bluuebunny/crossref_metadata_2025_split huggingface dataset:
All‐trans retinoic acid exhibits anti‐proliferative and differentiating activity in Merkel cell carcinoma cells via retinoid pathway modulation
Authors: Mazziotta Chiara , Badiale Giada , Cervellera Christian Felice , Morciano Giampaolo , Di Mauro Giulia , Touzé Antoine , Pinton Paolo , Tognon Mauro , Martini Fernanda , Rotondo John Charles 
Published: March 2024

AbstractBackgroundThe limited therapies available for treating Merkel cell carcinoma (MCC), a highly aggressive skin neoplasm, still pose clinical challenges, and novel treatments are required. Targeting retinoid signalling with retinoids, such as all‐trans retinoic acid (ATRA), is a promising and clinically useful antitumor approach. ATRA drives tumour cell differentiation by modulating retinoid signalling, leading to anti‐proliferative and pro‐apoptotic effects. Although retinoid signalling is dysregulated in MCC, ATRA activity in this tumour is unknown. This study aimed to evaluate the impact of ATRA on the pathological phenotype of MCC cells.MethodsThe effect of ATRA was tested in various Merkel cell polyomavirus‐positive and polyomavirus‐negative MCC cell lines in terms of cell proliferation, viability, migration and clonogenic abilities. In addition, cell cycle, apoptosis/cell death and the retinoid gene signature were evaluated upon ATRA treatments.ResultsATRA efficiently impaired MCC cell proliferation and viability in MCC cells. A strong effect in reducing cell migration and clonogenicity was determined in ATRA‐treated cells. Moreover, ATRA resulted as strongly effective in arresting cell cycle and inducing apoptosis/cell death in all tested MCC cells. Enrichment analyses indicated that ATRA was effective in modulating the retinoid gene signature in MCC cells to promote cell differentiation pathways, which led to anti‐proliferative and pro‐apoptotic/cell death effects.ConclusionsThese results underline the potential of retinoid‐based therapy for MCC management and might open the way to novel experimental approaches with other retinoids and/or combinatorial treatments.
Does Alternative Data Improve Financial Forecasting? The Horizon Effect
Authors: DESSAINT OLIVIER , FOUCAULT THIERRY , FRESARD LAURENT 
Published: March 2024

ABSTRACTExisting research suggests that alternative data are mainly informative about short‐term future outcomes. We show theoretically that the availability of short‐term‐oriented data can induce forecasters to optimally shift their attention from the long term to the short term because it reduces the cost of obtaining short‐term information. Consequently, the informativeness of their long‐term forecasts decreases, even though the informativeness of their short‐term forecasts increases. We test and confirm this prediction by considering how the informativeness of equity analysts' forecasts at various horizons varies over the long run and with their exposure to social media data.
Gender, age and nationality differences in chronic kidney disease prevalence in the emirate of Abu Dhabi, UAE
Authors: Almadani Ayman Kamal , Ahmed Wasim , Al Obaidli Ali Abdul Kareem , Holt Stephen G. 
Published: March 2024

AbstractAimWe aimed to better understand the prevalence of chronic kidney disease in Abu Dhabi, UAE, where a very diverse ethnic population lives, each with their own risk profile.MethodsData were analysed on all patients who were tested for serum creatinine in December 2019 for 4 years within our healthcare network. We analysed data for kidney disease by age, gender and nationality to study differences in prevalence and risk.ResultsThe entire cohort (EC) consisted 1 925 672 samples from 703 122 patients. 24% of patients had GFR < 90 mL/min/1.73 m2 (CKD2‐5), 4% had more severe kidney dysfunction (CKD3‐5) and 2% had UACR >3 mg/mmol and with GFR > 90 (CKD1).The long follow‐up (LFU) group comprised 45.6% of patients who had eGFR on at least two occasions more than 90 days apart, and of these 19.5% had sustained eGFR <90, and 5.2% had CKD3‐5.Males had lower eGFR than females in the EC (RR 1.68) and the LFU group (RR 1.76). Emirati Females had the lowest prevalence in the EC (2.9%) and expatriate females in the LFU (3.5%) groups. The relative risks of CKD in expatriate males were highest in the EC (2.14) and the LFU (2.39) groups.When we looked at the age distribution by nationality there were highly significant differences in some populations being highly represented at younger ages.ConclusionThe prevalence of kidney disease in Abu Dhabi has a male predominance, with younger expatriates highly represented. A targeted strategy to identify those at high risk may identify early CKD to prevent progression to end‐stage kidney disease.image
Genome‐wide DNA methylation dynamics following recent polyploidy in the allotetraploid Tragopogon miscellus (Asteraceae)
Authors: Shan Shengchen , Gitzendanner Matthew A. , Boatwright J. Lucas , Spoelhof Jonathan P. , Ethridge Christina L. , Ji Lexiang , Liu Xiaoxian , Soltis Pamela S. , Schmitz Robert J. , Soltis Douglas E. 
Published: March 2024

Summary

Polyploidy is an important evolutionary force, yet epigenetic mechanisms, such as DNA methylation, that regulate genome‐wide expression of duplicated genes remain largely unknown. Here, we use Tragopogon (Asteraceae) as a model system to discover patterns and temporal dynamics of DNA methylation in recently formed polyploids.

The naturally occurring allotetraploid Tragopogon miscellus formed in the last 95–100 yr from parental diploids Tragopogon dubius and T. pratensis. We profiled the DNA methylomes of these three species using whole‐genome bisulfite sequencing.

Genome‐wide methylation levels in T. miscellus were intermediate between its diploid parents. However, nonadditive CG and CHG methylation occurred in transposable elements (TEs), with variation among TE types. Most differentially methylated regions (DMRs) showed parental legacy, but some novel DMRs were detected in the polyploid. Differentially methylated genes (DMGs) were also identified and characterized.

This study provides the first assessment of both overall and locus‐specific patterns of DNA methylation in a recent natural allopolyploid and shows that novel methylation variants can be generated rapidly after polyploid formation. Together, these results demonstrate that mechanisms to regulate duplicate gene expression may arise soon after allopolyploid formation and that these mechanisms vary among genes.
David versus Goliath? Indigenous people, carbon majors and climate litigation in South Africa
Authors: du Toit Louise , Soyapi Caiphas , Kotzé Louis J. 
Published: March 2024

AbstractIn two recent South African cases, Indigenous communities successfully challenged proposed fossil fuel exploration activities by the Shell petroleum company off South Africa's pristine West Coast. In contrast to earlier climate litigation cases in South Africa, the litigants relied specifically on their Indigenous rights and knowledge. In this case note, we highlight the ways in which the two courts engaged with the communities' cultural beliefs and practices as well as their knowledge related to sustainability and how this relates to protecting their livelihoods, cultural practices and identities that are threatened by the proposed activities. We highlight the important role played by Indigenous communities in the climate movement and argue that, in the future, Indigenous and related considerations could provide a strong basis for climate litigation in South Africa and potentially contribute to efforts to protect Indigenous communities against the activities of carbon majors.
The formation mechanism of the Xilekuduke porphyry Mo‐Cu deposit, NW China, revealed by the fluid inclusions and H‐O‐S isotopes
Authors: Ma Jing , You Jun , Hong Tao , Gao Jun , Wu Chu , Xu Xing‐Wang , Wu Qi 
Published: March 2024

AbstractThe Xilekuduke porphyry Mo‐Cu deposit is located in the Altay‐East Junggar region of the Central Asian Orogenic Belt, northwest China. The orebodies occurring as vein type are host within the monzogranite and granite porphyry. Ore minerals include mainly molybdenite, pyrite, and chalcopyrite, whilst the major alteration include potassic, sericite, carbonate, and silicic. Mineralization can be divided into three stages: quartz‐K‐feldspar–polymetallic stage (Stage I), quartz‐polymetallic stage (Stage II), and quartz–calcite–pyrite (minor) stage (Stage III). Three types of fluid inclusion are present in the Mo‐Cu sulfide–calcite–quartz veins: CO2‐bearing (C‐type), aqueous (W‐type), and daughter mineral‐bearing (S‐type). Petrographic and microthermometric analyses of the fluid inclusions yielded homogenization temperatures for Stage I, II, and III to be 402–499°C, 214–391°C, and 136–254°C, respectively, with corresponding salinities of 39.2–59.6, 3.7–44.9 and 4.1–14.4 wt% NaCl equivalent. The δ18OH₂O and δD values of fluid inclusions in quartz are determined to be 5.3–6.0 ‰ and −76 to −60 ‰ (Stage I), 1.7–3.2 ‰ and −96 to −90 ‰ (Stage II), and −2.6 to −2.4 ‰ and −106 ‰ (Stage III), respectively. These results indicate that the primary ore‐forming fluids (stages I and II) were derived from granitic magma and were mixed with meteoric water in stage III. For the sulfide and sulfate (anhydrite), their δ34S values are of 0.4–5.8 ‰, 13.9–14.4 ‰, respectively, also that suggest a magmatic source. Fluid immiscibility, meteoric water interaction, and ore fluid‐wallrock interactions may have been critical for molybdenum precipitation.
Size Effect of Yielding of Particle-Reinforced Composites
Authors: Zhang R. J. , Liu Yan 
Published: March 2024

Abstract
This paper illustrates how particle size affects the initial yield stress of particle-reinforced composites. A formulation in a closed form is presented to demonstrate the size effect of yielding of the composites. This paper also demonstrates that there is an upper bound and a lower bound for the size-dependent yield stress with the change of particle size. This means that decreasing particle size increases its yield stress up to an upper bound. Similarly, increasing particle size decrease its yield stress up to a lower bound. In this paper the asymptotic homogenization method is used in framework of the Cosserat elasticity. A virtual “unreinforced matrix” is introduced as a reference configuration. As a numerical example, the size effect of yielding of SiCp/Al is predicted.
Automatically Discovering Mechanical Functions From Physical Behaviors via Clustering
Authors: Chiu Kevin N. , Fuge Mark D. 
Published: March 2024

AbstractComputational design methods provide opportunities to discover novel and diverse designs that traditional optimization approaches cannot find or that use physical phenomena in ways that engineers have overlooked. However, existing methods require supervised objectives to search or optimize for explicit behaviors or functions—e.g., optimizing aerodynamic lift. In contrast, this article unpacks what it means to discover interesting behaviors or functions we do not know about a priori using data from experiments or simulation in a fully unsupervised way. Doing so enables computers to invent or re-invent new or existing mechanical functions given only measurements of physical fields (e.g., fluid velocity fields) without directly specifying a set of objectives to optimize. This article explores this approach via two related parts. First, we study clustering algorithms that can detect novel device families from simulation data. Specifically, we contribute a modification to the hierarchical density-based spatial clustering of applications with noise algorithm via the use of the silhouette score to reduce excessively granular clusters. Second, we study multiple ways by which we preprocess simulation data to increase its discriminatory power in the context of clustering device behavior. This leads to an insight regarding the important role that a design’s representation has in compactly encoding its behavior. We test our contributions via the task of discovering simple fluidic devices and show that our proposed clustering algorithm outperforms other density-based algorithms, but that K-means clustering outperforms density-based algorithms, as measured by adjusted Rand score. However, the device types may have an even stronger impact on the clustering. This opens up new avenues of research wherein computers can automatically derive new device functions, behaviors, and structures without the need for human labels or guidance.
The human adenovirus PI3K-Akt activator E4orf1 is targeted by the tumor suppressor p53
Authors: Göttig Lilian , Jummer Simone , Staehler Luisa , Groitl Peter , Karimi Maryam , Blanchette Paola , Kosulin Karin , Branton Philip E. , Schreiner Sabrina 
Published: March 2024

ABSTRACT

Human adenoviruses (HAdV) are classified as DNA tumor viruses due to their potential to mediate oncogenic transformation in non-permissive mammalian cells and certain human stem cells. To achieve transformation, the viral early proteins of the E1 and E4 regions must block apoptosis and activate proliferation: the former predominantly through modulating the cellular tumor suppressor p53 and the latter by activating cellular pro-survival and pro-metabolism protein cascades, such as the phosphoinositide 3-kinase (PI3K-Akt) pathway, which is activated by HAdV E4orf1. Focusing on HAdV-C5, we show that E4orf1 is necessary and sufficient to stimulate Akt activation through phosphorylation in H1299 cells, which is not only hindered but repressed during HAdV-C5 infection with a loss of E4orf1 function in p53-positive A549 cells. Contrary to other research, E4orf1 localized not only in the common, cytoplasmic PI3K-Akt-containing compartment, but also in distinct nuclear aggregates. We identified a novel inhibitory mechanism, where p53 selectively targeted E4orf1 to destabilize it, also stalling E4orf1-dependent Akt phosphorylation. Co-IP and immunofluorescence studies showed that p53 and E4orf1 interact, and since p53 is bound by the HAdV-C5 E3 ubiquitin ligase complex, we also identified E4orf1 as a novel factor interacting with E1B-55K and E4orf6 during infection; overexpression of E4orf1 led to less-efficient E3 ubiquitin ligase-mediated proteasomal degradation of p53. We hypothesize that p53 specifically subverts the pro-survival function of E4orf1-mediated PI3K-Akt activation to protect the cell from metabolic hyper-activation or even transformation.

IMPORTANCE
Human adenoviruses (HAdV) are nearly ubiquitous pathogens comprising numerous subtypes that infect various tissues and organs. Among many encoded proteins that facilitate viral replication and subversion of host cellular processes, the viral E4orf1 protein has emerged as an intriguing yet under-investigated player in the complex interplay between the virus and its host. Nonetheless, E4orf1 has gained attention as a metabolism activator and oncogenic agent, while recent research is showing that E4orf1 may play a more important role in modulating the cellular pathways such as phosphoinositide 3-kinase-Akt-mTOR. Our study reveals a novel and general impact of E4orf1 on host mechanisms, providing a novel basis for innovative antiviral strategies in future therapeutic settings. Ongoing investigations of the cellular pathways modulated by HAdV are of great interest, particularly since adenovirus-based vectors actually serve as vaccine or gene vectors. HAdV constitute an ideal model system to analyze the underlying molecular principles of virus-induced tumorigenesis.
Human trophoblast stem cells restrict human cytomegalovirus replication
Authors: Rollman Tyler B. , Berkebile Zachary W. , Okae Hiroaki , Bardwell Vivian J. , Gearhart Micah D. , Bierle Craig J. 
Published: March 2024

ABSTRACT

Placental infection plays a central role in the pathogenesis of congenital human cytomegalovirus (HCMV) infections and is a cause of fetal growth restriction and pregnancy loss. HCMV can replicate in some trophoblast cell types, but it remains unclear how the virus evades antiviral immunity in the placenta and how infection compromises placental development and function. Human trophoblast stem cells (TSCs) can be differentiated into extravillous trophoblasts (EVTs), syncytiotrophoblasts (STBs), and organoids, and this study assessed the utility of TSCs as a model of HCMV infection in the first-trimester placenta. HCMV was found to non-productively infect TSCs, EVTs, and STBs. Immunofluorescence assays and flow cytometry experiments further revealed that infected TSCs frequently only express immediate early viral gene products. Similarly, RNA sequencing found that viral gene expression in TSCs does not follow the kinetic patterns observed during lytic infection in fibroblasts. Canonical antiviral responses were largely not observed in HCMV-infected TSCs and TSC-derived trophoblasts. Rather, infection dysregulated factors involved in cell identity, differentiation, and Wingless/Integrated signaling. Thus, while HCMV does not replicate in TSCs, infection may perturb trophoblast differentiation in ways that could interfere with placental function.

IMPORTANCE
Placental infection plays a central role in human cytomegalovirus (HCMV) pathogenesis during pregnancy, but the species specificity of HCMV and the limited availability and lifespan of primary trophoblasts have been persistent barriers to understanding how infection impacts this vital organ. Human trophoblast stem cells (TSCs) represent a new approach to modeling viral infection early in placental development. This study reveals that TSCs, like other stem cell types, restrict HCMV replication. However, infection perturbs the expression of genes involved in differentiation and cell fate determination, pointing to a mechanism by which HCMV could cause placental injury.
Complete genome sequences of seven
Microbacterium foliorum
phages Albedo, Kenzers, Swervy, Cranjis, JaimeB, Fullmetal, and Stormbreaker
Authors: Valentin Caban Keyshla , Kalesnik Elizabeth , Green Kaitlyn A. , Negro Christopher J. , Nunez Rodriguez Ulises , Peele Milan C. , Nguyen Casandra T. , Cahill Sydney , Dougherty Keara , Logue Melissa , Hargraves Star , Radziak Hannah , Willette Luke , Ogunyinka Esther , Campbell Davia C. , Adebamiro Oluwatomiwa , Schmeltzer Cecelia , Onimus Jonathan , Asaka Hannah A. , Bangura Wilfred , Shimp Christina M. , Alade Ameera , Sequira Daekwon M. , Jimenez Tommy ,   Neumann University Phage Discovery Group, Swerdlow Sarah J. , Harrison Melinda K. , Fallest-Strobl Patricia C. , Mastropaolo Matthew D. 
Published: March 2024

ABSTRACT

Seven bacteriophages were isolated from soil in Pennsylvania and Wisconsin using the host
Microbacterium foliorum
. These bacteriophages range in the number of predicted genes encoded, from 25 to 91, and are distributed across actinobacteriophage clusters EB, EC, EE, and EK.
Synglacial carbonate records of snowball Earth ocean composition—Evidence from the Nantuo Formation, South China
Authors: Zhu Guangyou , Zhao Kun , Ding Weiming , Wang Ruimin , Ma Haoran , Lang Xianguo , Li Tingting , Li Chao , Shen Bing 
Published: March 2024

Abstract
The Cryogenian (ca. 717–635 Ma) snowball Earth glaciations ended with the precipitation of “cap” carbonate successions with negative carbon isotope (δ13Ccarb) values, which have been explained by the addition of various 13C-depleted carbon sources in the deglacial process. These arguments assumed that marine dissolved inorganic carbon (DIC) was enriched in 13C in the synglacial ocean. However, this assumption has not yet been tested, because the synglacial ocean chemistry is unknown. In this study, we carried out detailed analyses of the petrology, carbonate carbon (δ13Ccarb) and oxygen (δ18Ocarb) isotopes, organic carbon (δ13Corg) isotopes, major and minor elemental compositions (Ca, Mg, Mn, Fe, Sr), and iron speciation (total Fe, highly reactive Fe, pyrite Fe) of the carbonate layers (also called synglacial carbonate layers) from the Nantuo Formation (ca. 650–635 Ma) on the Yangtze block, South China. Petrographic observations indicated that the synglacial carbonate comprises dolomicrite, mud-crystal powder dolomite, lime dolomite, and dolomitic limestone, supporting an authigenic carbonate origin, and thus, it potentially recorded the ocean chemistry during the Marinoan ice age. The synglacial carbonate is characterized by extreme Mn enrichment, low Fe/Mn ratios, and low δ13Ccarb (−7‰) values. High Mn contents and low Fe/Mn ratios imply marine redox conditions favoring Mn2+ accumulation and Fe2+ oxidation, while low δ13Ccarb values might be attributed to CO2 degassing of submarine volcanoes as well as low primary burial during the glaciation. Since the δ13CDIC value of the synglacial ocean was lower than the δ13Ccarb values of most cap carbonates, we infer the addition of 13C-enriched DIC or removal of 12C during cap carbonate precipitation, such as through carbonate weathering or organic carbon burial. These findings provide new insights into the nature of Cryogenian glaciation, the origin of cap carbonates, and the aftermath of global glaciation.
Comparison of prior authorization across insurers: cross sectional evidence from Medicare Advantage
Authors: Gupta Ravi , Fein Jay , Newhouse Joseph P , Schwartz Aaron L 
Published: March 2024

Abstract

Objective
To measure and compare the scope of US insurers’ policies for prior authorization (PA), a process by which insurers assess the necessity of planned medical care, and to quantify differences in PA across insurers, physician specialties, and clinical service categories.

Design
Cross sectional analysis.

Setting
PA policies for five insurers serving most of the beneficiaries covered by privately administered Medicare Advantage in the US, 2021, as applied to utilization patterns observed in Medicare Part B.

Participants
30 540 086 beneficiaries in traditional Medicare Part B.

Main outcome measures
Proportions of government administered traditional Medicare Part B spending and utilization that would have required PA according to Medicare Advantage insurer rules.

Results
The insurers required PA for 944 to 2971 of the 14 130 clinical services (median 1899; weighted mean 1429) constituting 17% to 33% of Part B spending (median 28%; weighted mean 23%) and 9% to 41% of Part B utilization (median 22%; weighted mean 18%). 40% of spending ($57bn; £45bn; €53bn) and 48% of service utilization would have required PA by at least one insurer; 12% of spending and 6% of utilization would have required PA by all insurers. 93% of Part B medication spending, or 74% of medication use, would have required PA by at least one Medicare Advantage insurer. For all Medicare Advantage insurers, hematology and oncology drugs represented the largest proportion of PA spending (range 27-34%; median 33%; weighted mean 30%). PA rates varied widely across specialties.

Conclusion
PA policies varied substantially across private insurers in the US. Despite limited consensus, all insurers required PA extensively, particularly for physician administered medications. These findings indicate substantial differences in coverage policies between government administered and privately administered Medicare. The results may inform ongoing efforts to focus PA more effectively on low value services and reduce administrative burdens for clinicians and patients.