bluuebunny/crossref_metadata_2025 huggingface dataset:
Deficiency of the hemoglobin-haptoglobin receptor, CD163, worsens insulin sensitivity in obese male mice
Authors: Schleh Michael W. , Ameka Magdalene , Rodriguez Alec , Hasty Alyssa H.
Published: June 2024

Excessive iron accumulation in metabolic organs such as the adipose tissue, liver, and skeletal muscle is associated with increased diabetes risk. Tissue-resident macrophages serve multiple roles including managing inflammatory tone and regulating parachymal iron homeostasis; thus protecting against metabolic dysfunction upon iron overload. The scavenger receptor CD163 is uniquely present on tissue-resident macrophages, and plays a significant role in iron homeostasis by clearing extracellular hemoglobin-haptoglobin complexes, thereby limiting oxidative damage caused by free hemoglobin in metabolic tissues. We show that the absence of CD163 exacerbates glucose intolerance and insulin resistance in male mice with obesity. Additionally, loss of CD163 reduced the expression of iron regulatory genes(Tfr1, Cisd1, Slc40a1)in adipose tissue macrophages and anti-inflammatory (M2-like) bone marrow-derived macrophages (BMDMs). Further, CD163 deficiency mediated a pro-inflammatory shift and limited hemoglobin scavenging specifically in M2-like BMDMs. To this end, iron buffering was diminished in inguinal white adipose tissue (iWAT) macrophagesin vivo, which culminated in iron spillover into adipocytes and CD45+CD11B-non-myeloid immune cells in iWAT. These findings show that CD163 on tissue-resident macrophages is critical for their anti-inflammatory and hemoglobin scavenging roles, and its absence results in impaired systemic insulin action in an obese setting.

Article Highlights

Loss of CD163 mediates a phenotypic switch in M2-like macrophages towards a pro-inflammatory state.

CD163 is involved in free hemoglobin uptake and catabolism as well as oxidative metabolism, specifically in M2-like macrophages.

In inguinal white adipose tissue (iWAT) of CD163 defficient mice, macrophage iron is reduced; while concomitantly, adipocyte and other immune cell iron content is increased.

Loss of CD163 provokes glucose intolerance and insulin resistance in obese male mice.
Histopathology and proteomics are synergistic for High-Grade Serous Ovarian Cancer platinum response prediction
Authors: Kilim Oz , Olar Alex , Biricz András , Madaras Lilla , Pollner Péter , Szállási Zoltán , Sztupinszki Zsofia , Csabai István
Published: June 2024

Patients with High-Grade Serous Ovarian Cancer (HGSOC) exhibit varied responses to treatment, with 20-30% showingde novoresistance to platinum-based chemotherapy. While hematoxylin-eosin (H&E) pathological slides are used for routine diagnosis of cancer type, they may also contain diagnostically useful information about treatment response. Our study demonstrates that combining H&E-stained Whole Slide Images (WSIs) with proteomic signatures using a multimodal deep learning framework significantly improves the prediction of platinum response in both discovery and validation cohorts. This method outperforms the Homologous Recombination Deficiency (HRD) score in predicting platinum response and overall patient survival. The study sets new performance benchmarks and explores the intersection of histology and proteomics, highlighting phenotypes related to treatment response pathways, including homologous recombination, DNA damage response, nucleotide synthesis, apoptosis, and ER stress. This integrative approach has the potential to improve personalized treatment and provide insights into the therapeutic vulnerabilities of HGSOC.
Using Simulated Encounters with Standardized Patients to Teach Medical Students to Address Implicit Biases and Microaggressions in the Clinical Setting
Authors: Thommen Rachel , Weber Harli , Lo Katherine , Ayhan Deelan , Vellek John , Levy Lior , Smith Sarah , Hoke Christopher , Alnifaidy Redab , Vargas Danielle , Yamulla Katharine , Liberatos Penny , Etienne Mill , Ludmer Pamela
Published: June 2024

Purpose

Structural obstacles in healthcare related to social, economic, and political factors contribute to inequities in patient care. Combined didactic and experiential learning may be more effective to teach medical students how to address implicit bias and microaggression in the clinical setting.

Methods

Rising third year medical students at New York Medical College participated in a student-led implicit bias and microaggression training program, including experiential learning through standardized patient (SP) encounters and self-reflection via student-led debrief sessions. The SP encounters simulated instances of xenophobia and perceived language barriers in a hospital setting, in which students were expected to address microaggressions in real time utilizing the VITALS (Validate, Inquire, Take time, Assume the best, Leave opportunities, Speak up for others) framework.

Results

200 students participated in the program. Survey responses on attitudes regarding implicit bias and microaggressions were collected prior to participating in the program (T1), after the VITALS video presentation (T2), and after the SP encounter and debrief sessions (T3). Students felt more likely to interrupt a microaggression from T1 to T3.

Conclusions

Our implicit bias training, equipped students with the tools and practice needed to interrupt microaggressions in the clinical setting.

Practice Points

Combined didactic and experiential learning may be more effective than didactics alone for teaching medical students how to address implicit bias and microaggression in the clinical setting.

Students overestimated their comfort level to interrupt a microaggression after watching the training video alone, underscoring the importance of experiential learning.

Students valued the opportunity to practice interrupting microaggressions in a safe space with the SPs.

The SP encounter positively impacted students’ likelihood to interrupt a microaggression in the future.

Students felt more comfortable interrupting a microaggression from a peer than from a person in power.
ACKR5/GPR182 is a scavenger receptor for the atypical chemokine CXCL17, GPR15L and various endogenous peptides
Authors: Meyrath Max , Palmer Christie B. , Plesseria Jean-Marc , Darcis Joy , Nesheva Desislava , Thelen Marcus , Legler Daniel F. , Leurs Rob , Hanson Julien , Szpakowska Martyna , Chevigné Andy
Published: June 2024

GPR182/ACKR5, the most recently deorphanized chemokine receptor, is mainly expressed on endothelial cells and was proposed to act as a scavenger regulating the availability of a large set of chemokines. In this study, we first established the exact profiles and ranking of the chemokines binding to the human and mouse GPR182. We confirmed the high promiscuity of GPR182 towards XC, CC and CXC chemokines and a clear difference in the chemokine repertoires of the human and mouse orthologues. We next demonstrated that, beyond classical chemokines, GPR182 exhibits potent binding to the chemoattractant protein GPR15L/C10orf99, the atypical chemokine CXCL17 and various endogenous peptides, mainly from the opioid, apelin, and PACAP families. We also showed that these newly identified ligands engage GPR182 through varied binding modes. While GPR15L, just like classical chemokines, predominantly engages GPR182 via its N terminus, conversely to the C terminus-dependent binding to its cognate receptor GPR15, CXCL17 exhibits a more complex interaction, relying on both the N and C terminus. The binding mode of the newly identified peptide ligands also differ from the interactions with their cognate receptors. Our findings establish the first scavenger receptor for CXCL17 and GPR15L and advance the understanding of GPR182 ligand interactions, suggesting a regulatory role beyond chemokines.
Chromosome-level reference genome assembly for the protected resource plant,Zenia insignis
Authors: Chen Si-Yun , Yang Zhi-Yun , Zhang Rong , Liu Hui , Yi Ting-Shuang
Published: June 2024

Zenia insignisChun, from the subfamily Dialioideae of Fabaceae, is a tree species of significant economic and ecological values. It is a threatened species as per the IUCN Red List. The absence of a reference genome has impeded research onZ. insignisdespite its importance. In this study, we generated a reference genome forZ. insig n,iwsith a contig N50 of 6.02Mb, a total length of 361.11 Mb, and 97.71% of the sequences assembled into 14 pseudo-chromosomes. The BUSCO assessment score for completeness is 97.30%, and the LAI index assessment score for continuity is 14.57. To our knowledge, this is the first reported nuclear genome of a species belonging to subfamily Dialioideae. The reference genome will provide a valuable resource for the phylogenomic studies of the Fabaceae family and facilitate further research onZ. insignis.
Blood to Biomarker Quantitation in Under One Hour with Rapid Proteomics using a Hyperthermoacidic Protease
Authors: Yannone Steven M. , Tuteja Vikas , Goleva Olena , Leung Donald Y.M. , Stotland Aleksandr , Keoseyan Angel J. , Hendricks Nathan G. , Van Eyk Jennifer E. , Kreimer Simion
Published: June 2024

Multi-step multi-hour tryptic proteolysis has limited the utility of bottom-up proteomics for cases that require immediate quantitative information. The recently available hyperthermoacidic (HTA) protease “Krakatoa” digests samples in a single 5 to 30-minute step at pH 3 and >80 °C; conditions that disrupt most cells and tissues, denature proteins, and block disulfide reformation. The combination of quick single-step sample preparation with high throughput dual trapping column single analytical column (DTSC) liquid chromatography-mass spectrometry (LC-MS) achieves “Rapid Proteomics” in which the time from sample collection to actionable data is less than 1 hour. The presented development and systematic evaluation of this methodology found reproducible quantitation of over 160 proteins from just 1 microliter of whole blood. Furthermore, the preference of the HTA-protease for intact proteins over peptides allows for sensitive targeted quantitation of the Angiotensin I and II bioactive peptides in under half an hour. With these methods we analyzed serum and plasma from 53 individuals and quantified Angiotensin and proteins that were not detected with trypsin. This assessment of Rapid Proteomics suggests that concentration of circulating protein and peptide biomarkers could be measured in almost real-time by LC-MS.

TOC Figure

Rapid proteomics enables near real-time monitoring of circulating blood biomarkers. One microliter of blood is collected every 8 minutes, digested for 20 minutes, and then analyzed by targeted mass spectrometry for 8 minutes. This results in a 30-minute delay with datapoints every 8 minutes.
HCV infection activates the proteasome via PA28γ acetylation and heptamerization to facilitate the degradation of RNF2, a catalytic component of polycomb repressive complex 1
Authors: Kasai Hirotake , Yamashita Atsuya , Akaike Yasunori , Tanaka Tomohisa , Matsuura Yoshiharu , Moriishi Kohji
Published: June 2024

We previously reported that hepatitis C virus (HCV) infection or HCV core protein expression induces HOX gene expression by impairing histone H2A monoubiquitination via a proteasome-dependent reduction in the level of RNF2, a key catalytic component of polycomb repressive complex 1 (PRC1) (J. Virol, 2021, 95, e01784-20). In this study, we aimed to investigate the mechanism by which HCV infection accelerates RNF2 degradation. Yeast two-hybrid screening and an immunoprecipitation assay revealed that RNF2 is a PA28γ-binding protein. The proteasome activator PA28γ destabilized the RNF2 protein in a proteasome-dependent manner, since RNF2 degradation was impaired by PA28γ knockout or MG132 treatment. HCV infection or core protein expression reduced the levels of RNF2 and histone H2A K119 monoubiquitination and induced the expression of HOX genes in the presence of PA28γ, while PA28γ knockout reversed these changes. Treatment with a lysine acetyltransferase inhibitor inhibited the acetylation of PA28γ at K195 and the degradation of the RNF2 protein, while treatment with a lysine deacetylase inhibitor accelerated these events in a PA28γ-dependent manner. RNF2 protein degradation was increased by expression of the acetylation mimetic PA28γ mutant but not by expression of the acetylation-defective mutant or the proteasome activation-defective mutant. Furthermore, HCV infection or core protein expression facilitated the interaction between PA28γ and the lysine acetyltransferase CBP/p300 and then accelerated PA28γ acetylation and heptamerization to promote RNF2 degradation. These data suggest that HCV infection accelerates the acetylation-dependent heptamerization of PA28γ to increase the proteasomal targeting of RNF2.

IMPORTANCE

HCV is a causative agent of HCV-related liver diseases, including hepatic steatosis, cirrhosis and hepatocellular carcinoma. PA28γ, which, in heptameric form, activates the 20S core proteasome for the degradation of PA28γ-binding proteins, is responsible for HCV-related liver diseases. HCV core protein expression or HCV infection accelerates RNF2 degradation, leading to the induction of HOX gene expression via a decrease in the level of H2Aub on HOX gene promoters. However, the mechanism of RNF2 degradation in HCV-infected cells has not been clarified. The data presented in this study suggest that PA28γ acetylation and heptamerization are promoted by HCV infection or by core protein expression to activate the proteasome for the degradation of RNF2 and are responsible for HCV propagation. This study provides novel insights valuable for the development of therapies targeting both HCV propagation and HCV-related diseases.
Identification of ABHD6 as a regulator of lysophosphatidylserines in the mammalian liver and kidneys
Authors: Chakraborty Arnab , Punnamraju Prajwal , Sajeevan Theja , Kaur Arshdeep , Kolthur-Seetharam Ullas , Kamat Siddhesh S.
Published: June 2024

Lysophosphatidylserine (lyso-PS) is a potent hormone-like signaling lysophospholipid, which regulates many facets of mammalian biology and dysregulation in its metabolism is associated with several human neurological and autoimmune diseases. Despite the physiological importance and causal relation with human pathophysiology, little is known about the metabolism of lyso-PS in tissues other than the nervous and immune systems. To address this problem, here, we attempted to identify one (or more) lipase(s) capable of degrading lyso-PS in different mammalian tissues. We found that the membrane proteomic fraction of most mammalian tissues possess lyso-PS lipase activity, yet interestingly, the only bona fide lyso-PS lipase ABHD12 displays this enzymatic activity and has control over lyso-PS metabolism only in the mammalian brain. Using anin vitroinhibitor screen against membrane proteomic fractions of different tissues, we find that another lipase from the metabolic serine hydrolase family, ABHD6, is a putative lyso-PS lipase in the mouse liver and kidney. Finally, using pharmacological tools, we validate the lyso-PS lipase activity of ABHD6in vivo, and functionally designate this enzyme as a major lyso-PS lipase in primary hepatocytes, and the mammalian liver and kidneys.

HIGHLIGHTS

Lyso-PS lipase enzymatic activity is present in the membrane proteomic fraction of most mammalian tissues

Anin vitroinhibitor screen identifies ABHD6 as a putative lyso-PS lipase in the liver and kidney

ABHD6 functions as a lyso-PS lipase in primary hepatocytes

ABHD6 also performs lyso-PS lipase activityin vivoand regulates lyso-PS levels in the liver and kidney
Functional and Clinical Implications of Extrachromosomal Circular DNA in the Human Germline
Authors: Evans Melanie , Rajachandran Shreya , Zhang Xin , Zhang Yanfeng , Saner Karla , Xu Lin , Orwig Kyle E. , Bukulmez Orhan , Chen Haiqi
Published: June 2024

Extrachromosomal circular DNA (eccDNA) originates from linear chromosomal DNA and can be found in various human cell types including the male germline. However, the functional effects and biogenesis mechanisms of the eccDNA in the human male germline are not well understood. Here, we developed a sequencing approach to extract eccDNA sequence information and the paired transcriptome information from the same cells. By applying this approach to human samples, we found evidence of transcriptional activities of germline eccDNAs. We also showed that patients with chronic diseases such as hypertension and diabetes had a significantly higher number of eccDNAs in the sperm than their healthy counterparts. This was, at least partly, due to an increased apoptosis signaling in the germline. Analysis of single cell RNA sequencing data of spermatogenic cells from diabetic patientsvs. healthy individuals suggested that a dysregulation in the expression levels of multiple poly (ADP-ribose) polymerases may contribute to the increased amount of germline eccDNAs in diseased patients. In addition, we identified a potential horizontal transfer mechanism through which healthy sperm can take up eccDNAs from their surrounding microenvironment. Together, our results suggest that eccDNA may have functional effects on the germline, and it may serve as a non-invasive clinical biomarker for human health.
Uncontrolled glycemia and PTSD in diabetic patients living in high conflict zones: A cross-sectional study
Authors: Bleibel Mohammad , Nasser Bilal , Dorra Lana El , Jomaa Leya Al , Deek Hiba
Published: June 2024

Background

Local conflicts such as those occurring in Palestinian camps in Lebanon have led to detrimental effects on the physical and psychological aspects of the people living in these regions. PTSD and uncontrolled glycemia are expected to be the consequences of these events.

Aim

To determine the impact of the Ein El Helwe events on blood glycemic levels and the possibility of developing post-traumatic stress disorders.

Design

A cross-sectional questionnaire with self-administered questionnaires.

Methods

Participants were identified from the community of South Lebanon in the area surrounding, or inside, the Ein El Helwe Camp during the time of the events. The participants completed an electronic questionnaire which included sociodemographic data, diabetes condition and the DSM-IV symptoms of PTSD and its level. The Scale is a validated scale that had previously been translated to Arabic.

Results

A total of 234 participants were included in the final analysis of the study with almost 30% having uncontrolled glycemia. The mean age of the study participants was 53.49+13.09 years with more female than male participants and more living around rather than inside the camp. Glycemic control was associated with gender, educational level, living in or outside the camp and the body mass index. Multivariate analysis confirmed the impact of educational level, living area and PTSD on the glycemic control. The relationship between glycemic control and PTSD was based on some of the latter’s symptoms.

Conclusion

The study highlighted the impact of conflicts and wars on the development of uncontrolled glycemia among participants living in and around Ein El Helwe Camp. Multiple factors contributed to the findings including sociodemographic, lifestyle factors and cultural aspects which should further be analysed in future studies. Additionally, glycemia levels should be monitored for more reliable findings in future studies.
YAP dysregulation triggers hypertrophy by CCN2 secretion and TGFβ uptake in human pluripotent stem cell-derived cardiomyocytes
Authors: Chirikian Orlando , Faynus Mohamed A. , Merk Markus , Singh Zachary , Muray Christopher , Pham Jeffrey , Chialastri Alex , Vander Roest Alison , Goldstein Alex , Pyle Trevor , Lane Kerry V. , Roberts Brock , Smith Jacqueline E. , Gunawardane Ruwanthi N. , Sniadecki Nathan J. , Mack David L. , Davis Jennifer , Bernstein Daniel , Streichan Sebastian J. , Clegg Dennis O. , Dey Siddharth S. , Wilson Maxwell Z. , Pruitt Beth L.
Published: June 2024

Hypertrophy Cardiomyopathy (HCM) is the most prevalent hereditary cardiovascular disease – affecting >1:500 individuals. Advanced forms of HCM clinically present with hypercontractility, hypertrophy and fibrosis. Several single-point mutations in b-myosin heavy chain (MYH7) have been associated with HCM and increased contractility at the organ level. Different MYH7 mutations have resulted in increased, decreased, or unchanged force production at the molecular level. Yet, how these molecular kinetics link to cell and tissue pathogenesis remains unclear. The Hippo Pathway, specifically its effector molecule YAP, has been demonstrated to be reactivated in pathological hypertrophic growth. We hypothesized that changes in force production (intrinsically or extrinsically) directly alter the homeostatic mechano-signaling of the Hippo pathway through changes in stresses on the nucleus. Using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), we asked whether homeostatic mechanical signaling through the canonical growth regulator, YAP, is altered 1) by changes in the biomechanics of HCM mutant cardiomyocytes and 2) by alterations in the mechanical environment. We use genetically edited hiPSC-CM with point mutations in MYH7 associated with HCM, and their matched controls, combined with micropatterned traction force microscopy substrates to confirm the hypercontractile phenotype in MYH7 mutants. We next modulate contractility in healthy and disease hiPSC-CMs by treatment with positive and negative inotropic drugs and demonstrate a correlative relationship between contractility and YAP activity. We further demonstrate the activation of YAP in both HCM mutants and healthy hiPSC-CMs treated with contractility modulators is through enhanced nuclear deformation. We conclude that the overactivation of YAP, possibly initiated and driven by hypercontractility, correlates with excessive CCN2 secretion (connective tissue growth factor), enhancing cardiac fibroblast/myofibroblast transition and production of known hypertrophic signaling molecule TGFβ. Our study suggests YAP being an indirect player in the initiation of hypertrophic growth and fibrosis in HCM. Our results provide new insights into HCM progression and bring forth a testbed for therapeutic options in treating HCM.

Graphical Abstract
CDK12 controls transcription at damaged genes and prevents MYC-induced transcription-replication conflicts
Authors: Curti Laura , Rohban Sara , Bianchi Nicola , Croci Ottavio , Andronache Adrian , Barozzi Sara , Mattioli Michela , Ricci Fernanda , Pastori Elena , Sberna Silvia , Bellotti Simone , Accialini Anna , Ballarino Roberto , Crosetto Nicola , Wade Mark , Parazzoli Dario , Campaner Stefano
Published: June 2024

Oncogene-induced replicative stress is a potent tumor-suppressive mechanism that must be kept in check for cancer cells to thrive. Thus, the identification of genes and pathways involved in replicative stress is key to understand cancer evolution and to identify prospective therapeutic targets. Here, we investigated factors that modulate replicative stress upon deregulation of the MYC oncogene. We identified the cyclin-dependent kinase CDK12 as selectively required to prevent transcription-replication conflicts and the activation of a cytotoxic DNA-damage response (DDR). At the mechanistic level, CDK12 was recruited to damaged genes by PARP-dependent DDR-signaling and elongation-competent RNAPII. Once recruited, CDK12 repressed transcription by preventing the association of CDK9 with RNAPII. Either loss or chemical inhibition of CDK12 led to DDR-resistant transcription at damaged genes. Genome-wide profiling revealed that loss of CDK12 exacerbated transcription-replication conflicts in MYC-overexpressing cells and led to the accumulation of double-strand DNA breaks (DSBs), occurring preferentially between early- replicating regions and transcribed genes, organized in a co-directional head-to-tail orientation. Overall, our data demonstrate that CDK12 protects genome integrity by repressing transcription of damaged genes, which is required for proper resolution of DSBs at oncogene-induced transcription-replication conflicts. This provides a rationale that explains both how CDK12 deficiency can promote tandem duplications of early-replicated regions during tumor evolution, and how CDK12 targeting can exacerbate replicative-stress in tumors.
HDAC1 acts as tumor suppressor in ALK-positive anaplastic large-cell lymphoma: Implications for HDAC inhibitor therapy
Authors: Zrimšek Maša , Draganić Kristina , Malzer Anna , Doblmayr Verena , de Freitas e Silva Rafael , Wohlhaupter Sabrina , Perez Malla Carlos Uziel , Mišura Katarina , Fischer Heinz , Schachner Helga , Schiefer Ana-Iris , Sheibani-Tezerji Raheleh , Ellmeier Wilfried , Seiser Christian , Egger Gerda
Published: June 2024

Histone deacetylases (HDACs) play essential roles in T cell development, and several HDAC inhibitors (HDACi) have gained approval for treating peripheral T cell lymphomas. In this study, we investigated the effects of genetic or pharmacological HDAC inhibition on NPM-ALK positive anaplastic large cell lymphoma (ALCL) development to elucidate potential contraindications or indications for the use of HDACi for the treatment of this rare T-cell lymphoma. Short-term systemic pharmacological inhibition of HDACs using the class I-specific HDACi Entinostat in a premalignant ALCL mouse model postponed or even abolished lymphoma development, despite high expression of the NPM-ALK fusion oncogene. To further disentangle the effects of systemic HDAC inhibition from thymocyte intrinsic effects, conditional genetic deletions of highly homologous class I HDAC1 and HDAC2 enzymes were employed. In sharp contrast to the systemic inhibition, T cell-specific deletion ofHdac1orHdac2in the ALCL mouse model significantly accelerated NPM-ALK-driven lymphomagenesis, withHdac1loss having a more pronounced effect. Integration of gene expression and chromatin accessibility data revealed thatHdac1deletion selectively perturbed cell type specific transcriptional programs, crucial for T cell differentiation and signaling. Moreover, multiple oncogenic signaling pathways, including PDGFRB signaling, were highly upregulated. The accelerated lymphomagenesis primarily depended on the catalytic activity of HDAC1, as the expression of a catalytically inactive HDAC1 protein showed similar effects to the complete knockout. Our findings underscore the tumor-suppressive function of class I HDAC1 and HDAC2 in T cells during ALCL development, however systemic pharmacological inhibition of HDACs is still a valid treatment strategy, which could potentially improve current therapeutic outcomes.
Transcription network of SLC7A11 (xCT) in colon cancer provides clinical targets for metabolic regulation and cell proliferation
Authors: Zohar Keren , Wartmann Thomas , Strecker Marco , Doelling Maximilian , Andric Mihailo , Shi Wenjie , Croner Roland S , Kakhlon Or , Zhao Yue , Kahlert Ulf D , Linial Michal
Published: June 2024

Colorectal cancer (CRC) represents the third leading cause of cancer-related deaths. Knowledge covering diverse cellular and molecular data from individual patients has become valuable for diagnosis, prognosis, and treatment selection. Here, we present in-depth comparative RNA-seq analysis of 32 CRC patients pairing tumor and healthy tissues (total of 73 samples). Strict thresholds for differential expression genes (DEG) analysis revealed an interconnection between nutrients, metabolic program, and cell cycle pathways. Among the upregulated DEGs, we focused on the Xc- system, composed of the proteins from SLC7A11 (xCT) and SLC3A2 genes, along with several interacting genes. To assess the oncogenic potency of the Xc- system in a cellular setting, we applied a knowledge-based approach, analyzing gene perturbations from CRISPR screens. The study focused on a set of 27 co-dependent genes that were strongly correlated with the fitness of SLC7A11 and SLC3A2 across many cell types. Alterations in these genes in 13 large-scale studies (e.g., by mutations and copy number variation) were found to enhance overall survival and progression-free survival in CRC patients. In agreement, the overexpression of these genes in cancer cells drives cancer progression by allowing effective management of the redox level, induction of stress response mechanisms, and most notably, enhanced activity of ion/amino acid transporters, and enzymes acting in de novo nucleotide synthesis. We also highlight the positive correlation between the Xc- system gene expression level, patient responsiveness to different chemotherapy treatments, and immune cell infiltration (e.g.,myeloid-derived suppressor cells) in CRC tumors as a measure for their immunosuppressive activity. This study illustrates that knowledge-based interpretation by synthesizing multiple layers of data leads to functional and mechanistic insights into the role of SLC7A11 and its associated genes in CRC tumorigenesis and therapeutics.
Active learning for quantum mechanical measurements
Authors: Zhu Ruidi , Pike-Burke Ciara , Mintert Florian
Published: June 2024

The experimental evaluation of many quantum mechanical quantities requires the estimation of several directly measurable observables, such as local observables. Due to the necessity to repeat experiments on individual quantum systems in order to estimate expectation values of observables, the question of how many repetitions to allocate to a given directly measurable observable arises. We show that an active learning scheme can help to improve such allocations, and the resultant decrease in experimental repetitions required to evaluate a quantity with the desired accuracy increases with the size of the underlying quantum mechanical system.

Published by the American Physical Society
2024
Selection rules in the excitation of the divacancy and the nitrogen-vacancy pair in 4
H
- and 6
H
-SiC
Authors: Shafizadeh Danial , Davidsson Joel , Ohshima Takeshi , Abrikosov Igor A. , Son Nguyen T. , Ivanov Ivan G.
Published: June 2024

In this study, we address selection rules with respect to the polarization of the optical excitation of two color centers in 4H−SiC and 6H−SiC with potential for applications in quantum technology, the divacancy and the nitrogen-vacancy pair. We show that the photoluminescence of the axial configurations of higher symmetry (C3v) than the basal ones (C1h) can be canceled using any excitation (resonant or nonresonant) with polarization parallel to the crystal axis (EL||c). The polarization selection rules are determined using group-theoretical analysis and simple physical arguments showing that phonon-assisted absorption with EL||c is prohibited despite being formally allowed by group theory. A comparison with the selection rules for the silicon vacancy, another defect with C3v symmetry, is also carried out. Using the selection rules, we demonstrate selective excitation of only one basal divacancy configuration in 4H−SiC, the PL3 line, and discuss the higher contrast and increased Debye-Waller factor in the selectively excited spectrum.

Published by the American Physical Society
2024
Eigenvalue spectra of finely structured random matrices
Authors: Poley Lyle , Galla Tobias , Baron Joseph W.
Published: June 2024

Random matrix theory allows for the deduction of stability criteria for complex systems using only a summary knowledge of the statistics of the interactions between components. As such, results like the well-known elliptical law are applicable in a myriad of different contexts. However, it is often assumed that all components of the complex system in question are statistically equivalent, which is unrealistic in many applications. Here we introduce the concept of a finely structured random matrix. These are random matrices with element-specific statistics, which can be used to model systems in which the individual components are statistically distinct. By supposing that the degree of “fine structure” in the matrix is small, we arrive at a succinct “modified” elliptical law. We demonstrate the direct applicability of our results to the niche and cascade models in theoretical ecology, as well as a model of a neural network, and a directed network with arbitrary degree distribution. The simple closed form of our central results allow us to draw broad qualitative conclusions about the effect of fine structure on stability.

Published by the American Physical Society
2024
Motivation on training transfer: a moderated moderation model of personal capacity for transfer and gender
Authors: Gara Bach Ouerdian Emna
Published: June 2024

Purpose

Previous research suggests that motivation to transfer is related to the effective transfer of training, but less is known about the boundary conditions of this relationship. Therefore, this study aims to propose that motivation to transfer is more strongly related to training transfer when employees have a stronger personal capacity for transfer. The author also hypothesizes that this two-way interaction is further moderated by gender.

Design/methodology/approach

Using a cross-sectional design and a sample of 257 Tunisian workers, a three-way interaction model with the PROCESS macro (Hayes, 2018) was used to test the hypotheses.

Findings

Results show that workers respond to motivation to transfer with increased training transfer. Personal capacity for transfer and gender moderated the proposed relationship. Thus, the interaction effect between motivation to transfer and personal capacity for transfer is significant for women but not significant for men. More specifically, motivation to transfer is more likely to predict training transfer among women with high personal capacity for transfer than among those with low.

Originality/value

This study adds to the literature on motivation to transfer and training transfer by explaining two boundary conditions in this relationship and by recognizing the conditional interaction effect of gender on the moderating effect of personal capacity for transfer.
Research trends in memes: insights from bibliometric analysis
Authors: Kamath Charunayan , Alur Sivakumar
Published: June 2024

Purpose

The growth of social media globally has led to brands adopting memes as a tool for communication. They have influenced digital culture, politics and marketing. This study aims to highlight the research gap in meme literature by profiling and science mapping.

Design/methodology/approach

This study has performed a bibliometric analysis of research papers on memes from the Scopus database. The authors profiled the literature and found the most relevant journal, author and document. Science mapping techniques such as thematic analysis, thematic evolution and co-citation of papers with content analysis were used.

Findings

Profiling of literature revealed that the most relevant journal, based on a number of papers and citations, is New Media and Society. The top researcher on memes is Shiffman L (seven papers), and the most cited author is Menczer F (717 citations). The paper titled “Towards A Unified Science of Cultural Evolution” has the highest number of citations (402). Thematic mapping revealed “Social Movements” and “Twitter” are the currently trending themes. The co-citation analysis clustered the literature into two. The first cluster elucidates the theoretical underpinnings of memes, while the second cluster explicates the various contexts in which memes are studied.

Practical implications

This study will be vital to researchers hoping to study internet memes by providing directions for future research. Furthermore, the insights from this study will enable social media managers to use memes effectively.

Originality/value

To the best of the authors’ knowledge, this study seems to be the first to use bibliometric analysis to profile and map meme literature. This study provides a new perspective for meme researchers to explore memes and suggests marketers implement novel meme-based strategies in their marketing communications.
Masculinity in Scandinavian tech entrepreneurship: male technology entrepreneurs negotiating gender (in)equality
Authors: Balkmar Dag , Lindvert Marta , Ljunggren Elisabet Carine
Published: June 2024

Purpose

Both entrepreneurship and technology are significantly gendered, and when combined in technology entrepreneurship, they make up a fundamentally masculine field. This article investigates men tech entrepreneurs' negotiations of gender and gender (in)equality. The purpose is to gain knowledge on masculinity in tech entrepreneurship and to explore what role this might play in any change towards more gender-equal entrepreneurship.

Design/methodology/approach

Semi-structured interviews were conducted with ten Swedish and Norwegian male tech entrepreneurs in tech incubators. The interviews dealt with gender (in)equality and masculinity in tech entrepreneurship. The data were coded in NVivo and inductively analysed using thematic analysis. We apply a social constructivist understanding of gender.

Findings

We categorise the male entrepreneurs' views of gender equality along “privileged”, “paradoxical” and “potential” articulations of gender (in)equality. Building on these articulations, we discuss the potential entrepreneurial men and masculinities could have for changing gender inequality in the Scandinavian tech entrepreneurship context. The findings are applicable to several entrepreneurial contexts.

Originality/value

The study contributes to further the theoretical understanding of tech entrepreneurship as a gendered phenomenon, its dynamics and its potential for change, particularly in promoting gender equality in tech entrepreneurship. Empirically, it investigates the perceptions about gender (in)equality and gender as negotiated concepts amongst male tech entrepreneurs.
Conditional accounting conservatism and financial flexibility: the Corona pandemic in the formation of legal claims
Authors: Mahmoodi Ali Asghar , Abdoli Mohammadreza , Shahri Maryam , Dehdar Farhad
Published: June 2024

Purpose

The purpose of this research is to investigate the importance and status of conditional accounting conservatism indicators and financial flexibility for the management of legal claims of the company during the outbreak of Corona.

Design/methodology/approach

The research method was implemented using statistical analysis in the SPSS environment. The participants of this research can be experts and specialists working in companies admitted to the stock exchange and expert professors in accounting fields; auditing; economy; financial engineering and financial management, categorized. The data related to the localization tool of research variables were collected by snowball sampling method in the summer of 2022.

Findings

One of the main results of the research is that based on the opinions and professional experience of experts and professionals working in companies admitted to the stock exchange and academic experts, within a range of seven, “The number of legal claims of the company with electronic businesses” under the title of the main indicator in the legal claims of the company in the outbreak of Corona from the importance dimension; “Exchange rate fluctuations in financial resilience” under the title of the main indicator in financial resilience in the Corona outbreak from the functional dimension; “The number of legal claims of the company with government institutions” under the title of the main indicator in the company’s legal claims in the Corona outbreak from the functional dimension; “The company’s conservatism score” under the title of the main indicator in the conditional conservatism of accounting in the Corona outbreak from the functional dimension; “oil price fluctuations in financial resilience” under the title of the main indicator in financial resilience in the Corona outbreak from the importance dimension; and “type of industry based on total assets” under the title of the main indicator in the conditional conservatism of accounting in the Corona outbreak was calculated from the importance dimension.

Originality/value

Although the previous literature has studied the direct correlation between accounting conservatism and financial flexibility, this work focuses on examining the direct association between accounting conservatism and financial flexibility in the post-Corona era and is carried out to resolve legal claims.
A bibliometric analysis on gamifying adult learning: past, present and future trends of learner-centered pedagogies
Authors: Por Fei Ping , Ong Christina Sook Beng , Ng Siew Keow , Din Eak Arathai
Published: June 2024

Purpose

The psychological theory of self-determination postulated that gamification enhances learning engagement by intrinsically motivating learners to undertake tasks spontaneously. Gamification has then been integrated into adult learning as part of the initiative of learner-centred pedagogies to curb the low retention rates of adult learners who struggle with heavy work commitments, family obligations and financial pressure. Gamification, being one of the technological mediations, assumes the crucial role of engaging and retaining adult learners. Adult learners have received less attention in research when compared with conventional university students. The purpose of this study is to conduct a bibliographic analysis to assess the past, present and future publication trends of gamifying adult learning and to identify the research gap.

Design/methodology/approach

This study included publications related to gamification and adult learning from 2014 to 2022, extracted from Dimensions. A total of 79,864 publications were retrieved initially, and 3,469 publications were ultimately selected for final analysis after the refinement of the keyword search. VOSviewer was used for bibliographic coupling, keyword co-occurrence, clustering and co-citation analysis of countries.

Findings

The number of publications related to gamification in adult learning has decreased since its peak in 2020. The saturation is mainly concentrated in the USA, the UK and China, with similar levels of national income and technology advancement skills. However, gamification in adult learning remains a popular and growing research area in developing countries like Malaysia, which has huge potential due to government investments in education, technology and lifelong learning. There is also an evident research gap on gamification, adult learning and personality traits, which have not been covered in previous studies.

Originality/value

Prior research mostly focused on systematic literature reviews, while the use of bibliometric analysis could be a missing link in this research domain. This paper unveils the evolution of publications on this topic over time by scientifically analysing a large number of publications and rigorously identifying research gaps contributing to future research avenues.
Bank fundamental dynamics: the role of optimal bank management
Authors: Ariefianto Moch. Doddy , Sutanto Tasha , Jesslyn Cecilia
Published: June 2024

Purpose

This study aims to investigate the dynamic relationships between profitability, credit risk, liquidity risk and capital in Indonesian banking industry.

Design/methodology/approach

The authors use a panel vector autoregression model that incorporates macroeconomic variables: growth, interest rate, foreign exchange. The analysis is based on a monthly panel data set of 88 banks spanning from January 2012 to September 2021, which comprises 10,296 bank-month observations.

Findings

Our key findings highlight (i) permanent credit cost and liquidity cost pass through practices, (ii) complementary function of liquidity and capital, (iii) earning management motivated asset write off and (iv) credit risk-liquidity risk neutrality. In addition, the authors observe that the banks demonstrated resilience to macroeconomic shocks.

Research limitations/implications

Our study have shown some interesting dynamic patterns of fundamentals; nevertheless, unified theoretical underpinning of the process is still unavailable. This should be an important future reasearch avenue.

Practical implications

The study brings significant implications for regulatory and supervisory practices aimed at enhancing the financial stability of banks.

Originality/value

We conduct estimation of Indonesian banks system in dynamic perspective and perform impulses responses.
Campus entrepreneurs’ research habits and needs: a five-year study
Authors: Toane Carey , Shujah Sarah
Published: June 2024

Purpose

This study surveyed the entrepreneurship community on a large university campus in 2016 and in 2020 to identify and understand its information habits and needs. User needs can inform service design and assessment, as well as inform approaches to reference interactions. Librarians are encouraged to conduct similar surveys to better understand this niche population.

Design/methodology/approach

Investigators employed repeated cross-sectional design, a longitudinal research approach that draws on samples of non-overlapping or minimally overlapping cases over time. Qualitative and quantitative data were collected using online survey instruments. Data collected included demographic information, venture characteristics, participation in institutional activities such as accelerator programs and credit courses, general startup research behaviors and needs, and details of a specific instance of business or market research as well as interaction with the library and access to training. Triangulation of semantic and episodic was applied to draw reliable conclusions about respondent behavior.

Findings

In both surveys, over half of respondents were students and 75% of respondents were engaged in startup activity, most at the early stages. While respondent demographics, type and purpose of information sought remained constant between the two surveys, awareness and use of the library rose on several metrics. Coding revealed insights into respondents’ attitudes toward and strategies for secondary business research. Information obtained during the research process had a moderate impact on their ventures. These findings informed the development of library research and instruction services, programs, and collections for entrepreneurs.

Originality/value

The repeated cross-sectional design of the study is unique and shows trends in the community over time. The mixed-methods approach provides a robust and nuanced portrait of the community. These findings informed the development and assessment of library research and instruction services, programs and collections for entrepreneurs.