cyber Governance: Unpacking the Domestic Discourse of ‘Internet Sovereignty.’” Politics & Policy 45(3): 432–64. https://doi.org/10.1111/polp.12202.
Tollmien–Schlichting waves in the subsonic regime
Authors: Masmoudi Nader , Wang Yuxi , Wu Di , Zhang Zhifei
Published: March 2024

The Tollmien–Schlichting (T‐S) waves play a key role in the early stages of boundary layer transition. In a breakthrough work, Grenier, Guo, and Nguyen gave the first rigorous construction of the T‐S waves of temporal mode for the incompressible fluid. Yang and Zhang recently made an important contribution by constructing the compressible T‐S waves of temporal mode for certain boundary layer profiles with Mach number . In this paper, we construct the T‐S waves of both temporal mode and spatial mode to the linearized compressible Navier–Stokes system around the boundary layer flow in the whole subsonic regime , including the Blasius profile. Our approach is based on a novel iteration scheme between the quasi‐incompressible and quasi‐compressible systems, with a key ingredient being the solution of an Orr–Sommerfeld‐type equation using a new Airy–Airy–Rayleigh iteration instead of Rayleigh–Airy iteration introduced by Grenier, Guo, and Nguyen. We believe that the method developed in this work can be applied in solving other related problems for subsonic flows.
Current Status and Emerging Techniques for Measuring the Dielectric Properties of Biological Tissues
Authors: Porter Emily , Farrugia Lourdes , Prakash Punit , Conceição Raquel C. , Shrivastava Devashish , Scapaticci Rosa , Mandija Stefano , Cavagnaro Marta , Curto Sergio
Published: March 2024

The dielectric properties of biological tissues are key parameters that support the design and usability of a wide range of electromagnetic-based medical applications, including for diagnostics and therapeutics, and allow the determination of safety and health effects due to exposure to electromagnetic fields. While an extensive body of literature exists that reports on values of these properties for different tissue types under different measurement conditions, it is now evident that there are large uncertainties and inconsistencies between measurement reports. Due to varying measurement techniques, limited measurement validation strategies, and lack of metadata reporting and confounder control, reported dielectric properties suffer from a lack of repeatability and questionable accuracy. Recently, the American Society of Mechanical Engineers (ASME) Thermal Medicine Standards Committee was formed, which included a Tissue Properties working group. This effort aims to support the translation and commercialization of medical technologies, through the development of a standard lexicon and standard measurement protocols. In this work, we present initial results from the Electromagnetic Tissue Properties subgroup. Specifically, this paper reports a critical gap analysis facing the standardization pathway for the dielectric measurement of biological tissues. All established measurement techniques are examined and compared, and emerging ones are assessed. Perspectives on the importance and challenges in measurement validation, accuracy calculation, metadata collection, and reporting are also discussed.
Optimized Ray-Based Method for Workspace Determination of Kinematic Redundant Manipulators
Authors: Ginnante Angelica , Caro Stéphane , Simetti Enrico , Leborne François
Published: March 2024

Determining the workspace of a robotic manipulator is highly significant for knowing its abilities and planning the robot application. Several techniques exist for robot workspace determination. However, these methods are usually affected by computational redundancy, like in the Monte Carlo based method case, and their implementation can be complex. The workspace analysis of kinematic redundant manipulators is even more complex. This paper proposes a kinematically optimized ray-based workspace determination algorithm based on a simple idea and not affected by computational redundancy. The proposed method can be applied to any serial robot but is tested only on spatial kinematic redundant robots. The results show how the approach can correctly determine the robot workspace boundaries in a short time. Then, the correctness and computational time of the proposed optimized ray-based method are compared to pseudo-inverse Jacobian ray-based and Monte Carlo methods. The comparison demonstrates that the proposed method has better results in a shorter time. Finally, some limitations of the proposed algorithm are discussed.
Near-Zero Parasitic Shift Flexure Pivots Based on Coupled n-RRR Planar Parallel Mechanisms
Authors: Tissot-Daguette Loïc , Cosandier Florent , Thalmann Etienne , Henein Simon
Published: March 2024

Flexure pivots, which are widely used for precision mechanisms, generally have the drawback of presenting parasitic shifts accompanying their rotation. The known solutions for canceling these undesirable parasitic translations usually induce a loss in radial stiffness, a reduction of the angular stroke, and nonlinear moment–angle characteristics. This article introduces a novel family of kinematic structures based on coupled n-RRR planar parallel mechanisms, which presents exact zero parasitic shifts while alleviating the drawbacks of some known pivoting structures. Based on this invention, three symmetrical architectures have been designed and implemented as flexure-based pivots. The performance of the newly introduced pivots has been compared with two known planar flexure pivots having theoretically zero parasitic shift via Finite Element models and experiments performed on plastic mockups. The results show that the newly introduced flexure pivots are an order of magnitude radially stiffer than the considered pivots from the state-of-the-art while having equivalent angular strokes. To experimentally evaluate the parasitic shift of the novel pivots, one of the architectures was manufactured in titanium alloy using wire-cut electrical discharge machining. This prototype exhibits a parasitic shift under 1.5 µm over a rotation stroke of ±15 deg, validating the near-zero parasitic shift properties of the presented designs. These advantages are key to applications such as mechanical time bases, surgical robotics, or optomechanical mechanisms.
Grid-less wideband direction of arrival estimation based on variational Bayesian inference
Authors: Dou Rui , Ding Feilong , Chen Xi , Wang Jian , Yu Deyong , Tang Yuangui
Published: March 2024

Many recent works have addressed the problem of wideband direction of arrival (DOA) estimation using grid-less sparse techniques, and these methods have been shown to outperform the traditional wideband DOA estimation methods. However, these methods often suffer from the problem of requiring manual parameter tuning or high computational complexity, which reduces their practicality. To alleviate this problem, a grid-less wideband DOA estimation method based on variational Bayesian inference is proposed in this paper. The method approximates the posterior probability density function of DOA with the help of variational Bayesian inference, which does not require manual adjustment of parameters and can obtain accurate DOA estimation results with low computational complexity. Numerical simulations and real measurement data processing show that the proposed method has a higher DOA estimation accuracy than other grid-less wideband methods while providing higher computational speed.
Sister chromatid cohesion establishment during DNA replication termination
Authors: Cameron George , Gruszka Dominika T. , Gruar Rhian , Xie Sherry , Kaya Çağla , Nasmyth Kim A. , Baxter Jonathan , Srinivasan Madhusudhan , Yardimci Hasan
Published: March 2024

Newly copied sister chromatids are tethered together by the cohesin complex, but how sister chromatid cohesion coordinates with DNA replication is poorly understood. Prevailing models suggest that cohesin complexes, bound to DNA before replication, remain behind the advancing replication fork to keep sister chromatids together. By visualizing single replication forks colliding with preloaded cohesin complexes, we find that the replisome instead pushes cohesin to where a converging replisome is met. Whereas the converging replisomes are removed during DNA replication termination, cohesin remains on nascent DNA and provides cohesion. Additionally, we show that CMG (CDC45–MCM2-7–GINS) helicase disassembly during replication termination is vital for proper cohesion in budding yeast. Together, our results support a model wherein sister chromatid cohesion is established during DNA replication termination.
Cryptic diversity of cellulose-degrading gut bacteria in industrialized humans
Authors: Moraïs Sarah , Winkler Sarah , Zorea Alvah , Levin Liron , Nagies Falk S. P. , Kapust Nils , Lamed Eva , Artan-Furman Avital , Bolam David N. , Yadav Madhav P. , Bayer Edward A. , Martin William F. , Mizrahi Itzhak
Published: March 2024

Humans, like all mammals, depend on the gut microbiome for digestion of cellulose, the main component of plant fiber. However, evidence for cellulose fermentation in the human gut is scarce. We have identified ruminococcal species in the gut microbiota of human populations that assemble functional multienzymatic cellulosome structures capable of degrading plant cell wall polysaccharides. One of these species, which is strongly associated with humans, likely originated in the ruminant gut and was subsequently transferred to the human gut, potentially during domestication where it underwent diversification and diet-related adaptation through the acquisition of genes from other gut microbes. Collectively, these species are abundant and widespread among ancient humans, hunter-gatherers, and rural populations but are rare in populations from industrialized societies thus indicating potential disappearance in response to the westernized lifestyle.
Statements by scientific organizations can, and should, shape society
Authors: Fuentes Agustín
Published: March 2024

Statements based on the best current scientific data and analyses that bear directly on societal issues, especially ones that are critical to societal justice, equity, and health, are practical responsibilities of professional scientific organizations. And they often have impact.
Misconduct’s forgotten victims
Authors: Thorp H. Holden
Published: March 2024

The drumbeat of complaints over the poor treatment of graduate students and postdocs in academic science continues. As explained on this page, there is a seemingly endless “slow-motion crisis” of strikes, failures at collective bargaining, and damaging news stories about the mistreatment of and poor working conditions for graduate students. Meanwhile, a parade of stories about academic fraud and failures to address research integrity undermine public trust in science. These two threads are connected. Although media coverage of research misconduct tends to focus on the motives and actions of high-flying faculty members and their institutions, the casualties of such tumult are hardly mentioned: the trainees who may be traumatized personally and harmed professionally by the clumsy, opaque, and slow way that institutions deal with these incidents.
Suicide risk assessment tools and prediction models: new evidence, methodological innovations, outdated criticisms
Authors: Seyedsalehi Aida , Fazel Seena
Published: March 2024

The number of prediction models for suicide-related outcomes has grown substantially in recent years. These models aim to assist in stratifying risk, improve clinical decision-making, and facilitate a personalised medicine approach to the prevention of suicidal behaviour. However, there are contrasting views as to whether prediction models have potential to inform and improve assessment of suicide risk. In this perspective, we discuss common misconceptions that characterise criticisms of suicide risk prediction research. First, we discuss the limitations of a classification approach to risk assessment (eg, categorising individuals as low-risk vs high-risk), and highlight the benefits of probability estimation. Second, we argue that the preoccupation with classification measures (such as positive predictive value) when assessing a model’s predictive performance is inappropriate, and discuss the importance of clinical context in determining the most appropriate risk threshold for a given model. Third, we highlight that adequate discriminative ability for a prediction model depends on the clinical area, and emphasise the importance of calibration, which is almost entirely overlooked in the suicide risk prediction literature. Finally, we point out that conclusions about the clinical utility and health-economic value of suicide prediction models should be based on appropriate measures (such as net benefit and decision-analytic modelling), and highlight the role of impact assessment studies. We conclude that the discussion around using suicide prediction models and risk assessment tools requires more nuance and statistical expertise, and that guidelines and suicide prevention strategies should be informed by the new and higher quality evidence in the field.
Exposure to early-life adversity and long-term trajectories of multimorbidity among older adults in China: analysis of longitudinal data from the China Health and Retirement Longitudinal Study
Authors: Liu Huiying , Zhang Mi , Zhang Xinyan , Zhao Xinyi
Published: March 2024

Objectives

This study aimed to identify long-term distinct trajectories of multimorbidity with ageing from 50 to 85 years among Chinese older adults and examine the relationship between exposure to early-life adversity (ELA; including specific types of adversity and accumulation of different adversities) and these long-term multimorbidity trajectories.

Design

The group-based trajectory models identified long-term multimorbidity trajectories. Multinomial logistic regression models were used to examine the relationship between ELA and the identified multimorbidity trajectories.

Setting

This study used data from the China Health and Retirement Longitudinal Study (CHARLS, 2011–2018) and the 2014 Life History Survey.

Participants

We used data from 9112 respondents (aged 60 and above) of the 2018 wave of CHARLS.

Outcome measures

Each respondent’s history of chronic conditions and experiences of ELA were collected from the 2011–2018 waves of CHARLS and the 2014 Life History Survey.

Results

Four heterogeneous long-term trajectories of multimorbidity development were identified: ‘maintaining-low’ (19.1%), ‘low onset-rapidly increasing’ (23.3%), ‘middle onset-moderately increasing’ (41.5%) and ‘chronically-high’ (16.2%). Our findings indicated that the heterogeneity can be explained by ELA experiences. Across various types of different ELA experiences, exposure to food insufficiency (relative risk ratios from 1.372 (95% CI 1.190 to 1.582) to 1.780 (95% CI 1.472 to 2.152)) and parental quarrel/divorce (relative risk ratios from 1.181 (95% CI 1.000 to 1.394) to 1.262 (95% CI 1.038 to 1.536)) had the most prominent associations with health deterioration. The accumulation of more different ELA experiences was associated with a higher relative risk of developing more severe multimorbidity trajectories (relative risk ratio for five to seven ELAs and chronically high trajectory: 7.555, 95% CI 4.993 to 11.431).

Conclusions

There are heterogeneous long-term trajectories of multimorbidity in Chinese older adults, and the risk of multimorbidity associated with ELA accumulates over the lifespan. Our findings highlight the role of a supportive early-life family environment in promoting health development across the lifespan, advocating for the integration of life-course approaches to implementing health disparity interventions.
Patient characteristics, surgery outcomes, presumed aetiology and other characteristics of fistula surgeries and related procedures supported by Fistula Foundation from 2019 to 2021: a multicentre, retrospective observational study
Authors: Pollaczek Lindsey , Rajagopal Keerthana , Chu Jesse
Published: March 2024

Objectives

Obstetric fistula is a devastating childbirth injury primarily caused by prolonged, obstructed labour. It leaves women incontinent, severely stigmatised and isolated. Fistula repair surgery can restore a woman’s health and well-being. Fistula Foundation, a non-profit organisation, works in partnership with local hospitals and community organisations in Africa and Asia to address key barriers to treatment and to increase the number of women receiving surgical care. This paper presents data on fistula and fistula repair surgery across a large global network of hospitals supported by Fistula Foundation. The data were collected between 2019 and 2021.

Design

Multicentre, retrospective, observational, descriptive study.

Setting and participants

The study analysed deidentified data from 24 568 surgical repairs supported by Fistula Foundation to treat women with obstetric fistula at 110 hospitals in 27 countries.

Results

The data highlight patient characteristics and key trends and outcomes from obstetric fistula repair surgeries and related procedures. Of those surgeries, 87% resulted in a successful outcome (fistula dry and closed) at the time of discharge, highlighting the effectiveness of fistula repair in restoring continence and improving quality of life. Over the period studied, the number of supported surgeries increased by 14%, but there remains an urgent need to strengthen local surgical capacity and improve access to treatment. Women suffered an average of 5.7 years before they received surgery and only 4% of women sought care independently. This underscores the importance of enhancing community awareness and strengthening referral networks.

Conclusions

This research provides essential insight from a vast, global network of hospitals providing highly effective fistula repair surgery. Further investment is needed to strengthen surgical capacity, increase awareness of fistula and remove financial barriers to treatment if stakeholders are to make significant progress towards the United Nations’ ambitious vision of ending fistula by 2030.
Cross-sectional study to assess the impact of the COVID-19 pandemic on healthcare services and clinical admissions using statistical analysis and discovering hotspots in three regions of the Greater Toronto Area
Authors: Movahedi Nia Zahra , Prescod Cheryl , Westin Michelle , Perkins Patricia , Goitom Mary , Fevrier Kesha , Bawa Sylvia , Kong Jude
Published: March 2024

Objectives

The COVID-19 pandemic disrupted healthcare services, leading to the cancellation of non-urgent tests, screenings and procedures, a shift towards remote consultations, stalled childhood immunisations and clinic closures which had detrimental effects across the healthcare system. This study investigates the impact of the COVID-19 pandemic on clinical admissions and healthcare quality in the Peel, York and Toronto regions within the Greater Toronto Area (GTA).

Design

In a cross-sectional study, the negative impact of the pandemic on various healthcare sectors, including preventive and primary care (PPC), the emergency department (ED), alternative level of care (ALC) and imaging, procedures and surgeries is investigated. Study questions include assessing impairments caused by the COVID-19 pandemic and discovering hotspots and critical subregions that require special attention to recover. The measuring technique involves comparing the number of cases during the COVID-19 pandemic with before that, and determining the difference in percentage. Statistical analyses (Mann-Whitney U test, analysis of variance, Dunn’s test) is used to evaluate sector-specific changes and inter-relationships.

Setting

This work uses primary data which were collected by the Black Creek Community Health Centre. The study population was from three regions of GTA, namely, the city of Toronto, York and Peel. For all health sectors, the sample size was large enough to have a statistical power of 0.95 to capture 1% variation in the number of cases during the COVID-19 pandemic compared with before that.

Results

All sectors experienced a significant decline in patient volume during the pandemic. ALC admissions surged in some areas, while IPS patients faced delays. Surgery waitlists increased by an average of 9.75%, and completed IPS procedures decreased in several subregions.

Conclusions

The COVID-19 pandemic had a universally negative impact on healthcare sectors across various subregions. Identification of the hardest-hit subregions in each sector can assist health officials in crafting recovery policies.
Improving availability and accuracy of the junior doctors’ on-call handover through digitalisation
Authors: Haysom Alexia , Loveday William Harry , Ratneswaran Kajanesh , Nerantzis Georgios , Hakim Nahid , Dineva Darena , Richards Adam
Published: March 2024

Clinical handovers from out-of-hours activity are essential for relaying information about events such as new admissions, outstanding or complete investigations, physical health reviews, ward jobs and risk. This information enables the day team to effectively prioritise and follow-up any necessary tasks.

Junior doctors at a hospital site in the London Borough of Newham were aware that the existing handover system, constituted of a word document circulated via email, was lacking robustness and that the handover was not sent out reliably on a daily basis.

Quality improvement (QI) methods including process mapping, PDSA ('Plan, Do, Study, Act') cycles, driver diagrams and run charts were used to understand the issue, create a more robust process and measure the improvements made, all supported by regular QI project meetings. The change ideas included moving from an informal Microsoft (MS) Word document, which was emailed out, to an Excel spreadsheet stored centrally on MS Teams. Column headers were added for admissions, ward jobs, seclusion reviews, matters relating to mental health law and Accident and Emergency (A&E) assessments, as well as defined columns for outstanding jobs and standard tasks that need to be completed for all admissions. Responsibility for circulating the handover list was given to the incoming day duty doctor if the night doctor was too busy, with admin support to chase the circulation of the handover. Results were studied for the following 18 months.

The percentage of handovers being appropriately sent out increased from a median of 80% to 100% during the project period, and the availability of handover data where the data were visible to doctors on MS Teams but had not been sent out also increased from a median of 80% to 100%. The system was deemed safe, effective and easy to use, and has already been replicated at neighbouring hospitals.
Socioeconomic disparity in stage at cancer diagnosis among patients with type 2 diabetes in Dutch primary care: a cross-sectional study
Authors: de Haan-Du Jing , Groenier Klaas H , Kleefstra Nanne , van der Vegt Bert , Siesling Sabine , Landman Gijs W D , de Bock Geertruida H
Published: March 2024

Introduction

Disparities in cancer stage appear to exist by socioeconomic status (SES) in the Netherlands. We evaluated the association of SES and cancer stage among patients with type 2 diabetes (T2DM) treated in primary care.

Research design and methods

This cross-sectional study linked data from the primary care Zwolle Outpatient Diabetes Project Integrating Available Care database for T2DM (n=71 648, 1998–2019) to a cancer registry and personal records database in the Netherlands. Only cancers (excluding all skin cancers) diagnosed after the onset of diabetes were included and grouped by stages (III–IV or 0–II). SES was estimated as low, intermediate or high based on postal codes and Dutch social research status scores. Logistic regression was performed, with stratification by sex and correction for age, body mass index, smoking, diabetes duration, glycaemic control and metformin use. ORs and 95% CI are reported.

Results

Of the 5087 males and 4021 females with any cancer, 50.1% and 53.7% had low SES, respectively. Compared with patients with high SES, the ORs for diagnosing cancer at stages III–IV in patients with low SES were 1.00 (95% CI 0.84 to 1.19) for males and 1.32 (95% CI 1.06 to 1.67) for females. However, the ORs varied by cancer type: breast, 1.46 (95% CI 0.90 to 2.39); male colorectal, 1.00 (95% CI 0.70 to 1.43); female colorectal, 1.72 (95% CI 1.06 to 2.77); prostate, 0.81 (95% CI 0.57 to 1.15); male lung, 1.06 (95% CI 0.62 to 1.80) and female lung, 2.56 (95% CI 1.32 to 4.95).

Conclusions

Among patients treated for T2DM in Dutch primary care, our data suggest the need to target females with low SES to decrease inequalities in the early detection of colorectal and lung cancer.
Oral nicotine product marketing expenditures in the USA from 2016 to 2023: trends over time by brand and targeted media outlets
Authors: Ozga Jenny E , Cornacchione Ross Jennifer , Hrywna Mary , Sharma Akshika , Ling Pamela M , Stanton Cassandra A
Published: March 2024

Background

Oral nicotine products (ONPs) are increasing in sales, availability and flavours. In April 2022, the US Food and Drug Administration (FDA) obtained regulatory authority over non-tobacco nicotine products, which include many ONPs. Advertising practices for ONPs need monitoring to understand marketing strategies and inform FDA marketing authorisation decisions.

Methods

ONP advertisement (ad) expenditure data (January 2016–June 2023) were purchased (print, TV, radio, online video, online display and mobile; N=125 236) and adjusted to 2023 dollars. Descriptive statistics examined expenditures by ONP brand and media outlet over time.

Results

Velo spent the most on ONP advertising (89.8%), followed by Zyn (5.7%) and Black Buffalo (1.2%). Velo encompassed the majority of TV (98.1%), radio (99.9%) and mobile ad spend (87.3%); Zyn was the leader for online display (46.2%) and online video (71.1%); and Black Buffalo accounted for 100% of print ads. In 2023, (January–June), Zyn accounted for 88.0% of ad expenditures and Velo spent $0, though the total amount spent by Zyn was far less than Velo in prior years. TV ads (98.1% Velo) aired primarily on prime time/late night or 09:00–17:00 on weekends. Radio ads (99.9% Velo) aired primarily from 06:00 to 10:00, 12:00 to 14:00 and 15:00 to 19:00 on weekdays. Overall, expenditures focused on reaching a national audience, though print ads indicated potential male-targeted marketing.

Conclusions

Following FDA’s regulatory authority over non-tobacco nicotine products, ad expenditures for Velo dropped to $0. Ongoing surveillance of ONP ad trends can inform FDA marketing authorisation decisions by revealing brand-specific marketing strategies that may be targeted toward populations at increased risk of tobacco use.