bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychometric properties of Turkish Orthorexia Nervosa Inventory in a clinical adolescent sample
Authors: Turan Bahadir , Yıldırım Selman , Bilginer Samiye Çilem , Akıncı Mehmet Akif
Published: September 2023

Purpose

Orthorexic tendencies are increasingly prevalent among children and adolescents. This study set out to investigate the reliability and validity of the Turkish version of the Orthorexia Nervosa Inventory (ONI) in a clinical adolescent sample.

Methods

266 adolescents aged 12–18 years, who applied to the Department of Child and Adolescents Psychiatry were included in the study. Participants completed sociodemographic data form, ONI, Eating Attitude Test, Revised Child Anxiety and Depression Scale-Child Version and ORTO-15.

Results

The Cronbach’s alpha coefficient for the ONI reached 0.92, indicating very good internal consistency. Total factor scores and Cronbach alpha values for behaviors, impairments, and emotions were found to be 0.84, 0.84, and 0.83, respectively. The CFA performed supported the three-factor structure of the ONI obtained in the first sample. The minimum discrepancy per degree of freedom = 1.89 and the model generally fit well to the structure (RMSEA = 0.058, SRMR = 0.033, CFI = 0.92, TLI = 0.91).

Discussion

This study has shown that the Turkish version of the ONI is a valid and reliable scale for specifying the tendency for Orthorexia Nervosa in a Turkish adolescent population. These findings contribute in several ways to our understanding of orthorexic tendencies and provide a basis for more concrete research data that can be obtained by using the ONI, which is a reliable scale in studies to be conducted among adolescents.

Level of evidence

Level V, descriptive cross-sectional study.
Flexible Modelling of Diel and Other Periodic Variation in Hidden Markov Models
Authors: Feldmann Carlina C. , Mews Sina , Coculla Angelica , Stanewsky Ralf , Langrock Roland
Published: September 2023

Animal behaviour is often characterised by periodic patterns such as seasonality or diel variation. Such periodic variation can be comprehensively studied from the increasingly detailed ecological time series that are nowadays collected, e.g. using GPS tracking. Within the class of hidden Markov models (HMMs), which is a popular tool for modelling time series driven by underlying behavioural modes, periodic variation is commonly modelled by including trigonometric functions in the linear predictors for the state transition probabilities. This parametric modelling can be too inflexible to capture complex periodic patterns, e.g. featuring multiple activity peaks per day. Here, we explore an alternative approach using penalised splines to model periodic variation in the state-switching dynamics of HMMs. The challenge of estimating the corresponding complex models is substantially reduced by the expectation–maximisation algorithm, which allows us to make use of the existing machinery (and software) for nonparametric regression. The practicality and potential usefulness of our approach is demonstrated in two real-data applications, modelling the movements of African elephants and of common fruit flies.
Mobility, Lineage, and Land Tenure: Interpreting House Groups at Early Agricultural Settlements in the Tucson Basin, Southern Arizona
Authors: Gruner Erina P.
Published: September 2023

During the Early Agricultural period (2100 BC–AD 50), preceramic farmers in the Sonoran Desert invested considerable labor in canal-irrigated field systems while remaining very residentially mobile. The degree to which they exercised formal systems of land tenure, or organized their communities above the household level, remains contested. This article discusses the spatial and social organization of Early Cienega–phase settlements in the Los Pozos site group, an Early Agricultural site complex located along the Santa Cruz River in southern Arizona. At Los Pozos, the formal spatial organization of seasonal farmsteads suggests that despite continued residential mobility, multihousehold lineages maintained distinct territories. Enduring “house groups”—likely lineal groups—are associated with disproportionately large cemeteries, suggesting the revisitation of ancestral territory through occupational hiatuses. However, variability in the formality and permanence of Early Cienega–phase settlements throughout the region indicates a flexible continuum of occupational mobility. These higher-order affiliations were only expressed in persistent settlements near highly productive farmland, where the relative priority of households over improved land might be contested.
How equestrians conceptualise horse welfare: Does it facilitate or hinder change?
Authors: Luke Karen L , Rawluk Andrea , McAdie Tina , Smith Bradley P , Warren-Smith Amanda K
Published: September 2023

More than ever the welfare of horses in equestrian sport is in the spotlight. In response to this scrutiny, one peak body, the Federation Equestre Internationale (FEI) has created an Equine Ethics and Wellbeing Commission to protect their sport’s longevity. However, for welfare-based strategies to be successful, the conceptualisation of horse welfare must align across various stakeholders, including the general public. The value-laden nature of welfare makes agreement on its definition, even among scientists, difficult. Given little is known about how equestrians conceptualise horse welfare, we interviewed 19 Australian amateur equestrians using a semi-structured format. Systems thinking and the Five Domains Model provided the theoretical framework and informed our methods. Using reflexive thematic analysis, three themes were identified: (1) good horse welfare is tangible; (2) owners misinterpret unwanted horse behaviour; and (3) equestrians publicly minimise horse welfare issues but are privately concerned. Our results highlight participants’ conceptualisations of horse welfare do not align with the Five Domains Model; participants’ ideal of prioritising horse welfare does not align with their practice; and there is inconsistency between what participants share publicly and what they think privately about horse welfare. These findings can inform the development of programmes to improve ridden horse welfare throughout the horse industry. As a starting point, programmes that provide a safe space for equestrians to explore their private horse welfare concerns, and programmes that build a partnership mindset to facilitate knowledge exchange between all stakeholders are needed.
A spectral refinement of the Bergelson–Host–Kra decomposition and new multiple ergodic theorems – CORRIGENDUM
Authors: MOREIRA JOEL , RICHTER FLORIAN K.
Published: September 2023

This is a corrigendum to the paper ‘A spectral refinement of the Bergelson–Host–Kra decomposition and new multiple ergodic theorems’ [3]. Theorem 7.1 in that paper is incorrect as stated, and the error originates with Proposition 7.5, part (iii), which was incorrectly quoted from a paper by Bergelson, Host, and Kra [1]. Consequently, this invalidates the proof of Theorem 4.2, which was used in the proofs of the main results in [3]. In this corrigendum we fix the problem by establishing a slightly weaker version of Theorem 7.1 (see §2 below) and use it to give a new proof of Theorem 4.2 (see §3 below). This ensures that all main results in [3] remain correct. We thank Zhengxing Lian and Jiahao Qiu for bringing this mistake to our attention.
State-Specific Barriers to Methadone for Opioid Use Disorder Treatment
Authors: Russoniello Kellen , Harrington Cailin , Beydoun Sarah , Borrego Lucrece
Published: September 2023

Opioid agonist treatment, including methadone, is the safest and most effective method for treating opioid use disorders and reduces opioid overdose deaths. While access to methadone is highly regulated by federal law, a substantial portion of states impose stricter barriers.
Improving precision through design and analysis in experiments with noncompliance
Authors: Hartman Erin , Huang Melody
Published: September 2023

Even in the best-designed experiment, noncompliance can complicate analysis. While the intent-to-treat effect remains identified, randomization alone no longer identifies the complier average causal effect (CACE). Instrumental variables approaches, which rely on the exclusion restriction, can suffer from high variance, particularly when the experiment has a low compliance rate. We provide a framework which broadens the set of design and analysis techniques political science researchers can use when addressing noncompliance. Building on the growing literature about the advantages of ex-ante design decisions to improve precision, we show blocking on variables related to both compliance and the outcome can greatly improve all the estimators we propose. Drawing on work in statistics, we introduce the principal ignorability assumption and a class of principal score weighting estimators, which can exhibit large gains in precision in low compliance settings. We then combine principal ignorability and blocking with a simple estimation strategy to derive a more efficient estimation strategy for the CACE. In a re-evaluation of a study on the effect of GOTV on turnout, we find that the principal ignorability approaches result in confidence intervals roughly half the size of traditional instrumental variable approaches.
Alsace in Algeria and the Notion of ‘Failure’ in Settler Political Culture, c. 1870–1960
Authors: Ofrath Avner
Published: September 2023

This article explores a key trope in the history of French colonial Algeria: the idea of the colony as a failure. The focus is on the resettlement of Alsatians and Lorrainers in Algeria in the aftermath of the Franco-Prussian War. What started as a wave of nationalist elan that sought to rebuild the lost provinces in France’s largest colony soon became the object of criticism and controversy, depicted by contemporaries from early on as failure. While this perceived failure was itself a colonial category – the failure to recruit settlers, expulse Algerians, and seize land – it tells us a great deal about the political culture of the colony. How was this resettlement project conceived? What visions of colonization and colonial settlement were projected upon it? And what mechanisms of coercion, dispossession, and violence did different colonial players seek to deploy? Through these questions, this article seeks to demonstrate that the verdict of ‘failure’ by settlers and lobbyists did not emerge in hindsight but was rather the product of the inherent tension between the sheer force that was necessary to seize the land and the metropolitan attempt to establish in the colony a form of unequal yet standardized civilian governance.
Gastrointestinal parasites in captive olive baboons in a UK safari park
Authors: Juhasz Alexandra , Spiers Elly , Tinsley Ellie , Chapman Emma , Shaw William , Head Marion , Cunningham Lucas J. , Archer John , Jones Sam , Haines Lee R. , Davies Walsh Naomi , Johnson Bridget , Quayle Jen , Jones Jayne , LaCourse Elwyn James , Cracknell Jonathan , Stothard John Russell
Published: September 2023

From the safety inside vehicles, Knowsley Safari offers visitors a close-up encounter with captive olive baboons. As exiting vehicles may be contaminated with baboon stool, a comprehensive coprological inspection was conducted to address public health concerns. Baboon stools were obtained from vehicles, and sleeping areas, inclusive of video analysis of baboon–vehicle interactions. A purposely selected 4-day sampling period enabled comparative inspections of 2662 vehicles, with a total of 669 baboon stools examined (371 from vehicles and 298 from sleeping areas). As informed by our pilot study, front-line diagnostic methods were: QUIK-CHEK rapid diagnostic test (RDT) (Giardia and Cryptosporidium), Kato–Katz coproscopy (Trichuris) and charcoal culture (Strongyloides). Some 13.9% of vehicles were contaminated with baboon stool. Prevalence of giardiasis was 37.4% while cryptosporidiosis was <0.01%, however, an absence of faecal cysts by quality control coproscopy, alongside lower than the expected levels of Giardia-specific DNA, judged RDT results as misleading, grossly overestimating prevalence. Prevalence of trichuriasis was 48.0% and strongyloidiasis was 13.7%, a first report of Strongyloides fuelleborni in UK. We advise regular blanket administration(s) of anthelminthics to the colony, exploring pour-on formulations, thereafter, smaller-scale indicator surveys would be adequate.
Mindfulness training and exercise differentially impact fear extinction neurocircuitry
Authors: Leibovitz Shaked E. , Sevinc Gunes , Greenberg Jonathan , Hölzel Britta , Gard Tim , Calahan Thomas , Vangel Mark , Orr Scott P. , Milad Mohammed R. , Lazar Sara W.
Published: September 2023

Background

The ability to extinguish a maladaptive conditioned fear response is crucial for healthy emotional processing and resiliency to aversive experiences. Therefore, enhancing fear extinction learning has immense potential emotional and health benefits. Mindfulness training enhances both fear conditioning and recall of extinguished fear; however, its effects on fear extinction learning are unknown. Here we investigated the impact of mindfulness training on brain mechanisms associated with fear-extinction learning, compared to an exercise-based program.

Methods

We investigated BOLD activations in response to a previously learned fear-inducing cue during an extinction paradigm, before and after an 8-week mindfulness-based stress reduction program (MBSR, n = 49) or exercise-based stress management education program (n = 27).

Results

The groups exhibited similar reductions in stress, but the MBSR group was uniquely associated with enhanced activation of salience network nodes and increased hippocampal engagement.

Conclusions

Our results suggest that mindfulness training increases attention to anticipatory aversive stimuli, which in turn facilitates decreased aversive subjective responses and enhanced reappraisal of the memory.
Haemolytic uraemic syndrome in children England, Wales, Northern Ireland, and Ireland: A prospective cohort study
Authors: Byrne Lisa , Douglas Amy , Launders Naomi , Godbole Gauri , Lynn Richard , Inward Carol , Jenkins Claire
Published: September 2023

Haemolytic uraemic syndrome (HUS) caused by infection with Shiga toxin-producing Escherichia coli (STEC) is a relatively rare but potentially fatal multisystem syndrome clinically characterised by acute kidney injury. This study aimed to provide robust estimates of paediatric HUS incidence in England, Wales, Northern Ireland, and the Republic of Ireland by using data linkage and case reconciliation with existing surveillance systems, and to describe the characteristics of the condition. Between 2011 and 2014, 288 HUS patients were included in the study, of which 256 (89.5%) were diagnosed as typical HUS. The crude incidence of paediatric typical HUS was 0.78 per 100,000 person-years, although this varied by country, age, gender, and ethnicity. The majority of typical HUS cases were 1 to 4 years old (53.7%) and female (54.0%). Clinical symptoms included diarrhoea (96.5%) and/or bloody diarrhoea (71.9%), abdominal pain (68.4%), and fever (41.4%). Where STEC was isolated (59.3%), 92.8% of strains were STEC O157 and 7.2% were STEC O26. Comparison of the HUS case ascertainment to existing STEC surveillance data indicated an additional 166 HUS cases were captured during this study, highlighting the limitations of the current surveillance system for STEC for monitoring the clinical burden of STEC and capturing HUS cases.
Health effects of 100% fruit and vegetable juices: evidence from human subject intervention studies
Authors: Rossi Irene , Mignogna Cristiana , Del Rio Daniele , Mena Pedro
Published: September 2023

The health effects of 100% fruit and vegetable juices (FVJ) represent a controversial topic. FVJ contain notable amounts of free sugars, but also vitamins, minerals, and secondary compounds with proven biological activities like (poly)phenols and carotenoids. The review aimed to shed light on the potential impact of 100% FVJ on human subject health, comprehensively assessing the role each type of juice may have in specific health outcomes for a particular target population, as reported in dietary interventions. The effects of a wide range of FVJ (orange, grapefruit, mandarin, lemon, apple, white, red, and Concord grapes, pomegranate, cranberry, chokeberry, blueberry, other minor berries, sweet and tart cherry, plum, tomato, carrot, beetroot, and watermelon, among others) were evaluated on a series of outcomes (anthropometric parameters, body composition, blood pressure and vascular function, lipid profile, glucose homeostasis, biomarkers of inflammation and oxidative stress, cognitive function, exercise performance, gut microbiota composition and bacterial infections), providing a thorough picture of the contribution of each FVJ to a health outcome. Some juices demonstrated their ability to exert potential preventive effects on some outcomes while others on other health outcomes, emphasising how the differential composition in bioactive compounds defines juice effects. Research gaps and future prospects were discussed. Although 100% FVJ appear to have beneficial effects on some cardiometabolic health outcomes, cognition and exercise performance, or neutral effects on anthropometric parameters and body composition, further efforts are needed to better understand the impact of 100% FVJ on human subject health.
Primary Health Care and Disasters: Applying a “Whole-of-Health System” Approach through Reverse Triage in Mass-Casualty Management
Authors: Alesi Andrea , Bortolin Michelangelo , Ragazzoni Luca , Lamberti-Castronuovo Alessandro
Published: September 2023

Introduction:

In 2019, the World Health Organization (WHO) published the Health Emergency and Disaster Risk Management (H-EDRM) framework detailing how effective management of disasters, including mass-casualty incidents (MCIs), can be achieved through a whole-of-health system approach where each level of the health care system is involved in all phases of the disaster cycle. In light of this, a primary health care (PHC) approach can contribute to reducing negative health outcomes of disasters, since it encompasses the critical roles that primary care services can play during crises. Hospitals can divert non-severe MCI victims to primary care services by applying reverse triage (RT), thereby preventing hospital overloading and ensuring continuity of care for those who do not require hospital services during the incident.

Study Objective:

This study explores the topic by reviewing the literature published on early discharge of MCI victims through RT criteria and existing referral pathways to primary care services.

Methods:

A scoping literature review was performed and a total of ten studies were analyzed.

Results:

The results showed that integrating primary care facilities into disaster management (DM) through the use of RT may be an effective strategy to create surge during MCIs, provided that clear referral protocols exist between hospitals and primary care services to ensure continuity of care. Furthermore, adequate training should be provided to primary care professionals to be prepared and be able to provide quality care to MCI victims.

Conclusion:

The results of this current review can serve as groundwork upon which to design further research studies or to help devise strategies and policies for the integration of PHC in MCI management.
Looking Backward, Looking Forward
Authors: Bernhard Michael , O’Neill Daniel
Published: September 2023

This issue marks the last of our six years as the editorial team of Perspectives on Politics. It has been both a richly rewarding and exhausting journey, as well as a labor of love. As with all journeys, some of what we encountered along the way was foreseeable, but much of it was not. For example, we knew that Donald Trump’s presidency would be consequential and in many ways unprecedented when we assumed the helm in June 2017, but not that he would become the first president to be impeached twice, or the first to attempt to overturn presidential election results and violently prevent the peaceful transfer of power, thereby threatening the republic’s very foundations. We had no idea what COVID-19 was, or that it would go on to kill more than one million people in the United States alone. Nor could we foresee that the murder of George Floyd would spark the greatest wave of protest in the United States since the 1960s. Nor yet again did we know that more than seventy-five years after the end of World War II, there would be a major European land war between two former Soviet Republics. Yet we felt compelled to respond to each of these world historical moments as they unfolded in real time, while also attempting to modernize and innovate with respect to the journal’s publication procedures and to stay true to its substantive mission.
Earth stewardship, water resilience, and ethics in the Anthropocene
Authors: Schmidt Jeremy J.
Published: September 2023

Non-technical summary

This article uses water to examine how the relationships of ethics to science are modified through the pursuit of Earth stewardship. Earth stewardship is often defined as the use of science to actively shape social–ecological relations by enhancing resilience. The changing relations of science to values are explored by considering how ideas of resilience operate to translate different ways of knowing water into the framework of Earth stewardship. This is not a neutral process, and Earth stewardship requires careful appraisal to ensure other ways of knowing water are not oppressed.

Technical summary

Scientific disclosures of anthropogenic impacts on the Earth system – the Anthropocene – increasingly come with ethical diagnoses for value transformation and, often, Earth stewardship. This article examines the changing relationship of science to values in calls for Earth stewardship with special attention to water resilience. The article begins by situating recent efforts to reconceptualize human–water relations in view of anthropogenic impacts on the global water system. It then traces some of the ways that Earth stewardship has been articulated, especially as a framework supporting the use of science to actively shape social–ecological relations by enhancing resilience. The shift in relations of ethics and science entailed by Earth stewardship is placed in historical context before the issues of water resilience are examined. Resilience, and critiques of it, are then discussed for how they operate to translate different ways of knowing water into the framework of Earth stewardship. The ethical stakes of such translations are a core concern of the conclusion. Rather than reducing different ways of knowing water to those amendable to the framework of Earth stewardship, the article advances a pluralized approach as needed to respect multiple practices for knowing and relating to water – and resilience.

Social media summary

Water resilience is key to Earth stewardship; Jeremy Schmidt examines how it changes relations of science and ethics.
The Co-Twin Control Design: Implementation and Methodological Considerations
Authors: Gonggrijp Bodine M. A. , van de Weijer Steve G. A. , Bijleveld Catrien C. J. H. , van Dongen Jenny , Boomsma Dorret I.
Published: September 2023

Establishing causal relationships in observational studies is an important step in research and policy decision making. The association between an exposure and an outcome can be confounded by multiple factors, often making it hard to draw causal conclusions. The co-twin control design (CTCD) is a powerful approach that allows for the investigation of causal effects while controlling for genetic and shared environmental confounding factors. This article introduces the CTCD and offers an overview of analysis methods for binary and continuous outcome and exposure variables. Tools for data simulation are provided, along with practical guidance and accompanying scripts for implementing the CTCD in R, SPSS, and Stata. While the CTCD offers valuable insights into causal inference, it depends on several assumptions that are important when interpreting CTCD results. By presenting a broad overview of the CTCD, this article aims to equip researchers with actionable recommendations and a comprehensive understanding of the design’s strengths and limitations.
Wir pflegen unser Image
Authors: Hilberger-Kirlum Pascale , Hauck Claudia
Published: September 2023

Zusammenfassung: In einer von Bildern dominierten Zeit (pictural turn) ist die Beschäftigung mit deren Wirkmacht essenziell. Hier ist zum einen die bildliche Darstellung von Pflege gemeint. Zum anderen sind auch die imaginären, inhärenten und impliziten Bilder von Pflege relevant. Welches Bild wollen wir als Professionsangehörige erzeugen und vertreten und wie sieht die Öffentlichkeit bzw. Gesellschaft die Profession Pflege?
Planspiele im Pflegeunterricht
Authors: Stober Stefanie
Published: September 2023

Zusammenfassung: Um den kontinuierlich wachsenden Herausforderungen an professionell Pflegende in der theoretischen Ausbildung gerecht zu werden, ist ein Überdenken traditioneller Lehrmethoden notwendig. Planspiele werden seit vielen Jahren erfolgreich als Methodik in der Wirtschaft eingesetzt und gelten dort als fester Bestandteil der Berufsausbildung. „Learning by Doing“ steht im Vordergrund, wodurch „träges Wissen“ vermieden wird.
Formation of Electron Butterfly Distribution by a Contracting Dipolarization Front
Authors: Yu Y. , Fu H. S. , Wang Z. , Fu W. D. , Cao J. B.
Published: September 2023

The electron butterfly distribution, characterized by pitch angles (PA) primarily at 45° and 135°, was rarely observed in Earth's magnetotail. Here using the high‐resolution measurements from Magnetospheric Multiscale mission, we present the observation of electron butterfly distribution in a contracting dipolarization front (DF), and propose a new physical mechanism to explain its formation. Specifically, we discover that the electron butterfly distribution only exhibited in the locally contracted DF and was observed above 1.7 keV. We infer that local contraction of the DF transformed its configuration from a magnetic bottle to an hourglass‐shaped magnetic structure, and the butterfly distribution was formed by the magnetic mirror effect of this magnetic hourglass. Additionally, the theoretically estimated loss cone of the magnetic hourglass fits well with the observations of electrons, validating our inference about the formation mechanism. These findings can improve our understanding of electron dynamics in Earth's magnetosphere.
Three-dimensional growth sensitizes breast cancer cells to treatment with ferroptosis-promoting drugs
Authors: Chipurupalli Sandhya , Jiang Peijia , Liu Xiaoyang , Santos Julia Linhares , Marcato Paola , Rosen Kirill V.
Published: September 2023

Drugs causing ferroptosis, iron-mediated cell death, represent promising tools for cancer treatment. While exploring the effect of these drugs on breast cancer (BC), we found that a ferroptosis-inducing drug erastin dramatically inhibits tumorigenicity of human BC cells in mice but when used at a concentration known to effectively kill other cell types only modestly reduces such growth in 2D monolayer culture. BCs grow in vivo as 3D masses, and we found that ferroptosis inducers erastin and sulfasalazine inhibit growth of multiple human BC cell lines in 3D culture significantly stronger than in 2D culture. To understand the mechanism of this differential effect, we found that ferroptosis inducers upregulate mRNAs encoding multiple direct and indirect autophagy stimulators, such as ATG16L2, ATG9A, ATG4D, GABARAP, SQSTM/p62, SEC23A and BAX, in tumor cells growing in 2D but not in 3D culture. Furthermore, these drugs promoted autophagy of tumor cells growing in a 2D but not in a 3D manner. We observed that pharmacological inhibition of autophagy-stimulating protein kinase ULK1 or RNA interference-mediated knockdown of autophagy mediator ATG12 significantly sensitized tumor cells to erastin treatment in 2D culture. We also found that ferroptosis-promoting treatments upregulate heme oxygenase-1 (HO-1) in BC cells. HO-1 increases cellular free iron pool and can potentially promote ferroptosis. Indeed, we observed that HO-1 knockdown by RNA interference reversed the effect of ferroptosis inducers on BC cell 3D growth. Hence, the effect of these drugs on such growth is mediated by HO-1. In summary, autophagy triggered by ferroptosis-promoting drugs reduces their ability to kill BC growing in a 2D manner. This protection mechanism is inhibited in BC cells growing as a 3D mass, and ferroptosis-promoting drugs kill such cells more effectively. Moreover, this death is mediated by HO-1. Thus, ferroptosis induction represents a promising strategy for blocking 3D BC growth.
Tumor-associated macrophages confer colorectal cancer 5-fluorouracil resistance by promoting MRP1 membrane translocation via an intercellular CXCL17/CXCL22–CCR4–ATF6–GRP78 axis
Authors: Zhang Lichao , Lu Xiaoqing , Xu Yuanzhi , La Xiaoqin , Tian Jinmiao , Li Aiping , Li Hanqing , Wu Changxin , Xi Yanfeng , Song Guisheng , Zhou Zhaocai , Bai Wenqi , An Liwei , Li Zhuoyu
Published: September 2023

Chemotherapy represents a major type of clinical treatment against colorectal cancer (CRC). Aberrant drug efflux mediated by transporters acts as a key approach for tumor cells to acquire chemotherapy resistance. Increasing evidence implies that tumor-associated macrophages (TAMs) play a pivotal role in both tumorigenesis and drug resistance. Nevertheless, the specific mechanism through which TAMs regulate drug efflux remains elusive. Here, we discovered that TAMs endow CRC cells with resistance to 5-fluorouracil (5-FU) treatment via a cell-cell interaction-mediated MRP1-dependent drug efflux process. Mechanistically, TAM-secreted C-C motif chemokine ligand 17 (CCL17) and CCL22, via membrane receptor CCR4, activated the PI3K/AKT pathway in CRC tumor cells. Specifically, phosphorylation of AKT inactivated IP3R and induced calcium aggregation in the ER, resulting in the activation of ATF6 and upregulation of GRP78. Accordingly, excessive GRP78 can interact with MRP1 and promote its translocation to the cell membrane, causing TAM-induced 5-FU efflux. Taken together, our results demonstrated that TAMs promote CRC chemotherapy resistance via elevating the expression of GRP78 to promote the membrane translocation of MRP1 and drug efflux, providing direct proof for TAM-induced drug resistance.
Metallo-sideromycin as a dual functional complex for combating antimicrobial resistance
Authors: Wang Chenyuan , Xia Yushan , Wang Runming , Li Jingru , Chan Chun-Lung , Kao Richard Yi-Tsun , Toy Patrick H. , Ho Pak-Leung , Li Hongyan , Sun Hongzhe
Published: September 2023

The rapid emergence of antimicrobial resistance (AMR) pathogens highlights the urgent need to approach this global burden with alternative strategies. Cefiderocol (Fetroja®) is a clinically-used sideromycin, that is utilized for the treatment of severe drug-resistant infections, caused by Gram-negative bacteria; there is evidence of cefiderocol-resistance occurring in bacterial strains however. To increase the efficacy and extend the life-span of sideromycins, we demonstrate strong synergisms between cefiderocol and metallodrugs (e.g., colloidal bismuth citrate (CBS)), against Pseudomonas aeruginosa and Burkholderia cepacia. Moreover, CBS enhances cefiderocol efficacy against biofilm formation, suppresses the resistance development in P. aeruginosa and resensitizes clinically isolated resistant P. aeruginosa to cefiderocol. Notably, the co-therapy of CBS and cefiderocol significantly increases the survival rate of mice and decreases bacterial loads in the lung in a murine acute pneumonia model. The observed phenomena are partially attributable to the competitive binding of Bi3+ to cefiderocol with Fe3+, leading to enhanced uptake of Bi3+ and reduced levels of Fe3+ in cells. Our studies provide insight into the antimicrobial potential of metallo-sideromycins.
Transcranial focused ultrasound-mediated neurochemical and functional connectivity changes in deep cortical regions in humans
Authors: Yaakub Siti N. , White Tristan A. , Roberts Jamie , Martin Eleanor , Verhagen Lennart , Stagg Charlotte J. , Hall Stephen , Fouragnan Elsa F.
Published: September 2023

Low-intensity transcranial ultrasound stimulation (TUS) is an emerging non-invasive technique for focally modulating human brain function. The mechanisms and neurochemical substrates underlying TUS neuromodulation in humans and how these relate to excitation and inhibition are still poorly understood. In 24 healthy controls, we separately stimulated two deep cortical regions and investigated the effects of theta-burst TUS, a protocol shown to increase corticospinal excitability, on the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and functional connectivity. We show that theta-burst TUS in humans selectively reduces GABA levels in the posterior cingulate, but not the dorsal anterior cingulate cortex. Functional connectivity increased following TUS in both regions. Our findings suggest that TUS changes overall excitability by reducing GABAergic inhibition and that changes in TUS-mediated neuroplasticity last at least 50 mins after stimulation. The difference in TUS effects on the posterior and anterior cingulate could suggest state- or location-dependency of the TUS effect—both mechanisms increasingly recognized to influence the brain’s response to neuromodulation.
Neural tuning instantiates prior expectations in the human visual system
Authors: Harrison William J. , Bays Paul M. , Rideaux Reuben
Published: September 2023

Perception is often modelled as a process of active inference, whereby prior expectations are combined with noisy sensory measurements to estimate the structure of the world. This mathematical framework has proven critical to understanding perception, cognition, motor control, and social interaction. While theoretical work has shown how priors can be computed from environmental statistics, their neural instantiation could be realised through multiple competing encoding schemes. Using a data-driven approach, here we extract the brain’s representation of visual orientation and compare this with simulations from different sensory coding schemes. We found that the tuning of the human visual system is highly conditional on stimulus-specific variations in a way that is not predicted by previous proposals. We further show that the adopted encoding scheme effectively embeds an environmental prior for natural image statistics within the sensory measurement, providing the functional architecture necessary for optimal inference in the earliest stages of cortical processing.
The interplay between dietary fatty acids and gut microbiota influences host metabolism and hepatic steatosis
Authors: Schoeler Marc , Ellero-Simatos Sandrine , Birkner Till , Mayneris-Perxachs Jordi , Olsson Lisa , Brolin Harald , Loeber Ulrike , Kraft Jamie D. , Polizzi Arnaud , Martí-Navas Marian , Puig Josep , Moschetta Antonio , Montagner Alexandra , Gourdy Pierre , Heymes Christophe , Guillou Hervé , Tremaroli Valentina , Fernández-Real José Manuel , Forslund Sofia K. , Burcelin Remy , Caesar Robert
Published: September 2023

Dietary lipids can affect metabolic health through gut microbiota-mediated mechanisms, but the influence of lipid-microbiota interaction on liver steatosis is largely unknown. We investigate the impact of dietary lipids on human gut microbiota composition and the effects of microbiota-lipid interactions on steatosis in male mice. In humans, low intake of saturated fatty acids (SFA) is associated with increased microbial diversity independent of fiber intake. In mice, poorly absorbed dietary long-chain SFA, particularly stearic acid, induce a shift in bile acid profile and improved metabolism and steatosis. These benefits are dependent on the gut microbiota, as they are transmitted by microbial transfer. Diets enriched in polyunsaturated fatty acids are protective against steatosis but have minor influence on the microbiota. In summary, we find that diets enriched in poorly absorbed long-chain SFA modulate gut microbiota profiles independent of fiber intake, and this interaction is relevant to improve metabolism and decrease liver steatosis.
Unconventional specular optical rotation in the charge ordered state of Kagome metal CsV3Sb5
Authors: Farhang Camron , Wang Jingyuan , Ortiz Brenden R. , Wilson Stephen D. , Xia Jing
Published: September 2023

Kagome metals AV3Sb5 (A = K, Cs, Rb) provide a rich platform for intertwined orders, where evidence for time-reversal symmetry breaking, likely due to the long-sought loop currents, has emerged in STM and muon spin relaxation experiments. An isotropic component in the spontaneous optical rotation has also been reported and was interpreted as the magneto-optic Kerr effect. Intriguingly, the observed rotations differ by five orders of magnitude between different wavelengths and samples, suggesting more intricate physics. Here we report optical rotation and polar Kerr measurements in CsV3Sb5 crystals at the same wavelength. We observe large isotropic components of 1 milliradian in the optical rotation that do not respond to applied magnetic fields, while the spontaneous Kerr signal is less than 20 nanoradians. Our results prove unambiguously that the reported isotropic rotation is not from time-reversal symmetry breaking but represents the long-sought specular optical rotation and indicates a new intertwined order.
CENP-E activation by Aurora A and B controls kinetochore fibrous corona disassembly
Authors: Eibes Susana , Rajendraprasad Girish , Guasch-Boldu Claudia , Kubat Mirela , Steblyanko Yulia , Barisic Marin
Published: September 2023

Accurate chromosome segregation in mitosis depends on multiprotein structures called kinetochores that are built on the centromeric region of sister chromatids and serve to capture mitotic spindle microtubules. In early mitosis, unattached kinetochores expand a crescent-shaped structure called fibrous corona whose function is to facilitate initial kinetochore-microtubule attachments and chromosome transport by microtubules. Subsequently, the fibrous corona must be timely disassembled to prevent segregation errors. Although recent studies provided new insights on the molecular content and mechanism of fibrous corona assembly, it remains unknown what triggers the disassembly of the outermost and dynamic layer of the kinetochore. Here, we show that Aurora A and B kinases phosphorylate CENP-E to release it from an autoinhibited state. At kinetochores, Aurora B phosphorylates CENP-E to prevent its premature removal together with other corona proteins by dynein. At the spindle poles, Aurora A phosphorylates CENP-E to promote chromosome congression and prevent accumulation of corona proteins at the centrosomes, allowing for their intracellular redistribution. Thus, we propose the Aurora A/B-CENP-E axis as a critical element of the long-sought-for mechanism of fibrous corona disassembly that is essential for accurate chromosome segregation.
Suppression of alpha-carbon racemization in peptide synthesis based on a thiol-labile amino protecting group
Authors: Zhou Yifei , Li Hongjun , Huang Yi , Li Jiahui , Deng Guiyu , Chen Gong , Xi Zhen , Zhou Chuanzheng
Published: September 2023

In conventional solid-phase peptide synthesis (SPPS), α-amino groups are protected with alkoxycarbonyl groups (e.g., 9-fluorenylmethoxycarbonyl [Fmoc]). However, during SPPS, inherent side reactions of the protected amino acids (e.g., α-C racemization and aspartimide formation) generate by-products that are hard to remove. Herein, we report a thiol-labile amino protecting group for SPPS, the 2,4-dinitro-6-phenyl-benzene sulfenyl (DNPBS) group, which is attached to the α-amino group via a S–N bond and can be quantitatively removed in minutes under nearly neutral conditions (1 M p-toluenethiol/pyridine). The use of DNPBS greatly suppresses the main side reactions observed during conventional SPPS. Although DNPBS SPPS is not as efficient as Fmoc SPPS, especially for synthesis of long peptides, DNPBS and Fmoc are orthogonal protecting groups; and thus DNPBS SPPS and Fmoc SPPS can be combined to synthesize peptides that are otherwise difficult to obtain.
Integration of microbattery with thin-film electronics for constructing an integrated transparent microsystem based on InGaZnO
Authors: Jia Bin , Zhang Chao , Liu Min , Li Zhen , Wang Jian , Zhong Li , Han Chuanyu , Qin Ming , Huang Xiaodong
Published: September 2023

A full integration of miniaturized transparent energy device (lithium-ion battery), electronic device (thin-film transistor) and sensing device (photodetector) to form a monolithic integrated microsystem greatly enhances the functions of transparent electronics. Here, InGaZnO is explored to prepare the above devices and microsystem due to its multifunctional properties. A transparent lithium-ion battery with InGaZnO as anode (capacity~9.8 μAh cm−2) is proposed as the on-chip power source. Then, thin-film transistor with InGaZnO as channel (mobility~23.3 cm2 V−1 s−1) and photodetector with InGaZnO as photosensitive layer (responsivity~0.35 A W−1) are also prepared on the substrate for constructing an fully integrated transparent microsystem. Each device displays acceptable performance. Moreover, alternating-current signals can be successfully charged into the lithium-ion battery by using the thin-film transistor as the on-chip rectifier and also the photodetector works well by using the charged battery as the on-chip power, demonstrating collaborative capabilities of each device to achieve systematic functions.
Theranostic approach to specifically targeting the interloop region of BCL2 i-motif DNA by crystal violet
Authors: Das Sinjan , Takahashi Shuntaro , Ohyama Tatsuya , Bhowmik Sudipta , Sugimoto Naoki
Published: September 2023

Ligands that recognise specific i-motif DNAs are helpful in cancer diagnostics and therapeutics, as i-motif formation can cause cancer. Although the loop regions of i-motifs are promising targets for ligands, the interaction between a ligand and the loop regions based on sequence information remains unexplored. Herein, we investigated the loop regions of various i-motif DNAs to determine whether these regions specifically interact with fluorescent ligands. Crystal violet (CV), a triphenylmethane dye, exhibited strong fluorescence with the i-motif derived from the promoter region of the human BCL2 gene in a sequence- and structure-specific manner. Our systematic sequence analysis indicated that CV was bound to the site formed by the first and third loops through inter-loop interactions between the guanine bases present in these loops. As the structural stability of the BCL2 i-motif was unaffected by CV, the local stabilisation of the loops by CV could inhibit the interaction of transcription factors with these loops, repressing the BCL2 expression of MCF-7 cells. Our finding suggests that the loops of the i-motif can act as a novel platform for the specific binding of small molecules; thus, they could be utilised for the theranostics of diseases associated with i-motif DNAs.
Association between anti-thyroid peroxidase antibody and thyroid stimulating hormone: a cross-sectional study
Authors: Shimizu Yuji , Matsuyama Mutsumi , Noguchi Yuko , Takada Midori , Kawashiri Shin-Ya , Fukui Shoichi , Nakamichi Seiko , Nagata Yasuhiro , Maeda Takahiro , Hayashida Naomi
Published: September 2023

To maintain normal level of thyroid hormone, especially for free thyroxine (FT4), individuals with latent thyroid gland damage might have required higher thyroid stimulating hormone (TSH) than those without latent thyroid gland damage. Anti-thyroid peroxidase antibody (TPO-Ab) is a main cause of auto-immune thyroiditis, and therefore euthyroid individuals positive for TPO-Ab might have latent damage to the thyroid gland. Therefore, the association between TSH values and TPO-Ab positivity may be useful to determine the influence of latent thyroid gland damage on requirement of TSH. Furthermore, because latent damage of thyroid might elevate TSH level but not FT4 level, those associations should be observed independent from FT4. This cross-sectional study analyzed 1431 Japanese with normal ranges of free triiodothyronine (FT3) and FT4. Since TPO-Ab is associated with atherosclerosis in euthyroid individuals, cardiovascular risk factors might underlie the association between TPO-Ab and TSH values. After adjusting for FT4 and known cardiovascular risk factors, the adjusted odds ratio (95% confidence interval) of TPO-Ab positivity for logarithmic value of TSH was 1.53 (1.20, 1.95). Essentially the same association was observed when the analysis was restricted to individuals without subclinical hypothyroidism (1.54 [1.15, 2.13]). Euthyroid individuals with latent thyroid gland damage might have increased the requirement of TSH.
Pathogenic Leptospira are widespread in the urban wildlife of southern California
Authors: Helman Sarah K. , Tokuyama Amanda F. N. , Mummah Riley O. , Stone Nathan E. , Gamble Mason W. , Snedden Celine E. , Borremans Benny , Gomez Ana C. R. , Cox Caitlin , Nussbaum Julianne , Tweedt Isobel , Haake David A. , Galloway Renee L. , Monzón Javier , Riley Seth P. D. , Sikich Jeff A. , Brown Justin , Friscia Anthony , Sahl Jason W. , Wagner David M. , Lynch Jessica W. , Prager Katherine C. , Lloyd-Smith James O.
Published: September 2023

Leptospirosis, the most widespread zoonotic disease in the world, is broadly understudied in multi-host wildlife systems. Knowledge gaps regarding Leptospira circulation in wildlife, particularly in densely populated areas, contribute to frequent misdiagnoses in humans and domestic animals. We assessed Leptospira prevalence levels and risk factors in five target wildlife species across the greater Los Angeles region: striped skunks (Mephitis mephitis), raccoons (Procyon lotor), coyotes (Canis latrans), Virginia opossums (Didelphis virginiana), and fox squirrels (Sciurus niger). We sampled more than 960 individual animals, including over 700 from target species in the greater Los Angeles region, and an additional 266 sampled opportunistically from other California regions and species. In the five target species seroprevalences ranged from 5 to 60%, and infection prevalences ranged from 0.8 to 15.2% in all except fox squirrels (0%). Leptospira phylogenomics and patterns of serologic reactivity suggest that mainland terrestrial wildlife, particularly mesocarnivores, could be the source of repeated observed introductions of Leptospira into local marine and island ecosystems. Overall, we found evidence of widespread Leptospira exposure in wildlife across Los Angeles and surrounding regions. This indicates exposure risk for humans and domestic animals and highlights that this pathogen can circulate endemically in many wildlife species even in densely populated urban areas.