bluuebunny/crossref_metadata_2025 huggingface dataset:
Animal Models Relevant for Geroscience: Current Trends and Future Perspectives in Biomarkers, and Measures of Biological Aging
Authors: Bartolomucci Alessandro , Kane Alice E , Gaydosh Lauren , Razzoli Maria , McCoy Brianah M , Ehninger Dan , Chen Brian H , Howlett Susan E , Snyder-Mackler Noah
Published: August 2024

For centuries, aging was considered inevitable and immutable. Geroscience provides the conceptual framework to shift this focus toward a new view that regards aging as an active biological process, and the biological age of an individual as a modifiable entity. Significant steps forward have been made toward the identification of biomarkers for and measures of biological age, yet knowledge gaps in geroscience are still numerous. Animal models of aging are the focus of this perspective, which discusses how experimental design can be optimized to inform and refine the development of translationally relevant measures and biomarkers of biological age. We provide recommendations to the field, including: the design of longitudinal studies in which subjects are deeply phenotyped via repeated multilevel behavioral/social/molecular assays; the need to consider sociobehavioral variables relevant for the species studied; and finally, the importance of assessing age of onset, severity of pathologies, and age-at-death. We highlight approaches to integrate biomarkers and measures of functional impairment using machine learning approaches designed to estimate biological age as well as to predict future health declines and mortality. We expect that advances in animal models of aging will be crucial for the future of translational geroscience but also for the next chapter of medicine.
Multimode ambient noise double-beamforming tomography with a dense linear array: revealing accretionary wedge architecture across Central Taiwan
Authors: Liu Cheng-Nan , Lin Fan-Chi , Huang Hsin-Hua , Wang Yu , Gkogkas Konstantinos
Published: August 2024

Taiwan, one of the most active orogenic belts in the world, undergoes orogenic processes that can be elucidated by the doubly vergent wedge model, explaining the extensive island-wide geological deformation. To provide a clearer depiction of its cross-island orogenic architecture, we apply ambient noise tomography across an east–west linear seismic array in central Taiwan, constructing the first high-resolution 2-D shear velocity model of the upper crust in the region. We observe robust fundamental- and higher-mode Rayleigh waves, with the latter being mainly present in the western Coastal Plain. We develop a multimode double-beamforming method to determine local phase velocities across the array between 2- and 5-s periods. For each location, we jointly invert all available fundamental- and higher-mode phase velocities using a Bayesian-based inversion method to obtain a 1-D model. All 1-D models are then combined to form a final 2-D model from the surface to ∼10 km depth. Our newly developed 2-D model clearly delineates major structural boundaries and fault geometries across central Taiwan, thereby corroborating the previously proposed pro-wedge and retro-wedge models while offering insight into regional seismic hazards.
Genome-wide association study identifies the genetic basis of key agronomic traits in 207 sugar beet accessions
Authors: Wang Sufang , Yue Zhiyong , Yu Chao , Wang Ruili , Sui Yang , Hou Yaguang , Zhao Ying , Zhao Lingling , Chen Chunmei , Yang Zhimin , Shao Ke
Published: August 2024

Sugar beet (Beta vulgaris) has emerged as one of the two primary crops, alongside sugarcane, for global sugar production. Comprehensively understanding sucrose synthesis, transport, and accumulation in sugar beet holds great significance for enhancing sugar production. In this study, we collected a diverse set of 269 sugar beet accessions worldwide and measured 12 phenotypes, comprising biomass, soluble sugar content, and 10 taproot-related traits. We re-sequenced 207 accessions to explore genetic diversity and population structure. Then we employed a genome-wide association study (GWAS) and RNA-seq to identify single-nucleotide polymorphisms and genes associated with natural phenotypic variations. Our findings revealed a panel of genes potentially regulating biomass and sugar accumulation, notably the dual-role gene UDP-glucose 4-epimerase, which genetically balances sugar accumulation and cell wall synthesis. In summary, this study provides a foundation for molecular breeding in sugar beet.
Developing a Machine-Learning Prediction Model for Infliximab Response in Crohn’s Disease: Integrating Clinical Characteristics and Longitudinal Laboratory Trends
Authors: Qiu Yun , Hu Shixian , Chao Kang , Huang Lingjie , Huang Zicheng , Mao Ren , Su Fengyuan , Zhang Chuhan , Lin Xiaoqing , Cao Qian , Gao Xiang , Chen Minhu
Published: August 2024

Background

Achieving long-term clinical remission in Crohn’s disease (CD) with antitumor necrosis factor α (anti-TNF-α) agents remains challenging.

Aims

This study aims to establish a prediction model based on patients’ clinical characteristics using a machine-learning approach to predict the long-term efficacy of infliximab (IFX).

Methods

Three cohorts comprising 746 patients with CD were included from 3 inflammatory bowel disease (IBD) centers between June 2013 and January 2022. Clinical records were collected from baseline, 14-, 30-, and 52-week post-IFX treatment. Three machine-learning approaches were employed to develop predictive models based on 23 baseline predictors. The SHapley Additive exPlanations (SHAP) algorithm was used to dissect underlying predictors, and latent class mixed model (LCMM) was applied for trajectory analysis of the longitudinal change of blood routine tests along with long-term IFX therapy.

Results

The XGBoost model exhibited the best discrimination between long-term responders and nonresponders. In the internal training and testing set, the model achieved an AUC of 0.91 (95% CI, 0.86-0.95) and 0.71 (95% CI, 0.66-0.87), respectively. Moreover, it achieved a moderate predictive performance in the independent external cohort, with an AUC of 0.68 (95% CI, 0.59-0.77). The SHAP algorithm revealed disease-relevant laboratory measurements, notably hemoglobin (HB), white blood cells (WBC), erythrocyte sedimentation rate (ESR), albumin (ALB), and platelets (PLT), alongside age at diagnosis and the Montreal classification, as the most influential predictors. Furthermore, 2 distinct patient clusters based on dynamic laboratory tests were identified for monitoring the long-term remission.

Conclusions

The established prediction model demonstrated remarkable discriminatory power in distinguishing long-term responders from nonresponders to IFX therapy. The identification of distinct patient clusters further emphasizes the need for tailored therapeutic approaches in CD management.
Poor performance of regime shift detection methods in marine ecosystems
Authors: Haines Hannah , Planque Benjamin , Buttay Lucie
Published: August 2024

Regime shifts have been reported as ubiquitous features across the world’s oceans. Many regime shift detection methods are available, but their performance is rarely evaluated, and the supporting evidence for regime shifts may be thin because of the nature of marine ecological time series that are often short, autocorrelated, and uncertain. In the Norwegian Sea, a regime shift has been reported to have occurred in the mid-2000s, with simultaneous changes in oceanography, plankton, and fish. Here, we evaluate the evidence for this regime shift using four commonly used regime shift detection methods (Strucchange, STARS, EnvCpt, and Chronological Clustering) on 32 annual time series that describe the main components of the Norwegian Sea ecosystem, from hydrography and primary production up to fish population metrics. We quantify the performance of each method by measuring its false-positive rate, i.e. the proportion of times the method detects a regime shift that was not present in simulated control time series. Our results show that all methods have high to very high false-positive rates. This challenges the evidence for a regime shift in the Norwegian Sea and questions earlier reviews of regime shifts across the world’s oceans.
Dialogic incrementalism in deeply divided societies
Authors: Pasarlay Shamshad
Published: August 2024

A number of the world’s “deeply divided” societies are mired in violent conflicts which often grow out of historic tensions between the nation’s ethno-religious or linguistic groups. Elites within these societies tried to end these conflicts by drafting a constitution that would address the underlying grievances which fuel intergroup conflict. In many cases, however, rather than promoting peaceful political engagement, the process of constitution drafting seemed only to aggravate existing conflicts and create fresh sources of political unrest. Some deeply divided polities have avoided these worst-case outcomes by deploying an “incrementalist” approach to making constitutions. This approach asserts that deeply divided societies need not, and indeed should not, try to answer all constitutional questions. Rather, they can defer the most divisive questions for later resolution. By doing this, incrementalism focuses attention on issues over which some measure of agreement can be forged and enables constitutional ratification under fraught conditions. Critics have, however, identified two real problems with the incrementalist approach: first, once ethnopolitical elites agree to defer important questions, new developments may empower one group and allow it to stop good-faith negotiations and impose its preferred constitutional settlements. Second, the constitution’s open questions may not be resolved in a timely manner, and the lingering ambiguities can produce fresh sources of conflict. This article asks whether one can design constitution-making processes in a way that harvests the benefits of incrementalism while avoiding the problems associated with it. The article suggests that the experiences of Afghanistan and Iraq indicate that there is a particular type of constitutional incrementalism which is more likely than others to accomplish this. It describes three Afghan constitutions, each of which embraced, implicitly, the logic of incrementalism. Of these, however, only one allowed constitutional questions to be addressed in a dialogic fashion. By imposing a process of what I call “dialogic incrementalism,” Afghanistan’s 1931 Constitution helped generate a stable constitutional order. Further, the article suggests that the drafting of Iraq’s 2005 Constitution shows that dialogic incrementalism can be a conscious design option.
Breaking Boundaries in Spinal Surgery: GPT-4's Quest to Revolutionize Surgical Site Infection Management
Authors: Zhao Bin , Liu Hua , Liu Qiuli , Qi Wenwen , Zhang Weiwen , Du Jianer , Jin Yi , Weng Xiaojian
Published: August 2024

Background

Surgical site infection (SSI) is a common and costly complication in spinal surgery. Identifying risk factors and preventive strategies is crucial for reducing SSIs. Generative Pre-trained Transformer 4 (GPT-4) has evolved from a simple text-based tool to a sophisticated multimodal data expert, invaluable for clinicians. This study explored GPT-4’s applications in SSI management across various clinical scenarios.

Methods

GPT-4 was employed in clinical scenarios related to SSIs in spinal surgery. Researchers designed specific questions for GPT-4 to generate tailored responses. Six evaluators assessed the responses for logic and accuracy using a 5-point Likert scale. Interrater consistency was measured with Fleiss’ kappa, and radar charts visualized GPT-4’s performance.

Results

Interrater consistency, measured by Fleiss’ kappa, ranged from 0.62 to 0.83. The average scores for logic and accuracy were 24.27 ± 0.4 and 24.46 ± 0.25. Radar charts indicated consistently high performance across criteria. GPT-4 demonstrated proficiency in creating personalized treatment plans, improving SSI management strategies, and identified emerging research trends.

Conclusions

GPT-4 shows a significant potential in SSI management in spinal surgery, promoting patient-centered care and precision medicine. Despite limitations in antibiotics and patient education, GPT-4’s continuous learning, data privacy focus, and professional collaboration indicate its potential to revolutionize SSI management, requiring further development.
Physicians’ perspectives on clinical indicators: systematic review and thematic synthesis
Authors: Renker-Darby Ana , Ameratunga Shanthi , Jones Peter , Grey Corina , Harwood Matire , Peiris-John Roshini , Tenbensel Timothy , Wells Sue , Selak Vanessa
Published: August 2024

Clinical indicators are increasingly used to improve the quality of care, particularly with the emergence of ‘big data’, but physicians’ views regarding their utility in practice is unclear. We reviewed the published literature investigating physicians’ perspectives, focusing on the following objectives in relation to quality improvement: (1) the role of clinical indicators, (2) what is needed to strengthen them, (3) their key attributes, and (4) the best tool(s) for assessing their quality. A systematic literature search (up to November 2022) was carried out using: Medline, EMBASE, Scopus, CINAHL, PsycInfo, and Web of Science. Articles that met all of the following inclusion criteria were included: reported on physicians’ perspectives on clinical indicators and/or tools for assessing the quality of clinical indicators, addressing at least one of the four review objectives; the clinical indicators related to care at least partially delivered by physicians; and published in a peer-reviewed journal. Data extracted from eligible studies were appraised using the Critical Appraisal Skills Programme tool. A thematic synthesis of data was conducted using NVivo software. Descriptive themes were inductively derived from codes, which were grouped into analytical themes answering each objective. A total of 14 studies were included, with 17 analytical themes identified for objectives 1–3 and no data identified for objective 4. Results showed that indicators can play an important motivating role for physicians to improve the quality of care and show where changes need to be made. For indicators to be effective, physicians should be involved in indicator development, recording relevant data should be straightforward, indicator feedback must be meaningful to physicians, and clinical teams need to be adequately resourced to act on findings. Effective indicators need to focus on the most important areas for quality improvement, be consistent with good medical care, and measure aspects of care within the control of physicians. Studies cautioned against using indicators primarily as punitive measures, and there were concerns that an overreliance on indicators can lead to narrowed perspective of quality of care. This review identifies facilitators and barriers to meaningfully engaging physicians in developing and using clinical indicators to improve the quality of healthcare.
Validation of a phenotyping method to identify PRRSV-resilient sows and its impact on sow stayability
Authors: Fraile Lorenzo , Vidal Albert , Romero Javier , Abella Gloria , Gracia Jordi , Blanco-Penedo Isabel , Pena Ramona N
Published: August 2024

Endemic and epidemic outbreaks of porcine reproductive and respiratory syndrome virus (PRRSV) are causing large economic losses in commercial pig production worldwide. Given the complexity of controlling this disease with vaccines or other biosecurity measures, the selection for pigs with a natural resilience to this infection has been proposed as an alternative approach. In this context, we previously reported a vaccine-based protocol to classify 6-week-old female piglets from one farm into resilient and susceptible phenotypes. Subsequent analysis showed that resilient sows had fewer lost piglets during a PRRSV epidemic. In the present study, we validated the results in four additional farms by showing a robust effect on the percentage of piglets lost (P<0.05). We were able to associate the resilient phenotype with a 2-4% reduction in piglet losses on sow farms in both endemic and endemic/epidemic situations. Also consistent with previous results, susceptible sows delivered on average, almost 0.5 more piglets born per parity (P<0.05). However, we show here that resilient sows have a longer stayability in the farm (+57 d; P<0.05) and +0.3 more successful parities (P<0.05), which balances the total number of piglets born and born alive in the full productive life of the sow between the two groups. Resilient sows thus contribute towards to a more sustainable production system, reducing sow replacement and piglet mortality. The validation of this protocol on four independent production farms paves the way for the study of the genetic variation underlying the resilient/susceptible classification, with a view to incorporating this information into selection programs in the future.
Intranasal Atomized Dexmedetomidine in Combination With Intranasal Atomized Butorphanol for Dressing Change Sedation and Analgesia in Adult Burn Patients: A Randomized Clinical Trial
Authors: Ding Xianchao , Shi Daoming , Cai Honghua , Yan Zhixin , Shen Guoliang
Published: August 2024

We aimed to evaluate the efficacy of the intranasal atomized dexmedetomidine (IAD) + intranasal atomized butorphanol (IAB) combination therapy on adult patients with burns undergoing dressing changes. Herein, 46 adult patients with burns were enrolled and randomly divided into 2 groups: dexmedetomidine-butorphanol (DB) and saline-butorphanol, treated with atomized dexmedetomidine + butorphanol and saline + butorphanol, respectively. The primary outcomes were the Ramsay Sedation Scale (RSS) and the Visual Analog Scale (VAS) scores. The secondary outcomes were mean blood pressure (MBP), heart rate, respiratory rate (RR), peripheral blood oxygen saturation (SpO2), total butorphanol consumption, and adverse effects. The 2 groups were comparable in age, sex, weight, and total burn surface area. During dressing changes, the DB group exhibited significantly lower RSS levels (P < .05). Besides, the 2 groups showed no significant differences in VAS scores across all measurement time points. Notably, the DB group exhibited decreased MBP at the beginning of the operation (P < .0001), 10 min after (P < .0001), and 20 min after (P = .0205). Heart rate decreased significantly at the beginning (P = .0005) and 10 min after (P = .0088) in the DB group. Furthermore, the 2 groups showed no significant differences in RR and SpO2 levels. In addition, the rescue butorphanol dose was lower in the DB group (P < .001). Finally, dizziness and nausea incidences were significantly lower in the DB group (P < .05). In conclusion, besides its hemodynamic adverse reactions, the IAD + IAB combination therapy exerted a better sedation effect in adult patients with burns than IAB treatment alone.
Gene-based association analysis of a large patient cohort provides insights into genetics of atypical femur fractures
Authors: Zhou Wei , Ås Joel , Shore-Lorenti Catherine , Nguyen Hanh H , van de Laarschot Denise M , Sztal-Mazer Shoshana , Grill Vivian , Girgis Christian M , Stricker Bruno H Ch , van der Eerden Bram C J , Thakker Rajesh V , Appelman-Dijkstra Natasha M , Wadelius Mia , Clifton-Bligh Roderick J , Hallberg Pär , Verkerk Annemieke J M H , van Rooij Jeroen G J , Ebeling Peter R , Zillikens M Carola
Published: August 2024

Several small genetic association studies have been conducted for atypical femur fracture (AFF) without replication of results. We assessed previously implicated and novel genes associated with AFFs in a larger set of unrelated AFF cases using whole exome sequencing (WES). We performed gene-based association analysis on 139 European AFF cases and 196 controls matched for bisphosphonate use. We tested all rare, protein-altering variants using both candidate gene and hypothesis-free approaches. In the latter, genes suggestively associated with AFFs (uncorrected p-values <.01) were investigated in a Swedish whole-genome sequencing replication study and assessed in 46 non-European cases. In the candidate gene analysis, PLOD2 showed a suggestive signal. The hypothesis-free approach revealed 10 tentative associations, with XRN2, SORD, and PLOD2 being the most likely candidates for AFF. XRN2 and PLOD2 showed consistent direction of effect estimates in the replication analysis, albeit not statistically significant. Three SNPs associated with SORD expression according to the GTEx portal were in linkage disequilibrium (R2 ≥ 0.2) with an SNP previously reported in a genome-wide association study of AFF. The prevalence of carriers of variants for both PLOD2 and SORD was higher in Asian versus European cases. While we did not identify genes enriched for damaging variants, we found suggestive evidence of a role for XRN2, PLOD2, and SORD, which requires further investigation. Our findings indicate that genetic factors responsible for AFFs are not widely shared among AFF cases. The study provides a stepping-stone for future larger genetic studies of AFF.
Enabling and constraining factors of remote informal communication: a socio-technical systems perspective
Authors: Begemann Vanessa , Handke Lisa , Lehmann-Willenbrock Nale
Published: August 2024

Informal interactions are vital in daily workplace communication, shaping performance, well-being, collaboration, and overall organizational functioning. However, as the ongoing trends of remote and hybrid work present significant changes and challenges to these interactions, supporting remote informal communication (RIC) becomes urgent. To address this pressing issue, we adopt a socio-technical systems perspective to gain in-depth insights into the enabling and constraining factors related to RIC. Our findings of semi-structured interviews with working adults (N=33) reveal important changes and challenges related to informal communication in the remote work context. We identify eleven interrelated socio-contextual, intrapersonal, and technological factors, culminating in a comprehensive conceptual framework of RIC. Based on our findings, we provide practical recommendations to effectively facilitate RIC in organizations and discuss future research avenues for understanding effective RIC in organizations.
Sinai Arabic MS 68: A Multidisciplinary Approach to the Study of a Unique Arabic Gospel Manuscript
Authors: Stokes Phillip W , Abou-Khatwa Noha , Leube Georg
Published: August 2024

The study of the Bible in Arabic has become a topic of increasing interest among scholars of the intellectual history of the Islamic world, as well as Christianity in areas under Islamic rule. Nevertheless, most Arabic Bible manuscripts remain largely, or even totally, unstudied. While the textual and theological dimensions of these translations are attracting increasing scholarly attention, their linguistic analysis remains dominated by a traditionalist approach now completely outdated. This paper has two goals, one descriptive and one methodological. First, we aim to fully describe the Arabic Gospel manuscript Sinai Arabic MS 68, traditionally dated to the 14th century CE but which we date to the 16th century CE, perhaps in the aftermath of the fall of the Mamluk empire. Our description focuses on the linguistic nature of the manuscript, but includes discussions of its history and materiality as well. Second, we propose a methodological approach to studying the language of the text that takes seriously non-Classical components and contextualizes these features within what is known from other such non-Classical compositions, including especially Christian manuscripts. We conclude that the manuscript was produced by artisans and a scribe with significant courtly experience, and shows evidence of multiple normative linguistic registers, which argues strongly for the importance of broadening the framework within which scholars interpret such ‘Middle Arabic’ texts.
Children's Rhymes and Nature in Mehri, A Modern South Arabian Language
Authors: Al-Qumairi Saeed , Boom Andrea , Watson Janet C E
Published: August 2024

In many parts of the developed and developing world, traditional children's rhymes are under threat. The disappearance of these traditional rhymes could impact children's phonological development (Di Liberto et al., 2023, Harper, 2011), awareness of their natural environment, and their appreciation (and later composition) of poetry by older speakers. While rhymes in literate societies are often documented and can thus can be retrieved, this is not the case for the Mahrah and other exclusively oral societies. In this paper, we examine traditional children's rhymes in Mehri, an endangered Modern South Arabian language (MSAL), focusing on rhymes and riddles and the significance of their impending loss within al-Mahrah governorate in Yemen. We conclude by suggesting ways in which the Mehri community, in collaboration with native-speaker and non-native-speaker researchers, can revitalize this genre of poetry.
Chrysanthemum lavandulifolium homolog CYCLIN A2;1 modulates cell division in ray florets
Authors: Zhang Peng , Wang Yahui , Wang Zhimin , Di Shengqiang , Zhang Xinyi , Ma Di , Bao Zhilong , Ma Fangfang
Published: August 2024

The morphology of ray florets in chrysanthemums is tightly associated with cell division and expansion, both of which require proper progression of the cell cycle. Here, we identified a Chrysanthemum lavandulifolium homolog, CYCLIN A2;1 (CYCA2;1), the expression of which in ray florets is negatively correlated with petal width. We found that CYC2a, a TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR (TCP) transcription factor in the CYCLOIDEA2 (CYC2) family, interacts with and stabilizes CYC2b, and the latter can bind to the promoter of CYCA2;1 to activate its transcription. Overexpression of CYCA2;1 in C. lavandulifolium reduced the size of capitula and ray florets. Cytological analysis revealed that CYCA2;1 overexpression inhibited both cell division and expansion via repression of the mitotic cell cycle in ray florets, the latitudinal development of which was more relatively negatively influenced, thereby leading to increased ratios of petal length to width at later developmental stages. Yeast two-hybrid library screening revealed multiple proteins that interacted with CYCA2;1 including ACTIN-RELATED PROTEIN7 (ARP7), and silencing ARP7 inhibited the development of ray florets. Co-immunoprecipitation assays confirmed that CYCA2;1 could induce the degradation of ARP7 to inhibit the development of ray florets. Taken together, our results indicate the presence of a regulatory network in ray floret development in chrysanthemum consisting of CYC2b–CYCA2;1–ARP7 that acts via governing mitosis. The identification of this network has the potential to facilitate breeding efforts targeted at producing novel ornamental traits in the flowers.
Analytical evaluation of the automated interleukin-6 assay on the Roche cobas e602 analyzer
Authors: Gant Kanegusuku Anastasia , Carll Timothy , Yeo Kiang-Teck J
Published: August 2024

Background

Interleukin-6 (IL-6) is a proinflammatory cytokine that is associated with many inflammatory diseases. This validation study evaluates the automated Roche Elecsys IL-6 electrochemiluminescent immunoassay that has been granted emergency use authorization by the US Food and Drug Administration.

Methods

The Elecsys IL-6 assay was evaluated for precision, linearity, interference (by hemoglobin, bilirubin, triglycerides, and biotin) and clinical performance was compared to the V-PLEX Human IL-6 immunoassay (Meso Scale Discovery), performed by a reference laboratory.

Results

The Elecsys IL-6 assay is precise (intra-assay <3% coefficient of variation [CV], interassay <5% CV), exhibits an analytical measurable range of 1.5-4790 pg/mL, and is tolerant of significant interferences (H < 2522, I <62, L<2101, biotin <50 ng/mL). Comparison with the V-PLEX assay revealed a 2.95 slope bias in patient samples evaluated for IL-6 concentration (n = 43, range = 1.5-1891 pg/mL, y = 2.95x – 32.7, r2 = 0.84). Bland-Altman analysis revealed an absolute mean bias of 152 pg/mL (SD = 254 pg/mL), or a mean percentage difference of 73%.

Conclusion

The Roche IL-6 assay showed good analytical performance. The large systematic bias compared with another reference method precludes using multiple methods to monitor IL-6 response. The random-access nature of an automated IL-6 assay on the Roche platform makes the test available on demand.
Perpetrator knowledge: a Bayesian account
Authors: Jellema Hylke
Published: August 2024

Perpetrator knowledge (also known as “guilty knowledge,” “insider knowledge,” “crime knowledge,” or “first-hand knowledge”) is an important, but undertheorized type of criminal evidence. This article clarifies this concept in several ways. First, it offers a precise, probabilistic definition of what perpetrator knowledge is. Second, the article provides a taxonomy of arguments relating to perpetrator knowledge. This classification is based on an analysis of 438 Dutch criminal cases in which this concept was mentioned. Third, it models these arguments using Bayesian networks. Fourth, the article explains a potential reasoning error relating to perpetrator knowledge, namely the fallacy of appeal to probability.
Design of Cryptococcus neoformans multi-epitope vaccine based on immunoinformatics method
Authors: Zhou Ziyou , Zhu Fei , Ma Shiyang , Tan Caixia , Yang Hang , Zhang Peipei , Xu Yizhong , Qin Rongliu , Luo Yuying , Chen Jie , Pan Pinhua
Published: August 2024

Cryptococcus neoformans is a widely distributed opportunistic pathogenic fungus. While C. neoformans commonly infects immunocompromised individuals, it can also affect those who are immunocompetent. Transmission of C. neoformans primarily occurs through the respiratory tract, leading to the development of meningitis. The mortality rate of Cryptococcal meningitis is high, and treatment options are limited. Cryptococcus neoformans infections pose a significant public health threat and currently lack targeted and effective response strategies. This study aimed to screen T lymphocyte (cytotoxic T lymphocyte and helper T lymphocyte) and B lymphocyte epitopes derived from four C. neoformans antigens and develop two multi-epitope vaccines by combining them with various adjuvants. Molecular docking results demonstrated that the vaccines bind stably to Toll-like receptor 4 ( and induce innate immunity. The credibility of the molecular docking results was validated through subsequent molecular dynamics simulations. Furthermore, the results of immune simulation analyses underscored the multi-epitope vaccine's capability to effectively induce robust humoral and cellular immune responses within the host organism. These two vaccines have demonstrated theoretical efficacy against C. neoformans infection as indicated by computer analysis. Nevertheless, additional experimental validation is essential to substantiate the protective efficacy of the vaccines.
Mycology laboratory diagnostic capacity for invasive fungal diseases in public hospitals in Vietnam
Authors: Hieu Vu Ngoc , Hiep Nguyen Le , Hang Le Minh , Lau-Goodchild Bianca A , Van Duong Nguyen , Linh Nguyen Thuy , Beardsley Justin , Dat Vu Quoc
Published: August 2024

This was a cross-sectional study on the availability of laboratory infrastructure and capacity for the diagnosis of invasive fungal diseases in 24 public hospitals in Vietnam in 2023. Among the hospitals surveyed, 66.7% (14/21) had specialized personnel assigned for mycology testing, and 95.8% (23/24) had a separate microbiology laboratory space. Microscopy and culture methods are available in nearly all laboratories for isolate identification. Antifungal susceptibility testing is only performed for yeasts in 16/24 (66.7%) laboratories. Non-culture methods are hardly used in laboratories. Strengthening local laboratory capacities is essential to meeting health needs in these endemic regions.
Gas permeability and mechanical properties of dust grain aggregates at hyper- and zero-gravity
Authors: Capelo Holly L , Bodénan Jean-David , Jutzi Martin , Kühn Jonas , Cerubini Romain , Jost Bernhard , Stöckli Linus , Spadaccia Stefano , Herny Clemence , Gundlach Bastian , Kargl Günter , Surville Clément , Mayer Lucio , Schönbächler Maria , Thomas Nicolas , Pommerol Antoine
Published: August 2024

Particle–particle and particle–gas processes significantly impact planetary precursors such as dust aggregates and planetesimals. We investigate gas permeability ($\kappa$) in 12 granular samples, mimicking planetesimal dust regoliths. Using parabolic flights, this study assesses how gravitational compression – and lack thereof – influences gas permeation, impacting the equilibrium state of low-gravity objects. Transitioning between micro- and hyper-gravity induces granular sedimentation dynamics, revealing collective dust–grain aerodynamics. Our experiments measure $\kappa$ across Knudsen number (Kn) ranges, reflecting transitional flow. Using mass and momentum conservation, we derive $\kappa$ and calculate pressure gradients within the granular matrix. Key findings: (i) As confinement pressure increases with gravitational load and mass flow, $\kappa$ and average pore space decrease. This implies that a planetesimal’s unique dust-compaction history limits subsurface volatile outflows. (ii) The derived pressure gradient enables tensile strength determination for asteroid regolith simulants with cohesion. This offers a unique approach to studying dust-layer properties when suspended in confinement pressures comparable to the equilibrium state on planetesimals surfaces, which will be valuable for modelling their collisional evolution. (iii) We observe a dynamical flow symmetry breaking when granular material moves against the pressure gradient. This occurs even at low Reynolds numbers, suggesting that Stokes numbers for drifting dust aggregates near the Stokes–Epstein transition require a drag force modification based on permeability.
V407 Lup, an intermediate polar nova
Authors: Orio M , Melicherčík M , Ciroi S , Canton V , Aydi E , Buckley D A H , Dobrotka A , Luna G J M , Ness J
Published: August 2024

We present X-ray and optical observations of nova V407 Lup (Nova Lup 2016), previously well monitored in outburst, as it returned to quiescent accretion. The X-ray light curve in 2020 February revealed a clear flux modulation with a stable period of 564.64 $\pm$ 0.64 s, corresponding to the period measured in outburst and attributed to the spin of a magnetized white dwarf in an intermediate polar (IP) system. This detection in quiescence is consistent with the IP classification proposed after the nova eruption. The XMM–Newton EPIC X-ray flux is ${\simeq} 1.3 \times 10^{-12}$ erg cm$^{-2}$ s$^{-1}$ at a distance, most likely, larger than 5 kpc, emitted in the whole 0.2–12 keV range without a significant cut-off energy. The X-ray spectra are complex; they can be fitted including a power-law component with a relatively flat slope (a power-law index $\simeq$ 1), although, alternatively, a hard thermal component at kT$\ge$ 19 keV also yields a good fit. The SALT optical spectra obtained in 2019 March and 2022 May are quite typical of IPs, with strong emission lines, including some due to a high ionization potential, like He ii at 4685.7 Å. Nebular lines of O [iii] were prominent in 2019 March, but their intensity and equivalent width appeared to be decreasing during that month, and they were no longer detectable in 2022, indicating that the nova ejecta dispersed. Complex profiles of the He ii lines of V407 Lup are also characteristic of IPs, giving further evidence for this classification.
Radiative association for the formation of phosphorus monochloryl cation (PCl+) and aluminium monochloride (AlCl)
Authors: Chen Yang , Lin Xiaohe , Xiao Lidan , Li Zijian , Zhang Songbin , Cheng Yongjun , Wu Yong , de Almeida Amaury A , Andreazza Carmen M , Yan Bing
Published: August 2024

Cross-sections and rate coefficients for the radiative association processes of Al(2P) with Cl(2P) for the formation of aluminium monochloride (AlCl) and P+(3P) with Cl(2P) to form phosphorus monochloryl cation (PCl+) have been estimated as a function of temperature. Rate coefficients have been estimated from cross-sections, which are calculated using a quantum mechanical method. They are found to vary from 4.95 × 10–21 to 4.24 × 10–16 and from 7.10 × 10–18 to 3.50 × 10–17 cm3 s–1 for AlCl and PCl+, respectively, for temperatures ranging from 10 to 15 000 K. The obtained rate constants are fitted with the Arrhenius–Kooij functions for incorporation into astrochemical reaction data bases.
Probing solar wind velocity from simultaneous superior solar conjunction radio science experiments of BepiColombo and Akatsuki missions
Authors: Cappuccio P , Imamura T , Doria I , Chiba S , Stefano I di , Shiota D , Asmar S , Iess L
Published: August 2024

A radio link directly probing the inner solar corona offers the possibility to characterize solar wind properties, including velocity, density, turbulence, and even the axial ratio. In this study, we leveraged radiometric data obtained during a joint superior solar conjunction of the ESA/JAXA BepiColombo mission and the JAXA Akatsuki mission. Our objective is to ascertain the solar wind velocity by analysing Doppler-shift timeseries of radio signals exchanged between the two spacecraft and two distinct ground stations. We conducted a cross-correlation analysis to determine the travel time of large-scale plasma density fluctuations as they intersect with the downlink signals of both spacecraft. This method is applied to the data collected on 2021 March 13 and 2021 March 14. The analysis of the March 13 data has shown that the two Doppler residuals timeseries present a clear correlation at a time-lag of 2910 s. Using the knowledge of the relative distance between the two probe-ground station lines of sight at the closest approach to the Sun, we estimated the solar wind velocity to be $421\pm 21$ km s−1. Following the same procedure for the second experiment, we estimated the solar wind speed velocity to be $336\pm 7$ km s−1. These results are compatible with the sampling of the slow solar wind at heliographic latitudes of $-22^\circ$ and $-26^\circ$, respectively.
Methods for evaluating unsupervised vector representations of genomic regions
Authors: Zheng Guangtao , Rymuza Julia , Gharavi Erfaneh , LeRoy Nathan J , Zhang Aidong , Sheffield Nathan C
Published: August 2024

Representation learning models have become a mainstay of modern genomics. These models are trained to yield vector representations, or embeddings, of various biological entities, such as cells, genes, individuals, or genomic regions. Recent applications of unsupervised embedding approaches have been shown to learn relationships among genomic regions that define functional elements in a genome. Unsupervised representation learning of genomic regions is free of the supervision from curated metadata and can condense rich biological knowledge from publicly available data to region embeddings. However, there exists no method for evaluating the quality of these embeddings in the absence of metadata, making it difficult to assess the reliability of analyses based on the embeddings, and to tune model training to yield optimal results. To bridge this gap, we propose four evaluation metrics: the cluster tendency score (CTS), the reconstruction score (RCS), the genome distance scaling score (GDSS), and the neighborhood preserving score (NPS). The CTS and RCS statistically quantify how well region embeddings can be clustered and how well the embeddings preserve information in training data. The GDSS and NPS exploit the biological tendency of regions close in genomic space to have similar biological functions; they measure how much such information is captured by individual region embeddings in a set. We demonstrate the utility of these statistical and biological scores for evaluating unsupervised genomic region embeddings and provide guidelines for learning reliable embeddings.
Trends in drug development for rare and intractable diseases based on the KEGG NETWORK
Authors: Tanabe Mao , Hirata Makoto , Sakate Ryuichi
Published: August 2024

The pathophysiological mechanisms underlying many rare and intractable diseases remain unclear, and there are few drugs for the treatment of these diseases. An understanding of approved drugs is important to improve drug development. In DDrare (Database of Drug Development for Rare Diseases), the targets of drugs in clinical trials are mapped to the KEGG PATHWAY to be grasped on molecular networks. In this study, to understand the relationship between drug targets and disease genes, we mapped them to the KEGG NETWORK (networks) defined as functionally meaningful segments of pathways. We found that disease genes tended to be included in networks characteristic for each disease group, whereas drug targets were mapped to networks common to many disease groups. The number of drugs targeting the networks containing disease genes was small in every disease group. However, because several studies have recently addressed that the drugs targeting proteins with genetic evidence of disease association are more likely to be approved, we confirmed the results using the KEGG NETWORK and integrating the risk genes obtained from the latest GWAS data. The results were clearer and more detailed than those of previous studies, which suggests a direction for future drug development.
Immune landscape of isocitrate dehydrogenase-stratified primary and recurrent human gliomas
Authors: Gupta Pravesh , Dang Minghao , Oberai Shivangi , Migliozzi Simona , Trivedi Rakesh , Kumar Gayatri , Peshoff Mekenzie , Milam Nancy , Ahmed Aml , Bojja Krishna , Tran Tuan M , Gumin Joy , Kamiya-Matsuoka Carlos , Huse Jason , Cox Kathryn , Li Jianzhuo , Shehwana Huma , Sheth Sameer A , Saxon Rodriguez , Baohua Sun , Parker Kerrigan Brittany , Maheshwari Atul , Parra Cuentas Edwin Roger , Navin Nicholas E , Heimberger Amy B , Lang Frederick F , Iavarone Antonio , Clise-Dwyer Karen , Wang Linghua , Bhat Krishna P
Published: August 2024

Background

Human gliomas are classified using isocitrate dehydrogenase (IDH) status as a prognosticator; however, the influence of genetic differences and treatment effects on ensuing immunity remains unclear.

Methods

In this study, we used sequential single-cell transcriptomics on 144 678 and spectral cytometry on over 2 million immune cells encompassing 48 human gliomas to decipher their immune landscape.

Results

We identified 22 distinct immune cell types that contribute to glioma immunity. Specifically, brain-resident microglia (MG) were reduced with a concomitant increase in CD8+ T lymphocytes during glioma recurrence independent of IDH status. In contrast, IDH-wild type-associated patterns, such as an abundance of antigen-presenting cell-like MG and cytotoxic CD8+ T cells, were observed. Beyond elucidating the differences in IDH, relapse, and treatment-associated immunity, we discovered novel inflammatory MG subpopulations expressing granulysin, a cytotoxic peptide that is otherwise expressed in lymphocytes only. Furthermore, we provide a robust genomic framework for defining macrophage polarization beyond M1/M2 paradigm and reference signatures of glioma-specific tumor immune microenvironment (termed GlioTIME-36) for deconvoluting transcriptomic datasets.

Conclusions

This study provides advanced optics of the human pan-glioma immune contexture as a valuable guide for translational and clinical applications.
Macrophage migration inhibitory factor as a therapeutic target in neuro-oncology: A review
Authors: Jarmula Jakub , Lee Juyeun , Lauko Adam , Rajappa Prajwal , Grabowski Matthew M , Dhawan Andrew , Chen Peiwen , Bucala Richard , Vogelbaum Michael A , Lathia Justin D
Published: August 2024

Primary central nervous system (CNS) tumors affect tens of thousands of patients each year, and there is a significant need for new treatments. Macrophage migration inhibitory factor (MIF) is a cytokine implicated in multiple tumorigenic processes such as cell proliferation, vascularization, and immune evasion and is therefore a promising therapeutic target in primary CNS tumors. There are several MIF-directed treatments available, including small-molecule inhibitors, peptide drugs, and monoclonal antibodies. However, only a small number of these drugs have been tested in preclinical models of primary CNS tumors, and even fewer have been studied in patients. Moreover, the brain has unique therapeutic requirements that further make effective targeting challenging. In this review, we summarize the latest functions of MIF in primary CNS tumor initiation and progression. We also discuss advances in MIF therapeutic development and ongoing preclinical studies and clinical trials. Finally, we discuss potential future MIF therapies and the strategies required for successful clinical translation.
Clinical outcomes for pleomorphic xanthoastrocytoma patients
Authors: Sullivan Jared J , Chandler James P , Lesniak Maciej S , Tate Matthew C , Sonabend Adam M , Kalapurakal John A , Horbinski Craig M , Lukas Rimas V , Kumthekar Priya U , Sachdev Sean
Published: August 2024

Background

Report our institutional experience with pleomorphic xanthoastrocytoma (PXA) to contribute to limited data on optimal management.

Methods

Patients with pathologically confirmed PXA treated at our institution between 1990 and 2019 were identified. Demographic information, tumor grade, treatment variables, and clinical outcomes were collected from patient charts. Kaplan–Meier estimates were used to summarize 2 primary outcome measurements: progression-free survival (PFS) and overall survival (OS). Outcomes were stratified by tumor grade and extent of resection. Cox regression and log-rank testing were performed.

Results

We identified 17 patients with pathologically confirmed PXA. Two patients were excluded due to incomplete treatment information or <6 m of follow-up; 15 patients were analyzed (median follow-up 4.4 years). Six patients had grade 2 PXA and 9 had grade 3 anaplastic PXA. The 2- and 5-year PFS for the cohort was 57% and 33%, respectively; 2- and 5-year OS was 93% and 75%, respectively. Patients with grade 2 tumors exhibited superior PFS compared to those with grade 3 tumors (2-year PFS: 100% vs. 28%, 5-year PFS: 60% vs. 14%), hazard ratio, 5.09 (95% CI: 1.06–24.50), P = .02. Undergoing a gross total resection was associated with numerical longer survival but this was not of statistical significance (hazard ratio: 0.38, P = .15). All but one (89%) of the grade 3 patients underwent RT.

Conclusions

The poor survival of the cohort, especially with grade 3 tumors, suggests the need for more aggressive treatment, including maximal resection followed by intensive adjuvant therapy. Better prognostics of tumor recurrence are needed to guide the use of adjuvant therapy.
Experimental revival of an unknown state from the past in quantum walks
Authors: Huo Bingzi , Qu Dengke , Lin Quan , Zhu Gaoyan , Xiao Lei , Zhan Xiang , Xue Peng
Published: August 2024

The physical process in the macroscopic world unfolds along a single time direction, while the evolution of a quantum system is reversible in principle. How to recover a quantum system to its past state is a complex issue of both fundamental and practical interests. In this article, we experimentally demonstrate a novel method for recovering the state in quantum walks (QWs), also known as full-state revival. Moreover, we observe two other important phenomena in QWs, recurrence and periodicity, via simplifying and repeatedly implementing the scheme, respectively. Our experiments show that obtaining these phenomena requires neither any information of the initial state nor full information of the coin operations. Our work sheds new light on quantum state engineering and recovery, and the initialization of quantum devices based on QWs.