bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards anchoring evolutionary fitness for protein stability with virtual chemical environment recovery
Authors: Nie Zhiwei , Ma Yiming , Chen Jie , Liu Yutian , Liu Zhihong , Yang Peng , Xu Fan , Huang Xiansong , Yin Feng , Li Zigang , Fu Jie , Ren Zhixiang , Zhang Wen-Bin , Gao Wen , Tian Yonghong
Published: April 2024

Protein stability offers valuable insights into protein folding and functionality, making it an integral component of evolutionary fitness. Previous computational methods possess both strengths and weaknesses, leading to practical and inter-pretational limitations. Here, we propose an interpretable protein stability change prediction method, S3C, to anchor evolutionary fitness for protein stability with virtual chemical environment recovery. S3C first gets rid of the shackles of high-resolution protein structure data and restores the local chemical environments of the mutations at the sequence level. Subsequently, S3C promotes the evolutionary fitness of protein stability to dominate the fitness landscape under the selective pressure. Naturally, S3C comprehensively outperforms state-of-the-art methods on benchmark datasets while showing ideal generalization when migrated to unseen protein families. More importantly, S3C is demonstrated to be interpretable at multiple scales, including high-fidelity recovery of local structure micro-environment, perception of intricate interaction reconstruction, and accurate mining of rare beneficial mutations. S3C expands the boundaries of protein evolution prediction and provides an ideal candidate for large-scale optimization of protein engineering.
Differences in chromatin accessibility between renal cortex and inner medulla correlate with spatial differences in gene expression and are modulated by NFAT5 function
Authors: Engel Kristina , Chernyakov Dmitry , Nerger Katrin , Sameith Katrin , Dahl Andreas , Edemir Bayram
Published: April 2024

A spatial gene expression pattern between the cortex (CTX) and inner medulla (IM) of the kidney has been observed, but the underlying mechanisms are unclear. Understanding these mechanisms is essential for elucidating renal function. Using the Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) we analyzed the open chromatin structures and the involvement of epigenetic mechanisms in mediating gene expression differences between the renal CTX and IM. We also examined the role of the nuclear factor of activated T cells 5 (NFAT5), a key regulator of hypertonicity. ATAC-seq analysis was performed on CTX and IM samples from both wild-type (WT) and NFAT5 knockout (KO) mice.

This work demonstrates for the first time that these differences in gene expression between renal CTX and IM are associated with an epigenetic mechanism driven by chromatin accessibility, which is partially modulated by the nuclear factor of activated T-cells 5 (NFAT5) in mice. Furthermore, spatial localization and NFAT5-promoted chromatin accessibility correlate with differential gene expression and altered promoter binding motif enrichment in CTX and IM.

This study provides new insights into the spatial and NFAT5-mediated regulation of chromatin accessibility and gene expression in CTX and IM. This work advances our understanding of kidney physiology by uncovering previously unknown epigenetic factors influencing gene expression and provides a new perspective on renal adaptive mechanisms.

TRANSLATIONAL STATEMENT

The study reveals new insights into the spatial and epigenetic regulation of gene expression in the renal cortex (CTX) and inner medulla (IM) in the mouse kidney. We used the Assay for Transposase-Accessible Chromatin with High-Throughput Sequence Analysis (ATAC-seq) to identify a key role of NFAT5 in modulating chromatin accessibility and to uncover previously unknown epigenetic factors. This research enhances our understanding of renal physiology and has important implications for clinical care by providing insights into potential adaptive mechanisms in the kidney. These findings suggest future investigations targeting epigenetic signaling pathways for therapeutic intervention in renal diseases.
CTHRC1+Fibroblasts andSPP1+Macrophages Synergistically Contribute to Pro-Tumorigenic Tumor Microenvironment in Pancreatic Ductal Adenocarcinoma
Authors: Li Evan , Cheung Hoi Ching , Ma Shuangge
Published: April 2024

Pancreatic ductal adenocarcinoma (PDAC) is an extremely lethal cancer that accounts for over 90% of all pancreatic cancer cases. With a 5-year survival rate of only 13%, PDAC has proven to be extremely desmoplastic and immunosuppressive to most current therapies, including chemotherapy and surgical resection. In recent years, focus has shifted to understanding the tumor microenvironment (TME) around PDAC, enabling a greater understanding of biological pathways and intercellular interactions that can ultimately lead to potential for future drug targets. In this study, we leverage a combination of single-cell and spatial transcriptomics to further identify cellular populations and interactions within the highly heterogeneous TME. We demonstrate thatSPP1+APOE+tumor-associated macrophages (TAM) andCTHRC1+GREM1+cancer-associated myofibroblasts (myCAF) not only act synergistically to promote an immune-suppressive TME through active extracellular matrix (ECM) deposition and epithelial mesenchymal transition (EMT), but are spatially colocalized and correlated, leading to worse prognosis. Our results highlight the crosstalk between stromal and myeloid cells as a significant area of study for future therapeutic targets to treat cancer.
Mating proximity blinds threat perception.
Authors: Cazale Debat Laurie , Scheunemann Lisa , Day Megan , Fernandez d V Alquicira Tania , Dimtsi Anna , Zhang Youchong , Blackburn Lauren Amelia , Ballardini Charles Henry Maurice , Greenin Whitehead Katie , Reynolds Eric , Lin Andrew C , Owald David , Rezaval Carolina
Published: April 2024

Romantic engagement can bias sensory perception. This 'love blindness' reflects a common behavioral principle across organisms: favoring pursuit of a coveted reward over potential risks. In the case of animal courtship, such sensory biases may support reproductive success but can also expose individuals to danger, such as predation. How do neural networks balance the trade-off between risk and reward? Here, we discover a dopamine-governed filter mechanism in male Drosophila that reduces threat perception as courtship progresses. We show that during early courtship stages, threat-activated visual neurons inhibit central courtship nodes via specific serotonergic neurons. This serotonergic inhibition prompts flies to abort courtship when they see imminent danger. However, as flies advance in the courtship process, the dopaminergic filter system reduces visual threat responses, shifting the balance from survival to mating. By recording neural activity from males as they approach mating, we demonstrate that progress in courtship is registered as dopaminergic activity levels ramping up. This dopamine signaling inhibits the visual threat detection pathway via Dop2R receptors, allowing male flies to focus on courtship when they are close to copulation. Thus, dopamine signaling biases sensory perception based on perceived goal proximity, in order to prioritize between competing behaviors.
Advanced MRI Prediction Model for Anatomical Site Identification in Uterine Carcinoma: Enhancing Diagnostic Accuracy and Treatment Planning
Authors: Malek Mahrooz , moayeri Moneereh , Akhavan Setareh , Hasani Shahrzad Sheikh , Nili Fatemeh , Mahboubi-Fooladi Zahra
Published: April 2024

Introduction

The uterine carcinoma is the most commonly diagnosed malignancy in female pelvis. Accurate identification of tumor origin is crucial for determining appropriate treatment approaches. This study aims to develop a prediction model using multiple MRI parameters to accurately diagnose uterine cancer with an indistinctive origin and those involving both the endometrium and cervix prior to treatment.

Material and methods

This prospective cohort study was conducted from January 2020 to January 2021, and included patients aged 20-80 who were newly diagnosed with uterine carcinoma who underwent MRI and were considered for hysterectomy within 6 months after MRI.

Results

In our study, a total of 78 patients with uterine carcinoma were enrolled. the final diagnosis was confirmed as follows: 20 were adenocarcinoma of the cervix, 27 were SCC of the cervix, and 31 were endometrial adenocarcinoma. Certain imaging features were found to be consistent with cervical carcinoma, included parametrial invasion (69.6%), vaginal invasion (66%), stromal invasion (95.7%), and peripheral rim enhancement (68.9%). On post-contrast sequences, cervical cancer appeared hyperintense compared to the myometrium, while endometrial cancer appeared hypointense (96.8%). Endometrial carcinoma was well diagnosed by the presence of an endometrial cavity mass (100%), deep myometrium invasion (>50%) (54.8%), and a greater size in the craniocaudal dimension compared to the transverse dimension (100%).

Discussion

The study found that certain morphologic features were reliable indicators for detecting cervical carcinoma, including vaginal, stromal, and parametrial invasions, the presence of hypervascularity and peripheral rim enhancement. On the other hand, myometrial invasion and the presence of a mass in the endometrial cavity were significantly higher in endometrial carcinoma.
Glutaredoxin 3 (GLRX3) confers a fusion oncogene-dependent vulnerability to Ewing sarcoma
Authors: Vinca Endrit , Ehlers Anna C. , Ritter Alina , Obermeier David , Funk Cornelius M. , Geyer Florian H. , Schmucker Melissa , Li Jing , Zimmermann Malenka , Ceranski A. Katharina , Fuchslocher Fabia , Mertens Christina , Qiu Ruiyue , Muckenthaler Martina M. , Dahlhaus Alina , von Karstedt Silvia , Imle Roland , Banito Ana , Alonso Javier , Peterziel Heike , Witt Olaf , Oehme Ina , Cidre-Aranaz Florencia , Grünewald Thomas G. P. , Ohmura Shunya
Published: April 2024

Ewing sarcoma (EwS) is a highly aggressive bone and soft-tissue associated cancer for which there are no effective targeted therapeutics available. Genetically, EwS is driven by aberrantly active EWSR1::ETS fusion transcription factors, most commonly EWSR1::FLI1. Despite their unique expression in EwS, all attempts to effectively target these fusion oncoproteins clinically were not yet successful, wherefore alternative targets are required.

Here, we functionally characterize the evolutionarily conserved oxidative stress regulator glutaredoxin 3 (GLRX3) as a EwS-specific and EWSR1::FLI1-dependent vulnerability. Through integration of transcriptome-profiling, conditional drug screens in 3D cultures, and functional experiments, we discover that GLRX3 promotes EwS growth in vitro and in vivo, and that it has a key role in mitigation of oxidative stress and maintenance of iron homeostasis. These GLRX3 functions can be exploited in both GLRX3-high and -low expressing EwS cells by targeted therapeutics including CDK4/6 inhibitors and inducers of apoptotic and ferroptotic cell death. Collectively, our results exemplify how the interplay of an evolutionarily conserved oxidative stress regulator with a dominant oncogene can promote malignancy but provide opportunities for predictive diagnostics and personalized therapy.
Evidence of SARS-CoV-2 JN.2.5 variant circulation in Rio de Janeiro, Brazil
Authors: de Menezes Mariane Talon , Velozo Camila de Almeida , Moreira Filipe Romero Rebello , Mariani Diana , Nascimento Érica Ramos dos Santos , Gonçalves Cássia Cristina Alves , Boullosa Lídia Theodoro , Cordeiro Thais Félix , Oliveira Gleidson Silva , Carneiro Maria Cecília da Cunha , Valdez Cinthia Francisca , Faria Natacha Cunha de Araujo , da Silva Bianca Ortiz , Galliez Rafael Mello , Rossi Átila Duque , Voloch Carolina Moreira , Castiñeiras Terezinha Marta Pereira Pinto , Tanuri Amilcar
Published: April 2024

New SARS-CoV-2 variants are continually emerging and have the potential to present challenges to public health responses worldwide. This report discusses the early detection of the lineage JN.2.5 (alias of B.1.1.529.2.86.1.2.5) in Rio de Janeiro, Brazil. The variant was identified in early 2024 through viral whole-genome sequencing and phylogenetic analysis, revealing that circulating strains present genetic similarities to sequences reported in Canada, Poland, Belgium, and England. While the circulation of diverse Omicron sub lineages has significantly impacted COVID-19 epidemiology in Brazil, the consequences of the circulation of the novel variant are uncertain. Considering its immunological escape capabilities and epidemiological behavior observed elsewhere, close monitoring of this variant epidemiology is recommended.
Increased galanin-galanin receptor 1 signaling, inflammation, and insulin resistance are associated with affective symptoms and chronic fatigue syndrome due to Long COVID
Authors: Al Masoodi Wasim Talib Mahdi , Radhi Sami Waheed , Abdalsada Habiba Khdair , Niu Menqi , Al-Hakeim Hussein Kadhem , Maes Michael
Published: April 2024

Background

Long COVID (LC) patients frequently suffer from neuropsychiatric symptoms, including depression, anxiety, and chronic fatigue syndrome (CFS), relabeled as the physio-affective phenome of LC. Activated immune-inflammatory pathways and insulin resistance key play a role in these physio-affective symptoms due to LC.

Aims

To examine the associations between the Hamilton Depression (HAMD), Hamilton Anxiety (HAMA) and Fibro-Fatigue (FF) Rating Scale scores and serum C-reactive protein (CRP), prostaglandin E2 (PGE2), galanin-galanin receptor 1 (GAL-GALR1) signaling, insulin resistance, insulin-like growth factor (IGF-1), plasminogen activator inhibitor-1 (PAI1), and damage biomarkers such as S100B and neuron-specific enolase (NSE) in 90 subjects 3-6 months after acute SARS-CoV-2 infection.

Results

LC patients show higher HAMD, HAMA, and FF scores, CRP, PGE2, GAL-GALR1 signaling, insulin resistance, PAI1, NSE, and S100B than participants without LC. The HAMD/HAMA/FF scores were significantly correlated with PGE, CRP, GAL, GALR1, insulin resistance, and PAI1 levels, and a composite score based on peak body temperature (PBT) – oxygen saturation (SpO2) (PBT/SpO2 index) during the acute infectious phase. A large part of the variance in the affective and CFS symptoms (33.6%-42.0%) was explained by a combination of biomarkers; the top-3 most important biomarkers were GAL-GALR1 signaling, PGE2, and CRP. Inclusion of the PBT/SpO2 index increased the prediction considerably (55.3%-67.1%). The PBT/SpO2 index predicted the increases in GAL-GALR1 signaling.

Conclusions

These findings suggest that the affective symptoms and CFS of Long COVID are largely the consequence of activated immune-inflammatory pathways, metabolic aberrations, and the severity of the inflammation during acute SARS-CoV-2 infection.
Incidence and risk factors associated with acquired syphilis in HIV pre-exposure prophylaxis users
Authors: Pedrosa Nathália Lima , Pinheiro Patrícia Matias , Filho Fernando Wagner Brito Hortêncio , de Araujo Wildo Navegantes
Published: April 2024

Background

Acquired syphilis continues to affect millions of people around the world. It is crucial to study it in the context of HIV Pre-Exposure Prophylaxis (PrEP) to achieve the goals set out in the 2030 Agenda since the literature suggests increased risk behaviors for sexually transmitted infections. This study aimed to investigate the incidence and factors associated with acquired syphilis among PrEP users.

Materials and methods

This retrospective cohort included data on PrEP users from all over Brazil from 2018 to 2020, obtained from the national antiretroviral logistics system. We calculated the proportion of syphilis before PrEP, the incidence during the user’s follow-up, reinfections, and their possible associated factors. We conducted descriptive, bivariate, and multivariate analysis, estimating the crude Relative Risk, adjusted Odds Ratio (aOR), and their respective confidence intervals (95%CI).

Results

Most of the 34,000 individuals who started PrEP were male (89.0%), white (53.7%), self-identified as male (85.2%), homosexual, gay, or lesbian (72.2%), and had 12 schooling years or more (67.8%). Of these, 8.3% had syphilis in the six months before starting PrEP, and 4% had it in the first 30 days of using the prophylaxis. In the 19,820 individuals effectively monitored, the incidence of acquired syphilis was 19.1 cases per 100 person-years, and 1.9% of users had reinfection. The multivariate analysis identified female gender (aOR 0.3; 95%CI 0.2-0.5), being white or Black (aOR 0.9; 95%CI 0.7-0.9 and aOR 0.7; 95%CI 0.7-0.99, respectively) as protective factors for syphilis. Being homosexual, gay, lesbian (aOR 2.7; 95%CI 2.0-3.7) or having a history of syphilis in the six months before PrEP (aOR 2.2; 95%CI 1.9-2.5) were risk factors for syphilis during PrEP use. Behaviors related to the risk of syphilis included accepting something in exchange for sex (aOR 1.6; 95%CI 1.3-1.9), irregular condom use (use in less than half of sexual intercourse sessions; aOR 1.7; 95%CI 1.53-2.1) and recreational drug use (poppers; aOR 1.5; 95%CI 1.53-2.1).

Conclusion

Syphilis in the context of PrEP has high rates and is associated with sociodemographic and behavioral factors. We recommend additional studies targeting prevention in this population to curb these figures.
Pace of Aging in older adults matters for healthspan and lifespan
Authors: Balachandran A , Pei H , Shi Y , Beard J , Caspi A , Cohen A , Domingue BW , Eckstein Indik C , Ferrucci L , Furuya A , Kothari M , Moffitt TE , Ryan C , Skirbekk V , Zhang Y , Belsky DW
Published: April 2024

As societies age, policy makers need tools to understand how demographic aging will affect population health and to develop programs to increase healthspan. The current metrics used for policy analysis do not distinguish differences caused by early-life factors, such as prenatal care and nutrition, from those caused by ongoing changes in people’s bodies due to aging. Here we introduce an adapted Pace of Aging method designed to quantify differences between individuals and populations in the speed of aging-related health declines. The adapted Pace of Aging method, implemented in data from the US Health and Retirement Study and English Longitudinal Study of Aging (N=21,463), integrates longitudinal data on blood biomarkers, physical measurements, and functional tests. It reveals stark differences in rates of aging between population subgroups and demonstrates strong and consistent prospective associations with incident morbidity, disability, and mortality. Pace of Aging can advance the population science of healthy longevity.
Accurate spatial quantification in computational pathology with multiple instance learning
Authors: Gao Zeyu , Mao Anyu , Dong Yuxing , Wu Jialun , Liu Jiashuai , Wang ChunBao , He Kai , Gong Tieliang , Li Chen , Crispin-Ortuzar Mireia
Published: April 2024

Spatial quantification is a critical step in most computational pathology tasks, from guiding pathologists to areas of clinical interest to discovering tissue phenotypes behind novel biomarkers. To circumvent the need for manual annotations, modern computational pathology methods have favoured multiple-instance learning approaches that can accurately predict whole-slide image labels, albeit at the expense of losing their spatial awareness. We prove mathematically that a model using instance-level aggregation could achieve superior spatial quantification without compromising on whole-slide image prediction performance. We then introduce a superpatch-based measurable multiple instance learning method, SMMILe, and evaluate it across 6 cancer types, 3 highly diverse classification tasks, and 8 datasets involving 3,850 whole-slide images. We benchmark SMMILe against 9 existing methods, and show that in all cases SMMILe matches or exceeds state-of-the-art whole-slide image classification performance while simultaneously achieving outstanding spatial quantification.
Cohort profile: the Johns Hopkins COVID Long Study (JHCLS), a United States Nationwide Prospective Cohort Study
Authors: Wentz Eryka , Ni Zhanmo , Yenokyan Karine , Vergara Candelaria , Pahwa Jessica , Kammerling Thea , Xiao Pu , Duggal Priya , Lau Bryan , Mehta Shruti H.
Published: April 2024

Purpose

COVID-19 disease continues to affect millions of individuals worldwide, both in the short and long term. The post-acute complications of SARS-CoV-2 infection, referred to as long COVID, result in diverse symptoms affecting multiple organ systems. Little is known regarding how the symptoms associated with long COVID progress and resolve over time. The Johns Hopkins COVID Long Study aims to prospectively examine the short- and long-term consequences of COVID-19 disease in individuals both with and without a history of SARS-CoV-2 infection using self-reported data collected in an online survey.

Participants

Sixteen thousand, seven hundred sixty-four adults with a history of SARS-CoV-2 infection and 799 adults without a history of SARS-CoV-2 infection who completed an online baseline survey.

Findings to date

This cohort profile describes the baseline characteristics of the Johns Hopkins COVID Long Study. Among 16,764 participants with a history of SARS-CoV-2 infection and defined long COVID status, 75% reported a good or excellent health status prior to infection, 99% reported experiencing at least one COVID-19 symptom during the acute phase of infection, 9.9% reported a hospitalization, and 63% were defined as having long COVID using the WHO definition.

Future plans

Analysis of longitudinal data will be used to investigate the progression and resolution of long COVID symptoms over time.
MOSAIC enablesin situsaturation mutagenesis of genes and CRISPR prime editing guide RNA optimization in human cells
Authors: Hsu Jonathan Y. , Lam Kin Chung , Shih Justine , Pinello Luca , Joung J. Keith
Published: April 2024

CRISPR prime editing offers unprecedented versatility and precision for the installation of genetic editsin situ. Here we describe the development and characterization of the Multiplexing Of Site-specific Alterations forIn situCharacterization (MOSAIC) method, which leverages a non-viral PCR-based prime editing method to enable rapid installation of thousands of defined edits in pooled fashion. We show that MOSAIC can be applied to performin situsaturation mutagenesis screens of: (1) theBCR-ABL1fusion gene, successfully identifying known and potentially new imatinib drug-resistance variants; and (2) theIRF1untranslated region (UTR), re-confirming non-coding regulatory elements involved in transcriptional initiation. Furthermore, we deployed MOSAIC to enable high-throughput, pooled screening of hundreds of systematically designed prime editing guide RNA (pegRNA) constructs for a large series of different genomic loci. This rapid screening of >18,000 pegRNA designs identified optimized pegRNAs for 89 different genomic target modifications and revealed the lack of simple predictive rules for pegRNA design, reinforcing the need for experimental optimization now greatly simplified and enabled by MOSAIC. We envision that MOSAIC will accelerate and facilitate the application of CRISPR prime editing for a wide range of high-throughput screens in human and other cell systems.
Detection of tomato brown rugose fruit virus in environmental residues: the importance of contextualizing test results
Authors: Giesbers Anne K.J. , Vogel Elise , Skelton Anna , Zisi Zafeiro , Wildhagen Mandy , Loh Yue L. , Ghijselings Lucas , Groothuismink Johanne , Westenberg Marcel , Matthijnssens Jelle , Roenhorst Annelien , Vos Christine , Fox Adrian , Botermans Marleen
Published: April 2024

Tomato brown rugose fruit virus (ToBRFV) is regulated as a quarantine pest in many countries worldwide. To assess whether ToBRFV is present in cultivations, plants or seed lots, testing is required. The interpretation of test results, however, can be challenging. Real-time RT-PCR results, even though considered “positive”, may not always signify plant infection or indicate the presence of infectious virus, but could be due to the presence of viral residues in the environment. Here, case studies from the Netherlands, Belgium, and the United Kingdom address questions regarding the detection of ToBRFV in various settings, and the infectiousness of ToBRFV positive samples. These exploratory analyses demonstrate widespread detection of ToBRFV in diverse samples and environments. ToBRFV was detected inside and around greenhouses with no prior history of ToBRFV infection, on different materials and surfaces including those that were untouched by individuals, plants, or objects. This suggested the dispersal of viral residues through aerosols. ToBRFV or its residues were more often detected in areas with nearby tomato production yet were also found in a wider environment extending beyond infected crops. Given that ToBRFV originating from environmental contamination may or may not be infectious, adds complexity to decision-making in response to positive test results. Contextual information, such as the origin of the sample and the likelihood of residues from prior cultivations and/or the broader environment, is important for interpreting test results. A nuanced approach is crucial to correctly interpret ToBRFV test results, necessitating further research to support risk assessment.
The transcription factor ZNF469 regulates collagen production in liver fibrosis
Authors: Steinhauser Sebastian , Estoppey David , Buehler Dennis P. , Xiong Yanhua , Pizzato Nicolas , Rietsch Amandine , Wu Fabian , Leroy Nelly , Wunderlin Tiffany , Claerr Isabelle , Tropberger Philipp , Müller Miriam , Davison Lindsay M. , Sheng Quanhu , Bergling Sebastian , Wild Sophia , Moulin Pierre , Liang Jiancong , English Wayne J. , Williams Brandon , Knehr Judith , Altorfer Marc , Reyes Alejandro , Mickanin Craig , Hoepfner Dominic , Nigsch Florian , Frederiksen Mathias , Flynn Charles R. , Fodor Barna D. , Brown Jonathan D. , Kolter Christian
Published: April 2024

Non-alcoholic fatty liver disease (NAFLD) - characterized by excess accumulation of fat in the liver - now affects one third of the world’s population. As NAFLD progresses, extracellular matrix components including collagen accumulate in the liver causing tissue fibrosis, a major determinant of disease severity and mortality. To identify transcriptional regulators of fibrosis, we computationally inferred the activity of transcription factors (TFs) relevant to fibrosis by profiling the matched transcriptomes and epigenomes of 108 human liver biopsies from a deeply-characterized cohort of patients spanning the full histopathologic spectrum of NAFLD. CRISPR-based genetic knockout of the top 100 TFs identified ZNF469 as a regulator of collagen expression in primary human hepatic stellate cells (HSCs). Gain- and loss-of-function studies established that ZNF469 regulates collagen genes and genes involved in matrix homeostasis through direct binding to gene bodies and regulatory elements. By integrating multiomic large-scale profiling of human biopsies with extensive experimental validation we demonstrate that ZNF469 is a transcriptional regulator of collagen in HSCs. Overall, these data nominate ZNF469 as a previously unrecognized determinant of NAFLD-associated liver fibrosis.
Post-translational cleavage of Mei5 of Dmc1 mediator, Mei5-Sae3 complex, in yeast meiosis
Authors: Mwaniki Stephen , Sawant Priyanka , Osemwenkhae Osaretin P. , Fujita Yurika , Ito Masaru , Furukohri Asako , Shinohara Akira
Published: April 2024

Interhomolog recombination in meiosis is mediated by the Dmc1 recombinase. The Mei5-Sae3 complex ofS. cerevisiaepromotes Dmc1 assembly and functions with Dmc1 for homology-mediated repair of meiotic DNA double-strand breaks. How Mei5-Sae3 facilitates Dmc1 assembly remains poorly understood. In this study, we created and characterized severalmei5mutants featuring the amino acid substitutions of basic residues. We found that Arg97 of Mei5, conserved in its ortholog, SFR1(complex with SWI5), RAD51 mediator, in humans and other organisms, is critical for complex formation with Sae3 for Dmc1 assembly. Moreover, the substitution of Arg117 with Ala in Mei5 resulted in the production of a C-terminal truncated Mei5 protein during yeast meiosis. Notably, the shorter Mei5-R117A protein was observed in meiotic cells but not in mitotic cells when expressed, suggesting a unique regulation of Dmc1-mediated recombination by post-translational processing of Mei5-Sae3.
Promise of Future Searches for Cosmic Topology
Authors: Akrami Yashar , Anselmi Stefano , Copi Craig J. , Eskilt Johannes R. , Jaffe Andrew H. , Kosowsky Arthur , Petersen Pip , Starkman Glenn D. , González-Quesada Kevin , Güngör Özenç , Mihaylov Deyan P. , Saha Samanta , Tamosiunas Andrius , Taylor Quinn , Vardanyan Valeri ,   COMPACT Collaboration
Published: April 2024

The shortest distance around the Universe through us is unlikely to be much larger than the horizon diameter if microwave background anomalies are due to cosmic topology. We show that observational constraints from the lack of matched temperature circles in the microwave background leave many possibilities for such topologies. We evaluate the detectability of microwave background multipole correlations for sample cases. Searches for topology signatures in observational data over the large space of possible topologies pose a formidable computational challenge.

Published by the American Physical Society
2024
Chern-Simons Modified RPA-Eliashberg Theory of the
ν=12+12
Quantum Hall Bilayer
Authors: Lotrič Tevž , Simon Steven H.
Published: April 2024

The ν=12+12 quantum Hall bilayer has been previsously modeled using Chern-Simons-RPA-Eliashberg (CSRPAE) theory to describe pairing between the two layers. However, these approaches are troubled by a number of divergences and ambiguities. By using a “modified” RPA approximation to account for mass renormalization, we can work in a limit where the cyclotron frequency is taken to infinity, effectively projecting to a single Landau level. This, surprisingly, controls the important divergences and removes ambiguities found in prior attempts at CSRPAE. Examining BCS pairing of composite fermions we find that the angular momentum channel l=+1 dominates for all distances d between layers and at all frequency scales. Examining BCS pairing of composite fermion electrons in one layer with composite fermion in the opposite layer, we find the l=0 pairing channel dominates for all d and all frequencies. The strength of the pairing in these two different descriptions of the same phase of matter is found to be almost identical. This agrees well with our understanding that these are two different but dual descriptions of the same phase of matter.

Published by the American Physical Society
2024
How to evaluate students’ decisions in a data comparison problem: Correct decision for the wrong reasons?
Authors: Kok Karel , Chroszczinsky Sophia , Priemer Burkhard
Published: April 2024

Data comparison problems are used in teaching and science education research that focuses on students’ ability to compare datasets and their conceptual understanding of measurement uncertainties. However, the evaluation of students’ decisions in these problems can pose a problem: e.g., students making a correct decision for the wrong reasons. Three previous studies, that share the same context and data comparison problem but where participants had increasing conceptual knowledge of measurement uncertainties, are revisited. The comparison shows a troublesome result: increasing conceptual knowledge does not lead to better decision making in the data comparison problem. In this research, we have looked into this apparent discrepancy by comparing and reanalyzing the data from these three studies. We have analyzed students’ justifications by coding them based on the compared quantity and the deciding criterion, giving a highly detailed insight into what they do when comparing the datasets. The results show clear differences in the quality of the justifications across the studies and by combining the results with the decisions, we could successfully identify four cases of correct and incorrect decisions for right or wrong reasons. This analysis showed a high prevalence of correct decisions for wrong reasons in two of the studies, resolving the discrepancy in the initial comparison of these studies. The implication of our analysis is that simply asking students to make a decision in data comparison problems is not a suitable probe to gauge their ability to compare datasets or their conceptual understanding of measurement uncertainties and a probe like this should always be complemented by an analysis of the justification.

Published by the American Physical Society
2024
Frugal random exploration strategy for shape recognition using statistical geometry
Authors: Hidalgo-Caballero Samuel , Cassinelli Alvaro , Fort Emmanuel , Labousse Matthieu
Published: April 2024

Very distinct strategies can be deployed to recognize and characterize an unknown environment or a shape. A recent and promising approach, especially in robotics, is to reduce the complexity of the exploratory units to a minimum. Here, we show that this frugal strategy can be taken to the extreme by exploiting the power of statistical geometry and introducing different invariant features. We show that an elementary robot devoid of any orientation or location system, exploring randomly, can access global information about an environment such as the values of the explored area and perimeter. The explored shapes are of arbitrary geometry and may even nonconnected. From a dictionary, this most simple robot can thus identify various shapes such as famous monuments and even read a text.

Published by the American Physical Society
2024
Dimeric ethyltin(IV)–dibromide–hydroxide–N,N-dimethylformamide
Authors: Klecker Christopher Jan , Reuter Hans
Published: April 2024

Di-μ-hydroxido-bis[dibromido(dimethylformamide-κO)ethyltin(IV)], [Sn2Br4(C2H5)2(OH)2(C3H7NO)2], was prepared from ethyltin(IV) bromide and N,N-dimethylformamide (DMF) in air. The crystal structure exhibits the typical structural features of dimeric Lewis-base-stabilized monoorganotin(IV)–dihalide–hydroxides, RSnHal2(OH), i.e. two octahedrally coordinated Sn atoms are linked together via two bridging hydroxide groups, resulting in a centrosymmetric four-membered rhomboid-like Sn–OH ring with acute angles at the Sn atom, obtuse angles at the O atoms and two different tin–oxygen bond lengths. With the shorter bond trans to the ethyl group, this observation underlines once more the so-called trans-strengthening effect in monoorganotin(IV) compounds with octahedrally coordinated Sn atoms. Differences and similarities in the bond lengths and angles in the four-membered Sn–OH rings have been worked out for the rings in dimeric diorganotin(IV)–halide–hydroxides, [R
2SnHal(OH)]2, and hydrates of dimeric tin(IV)–trihalide–hydroxide–aqua–hydrates, [SnHal3(OH)(H2O)]2·nH2O.
13-Nitrobenzo[a][1,4]benzothiazino[3,2-c]phenoxazine
Authors: Bader Mamoun M. , Fiester Cameron , Pham Phuong-Truc T. , Bradely Amy , Nazzal Amjad
Published: April 2024

In the title compound, C22H11N3O3S, dihedral angle between the phenyl rings on the periphery of the molecule is 8.05 (18)°. In the crystal, aromatic π–π stacking distance and short C—H...O contacts are observed. The maximum absorption occurs at 688 nm.
Digital technology uses, purposes, barriers and training programs for culturally and linguistically diverse older adults: a systematic scoping review
Authors: Cunningham Teagan , Murray Carolyn , Du Jia Tina , Evans Nina , Ziaian Tahereh
Published: April 2024

Purpose

This scoping review article aimed to systematically search the literature on the use, purpose and barriers of information and communication technology (ICT) for culturally and linguistically diverse (CALD) older adults in the host country. The review also conducted a search for literature on programs that aim to develop digital literacy skills for CALD older adults.

Design/methodology/approach

A scoping review approach was utilized to identify and search the available literature, and to map the key concepts. A total of 23 relevant articles were included following a systematic search across seven databases.

Findings

The review suggests that CALD older adults use ICT for various purposes, including social interaction, health management, information gathering, immigration, everyday routines and leisure. The barriers faced by these older adults in using ICT encompass fear and limited knowledge, language issues, lack of interest, limited access to technology and health concerns. The existing training programs focus on enhancing self-efficacy and confidence and promoting attitudinal changes toward ICT.

Originality/value

Despite the presence of empirical studies, few scoping or systematic reviews have focused on CALD older adults and technology. Research developments related to the technology use of CALD older adults and associated training programs have been fragmented and sporadic, resulting in gaps in the evidence base. This review fills such a gap to better understand the research status connected to CALD older people’s technology adoption and use.
The relationship between financial stability and transparency in social-environmental policies
Authors: De Moraes Claudio , Pinto Bandeira de Mello André
Published: April 2024

Purpose

This work analyzes, through social-environmental reports, whether banks with higher transparency in social-environmental policies better safeguard financial stability in Brazil.

Design/methodology/approach

The analysis is carried out through a panel database analysis of the 42 largest Brazilian banks, representing 98% of the Brazilian financial system. Seeking to avoid spurious results, we followed rigorous methodological standards. Hence, we conducted an empirical analysis using a dynamic panel data model, we used the difference generalized method of moments (D-GMM) and the system generalized method of moments (S-GMM).

Findings

The results show that the higher the transparency of social-environmental policies, the lower the chance of possible stress on the financial stability of Brazilian banks. In sum, this study builds evidence that disclosing risks related to policies about sustainability can enhance financial stability. It is essential to highlight that social-environmental transparency does not have as direct objective financial stability.

Originality/value

The manuscript submitted represents an original work that analyzes whether banks with higher transparency in social-environmental policies better safeguard financial stability. Some countries, such as Brazil, have their potential for sustainable policies spotlighted due to their green territory and diverse natural ecosystems. Besides having green potential, Brazil is a developing country with a well-developed financial system. These characteristics make Brazil one of the best laboratories for studying the relationship between transparency in social-environmental policies and financial stability.
Open innovation at the digital frontier: unraveling the paradoxes and roadmaps for SMEs' successful digital transformation
Authors: Appio Francesco Paolo , Cacciatore Emanuele , Cesaroni Fabrizio , Crupi Antonio , Marozzo Veronica
Published: April 2024

Purpose

The purpose of this paper is to fill a gap in the literature regarding the open innovation management approaches that small and medium-sized enterprises (SMEs) can use to access digital technologies and incorporate them into their organizational processes. The research question is: What organizational and process-level managerial actions do SMEs take to successfully access and implement digital technologies within their organizational processes?

Design/methodology/approach

Using Guertler et al.'s (2020) Action Innovation Management Research (AIM-R) framework, this study examines the digital transformation experiences of 10 European SMEs to gain insights into the managerial actions that foster successful digital transformation.

Findings

The findings of the paper reveal two major contributions. First, a digital transformation roadmap for SMEs is proposed, with a focus on accessing external resources and reconfiguring internal ones to ease their digital transformation journey. Second, three distinct paradoxes that influence the digital transformation process in SMEs are highlighted, providing useful insights into the challenges and tensions SMEs face during this journey.

Originality/value

This paper provides a unique perspective on the digital transformation of SMEs by examining the managerial actions required for successful technology adoption and revealing the paradoxes that may emerge during this transformative process. The findings form the basis for future research, deepening our understanding of digital transformation in SMEs and providing actionable advice to managers and practitioners navigating this journey.
Role of age, gender and cultural factors as moderator on technology acceptance of online entertainment
Authors: Harnadi Bernardinus , Widiantoro Albertus Dwiyoga , Prasetya FX Hendra , Sanjaya Ridwan , Sihombing Ranto Partomuan
Published: April 2024

Purpose

Research on technology acceptance of online entertainment with age, gender and cultural factors as moderator, is rarely conducted. Previous research predominantly focused on age or gender as moderator, neglecting the influence of cultural factors. Therefore, this study aims to investigate acceptance of online entertainment technology, incorporating age, gender and cultural factors as moderator.

Design/methodology/approach

Data were collected through a survey comprising 1,121 individuals aged 14–24 years from three cities in Indonesia. The proposed theoretical model examined the causal effect of acceptance and moderating effects due to individual gender, age, power distance, individualism, feminism and uncertainty avoidance (AU). Subsequently, structural equation modeling was used to evaluate the theoretical model, and the results confirmed several findings from previous research.

Findings

The findings confirmed the positive direct impact of habit and price value (PV) on behavioral intention and hedonic motivation, as well as social influence on habit. The recent findings derived from the moderating effect analysis showed that age, individualism and feminism played a moderating role in the effects on individual intention due to habit. Additionally, gender and AU moderated the effects on individual habits due to hedonic motivation.

Originality/value

This research contributes to the limited knowledge of technology acceptance of online entertainment, and also integrates the causal effects of individual intention due to habit, PV, hedonic motivation and social influence, considering the moderating role of culture, age and gender. Consequently, the investigation provides valuable insights into the literature by presenting evidence of age, gender and cultural differences in acceptance. Furthermore, it offers practical guidance to online entertainment application developers on designing applications to satisfy consumers of different ages, genders and cultures.
Detection of black hole attacks in vehicle-to-vehicle communications using ad hoc networks and on demand protocols
Authors: Bharanidharan C. , Malathi S. , Manoharan Hariprasath
Published: April 2024

Purpose

The potential of vehicle ad hoc networks (VANETs) to improve driver and passenger safety and security has made them a hot topic in the field of intelligent transportation systems (ITSs). VANETs have different characteristics and system architectures from mobile ad hoc networks (MANETs), with a primary focus on vehicle-to-vehicle (V2V) and vehicle-to-infrastructure (V2I) communication. But protecting VANETs from malicious assaults is crucial because they can undermine network security and safety.

Design/methodology/approach

The black hole attack is a well-known danger to VANETs. It occurs when a hostile node introduces phony routing tables into the network, potentially damaging it and interfering with communication. A safe ad hoc on-demand distance vector (AODV) routing protocol has been created in response to this issue. By adding cryptographic features for source and target node verification to the route request (RREQ) and route reply (RREP) packets, this protocol improves upon the original AODV routing system.

Findings

Through the use of cryptographic-based encryption and decryption techniques, the suggested method fortifies the VANET connection. In addition, other network metrics are taken into account to assess the effectiveness of the secure AODV routing protocol under black hole attacks, including packet loss, end-to-end latency, packet delivery ratio (PDR) and routing request overhead. Results from simulations using an NS-2.33 simulator show how well the suggested fix works to enhance system performance and lessen the effects of black hole assaults on VANETs.

Originality/value

All things considered, the safe AODV routing protocol provides a strong method for improving security and dependability in VANET systems, protecting against malevolent attacks and guaranteeing smooth communication between cars and infrastructure.
The impact of potential and realized absorptive capacity on open innovation: the moderating role of knowledge-oriented leadership
Authors: Gonzalez Rodrigo Valio Dominguez
Published: April 2024

Purpose

This study aims to analyze the effects of the components of absorptive capacity (ACAP) – potential absorptive capacity (PACAP) and realized absorptive capacity (RACAP) on inbound and outbound open innovation (OI). In addition, this study investigates the moderating role that knowledge-oriented leadership (KOL) plays in the relationship between ACAP and OI.

Design/methodology/approach

This research adopts a quantitative approach, using structural equation modeling, in a sample of 218 companies in the Brazilian manufacturing sector, using a random sampling technique and self-administered questionnaire.

Findings

The results indicate that while PACAP positively influences inbound and outbound OI, RACAP has a significant relationship only with outbound OI. In addition, KOL moderates the significant relationships between PACAP and RACAP and OI, indicating that the development of a leadership that fosters learning and interaction between employees and sectors of the organization impacts the innovation results of companies in the manufacturing sector.

Practical implications

This study also shows that managers must have an active role in the construction of an organizational context that supports learning through initiatives that encourage the process of trial and error, teamwork and cooperation between employees.

Originality/value

This research advances previous studies by relating the two components of ACAP (PACAP and RACAP) with the two OI models (inbound and outbound), in addition to analyzing the moderating role that KOL plays in this relationship between ACAP and OI.