bluuebunny/crossref_metadata_2025_split huggingface dataset:
Annotation-Free Deep Learning for Predicting Gene Mutations from Whole Slide Images of Acute Myeloid Leukemia
Authors: Wei Bo-Han , Tsai Xavier Cheng-Hong , Sun Kuo-Jui , Lo Min-Yen , Hung Sheng-Yu , Chou Wen-Chien , Tien Hwei-Fang , Hou Hsin-An , Chen Chien-Yu 
Published: November 2023

AbstractThe rapid development of deep learning in recent years has revolutionized the field of medical image processing, including the applications of using high-resolution whole slide images (WSIs) in acute myeloid leukemia (AML) diagnosis. Although the potential of characterizing gene mutations directly from WSIs has been demonstrated in some cancers, it still faces challenges due to image resolutions and manual annotations. To address this, we propose a deep learning model based on multiple instance learning (MIL) with ensemble learning to predict gene mutations from AML annotation-free WSIs. Our deep learning model offers a promising solution for gene mutation prediction onNPM1mutations andFLT3-ITD without the need for patch-level or cell-level manual annotations, reducing the manpower and time costs associated with traditional supervised learning approaches. The dataset of 572 WSIs from AML patients that we used to train our MIL models is currently the largest independent database with both WSI and genetic mutation information. By leveraging upsampling and ensemble learning techniques, our final model achieved an AUC of 0.90 for predictingNPM1mutations and 0.81 forFLT3-ITD. This confirms the feasibility of directly obtaining gene mutation data through WSIs without the need for expert annotation and training involvement. Our study also compared the proportional representation of cell types before and after applying the MIL model, finding that blasts are consistently important indicators for gene mutation predictions, with their proportion increasing in mutated WSIs and decreasing in non-mutated WSIs after MIL application. These enhancements, leading to more precise predictions, have brought AML WSI analysis one step closer to being utilized in clinical practice.
A single-cell atlas of transcribedcis-regulatory elements in the human genome
Authors: Moody Jonathan , Kouno Tsukasa , Kojima Miki , Koya Ikuko , Leon Julio , Suzuki Akari , Hasegawa Akira , Akiyama Taishin , Akiyama Nobuko , Amagai Masayuki , Chang Jen-Chien , Fukushima-Nomura Ayano , Handa Mika , Hino Kazunori , Hino Mizuki , Hirata Tomoko , Imai Yuuki , Inoue Kazunori , Kawasaki Hiroshi , Kimura Toshihiro , Kinoshita Tomofumi , Kubo Ken-ichiro , Kunii Yasuto , López-Redondo Fernando , Manabe Riichiro , Miyai Tomohiro , Morimoto Satoru , Nagaoka Atsuko , Nakajima Jun , Noma Shohei , Okazaki Yasushi , Ozaki Kokoro , Saeki Noritaka , Sakai Hiroshi , Seyama Kuniaki , Shibayama Youtaro , Sujino Tomohisa , Tagami Michihira , Takahashi Hayato , Takao Masaki , Takeshita Masaru , Takiuchi Tsuyoshi , Terao Chikashi , Yip Chi Wai , Yoshinaga Satoshi , Okano Hideyuki , Yahamoto Kazuhiko , Kasukawa Takeya , Ando Yoshinari , Carninci Piero , Shin Jay W. , Hon Chung-Chau 
Published: November 2023

SummaryTranscribed cis-regulatory elements (tCREs), such as promoters and enhancers, are fundamental to modulate gene expression and define cell identity. The detailed mapping of tCREs at single-cell resolution is essential for understanding the regulatory mechanisms that govern cellular functions. Prior tCRE catalogs, limited by bulk analysis, have often overlooked cellular heterogeneity. We have constructed a tCRE atlas using single-cell 5’-RNA-seq, capturing over 340,000 single-cells from 23 human tissues and annotating more than 175,000 tCREs, substantially enhancing the scope and granularity of existingcis-regulatory element annotations in the human genome. This atlas unveils patterns of gene regulation, revealing connections between broadly expressed promoters and cell type-specific distal tCREs. Assessing trait heritability at single-cell resolution with a novel tCRE module-based approach, we uncovered the nuanced trait-gene regulatory relationships across a continuum of cell populations, offering insights beyond traditional gene-level and bulk-sample analyses. Our study bridges the gap between gene regulation and trait heritability, underscoring the potential of single-cell analysis to elucidate the genetic foundations of complex traits. These insights set the stage for future research to investigate the impact of genetic variations on diseases at the individual level, advancing the understanding of cellular and molecular basis of trait heritability.
Facultatively intra-bacterial localization of a planthopper endosymbiont as an adaptation to its vertical transmission
Authors: Michalik Anna , Franco Diego C. , Szklarzewicz Teresa , Stroiński Adam , Łukasik Piotr 
Published: November 2023

AbstractTransovarial transmission is the most reliable way of passing on essential nutrient- providing endosymbionts from mothers to offspring. However, not all endosymbiotic microbes follow the complex path through the female host tissues to oocytes on their own. Here we demonstrate an unusual transmission strategy adapted by one of the endosymbionts of the planthopperTrypetimorpha occidentalis(Hemiptera: Tropiduchidae) from Bulgaria. In this species, anAcetobacteraceaeendosymbiont is transmitted transovarially within deep invaginations of cellular membranes of an ancient endosymbiontSulcia- strikingly resembling recently described plant virus transmission. However, in males,Acetobacteraceaecolonizes the same bacteriocytes asSulciabut remains unenveloped. Then, the unusual endobacterial localization ofAcetobacteraceaeobserved in females appears to be a unique adaptation to maternal transmission. Further, symbiont’s genomic features, including encoding essential amino acid biosynthetic pathways and very similar to a recently described psyllid symbiont, suggest a unique combination of ability to horizontally transmit among species and confer nutritional benefits. The close association withAcetobacteraceaesymbiont correlates with the so-far- unreported level of genomic erosion of ancient nutritional symbionts of this planthopper. InSulcia, this is reflected in substantial changes in genomic organization, reported for the first time in the symbiont renown for its genomic stability. InVidania, substantial gene loss resulted in one of the smallest genomes known, at 109 kb. Thus, the symbionts ofT. occidentalisdisplay a combination of unusual adaptations and genomic features that expand our understanding of how insect-microbe symbioses may transmit and evolve.Significance StatementReliable transmission across host generations is a major challenge for bacteria that associate with insects, and independently established symbionts have addressed this challenge in different ways. The facultatively endobacterial association ofAcetobacteraceaesymbiont, enveloped by cells of ancient nutritional endosymbiontSulciain females but not males of the planthopperTrypetimorpha occidentalis, appears to be a unique adaptation to maternal transmission. Acetobacteraceae’s genomic features indicate its unusual evolutionary history, and the genomic erosion experienced by ancient nutritional symbionts demonstrates apparent consequences of such close association. Combined, this multi-partite symbiosis expands our understanding of the diversity of strategies that insect symbioses form and some of their evolutionary consequences.
Structural basis for the concerted antiphage activity in the SIR2-HerA system
Authors: Yu Guimei , Liao Fumeng , Zhang Chendi , Li Xuzichao , He Qiuqiu , Yin Hang , Li Zhuang , Zhang Heng 
Published: November 2023

AbstractRecently, a novel two-gene bacterial defense system against phages, encoding a SIR2 NADase and a HerA translocase, has been identified. However, the molecular mechanism of the bacterial SIR2-HerA immune system remains unclear. Here, we determine the cryo-EM structures of SIR2, HerA and their complex in different functional states. The SIR2 proteins oligomerize into a dodecameric ring-shaped structure consisting of two layers of interlocked hexamers, in which each SIR2 unit exhibits an auto-inhibited conformation. Distinct from the canonical AAA+ proteins, the HerA hexamer in this antiphage system adopts a split spiral arrangement, resembling the substrate-binding state, which is stabilized by a unique C-terminal extension. SIR2 and HerA proteins assemble into a ∼ 1.1 MDa torch-shaped complex to fight against phage infection. Importantly, disruption of the interactions between SIR2 and HerA largely abolishes the antiphage activity. Interestingly, HerA binding alters the oligomer state of SIR2, switching from a 12-mer state to a 14-mer state. On the other hand, binding of SIR2 stimulates the ATPase activity of HerA. Together, our study not only provides a structural basis for the functional communications between SIR2 and HerA proteins, but also unravels a novel concerted antiviral mechanism through nucleotide (NAD+and ATP) depletion.
Differences in the neural representation of binaural sound localization cues in the auditory midbrain of chicken and barn owl
Authors: Aralla Roberta , Pauley Claire , Köppl Christine 
Published: November 2023

AbstractThe sound localisation behaviour of the nocturnally hunting barn owl and its underlying neural computations is a textbook example of neuroethology. Differences in sound timing and level at the two ears are integrated in a series of well characterised steps, from brainstem to inferior colliculus, resulting in a topographical neural representation of auditory space. It remains an important question of brain evolution how this specialised case derived from a more plesiomorphic pattern. The present study is the first to match physiology and anatomical subregions in the non-owl avian inferior colliculus. Single-unit responses in the chicken inferior colliculus were tested for selectivity to different frequencies and to the binaural difference cues. Their anatomical origin was reconstructed with the help of electrolytic lesions and immunohistochemical identification of different subregions of the inferior colliculus, based on previous characterisations in owl and chicken. In contrast to barn owl, there was no distinct differentiation of responses in the different subregions. We found neural topographies for both binaural cues but no evidence for a coherent representation of auditory space. The results are consistent with previous work in pigeon inferior colliculus and chicken higher-order midbrain and suggest a plesiomorphic condition of multisensory integration in the midbrain that is dominated by lateral panoramic vision.
Impaired migration and metastatic spread of human melanoma by a novel small molecule targeting the transmembrane domain of death receptor p75NTR
Authors: Lopes-Rodrigues Vanessa , Nyantakyi Samuel A. , Lun Xueqing , Zhang Jianbo , Ramanujuan Ajeena , Salim Shuhailah , Saleeb Michael , Senger Donna L. , Ibáñez Carlos F. 
Published: November 2023

AbstractReceptor transmembrane domains (TMDs) are crucially involved in relaying ligand information from extracellular to intracellular spaces and represent attractive targets for small molecule manipulation of receptor function. Screening a library of over 8,000 drug-like compounds with an assay based on the TMD of death receptor p75NTR, we identified a novel small molecule capable of inhibiting p75NTR-mediated migration of human melanoma cells. Employing medicinal chemistry, a more potent derivative termed Np75-4A22 was identified that blocks nerve growth factor (NGF)-mediated melanoma invasion at submicromolar concentrations. Mechanistically, Np75-4A22 was found, at least in part, to function by antagonizing NGF-mediated recruitment of the actin-bundling protein fascin to p75NTRand its association with the actin cytoskeleton. Importantly, preclinical assessment of Np75-4A22 showed high oral bioavailability, low toxicity, and significant inhibition of melanoma lung metastases in a highly metastatic mouse model. These results support further development of this approach as an alternative or complementary strategy for patients that do not respond to conventional chemotherapy or immune checkpoint inhibitors.
Combining full-length gene assay and SpliceAI to interpret the splicing impact of all possibleSPINK1coding variants
Authors: Wu Hao , Lin Jin-Huan , Tang Xin-Ying , Zou Wen-Bin , Schutz Sacha , Masson Emmanuelle , Fichou Yann , Le Gac Gerald , Férec Claude , Liao Zhuan , Chen Jian-Min 
Published: November 2023

AbstractBackgroundSingle-nucleotide variants (SNVs) within gene coding sequences can significantly impact pre-mRNA splicing, bearing profound implications for pathogenic mechanisms and precision medicine. However, reliable splicing analysis often faces practical limitations, especially when the relevant tissues are challenging to access. Whilein silicopredictions are valuable, they alone do not meet clinical classification standards. In this study, we aim to harness the well-established full-length gene splicing assay (FLGSA) in conjunction with SpliceAI to prospectively interpret the splicing effects of all potential coding SNVs within the four-exonSPINK1gene, a gene associated with chronic pancreatitis.ResultsWe initiated the study with a retrospective correlation analysis (involving 27 previously FLGSA-analyzedSPINK1coding SNVs), progressed to a prospective correlation analysis (incorporating 35 newly FLGSA-testedSPINK1coding SNVs), followed by data extrapolation, and ended with further validation. In total, we analyzed 67SPINK1coding SNVs, representing 9.3% of all 720 possible coding SNVs and affecting 19.2% of the 240 coding nucleotides. Among these 67 FLGSA-analyzed SNVs, 12 were found to impact splicing. Through extensive cross-correlation of the FLGSA-obtained and SpliceAI-predicted data, we reasonably extrapolated that none of the unanalyzed 653 coding SNVs in theSPINK1gene are likely to exert a significant effect on splicing. Out of these 12 splice-altering events, nine produced both wild-type and aberrant transcripts, while the remaining three exclusively generated aberrant transcripts. These splice-altering SNVs were predominantly concentrated in exons 1 and 2, particularly affecting the first and/or last coding nucleotide of each exon. Among the 12 splice-altering events, 11 were missense variants, constituting 2.17% of the 506 potential missense variants, while one was synonymous, accounting for 0.61% of the 164 potential synonymous variants.ConclusionsIntegrating FLGSA with SpliceAI, we conclude that less than 2% (1.67%) of all possibleSPINK1coding SNVs have a discernible influence on splicing outcomes. Our findings underscore the importance of performing splicing analysis in the broader genomic sequence context of the study gene, highlight the inherent uncertainties associated with intermediate SpliceAI scores (i.e., those ranging from 0.20 to 0.80), and have general implications for the shift from “retrospective” to “prospective” analysis in terms of variant classification.
Prior Fc Receptor activation primes macrophages for increased sensitivity to IgG via long term and short term mechanisms
Authors: Bond Annalise , Fiaz Sareen , Rollins Kirstin R , Nario Jazz Elaiza Q , Rosen Samuel J , Granados Alyssa , Wilson Maxwell Z , Morrissey Meghan A 
Published: November 2023

SummaryMacrophages measure the ‘eat-me’ signal IgG to identify targets for phagocytosis. We wondered if prior encounters with IgG influence macrophage appetite. IgG is recognized by the Fc Receptor. To temporally control Fc Receptor activation, we engineered an Fc Receptor that is activated by light-induced oligomerization of Cry2, triggering phagocytosis. Using this tool, we demonstrate that Fc Receptor activation primes macrophages to be more sensitive to IgG in future encounters. Macrophages that have previously experienced Fc Receptor activation eat more IgG-bound cancer cells. Increased phagocytosis occurs by two discrete mechanisms – a short- and long-term priming. Long term priming requires new protein synthesis and Erk activity. Short term priming does not require new protein synthesis and correlates with an increase in Fc Receptor mobility. Our work demonstrates that IgG primes macrophages for increased phagocytosis, suggesting that therapeutic antibodies may become more effective after initial priming doses.
Exploring a Soccer Society: dreams, themes and the beautiful game
Authors: Hyndman Noel , Lapsley Irvine , Philippou Christina 
Published: November 2023

PurposeThe primary purpose of this paper is to provide an analysis of the key perspectives that emerge in this Accounting, Auditing & Accountability Journal (AAAJ) Special Issue as a basis for determining the existence or otherwise of a Soccer Society, as well as reflecting on the challenges that evidence of corruption in soccer (the beautiful game) has had on the game to date. Reflections on these matters are then utilised to offer a prospective analysis of issues for further research.Design/methodology/approachThe paper is a reflective analysis that draws on existing societal work to provide key dimensions of accounting and accountability for significant organisations in the world of sport in general and soccer in particular.FindingsMuch prior research on soccer has largely focussed on the internal workings of soccer organisations, with little discussion of the importance of context. This paper explores the influence of the game more broadly. Moreover, a number of the papers included illustrate an overwhelming sense of joy and pleasure from experiences of the beautiful game, as well as providing evidence of the general societal good that can flow from it. However, the study also highlights concerns emanating from weak, and seemingly pliable, governance, regulatory and accountability regimes that provide a fertile field for corruption and sportswashing.Research limitations/implicationsThis paper highlights a research agenda as an encouragement to interdisciplinary accounting researchers to investigate accountability and governance issues as a basis for evidence-based discussions of the impact of soccer and its regulation.Originality/valueThis paper specifically, and the Special Issue more broadly, offers a set of original empirical and theoretical contributions with respect to an activity that has faced limited scrutiny and consideration by academic accountants. Together, they offer a substantive body of work to enable future research in this area.
Impact of financial literacy and financial confidence on the savings behaviour of the farmers: the Indian scene
Authors: Das Soumyadwip , Maji Sumit Kumar 
Published: November 2023

PurposeThe study aims to explore the savings behaviour of Indian farmers. An attempt is also made to inspect the effect of financial literacy (FL) and financial confidence (FC) on the savings behaviour of the farmers in India.Design/methodology/approach This study used secondary data on 10,263 Indian farmers from Financial Inclusion Insights, 2017 database. Relevant statistical techniques and ordered probit regression were used to unfold the effect of FL and FC on the savings behaviour of farmers.Findings The outcome of the study revealed that the majority of the Indian farmers exhibited poor levels of FL and FC. Of the total, 42.99% were found to save regularly. FL and FC were observed to play instrumental roles in steering the savings behaviour of the Indian farmers. Household size, financial shocks, gender, farm ownership, income, household financial decision-making process, religion and educational attainment have emerged to be significant predictors of the savings behaviour of Indian farmers.Originality/value The present study makes an original contribution to the extant literature by unfolding the savings behaviour of Indian farmers and the effect of FL and FC on such behaviour using a rich sample of 10,263 farmers for the first time.
The association between managerial short-termism and green innovation: the moderating role of firms’ digital transformation
Authors: Xu Xiaohui , Liu Yi 
Published: November 2023

Purpose
The purpose of this study is to examine the impact of managerial short-termism on green innovation of firms and the moderating role of digital transformation of enterprises in the association between managerial short-termism and green innovation.

Design/methodology/approach
This study uses data from Chinese A-share listed companies from 2001 to 2021 and employ panel fixed model and moderating effect model to examine the impact of managerial short-termism on green innovation of firms and the moderating role of digital transformation of enterprises in the association between managerial short-termism and green innovation.

Findings
The findings of this study reveal that managerial short-termism exerts negative influence on green innovation. Digital transformation enables firms to reduce the adverse effect of managerial short-termism on green innovation because digital transformation enhances information processing ability and then improves internal corporate governance and analyst coverage. Moreover, the moderating role of digital transformation is more prominent for firms with lower internal corporate governance, for firms with less analyst coverage and for non-state-owned enterprises.

Originality/value
This paper intends to address the following two questions: what is the impact of managerial short-termism on green innovation and what is the role of digital transformation in the two variables’ association? By using data of Chinese A-share listed companies from 2001 to 2021 and developing two individual indexes to measure managerial short-termism and digital transformation, the authors empirically test these above two questions. The results of this study indicate that: First, drawn on time-oriented theory and upper echelon theory, managerial short-termism has an adverse effect on firms’ green innovation. Second, digital transformation enables firms to reduce the negative effect of managerial short-termism on green innovation. Furthermore, the moderating mechanism tests show that the corporate governance effects of digital transformation play a supervisory role that impels managers to reduce short-term investments and promote firms’ green R&D investments, which helps to reduce the negative effect of managerial short-termism on green innovation. Additionally, the heterogeneity checks show that the moderating role of digital transformation in the relation between managerial short-termism and green innovation is more prominent for firms with lower internal corporate governance, with less analyst coverage and for non-state-owned enterprises.
Micro Housing Finance Corporation
Authors: Niendorf Elisabeth , Milap Akshay , Mendonca Valerie , Kathuria Ajay Kumar , Karna Amit 
Published: November 2023

This case describes the evolution of MHFC, a player in the Indian informal housing sector. As a new entrant offering micro home loans to the financially excluded lower income families of urban India in 2008, MHFC had grown to an annual number of 18,000 loans worth INR 8 billion with an average ticket size of INR 0.43 million (USD 6,000).
With a 53.5% purchasable equity stake in MHFC, Chopra and his team were left with certain decisions to make. Should the company on-board a new social investor? Or should it bring on the more readily available and capital-rich private equity investors interested in the lucrative prospects of the microfinance housing sector?
The case discusses two key objectives: (1) to understand the entire entrepreneurial journey of a group of entrepreneurs and how they plan to exit the venture, and (2) to enable classroom discussion on how to develop a business model from scratch, get it funded, achieve scale and then exit.