bluuebunny/crossref_metadata_2025 huggingface dataset:
Oncointerpreter.ai enables interactive, personalized summarization of cancer diagnostics data
Authors: Tripathi Arihant , Ecker Brett , Boland Patrick , Ghodoussipour Saum , Riedlinger Gregory R , De Subhajyoti
Published: November 2024

Objectives

Cancer diagnosis comes as a shock to many patients, and many of them feel unprepared to handle the complexity of the life-changing event, understand technicalities of the diagnostic reports, and fully engage with the clinical team regarding the personalized clinical decision-making.

Materials and Methods

We develop Oncointerpreter.ai an interactive resource to offer personalized summarization of clinical cancer genomic and pathological data, and frame questions or address queries about therapeutic opportunities in near-real time via a graphical interface. It is built on the Mistral-7B and Llama-2 7B large language models trained on a local database trained using a large, curated corpus.

Results

We showcase its utility with case studies, where Oncointerpreter.ai extracted key clinical and molecular attributes from deidentified pathology and clinical genomics reports, summarized their contextual significance and answered queries on pertinent treatment options. Oncointerpreter also provided personalized summary of currently active clinical trials that match the patients’ disease status, their selection criteria, and geographic locations. Benchmarking and comparative assessment indicated that the model responses were generally consistent, and hallucination, ie, factually incorrect or nonsensical response was rare; treatment- and outcome related queries led to context-aware responses, and response time correlated with verbosity.

Discussion

The choice of model and domain-specific training also affected the response quality.

Conclusion

Oncointerpreter.ai can aid the existing clinical care with interactive, individualized summarization of diagnostics data to promote informed dialogs with the patients with new cancer diagnoses.

Availability

https://github.com/Siris2314/Oncointerpreter
Trabecular bone structural units and their cement lines change with age, bone volume fraction, structure, and strength in female human vertebrae
Authors: Lamarche Britney A , Thomsen Jesper Skovhus , Andreasen Christina Møller , Andersen Thomas Levin , Lievers W Brent
Published: November 2024

A lifetime of successive bone remodeling events leads to trabeculae which are composed of a patchwork of bone structural units (BSUs) called hemi-osteons or trabecular packets. Traditionally, only intact surface BSUs have been studied, which are those that have been created most recently. Accordingly, the complex changes in the size and distribution of BSU throughout the trabeculae have been overlooked. In this study, the BSUs within the trabeculae of the second lumbar vertebrae were manually traced, using ImageJ software, in osteopontin immunostained sections of eight young women (aged 19-38 yr) and eight older women (aged 69-96 yr). A series of BSU profile properties including area, width, length, and perimeter were quantified, along with properties of each trabecular profile such as the number of BSU and cement line length. The relationships between these properties and age, as well as selected trabecular microstructural properties assessed with microcomputed tomography, and bone strength assessed on the neighboring third lumbar vertebrae, were investigated. The median BSU profile length and perimeter decreased with age, while the median BSU profile area and width was unchanged. Moreover, age was associated with an increase in the number of BSU profiles and cement line length per trabecular profile area. However, changes in BSU profile geometry, the number of BSU profiles, and the cement line length per trabecular profile were strongly correlated with trabecular bone volume fraction, structure model index, and bone strength. Further research is needed to understand how these changes in BSU properties affect the mechanical and failure properties of trabecular bone.
BMO-GNN: Bayesian mesh optimization for graph neural networks to enhance engineering performance prediction
Authors: Park Jangseop , Kang Namwoo
Published: November 2024

Surrogate models are commonly used in engineering design to reduce the computational costs of simulations by approximating design variables and geometric parameters from computer-aided design (CAD) models. However, traditional surrogate models often lose critical information when simplified to lower dimensions and face challenges in handling the complexity of 3D shapes, especially in industrial datasets. To address these limitations, we propose a Bayesian graph neural network (GNN) framework that directly learns geometric features from CAD mesh representations for accurate engineering performance prediction. Our framework leverages Bayesian optimization (BO) to dynamically determine the optimal mesh element size, significantly improving model accuracy while balancing computational efficiency. This approach optimizes mesh resolution to preserve critical geometric features in 3D deep-learning-based surrogate models, adapting mesh size based on the task for high flexibility across various engineering applications. Experimental results demonstrate that mesh quality directly impacts prediction accuracy. The proposed BO-EI GNN model outperforms state-of-the-art models, including 3D CNN, SubdivNet, GCN, and GNN, in predicting mass, rim stiffness, and disk stiffness. Our method also significantly reduces computational costs compared to traditional optimization techniques. The proposed framework shows promising potential for application in finite element analysis (FEA) and other mesh-based simulations, enhancing the utility of surrogate models across various engineering fields.
Cumulative psychosocial and health disparities in US adolescent cigarette smoking, 2002-2019
Authors: Erath Tyler G , Chen Fang Fang , DeSarno Michael , Devine Derek , Leventhal Adam M , Bickel Warren K , Higgins Stephen T
Published: November 2024

Background

Understanding disparities in adolescent cigarette smoking is important for effective prevention.

Methods

We investigated disparities in adolescent smoking based on cumulative reported psychosocial and health risk among respondents ages 12-17 years in the US National Survey of Drug Use and Health from 2002 to 2019. Multivariable regression estimated associations of cumulative risk, survey years, and their interaction predicting past-month and daily smoking. Eleven psychosocial and health variables associated with youth smoking formed composite measures of cumulative risk, categorizing risk as low (0-2), moderate (3-4), or high (≥5). The main outcomes were weighted past-month and daily smoking by cumulative risk and time, examining prevalence and proportional change across years.

Results

Among 244 519 adolescents, greater cumulative risk predicted higher smoking prevalence across all outcomes. Compared with the low-risk category, past-month smoking odds (adjusted odds ratio) were 9.14 (95% confidence interval [CI] = 8.58 to 9.72) and 46.15 (95% CI = 43.38 to 49.10) times greater in the moderate-risk and high-risk categories. For daily smoking, odds were 14.11 (95% CI = 11.92 to 16.70) and 97.32 (95% CI = 83.06 to 114.03) times greater among the moderate-risk and high-risk categories. Regarding proportional change, the low-risk category exhibited the steepest decline (−85.1%) in past-month smoking from 2002-2003 to 2018-2019, followed by the moderate-risk (−79.2%) and high-risk (−65.7%) categories. Daily smoking declined more steeply among the low-risk (−96.5%) and moderate-risk (−90.5%) than high-risk category (−86.4%).

Conclusions

Cumulative risk is a robust predictor of adolescent smoking. Although record-setting reductions in adolescent smoking extend across risk categories, disparities favoring youth with fewer risks are evident throughout. Recognizing cumulative risk can inform the development of more targeted and effective prevention efforts.
Stacking Fault Segregation Imaging With Analytical Field Ion Microscopy
Authors: F. Morgado Felipe , Stephenson Leigh T , Bhatt Shalini , Freysoldt Christoph , Neumeier Steffen , Katnagallu Shyam , Subramanyam Aparna P A , Pietka Isabel , Hammerschmidt Thomas , Vurpillot François , Gault Baptiste
Published: November 2024

Stacking faults (SFs) are important structural defects that play an essential role in the deformation of engineering alloys. However, direct observation of SFs at the atomic scale can be challenging. Here, we use the analytical field ion microscopy, including density functional theory–informed contrast estimation, to image local elemental segregation at SFs in a creep-deformed solid-solution single-crystal alloy of Ni–2 at% W. The segregated atoms are imaged brightly, and time-of-flight spectrometry allows for their identification as W. We also provide the first quantitative analysis of trajectory aberration, with a deviation of approximately 0.4 nm, explaining why atom probe tomography could not resolve these segregations. Atomistic simulations of substitutional W atoms at an edge dislocation in face-centered cubic Ni using an analytic bond-order potential indicate that the experimentally observed segregation is due to the energetic preference of W for the center of the SF, contrasting with, for example, Re segregating to partial dislocations. Solute segregation to SF can hinder dislocation motion, increasing the strength of Ni-based superalloys. Yet, direct substitution of Re by W, envisaged to lower the superalloys’ costs, requires extra consideration in alloy design since these two solutes do not have comparable interactions with structural defects during deformation.
PEPSI’s non-detection of escaping hydrogen and metal lines adds to the enigma of WASP-12 b
Authors: Pai Asnodkar Anusha , Wang Ji , Broome Madelyn , Huang Chenliang , Johnson Marshall C , Ilyin Ilya , Strassmeier Klaus G , Jensen Adam
Published: November 2024

WASP-12 b is an ultra-hot Jupiter of special interest for atmospheric studies since it is on an inspiraling orbit in an extreme environment of intense radiation and circumstellar gas. Previously claimed detections of active mass-loss from this planet are controversial across the literature. To address this controversy, we obtain two new transit observations of WASP-12 b with the optical high-resolution PEPSI spectrograph on the Large Binocular Telescope. Contrary to previous work, we do not observe planetary H$\alpha$ absorption and rule out the amplitude of previously reported detections. Our non-detection may be limited by the sensitivity of our data or could indicate weaker mass-loss than suggested by previous studies. We conduct injection-recovery experiments to place constraints on the radial extent of WASP-12 b’s escaping atmosphere as probed by Balmer lines, but find that our data do not have the sensitivity to probe down to the planet’s Roche lobe. Using physically motivated models of atmospheric escape, we explore upper limit constraints on the planet’s mass-loss rate and deem the data quality in the wavelength regime of Balmer lines insufficient to determine a physically meaningful constraint. We also conduct a spectral survey of other optical absorbers to trace atmospheric circulation but detect no additional absorption. We conclude that previous claims of H$\alpha$ absorption from the atmosphere of WASP-12 b should be reevaluated. Given the anticipated line strength of Balmer/optical features, observing the atmosphere of this faint target will require stacking more observations even with the largest telescope facilities available.
OncoSexome: the landscape of sex-based differences in oncologic diseases
Authors: Shen Xinyi , Zhang Yintao , Li Jiamin , Zhou Ying , Butensky Samuel D , Zhang Yechi , Cai Zongwei , DeWan Andrew T , Khan Sajid A , Yan Hong , Johnson Caroline H , Zhu Feng
Published: November 2024

The NIH policy on sex as biological variable (SABV) emphasized the importance of sex-based differences in precision oncology. Over 50% of clinically actionable oncology genes are sex-biased, indicating differences in drug efficacy. Research has identified sex differences in non-reproductive cancers, highlighting the need for comprehensive sex-based cancer data. We therefore developed OncoSexome, a multidimensional knowledge base describing sex-based differences in cancer (https://idrblab.org/OncoSexome/) across four key topics: antineoplastic drugs and responses (SDR), oncology-related biomarkers (SBM), risk factors (SRF) and microbial landscape (SML). SDR covers sex-based differences in 2051 anticancer drugs; SBM describes 12 551 sex-differential biomarkers; SRF illustrates 350 sex-dependent risk factors; SML demonstrates 1386 microbes with sex-differential abundances associated with cancer development. OncoSexome is unique in illuminating multifaceted influences of biological sex on cancer, providing both external and endogenous contributors to cancer development and describing sex-based differences for the broadest oncological classes. Given the increasing global research interest in sex-based differences, OncoSexome is expected to impact future precision oncology practices significantly.
canSAR 2024—an update to the public drug discovery knowledgebase
Authors: Gingrich Phillip W , Chitsazi Rezvan , Biswas Ansuman , Jiang Chunjie , Zhao Li , Tym Joseph E , Brammer Kevin M , Li Jun , Shu Zhigang , Maxwell David S , Tacy Jeffrey A , Mica Ioan L , Darkoh Michael , di Micco Patrizio , Russell Kaitlyn P , Workman Paul , Al-Lazikani Bissan
Published: November 2024

canSAR (https://cansar.ai) continues to serve as the largest publicly available platform for cancer-focused drug discovery and translational research. It integrates multidisciplinary data from disparate and otherwise siloed public data sources as well as data curated uniquely for canSAR. In addition, canSAR deploys a suite of curation and standardization tools together with AI algorithms to generate new knowledge from these integrated data to inform hypothesis generation. Here we report the latest updates to canSAR. As well as increasing available data, we provide enhancements to our algorithms to improve the offering to the user. Notably, our enhancements include a revised ligandability classifier leveraging Positive Unlabeled Learning that finds twice as many ligandable opportunities across the pocketome, and our revised chemical standardization pipeline and hierarchy better enables the aggregation of structurally related molecular records.
A survey on multimodal large language models
Authors: Yin Shukang , Fu Chaoyou , Zhao Sirui , Li Ke , Sun Xing , Xu Tong , Chen Enhong
Published: November 2024

Recently, the multimodal large language model (MLLM) represented by GPT-4V has been a new rising research hotspot, which uses powerful large language models (LLMs) as a brain to perform multimodal tasks. The surprising emergent capabilities of the MLLM, such as writing stories based on images and optical character recognition–free math reasoning, are rare in traditional multimodal methods, suggesting a potential path to artificial general intelligence. To this end, both academia and industry have endeavored to develop MLLMs that can compete with or even outperform GPT-4V, pushing the limit of research at a surprising speed. In this paper, we aim to trace and summarize the recent progress of MLLMs. First, we present the basic formulation of the MLLM and delineate its related concepts, including architecture, training strategy and data, as well as evaluation. Then, we introduce research topics about how MLLMs can be extended to support more granularity, modalities, languages and scenarios. We continue with multimodal hallucination and extended techniques, including multimodal in-context learning, multimodal chain of thought and LLM-aided visual reasoning. To conclude the paper, we discuss existing challenges and point out promising research directions.
Risk Factors for Spotted Fever Group Rickettsioses in Kilimanjaro Region, Tanzania
Authors: Bowhay Thomas R , Rubach Matthew P , Mendes Ângelo J F , Nicholson William L , Perniciaro Jamie L , Maze Michael J , Moorthy Ganga S , Halliday Jo E B , Allan Kathryn J , Mmbaga Blandina T , Saganda Wilbrod , Lwezaula Bingileki F , Kazwala Rudovick R , Cleaveland Sarah , Sharples Katrina J , Maro Venance P , Crump John A
Published: November 2024

Background

Knowledge gaps exist on risk factors for spotted fever group rickettsioses (SFGR) in sub-Saharan Africa. We sought to identify SFGR risk factors in Kilimanjaro Region, Tanzania.

Methods

We recruited febrile patients presenting at 2 hospitals in Moshi from February 2012 through May 2014. Standardized clinical and risk factor questionnaires were administered. SFGR exposure was defined as a Rickettsia africae immunofluorescence antibody reciprocal titer ≥64, and acute SFGR as a ≥4-fold rise between paired sera. Logistic regression was used to identify associations.

Results

Of 1190 participants providing ≥1 serum sample, the median age was 21.8 (range, 0.3–100.2) years, 646 (54.3%) were female, and 650 (54.6%) had SFGR exposure. Of 731 participants with paired sera, 67 (9.2%) had acute SFGR. On multivariable analysis, odds of acute SFGR were higher in the age group 0–2 years (adjusted odds ratios [aORs] for older age groups, <0.36; P < .011), rural residence (aOR, 4.1; P = .007), and areas with maximum daily temperature <26°C (aORs for higher temperature groups, <0.42; P < .035). Odds of SFGR exposure were higher in those working in the garden (aOR, 1.8; P = .010) and seeing a dog (aOR, 1.5; P = .010). Odds of SFGR exposure were lower in the age group 0–2 years (aORs for older age groups, >1.5; P < .026), female sex (aOR, 0.62; P < .001), and being from the Chaga tribe (aOR, 0.68; P = .003).

Conclusions

Those aged <2 years, rural residents, and persons residing in areas with cooler temperatures had increased odds of SFGR. Our results identify groups for further research on tick exposure and for targeted prevention interventions.
The transcription factor CaBBX10 promotes chlorophyll and carotenoid pigment accumulation in Capsicum annuum fruit
Authors: Wang Jin , Shan Qingyun , Yuan Qiaoling , Pan Luzhao , Wang Meiqi , Zhao Pei , Yu Feng , Dai Li , Xie Lingling , Wang Zhongyi , Dai Xiongze , Chen Li , Zou Xuexiao , Xiong Cheng , Zhu Fan , Liu Feng
Published: November 2024

Chlorophylls and carotenoids are 2 pivotal photosynthetic pigments directly influencing the economic value of pepper (Capsicum annuum L.) fruits. However, the coordinated regulatory mechanisms governing the accumulation of both chlorophylls and carotenoids during pepper fruit development remain elusive. In this study, pepper B-box 10 (CaBBX10), a candidate hub transcription factor, was found to play dual roles in the early development of pepper fruit. CaBBX10 virus-induced gene silencing and overexpression experiments demonstrated that the encoded transcription factor promotes both chlorophyll and carotenoid accumulation in pepper fruit. Further comprehensive analyses showed that CaBBX10 directly binds to the promoter of magnesium chelatase subunit D subunit (CaCHLD) and phytoene synthase 1 (CaPSY1), thereby activating their expression in the chlorophyll and carotenoid biosynthesis pathways, respectively. Additionally, the photomorphogenic factor CaCOP1 was found to physically interact with CaBBX10 and lead to its degradation. Therefore, CaBBX10 may serve as a critical link connecting chlorophyll and carotenoid biosynthesis to light signaling. Altogether, our findings reveal a mechanism for the complex transcriptional regulation that simultaneously promotes chlorophyll and carotenoid accumulation in pepper fruit.
Expression of the polyphenol oxidase gene MdPPO7 is modulated by MdWRKY3 to regulate browning in sliced apple fruit
Authors: Zou Hui , Li Chengzhu , Wei Xiaoyu , Xiao Qian , Tian Xiaocheng , Zhu Lingcheng , Ma Baiquan , Ma Fengwang , Li Mingjun
Published: November 2024

Browning is a pervasive problem in horticultural products, substantially diminishing the appearance, flavor, and nutritional value of fruit, including important fruits like apple (Malus × domestica Borkh.). In this study, we compared the physiological characteristics of the browning-resistant line ‘Rb-18’ with the susceptible variety ‘Fuji’ and found that the polyphenol oxidase (PPO) enzyme activity and phenolic content of ‘Rb-18’ were significantly lower than those in ‘Fuji’. In addition, the PPO enzyme in ‘Fuji’ showed a stronger affinity for its substrate, catechol, compared to ‘Rb-18’. Through transcriptome and RT-qPCR analyses, MdPPO7 expression was identified as contributing to flesh browning after cutting. Subsequent fruit injection and stable genetic transformation of the MdPPO7 gene into apple fruit and calli determined that syringic acid, procyanidin, phloridzin, chlorogenic acid, gallic acid, catechin, and caffeic act as its catalytic substrates in the process involved in browning. Furthermore, luciferase reporter, yeast 1-hybrid, β-glucuronidase reporter assays and ChIP-qPCR analysis demonstrated that a WRKY transcription factor (MdWRKY3) binds to the promoter region of polyphenol oxidase gene (MdPPO7) and positively regulates its expression to promote apple flesh browning. This study provides insights into the molecular regulatory mechanisms of fruit browning in fresh-cut apples and provides a theoretical basis for the generation of high-quality apple germplasm resources.
Warm glow feelings can promote green behavior
Authors: Jerit Jennifer , Shin Hwayong , Barabas Jason
Published: November 2024

For climate mitigation to be successful, vast numbers of people must change how they go about daily life. Social scientists have tried to promote environmentally sustainable (i.e. “green”) behavior with interventions involving cues, frames, and information, but the cumulative impact of those efforts has been modest. A growing number of studies—largely observational—suggests the promise of “warm glow” messaging that features the pleasure and satisfaction one experiences from acting sustainably. While past work has established the association between intrinsic motivations and green behavior, our study offers evidence regarding the causal effect of warm glow feelings in the climate domain. In three survey experiments administered on different national samples, we induce feelings of warm glow and examine the impact on green behavioral intentions. The treatment, an adaptation of a standard feeling induction, has a significant influence on a wide range of actions—an effect that is distinct from the influence of general positivity. Most importantly, we observe the largest treatment effects in surprising places: among Republicans, and within this subgroup, on more socially visible activities. Manipulated warm glow also increases intentions to engage in more difficult (e.g. costly, effortful) activities. Our findings are valuable for scholars and practitioners seeking to promote broad-based climate mitigation across the ideological spectrum.
An immunoregulatory and metabolism-improving injectable hydrogel for cardiac repair after myocardial infarction
Authors: Sun Yage , Zhao Xinrui , Zhang Qian , Yang Rong , Liu Wenguang
Published: November 2024

The hypoxia microenvironment post-myocardial infarction (MI) critically disturbs cellular metabolism and inflammation response, leading to scarce bioenergy supplying, prolonged inflammatory phase and high risk of cardiac fibrosis during cardiac restoration. Herein, an injectable hydrogel is prepared by Schiff base reaction between fructose-1,6-bisphosphate (FBP)-grafted carboxymethyl chitosan (CF) and oxidized dextran (OD), followed by loading fucoidan-coated baicalin (BA)-encapsulated zein nanoparticles (BFZ NPs), in which immunoregulatory and metabolism improving functions are integrally included. The grafted FBP serves to enhance glycolysis and provide more bioenergy for cardiomyocytes survival under hypoxia microenvironment, and elevating cellular antioxidant capacity via pentose phosphate pathway. OD with intrinsic anti-inflammatory effect can induce M2 polarization of macrophages to accelerate inflammatory elimination. While facing the possibility of endothelial-to-mesenchymal transition (EndoMT) caused by excessive expressed TGF-β1 secreted from M2 macrophages, BFZ NPs can target endothelia cells and intracellularly release BA to regulate the level of fatty acid oxidation, resulting in retained endothelial features and decreased risk of cardiac fibrosis. After being injecting the hydrogel into rats’ infarcted cardiac, the 28-day-post surgical outcomes demonstrate its benign effects on restoring cardiac functions and attenuating adverse left ventricular remodeling. This study shows a promising measure for MI treatment with immunoregulating and metabolism regulation comprehensively.
Lipid-core nanocapsules containing simvastatin do not affect the biochemical and hematological indicators of toxicity in rats
Authors: Lorenzoni Ricardo , Davies Samuel , Cordenonsi Leticia Malgarim , Roggia Isabel , Viçosa José Alcides da Silva , Mezzomo Nathana Jamille , de Oliveira Amanda Lima , do Carmo Guilherme Machado , Vitalis Graciela , Gomes Patrícia , Raffin Renata Platcheck , Alves Oswaldo Luiz , Vaucher Rodrigo De Almeida , Rech Virginia Cielo
Published: November 2024

Our research group previously studied the effectiveness of lipid-core nanocapsules (LNC) containing simvastatin (SV-LNC) in treating cognitive impairment in rats. While our results were promising, we needed to evaluate the potential toxicity of the nanoparticles themselves. This study aimed to compare the biochemical and hematological parameters of adult Wistar rats receiving LNC or SV-LNC to those receiving low doses of simvastatin crystals dispersed in a saline solution over 45 days. We discovered that LNC and SV-LNC, which are both nanometers in size with low polydispersity index, negative zeta potential, and high SV encapsulation efficacy, were not more toxic than SV crystals based on various biochemical markers of hepatic, pancreatic, renal, mineral, bony, alkaline phosphatase, glucose, and uric acid damage. Furthermore, LNC exhibited no toxicity for hematological parameters, including red and white blood cell counts. Based on this animal model of toxicological study, our findings suggest that long-term administration of LNC is a safe and promising nanocarrier.
The Molecular Dialogue Between Zymoseptoria tritici and Wheat
Authors: Meile Lukas , Carrasco-López Cristian , Lorrain Cécile , Kema Gert H. J. , Saintenac Cyrille , Sánchez-Vallet Andrea
Published: November 2024

Zymoseptoria tritici is a highly damaging pathogen that causes high wheat yield losses in temperate climates. Z. tritici emerged during the domestication of wheat in the Fertile Crescent and has been extensively used as a model system for population genetic and genomic studies. New genetic tools and resources have provided a better understanding of the molecular components involved in the wheat- Z. tritici interaction, which is highlighted by the cloning of three wheat resistance genes and four Z. tritici avirulence genes. Despite the considerable progress made in the last few years, the mechanisms that mediate Z. tritici colonization remain largely unknown. In this review, we summarize the latest advances in understanding the molecular components mediating wheat- Z. tritici interactions, and we discuss future research lines to close current knowledge gaps.

[Formula: see text] Copyright © 2025 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
GATA1‐activated lncRNA OIP5‐AS1 and GAS5 promote pyroptosis to exacerbate asthma through regulating miR‐136‐5p/LIFR axis
Authors: Zhao Suzhi , Huang Sini , Wu Yawei , Yao Xiaozhou , Cai Xingjun
Published: November 2024

Pyroptosis plays a pivotal role in airway epithelial inflammation during the progression of asthma. This study aimed to explore the influence and mechanisms of opa‐interacting protein 5 antisense RNA1 (OIP5‐AS1) and growth arrest‐specific transcript 5 (GAS5) on pyroptosis in asthmatic models. Pyroptosis was induced in Dermatophagoides pteronyssinus 1 (Der p1)‐exposed 16HBE cells and ovalbumin (OVA)‐challenged rats. Subsequently, pyroptosis and its related molecular mechanisms were investigated. Our results indicated that GATA1, OIP5‐AS1, GAS5, and LIFR were upregulated, while miR‐136‐5p was downregulated in the patients and experimental models of asthma. OIP5‐AS1/GAS5 knockdown repressed NLRP3 inflammasome‐mediated pyroptosis in 16HBE cells. Mechanistically, OIP5‐AS1/GAS5 sponged miR‐136‐5p to enhance LIFR expression and subsequently activated NF‐κB pathway. OIP5‐AS1, GAS5, or LIFR‐mediated induction of pyroptosis was abrogated by miR‐136‐5p mimics or NF‐κB inhibitors (BAY11‐7082). Finally, GATA1 transcriptionally activated OIP5‐AS1/GAS5 to trigger pyroptosis, thereby driving asthma progression in vivo and in vitro. In conclusion, OIP5‐AS1/GAS5 transcriptionally activated by GATA1 promoted NLRP3 inflammasome‐mediated pyroptosis via the modulation of miR‐136‐5p/LIFR/NF‐κB axis and consequently resulted in airway inflammation in asthma. Our results may provide novel therapeutic strategies for asthma.
Characterizing Research Teams
Authors: Young Meredith E. , Dubé Tim , Schumacher Daniel J. , Lubarsky Stuart , Ryan Anna T. , O’Brien Bridget C.
Published: November 2024

Research in health professions education (HPE) is often executed by teams—groups of individuals working together to solve a problem, reconceptualize an issue, or conduct a study. Teams frequently involve individuals from different disciplinary backgrounds or professions1,2 who work collaboratively to accomplish specific scholarly goals. Matching team composition to research goals is critical for ensuring the team has the skills and perspectives necessary to generate, integrate, and mobilize the desired knowledge. Drawing on literature,3,4 we describe the who, what, how, and when of 4 types of research teams.
Minimally Invasive Transthoracic Intramyocardial Cellular Transplantation Under Echocardiographic Guidance for Myocardial Impairment
Authors: Li Sulei , Tao Bo , Liu Junsong , Liu Dongyue , Wang Yujia , Zhang Jibin , Tian Lei , Xu Baixuan , Fang Yan , Wang Yabin , Lou Xin , Zhang Jinming , Lan Feng , Cao Feng
Published: November 2024

Objective:

To explore the approach of minimally invasive transthoracic intramyocardial cellular transplantation under echocardiographic guidance to promote ischemic myocardial repair in a preclinical big-animal study.

Methods:

Female Guangxi Bama miniature pigs (weight: 25–30 kg) were randomly allocated into the sham group, untreated myocardial infarction (MI) group (MI group), the MI and surgical intramyocardial injection (SIM) group (MI-SIM group), and the MI and transthoracic echocardiography-guided percutaneous intramyocardial injection (TTEPIM) group (MI-TTEPIM group) (n = 4 each) using a lottery method. A swine MI model was established in the 3 groups excluding the sham group, and human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM) labeled with the herpes simplex virus type-1 thymidine kinase reporter gene (hiPS-CMTK+) were transplanted by SIM in MI-SIM group and TTEPIM in MI-TTEPIM group. The operation time, postoperative recovery time of animals and volume of blood loss were collected for comparison between MI-SIM group and MI-TTEPIM group. 9-(4-[18F] fluoro-3-(hydroxymethyl) butyl) guanine positron emission tomography/computed tomography imaging was performed to track the hiPS-CMTK+
in vivo. Cardiac function and morphology were evaluated by echocardiography.

Results:

The operation time and postoperative recovery time of MI-TTEPIM group were significantly shorter than those of MI-SIM group ((28.3 ± 3.6) min vs. (97.0 ± 6.7) min, P < 0.001; (1.3 ± 0.3) d vs. (7.5 ± 0.9) d, P < 0.001). MI-TTEPIM also showed significantly lesser volume of blood loss during cell transplantation than MI-SIM group ((4.3 ± 0.8) mL vs. (47.0 ± 4.1) mL, P < 0.001). The transplanted cells could be traced more accurately in vivo in MI-TTEPIM than in MI-SIM. The circumferential strain of intervention region in the MI-TTEPIM group (–25.07% ± 0.27%) was significantly higher than that of the MI-SIM (–20.39% ± 0.67%) and MI groups (–19.68% ± 0.67%), respectively (P < 0.01).

Conclusion:

A minimally invasive TTEPIM protocol with stem cells for treating the ischemic myocardium was established in this study. Transplantation of hiPS-CMTK+ with this method could promote the recovery of the circumferential strain of the ischemic myocardium. The findings of this study lay a foundation for the clinical transformation of this auxiliary means of treatment in the future.
Global, regional, and national lifetime risk of developing and dying from lung cancer in 2022: A population-based study in 185 countries
Authors: Li Meng , Wen Xin , Liang Xin , Liu Mengwen , Zhang Li , Zheng Rongshou
Published: November 2024

Background:

Lifetime cancer risk is an index that indicates the cumulative probability of cancer at some age during a person’s lifetime. Nevertheless, comparative evaluations regarding the probability of developing lung cancer and dying from the disease among diverse populations at the global, regional, and national levels are scarce.

Methods:

Lung cancer data from 185 countries were obtained from GLOBOCAN 2022, and data on any other cause of death were acquired from the United Nations. The lifetime risks of lung cancer development and death were estimated using adjustment for multiple primary cancers (AMP) method. The lung cancer risks in countries or regions worldwide were compared by region and the Human Development Index (HDI).

Results:

The global lifetime risk of developing and dying from lung cancer in 2022 was 3.49% and 2.69%, respectively. The lifetime probabilities of developing lung cancer in countries/areas with low, medium, high, and very high HDIs were 0.33%, 0.95%, 4.72%, and 5.29%, and dying from lung cancer in low, medium, high and very high HDI countries were 0.30%, 0.86%, 3.69% and 3.92%, respectively. After the age of 40 years, the remaining probability of lung cancer development and death decreased with age, leaving a residual risk of 2.00% and 1.71%, respectively, starting at 70 years.

Conclusions:

The probability of developing lung cancer during one’s lifetime is equivalent to 1 in 28 and 1 in 37 people suffering and dying from lung cancer. The age-related risk of developing and dying of lung cancer varies among geographic locations with different HDIs.
Comparison of Traditional and Intensive Cardiac Rehabilitation on Dietary Behavior and Clinical Risk Factor Outcomes
Authors: Rasmussen Ruth A. , Sisson Susan B. , Baldwin Jonathan D. , Hord Norman , Eliot Kathrin , Anderson Leah , Gowin Mary J. , Scott Brook D. , Wortham Darlene
Published: November 2024

Purpose:

The objective of this study was to assess differences in dietary behavior and clinical risk factor outcomes and explore predictors of change among patients participating in traditional and Pritikin intensive cardiac rehabilitation (CR).

Methods:

This secondary analysis of cardiac registry data from 2015 to 2021 included patients participating in traditional CR (n = 420) or Pritikin intensive CR (n = 1005) at a single hospital site. Dietary behavior outcomes included the Rate Your Plate measure, while clinical risk factor outcomes included fasting lipids, blood pressure, anthropometrics, functional outcomes, and psychosocial assessment. Analysis of covariance examined a difference in Rate Your Plate scores between CR groups. Multivariate analysis of covariance was used to determine differences in clinical risk factor variables between CR groups. Predictors of change in dietary behavior and clinical risk factors were determined through multiple bivariate linear regression models within each CR group.

Results:

Both CR programs led to significant improvements though more change was observed among Pritikin intensive CR participants in dietary behavior, anthropometrics, and fasting lipids. Status as a current or recent smoker was not a significant predictor of dietary behavior. Male sex, status as a current or recent smoker, beta-blockers, and angiotensin-converting enzyme inhibitors prescribed were not significant predictors of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or non–high-density lipoprotein cholesterol for traditional and Pritikin intensive CR groups. There were not significant predictors of blood pressure, body mass, or waist circumference.

Conclusion:

Although participation in either CR program yielded cardiometabolic benefits, Pritikin intensive CR patients exhibited significantly greater improvements in dietary behavior and clinical risk factors.
ArtiSential versus conventional laparoscopic colorectal cancer surgery: a multicenter retrospective matched cohort study
Authors: Pyo Dae Hee , Lee Yoon Suk , Min Byung Soh , Lee Jaeim , Kim Chang Hyun , Oh Heung-Kwon , Yoon Yong Sik , Bae Donghwan , Huh Jung Wook
Published: November 2024

Background:

This study aims to compare outcomes of colorectal cancer surgeries performed using the newly developed articulating laparoscopic instrument, ArtiSential, with those using conventional non-articulating or rigid laparoscopic instruments.

Methods:

This multicenter, retrospective, matched cohort study enrolled patients with colorectal cancer undergoing laparoscopic surgery in seven tertiary referral hospitals from January 2021 to October 2022. A 1:1 propensity score matching was performed between the articulating (Arti-LAP) and conventional (Rigid-LAP) laparoscopic groups. The primary outcome was the overall incidence of short-term complications.

Results:

The study initially comprised 694 and 2008 patients in the Arti-LAP and Rigid-LAP groups, respectively. After matching, each group consisted of 694 patients, with no significant differences in baseline clinical characteristics. The mean operation time was 161±32 min in Arti-LAP and 152±25 min in Rigid-LAP groups (P=0.105). Open conversion rates were 0% (0/694) in Arti-LAP and 1.0% (7/694) in Rigid-LAP groups (P=0.024). Overall morbidity rates were 9.5% (66/694) in Arti-LAP and 12.8% (89/694) in Rigid-LAP (P=0.061), with similar rates of severe morbidities. Specimen quality was acceptable in both groups. Multivariable regression analysis showed that the choice of instrument type (articulating or rigid) was not associated with perioperative morbidity. Despite a short median follow-up period of 19.5 months, no significant difference in disease-free survival was observed between the groups.

Conclusion:

Laparoscopic surgery using ArtiSential was performed safely and effectively for patients with colorectal cancer. Articulating laparoscopic instruments may offer an advantage in reducing open conversion rates.
Successful Treatment of Mycoplasma genitalium Urethritis With High-Dose Tinidazole
Authors: Liscynesky Christina , Lipps Ashley , Bazan Jose A.
Published: November 2024

A 30-year-old male patient with symptomatic Mycoplasma genitalium urethritis failed treatment with oral azithromycin, 2-stage doxycycline-moxifloxacin, and minocycline. Molecular testing confirmed the presence of macrolide resistance mutations. Treatment with oral tinidazole 2 g daily for 7 days resulted in clinical and microbiologic cure.
Parametric analysis of 3D printing parameters on stiffness and hysteresis characteristics of pediatric prosthetic foot coupon samples
Authors: Batley Abigail , Glithro Richard , Montalvão Diogo , Dyer Bryce , Sewell Philip
Published: November 2024

Background:

This research paper presents a comprehensive parametric study that investigates the influence of various 3D printing parameters on the mechanical properties of a pediatric prosthetic keel using coupon samples.

Objective:

To analyze how 3D printing parameters impact upon on 2 crucial mechanical properties: stiffness and hysteresis.

Methods:

Key 3D printing parameters including the amount of continuous carbon fiber layers, fiber distribution, and matrix fill pattern, are systematically varied, and mechanically tested through compression to analyze the results.

Results:

The results demonstrate the substantial impact that printing parameters have on the mechanical characteristics of 3D-printed pediatric prosthetic feet. Notably, the selection of these parameters for the prosthetic keel plays a pivotal role in shaping the overall performance and functionality of the prosthetic foot, emphasizing the need for precise parameter optimization in pediatric prosthetic design, if 3D printing is the manufacturing process.

Conclusions:

The findings of this study contribute to a better understanding of the manufacturing process for pediatric prosthetic feet via 3D printing and offer valuable insights for optimizing their design. By identifying the ideal combination of 3D printing parameters that yield the desired stiffness and minimize hysteresis, we aim to enhance the performance and comfort of pediatric prosthetic devices, ultimately improving the quality of life for young users.
Nonselective beta blockade enhances gut microbiome diversity in a rodent model of trauma, hemorrhage, and chronic stress
Authors: Munley Jennifer A. , Kelly Lauren S. , Park Gwoncheol , Pons Erick E. , Apple Camille G. , Kannan Kolenkode B. , Bible Letitia E. , Efron Philip A. , Nagpal Ravinder , Mohr Alicia M.
Published: November 2024

BACKGROUND

Traumatic injury leads to gut dysbiosis with changes in microbiome diversity and conversion toward a “pathobiome” signature characterized by a selective overabundance of pathogenic bacteria. The use of non-selective beta antagonism in trauma patients has been established as a useful adjunct to reduce systemic inflammation. We sought to investigate whether beta-adrenergic blockade following trauma would prevent the conversion of microbiome to a “pathobiome” phenotype.

METHODS

Sprague-Dawley rats (n = 6–8/group) were subjected to routine daily handling (naïve), lung contusion with hemorrhagic shock (LCHS), or LCHS with daily chronic stress (LCHS/CS), each with or without administration of intraperitoneal propranolol (BB) (10 mg/kg/day). Fecal microbiome was measured on Days 0, 7, and 14 using high-throughput 16S rRNA sequencing and QIIME2 bioinformatics analyses. Alpha- and beta-diversity and microbiome composition were assessed with significance defined as *p < 0.05.

RESULTS

Use of propranolol following LCHS or LCHS/CS demonstrated a significant increase in the number of bacterial species (Chao1 index), as well as overall richness and evenness (Shannon index) compared with their untreated counterparts at Day 7. By Day 14, these differences were no longer apparent between BB and untreated groups subjected to LCHS/CS. There was an abundance of commensal bacteria such as Oscillospiraceae and Clostridia in LCHS and LCHS/CS treated with BB after 7 days which persisted at 14 days.

CONCLUSION

These findings suggest a role for beta-antagonism in altering the diversity of the gut microbiome and the need for further studies to elucidate the cellular and molecular mechanisms underlying this intriguing connection of microbiome with trauma and beta-blockade.
Learning-induced remodelling of inhibitory synapses in the motor cortex
Authors: Bhembre Nishita , Paolino Annalisa , Das Sooraj S. , Guntupalli Sumasri , Fenlon Laura R. , Anggono Victor
Published: November 2024

Robust structural and functional plasticity occurs at excitatory synapses in the motor cortex in response to learning. It is well established that local spinogenesis and the subsequent maintenance of newly formed spines are crucial for motor learning. However, despite local synaptic inhibition being essential for shaping excitatory synaptic input, less is known about the structural rearrangement of inhibitory synapses following learning. In this study, we co-expressed the structural marker tdTomato and a mEmerald-tagged intrabody against gephyrin to visualize inhibitory synapses in layer 2/3 cortical neurons of wild-type CD1 mice. We found that a 1-day accelerated rotarod paradigm induced robust motor learning in male and female adult CD1 mice. Histological analyses revealed a significant increase in the surface area of gephyrin puncta in neurons within the motor cortex but not in the somatosensory cortex upon motor learning. Furthermore, this learning-induced reorganization of inhibitory synapses only occurred in dendritic shafts and not in the spines. These data suggest that learning induces experience-dependent remodelling of existing inhibitory synapses to fine-tune intrinsic plasticity and input-specific modulation of excitatory connections in the motor cortex.
Mathematical model of RNA-directed DNA methylation predicts tuning of negative feedback required for stable maintenance
Authors: Dale Renee , Mosher Rebecca
Published: November 2024

RNA-directed DNA methylation (RdDM) is a plant-specific de novo methylation pathway that is responsible for maintenance of asymmetric methylation (CHH, H = A, T or G) in euchromatin. Loci with CHH methylation produce 24 nucleotide (nt) short interfering (si) RNAs. These siRNAs direct additional CHH methylation to the locus, maintaining methylation states through DNA replication. To understand the necessary conditions to produce stable methylation, we developed a stochastic mathematical model of RdDM. The model describes DNA target search by siRNAs derived from CHH methylated loci bound by an Argonaute. Methylation reinforcement occurs either throughout the cell cycle (steady) or immediately following replication (bursty). We compare initial and final methylation distributions to determine simulation conditions that produce stable methylation. We apply this method to the low CHH methylation case. The resulting model predicts that siRNA production must be linearly proportional to methylation levels, that bursty reinforcement is more stable and that slightly higher levels of siRNA production are required for searching DNA, compared to RNA. Unlike CG methylation, which typically exhibits bi-modality with loci having either 100% or 0% methylation, CHH methylation exists across a range. Our model predicts that careful tuning of the negative feedback in the system is required to enable stable maintenance.
Increased threat learning after social isolation in human adolescents
Authors: Towner E. , Thomas K. , Tomova L. , Blakemore S-J.
Published: November 2024

In animal models, social isolation impacts threat responding and threat learning, especially during development. This study examined the effects of acute social isolation on threat learning in human adolescents using an experimental, within-participant design. Participants aged 16–19 years underwent a session of complete isolation and a separate session of isolation with virtual social interactions, counterbalanced between participants, as well as a baseline session. At baseline and following each isolation session, participants reported their psychological state and completed a threat learning task in which self-report ratings and physiological responses to learned threat and safety cues were measured. Threat learning increased after both isolation sessions in two ways. First, participants found the learned threat cue more anxiety-inducing and unpleasant after isolation compared with baseline. Second, during threat extinction, electrodermal activity was partially elevated after isolation compared with baseline. Further, the results suggested that isolation influenced threat learning through state loneliness. Threat learning is central to threat-related disorders including anxiety, phobias, obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD), and our findings suggest that isolation and loneliness in adolescence might increase vulnerability to the emergence of these disorders through increased threat learning.