bluuebunny/crossref_metadata_2025 huggingface dataset:
A dataset and benchmark for hospital course summarization with adapted large language models
Authors: Aali Asad , Van Veen Dave , Arefeen Yamin Ishraq , Hom Jason , Bluethgen Christian , Reis Eduardo Pontes , Gatidis Sergios , Clifford Namuun , Daws Joseph , Tehrani Arash S , Kim Jangwon , Chaudhari Akshay S
Published: December 2024

Objective

Brief hospital course (BHC) summaries are clinical documents that summarize a patient’s hospital stay. While large language models (LLMs) depict remarkable capabilities in automating real-world tasks, their capabilities for healthcare applications such as synthesizing BHCs from clinical notes have not been shown. We introduce a novel preprocessed dataset, the MIMIC-IV-BHC, encapsulating clinical note and BHC pairs to adapt LLMs for BHC synthesis. Furthermore, we introduce a benchmark of the summarization performance of 2 general-purpose LLMs and 3 healthcare-adapted LLMs.

Materials and Methods

Using clinical notes as input, we apply prompting-based (using in-context learning) and fine-tuning-based adaptation strategies to 3 open-source LLMs (Clinical-T5-Large, Llama2-13B, and FLAN-UL2) and 2 proprietary LLMs (Generative Pre-trained Transformer [GPT]-3.5 and GPT-4). We evaluate these LLMs across multiple context-length inputs using natural language similarity metrics. We further conduct a clinical study with 5 clinicians, comparing clinician-written and LLM-generated BHCs across 30 samples, focusing on their potential to enhance clinical decision-making through improved summary quality. We compare reader preferences for the original and LLM-generated summary using Wilcoxon signed-rank tests. We further request optional qualitative feedback from clinicians to gain deeper insights into their preferences, and we present the frequency of common themes arising from these comments.

Results

The Llama2-13B fine-tuned LLM outperforms other domain-adapted models given quantitative evaluation metrics of Bilingual Evaluation Understudy (BLEU) and Bidirectional Encoder Representations from Transformers (BERT)-Score. GPT-4 with in-context learning shows more robustness to increasing context lengths of clinical note inputs than fine-tuned Llama2-13B. Despite comparable quantitative metrics, the reader study depicts a significant preference for summaries generated by GPT-4 with in-context learning compared to both Llama2-13B fine-tuned summaries and the original summaries (P<.001), highlighting the need for qualitative clinical evaluation.

Discussion and Conclusion

We release a foundational clinically relevant dataset, the MIMIC-IV-BHC, and present an open-source benchmark of LLM performance in BHC synthesis from clinical notes. We observe high-quality summarization performance for both in-context proprietary and fine-tuned open-source LLMs using both quantitative metrics and a qualitative clinical reader study. Our research effectively integrates elements from the data assimilation pipeline: our methods use (1) clinical data sources to integrate, (2) data translation, and (3) knowledge creation, while our evaluation strategy paves the way for (4) deployment.
Understanding the structural biology of osteomalacia through multiscale 3D X-ray and electron tomographic imaging: a review of X-linked hypophosphatemia, the Hyp mouse model, and imaging methods
Authors: Buss Daniel J , Deering Joseph , Reznikov Natalie , McKee Marc D
Published: December 2024

Biomineralization in bones and teeth is a highly regulated extracellular event. In the skeleton, mineralization at the tissue level is controlled within the collagenous extracellular matrix by both circulating and local factors. While systemic regulation of mineral ion homeostasis has been well-studied over many decades, much less is known about the regulation of mineralization at the local level directly within the extracellular matrix. Some local regulators have been identified, such as tissue-nonspecific alkaline phosphatase (TNAP), phosphate-regulating endopeptidase homolog X-linked (PHEX), pyrophosphate, and osteopontin, and others are currently under investigation. Dysregulation of the actions of enzyme-inhibitor substrate pairs engaged in mineralization (as we describe by the Stenciling Principle for extracellular matrix mineralization) leads to osteomalacic “soft bone” diseases, such as hypophosphatasia (HPP) and X-linked hypophosphatemia (XLH). This review addresses how advances in 3D imaging tools and software now allow contextual and correlative viewing and interpretation of mineralized tissue structure across most length scales. Contextualized and integrated 3D multiscale data obtained from these imaging modalities have afforded an unprecedented structural biology view of bone from the macroscale to the nanoscale. Such correlated volume imaging data is highly quantitative, providing not only an integrated view of the skeleton in health, but also a means to observe alterations that occur in disease. In the context of the many hierarchical levels of skeletal organization, here we summarize structural features of bone over multiple length scales, with a focus on nano- and microscale features as viewed by X-ray and electron tomography imaging methods (submicron μCT and FIB-SEM). We additionally summarize structural changes observed after dysregulation of the mineralization pathway, focusing here on the Hyp mouse model for XLH. More specifically, we summarize how mineral patterns/packs at the microscale (3D crossfibrillar mineral tessellation), and how this is defective in Hyp mouse bone and Hyp enthesis fibrocartilage.
Allometric equations for estimating above- and below-ground biomass of reed (Phragmites australis) marshes
Authors: Jin Xianglong , Lou Yanjing , Zhang Peng , Tang Haoran , Zhang Qiyao , Smith Pete
Published: December 2024

Accurate estimate of vegetation biomass is a critical component for estimating terrestrial ecosystem carbon stocks. However, knowledge of vegetation biomass estimation for herbaceous marsh is scant. Here, 270 paired above-ground biomass (AGB) and trait data on reed marshes in Northeast China were sampled to estimate AGB, and 70 paired AGB and below-ground biomass (BGB) data from global papers to estimate BGB. The results showed that dividing reed marshes into salt and freshwater marshes greatly improved the fit of the models (R2 of classification vs overall: above 0.50 vs 0.31 and above 0.50 vs 0.10 for AGB and BGB estimation, respectively). A power-law allometric model with plant height alone as a predictor was appropriate for AGB estimation, and inclusion of plant density did not markedly improve prediction accuracy. The power function also fitted well with the relationship between AGB and BGB, with a scaling exponent of 1.13 and 0.60 for salt and freshwater marshes, respectively. Our results indicate that salt and freshwater marsh classification is necessary for estimating wetland vegetation carbon. These findings provide a profound insight into the prediction performance of carbon dynamics in wetland ecosystem.
Solar radiation shapes the spatial pattern of spring phenology on the Qinghai-Tibetan Plateau
Authors: Meng Fandong , Yan Yanzi , Li Lili , Zhang Lirong , Guo Bixi , Yang Zhiyong , Dorji Tsechoe
Published: December 2024

Spatial pattern of phenology reflects long-term plant adaptation to local environments, yet the drivers of these patterns remain understudied. Using satellite data from 2001-2018, this study employed the Normalized Difference Vegetation Index (NDVI) for vegetation structural greenness and Solar-Induced Chlorophyll Fluorescence (SIF) for vegetation functional photosynthesis to analyze spring phenology on the Qinghai-Tibetan Plateau (hereafter, QTP). A machine learning method, Boosted Regression Trees (BRT), was applied to evaluate the contributions of 19 abiotic and biotic factors to the spring phenology. Studies showed that both the spring leaf phenology (SOSNDVI) and photosynthesis phenology (SOSCISF) exhibited a delayed trend decreasing from east to west across the QTP. BRT analysis demonstrated shortwave radiation or/and elevation as key drivers, with higher radiation or elevation associated with more delayed spring phenology spatially, likely due to the constraints of extreme radiation and elevations on spring phenology. Furthermore, we also noted that plants were acclimated to strong radiation to some extent with elevation increasing, namely declined negative effect of radiation/elevation on spring phenology. This acclimation likely enhances plants fitness in QTP's harsh environments. Our study provides novel insights into plant phenology researches on the QTP, and highlight the importance of coupling spatial and temporal analysis on phenology to improve the localization of phenology models.
Exploring Evolution to Uncover Insights Into Protein Mutational Stability
Authors: Hermans Pauline , Tsishyn Matsvei , Schwersensky Martin , Rooman Marianne , Pucci Fabrizio
Published: December 2024

Determining the impact of mutations on the thermodynamic stability of proteins is essential for a wide range of applications such as rational protein design and genetic variant interpretation. Since protein stability is a major driver of evolution, evolutionary data are often used to guide stability predictions. Many state-of-the-art stability predictors extract evolutionary information from multiple sequence alignments of proteins homologous to a query protein, and leverage it to predict the effects of mutations on protein stability. To evaluate the power and the limitations of such methods, we used the massive amount of stability data recently obtained by deep mutational scanning to study how best to construct multiple sequence alignments and optimally extract evolutionary information from them. We tested different evolutionary models and found that, unexpectedly, independent-site models achieve similar accuracy to more complex epistatic models. A detailed analysis of the latter models suggests that their inference often results in noisy couplings, which do not appear to add predictive power over the independent-site contribution, at least in the context of stability prediction. Interestingly, by combining any of the evolutionary features with a simple structural feature, the relative solvent accessibility of the mutated residue, we achieved similar prediction accuracy to supervised, machine learning-based, protein stability change predictors. Our results provide new insights into the relationship between protein evolution and stability, and show how evolutionary information can be exploited to improve the performance of mutational stability prediction.
Animal and vegetal materials of mouse oocytes segregate at first zygotic cleavage: a simple mechanism that makes the two-cell blastomeres differ reciprocally from the start
Authors: Nolte Thomas , Halabian Reza , Israel Steffen , Suzuki Yutaka , Avelar Roberto A , Palmer Daniel , Fuellen Georg , Makalowski Wojciech , Boiani Michele
Published: December 2024

Recent advances in embryology have shown that the sister blastomeres of two-cell mouse and human embryos differ reciprocally in potency. An open question is whether the blastomeres became different as opposed to originating as different. Here we wanted to test two relevant but conflicting models: one proposing that each blastomere contains both animal and vegetal materials in balanced proportions because the plane of first cleavage runs close to the animal–vegetal axis of the fertilized oocyte (meridional cleavage); and the other model proposing that each blastomere contains variable proportions of animal and vegetal materials because the plane of the first cleavage can vary – up to an equatorial orientation – depending on the topology of fertilization. Therefore, we imposed the fertilization site in three distinct regions of mouse oocytes (animal pole, vegetal pole, equator) via ICSI. After the first zygotic cleavage, the sister blastomeres were dissociated and subjected to single-cell transcriptome analysis, keeping track of the original pair associations. Non-supervised hierarchical clustering revealed that the frequency of correct pair matches varied with the fertilization site (vegetal pole > animal pole > equator), thereby, challenging the first model of balanced partitioning. However, the inter-blastomere differences had similar signatures of gene ontology across the three groups, thereby, also challenging the competing model of variable partitioning. These conflicting observations could be reconciled if animal and vegetal materials were partitioned at the first cleavage: an event considered improbable and possibly deleterious in mammals. We tested this occurrence by keeping the fertilized oocytes immobilized from the time of ICSI until the first cleavage. Image analysis revealed that cleavage took place preferentially along the short (i.e. equatorial) diameter of the oocyte, thereby partitioning the animal and vegetal materials into the two-cell blastomeres. Our results point to a simple mechanism by which the two sister blastomeres start out as different, rather than becoming different.
Mastering Mālikī Law: A Moroccan Case Study
Authors: Sayeed Asma , Qaouar Nour-Eddine
Published: December 2024

Pedagogical canons, loosely defined as frameworks and instructional content to impart disciplinary literacy, can be vital sources for understanding stability and transformation in diverse historical contexts. This article documents and contextualizes the curriculum of fiqh and uṣūl al-fiqh during a period of far-reaching reform at Dar El hadith El Hassania, a Moroccan institute for training elite ʿulamāʾ. The balance of pre-modern canonical material with more recent sources anchors the institution in a centuries-long tradition of Mālikī fiqh while facilitating adaptation to political, social, and economic transformations.
BpMYB06 acts as a positive regulatory factor in saline–alkaline stress resistance by binding to two novel elements
Authors: Zhou Xuemei , Ren Ruyi , Sun Hu , Wang Luyao , He Wenjie , Guo Huiyan
Published: December 2024

Saline–alkaline salinity is recognized as one of the most severe abiotic stress factors, limiting plant growth and resulting in significant yield losses. MYB transcription factors (TFs) are crucial for plant tolerance to abiotic stress. However, the roles and regulatory mechanism of MYB TFs underlying saline–alkaline stress tolerance have not yet been investigated in Betula platyphylla. In this report, BpMYB06, an R2R3-MYB TF, is induced in response to saline–alkaline stress in B. platyphylla. This protein functions as a nuclear-localized transcriptional activator. Both gain- and loss-of-function analyses indicate that the transcript level of BpMYB06 is positively correlated with saline–alkaline stress tolerance, primarily through the enhancement of reactive oxygen species scavenging and the regulation of osmotic and ionic balance. Additionally, BpMYB06 is implicated in the control of stomatal aperture. Quantitative real-time PCR results show that BpMYB06 regulates the expression of genes associated with stress tolerance. Furthermore, TF-centered Y1H and chromatin immunoprecipitation assays reveal that BpMYB06 binds to two novel core sequences ([A/C]CGG and TAG[C/A]), thereby inducing the expression of stress-related genes. Our findings provide new insights into the role of BpMYB06 in B. platyphylla under soda saline–alkaline stress and suggest that it could serve as a potential target gene for developing saline–alkaline stress-tolerant B. platyphylla plants.
Endogenous C-type natriuretic peptide offsets the pathogenesis of steatohepatitis, hepatic fibrosis, and portal hypertension
Authors: Perez-Ternero Cristina , Li Wenhao , Aubdool Aisah A , Goldin Robert D , Loy John , Devalia Kalpana , Alazawi William , Hobbs Adrian J
Published: December 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD), hepatic fibrosis, and portal hypertension constitute an increasing public health problem due to the growing prevalence of obesity and diabetes. C-type natriuretic peptide (CNP) is an endogenous regulator of cardiovascular homeostasis, immune cell reactivity, and fibrotic disease. Thus, we investigated a role for CNP in the pathogenesis of MASLD. Wild-type (WT), global CNP (gbCNP−/−), and natriuretic peptide receptor-C (NPR-C−/−) knockout mice were fed a choline-deficient defined amino acid diet or administered CCl4. Liver damage was assessed by histological and biochemical analyses, with steatosis and portal vein size determined by ultrasound. Portal vein pressure and reactivity were measured in vivo and ex vivo, respectively. Pharmacological CNP delivery was used to evaluate prospective therapeutic benefit, and plasma CNP concentration was compared in controls and patients with cirrhosis. Circulating CNP concentration was lower in patients with cirrhosis compared with controls. gbCNP−/− mice were more susceptible, versus WT, to advanced steatohepatitis and hepatic fibrosis, characterized by increased immune cell infiltration, fibrosis, ballooning, plasma alanine aminotransferase concentration, and up-regulation of markers driving these processes. gbCNP−/− mice had increased portal vein diameter and pressure, underpinned by CNP insensitivity. NPR-C−/− animals recapitulated, comparatively, the exaggerated pathogenic phenotype in gbCNP−/− mice, whereas CNP reduced hepatic stellate cell proliferation via NPR-B-dependent inhibition of extracellular signal-related kinase 1/2. Administration of CNP reversed many aspects of disease severity. These data define a new intrinsic role for CNP in offsetting the pathogenesis of MASLD, hepatic fibrosis, and portal hypertension and the potential for targeting CNP signaling for treating these disorders.
A randomized, clinical trial of intravenous N-acetylcysteine as an antioxidant therapy in acute organophosphorus pesticide poisoning
Authors: Mohammed Sarah S , Zaaqoq Ayman , Talaat Shimaa , Abdelkader Salma I
Published: December 2024

The incidence of acute organophosphate (OP) poisoning has steadily increased in developing countries. Many studies showed that oxidative stress could have a significant role in its mechanism. The current study aimed to evaluate the role of N acetylcysteine (NAC) as an antioxidant in acute OP poisoned. A randomized, controlled, parallel-group trial was conducted in the period from the beginning of January 2022 to the end of June 2022. The study included 56 acute OP poisoned patients admitted to the intensive care unit (ICU) at the Poison Control Center of Ain Shams University Hospitals within 6 h after the exposure. The patients were randomly allocated in two equal groups; group (A): received the standard treatment plus NAC in a total dose of 300 mg/kg administered intravenously (IV) while group (B) received the standard treatment. Then both groups were compared as regards clinical parameters, laboratory investigations, ECG, and outcomes. Baseline parameters were comparable between the groups. However, NAC treatment significantly elevated concentrations of both serum catalase and glutathione peroxidase levels at 24 h, it did not significantly affect the total dose of atropine required, duration of atropine and oximes treatment or need for mechanical ventilation, and length of hospital stay. Mortality was lower in the NAC group (2 out of 28) than the standard treatment-only group (5 out of 28) but the difference was not statistically significant. This trial found that NAC improved antioxidant enzyme levels including serum CAT and GPX but did not affect clinically relevant outcomes.
Achieving the Needed Correction in Vertebral Body Tethering: The Relationship Between Preoperative Flexibility, Intraoperative Correction, and First Erect Imaging
Authors: Todderud Julia , Milbrandt Todd A. , Potter D. Dean , Larson A. Noelle
Published: December 2024

Background:

Vertebral body tethering (VBT) is a nonfusion surgical treatment for scoliosis. Recent data have shown that intraoperative correction is critical for successful curve correction over time. This study aims to evaluate the relationship between preoperative, intraoperative, and postoperative correction. We hypothesize that preoperative flexibility will match first erect imaging, intraoperative correction will overestimate postoperative correction, and correction has improved over time with increased surgeon experience.

Methods:

This study is a retrospective review of patients who underwent VBT at a single center between 2015 and 2023. Patient radiographs were reviewed preoperatively (standing and fulcrum bending), intraoperatively, and postoperatively first erect.

Results:

Our study included 157 patients: 127 females (81%) with a mean age of 13.2 years (range: 9 to 17) at surgery and a mean of 7.9 vertebrae instrumented (range: 5 to 12 vertebrae). Twenty-three had 2 curves instrumented (85% single curve). One hundred eight patients had thoracic curves (69%), 33 thoracolumbar (21%), and 16 lumbar (10%). Preoperative curve magnitude averaged 51 degrees (range: 36 to 72). The mean bending radiograph curve measurement was 24 degrees (53% correction). The mean intraoperative curve magnitude was 15 degrees (72% correction). Intraoperative curve magnitude and correction were significantly different between curve types, with increased correction in lumbar curves (7 degrees, 86% correction) and less correction in thoracic curves (16 degrees, 68% correction). On first erect postoperative imaging (mean 8 d post-op, range: 1 to 44), the curve magnitude was 26 degrees (49% correction). The R
2 correlation of the first erect radiograph was 0.209 for preoperative bending and 0.554 for intraoperative measurements. The mean difference in first erect curve magnitude was +2 degrees from preoperative flexibility radiographs and +11 degrees from intraoperative radiographs. Pre-2020, the intraoperative curve averaged 18 degrees, and >2020 averaged 13 degrees (P=0.001). Pre-2020, the first erect averaged 30 degrees, and >2020 improved to 24 degrees (P<0.001), despite equivalent preoperative metrics (both 51 degrees curves, P=0.98, with 54 vs. 52% flexibility, P=0.31).

Conclusions:

Our study indicates that preoperative bending films can provide a practical approximation of the correction on first erect imaging. Intraoperative correction has the strongest relationship and averages 11 degrees less than the postoperative standing curve magnitude. Further, our site’s intraoperative and postoperative correction has improved over time with increased surgeon experience.

Level of Evidence:

Level III—retrospective cohort.
Impact of Post-COVID-19 Condition on Health Status and Functional Capacity: A Cross-Sectional Study
Authors: Pereira Andreia , Amaral Luísa , Dias Inês , Magalhães André , Abreu Verónica , Esteves Mário , Vilarinho Rui , Cervaens Mariana
Published: December 2024

Purpose:

To assess health status and functional capacity in adults with post-COVID-19 condition.

Methods:

Observational, retrospective cross-sectional study. Outpatients from the Physical Medicine and Rehabilitation Department of the Hospital Fernando Pessoa, Porto, Portugal, were included. A convenient sample included 54 participants aged over 18 years old (52.4 ± 15.5 years, 61% female), with diagnosis of SARS-CoV-2 infection at least 12 weeks before the study, persistent or new-onset symptomatology consistent with post-COVID-19 condition. Clinical assessment included the collection of symptoms (COVID-19 Questionnaire and Modified Medical Research Council Dyspnea scale), lung function (spirometry), functional capacity (1-minute-sit-to-stand test and the 6-minute walk test), and emotional status (Anxiety, Depression, and Stress Scale).

Results:

A total of 46.3% of participants reported fatigue, 29.6% dry cough, 24.1% dyspnea, 24.1% myalgia, 22.2% weakness, and 20.4% memory loss. On functional capacity, 1-minute-sit-to-stand (20.1 ± 5.7) and 6-minute walk test (483.0 ± 110.3) performances were lower than the predicted values (P < .001).

Conclusions:

Adults with post-COVID condition in this study demonstrated evidence of reduced health status and functional capacity. These findings highlight the potential long-term effects of COVID-19.
Integrating Manual Therapy Techniques in the Treatment of Long COVID: A Case Report
Authors: Bates James , Gustavson Allison M.
Published: December 2024

Purpose:

Growing evidence suggests long COVID in some can result in nervous system dysfunction, which translates to difficulty completing daily activities. Physical therapists play an important role in regulating the autonomic system through the use of manual techniques that can decrease sympathetic tone. The purpose of this case report was to outline the physical therapy management of a person with long COVID and associated autonomic nervous system dysfunction.

This case report discusses a patient who is a 70-year-old man referred to physical therapy for fatigue and shortness of breath related to physician-diagnosed long COVID.

Methods:

The following manual therapy techniques were applied at each treatment session to address rib cage dysfunctions, muscle hypertonicity, and sympathetic tone for improved breathing: suboccipital release, cervical paraspinal release, and rib raising. Concurrently, the patient was instructed and prescribed a diaphragmatic breathing home exercise program.

Results:

After 11 physical therapy visits over 20 weeks, the patient demonstrated functional improvement with an associated decrease in symptoms.

Conclusions:

Manual therapy techniques, in combination with other physical therapy interventions, may be a first-line, less invasive means of addressing sympathetic tone and the downstream effects of nervous system dysfunction on daily living.
Treatment of Long COVID With Enoxaparin
Authors: Wright Ciara , Kell Douglas , Pretorius Resia , Putrino David
Published: December 2024

Background and Purpose:

Long COVID is a complex multisystemic disease state, which represents a huge economic and health burden worldwide. Hypercoagulation and the formation of fibrinaloid microclots have been proposed as an underlying pathology, which may underpin a wide variety of presenting symptoms, via reduced blood flow and cellular energy production. Postexertional malaise (PEM) is common and exercise therapy should not be recommended without addressing the underlying pathology.

Case Presentation:

Patient was female, 43, with Long COVID for 21 months characterized primarily by extreme fatigue, exercise intolerance, PEM, cognitive dysfunction, and postural orthostatic tachycardia syndrome. She was unable to work or leave the house unless for essential medical appointments. Before her initial severe acute respiratory syndrome coronavirus 2 infection, she had no prior health conditions or comorbidities, a body mass index of 20.8, and engaged in regular vigorous exercise.

Intervention:

This case report describes a patient treated with enoxaparin, a low molecular weight heparin, at 20 mg per day subcutaneously, with assessment at 8 weeks.

Outcomes:

The patient's function and quality of life improved markedly, as reported subjectively, and with objective measurements at 8 weeks. Levels of activity improved markedly with no adverse events. The severity of PEM decreased dramatically, and postural orthostatic tachycardia syndrome was better controlled. The FUNCAP score, used to measure functional capacity, increased from 3.3 (moderately affected) to 5.07 (mildly affected) after treatment.

Discussion:

It is recommended that this treatment should be further investigated to elucidate the role of enoxaparin in addressing underlying pathology in Long COVID, including hypercoagulation and microclots.
Esophageal cancer burden attributable to alcohol use and low consumption of vegetables from 1990 to 2021 across countries with different sociodemographic characteristics
Authors: Ma Yi-Kai , Zhou Yue-Ting , Liu Cai-Xia
Published: December 2024

Background

Esophageal cancer (EC) is a lethal malignancy. The sociodemographic index (SDI) is a critical factor influencing the disease burden of EC. Risk factors, including alcohol use and diet, vary significantly by SDI level, affecting the disease outcomes. This study utilized the Global Burden of Disease Study 2021 database to determine the age-standardized mortality rates (ASMR) and age-standardized disability-adjusted life-year rates (ASDRs) for EC attributable to alcohol use and a diet low in vegetables across countries with different SDI.

Methods

Data from the Global Burden of Disease Study 2021, covering from 1990 to 2021, were analyzed for 204 areas categorized into quintiles based on the SDI. Exposure levels for alcohol and vegetable intake were defined, and data were standardized using the global population structure to ensure comparability. Trend lines for the disease burden were plotted using R version 4.3.0 (R Foundation for Statistical Computing, Vienna, Austria). Statistical analyses were conducted using Joinpoint 4.9.1.0 (The Division of Cancer Control and Population Sciences, USA) regression to assess temporal trends in mortality and ASDRs, focusing on the annual percent change and average annual percent change across various SDI categories.

Results

From 1990 to 2021, the ASMR and ASDR for EC decreased globally across all SDI levels and in both sexes. The areas with a middle SDI initially had the highest rates but experienced the fastest declines, falling below high-middle–SDI countries by 2021. The ASMRs attributable to alcohol use generally declined, except in low-middle– and low-SDI nations. The greatest rates among males and the total population were found in high-middle–SDI nations, whereas high-SDI nations had the highest rates among females. The ASMRs associated with a diet low in vegetables decreased in all areas.

Conclusions

Despite the overall declining trend in the EC burden associated with alcohol use and diets low in vegetables, EC remains a significant global health concern. Strengthening the focus on key populations, implementing public health policies to reduce alcohol consumption, and promoting increased vegetable intake may collectively reduce the global burden of EC.
Comparing robotic, laparoscopic, and laparotomy in endometrial cancer: a network meta-analysis
Authors: Huang Wen-Rui , Ou Xing-Yan , Fang Xing-Zi , Tang Xiao-Xuan , Chen Lei , Ling Jing , Song Wen-Cong , Du Xue-Lian
Published: December 2024

Background:

This study aims to assess the comparative effectiveness and safety of robotic-assisted surgery (RAS), laparoscopy (LPS), and laparotomy (LPT) in improving perioperative indicators, lymph node dissection, and tumor survival outcomes in patients with endometrial carcinoma (EC) through a systematic review and network meta-analysis (NMA).

Materials and methods:

We searched China National Knowledge Infrastructure, Wanfang, WeiPu, China Biology Medicine Disc, Embase, PubMed, Web of Science, and the Cochrane Library for randomized controlled trials (RCTs) and cohort studies (CSs) involving RAS, LPS and LPT in individuals with EC. The NMA employed a Bayesian framework to integrate direct and indirect evidence, calculating odds ratios (OR) and mean difference (MD). Markov chain Monte Carlo methods generated posterior distributions, comparing and ranking treatments using surface under the cumulative ranking (SUCRA) values. Regression and sensitivity analyses assessed the impact of different variables on the results.

Results:

37 eligible trials involving 3 surgical techniques and 6,558 participants were included in this NMA. Our data showed that RAS was the most effective way for reducing estimated blood loss (MD −193; 95% CI [−279.38 to −106.95]; SUCRA 80.3%), length of hospital stay (MD −3.8; 95% CI [−5.37 to −2.31]; SUCRA 90.2%), transfusion rate (OR 0.13; 95% CI [0.06 to 0.28]; SUCRA 87%), intraoperative complications (OR 0.23; 95% CI [0.06 to 0.8]; SUCRA 91.3%), postoperative complications (OR 0.29; 95% CI [0.18 to 0.51]; SUCRA 98.8%), and total complications (OR 0.24; 95% CI [0.1 to 0.61]; SUCRA 96%). However, the analysis showed no significant differences in the dissection of lymph nodes and tumor survival outcomes.

Conclusion:

Our results showed that RAS was the most effective surgical method for improving perioperative indicators in EC. If hospital resources are limited, LPS is a suitable alternative. Further research is needed to confirm these findings and ensure that the benefits of minimally invasive surgeries extend to long-term survival outcomes.
Single-cell and spatial transcriptomic analyses reveal heterogeneity characteristics and specific cell subtype regulators in growth hormone-secreting pituitary adenomas
Authors: Zhang Yu , Wang Lifeng , Yi Xingcheng , Ma Xin , Wu Hongyu , Zhang Mingzhao , Yang Zhenqi , Ma Lizhen , Mi Zenghua , Zhi Weijia , Fu Cong , Liu Pinan , Yang Zhijun
Published: December 2024

Background:

Growth hormone-secreting pituitary adenomas (GHPA) display diverse biological behaviors and clinical outcomes, necessitating the identification of tumor heterogeneity and prognostically relevant markers.

Methods:

In this study, we performed single-cell RNA sequencing (scRNA-seq) on 10 GHPA samples, four of which also underwent spatial transcriptome sequencing, and used scRNA-seq data from four normal pituitary samples as controls. Cell subtype characterization in GHPA was analyzed using multiple algorithms to identify malignant bias regulators, which were then validated using a clinical cohort.

Results:

We constructed the first single-cell and spatial transcriptome profiles of GHPA, which contained 87 862 cells and revealed 16 tumor cell subtypes. Among the tumor cells, we identified distinct developmental trajectories and three malignant-biased subtypes (PIT1_C05, PIT1_C06, and PIT1_C10). The spatial distribution characteristics of these malignant-biased cells may influence the growth characteristics and prognosis of GHPA. We screened specific regulatory transcription factors, including FOXO1, GTF2IRD1, and MAX. Clinical cohort validation indicated that FOXO1 might be associated with tumor invasion and progression, while high expression of MAX could result in poor endocrine outcomes.

Conclusion:

GHPA exhibits rich heterogeneity and diverse cell subtypes, with specific transcription factors potentially regulating cell malignant bias, thereby influencing tumor characteristics and prognosis.
Unraveling the impact of noncoding RNAs in osteosarcoma drug resistance: a review of mechanisms and therapeutic implications
Authors: Pei Yi , Li Shenglong
Published: December 2024

Osteosarcoma (OS) is a prevalent primary malignant bone tumor, typically managed through a combination of neoadjuvant chemotherapy and surgical interventions. Recent advancements in early detection and the use of novel chemotherapeutic agents have significantly improved the 5-year survival rate of OS patients. However, some patients fail to achieve the desired treatment outcomes despite undergoing intensive chemotherapy and surgical procedures, with chemotherapy resistance emerging as a critical factor contributing to therapeutic failure in OS. Noncoding RNAs (ncRNAs) are a group of RNAs that lack protein-coding capacity but play a crucial role in tumor progression by modulating various biological characteristics of cancer cells, such as proliferation, apoptosis, migration, invasion, and drug resistance. Emerging evidence indicates that the dysregulated expression of numerous ncRNAs in OS cells can influence the response to chemotherapeutic agents by modulating processes such as cell apoptosis, signaling pathways, intracellular drug concentrations, and cell autophagy. This review aims to elucidate the roles and mechanisms of ncRNAs in mediating drug resistance in OS, offering new insights for investigating novel pathways underlying drug resistance, overcoming tumor resistance to therapeutics, and developing innovative chemotherapeutic strategies.
Preventing Community-Acquired Pressure Injury in Spinal Cord Injury: Simulation for Registered Nurses
Authors: Desmond Mary E. , Aguina Keith , Burkhart Elizabeth (Lisa)
Published: December 2024

Purpose

The study purpose was to develop and assess a simulation for registered nurses to apply knowledge, skills, and attitudes in conducting a focused assessment in the clinic setting to prevent community-acquired pressure injuries (CAPrIs) in individuals living with spinal cord injury (SCI).

Methods

Development, psychometric assessment, and pilot of a simulation for a nurse–patient clinic appointment to prevent CAPrIs at home. Evaluations were conducted via focus group.

Results

The simulation required one round with five experts in preventing CAPrIs in SCI to reach 80% agreement. The simulation with a standardized patient and companion checklist was piloted with (n = 4) post-baccalaureate registered nurse residents. Evaluation results indicated participants grew in knowledge, skills, and attitudes in conducting a focused assessment on prevention of CAPrIs.

Clinical Relevance

Evidence-based nursing education is needed for CAPrI prevention for individuals living with SCI in the community setting. The simulation is replicable.

Conclusions

The online educational program, simulation, and checklist for nurses promoted knowledge, skills, and attitudes in assessment of CAPrI prevention.
The Impact of Tranexamic Acid Administration in Reduction Mammaplasty
Authors: Pontes André , Barreiro Diogo , Costa-Ferreira António
Published: December 2024

Background

Previous studies demonstrated the effectiveness and safety of tranexamic acid (TXA) in several surgical specialties. Recent publications suggested that TXA may also be beneficial in plastic surgery, including breast procedures.

Objective

The aim of this study is to evaluate the impact of TXA in reduction mammaplasty by assessing several intraoperative and postoperative outcomes and the safety of its administration.

Methods

A systematic search was conducted according to PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analysis) guidelines on several online databases. Studies evaluating the outcomes of TXA administration in patients undergoing reduction mammaplasty, regardless of TXA dose and administration route were eligible for inclusion. Only studies with a control group were included. Risk-of-bias assessment was conducted using Cochrane and MINORS (Methodological Index for Non-Randomized Studies) tools.

Results

Our systematic review included 7 studies: 3 randomized controlled trials and 4 retrospective cohorts involving 1234 female patients (2232 breasts), 741 of whom received TXA (60%). Four studies used topical TXA, 2 used intravenous (IV) TXA, one used locally infiltrated TXA, and another combined locally infiltrated TXA with IV TXA. Four studies demonstrated benefits from TXA administration, whereas 3 studies did not. Topical TXA used just before wound closure resulted in a 42% reduction in drain fluid output and a 10-times reduction in major hematoma. The administration of IV TXA during induction resulted in a 12-times reduction in major and minor hematoma. The combined use of IV and locally infiltrated TXA reduced intraoperative blood loss. No adverse effects were reported.

Conclusions

There is scientific evidence suggesting TXA may be effective and safe in reduction mammaplasty.
Facial Thread Lifting Complications: Underlying Causes
Authors: Park Soo Yeon , Wan Jovian , Yoon Song-Eun , Kim Soo-Bin , Yi Kyu-Ho
Published: December 2024

Introduction:

Thread lifting procedures are becoming increasingly popular for facial rejuvenation. However, various complications can arise during these procedures, many of which are influenced by anatomic factors.

Methods:

In this section, the authors explore the potential side effects associated with thread lifting and emphasize the anatomic structures that require careful attention. Techniques to mitigate these risks are also discussed, focusing on methods such as reticular cutis gathering and pinching techniques.

Results:

Complications from thread lifting can include dimpling, protrusion, skin penetration due to skin tagging, parotitis, and nerve damage. These issues often stem from anatomic causes. In addition, granulomas, infections, and excessive fibrosis may occur, sometimes necessitating thread removal as the safest course of action.

Discussion:

Proper techniques, such as reticular cutis gathering and pinching, can help minimize side effects and ensure the safe placement of threads within the intended layer. Aligning threads with tissue movement and the superficial musculoaponeurotic system (SMAS) layer is crucial to preventing complications or deep penetration.

Conclusion:

By focusing on anatomic structures and using careful techniques, the risks associated with thread lifting can be significantly reduced, leading to safer and more effective outcomes.
Long-term immune changes after COVID-19 and the effect of BCG vaccination and latent infections on disease severity
Authors: Bendíčková Kamila , Papatheodorou Ioanna , Blažková Gabriela , Helán Martin , Haláková Michaela , Bednář Petr , Spearing Erin , Obermannová Lucie , Štíchová Julie , Heroldová Monika Dvořáková , Tomáš Tomáš , Panovský Roman , Šrámek Vladimír , De Zuani Marco , Vlková Marcela , Růžek Daniel , Hortová-Kohoutková Marcela , Frič Jan
Published: December 2024

Background

Several years after the COVID-19 pandemic, the role of trained immunity in COVID-19 remains controversial, and questions regarding the long-term effects of COVID-19 on immune cells remain unresolved. We investigated the roles of Bacillus Calmette–Guérin (BCG) vaccination and latent infections in the progression of COVID-19 and sepsis.

Methods

We conducted a prospective analysis of 97 individuals recovering from mild-to-critical COVID-19 and 64 sepsis patients. Immune cell frequencies, expression of functional markers, and plasma titres of anti-Toxoplasma gondii/cytomegalovirus/BCG antibodies were assessed and their impact on disease severity and outcomes were determined. To examine monocyte responses to secondary challenge, monocytes isolated from COVID-19 convalescent patients, BCG vaccinated and unvaccinated volunteers were stimulated with SARS-CoV-2 and LPS.

Results

Post COVID-19 patients showed immune dysregulation regardless of disease severity characterized mainly by altered expression of activation and functional markers in myeloid (CD39, CD64, CD85d, CD11b) and lymphoid cells (CD39, CD57, TIGIT). Strikingly, post-critical COVID-19 patients showed elevated expression of CD57 in CD8+T cells compared to other severity groups. Additionally, a higher frequency of CMV andT. gondiiseropositive-alongside a lower frequency of BCG seropositive-patients were associated with severe and critical COVID-19. However, the monocyte response to stimulation was unaffected by the severity of COVID-19.

Conclusion

These findings highlight the long-term alterations of immune cells in post-COVID-19 patients emphasizing the substantial impact of COVID-19 on immune function. However, our data showed no relationship between previous BCG vaccination and protection against SARS-CoV-2 infection.
Alzheimer Disease Plasma Biomarkers in the Mid-Western Amish
Authors: Wang Ping , Song Yeunjoo E. , Lynn Audrey , Miskimen Kristy , Gulyayev Alex , Prough Michael B. , Dorfsman Daniel A. , Laux Renee A. , Fuzzell Sarada L. , Hochstetler Sherri D. , Zaman Andrew F. , Adams Larry D. , Caywood Laura J. , Clouse Jason E. , Herington Sharlene D. , Whitehead Patrice , Liu Yining , Moore Noel , Ogrocki Paula , Lerner Alan J. , Griswold Anthony J. , Vance Jeffery M. , Cuccaro Michael L. , Scott William K. , Pericak-Vance Margaret A. , Haines Jonathan L.
Published: December 2024

INTRODUCTION

Alzheimer disease (AD) plasma biomarkers are noninvasive measures of the key amyloid beta (Aβ) and tau pathologies. Validation and generalization studies are needed to fully understand their potential for AD prediction and diagnosis in the elderly population.

METHODS

In 1,067 Amish individuals aged ≥ 65, we measured plasma Aβ and tau to assess their relationships with AD-related outcomes.

RESULTS

Among Amish individuals with AD, plasma p-tau181 was significantly higher (p= 0.04), and plasma Aβ42/p-tau181 ratio was significantly lower (p= 0.01) than cognitively normal individuals. The association of AD with elevated p-tau181 was driven by APOE ε4 carriers (OR = 6.02,p< 0.001). Cluster analysis identified two subgroups defined by differing Aβ and tau levels, with the high-risk cluster having more APOE ε4 carriers (p< 0.001).

DISCUSSION

Plasma biomarkers, particularly p-tau181, Aβ42/Aβ40, and Aβ42/p- tau181 ratio, are promising surrogate biomarkers for AD-related pathology and clinical outcomes in the Amish.
p75NTR modulation by LM11A-31 counteracts oxidative stress and cholesterol dysmetabolism in a rotenone-induced cell model of Parkinson’s disease
Authors: Pensabene Daniele , Martella Noemi , Scavo Giuseppe , Varone Michela , Bisesto Emanuele , Cavicchia Francesca , Colardo Mayra , Moreno Sandra , Segatto Marco
Published: December 2024

Neurotrophins play pivotal roles in the development and proper functioning of the nervous system. The effects of these growth factors are mediated through the binding of high-affinity receptors, known as Trks, as well as the low-affinity receptor p75NTR. The latter has the capacity to induce complex signal pathways, as it favors both pro-survival and pro-apoptotic cascades depending on the physiopathological condition. Recent findings have indicated that p75NTR expression is increased in post-mortem Parkinson’s disease (PD) brains, and this upregulation is associated with a significant reduction in neuroprotection. Given its double-edged sword nature, p75NTR has recently been identified as a promising therapeutic target to counteract neurodegenerative events. The present study aims to assess the neuroprotective effects of p75NTR modulation in a rotenone-induced neuronal model of PD. To this end, differentiated SH-SY5Y cells were exposed to rotenone to mimic the PD phenotype, and the small molecule LM11A-31 was used to modulate p75NTR activity. The main results revealed that LM11A-31 significantly mitigated the hallmarks of PD, including cell death, neuromorphological aberrations, and α-synuclein accumulation. Pharmacological manipulation of p75NTR also reduced oxidative damage by increasing the expression of transcriptional factors that regulate the antioxidant response and by decreasing the expression of the pro-oxidant NADPH-oxidase modulatory subunits. Furthermore, LM11A-31 hampered cholesterol buildup induced by rotenone, normalizing the expression of proteins involved in cholesterol biosynthesis, uptake and intracellular trafficking. Taken together, these findings suggest that p75NTR modulation may represent a novel approach to counteracting PD abnormalities of redox and cholesterol metabolism.
Implementing Trust in Non-Small Cell Lung Cancer Diagnosis with a Conformalized Uncertainty-Aware AI Framework in Whole-Slide Images
Authors: Zhang Xiaoge , Wang Tao , Yan Chao , Najdawi Fedaa , Zhou Kai , Ma Yuan , Cheung Yiu-ming , Malin Bradley A.
Published: December 2024

Ensuring trustworthiness is fundamental to the development of artificial intelligence (AI) that is considered societally responsible, particularly in cancer diagnostics, where a misdiagnosis can have dire consequences. Current digital pathology AI models lack systematic solutions to address trustworthiness concerns arising from model limitations and data discrepancies between model deployment and development environments. To address this issue, we developed TRUECAM, a framework designed to ensure both data and model trustworthiness in non-small cell lung cancer subtyping with whole-slide images. TRUECAM integrates 1) a spectral-normalized neural Gaussian process for identifying out-of-scope inputs and 2) an ambiguity-guided elimination of tiles to filter out highly ambiguous regions, addressing data trustworthiness, as well as 3) conformal prediction to ensure controlled error rates. We systematically evaluated the framework across multiple large-scale cancer datasets, leveraging both task-specific and foundation models, illustrate that an AI model wrapped with TRUECAM significantly outperforms models that lack such guidance, in terms of classification accuracy, robustness, interpretability, and data efficiency, while also achieving improvements in fairness. These findings highlight TRUECAM as a versatile wrapper framework for digital pathology AI models with diverse architectural designs, promoting their responsible and effective applications in real-world settings.