bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic impact of RNA-based next-generation sequencing fusion panel for solid tumors: A single-institution experience
Authors: Fei Fei , Kunder Christian A , Ho Chandler , Zehnder James L , Tomasello Gianna , Fung Eula , Suarez Carlos J 
Published: November 2023

Abstract

Objectives
Gene rearrangements frequently act as oncogenic driver mutations and determine the onset and progression of cancer. RNA-based next-generation sequencing (NGS) is being used with increasing frequency for solid tumors. The purpose of our study is to investigate the feasibility and utility of an RNA-based NGS fusion panel for solid tumors.

Methods
We conducted a retrospective, single-institution review of fusion panels requested between May 2022 and March 2023. Demographic, clinical, pathologic, and molecular findings of the patients were reviewed. The utility of the RNA-based NGS fusion panel for the pathologic diagnosis of solid tumors was assessed.

Results
Our study included 345 cases, and a fusion event was identified in 24.3% (78/321) of cases. Among the 110 cases submitted for diagnostic purposes, a fusion event was detected in 42.7% (47/110) of cases. The results led to refinement or clarification of the initial diagnosis in 31.9% (15/47) of cases and agreement or support for the initial diagnosis in 59.6% (28/47) of cases. Furthermore, our study indicated that the overall cellularity (tumor and normal tissue) of the tested specimen influences the success of the testing process.

Conclusions
In summary, this study demonstrated the feasibility and utility of an RNA-based NGS fusion panel for a wide variety of solid tumors in the appropriate clinicopathologic context. These findings warrant further validation in larger studies involving multiple institutional patient cohorts.
A mixed-methods study on the use of a nongynecological virtual microscopy platform in cytology education
Authors: Chiou Paul Z , Jia Yuane 
Published: November 2023

Abstract

Objectives
Expanding the virtual microscopy (VM) slide collection for nongynecological cytology is important to teaching. In a mixed-methods approach, this study evaluated VM’s performance and user experience to determine its feasibility and usage in an educational setting.

Methods
From September through October 2022, the students reviewed 44 whole-slide imaged nongynecological slides. The concordance rate with reference diagnosis was compared with that from light microscopy (LM) from 4 months earlier. In addition to assessing the overall performance from VM, imaged urinary cytology’s accuracy was reviewed for both urinary and nonurinary cytology. Finally, the students’ weekly feedback logs were analyzed to gain insights for improving the digital screening experience.

Results
The overall nongynecological diagnostic accuracy was significant between the 2 screening platforms (P &lt; .001), favoring LM over the VM platform. Light microscopy also performed better than VM in urine cytology cases, with 84.2% concordance against reference diagnosis, compared with 61.1% for the VM platform (P = .03). As for the accuracy of nonurinary cases, its glass slide (LM) agreement with the reference diagnosis was also superior at 84.8%, compared with 58.8% for VM (P = .03). Finally, the overarching theme discerned from reviewing the user logs was concern over image quality, which was mentioned 76 times.

Conclusions
The VM results were poorer compared with LM in our validation. Its use seems promising, but more focus is needed to improve the VM screening platform.
scTopoGAN: unsupervised manifold alignment of single-cell data
Authors: Singh Akash , Biharie Kirti , Reinders Marcel J T , Mahfouz Ahmed , Abdelaal Tamim 
Published: November 2023

Abstract

Motivation
Single-cell technologies allow deep characterization of different molecular aspects of cells. Integrating these modalities provides a comprehensive view of cellular identity. Current integration methods rely on overlapping features or cells to link datasets measuring different modalities, limiting their application to experiments where different molecular layers are profiled in different subsets of cells.

Results
We present scTopoGAN, a method for unsupervised manifold alignment of single-cell datasets with non-overlapping cells or features. We use topological autoencoders (topoAE) to obtain latent representations of each modality separately. A topology-guided Generative Adversarial Network then aligns these latent representations into a common space. We show that scTopoGAN outperforms state-of-the-art manifold alignment methods in complete unsupervised settings. Interestingly, the topoAE for individual modalities also showed better performance in preserving the original structure of the data in the low-dimensional representations when compared to other manifold projection methods. Taken together, we show that the concept of topology preservation might be a powerful tool to align multiple single modality datasets, unleashing the potential of multi-omic interpretations of cells.

Availability and implementation
Implementation available on GitHub (https://github.com/AkashCiel/scTopoGAN). All datasets used in this study are publicly available.
A Bayesian approach to differential edges with probabilistic interactions: applications in association and classification
Authors: Huang Yu-Jyun , Lai Ying-Ju , Hsiao Chuhsing Kate 
Published: November 2023

AbstractMotivationDifferential network (D-Net) analysis has attracted great attention in systems biology for its ability to identify genetic variations in response to different conditions. Current approaches either estimate the condition-specific networks separately followed by post-procedures to determine the differential edges or estimate the D-Net directly. Both types of analysis overlook the probabilistic inference and can only provide deterministic inference of the edges.ResultsHere, we propose a Bayesian solution and translate the probabilistic estimation in the regression model to an inferential D-Net analysis for genetic association and classification studies. The proposed PRobabilistic Interaction for Differential Edges (PRIDE) focuses on inferring the D-Net with uncertainty so that the existence of the differential edges can be evaluated with probability and even prioritized if comparison among these edges is of interest. The performance of the proposed model is compared with state-of-the-art methods in simulations and is demonstrated in glioblastoma and breast cancer studies. The proposed PRIDE performs comparably to or outperforms most existing tools under deterministic evaluation criteria. Additionally, it offers the unique advantages, including prioritizing the differential edges with probabilities, highlighting the relative importance of hub nodes, and identifying potential sub-networks in a D-Net.Availability and implementationAll the data analyzed in this research can be downloaded at https://xenabrowser.net/datapages/. The R code for implementing PRIDE is available at https://github.com/YJGene0806/PRIDE_Code.
Term-BLAST-like alignment tool for concept recognition in noisy clinical texts
Authors: Groza Tudor , Wu Honghan , Dinger Marcel E , Danis Daniel , Hilton Coleman , Bagley Anita , Davids Jon R , Luo Ling , Lu Zhiyong , Robinson Peter N 
Published: November 2023

Abstract

Motivation
Methods for concept recognition (CR) in clinical texts have largely been tested on abstracts or articles from the medical literature. However, texts from electronic health records (EHRs) frequently contain spelling errors, abbreviations, and other nonstandard ways of representing clinical concepts.

Results
Here, we present a method inspired by the BLAST algorithm for biosequence alignment that screens texts for potential matches on the basis of matching k-mer counts and scores candidates based on conformance to typical patterns of spelling errors derived from 2.9 million clinical notes. Our method, the Term-BLAST-like alignment tool (TBLAT) leverages a gold standard corpus for typographical errors to implement a sequence alignment-inspired method for efficient entity linkage. We present a comprehensive experimental comparison of TBLAT with five widely used tools. Experimental results show an increase of 10% in recall on scientific publications and 20% increase in recall on EHR records (when compared against the next best method), hence supporting a significant enhancement of the entity linking task. The method can be used stand-alone or as a complement to existing approaches.

Availability and implementation
Fenominal is a Java library that implements TBLAT for named CR of Human Phenotype Ontology terms and is available at https://github.com/monarch-initiative/fenominal under the GNU General Public License v3.0.
Parallel phenotypic plasticity and divergent ecological strategies in morphologically and molecularly similar sympatric sponge species
Authors: Wulff Janie 
Published: November 2023

Abstract
How can phenotypic plasticity promote or impede adaptive change and diversification? Answering this key question can be experimentally intractable, but closely related clonal species allow a direct approach: experimentally provoking phenotypic plasticity to assess the adaptive significance of both plastic traits and species differences. Two common Caribbean sponge species, Aplysina fulva and A. cauliformis, are nearly indistinguishable molecularly, and share growth form, habitat, and geographical range. This raises questions about species boundaries, within-species variability, and mechanisms of speciation. To distinguish phenotypic plasticity from genetic variation, and learn how plasticity might influence adaptive—and divergent—evolution, I: (i) quantified morphological and ecological characters, (ii) revealed phenotypic plasticity by growing clonemates in different environments, and (iii) related plastic morphological features to ecological function. Characters included skeletal fibre density, biomechanical properties, vulnerability to parasites and predators, wound healing, transport pathways, propagation by fragments, population dynamics, and growth and survival in settings differing in food, sunlight, predators, and water motion. Transplanting both species to a different environment elicited parallel plasticity in the same traits. Combined comparative and experimental data reveal integrated suites of ecologically relevant characters that clearly distinguish these species and allow interpretation of adaptive significance of plastic characters that may underlie divergence.
EHD1 impaired decidualization of endometrial stromal cells in recurrent implantation failure: role of SENP1 in modulating progesterone receptor signalling
Authors: Zhang Hui , Kong Liping , Cao Zhiwen , Zhu Yinchun , Jiang Yue , Wang Xiaoying , Jiang Ruiwei , Liu Yang , Zhou Jidong , Kang Yu , Zhen Xin , Kong Na , Wu Min , Yan Guijun , Sun Haixiang 
Published: November 2023

Abstract
Recurrent implantation failure (RIF) patients exhibit poor endometrial receptivity and abnormal decidualization with reduced effectiveness and exposure to progesterone, which is an intractable clinical problem. However, the associated molecular mechanisms remain elusive. We found that EH domain containing 1 (EHD1) expression was abnormally elevated in RIF and linked to aberrant endometrial decidualization. Here we show that EHD1 overexpressed in human endometrial stromal cells significantly inhibited progesterone receptor (PGR) transcriptional activity and the responsiveness to progesterone. No significant changes were observed in PGR mRNA levels, while a significant decrease in progesterone receptor B (PRB) protein level. Indeed, EHD1 binds to the PRB protein, with the K388 site crucial for this interaction. Overexpression of EHD1 promotes the SUMOylation and ubiquitination of PRB, leading to the degradation of the PRB protein. Supplementation with the de-SUMOylated protease SENP1 ameliorated EHD1–repressed PRB transcriptional activity. To establish a functional link between EHD1 and the PGR signalling pathway, sg-EHD1 were utilized to suppress EHD1 expression in HESCs from RIF patients. A significant increase in the expression of prolactin and insulin-like growth factor-binding protein 1 was detected by interfering with the EHD1. In conclusion, we demonstrated that abnormally high expression of EHD1 in endometrial stromal cells attenuated the activity of PRB associated with progesterone resistance in a subset of women with RIF.
Maximum likelihood estimation for semiparametric regression models with interval-censored multistate data
Authors: Gu Yu , Zeng Donglin , Heiss Gerardo , Lin D Y 
Published: November 2023

Summary
Interval-censored multistate data arise in many studies of chronic diseases, where the health status of a subject can be characterized by a finite number of disease states and the transition between any two states is only known to occur over a broad time interval. We relate potentially time-dependent covariates to multistate processes through semiparametric proportional intensity models with random effects. We study nonparametric maximum likelihood estimation under general interval censoring and develop a stable expectation-maximization algorithm. We show that the resulting parameter estimators are consistent and that the finite-dimensional components are asymptotically normal with a covariance matrix that attains the semiparametric efficiency bound and can be consistently estimated through profile likelihood. In addition, we demonstrate through extensive simulation studies that the proposed numerical and inferential procedures perform well in realistic settings. Finally, we provide an application to a major epidemiologic cohort study.
Hate Crime and Class Vulnerability: A Case Study of White Nationalist Violence Against Unhoused Indigenous People
Authors: Urbanik Marta-Marika , Maier Katharina , Tetrault Justin E C , Greene Carolyn 
Published: November 2023

Abstract
Advocates and academics have increasingly called on governments to recognize anti-homeless violence as a hate crime and type of domestic extremism, representing a broader trend in Westernized countries for responding to social issues through anti-hate policies. Can these approaches protect unhoused people? Drawing upon ethnographic interviews and observation with 50 unhoused community members in a Canadian city, we outline their experiences with anti-homeless and anti-Indigenous violence. Our findings show how hate crime approaches often (1) fail to consider intersectionality, especially how class contributes to vulnerability, and (2) overlook place-based victimization and how institutions enable class vulnerability. We call for more localized analyses of hate crime and introduce the concept of ‘cumulative risk of hate crime victimization’ to help address intersectionality.
Working Together to Create Meaning: Narratives of Care Leavers in Eastern Europe
Authors: Kessler Zoë , Levy Susan , Smith Mark 
Published: November 2023

Abstract
This article uses life history research to reveal a new understanding of institutional care. The study draws on interviews with care leavers from a Latvian orphanage who narrate life histories and identify critical life events and moments of resistance to times of adversity. The methodology intentionally positioned study nineteen care leavers as experts on their own experiences, focusing on three main life phases: before, during and after living in care. Findings deconstructed and brought nuance to stereotypes and dominant assumptions about people growing up in care, providing alternative narratives of self-reliance and resistance to adversity. Recommendations for practice and policy are discussed. This rich knowledge base can be used to support and inform the practice of children in the care system in Latvia and more widely.
Nigrostriatal tau pathology in parkinsonism and Parkinson’s disease
Authors: Chu Yaping , Hirst Warren D , Federoff Howard J , Harms Ashley S , Stoessl A Jon , Kordower Jeffrey H 
Published: November 2023

Abstract
While Parkinson’s disease remains clinically defined by cardinal motor symptoms resulting from nigrostriatal degeneration, it is now appreciated that the disease commonly consists of multiple pathologies, but it is unclear where these co-pathologies occur early in disease and whether they are responsible for the nigrostriatal degeneration.
For the past number of years, we have been studying a well-characterized cohort of subjects with motor impairment that we have termed mild motor deficits. Motor deficits were determined on a modified and validated Unified Parkinson’s Disease Rating Scale III but were insufficient in degree to diagnose Parkinson’s disease. However, in our past studies, cases in this cohort had a selection bias, as both a clinical syndrome in between no motor deficits and Parkinson’s disease, plus nigral Lewy pathology as defined post-mortem, were required for inclusion. Therefore, in the current study, we only based inclusion on the presence of a clinical phenotype with mild motor impairment insufficient to diagnose Parkinson’s disease. Then, we divided this group further based upon whether or not subjects had a synucleinopathy in the nigrostriatal system.
Here we demonstrate that loss of nigral dopaminergic neurons, loss of putamenal dopaminergic innervation and loss of the tyrosine hydroxylase-phenotype in the substantia nigra and putamen occur equally in mild motor deficit groups with and without nigral alpha-synuclein aggregates. Indeed, the common feature of these two groups is that both have similar degrees of AT8 positive phosphorylated tau, a pathology not seen in the nigrostriatal system of age-matched controls. These findings were confirmed with early (tau Ser208 phosphorylation) and late (tau Ser396/Ser404 phosphorylation) tau markers. This suggests that the initiation of nigrostriatal dopaminergic neurodegeneration occurs independently of alpha-synuclein aggregation and can be tau mediated.
Efficient transmission of human prion diseases to a glycan-free prion protein-expressing host
Authors: Cracco Laura , Cali Ignazio , Cohen Mark L , Aslam Rabail , Notari Silvio , Kong Qingzhong , Newell Kathy L , Ghetti Bernardino , Appleby Brian S , Gambetti Pierluigi 
Published: November 2023

Abstract
It is increasingly evident that the association of glycans with the prion protein (PrP), a major post-translational modification, significantly impacts the pathogenesis of prion diseases. A recent bioassay study has provided evidence that the presence of PrP glycans decreases spongiform degeneration and disease-related PrP (PrPD) deposition in a murine model. We challenged (PRNPN181Q/197Q) transgenic (Tg) mice expressing glycan-free human PrP (TgGlyc−), with isolates from sporadic Creutzfeldt–Jakob disease subtype MM2 (sCJDMM2), sporadic fatal insomnia and familial fatal insomnia, three human prion diseases that are distinct but share histotypic and PrPD features. TgGlyc− mice accurately replicated the basic histotypic features associated with the three diseases but the transmission was characterized by high attack rates, shortened incubation periods and a greatly increased severity of the histopathology, including the presence of up to 40 times higher quantities of PrPD that formed prominent deposits. Although the engineered protease-resistant PrPD shared at least some features of the secondary structure and the presence of the anchorless PrPD variant with the wild-type PrPD, it exhibited different density gradient profiles of the PrPD aggregates and a higher stability index. The severity of the histopathological features including PrP deposition appeared to be related to the incubation period duration. These findings are clearly consistent with the protective role of the PrP glycans but also emphasize the complexity of the conformational changes that impact PrPD following glycan knockout. Future studies will determine whether these features apply broadly to other human prion diseases or are PrPD-type dependent.
Delusional infestation treated with risperidone: a series of 27 patients
Authors: Guedes Nycolle L K O , Dwan Alexandre J , Gerlero Paula , Nico Marcello M S 
Published: November 2023

Abstract

Background
Patients with delusional infestation (DI) frequently refuse to be treated with psychoactive drugs. In the past, pimozide was commonly used as a first-line agent but is now prescribed more rarely. Risperidone was first used to treat DI in 1995. A recent review identified 12 studies that evaluated the use of risperidone in 43 patients with DI.

Objectives
To study the characteristics of and therapeutic results in patients with DI treated with risperidone at a university medical centre in São Paulo, Brazil.

Methods
We performed a retrospective study of patients with DI treated with risperidone at a dermatological university clinic since 2016. Records were reviewed for personal data and findings related to treatment.

Results
Twenty-seven patients were studied (20 women and 7 men). The maintenance dose of risperidone varied from 1 mg three times weekly to 8 mg daily. Control of symptoms was achieved in the majority of patients. A reduction in dosage due to side-effects was seen in four patients; risperidone had to be switched to another antipsychotic in three cases, despite a good response. Only one patient did not respond to risperidone.

Conclusions
Risperidone is an effective, well-tolerated and safe treatment for delusional parasitosis. Adequate follow-up is mandatory in order to obtain long-term control of symptoms.
Fasting durations of Steller sea lion pups vary among subpopulations—evidence from two plasma metabolites
Authors: Crawford Stephanie G , Coker Robert H , O’Hara Todd M , Breed Greg A , Gelatt Tom , Fadely Brian , Burkanov Vladimir , Rivera Patricia M , Rea Lorrie D 
Published: November 2023

ABSTRACT
Geographic differences in population growth trends are well-documented in Steller sea lions (Eumetopias jubatus), a species of North Pacific pinniped listed under the U.S. Endangered Species Act in 1990 following a marked decline in population abundance that began during the 1970s. As population growth is intrinsically linked to pup production and survival, examining factors related to pup physiological condition provides useful information to management authorities regarding potential drivers of regional differences. During dam foraging trips, pups predictably transition among three fasting phases, distinguished by the changes in the predominant metabolic byproduct. We used standardized ranges of two plasma metabolites (blood urea nitrogen and β–hydroxybutyrate) to assign pups to fasting categories (n = 1528, 1990–2016, 12 subpopulations): Recently Fed–Phase I (digestion/assimilation–expected hepatic/muscle glycogen usage), Phase II (expected lipid utilization), transitioning between Phases II–III (expected lipid utilization with increased protein reliance), or Phase III (expected protein catabolism). As anticipated, the majority of pups were classified as Recently Fed–Phase I (overall mean proportion = 0.72) and few pups as Phase III (overall mean proportion = 0.04). By further comparing pups in Short (Recently Fed–Phase II) and Long (all other pups) duration fasts, we identified three subpopulations with significantly (P &lt; 0.03) greater proportions of pups dependent upon endogenous sources of energy for extended periods, during a life stage of somatic growth and development: the 1) central (0.27 ± 0.09) and 2) western (0.36 ± 0.13) Aleutian Island (declining population trend) and 3) southern Southeast Alaska (0.32 ± 0.06; increasing population trend) subpopulations had greater Long fast proportions than the eastern Aleutian Islands (0.10 ± 0.05; stabilized population). Due to contrasting population growth trends among these highlighted subpopulations over the past 50+ years, both density-independent and density-dependent factors likely influence the dam foraging trip duration, contributing to longer fasting durations for pups at some rookeries.