bluuebunny/crossref_metadata_2025 huggingface dataset:
A New Class of Simple, General and Efficient Finite Volume Schemes for Overdetermined Thermodynamically Compatible Hyperbolic Systems
Authors: Busto Saray , Dumbser Michael
Published: December 2023

In this paper, a new efficient, and at the same time, very simple and general class of thermodynamically compatible finite volume schemes is introduced for the discretization of nonlinear, overdetermined, and thermodynamically compatible first-order hyperbolic systems. By construction, the proposed semi-discrete method satisfies an entropy inequality and is nonlinearly stable in the energy norm. A very peculiar feature of our approach is that entropy is discretized directly, while total energy conservation is achieved as a mere consequence of the thermodynamically compatible discretization. The new schemes can be applied to a very general class of nonlinear systems of hyperbolic PDEs, including both, conservative and non-conservative products, as well as potentially stiff algebraic relaxation source terms, provided that the underlying system is overdetermined and therefore satisfies an additional extra conservation law, such as the conservation of total energy density. The proposed family of finite volume schemes is based on the seminal work of Abgrall [1], where for the first time a completely general methodology for the design of thermodynamically compatible numerical methods for overdetermined hyperbolic PDE was presented. We apply our new approach to three particular thermodynamically compatible systems: the equations of ideal magnetohydrodynamics (MHD) with thermodynamically compatible generalized Lagrangian multiplier (GLM) divergence cleaning, the unified first-order hyperbolic model of continuum mechanics proposed by Godunov, Peshkov, and Romenski (GPR model) and the first-order hyperbolic model for turbulent shallow water flows of Gavrilyuk et al. In addition to formal mathematical proofs of the properties of our new finite volume schemes, we also present a large set of numerical results in order to show their potential, efficiency, and practical applicability.
Proposing mobility visas as an alternative to employer sponsorship: Addressing inequalities in the treatment of temporary migrant workers
Authors: Clibborn Stephen , Wright Chris F.
Published: December 2023

Many countries use employer-sponsored visas to regulate migrant worker recruitment. By tying each sponsored migrant to a single employer, employer-sponsored visas have contributed to problems of workers being underpaid and mistreated. Through a critical assessment of temporary visas in Australia, particularly the Temporary Skill Shortage visa, and an analysis of relevant Australian and international literature, we argue that employer-sponsored visas are fundamentally flawed in their design and should be replaced. We consider various alternative options to employer sponsorship for regulating migrant worker recruitment before proposing the creation of a ‘mobility visa’, which would allow migrant workers to move freely between employers. We argue a mobility visa is a superior model for protecting worker equity and voice while also helping to address labour market needs.
Comparative genomics reveals evolutionary drivers of the dietary shift in Hemiptera
Authors: Wu Guangyao , Wu Chunyan , Dewer Youssef , Li Peiyao , Hao Baojun , Zang Liansheng , Li Fengqi
Published: December 2023

Hemiptera insects exhibit a close relationship to plants and demonstrate a diverse range of dietary preferences, encompassing phytophagy as the predominant feeding habit while a minority engages in carnivorous or haematophagous behaviour. To counteract the challenges posed by phytophagous insects, plants have developed an array of toxic compounds, causing significant evolutionary selection pressure on these insects. In this study, we employed a comparative genomics approach to analyse the expansion and contraction of gene families specific to phytophagous insect lineages, along with their adaptive evolutionary traits, utilising representative species from the Hemiptera order. Our investigation revealed substantial expansions of gene families within the phytophagous lineages, especially in the Pentatomomorpha branch represented by Oncopeltus fasciatus and Riptortus pedestris. Notably, these expansions of gene families encoding enzymes are potentially involved in hemipteran-plant interactions. Moreover, the adaptive evolutionary analysis of these lineages revealed a higher prevalence of adaptively evolved genes in the Pentatomomorpha branch. The observed branch-specific gene expansions and adaptive evolution likely contribute significantly to the diversification of species within Hemiptera. These results help enhance our understanding of the genomic characteristics of the evolution of different feeding habits in hemipteran insects.
Going It Alone or Acting as a Collective? Evaluating the East African Community Policy on Implementing TRIPS Obligations
Authors: Olatunji Olugbenga Ajani
Published: December 2023

The grim realities of the COVID-19 pandemic have resuscitated discussions about the effectiveness of the flexibilities entrenched in the World Trade Organization Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) for improving access to medicines. This article revisits this vexed issue by examining whether a regional approach to implementing TRIPS obligations could deliver a better outcome for access, especially in low- and middle-income countries, where manufacturing capacity is almost non-existent. Using the East African Community (EAC) as a case study, the article critiques recommended implementation options under the EAC policy on TRIPS flexibilities, concluding that, if significantly implemented, these recommendations could yield a better outcome for access.
BRATTELI–VERSHIKISABILITY OF POLYGONAL BILLIARDS ON THE HYPERBOLIC PLANE
Authors: NAGAR ANIMA , SINGH PRADEEP
Published: December 2023

Bratteli–Vershik models of compact, invertible zero-dimensional systems have been well studied. We take up such a study for polygonal billiards on the hyperbolic plane, thus considering these models beyond zero-dimensions. We describe the associated Bratteli models and show that these billiard dynamics can be described by Vershik maps.
From Talking Machines to Music Machines: The Early Years of Recorded Sound and Playback in Pictures and Audio
Authors: Stephens Carlene E.
Published: December 2023

Between Thomas Edison’s invention of the phonograph in 1877 and World War I, inventors, entrepreneurs, performers, and listeners transformed the singular talking machines of the late 1870s to the ubiquitous music machines of the twentieth century. Through selected images, objects, and links to period sounds, this essay offers a chronological glimpse of interacting social, technical, and entrepreneurial forces at work. Combining visual, aural, and material sources in this way enlarges the historian’s toolbox for understanding the late nineteenth and early twentieth centuries.
Between militant democracy and citizen vigilantism: Using citizens’ assemblies to keep parties democratic
Authors: Olsen Tore Vincents , Tuovinen Juha
Published: December 2023

The essential role of parties in democracies makes it important to keep them democratic. This article argues for sortition-based citizens’ assemblies (CAs) organized in and by civil society to formulate democratic standards for political parties to follow, to evaluate them individually and to criticize them publicly if they do not. This is a third and potentially complementary way to keeping parties democratic, placed between militant democracy on the one hand and citizen vigilantism on the other. Militant democracy is challenged by the fact that few democratically problematic parties are ostensibly anti-democratic and therefore likely to fall under the legal criteria for issuing party bans and other legal sanctions. Militant democratic measures are also likely to be ineffective and are vulnerable to abuse. Citizen vigilantism, whereby active democratic citizens take on the responsibility for protecting democracy, deals better with the ambiguous nature of democratically problematic parties but suffers from a lack of democratic authorization and clear standards of critique. While not perfect, the proposed model remedies many of the shortcomings of both approaches. Contributing to an emerging literature on CAs as instruments in the protection of democracy, the article evaluates the model’s normative justifiability, feasibility and likely effectiveness.
Mesospheric Water Vapor From SABER as a Tracer for the Residual Mean Circulation During SSW Events
Authors: Zhang Jiarong , Oberheide Jens , Pedatella Nicholas M. , Koushik Neelakantan
Published: December 2023

The sparse wind observations and reanalysis winds in the mesosphere make it challenging to accurately determine the residual mean meridional circulation (MMC). As winds distribute tracers, an alternative approach is to utilize long‐lived trace species such as water vapor (H2O). The recently released H2O data from Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) version 2.07, combined with simulations by the Whole Atmosphere Community Climate Model eXtension with specified dynamics (SD‐WACCM‐X) and with the Data Assimilation Research Testbed (WACCMX + DART), provide an opportunity to assess the accuracy of using H2O isopleths to derive the vertical component of the residual MMC during the 2009 sudden stratospheric warming (SSW) event. In winter, the impact of photochemistry and diffusion on the distribution of mesospheric H2O is negligible compared to advective processes. H2O poleward of 70°N accurately captures the anomalous ascent that occurs a few days prior to the onset of the SSW and the subsequent descent. The derived vertical velocity in SD‐WACCM‐X and WACCMX + DART is qualitatively consistent with SABER observations. However, the derivation of vertical motion from isopleth analysis has limitations at the beginning of 2009 when the meridional transport is stronger than the vertical transport. While measuring winds in the mesosphere is challenging, satellite observations of mesospheric H2O prove to be an effective dynamical tracer during time periods characterized by strong vertical coupling.
Links Between Stream Water Nitrogen and Terrestrial Vegetation in Northeast Greenland
Authors: Riis Tenna , Tank Jennifer L. , Holmboe Cecilie M. H. , Giménez‐Grau Pau , Mastepanov Mikhail , Catalán Núria , Stott David , Hansen Birgitte , Kristiansen Søren M. , Pastor Ada
Published: December 2023

The Arctic is warming and significant changes to the landscape, including increased vegetative cover (“greening”), are expected in the near future. These landscape changes may alter nitrogen (N) availability in terrestrial, stream, and coastal ecosystems, where production is often N limited, but the exact changes in nutrient cycling are uncertain. Here, we analyzed the relationship between vegetation greenness (i.e., NDVI) and dissolved inorganic (DIN) and organic (DON) concentrations in streams draining 14 headwater catchments (mean 3.6 km2, range 0.4–11 km2) across three samplings in the Zackenberg area, Northeast Greenland. We found large variation in DIN and DON concentrations across the sampled streams. We further show that this variation is correlated to water temperature and catchment NDVI, such that increased vegetation greenness and temperature correlated with lower DIN, and increased greenness also correlated with higher DON concentrations in streams. The results suggest that increased terrestrial vegetation due to rising air temperature could substantially alter dissolved N concentrations and form in streams, with potentially cascading impacts on coastal areas.
Microphysiological systems for solid tumor immunotherapy: opportunities and challenges
Authors: Abizanda-Campo Sara , Virumbrales-Muñoz María , Humayun Mouhita , Marmol Ines , Beebe David J. , Ochoa Ignacio , Oliván Sara , Ayuso Jose M.
Published: December 2023

Immunotherapy remains more effective for hematologic tumors than for solid tumors. One of the main challenges to immunotherapy of solid tumors is the immunosuppressive microenvironment these tumors generate, which limits the cytotoxic capabilities of immune effector cells (e.g., cytotoxic T and natural killer cells). This microenvironment is characterized by hypoxia, nutrient starvation, accumulated waste products, and acidic pH. Tumor-hijacked cells, such as fibroblasts, macrophages, and T regulatory cells, also contribute to this inhospitable microenvironment for immune cells by secreting immunosuppressive cytokines that suppress the antitumor immune response and lead to immune evasion. Thus, there is a strong interest in developing new drugs and cell formulations that modulate the tumor microenvironment and reduce tumor cell immune evasion. Microphysiological systems (MPSs) are versatile tools that may accelerate the development and evaluation of these therapies, although specific examples showcasing the potential of MPSs remain rare. Advances in microtechnologies have led to the development of sophisticated microfluidic devices used to recapitulate tumor complexity. The resulting models, also known as microphysiological systems (MPSs), are versatile tools with which to decipher the molecular mechanisms driving immune cell antitumor cytotoxicity, immune cell exhaustion, and immune cell exclusion and to evaluate new targeted immunotherapies. Here, we review existing microphysiological platforms to study immuno-oncological applications and discuss challenges and opportunities in the field.
Increased volume of the left hippocampal dentate gyrus after 4 weeks of bright light exposure in patients with mood disorders: a randomized controlled study
Authors: Hirakawa Hirofumi , Terao Takeshi , Hatano Koji , Shirahama Masanao , Kugimiya Tsuyoshi , Kohno Kentaro , Matsuta Hiroyuki , Shimomura Tsuyoshi , Fujiki Minoru
Published: December 2023

Bright light exposure (BL) induces neurogenesis in the rat hippocampal dentate gyrus (DG). We had previously conducted a randomized controlled trial (RCT) in which a 4-week period of BL in healthy participants resulted in increased volume of the left DG-head. This study aimed to investigate the effects of BL on the DG in patients with mood disorders. A 4-week RCT was conducted in which patients with mood disorders were randomly assigned to either a BL group (10,000 lx) or dim light exposure group (DL group; 50 lx). All patients underwent clinical assessment and magnetic resonance imaging at baseline and after the intervention. The study registration number is UMIN000019220. Our final sample included 24 patients (BL group, n = 12; DL group, n = 12). A significant effect of time and group was detected in the volumes of the left DG-head (F (1, 22) = 11.6, partial η2 = 0.35, p = 0.003) and left DG-total (left DG-total = left DG-head + left DG-body; [F (1, 22) = 6.5, partial η2 = 0.23, p = 0.02]). Additionally, the BL group demonstrated a significant increase in the volume of the left DG-head (95% CI: −5.4 to −1.6, d = 1.2, p = 0.002) and left DG-total (95% CI: −6.3 to −1.5, d = 1.06, p = 0.005) as well as a positive correlation between the percentage change in the volume of the left DG-total and the percentage change in the scores of the mood visual analog scale (r = 0.58, p = 0.04). In conclusion, our study results suggest that compared to DL, BL leads to a significantly greater increase in the left DG volume in patients with mood disorders. This increase in the left DG volume may be associated with mood improvement in the patients.
Metabolic features of treatment-refractory major depressive disorder with suicidal ideation
Authors: Pan Lisa A. , Naviaux Jane C. , Wang Lin , Li Kefeng , Monk Jonathan M. , Lingampelly Sai Sachin , Segreti Anna Maria , Bloom Kaitlyn , Vockley Jerry , Tarnopolsky Mark A. , Finegold David N. , Peters David G. , Naviaux Robert K.
Published: December 2023

Peripheral blood metabolomics was used to gain chemical insight into the biology of treatment-refractory Major Depressive Disorder with suicidal ideation, and to identify individualized differences for personalized care. The study cohort consisted of 99 patients with treatment-refractory major depressive disorder and suicidal ideation (trMDD-SIn = 52 females and 47 males) and 94 age- and sex-matched healthy controls (n = 48 females and 46 males). The median age was 29 years (IQR 22–42). Targeted, broad-spectrum metabolomics measured 448 metabolites. Fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) were measured as biomarkers of mitochondrial dysfunction. The diagnostic accuracy of plasma metabolomics was over 90% (95%CI: 0.80–1.0) by area under the receiver operator characteristic (AUROC) curve analysis. Over 55% of the metabolic impact in males and 75% in females came from abnormalities in lipids. Modified purines and pyrimidines from tRNA, rRNA, and mRNA turnover were increased in the trMDD-SI group. FGF21 was increased in both males and females. Increased lactate, glutamate, and saccharopine, and decreased cystine provided evidence of reductive stress. Seventy-five percent of the metabolomic abnormalities found were individualized. Personalized deficiencies in CoQ10, flavin adenine dinucleotide (FAD), citrulline, lutein, carnitine, or folate were found. Pathways regulated by mitochondrial function dominated the metabolic signature. Peripheral blood metabolomics identified mitochondrial dysfunction and reductive stress as common denominators in suicidal ideation associated with treatment-refractory major depressive disorder. Individualized metabolic differences were found that may help with personalized management.
Discordance between GCIG CA-125 progression and RECIST progression in the CALYPSO trial of patients with platinum-sensitive recurrent ovarian cancer
Authors: Zebic Danka Sinikovic , Tjokrowidjaja Angelina , Francis Katherine Elizabeth , Friedlander Michael , Gebski Val , Lortholary Alain , Joly Florence , Hasenburg Annette , Mirza Mansoor , Denison Ursula , Cecere Sabrina Chiara , Ferrero Annamaria , Pujade-Lauraine Eric , Lee Chee Khoon
Published: December 2023

Background

CA-125 alone is widely used to diagnose progressive disease (PD) in platinum-sensitive recurrent ovarian cancer (PSROC) on chemotherapy. However, there are increasing concerns regarding its accuracy. We assessed concordance between progression defined by CA-125 and RECIST using data from the CALYPSO trial.

Methods

We computed concordance rates for PD by CA-125 and RECIST to determine the positive (PPV) and negative predictive values (NPV).

Results

Of 769 (79%) evaluable participants, 387 had CA-125 PD, where only 276 had concordant RECIST PD (PPV 71%, 95% CI 67–76%). For 382 without CA-125 PD, 255 had RECIST PD but 127 did not (NPV 33%, 95% CI 29–38). There were significant differences in NPV according to baseline CA-125 (≤100 vs >100: 42% vs 25%, P < 0.001); non-measurable vs measurable disease (51% vs 26%, P < 0.001); and platinum-free-interval (>12 vs 6–12 months: 41% vs 14%, P < 0.001). We observed falling CA-125 levels in 78% of patients with RECIST PD and CA-125 non-PD.

Conclusion

Approximately 2 in 3 women with PSROC have RECIST PD but not CA-125 PD by GCIG criteria. Monitoring CA-125 levels alone is not reliable for detecting PD. Further research is required to investigate the survival impact of local therapy in radiological detected early asymptomatic PD.
Hsa_circ_0013561 promotes epithelial-mesenchymal transition and tumor progression by regulating ANXA2 via miR-23b-3p in ovarian cancer
Authors: Lv Jia , Zhang Yijun , Yang Mengying , Qiao Lianqiao , Wang Huihui , Jiang Huici , Fu Mingxu , Qin Jinlong , Xu Shaohua
Published: December 2023

Our preliminary experiment discovered that hsa_circ_0013561 was aberrantly expressed in OC. However, the underlying mechanism is unclear. The expression of hsa_circ_0013561 in OC cells and tissues was detected by RT-qPCR and fluorescence in situ hybridization. The effects of hsa_circ_0013561 on the proliferation and metastasis of OC were explored by functional experiments such as cell counting kit-8, transwell, and tumor xenograft models. To mechanistically understand the regulatory role of hsa_circ_0013561, bioinformatics analysis, Western blot, luciferase reporter assay, and a series of rescue experiments were applied. We found that the hsa_circ_0013561 expression was elevated in OC cells and tissues, and was correlated with metastasis formation. Downregulation of hsa_circ_0013561 suppressed the proliferation and migration of OC cells both in vitro and in vivo. Regarding the interactions of hsa_circ_0013561, the luciferase reporter assay verified that miR-23b-3p and Annexin A2 (ANXA2) were its downstream targets. MiR-23b-3p inhibition or ANXA2 overexpression reversed OC cell proliferation, migration, and epithelial-mesenchymal transition (EMT) post-hsa_circ_0013561 silencing. Moreover, ANXA2 overexpression also reversed OC cell migration, proliferation, and EMT after miR-23b-3p upregulation. Our data suggest that hsa_circ_0013561 increases the expression of ANXA2 by regulating miR-23b-3p competitively, resulting in EMT and metastasis of OC. Thus, hsa_circ_0013561 may serve as a novel oncogenic biomarker for OC progression.
All-optical geometric image transformations enabled by ultrathin metasurfaces
Authors: Zhang Xingwang , Zhang Xiaojie , Duan Yao , Zhang Lidan , Ni Xingjie
Published: December 2023

Image processing plays a vital role in artificial visual systems, which have diverse applications in areas such as biomedical imaging and machine vision. In particular, optical analog image processing is of great interest because of its parallel processing capability and low power consumption. Here, we present ultra-compact metasurfaces performing all-optical geometric image transformations, which are essential for image processing to correct image distortions, create special image effects, and morph one image into another. We show that our metasurfaces can realize binary image transformations by modifying the spatial relationship between pixels and converting binary images from Cartesian to log-polar coordinates with unparalleled advantages for scale- and rotation-invariant image preprocessing. Furthermore, we extend our approach to grayscale image transformations and convert an image with Gaussian intensity profile into another image with flat-top intensity profile. Our technique will potentially unlock new opportunities for various applications such as target tracking and laser manufacturing.
The function of ER-phagy receptors is regulated through phosphorylation-dependent ubiquitination pathways
Authors: Berkane Rayene , Ho-Xuan Hung , Glogger Marius , Sanz-Martinez Pablo , Brunello Lorène , Glaesner Tristan , Kuncha Santosh Kumar , Holzhüter Katharina , Cano-Franco Sara , Buonomo Viviana , Cabrerizo-Poveda Paloma , Balakrishnan Ashwin , Tascher Georg , Husnjak Koraljka , Juretschke Thomas , Misra Mohit , González Alexis , Dötsch Volker , Grumati Paolo , Heilemann Mike , Stolz Alexandra
Published: December 2023

Selective autophagy of the endoplasmic reticulum (ER), known as ER-phagy, is an important regulator of ER remodeling and essential to maintain cellular homeostasis during environmental changes. We recently showed that members of the FAM134 family play a critical role during stress-induced ER-phagy. However, the mechanisms on how they are activated remain largely unknown. In this study, we analyze phosphorylation of FAM134 as a trigger of FAM134-driven ER-phagy upon mTOR (mechanistic target of rapamycin) inhibition. An unbiased screen of kinase inhibitors reveals CK2 to be essential for FAM134B- and FAM134C-driven ER-phagy after mTOR inhibition. Furthermore, we provide evidence that ER-phagy receptors are regulated by ubiquitination events and that treatment with E1 inhibitor suppresses Torin1-induced ER-phagy flux. Using super-resolution microscopy, we show that CK2 activity is essential for the formation of high-density FAM134B and FAM134C clusters. In addition, dense clustering of FAM134B and FAM134C requires phosphorylation-dependent ubiquitination of FAM134B and FAM134C. Treatment with the CK2 inhibitor SGC-CK2-1 or mutation of FAM134B and FAM134C phosphosites prevents ubiquitination of FAM134 proteins, formation of high-density clusters, as well as Torin1-induced ER-phagy flux. Therefore, we propose that CK2-dependent phosphorylation of ER-phagy receptors precedes ubiquitin-dependent activation of ER-phagy flux.
Approaching national climate targets in China considering the challenge of regional inequality
Authors: Yu Biying , Zhao Zihao , Wei Yi-Ming , Liu Lan-Cui , Zhao Qingyu , Xu Shuo , Kang Jia-Ning , Liao Hua
Published: December 2023

Achievement of national climate targets and the corresponding costs would entirely depend on regional actions within the country. However, because of substantial inequalities and heterogeneities among regions, especially in developing economies, aggressive or uniform actions may exacerbate inequity and induce huge economic losses, which in turn challenges the national climate pledges. Hence, this study extends prior research by proposing economically optimal strategies that can achieve national climate targets and ensure the greatest local and national benefits as well as regional equality. Focusing on the biggest developing country China, we find this strategy can avoid up to 1.54% of cumulative GDP losses for approaching carbon neutrality, and more than 90% of regions would obtain economic gains compared either with existing independently launched targets or with the uniform strategy that all regions achieve peak carbon emissions before 2030. We also provide optimal carbon mitigation pathways to regional peak carbon, carbon intensity and energy consumption.
Mapping protein states and interactions across the tree of life with co-fractionation mass spectrometry
Authors: Skinnider Michael A. , Akinlaja Mopelola O. , Foster Leonard J.
Published: December 2023

We present CFdb, a harmonized resource of interaction proteomics data from 411 co-fractionation mass spectrometry (CF-MS) datasets spanning 21,703 fractions. Meta-analysis of this resource charts protein abundance, phosphorylation, and interactions throughout the tree of life, including a reference map of the human interactome. We show how large-scale CF-MS data can enhance analyses of individual CF-MS datasets, and exemplify this strategy by mapping the honey bee interactome.
Histopathological growth patterns and tumor-infiltrating lymphocytes in breast cancer liver metastases
Authors: Leduc Sophia , De Schepper Maxim , Richard François , Maetens Marion , Pabba Anirudh , Borremans Kristien , Jaekers Joris , Latacz Emily , Zels Gitte , Bohlok Ali , Van Baelen Karen , Nguyen Ha Linh , Geukens Tatjana , Dirix Luc , Larsimont Denis , Vankerckhove Sophie , Santos Eva , Oliveira Rui Caetano , Dede Kristòf , Kulka Janina , Borbala Székely , Salamon Ferenc , Madaras Lilla , Marcell Szasz A. , Lucidi Valerio , Meyer Yannick , Topal Baki , Verhoef Cornelis , Engstrand Jennie , Moro Carlos Fernandez , Gerling Marco , Bachir Imane , Biganzoli Elia , Donckier Vincent , Floris Giuseppe , Vermeulen Peter , Desmedt Christine
Published: December 2023

Liver is the third most common organ for breast cancer (BC) metastasis. Two main histopathological growth patterns (HGP) exist in liver metastases (LM): desmoplastic and replacement. Although a reduced immunotherapy efficacy is reported in patients with LM, tumor-infiltrating lymphocytes (TIL) have not yet been investigated in BCLM. Here, we evaluate the distribution of the HGP and TIL in BCLM, and their association with clinicopathological variables and survival. We collect samples from surgically resected BCLM (n = 133 patients, 568 H&E sections) and post-mortem derived BCLM (n = 23 patients, 97 H&E sections). HGP is assessed as the proportion of tumor liver interface and categorized as pure-replacement (‘pure r-HGP’) or any-desmoplastic (‘any d-HGP’). We score the TIL according to LM-specific guidelines. Associations with progression-free (PFS) and overall survival (OS) are assessed using Cox regressions. We observe a higher prevalence of ‘any d-HGP’ (56%) in the surgical samples and a higher prevalence of ‘pure r-HGP’ (83%) in the post-mortem samples. In the surgical cohort, no evidence of the association between HGP and clinicopathological characteristics is observed except with the laterality of the primary tumor (p value = 0.049) and the systemic preoperative treatment before liver surgery (p value = .039). TIL is less prevalent in ‘pure r-HGP’ as compared to ‘any d-HGP’ (p value = 0.001). ‘Pure r-HGP’ predicts worse PFS (HR: 2.65; CI: (1.45–4.82); p value = 0.001) and OS (HR: 3.10; CI: (1.29–7.46); p value = 0.011) in the multivariable analyses. To conclude, we demonstrate that BCLM with a ‘pure r-HGP’ is associated with less TIL and with the worse outcome when compared with BCLM with ‘any d-HGP’. These findings suggest that HGP could be considered to refine treatment approaches.
Exploitable magnetic anisotropy and half-metallicity controls in multiferroic van der Waals heterostructure
Authors: Wang Yaping , Xu Xinguang , Ji Weixiao , Li Shengshi , Li Yanlu , Zhao Xian
Published: December 2023

Two-dimensional (2D) XY ferromagnets have drawn pronounced interest in recent years, but the characteristic of easy-plane magnetization restricts their application in spintronics to some extent. Here, we propose a general strategy for constructing multiferroic van der Waals heterostructures, aiming to achieve electrical control over the magnetic anisotropy in 2D XY ferromagnets. The validity of this strategy is verified by the heterostructure composed of ferromagnetic VBi2Te4 and ferroelectric In2Se3 monolayers. By manipulating the polarized states of In2Se3, the VBi2Te4 can be reversibly transformed between 2D XY and Heisenberg ferromagnets, characterized by the switching of easy magnetization axis between in-plane and out-of-plane directions. More interestingly, accompanied by the changes in magnetic anisotropy, the VBi2Te4 also demonstrates a phase transition from a semiconductor to a half-metal state, which can be ascribed to the band alignment and interfacial charge transfer. The switchable magnetic and electronic properties enable the heterostructure to be utilized in nonvolatile memory and logic devices. Additionally, the half-metallicity and magnetocrystalline anisotropy energy of the heterostructure can be effectively tuned by biaxial strain. These findings not only pave the way for electrically nonvolatile control of 2D XY ferromagnet, but also facilitate the development of interfacial magnetoelectric physics and applications.
Transcriptional profiling upon T cell stimulation reveals down-regulation of inflammatory pathways in T and B cells in SLE versus Sjögren’s syndrome
Authors: Kwon Gino , Wiedemann Annika , Steinheuer Lisa M. , Stefanski Ana-Luisa , Szelinski Franziska , Racek Tomas , Frei Andreas Philipp , Hatje Klas , Kam-Thong Tony , Schubert David , Schindler Thomas , Dörner Thomas , Thurley Kevin
Published: December 2023

Systemic lupus erythematosus (SLE) and primary Sjögren’s syndrome (pSS) share clinical as well as pathogenic similarities. Although previous studies suggest various abnormalities in different immune cell compartments, dedicated cell-type specific transcriptomic signatures are often masked by patient heterogeneity. Here, we performed transcriptional profiling of isolated CD4, CD8, CD16 and CD19 lymphocytes from pSS and SLE patients upon T cell stimulation, in addition to a steady-state condition directly after blood drawing, in total comprising 581 sequencing samples. T cell stimulation, which induced a pronounced inflammatory response in all four cell types, gave rise to substantial re-modulation of lymphocyte subsets in the two autoimmune diseases compared to healthy controls, far exceeding the transcriptomic differences detected at steady-state. In particular, we detected cell-type and disease-specific down-regulation of a range of pro-inflammatory cytokine and chemokine pathways. Such differences between SLE and pSS patients are instrumental for selective immune targeting by future therapies.
Research on the causal mechanism of a rock burst accident in a longwall roadway and its prevention measures
Authors: Chen Ying , Zhang Zikai , Cao Chen , Bao Shiji , Wang Shuai , Xu Guangyuan
Published: December 2023

Based on the disaster characteristics and the geo-conditions at the scene, in this study, the occurrence mechanism of a serious rock burst accident that occurred in the Tangshan Coal Mine, China, was analysed. Ground stress measurements showed that the mine is in a high ground stress area dominated by horizontal tectonic stress around 33 MPa. Laboratory testing revealed that the coal was a hard seam of 8.3 MPa over bedded by a thick and hard roof stratum with uniaxial compressive strength of 66 MPa. The calculation results indicated that the accident occurred in the roof rebounding area. It is proposed that the hard roof and the hard coal seam formed a seesaw structure around the working face. The vertical pressure relief caused the rib coal mass to lose its clamping forces from the roof and floor and rush into the roadway, resulting in a rock burst accident. Based on the causality mechanism of the rock burst disaster developed in this study, pertinent coal bump prevention measures have been undertaken in practice. Large-diameter boreholes were drilled to eliminate the pivot effect of the seam. Roof blasting was undertaken to prevent the roof from forming a seesaw plank. To summarize, a new causality mechanism for rock burst in coal mines under hard roof and hard seam geo-conditions was developed.
Ideological asymmetries in online hostility, intimidation, obscenity, and prejudice
Authors: Badaan Vivienne , Hoffarth Mark , Roper Caroline , Parker Taurean , Jost John T.
Published: December 2023

To investigate ideological symmetries and asymmetries in the expression of online prejudice, we used machine-learning methods to estimate the prevalence of extreme hostility in a large dataset of Twitter messages harvested in 2016. We analyzed language contained in 730,000 tweets on the following dimensions of bias: (1) threat and intimidation, (2) obscenity and vulgarity, (3) name-calling and humiliation, (4) hatred and/or racial, ethnic, or religious slurs, (5) stereotypical generalizations, and (6) negative prejudice. Results revealed that conservative social media users were significantly more likely than liberals to use language that involved threat, intimidation, name-calling, humiliation, stereotyping, and negative prejudice. Conservatives were also slightly more likely than liberals to use hateful language, but liberals were slightly more likely than conservatives to use obscenities. These findings are broadly consistent with the view that liberal values of equality and democratic tolerance contribute to ideological asymmetries in the expression of online prejudice, and they are inconsistent with the view that liberals and conservatives are equally prejudiced.
Atomic-scale view of the photoinduced structural transition to form sp3-like bonded order phase in graphite
Authors: Inami Eiichi , Nishioka Keita , Kanasaki Jun’ichi
Published: December 2023

Photoexcitation of solids often induces structural phase transitions between different ordered phases, some of which are unprecedented and thermodynamically inaccessible. The phenomenon, known as photoinduced structural phase transition (PSPT), is of significant interest to the technological progress of advanced materials processing and the fundamental understanding of material physics. Here, we applied scanning tunnelling microscopy (STM) to directly characterise the primary processes of the PSPT in graphite to form a sp3-like carbon nano-phase called diaphite. The primary challenge was to provide microscopic views of the graphite-to-diaphite transition. On an atomic scale, STM imaging of the photoexcited surface revealed the nucleation and proliferation processes of the diaphite phase; these were governed by the formation of sp3-like interlayer bonds. The growth mode of the diaphite phase depends strongly on the photon energy of excitation laser light. Different dynamical pathways were proposed to explain the formation of a sp3-like interlayer bonding. Potential mechanisms for photon-energy-dependent growth were examined based on the experimental and calculated results. The present results provide insight towards realising optical control of sp2-to-sp3 conversions and the organisation of nanoscale structures in graphene-related materials.
Contingent convertible bonds in financial networks
Authors: Calice Giovanni , Sala Carlo , Tantari Daniele
Published: December 2023

We study the role of contingent convertible bonds (CoCos) in a complex network of interconnected banks. By studying the system’s phase transitions, we reveal that the structure of the interbank network is of fundamental importance for the effectiveness of CoCos as a financial stability enhancing mechanism. Our results show that, under some network structures, the presence of CoCos can increase (and not reduce) financial fragility, because of the occurring of unneeded triggers and consequential suboptimal conversions that damage CoCos investors. We also demonstrate that, in the presence of a moderate financial shock, lightly interconnected financial networks are more robust than highly interconnected networks. This makes them a potentially optimal choice for both CoCos issuers and buyers.
Reward conditioning may not have an effect on category-specific memory
Authors: Sukumaran Priyanka , Kazanina Nina , Houghton Conor
Published: December 2023

Behavioural tagging facilitates the temporary storage of seemingly insignificant episodic events, which may later become salient and enhanced in memory. Human behavioural studies have demonstrated selective memory enhancement for neutral stimuli from one category when this category is subsequently paired with reward. Although this phenomenon has implications for the role of reward conditioning on emotional and adaptive memory, its generalisability is underexplored. We conducted four experiments to investigate whether pairing items from a semantic category, animals or objects, with high or low rewards resulted in preferential memory for the high-reward category. Three of these experiments also aimed to replicate the category-specific retrospective enhancement effect reported by Patil et al. and two explored the corresponding prospective memory effect. None of our experiments showed consistent evidence for an effect of reward on category-specific memory enhancement, despite employing the same reward paradigm and incidental encoding protocol as in the original study. Consequently, we found no evidence for category-specific retrospective or prospective enhancement effects. Our experiments were conducted online which is an equally relevant method for assessing behavioural phenomenon as the in-person studies conducted by Patil et al. Overall, our results question the generalisability of previously reported category-specific memory enhancement effects due to reward.
Intensified discrimination against tenants and its health effects during the COVID-19 pandemic in large Chinese cities
Authors: Shan Lu , He Shenjing
Published: December 2023

The COVID-19 pandemic in many senses reconstructs social norms and reshapes social behaviour, which typically assumes a close correlation between mobility with a higher risk of COVID-19 infection. This may intensify the pre-existing discrimination against tenants and widen tenure-based health inequalities. Drawing on an online questionnaire survey conducted in five major cities in China in 2020, we employ multi-level regression models to examine the intensified discrimination against tenants during COVID-19 and its impacts on residents’ physical and mental health inequalities. Results show that the pre-existing inequalities have been intensified during COVID-19 and the perceived discrimination has rendered worsened self-rated health and mental health and enlarged health inequalities. The discrimination particularly affected tenants with better economic profiles or worse health conditions; by contrast, despite being exposed to more tenant-related discriminatory experiences, rural hukou holders suffered from less severe health inequalities. A clear linkage is found between renting in poorly-managed and larger health gaps generated by discrimination. The negative health impact of intensified discrimination is found to be more significant in communities with lower infection risk, which points to the necessity of understanding the long-term health impact of discrimination against tenants in a more holistic way. In terms of community environment, we discover a positive effect of community social capital, i.e., higher level social capital helps mitigate the health threat of discrimination against tenants during COVID-19. Besides, public housing tenants reported better health outcomes and were less exposed to intensified discrimination during COVID-19 than private housing tenants. These findings provide a nuanced understanding of variations determined by individual and territorial factors, thus present timely policy implications for promoting healthy and inclusive urban development in the post-pandemic era.
Enhanced anti-tumor activity of transferrin/folate dual-targeting magnetic nanoparticles using chemo-thermo therapy on retinoblastoma cancer cells Y79
Authors: Sadri Elaheh , Khoee Sepideh , Moayeri Samaneh , Haji Ali Bahareh , Pirhajati Mahabadi Vahid , Shirvalilou Sakine , Khoei Samideh
Published: December 2023

Malignant neoplasms are one of the main causes of death, especially in children, on a global scale, despite strenuous efforts made at advancing both diagnostic and therapeutic modalities. In this regard, a new nanocarrier Vincristine (VCR)-loaded Pluronic f127 polymer-coated magnetic nanoparticles conjugated with folic acid and transferrin (PMNP-VCR-FA-TF) were synthesized and characterized by various methods. The cytotoxicity of these nanoparticles was evaluated in vitro and ex vivo conditions. The in vitro anti-tumor effect of the nanoparticles was evaluated by colony formation assay (CFA) and reactive oxygen species (ROS) in Y79 cell line. The results showed that nanoparticles with two ligands conferred greater toxicity toward Y79 cancer cells than ARPE19 normal cells. Under an alternating magnetic field (AMF), these nanoparticles demonstrated a high specific absorption rate. The CFA and ROS results indicated that the AMF in combination with PMNP-VCR-FA-TF conferred the highest cytotoxicity toward Y79 cells compared with other groups (P < 0.05). PMNP-VCR-FA-TF could play an important role in converting externally applied radiofrequency energy into heat in cancer cells. The present study confirmed that dual targeting chemo-hyperthermia using PMNP-VCR-FA-TF was significantly more effective than hyperthermia or chemotherapy alone, providing a promising platform for precision drug delivery as an essential component in the chemotherapy of retinoblastoma.
Structural insights into N-terminal methionine cleavage by the human mitochondrial methionine aminopeptidase, MetAP1D
Authors: Lee Yeon , Kim Hayoung , Lee Eunji , Hahn Hyunggu , Heo Yoonyoung , Jang Dong Man , Kwak Kihyuck , Kim Hyo Jung , Kim Hyoun Sook
Published: December 2023

Isozymes are enzymes that catalyze identical biological reactions, yet exhibit slight variations in structures and catalytic efficiency, which enables the precise adjustment of metabolism to fulfill the specific requirements of a particular tissue or stage of development. Methionine aminopeptidase (MetAP) isozymes function a critical role in cleaving N-terminal methionine from nascent proteins to generate functional proteins. In humans, two distinct MetAP types I and II have been identified, with type I further categorized into cytosolic (MetAP1) and mitochondrial (MetAP1D) variants. However, despite extensive structural studies on both bacterial and human cytosolic MetAPs, the structural information remains unavailable for human mitochondrial MetAP. This study was aimed to elucidate the high-resolution structures of human mitochondrial MetAP1D in its apo-, cobalt-, and methionine-bound states. Through a comprehensive analysis of the determined structures and a docking simulation model with mitochondrial substrate peptides, we present mechanistic insights into the cleavage process of the initiator methionine from mitochondrial proteins. Notably, despite the shared features at the active site between the cytosolic and mitochondrial MetAP type I isozymes, we identified distinct structural disparities within the active-site pocket primarily contributed by two specific loops that could play a role in accommodating specific substrates. These structural insights offer a basis for the further exploration of MetAP isozymes as critical players in cellular processes and potential therapeutic applications.
Clinical significance of polymorphisms of genes encoding collagen (COL1A1, COL5A1) and their correlation with joint laxity and recurrent patellar dislocation in adolescents
Authors: Małecki Krzysztof , Fabiś-Strobin Anna , Sałacińska Kinga , Kwas Katarzyna , Stelmach Wojciech , Beczkowski Jacek , Niedzielski Kryspin , Gach Agnieszka
Published: December 2023

The aim of this study was to assess the coexistence of polymorphisms of the COL1A1 and COL5A1 genes with clinically diagnosed laxity and the occurrence of recurrent patellar dislocation in adolescents. The research group comprised 50 cases of recurrent patellar dislocation. The mean age at diagnosis was 14.2 years (10–17, SD 2.6). The control group consisted of 199 participants without a diagnosis of recurrent patellar dislocation, with a mean age of 15.2 (10–17 years, SD 2.7). Joint laxity by the Beighton scale was assessed. Analysis of the allele distribution of the analysed genes COL1A1 and COL5A1 revealed no statistically significant difference between the study group and the control group (p = 0.859 and p = 0.205, respectively). Analysis of the Beighton score showed a statistically significantly higher result in the study group than in the control group (p < 0.001). No correlation between the presence of polymorphisms and joint laxity diagnosis was confirmed. In conclusion, COL1A1 and COL5A1 gene polymorphisms are not significantly more common in adolescents with recurrent patellar dislocation than in healthy peers; there is also no correlation between joint laxity and polymorphisms of the COL1A1 and COL5A1 genes.

Registered on ClinicalTrials.gov with ID: PMMHRI-2021.2/1/7-GW.