bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteasome inhibition enhances latency reversal and boosts NK cell-mediated elimination of HIV-1 infected cells through HLA-E downregulation
Authors: Laeremans Thessa , den Roover Sabine , Nezic Stefan Johan , Allard Sabine D. , Aerts Joeri L. 
Published: October 2024

AbstractThe shock and kill strategy primarily depends on using latency reversal agents (LRAs) to reactivate the dormant viral reservoir, rendering it visible for recognition and subsequent elimination by the host’s immune system. While this approach has shown high efficacyin vitroandex vivo, itsin vivoapplication has yet to show significant delays in time to viral rebound. This lack ofin vivoefficacy is most likely due to the insufficient elimination of reactivated reservoir cells by the host’s immune effector cells, including natural killer (NK) cells. Given the pivotal role of NK cells in antiviral immune responses, we hypothesized that they are crucial players in pursuing a functional cure against HIV-1. However, the inhibitory interaction between NKG2A and HLA-E diminishes their effectiveness. Notably, proteasome inhibition has been effective in reducing HLA-E expression on various tumor cell types, thereby enhancing NK-cell mediated killing. However, its impact on HIV-1 latency remains unexplored. We found that the proteasome inhibition could reverse the latent state of J-Lat cells while substantially reducing HLA-E expression. Additionally, a reduced expression of NKGA on primary NK cells was observed which led to an increase in NK-cell cytotoxicity. These results suggest that disrupting the NKG2A/HLA-E interaction could potentially augment the effectiveness of the shock and kill strategy by improving NK cell-mediated clearance of reactivated cells.ImportanceDespite promisingin vitroresults, purging the viral reservoir using LRAs has yet to demonstrate clinical benefits. A significant challenge lies in the inadequate activation of immune effector cells, such as CD8+T cells and NK cells. Therefore, developing therapeutic strategies to address these challenges could enhance the effectiveness of the shock and kill strategy. This study highlights the need for therapeutic interventions to overcome these hurdles. Our findings show that proteasome inhibition not only triggers latency reversal but also enhances NK-cell mediated elimination of latently infected cellsin vitroby downregulating HLA-E. This suggests that targeting the proteasome could be a novel therapeutic approach in the shock and kill strategy, potentially improving clinical outcomes.
Lifting the degeneracy of optical fiber neural interfaces for optogenetics and electrophysiology by using axialtrodes
Authors: Sui Kunyang , Codadu Neela K. , Rathore Daman , Li Guanghui , Meneghetti Marcello , Berg Rune W , Wykes Rob C. , Markos Christos 
Published: October 2024

AbstractOptogenetics and electrophysiology are powerful methods in neuroscience for precise spatiotemporal control and recording of neural activity. Conventional flat optical fibers, commonly used in deep brain regions, can only interface with limited tissue volume at their distal end. However, depth-resolved neuromodulation and recordings are crucial for decoding neuronal connections across various brain domains. In this work, we address this limitation by introducing an axialtrode developed using soft polymers integrated with multiple metal electrodes via a scalable thermal drawing process. We employ the developed fiber-based neural interface, controllably angled-cleaved, for multisite optogenetics and electrophysiology at different brain regions. Its suppressed inflammatory responses indicate improved biocompatibility compared to conventional fibers. This concept can be adapted to any fiber material and application where depth-resolved stimulation and electrical recordings are important, bringing the community a step closer to understanding complex neuronal dynamics.
Analytical and clinical validation of a genome sequencing-based comprehensive rare disease genomic profiling test
Authors: Sriram Shruthi , Lee Sang Yeon , Ferguson Stephanie , Koh June-Young , Wallace Jonathan Kyle , Lee Jeonghoon , Kim Jung-Ah , Lee Yoonsuh , Oh Brian Baek-Lok , Lee Won Chul , Lee Sangmoon , Connolly-Strong Erin 
Published: October 2024

AbstractThis study evaluates the performance of the RareVision Whole Genome Sequencing (WGS) assay for comprehensive genomic profiling in rare genetic diseases. The analytical validation assessed the assay’s sensitivity and positive predictive values (PPV) for single nucleotide variants (SNVs), insertions/deletions (indels), and structural variants (SVs), revealing a sensitivity of 99.4% for SNVs and 98.7% for indels, with PPVs of 99.3% for SNVs and 98.7% for indels. Clinical validation involved benchmarking against established orthogonal methods, demonstrating high concordance in variant detection with reference laboratories. The assay’s reproducibility was confirmed with 100% inter-precision and intra-precision concordance. The RareVision WGS assay provides detailed genomic insights, enhancing the diagnosis and management of rare genetic disorders by offering a comprehensive and accurate genomic profiling tool.
Bridging the Gap between Database Search andDe NovoPeptide Sequencing with SearchNovo
Authors: Xia Jun , Liu Sizhe , Zhou Jingbo , Chen Shaorong , Xiang Hongxin , Liu Zicheng , Liu Yue , Li Stan Z. 
Published: October 2024

AbstractAccurate protein identification from mass spectrometry (MS) data is fundamental to unraveling the complex roles of proteins in biological systems, with peptide sequencing being a pivotal step in this process. The two main paradigms for peptide sequencing are database search, which matches experimental spectra with peptide sequences from databases, andde novosequencing, which infers peptide sequences directly from MS without relying on pre-constructed database. Although database search methods are highly accurate, they are limited by their inability to identify novel, modified, or mutated peptides absent from the database. In contrast,de novosequencing is adept at discovering novel peptides but often struggles with missing peaks issue, further leading to lower precision. We introduce SearchNovo, a novel framework that synergistically integrates the strengths of database search andde novosequencing to enhance peptide sequencing. SearchNovo employs an efficient search mechanism to retrieve the most similar peptide spectrum match (PSM) from a database for each query spectrum, followed by a fusion module that utilizes the reference peptide sequence to guide the generation of the target sequence. Furthermore, we observed that dissimilar (noisy) reference peptides negatively affect model performance. To mitigate this, we constructed pseudo reference PSMs to minimize their impact. Comprehensive evaluations on multiple datasets reveal that SearchNovo significantly outperforms state-of-the-art models. Also, analysis indicates that many retrieved spectra contain missing peaks absent in the query spectra, and the retrieved reference peptides often share common fragments with the target peptides. These are key elements in the recipe for SearchNovo’s success. The code for reproducing the results are available in the supplementary materials.
Data Science in Olfaction
Authors: Agarwal Vivek K , Harvey Joshua S. , Rinberg Dmitry , Dhar Vasant 
Published: October 2024

AbstractAdvances in neural sensing technology are making it possible to observe the olfactory process in great detail. In this paper, we conceptualize smell from a Data Science and AI perspective, that relates the properties of odorants to how they are sensed and analyzed in the olfactory system from the nose to the brain. Drawing distinctions to color vision, we argue that smell presents unique measurement challenges, including the complexity of stimuli, the high dimensionality of the sensory apparatus, as well as what constitutes ground truth. In the face of these challenges, we argue for the centrality of odorant-receptor interactions in developing a theory of olfaction. Such a theory is likely to find widespread industrial applications, and enhance our understanding of smell, and in the longer-term, how it relates to other senses and language. As an initial use case of the data, we present results using machine learning-based classification of neural responses to odors as they are recorded in the mouse olfactory bulb with calcium imaging. Our larger objective is to create the equivalent of an “MNIST database for olfaction,” which we call ‘oMNIST,’ so that researchers are able to work from a standard dataset to further the state of the art, similar to how the availability of standard datasets catalyzed research in computer vision.
Multi-Channel Funnel Adapted Sensing Tube (MFAST) for the Simple and Duplex Detection of Parasites
Authors: Peng Ruonan , Yuqing Fnu , Wiggins Taralyn J. , Bahadori Negin , Dollery Stephen J. , Waitkus Jacob , Rogers Joshua S. , Chen Yun , Tobin Gregory J. , Du Ke 
Published: October 2024

AbstractLeishmaniasis poses a significant global health threat, infecting millions of people annually, particularly in tropical and subtropical regions. Timely and accurate detection ofLeishmaniaspecies is crucial for effective treatment and control of this debilitating disease. This study introduces the Multi-channel Funnel Adapted Sensing Tube (MFAST) chip, an innovative diagnostic tool designed for the rapid detection ofLeishmania panamensis. MFAST is fabricated through 3D printing and sacrificial molding of acrylonitrile butadiene styrene (ABS) and the reagents are transported between the reservoirs by gravity. We combine experiments and finite element analysis to reduce the leaking issues and facilitate smoother fluid flow, improving the overall performance of the device. Highly sensitive and specific RPA-CRISPR/Cas12a assay is utilized in the chip, achieving a detection limit as low as 1,000 parasites/mL (detecting as few as 5 parasites per reaction). The multi-channel design enables duplex detection, allowing for simultaneous identification of bothL. braziliensisandL. panamensisthrough distinct channels. Furthermore, stability tests indicate that lyophilized reagents retain functionality for up to 15 days when stored at 4 °C, underscoring the potential of this chip for practical diagnostic applications in low-resource settings.
Economic Gains from Health Equity: A Model for Pregnancy and Childbirth Policy Decisions
Authors: Evans Mark I. , Ryan Gregory F. , Devoe Lawrence D. , Mussalli George M. , Britt David W. , Worth Jaqueline M. , Mondestin-Sorrentino Myriam , Macedonia Christian R. 
Published: October 2024

ABSTRACTImportanceAmerican maternal and neonatal mortality rates are the worst of the world’s high-income countries. These rates are particularly low among patients of color, who have higher Cesarean delivery rates (CDR), higher healthcare costs, and poorer outcomes than White patients. However, common economic analyses do not address interlinked issues and therefore underestimate both the hidden causes of health inequities and the resultant costs to taxpayers. We have therefore designed a more comprehensive health economic model and metric (DEVELOP) that incorporates population health, equity, and economic integration.Design & MeasuresThe DEVELOP model, a childbirth-specific model of the societal economic gain or loss related to healthcare outcomes, incorporates an individual’s long-term economic contributions into its calculations of economic benefits. We first used our model to estimate fiscal outcomes if each state’s CDR for Black patients was lowered to that of White patients. Second, we calculated the costs of “excess” CDR and mortalities among Black patients. Third, we incorporated the additional long-term economic contributions of mothers and their children.ResultsIn the U.S., maternal and neonatal mortality rates and associated costs were higher for Black patients than White patients, and states with the lowest per capita health expenditures showed worse maternal outcomes and higher continuing costs. If the Black patient CDR were reduced to the White patient CDR, taxpayer-funded healthcare programs would save $263 million annually. Reducing the Black patient MMR would improve economic output by $224 million per year, and reducing the Black patient NMR would save $3.1 billion per year, for a combined economic improvement of $3.3 billion annually.Conclusions and RelevanceThe costs of improved prenatal care should be reconceptualized as investments for future economic growth rather than as short-term burdens. Policies blocking reasonable investments in health equity are counterproductive.
Precise prostate contours: setting the bar and meticulously evaluating AI performance
Authors: Song Yuze , Dornisch Anna , Dess Robert T , Margolis Daniel JA , Weinberg Eric P , Barrett Tristan , Cornell Mariel , Fan Richard E , Harisinghani Mukesh , Kamran Sophia C. , Lee Jeong Hoon , Li Cynthia Xinran , Liss Michael A , Rusu Mirabela , Santos Jason , Sonn Geoffrey A , Vidic Igor , Woolen Sean A , Dale Anders M , Seibert Tyler M 
Published: October 2024

AbstractIntroductionEvaluation of artificial intelligence (AI) algorithms for prostate segmentation is challenging because ground truth is lacking. We aimed to (1) create a reference standard dataset with precise prostate contours by expert consensus and (2) evaluate various AI tools against this standard.Materials and methodsWe obtained prostate MRI cases from six institutions from the Quantitative Prostate Imaging Consortium. A panel of four experts (two genitourinary radiologists, two prostate radiation oncologists) meticulously developed consensus prostate segmentations on axialT2-weighted series. We evaluated the performance of six AI tools (three commercially available, three academic) using Dice scores, distance from reference contour, and volume error.ResultsThe panel achieved consensus prostate segmentation on each slice of all 68 patient cases included in the reference dataset. We present two patient examples to serve as contouring guides. Depending on the AI tool, median Dice scores (across patients) ranged from 0.80 to 0.94 for whole prostate segmentation.For a typical (median) patient, AI tools had a mean error over the prostate surface ranging from 1.3 to 2.4 mm. They maximally deviated 3.0 to 9.4 mm outside the prostate and 3.0 to 8.5 mm inside the prostate for a typical patient. Error in prostate volume measurement for a typical patient ranged from 4.3% to 31.4%.DiscussionWe established an expert consensus benchmark for prostate segmentation. The best-performing AI tools have typical accuracy greater than that reported for radiation oncologists using CT scans (most common clinical approach for radiotherapy planning). Physician review remains essential to detect occasional major errors.
Olduvai domain expression downregulates mitochondrial pathways: implications for human brain evolution and neoteny
Authors: Keeney Jonathon G. , Astling David , Andries Vanessa , Vandepoele Karl , Anderson Nathan , Davis Jonathan M. , Lopert Pamela , Vandenbussche Jonathan , Gevaert Kris , Staes An , Paukovich Natasia , Vögeli Beat , Jones Kenneth l. , van Roy Frans , Patel Manisha , Sikela James M. 
Published: October 2024

AbstractEncoded by the NBPF gene family, Olduvai (formerly DUF1220) protein domains have undergone the largest human lineage-specific copy number expansion of any coding region in the genome. Olduvai copy number shows a linear relationship with several brain size-related measures and cortical neuron number among primates and with normal and disease-associated (micro- and macrocephaly) variation in brain size in human populations. While Olduvai domains have been shown to promote proliferation of neural stem cells, the mechanism underlying such effects has remained unclear. Here, we investigate the function of Olduvai by transcriptome and proteome analyses of cells overexpressingNBPF1, a gene encoding 7 Olduvai domains. Our results from both RNAseq and mass spectrometry approaches suggest a potential downregulation of mitochondria. In our proteomics study, a Gene Ontology (GO) enrichment analysis for the downregulated proteins revealed a striking overrepresentation of the biological process related to the mitochondrial electron transport chain (pvalue: 1.81e−11) and identified deregulation of the NADH dehydrogenase activity (pvalue: 2.43e−11) as the primary molecular function. We verify the reduction of apparent mitochondria via live-cell imaging experiments. Given these and previous Olduvai findings, we suggest that the Olduvai-mediated, dosage-dependent reduction in available energy via mitochondrial downregulation may have resulted in a developmental slowdown such that the neurogenic window among primates, and most extremely in humans, was expanded over a greater time interval, allowing for production of greater numbers of neurons and a larger brain. We further suggest that such a slowdown may extend to other developmental processes that also exhibit neotenic features.
Exploring female entrepreneurship experience of Ireland’s business ecosystem: implications for business support
Authors: Turley Anna-Marie , Ryan Marie , Doyle Eleanor 
Published: October 2024

PurposeThis paper investigates the motivations and challenges of women entrepreneurs in Ireland, assessing the role of policies and Enterprise Ireland (EI) support for women-led companies and high potential start-ups (HPSUs). It employs the gendered theory of entrepreneurship and opportunity recognition theory to analyse the enablers and obstacles to women’s entrepreneurship, particularly in the context of EI’s support, aiming to suggest improvements.Design/methodology/approachGrounded in a feminist epistemology and employing a mixed-methods approach, a targeted survey explores motivations, barriers and supports the needs of female entrepreneurs in Ireland, offering a comprehensive gender perspective evaluation for policy enhancement.FindingsFindings note a shift in Irish women’s entrepreneurship motivations and outlines major hurdles like limited funding and work–life balance issues. It recommends policy enhancements in data collection, website usability, financial guidance and childcare support.Practical implicationsThis paper aims to highlight the impact of gender-specific factors on entrepreneurship, the study highlights the importance of ongoing data collection and gender comparative analyses. It advocates for women mentoring networks and improved financial support to build a more inclusive entrepreneurial environment in Ireland, with potential global implications.Originality/valueThis study is unique for its in-depth exploration into Irish female entrepreneurship challenges, this study proposes actionable strategies with local and global relevance. Advocating for caregiving support integration and women’s increased involvement in tech, it offers a blueprint for fostering female entrepreneurship. It contributes to global discussions on creating supportive, equitable entrepreneurial ecosystems, serving as a valuable resource for advancing gender inclusivity and equity in entrepreneurship worldwide. It identifies scope for integration of a feminist epistemology in policy development.
Family affairs or Government's duty? The tax morality of a mobile society
Authors: Caferra Rocco , Cascavilla Alessandro , Morone Andrea 
Published: October 2024

PurposeThis paper aims to shed light on the relationship between intergenerational labor mobility and tax morale among European citizens, given the relatively limited evidence on the potential influence of tax compliance behavior on future inequalities.Design/methodology/approachExploiting data from the European Values Study (2008), we show that the larger the intergenerational mobility, i.e. better economic conditions of children respect to their parents, the larger the willingness to pay taxes. In this vein, the subjective tax payment may be meant as an investment which could be rewarded with a more mobile society result by considering different estimation strategies. This evidence remarks the importance to foster intergenerational mobility to build a more tax-compliant society.FindingsThe linkage between mobility and tax morale is stronger and significant across citizens living in high income classes, and in countries where there is a commitment of the Government in guaranteeing more opportunities to citizens regardless of their familiar starting conditions (more defamiliarized countries). We further show that the intergenerational mobility significantly shapes the attitude towards tax payment only among individuals who claim for independence from their family context (i.e. those showing less family ties). This evidence remarks the importance to foster intergenerational mobility to build a more tax-compliant society.Originality/valueWe revisit the linkage between attitude toward tax compliance and inequality, on the light of the intergenerational labor mobility, that may be seen as the dependence between children's and parents' earnings. Given the insights from the existing studies, this paper represents the first empirical work that aims to analyze the potential relationship between intergenerational mobility and personal attitude toward tax payment across European citizens.
How and when does benevolent leadership promote followers’ proactive customer service behavior?
Authors: Elsaied Mervat 
Published: October 2024

PurposeThis study aimed to investigate the impact of benevolent leadership on proactive customer service performance by creating a moderated mediation model. The model focuses on the role of harmonious passion as a mediator in the relationship between benevolent leadership and proactive customer service performance as well as the moderating influence of proactive personality on this mediation.Design/methodology/approachThe model was tested using data from 339 immediate supervisor-subordinate pairs in eight five-star hotels in Egypt. Frontline service employees and their immediate supervisors completed separate questionnaires, and the responses were matched using identification numbers.FindingsThe results indicate that harmonious passion fully mediates the positive relationship between benevolent leadership and proactive customer service performance. Additionally, proactive personality was found to moderate the mediated relationship between benevolent leadership and proactive customer service performance through harmonious passion, such that the mediation was stronger for employees with higher proactive personalities.Research limitations/implicationsBy testing the moderated mediation model, this study contributes to our theoretical understanding of the motivational mechanism through which benevolent leadership influences proactive customer service performance.Originality/valueThis research offers initial evidence of the mediating role of harmonious passion in the positive relationship between benevolent leadership and proactive customer service performance. The moderated mediation model extends existing findings by incorporating proactive personality as a significant moderator in explaining the impact of benevolent leadership on proactive customer service performance.