bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic liability to suicidal thoughts and behaviors and risk of suicide attempt in US military veterans: moderating effects of cumulative trauma burden
Authors: Nichter Brandon , Koller Dora , De Angelis Flavio , Wang Jiawei , Girgenti Matthew J. , Na Peter J. , Hill Melanie L. , Norman Sonya B. , Krystal John H. , Gelernter Joel , Polimanti Renato , Pietrzak Robert H. 
Published: November 2022

AbstractBackgroundLittle is known about environmental factors that may influence associations between genetic liability to suicidality and suicidal behavior.MethodsThis study examined whether a suicidality polygenic risk score (PRS) derived from a large genome-wide association study (N = 122,935) was associated with suicide attempts in a population-based sample of European-American US military veterans (N = 1664; 92.5% male), and whether cumulative lifetime trauma exposure moderated this association.ResultsEighty-five veterans (weighted 6.3%) reported a history of suicide attempt. After adjusting for sociodemographic and psychiatric characteristics, suicidality PRS was associated with lifetime suicide attempt (odds ratio 2.65; 95% CI 1.37–5.11). A significant suicidality PRS-by-trauma exposure interaction emerged, such that veterans with higher levels of suicidality PRS and greater trauma burden had the highest probability of lifetime suicide attempt (16.6%), whereas the probability of attempts was substantially lower among those with high suicidality PRS and low trauma exposure (1.4%). The PRS-by-trauma interaction effect was enriched for genes implicated in cellular and developmental processes, and nervous system development, with variants annotated to the DAB2 and SPNS2 genes, which are implicated in inflammatory processes. Drug repurposing analyses revealed upregulation of suicide gene-sets in the context of medrysone, a drug targeting chronic inflammation, and clofibrate, a triacylglyceride level lowering agent.ConclusionResults suggest that genetic liability to suicidality is associated with increased risk of suicide attempt among veterans, particularly in the presence of high levels of cumulative trauma exposure. Additional research is warranted to investigate whether incorporation of genomic information may improve suicide prediction models.
Capacitating militarised masculinity: Genitourinary injuries, sex/sexuality, and US military medicine
Authors: Hobbs Jenn 
Published: November 2022

AbstractThis article examines the soldiering body in relation to the increasing prevalence of genitourinary injuries in military personnel. Feminist scholars have demonstrated that the idealised masculine soldiering body are central to the workings of international politics. The article shows that US militarised masculinity operates through the selective distribution of bodily capacities. The article draws upon critical disability studies, particularly Jasbir Puar's work on capacity and debility, to argue that treatments for genitourinary injuries revolve around the production of seminal capacity. Queer and trans bodies are debilitated in these arrangements through the denial of heterosexual and cisgender capabilities to them. To unpack this argument the article analyses treatments for genitourinary injuries. The article shows that genitourinary injuries destabilise the gender identity of US service members. Through an exploration of surgical treatments, including penis transplants and reconstructive surgeries, and fertility treatments, the article shows how masculine capacitation is achieved for some US service members through the debilitation of others; in particular, queer and trans bodies, and the bodies of Iraqi and Afghan civilians.
Do scientific objects have a life (which may end)?
Authors: Arabatzis Theodore 
Published: November 2022

ArgumentThe aim of this article is to make a case for the pertinence of a biographical approach to the history of scientific objects. I first lay out the rationale of that approach by revisiting and extending my earlier work on the topic. I consider the characteristics of scientific objects that motivate the biographical metaphor, and I indicate its virtues and limitations by bringing out the positive and negative analogies between biographies of scientific objects and ordinary biographies. I then point out various ways in which scientific objects may pass away and argue that their demise should be conceptualized as a process. Finally, I sketch the history of the concept of “ether” in nineteenth and early twentieth century physics and suggest that it lends itself particularly well to a biographical treatment. To that effect, I discuss the identity, heuristic character, and recalcitrance of the ether and examine the reasons that may have led to its passing.
Special issue introduction: Contemporary international anti-feminism
Authors: Sanders Rebecca , Jenkins Laura Dudley 
Published: November 2022

AbstractIn recent years, conservative governments and their civil society allies have undermined international women’s rights treaties and SOGI rights initiatives and challenged domestic rights protections. The articles in this special issue grapple with these trends by analysing the ideologies, discourses, and strategies of contemporary anti-feminism in global and comparative contexts. Several prominent patterns emerge: the core significance of social hierarchy and biological essentialism to anti-feminist conservative thought; the polarizing demonization of feminists by religious conservatives and populist nationalists; the appropriation of rights discourses and advocacy tactics by anti-feminist campaigns; and the strategic importance of law and legal language as a terrain of rights contestation. Taken together, this research suggests that anti-feminism is not incidental to reactionary anti-democratic politics, but instead a constitutive element of political movements that seek to naturalize inequality and legally enforce conformity with conservative social norms.
Chasing Tails: Insights From Micromagnetic Modeling for Thermomagnetic Recording in Non‐Uniform Magnetic Structures
Authors: Nagy Lesleis , Williams Wyn , Tauxe Lisa , Muxworthy Adrian 
Published: November 2022

AbstractPaleointensities are key to understanding the formation and evolution of Earth and are determined from rocks which record magnetic fields upon cooling; however, experimental protocols for estimating paleointensities frequently fail. The primary reason is that laboratory protocols assume that rocks are dominated by uniformly magnetized, single‐domain grains, instead of much more common non‐uniformly magnetized grains. Our model for larger grains shows a multiplicity of stable domain states; with preferred states changing as a function of temperature. We show that domain state distribution depends on the thermal history of the sample—in nature and the laboratory. From numerical thermomagnetic modeling, we show that particles with non‐uniform domain states will theoretically fail standard experimental paleointensity protocols, preventing us from determining reliable ancient geomagnetic field intensities. We propose that recognizing this type of behavior, and the resulting bias, will yield more reliable paleointensity records, and a better understanding of the Earth.
Glacial Isostatic Adjustment Shapes Proglacial Lakes Over Glacial Cycles
Authors: Austermann J. , Wickert A. D. , Pico T. , Kingslake J. , Callaghan K. L. , Creel R. C. 
Published: November 2022

AbstractAs ice sheets load Earth's surface, they produce ice‐marginal depressions which, when filled with meltwater, become proglacial lakes. We include self‐consistently evolving proglacial lakes in a glacial isostatic adjustment (GIA) model and apply it to the Laurentide ice sheet over the last glacial cycle. We find that the locations of modeled lakes and the timing of their disappearance is consistent with the geological record. Lake loads can deflect topography by >10 m, and volumes collectively approach 30–45 cm global mean sea‐level equivalent. GIA increases deglaciation‐phase lake volume up to five‐fold and average along‐ice‐margin depth ≤90 m compared to glaciation‐phase ice volume analogs—differences driven by changes in the position and size of the peripheral bulge. Since ice‐marginal lake depth affects grounding‐line outflow, GIA‐modulated proglacial lake depths could affect ice‐sheet mass loss. Indeed, we find that Laurentide ice‐margin retreat rate sometimes correlates with proglacial lake presence, indicating that proglacial lakes aid glacial collapse.
Unraveling the Synoptic‐Scale Penetration of the Yellow Sea Coastal Water Into the Changjiang River Estuary
Authors: Lian Ergang , Wang Shuo , Artigue Lise , Wu Hui , Ran Xiangbin , Zhou Peng , Lin Lei , Jin Xiaobo , Li Chao , Yang Shouye 
Published: November 2022

AbstractAs one of the most important coastal currents in the Northeast Pacific marginal seas, the Yellow Sea Coastal Water (YSCW) plays an essential role in modulating regional ocean circulation and the transregional exchange of biogeochemical materials. However, the wintertime transport pattern of the YSCW and its interaction with the Changjiang River Estuary (CJE) are intensely debated. Herein, we used a combination method of Principal Component Analysis‐based cluster analysis and Optimum Multiparameter Analysis, together with remote sensing data, to investigate the classification, distributions, pathways and mixture ratios of various water masses off the CJE in winter. Results clearly suggest that in winter the YSCW can repeatedly penetrate to the CJE in response to northerly wind bursts, and flows southward around 10–30 m isobaths off the CJE, with its impact scope reaching as far as at least 29.5°N. Furthermore, we propose a refined circulation pattern that the YSCW flows southward along 20–30 m isobaths on the Changjiang Bank, and thereby feeds the synoptic‐scale YSCW penetration into the CJE. Crucially, this work also highlights that the combination methodologies in a mathematic framework is useful for unraveling an implicit synoptic‐scale water mass interaction in highly dynamic estuaries and shelf seas, and thus provides better insight to ecological and environmental variability.
Drought Impacts on PM2.5 Composition and Amount Over the US During 1988–2018
Authors: Wang Yi , Wang Jun , Wang Yuxuan , Li Wei 
Published: November 2022

AbstractThis study uses PM2.5 species concentrations from Interagency Monitoring of Protected Visual Environments and Standardized Precipitation Evapotranspiration Index (SPEI) during 1988–2018 over the continental US to investigate the association of spatial‐temporal variations of surface PM2.5 species with droughts. Ubiquitous decreasing trends in seasonal mean reconstructed PM2.5 are detected in all seasons except for the summer over the northwestern US. The increasing trend in the reconstructed PM2.5 in summer over northwestern US is primary due to the positive trend in total carbonaceous aerosols (TCAs), which more than offsets the negative trends in sulfate and nitrate aerosols. This also causes the contribution of TCA to the reconstructed PM2.5 to show an increasing trend in summer over the same region. The positive trend in TCA in summer over northwestern US is stronger under the drought than the wet conditions, hence resulting in a stronger positive trend in the contribution of TCA to the reconstructed PM2.5 in the drought conditions. Drought enhances TCA over northwestern US through its impact on wildfire, and the temporal change of TCA mainly follows the non‐linear variation of SPEI. Although droughts are found to have statistically significant impacts on the trends in sulfate, nitrate, and dust in other regions and seasons, the small contributions of these species to the reconstructed PM2.5 make their trend variations not sufficient to affect trends in the reconstructed PM2.5.
Dissecting exosome inhibitors: therapeutic insights into small-molecule chemicals against cancer
Authors: Kim Jong Hyun , Lee Chan-Hyeong , Baek Moon-Chang 
Published: November 2022

AbstractIntensive research in the field of cancer biology has revealed unique methods of communication between cells through extracellular vesicles called exosomes. Exosomes are released from a broad spectrum of cell types and serve as functional mediators under physiological or pathological conditions. Hence, blocking the release of exosome bio carriers may prove useful for slowing the progression of certain types of cancers. Therefore, efforts are being made to develop exosome inhibitors to be used both as research tools and as therapies in clinical trials. Thus, studies on exosomes may lead to a breakthrough in cancer research, for which new clinical targets for different types of cancers are urgently needed. In this review, we briefly outline exosome inhibitors and discuss their modes of action and potential for use as therapeutic tools for cancer.
Neurovascular coupling in bone regeneration
Authors: Qin Qizhi , Lee Seungyong , Patel Nirali , Walden Kalah , Gomez-Salazar Mario , Levi Benjamin , James Aaron W. 
Published: November 2022

AbstractThe mammalian skeletal system is densely innervated by both neural and vascular networks. Peripheral nerves in the skeleton include sensory and sympathetic nerves. The crosstalk between skeletal and neural tissues is critical for skeletal development and regeneration. The cellular processes of osteogenesis and angiogenesis are coupled in both physiological and pathophysiological contexts. The cellular and molecular regulation of osteogenesis and angiogenesis have yet to be fully defined. This review will provide a detailed characterization of the regulatory role of nerves and blood vessels during bone regeneration. Furthermore, given the importance of the spatial relationship between nerves and blood vessels in bone, we discuss neurovascular coupling during physiological and pathological bone formation. A better understanding of the interactions between nerves and blood vessels will inform future novel therapeutic neural and vascular targeting for clinical bone repair and regeneration.
Discriminative binding of tau PET tracers PI2620, MK6240 and RO948 in Alzheimer’s disease, corticobasal degeneration and progressive supranuclear palsy brains
Authors: Malarte Mona-Lisa , Gillberg Per-Göran , Kumar Amit , Bogdanovic Nenad , Lemoine Laëtitia , Nordberg Agneta 
Published: November 2022

AbstractRecent mechanistic and structural studies have challenged the classical tauopathy classification approach and revealed the complexity and heterogeneity of tau pathology in Alzheimer’s disease (AD) and primary tauopathies such as corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP), progressing beyond distinct tau isoforms. In this multi-tau tracer study, we focused on the new second-generation tau PET tracers PI2620, MK6240 and RO948 to investigate this tau complexity in AD, CBD, and PSP brains using post-mortem radioligand binding studies and autoradiography of large and small frozen brain sections. Saturation binding studies indicated multiple binding sites for 3H-PI2620 in AD, CBD and PSP brains with different binding affinities (Kd ranging from 0.2 to 0.7 nM) and binding site densities (following the order: BmaxAD > BmaxCBD > BmaxPSP). Competitive binding studies complemented these findings, demonstrating the presence of two binding sites [super-high affinity (SHA): IC50(1) = 8.1 pM; and high affinity (HA): IC50(2) = 4.9 nM] in AD brains. Regional binding distribution studies showed that 3H-PI2620 could discriminate between AD (n = 6) and control cases (n = 9), especially in frontal cortex and temporal cortex tissue (p < 0.001) as well as in the hippocampal region (p = 0.02). 3H-PI2620, 3H-MK6240 and 3H-RO948 displayed similar binding behaviour in AD brains (in both homogenate competitive studies and one large frozen hemispherical brain section autoradiography studies) in terms of binding affinities, number of sites and regional patterns. Our small section autoradiography studies in the frontal cortex of CBD (n = 3) and PSP brains (n = 2) showed high specificity for 3H-PI2620 but not for 3H-MK6240 or 3H-RO948. Our findings clearly demonstrate different binding properties among the second-generation tau PET tracers, which may assist in further understanding of tau heterogeneity in AD versus non-AD tauopathies and suggests potential for development of pure selective 4R tau PET tracers.
Elevated FSP1 protects KRAS-mutated cells from ferroptosis during tumor initiation
Authors: Müller Fabienne , Lim Jonathan K. M. , Bebber Christina M. , Seidel Eric , Tishina Sofya , Dahlhaus Alina , Stroh Jenny , Beck Julia , Yapici Fatma Isil , Nakayama Keiko , Torres Fernández Lucia , Brägelmann Johannes , Leprivier Gabriel , von Karstedt Silvia 
Published: November 2022

AbstractOncogenic KRAS is the key driver oncogene for several of the most aggressive human cancers. One key feature of oncogenic KRAS expression is an early increase in cellular reactive oxygen species (ROS) which promotes cellular transformation if cells manage to escape cell death, mechanisms of which remain incompletely understood. Here, we identify that expression of oncogenic as compared to WT KRAS in isogenic cellular systems renders cells more resistant to ferroptosis, a recently described type of regulated necrosis. Mechanistically, we find that cells with mutant KRAS show a specific lack of ferroptosis-induced lipid peroxidation. Interestingly, KRAS-mutant cells upregulate expression of ferroptosis suppressor protein 1 (FSP1). Indeed, elevated levels of FSP1 in KRAS-mutant cells are responsible for mediating ferroptosis resistance and FSP1 is upregulated as a consequence of MAPK and NRF2 pathway activation downstream of KRAS. Strikingly, FSP1 activity promotes cellular transformation in soft agar and its overexpression is sufficient to promote spheroid growth in 3D in KRAS WT cells. Moreover, FSP1 expression and its activity in ferroptosis inhibition accelerates tumor onset of KRAS WT cells in the absence of oncogenic KRAS in vivo. Consequently, we find that pharmacological induction of ferroptosis in pancreatic organoids derived from the LsL-KRASG12D expressing mouse model is only effective in combination with FSP1 inhibition. Lastly, FSP1 is upregulated in non-small cell lung cancer (NSCLC), colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC) as compared to the respective normal tissue of origin and correlates with NRF2 expression in PDAC patient datasets. Based on these data, we propose that KRAS-mutant cells must navigate a ferroptosis checkpoint by upregulating FSP1 during tumor establishment. Consequently, ferroptosis-inducing therapy should be combined with FSP1 inhibitors for efficient therapy of KRAS-mutant cancers.
m6A-modified circFNDC3B inhibits colorectal cancer stemness and metastasis via RNF41-dependent ASB6 degradation
Authors: Zeng Wei , Zhu Jin-Feng , Guo Jian , Huang Gen-Jie , Ai Li-Sha , Zeng Yu , Liao Wang-Jun 
Published: November 2022

AbstractColorectal cancer (CRC) is the third most frequently diagnosed cancer with unfavorable clinical outcomes worldwide. circFNDC3B plays as a tumor suppressor in CRC, however, the mechanism of circFNDC3B in CRC remains ambiguous. The stem-like properties of CRC cells were detected by the evaluation of stemness markers, sphere formation assay and flow cytometry. qRT-PCR, FISH, IHC, and western blotting assessed the expression and localization of circFNDC3B, RNF41, ASB6, and stemness markers in CRC. The metastatic capabilities of CRC cells were examined by wound healing and Transwell assays, as well as in vivo liver metastasis model. Bioinformatics analysis, RNA immunoprecipitation (RIP), RNA pull-down assay and co-IP were used to detect the associations among circFNDC3B, FXR2, RNF41, and ASB6. Downregulated circFNDC3B was associated with unfavorite survival in CRC patients, and circFNDC3B overexpression suppressed CRC stemness and metastasis. Mechanistically, studies revealed that YTHDC1 facilitated cytoplasmic translocation of m6A-modified circFNDC3B, and circFNDC3B enhanced RNF41 mRNA stability and expression via binding to FXR2. circFNDC3B promoted ASB6 degradation through RNF41-mediated ubiquitination. Functional studies showed that silencing of RNF41 counteracted circFNDC3B-suppressed CRC stemness and metastasis, and ASB6 overexpression reversed circFNDC3B- or RNF41-mediated regulation of CRC stemness and metastasis. Elevated ASB6 was positively correlated with unfavorite survival in CRC patients. In vivo experiments further showed that circFNDC3B or RNF41 overexpression repressed tumor growth, stemness and liver metastasis via modulating ASB6. Taken together, m6A-modified circFNDC3B inhibited CRC stemness and metastasis via RNF41-dependent ASB6 degradation. These findings provide novel insights and important clues for targeted therapeutic strategies of CRC.
Identification of common and distinct origins of human serum and breastmilk IgA1 by mass spectrometry-based clonal profiling
Authors: Dingess Kelly A. , Hoek Max , van Rijswijk Danique M. H. , Tamara Sem , den Boer Maurits A. , Veth Tim , Damen Mirjam J. A. , Barendregt Arjan , Romijn Michelle , Juncker Hannah G. , van Keulen Britt J. , Vidarsson Gestur , van Goudoever Johannes B. , Bondt Albert , Heck Albert J. R. 
Published: November 2022

AbstractThe most abundant immunoglobulin present in the human body is IgA. It has the highest concentrations at the mucosal lining and in biofluids such as milk and is the second most abundant class of antibodies in serum. We assessed the structural diversity and clonal repertoire of IgA1-containing molecular assemblies longitudinally in human serum and milk from three donors using a mass spectrometry-based approach. IgA-containing molecules purified from serum or milk were assessed by the release and subsequent analysis of their Fab fragments. Our data revealed that serum IgA1 consists of two distinct structural populations, namely monomeric IgA1 (∼80%) and dimeric joining (J-) chain coupled IgA1 (∼20%). Also, we confirmed that IgA1 in milk is present solely as secretory (S)IgA, consisting of two (∼50%), three (∼33%) or four (∼17%) IgA1 molecules assembled with a J-chain and secretory component (SC). Interestingly, the serum and milk IgA1-Fab repertoires were distinct between monomeric, and J-chain coupled dimeric IgA1. The serum dimeric J-chain coupled IgA1 repertoire contained several abundant clones also observed in the milk IgA1 repertoire. The latter repertoire had little to no overlap with the serum monomeric IgA1 repertoire. This suggests that human IgA1s have (at least) two distinct origins; one of these produces dimeric J-chain coupled IgA1 molecules, shared in human serum and milk, and another produces monomeric IgA1 ending up exclusively in serum.