bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upper tract urothelial carcinoma: conservative management - intraluminal adjuvant therapy, and surveillance
Authors: Lasmanovich Rinat , Shvero Asaf , Kleinmann Nir 
Published: November 2024

Purpose of review
In recent years, intraluminal therapies have become a valid alternative for low grade upper tract urothelial carcinoma (UTUC) patients, as overall survival and cancer-specific survival rates were shown to be comparable to those achieved with radical nephroureterectomy for selected cases. Nonetheless, endoscopic treatment has its limitations. As technology progresses and the demand for endoscopic treatments increases, intraluminal chemotherapy and immunotherapy instillations within the upper tract have increasingly become the subject areas of research.

Recent findings
The main intraluminal therapies and relevant instillation approaches are reviewed in this study, including recent publications and their main outcomes. The recurrence rates demonstrated in the literature strengthen the notion that patients with UTUC following current intraluminal treatments have a better prognosis than in the past. Updated relevant guidelines regarding surveillance among this population are also reviewed and summarized.

Summary
The treatment of upper tract urothelial carcinoma is clinically challenging. Developments in recent years show promising results in this field and ongoing research with new developments is emerging. Further studies are required to better understand the contribution of intraluminal therapies to the management of this disease.
Detection of Small Brain Metastases by 18F-Thretide PET/CT in Clear Cell Renal Cell Carcinoma
Authors: Cheng Xin , Hou Guozhu , Zheng Rong , Zhang Jingjing , Wang Xuejuan 
Published: October 2024

Abstract
A 46-year-old woman with a history of radical nephrectomy for clear cell renal cell carcinoma underwent 18F-FDG and 18F-Thretid (also known as Al18F-PSMA-BCH) PET/CT. Although the 18F-FDG PET/CT failed to detect any brain metastases, the 18F-Thretide PET/CT revealed 2 small metastases: one measuring 1.0 × 0.7 cm in the right cerebellum and the other measuring 0.4 cm in the right frontal lobe. These metastatic lesions were subsequently confirmed by brain MRI.
Hepatic Recurrence of Neuroendocrine Tumor Component in Gallbladder Cancer
Authors: Ikejiri Tatsuki , Yoh Tomoaki , Kasai Yosuke , Nagai Kazuyuki , Hatano Etsuro 
Published: October 2024

Abstract
A 60-year-old man underwent an extended cholecystectomy with regional lymphadenectomy for T2N0M0 gallbladder cancer (GBC), which showed significant FDG uptake (SUVmax = 6.5). However, CT scan at 24 months postsurgery revealed multiple hepatic masses. Unlike the primary GBC, the hepatic masses showed limited FDG uptake (SUVmax = 3.7). A tumor biopsy revealed the diagnosis of a grade 3 neuroendocrine tumor. Furthermore, the hepatic masses showed significant uptake on somatostatin receptor scintigraphy. Upon reevaluation, the primary resected specimen was found to include approximately 10% of neuroendocrine tumor components. This case suggests that different FDG uptake between primary and metastatic cancer may necessitate differential diagnosis.
Cleft Lip Scar Appearance is Associated With Speech Outcomes After Primary Palatoplasty
Authors: Prezelski Kayla , Carter Lillian , Peters Victoria , Rizvi Imran , Furtado Kailee , Kane Alex A. , Seaward James R. 
Published: November 2024

Objective:
This study aims to investigate the correlation between the quality of cleft lip scar and velopharyngeal insufficiency (VPI).

Methods:
Clinical photographs from 56 patients with repaired cleft lip and palate (CLP) were collected and anonymized by cropping the image to the region of interest around the lip and nose. A survey displaying each cleft lip scar image with five associated scar quality features, including scar color, thickness, width, lip shortening, and overall appearance, was distributed. Surveys were distributed using Amazon Mechanical Turk (MTurk), an online crowdsourcing platform, to obtain ratings from 330 laypeople. The same surveys were also distributed to 45 medical students.

Main Outcome Measure:
Hypernasality was used as the primary speech outcome measure. Ordinal logistic regression was used to compare the ratings for each of the five scar quality categories with the patients’ CAPS-A-AM hypernasality rating for both MTurk and medical student raters. Significance was set at α = 0.05.

Results:
For medical student ratings’, ordinal logistic regression showed a statistically significant relationship between lip shortening (P=0.019) and overall appearance (P=0.044) with CAPS-A-AM hypernasality score, whereas the other scar categories showed no significant association. There was no statistically significant relationship between MTurk ratings and hypernasality for any of the scar categories.

Conclusions:
The association found between lip shortening and overall scar appearance, thought by the authors to indicate scar contracture, and hypernasality, an indicator of VPI severity, provides an interesting insight into how to potentially identify patients who may be at increased risk for developing VPI.
Mechanical stretch induced collective cell alignment
Authors: Shi Xuechen , Zhang Sulin 
Published: October 2024

AbstractCell alignment is a fundamental process in development and plays an essential role in tissue function. Although it has been found that cell alignment exhibits a density-dependent collective behavior, the collective mechanisms within this process remain elusive. In this study, we present a model of collective cell alignment induced by uniaxial mechanical stretch and explore the mechanisms driving this phenomenon. We demonstrate that alignment occurs in a density-dependent manner, with dense cell populations aligning while sparse populations do not. Contrary to previous findings, our results show that this alignment is initiated by substrate deformation upon stretch, which biases cell orientations towards the stretched direction. This deformation-induced alignment occurs passively and simultaneously, allowing us to isolate and identify the factors contributing to the collective behavior. Importantly, we find that once stretched, cells in low-density cultures lose alignment over time, while cells in high-density cultures are able to maintain the alignment level, exhibiting positional adaptation. Furthermore, we observe a self-organization process in high-density cultures, where cells actively reorient towards the stretched direction through cell-cell interactions, enhancing the overall alignment level over time. The emergence of the alignment response has implications for how cell alignment is achieved and sheds light on the cooperative mechanisms underlying collective cell behaviors. Additionally, our findings introduce a novel methodology for aligning cells that could be used for biomedical and tissue engineering applications.
Automated Extraction of Mortality Information from Publicly Available Sources Using Language Models
Authors: Al-Garadi Mohammed , LeNoue-Newton Michele , Matheny Michael E. , McPheeters Melissa , Whitaker Jill M. , Deere Jessica A. , McLemore Michael F. , Westerman Dax , Khan Mirza S. , Hernández-Muñoz José J. , Wang Xi , Kuzucan Aida , Desai Rishi J. , Reeves Ruth 
Published: November 2024

AbstractBackgroundMortality is a critical variable in healthcare research, but inconsistencies in the availability of death date and cause of death (CoD) information limit the ability to monitor medical product safety and effectiveness.ObjectiveTo develop scalable approaches using natural language processing (NLP) and large language models (LLM) for the extraction of mortality information from publicly available online data sources, including social media platforms, crowdfunding websites, and online obituaries.MethodsData were collected from public posts on X (formerly Twitter), GoFundMe campaigns, memorial websites (EverLoved.comandTributeArchive.com), and online obituaries from 2015 to 2022. We developed a natural language processing (NLP) pipeline using transformer-based models to extract key mortality information such as decedent names, dates of birth, and dates of death. We then employed a few-shot learning (FSL) approach with large language models (LLMs) to identify primary and secondary causes of death. Model performance was assessed using precision, recall, F1-score, and accuracy metrics, with human-annotated labels serving as the reference standard for the transformer-based model and a human adjudicator blinded to labeling source for the FSL model reference standard.ResultsThe best-performing model obtained a micro-averaged F1-score of 0.88 (95% CI, 0.86-0.90) in extracting mortality information. The FSL-LLM approach demonstrated high accuracy in identifying primary CoD across various online sources. For GoFundMe, the FSL-LLM achieved 95.9% accuracy for primary cause identification, compared to 97.9% for human annotators. In obituaries, FSL-LLM accuracy was 96.5% for primary causes, while human accuracy was 99.0%. For memorial websites, FSL-LLM achieved 98.0% accuracy for primary causes, with human accuracy at 99.5%.ConclusionsThese findings highlight the potential of leveraging advanced NLP techniques and publicly available data to enhance the timeliness, comprehensiveness, and granularity of mortality surveillance.Funding statementThis project was supported by Task Order 75F40123F19010 under Master Agreement 75F40119D10037 from the US Food and Drug Administration (FDA). FDA coauthors reviewed the study protocol, statistical analysis plan, and the manuscript for scientific accuracy and clarity of presentation. Representatives of the FDA reviewed a draft of the manuscript for the presence of confidential information and accuracy regarding the statement of any FDA policy. The views expressed are those of the authors and not necessarily those of the US FDA.
Age-Related Changes in the Cholinergic System in Adults with Down Syndrome Assessed Using [18F]-Fluoroethoxybenzovesamicol Positron Emission Tomography Imaging
Authors: Russell Jason K , Conley Alexander C. , Boyd Brian D. , Begnoche J. Patrick , Schlossberg Rachel , Stranick Allison , Rosenberg Adam J. , Acosta Lealani Mae Y , Martin Dann , Neal Yasmeen , Kanel Prabesh , Albin Roger L. , Rafii Michael S. , Dumas Julie , Newhouse Paul A. 
Published: November 2024

AbstractAdults with Down syndrome are genetically predisposed to developing Alzheimer’s disease after the age of 40. The cholinergic system, which is critical for cognitive functioning, is known to decline in Alzheimer’s disease and although first investigated in individuals with Down syndrome 40 years ago, remains relatively understudied. Existing studies suggest individuals with Down syndrome have an intact cholinergic system at birth that declines through adulthood alongside the development of Alzheimer’s disease pathology. The present study provides the first description of cholinergic terminals in vivo in non-demented adults with Down syndrome utilizing [18F]-fluoroethoxybenzovesamicol PET imaging. In addition, we investigated age-associated decline in cholinergic terminal density. Sixteen non-demented adults with Down syndrome and 20 neurotypically developed individuals were studied, comparing radiotracer uptake groupwise and associations with age utilizing a voxel-based approach. Adults with Down syndrome displayed significantly increased [18F]-fluoroethoxybenzovesamicol uptake in the cerebellum, brainstem, thalamus, and numerous cortical regions compared to age-matched controls. Cholinergic terminal density in numerous cortical regions showed a steeper decline associated with increasing age in adults with Down syndrome than observed in neurotypically developed adults in the age range tested. These data suggest increased cholinergic terminal density in early adulthood in individuals with Down syndrome with a more rapid or earlier age-associated decline than is observed in neurotypically developed individuals.
Computational design of Bax-inhibiting peptides
Authors: Vlaar Tom , Mayer Bernadette , van der Heide Lars , Ilie Ioana M. 
Published: October 2024

AbstractThe proteins of the Bcl-2 family play crucial roles in regulating apoptosis. It is divided into pro-survival and pro-apoptotic proteins that determine cellular fate. In particular, Bax is a crucial executor of apoptosis as its activation initiates the apoptotic phenotype. Hence, targeting this protein represents an attractive therapeutic approach, which can aid in regulating apoptotic signalling and potentially contribute to the development of novel therapies against cancer and neurodegenerative diseases. Here, we introduce a digital paradigm, which relies on rational design and computer simulations to develop and validate peptide-based agents that bind to Bax, thereby inhibiting its apoptotic properties. The peptides are rationally designed and optimized to bind to Bax starting from the crystal structures of affimers in complex with Bcl-2 proteins. Next, molecular dynamics simulations (MD) are employed to probe the stability of the Bax-peptide complexes and to estimate the binding free energies. The results show that the designed peptides bind with high affinity to Bax. Two of the designed peptides bind in the canonical hydrophobic groove (BH1 domain) of Bax and one peptide binds to the outside of the BH3 domain (α2-helix). Notably, the peptides restrict the flexibility of theα1-α2loop, modulating the bottom trigger site associated with toxicity. All in all, the results highlight the potential of these peptides as valuable tools for further exploration in modulating apoptotic pathways and set the structural foundation for a machine learning powered engine for peptide design.
Co-evolution of host dispersal and parasite virulence in complex landscapes
Authors: Deshpande Jhelam N. , Pallagatti Ruthvik S. , Dakos Vasilis , Kaltz Oliver , Fronhofer Emanuel A. 
Published: October 2024

AbstractSpatial network structure impacts the ecological and evolutionary dynamics of species interactions. Previous work on host-parasite systems has shown that parasite virulence is driven by dispersal rates and spatial structure, assuming that dispersal is an ecologically fixed parameter. However, dispersal is also a trait under selection and can evolve. In this context, we develop an individual-based eco-evolutionary model, in which both parasite virulence and host dispersal can evolve in representative terrestrial (random-geometric graphs; RGGs) and riverine aquatic (optimal channel networks; OCNs) landscapes. We find that in riverine aquatic landscapes, evolutionarily stable (ES) dispersal rates are lower and ES virulence is greater relative to terrestrial landscapes when dispersal mortality is low. When dispersal mortality is high, both dispersal and virulence evolve to lower values in both landscape types. Diverging co-evolutionary patterns between landscapes are explained by differences in network topology. Specifically, the highly heterogeneous degree distribution in riverine aquatic landscapes 1) leads to low parasite relatedness allowing for the evolution of greater virulence and 2) leads to spatial heterogeneity in host densities that constrains the evolution of dispersal to lower values. Our work highlights the importance of considering the concurrent and co-evolution of dispersal when studying trait evolution in complex landscapes.
Crystal structure of a Photosystem II-related, Manganese-binding, TPM-domain protein at a 1.6 Å resolution
Authors: Vidal-Meireles André , Malesinski Soazig , Horrenberger Yann , Monteil Caroline , Alric Jean , Siponen Marina , Johnson Xenie 
Published: October 2024

AbstractConserved proteins across oxygenic phototrophic organisms are important players in photosynthetic acclimation, yet many remain poorly or completely uncharacterized. In the green algaChlamydomonas reinhardtiiwe identified Cre15.g636050, previously annotated asCPLD31, that encodes such an uncharacterized, conserved, thylakoid lumenal protein belonging to the “TPM” domain family (PF04536). TPM refers to a protein fold named after the three founding proteins of this family, TLP18.3, Psb32, and MOLO-1, with the first two being Photosystem II-related proteins. We also found a paralogue ofCPLD31, Cre03.g154600, previously annotated asTLP15.2. In this work, we generated knock-out mutants of these genes in Chlamydomonas and produced the recombinant proteins. We showed both proteins are regulated by light and phototrophy, and while the former binds manganese in a TPM-domain metal binding site, the latter does not. Therefore, we reannotated them asLumenalMn-bindingTPM-domainProtein1(LMTP1) andThylakoidLumenalProtein26kDa (TLP26), respectively.
Interactions of N- and C-terminal parts of Ana1 permitting centriole duplication but not elongation
Authors: Nagy Agota , Kovacs Levente , Rangone Helene , Fu Jingyan , Ladinsky Mark , Glover David M. 
Published: October 2024

SummaryThe conserved process of centriole duplication requires establishment of a Sas6-centred cartwheel initiated by Plk4’s phosphorylation of Ana1/STIL. Subsequently the centriole undergoes conversion to a centrosome requiring its radial expansion and elongation, mediated by a network requiring interactions between Cep135, Ana1/Cep295, and Asterless/Cep152. Here we show that mutant alleles encoding overlapping N- and C-terminal parts of Ana1 are capable of intragenic complementation to rescue radial expansion. This permits recruitment of Asl and thereby centriole duplication and mechanosensory cilia formation to restore the coordination defects of these mutants. This genetic combination also rescues centriole duplication in the male germ line but does not rescue the elongation of the triplet microtubule-containing centrioles of primary spermatocytes and consequently these males are coordinated but sterile. Such centriole elongation is rescued by the continuous, full-length Ana1 sequence. We define a region that when deleted within otherwise intact Ana1 does not permit primary spermatocyte centrioles to elongate but still allows recruitment of Asl. Our findings point to differing demands upon the physical organization of Ana1 for the distinct processes of radial expansion and elongation of centrioles.IMPACT STATEMENTThe centriole can undergo radial development and duplication using separated parts of the conserved Ana1 protein whereas elongation of centriolar microtubule triplets requires the continuous Ana1 primary sequence.
GBRAP: A Comprehensive Database and Tool for Exploring Genomic Diversity Across All Domains of Life
Authors: Yaddehige Sachithra Kalhari , Vischioni Chiara , Alberghini Leonardo , Berselli Michele , Taccioli Cristian 
Published: October 2024

AbstractEvolutionary studies require extensive examination of genomic information across all domains of life. Despite the availability of a large number of genomes through GenBank, the effective visualisation or comparison of the information they contain is challenging due to many reasons including their size. We introduce GBRAP, a comprehensive software tool to analyse GenBank files, and an online database housing an extensive collection of carefully curated, high-quality genome statistics for all the organisms available in the RefSeq database of NCBI. Users can either directly search, or select from pre-categorized groups, the organisms of their choice and retrieve data, which eventually output as tables containing more than 200 columns of useful genomic information (Base counts, GC content, Shannon Entropy, Codon Usage etc.) separately calculated for different genomic elements (eg. CDS, Introns, tRNA, rRNA, ncRNA, etc.). The data are independently displayed (if applicable) for each chromosomal, mitochondrial, plastid, or plasmid sequence. All the data can be visualised on the database or downloaded as CSV or Excel files. The GBRAP database is free to access without any registration and is publicly available at <GBRAP database link will be available here>.
A Bayesian Framework for Genome-wide Circadian Rhythmicity Biomarker Detection
Authors: Ding Haocheng , Meng Lingsong , Zhang Yutao , Bryant Andrew J. , Xing Chengguo , Esser Karyn A. , Chen Li , Huo Zhiguang 
Published: November 2024

AbstractCircadian rhythms are endogenous ∼24-hour cycles that significantly influence physiological and behavioral processes. These rhythms are governed by a transcriptional-translational feedback loop of core circadian genes and are essential for maintaining overall health. The study of circadian rhythms has expanded into various omics datasets, necessitating accurate analytical methodology for circadian biomarker detection. Here, we introduce a novel Bayesian framework for the genome-wide detection of circadian rhythms that is capable of incorporating prior biological knowledge and adjusting for multiple testing issue via a false discovery rate approach. Our framework leverages a Bayesian hierarchical model and employs a reverse jump Markov chain Monte Carlo (rjMCMC) technique for model selection. Through extensive simulations, our method, BayesCircRhy, demonstrated superior false discovery rate control over competing methods, robustness against heavier-tailed error distributions, and better performance compared to existing approaches. The method’s efficacy was further validated in two RNA-Sequencing data, including a human resitrcted feeding data and a mouse aging data, where it successfully identified known and novel circadian genes. R package “BayesianCircadian” for the method is publicly available on GitHubhttps://github.com/jxncdhc/BayesianCircadian.
Role of Complexin 2 in the regulation of hormone secretion from the islet of Langerhans
Authors: Ng Xue Wen , DiGruccio Michael R. , Kong Chen , Lee Jeongmin , Piston David W. 
Published: October 2024

AbstractRegulated secretion of insulin from β-cells, glucagon from α-cells, and somatostatin from δ-cells is necessary for the maintenance of glucose homeostasis. The release of these hormones from pancreatic islet cells requires the assembly and disassembly of the SNARE protein complex to control vesicle fusion and exocytosis. Complexin 2 (Cplx 2) is a small soluble synaptic protein that participates in the priming and release steps of vesicle fusion. It plays a dual role as a molecular switch that first clamps and prevents fusion pore opening, and subsequently undergoes a conformational change upon Ca2+binding to synaptotagmin to facilitate exocytosis. Using a Cplx 2 knockout (KO) mouse model, we show a direct inhibitory role of Cplx 2 for glucagon and somatostatin secretion, along with an indirect role in the paracrine inhibition of insulin secretion by somatostatin. Deletion of Cplx 2 increases glucagon and somatostatin secretion from intact mouse islets, while there is no difference in insulin secretion between WT and Cplx 2 KO islets. The normal paracrine inhibition of insulin secretion by somatostatin is disrupted in Cplx 2 KO islets. On the contrary, deletion of Cplx 2 did not affect the known role of somatostatin in the paracrine inhibition of glucagon at elevated glucose levels, since the paracrine inhibition of glucagon secretion by somatostatin is similar for both WT and Cplx 2 KO islets. In both β- and α-cells, the secretion profiles are parallel to Ca2+activity changes following somatostatin treatment of WT and Cplx 2 KO islets. The loss of paracrine inhibition of insulin secretion is substantiated by direct measurements of insulin vesicle fusion events in Cplx 2 KO islets. Together, these data show a differential role for Cplx 2 in regulating hormone secretion from pancreatic islets.