bluuebunny/crossref_metadata_2025 huggingface dataset:
Collaboration between ambulance services and primary care: a scoping review protocol
Authors: Hedqvist Ann-Therese , Ljungholm Linda , Svensson Anders , Holmberg Mats , Fagerström Cecilia , Elmqvist Carina , Forsgärde Elin-Sofie
Published: January 2025

Introduction

Making decisions about the appropriate level of care is a significant challenge for healthcare professionals, especially when older patients present with diffuse symptoms. Collaboration between ambulance services and primary care may promote a comprehensive understanding of patient needs. However, such collaboration remains limited, potentially leading to lower care quality and higher costs. There is a need to understand how collaboration can be effectively implemented. This scoping review aims to explore existing models of collaboration between ambulance services and primary care, identifying their characteristics, outcomes and current research gaps.

Methods and analysis

This scoping review will follow the methodological framework proposed by Arksey and O’Malley, supplemented with recommendations from the Joanna Briggs Institute Handbook for Scoping Reviews. A comprehensive literature search will be conducted in PubMed, CINAHL, Web of Science and Scopus. In addition, Google Scholar, Overton, SwePub and the Swedish national library database Libris will be searched for relevant grey literature. The review will include studies published from January 2014 to the present. Data will be analysed descriptively, with findings categorised by collaboration models and patterns identified through inductive analysis to address the research questions. The review will apply the Preferred Reporting Items for Systematic Review and Meta-Analysis extension for Scoping Reviews to present the results.

Ethics and dissemination

This review is the first stage of an overarching research study to develop a model for extended collaboration between ambulance services and primary care (the ECAP project). Results will be disseminated through peer-reviewed publications, conference presentations and sharing with ambulance services and primary care stakeholders to inform practice and policy. This scoping review protocol has been registered on the Open Science Framework (
https://osf.io/nrkm5/
). No participants will be involved at this stage, and the selected literature is publicly available, so no ethical approval will be required for this scoping review.
Targeting MXD1 sensitises pancreatic cancer to trametinib
Authors: Zhang Shaoping , Deng Shuang , Liu Ji , Liu Shuang , Chen Ziming , Liu Shaoqiu , Xue Chunling , Zeng Lingxing , Zhao Hongzhe , Xu Zilan , Zhao Sihan , Zhou Yifan , Peng Xinyi , Wu Xiaoyu , Bai Ruihong , Wu Shaojia , Li Mei , Zheng Jian , Lin Dongxin , Zhang Jialiang , Huang Xudong
Published: January 2025

Background

The resistance of pancreatic ductal adenocarcinoma (PDAC) to trametinib therapy limits its clinical use. However, the molecular mechanisms underlying trametinib resistance in PDAC remain unclear.

Objective

We aimed to illustrate the mechanisms of resistance to trametinib in PDAC and identify trametinib resistance-associated druggable targets, thus improving the treatment efficacy of trametinib-resistant PDAC.

Design

We established patient-derived xenograft (PDX) models and primary cell lines to conduct functional experiments. We also applied single-cell RNA sequencing, Assay for Transposase-accessible Chromatin with sequencing and Cleavage Under Targets and Tagmentation sequencing to explore the relevant molecular mechanism.

Results

We have identified a cancer cell subpopulation featured by hyperactivated viral mimicry response in trametinib-resistant PDXs. We have demonstrated that trametinib treatment of PDAC PDXs induces expression of transcription factor MAX dimerisation protein 1 (MXD1), which acts as a cofactor of histone methyltransferase mixed lineage leukaemia 1 to increased H3K4 trimethylation in transposable element (TE) loci, enhancing chromatin accessibility and thus the transcription of TEs. Mechanistically, enhanced transcription of TEs produces excessive double-stranded RNAs, leading to the activation of viral mimicry response and downstream oncogenic interferon-stimulated genes. Inhibiting MXD1 expression can recover the drug vulnerability of trametinib-resistant PDAC cells to trametinib.

Conclusions

Our study has discovered an important mechanism for trametinib resistance and identified MXD1 as a druggable target in treatment of trametinib-resistant PDAC.
Determinants of medication adherence in patients with acute coronary syndrome: a secondary analysis of a randomised clinical trial
Authors: Kha Richard , Min Haeri , Marschner Simone , Mahendran Shehane , Thiagalingam Aravinda , Poulter Rohan , Redfern Julie , Brieger David , Thompson Peter L , Hillis Graham S , Collins Nicholas , Shetty Pratap , McGrady Michele , Hamilton-Craig Christian , Kangaharan Nadarajah , Atherton John , Maiorana Andrew , Klimis Harry , Juergens Craig , Chow Clara K
Published: January 2025

Background

Coronary heart disease (CHD) remains a leading cause of mortality and disability worldwide. Approximately half of the patients who have had a prior hospital admission for CHD will have a recurrent coronary event, with the majority of these occurring within 12 months. Despite well-established evidence-based therapies, medication non-adherence is highly prevalent and reasons for medication non-adherence are poorly understood. This study evaluates factors influencing adherence to secondary prevention medications in people with acute coronary syndrome (ACS).

Methods

We performed a secondary analysis of TEXT messages to improve MEDication adherence and Secondary prevention after ACS (TEXTMEDS), a single-blind randomised clinical trial of 1424 patients with ACS from 18 hospitals across Australia. The primary outcome was self-reported medication adherence to each of up to five classes of guideline-recommended cardioprotective medications indicated for secondary prevention after ACS. Patients were followed up at 6-month and 12-month time points and were defined as adherent if at both time points, the proportion of indicated medications taken was >80% (>24/30 days in the preceding 1 month) for all five classes if not otherwise contraindicated. Logistic regression analysis and the Least Absolute Shrinkage and Selection Operator regularisation technique were used to assess the effect of sociodemographic and clinical factors on medication adherence.

Results

The analyses included 1379 participants with complete adherence data (mean age 58.5±10.7 years; 1095 (79.4%) men). The following variables were associated with adherence to cardiovascular medications at both 6 and 12 months: greater number of total medications taken (OR: 1.33; 95% CI: 1.25 to 1.42) and attending a cardiac rehabilitation programme (1.47; 95% CI: 1.17 to 1.86). In contrast, female sex (0.67; 95% CI: 0.50 to 0.90) and physical disability (0.43; 95% CI: 0.23 to 0.77) were associated with lower likelihood of medication adherence.

Conclusions

Sociodemographic and clinical factors may influence medication adherence. Greater awareness, discussion and monitoring of these factors during patient follow-up may help improve medication adherence.

Trial registration number

Australian New Zealand Clinical Trials Registry; URL:https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=364448;registration number: ACTRN12613000793718.
A Roadmap for Simulation-Based Testing of Autonomous Cyber-Physical Systems: Challenges and Future Direction
Authors: Birchler Christian , Khatiri Sajad , Rani Pooja , Kehrer Timo , Panichella Sebastiano
Published: January 2025

As the era of autonomous cyber-physical systems (ACPSs), such as unmanned aerial vehicles and self-driving cars, unfolds, the demand for robust testing methodologies is key to realizing the adoption of such systems in real-world scenarios. However, traditional software testing paradigms face unprecedented challenges in ensuring the safety and reliability of these systems. In response, this paper pioneers a strategic roadmap for simulation-based system-level testing of ACPSs, specifically focusing on autonomous systems. Our paper discusses the relevant challenges and obstacles of ACPSs, focusing on test automation and quality assurance, hence advocating for tailored solutions to address the unique demands of autonomous systems. While providing concrete definitions of test cases within simulation environments, we also accentuate the need to create new benchmark assets and the development of automated tools tailored explicitly for autonomous systems in the software engineering community. This paper not only highlights the relevant, pressing issues the software engineering community should focus on (in terms of practices, expected automation, and paradigms), but it also outlines ways to tackle them. By outlining the various domains and challenges of simulation-based testing/development for ACPSs, we provide directions for future research efforts.
AI for DevSecOps: A Landscape and Future Opportunities
Authors: Fu Michael , Pasuksmit Jirat , Tantithamthavorn Chakkrit
Published: January 2025

DevOps has emerged as one of the most rapidly evolving software development paradigms. With the growing concerns surrounding security in software systems, the DevSecOps paradigm has gained prominence, urging practitioners to incorporate security practices seamlessly into the DevOps workflow. However, integrating security into the DevOps workflow can impact agility and impede delivery speed. Recently, the advancement of artificial intelligence (AI) has revolutionized automation in various software domains, including software security. AI-driven security approaches, particularly those leveraging machine learning or deep learning, hold promise in automating security workflows. They have the potential to reduce manual efforts and can be incorporated into DevOps practices to support consistent delivery speed while aligning with the principles of the DevSecOps paradigm. This paper seeks to contribute to the critical intersection of AI and DevSecOps by presenting a comprehensive landscape of AI-driven security techniques applicable to DevOps and identifying avenues for enhancing security, trust, and efficiency in software development processes. We analyzed 99 research papers spanning from 2017 to 2023. Specifically, we address two key research questions (RQs). In RQ1, we identified 12 security tasks associated with the DevSecOps process and reviewed existing AI-driven security approaches, the problems they addressed, and the 65 benchmarks used to evaluate those approaches. Drawing insights from our findings, in RQ2, we discussed state-of-the-art AI-driven security approaches, highlighted 15 challenges in existing research, and proposed 15 corresponding avenues for future opportunities.
Differentially Private Real Time Pricing Control for Smart grids
Authors: Ghosh Soumyadyuti , Maiti Suman , Mukhopadhyay Debdeep , Dey Soumyajit
Published: January 2025

Smart meters provide fine-grained power usage profiles of consumers to various utility providers, thus facilitating multiple grid functionalities such as load monitoring, real-time pricing, demand response, etc. However, information leakage from such usage profiles reveals consumers’ private day-to-day life patterns and their home presence/absence, as the state-of-the-art metering strategies lack adequate security and privacy measures. Since Smart grid communication infrastructure supports low bandwidth, it prohibits the usage of computation-intensive cryptographic solutions. Among different privacy-preserving smart meter streaming methods, data manipulation techniques can easily be implemented in smart meters and do not require installing any storage devices or alternative energy sources. For this purpose, Differential Privacy (DP) is widely adopted in the literature due to its solid mathematical foundation. However, the effect of such manipulations on the Real Time Pricing (RTP) control is worth exploring since pricing signals operate in a closed-loop between consumers and utilities. This brings up the privacy-utility trade-off problem between the user's achieved privacy and the performance of the pricing loop of Smart grids, an area where the characterization between privacy and pricing control performance is not yet established. We analytically highlight such privacy-utility trade-off in the closed-loop RTP systems in terms of achieved privacy and the overall generation scheduling errors. We utilize the notion of

\(w\)

-event privacy
and present a real-time pricing aware differential privacy scheme that promises strong user privacy and guarantees pricing signal stabilization irrespective of the privacy level of the DP mechanism. Finally, we show the efficiency and robustness of our scheme by performing extensive experimental validation on MATLAB and, subsequently, on an in-house smart meter test bed.
NADPH Oxidases: Redox Regulation of Cell Homeostasis & Disease
Authors: Kračun Damir , Lopes Lucia R. , Cifuentes-Pagano Eugenia , Pagano Patrick J.
Published: January 2025

The redox signaling network in mammals has garnered enormous interest and taken on major biological significance in recent years as the scope of NADPH oxidases (NOXs) as regulators of physiological signaling and cellular degeneration has grown exponentially. All NOX subtypes have in common the capacity to generate reactive oxygen species (ROS) superoxide anion (O2.-) and/or hydrogen peroxide (H2O2). A baseline, normal level of ROS formation supports a wide range of processes under physiological conditions. A disruption in redox balance caused by either the suppression or "super" induction of NOX off balance with antioxidant systems is associated with myriad diseases and cell/tissue damage. Over the past two to three decades sour understanding of NOXs has progressed from almost entirely a phagocyte-, antimicrobial-centered perspective to that of a family of enzymes that is vital to broad cellular function and organismal homeostasis. It is becoming increasingly evident that highly regulated, targeted oxidative protein modifications are elicited in a spatiotemporal manner and initiated at cell membranes in humans by seven NOX isoforms (NOXs 1, 2, 3, 4, 5 and DUOXs 1 & 2). In a sense, this renders NOX-ROS signaling akin to that of other second messenger systems involving localized Ca2+ dynamics and tyrosine kinase transactivation. Accordingly, the study of ROS compartmentalization in subcellular organelles has been shown to be crucial to elucidating their role in cell phenotype modulation under physiological and pathophysiological conditions. The NOXs are as distinct in their distribution and activation as they are in their cellular functions, ranging from host defense, second messenger PTMs to transcriptional, epigenetic and (de)differentiating effects. The review integrates past knowledge in the field with new focus areas on the leading-edge of NOX-centered ROS signaling including how a new wave of structural information provides insights for NOX biology and targeted therapies.
Supplemental Table 5 from Single-Cell RNA Sequencing before and after Light Chain Escape Reveals Intrapatient Multiple Myeloma Subpopulations with Divergent Osteolytic Gene Expression
Authors: Ohlstrom Denis , Walker Zachary J. , Pandey Abhishek , Davis Lorraine N. , Engel Krysta L. , Pan Zenggang , Forsberg Peter A. , Mark Tomer M. , Gillen Austin E. , Sherbenou Daniel W.
Published: January 2025

Top 15 genes increased in diagnosis vs relapsed LCE-MM.
Supplemental Table 2 from Single-Cell RNA Sequencing before and after Light Chain Escape Reveals Intrapatient Multiple Myeloma Subpopulations with Divergent Osteolytic Gene Expression
Authors: Ohlstrom Denis , Walker Zachary J. , Pandey Abhishek , Davis Lorraine N. , Engel Krysta L. , Pan Zenggang , Forsberg Peter A. , Mark Tomer M. , Gillen Austin E. , Sherbenou Daniel W.
Published: January 2025

Top 15 genes higher in LCE-MM vs IGH-MM at diagnosis.
Supplemental Figure 7 from Single-Cell RNA Sequencing before and after Light Chain Escape Reveals Intrapatient Multiple Myeloma Subpopulations with Divergent Osteolytic Gene Expression
Authors: Ohlstrom Denis , Walker Zachary J. , Pandey Abhishek , Davis Lorraine N. , Engel Krysta L. , Pan Zenggang , Forsberg Peter A. , Mark Tomer M. , Gillen Austin E. , Sherbenou Daniel W.
Published: January 2025

The IGH-MM Gene Signature Was Not Associated with Adverse Prognosis.
Supplemental Figure 4 from Single-Cell RNA Sequencing before and after Light Chain Escape Reveals Intrapatient Multiple Myeloma Subpopulations with Divergent Osteolytic Gene Expression
Authors: Ohlstrom Denis , Walker Zachary J. , Pandey Abhishek , Davis Lorraine N. , Engel Krysta L. , Pan Zenggang , Forsberg Peter A. , Mark Tomer M. , Gillen Austin E. , Sherbenou Daniel W.
Published: January 2025

Oxidative Phosphorylation Pathway Genes Overexpressed in LCE-MM.
Figure 6 from Single-Cell RNA Sequencing before and after Light Chain Escape Reveals Intrapatient Multiple Myeloma Subpopulations with Divergent Osteolytic Gene Expression
Authors: Ohlstrom Denis , Walker Zachary J. , Pandey Abhishek , Davis Lorraine N. , Engel Krysta L. , Pan Zenggang , Forsberg Peter A. , Mark Tomer M. , Gillen Austin E. , Sherbenou Daniel W.
Published: January 2025

The LCE-multiple myeloma (MM) subpopulation conferred a poor prognosis and represented a genetic subclone of MM cells. A, FGFR3 expression distribution was high across all MM cells at diagnosis, but low or undetectable in normal cell populations, supporting clonal distribution of t(4;14) in all malignant cells. B and C, InferCNV analysis identified clonal chromosome 1 gain and chromosome 13 loss in both subpopulations, consistent with findings by FISH. D, Alluvial plot showing that seven subclones were present at diagnosis, five were eliminated with treatment, and two persisted across timepoints. E, InferCNV also identified a chromosome 19 gain that was subclonal and mostly specific to LCE-MM (left), and this increased in proportion with the disease progression (box and whiskers show median, quartiles, and 1.5 times the interquartile range). F, InferCNV also detected a chromosome 22 gain in a subset of LCE-MM at diagnosis (left), which increased in proportion over time. G, Hematoxylin and eosin staining of bone marrow samples contained some large plasmablasts at diagnosis, but at first relapse the bone marrow consisted of predominantly plasmablasts. H, Ki67 staining from samples at diagnosis were positive in 10% of cells, increased to 50%–60% at first relapse. Rel, relapse; R/R, relapsed/refractory timepoint.
Association of Mobile Stroke Unit Care and Spending, Utilization, and Death in New York City
Authors: Khullar Dhruv , Navi Babak B. , Mir Saad , Fink Matthew E. , Tinapay Luisa , Asaeda Glenn , Kaushal Rainu , Pareek Eshani , Bond Amelia M.
Published: January 2025

Background

Transport by mobile stroke units (MSUs), which provide access to computed tomography scanning and intravenous blood pressure medications and thrombolytics, reduces time to treatment and may improve short‐term functional outcomes for patients with acute stroke. The longer‐term clinical and financial impacts remain incompletely understood. The aim of the study was to determine whether MSU care is associated with better health, utilization, and spending outcomes for patients with suspected acute stroke.

Methods and Results

This was a retrospective, observational study of Medicare patients transported by MSUs versus traditional ambulances in New York City, from October 2016 to December 2019. The study included 167 Medicare patients with suspected acute stroke transported by MSU and 2518 propensity score–matched controls. Primary outcomes included length of stay and discharge destination at the index hospitalization, as well as risk of repeat hospitalization, number of emergency department visits, total costs of care, and death at 1 year. Of 167 patients (mean age, 79.9 years; 56.3% women) transported by an MSU for suspected acute stroke, 61.1% had an ischemic stroke/transient ischemic attack, 7.8% had an intracerebral hemorrhage, and 31.1% had a stroke mimic or other diagnosis. Compared with propensity score–matched control patients, MSU patients were significantly more likely to receive tissue‐type plasminogen activator (49.9% versus 9.4%; difference, 37.5 percentage points [95% CI, 30.2–45.6];
P
<0.001) but experienced similar lengths of stay (5.9 versus 6.7 days,
P
=0.13) and were similarly likely to be discharged to a skilled nursing facility (15.6% versus 15.1%,
P
=0.86). At 1 year, MSU patients had a mortality rate of 21.6%, and control patients had a mortality rate of 28.4%, although the difference did not reach statistical significance (difference, 6.8 percentage points [95% CI, −13.3 to 0.3];
P
=0.058). They had similar rates of any repeat hospitalization (24% versus 23.2%,
P
=0.82) and emergency department visits without hospitalization (14% versus 12%,
P
=0.86), and there were no significant differences in total spending or specific types of spending.

Conclusions

In this study of patients presenting with suspected acute stroke in New York City, transport by MSUs, compared with traditional ambulances, was associated with a trend toward a lower mortality rate at 1 year. Prospective trials and replication in other regions are warranted.
Prognostic Value of D‐Dimer in Acute Type A Aortic Dissection and Intramural Hematoma: Observations from the Acute Aortic Syndrome Group of the Registry of Acute Non‐Traumatic Chest Pain in China
Authors: Qiu Lingyue , Ji Qingwei , Miao Huangtai , Long Meiying , Gong Ming , Ye Jing , Liu Tianxiao , Zhang Tianlong , Huang Zhaohe , Liu Yan , Yin Na , Wu Xiaoyan , Shi Ying , Zeng Huayuan , Liu Ling , Lin Yingzhong , Lyu Liwen , Chen Wei , Su Hua , Shi Guoping , Gao Hai , Zhang Hongjia
Published: January 2025

Background

Acute type A aortic dissection (AAD) and acute type A intramural hematoma (AIMH) are life‐threatening conditions with high mortality rates, and prognostic indicators are critical for guiding urgent treatment decisions. We assessed the prognostic significance of admission D‐dimer levels in patients with AAD and AIMH.

Methods and Results

The prospective, multicenter, observational study in China recruited participants from 2013 to 2019. Patients with AAD and AIMH were respectively categorized into quartiles based on admission D‐dimer levels. Cox regression analysis was used to assess the association between D‐dimer levels and mortality. A total of 3132 patients with AAD (mean age: 50.63 years [SD, 12.56]) and 353 patients with AIMH (mean age: 59.63 years [SD, 11.00]) were included. In patients with AAD, overall mortality rates increased across D‐dimer quartiles: 13.7% (Q1, ≤0.72 mg/L), 16.7% (Q2, 0.72–1.91 mg/L), 22.8% (Q3, 1.91–4.21 mg/L), and 28.5% (Q4, 4.21–20.00 mg/L). In patients with AIMH, mortality rates by quartile were 3.4% (Q1, ≤0.51 mg/L), 5.7% (Q2, 0.51–1.25 mg/L), 4.6% (Q3, 1.25–3.44 mg/L), and 10.2% (Q4, 3.44–20.00 mg/L). After adjusting for confounders, D‐dimer was an independent predictor of overall mortality (hazard ratio [HR], 1.42 [95% CI, 1.11–1.80]) and in‐hospital mortality (HR, 1.47 [95% CI, 1.13–1.92]) in patients with AAD. D‐dimer levels were not significantly associated with the overall (HR, 2.61 [95% CI, 0.70–9.73]) or in‐hospital mortality (HR, 1.78 [95% CI, 0.44–7.24]) of patients with AIMH by multivariable adjustment.

Conclusions

Elevated admission D‐dimer levels are independently associated with higher mortality in patients with AAD but are not significantly associated with prognosis in patients with AIMH. Our findings suggest that D‐dimer may serve as a useful prognostic marker in patients with AAD.

Registration

www.chictr.org.cn
. Unique identifier: ChiCTR230006854.
Disopyramide Revisited for Treatment of Symptomatic Obstructive Hypertrophic Cardiomyopathy: Efficacy and Safety in Patients Treated for at Least 5 Years
Authors: Massera Daniele , Sherrid Mark V. , Adlestein Elizabeth , Bokhari Nadia , Alvarez Isabel C. , Wu Woon Y. , Reuter Maria C. , Maron Martin S. , Maron Barry J. , Rowin Ethan J.
Published: January 2025

Background

Disopyramide is used to treat heart failure symptoms in patients with obstructive hypertrophic cardiomyopathy (HCM) with known medium‐term efficacy and safety, while long‐term outcomes are unknown.

Methods and Results

A total of 92 consecutive patients with symptomatic obstructive HCM with peak left ventricular outflow tract gradients of ≥30 mm Hg at rest or with provocation who were maintained on disopyramide for ≥5 years at 2 dedicated HCM centers were included: 92 patients; mean age, 62.5 years; 54% women; treated with disopyramide for median 7.2 years (left ventricular wall thickness 18±4 mm; median peak outflow gradient 95 mm Hg). At last follow‐up, 62 (67%) patients continued disopyramide, including 57 with symptom improvement ≥1 New York Heart Association class. The other 30 (33%) patients discontinued disopyramide due primarily to incomplete symptom resolution and required surgical myectomy or alcohol septal ablation (n=23) at 7.4 years from initiation. With disopyramide, resting left ventricular outflow gradients were reduced by 37% (to median 19 mm Hg), and provoked gradients decreased by 57% (to median 41 mm Hg), with no residual outflow obstruction (<30 mm Hg at rest or with provocation) in 42 (46%) patients and no change in ejection fraction (69%±6% versus 69%±9%,
P
=0.51). Ventricular tachyarrhythmias and left ventricular systolic dysfunction were uncommon (n=3 and n=1) and were not attributed to disopyramide. Death on disopyramide was exceedingly rare (n=3 [5%]) and non–HCM‐related occurring at age ≥90 years.

Conclusions

In patients with obstructive HCM, disopyramide is safe and effective at relieving heart failure symptoms from outflow obstruction in a subgroup of patients who were maintained on disopyramide for >5 years.
Assessing the Likelihood of Procedural Intubation During Percutaneous Coronary Intervention
Authors: Herson Megan , Tan Sean , O'Brien Joseph , Teoh Zhi Hao , Manmathan Gavin P. R. , Dinh Diem , Brennan Angela , Brown Adam J. , Chew Derek P.
Published: January 2025

Background

Preprocedural fasting is widely used before percutaneous coronary intervention (PCI). However, the incidence of procedural intubation during PCI is unknown. This study aims to identify the incidence and predictors for procedural intubation during PCI.

Methods and Results

A retrospective cohort study was performed on patients undergoing PCI between 2014 and 2021 within the Victorian Cardiac Outcomes Registry. Patients were classified into urgent, semiurgent, or elective PCI on the basis of recorded PCI indication. Those undergoing semiurgent or elective PCI were presumed to be fasted preprocedurally. The incidence of procedural intubation was reported for each PCI group. Inverse probability treatment weighting was used to determine the association between 30‐day death and procedural intubation. Logistic regression was performed to determine clinical, procedural, and lesion characteristics associated with procedural intubation among fasted patients. Among 83 929 patients, the incidence of procedural intubation was 0.5%. Patients undergoing urgent PCI (odds ratio [OR], 19.68 [95% CI, 13.91–27.86];
P
<0.01) had the highest risk of procedural intubation. Procedural intubation was associated with increased 30‐day death (OR, 4.79 [95% CI, 3.29–6.96];
P
<0.01). Among fasted patients, estimated glomerular filtration rate (OR, 0.99 [95% CI, 0.98–0.99];
P
<0.01), cardiogenic shock (OR, 96.24 [95% CI, 56.01–165.35];
P
<0.01), out‐of‐hospital cardiac arrest (OR, 3.42 [95% CI, 1.30–8.97];
P
=0.01), femoral access (OR, 2.09 [95% CI, 1.38–3.19];
P
<0.01), left main disease (OR, 5.77 [95% CI, 3.16–10.54];
P
<0.01), type C lesions (OR, 3.86 [95% CI, 1.19–12.56];
P
=0.03), and rotational atherectomy (OR, 2.20 [95% CI, 1.03–4.69];
P
=0.04) were associated with procedural intubation.

Conclusions

Despite an association with a worse 30‐day mortality rate, the incidence of procedural intubation during PCI was low. Universal preprocedural fasting may be unnecessary and could be targeted at higher‐risk groups.
Number of Previous Strokes and the Association With Clinical Outcomes of Patients With Atrial Fibrillation: Longitudinal Data From the GLORIA‐AF Registry
Authors: Lam Steven Ho Man , Romiti Giulio Francesco , Corica Bernadette , Bucci Tommaso , Olshansky Brian , Chao Tze‐Fan , Huisman Menno V. , Lip Gregory Y. H. ,   the GLORIA‐AF Investigators
Published: January 2025

Background

Patients with atrial fibrillation (AF) who suffered a previous stroke are at increased risk of recurrent thromboembolic events and other major outcomes. The impact of the number of stroke episodes on the natural history of patients with AF is still unclear.

Methods and Results

Using data from the international, multicenter, and prospective GLORIA‐AF (Global Registry on Long‐Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation) Registry Phase III, we categorized patients with a recent diagnosis of non‐valvular AF according to the number of previous strokes (either 0, 1, or ≥2 episodes). We analyzed use of oral anticoagulants through multiple logistic regression model, and risk of major outcomes using multiple Cox‐regression models; our primary outcome was all‐cause death. Among 21 223 patients (mean age: 70.2±10.3 years; 44.9% female) included, 2251 (10.6%) had a previous history of stroke, and 216 (1.0%) had ≥2 or more strokes. Oral anticoagulants were used in ≥80% of patients regardless of the numbers of previous stroke, although those with 1 (versus >1) prior stroke showed lower odds of receiving oral anticoagulants (odds ratio [95% CI]: 0.83 [0.73–0.94]). During 3‐years follow‐up, the risk of all‐cause mortality increased with the number of previous strokes (hazard ratio [95% CI]: 1.46 [1.28–1.67] and 2.43 [1.79–3.29] for 1 versus 0 and ≥2 versus 0 previous strokes, respectively). Similar results were observed for other secondary outcomes, including thromboembolism, but not for major bleeding.

Conclusions

History of stroke still represents a key risk factor in patients with AF. Patients who suffered more than 1 episodes of stroke had significantly worse prognosis and further efforts may be required to improve their clinical outcomes.
A taxonomic note on Chinese species of the Neolucanus fuscus group with the description of a new species (Coleoptera: Lucanidae: Lucaninae)
Authors: XIN FEI-YI , ZHONG XIAO-TIAN , GUO WEN-CHI , ZHANG YI-FENG , QI ZHI-HAO , WU SONG-QING
Published: January 2025

In this paper, we describe a new stag beetle species from Yunnan, China, i.e., Neolucanus horizontalis Xin, Zhong & Qi, new species which exhibits significant structural differences in mandible, labial vestiture, protibia and male genitalia compared to related species. We also provide redescription of the male of N. fuscus Didier, 1926 and N. brochieri Bomans & Miyashita, 1997. Neolucans fuscus zhongguo Schenk, 2012 is synonymized with N. fuscus fuscus Didier, 1926. We also present a distribution map and an identification key for the telodont males of the N. fuscus group. Finally, we discuss the species group affiliation of N. baongocae Nguyen, 2013.
Phase 1 Study of Quercetin, a Natural Antioxidant in Children and Young Adults with Fanconi Anemia (FA)
Authors: Mehta Parinda A , Nelson Adam S , Loveless Sara Katharine , Lane Adam , Fukuda Tsuyoshi , Teusink-Cross Ashley , Elder Deborah , Lagory Denise , Miller Erica , Cancelas Jose A. , Howell Jonathan , Zhao Junfang , Mizuno Kana , Myers Kasiani C. , Lake Kelly , McIntosh Kelly , Setchell Kenneth D. R. , Luebbering Nathan , Edwards Stephanie , Chihanga Tafadzwa , Wells Susanne I , Davies Stella M
Published: January 2025

Fanconi anemia (FA) is a rare inherited disorder characterized by progressive bone marrow failure (BMF) and a predisposition to malignancy. Systemic reactive-oxygen species (ROS) and increased sensitivity of FA hematopoietic progenitors to ROS play a key role in the pathogenesis of BMF. Treatment with antioxidants improve hematopoietic function in Fancc-/- mice. We report the safety, tolerability, and pharmacokinetics (PK) of quercetin, a naturally occurring antioxidant in the first dose-finding Phase 1 study in patients with FA. Twelve patients (median age 7 years, range: 3-21) received oral quercetin twice daily for 4 months. Quercetin was well tolerated at all dose levels. Allometrically bodyweight-adjusted dose with a maximum adult daily dose of 4000mg/day was established as the recommended dose of quercetin. Patients in an expansion cohort (n=18) were treated using this recommended dose for 6 months. A subset of patients showed reduced ROS levels in the peripheral blood and bone marrow stem cell compartment. Patients in the analysis cohort treated with the recommended dose of quercetin achieved an a priori defined optimal response of 25% reduction in the peripheral blood (PB) ROS level compared to baseline. Platelet counts remained stable to slightly improved over the study period (p=0.06). Absolute neutrophil counts (p=0.01) and hemoglobin levels gradually declined (p=0.001). In those with evidence of BMF at baseline, 8 out of 15 patients (53%) had a hematological response at some point following quercetin treatment. Fluctuations in counts are common in patients with FA limiting accurate assessment of the impact of quercetin use in FA. NCT# 01720147
Nootkatone inhibits the progression of glioblastoma by activating the ATF4-CHOP-CHAC1 pathway
Authors: Wang Qian , Xue Xiumin , Chen Zhichao , Zhang Wei , Qian Yiming , Chen Danni , Lin Lin , Yuan Yinfeng , Zhao Weiqiao , Huang Zhihui , Wang Yongjie
Published: January 2025

Glioblastoma multiforme (GBM) represents a primary brain tumor that is widely prevalent, and clinical drugs available for its treatment exhibit varying degrees of resistance. Nootkatone (NKT) is a functional sesquiterpene sourced from traditional Chinese medicine --Alpinia Oxyphylla Miq and has been reported to have a diverse range of pharmacological properties. However, it remains unknown whether there are effects of NKT on GBM. In this study, we found that NKT inhibited the growth of GBM cells in a dose-dependent manner in vitro. Subsequently, we observed that NKT suppressed the migration and arrested cell cycle at G2/M phase of GBM cells. Furthermore, NKT induced the death of GBM cells accompanied by an increase in reactive oxygen species (ROS) production. Mechanistically, we found that NKT inhibited the progression of GBM cells through activating the ATF4-CHOP-CHAC1 pathway in GBM cells. Furthermore, NKT-induced inhibition of migration and proliferation in GBM cells was partially restored by ATF4 or CHAC1 knockdown. Finally, we found that NKT inhibited the growth of tumor in GBM orthotopic mice model through activation of ATF4-CHOP-CHAC1 axis. Taken together, our findings show that NKT suppresses the growth and migration of GBM cells by activating the ATF4-CHOP-CHAC1 pathway, which in turn prevents the tumorigenesis of GBMs and provides a novel perspective for the development of drugs against GBM.

Graphical Abstract
Brain computer interfaces for cognitive enhancement in older people - challenges and applications: a systematic review
Authors: Tsai Ping-Chen , Akpan Asangaedem , Tang Kea-Tiong , Lakany Heba
Published: January 2025

Background

Brain-computer interface (BCI) offers promising solutions to cognitive enhancement in older people. Despite the clear progress received, there is limited evidence of BCI implementation for rehabilitation. This systematic review addresses BCI applications and challenges in the standard practice of EEG-based neurofeedback (NF) training in healthy older people or older people with mild cognitive impairment (MCI).

Methods

Articles were searched via MEDLINE, PubMed, SCOPUS, SpringerLink, and Web of Science. 16 studies between 1st January 2010 to 1st November 2024 are included after screening using PRISMA. The risk of bias, system design, and neurofeedback protocols are reviewed.

Results

The successful BCI applications in NF trials in older people were biased by the randomisation process and outcome measurement. Although the studies demonstrate promising results in effectiveness of research-grade BCI for cognitive enhancement in older people, it is premature to make definitive claims about widespread BCI usability and applicability.

Significance

This review highlights the common issues in the field of EEG-based BCI for older people. Future BCI research could focus on trial design and BCI performance gaps between the old and the young to develop a robust BCI system that compensates for age-related declines in cognitive and motor functions.
Do orthodontists consider endodontic complications in their orthodontic management of teeth with a history of dental trauma? A vignette survey
Authors: Awad Kinda , Hourani Ammar Al , Kasperek Dariusz , Jarad Fadi , Albadri Sondos
Published: January 2025

Background

Dental trauma is a frequent injury seen commonly in young children. There is a link between malocclusion and the incidence of traumatic dental injuries. Orthodontic therapy has been suggested as a preventative measure in correcting unfavourable malocclusions and potentially avoiding traumatic dental injuries. To date, it is poorly understood if the complications reported following traumatic dental injuries are amplified during and following orthodontic treatment. The aim of this study was to evaluate whether orthodontists considered the endodontic implications associated with the orthodontic treatment of teeth with a history of dental trauma.

Method

A mixed methods vignette survey was designed, piloted, and distributed online to UK registered specialist orthodontists. The survey was split into three parts and consisted of three vignette clinical scenarios with open and closed questions.

Results

A total of 76 orthodontists responded from the United Kingdom. Of the participants, 46% (n = 35) of the orthodontists felt they had insufficient training in dental trauma and 42% (n = 32) lacked confidence in the treatment of traumatic injuries. The study participants reported non-standardised pre- treatment examination, limited dental trauma experience and insufficient training. In addition, 32% (n = 24) of clinicians felt that there is a lack of guidance in the orthodontic management of traumatised teeth and pulpal sequelae.

Conclusion

Orthodontists are not following a standardised protocol in their examination of teeth with a history of trauma prior to orthodontic treatment. There is a need within the orthodontic specialty to create a standardised protocol to assess teeth with a history of dental trauma.
Empowering personalized oncology: evolution of digital support and visualization tools for molecular tumor boards
Authors: Strantz Cosima , Böhm Dominik , Ganslandt Thomas , Börries Melanie , Metzger Patrick , Pauli Thomas , Blaumeiser Andreas , Scheiter Alexander , Jung Ian-Christopher , Christoph Jan , Manuilova Iryna , Strauch Konstantin , Ustjanzew Arsenij , Reimer Niklas , Busch Hauke , Unberath Philipp
Published: January 2025

Background

Molecular tumor boards (MTBs) play a pivotal role in personalized oncology, leveraging complex data sets to tailor therapy for cancer patients. The integration of digital support and visualization tools is essential in this rapidly evolving field facing fast-growing data and changing clinical processes. This study addresses the gap in understanding the evolution of software and visualization needs within MTBs and evaluates the current state of digital support. Alignment between user requirements and software development is crucial to avoid waste of resources and maintain trust.

Methods

In two consecutive nationwide medical informatics projects in Germany, surveys and expert interviews were conducted as stage 1 (n = 14), stage 2 (n = 30), and stage 3 (n = 9). Surveys, via the SoSci Survey tool, covered participants' roles, working methods, and support needs. The second survey additionally addressed requirements for visualization solutions in molecular tumor boards. These aimed to understand diverse requirements for preparation, implementation, and documentation. Nine semi-structured expert interviews complemented quantitative findings through open discussion.

Results

Using quantitative and qualitative analyses, we show that existing digital tools may improve therapy recommendations and streamline MTB case preparation, while continuous training and system improvements are needed.

Conclusions

Our study contributes to the field by highlighting the importance of developing user-centric, customizable software solutions that can adapt to the fast-paced environment of MTBs to advance personalized oncology. In doing so, it lays the foundation for further advances in personalized medicine in oncology and points to a shift towards more efficient, technology-driven clinical decision-making processes. This research not only enriches our understanding of the integration of digital tools into MTBs, but also signals a broader shift towards technological innovation in healthcare.
Solidarity and its decoloniality in global health ethics
Authors: Fayemi Ademola Kazeem , Kirchhoffer David Gerrard , Pratt Bridget
Published: January 2025

Solidarity is one of the emerging values in global health ethics, and a few pieces of bioethics literature link it to decoloniality. However, conceptions of solidarity in global health ethics are influenced primarily by Western perspectives, thus suggesting the decolonial needs to include non-Western perspectives. This article explores a decolonial interpretation of solidarity to enrich our understanding of solidarity. It employs a palaver approach, typical of African (Yorùbá) relational culture, in developing a conception of solidarity grounded in a beehive metaphor. Through a decolonial methodological approach, this article posits that a beehive metaphor allegorically symbolises solidarity. In this decolonial interpretive account, solidarity embeds relational virtues and duties that foster harmony. Solidarity is a positively oriented affective disposition with people with whom one shares similar circumstances for harmonious well-being through concerted efforts. This article addresses five potential objections to this account of solidarity in global health ethics and consequently explores what an African account of solidarity means for global health research funding. This article concludes that the palaver decolonial approach from the Global South has implications for expanding conceptual perspectives on solidarity in global health ethics.
Exploring the power of spectrophotometric technique in determination of oxytetracycline and lidocaine in their pharmaceutical dosage form as well as in the presence of toxic lidocaine impurity: univariate versus multivariate analysis
Authors: Ahmed Naglaa , Hemdan Ahmed , ZaaZaa Hala , Galal Maha
Published: January 2025

Lidocaine poses challenges when it comes to direct spectrophotometric measurement due to the lack of sharp peak within its spectra in zero-order. This lack of a distinct peak makes it difficult to accurately quantify lidocaine using traditional direct spectrophotometric methods. In our study, different univariate and multivariate spectrophotometric techniques have been established and their validity has been assessed for the determination of the mixture of Lidocaine HCl (LD), Oxytetracycline HCl (OTC) together with LD carcinogenic impurity [2,6- dimethylaniline] DMA. LD was resolved from the other two components using ratio difference and derivative ratio methods. OTC was determined in zero- order at 360 nm and by using constant value and concentration value methods, while DMA was determined by using constant multiplication at 237 nm as well as by using constant value and concentration value methods after elimination of OTC by ratio subtraction technique. Moreover, Partial Least Squares and Principal Component Regression multivariate approaches were applied to quantify and evaluate the mixture. The developed methods underwent validation following International Council for Harmonization guidelines. The validation process demonstrated that all suggested methods are accurate and selective in their measurements. Additionally, statistical analysis was conducted to compare the developed and reported methods. Furthermore, one-way analysis of variance was performed to compare both proposed and reported spectrophotometric methods.
Identification of Southeast Asian Anopheles mosquito species with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry using a cross-correlation approach
Authors: Chaumeau Victor , Sawasdichai Sunisa , Min Thu Zar Ma Ma Moe , Kularbkeeree Thithiwarada , Jaruwan Naw , Gloria Naw , Lee Naw Yu , Trackoolchengkaew Muesuwa , Phanaphadungtham Monticha , Rongthong Patcharamai , Inta Aritsara , Watthanaworawit Wanitda , Nosten François
Published: January 2025

Background

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI–TOF MS) is proposed for mosquito species identification. The absence of public repositories sharing mass spectra and open-source data analysis pipelines for fingerprint matching to mosquito species limits the widespread use of this technology. The objective of this study was to develop a free open-source data analysis pipeline for Anopheles species identification with MALDI–TOF MS.

Methods

Anopheles mosquitoes were captured in 33 villages in Karen (Kayin) state in Myanmar. A subset of 403 specimens was selected for inclusion in either the reference or the test panel (270 and 133 specimens, respectively). Three hundred fifty-nine specimens could be identified with DNA barcodes and were assigned to 21 sensu stricto species and five sibling species pairs or complexes. A total of 3584 mass spectra of the head of these specimens identified with DNA barcoding were acquired and the similarity between mass spectra was quantified using a cross-correlation approach adapted from the published literature. A reference mass spectra database was created using all spectra of the PCR-identified specimens assigned to the reference panel. A simulation experiment was carried out by querying the reference database with the spectra of the test panel to evaluate the performance of species identification with MALDI–TOF MS at varying thresholds of the cross-correlation index for the algorithm to output an identification result and with varying numbers of technical replicates for the tested specimens, considering PCR identification results as the reference.

Results

With one spot and a threshold value of −14 for the cross-correlation index on the log scale, the sensitivity was 0.99 [95% credible interval (CrI): 0.98–1.00], the predictive positive value was 0.99 (95% CrI: 0.98–0.99), and the accuracy was 0.98 (95% CrI: 0.97–0.99). It was not possible to directly estimate the sensitivity and negative predictive value because there was no true negative (i.e., queries of species not referenced in the database) in the assessment.

Conclusions

The cross-correlation approach can be used to match mass spectral fingerprints to predefined taxa. MALDI–TOF MS is a valuable tool for rapid, accurate, and affordable identification of Anopheles species.

Graphical abstract
Reviewing manuscripts for scientific journals: recommendations for early career scientists
Authors: Forero Diego A. , Glatt Stephen J. , Oermann Marilyn H.
Published: January 2025

Publication of articles in international scientific journals has been one of the main strategies for the communication of scientific findings and ideas. Prepublication peer review is a fundamental aspect of the publishing process in indexed scientific journals and, associated with the large growth in journals and articles, there has been a recent challenge in having adequate peer reviewers for international journals. In this article, we provide a short overview of the publishing process, give recommendations to early career researchers about writing peer reviews of adequate quality, and discuss some possibilities for the future.