bluuebunny/crossref_metadata_2025_split huggingface dataset:
DEK::AFF2 Fusion Sinonasal and Skull Base Nonkeratinizing Squamous Cell Carcinoma
Authors: Hart Stephanie A. , Hang Jen-Fan , Chernock Rebecca D. , Mikula Michael W. , Rooper Lisa , Amin Sara E. , Saluja Karan , Bishop Justin A. , Chen Yu Hsiu , Cipriani Nicole A. , David Stephanie N. , Dupont William D. , Plummer W. Dale , Ferrer Karen T. , Geromes Ariana , Hsieh Min-Shu , Hernandez-Prera Juan C. , Kuo Ying-Ju , Sasaki Eiichi , Shi Qiuying , Truong Tra , Velez Torres Jaylou M. , Lewis James S. 
Published: December 2024

DEK::AFF2 fusion nonkeratinizing squamous cell carcinoma (NKSCC) is an emerging entity in the sinonasal tract, temporal bone, and skull base. However, the clinical behavior of these tumors has not been well studied. Here, we report the largest cohort of DEK::AFF2 carcinomas to determine if morphology, mitotic rate, and/or Ki-67 IHC are associated with patient outcomes, including a comparison with high-risk human papillomavirus (HPV)-associated and independent patients. We solicited cases of molecularly or AFF2 immunohistochemistry (IHC) proven DEK::AFF2 SCC from surgical pathologists to collect patient demographic, clinical, and outcome data. Using representative H&E slides, we characterized the morphology and counted mitoses. Ki-67 immunohistochemistry was performed. We also compared the DEK::AFF2 survival rates to those in a cohort of AFF2 IHC-negative HPV-associated and HPV-independent SCC. DEK::AFF2 carcinomas most commonly arose in the nasal cavity (13/30, 43%), and the average number of recurrences was 1.8 (range: 0 to 10). At the last follow-up, most patients were disease free (19/30, 63%) or were alive with disease (9/30, 30%). There was an average mitotic rate of 2 per 2 mm2 (range: 0 to 9) and Ki-67 proliferation rate of 26% (range: 3% to 60%). Local recurrence was common, but morphology, mitotic activity, and Ki-67 index were not associated with recurrence or survival. On Kaplan-Meier survival analysis, DEK::AFF2 patients had lower disease-free survival but otherwise had similar outcomes to conventional SCC patients. Our multi-institutional study shows that local recurrence is common in DEK::AFF2 fusion nonkeratinizing SCC patients, but patients have survival rates similar to conventional SCC. Despite showing a range of different features and proliferation rates, traditional grading by morphology, mitotic rate, and/or Ki-67 activity does not seem to be predictive of outcome.
Long-term Changes in Pain, Depression, Function and Informal Caregiving after Major Elective Surgeries Among Seriously Ill Older Adults
Authors: Min Jolene Wong Si , Wang Yihan , Bollens-Lund Evan , Reich Amanda J. , Dhanani Hiba , Ankuda Claire K. , Lipsitz Stuart , Gray Tamryn F. , Kim Dae Hyun , Ritchie Christine S. , Kelley Amy S. , Cooper Zara 
Published: December 2024

Objective:
To compare differences in pain, depression, function, and informal caregiving pre-and-post major elective surgery among older adults with and without serious illness; and determine if serious illness was independently associated with increasing pain, depression, assistance in activities of daily living (ADLs) and informal caregiving post-surgery.

Background:
The American College of Surgeons has endorsed the integration of palliative care (PC) into surgical care in adults with serious illness but targets for PC during surgical episodes such as pain, depression, function, and informal caregiving are understudied.

Methods:
We used Health and Retirement Study-linked Medicare data (2008-2018) to identify older (≥66 y) adults with and without serious illness who had major elective surgery. We performed difference-in-difference analysis to measure changes in pain, depression, function and informal caregiving pre-and-post-surgery between groups. We tested associations between serious illness and changes in pain, depression, function and informal caregiving using multivariable regression.

Results:
Among 1896 adults who had major surgery, 1139 (60%) were seriously ill. Compared to adults without serious illness, those with serious illness had greater baseline pain (43 vs. 38%), depression (22 vs.13%), assistance with ADLs(12 vs.0%) and informal caregiving (18 vs.4%); and, greater increases in assistance with ADLs pre-and-post-surgery(DID 6%, 95%CI 3.7-8.3). Serious illness was independently associated with increasing pain (OR 1.6, 95%CI 1.1-2.2), depression (OR 1.5, 95%CI 1.1-2.2), assistance with ADLs (OR 2.1, 95%CI 1.3-3.4) and informal caregiving (OR 2.1, 95%CI 1.4-3.1) post-surgery.

Conclusions:
Most older adults having elective surgery are seriously ill. Pain, depression, function, and caregiving are targets for PC to improve post-surgical outcomes.
Automating Candidate Gene Prioritization with Large Language Models: Development and Benchmarking of an API-Driven Workflow Leveraging GPT-4
Authors: Khan Taushif , Toufiq Mohammed , Yurieva Marina , Indrawattana Nitaya , Jittmittraphap Akanitt , Kosoltanapiwat Nathamon , Pumirat Pornpan , Sukphopetch Passanesh , Vanaporn Muthita , Palucka Karolina , Kabeer Basirudeen , Rinchai Darawan , Chaussabel Damien 
Published: December 2024

ABSTRACTIn this exploratory study, we developed an automated workflow that leverages Large Language Models, specifically GPT-4, to prioritize candidate genes for targeted assay development. The workflow automates interaction with OpenAI models and enables prompt creation, submission. It features customizable prompts designed to evaluate candidate genes based on criteria such as association with biological processes, biomarker potential, and therapeutic implications, which can be tailored for specific diseases or processes. Benchmarking experiments comparing the performance of the Application Programming Interface (API)-based automated prompting approach with manual prompting demonstrated high consistency and reproducibility in gene prioritization results. The automated method exhibited scalability by successfully prioritizing genes relevant to sepsis from the BloodGen3 repertoire, comprising 11,465 genes, distributed among 382 modules. The workflow efficiently identified sepsis-associated genes across the repertoire, revealing distinct gene clusters and providing insights into their distribution within module aggregates and individual modules. This proof-of-concept study demonstrates how LLMs can enhance gene prioritization, streamlining the identification process for targeted assays across various biological contexts. However, it also reveals the need for further validation and highlights the exploratory nature of this work due to scoring inconsistencies and the necessity for manual fact-checking. Despite these challenges, the automated workflow holds promise for accelerating targeted assay development for disease management and paves the way for future research.
A Model of Place Field Reorganization During Reward Maximization
Authors: Kumar M Ganesh , Bordelon Blake , Zavatone-Veth Jacob A. , Pehlevan Cengiz 
Published: December 2024

AbstractWhen rodents learn to navigate in a novel environment, a high density of place fields emerges at reward locations, fields elongate against the trajectory, and individual fields change spatial selectivity while demonstrating stable behavior. Why place fields demonstrate these characteristic phenomena during learning remains elusive. We develop a normative framework using a reward maximization objective, whereby the temporal difference (TD) error drives place field reorganization to improve policy learning. Place fields are modeled using Gaussian radial basis functions to represent states in an environment, and directly synapse to an actorcritic for policy learning. Each field’s amplitude, center, and width, as well as downstream weights, are updated online at each time step to maximize cumulative reward. We demonstrate that this framework unifies three disparate phenomena observed in navigation experiments. Furthermore, we show that these place field phenomena improve policy convergence when learning to navigate to a single target and relearning multiple new targets. To conclude, we develop a normative model that recapitulates several aspects of hippocampal place field learning dynamics and unifies mechanisms to offer testable predictions for future experiments.
Pre-trained protein language model for codon optimization
Authors: Pathak Shashank , Lin Guohui 
Published: December 2024

AbstractMotivationCodon optimization of Open Reading Frame (ORF) sequences is essential for enhancing mRNA stability and expression in applications like mRNA vaccines, where codon choice can significantly impact protein yield which directly impacts immune strength. In this work, we investigate the use of a pre-trained protein language model (PPLM) for getting a rich representation of amino acids which could be utilized for codon optimization. This leaves us with a simpler fine-tuning task over PPLM in optimizing ORF sequences.ResultsThe ORFs generated by our proposed models outperformed their natural counterparts encoding the same proteins on computational metrics for stability and expression. They also demonstrated enhanced performance against the benchmark ORFs used in mRNA vaccines for the SARS-CoV-2 viral spike protein and the varicella-zoster virus (VZV). These results highlight the potential of adapting PPLM for designing ORFs tailored to encode target antigens in mRNA vaccines.
Targeted Culture-Independent Sequencing Identifies Emergence of Macrolide-ResistantBordetella Pertussisin Australia
Authors: Fong Winkie , Rockett Rebecca J , Tam Kingsley King-Gee , Nguyen Trang , Sim Eby M , Tay Enoch , Suster Carl J.E. , Agius Jessica E , Chandra Shona , Watt Anne E , Speers David , Graham Maryza , Tran Thomas , Lim Chuan Kok , Wehrhahn Michael C , Ginn Andrew N , Gray Darcy , Robson Jennifer , Gardner Indya , McDougall Rodney , Papanicolas Lito , Howard-Jones Annaleise R , Outhred Alexander C , Kennedy Karina , Cooley Louise , Wang Qinning , Jeoffreys Neisha , Chen Sharon C-A , Basile Kerri , Golubchik Tanya , Kok Jen , Sintchenko Vitali 
Published: December 2024

ABSTRACTBordetella pertussiscontinues to circulate globally despite wide-spread vaccination, with an emergent international epidemic in 2024. The resurgence of disease is confounded by the emergence of pertactin-deficient, macrolide-resistantB. pertussis(MRBP) strains in Asia and Europe, which are under-recognised using traditional diagnostic and surveillance methods. This study addressed these gaps by applying a probe-capture hybridisation technique, which enables targeted culture-independent sequencing of genomes (tNGS) directly from respiratory specimens. Seven co-circulating lineages ofB. pertussiswere identified in Australia, including two associated with MRBP. Eight epidemiologically unrelated and geographically dispersed cases of MRBP in Australia with a A2037G mutation in all three copies of 23S rRNA were documented, three of which were confirmed by phenotypic testing and sequencing of corresponding isolates. The estimated rate of MRBP amongB. pertussisPCR positive cases was 4.4%. This study demonstrated the value of tNGS based on target enrichment and probe capture sets designed for respiratory pathogens for public health laboratory surveillance of pertussis. This approach can improve the resolution and completeness ofB. pertussissurveillance given the increasing diversity and vaccine evasion capability of this pathogen.
Evaluating the Quality of Mental Health Information Generated by Large Language Model Chatbots
Authors: Porwal Gargi , Jeenger Jitendra 
Published: December 2024

AbstractArtificial intelligence (AI) large language models (LLMs) hold great potential to transform psychiatry and mental health care by delivering relevant and tailored mental health information. This study aimed to evaluate the quality of mental health information generated by LLMs by determining their level of accessibility, reliability, and interpreting any bias present. Generative Pre-trained Transformer-4 (GPT-4) (San Francisco, California: Open AI), Gemini 1.5 Flash (Mountain View, California: Google LLC), and Large Language Model Meta AI 3.2 (Llama 3.2) (Menlo Park, California: Meta Inc.) were prompted with 20 questions commonly asked about anxiety and depression. The responses were evaluated using Flesch-Kincaid readability tests to quantify their ease of understanding through grade level and reading ease score measures. The text was subsequently analyzed using a modern DISCERN score to assess the reliability of the health-related information presented. Finally, the LLM responses were evaluated for stigmatizing language using communication and language guidelines for mental health. A significant difference in grade levels and reading ease scores was observed between GPT-4 and Llama (p < 0.01) and Gemini and Llama(p < 0.01), with both GPT-4 and Gemini having higher readability scores. No significant difference was observed in the grade level and reading ease scores between GPT-4 and Gemini (p > 0.05). All three models reported moderate reliability scores but no significant differences were observed (p > 0.05). GPT-4, Gemini, and Llama included stigmatizing phrases in 10%, 15%, and 20% of their responses respectively. These phrases were attributed to descriptions of mental health conditions and substance use; however, no significant differences were observed in the proportions of stigmatizing phrases present across the three models (p > 0.05). Furthermore, comparisons between anxiety and depression responses for each model revealed no significant differences in readability, reliability, or bias. All models demonstrated the ability to generate mental health information that generally satisfied criteria for accessibility, reliability, and minimal bias, with GPT-4 and Gemini reporting higher readability than Llama. However, the lack of additional resources cited in responses and the occasional presence of certain stigmatizing phrases, indicate that additional model training and fine-tuning, specifically for mental health applications, may be necessary before these tools can be deployed on a large scale for mental health care.
Technical Feasibility Study for a Retinal Camera System
Authors: Makedonsky Katherine , Patwardhan Anil , Kim Angela , Silvestrini Matthew , Lui Clarissa , Kavusi Sam 
Published: December 2024

AbstractBackground/ObjectivesImprovements in diabetic retinopathy (DR) screening could boost early detection rates and contribute to better patient outcomes. The availability of primary care-based DR screening could address this issue, although operational challenges remain. This study represents a preliminary evaluation of the feasibility and operational performance of a retinal screening system suitable for integration into a primary care setting.MethodsThis was a multi-center, data collection study for a non-mydriatic retinal camera system, conducted in 4 iterative development phases; phase 4 simulated a clinical workflow. Study endpoints evaluated image quality (gradability) and operational characterization in phase 4 (time to complete image capture). Participants were required to be at least 22 years of age, and separate participant pools were recruited throughout study phases. In each phase, multiple images per eye were collected, and graded independently by sponsor-employed and external graders.ResultsThe study included 212 participants. In phases 1-3 (n=192), evaluation of the first image captured per eye for all participants (k=383) by non-sponsor graders showed 93.7% of images (359/383) as gradable; in phase 4 (n=20; k=55), there were 81.8% (45/55) gradable images. Regarding operational results, 90.1% of first-attempts trigger times were less than 30 seconds; by the third attempt, 96.7% were less than 30 seconds,ConclusionsThese are encouraging preliminary results in terms of performance and usability for the retinal camera system in this study, which may have potential application in primary care clinics.
Ilastik: a machine learning image analysis platform to interrogate stem cell fate decisions across multiple vertebrate species
Authors: Munoz Alma Zuniga , Soni Kartik , Li Angela , Lakkundi Vedant , Iyer Arundati , Adler Ari , Kirkendall Kathryn , Petrigliano Frank , Benayoun Bérénice A. , Lozito Thomas P. , Almada Albert E. 
Published: December 2024

SummaryStem cells are the key cellular source for regenerating tissues and organs in vertebrate species. Historically, the investigation of stem cell fate decisionsin vivohas been assessed in tissue sections using immunohistochemistry (IHC), where a trained user quantifies fluorescent signal in multiple randomly selected images using manual counting—which is prone to inaccuracies, bias, and is very labor intensive. Here, we highlight the performance of a recently developed machine-learning (ML)-based image analysis program called Ilastik using skeletal muscle as a model system. Interestingly, we demonstrate that Ilastik accurately quantifies Paired Box Protein 7 (PAX7)-positive muscle stem cells (MuSCs) before and during the regenerative process in whole muscle sections from mice, humans, axolotl salamanders, and short-lived African turquoise killifish, to a precision that exceeds human capabilities and in a fraction of the time. Overall, Ilastik is a free user-friendly ML-based program that will expedite the analysis of stained tissue sections in vertebrate animals.
DOC2b enrichment mitigates proinflammatory cytokine-induced CXCL10 expression by attenuating IKKβ and STAT-1 signaling in human islets
Authors: Chatterjee Bhowmick Diti , Ahn Miwon , Bhattacharya Supriyo , Aslamy Arianne , Thurmond Debbie C. 
Published: December 2024

ABSTRACTIntroductionType 1 diabetic human islet β-cells are deficient in double C 2 like domain beta (DOC2b) protein. Further, DOC2b protects against cytokine-induced pancreatic islet β-cell stress and apoptosis. However, the mechanisms underpinning the protective effects of DOC2b remain unknown.MethodsBiochemical studies, qPCR, proteomics, and immuno-confocal microscopy were conducted to determine the underlying protective mechanisms of DOC2b in β-cells. DOC2b- enriched or-depleted primary islets (human and mouse) and β-cell lines challenged with or without proinflammatory cytokines, global DOC2b heterozygous knockout mice subjected to multiple-low-dose-streptozotocin (MLD-STZ), were used for these studies.ResultsA significant elevation of stress-induced CXCL10 mRNA was observed in DOC2b- depleted β-cells and primary mouse islets. Further, DOC2b enrichment markedly attenuated cytokine-induced CXCL10 levels in primary non-diabetic human islets and β-cells. DOC2b enrichment also reduced total-NF-κB p65 protein levels in human islets challenged with T1D mimicking proinflammatory cytokines. IKKβ, NF-κB p65, and STAT-1 are capable of associating with DOC2b in cytokine-challenged β-cells. DOC2b enrichment in cytokine-stressed human islets and β-cells corresponded with a significant reduction in activated and total IKKβ protein levels. Total IκBβ protein was increased in DOC2b-enriched human islets subjected to acute cytokine challenge. Cytokine-induced activated and total STAT-1 protein and mRNA levels were markedly reduced in DOC2b-enriched human islets. Intriguingly, DOC2b also prevents ER-stress-IKKβ and STAT-1 crosstalk in the rat INS1-832/13 β-cell line.ConclusionThe mechanisms underpinning the protective effects of DOC2b involve attenuation of IKKβ-NF-κB p65 and STAT-1 signaling, and reduced CXCL10 expression.Graphical abstract
Comprehensive analysis of macrophages infected with avirulent and virulentMycobacterium tuberculosisuncovers distinct immune mechanisms and anti-TB effect of treated exosomes
Authors: Yang Li , Lyu Lingna , Li Cuidan , Zhang Xiuli , Ju Yingjiao , Zhang Ju , Liu Jie , Yue Liya , Zhang Xiangli , Lu Dandan , Yang Tingting , Wang Peihan , Wang Jie , Wang Xiaotong , Xu Sihong , Sheng Yongjie , Jiang Chunlai , Wang Jing , Hu Xin , Bahetibieke Tuohetaerbaike , Zhang Zongde , Chen Fei 
Published: December 2024

AbstractTuberculosis (TB) is now the world’s second deadliest infectious killer after COVID-19. Human-macrophages and their secreted exosomes play important roles in combating invadingMtb. However, the panoramic analysis of the underlying immune mechanism for the infected macrophages, package or secretion mechanism, and anti-TB effect ofMtbtreated exosomes remain poorly understood. Here we conducted comprehensive analyses of the macrophages infected with avirulent and virulentMtb(H37Ra & H37Rv) and their secreted exosomes, collected cells and corresponding exosomes for omics and phenotypic analysis. The results showed that avirulentMtbstimulated robust immune-responses and apoptosis in macrophages to eliminate the invadingMtb; virulentMtbinduced severe necrosis and immune-escape for survival. The HMGB1 signaling pathway andTNFRSF1Bplays important roles in the immune escape of virulentMtb. Interestingly, our results suggest that macrophages killMtbin an IFN-γ independent but simulative way, highlighting the central role of IFN signaling pathway in anti-TB immune response. Moreover, we observed selective transport of host andMtbRNAs from macrophages to exosomes. Notably, “H37Ra-treated exosomes” displayed a higher anti-TB effect than “H37Rv-treated exosomes” due to some enriched pro-inflammation and immune-escape relatedMtbproteins in these two exosomes, respectively. Conclusively, our findings shed new light on the immune mechanism of macrophages in response toMtbinfection, offering a new TB-treatment strategy and some promising vaccine candidates.
“Let’s stick together”: toward a serial mediation model about the impact of relational leadership on workers’ employability
Authors: Hoedemakers Joost , Vanderstukken Arne , Stoffers Jol , Van der Heijden Beatrice 
Published: December 2024

PurposeThis paper explores whether relational leadership enhances nurses’ employability. An empirical study was conducted to investigate associations between relational leadership, perceived supervisory support, perceived opportunities for competence development and employability.Design/methodology/approachA serial mediation model was constructed to investigate our hypothesized relationships. We applied a two-wave panel design and collected self-reported survey data from 109 nurses who worked in a Dutch homecare organization. Relationships were tested using PLS-SEM.FindingsOur findings suggest no direct association between relational leadership and employability. However, we found support for a serial mediation model, in which perceived supervisory support and perceived opportunities for competence development fully mediated the relationship between relational leadership and employability.Research limitations/implicationsThis scholarly work contributes to the employability literature; a supervisor who fosters high-quality relationships with nurses communicates a willingness to support their development and provides them competence development opportunities, which, in turn, fosters nurses’ employability.Practical implicationsHR managers and supervisors in homecare organizations should create leadership development policies and practices that encourage relational leadership, particularly empowering leadership.Originality/valueTo the best of our knowledge, up until now, this study is the first to use supervisors’ relational leadership to predict employees’ employability.