bluuebunny/crossref_metadata_2025 huggingface dataset:
Frühe feministische Petitionen aus der Schweiz
Authors: Schröter Juliane
Published: November 2024

In diesem Beitrag werden die ältesten heute noch bekannten und auffindbaren Petitionen analysiert, mit denen Frauen in der Schweiz versucht haben, ihre Lebensbedingungen zu verbessern. Sechs Petitionen, die zwischen 1846 und 1872 entstanden sind, werden in den Dimensionen Lexik, Sprechakte und Argumentationen mit Blick auf Bezeichnungen von Personen, für die Partei ergriffen wird, Zielbezeichnungen, politische Bitten bzw. Forderungen, Standpunkte sowie wiederkehrende Prämissen und Argumente untersucht. Die Ergebnisse deuten darauf hin, dass Frauen erst in den 1870er Jahren im politischen Diskurs als klar benennbare Interessensgruppe relativ etabliert waren, dass die Frauenbewegungen in ihren ersten Anfängen noch keine politischen Forderungen sensu stricto stellten, dass ihre Petitionserfahrung und ihr Politikwissen zu Beginn noch nicht groß genug waren, um unklare, wechselnde und falsch adressierte Standpunkte zu verhindern, dass sie aber bereits auf ein Repertoire zentraler Argumente zurückgreifen konnten, die bis heute bekannt sind. Mit Hilfe der gewonnenen Ergebnisse werden am Ende des Beitrags diachrone Hypothesen zum Sprachgebrauch der Frauenbewegungen in der Schweiz aufgestellt, die von der zukünftigen Forschung überprüft werden könnten.
Burnout: a comprehensive review
Authors: Demerouti Evangelia
Published: November 2024

Burnout has been the focus of extensive scientific research. The World Health Organization officially recognized burnout as an occupational phenomenon, defined as a syndrome resulting from chronic workplace stress that remains unmanaged and characterized by three dimensions: exhaustion, cynicism, and inefficacy. Existing literature highlights limitations in current measurement instruments for diagnostic purposes. These tools often yield scores that overlap with other conditions such as fatigue, anxiety, and depression. Chronic exposure to high job demands and low job resources emerges as the primary trigger for burnout. While individual characteristics (such as neuroticism) may increase susceptibility, specific personality traits associated with higher risk remain unclear. Burnout has adverse effects on both individuals and organizations. Typical interventions focus on stress relief and coping strategies to manage high job demands, but their effectiveness diminishes over time. Evidence from organizational interventions suggests that improving employees’ working conditions can reduce burnout risk. Combined interventions offer promise by creating a healthy work environment while empowering employees to handle occasional stress. Social partners should advocate for support in researching burnout, aiming for a clear diagnosis, effective treatment, and preventive measures to mitigate psychosocial risks in the workplace.

Practical Relevance: The findings of this article highlight the importance of addressing both job demands and job resources to mitigate burnout in organizational settings. Implementing interventions that improve working conditions and provide adequate support can significantly reduce burnout risk and enhance employee well-being. Organizations should prioritize creating a healthy work environment and empowering employees with the necessary resources to manage workload effectively.
Information geometry of the Otto metric
Authors: Ay Nihat
Published: November 2024

We introduce the dual of the mixture connection with respect to the Otto metric which represents a new kind of exponential connection. This provides a dual structure consisting of the mixture connection, the Otto metric as a Riemannian metric, and the new exponential connection. We derive the geodesic equation of this exponential connection, which coincides with the Kolmogorov forward equation of a gradient flow. We then derive the canonical contrast function of the introduced dual structure.
Association of oral frailty with falls in long-term care residents
Authors: Puranen Taija , Hiltunen Kaija , Pitkälä Kaisu H. , Roitto Hanna-Maria , Mäntylä Päivi , Saarela Riitta K. T.
Published: November 2024

Purpose

We investigated the relationship between oral frailty (OFr) and falls among long-term care residents.

Methods

Residents (N = 254, mean age 84 y, 79% women) participated in this longitudinal cohort study in 2018–2021. OFr was defined by six signs. Demographics, diagnoses, and medications were retrieved from the medical records. Frailty phenotype, sarcopenia and disability were assessed. Number of falls was collected from medical records over 12 months following baseline assessment.

Results

Of participants, 35% fell during follow-up. Of the fallers, 28% were bedridden or needed a wheelchair; among non-fallers, this figure was 73%. In logistic regression analysis after adjusting for age, sex, BMI, stroke, dementia, diabetes, coronary heart disease, number of medications, mobility, walking speed and sarcopenia, OFr did not predict falls (OR for severe OFr 0.13 (95% CI 0.01—1.27). Male sex predicted falls.

Conclusions

No association was found between severe OFr and falls over a 12-month follow-up.
Exploring the power of natural outdoor spaces in enhancing early childhood practitioners’ wellbeing
Authors: Geuens Nina , Willockx Dietlinde , Janssen Jeroen
Published: November 2024

While there is growing consensus on the benefits of natural outdoor play environments for children, the impact of such spaces on the wellbeing of early childhood practitioners remains unknown. Using an exploratory qualitative design, this study unraveled the positive outcomes of greening outdoor spaces in childcare centers in Flanders (Belgium) and the challenges that it may encompass. Eleven in-depth interviews were conducted with professionals who were recently involved in such transformations. Through a thematic analysis seven outcomes were identified: (1) reduced workload, (2) calmer children and less conflicts, (3) more job fulfillment, (4) a sense of peace, (5) a place to enjoy, (6) more little pleasures, and (7) more chances for meeting up with colleagues. Challenges arose mainly in relation to (1) health and safety concerns, (2) transitions, (3) resources, and (4) team spirit. The results indicate that the establishment of natural outdoor spaces in childcare centers can benefit practitioners’ wellbeing in several ways. As such, this study calls for a broader understanding of the importance of green experiences in early childhood education and care. Our insights should be taken into consideration when designing natural outdoor spaces for childcare centers as well as in developing personnel policies on staff wellbeing. Further research is needed, however, to determine the generalizability of research findings and the extent and kind of green experience that is necessary to obtain the positive outcomes.
Human Dynamics Research in GIScience: challenges and opportunities
Authors: Shaw Shih-Lung , Ye Xinyue , Goodchild Michael , Sui Dan
Published: November 2024

The Symposium on Human Dynamics Research, first organized at the 2015 AAG Meeting in Chicago, celebrated its 10th anniversary at the 2024 AAG Meeting in Honolulu, marking a decade of transformative advancements in the field. Over the past decade, the focus of human dynamics research has shifted from traditional spatial-temporal analyses to sophisticated modeling of human behavior in a hybrid physical-virtual world. This evolving field now examines the intricate interdependencies between physical and digital environments, addressing critical issues such as urban resilience, public health, social equity, and community sustainability. The symposium emphasized the growing importance of interdisciplinary collaboration, advanced data-driven analytical platforms, and innovative theoretical frameworks to better understand human interactions across these spaces. As human dynamics continue to shape global urban systems, these advancements are pivotal for future research and real-world problem-solving, offering novel insights into the interconnectedness of mobility, technology, and societal well-being in a rapidly changing world.
Effect of synthesis temperature on the properties and photocatalytic performance of peroxo-titanate nanotubes prepared by bottom-up synthesis method
Authors: Han Do Hyung , Park Hyunsu , Goto Tomoyo , Cho Sunghun , Seo Yeongjun , Kondo Yoshifumi , Nishida Hisataka , Sekino Tohru
Published: November 2024

The alkaline treatment synthesis of titania/titanate nanotubes (TNTs) requires highly concentrated alkaline solutions (≥ 10 mol/L), which pose environmental and productivity limitations. In contrast, a bottom-up synthesis method for peroxo-titanate nanotubes (PTNTs) has been developed. This method offers two advantages: it can synthesize materials using low-concentration alkaline solutions (1.5 mol/L) and produce photocatalytic materials that are responsive to visible light. In general, the higher the crystallinity of a catalyst, the better its properties. However, PTNTs synthesized at temperatures close to their boiling point (around 100 °C) exhibit low crystallinity. This study hypothesizes a hydrothermal synthesis method at higher temperatures will enhance the crystallinity and photocatalytic performance of PTNTs, synthesizing them at temperatures ranging from 120 to 200 °C using a method capable of exceeding the boiling point. Higher synthesis temperatures resulted in improved morphological and crystallographic properties of the PTNTs. However, the formation of peroxo-bonding, crucial for visible light responsiveness, decreased. Nevertheless, peroxo-bonding formation was still achievable at the highest temperature of 200 °C, and the sample exhibited the best Rhodamine B (Rh B) photodegradation performance under visible light due to its enhanced specific surface area and crystallinity. This study highlights the novelty and environmental significance of hydrothermally synthesized PTNTs as superior photocatalysts by optimizing the synthesis temperature while using lower concentration alkaline solutions.
Population-based cross-sectional survey of cervical cancer screening prevalence and socio-demographic correlates in Bangladeshi women
Authors: Khan Mohammad Jobair , Kannan Priya , Sayma  , Winser Stanley John
Published: November 2024

Background

Cervical cancer, albeit preventable, is the second-most deadly gynecological cancer in developing nations. Little is known about cervical cancer among Bangladeshi women. This study aims to estimate the prevalence of cervical cancer screening and demographic correlates to identify potential variabilities in screening rates among different demographic groups and regions.

Methods

This study used secondary data from the WHO STEPS 2018 Survey. We used Bayesian regression to perform the bivariate analyses between the outcome and each explanatory factor, as it generates more acceptable results and improves parameter estimates. The top-ranked socio-demographic factors were identified using a two-step cluster analysis. This method determines the relevance of predictor variables and automatically establishes the number of clusters.

Results

The prevalence of Bangladeshi women who had ever been screened for cervical cancer was 6.2%. In the adjusted model, women with the following socio-demographic factors had a higher likelihood of developing cervical cancer: being 18–29 years old (AOR = 3.3, 95% CI: 0.24, 15.27) or 45–59 years old (AOR = 2.8, 95% CI: 1.22, 6.0), currently married (AOR = 2.3, 95% CI: 1.36, 3.70), and employed (AOR = 2.4, 95% CI: 1.40, 4.06). Women in the Barisal division were found to have higher odds of being screened for cervical cancer (AOR = 21, 95% CI: 0.66, 121.97). Cluster analysis found residence status predisposes women to cervical cancer screening.

Conclusion

There is a significant potential for substantial reductions in the burden of cervical cancer in Bangladesh by strengthening the application of cervical cancer screening. Future studies should examine how socioeconomic status, culture, and healthcare access affect cervical cancer screening trends for different divisions in Bangladesh. An independent national cancer registry is urgently needed to evaluate screening trends and outcomes.
Subthalamic nucleus deep brain stimulation modulates speech graphs in patients with Parkinson’s disease
Authors: Zhang Guanyu , Xiao Haoyun , Ma Jinghong , Lang Liqin , Wu Jianjun , Ye Zheng
Published: November 2024

Graph theory enables a direct quantification of topological properties of any arbitrary network. Its application in neuroscience has unveiled topological changes of brain networks associated with various neurodegenerative diseases. This study used the graph theory to understand speech deficits in patients with Parkinson’s disease (PD). In particular, this study investigated the effect of subthalamic nucleus deep brain stimulation (STN-DBS) on the topology of speech graphs. Sixty patients with PD completed a standard semantic fluency test with DBS switched ON and OFF. A control group of sixty matched nonsurgical PD patients completed the test once. All verbal responses were recorded, transcripted, and transformed into directed speech graphs. Volumes of tissue activated (VTA) were estimated for three STN subregions, including sensorimotor, associative, and limbic parts. First, the patients with DBS OFF produced smaller and denser speech graphs than nonsurgical patients, showing fewer nodes, higher density, shorter diameter, and shorter average shortest path. Second, DBS partially reversed the effect of surgery, leading to larger and sparser speech graphs with more nodes, lower density, longer diameter, and longer average shortest path (ON versus OFF). Third, however, the left associative VTA negatively correlated with the DBS-induced diameter and average shortest path changes (ON versus OFF), suggesting that the patients with greater left associative STN stimulation tended to produce smaller and denser speech graphs. This study demonstrates that STN-DBS can partially restore the topological structure of speech graphs in PD patients. However, stimulating the left associative STN appears to disrupt speech graphs.
Bayesian recalibration ofPlanckgalaxy cluster scaling relations including relativistic Sunyaev-Zel’dovich corrections
Authors: Perrott Yvette
Published: November 2024

We investigate the impact of relativistic SZ corrections onPlanckmeasurements of massive galaxy clusters, finding that they have a significant impact at the$\approx$5–15% and up to$\approx$3$\sigma$level. We investigate the possibility of constraining temperature directly from these SZ measurements but find that only weak constraints are possible for the most significant detections; for most clusters, an external temperature measurement is required to correctly measure integrated Compton-y. We also investigate the impact of profile shape assumptions and find that these have a small but non-negligible impact on measured Compton-y, at the$\approx$5% level. Informed by the results of these investigations, we recalibrate thePlanckSZ observable-mass scaling relation, using the updated NPIPE data release and a larger sample of X-ray mass estimates. Along with the expected change in the high-mass end of the scaling relation, which does not impactPlanckmass estimation, we also find hints of a low-mass deviation, but this requires better understanding of the selection function in order to confirm.
Causal associations of tea consumption on risk of pancreatic adenocarcinoma and the mediating role of vascular endothelial growth factor D levels
Authors: Ouyang Yonghao , Zhou Beini , Chu Lihua , Chen Xin , Hao Qiang , Lei Jiajia
Published: November 2024

Tea is one of the most widely consumed beverages in the world. However, the association between tea and risk of pancreatic adenocarcinoma remains controversial. This study aimed to investigate the causal relationship between tea consumption and risk of pancreatic adenocarcinoma and to explore their mediating effects. The two-sample Mendelian randomisation (MR) analysis showed an inverse causal relationship between tea intake and pancreatic adenocarcinoma (OR: 0·111 (0·02, 0·85), P < 0·04). To examine the mediating effects, we explored the potential mechanisms by which tea intake reduces the risk of pancreatic adenocarcinoma. Based on the oral bioavailability and drug-like properties in Traditional Chinese Medicine Systems Pharmacology database, we selected the main active ingredients of tea. We screened out the fifteen representative targeted genes by Pharmmapper database, and the gene ontology enrichment analysis showed that these targeted genes were related to vascular endothelial growth factor (VEGF) pathway. The two-step MR analysis of results showed that only VEGF-D played a mediating role, with a mediation ratio of 0·230 (0·066, 0·394). In conclusion, the findings suggest that VEGF-D mediates the effect of tea intake on the risk of pancreatic adenocarcinoma.
Neogene Hydrothermal Fe‐ and Mn‐Oxide Mineralization of Paleozoic Continental Rocks, Amerasia Basin, Arctic Ocean
Authors: Hein James R. , Mizell Kira , Gartman Amy
Published: November 2024

Rocks dredged from water depths of 1,605, 2,500, 3,300, and 3,400 m in the Arctic Ocean included Paleozoic continental rocks pervasively mineralized during the Neogene by hydrothermal Fe and Mn oxides. Samples were recovered in three dredge hauls from the Chukchi Borderland and one from Mendeleev Ridge north of Alaska and eastern Siberia, respectively. Many of the rocks were so pervasively altered that the protolith could not be identified, while others had volcanic, plutonic, and metamorphic protoliths. The mineralized rocks were cemented and partly to wholly replaced by the hydrothermal oxides. The Amerasia Basin, where the Chukchi Borderland and Mendeleev Ridge occur, supports a series of faults and fractures that serve as major zones of crustal weakness. We propose that the stratabound hydrothermal deposits formed through the flux of hydrothermal fluids along Paleozoic and Mesozoic faults related to block faulting along a rifted margin during minor episodes of Neogene tectonism and were later exposed at the seafloor through slumping or other gravity processes. Tectonically driven hydrothermal circulation most likely facilitated the pervasive mineralization along fault surfaces via frictional heating, hydrofracturing brecciation, and low‐ to moderate temperature Fe‐ and Mn‐rich hydrothermal fluids, which mineralized the crushed, altered, and brecciated rocks.
Biofilm Growth in Porous Media Well Approximated by Fractal Multirate Mass Transfer With Advective‐Diffusive Solute Exchange
Authors: Wang Jingjing , Carrera Jesús , Saaltink Maarten W. , Petchamé‐Guerrero Jordi , Herrera Graciela S. , Valhondo Cristina
Published: November 2024

Biofilm growth in porous media changes not only the hydrodynamic properties of the medium (reduction in porosity and permeability, and increase in dispersivity), but also the transport itself (breakthrough curves display increasingly fast first arrivals and long tails). These features are well reproduced by multicontinuum models (Multi‐Rate Mass Transfer, MRMT) which can be used to describe reactive transport in heterogeneous porous media and facilitate the simulation of reactions that are localized within biofilms. Here, we present a conceptual and numerical model of biochemical reactive transport with dynamic biofilm growth based on MRMT formulations. Mass exchange between mobile water and immobile biofilm aggregates is represented by a memory function, which simplifies definition of MRMT parameters. We successfully tested this model on two sets of laboratory data and found that (a) a basic model based on the growth of uniformly sized biofilm aggregates fails to reproduce laboratory tracer tests and rate of biofilm growth, while a fractal growth model, which we obtain by integrating the memory functions of biofilm aggregates with a power law distribution, does; (b) the biofilm memory function evolves as the biofilm grows; and (c) the early time portion of eluted volume tracer breakthrough curves are independent of flow rate, whereas the tail becomes heavier when the flow rate is decreased, which implies that both advection controlled and diffusion controlled mass exchange coexist in biofilms. These findings imply that porous media biofilms are essentially different from those developing in human tissues or open spaces.
Matrix Corrected SIMS In Situ Oxygen Isotope Analyses of Marine Shell Aragonite for High Resolution Seawater Temperature Reconstructions
Authors: Medd Oliver M. , Otter Laura M. , Williams Ian S. , Stern Richard A. , Förster Michael W. , Eggins Stephen M. , Rodriguez‐Sanz Laura , Abram Nerilie J. , He Miaohong , Ellwood Michael J. , Hargreaves Jessica A. , Fallon Stewart J. , Knowles Brett M.
Published: November 2024

Marine shells incorporate oxygen isotope signatures during growth, creating valuable records of seawater temperature and marine oxygen isotopic compositions. Secondary ion mass spectrometry (SIMS) measures these compositions in situ at finer length‐scales than traditional stable isotope analyses. However, determining oxygen isotope ratios in aragonite, the most common shell mineral, is hampered by a lack of ideal reference materials, limiting the accuracy of SIMS‐based seawater temperature reconstructions. Here, we tested the capability of SIMS to produce seawater temperature reconstructions despite the matrix calibration challenges associated with aragonite. We cultured Anadara trapezia bivalves at four controlled seawater temperatures (13–28°C) and used strontium labeling to mark the start of the temperature‐controlled shell increment, allowing for more spatially precise SIMS analysis. An improved matrix calibration was developed to ensure more accurate bio‐aragonite analyses that addressed matrix differences between the pure abiotic reference materials and the bio‐aragonite samples with intricate mineral‐organic architectures and distinct minor and trace element compositions. We regressed SIMS‐IRMS biases of abiotic and biogenic aragonites that account for their systematic differences in major, minor, and trace elements, allowing for more accurate SIMS analyses of the temperature‐controlled shell increment. The thorough matrix calibration allowed us to provide a SIMS‐based seawater‐corrected oxygen isotope thermometer of T(°C) = 23.05 ± 0.36 − 4.48 · (δ18Oaragonite [‰ VPDB] − δ18Oseawater [‰ VSMOW] ± 0.25) and 103lnαaragonite‐seawater = (17.78 ± 0.88) · 103/T (K) − (29.44 ± 2.40) that agrees with existing aragonitic IRMS‐based thermometer relationships and improves the applicability of SIMS‐based paleo‐environmental reconstructions of marine bio‐aragonites.
Attention and executive delays in early childhood: a meta-analysis of neurodevelopmental conditions
Authors: Lee Dabin , Boulton Kelsie A. , Sun Carter , Phillips Natalie L. , Munro Martha , Kumfor Fiona , Demetriou Eleni A. , Guastella Adam J.
Published: November 2024

The objective of this review was to evaluate attention and executive function performance in children with neurodevelopmental conditions across the first 5 years of life, compared to neurotypical peers. MEDLINE, EMBASE, and PsycINFO databases were searched until June 30, 2023, and studies comparing attention or executive function between children with (or at risk for) neurodevelopmental conditions and neurotypical (or low risk) peers, 0 to 5 years old, were included. Of the 4338 studies identified, 111 studies with 12292 participants were included in the meta-analysis. The qualitative analysis of brain development included 5 studies. Primary outcomes were the standardised mean difference (Hedges’ g) in attention and executive function between groups. Meta-regressions examined moderating effects of age, biological sex, diagnosis, and measure type. Children with neurodevelopmental conditions showed small delays in attention (n = 49 studies, k = 251 outcomes, g = 0.36, 95% CI 0.23-0.48, p < 0.001) and moderate delays in executive function (n = 64 studies, k = 368 outcomes, g = 0.64,95% CI 0.53–0.76, p < 0.001). Attention and executive function delays could not be identified in the first year (equivalence tests, p < 0.001), small to moderate delays were found in toddlerhood and moderate delays by preschool. Delays identified were largely transdiagnostic, although there was some evidence of diagnosis-specific delays for attention and moderation by measure type (informant rating vs performance-based vs physiological). Qualitative analysis described how delays were underpinned by a divergence of brain development in medial prefrontal regions. These findings highlight the potential of using attention and executive measures to detect delay and to intervene in neurodevelopmental conditions early in life.
Manipulating the EphB4-ephrinB2 axis to reduce metastasis in HNSCC
Authors: Abdelazeem Khalid N. M. , Nguyen Diemmy , Corbo Sophia , Darragh Laurel B. , Matsumoto Mike W. , Van Court Benjamin , Neupert Brooke , Yu Justin , Olimpo Nicholas A. , Osborne Douglas Grant , Gadwa Jacob , Ross Richard B. , Nguyen Alexander , Bhatia Shilpa , Kapoor Mohit , Friedman Rachel S. , Jacobelli Jordan , Saviola Anthony J. , Knitz Michael W. , Pasquale Elena B. , Karam Sana D.
Published: November 2024

The EphB4-ephrinB2 signaling axis has been heavily implicated in metastasis across numerous cancer types. Our emerging understanding of the dichotomous roles that EphB4 and ephrinB2 play in head and neck squamous cell carcinoma (HNSCC) poses a significant challenge to rational drug design. We find that EphB4 knockdown in cancer cells enhances metastasis in preclinical HNSCC models by augmenting immunosuppressive cells like T regulatory cells (Tregs) within the tumor microenvironment. EphB4 inhibition in cancer cells also amplifies their ability to metastasize through increased expression of genes associated with hallmark pathways of metastasis along with classical and non-classical epithelial-mesenchymal transition. In contrast, vascular ephrinB2 knockout coupled with radiation therapy (RT) enhances anti-tumor immunity, reduces Treg accumulation into the tumor, and decreases metastasis. Notably, targeting the EphB4-ephrinB2 signaling axis with the engineered ligands ephrinB2-Fc-His and Fc-TNYL-RAW-GS reduces local tumor growth and distant metastasis in a preclinical model of HNSCC. Our data suggests that targeted inhibition of vascular ephrinB2 while avoiding inhibition of EphB4 in cancer cells could be a promising strategy to mitigate HNSCC metastasis.
Impact of cytopenias and early versus late treatment with ruxolitinib in patients with steroid-refractory acute or chronic graft-versus-host disease
Authors: Mahmoudjafari Zahra , Bhatt Valkal , Galvin John , Xue Zhenyi , Zeiser Robert , Locatelli Franco , Socié Gérard , Mohty Mohamad
Published: November 2024

REACH2 and REACH3 were randomized, multicenter, open-label phase 3 studies comparing the selective Janus kinase (JAK)1/JAK2 inhibitor ruxolitinib versus investigators’ choice of best available therapy (BAT) in steroid-refractory (SR) acute (REACH2) or chronic (REACH3) graft-versus-host disease (aGVHD/cGVHD). Moderate-severe aGVHD/cGVHD can progress rapidly; thus, key clinical considerations driving management of patients with SR-aGVHD/SR-cGVHD are prompt treatment initiation and concomitant cytopenias. These post hoc analyses of REACH2/REACH3 describe the impact of timing of treatment initiation after SR-aGVHD/SR-cGVHD diagnosis and development of concomitant cytopenias on treatment outcomes. Ruxolitinib initiation within 3 days from SR-aGVHD diagnosis yielded an extended duration of response and higher Day 28 complete response rates compared with initiation ≥7 days after SR-aGVHD diagnosis (median 178 vs 167 days and 36.6% vs 25.0%, respectively). For patients with SR-cGVHD, Week 24 overall response was not impacted by time to treatment (54.5% vs 42.6% for <14 vs >28 days). Clinically relevant cytopenias were manageable, allowing for maintenance of dose intensity (median 20 mg/d), and did not impact the favorable efficacy outcomes from ruxolitinib treatment. This analysis highlights the practical importance of considering earlier ruxolitinib initiation after SR diagnosis in GVHD and the benefits of ruxolitinib treatment compared with BAT even for patients with cytopenias.
Cancer and treatment specific incidence rates of immune-related adverse events induced by immune checkpoint inhibitors: a systematic review
Authors: Jayathilaka Bishma , Mian Farah , Franchini Fanny , Au-Yeung George , IJzerman Maarten
Published: November 2024

Background

Immune-related adverse events (irAE) induced by immune checkpoint inhibitors (ICI) are a treatment-limiting barrier. There are few large-scale studies that estimate irAE prevalence. This paper presents a systematic review that reports the prevalence of irAE by cancer type and ICI.

Methods

A systematic review was undertaken in MEDLINE OVID, EMBASE and Web of Science databases from 2017–2021. A total of 293 studies were identified for analysis and, of these, event rate was calculated for 272 studies, which involved 58,291 patients with irAE among 305,879 total patients on ICI. Event rate was calculated by irAE and ICI type.

Results

Mean event rate for general irAE occurrence across any grade was 40.0% (37.3–42.7%) and high grade was 19.7% (15.8–23.7%). Mean event rates for six specific types of irAE are reported. Mean event rate for ICI monotherapy was 30.5% (28.1–32.9%), 45.7% (29.6–61.7%) for ICI combination therapy, and 30.0% (25.3–34.6%) for both ICI monotherapy and combination therapy.

Conclusion

This systematic review characterises irAE prevalence across current research that examines irAE risk factors across cancers and ICI. The findings confirms that irAE occurrence is very common in the real-world setting, both high grade and irAE across any grade.
VCP enhances autophagy-related osteosarcoma progression by recruiting USP2 to inhibit ubiquitination and degradation of FASN
Authors: Wang Shijiang , Nie Jiangbo , Jiang Haoxin , Li Anan , Zhong Nanshan , Tong Weilai , Yao Geliang , Jiang Alan , Xie Xinsheng , Zhong Yanxin , Shu Zhiguo , Liu Jiaming , Yang Feng , Liu Zhili
Published: November 2024

Osteosarcoma (OS) is a highly aggressive malignant tumor with a high rate of disability and mortality rates, and dysregulated autophagy is a crucial factor in cancer. However, the molecular mechanisms that regulate autophagy in OS remain unclear. This study aimed to explore key molecules that affect autophagy in OS and their regulatory mechanisms. We found that fatty acid synthase (FASN) was significantly increased in activated autophagy models of OS and promoted OS proliferation in an autophagy-dependent manner, as detected by LC3 double-labeled fluorescence confocal microscopy, western blotting, transmission electron microscopy (TEM), and cell functional experiments. Furthermore, co-immunoprecipitation combined with mass spectrometry (Co-IP/MS), ubiquitination modification, molecular docking, and protein truncation methods were used to identify FASN-interacting proteins and analyze their effects on OS. Valosin-containing protein (VCP) enhanced the FASN stability by recruiting ubiquitin specific peptidase-2 (USP2) to remove the K48-linked ubiquitin chains from FASN; domain 2 of VCP and the amino acid sequence () of USP2 were critical for their interactions. Gain- and loss-of-function experiments showed that the inhibition of FASN or USP2 attenuated the stimulatory effect of VCP overexpression on autophagy and the malignant phenotypes of OS cells in vitro and in vivo. Notably, micro-CT indicated that VCP induced severe bone destruction in nude mice, which was abrogated by FASN or USP2 downregulation. In summary, VCP recruits USP2 to stabilize FASN by deubiquitylation, thereby activating autophagy and promoting OS progression. The identification of the VCP/USP2/FASN axis, which mediates autophagy regulation, provides important insights into the underlying mechanisms of OS and offers potential diagnostic and therapeutic strategies for patients with OS.
Overexpressed nicotinamide N‑methyltransferase in endometrial stromal cells induced by macrophages and estradiol contributes to cell proliferation in endometriosis
Authors: Hou Shuhui , Xu Hui , Lei Shating , Zhao Dong
Published: November 2024

Endometriosis, an estrogen-dependent chronic inflammatory condition, afflicts reproductive-aged women. However, the underlying pathological mechanisms remain to be elucidated. Nicotinamide N-methyltransferase (NNMT) is a critical enzyme involved in cellular metabolism and methylation regulation. This study investigated the role of NNMT in endometriosis. By analyzing datasets GSE5108, GSE7305, GSE141549, GSE23339, and GSE25628, we identified a significant overexpression of NNMT in the eutopic endometrium and ectopic lesions of endometriosis patients compared to normal endometrium. Furthermore, NNMT was upregulated in collected endometrioma specimens and isolated primary endometrial stromal cells (ESCs) compared to their respective controls. Inhibition of NNMT using JBSNF-000088 attenuated the proliferation, migration, and invasion of ESCs. In vivo, treatment of mouse models of endometriosis with JBSNF-000088 resulted in a marked reduction in lesion weight and quantity. NNMT expression in ESCs was dose-dependently upregulated by 17β-estradiol at concentrations of 1 nM, 10 nM, and 100 nM, an effect that was attenuated by 10 nM progesterone. Additionally, treating HESCs with macrophage-conditioned medium elevated NNMT expression at both mRNA and protein levels. Knockdown of NNMT impeded the proliferation, migration, and invasion of ESCs, which was paralleled by decreased phosphorylation levels of Erb-b2 receptor tyrosine kinase 4 (ERBB4), PI3K, and AKT. Conversely, overexpressing ERBB4 mitigated the NNMT knockdown-induced decline in phosphorylated PI3K and AKT and rescued the proliferation of ESCs. Altogether, these results indicate that the overexpression of NNMT induced by estrogen and macrophage interaction modulates ESC proliferation via the NNMT-ERBB4-PI3K/AKT signaling pathway, as well as promotes cellular migration and invasion, contributing to the development of endometriosis.
Clinical outcomes with a new diffractive multifocal intraocular lens optimized by the dynamic light utilization algorithm
Authors: Alió Jorge L. , Megiddo Barnir Elinor , Medalle Ronald Steven S. , Plaza-Puche Ana B. , Martínez Antonio , Yébana Pilar , Poyales Blanca , Poyales Francisco
Published: November 2024

Background/objectives

To evaluate the refractive outcomes, optical performance, and the quality of vision in patients implanted with a new diffractive intraocular lens (IOL), the Intensity Hanita.

Subjects/methods

This observational, prospective, longitudinal study included 64 eyes underwent bilateral cataract surgery with the Intensity IOL (Hanita Israel) implantation. Main outcome measures after 6 months were the following visual acuities (VAs) of uncorrected and corrected distance (UDVA and CDVA), uncorrected and distance corrected intermediate VAs (UIVA and DCIVA), uncorrected and distance corrected near (UNVA and DCNVA), refraction, slitlamp biomicroscopy, defocus curve (DFC), high ocular aberrations (HOA), contrast sensitivity (CS), optical quality, subjective quality of vision (QoV) and near activity visual questionnaires (NAVQ).

Results

Sixty-six percent of eyes having UDVA 0.10 logMAR or better. DFC showed maximum vision at distance (0.02 ± 0.07 LogMAR at 0.0 D), with flat decline through intermediate and near vision (0.11 ± 0.08 LogMAR at −1.5 D and 0.12 ± 0.12 at −2.5 D). No significant changes in CS were found (all spatial frequencies, p ≥ 0.06). The RMS of HOA, coma, trefoil, and SA were 0.21 ± 0.10, 0.10 ± 0.06, 0.11 ± 0.07, and 0.00 ± 0.04 μm and the Strehl ratio was 0.12 ± .04 at 6 months. Subjective symptoms (halos and glare) were reported mild but well tolerated, not causing significant disturbance in daily activities. The NAVQ showed high levels of satisfaction performing daily near-vision tasks.

Conclusions

The Hanita Intensity diffractive IOL successfully restores all distances of vision. The flat profile of the monocular defocus curve confirms the five-foci distribution principle that provides vision at all ranges while increasing the depth of focus.
The value of long-duration energy storage under various grid conditions in a zero-emissions future
Authors: Staadecker Martin , Szinai Julia , Sánchez-Pérez Pedro A. , Kurtz Sarah , Hidalgo-Gonzalez Patricia
Published: November 2024

Long-duration energy storage (LDES) is a key resource in enabling zero-emissions electricity grids but its role within different types of grids is not well understood. Using the Switch capacity expansion model, we model a zero-emissions Western Interconnect with high geographical resolution to understand the value of LDES under 39 scenarios with different generation mixes, transmission expansion, storage costs, and storage mandates. We find that a) LDES is particularly valuable in majority wind-powered regions and regions with diminishing hydropower generation, b) seasonal operation of storage becomes cost-effective if storage capital costs fall below US$5 kWh−1, and c) mandating the installation of enough LDES to enable year-long storage cycles would reduce electricity prices during times of high demand by over 70%. Given the asset and resource diversity of the Western Interconnect, our results can provide grid planners in many regions with guidance on how LDES impacts and is impacted by energy storage mandates, investments in LDES research and development, and generation mix and transmission expansion decisions.
Decoding the epigenetics and chromatin loop dynamics of androgen receptor-mediated transcription
Authors: Altıntaş Umut Berkay , Seo Ji-Heui , Giambartolomei Claudia , Ozturan Dogancan , Fortunato Brad J. , Nelson Geoffrey M. , Goldman Seth R. , Adelman Karen , Hach Faraz , Freedman Matthew L. , Lack Nathan A.
Published: November 2024

Androgen receptor (AR)-mediated transcription plays a critical role in development and prostate cancer growth. AR drives gene expression by binding to thousands of cis-regulatory elements (CRE) that loop to hundreds of target promoters. With multiple CREs interacting with a single promoter, it remains unclear how individual AR bound CREs contribute to gene expression. To characterize the involvement of these CREs, we investigate the AR-driven epigenetic and chromosomal chromatin looping changes by generating a kinetic multi-omic dataset comprised of steady-state mRNA, chromatin accessibility, transcription factor binding, histone modifications, chromatin looping, and nascent RNA. Using an integrated regulatory network, we find that AR binding induces sequential changes in the epigenetic features at CREs, independent of gene expression. Further, we show that binding of AR does not result in a substantial rewiring of chromatin loops, but instead increases the contact frequency of pre-existing loops to target promoters. Our results show that gene expression strongly correlates to the changes in contact frequency. We then propose and experimentally validate an unbalanced multi-enhancer model where the impact on gene expression of AR-bound enhancers is heterogeneous, and is proportional to their contact frequency with target gene promoters. Overall, these findings provide insights into AR-mediated gene expression upon acute androgen simulation and develop a mechanistic framework to investigate nuclear receptor mediated perturbations.
Hierarchical regulation of functionally antagonistic neuropeptides expressed in a single neuron pair
Authors: Aoki Ichiro , Golinelli Luca , Dunkel Eva , Bhat Shripriya , Bassam Erschad , Beets Isabel , Gottschalk Alexander
Published: November 2024

Neuronal communication involves small-molecule transmitters, gap junctions, and neuropeptides. While neurons often express multiple neuropeptides, our understanding of the coordination of their actions and their mutual interactions remains limited. Here, we demonstrate that two neuropeptides, NLP-10 and FLP-1, released from the same interneuron pair, AVKL/R, exert antagonistic effects on locomotion speed in Caenorhabditis elegans. NLP-10 accelerates locomotion by activating the G protein-coupled receptor NPR-35 on premotor interneurons that promote forward movement. Notably, we establish that NLP-10 is crucial for the aversive response to mechanical and noxious light stimuli. Conversely, AVK-derived FLP-1 slows down locomotion by suppressing the secretion of NLP-10 from AVK, through autocrine feedback via activation of its receptor DMSR-7 in AVK neurons. Our findings suggest that peptidergic autocrine motifs, exemplified by the interaction between NLP-10 and FLP-1, might represent a widespread mechanism in nervous systems across species. These mutual functional interactions among peptidergic co-transmitters could fine-tune brain activity.
Distribution and diversity of classical deacylases in bacteria
Authors: Graf Leonie G. , Moreno-Yruela Carlos , Qin Chuan , Schulze Sabrina , Palm Gottfried J. , Schmöker Ole , Wang Nancy , Hocking Dianna M. , Jebeli Leila , Girbardt Britta , Berndt Leona , Dörre Babett , Weis Daniel M. , Janetzky Markus , Albrecht Dirk , Zühlke Daniela , Sievers Susanne , Strugnell Richard A. , Olsen Christian A. , Hofmann Kay , Lammers Michael
Published: November 2024

Classical Zn2+-dependent deac(et)ylases play fundamental regulatory roles in life and are well characterized in eukaryotes regarding their structures, substrates and physiological roles. In bacteria, however, classical deacylases are less well understood. We construct a Generalized Profile (GP) and identify thousands of uncharacterized classical deacylases in bacteria, which are grouped into five clusters. Systematic structural and functional characterization of representative enzymes from each cluster reveal high functional diversity, including polyamine deacylases and protein deacylases with various acyl-chain type preferences. These data are supported by multiple crystal structures of enzymes from different clusters. Through this extensive analysis, we define the structural requirements of substrate selectivity, and discovered bacterial de-d-/l-lactylases and long-chain deacylases. Importantly, bacterial deacylases are inhibited by archetypal HDAC inhibitors, as supported by co-crystal structures with the inhibitors SAHA and TSA, and setting the ground for drug repurposing strategies to fight bacterial infections. Thus, we provide a systematic structure-function analysis of classical deacylases in bacteria and reveal the basis of substrate specificity, acyl-chain preference and inhibition.
Enhancing transcription–replication conflict targets ecDNA-positive cancers
Authors: Tang Jun , Weiser Natasha E. , Wang Guiping , Chowdhry Sudhir , Curtis Ellis J. , Zhao Yanding , Wong Ivy Tsz-Lo , Marinov Georgi K. , Li Rui , Hanoian Philip , Tse Edison , Mojica Salvador Garcia , Hansen Ryan , Plum Joshua , Steffy Auzon , Milutinovic Snezana , Meyer S. Todd , Luebeck Jens , Wang Yanbo , Zhang Shu , Altemose Nicolas , Curtis Christina , Greenleaf William J. , Bafna Vineet , Benkovic Stephen J. , Pinkerton Anthony B. , Kasibhatla Shailaja , Hassig Christian A. , Mischel Paul S. , Chang Howard Y.
Published: November 2024

Extrachromosomal DNA (ecDNA) presents a major challenge for cancer patients. ecDNA renders tumours treatment resistant by facilitating massive oncogene transcription and rapid genome evolution, contributing to poor patient survival1–7. At present, there are no ecDNA-specific treatments. Here we show that enhancing transcription–replication conflict enables targeted elimination of ecDNA-containing cancers. Stepwise analyses of ecDNA transcription reveal pervasive RNA transcription and associated single-stranded DNA, leading to excessive transcription–replication conflicts and replication stress compared with chromosomal loci. Nucleotide incorporation on ecDNA is markedly slower, and replication stress is significantly higher in ecDNA-containing tumours regardless of cancer type or oncogene cargo. pRPA2-S33, a mediator of DNA damage repair that binds single-stranded DNA, shows elevated localization on ecDNA in a transcription-dependent manner, along with increased DNA double strand breaks, and activation of the S-phase checkpoint kinase, CHK1. Genetic or pharmacological CHK1 inhibition causes extensive and preferential tumour cell death in ecDNA-containing tumours. We advance a highly selective, potent and bioavailable oral CHK1 inhibitor, BBI-2779, that preferentially kills ecDNA-containing tumour cells. In a gastric cancer model containing FGFR2 amplified on ecDNA, BBI-2779 suppresses tumour growth and prevents ecDNA-mediated acquired resistance to the pan-FGFR inhibitor infigratinib, resulting in potent and sustained tumour regression in mice. Transcription–replication conflict emerges as a target for ecDNA-directed therapy, exploiting a synthetic lethality of excess to treat cancer.
A dual-band high-gain beam steering antenna array for 5G sub-6 GHz base station
Authors: Siddiqui Salman Ilahi , Bashir Shahid , Khan Awais , Ghafoor Salman , Aziz Imran
Published: November 2024

An antenna array having a size of 45 $$\:\times\:$$ 40 cm2 (5.7 $$\:\times\:$$ 5 $$\:{\lambda\:}_{0}$$2) and consisting of four pairs of printed U-shaped dipoles positioned above a metal reflector, for 5G Sub-6 GHz base station applications, is designed and tested. The array consists of eight excitation ports, one port for each dipole. Four parasitic square patches are etched on the bottom side of the dipole arms for producing radiations in 2.2 GHz and 3.8 GHz bands. The size of the reflector and height of the dipoles are optimized in order to enhance antenna gain up to 11.5 dB at 2.2 GHz and 14.5 dB at 3.8 GHz. Beam steering up to 20$$\:^\circ\:$$ is achieved, using phase shifted simultaneous excitation of different ports. The proposed antenna array not only fulfills 5G base station requirements but is also simple and compact as it only requires eight ports to achieve dual-band, high-gain and beam steering operation in a single design. It also offers a unique feature of dual-sector coverage per panel, which results in an increased coverage capacity of the base station without increasing the system resources.
Shape optimized acoustic metagratings for anomalous refraction under strong thermoviscous effects
Authors: Melnikov Anton , Köble Sören , Schweiger Severin , Marburg Steffen , Powell David A.
Published: November 2024

The recent development of microacoustic metagratings opens up promising possibilities for manipulating acoustic wavefronts passively, particularly in applications such as flat acoustic lenses and ultra-high frequency ultrasound imaging. The emergence of two-photon polymerization has made it feasible to precisely manufacture microscopic structures, as required when metagratings are scaled to MHz frequencies in airborne ultrasound. Nevertheless, the downsizing process presents another hurdle as the increased thermoviscous effects result in substantial losses that must be considered during the design phase. In this study, we propose two designs for microacoustic metagratings that refract a normally incident wave towards –35 ° at 2 MHz, consisting of single-body and two-body meta-atoms. The designs are created by employing shape optimization techniques that incorporate the linearized Navier–Stokes equations in every iteration starting from a neutral geometry. This ensures that the evolution of geometric key features responsible for anomalous refraction fully accounts for thermoviscous effects, as would be the case during evolution in nature where the full set of physics is always active. Subsequently, we experimentally evaluate the effectiveness of these metagratings by employing a capacitive micromachined ultrasonic transducer as the sound source and an optical microphone as the detector, covering a frequency range from 1.8 to 2.2 MHz. Our findings confirm the single-body geometry reported in the literature and show an alternative geometry for two-body design, showcasing the successful utilization of two-photon polymerization for manufacturing microscopic acoustic metamaterials.