bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting MGST1 Makes Non-Small Cell Lung Cancer Cells Sensitive to Radiotherapy by Epigenetically Enhancing ALOX15-Mediated Ferroptosis
Authors: Ma Yechen , Peng Yuping , Cheng Shulin , Jin Long 
Published: October 2024

Background:
Ferroptosis is closely related to radiotherapy resistance in multiple can-cers. Herein, the role of microsomal glutathione S-transferase 1 (MGST1) in regulating ferropto-sis and radiotherapy resistance in non-small cell lung cancer (NSCLC) was investigated.

Methods:
Radiation-resistant NSCLC cells (NCI-1299-IR and HCC827-IR cells) were estab-lished. After exposure to X-ray, cell proliferation and survival were assessed by colony formation assay and CCK-8 assay, and lipid ROS level was examined by the fluorophore BODIPY™ 581/591 C11. MDA, GSH, and Fe2+ levels were measured by ELISA kits. The molecular interac-tion was analyzed using ChIP and MSP assays.

Results:
Our results showed that RSL3 treatment greatly enhanced the radiotherapy sensitivity of NCI-1299-IR and HCC827-IR cells. It was subsequently revealed that MGST1 was highly ex-pressed in NCI-1299-IR and HCC827-IR cells than its parent cells, and silencing of MGST1 re-duced radioresistance of NCI-1299-IR and HCC827-IR cells by facilitating ferroptosis. Mechanis-tically, MGST1 knockdown greatly reduced HO-1 and DNMT1/3A protein levels, leading to re-duced DNA methylation on the ALOX15 promoter region, thereby epigenetically upregulating ALOX15 expression. As expected, the promoting effects of MGST1 silencing on radiosensitivity and ferroptosis in radiation-resistant NSCLC cells were strikingly eliminated by ALOX15 knock-down.

Conclusion:
MGST1 knockdown epigenetically enhanced radiotherapy sensitivity of NCSLC cells by promoting ALOX15-mediated ferroptosis through regulating the HO-1/DNMT1 pathway.

other:
None.
An Overview of the Phytochemical and Therapeutic Potential of Wrightia Tinctoria
Authors: Jurel Priyanka , Bahadur Shiv , Bajpai Meenakshi 
Published: October 2024

Introduction:
Several natural phytomedicines derived from Chinese herbs demonstrate
a wide range of pharmacological effects. Wrightia tinctoria (WT) is a small deciduous tree
known as sweet indrajao. It belongs to the Apocynaceae family. Many diseases have been treated
with this plant's phytoconstituents, such as skin disorders, dysenteric, diarrhea, and hair treatments.
In addition, the therapeutic elements of WT demonstrate significant anti-inflammatory and
anti-dandruff properties. However, there is a difference between this plant's preclinical and clinical
significance. The purpose of this study is to collect and evaluate the various chemical, medicinal,
and pharmacological characteristics of WT in relation to multiple disorders using preclinical
evidence. This will serve as a valuable foundation for researchers to explore its effectiveness in
clinical trials further.

Materials and Methods:
A comprehensive search was conducted across several databases, including
PubMed, Web of Science, Scopus, Academic Journals Embase, Google Scholar, and Science
Direct. The search utilized specific keywords such as "Wrightia tinctoria" as well as terms
like "Traditional Chinese Medicine," "Pharmacological activities," "Anti-cancer," "Anti-viral,"
"Anti-microbial," "Anti-psoriatic," "Anti-Inflammatory," "Quercetin" and their combinations
mainly from 1993 to 2024.

Results:
The pharmacological and therapeutic potential of WT is gathered and summarized based
on existing research reports. WT substances consist of various phytoconstituents, including flavonoids,
steroids, alkaloids, volatile oils, esters, and others. These components are primarily responsible
for the various pharmacological effects of WT, such as anti-oxidant, anti-bacterial, antifungal,
anti-diabetic, anti-cancer, anti-microbial, anti-inflammatory, and anti-ulcer effects.

Conclusion:
This review focuses on current research findings regarding WT's therapeutic potential
and pharmacological activities. Additionally, it addresses the major safety and toxicity issues
related to WT.
An Overview of Pharmacological Profile of Flavonoids as Potential Molecules of Therapeutic Importance
Authors: Kumar Abhay , Rakhi  , Kumar Vipul , Dahiya Saurabh , Kumar Sahil , Kumar Vijender 
Published: October 2024

Abstract:
A growing number of research investigations have shown the multiple health benefits of
flavonoids derived from plants, leading to interest in the field. Many recent studies have concentrated
on flavonoids effects on human health. Flavonoids are effective against a wide spectrum of bacteria,
viruses, and other pathogens. Numerous flavonoids have been demonstrated to possess antioxidative,
free radical scavenging, hepatoprotective, antiinflammatory, anticancer, and coronary heart disease
preventive properties. Some of novel flavonoids having therapeutic potential as new medication have
been identified which include hesperetin-5′-O-β-rhamnoglucoside, Resveratrol, Astragalin (AST)
Desmodinosides A-E: New Flavonoid C-glycosides, Apigenin, Luteolin, and Baicalein, rutin, hyperoside
etc. Some recent developments including clinical trials of a few of the flavonoids discussed in
the review provide a novel library of pharmacologically potential molecules which provides a paradigm
for the treatment of several ailments such as SARS-CoV-2, Alzheimer's disease, diabetes, angina
pectoris, Hepatitis C virus and Sickle cell disease (SCD) etc. The present review aims at updating
recent flavonoid advancements for various pharmacological actions, from conventional therapeutic
implications to upcoming clinical trials. We encourage researchers to focus on flavonoids for a variety
of medicinal applications since the industrial acceptance of these compounds will determine the future
growth of this field.
The PARK2_e01(-697) Polymorphism does not Associate with Susceptibility to Typhoid in Punjabi Population, Pakistan: A Case Control Study
Authors: Kousar Rizwana , Waheed Ayesha , Naz Rida , Raja Ghazala Kaukab , Kalsoom Umm-e , Latif Sadia 
Published: October 2024

Background:
SNP based association studies have revolutionized the field of biomed-icines. Enteric fever is a systemic disease with etiologic agents Salmonella enterica serovar typhi and paratyphi. It is a serious health issue worldwide and presents wide variations in incidence, rates, and severity. Previous investigations have revealed that genetic variations may lead to sus-ceptibility to typhoid fever. A current study was performed to investigate the potential association of PARK2_e01(−697) polymorphism with the susceptibility to typhoid in the Punjabi population.

Methods:
For this case-control study, blood samples obtained from typhoid patients with positive Typhidot or blood culture test (n=72) and healthy controls (n=73) were processed for DNA ex-traction. The polymorphism PARK2_e01(-697) analysis was carried out by using PCR and RFLP.

Results:
No allelic association was found between PARK2_e01(-697) and susceptibility to ty-phoid fever in the understudy population.

Conclusion:
This case control study is the demonstration of the non-association of PARK2_e01(-697) with typhoid in the Pakistani population. Future research, using a larger population size, will help to elucidate the role of PARK2_e01(-697) polymorphism in typhoid pathogenesis.
Synergistic Structural Inhibition of MMP-9 by Natural Flavonoids: A Natural Combinatorial Therapy against Cancer
Authors: Singh Mahendra Pratap , Shivhare Brijesh , Pandey Anand Kumar 
Published: October 2024

Introduction:
Cancer is the uncontrolled proliferation of cells leading to metastasis due
to genetic alterations resulting in oncogenes activation and tumor suppressor genes deactivation. It
is the 2nd leading cause of death across the world. MMP-9 or gelatinase B, plays an effective role
in ECM degradation, normal tissue turnover, and tissue remodelling. Overexpression of MMP-9
has been studied in almost all types of cancers proving the effective role of MMP-9 in accelerating
malignant conditions. Thus, targeting MMP-9 to treat cancer seems to be a potential strategy
to deal with adverse pathologies of cancer. Chemotherapy and radiotherapy are frequently utilized
for the treatment of cancer but are associated with diverse side effects. Flavonoids are natural compounds
frequently found in plants and have been analysed for the structural inhibition potential
against MMP-9 by several researchers to develop natural treatments against cancer, but none of
the flavonoids have landed into clinical use.

Methods:
In the present study, in-depth in-silico analysis to investigate the synergistic effects of
flavonoids for structural inhibition of MMP-9 was done.

Results:
The ADMET and bioactive properties analysis revealed effective drug-like properties of
the considered flavonoids. Principal component analysis of ADMET and bioactive properties revealed
high similarity in the chemical nature of luteolin and quercetin. Molecular docking analysis
of MMP-9 with the considered flavonoids individually revealed the highest effective binding energy
of luteolin. Combination docking analysis of MMP-9 with different combinations of flavonoids
led to the identification of two combinations including Quercetin with Genistein and Luteolin and
Genistein revealing high negative binding energies of -15.48kcal/mol and -15.31kcal/mol which
were significantly greater than the binding energies identified for respective ligands in individual
dockings.

Conclusion:
Thus, the present study put forward synergistic natural flavonoid combinations
against cancer via the MMP-9 inhibition approach that can be further evaluated to develop high-efficacy
treatments.
Preparations, Applications, Patents, and Marketed Formulations of Nanoemulsions - A Comprehensive Review
Authors: Chauhan Mansi , Mazumder Rupa , Rani Anjana , Mishra Rashmi , Pal Rashmi Saxena 
Published: October 2024

Abstract:
Nanoemulsions have emerged as versatile colloidal dispersions with promising applications
in various fields, including pharmaceuticals, food, and cosmetics. These nano-sized emulsions,
stabilized by surfactants, offer unique advantages such as enhanced ingredient penetration
efficacy and versatile dosage forms. This article provides an extensive overview of nanoemulsions,
covering their composition, methods of preparation, and applications in drug delivery, the
food industry, and cosmetics. Various high-energy and low-energy methods for nanoemulsion preparation
are discussed, along with their advantages and limitations. Additionally, the article highlights
the potential of nanoemulsions in improving drug bioavailability, stability, and therapeutic
efficacy, especially in oral, topical, parenteral, intranasal, ocular, and pulmonary drug delivery.
Furthermore, nanoemulsions are explored as carriers for encapsulating flavoring agents, nutraceuticals,
and natural preservatives in the food industry, as well as their use in cosmetic formulations.
Current clinical trials involving nanoemulsions and recent patents in the field are also summarized,
providing insights into ongoing research and development efforts. Lastly, a selection of
marketed nanoemulsion formulations is presented, showcasing their practical applications and
commercial availability. Overall, nanoemulsions hold great promise as effective delivery systems
with broad applications across various industries.
Features of atherosclerotic lesions of the coronary arteries in patients with myocardial infarction and concomitant newly diagnosed hypothyroidism
Authors: Gridneva Yu. Yu. , Chesnikova A. I. , Khripun A. V. , Safronenko V. A. , Pashchenko E. V. 
Published: October 2024

Objective: to assess the incidence of newly diagnosed subclinical and manifest hypothyroidism in patients with ST-segment elevation myocardial infarction (STEMI) and to identify angiographic features of coronary artery lesions in this combined pathology.Materials and methods: in all patients with STEMI, the level of thyroid-stimulating hormone (TSH) was determined, and thyroid function was assessed if the TSH level deviated from the norm. Stage I of the study included 441 patients, stage II included 133 patients with STEMI. Depending on the presence of newly diagnosed hypothyroidism, patients were divided into 3 groups: 1st — patients without hypothyroidism (n = 57), 2A group — with subclinical hypothyroidism (n = 42) and 2B group — with manifest hypothyroidism (n = 34). All patients underwent coronary angiography and percutaneous coronary intervention.Results: newly diagnosed hypothyroidism occurred in 27.44% of patients with STEMI: subclinical — in 19.73%, manifest — in 7.7% of cases. Patients with concomitant overt hypothyroidism had significantly more severe atherosclerotic lesions of the coronary arteries compared to patients without hypothyroidism.Conclusion: a high incidence of newly diagnosed hypothyroidism in patients with STEMI was established (27.44% of cases). Multivessel coronary lesions were recorded more often in patients with overt hypothyroidism than in patients with subclinical hypothyroidism and without hypothyroidism.
Unlocking the Potential of Secondary Data for Public Health Research: Retrospective Study With a Novel Clinical Platform
Authors: Gundler Christopher , Gottfried Karl , Wiederhold Alexander Johannes , Ataian Maximilian , Wurlitzer Marcus , Gewehr Jan Erik , Ückert Frank 
Published: October 2024

Background
Clinical routine data derived from university hospitals hold immense value for health-related research on large cohorts. However, using secondary data for hypothesis testing necessitates adherence to scientific, legal (such as the General Data Protection Regulation, federal and state protection legislations), technical, and administrative requirements. This process is intricate, time-consuming, and susceptible to errors.

Objective
This study aims to develop a platform that enables clinicians to use current real-world data for testing research and evaluate advantages and limitations at a large university medical center (542,944 patients in 2022).

Methods
We identified requirements from clinical practitioners, conceptualized and implemented a platform based on the existing components, and assessed its applicability in clinical reality quantitatively and qualitatively.

Results
The proposed platform was established at the University Medical Center Hamburg-Eppendorf and made 639 forms encompassing 10,629 data elements accessible to all resident scientists and clinicians. Every day, the number of patients rises, and parts of their electronic health records are made accessible through the platform. Qualitatively, we were able to conduct a retrospective analysis of Parkinson disease over 777 patients, where we provide additional evidence for a significantly higher proportion of action tremors in patients with rest tremors (340/777, 43.8%) compared with those without rest tremors (255/777, 32.8%), as determined by a chi-square test (P<.001). Quantitatively, our findings demonstrate increased user engagement within the last 90 days, underscoring clinicians’ increasing adoption of the platform in their regular research activities. Notably, the platform facilitated the retrieval of clinical data from 600,000 patients, emphasizing its substantial added value.

Conclusions
This study demonstrates the feasibility of simplifying the use of clinical data to enhance exploration and sustainability in scientific research. The proposed platform emerges as a potential technological and legal framework for other medical centers, providing them with the means to unlock untapped potential within their routine data.
Associations Between Acute COVID-19 Symptom Profiles and Long COVID Prevalence: Population-Based Cross-Sectional Study
Authors: Hirschtick Jana L , Slocum Elizabeth , Xie Yanmei , Power Laura E , Elliott Michael R , Orellana Robert C , Fleischer Nancy L 
Published: October 2024

Abstract

Background
Growing evidence suggests that severe acute COVID-19 illness increases the risk of long COVID (also known as post–COVID-19 condition). However, few studies have examined associations between acute symptoms and long COVID onset.

Objective
This study aimed to examine associations between acute COVID-19 symptom profiles and long COVID prevalence using a population-based sample.

Methods
We used a dual mode (phone and web-based) population-based probability survey of adults with polymerase chain reaction–confirmed SARS-CoV-2 between June 2020 and May 2022 in the Michigan Disease Surveillance System to examine (1) how acute COVID-19 symptoms cluster together using latent class analysis, (2) sociodemographic and clinical predictors of symptom clusters using multinomial logistic regression accounting for classification uncertainties, and (3) associations between symptom clusters and long COVID prevalence using modified Poisson regression.

Results
In our sample (n=4169), 15.9% (n=693) had long COVID, defined as new or worsening symptoms at least 90 days post SARS-CoV-2 infection. We identified 6 acute COVID-19 symptom clusters resulting from the latent class analysis, with flu-like symptoms (24.7%) and fever (23.6%) being the most prevalent in our sample, followed by nasal congestion (16.4%), multi-symptomatic (14.5%), predominance of fatigue (10.8%), and predominance of shortness of breath (10%) clusters. Long COVID prevalence was highest in the multi-symptomatic (39.7%) and predominance of shortness of breath (22.4%) clusters, followed by the flu-like symptom (15.8%), predominance of fatigue (14.5%), fever (6.4%), and nasal congestion (5.6%) clusters. After adjustment, females (vs males) had greater odds of membership in the multi-symptomatic, flu-like symptom, and predominance of fatigue clusters, while adults who were Hispanic or another race or ethnicity (vs non-Hispanic White) had greater odds of membership in the multi-symptomatic cluster. Compared with the nasal congestion cluster, the multi-symptomatic cluster had the highest prevalence of long COVID (adjusted prevalence ratio [aPR] 6.1, 95% CI 4.3‐8.7), followed by the predominance of shortness of breath (aPR 3.7, 95% CI 2.5‐5.5), flu-like symptom (aPR 2.8, 95% CI 1.9‐4.0), and predominance of fatigue (aPR 2.2, 95% CI 1.5‐3.3) clusters.

Conclusions
Researchers and clinicians should consider acute COVID-19 symptom profiles when evaluating subsequent risk of long COVID, including potential mechanistic pathways in a research context, and proactively screen high-risk patients during the provision of clinical care.
Disambiguating Clinical Abbreviations by One-to-All Classification: Algorithm Development and Validation Study
Authors: Sung Sheng-Feng , Hu Ya-Han , Chen Chong-Yan 
Published: October 2024

Abstract

Background
Electronic medical records store extensive patient data and serve as a comprehensive repository, including textual medical records like surgical and imaging reports. Their utility in clinical decision support systems is substantial, but the widespread use of ambiguous and unstandardized abbreviations in clinical documents poses challenges for natural language processing in clinical decision support systems. Efficient abbreviation disambiguation methods are needed for effective information extraction.

Objective
This study aims to enhance the one-to-all (OTA) framework for clinical abbreviation expansion, which uses a single model to predict multiple abbreviation meanings. The objective is to improve OTA by developing context-candidate pairs and optimizing word embeddings in Bidirectional Encoder Representations From Transformers (BERT), evaluating the model’s efficacy in expanding clinical abbreviations using real data.

Methods
Three datasets were used: Medical Subject Headings Word Sense Disambiguation, University of Minnesota, and Chia-Yi Christian Hospital from Ditmanson Medical Foundation Chia-Yi Christian Hospital. Texts containing polysemous abbreviations were preprocessed and formatted for BERT. The study involved fine-tuning pretrained models, ClinicalBERT and BlueBERT, generating dataset pairs for training and testing based on Huang et al’s method.

Results
BlueBERT achieved macro- and microaccuracies of 95.41% and 95.16%, respectively, on the Medical Subject Headings Word Sense Disambiguation dataset. It improved macroaccuracy by 0.54%‐1.53% compared to two baselines, long short-term memory and deepBioWSD with random embedding. On the University of Minnesota dataset, BlueBERT recorded macro- and microaccuracies of 98.40% and 98.22%, respectively. Against the baselines of Word2Vec + support vector machine and BioWordVec + support vector machine, BlueBERT demonstrated a macroaccuracy improvement of 2.61%‐4.13%.

Conclusions
This research preliminarily validated the effectiveness of the OTA method for abbreviation disambiguation in medical texts, demonstrating the potential to enhance both clinical staff efficiency and research effectiveness.
Enhancing Mixed Reality Simulation Training Technology With Real-Time Performance Visualization: Mixed Methods Study With Medical First Responders
Authors: Zechner Olivia , Schrom-Feiertag Helmut , Wespi Rafael , Pretolesi Daniele , Nguyen Quynh , Tscheligi Manfred 
Published: October 2024

Abstract

Background
Mixed reality (MR) simulation training is emerging in paramedical education as a way to practice responding to stress-intensive scenarios like mass casualty incidents in a safe and controlled environment. Current training platforms, however, lack real-time stress and human performance monitoring tools.

Objective
The study aims to enhance MR training for medical first responders through real-time evaluation of performance and stress levels, leveraging biosignal monitoring and advanced analytics to allow instructors to tailor feedback and maintain optimal challenge and safety levels.

Methods
The study includes a structured, multiphase approach including initial requirement gathering (structured interviews and cocreation workshops), an online design survey, iterative prototype development, and a field trial (including training observations and interviews). Data were collected from 5 end user consortium members across Europe. Quantitative data from checklists were analyzed using frequencies and percentages to understand feature usage and event occurrences. Qualitative data from semistructured interviews and cocreation workshops were transcribed, coded, and subjected to thematic analysis to identify patterns and insights into the usability and effectiveness of the enhanced features in the MR training.

Results
The study identified a number of requirements that medical first responders have for an MR training system, including requirements not included in currently available solutions. A total of 80 performance metrics were initially identified and refined to a set of 54 metrics, which were categorized into key performance indicator groups such as scene safety, triage performance, and communication. Requirements for smart wearables to monitor stress levels are provided and highlight the importance of a user-centered design process to provide users with effective tools that fit their needs. Stress visualization preferences are described in the form of a dashboard as well as in virtual environments surrounding the avatar. Using an iterative design process and user feedback, a training system was developed, integrating real-time performance tracking and stress monitoring. The field trial provided insights into the practical use of these features during a real training exercise, showed interaction preferences between trainer and trainees, and highlighted further improvement opportunities.

Conclusions
This research enhances MR training for paramedics by integrating real-time performance metrics and stress indicators based on a human-centered design approach that aligns with end user needs, thereby laying the foundation for developing more effective and immersive training solutions for high-stress professions.