bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractMarine 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

AbstractThe 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

Abstract
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

AbstractREACH2 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

Abstract
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

AbstractOsteosarcoma (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

AbstractEndometriosis, 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

Abstract

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

AbstractLong-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

AbstractAndrogen 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

AbstractNeuronal 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

AbstractClassical 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.