bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel framework to assess haematology and oncology registration trials: The THEOREMM project
Authors: Olivier Timothée , Haslam Alyson , Burke Patricia , Boutron Isabelle , Naudet Florian , Ioannidis John P. A. , Prasad Vinay
Published: June 2024

Background

Methodological limitations affect a significant number of oncology and haematology trials, raising concerns about the applicability of their results. For example, a suboptimal control arm or limited access to best care upon progression may skew the trial results toward a benefit in the experimental arm. Beyond the fact that such limitations do not prevent drugs reaching the market, other assessment tools, such as those developed by professional societies—ESMO‐MCBS and ASCO Value Framework—do not integrate these important shortcomings.

Methods

We propose creating a novel framework with the scope of assessing registration cancer clinical trials in haematology and oncology (randomized or single arm)—that is trials leading to a marketing authorization. The main steps of the methods are (1) assembling a scientific board; (2) defining the scope, goal and methods through pre‐specified, pre‐registered and protocolized methodology; (3) preregistration of the protocol; (4) conducting a scoping review of limitations and biases affecting oncology trials and assessing existing scores or methods; (5) developing a list of features to be included and assessed within the framework; (6) assessing each feature through a questionnaire sent to highly cited haematologists and oncologists involved in clinical trials; and (7) finalizing the first version of framework.

Results

Not applicable.

Conclusions

Our proposal emerged in response to the lack of consideration for key limitations in current trial assessments. The goal is to create a framework specifically designed to assess single trials leading to marketing authorization in the field of oncology and haematogy.
An integrated approach for detecting and classifying pores and surface topology for fatigue assessment 316L manufactured by powder bed fusion of metals using a laser beam using μCT and machine learning algorithms
Authors: Diller Johannes , Siebert Ludwig , Winkler Michael , Siebert Dorina , Blankenhagen Jakob , Wenzler David , Radlbeck Christina , Mensinger Martin
Published: June 2024

This research aims to detect and analyze critical internal and surface defects in metal components manufactured by powder bed fusion of metals using a laser beam (PBF‐LB/M). The aim is to assess their impact on the fatigue behavior. Therefore, a combination of methods, including image processing of micro‐computed tomography (
CT) scans, fatigue testing, and machine learning, was applied. A workflow was established to contribute to the nondestructive assessment of component quality and mechanical properties. Additionally, this study illustrates the application of machine learning to address a classification problem, specifically the categorization of pores into gas pores and lack of fusion pores. Although it was shown that internal defects exhibited a reduced impact on fatigue behavior compared with surface defects, it was noted that surface defects exert a higher influence on fatigue behavior. A machine learning algorithm was developed to predict the fatigue life using surface defect features as input parameters.
Self‐directed use of machine translation among language learners: Does it lead to disruptive L2 avoidance?
Authors: Murtisari Elisabet Titik , Kristianto Andreas Kukuh , Bonar Gary
Published: June 2024

Rapid improvements in the capabilities of machine translation (MT) raise questions about possible increases in overreliance on MT among lower‐proficiency or novice level language learners. This study investigated how such learners described their use of online MT for independent reading and writing tasks, and whether this included descriptions of second language (L2) avoidance behavior. We also explored learners' reasons for using MT and the perceived effects on their language learning. Findings from in‐depth interviews with eight second‐year tertiary language learners suggest that using MT could exceed desirable use among such learners in relation to the language learning objectives, resulting in language avoidance. Although MT helped them in completing language tasks, its effects were perceived to be detrimental toward their abilities to express themselves in the L2. As such, the use of MT may lead to purely superficial language learning in formal language programs. These findings suggest language educators need to consider instructional scaffolding in language programs for such learners and guidelines to assist their autonomous use of the tool.
Transpositions as a hopeful methodology for organizational studies
Authors: Martin Lydia A. , Sayers Janet G. , Carroll Brigid
Published: June 2024

In this paper, we introduce Braidotti’s notion of transpositions as a methodology and strategy for ‘hopeful disruptions’ in the context of organizational inquiry. Transpositions consist of six interwoven practices―(1) embracing alternative ways of seeing and understanding the world, (2) assessing and critiquing imaginary forms, (3) preparing to make the ‘creative leap’, (4) accounting for locations and positioning, (5) storying the ‘in‐between’ space, and (6) developing new frames of resonance for existing cultural formations, such as heroic leadership. Underpinned by feminist posthumanist thinking, transposition practices produce ‘generative cracks’ in hegemonic systems and in dominant social imaginaries, as well as bringing forth affirmative alternatives for thought and practice. As a feminist approach, it is also concerned with engaging gender differently and strategically to chart paths out of restrictive categories and reductive, individualist notions of being. Playing with the inherently subversive nature of this approach and tapping into our desire to disrupt the masculine ‘common sense’ of much social science research, we draw on the insights and writings of feminist speculative fiction authors to elaborate on the six practices and their implications for researchers. We further demonstrate the potential for transpositions in organizational studies through a discussion of radical empiricist approaches to inquiry and collaborative research projects.
Host plants and landscape predict use of roadside habitat by breeding monarchs
Authors: Cariveau Alison J. Banks , Haynes Grace A. , Perish Patrick , Tuerk Karen , Nootenboom Chris , Mitchell Timothy , Lonsdorf Eric , Oberhauser Karen , Snell‐Rood Emilie C.
Published: June 2024

Vegetation along roadside edges, while posing some risks, can also provide breeding habitat for monarch butterflies.

We investigated how landscape and site‐specific factors affect the quality of roadsides as monarch breeding habitat. We surveyed more than 250 sites along roadsides throughout Minnesota for milkweeds, floral resources and monarch eggs and larvae.

We found that milkweed distribution was affected by adjacent land use and geography, with milkweeds more likely to be present in roadsides adjacent to crop and grassland and the south and west of the state.

The presence and density of monarch eggs and larvae were primarily driven by milkweed density, with the likelihood of monarch presence at each site increasing with milkweed density. The density of monarchs per plant increased in sites with lower densities of milkweed, suggesting that monarch eggs are concentrated more densely on fewer plants where milkweed is scarce and spread more thinly across plants where milkweed is common. Monarch density per milkweed increased as sites were farther from core grasslands, to the south, and on narrower roadsides, also suggesting use may be higher in areas with a scarcity of habitat. The density of monarch eggs and larvae was higher in mowed than unmowed milkweed.

Our study suggests that roadside habitats effectively provide breeding locations for monarchs, regardless of adjacent land use type and even when distant to high‐quality natural areas. Our findings assist conservation practitioners in planning and managing roadside habitats for monarchs and other pollinators.
Successfully initiating an escalation of care in acute ward settings—A qualitative observational study
Authors: Ede J. , Kent B. , Watkinson P. , Endacott R.
Published: June 2024

Aims

To address knowledge gaps by (i) developing a theoretical understanding of escalation and (ii) identifying escalation success factors.

Design

Non‐participant observations were used to examine deteriorating patient escalation events.

Methods

Escalation event data were collected by a researcher who shadowed clinical staff, between February 16th 2021 and March 17th 2022 from two National Health Service Trusts. Events were analysed using Framework Analysis. Escalation tasks were mapped using a Hierarchical Task Analysis diagram and data presented as percentages, frequency and 95% CI.

Results

A total of 38 observation sessions were conducted, totaling 105 h, during which 151 escalation events were captured. Half of these were not early warning score‐initiated and resulted from bleeding, infection, or chest pain. Four communication phenotypes were observed in the escalation events. The most common was Outcome Focused Escalation, where the referrer expected specific outcomes like blood cultures or antibiotic prescriptions. Informative Escalations were often used when a triggering patient's condition was of low clinical concern and ranked as the second most frequent escalation communication type. General Concern Escalations occurred when the referrer did not have predetermined expectations. Spontaneous Interaction Escalations were the least frequently observed, occurring opportunistically in communal workspaces.

Conclusion

Half of the events were non‐triggering escalations and understanding these can inform the design of systems to support staff better to undertake them. Escalation is not homogenous and differing escalation communication phenotypes exist. Informative Escalations represent an organizational requirement to report triggering warning scores and a targeted reduction of these may be organizationally advantageous. Increasing the frequency of Spontaneous Escalations, through hospital designs, may also be beneficial.

Impact Statement

Our work highlights that a significant proportion of escalation workload occurs without a triggering early warning score and there is scope to better support these with designed systems. Further examination of reducing Informative and increasing Spontaneous Escalations is also warranted.

Patient and Public Contribution

Extensive PPIE was completed throughout the lifecycle of this study. PPIE members validated the research questions and overarching aims of the overall study. PPIE members contributed to the design of the study reviewed documents and the final data generated.
Fecal microbiota transplantation ameliorates high‐fat diet‐induced memory impairment in mice
Authors: Pereira Louise Tavares Garcia , Vilela Wembley Rodrigues , Bellozi Paula Maria Quaglio , Engel Daiane Fátima , de Paula Gabriela Cristina , de Andrade Rafael Rocha , Mortari Márcia Renata , de Melo Teixeira Marcus , Coleine Claudia , Figueiredo Cláudia Pinto , de Bem Andreza Fabro , Amato Angélica Amorim
Published: June 2024

Gut dysbiosis is linked to metabolic and neurodegenerative diseases and comprises a plausible link between high‐fat diet (HFD) and brain dysfunction. Here we show that gut microbiota modulation by either antibiotic treatment for 5 weeks or a brief 3‐day fecal microbiota transplantation (FMT) regimen from low‐fat (control) diet‐fed mice decreased weight gain, adipose tissue hypertrophy, and glucose intolerance induced by HFD in C57BL/6 male mice. Notably, gut microbiota modulation by FMT completely reversed impaired recognition memory induced by HFD, whereas modulation by antibiotics had less pronounced effect. Improvement in recognition memory by FMT was accompanied by decreased HFD‐induced astrogliosis in the hippocampal cornu ammonis region. Gut microbiome composition analysis indicated that HFD diminished microbiota diversity compared to control diet, whereas FMT partially restored the phyla diversity. Our findings reinforce the role of the gut microbiota on HFD‐induced cognitive impairment and suggest that modulating the gut microbiota may be an effective strategy to prevent metabolic and cognitive dysfunction associated with unfavorable dietary patterns.

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Cdk5 inhibition in the SOD1G93A transgenic mouse model of amyotrophic lateral sclerosis suppresses neurodegeneration and extends survival
Authors: Kim Ahwon , Lee Do‐Yeon , Sung Jung‐Joon
Published: June 2024

Deregulated cyclin‐dependent kinase 5 (Cdk5) activity closely correlates with hyperphosphorylated tau, a common pathology found in neurodegenerative diseases. Previous postmortem studies had revealed increased Cdk5 immunoreactivity in amyotrophic lateral sclerosis (ALS); hence, we investigated the effects of Cdk5 inhibition on ALS model mice and neurons in this study. For the in vitro study, motor neuron cell lines with wild‐type superoxide dismutase 1 (SOD1) or SOD1G93A and primary neuronal cultures from SOD1G93A transgenic (TG) mice or non‐TG mice were compared for the expression of proteins involved in tau pathology, neuroinflammation, apoptosis, and neuritic outgrowth by applying Cdk5‐small interfering RNA or Cdk5‐short hairpin RNA (shRNA). For the in vivo study, SOD1G93A mice and non‐TG mice were intrathecally injected with adeno‐associated virus 9 (AAV9)‐scramble (SCR)‐shRNA or AAV9‐Cdk5‐shRNA at the age of 5 weeks. Weight and motor function were measured three times per week from 60 days of age, longevity was evaluated, and the tissues were collected from 90‐day‐old or 120‐day‐old mice. Neurons with SOD1G93A showed increased phosphorylated tau, attenuated neuritic growth, mislocalization of SOD1, and enhanced neuroinflammation and apoptosis, all of which were reversed by Cdk5 inhibition. Weights did not show significant differences among non‐TG and SOD1G93A mice with or without Cdk5 silencing. SOD1G93A mice treated with AAV9‐Cdk5‐shRNA showed significantly delayed disease onset, delayed rotarod failure, and prolonged survival compared with those treated with AAV9‐SCR‐shRNA. The brain and spinal cord of SOD1G93A mice intrathecally injected with AAV9‐Cdk5‐shRNA exhibited suppressed tau pathology, neuroinflammation, apoptosis, and an increased number of motor neurons compared to those of SOD1G93A mice injected with AAV9‐SCR‐shRNA. Cdk5 inhibition could be an important mechanism in the development of a new therapeutic strategy for ALS.

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The dual‐path mechanism underlying the influence of customers' negative feedback on the job crafting
Authors: Liu Bo , Yun Jiang , Zhao Jinjin
Published: June 2024

Although previous studies have generally explored the important role played by customers' negative feedback in shaping employees' behaviour, these studies have only briefly discussed the one‐sided effects of such feedback on employees' cognition or emotions. In addition, previous studies have not discussed in depth whether customers' negative feedback has both positive and negative effects. Based on the theoretical background of the cognitive–affective processing system, we constructed a dual‐path model of the impact of customers' negative feedback on job crafting via both cognitive and affective paths and investigated the moderating effect of the error management climate in this context. A three‐stage survey design was used to examine these assumptions by referencing data collected from 382 frontline employees working in various tourism and hospitality companies. In line with our expectations, we found that customers' negative feedback can have a double‐edged sword effect via these two paths and that the error management climate moderates this dual‐path mechanism. We conclude this research by discussing the theoretical and practical implications of our findings.
Respiratory reference values for bottlenose dolphins (Tursiops spp.) and its importance for conservation
Authors: Cauture Fabien , Sweeney Jay , Stone Rae , Fahlman Andreas
Published: June 2024

Respiratory disease is one of the main causes for morbidity and mortality in cetaceans, which highlights the importance of understanding normal lung function and how it may impede homeostasis, and diving capacity. In addition, the use of breathing frequency as a proxy for metabolic rate requires a better estimate of the normal range of tidal volume, respiratory flow, and breath durations. In the current study, we use data on clinically healthy bottlenose dolphins (Tursiops spp.) collected over a decade to define how lung function varies with body mass, age, and sex while in water or during voluntary beaching. The data show that tidal volume consistently varies with body mass both during spontaneous and forced breaths both in water and while beached. Both peak expiratory and inspiratory flow varies with body mass, but also in some circumstances with sex and age. Total and inspiratory breath durations only varied with body mass during forced breaths on land. Expired tidal volume varied with both body mass and either total or expiratory breath duration. These data provide baseline for respiratory function in healthy bottlenose dolphins and suggest that either total or expiratory breath duration provide a useful proxy for tidal volume.
Algorithms or biomarkers in patients with lower DGBI?
Authors: Camilleri Michael , Yang David Yi
Published: June 2024

Background

Several organizations have proposed guidelines or clinical decision tools for the management of patients with disorders of gut‐brain interactions (DGBI) affecting the lower digestive tract including irritable bowel syndrome and chronic idiopathic constipation. Such algorithms are based on sequential therapeutic trials and modifying the treatment strategy based on efficacy and adverse events.

Purpose

The aims of this review are to evaluate the evidence for efficacy of second‐ and third‐line pharmacotherapies and to assess the evidence for the alternative option to manage subgroups of patients with symptoms suggestive of lower DGBI based on diagnostic tests or documented dysfunctions. The preeminent tests to identify such subgroups that present with symptoms that overlap with lower DGBI are detailed: digital rectal examination as well as anorectal manometry and balloon expulsion for evacuation disorders, detailed measurements of colonic transit, and diagnosis of bile acid diarrhea or carbohydrate malabsorption based on biochemical measurements. The review also addresses the cost implications of screening to exclude alternative diagnoses and the costs of therapy associated with the therapeutic options following an algorithmic approach to treatment from the perspective of society, insurer, or patient. Finally, the costs of the diagnostic tests to identify actionable biomarkers and the evidence of efficacy of individualized therapy based on formal diagnosis or documentation of abnormal functions are detailed in the review.
Indoxyl sulfate exacerbates alveolar bone loss in chronic kidney disease through ferroptosis
Authors: Chen Huiwen , Zhou Yining , Liu Yingli , Zhou Wei , Xu Lina , Shang Dihua , Ni Jing , Song Zhongchen
Published: June 2024

Objectives

The purpose of this study was to determine whether indoxyl sulfate (IS) is involved in alveolar bone deterioration and to elucidate the mechanism underlying alveolar bone loss in chronic kidney disease (CKD) patients.

Materials and Methods

Mice were divided into the control group, CP group (ligature‐induced periodontitis), CKD group (5/6 nephrectomy), and CKD + CP group. The concentration of IS in the gingival crevicular fluid (GCF) was determined by HPLC. The bone microarchitecture was evaluated by micro‐CT. MC3T3‐E1 cells were stimulated with IS, and changes in mitochondrial morphology and ferroptosis‐related factors were detected. RT‐PCR, western blotting, alkaline phosphatase activity assays, and alizarin red S staining were utilized to assess how IS affects osteogenic differentiation.

Results

Compared with that in the other groups, alveolar bone destruction in the CKD + CP group was more severe. IS accumulated in the GCF of mice with CKD. IS activated the aryl hydrocarbon receptor (AhR) in vitro, inhibited MC3T3‐E1 cell osteogenic differentiation, caused changes in mitochondrial morphology, and activated the SLC7A11/GPX4 signaling pathway. An AhR inhibitor attenuated the aforementioned changes induced by IS.

Conclusions

IS activated the AhR/SLC7A11/GPX4 signaling pathway, inhibited osteogenesis in MC3T3‐E1 cells, and participated in alveolar bone resorption in CKD model mice through ferroptosis.
An updated reappraisal of dupilumab in children and adolescents with moderate–severe atopic dermatitis
Authors: Ciprandi Giorgio , Licari Amelia , Tosca Maria Angela , Miraglia del Giudice Michele , Belloni Fortina Anna , Marseglia Gian Luigi
Published: June 2024

Atopic dermatitis (AD) is still a demanding challenge in clinical practice. Type 2 inflammation is the most common inflammatory pathway in children and adolescents with AD. Anti‐inflammatory drugs, mainly corticosteroids (CS) and immunomodulant agents are the primary therapeutic approach to dampening type 2 inflammation. However, AD patients may require long‐term high CS doses or drug combinations with possibly significant adverse effects to achieve and maintain disease control. In this regard, the advent of biologics constituted a breakthrough in managing this condition. Dupilumab is a monoclonal antibody directed against the IL‐4 receptor α‐subunit (IL‐4Rα), antagonizing both IL‐4 and IL‐13 and is approved for pediatric severe AD. This review presents and discusses the most recent published studies on dupilumab in children and adolescents with AD. There is convincing evidence that dupilumab is safe and effective in managing AD. It can reduce skin lesions and associated itching, reduce the need for additional medications, and improve disease control and quality of life. However, a thorough diagnostic pathway is mandatory, especially considering the different AD phenotypes. The ideal eligible candidate is a child or adolescent with AD requiring systemic treatment because of severe clinical manifestations and impaired quality of life.
The fnr‐like mutants confer isoxaben tolerance by initiating mitochondrial retrograde signalling
Authors: Broad Ronan C. , Ogden Michael , Dutta Arka , Dracatos Peter M. , Whelan James , Persson Staffan , Khan Ghazanfar Abbas
Published: June 2024

Isoxaben is a pre‐emergent herbicide used to control broadleaf weeds. While the phytotoxic mechanism is not completely understood, isoxaben interferes with cellulose synthesis. Certain mutations in cellulose synthase complex proteins can confer isoxaben tolerance; however, these mutations can cause compromised cellulose synthesis and perturbed plant growth, rendering them unsuitable as herbicide tolerance traits. We conducted a genetic screen to identify new genes associated with isoxaben tolerance by screening a selection of Arabidopsis thaliana T‐DNA mutants. We found that mutations in a FERREDOXIN‐NADP(+) OXIDOREDUCTASE‐LIKE (FNRL) gene enhanced tolerance to isoxaben, exhibited as a reduction in primary root stunting, reactive oxygen species accumulation and ectopic lignification. The fnrl mutant did not exhibit a reduction in cellulose levels following exposure to isoxaben, indicating that FNRL operates upstream of isoxaben‐induced cellulose inhibition. In line with these results, transcriptomic analysis revealed a highly reduced response to isoxaben treatment in fnrl mutant roots. The fnrl mutants displayed constitutively induced mitochondrial retrograde signalling, and the observed isoxaben tolerance is partially dependent on the transcription factor ANAC017, a key regulator of mitochondrial retrograde signalling. Moreover, FNRL is highly conserved across all plant lineages, implying conservation of its function. Notably, fnrl mutants did not show a growth penalty in shoots, making FNRL a promising target for biotechnological applications in breeding isoxaben tolerance in crops.
Defending The Open Future: Replies to MacFarlane, Green, Wasserman, and Bigg & Miller
Authors: Todd Patrick
Published: June 2024

In this symposium piece, I reply to the diverse and wide‐ranging set of objections to my book (The Open Future: Why Future Contingents are All False) set forth by MacFarlane, Green, Wasserman, and Bigg & Miller.
Indicators for ecological carrying capacity of bivalve and seaweed aquaculture
Authors: Byron Carrie J. , Koch Sophie J. I. , Callier Myriam D. , Kluger Lotta , Angel Dror L. , Vanaverbeke Jan , Filgueira Ramon
Published: June 2024

Within the framework of Ecosystem Approach to Aquaculture (EAA), ecological carrying capacity (ECC) is a key concept that helps to determine the upper limit of production without compromising ecosystem functioning. The implementation of ECC is complex as ECC differs between type of farms and location and standardised methods should be developed for management. There is therefore a clear need for operational indicators. The objectives of this paper were: (1) to carry out a systematic literature review on shellfish and seaweed aquaculture‐environment interactions to list the most used environmental indicators, (2) to classify the indicators according to the effects they measure (i.e., benthic, water quality, food web interactions, cultured organism health, resource use) and the scale at which they are applied, and (3) to assess their potential based on four indicator criteria categories: sensitivity, accuracy and precision, feasibility and utility, and ecosystem‐level scalability. Overall, indicators describing benthic effects were the most highly cited and scored. Indicators identified for bivalve and seaweed culture were discussed and compared to previous work on salmon aquaculture indicators to highlight similarities and differences across trophic levels. In addition, questions related to the challenges of ECC indicators implementation were presented to a panel of experts. The scoring and consultation provided the source of discussion on environmental management consistent with EAA.
Fluid evolution and genesis of the Changchunling Pb–Zn deposit in the Southern Great Xing'an Range, Northeast China: Constraints from fluid inclusions and H–O–S–Pb isotopes
Authors: Ma Xue‐li , Shi Kai‐tuo , Song Kai‐rui , Wang Rui
Published: June 2024

The southern Great Xing'an Range (SGXR), an important polymetallic metallogenic province in the eastern Central Asian Orogenic Belt (CAOB) in Northeast China, containing numerous ore deposits of Cu, Fe, Pb, Zn, Au, and so forth. The Changchunling Pb–Zn deposit, located in the eastern segment of the SGXR, is primarily hosted by a Permian conglomerate and siltstone unit. The paragenetic sequence of the deposit can be divided into three stages involving arsenopyrite–quartz (stage I); pyrite–sphalerite–galena–quartz (stage II); and barren quartz–carbonate (stage III). Fluid inclusion (FIs) microthermometric studies revealed that only liquid‐rich aqueous inclusions (VL‐type FIs) are observed in the ore‐bearing quartz veins. The FIs of stages I, II, and III yield homogenization temperatures of 190–314, 170–268, and 140–195°C with salinities of 9.73–13.44, 7.86–10.74, and 4.94–5.99 wt% NaCl eqv., respectively. The ore‐forming fluids are characterized by low temperature and low salinity of the H2O–NaCl fluid system. The δ18OH2O and δD values range from −11.8‰ to 0‰ and −120.4‰ to −99.9‰, respectively, indicating that the source of the fluids was primarily derived from a mixed fluid of magmatic water and meteoric water. Fluid cooling, mixing and fluid‐rock reactions were the major ore precipitation mechanisms at Chanchunling. Sulfur‐lead isotopes of pyrite and sphalerite (δ34S = 2.3‰–3.7‰, 206Pb/204Pb = 18.259–18.285, 207Pb/204Pb = 15.544–15.57, and 208Pb/204Pb = 38.136–38.215) indicate that ore metals had a magmatic source. Integrating the available geological, mineralization, fluid inclusion, and H–O–S–Pb isotope evidence, we conclude that the Changchunling Pb–Zn deposit is an epithermal system, which shares many similar features with the regional Pb–Zn polymetallic deposit.
A taxonomy of business models of digital care platforms in Spain
Authors: Rodríguez‐Modroño Paula
Published: June 2024

In the last few years, the proliferation of digital labour platforms has led to the transformation of business models and labour relations in an increasing number of economic activities, including highly feminized and informal traditional sectors, such as care and domestic work. Drawing on an analysis of 37 digital care platforms in Spain, this research compares the distinctive features and structural power dynamics they engender, and it constructs a taxonomy of business models of these care platforms. By analysing the main features of their operational models, we are capable of distinguishing three main types of platforms: marketplace, on‐demand, and digital placement agencies. First, the paper argues that the distinctive features of each digital platform business model have differentiated impacts on working conditions in terms of access to tasks, remuneration, flexibility and means of control. This differentiation allows us to understand what is transformative and what is continuous in platforms' precarization or formalisation of care work and working conditions of carers, mainly women and migrants. Each business model has its differentiated outcomes in terms of labour control and reorganization of women's and migrants' reproductive work. Second, more broadly, while digital care platforms may have contributed to facilitating workers' access to jobs, reducing transaction costs and standardising processes, this has often been through the creation of more flexible and insecure forms of work and to increased market pressures. Therefore, this study contributes to existing research addressing the degree of formalization of labour relations in digital platform work through a nuanced analysis of their business models.
Serum lipids may causally affect the occurrence of alopecia areata: A Mendelian randomization study
Authors: Chen Jiazhen , Dai Xiangnong , Lin Sifan , Liu Jiahui , Li Qingqing , Xie Zhimin , He Zezhi , Ye Xingdong
Published: June 2024

Purpose

The etiology of alopecia areata (AA) in relation to serum lipids remains unclear, thereby prompting our intention to do Mendelian study on this subject.

Design

Two‐sample Mendelian randomization (MR) analysis was performed in the study. The inverse variance‐weighted method was used as the primary method.

Methods

In our study, we integrated a set of 123 single‐nucleotide polymorphisms (SNPs) into our analysis. These SNPs have been extensively studied and are known to exhibit associations with serum lipids. We sourced these SNPs from a variety of relevant studies and consortia that specifically focus on lipid‐related research, such as the MRC Integrative Epidemiology Unit. These carefully curated SNPs were then utilized as instrumental variables in our analysis, allowing us to explore and evaluate the causal relationships between these genetic variants and serum lipids. By incorporating this comprehensive set of SNPs, we aimed to enhance the precision and robustness of our findings, shedding light on the intricate interplay between genetics and serum lipids.

Results

In the MR analysis, a higher total lipid concentration in large low‐density lipoprotein (LDL) particles (odds ratio [OR] = 1.502; 95% confidence interval [CI] = 1.086–1.953; p = 0.006), a greater ratio of cholesteryl esters to total lipids in chylomicrons and extremely large very LDL (VLDL) particles (OR = 2.174; 95% CI = 1.300–2.500; p = 0.010), and a greater ratio of cholesterol to total lipids in chylomicrons and extremely large VLDL particles (OR = 2.363;95% CI = 1.556–4.438; p = 0.004), were genetically predicted to be causally associated with an increased risk of AA, while patients with a higher triglyceride to total lipids ratio in chylomicrons and extremely large VLDL particles had a lower risk of AA (OR = 0.481; 95% CI = 0.191–1.270; p = 0.002).

Conclusion

This study found that serum lipids may be causally implicated in AA.
Sensitive HLA antibody testing and the risk of antibody‐mediated rejection and graft failure
Authors: Debyser Tim , Callemeyn Jasper , Coemans Maarten , Kerkhofs Johan , Koshy Priyanka , Kuypers Dirk , Senev Aleksandar , Tambur Anat R. , Van Loon Elisabet , Wellekens Karolien , Naesens Maarten , Emonds Marie‐Paule
Published: June 2024

Solid phase detection and identification of HLA antibodies in kidney transplantation currently relies on single antigen bead (Luminex®) assays, which is more sensitive than the previously used enzyme‐linked immunosorbent assays (ELISA). To evaluate the impact of more sensitive HLA testing on antibody‐mediated rejection (AMR) occurrence and allograft survival, we analysed 1818 renal allograft recipients transplanted between March 2004 and May 2021. In 2008, solid phase testing switched from ELISA to Luminex. We included 393 (21.6%) transplantations before and 1425 (78.4%) transplantations after transition from ELISA‐ to Luminex‐based testing. For this study, bio‐banked ELISA era samples were tested retrospectively with Luminex. Significantly less pretransplant DSA were found in patients transplanted with pre‐existing HLA antibodies in the Luminex (109/387) versus the ELISA period (43/90) (28% vs. 48%, p < 0.01). Throughout histological follow‐up, 169 of 1818 (9.3%) patients developed AMR. After implementing Luminex‐based testing, the rate of AMR significantly decreased (p = 0.003). However, incidence of graft failure did not significantly differ between both eras. In conclusion, less patients with pretransplant DSA were transplanted since the implementation of Luminex HLA testing. Transition from ELISA‐ to Luminex‐based HLA testing was associated with a significant decrease in AMR occurrence post‐transplantation. Since the decline of AMR did not translate into improved graft survival, Luminex‐based testing has the added value of preventing low‐risk AMR cases. Therefore, Luminex' high sensitivity must be balanced against waiting time for a suitable organ.
Characterisation of the novel HLA‐DRB1*03:215 allele using short‐ and long‐read sequencing technologies
Authors: Secco Danielle , Andrade Gabriela , Oliveira Victoria , Vianna Romulo , Porto Luís Cristóvão
Published: June 2024

The novel HLA‐DRB1*03:215 allele, first described in a potential bone marrow donor from Brazil.
Students' Perception on the Use of English Pop Song in Improving the Skill of Pronunciation
Authors: Judijanto Loso , Sitompul Mega Silvia , Herman Herman , Manihuruk Leonita Maria Efipanias , Fatmawati Endang , Munthe Melda Veby Ristella , Batubara Junita , Saputra Nanda
Published: June 2024

This research aimed to find out or to investigate the students’ perception on the use of English pop song in enhancing pronunciation those are internal and external factors of perception. This research design was descriptive qualitative research method with study case approach. The research conducted focused on tenth-grade students of SMA Swasta YP HKBP 1 Pematangsiantar, comprising four classes with a total population of 78 students. Data collection was carried out through questionnaires containing 25 statements regarding students' perceptions on the use of English pop songs in improving pronunciation. These questionnaires were presented in the form of a Likert scale, ranging from strongly agree to strongly disagree. The data analyzed in form of words, definitions, quotations, statements and figure that supporting in this research. The result showed that students had good or positive perceptions on the use of English pop song in enhancing pronunciation. From 25 questionnaires, only one items that students mostly chose disagree and strongly disagree which is never practice to pronounce cleary by repeating unique words or sentences in the lyrics. The rest of questionnaires were perceived positively where most of students chose agree as their responses to the statements. It can be concluded that English pop song gave a good and positive perception or impact and can be alternative way in teaching and learning process especially in learning pronunciation.
Taylor dispersion and phase mixing in the non‐cutoff Boltzmann equation on the whole space
Authors: Bedrossian Jacob , Coti Zelati Michele , Dolce Michele
Published: June 2024

In this paper we describe the long‐time behavior of the non‐cutoff Boltzmann equation with soft potentials near a global Maxwellian background on the whole space in the weakly collisional limit (that is, infinite Knudsen number ). Specifically, we prove that for initial data sufficiently small (independent of the Knudsen number), the solution displays several dynamics caused by the phase mixing/dispersive effects of the transport operator and its interplay with the singular collision operator. For ‐wavenumbers with , one sees an enhanced dissipation effect wherein the characteristic decay time‐scale is accelerated to , where is the singularity of the kernel ( being the Landau collision operator, which is also included in our analysis); for , one sees Taylor dispersion, wherein the decay time‐scale is accelerated to . Additionally, we prove almost uniform phase mixing estimates. For macroscopic quantities such as the density , these bounds imply almost uniform‐in‐ decay of in due to phase mixing and dispersive decay.
Maximizing Building Energy Efficiency Through Zone-Based Conditions: An Advanced Dynamic Simulation Approach
Authors: Fil Burak , Sözer Hatice
Published: June 2024

The primary objective of this research is to maximize the building energy efficiency by identifying the zone-based conditions and employing an advanced energy simulation model. It is possible to achieve this by reducing periods of excessive heating and cooling by utilizing a calibrated energy model with 15-minute measured data. Further, by regulating the energy consumption of various functional zones corresponding to the work schedules, building's energy system timetables, and the sensible temperature comfort requirements, additional energy savings can be achieved. To show the effect of dynamic simulation on building energy consumption, periodic 15-min temperature data were collected in different zones to be used both in the calibration of the energy model and in the improvement of the current energy profile. Mean bias error and cumulative variation of the root mean squared error were chosen as a performance indicator. Utilizing measured data, over-heated and over-cooled periods were defined by manually identifying zone-based indoor comfort conditions to predict improvements in overall building energy performance. The potential energy savings that can be achieved by largely eliminating over-heating periods are calculated. In addition, energy needs of different zones were considered and zone-based scheduling and zone-based comfort conditions were applied with the implementation of demand-side management. As a result, 17% energy efficiency can be achieved with an automated heating system that controls the indoor temperatures and ensures that the temperature is always kept at the desired level. As a further improvement, 32% energy efficiency can be achieved by applying zone-based scheduling and comfort conditions.
Exploring the Relationship of Declarative Tactical Knowledge With Participation, Football Competence, and Potentiality in a Professional Club (Real Sociedad)
Authors: Sánchez-López Rubén , Echeazarra Ibon , Arrieta Jon Mikel , Castellano Julen
Published: June 2024

We compared the declarative tactical knowledge (DTK) of 196 male and female players (16.9 ± 2.4 years) belonging to the academy of a Spanish professional football club with their participation (minutes played), football competence (coaching staff assessment), and future potential (technical direction prediction). The DTK had no correlation with the minutes played (%) by the participants during the 2021–22 season (r = −.162, p = .045). Student’s t test for independent samples compared the football competence of the participants with high DTK (n = 74) and low DTK (n = 76), proving a small impact (p = .021, d = 0.39) in favor of the first group. Although the high-DTK group showed a better average of potentiality, the technical direction identified more potential players for the first team in the low-DTK group. In conclusion, no solid evidence was found to justify that participants with higher DTK in each team were those who played more minutes and showed greater football competence and potentiality.
Field Hip Stability Isometric Test (F-HipSIT): Reliability of Assessing the Hip Posterolateral Muscle Strength in Sports Settings
Authors: de Lima e Silva Felipe Xavier , de Araujo Ribeiro-Alvares João Breno , de Souza Roberti Lucas , Mocellin Matheus Pitrez , Baroni Bruno Manfredini
Published: June 2024

Context: The Hip Stability Isometric Test (HipSIT) is commonly employed in clinical settings for evaluating the hip posterolateral muscle strength. In this study, we introduced the “Field Hip Stability Isometric Test” (F-HipSIT) and assessed the intrarater and interrater reliability of this strength assessment specifically designed for sports settings. Design: Reliability study. Methods: Two independent raters (A and B) went to athletes’ training facilities to conduct 2 sessions of F-HipSIT spaced at least 1 week apart. The average peak force value from 3 valid attempts of each leg was recorded and normalized by the participant’s body mass for statistical analysis. Results: Thirty male and 30 female amateur athletes took part in this study. Rater A obtained similar values in the first (0.39 [0.05] and 0.44 [0.07] kg·f/kg) and second (0.39 [0.06] and 0.45 [0.07] kg·f/kg) testing days for men and women, respectively. Rater B also found similar values in the first (0.35 [0.06] and 0.42 [0.08] kg·f/kg) and second (0.36 [0.06] and 0.45 [0.08] kg·f/kg) testing days for men and women, respectively. Excellent intrarater intraclass correlation coefficient (ICC) values were found for men (ICC = .922) and women (ICC = .930), with coefficient of variation of 6% to 8% and minimal detectable change of 0.06 to 0.10 kg·f/kg. The F-HipSIT presented good interrater reliability for men (ICC = .857) and women (ICC = .868), with coefficient of variation of 5% and minimal detectable change of 0.05 to 0.06 kg·f/kg. Conclusion: The F-HipSIT intrarater and interrater reliability among male and female recreational athletes supports this field test as a quick and convenient screening tool to monitor hip posterolateral muscle strength in sports settings.
Type I conventional dendritic cells facilitate immunotherapy in pancreatic cancer
Authors: Mahadevan Krishnan K. , Dyevoich Allison M. , Chen Yang , Li Bingrui , Sugimoto Hikaru , Sockwell Amari M. , McAndrews Kathleen M. , Sthanam Lakshmi Kavitha , Wang Huamin , Shalapour Shabnam , Watowich Stephanie S. , Kalluri Raghu
Published: June 2024

Inflammation and tissue damage associated with pancreatitis can precede or occur concurrently with pancreatic ductal adenocarcinoma (PDAC). We demonstrate that in PDAC coupled with pancreatitis (ptPDAC), antigen-presenting type I conventional dendritic cells (cDC1s) are specifically activated. Immune checkpoint blockade therapy (iCBT) leads to cytotoxic CD8
+
T cell activation and elimination of ptPDAC with restoration of life span even upon PDAC rechallenge. Using PDAC antigen-loaded cDC1s as a vaccine, immunotherapy-resistant PDAC was rendered sensitive to iCBT with elimination of tumors. cDC1 vaccination coupled with iCBT identified specific CDR3 sequences in the tumor-infiltrating CD8
+
T cells with potential therapeutic importance. This study identifies a fundamental difference in the immune microenvironment in PDAC concurrent with, or without, pancreatitis and provides a rationale for combining cDC1 vaccination with iCBT as a potential treatment option.
Brainwide silencing of prion protein by AAV-mediated delivery of an engineered compact epigenetic editor
Authors: Neumann Edwin N. , Bertozzi Tessa M. , Wu Elaine , Serack Fiona , Harvey John W. , Brauer Pamela P. , Pirtle Catherine P. , Coffey Alissa , Howard Michael , Kamath Nikita , Lenz Kenney , Guzman Kenia , Raymond Michael H. , Khalil Ahmad S. , Deverman Benjamin E. , Minikel Eric Vallabh , Vallabh Sonia M. , Weissman Jonathan S.
Published: June 2024

Prion disease is caused by misfolding of the prion protein (PrP) into pathogenic self-propagating conformations, leading to rapid-onset dementia and death. However, elimination of endogenous PrP halts prion disease progression. In this study, we describe Coupled Histone tail for Autoinhibition Release of Methyltransferase (CHARM), a compact, enzyme-free epigenetic editor capable of silencing transcription through programmable DNA methylation. Using a histone H3 tail-Dnmt3l fusion, CHARM recruits and activates endogenous DNA methyltransferases, thereby reducing transgene size and cytotoxicity. When delivered to the mouse brain by systemic injection of adeno-associated virus (AAV),
Prnp
-targeted CHARM ablates PrP expression across the brain. Furthermore, we have temporally limited editor expression by implementing a kinetically tuned self-silencing approach. CHARM potentially represents a broadly applicable strategy to suppress pathogenic proteins, including those implicated in other neurodegenerative diseases.
Enhanced catabolism of glycine betaine and derivatives provides improved osmotic stress protection in
Methylorubrum extorquens
PA1
Authors: Bruger Eric L. , Hying Zachary T. , Singla Deepanshu , Márquez Reyes Nicole L. , Pandey Shubham Kumar , Patel Jagdish Suresh , Bazurto Jannell V.
Published: June 2024

Integration of metabolites into the overall metabolic network of a cell requires careful coordination dependent upon the ultimate usage of the metabolite. Different stoichiometric needs, and thus pathway fluxes, must exist for compounds destined for diverse uses, such as carbon sources, nitrogen sources, or stress-protective agents. Herein, we expand upon our previous work that highlighted the nature of glycine betaine (GB) metabolism in Methylobacteria to examine the utilization of GB-derivative compounds dimethylglycine (DMG) and sarcosine into
Methylorubrum extorquens
in different metabolic capacities, including as sole nitrogen and/or carbon sources. We isolated gain-of-function mutations that allowed
M. extorquens
PA1 to utilize dimethylglycine as a carbon source and dimethylglycine and sarcosine as nitrogen source. Characterization of mutants demonstrated selection for variants of the AraC-like regulator Mext_3735 that confer constitutive expression of the GB metabolic gene cluster, allowing direct utilization of the downstream GB derivatives. Finally, among the distinct isolates examined, we found that catabolism of the osmoprotectant used for selection (GB or dimethylglycine) enhanced osmotic stress resistance provided in the presence of that particular osmolyte. Thus, access to the carbon and nitrogen and osmoprotective effects of GB and DMG are made readily accessible through adaptive mutations. In
M. extorquens
PA1, the limitations to exploiting this group of compounds appear to exist predominantly at the levels of gene regulation and functional activity, rather than being constrained by transport or toxicity.

IMPORTANCE

Osmotic stress is a common challenge for bacteria colonizing the phyllosphere, where glycine betaine (GB) can be found as a prevalent osmoprotectant. Though
Methylorubrum extorquens
PA1 cannot use GB or its demethylation products, dimethylglycine (DMG) and sarcosine, as a sole carbon source, utilization is highly selectable via single nucleotide changes for both GB and DMG growth. The innate inability to use these compounds is due to limited flux through steps in the pathway and regulatory constraints. Herein, the characterization of the transcriptional regulator, Mext_3735 (GbdR), expands our understanding of the various roles in which GB derivatives can be used in
M. extorquens
PA1. Interestingly, increased catabolism of GB and derivatives does not interfere with, but rather improves, the ability of cells to thrive under increased salt stress conditions, suggesting that metabolic flux improves stress tolerance rather than providing a distinct tension between uses.