bluuebunny/crossref_metadata_2025_split huggingface dataset:
Large-scale heterogeneity gradient drives the structure and biodiversity of branchiopod (Anostraca, Cladocera) egg-banks in the Nebraska Sandhills wetlands, USA
Authors: Mausbach William E , Dzialowski Andrew R 
Published: July 2024

Abstract
Branchiopods use resting eggs to maintain permanent populations in temporally dynamic environments as well as for dispersing to neighboring habitat patches. We used a large-scale longitudinal salinity gradient that overlays the Nebraska Sandhills, USA to determine how changes in metacommunity environmental heterogeneity influences species composition and biodiversity of branchiopod egg banks from freshwater and saline temporary wetlands. We sampled the egg banks of 54 wetlands from three metacommunities across the Nebraska Sandhills (eastern, central, and western) in which the relative abundance and salinity of saline wetlands increased westwards. Salinity had a strong effect on structuring the egg-bank metacommunities with a clear shift in species composition and species richness from the eastern to western metacommunities. Egg-bank alpha richness of the freshwater wetlands and metacommunity gamma richness declined westwards as the abundance of freshwater wetlands decreased relative to the saline wetlands. The low-salinity wetlands represented an intermediate stage between the freshwater and high-salinity wetlands, overlapping in species composition with both habitat types and supporting similar numbers of species as freshwater wetlands. High-salinity wetlands had the lowest alpha richness with only halotolerant and halophilic species.
Two semantic interpretations of probabilities in description logics of typicality
Authors: Lieto Antonio , Pozzato Gian Luca 
Published: July 2024

Abstract
In this work we focus on extensions of Description Logics (DLs) of typicality by means of probabilities. We introduce a novel extension of the logic of typicality $\mathcal{ALC}+\mathbf{T}_{\mathbf{R}}$, able to represent and reason about typical properties and defeasible inheritance in DLs. The novel logic ($\mathcal{ALC}\mathbf{T}^{\textsf{P}}$: Typical $\mathcal{ALC}$ with Probabilities as Proportions) allows inclusions of the form $\mathbf{T}(C) \sqsubseteq ^{p} D$, with probability $p$ representing a proportion, meaning that “all the typical $C$s are $D$s, and the probability that a $C$ element is not a $D$ element is $1-p$”. We also compare and confront this novel logic with a similar one already presented in the literature ($\mathbf{T}^{\textsf{CL}}$, introduced in Lieto and Pozzato (2020, J. Exp. Theor. Artif. Intell., 32, 769–804)), inspired by the DISPONTE semantics and that allows inclusions of the form $p \:: \ \mathbf{T}(C) \sqsubseteq D$ with probability $p$, where $p$ represents a degree of belief, whose meaning is that “we believe with a degree $p$ that typical $C$s’ are also $D$s.”. We then show that the proposed $\mathcal{ALC}\mathbf{T}^{\textsf{P}}$ extension (like the previous $\mathbf{T}^{\textsf{CL}}$) can be applied in order to tackle a specific and challenging problem in the field of common-sense reasoning, namely the combination of prototypical concepts, that have been shown to be problematic to model for other symbolic approaches like fuzzy logic. We show that, for the proposed extension, the complexity of reasoning remains ExpTime-complete as for the underlying standard monotonic DL $\mathcal{ALC}$.
Interrogative logic as underlying logic in scientific practices
Authors: Nepomuceno-Fernández Angel 
Published: July 2024

Abstract
In this paper I propose a version of interrogative logic as a form of representation of the underlying logic of scientific practices—a kind of model-based reasoning, since it takes into account an oracle or model that can be consulted—by means of modified tableaux that can represent a game with two types of moves: logical steps and queries, governed by (modified) tales and a query rule, respectively. In this way, the process of acquiring knowledge is analogous to the justification of a thesis through the method of modified tableaux.
Deciphering prefrontal circuits underlying stress and depression: exploring the potential of volume electron microscopy
Authors: Nagai Hirotaka 
Published: July 2024

Abstract
Adapting to environmental changes and formulating behavioral strategies are central to the nervous system, with the prefrontal cortex being crucial. Chronic stress impacts this region, leading to disorders including major depression. This review discusses the roles for prefrontal cortex and the effects of stress, highlighting similarities and differences between human/primates and rodent brains. Notably, the rodent medial prefrontal cortex is analogous to the human subgenual anterior cingulate cortex in terms of emotional regulation, sharing similarities in cytoarchitecture and circuitry, while also performing cognitive functions similar to the human dorsolateral prefrontal cortex. It has been shown that chronic stress induces atrophic changes in the rodent mPFC, which mirrors the atrophy observed in the subgenual anterior cingulate cortex and dorsolateral prefrontal cortex of depression patients. However, the precise alterations in neural circuitry due to chronic stress are yet to be fully unraveled. The use of advanced imaging techniques, particularly volume electron microscopy, is emphasized as critical for the detailed examination of synaptic changes, providing a deeper understanding of stress and depression at the molecular, cellular and circuit levels. This approach offers invaluable insights into the alterations in neuronal circuits within the medial prefrontal cortex caused by chronic stress, significantly enriching our understanding of stress and depression pathologies.
Adverse events in men with advanced prostate cancer treated with androgen biosynthesis inhibitors and androgen receptor inhibitors
Authors: Faraj Kassem S , Oerline Mary , Kaufman Samuel R , Dall Christopher , Srivastava Arnav , Caram Megan E V , Shahinian Vahakn B , Hollenbeck Brent K 
Published: July 2024

Abstract

Background
The use of androgen biosynthesis and second-generation androgen receptor inhibitors for advanced prostate cancer is increasing. Because these therapies alter the androgen pathway, they have been associated with cardiometabolic and neurocognitive toxicities. Although their safety profiles have been assessed in clinical trials, real-world data are limited.

Methods
A 20% sample of national Medicare claims was used to perform a retrospective cohort study of Medicare beneficiaries with advanced prostate cancer treated with androgen biosynthesis (ie, abiraterone) and second-generation androgen receptor inhibitors between 2012 and 2019. Outcomes were assessed after the first fill of either class of drug for the 12-month period after starting therapy. The primary outcome was a hospital admission or emergency department visit for a cardiometabolic event. Secondary outcomes included neurocognitive events and fractures. Multivariable regression was used to assess the association between the class of drug and occurrence of an adverse event.

Results
There were 3488 (60%) men started on an androgen biosynthesis inhibitor and 2361 (40%) started on an androgen receptor inhibitor for the first time. Cardiometabolic adverse events were more common in men managed with androgen biosynthesis inhibitor (9.2% vs 7.5%, P = .027). No difference between androgen biosynthesis and androgen receptor inhibitors was observed for neurocognitive events (3.3% vs 3.4%, respectively; P = .71) or fractures (4.2% vs 3.6%, respectively; P = .26).

Conclusions
Men with advanced prostate cancer initiating an androgen biosynthesis inhibitor for the first time more commonly had cardiometabolic events than those started on androgen receptor inhibitors. Neurocognitive events and fractures did not differ by drug class.
Variation to biology: optimizing functional analysis of cancer risk variants
Authors: Nelson Stefanie , Carrick Danielle , Daee Danielle , Fingerman Ian , Gillanders Elizabeth 
Published: July 2024

Abstract
Research conducted over the past 15+ years has identified hundreds of common germline genetic variants associated with cancer risk, but understanding the biological impact of these primarily non-protein coding variants has been challenging. The National Cancer Institute sought to better understand and address those challenges by requesting input from the scientific community via a survey and a 2-day virtual meeting, which focused on discussions among participants. Here, we discuss challenges identified through the survey as important to advancing functional analysis of common cancer risk variants: 1) When is a variant truly characterized; 2) Developing and standardizing databases and computational tools; 3) Optimization and implementation of high-throughput assays; 4) Use of model organisms for understanding variant function; 5) Diversity in data and assays; and 6) Creating and improving large multidisciplinary collaborations. We define these 6 challenges, describe how success in addressing them may look, propose potential solutions, and note issues that span all the challenges. Implementation of these ideas could help develop a framework for methodically analyzing common cancer risk variants to understand their function and make effective and efficient use of the wealth of existing genomic association data.
Racial and ethnic disparities in robot-assisted radical prostatectomy: testing the physician-level segregated and differential treatment hypotheses
Authors: Mao Jialin , Genkinger Jeanine M , Rundle Andrew G , Wright Jason D , Insaf Tabassum Z , Schymura Maria J , Hu Jim C , Tehranifar Parisa 
Published: July 2024

Abstract

Background
Mechanisms underlying racial and ethnic disparities in robot-assisted radical prostatectomy (RARP) vs open radical prostatectomy (ORP) are unclear. We sought to test 2 physician-level hypotheses: 1) Segregated Treatment and 2) Differential Treatment.

Methods
This observational study used the New York State Cancer Registry linked to discharge records and included patients undergoing radical prostatectomy for localized prostate cancer from October 1, 2008 to December 31, 2018. For hypothesis 1, we examined the association between patient race and ethnicity and treating surgeon RARP use (high-use surgeons, low-use surgeons, and surgeons at non-RARP facilities). For hypothesis 2, we determined the association between patient race and ethnicity and receipt of RARP when matching on treating surgeon, age, year of procedure, and Gleason group. We explored the role of insurance in both analyses.

Results
This study included 18 926 patients (8.0% Hispanic, 16.9% non-Hispanic Black, 75.1% non-Hispanic White), with a mean age of 60.4 ± 7.1 years. Compared with non-Hispanic White patients, Hispanic and non-Hispanic Black patients had higher odds of being treated by low-RARP-use surgeons (odds ratio [OR] = 2.16, 95% confidence interval [CI] = 1.20 to 3.88; OR = 1.76, 95% CI = 1.06 to 2.94, respectively) and by surgeons at non-RARP facilities (OR = 4.19, 95% CI = 2.18 to 8.07; OR = 4.60, 95% CI = 2.58 to 8.23, respectively). In the matched cohorts, Hispanic and non-Hispanic Black patients were less likely to receive RARP than non-Hispanic White patients (OR = 0.78, 95% CI = 0.62 to 0.98; OR = 0.75, 95% CI = 0.57 to 1.00, respectively). These associations were partially attenuated after accounting for insurance.

Conclusions
Racial and ethnic disparities in RARP use are related to patients being treated by different surgeons and treated differently by the same surgeons. Identifying and addressing multilevel barriers to equitable surgical treatment is needed to reduce disparities among prostate cancer patients.
Dihydroisotanshinone I regulates ferroptosis via PI3K/AKT pathway to enhance cisplatin sensitivity in lung adenocarcinoma
Authors: Li Feng-Jiao , Gao Li-Chen , Long Hui-Zhi , Zhou Zi-Wei , Luo Hong-Yu , Xu Shuo-Guo , Dai Shang-Ming , Hu Jin-Da 
Published: July 2024

Abstract

Objectives
Dihydroisotanshinone I (DT) is a kind of diterpenoid compound extracted from the dried roots of Salvia miltiorrhiza Bunge, and exhibits multiple biological activities including anti-tumor activity. Cisplatin is one of the first-line drugs for the treatment of lung adenocarcinoma (LAUD), but the drug resistance and toxicity limit its efficacy. DT is known to induce apoptosis and ferroptosis, but it is unclear whether DT can inhibit the cisplatin-resistant LAUD cells and reverse the drug resistance in LAUD. Therefore, our study intends to establish the cisplatin-resistant human LAUD cells (A549/DDP), and figure out the influence and related mechanisms of DT reversing cisplatin resistance in A549/DDP cells, so as to provide a theoretical basis for the DT as a new natural candidate for the treatment of LAUD.

Methods
The establishment of A549/DDP was the continuous stimulation by exposing A549 to gradient concentrations of Cisplatin. The cell viability of A549 and A549/DDP was detected by CCK-8 kit, and the IC50 value was calculated. The morphological changes of A549 and A549/DDP cells were observed by an inverted microscope. The contents of malondialdehyde (MDA) and glutathione (GSH) in A549/DDP cells after drug treatment were detected by related kits. The levels of Fe2+, cytosolic reactive oxygen species (ROS), and lipid reactive oxygen species (lipid ROS) were detected by a fluorescence microplate reader or fluorescence cell imager according to the related fluorescent probe kit instructions. Western blot was used to detect the expressions of PI3K, phospho-PI3K, AKT, phospho-AKT, MDM2, p53, GPX4, and SLC7A11 in A549/DDP after different drug treatments.

Key findings
Our study demonstrated that the inhibitory effect of DT on A549 and A549/DDP cells was time-dependent and concentration-dependent, and DT and DDP had a synergistic effect on inhibiting the proliferation of A549/DDP cells. Furthermore, DT mainly induced ferroptosis in A549/DDP cells and synergized with cisplatin to promote ferroptosis in A549/DDP cells. The result of KEGG pathway analysis, molecular docking and western blot showed that DT could enhance the cisplatin sensitivity of A549/DDP by inhibiting PI3K/MDM2/P53 signaling pathway.

Conclusions
Consequently, we concluded that DT promotes ferroptosis in cisplatin-resistant LAUD A549/DDP cells. Additionally, DT reverses cisplatin resistance by promoting ferroptosis via PI3K/MDM2/P53 pathway in A549/DDP cells.
Co-administration of Ceratonia siliqua extract nanoparticles promotes the oral bioavailability and neurotherapeutic efficacy of donepezil in a dementia model
Authors: Shaker Sylvia E , Fayed Dalia B , Shawky Heba , Farrag Ebtehal K 
Published: July 2024

Abstract

Background
This study aimed to assess the herb–drug interactions between crude/silver nanoparticle (SNP)-loaded carob extract (Car, NCar, respectively) and donepezil-HCl (DPZ) and their impact on neurotherapeutic outcomes in a dementia model.

Methods
Carob pods were subjected to ethanol extraction, and their phytoconstituents were chromatographically analysed. SNP-loaded extract was synthesized and characterized, and dementia-like symptoms were induced in Wistar rats by repeated dosing with 175 mg/kg AlCl3 for 60 days, after which the animals were treated with Car, NCar, DPZ, and combinations of Car/NCar-DPZ for 30 days. The effect of carob formulations on DPZ bioavailability was in-silico profiled and the herb–drug interactions were mathematically assessed as combination indices.

Results
Different formulations significantly improved cognitive/spatial memory functions, restored dysregulated brain redox and cholinergic functions, and markedly inhibited cholinesterase, as reflected by the reduction/absence of amyloid plaques and neurofibrillary tangles. In silico profiling of the major phytoconstituents revealed their non-P-glycoprotein substrate nature and CYP3A4, 2C19, and 2C9 inhibition, which might have improved the oral bioavailability of DPZ. The combination index calculations revealed strong synergy between DPZ and both carob formulations, with the strongest effect exhibited by the DPZ/NCar combination.

Conclusion
The co-administration of carob extract/SNPs represents a promising approach for enhancing the neurotherapeutic efficacy of DPZ.
Tracking trend output using expectations data
Authors: Lee Kevin , Mahony Michael 
Published: July 2024

Abstract
This article proposes a new approach to measuring trend output that exploits survey data on expectations to distinguish the effects of permanent and transitory shocks and to track the time-variation in the processes underlying the determination of output. The approach is illustrated using measures of output expectations and output uncertainties based on a business survey conducted for UK manufacturing. The measures are employed in a time-varying vector autoregression (VAR) to track trend output and to provide a compelling characterization of the output fluctuations in UK manufacturing over the last 20 years.
Bias and excess variance in election polling: a not-so-hidden Markov model
Authors: Tierney Graham , Volfovsky Alexander 
Published: July 2024

Abstract
With historic misses in the 2016 and 2020 US Presidential elections, interest in measuring polling errors has increased. The most common method for measuring directional errors and non-sampling excess variability during a postmortem for an election is by assessing the difference between the poll result and election result for polls conducted within a few days of the day of the election. Analysing such polling error data is notoriously difficult with typical models being extremely sensitive to the time between the poll and the election. We leverage hidden Markov models traditionally used for election forecasting to flexibly capture time-varying preferences and treat the election result as a peek at the typically hidden Markovian process. Our results are much less sensitive to the choice of time window, avoid conflating shifting preferences with polling error, and are more interpretable despite a highly flexible model. We demonstrate these results with data on polls from the 2004 through 2020 US Presidential elections and 1992 through 2020 US Senate elections, concluding that previously reported estimates of bias in Presidential elections were too extreme by 10%, estimated bias in Senatorial elections was too extreme by 25%, and excess variability estimates were also too large.
Genomic and cell-specific regulation of benzylisoquinoline alkaloid biosynthesis in opium poppy
Authors: Hong Uyen Vu Thuy , Tamiru-Oli Muluneh , Hurgobin Bhavna , Lewsey Mathew G 
Published: July 2024

Abstract
Opium poppy is a crop of great commercial value as a source of several opium alkaloids for the pharmaceutical industries including morphine, codeine, thebaine, noscapine, and papaverine. Most enzymes involved in benzylisoquinoline alkaloid (BIA) biosynthesis in opium poppy have been functionally characterized, and opium poppy currently serves as a model system to study BIA metabolism in plants. BIA biosynthesis in opium poppy involves two biosynthetic gene clusters associated respectively with the morphine and noscapine branches. Recent reports have shown that genes in the same cluster are co-expressed, suggesting they might also be co-regulated. However, the transcriptional regulation of opium poppy BIA biosynthesis is not well studied. Opium poppy BIA biosynthesis involves three cell types associated with the phloem system: companion cells, sieve elements, and laticifers. The transcripts and enzymes associated with BIA biosynthesis are distributed across cell types, requiring the translocation of key enzymes and pathway intermediates between cell types. Together, these suggest that the regulation of BIA biosynthesis in opium poppy is multilayered and complex, involving biochemical, genomic, and physiological mechanisms. In this review, we highlight recent advances in genome sequencing and single cell and spatial transcriptomics with a focus on how these efforts can improve our understanding of the genomic and cell-specific regulation of BIA biosynthesis. Such knowledge is vital for opium poppy genetic improvement and metabolic engineering efforts targeting the modulation of alkaloid yield and composition.
Jasmonate/ethylene- and NaWRKY6/3-regulated Alternaria resistance depends on ethylene response factor 1B-like in Nicotiana attenuata
Authors: Ma Lan , Song Na , Duan Qing , Du Wenwen , Li Xiang , Jia Wenjie , Cui Guangfen , Wang Jihua , Wu Jinsong 
Published: July 2024

Abstract
Biosynthesis of the phytoalexins scopoletin and scopolin in Nicotiana species is regulated by upstream signals including jasmonate (JA), ethylene (ET), and NaWRKY3 in response to the necrotrophic fungus Alternaria alternata, which causes brown spot disease. However, how these signals are coordinated to regulate these phytoalexins remains unknown. By analyzing RNA sequencing data and RNAi, we identified NaERF1B-like (NaERF1B-L) as a key player in Nicotiana attenuata during A. alternata infection by regulating the transcripts of Feruloyl-CoA 6'-hydroxylase 1 (NaF6'H1), encoding a key enzyme for scopoletin biosynthesis, and NaVS1-like (NaVS1-L), a putative biosynthetic gene of the phytoalexin solavetivone. We further demonstrated that the synergistic induction of these two genes by JA and ET signaling is mediated by NaERF1B-L. Additionally, we found that the two closely related proteins, NaWRKY6 and NaWRKY3, physically interact to enhance NaERF1B-L expression by directly binding to and activating the NaERF1B-L promoter. Collectively, our current results demonstrate that NaERF1B-L plays a positive role in resistance to A. alternata by modulating phytoalexin biosynthesis through the integration of JA/ET and NaWRKY6/3 signaling. Our findings reveal a fine-tuned transcriptional regulatory hierarchy mediated by NaERF1B-L for brown spot disease resistance in wild tobacco.
Nuclear localization of Arabidopsis HD-Zip IV transcription factor GLABRA2 is driven by importin α
Authors: Ahmad Bilal , Lerma-Reyes Ruben , Mukherjee Thiya , Nguyen Hieu V , Weber Audra L , Cummings Emily E , Schulze Waltraud X , Comer Jeffrey R , Schrick Kathrin 
Published: July 2024

Abstract
GLABRA2 (GL2), a class IV homeodomain leucine-zipper (HD-Zip IV) transcription factor from Arabidopsis, is a developmental regulator of specialized cell types in the epidermis. GL2 contains a monopartite nuclear localization sequence (NLS) that is conserved in most HD-Zip IV members across the plants. We demonstrate that NLS mutations affect nuclear transport and result in a loss-of-function phenotypes. NLS fusions to enhanced yellow fluorescent protein (EYFP) show that it is sufficient for nuclear localization in roots and trichomes. Despite partial overlap of the NLS with the homeodomain, genetic dissection indicates that nuclear localization and DNA binding are separable functions. Affinity purification of GL2 from plants followed by MS-based proteomics identified importin α (IMPα) isoforms as potential GL2 interactors. NLS structural prediction and molecular docking studies with IMPα-3 revealed major interacting residues. Cytosolic yeast two-hybrid assays and co-immunoprecipitation experiments with recombinant proteins verified NLS-dependent interactions between GL2 and several IMPα isoforms. IMPα triple mutants (impα-1,2,3) exhibit abnormal trichome formation and defects in GL2 nuclear localization in trichomes, consistent with tissue-specific and redundant functions of IMPα isoforms. Taken together, our findings provide mechanistic evidence for IMPα-dependent nuclear localization of GL2 in Arabidopsis, a process that is critical for cell type differentiation of the epidermis.