bluuebunny/crossref_metadata_2025 huggingface dataset:
Tattoos embody autobiographical memories
Authors: Klug Kristina , Camia Christin , Rohrmann Sonja
Published: March 2024

Autobiographical memories play a vital role in shaping personal identity. Therefore, individuals often use various methods like diaries and photographs to preserve precious memories. Tattoos also serve as a means of remembering, yet their role in autobiographical memory has received limited attention in research. To address this gap, we surveyed 161 adults (68.9 per cent female, M = 26.93, SD = 6.57) to explore the life events that motivated their tattoos and to examine their most significant memories. We then compared these findings with significant memories of 185 individuals without tattoos (80.0 per cent female, M = 31.26, SD = 15.34). The results showed that the majority of tattoos were inspired by unique life events, including specific events about personal growth, relationships, leisure activities, losses, or diseases. Even when not directly tied to specific events in life, tattoos still reflect autobiographical content, such as mottos, beliefs, and values. Furthermore, the most significant memories of younger tattooed individuals (20–24 years) tended to be more normative and less stressful compared to those of their non-tattooed counterparts in the same age group, though the nature of these memories varied. This difference was not found among older participants (30–54 years). Additionally, those without tattoos indicated to use specific objects and methods for preserving important events, suggesting tattoos are only one of several ways to reminisce. However, tattoos uniquely allow for the physical embodiment of autobiographical memories, indicating that engraving significant life events in the skin aids in reflecting on one's life story.
Water and the Afterlife – Water-related Resources in the Burial Construction of the Nordic Bronze Age
Authors: HORN CHRISTIAN
Published: March 2024

The waterscape, including the sea, rivers, and lakes, was highly important to communities living during the Nordic Early Bronze Age (1800/1700–1100 bc). Waterways acted as highways that facilitated journeys, trade, and warfare, enabling maritime warriors and others to distinguish themselves. This is reflected in the maritime location of rock art and important Early Bronze Age burials, which have been used to reconstruct the Nordic Bronze Age cosmology. This centres on the journey of the sun across the sky during the day, and the underworld during night. This article analyses the use of water-related resources, such as seaweed, petrified organics, beach pebbles, and molluscs, in the construction of burials, which has received little attention despite renewed interest in the maritime seascape. The data demonstrate that local communities used different resources, indicating that a common belief system was realised in local differences. These marine materials were collected from the beach, which can be conceptualised as the liminal zone between the land of the living and the sea of the dead. It is suggested that these materials, in line with other funerary practices, helped to guide the recently deceased into the afterlife in the sea.
CHRONOLOGICAL STUDY OF COLLECTIVE BURIALS IN THE NORTHERN IBERIAN PLATEAU: ANALYSIS OF RADIOCARBON DATES ON HUMAN BONES FROM THE MEGALITHIC COMPLEX OF LA LORA (BURGOS, SPAIN)
Authors: Santa Cruz Angélica
Published: March 2024

This paper offers a temporal analysis of the megalithic group of La Lora in the context of northern Iberian Plateau megalithism. For this purpose, 67 accelerator mass spectrometry radiocarbon (AMS 14C) dates were obtained on human bone from the minimum number of individuals recovered from nine tombs. This is the first systematic dating project carried out in this dolmen group and has enabled the chronology of the main funerary series to be updated. The results reveal that the actual funerary use dates mainly to the 4th millennium BC, although, as deduced from the archaeological material, some tombs were reused in later periods. Additionally, the significant architectural polymorphism of the group, consisting mainly of simple dolmens and large corridor tombs, suggested a temporal evolution to monumentality. However, the dating shows a more complex reality, since it is likely that the large tombs functioned as funerary pantheons during the 4th millennium BC, characterized by a cyclical and recurrent use. In contrast, the simpler structures were preferred to be of shorter use and restricted to the first half of the 4th millennium.
The role of depression and use of alcohol and other drugs after partner suicide in the association between suicide bereavement and suicide: cohort study in the Danish population
Authors: Pitman Alexandra , McDonald Keltie , Logeswaran Yanakan , Lewis Glyn , Cerel Julie , Lewis Gemma , Erlangsen Annette
Published: March 2024

Background

Although suicide bereavement is associated with suicide and self-harm, evidence regarding mechanisms is lacking. We investigated whether depression and substance use (alcohol and/or other drugs) explain the association between partner suicide bereavement and suicide.

Methods

Linkage of nationwide, longitudinal data from Denmark for the period 1980–2016 facilitated a comparison of 22 668 individuals exposed to bereavement by a partner's suicide with 913 402 individuals bereaved by a partner's death due to other causes. Using causal mediation models, we estimated the degree to which depression and substance use (considered separately) mediated the association between suicide bereavement and suicide.

Results

Suicide-bereaved partners were found to have a higher risk of suicide (HRadj = 1.59, 95% CI 1.36–1.86) and of depression (ORadj 1.16, 95% CI 1.09–1.25) when compared to other-bereaved partners, but a lower risk of substance use (ORadj 0.83; 95% CI 0.78–0.88). An increased risk of suicide was found among any bereaved individuals with a depression diagnosis recorded post-bereavement (ORadj 3.92, 95% CI 3.55–4.34). Mediation analysis revealed that depression mediated 2% (1.68%; 95% CI 0.23%–3.14%; p = 0.024) of the association between suicide bereavement and suicide in partners when using bereaved controls.

Conclusions

Depression is a partial mediator of the association between suicide bereavement and suicide. Efforts to prevent and optimize the treatment of depression in suicide-bereaved people could reduce their suicide risk. Our findings might be conservative because we did not include cases of depression diagnosed in primary care. Further work is needed to understand this and other mediators.
L’impossible quête des préposées aux bénéficiaires pour actualiser la bientraitance visée dans les politiques publiques du Québec.The impossible quest of health care aides to actualize the good treatment targeted in Quebec’s public policies.
Authors: Ethier Sophie , Myrand Anne , Andrianova Anna , Smele Sandra , Gagnon Éric , Couture Mélanie , Aubry François
Published: March 2024

Notre recherche visait à mettre en lumière les pratiques bientraitantes des préposées aux bénéficiaires en milieux d’hébergement pour aînés au Québec. L’objet de l’article est de faire ressortir la dichotomie entre les définitions de la bientraitance et son opérationnalisation. Dans la première partie, la notion de bientraitance dans le cadre de deux politiques gouvernementales québécoises est présentée. Ensuite, il est question du travail des préposées aux bénéficiaires en tant que vectrices de cette bientraitance dans la pratique. La troisième partie présente les résultats de notre recherche qui viennent soulever trois constats remettant en cause l’applicabilité des politiques publiques en cette matière : l’absence de reconnaissance d’un métier par définition bientraitant; les injonctions normatives à l’encontre du sens attribué à la bientraitance, et les obstacles organisationnels et sociopolitiques à la bientraitance. Ces constats sont réexaminés à la lumière des écrits dans la discussion, laquelle ouvre sur la notion de maltraitance organisationnelle.
Texts, Politics and Identities: New Challenges on Iron Age Ethnicity. A Case from Northwest Iberia
Authors: Nión-Álvarez Samuel
Published: March 2024

This paper presents an approach to the study of European Iron Age ethnicity, a core topic for several decades which has begun to lose interest in the last years. A review of some of the uncertainties involved in the archaeology of ethnicity, focused on several key issues, is proposed. Moreover, some relevant topics that are usually undermined are suggested in order to address new challenges in the discipline: the introduction of political identity as a major focus of study, the reassessment of the etic perspective as an inner part of processes of collective differentiation, or the need for a holistic approach to join and combine different forms of expression. Finally, these approaches will be explored in a case study based on the northwest of the Iberian peninsula. This region has been chosen because of the feasibility of combining the results of different studies about social and political organizsation with relevant textual evidence to extract information about their ethnic dynamics.
Institutionalising global mining knowledge: the rise of engineering education in late Qing China, 1870–95
Authors: Chen Hailian
Published: March 2024

The history of mining education in late Qing China has received relatively little attention in scholarly literature. Through the lens of institutionalising global mining knowledge, this article addresses the following questions: How did the demand for expertise within the framework of mining bureaucracy evolve under the impact of Western imperialism? How did mining education enter scholarly discourse and become eventually institutionalised in the late Qing China? Drawing on evidence from the collections of Sheng Xuanhuai's archive series, it investigates two previously overlooked ‘failures’ of Sheng's mining-related enterprises, namely his earliest mining practices in Hubei in the 1870s and his proposal for establishing a mining school in Shandong in 1888–89. It then reconnects these efforts with the histories of Western learning, late Qing mining bureaucracy, the monetary crisis of that era, and the global recruitment of engineers despite a pronounced distrust of foreign expertise. It argues that these seemingly discrete efforts or ‘failures’ in fact paved the way for initiating China's first engineering university as well as other mining colleges in around 1895 and eventually led to the rise of engineering education before the entire educational system was transformed in China.
Type‐B Crystallographic Preferred Orientation in Olivine Induced by Dynamic Dehydration of Antigorite in Forearc Regions
Authors: Liu Wenlong , Cao Yi , Li Jianfeng , Song Maoshuang , Xu Haijun , Wang Yongfeng , Wu Xiang , Zhang Junfeng , Kohlstedt David L.
Published: March 2024

The crystallographic preferred orientation (CPO) of olivine, specifically the type‐B characterized by c‐axes aligned parallel to lineation and b‐axes concentrated perpendicular to foliation, is essential for explaining the trench‐parallel seismic anisotropy in the forearc regions of subduction zones. However, its origin remains a subject of ambiguity and controversy. In this study, we present experimental findings on the formation of a type‐B olivine CPO through the dehydration of foliated serpentinite under a compressive stress at a pressure of 300 MPa and temperature of 700–750°C. Our results reveal a progressive evolution of olivine CPO, transitioning from a type‐C fabric to a type‐B fabric, with increasing grain size and dehydration level. The type‐B CPO observed in coarse‐grained olivine within fully dehydrated samples primarily arises from mechanisms involving anisotropic growth, grain rotation, and oriented coalescence of newly formed, small olivine grains following the decomposition of antigorite under a compressive stress. This study provides the first experimental evidence for a novel, low‐temperature dynamic dehydration mechanism, in contrast to the mechanism of high‐temperature plastic flow, for explaining the development of type‐B olivine CPO in forearc regions. Hence, it contributes significantly to our understanding of the formation of olivine CPO with implications for seismic anisotropy in subduction zone forearcs.
Sensitivity of GNSS‐Derived Estimates of Terrestrial Water Storage to Assumed Earth Structure
Authors: Swarr Matthew J. , Martens Hilary R. , Fu Yuning
Published: March 2024

Geodetic methods can monitor changes in terrestrial water storage (TWS) across large regions in near real‐time. Here, we investigate the effect of assumed Earth structure on TWS estimates derived from Global Navigation Satellite System (GNSS) displacement time series. Through a series of synthetic tests, we systematically explore how the spatial wavelength of water load affects the error of TWS estimates. Large loads (e.g., >1,000 km) are well recovered regardless of the assumed Earth model. For small loads (e.g., <10 km), however, errors can exceed 75% when an incorrect model for the Earth is chosen. As a case study, we consider the sensitivity of seasonal TWS estimates within mountainous watersheds of the western U.S., finding estimates that differ by over 13% for a collection of common global and regional structural models. Errors in the recovered water load generally scale with the total weight of the load; thus, long‐term changes in storage can produce significant uplift (subsidence), enhancing errors. We demonstrate that regions experiencing systematic and large‐scale variations in water storage, such as the Greenland ice sheet, exhibit significant differences in predicted displacement (over 20 mm) depending on the choice of Earth model. Since the discrepancies exceed GNSS observational precision, an appropriate Earth model must be adopted when inverting GNSS observations for mass changes in these regions. Furthermore, regions with large‐scale mass changes that can be quantified using independent data (e.g., altimetry, gravity) present opportunities to use geodetic observations to refine structural properties of seismologically derived models for the Earth's interior structure.
A novel bioinformatic approach reveals cooperation between Cancer/Testis genes in basal-like breast tumors
Authors: Laisné Marthe , Rodgers Brianna , Benlamara Sarah , Wicinski Julien , Nicolas André , Djerroudi Lounes , Gupta Nikhil , Ferry Laure , Kirsh Olivier , Daher Diana , Philippe Claude , Okada Yuki , Charafe-Jauffret Emmanuelle , Cristofari Gael , Meseure Didier , Vincent-Salomon Anne , Ginestier Christophe , Defossez Pierre-Antoine
Published: March 2024

Breast cancer is the most prevalent type of cancer in women worldwide. Within breast tumors, the basal-like subtype has the worst prognosis, prompting the need for new tools to understand, detect, and treat these tumors. Certain germline-restricted genes show aberrant expression in tumors and are known as Cancer/Testis genes; their misexpression has diagnostic and therapeutic applications. Here we designed a new bioinformatic approach to examine Cancer/Testis gene misexpression in breast tumors. We identify several new markers in Luminal and HER-2 positive tumors, some of which predict response to chemotherapy. We then use machine learning to identify the two Cancer/Testis genes most associated with basal-like breast tumors: HORMAD1 and CT83. We show that these genes are expressed by tumor cells and not by the microenvironment, and that they are not expressed by normal breast progenitors; in other words, their activation occurs de novo. We find these genes are epigenetically repressed by DNA methylation, and that their activation upon DNA demethylation is irreversible, providing a memory of past epigenetic disturbances. Simultaneous expression of both genes in breast cells in vitro has a synergistic effect that increases stemness and activates a transcriptional profile also observed in double-positive tumors. Therefore, we reveal a functional cooperation between Cancer/Testis genes in basal breast tumors; these findings have consequences for the understanding, diagnosis, and therapy of the breast tumors with the worst outcomes.
Downregulation of UBB potentiates SP1/VEGFA-dependent angiogenesis in clear cell renal cell carcinoma
Authors: Wang Jinpeng , Zhao Enyang , Geng Bo , Zhang Wei , Li Zhuolun , Liu Qing , Liu Weiyang , Zhang Wenfu , Hou Wenbin , Zhang Nan , Liu Zhiming , You Bosen , Wu Pengfei , Li Xuedong
Published: March 2024

Clear cell renal cell carcinoma (ccRCC) presents a unique profile characterized by high levels of angiogenesis and robust vascularization. Understanding the underlying mechanisms driving this heterogeneity is essential for developing effective therapeutic strategies. This study revealed that ubiquitin B (UBB) is downregulated in ccRCC, which adversely affects the survival of ccRCC patients. UBB exerts regulatory control over vascular endothelial growth factor A (VEGFA) by directly interacting with specificity protein 1 (SP1), consequently exerting significant influence on angiogenic processes. Subsequently, we validated that DNA methyltransferase 3 alpha (DNMT3A) is located in the promoter of UBB to epigenetically inhibit UBB transcription. Additionally, we found that an unharmonious UBB/VEGFA ratio mediates pazopanib resistance in ccRCC. These findings underscore the critical involvement of UBB in antiangiogenic therapy and unveil a novel therapeutic strategy for ccRCC.
Inhibition of the AURKA/YAP1 axis is a promising therapeutic option for overcoming cetuximab resistance in colorectal cancer stem cells
Authors: Rio-Vilariño Anxo , Cenigaonandia-Campillo Aiora , García-Bautista Ana , Mateos-Gómez Pedro A. , Schlaepfer Marina I. , del Puerto-Nevado Laura , Aguilera Oscar , García-García Laura , Galeano Carlos , de Miguel Irene , Serrano-López Juana , Baños Natalia , Fernández-Aceñero María Jesús , Lacal Juan Carlos , Medico Enzo , García-Foncillas Jesús , Cebrián Arancha
Published: March 2024

Background

Primary resistance to anti-EGFR therapies affects 40% of metastatic colorectal cancer patients harbouring wild-type RAS/RAF. YAP1 activation is associated with this resistance, prompting an investigation into AURKA’s role in mediating YAP1 phosphorylation at Ser397, as observed in breast cancer.

Methods

We used transcriptomic analysis along with in vitro and in vivo models of RAS/RAF wild-type CRC to study YAP1 Ser397 phosphorylation as a potential biomarker for cetuximab resistance. We assessed cetuximab efficacy using CCK8 proliferation assays and cell cycle analysis. Additionally, we examined the effects of AURKA inhibition with alisertib and created a dominant-negative YAP1 Ser397 mutant to assess its impact on cancer stem cell features.

Results

The RAS/RAF wild-type CRC models exhibiting primary resistance to cetuximab prominently displayed elevated YAP1 phosphorylation at Ser397 primarily mediated by AURKA. AURKA-induced YAP1 phosphorylation was identified as a key trigger for cancer stem cell reprogramming. Consequently, we found that AURKA inhibition had the capacity to effectively restore cetuximab sensitivity and concurrently suppress the cancer stem cell phenotype.

Conclusions

AURKA inhibition holds promise as a therapeutic approach to overcome cetuximab resistance in RAS/RAF wild-type colorectal cancer, offering a potential means to counter the development of cancer stem cell phenotypes associated with cetuximab resistance.
mTORC1 accelerates osteosarcoma progression via m6A-dependent stabilization of USP7 mRNA
Authors: Yang Zhengming , Yu Wei , Xu Ankai , Liu Bing , Jin Libin , Tao Huimin , Wang Dimin
Published: March 2024

Osteosarcoma (OS) is considered a sex steroid hormone-dependent bone tumor. The development and progression of OS are regulated by 17β-estradiol (E2). However, the detailed mechanisms of E2-modulated OS progression remained to be elucidated. Here, we found that E2-activated mammalian target of rapamycin (mTOR) signaling promoted N6-methyladenosine (m6A) modification through regulating WTAP. Inhibition of mTOR complex 1 (mTORC1) reversed E2-activated WTAP expression. Meanwhile, inhibition of mTORC1 suppressed OS cell proliferation and migration. Deficiency of TSC2 activated mTORC1 signaling and enhanced OS cell proliferation and migration, while abrogated by Rapamycin. Interestingly, mTOMC1 promoted mRNA stability of ubiquitin-specific protease 7 (USP7) through m6A modification. Loss of USP7 suppressed the proliferation, migration, and ASC specks, while promoted apoptosis of OS cells. USP7 interacted with NLRP3 and deubiquitinated NLRP3 through K48-ubiquitination. USP7 was upregulated and positive correlation with NLRP3 in OS patients with high level of E2. Loss of USP7 suppressed the progression of OS via inhibiting NLRP3 inflammasome signaling pathway. Our results demonstrated that E2-activtated mTORC1 promoted USP7 stability, which promoted OS cell proliferation and migration via upregulating NLRP3 expression and enhancing NLRP3 inflammasome signaling pathway. These results discover a novel mechanism of E2 regulating OS progression and provide a promising therapeutic target for OS progression.
Multiple cancer cell types release LIF and Gal3 to hijack neural signals
Authors: Xu Qun , Cao Ying , Kong Fanni , Liu Jiaqi , Chen Xin , Zhao Yifei , Lai Chin-Hui , Zhou Xin , Hu Hao , Fu Wei , Chen Jian , Yang Jing
Published: March 2024

Neural signals can significantly influence cancer prognosis. However, how cancer cells may proactively modulate the nervous system to benefit their own survival is incompletely understood. In this study, we report an overlapping pattern of brain responses, including that in the paraventricular nucleus of the hypothalamus, in multiple mouse models of peripheral cancers. A multi-omic screening then identifies leukemia inhibitory factor (LIF) and galectin-3 (Gal3) as the key cytokines released by these cancer cell types to trigger brain activation. Importantly, increased plasma levels of these two cytokines are observed in patients with different cancers. We further demonstrate that pharmacologic or genetic blockage of cancer cell-derived LIF or Gal3 signaling abolishes the brain responses and strongly inhibits tumor growth. In addition, ablation of peripheral sympathetic actions can similarly restore antitumor immunity. These results have elucidated a novel, shared mechanism of multiple cancer cell types hijacking the nervous system to promote tumor progression.
Head to head comparison of diagnostic performance of three non-mydriatic cameras for diabetic retinopathy screening with artificial intelligence
Authors: Doğan Mehmet Erkan , Bilgin Ahmet Burak , Sari Ramazan , Bulut Mehmet , Akar Yusuf , Aydemir Mustafa
Published: March 2024

Background

Diabetic Retinopathy (DR) is a leading cause of blindness worldwide, affecting people with diabetes. The timely diagnosis and treatment of DR are essential in preventing vision loss. Non-mydriatic fundus cameras and artificial intelligence (AI) software have been shown to improve DR screening efficiency. However, few studies have compared the diagnostic performance of different non-mydriatic cameras and AI software.

Methods

This clinical study was conducted at the endocrinology clinic of Akdeniz University with 900 volunteer patients that were previously diagnosed with diabetes but not with diabetic retinopathy. Fundus images of each patient were taken using three non-mydriatic fundus cameras and EyeCheckup AI software was used to diagnose more than mild diabetic retinopathy, vision-threatening diabetic retinopathy, and clinically significant diabetic macular oedema using images from all three cameras. Then patients underwent dilation and 4 wide-field fundus photography. Three retina specialists graded the 4 wide-field fundus images according to the diabetic retinopathy treatment preferred practice patterns of the American Academy of Ophthalmology. The study was pre-registered on clinicaltrials.gov with the ClinicalTrials.gov Identifier: NCT04805541.

Results

The Canon CR2 AF AF camera had a sensitivity and specificity of 95.65% / 95.92% for diagnosing more than mild DR, the Topcon TRC-NW400 had 95.19% / 96.46%, and the Optomed Aurora had 90.48% / 97.21%. For vision threatening diabetic retinopathy, the Canon CR2 AF had a sensitivity and specificity of 96.00% / 96.34%, the Topcon TRC-NW400 had 98.52% / 95.93%, and the Optomed Aurora had 95.12% / 98.82%. For clinically significant diabetic macular oedema, the Canon CR2 AF had a sensitivity and specificity of 95.83% / 96.83%, the Topcon TRC-NW400 had 98.50% / 96.52%, and the Optomed Aurora had 94.93% / 98.95%.

Conclusion

The study demonstrates the potential of using non-mydriatic fundus cameras combined with artificial intelligence software in detecting diabetic retinopathy. Several cameras were tested and, notably, each camera exhibited varying but adequate levels of sensitivity and specificity. The Canon CR2 AF emerged with the highest accuracy in identifying both more than mild diabetic retinopathy and vision-threatening cases, while the Topcon TRC-NW400 excelled in detecting clinically significant diabetic macular oedema. The findings from this study emphasize the importance of considering a non mydriatic camera and artificial intelligence software for diabetic retinopathy screening. However, further research is imperative to explore additional factors influencing the efficiency of diabetic retinopathy screening using AI and non mydriatic cameras such as costs involved and effects of screening using and on an ethnically diverse population.
Disrupted sleep-wake regulation in the MCI-Park mouse model of Parkinson’s disease
Authors: Summa K. C. , Jiang P. , González-Rodríguez P. , Huang X. , Lin X. , Vitaterna M. H. , Dan Y. , Surmeier D. J. , Turek F. W.
Published: March 2024

Disrupted sleep has a profound adverse impact on lives of Parkinson’s disease (PD) patients and their caregivers. Sleep disturbances are exceedingly common in PD, with substantial heterogeneity in type, timing, and severity. Among the most common sleep-related symptoms reported by PD patients are insomnia, excessive daytime sleepiness, and sleep fragmentation, characterized by interruptions and decreased continuity of sleep. Alterations in brain wave activity, as measured on the electroencephalogram (EEG), also occur in PD, with changes in the pattern and relative contributions of different frequency bands of the EEG spectrum to overall EEG activity in different vigilance states consistently observed. The mechanisms underlying these PD-associated sleep-wake abnormalities are poorly understood, and they are ineffectively treated by conventional PD therapies. To help fill this gap in knowledge, a new progressive model of PD – the MCI-Park mouse – was studied. Near the transition to the parkinsonian state, these mice exhibited significantly altered sleep-wake regulation, including increased wakefulness, decreased non-rapid eye movement (NREM) sleep, increased sleep fragmentation, reduced rapid eye movement (REM) sleep, and altered EEG activity patterns. These sleep-wake abnormalities resemble those identified in PD patients. Thus, this model may help elucidate the circuit mechanisms underlying sleep disruption in PD and identify targets for novel therapeutic approaches.
Late Pleistocene emergence of an anthropogenic fire regime in Australia’s tropical savannahs
Authors: Bird Michael I. , Brand Michael , Comley Rainy , Fu Xiao , Hadeen Xennephone , Jacobs Zenobia , Rowe Cassandra , Wurster Christopher M. , Zwart Costijn , Bradshaw Corey J. A.
Published: March 2024

At the time of European arrival on the Australian continent, sophisticated Indigenous societies practiced land management across Australia’s extensive tropical savannahs. Fire was one of the main tools people used to manipulate fuel loads and connectivity to reduce uncontrolled wildfire, maintain vegetation structure and enhance biodiversity. When this alteration of a ‘natural’ fire regime to a human-dominated fire regime occurred is not known. Here we assessed fire incidence and intensity over the past 150,000 years through a continuous lacustrine record by comparing the accumulation rates of micro-charcoal and stable polycyclic aromatic hydrocarbon that form during the combustion of vegetation. We also compared grass (mainly C4) pollen as a percentage of total dryland pollen with the carbon isotope composition of the stable polycyclic aromatic hydrocarbon. We established with high statistical certainty that a change in fire regime occurred at least 11,000 years ago from less-frequent, more-intense fires to more-frequent, less-intense fires. This change marked the overprinting of a largely natural fire regime by one at least modulated by Indigenous management. Our findings demonstrate that human fire use has modified fire regimes throughout the Holocene and also show how people have managed the potential for the type of high-intensity fires that are likely to increase in the future.
Enhancer–promoter interactions become more instructive in the transition from cell-fate specification to tissue differentiation
Authors: Pollex Tim , Rabinowitz Adam , Gambetta Maria Cristina , Marco-Ferreres Raquel , Viales Rebecca R. , Jankowski Aleksander , Schaub Christoph , Furlong Eileen E. M.
Published: March 2024

To regulate expression, enhancers must come in proximity to their target gene. However, the relationship between the timing of enhancer–promoter (E–P) proximity and activity remains unclear, with examples of uncoupled, anticorrelated and correlated interactions. To assess this, we selected 600 characterized enhancers or promoters with tissue-specific activity in Drosophila embryos and performed Capture-C in FACS-purified myogenic or neurogenic cells during specification and tissue differentiation. This enabled direct comparison between E–P proximity and activity transitioning from OFF-to-ON and ON-to-OFF states across developmental conditions. This showed remarkably similar E–P topologies between specified muscle and neuronal cells, which are uncoupled from activity. During tissue differentiation, many new distal interactions emerge where changes in E–P proximity reflect changes in activity. The mode of E–P regulation therefore appears to change as embryogenesis proceeds, from largely permissive topologies during cell-fate specification to more instructive regulation during terminal tissue differentiation, when E–P proximity is coupled to activation.
A solid beta-sheet structure is formed at the surface of FUS droplets during aging
Authors: Emmanouilidis Leonidas , Bartalucci Ettore , Kan Yelena , Ijavi Mahdiye , Pérez Maria Escura , Afanasyev Pavel , Boehringer Daniel , Zehnder Johannes , Parekh Sapun H. , Bonn Mischa , Michaels Thomas C. T. , Wiegand Thomas , Allain Frédéric H.-T.
Published: March 2024

Phase transitions are important to understand cell dynamics, and the maturation of liquid droplets is relevant to neurodegenerative disorders. We combined NMR and Raman spectroscopies with microscopy to follow, over a period of days to months, droplet maturation of the protein fused in sarcoma (FUS). Our study reveals that the surface of the droplets plays a critical role in this process, while RNA binding prevents it. The maturation kinetics are faster in an agarose-stabilized biphasic sample compared with a monophasic condensed sample, owing to the larger surface-to-volume ratio. In addition, Raman spectroscopy reports structural differences upon maturation between the inside and the surface of droplets, which is comprised of β-sheet content, as revealed by solid-state NMR. In agreement with these observations, a solid crust-like shell is observed at the surface using microaspiration. Ultimately, matured droplets were converted into fibrils involving the prion-like domain as well as the first RGG motif.
Structure of the human 20S U5 snRNP
Authors: Schneider Sarah , Brandina Irina , Peter Daniel , Lagad Sonal , Fraudeau Angelique , Portell-Montserrat Júlia , Tholen Jonas , Zhao Jiangfeng , Galej Wojciech P.
Published: March 2024

The 20S U5 small nuclear ribonucleoprotein particle (snRNP) is a 17-subunit RNA–protein complex and a precursor of the U4/U6.U5 tri-snRNP, the major building block of the precatalytic spliceosome. CD2BP2 is a hallmark protein of the 20S U5 snRNP, absent from the mature tri-snRNP. Here we report a high-resolution cryogenic electron microscopy structure of the 20S U5 snRNP, shedding light on the mutually exclusive interfaces utilized during tri-snRNP assembly and the role of the CD2BP2 in facilitating this process.
Digital pathology with artificial intelligence analysis provides insight to the efficacy of anti-fibrotic compounds in human 3D MASH model
Authors: Kostadinova Radina , Ströbel Simon , Chen Li , Fiaschetti‑Egli Katia , Gadient Jana , Pawlowska Agnieszka , Petitjean Louis , Bieri Manuela , Thoma Eva , Petitjean Mathieu
Published: March 2024

Metabolic dysfunction-associated steatohepatitis (MASH) is a severe liver disease characterized by lipid accumulation, inflammation and fibrosis. The development of MASH therapies has been hindered by the lack of human translational models and limitations of analysis techniques for fibrosis. The MASH three-dimensional (3D) InSight™ human liver microtissue (hLiMT) model recapitulates pathophysiological features of the disease. We established an algorithm for automated phenotypic quantification of fibrosis of Sirius Red stained histology sections of MASH hLiMTs model using a digital pathology quantitative single-fiber artificial intelligence (AI) FibroNest™ image analysis platform. The FibroNest™ algorithm for MASH hLiMTs was validated using anti-fibrotic reference compounds with different therapeutic modalities-ALK5i and anti-TGF-β antibody. The phenotypic quantification of fibrosis demonstrated that both reference compounds decreased the deposition of fibrillated collagens in alignment with effects on the secretion of pro-collagen type I/III, tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-3 and pro-fibrotic gene expression. In contrast, clinical compounds, Firsocostat and Selonsertib, alone and in combination showed strong anti-fibrotic effects on the deposition of collagen fibers, however less pronounced on the secretion of pro-fibrotic biomarkers. In summary, the phenotypic quantification of fibrosis of MASH hLiMTs combined with secretion of pro-fibrotic biomarkers and transcriptomics represents a promising drug discovery tool for assessing anti-fibrotic compounds.
Assessing biologic/toxicologic effects of extractables from plastic contact materials for advanced therapy manufacturing using cell painting assay and cytotoxicity screening
Authors: Pahl Ina , Pahl Axel , Hauk Armin , Budde Dana , Sievers Sonja , Fruth Lothar , Menzel Roberto
Published: March 2024

Plastic components are essential in the pharmaceutical industry, encompassing container closure systems, laboratory handling equipment, and single-use systems. As part of their material qualification process, studies on interactions between plastic contact materials and process solutions or drug products are conducted. The assessment of single-use systems includes their potential impact on patient safety, product quality, and process performance. This is particularly crucial in cell and gene therapy applications since interactions with the plastic contact material may result in an adverse effect on the isolated therapeutic human cells. We utilized the cell painting assay (CPA), a non-targeted method, for profiling the morphological characteristics of U2OS human osteosarcoma cells in contact with chemicals related to plastic contact materials. Specifically, we conducted a comprehensive analysis of 45 common plastic extractables, and two extracts from single-use systems. Results of the CPA are compared with a standard cytotoxicity assay, an osteogenesis differentiation assay, and in silico toxicity predictions. The findings of this feasibility study demonstrate that the device extracts and most of the tested compounds do not evoke any measurable biological changes on the cells (induction  ≤ 5%) among the 579 cell features measured at concentrations  ≤ 50 µM. CPA can serve as an important assay to reveal unique information not accessible through quantitative structure–activity relationship analysis and vice versa. The results highlight the need for a combination of in vitro and in silico methods in a comprehensive assessment of single-use equipment utilized in advanced therapy medicinal products manufacturing.
Stress affects navigation strategies in immersive virtual reality
Authors: Varshney Apurv , Munns Mitchell E. , Kasowski Justin , Zhou Mantong , He Chuanxiuyue , Grafton Scott T. , Giesbrecht Barry , Hegarty Mary , Beyeler Michael
Published: March 2024

There are known individual differences in both the ability to learn the layout of novel environments and the flexibility of strategies for navigating known environments. However, it is unclear how navigational abilities are impacted by high-stress scenarios. Here we used immersive virtual reality (VR) to develop a novel behavioral paradigm to examine navigation under dynamically changing situations. We recruited 48 participants (24 female; ages 17–32) to navigate a virtual maze (7.5 m × 7.5 m). Participants learned the maze by moving along a fixed path past the maze’s landmarks (paintings). Subsequently, participants experienced either a non-stress condition, or a high-stress condition tasking them with navigating the maze. In the high-stress condition, their initial path was blocked, the environment was darkened, threatening music was played, fog obstructed more distal views of the environment, and participants were given a time limit of 20 s with a countdown timer displayed at the top of their screen. On trials where the path was blocked, we found self-reported stress levels and distance traveled increased while trial completion rate decreased (as compared to non-stressed control trials). On unblocked stress trials, participants were less likely to take a shortcut and consequently navigated less efficiently compared to control trials. Participants with more trait spatial anxiety reported more stress and navigated less efficiently. Overall, our results suggest that navigational abilities change considerably under high-stress conditions.
Engineered biosorbents of pomelo (Citrus maxima (Burm.f.) Merr) peels modified with zinc oxide and titanium dioxide for methylene blue dye sorption
Authors: Praipipat Pornsawai , Ngamsurach Pimploy , Srirat Pratchayaporn , Chaiphumee Punjaporn
Published: March 2024

The pomelo-doped zinc oxide beads (PZB), pomelo-doped titanium dioxide beads (PTB), and pomelo-doped zinc oxide and titanium dioxide beads (PZTB) were synthesized for sorbing methylene blue (MB) dye. Their characterizations were explored by X-Ray Diffractometer (XRD), Field Emission Scanning Electron Microscopy and Focus Ion Beam (FESEM-FIB), Energy Dispersive X-Ray Spectrometer (EDX), and Fourier Transform Infrared Spectroscopy (FT-IR). In addition, their sorbent efficiencies for sorbing MB dye were investigated through batch experiments, sorbent reusability studies, sorption isotherms, kinetics, and thermodynamic studies. They were crystalline phases presenting the specific peaks of zinc oxide (ZnO) or titanium dioxide (TiO2). Their surfaces had lamella structures with coarse surfaces, and they also found specific structures of ZnO or TiO2 on the surfaces. Zn–O or Ti–O–Ti was also detected in PZB or PTB or, PZTB depending upon metal oxide types added into pomelo beaded sorbents. For batch experiments, they could adsorb MB dye of more than 86%, and PZTB showed the highest MB dye removal efficiency. In addition, they could be reused for more than three cycles with high MB dye sorptions of more than 72%. They corresponded to Freundlich and pseudo-second-order kinetic models. Moreover, the increasing temperature affected their decreasing MB dye sorptions which were exothermic processes.
An investigation into the correlation between visual performance in simulated complex environments and academic attainment among primary school students
Authors: Tian Yu-Jing , Chen Chen , Zhang Xiao-Han , Cao Yu-Juan , Yu Ying-Qing
Published: March 2024

Traditional vision screenings in schools are limited to simple visual tasks, yet students in their daily learning face more complex visual environments. Binocular rivalry tasks can partially simulate the visual challenges of real visual environments and activate advanced visual processing mechanisms that simple visual tasks cannot. Therefore, by superimposing binocular rivalry-state tasks onto simple visual tasks, we have developed an innovative vision screening program to rapidly and extensively assess students’ visual performance in complex environments. This is a cross-sectional study in which we investigated the performance of 1126 grade 1–6 students from a primary school in Wuxi, China, in rivalry-state stereoscopic vision tasks. The correlation between the screening results of 1044 students and their academic achievements was also statistically analyzed. The study results revealed pass rates of 53.5–60.5% across various visual tests. Specifically, for first-grade students, there was a statistically significant difference in standardized Chinese scores between the group that failed and the group that passed the rivalry-state stereoscopic vision test (− 0.49 ± 3.42 vs. 0.22 ± 0.58, t =  − 2.081, P = 0.04). This result underscores the importance of focusing on the visual adaptability of first graders in complex environments.

Trail registration: Ethics Committee of Affiliated Children’s Hospital of Jiangnan University-Certificate number: WXCH2022-04-027
The transcriptomic insight into the differential susceptibility of African Swine Fever in inbred pigs
Authors: Banabazi Mohammad Hossein , Freimanis Graham , Goatley Lynnette C. , Netherton Christopher L. , de Koning Dirk-Jan
Published: March 2024

African swine fever (ASF) is a global threat to animal health and food security. ASF is typically controlled by strict biosecurity, rapid diagnosis, and culling of affected herds. Much progress has been made in developing modified live virus vaccines against ASF. There is host variation in response to ASF infection in the field and under controlled conditions. To better understand the dynamics underlying this host differential morbidity, whole transcriptome profiling was carried out in twelve immunized and five sham immunized pigs. Seventeen MHC homozygous inbred Large white Babraham pigs were sampled at three time points before and after the challenge. The changes in the transcriptome profiles of infected animals were surveyed over time. In addition, the immunization effect on the host response was studied as well among the contrasts of all protection subgroups. The results showed two promising candidate genes to distinguish between recovered and non-recovered pigs after infection with a virulent African swine fever virus (ASFV) pre-infection: HTRA3 and GFPT2 (padj < 0.05). Variant calling on the transcriptome assemblies showed a two-base pair insertion into the ACOX3 gene closely located to HTRA3 that may regulate its expression as a putative genomic variant for ASF. Several significant DGEs, enriched gene ontology (GO) terms, and KEGG pathways at 1 day and 7 days post-infection, compared to the pre-infection, indicate a significant inflammation response immediately after ASF infection. The presence of the virus was confirmed by the mapping of RNA-Seq reads on two whole viral genome sequences. This was concordant with a higher virus load in the non-recovered animals 7 days post-infection. There was no transcriptome signature on the immunization at pre-infection and 1 day post-infection. More samples and data from additional clinical trials may support these findings.
Binarized neural network of diode array with high concordance to vector–matrix multiplication
Authors: Shin Yunwoo , Cho Kyoungah , Kim Sangsig
Published: March 2024

In this study, a binarized neural network (BNN) of silicon diode arrays achieved vector–matrix multiplication (VMM) between the binarized weights and inputs in these arrays. The diodes that operate in a positive-feedback loop in their p+-n-p-n+device structure possess steep switching and bistable characteristics with an extremely low subthreshold swing (below 1 mV) and a high current ratio (approximately 108). Moreover, the arrays show a self-rectifying functionality and an outstanding linearity by an R-squared value of 0.99986, which allows to compose a synaptic cell with a single diode. A 2 × 2 diode array can perform matrix multiply-accumulate operations for various binarized weight matrix cases with some input vectors, which is in high concordance with the VMM, owing to the high reliability and uniformity of the diodes. Moreover, the disturbance-free, nondestructive readout, and semi-permanent holding characteristics of the diode arrays support the feasibility of implementing the BNN.
Towards a universal mechanism for successful deep learning
Authors: Meir Yuval , Tzach Yarden , Hodassman Shiri , Tevet Ofek , Kanter Ido
Published: March 2024

Recently, the underlying mechanism for successful deep learning (DL) was presented based on a quantitative method that measures the quality of a single filter in each layer of a DL model, particularly VGG-16 trained on CIFAR-10. This method exemplifies that each filter identifies small clusters of possible output labels, with additional noise selected as labels outside the clusters. This feature is progressively sharpened with each layer, resulting in an enhanced signal-to-noise ratio (SNR), which leads to an increase in the accuracy of the DL network. In this study, this mechanism is verified for VGG-16 and EfficientNet-B0 trained on the CIFAR-100 and ImageNet datasets, and the main results are as follows. First, the accuracy and SNR progressively increase with the layers. Second, for a given deep architecture, the maximal error rate increases approximately linearly with the number of output labels. Third, similar trends were obtained for dataset labels in the range [3, 1000], thus supporting the universality of this mechanism. Understanding the performance of a single filter and its dominating features paves the way to highly dilute the deep architecture without affecting its overall accuracy, and this can be achieved by applying the filter’s cluster connections (AFCC).
Impact of ecological presence in virtual reality tourism on enhancing tourists’ environmentally responsible behavior
Authors: Su Zhen , Lei Biman , Lu Dandan , Lai Shuchen , Zhang Xijing
Published: March 2024

In an era where environmental conservation is increasingly critical, identifying pathways through which technological innovations like virtual reality tourism (VRT) can promote sustainable behaviors is vital. This study investigates the impact of ‘ecological presence’, a newly proposed sub-dimension of presence in VRT, on tourists’ environmentally responsible behavior (TERB). Through structural equation modeling and fuzzy set qualitative comparative analysis of data from 290 participants, we unveil that ecological presence—defined as the authenticity and immersion of tourists in virtual ecological environments—significantly bolsters biospheric values, environmental self-identity, and personal norms. Additionally, our findings indicate that ecological presence in VRT indirectly promotes TERB, predominantly through the mediation of enhanced biospheric values and environmental self-identity. Notably, ecological presence, biospheric values, and environmental self-identity constitutes a sufficient condition for achieving a high level of TERB. This research highlights the potential of VRT as an innovative tool for tourism administrators to foster environmental stewardship, offering a novel approach to leveraging technology for conservation efforts.