bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of an acute 1-month cannabidiol treatment on pain and inflammation after a long bone fracture: a triple-blind randomised, placebo-controlled, clinical trial protocol
Authors: Brazeau Daphnée , Deshaies Amelie A , Williamson David , Bernard Francis , Arbour Caroline , Pinard Anne Marie , Rouleau Dominique , De Beaumont Louis
Published: February 2025

Introduction

Acute pain levels following orthopaedic injury (eg, fracture) are a predictor of the onset of chronic pain, which affects nearly 50% of fracture patients and impairs functional recovery. Among current pharmacological treatments for acute pain, non-steroidal anti-inflammatory drugs have been associated with delayed bone healing, while opioids inhibit effective bone remodelling, increase the risk of pseudarthrosis and carry a high risk of addiction. In light of this, the development of new pain treatments is essential. Cannabidiol (CBD), a non-addictive and non-psychotropic cannabis component stands out as a potential therapeutic agent, given its analgesic and anti-inflammatory properties as well as its potential benefits for bone healing. This randomised controlled trial aims to investigate the effect of acute CBD treatment, compared with placebo, on patients’ self-reported pain, inflammation and well-being following a fracture injury.

Methods and analysis

This is a triple-blind, randomised, placebo-controlled clinical trial. A total of 225 adults aged 18–70 years, who have suffered a long bone fracture and were treated at the Hôpital du Sacré-Coeur de Montréal, will be randomly assigned within 1 week to one of three treatment arms (25 mg or 50 mg of CBD or placebo) for 1 month. The primary outcome will be the difference in the pain score between groups at 1-month follow-up. Secondary outcomes will include measures of persistent pain, inflammation, opioid usage, quality of life, sleep quality, depression, anxiety, cognition and orthopaedic function. Data will be collected at baseline, 1-month and 3-month follow-ups.

Ethics and dissemination

This study obtained a Health Canada licence for use of cannabis products. It has also been approved by Health Canada and the Research Ethics Board of the CIUSSS du Nord-de-l’Île-de-Montréal (Project ID 2025-2105). The findings will be published in a peer-reviewed journal and presented at local, national and international conferences. The trial’s results will be made publicly available on the ClinicalTrials.gov database.

Trial registration number

NCT06448923.
Exploring barriers, motivators and facilitators for physical activity and exercise in a UK South Asian community: a qualitative study
Authors: Deshmukh Ashwini , Kumar Kanta , Quinlan Jonathan
Published: February 2025

Objectives

This study aimed to elucidate motivators, barriers and facilitators of physical activity (PA) and exercise in a UK adult South Asian (SA) population. In addition, we sought to understand the sources of information regarding PA and the awareness of UK PA guidelines. Finally, the study aimed to explore public understanding of the utility of exercise for health outcomes and the role in disease prevention.

Design

Explorative study using qualitative research methods including interviews and self-determination theory.

Setting

Birmingham, UK.

Participants

The study included 15 UK SA adults (8 male, 7 female) with a mean age of 53.1 years (SA defined as Indian, Pakistani, Bangladeshi or Sri Lankan).

Results

We here found three key themes: (1) Engagement in PA and exercise, (2) Factors influencing PA and exercise (both barriers and facilitators) and (3) Accessibility to information. Participants showed a thorough understanding of PA; however, they lacked knowledge of strength-building exercise (ie, resistance exercise). This was particularly evident in SA women. Barriers to exercise typically focused around concepts of time, while facilitators centred on sufficient support. Knowledge of PA and exercise was typically obtained via social media, with only 2/15 aware of UK guidelines.

Conclusions

While SA adults were aware of the importance of PA and its utility in health prevention, there was an evident lack of knowledge of guidelines and in particular the need for resistance exercise or other strength-building activities. We highlight a need to develop new routes to disseminate information within the SA population to increase knowledge and understanding of PA and resistance exercise for overall health.
Prevalence of dry eye disease among children: a systematic review and meta-analysis
Authors: Zou Yuhao , Li Dongfeng , Gianni Virgili , Congdon Nathan , Piyasena Prabhath , Prakalapakorn S Grace , Zhang Ruifan , Zhao Zixiang , Chan Ving Fai , Yu Man
Published: February 2025

Background

Dry eye disease (DED) is a multifactorial disorder of the tear film and ocular surface instability that causes ocular discomfort and visual impairment. The increasing use of digital devices and changing lifestyle patterns have raised concerns about a potential rise in DED among children. Understanding the prevalence of paediatric DED is crucial for developing effective diagnostic and management strategies tailored to this vulnerable population.

Method

An exhaustive literature search was performed on several databases covering the period from 1 January 2001 to 1 April 2024. Prevalence estimates of DED were combined using random effects models, and heterogeneity sources were explored through subgroup and regression analyses.

Results

Our literature search identified 7309 articles, of which 41 articles, representing 42 study cohorts (48 479 participants) included in the systematic review. The estimated prevalence of DED among children was 23.7% (95% CI 18.5% to 28.9%). The prevalence of DED by different diagnostic criteria (clinical signs vs reported symptoms by questionnaire) was 16.6% (95% CI 13.7% to 19.5%; 26 studies; 27 107 children) vs 34.6% (95% CI 23.7% to 45.6%; 16 studies; 21 372 children; p<0.01), respectively. The prevalence of DED after the COVID-19 pandemic outbreak was 44.1% (95% CI 25.5% to 62.7%; 8 studies; 9163 children), which was significantly higher than the 18.7% (95% CI 15.6% to 21.9%; 34studies, 39 316 children; p=0.01) before the COVID-19 outbreak. High between-study heterogeneity was noted (I2>92%). In meta-regression analysis, the prevalence of DED among children increased by 7.1% with each 10° decrease in latitude (p=0.015), and by 10.2% with each 10° increase in mean annual temperature (p=0.024).

Conclusions

DED is common in children up to 18 years of age and poses a significant disease burden. Standardisation of the diagnosis of DED in children and further study of other risk factors are needed to fully explain the epidemiology of DED in children.
Broadening the definition of patient-safety events: lessons from a multicentre learning health system collaborative
Authors: Huddleston Jeanne M , Whitford Daniel , Yaszemski Alexandra K , Schrieber Matthew P , Pollak Edward
Published: February 2025

Background

Improving safety in healthcare has been paramount for decades, yet despite major attention and investment, improvement has remained incremental. Patient safety is a major concern in US healthcare, leading to significant harm and economic losses annually. Accurately identifying safety events remains difficult due to methodological discrepancies and lack of standardisation. This study evaluated the feasibility of implementing a standardised case-review methodology and safety-event taxonomy across diverse hospital settings to assess opportunities for improvement (OFIs) and compare findings with traditional definitions.

Methods

This multicentre retrospective cohort study reports data from 103 hospitals across the USA and Canada between 2016 and 2023. A multivariable logistic regression was performed to test case reviews for differences in the presence of one or more OFIs across several hospital types (bed size, academic status, urban setting, trauma level and Centres for Medicare and Medicaid Services overall star rating) and patient characteristics (age, gender, length of stay, admission and discharge code status and mortality).

Results

19 181 cases were reviewed across the Learning Health System Collaborative, with a median of 107 reviews per hospital. Mortality was the most common cohort selection, studied by 91 hospitals (88%). At least one OFI was identified in 12 714 cases (66.3%). The logistic regression analysis found that all hospital characteristics and patient age, length of stay, code status and discharge disposition were significantly associated with at least one OFI. Of the 46 444 OFIs identified, 41 439 (89%) were from categories focused on omissions of care. The categories of end-of-life, documentation and treatment/care alone accounted for 25 980 OFIs (56%).

Conclusion

The highest volumes of safety-related OFIs were associated with omissions of care, as opposed to the traditional definition of patient safety, which primarily includes outcomes from acts of commission.
Reduced wait times for molecular-biomarker testing among patients with advanced lung cancer using parallel sample processing and closed-loop communication: the Continuous Oncopanel and ALK Status Tracking (COAST) Project
Authors: Yeo Sarah , Sun Jane , Zibrik Kelly , Shaipanich Tawimas , Carolan Hannah , Melosky Barbara , Ionescu Diana , Alex Deepu , Yip Stephen , Wang Ying
Published: February 2025

Background

Given how crucial molecular-biomarker testing is to treatment decisions for advanced non-small cell lung cancer (NSCLC), guidelines recommend a turnaround time (TAT) of 14 calendar days from receiving specimen to test result, and 3 days to receive a specimen from outside pathology lab. Current TAT for molecular-biomarker testing in British Columbia (BC), Canada frequently exceeds these recommendations. Thus, we launched a quality improvement (QI) initiative to improve TAT of molecular-biomarker testing.

Methods

We assembled a multidisciplinary team to identify areas contributing to delays in molecular-biomarker testing. We designed and conducted three Plan-Do-Study-Act (PDSA) cycles. Cycles 1 and 2 involved changing requisition delivery method from fax to email between BC Cancer Vancouver Centre (BCCV) and two outside hospitals with the highest volume of specimens. Cycle 3 introduced parallel processing of specimens at BCCV pathology lab and concurrent molecular-biomarker testing. TAT was evaluated before and after these process changes along with staff satisfaction via survey.

Results

The average TAT from test request to specimen received by BCCV was reduced from 6.4 days prechange to 4.6 days postchange. The TAT from specimen receipt by BCCV to report availability was reduced from a median of 22–16 days. Report availability for initial medical oncology consultation increased from a median of 13%–29%. The staff satisfaction survey revealed an enhanced experience with the new process, particularly for our nurse navigator.

Conclusion

The TAT for molecular-biomarker testing is an ongoing and complex challenge for healthcare systems worldwide. This QI project is a step towards addressing province-wide reduction in wait times for molecular-biomarker testing results in BC. We continue to explore further ideas to improve workflow metrics and patient care among patients with advanced NSCLC.
Health anxiety in a neurological setting
Authors: Green Huw , Stone Jon
Published: February 2025

Health anxiety is a common issue in neurology clinics. However, it needs to be separated from normal health concerns as well as from the category of functional symptoms and disorders. Reassurance in health anxiety, which the patient often seeks, is ineffective and can worsen the problem. There are effective and brief psychological treatments; however, for patients to engage with treatment, they need to receive accurate early diagnosis and education. This article explains the nature of health anxiety and introduces the rationale of its treatment. We make several practical suggestions to help neurologists to maximise the chances of successfully referring their patients for psychological therapy.
Evolution of grading and particle crushing of rockfills upon shearing and over creeping in large–scale triaxial tests
Authors: Liu Mengcheng , Chen Xuan
Published: February 2025

There is substantial evidence that crushable soils (e.g., sands, gravels and rockfills, etc.) undergo particle crushing upon shearing or over creeping. To investigate the evolution of grading and particle crushing of coarse-grained materials, a series of consolidated and drained (CD) triaxial compression and creep tests were conducted on rockfills using a large-scale triaxial (LST) apparatus. The test data from the sieve analysis test, both before and after the tests, were subjected to a comprehensive qualitative and quantitative analysis of the variation of grading or breakage index. Research findings indicate a decrease in the percentage of coarser particles in the particle components of rockfills, accompanied by an increase in the amount of particle crushing upon shearing or over creeping. Furthermore, a series of empirical expressions were proposed through nonlinear fit of test data to characterize the relationship between the breakage index and two variables (i.e., the normalized plastic work and mean effective stress) under various confining pressures and stress levels upon shearing or over creeping. These findings can provide a scientific basis for the design, construction and maintenance of rockfill dams or high rockfill embankments in practical engineering application.
Putting the Smarts into Robot Bodies
Authors: Fan Wang , Liu Shaoshan
Published: February 2025

Fan Wang and Shaoshan Liu provide guidance for the development of embodied AI systems.
Detecting Both Seen and Unseen Anomalies in Time Series
Authors: Liu Chen , He Shibo , Li Shizhong , Shi Zhenyu , Meng Wenchao
Published: February 2025

A plethora of methods for time series anomaly detection has surfaced recently, encompassing both supervised and unsupervised settings. However, few approaches are designed to accommodate both settings simultaneously. Moreover, methods tailored for supervised scenarios often struggle to identify out-of-distribution (OOD) anomalies, while those for unsupervised scenarios may easily overlook in-distribution (ID) anomalies. To bridge this gap, we propose InvAD, a unified framework capable of detecting both ID and OOD anomalies, which seamlessly scales between unsupervised and supervised settings. To address the potential information loss in existing feature extraction techniques, our framework incorporates an information-preserving invertible neural network (INN) with a mathematical guarantee. Specifically, InvAD adopts a dual-branch structure with a shared feature encoder stacked by INN blocks. This encoder decomposes original intricate signals into ID features and OOD features without discarding any information. For ID anomalies, we treat all training data as ID samples and push their OOD features close to a predefined constant value. This step aims to encode all valuable information of ID samples within the ID features, which are then employed to recognize seen anomalies through a classifier. For OOD anomalies, during the training stage, we endeavor to reconstruct original signals from ID features and the constant value through the backward process of the feature encoder. OOD anomalies are detected when a significant discrepancy exists between the reconstructed and original signals during the testing stage. Additionally, while contrastive learning has shown remarkable success in time series analysis, the construction of effective sample pairs remains underexplored. To address this, we introduce a label-guided contrastive learning module. This module leverages pseudo labels provided by the classifier to correct false positive pairs generated by conventional data augmentation methods. Extensive experiments on 12 real-world datasets validate the superiority of InvAD under unsupervised, supervised, and weakly supervised settings. Furthermore, ablation studies demonstrate that the pseudo labels can effectively enhance the performance of contrastive learning in time series anomaly detection.
PATCH: Empowering Large Language Model with Programmer-Intent Guidance and Collaborative-Behavior Simulation for Automatic Bug Fixing
Authors: Zhang Yuwei , Jin Zhi , Xing Ying , Li Ge , Liu Fang , Zhu Jiaxin , Dou Wensheng , Wei Jun
Published: February 2025

Bug fixing holds significant importance in software development and maintenance. Recent research has made substantial strides in exploring the potential of large language models (LLMs) for automatically resolving software bugs. However, a noticeable gap in existing approaches lies in the oversight of collaborative facets intrinsic to bug resolution, treating the process as a single-stage endeavor. Moreover, most approaches solely take the buggy code snippet as input for LLMs during the patch generation stage. To mitigate the aforementioned limitations, we introduce a novel stage-wise framework named PATCH. Specifically, we first augment the buggy code snippet with corresponding dependence context and intent information to better guide LLMs in generating the correct candidate patches. Additionally, by taking inspiration from bug management practices, we decompose the bug-fixing task into four distinct stages: bug reporting, bug diagnosis, patch generation, and patch verification. These stages are performed interactively by LLMs, aiming to simulate the collaborative behavior of programmers during the resolution of software bugs. By harnessing these collective contributions, PATCH effectively enhances the bug-fixing capability of LLMs. We implement PATCH by employing the powerful dialogue-based LLM ChatGPT. Our evaluation on the widely used bug-fixing benchmark BFP demonstrates that PATCH has achieved better performance than state-of-the-art LLMs.
Replicating Host–Microbiome Interactions: Harnessing Organ-on-a-Chip and Organoid Technologies to Model Vaginal and Lung Physiology
Authors: Coxon Jade , Linder Emily , Sweet Caden , Magness Scott , Green Leopold
Published: February 2025

Organ-on-a-chip (OOC) and organoid technologies are at the forefront of developing sophisticated in vitro systems that replicate complex host–microbiome interactions, including those associated with vaginal health and lung infection. We explore how these technologies provide insights into host–microbiome and host–pathogen interactions and the associated immune responses. Integrating omics data and high-resolution imaging in analyzing these models enhances our understanding of host–microbiome interactions' temporal and spatial aspects, paving the way for new diagnostic and treatment strategies. This review underscores the potential of OOC and organoid technologies in elucidating the complexities of vaginal health and lung disease, which have received less attention than other organ systems in recent organoid and OCC studies. Yet, each system presents notable characteristics, rendering them ideal candidates for these designs. Additionally, this review describes the key factors associated with each organ system and how to choose the technology setup to replicate human physiology.
Neuroimmune Circuits in Allergic Diseases
Authors: Han Cai , Zhu Xueping , Sokol Caroline L.
Published: February 2025

Communication between the nervous and immune systems is evolutionarily conserved. From primitive eukaryotes to higher mammals, neuroimmune communication utilizes multiple complex and complementary mechanisms to trigger effective but balanced responses to environmental dangers such as allergens and tissue damage. These responses result from a tight integration of the nervous and immune systems, and accumulating evidence suggests that this bidirectional communication is crucial in modulating the initiation and development of allergic inflammation. In this review, we discuss the basic mechanisms of neuroimmune communication, with a focus on the recent advances underlying the importance of such communication in the allergic immune response. We examine neuronal sensing of allergens, how neuropeptides and neurotransmitters regulate allergic immune cell functions, and how inflammatory factors derived from immune cells coordinate complex peripheral and central nervous system responses. Furthermore, we highlight how fundamental aspects of host biology, from aging to circadian rhythm, might affect these pathways. Appreciating neuroimmune communications as an evolutionarily conserved and functionally integrated system that is fundamentally involved in type 2 immunity will provide new insights into allergic inflammation and reveal exciting opportunities for the management of acute and chronic allergic diseases.
Vibrational Sum Frequency Generation Spectroscopy Study of Nanoscale to Mesoscale Polarity and Orientation of Crystalline Biopolymers in Natural Materials
Authors: Lee Jongcheol , Ryu Jihyeong , Choi Juseok , Chae Inseok , Kim Seong H.
Published: February 2025

As a nonlinear optical process, sum frequency generation (SFG) requires noncentrosymmetry across multiple length scales, ranging from individual molecular functional groups to their arrangements in space. This principle makes SFG not only intrinsically sensitive to molecular species at surfaces but also useful for studying 3D structures of crystalline biopolymers in natural materials. Examples of such biopolymers are cellulose, starch, and chitin in the polysaccharide family and collagen, silk, and keratin in the fibrous protein family. These biopolymers are noncentrosymmetric at multiple length scales, with chirality at the molecular scale, unit cell structure at the nanoscale, and crystallite orientation and polarity at the mesoscale; thus, they are SFG active. In this review, we describe how SFG can be used to determine nano- to mesoscale polarity and orientational orders of crystalline biopolymers interspersed in natural materials containing the same or similar biopolymers in amorphous states, which cannot be obtained with other characterization methods.
The Bezold–Jarisch Reflex Following an Endoscopic Endonasal Resection of an Intraosseous Clival Myxoma: A Case Report
Authors: Peterson Abigail , Hussain Omar , Zwagerman Nathan , Woehlck Harvey
Published: February 2025

In certain contexts, young and healthy patients with a strong heart and a history of vasovagal syncope are at increased risk of cardiac arrest. An increase in vagal tone results in the normal maintenance of arterial pressure shifting into parasympathetic activation and sympathetic suppression, amplifying afferent mechanoreceptors and, in rare instances, inducing asystole. We report the case of a 17‐year‐old patient with a past medical history of syncope who went into asystole while maintaining consciousness and protecting his airway when recovering from anesthesia in the postanesthesia care unit (PACU) following endoscopic endonasal resection of an intraosseous clival myxoma. Chest compressions were initiated and epinephrine was administered, allowing for return of spontaneous circulation to be quickly achieved. While being transferred to the intensive care unit, the patient’s heart rate dropped to 20 bpm while sitting in Fowler’s position, causing vasovagal syncope which was then resolved by laying the patient supine and 0.8 mg of glycopyrrolate administration. The altered sympathetic to parasympathetic tone resulting in asystole within this case and cardiac beta‐agonist stimulation by epinephrine injection provide evidence that the Bezold–Jarisch reflex occurred. This case suggests that the intracranial internal carotid arteries can potentially display similar mechanical sensitivity as the carotid sinus and questions the validity of electrocardiogram readings during this reflex, as the patient remained conscious while in asystole.
Gene Mutation Characteristics and Prognostic Significance in Acute Myeloid Leukemia Patients From Northeast China
Authors: Shen Yiyang , Fu Shuang , Liu Xuan , Liu Jianing , Fu Yu , Zhao Yue , Wang Xinxin , Jiang Xujian , Zhang Jihong
Published: February 2025

A great part of studies on the correlation between gene mutations and prognosis in acute myeloid leukemia (AML) patients are based on Western populations. To profile the genomic landscape of AML patients in Northeast China, we retrospectively analyzed the clinical data of 377 newly diagnosed AML patients in Shengjing Hospital of China Medical University from 2016 to 2022 and compared them with data from other populations with different genetic backgrounds. The mutation status of NPM1, FLT3-ITD, FLT3-TKD, CEBPA (CCAT enhancer binding protein alpha), ASXL1, TET2, KIT, DNMT3A (DNA methyltransferase 3A), IDH1, IDH2, EZH2 (enhancer of zeste 2), RUNX1, TP53, NRAS, and GATA2 was acquired by next‐generation sequencing (NGS) technology; meanwhile, the clinical data of the patients were collected. The Cox regression model was used to analyze factors affecting patient survival and the impact of CEBPA and DNMT3A mutation on prognosis, and the results were different from those in other populations. Seventy‐seven of 377 patients (20.4%) were detected with CEBPA mutations, which was higher than the 2%–6% in the Caucasian population. In the CEBPAdm patients who did not receive bone marrow transplantation, the prognosis of male patients (n = 18) was significantly better than that of female patients (n = 21) (p = 0.0242). Sixty‐three of 377 patients (16.7%) carried the DNMT3A mutation, which was lower than the mutation frequency of 20.9% in the German–Austrian population, and the prognosis of these patients was significantly poorer (p = 0.0052). In addition, the prognostic evaluation value of the DNMT3A mutation in AML patients was not affected regardless of the presence of the NPM1 and FLT3-ITD comutation (p > 0.05), nor the mutation site of DNMT3A. In conclusion, for the Northeastern Chinese population, the prognosis of male patients with CEBPAdm was more favorable than that of female patients, and the DNMT3A mutation serves as an independent predictor of poor prognosis in AML. These results highlighted the central role of genetic background in precision medicine strategies and further emphasized the importance of the clinical characteristics of AML gene mutations in the Chinese population.
Natural Partial Order on Generalized Semigroups of Transformation Semigroups That Preserve Order and an Equivalence Relation
Authors: Qin Meiqing , Fu Xuerong
Published: February 2025

Let X be a finite total order set and E be a convex equivalence relation on X. We denote that OE(X) = {f ∈ TE(X) : ∀x, y ∈ X, x ≤ y⟹f(x) ≤ f(y)} , where TE(X) is an E− preserving transformation semigroup. Obviously, OE(X) is a subsemigroup of TE(X), which is called an order‐preserving and equivalence‐preserving transformation semigroup. We fix an element θ in OE(X) and define a new operation ∘ on OE(X) by f∘g = fθg. Under the operation ∘, OE(X) forms a semigroup, which is called a generalized semigroup of OE(X) and is denoted by OE(X; θ). In this paper, we characterize the natural partial order on OE(X; θ), and the condition under which the two elements of OE(X; θ) are related to such natural partial order is also described. Furthermore, we investigate the elements of OE(X; θ) that are compatible with this partial order and find out the maximal (minimal) elements. This study not only contributes to a deeper understanding of the internal structure of semigroups and the interactions between elements but can also be used to analyze the optimal path selection in graph theory and optimize traffic distribution problems in networks.
Impact of Drying Methods on Bioactive Compounds and Antioxidant Properties of Kalanchoe ceratophylla
Authors: Manalu Lamhot Parulian , Adinegoro Himawan , Yustiningsih Nenie , Astuti  , Luthfiyanti Rohmah , Maisaroh  , Purwanto Wahyu , Subandrio  , Pongtuluran Olivia Bunga , Atmaji Priyo , Hidayat Taufik , Henanto Henky , Asgar Ali , Nasori Achmad Sofian , Triyono Agus , Elya Berna , Arif Abdullah Bin
Published: February 2025

Kalanchoe species have been used as herbal medicines in traditional Asian medicine. One of the Kalanchoe species that has the potential as a medicinal plant and is still limited in its studies is Kalanchoe ceratophylla. This study investigated the effects of drying methods, namely, freeze drying (FD) and hot air drying (HAD), on bioactive compounds, phenolics, flavonoids, and antioxidants in Kalanchoe ceratophylla leaves and stems. The content of bioactive compounds in K. ceratophylla leaves and stems was identified with gas chromatography‐mass spectrometry (GC‐MS) analysis. In addition, the antioxidant activity of K. ceratophylla was also measured. The results of GC‐MS on K. ceratophylla contain major bioactive compounds including gamma.‐Sitosterol, Glutinol, Friedelan‐3‐one, Squalene, Ergost‐5‐en‐3‐ol, (3.β.)‐, Erythritol, and Neophytadiene. The main component identified in the leaf and stem extracts of K. ceratophylla is gamma‐sitosterol (± 15%), which shows anticancer and antidiabetic effects. The antioxidant activity in K. ceratophylla with the FD method was higher than that with the HAD method. This study suggests that FD was considered appropriate and should be used to maintain the content of important bioactive compounds and antioxidant activity in K. ceratophylla. These findings suggest that further research and development of bioactive compounds essential for their pharmacological properties in K. ceratophylla may be warranted, with the potential for developing new drugs.
Timing of circulating tumor DNA analysis aimed at guiding adjuvant treatment in colorectal cancer
Authors: Henriksen Tenna V. , Demuth Christina , Frydendahl Amanda , Nors Jesper , Nesic Marijana , Rasmussen Mads H. , Larsen Ole H. , Jaensch Claudia , Løve Uffe S. , Andersen Per V. , Kolbro Thomas , Thorlacius-Ussing Ole , Monti Alessio , Kildsig Jeppe , Bondeven Peter , Schlesinger Nis H. , Iversen Lene H. , Gotschalck Kåre A. , Andersen Claus L.
Published: February 2025

Background: Multiple clinical trials investigate circulating tumor DNA (ctDNA) to guide adjuvant chemotherapy (ACT) in colorectal cancer. Timely ACT initiation necessitates early ctDNA testing, but the impact of postoperative cell-free DNA (cfDNA) and ctDNA dynamics remains unclear, particularly with cost-reducing input caps employed in some assays. This study investigates ctDNA detection at day14 versus day30, comparing whole-sample analysis with capping the cfDNA input, and evaluates single and dual timepoint assessments for ACT allocation. Patients and methods: In 2019-2023, 611 stage I-III colorectal cancer patients were enrolled. Blood was collected preoperatively, and postoperatively ~day14 and ~day30. The cfDNA levels were assessed using digital PCR, and ctDNA using tumor-informed digital PCR or targeted sequencing analyzing all cfDNA from 8mL of plasma. Results: Despite elevated cfDNA in 85% of day14 samples, performance was comparable between the two timepoints (sensitivity 31% vs 32%; specificity both 98%). A 50ng cfDNA input cap reduced ctDNA detection probability, impacting 78% of day14 samples and 65% of day30 samples. At both timepoints, ctDNA detection was prognostic of recurrence (day14: HR=9.0, 95%CI 5.5-14.8; day30: HR=12.5, 95%CI 7.6-20.4). In 74% of ctDNA-positive recurrence patients, both samples had ctDNA detected. An increase in ctDNA level from day14 to day30 was associated with shorter time to recurrence (Pearson R=-0.63, P=0.003). Combining the timepoints would increase sensitivity (36%) and allow earlier ACT start in 80% of patients. Conclusion: Early ctDNA sampling is feasible and highly prognostic. Supplemental later testing may improve sensitivity while allowing early ACT initiation for most ctDNA positive patients.
Identification of potential diagnostic biomarkers and drug targets for endometriosis from a genetic perspective: a mendelian randomization study
Authors: Zhu Yingjia , Cheng Feng , Zhu Linling , Yang Xinyun , He Mingjie , Wang Wenhui
Published: February 2025

Introduction: Endometriosis (EM) is a chronic disease severely impacting reproductive health, with its exact cause still unclear. In-depth understanding of the etiology and pathogenesis of EM from the perspective of genetics and exploring individualized treatment strategies can improve the health and quality of life of patients.
Methods: In this study, whole blood cis- expression quantitative trait loci (eQTL) data were used as exposure data, and data from the FinnGen database EM1-2 and EM3-4 were used as outcomes. Summary-data-based mendelian randomization (SMR) methods were used to select genes with causal relationship to the disease. These genes were validated through bioinformatics analysis and real-time quantitative polymerase chain reaction (RT-qPCR) analysis of clinical samples, and potential diagnostic and drug targets were screened through co-localization and molecular docking.
Results: Through SMR analysis, seven genes were selected as potential diagnostic markers of EM, namely Eukaryotic Elongation Factor, Selenocysteine-TRNA Specific (EEFSEC), INO80 complex subunit E (INO80E), RAP1 GTPase activating protein (RAP1GAP), Lipid Droplet Associated Hydrolase (LDAH), Ring Finger And SPRY Domain Containing 1 (RSPRY1), HLA Complex Group 22 (Non-Protein Coding) (HCG22) and Adenosine Kinase (ADK). Colocalization analysis showed that EEFSEC, HCG22, INO80E and RSPRY1 could be used as potential drug targets.
Conclusions: The study identifies potential diagnostic markers and drug targets for EM from a genetic perspective, providing new directions for drug development and precision medicine for EM treatment.
Clinical characteristics of women with surgical signs of superficial peritoneal endometriosis but a negative histology: A nested case-control study
Authors: Reis Fernando M. , Santulli Pietro , Marcellin Louis , Bourdon Mathilde , Maignien Chloé , Chapron Charles
Published: February 2025

Objectives: To investigate the clinical characteristics of women with superficial peritoneal endometriosis (SUP) diagnosed by surgery and not confirmed by histology, compared with histologically proven SUP.
Design: Single-center, nested case-control study.
Participants/Materials: Patients with a surgical report of SUP (n = 390), comprising a subgroup with histological confirmation of endometriosis (n = 245) and a subgroup without it (n = 145). In addition, we enrolled a control group (n = 390) among non-pregnant patients submitted to a laparoscopy or laparotomy for a benign gynecologic condition without any macroscopic sign of endometriosis.
Setting: University hospital.
Methods: Data synthesis, descriptive statistics, chi-square test and one-way analysis of variance followed by Tukey’s test.
Results: All groups had similar age, body mass index, smoking prevalence, serum AMH levels and menstrual cycle patterns. However, the two SUP subgroups had the same prevalence and intensity of endometriosis symptoms. The SUP/histology-negative subgroup was more likely to have a familial history of endometriosis (14% vs. 1%) or a personal history of primary infertility (29% vs. 19%) or primary dysmenorrhea (50% vs. 33%) compared to the control group (all p values <0.01). The intensity scores for dysmenorrhea, deep dyspareunia and non-cyclic chronic pelvic pain were severer in both SUP subgroups than in the control group (p<0.05).
Limitations: The participants underwent surgery, so their symptoms may not represent groups with initial or mild disease that responded to medical treatments. Due to the retrospective design, performance bias cannot be ruled out.
Conclusions: Patients with suspected SUP lesions and a negative histology had clinical characteristics resembling those with proven endometriosis. Further characterization with molecular biomarkers is needed to explain why these women are so symptomatic in the absence of histological hallmarks of the disease.
​​​Cardiovascular Safety of GnRH Agonist-Based Androgen Deprivation Therapy in a Real-World Setting: Results from a Prospective Cohort Study (LEAN)
Authors: Schmitz-Dräger Bernd J. , Bismarck Ekkehardt , Ebert Thomas , Starlinger Roland , Dienes Kerstin , Ottillinger Bertram , Goebell Peter J. , Mühlich Stephan , Benderska-Södera Natalya , Bergler-Klein Jutta , Hakenberg Oliver W.
Published: February 2025

Introduction: LEAN is a prospective, multicenter, noninterventional, German cohort study in patients with locally advanced and metastatic hormone-sensitive prostate cancer (PC). This analysis explores the efficacy and safety of leuprorelin in patients with PC and an indication for androgen deprivation therapy (ADT) in routine practice.
Methods: Safety assessment focused on the incidence of major adverse cardiovascular (CV) events (MACEs; a composite of all-cause death, myocardial infarction, or stroke) over the 12-month study period. Patients initiating ADT before enrollment were excluded from the analysis.
Results: Of the 1,372 patients included, MACEs occurred in 57 (4.2%) patients, and in 18/532 (3.4%) versus 39/840 (4.6%) patients without and with a pre-existing CV comorbidity, respectively (p=0.264). Of the 57 MACEs, 17 were CV events and 20 were considered PC related events; in 20 patients, events were classed as ‘other’ or the context remained unknown. Only one MACE, nonserious arrhythmia, was considered drug related by the urologist. Of the 51 deaths reported in patients with MACEs, 12 were related to a CV event and 20 were related to disease progression.
Conclusion: In a large European patient cohort, leuprorelin-based ADT demonstrated an acceptable safety profile, with a low incidence of CV events.
Magenkarzinom/Adenokarzinom des gastroösophagealen Übergangs: Hat eine präoperative Radiochemotherapie einen Stellenwert in der multimodalen Behandlung?
Authors: Haag Georg Martin
Published: February 2025

Background: In Western countries, the current standard of care for resectable gastric cancer is perioperative chemotherapy. Preoperative chemoradiotherapy has been considered, but data are limited regarding this treatment as compared with perioperative chemotherapy alone. Methods: We conducted an international, phase 3 trial in which patients with resectable adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned to receive preoperative chemoradiotherapy plus perioperative chemotherapy or perioperative chemotherapy alone (control). In both groups, patients received either epirubicin, cisplatin, and fluorouracil or fluorouracil, leucovorin, oxaliplatin, and docetaxel both before and after surgery; the preoperative-chemoradiotherapy group also received chemoradiotherapy (45 Gy in 25 fractions of radiation, plus fluorouracil infusion). The primary end point was overall survival, and secondary end points included progression-free survival, pathological complete response, toxic effects, and quality of life. Results: A total of 574 patients underwent randomization at 70 sites in Australasia, Canada, and Europe: 286 to the preoperative-chemoradiotherapy group and 288 to the perioperative-chemotherapy group. A higher percentage of patients in the preoperative-chemoradiotherapy group than in the perioperative-chemotherapy group had a pathological complete response (17% vs. 8%) and greater tumor downstaging after resection. At a median follow-up of 67 months, no significant between-group differences in overall survival or progression-free survival were noted. The median overall survival was 46 months with preoperative chemoradiotherapy and 49 months with perioperative chemotherapy (hazard ratio for death, 1.05; 95% confidence interval, 0.83 to 1.31), and the median progression-free survival was 31 months and 32 months, respectively. Treatment-related toxic effects were similar in the two groups.
Forschungsfortschritt zum Mechanismus der durch TTFields induzierten Antitumor-Immunantwort
Authors: Yue Lan , Shaomin Zhang , Yun Pan , Minmin Wang , Guangdi Chen
Published: February 2025

Tumortherapiefelder (TTFields), eine biophysikalische Therapietechnologie, die elektrische Wechselfelder zur Hemmung der Tumorproliferation einsetzt, wurden von der US-amerikanischen Food and Drug Administration (FDA) für die Behandlung von neu diagnostizierten oder rezidivierenden Glioblastomen (GBM) und malignen Pleuramesotheliomen (MPM) zugelassen. Klinische Studien haben bestätigt, dass TTFields das Tumorwachstum effektiv verlangsamen und das Überleben der Patienten verlängern. In den letzten Jahren haben viele Forscher herausgefunden, dass TTFields Antitumor-Immunreaktionen induzieren können. Zu ihren Hauptmechanismen gehören die Hochregulierung der Infiltrationsquote und der Funktion von Immunzellen, die Induktion des immunogenen Zelltods von Tumorzellen, die Modulation immunbezogener Signalwege und die Hochregulierung der Expression von Immuncheckpoints. Behandlungsschemata, die TTFields mit der Immuntherapie kombinieren, entwickeln sich in der klinischen Praxis zu einem vielversprechenden Therapieansatz. Angesichts der zunehmenden Anzahl kürzlich veröffentlichter Studien zu diesem Thema geben wir einen aktualisierten Überblick über die Mechanismen und klinischen Auswirkungen von TTFields bei der Induktion von Antitumor-Immunreaktionen. Diese Übersicht hat nicht nur einen wichtigen Referenzwert für eine eingehende Untersuchung des Antikrebs-Mechanismus von TTFields, sondern bietet auch Einblicke in die zukünftige klinische Anwendung von TTFields.
STW 5-II FOR TREATMENT OF FUNCTIONAL GASTROINTESTINAL DISORDERS: MECHANISM AND CLINICAL EFFICACY
Authors: Tursi Antonio , Marinoni Beatrice , Privitera Antonino Carlo , Privitera Lorenzo , Danese Silvio
Published: February 2025

Background: Functional Dyspepsia (FD) is currently defined as episodic or recurrent epigastric pain or discomfort in the absence of organic diseases, lasting at least four weeks. FD is estimated to affect 7.2% of the worldwide population. Due to the underlying complex pathogenetic mechanisms, the therapy for FD is generally prescribed to treat the main symptoms experienced by the patient.
Summary: Recently, a new herbal formulation has been proposed for treating FD. This plant-based preparation, called STW 5-II, is a fixed combination of six hydroethanolic herbal extracts from bitter candy tuft, peppermint leaf, chamomile flower, licorice root, caraway fruit, and melissa leaf. STW 5-II has been shown to be more effective than placebo in several controlled studies and clinical scenarios, allowing for its recent introduction into several European markets.
Key Messages: This review aims to describe the mechanisms of action of this herbal drug, its current and potential clinical indications, and to explore future perspectives for its use.
Assessment of enteral nutrition adequacy in patients hospitalized in adult intensive care units: a cross-sectional study
Authors: Özşenel Ekmel Burak , Kahveci Güldan , Dağcı Selma , Beyaz Fatma , Basat Sema
Published: February 2025

Introduction: In the principles of intensive care, nutritional support is an important part of critical care. This study was conducted to evaluate the adequacy of enteral nutrition in patients hospitalised in adult intensive care units.

Methods: The present study was designed as a cross-sectional study and it was carried out on 124 patients who received enteral nutrition in the adult intensive care unit of a training and research hospital between 01.03.2022 and 01.04.2022. Patients who received parenteral nutrition during the one-month follow-up were excluded from the study. The study used the Enteral Nutrition Information Form and the baseline NRS-2002 score. Energy needs of patients were calculated by Schofield method and addition of stress factors. Daily energy intake was recorded for each patient every day during hospitalization. Backward stepwise logistic regression analysis, Shapiro-Wilk, Student-t, Mann-Whitney U, Kruskal-Wallis, Dunn-Bonferroni, Pearson chi-squared, and Fisher's exact tests were used to evaluate the data.

Results: Mean age of the patients was 70.9±16.7 years (21-98) and 58.9% were male. The mean baseline NRS-2002 score was 5.88±1.23. Enteral nutrition started an average of 2.4±2.2 days (range 0-18) after ICU hospitalization. The mean target energy intake according to Schofield method was 1772.9±284.3 kcal, while the actual intake was 1463.5±386.2 kcal. Only 37.1% of patients achieved the target dose, taking an average of 4.5±4.2 days (1-20) to reach it In 25% of patients, feeding was interrupted due to residual volumes exceeding 500 ml, with 54.8% of these receiving hypercaloric products. Patients with neurological and cardiac diagnoses had significantly higher rates of reaching the target dose (p=0.001), while those with interruptions due to high residual volumes had lower rates (p=0.003). Finally, the overall mortality rate was 59.7%.

Conclusion: More than half of the patients did not meet the goals set for enteral nutrition therapy. A lower baseline NRS-2002 score and low energy requirements facilitated goal attainment. Patients with cardiac or neurological conditions were more likely to reach the target nutritional dose. However, those fed with hypercaloric products experienced more interruptions due to excess residue and achieved the nutritional target less frequently.
Development of fall risk classification models for community-dwelling older adults using latent class analysis and machine learning
Authors: Bae Suyeong , Lee Mi Jung , Pak Daewoo , Yoo Eun-Young , Kim Jongbae , Hong Ickpyo
Published: February 2025

Introduction: To identify fall risk groups among community-dwelling older adults in South Korea and build a classification model by investigating risk-associated factors.
Methods: This cross-sectional study analyzed data of 9,231 older adults from the the 2020 Elderly Survey. We used latent class analysis to identify fall risk groups based on fall indicators. Thereafter, classification models were developed with these identified groups as outcome variables.
Results: Latent class analysis results indicated that a three-class model was more interpretable and fit the data better than other models. Among the models, the XGBoost algorithm displayed superior performance (accuracy = 0.70, precision = 0.69, recall = 0.70, F1-score = 0.68). Key variables associated with fall risk groups included self-rated health, cognitive function, recent healthcare use, and assistance needed in instrumental activities of daily living.
Conclusion: The study adopted a preventive approach by differentiating among low-, moderate-, and high-fall-risk groups, thus providing valuable insights for healthcare professionals. Identifying these risk factors can support the development of customized fall prevention programs for older adults.