bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of education debt on PAs' specialty choice or preference
Authors: Kozikowski Andrzej , Bruza-Augatis Mirela , Morton-Rias Dawn , Puckett Kasey , Jeffery Colette , Quella Alicia , Mauldin Sheila , Goodman Joshua
Published: December 2024

Objective:

This study investigated educational debt, repayment strategies, and other factors potentially related to recently certified physician associates/assistants' (PAs') choice or preference for primary care versus all other specialties.

Methods:

A national dataset from 2023 of recently certified PAs was used to conduct quantitative and qualitative analyses. Analyses were conducted separately for PAs who had accepted a clinical position and those who had not accepted a clinical position.

Results:

Overall, 88% of respondents reported having educational debt, with 13.5% owing $200,000 or more. PAs from backgrounds underrepresented in medicine had accrued higher educational debt than their counterparts. Educational debt was significantly associated with specialty choices/preferences: PAs with higher debt were more likely to opt for nonprimary care specialties. Qualitative analyses revealed that PAs rely on different strategies for repaying their loans, depending on whether they choose or prefer primary care or nonprimary care specialties.

Conclusions:

These results suggest that educational debt plays a role in specialty selection, but other factors also are significant.
Aromatherapy with tanxiang prescription for mild to moderate anxiety: a randomized controlled pilot trial
Authors: Fang Yan , Fung Kandace , Xia Ying , Wei Wei , Liu Jiali , Wu Xiaqiu , Zhang Weijun
Published: December 2024

Objective:

To investigate the feasibility and preliminary effectiveness of Tanxiang Prescription (TXP) ointment for alleviating mild to moderate anxiety.

Methods:

A single-center pilot trial was conducted. Participants were randomly assigned to the experimental group or the control group. The experimental group received TXP treatment and health education, while the control group only received health education. The study evaluated the feasibility based on recruitment, retention, adherence, and adverse events. The primary outcome was assessed using the Self-Rating Anxiety Scale (SAS), while the secondary outcomes were evaluated using the Self-Rating Depression Scale (SDS) and Pittsburgh Sleep Quality Index (PSQI). Assessments were conducted at baseline, week 2, and week 4.

Results:

58 participants were successfully enrolled, with 56 in all have finished whole research, which illustrating a recruitment rate of 33.7%, a randomization rate of 100%, and a loss rate of 3.57% in this study. No adverse events were observed. Both the experimental (n=29) and control (n=29) groups showed a significant decrease in SAS, SDS, and PSQI scores in comparison to their baseline scores at week 4 (P<0.05). Additionally, the experimental group showed significantly greater reductions in SAS, SDS, and PSQI scores than those in the control group at week 4 (P<0.05).

Conclusions:

TXP may be a promising treatment option for mild to moderate anxiety, offering a duel benefit of alleviating depression and promoting better sleep without any adverse effects. This study also references the effectiveness of Traditional Chinese Medicine aromatherapy for anxiety management. Further pharmacological and clinical studies are needed to observe the impact of TXP on emotional regulation in patients with anxiety.
Multiphoton Microscopy: A Feasability Study to Explore the Potential Intraoperative Tool for TURBT Diagnosis
Authors: Treacy Patrick-Julien , Durand Matthieu , Dovey Zach S. , Jain Manu , Sfakianos John , Mehrazin Reza , Falagario Ugo Giovanni , Martini Alberto , Wajswol Ethan , Wagaskar Vinayak , Barthe Flora , Chevallier Daniel , Cabal Rafael , Tzavaras Nikos , Thanigasalam Ruban , Leslie Scott , Walz Jochen , Tewari Ashutosh K. , Wiklund Peter
Published: December 2024

Background:

Multiphoton microscopy (MPM) is a nonlinear optical imaging technology, allowing process-free imaging of fresh tissue up to a depth of 0.5 mm, with a combined signal of autofluorescence and second harmonic generation. The absence of bladder muscle in a transurethral resection of bladder tumor (TURBT) increases risk of residual disease, recurrence, and understaging, and an intraoperative assessment of resection depth and margins may avoid unnecessary second TURBTs.

Objective:

The objective of this study was to test the feasibility of MPM in the real-time detection of bladder muscle in cold cup biopsies of patients undergoing TURBT.

Methods:

This was a prospective feasibility study. Cold cup biopsies were taken intraoperatively from the resection bed during TURBT. Tissue was stored in phosphate buffered saline solution combined with fluorescent dyes (orange acridine and rhodamine). MPM imaging of the tissue was performed first, with z stack images of 100 µm maximum depth for 3D imaging. After MPM imaging, tissue was fixed in formalin and sent to the biorepository for standard histopathology. A descriptive analysis was performed between MPM tissue detection and final histopathology results.

Results:

Ten patients were included in this pilot study. Tissue was properly imaged for all patients, although 3 of them had artifacts, and we detected 5 times muscularis propria on MPM imaging. MPM average procedure time from biopsy to formalin fixation (MPM imaging) was 16.2 minutes (12-20 minutes). On final pathology, resection depth was correctly performed for only 4 patients of 10 (resection including bladder muscle). We found an 80% sensitivity on resection depth between first layer identified on MPM and final pathology (8/10 patients) and 100% correlation with final histopathology in specimens for the assessment of detrusor muscle.

Conclusions:

This study supports the use of MPM as a novel intraoperative tool which can evaluate cold cup biopsies during TURBT for resection depth and potentially avoid unnecessary second look procedure.
Integrating Broad Panel Somatic and Germline Testing in Prostate Cancer Care
Authors: Henderson R. Jonathan , Bailey Robert A. , Khilfeh Ibrahim , Reilly Jacqueline , Svoboda Kyra , Waterhouse David
Published: December 2024

Introduction:

Genetic testing, including germline and tumor testing, using broad panel-based approaches has transformed treatment strategies for metastatic prostate cancer. Despite guideline consensus that all men with metastatic prostate cancer should undergo tumor testing to identify mutations, suboptimal testing rates diminish the impact genetic testing can have on diagnosis, prognosis, and treatment decisions. This article outlines the various barriers to clinical adoption and implementation of broad panel genetic testing in the prostate cancer care continuum and opportunities for addressing these challenges.

Methods:

A landscape assessment and literature review were conducted across medical databases as well as oncologic and urologic websites to assess the current guidelines and state of broad panel genetic testing in prostate cancer.

Results:

There are numerous barriers and clinical practice gaps that hinder implementation and integration of broad panel somatic and germline testing in prostate cancer clinical care. Identified areas of concern include patient identification, test ordering considerations, cost and payer coverage, sample collection, genetic education and interpretation of test results, and social inequities. These barriers have prevented guideline concordance and optimal care for patients with prostate cancer.

Conclusions:

Overall outcomes significantly improve for patients whose treatments are tailored to findings from genetic testing. The development of comprehensive care pathways that close clinical care gaps is necessary to ensure the continued optimization of broad panel genetic testing.
Lipid-lowering therapy after acute coronary syndromes: a multinational European survey
Authors: Tsaban Gal , Perez Rafael Vidal , Krychtiuk Konstantin A. , Ahrens Ingo , Halvorsen Sigrun , Hassager Christian , Huber Kurt , Schiele Francois , Sionis Alessandro , Claeys Marc J.
Published: December 2024

Background

Recent guidelines on acute coronary syndromes (ACS) recommend initiating lipid-lowering therapy (LLT) as early as possible to obtain >50% low-density-lipoprotein cholesterol (LDL-c) reduction and an LDL-c < 1.4 mmol/l.

Methods

A multinational European survey study of ACS patients between 2021–2022 and acquired data on LLT and lipid levels on admission and during 1-year posthospitalization. We compared plasma lipid changes and adherence to post-ACS lipid targets across two in-hospital LLT groups: high-intensity statin (HIS) monotherapy (mono-HIS) and a combination of HIS and ezetimibe (combo-HIS).

Results

Of 286 patients, 268 (94%) received in-hospital HIS and were included in the final analysis. Patients (median age: 61.1 years) had a median baseline LDL-c of 3.3 mmol/l. Mono-HIS was the predominant in-hospital LLT (72.4%). In-hospital combo-HIS was administered in 27.6% of the cases. Patients from high-income countries (n = 141) were more likely to receive in-hospital combo-HIS than patients from middle-income countries [n = 127; 38.3% vs. 15.7% patients, P < 0.001). One-year post-ACS, 50 (26.5%) patients from the mono-HIS group received ezetimibe. The target of LDL-c ≤ 55 mg/dl was reached in 85 patients (31.7%), without significant difference between study groups [mono-HIS: 56 (28.9%) and combo-HIS: 29 (39.2%) patients, P = 0.10]. The target of >50% reduction was achieved more frequently among the combo-HIS group than in the mono-HIS group (50.0% vs. 29.9%, respectively, P = 0.002).

Conclusion

LDL-c targets were achieved in less than half of the patients post-ACS, regardless of the LLT regimen. Combo-HIS was initiated in-hospital post-ACS in only 28% and was associated with greater LDL-c reduction compared to a staged approach of mono-HIS with up-titration at follow-up.
Exploring the value and optimizing strategies of CA125, CA199, CEA, AFP, and PT in predicting adenomatous gastrointestinal polyps in elderly male patients
Authors: Zhou Jun , Li Qizhi , Rao Cheng
Published: December 2024

This study explores the application of serum biomarkers in the diagnosis of adenomatous polyps and evaluates the effectiveness of different markers and their combined diagnosis in adenomatous polyp detection. Using receiver operating characteristic curve analysis, this study assessed the efficacy of serum biomarkers such as carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), alpha-fetoprotein (AFP), carbohydrate antigen 199 (CA199), and prothrombin time (PT) in diagnosing adenomatous polyps in 90 patients. The study also compared the diagnostic accuracy of individual tests versus combined diagnostic approaches and analyzed the impact of polyp size and number on the levels of these markers. Among the individual tests, CA125 showed relatively high diagnostic efficacy. However, combined diagnostic approaches, such as the combination of CEA and CA125, the trio of CEA, CA125, and AFP, and the quartet of CEA, CA125, AFP, and PT, significantly improved diagnostic sensitivity and specificity. Additionally, the study found that the size and number of adenomatous polyps significantly influenced the levels of CEA, CA125, CA199, and PT, with larger and more numerous polyps associated with higher marker levels. This study demonstrates that combined diagnostic strategies have significant advantages in diagnosing adenomatous polyps, providing more accurate and comprehensive diagnostic information. Furthermore, the impact of polyp size and number on serum biomarker levels suggests that these clinical factors should be considered in clinical assessments. These findings offer new perspectives and approaches for the diagnosis of adenomatous polyps.
Navigating Nurse Wellness in Rural America
Authors: Robinson Karen R. , Gierach Michelle , Gramlick-Mueller Abigail , Smith Emily , Hickman Deborah , Holland Jordyn , Stow Martha , Tverstol Heather , Bartelt Samantha , McDaniel Becky , Wiik Jennifer , Ferguson Anna Kay
Published: December 2024

OBJECTIVE

The aim of this study's phase 1 was to determine the current wellness levels of RNs in rural America settings, including barriers to maintain and recommendations for wellness.

BACKGROUND

Nurses are experiencing more anxiety and burnout currently than prepandemic. A review of literature revealed a gap in describing nurses' wellness and strategies to maintain wellness in rural American healthcare settings.

METHODS

The Integrative Health and Wellness Assessment (IHWA) V2 2022 holistically measured participants' wellness. The survey was deployed in 2023 to 6989 clinical nurses, nurse leaders, and advanced practice nurses.

RESULTS

The IHWA V2 2022 mean was 134.72. Significant findings included age, years of experience, and role. Barriers of insufficient time, work environment, and family responsibilities were identified. Recommendations involved the work environment, stress management, and healthy boundaries with suggestions to implement in rural settings.

CONCLUSION

Study findings can assist leaders to implement interventions that positively impact nurse wellness in rural settings. Interventions promoting wellness are essential for nurses to meet these same needs of their patients.
Efficacy and safety of a patent hemostatic device (PHD) with quantitative pressure for radial artery hemostasis: a first-in-human feasibility study
Authors: Tao Zhenhui , Wang Xiuying , Xu Sha , Zhuang Nanhui , Gao Lingling , Zheng Yimei , Cao Lijia , Zheng Bo
Published: December 2024

Objectives:

Hemostatic devices are commonly used after coronary angiography (CAG) or percutaneous coronary intervention (PCI) via the transradial approach. However, radial artery occlusion (RAO) and bleeding still occur due to uncertainties regarding the hemostatic pressure. The aim of this study is to evaluate the safety and feasibility of a patent hemostatic device (PHD) with individualized hemostatic pressure settings to mitigate the risks of RAO and bleeding.

Methods:

A single-center, prospective, feasibility study was conducted in patients undergoing CAG/PCI. Adults recruited from Peking University First Hospital received the PHD. RAO, bleeding, hematoma, compression time, self-reported syndromes (pain, numbness, and swelling), and other access complications were measured.

Results:

PHD was attempted in 11 participants with a mean age of 59.0±10.8 years, of whom 90.9% were male. The average hemostatic pressure after CAG/PCI was 141.8±19.5 mm Hg with a compression time of 210.0±72.3 minutes. None of the participants exhibited RAO. Three participants had errhysis, and one participant suffered minor bleeding. In total, 72.7% (8 of 11) participants achieved successful hemostasis within 3 hours. No moderate or severe pain, numbness, or swelling were observed.

Conclusions:

This study shows the feasibility of the novel PHD for radial hemostasis in a small cohort of patients. Considering the potential benefits, particularly the prevention of RAO, a larger sample size is needed to evaluate the long-term safety and efficacy of the PHD.
Managing Low-Velocity Mandibular Gunshot Wounds: An Institutional Review and the “FLOSS” Severity Scoring System
Authors: Bourn Lynn , Slovacek Cedar , Lu Nathan , Pocha Ciri C. , Wilbert Hance , Chen Collin , Bernstein Michael , Chen Kevin
Published: December 2024

Objective:

Management of mandibular ballistic trauma is poorly delineated, given the variable injury complexity. This study examines surgical outcomes and presents a novel scoring system to define and guide the management of low-velocity ballistic mandibular fractures.

Methods:

A retrospective chart review was performed from 2015 to 2022 to collect data on patients who suffered ballistic mandibular fractures. Computerized tomography facial bone scans were analyzed to determine a mandible severity scoring based on the following “F.L.OS.S.” variables: fracture description (F), location of fracture (L), other surrounding fractures (OS), and soft tissue involvement (S).

Results:

Sixty-six patients suffered handgun-related mandibular fractures and 54 underwent surgical intervention. The mean FLOSS score was 7.9 for all surgical patients and significantly differed between treatment groups (P = 0.011). Certain injury-specific variables were significantly associated with higher FLOSS scores including >2 areas of comminution along load bearing, bony gap >10 mm, or intraoral involvement with soft tissue avulsion; however, the degree of displacement, bilateral involvement, or presence of concomitant fractures did not predict higher scores. The types of complications did not significantly vary for total FLOSS score or FLOSS subcategories; the only exception being, an association between bony gap (>10 mm) and hardware exposure (P = 0.045). Overall surgical complication rate was 26.9% and presence significantly varied between surgical treatments (P = 0.019); specifically, nonunion was the only significant subcategory (P = 0.030).

Conclusion:

The FLOSS scoring system may be a useful adjunct in defining fracture characteristics that guide appropriate surgical intervention for low-velocity ballistic mandibular injuries.
Electroacupuncture alleviates cerebral ischemia injury by regulating PI3K/AKT/NF-κB signaling in microglia of ischemic stroke rats
Authors: Rao Rao , Gan Lingling , Zhao Rui , Han Yongsheng
Published: December 2024

This study aimed to investigate the potential of electroacupuncture as an intervention for inducing ‘Awakening and Opening of the Brain’ in rats with stroke models induced by middle cerebral artery occlusion/reperfusion (MCAO/R). The efficacy of electroacupuncture in alleviating cerebral ischemic injury was evaluated using Longa scores, triphenyl tetrazolium chloride staining, and hematoxylin and eosin staining. Non-targeted metabolomics analysis was conducted to identify differential metabolite changes before and after electroacupuncture treatment in MCAO/R rats. Network pharmacology analysis was then performed to correlate these differential metabolites with ischemic stroke. The PI3K/AKT/NF-κB signaling pathway was identified as a key target. In vivo experiments further validated the mechanism by which electroacupuncture promotes M2 microglial polarization through inhibition of the PI3K/AKT/NF-κB signaling in MCAO/R rats. This study demonstrated that electroacupuncture reduces brain damage and inhibits inflammation in MCAO/R rats by modulating the PI3K/AKT/NF-κB signaling pathway and promoting the polarization of microglia from M1 to M2.
The influence of music elements on the understanding of emotional musical meaning: based on the perspective of interval structure
Authors: Liu Tiantian , Liu Shuyi , Ling Zirui , Liu Songhan , Fang Lele
Published: December 2024

Music has become an indispensable part of people’s lives, frequently encountered in various contexts of daily living. Understanding the emotional significance of music is a crucial foundation for its use. This study employed the cross-modal affective priming paradigm, combined with event-related potential technology to investigate the influence of music elements on the emotional musical meaning from the perspective of interval structure. Two different forms of musical intervals (melodic interval and harmonic interval) and intervals with different varying degrees of consonance were used as priming stimuli and emotional words as target stimuli. The research results found that, compared to melodic intervals, participants responded faster and with higher accuracy under the harmonic interval condition, which also elicited a larger N400 component. Furthermore, the N400 amplitudes were smaller in four conditions compared to the dissonant-positive and consonant-positive conditions, and the consonant-negative condition elicited a significantly larger N400 amplitude than the dissonant-negative and partially consonant-negative conditions. This finding suggest that both interval type and consonance level influence emotional musical meaning, and interval structure plays a critical role in the understanding of emotional musical meaning.
Platelet Count Normalization Following Romosozumab Treatment for Osteoporosis in Patient with Immune Thrombocytopenic Purpura: A Case Report and Literature Review
Authors: Sung Kyunghun , Ha Jeonghoon
Published: December 2024

Romosozumab, which is approved for the treatment of osteoporosis, has a dual-action mechanism that promotes bone formation and inhibits bone resorption. However, its association with an increased risk of major adverse cardiovascular events, as highlighted in the ARCH I study, raises concerns. The underlying pathophysiological mechanisms, possibly involving changes in platelet dynamics, are yet to be fully elucidated. Herein, we present a case of a 60-year-old Korean woman diagnosed with immune thrombocytopenic purpura and new-onset osteoporosis, who was treated with romosozumab. Subsequent to the administration of romosozumab, there was a notable elevation in her platelet count. This observation warrants further investigation into the off-target effects of romosozumab, especially its impact on hematopoietic stem cell function and platelet dynamics. This case accentuates the imperative for more comprehensive research into the systemic effects of romosozumab, particularly its involvement in hematopoiesis and cardiovascular risk, to thoroughly understand its extensive implications for patient health.
Hyaluronic Acid and Emergent Tissue Mechanics Orchestrate Digit Tip Regeneration
Authors: Mui Byron W.H. , Wong Joseph Y. , Bray Toni , Connolly Lauren , Wang Jia Hua , Winkel Alexander , Robey Pamela G. , Franze Kristian , Chalut Kevin J. , Storer Mekayla A.
Published: December 2024

Tissue regeneration is a dynamic process requiring coordinated cell fate decisions to restore structure and function. For instance, the tips of human and rodent digits fully regrow after amputation, although more proximal injuries fail to regenerate. While biochemical cues have been widely studied in wound healing, the role of the physical microenvironment remains less understood. Here, we discovered that tissue mechanics and extracellular matrix (ECM) composition differ markedly between non-regenerating and regenerating wounds. These differences are due to specific fibroblast sub-types which predominate in the non-regenerating wound and form fibrotic collagen networks. Conversely, bone-forming progenitors in regenerating digits synthesize abundant hyaluronic acid, which mediates collagen fibrillogenesis. By modeling the tissue mechanics of non-regenerative and regenerative wounds using hydrogels, we showed that substrate stiffness regulates the synthesis of fibrotic and regenerative ECM. We further revealed that mimicking the regenerative wound mechanics upregulated bone morphogenic protein signaling and osteogenic differentiation. We ultimately demonstrated that the link protein HAPLN1 promotes hyaluronic acid depositionin vivo, reduces scar formation, and induces bone repair after non-regenerative amputations. These findings emphasize the interplay among the ECM, tissue mechanics, and cell behavior in digit regeneration and point towards ECM modulation as a strategy to improve wound healing.

Highlights

Non-regenerating and regenerating digit tips diverge in their cellular and ECM composition

Regeneration requires hyaluronic acid matrix, which mediates collagen assembly and tissue mechanics

Soft substrates enhance BMP signaling and propagate the synthesis of regenerative ECM

HAPLN1 overexpression initiates rescue of non-regenerative digit tip amputations
No evidence that proteome composition is associated with realised thermal limit and dietary niche breadth in butterflies
Authors: Caron Fernanda S. , Pietras Zuzanna , Eddine-Lomas Arkan , von Hellfeld Rebecca , Morimoto Juliano
Published: December 2024

Amino acids are the building blocks of proteins that perform essential physiological functions. Theory suggests that the proteome composition, the amino acid frequencies across all proteins in a genome, is associated with an organism’s optimal growth temperature, offering insights into species’ temperature limits. However, this hypothesis, based on prokaryotes, has not been tested in complex multicellular eukaryotes where many amino acids are strictly acquired through diet. Here, we analysed amino acid frequencies in the proteomes of orthologous and non-orthologous genes from 35 butterfly species to test for correlations with maximum observed temperatures and diet breadth. Using a comparative approach, we found no evidence that proteome composition correlates with temperature or diet breadth. Our findings suggest that animal proteome composition is likely shaped more strongly by energetic and biophysical constraints rather than by ecological factors.
Identification of disease-specific vulnerability states at the single-cell level
Authors: D’Antuono Matthew , Sharp Madison , Chowdary Rishika , Ivan Michael E. , Komotar Ricardo J. , Suter Robert K. , Ayad Nagi G.
Published: December 2024

Extensive intratumor heterogeneity in glioblastoma (GBM) impedes successful treatment and complicates drug discovery as it is not obvious which cells a tumor is most dependent on. Here, we posit that single-cell-resolution transcriptomic data can be integrated with loss-of-function screens to identify the most critical cells to target within a tumor. We parsed CRISPR screen data from the Dependency Map (DepMap) Consortium and identified a GBM Dependency Signature (GDS) − 168 genes that are essential for GBM cell viabilityin vitro. Through similarity scoring of GDS transcriptomic profiles in single-cell RNA-sequencing (scRNA-seq) data and iterative hierarchical clustering, we identify and report here 3 single-cell vulnerability states (VS) characterized in 49 GBM tumors using both scRNA-seq and spatial transcriptomic data. These VS reflect single-cell gene dependencies and differ significantly in enrichment profiles and spatial distributions. Importantly, the proportion of VS in each GBM tumor is variable, suggesting a means of stratifying patients in clinical trials. Collectively, we have developed a novel computational pipeline to identify unique vulnerability states in GBM and other cancers, which can be used to identify existing or novel drugs for incurable diseases.
Integrative analysis of transcriptome and metabolism reveals functional roles of redox homeostasis in low light and salt combined stress inLeymus chinensis
Authors: Li Jikai , Fang Suyang , Zhang Hailing , Iqbal Zubair , Shang Chen , Han Weibo , Huang Kai , Meng Xiangshen , Dai Muyuan , Lu Zhiheng , Guo Bingnan , Qu Mingnan
Published: December 2024

Soil salinity (Salt) is one of the major limiting factors ofLeymus chinensis(named sheepgrass) performance and alters their primary metabolic process and gene expression. Salt stress could accelerate inhibitive effects concomitant with low light (LL-Salt). However, little is known about physiological and molecular mechanisms under such LL-Salt in sheepgrass. This study aims to uncover the key reprogrammed metabolic pathways induced by LL-Salt through an integrated analysis of transcriptome and metabolism. Plant seedlings were exposed to six combinations of light intensity (moderate light, ML, and LL) and NaCl concentrations (0, 50, and 200mM) for 20 days. Results suggest that the growth of sheepgrass seedlings was dramatically inhibited with severe lodging phenotype, especially when exposed to LL-Salt combined conditions. Activities of an antioxidant enzyme, catalase, were significantly increased in LL but significantly decreased in salt stress, leading to a reverse pattern for H2O2 in LL and salt stress. Transcriptome analysis reveals 4921 downregulated differentially expressed genes (DEGs) with carbon metabolism pathways were significantly enriched compared to light response without salt (ML_0 vs LL_0). There are 194 overlapped downregulated DEGs induced by two salt treatments (ML_50 vs ML_0 and ML_200 vs ML_0), where the carbon metabolism pathway was also significantly enriched. In terms of interactive effects of LL-Salt treatments, we found that there are 16 overlapped DEGs, including a phytochrome-interacting transcription factor 4 (PIF4) with upregulation in LL treatment while downregulation in salt treatment, which was validated by qPCR. Metabolism analysis confirmed that in carbon metabolism, the contents of seven differentially abundant metabolites (DAMs), including sucrose, were all downregulated in both LL and salt treatment. In contrast, serine and glycolate in the photorespiration pathway were downregulated in LL while upregulated in salt treatment. A photorespiration regulatory gene, glycolate oxidase expression, was confirmed by qPCR. Collectively, we found that serval antioxidant redox pathways, including photorespiration, GSG/GSSH redox, and ABA signaling, participated in response to LL and salt combined events and highlighted the roles of cellular redox homeostasis in LL-Salt response in sheepgrass.
Development and optimization of human deuterium MRSI at 3 T in the abdomen: feasibility in renal tumors following oral heavy water administration
Authors: McLean Mary A , Menih Ines Horvat , Wodtke Pascal , Kaggie Joshua D , Birchall Jonathan R , Schulte Rolf F , Grimmer Ashley , Latimer Elizabeth , Wylot Marta , Zamora Morales Maria J , Khan Alixander S , Wang Huanjun , Armitage James , Mitchell Thomas J , Stewart Grant D , Gallagher Ferdia A
Published: December 2024

Purpose

To establish and optimize abdominal deuterium MRSI in conjunction with orally administered2H-labelled molecules.

Methods

A flexible transmit-receive surface coil was used to image naturally abundant deuterium signal in phantoms and healthy volunteers and after orally administered2H2O in a patient with a benign renal tumor (oncocytoma).

Results

Water and lipid peaks were fitted with high confidence from both unlocalized spectra and from voxels within the liver, kidney, and spleen on spectroscopic imaging. Artifacts were minimal despite the high2H2O concentration in the stomach immediately after ingestion, which can be problematic with the use of a volume coil.

Conclusion

We have shown the feasibility of abdominal deuterium MRSI at 3 T using a flexible surface coil. Water measurements were obtained in healthy volunteers and images were acquired in a patient with a renal tumor after drinking2H2O. The limited depth penetration of the surface coil may have advantages in characterizing early uptake of orally administered agents in abdominal organs despite the high concentrations in the stomach which can pose challenges with other coil combinations.
Deep Chest: an artificial intelligence model for multi-disease diagnosis by chest x-rays
Authors: Bozcuk Hakan Şat , Artaç Mehmet , Uğrakli Muzaffer , Poyraz Necdet
Published: December 2024

Background

Artificial intelligence is increasingly being used for analyzing image data in medicine.

Objectives

We aimed to develop a computer vision artificial intelligence (AI) application using limited training material to aid in the multi-label, multi-disease diagnosis of chest X-rays.

Methods

We trained an EfficientNetB0 pre-trained model, leveraging transfer learning and deep learning techniques. Six thoracic disease categories were defined, and the model was initially trained on images sourced online and chest X-rays from a hospital database for training and internal validation. Subsequently, the model underwent external validation.

Results

In constructing and validating Deep Chest, we utilized 453 images, achieving an area under curve (AUC) of 0.98, sensitivity of 0.98, specificity of 0.80, and accuracy of 0.83. Notably, for diagnosing masses or nodules, the sensitivity, specificity, and accuracy were 0.97, 0.81, and 0.83, respectively. We deployed Deep Chest as a free experimental web application.

Conclusions

This tool demonstrated high accuracy in diagnosing both single and coexisting pulmonary pathologies, including pulmonary masses or nodules. Deep Chest thus represents a promising AI-based solution for enhancing diagnostic capabilities in thoracic radiology, with the potential to be utilized across various medical disciplines, especially in scenarios where expert support is limited.
Accurate diagnosis of high-risk pulmonary nodules using a non-invasive epigenetic biomarker test
Authors: Chen Pei-Hsing , Tsai Tung-Ming , Lu Tzu-Pin , Lu Hsiao-Hung , Pamart Dorian F. , Kotronoulas Aristotelis , Herzog Marielle , Micallef Jacob V. , Hsu Hsao-Hsun , Chen Jin-Shing
Published: December 2024

Background

Accurate non-invasive tests to improve the early detection and diagnosis of lung cancer are urgently needed, given that large tumors may metastasize or be resistant to treatment. However, no regulatory-approved blood tests are available for the early detection of lung cancer. We aimed to improve the classification of pulmonary nodules to identify malignant ones in a high-prevalence patient group.

Methods

A study involving 806 participants with undiagnosed nodules larger than 5 mm, identified via CT imaging, focused on assessing nucleosome levels and histone modifications in circulating blood. Nodules were classified as malignant or benign. A logistic regression analysis was performed. For model development, the data were randomly divided into training (n = 483) and validation (n = 121) datasets. The model’s performance was then evaluated using a separate testing dataset (n = 202).

Results

Among patients, 755 (93.7%) had a tissue diagnosis. The overall malignancy rate in the cohort was 80.4%. For all datasets, the AUCs were as follows: training, 0.74; validation, 0.86; and test, 0.79 (accuracy range: 0.80–0.88). Sensitivity showed consistent results across all datasets (0.91, 0.95, and 0.93, respectively), whereas specificity ranged from 0.37 to 0.64. For smaller nodules (5–10 mm), the model recorded accuracy values of 0.76, 0.88, and 0.85. Sensitivity values of 0.91, 1.00, and 0.94 further highlight the robust diagnostic capability of the model. The performance of the model across the RADS categories was evaluated, and it demonstrated consistent accuracy.

Conclusion

Our EB panel detected non-small cell lung cancer early in a high-risk patient group with high sensitivity and accuracy. The EB model was particularly effective in identifying high-risk lung nodules, including small, part-solid, and non-solid nodules, and provided further evidence for external validation.

Synopsis

An epigenetic biomarker (EB) model demonstrated high sensitivity and accuracy for early lung cancer detection in 806 patients with pulmonary nodules. It performed well across imaging types and stages, including small nodules, reducing false negatives in minimally invasive surgery.
Social determinants of cognitive aging trajectories across 39 countries
Authors: Gilles Victor , Salouhou Syrine , Vallée Rémi , Spiers Hugo , Hornberger Michael , Garnier-Crussard Antoine , Coutrot Antoine
Published: December 2024

Distinguishing between normal and pathological cognitive aging is challenging because there is no typical older person. Some people in their eighties have cognitive abilities similar to many 30-year-olds, while others experience significant cognitive decline at a much younger age. The variation in age-related cognitive decline is not arbitrary. Several non-modifiable (e.g. genetic) and potentially modifiable (e.g. high blood pressure, smoking, and hearing loss) risk factors are associated with faster cognitive aging. Beyond these individual-level risk factors, a growing body of evidence has identified associations between cognitive impairment and social, economic, and environmental factors. These associations are even more pronounced in developing countries, notably because of greater disparities in education and socioeconomic status. However, people from these countries are rarely studied in scientific research: a citizen of a high-income country is 37 times more likely to appear in a study in top medical journals than a citizen of a low-income country. Here, we examine the association between sociodemographic factors and cognitive aging trajectories among 715,295 participants in 46 countries. Cognition is assessed using Sea Hero Quest, a spatial navigation video game that predicts spatial ability in the real world. We find that the social, economic, and environmental well-being of older adults, as measured by the Global AgeWatch Index (GAWI), is negatively associated with age-related decline in spatial ability. In particular, the GAWI Health and Environment subscores are strongly correlated with the effect of age on wayfinding performance. We also found that gender differences in spatial navigation skills increase with age, and even more so in countries with greater gender inequality, as estimated by the Gender Inequality Index. Our results show that cognitive aging must be understood as a dynamic, heterogeneous process that is strongly linked to potentially modifiable environmental and social factors.
ARID1A-induced transcriptional reprogramming rewires signalling responses to drug treatment in melanoma
Authors: Barker Charlie George , Sharma Sumana , Santos Ana Mafalda , Nikolakopoulos Konstantinos-Stylianos , Velentzas Athanassios D. , Völlmy Franziska I. , Minia Angeliki , Pliaka Vicky , Altelaar Maarten , Wright Gavin J , Alexopoulos Leonidas G. , Stravopodis Dimitrios J. , Petsalaki Evangelia
Published: December 2024

Resistance to BRAF and MAPK inhibitors is a significant challenge in melanoma treatment, driven by adaptive and acquired mechanisms that allow tumour cells to evade therapy. Here, we examined early signalling responses to single and combined BRAF and MAPK inhibition in a BRAFV600E, drug-sensitive melanoma cell line and a drug-resistant ARID1A-knockout (KO) derivative. ARID1A, frequently mutated in melanoma, is associated with resistance and immune evasion. Using an innovative systems biology approach that integrates transcriptomics, proteomics, phosphoproteomics, and functional kinomics through matrix factorization and network analysis, we identified key signalling alterations and resistance mechanisms.

We found that ARID1A-KO cells exhibited transcriptional rewiring, sustaining MAPK1/3 and JNK activity post-treatment, bypassing feedback sensitivity observed in parental cells. This rewiring suppressed PRKD1 activation, increased JUN activity—a central resistance network node—and disrupted PKC dynamics through elevated basal RTKs (e.g., EGFR, ROS1) and Ephrin receptor activity post-treatment. ARID1A mutations also reduced HLA-related protein expression and enriched extracellular matrix components, potentially limiting immune infiltration and reducing immunotherapy efficacy. Our graph-theoretical multi-omics approach uncovered novel resistance-associated signalling pathways, identifying PRKD1, JUN, and NCK1 as critical nodes. While receptor activation redundancies complicate single-target therapies, they also present opportunities for combination strategies.

This study highlights ARID1A’s role in reshaping signalling and immune interactions, offering new insights into melanoma resistance mechanisms. By identifying actionable targets, including JUN and immune pathways, we provide a foundation for developing integrated therapeutic strategies to overcome resistance in BRAF/MAPK inhibitor-treated melanoma.

One sentence summary

This study reveals how ARID1A-mediated transcriptional rewiring drives resistance to MAPK inhibitors in melanoma by altering signalling pathways, immune interactions, and receptor dynamics, highlighting potential targets for combinatorial therapies.
CCR1 inhibition sensitizes multiple myeloma cells to glucocorticoid therapy
Authors: Luyckx Bert , Van Trimpont Maaike , Declerck Fien , Staessens Eleni , Verhee Annick , T’Sas Sara , Eyckerman Sven , Offner Fritz , Van Vlierberghe Pieter , Goossens Steven , Clarisse Dorien , De Bosscher Karolien
Published: December 2024

Glucocorticoids (GC) are cornerstone drugs in the treatment of multiple myeloma (MM). Because MM cells exploit the bone marrow microenvironment to obtain growth and survival signals, resistance to glucocorticoid-induced apoptosis emerges, yet the underlying mechanisms remain poorly characterized. Here, we identify that the chemokine receptor CCR1, together with its main ligand CCL3, plays a pivotal role in reducing the glucocorticoid sensitivity of MM cells. We show that blocking CCR1 signaling with the antagonist BX471 enhances the anti-MM effects of the glucocorticoid dexamethasone in MM cell lines, primary patient material and a myeloma xenograft mouse model. Mechanistically, the drug combination shifts the balance between pro- and antiapoptotic proteins towards apoptosis and deregulates lysosomal proteins. Our findings suggest that CCR1 may play a role in glucocorticoid resistance, as the GC-induced downregulation of CCR1 mRNA and protein is blunted in a GC-resistance onset model. Moreover, we demonstrate that inhibiting CCR1 partially reverses this resistance, providing a promising strategy for resensitizing MM cells to GC treatment.
From calamity to infestation: linking windstorm tree damage to bark beetle outbreak through forest structure and meteorological analysis
Authors: Torresani Michele , Tognetti Roberto
Published: December 2024

In recent years, we have witnessed worldwide, an increase in natural forest disturbances, particularly windstorms, which have caused significant direct and indirect forest damages, often triggering largescale bark beetle outbreaks. In this study, we investigated the interaction between windstorm-induced tree damage and subsequent bark beetle outbreaks in the northeastern Italian Alps (Province of Belluno and Bolzano), focusing on the 2018 Vaia windstorm and the successive bark beetle infestation started in 2021. Additionally, we aimed to determine whether this potential correlation is influenced by forest structural characteristics such as forest height heterogeneity (HH), forest density, and forest mean height using LiDAR data, or by meteorological factors (mean temperature and cumulative precipitation) through in-situ spatialized information.

Our research findings, based on a methodology centered on spatial interactions, indicate a potential link between the bark beetle outbreaks and the windstorm event Vaia occurred three years before. Our results suggest that forest structural variables are, in most of the cases, significantly similar across all areas affected by the bark beetle. This similarity is observed both in forests impacted by the Vaia windstorm and in otherPicea abiesforests not affected by the windstorm, indicating that these forest structural variables may not be a trigger for the bark beetle outbreak. Our findings do not show a clear and consistently significant difference in meteorological conditions. This variability can be attributed to the specific areas affected by the Vaia windstorm, which are predominantly mountainous regions characterized by distinct temperatures and precipitation compared to the rest of the provinces. When analyzing the combined influence of structural and meteorological variables in both study areas, our results indicate that none of these factors were ultimately significant predictors of the interaction between bark beetle infestations and areas affected by the Vaia windstorm. Our study suggests that, as climate change increases the frequency and severity of these disturbances, adaptable forest management framework to enhance forest resilience and sustainability are needed, helping forests to better withstand and recover from future natural disturbances.
A Comparative Study of Muscular, Vestibular, and Haptic Stimulation on Dream Incorporation
Authors: Peters Emma , Pöhlmann Jakob , Wang Xinlin , Dresler Martin , Erlacher Daniel
Published: December 2024

The connection between the dreamed body and the real physical body remains a subject of ongoing investigation. This study explored how the dreamed body responds to somatosensory stimulation of the physical body, aiming to shed light on the sensory processes that shape our dreaming experiences. We employed a novel within-subject design to compare the incorporation of three different types of bodily stimuli—electrical muscular, galvanic vestibular, and haptic vibration—into dream content, alongside a control sham condition for each stimulus. In total, 24 participants spent one adaptation night, followed by three consecutive test nights in the sleep laboratory. REM awakenings, after sham or stimulation periods, were carried out for dream report collection. In total, 165 dream reports were collected across conditions. While dream incorporation was observed across the three stimulation methods, it occurred equally in both the stimulation and sham conditions for all three modalities. These findings highlight broader methodological challenges in dream incorporation research and raise concerns about potential confounding factors affecting the interpretation of results. Future research with larger sample sizes is needed to detect smaller effect sizes and fully understand the influence of these somatosensory stimuli on dream content. This study employed a rigorous experimental approach to exploring dream incorporation and addressed many methodological challenges in this area. We further suggest areas of improvement to optimize dream incorporation of different sensory modalities.

Graphical Abstract
Structural and evolutionary features of red algal UV sex chromosomes
Authors: Lipinska Agnieszka P , Cossard Guillaume , Epperlein Paul , Woertwein Tobias , Molenier Cecile , Godfroy Olivier , Carli Sabrina , Ayres Ligia , Lavaut Emma , Marchi Fabiana , Mauger Stephane , Destombe Christophe , Oliveira Mariana C , Plastino Estela , Krueger-Hadfield Stacy , Guillemin Marie-Laure , Valero Myriam , Coelho Susana M
Published: December 2024

Background: Sex chromosomes in red algae have remained relatively understudied, despite their fundamental role in understanding the evolution of sex determination across eukaryotes. In this study, we investigate the structure, gene composition, and evolutionary history of the U and V sex chromosomes in four Gracilaria species, which diverged approximately 100 million years ago (MYA). Results: Our findings reveal that UV sex chromosomes, previously identified in green and brown algae as well as bryophytes, have also evolved in red algae, contributing to the diversity of sex determination systems across eukaryotes. The shared orthology of conserved sex-determining region (SDR) genes between Gracilaria and distantly related red algae suggests that this system may have originated approximately 390 MYA, making it one of the oldest known sex chromosome systems. The SDR in Gracilaria is relatively small but contains conserved gametologs and V-specific genes involved in transcriptional regulation and signaling, suggesting their essential role in sexual differentiation. Unlike the conserved V-specific genes, U-specific genes appear absent, pointing to a dominant role of the V chromosome in sex determination. The evolution of Gracilaria sex chromosomes involved recombination suppression, gene relocations, duplications, and potential gene loss. Despite their ancient origin, the sex chromosomes show low levels of degeneration, likely due to haploid purifying selection during the gametophytic phase of the life cycle. Conclusion: This study provides the first detailed characterization of the U and V sex chromosomes in red algae, preparing the ground for future studies on reproductive life cycles and speciation in this understudied group of eukaryotes.