bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune Checkpoint Receptor Expression Profiles of MAIT Cells in Moderate and Severe COVID‐19
Authors: Meggyes Matyas , Nagy David U. , Toth Ildiko , Feik Timoteus , Polgar Beata , Deen Iyad Saad Al , Sipos David , Szereday Laszlo , Peterfalvi Agnes
Published: February 2025

MAIT cells are one of the largest unconventional T cell populations and, recruited to the site of infection, play both protective and pathogenic roles during pulmonary viral infections. MAIT cell activation patterns change significantly during COVID‐19, with a notable decrease in their frequency in peripheral blood of severe cases. In the present study, we aimed to investigate the expression profiles of various immune checkpoint pathways on MAIT, MAIT‐like and non‐MAIT cells in moderate and severe COVID‐19 patients undergoing cytokine storm. Despite numerous studies comparing MAIT cell characteristics based on COVID‐19 disease severity, none have delved into the critical differences in MAIT cell immune checkpoint profiles between moderate and severe COVID‐19 patients, all experiencing a cytokine storm. Flow cytometry was used to analyse peripheral blood mononuclear cells from a cohort of 35 patients, comprising 18 moderate and 17 severe cases, alongside 14 healthy controls. Our investigation specifically focuses on severe COVID‐19 presentations, revealing a marked deletion of MAIT cells. Further exploration into the regulatory dynamics of MAIT cell functionality reveals shifts in the expression profiles of critical immune checkpoint receptors, notably PD‐1 and CD226. In severe COVID‐19 patients, MAIT cells showed a significant decrease in the expression of CD226, whereas MAIT‐like and non‐MAIT cells demonstrated a significant increase in the expression of PD‐1 compared to healthy individuals. The expression of the TIGIT receptor remained unaltered across all investigated groups. Our findings contribute to the existing knowledge by elucidating the changes in MAIT cell subpopulations and their potential role in COVID‐19 disease severity.
Modern and historical uses of plant grafting to engineer development, stress tolerance, chimeras, and hybrids
Authors: Augstein Frauke , Melnyk Charles W.
Published: February 2025

For millennia, people have grafted plants to propagate them and to improve their traits. By cutting and joining different species or cultivars together, the best properties of shoot and roots are combined in one plant to increase yields, improve disease resistance, modify plant growth or enhance abiotic stress tolerance. Today, grafting has evolved from what originated as an early form of trait engineering. The fundamental technique remains the same, but new species are being grafted, new techniques have developed and new applications for modifying development and stress tolerance are appearing. In addition, engineering possibilities such as graft chimeras, graft hybrids and the use of mobile RNAs are emerging. Here, we summarize advances in plant grafting with a focus on engineering novel traits. We discuss traditional uses of grafting to engineer traits but also focus on recent developments, challenges and opportunities for plant improvement through grafting.
Kinetic Degradation and Colour Stability in an Aqueous System of Spray-Dried Metal-Stabilised Amaranth Powder Encapsulated in Different Wall Materials
Authors: Mohd Amin Siti Faridah , Muhammad Kharidah , Yusof Yus Aniza , Abdul Aziz Ahmad Hazim , Mohd Noor Nor Qhairul Izreen
Published: February 2025

The present study aims to determine the kinetics of chlorophyll degradation and green colour stability of encapsulated copper (Cu)- and zinc (Zn)-amaranth powders stored under accelerated (45°C) and room (25°C) temperature for 16 weeks and six months, respectively. The powders were spray-dried using 10% maltodextrin (DE 10), resistant maltodextrin, N-Octenyl Succinate Anhydride starches (HI-CAP® 100 and CAPSUL®), and gum Arabic (GA). The effects of pH (4 to 8, in the absence of light at 25°C for 24 hours), temperature (40 to 100°C for 90 mins), and light exposure (fluorescent light at 25°C for five days) on the chlorophyll retention and colour stability of the powders in an aqueous system were also explored. The chlorophyll degradation kinetics of the powders followed a first-order reaction model. The Zn-amaranth powder encapsulated with CAPSUL® exhibited the lowest rate constant (k = 2.7 × 10−3 weeks−1) and the highest half-life (t1/2 = 256.72 weeks) under storage at 25°C. The Cu-amaranth powder encapsulated with GA demonstrated the highest greenness value during storage at both 25°C (six months) and 45°C (16 weeks). In the aqueous system, the Cu-amaranth powder encapsulated with GA possessed the highest chlorophyll retention (> 90%) in acidic conditions. Meanwhile, maltodextrin-encapsulated Cu-amaranth powder exhibited better chlorophyll retention and colour stability under light exposure and high temperatures.
ECG Signal Data Classification System Based on Hankel Dynamic Mode Decomposition
Authors: Liang Chuchu , Majahar Ali Majid Khan , Lili Wu  , Zhang Zhixiang
Published: February 2025

The modes in the electrocardiogram (ECG) signal can be divided into stable modes and unstable modes. The unstable modes are of great significance for signal analysis and classification. When the traditional dynamic mode decomposition (DMD) method is directly applied to these signals, it is difficult to effectively extract these key modes due to the rank mismatch problem of the data matrix. In order to better capture and analyze unstable modes, this study introduced the Hankel matrix to expand ECG data and used it as the input of DMD to propose the Hankel dynamic mode decomposition (HDMD) method. Although HDMD has been applied in other physiological signal processing, this study is the first to successfully apply it to multi-lead ECG signal analysis. By optimizing the delay parameters of the Hankel matrix and retaining the modes that account for 90% of the singular value decomposition energy, we significantly improve the effectiveness of feature extraction. Each type of abnormal ECG signal data is classified on the PTB Diagnostic ECG database. The experimental results of the proposed model are compared with the direct use of DMD for modal extraction. The highest classification accuracy of multi-modal ECG signal data extracted by HDMD is more than 10% higher than that using DMD. At the same time, the mean squared error (MSE) of the reconstruction using HDMD is 0.282 lower than that of DMD, indicating a significant improvement in reconstruction accuracy. Further illustrating the proposed method, the HDMD method can better capture and analyze the unstable modes in the ECG signal, thereby significantly improving the accuracy and robustness of signal classification. Future work will focus on further optimizing the parameter selection of the HDMD model and exploring its application potential in real-time heart disease monitoring and early warning systems.
Optimising Terung Asam (Solanum lasiocarpum Dunal.) Sauce for Enhanced Phenolics, Flavonoids, and Antioxidant Capacity with Physicochemical Properties and Storage Stability Analysis
Authors: Rushdy Muhammad Naufal Qaweim , Benjamin Mohammad Amil Zulhilmi , Awang Mohd Azrie
Published: February 2025

Solanum lasiocarpum Dunal, commonly referred to as ‘terung asam’, is a native plant of Borneo Island that is widely utilised in Sarawak, Malaysia, for its culinary and medicinal applications. While terung asam has been commercialised into products such as sauces, research on optimising its sauce formulations remains limited. This study utilised a D-optimal mixture design, a method from response surface methodology, to optimise terung asam sauce (TAS) formulations using terung asam (TA) purée, virgin coconut oil (VCO), and garlic powder (GP). The focus was on three key responses: total phenolic content (TPC), total flavonoid content (TFC), and antioxidant capacity via 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The physicochemical properties, including pH, colour, water activity, and storage stability analysis, were evaluated for the optimal TAS formulation. The optimal TAS formulation comprised 98.46%, 0.73%, and 0.81% for TA, VCO, and GP, respectively, with both predicted and actual values aligning and meeting acceptance error criteria. The physicochemical parameters for the optimal TAS formulation were within the optimal ranges, while TPC, TFC, and DPPH showed a slight decline over the storage period of 28 days. In conclusion, optimising TAS formulations offers an innovative approach to developing a healthy food product with high antioxidant properties and extended shelf life.
Ground states for aggregation–diffusion models on Cartan–Hadamard manifolds
Authors: Fetecau Razvan C. , Park Hansol
Published: February 2025

We consider a free energy functional on Cartan–Hadamard manifolds and investigate the existence of its global minimizers. The energy functional consists of two components: an entropy (or internal energy) and an interaction energy modelled by an attractive potential. The two components have competing effects, as they favour spreading by linear diffusion and blow‐up by non‐local attractive interactions, respectively. We find necessary and sufficient conditions for ground states to exist, in terms of the behaviours of the attractive potential at infinity and at zero. In particular, for general Cartan–Hadamard manifolds, superlinear growth at infinity of the attractive potential prevents the spreading. The behaviour can be relaxed for homogeneous manifolds, for which only linear growth of the potential is sufficient for this purpose. As a key tool in our analysis, we develop a new logarithmic Hardy–Littlewood–Sobolev inequality on Cartan–Hadamard manifolds.
Supplemental Material: Paleogene mid-crustal intrusions in the Ruby Mountains–East Humboldt Range metamorphic core complex, northeastern Nevada, USA
Authors: Snoke Arthur W. , al. et
Published: February 2025

File S1: Mineral analyses (amphibole, biotite, and plagioclase). File S2: SHRIMP-RG U-Pb data. File S3: LA-MC-ICP-MS age data and LA-Q-ICP-MS trace-element data with methods. File S4: LA-MC-ICP-MS Hf isotope (zircon) data. File S5: Supporting data and images for zircon geochronology. File S6: 40Ar/39Ar data on hornblende and biotite. File S7: Bulk-rock Sr, Nd, and Pb isotope data. File S8: Oxygen isotope values of quartz and bulk rocks with methods. Whole-rock chemical analyses of rocks of the middle to late Eocene and early Oligocene monzogranitic suite. Refer to U.S. Geological Survey Data Series 244 (du Bray et al., 2007).
CTA-based deep-learning integrated model for identifying irregular shape and aneurysm size of unruptured intracranial aneurysms
Authors: Tian Ke , Chang Zhenyao , Yang Yi , Liu Peng , Mossa-Basha Mahmud , Levitt Michael R , Zhai Dihua , Liu Danyang , Li Hao , Liu Yang , Zhang Jinhao , Cao Cijian , Zhu Chengcheng , Jiang Peng , Liu Qingyuan , He Hongwei , Xia Yuanqing
Published: February 2025

Background

Artificial intelligence can help to identify irregular shapes and sizes, crucial for managing unruptured intracranial aneurysms (UIAs). However, existing artificial intelligence tools lack reliable classification of UIA shape irregularity and validation against gold-standard three-dimensional rotational angiography (3DRA). This study aimed to develop and validate a deep-learning model using computed tomography angiography (CTA) for classifying irregular shapes and measuring UIA size.

Methods

CTA and 3DRA of UIA patients from a referral hospital were included as a derivation set, with images from multiple medical centers as an external test set. Senior investigators manually measured irregular shape and aneurysm size on 3DRA as the ground truth. Convolutional neural network (CNN) models were employed to develop the CTA-based model for irregular shape classification and size measurement. Model performance for UIA size and irregular shape classification was evaluated by intraclass correlation coefficient (ICC) and area under the curve (AUC), respectively. Junior clinicians’ performance in irregular shape classification was compared before and after using the model.

Results

The derivation set included CTA images from 307 patients with 365 UIAs. The test set included 305 patients with 350 UIAs. The AUC for irregular shape classification of this model in the test set was 0.87, and the ICC of aneurysm size measurement was 0.92, compared with 3DRA. With the model’s help, junior clinicians’ performance for irregular shape classification was significantly improved (AUC 0.86 before vs 0.97 after, P<0.001).

Conclusion

This study provided a deep-learning model based on CTA for irregular shape classification and size measurement of UIAs with high accuracy and external validity. The model can be used to improve reader performance.
Unrestricted insurance coverage of buprenorphine formulations remains sparse in comparison to conventional opioids
Authors: Andrassy Bennett , Mukhdomi Junaid , Bhaskar Nidhi , Harris Marcus , Mukhdomi Taif
Published: February 2025

Objective

Buprenorphine is an atypical opioid with analgesic efficacy and a more favorable safety profile than conventional opioids or tramadol. In 2019, access to on-label buprenorphine formulations was limited in comparison to conventional opioids, despite evidence supporting buprenorphine’s first-line analgesic use. Considering recent policy changes increasing buprenorphine accessibility, we determined differences in unrestricted insurance coverage between buprenorphine, conventional opioids, and other atypical opioids.

Methods

We used data from Managed Market Insights and Technology’s Coverage Search and Kaiser Family Foundation to generate estimates on percentages of US-covered lives with unrestricted access to oxycodone, morphine, tramadol, tapentadol, generic and on-label transdermal buprenorphine, on-label buccal buprenorphine, and on-label sublingual buprenorphine/naloxone in 2024.

Results

79.7% of commercial and 99.1% of Medicare lives had unrestricted oxycodone access. Morphine access was unrestricted for 45.7% of commercial and 62.8% of Medicare lives. Unrestricted access to tramadol was available for 88.2% of commercial and 96.3% of Medicare lives. 37.3% of commercial and 10.1% of Medicare lives had unrestricted tapentadol access. Unrestricted access to on-label transdermal buprenorphine was available for 21.0% of commercial and 2.59% of Medicare lives. Generic transdermal buprenorphine was available for 52.1% of commercial and 30.0% of Medicare lives. Buccal buprenorphine was available without restriction for 52.7% of commercial and 19.8% of Medicare lives. Sublingual buprenorphine/naloxone had unrestricted coverage for 34.6% of commercial and 32.7% of Medicare lives.

Conclusions

Access to buprenorphine formulations was limited in comparison to other opioids. This study emphasizes a need for commercial and Medicare health insurance plans to broaden buprenorphine coverage.
Phase Separation–Mediated Compartmentalization Underlies Synapse Formation and Plasticity
Authors: Wu Xiandeng , Shen Zeyu , Zhang Mingjie
Published: February 2025

The synapse is polarized and highly compartmentalized on both its pre- and postsynaptic sides. The compartmentalization of synaptic vesicles, as well as vesicle releasing and recycling machineries, allows neurotransmitters to be released with precisely controlled timing, speed, and amplitude. The compartmentalized and clustered organization of neurotransmitter receptors and their downstream signaling enzymes allows neuronal signals to be properly received and amplified. Synaptic adhesion molecules also form clustered assemblies to align pre- and postsynaptic subcompartments for synaptic formation, stability, and transmission. Recent studies indicate that such synaptic and subsynaptic compartmentalized organizations are formed via phase separation. This review discusses how such condensed subsynaptic compartments may form and function in the context of synapse formation and plasticity. We discuss how phase separation allows for the formation of multiple distinct condensates on both sides of a synapse and how such condensates communicate with each other. We also highlight how proteins display unique properties in condensed phases compared to the same proteins in dilute solutions.
Machine Learning Regression for Assessing Sensing Performance and Anticancer Potential of Oolong Tea-Derived Silver Nanoparticles
Authors: Sert Esra , Kalındemirtaş Ferdane Danışman , Karakuş Emir Ersel , Erol Ayşe , ÖZBAŞ Fatih , Küçükdeniz Tarık , Karakus Selcan
Published: February 2025

In this study, machine learning (ML) algorithms were employed to predict analyte concentrations using sensing results and evaluate the anticancer effects of nanostructures. Multifunctional oolong tea extract-mediated silver nanoparticles (OTE-Ag NPs) were synthesized via a photo/ultrasound method and utilized in various applications, including a smartphone-based H2O2 sensor and electrochemical sensors for urea and fructose. Key features were extracted from electrochemical results, and feature importance analysis was used to select the most predictive features. The artificial neural network (ANN) model provided accurate predictions, particularly strong for urea (R²=0.8575, RMSE=0.4266, MAE=0.3380). The study revealed the selective toxicity of OTE-Ag NPs to MCF-7 breast cancer cells through analyses of cytotoxicity, apoptosis, cell cycle phases, and CD44 surface marker expression using Annexin V/PI dye and flow cytometry. Experimental results demonstrated that OTE-Ag NPs suppressed MCF-7 cell proliferation while exhibiting lower cytotoxicity in normal HUVEC cells (46% cell death). OTE-Ag NPs arrested MCF-7 cells in the G2/M phase, induced apoptosis, and reduced CD44 expression, suggesting metastasis suppression. The CD44+/CD24- ratio decreased from 84.79% in control MCF-7 cells to 47.7% in OTE-Ag NP-treated cells. Overall, OTE-Ag NPs significantly inhibited MCF-7 cell proliferation through the apoptotic pathway by regulating the cell cycle in the G2/M phase.
Electrochemical Non-Enzymatic Biosensing of Cortisol Using ZnO-Graphene Nanocomposite
Authors: Loganathan Harini , Dinasekaran Durgalakshmi , Rajendran Ajay Rakkesh
Published: February 2025

Cortisol is a key factor in developmental and behavioural research, measured widely in blood, urine, and saliva. Electrochemical sensing has emerged as a reliable technique in the development of point-of-care devices for detecting cortisol. Here, a ZnO/Graphene coated graphite was used as a sensing electrode for the detection of cortisol. The performance of the sensing electrode was tested in the presence of cortisol using electrochemical techniques and the impact of scan rate, concentration, cycle numbers, linear range, and limit of detection is reported. The fabricated ZnO/Graphene/PGE sensing electrode demonstrated excellent performance for cortisol detection, exhibiting a linear response over a wide concentration range of 10.874 to 173.981 mg/ml and a low limit of detection of 6.162 μg/ml. Additionally, the sensor displayed high stability over 60 days, with good repeatability and reproducibility. This shows that the ZnO/Graphene nanocomposite can be used as a non-enzymatic sensor providing a more reliable and effective cortisol sensing.
HBV relapse after discontinuation of Tenofovir alafenamide or Entecavir in non-cirrhotic HBeAg-negative patients
Authors: Huang Yi-Jie , Lee Shou-Wu , Tung Chun-Fang , Liao Szu-Chia , Lee Teng-Yu , Peng Yen-Chun , Chang Chung-Hsin , Wang Jun-Sing
Published: February 2025

Background & Aims:
This study investigated the off-therapy relapse in hepatitis B e antigen (HBeAg)-negative non-cirrhotic patients who discontinued tenofovir alafenamide (TAF) or entecavir (ETV).
Methods:
Non-cirrhotic HBeAg-negative patients who discontinued TAF or ETV were enrolled. The propensity score -matching method at a ratio of 1:1 and Cox proportional hazard model were performed to analyze factors associated with virological relapse and clinical relapse.
Results:
A total of 62 patients were analyzed. The cumulative rates of virological relapse at 12-month after discontinuing TAF and ETV were 80.4% and 60.0%, respectively. The respective rates of clinical relapse at 12-month were 48.7% and 21.1%. Multivariable Cox regression analysis showed that discontinuation of TAF (vs ETV, HR=2.279; p=0.005) and HBsAg levels at EOT (HR=1.540; p=0.005) were independently associated with virological relapse. Discontinuation of TAF (vs ETV, HR=3.003; p=0.011) was independently associated with clinical relapse. HBsAg levels at EOT (<3 vs. ≥ 3 log10 IU/ml) had significant interactions with the treatment regimen (TAF vs ETV) in terms of the risk of clinical relapse after treatment cessation (p for interaction <0.05).
Conclusions:
Patients who discontinued TAF had a higher risk of virological relapse and clinical relapse than those who discontinued ETV. HBsAg levels at EOT may be an appropriate predictor to distinguish the different risks of clinical relapse between patients who have discontinued TAF or ETV.
The Ethics of War: John of Naples and the Use of Muslim Mercenaries by a Christian King
Authors: Palmén Ritva , Posti Mikko
Published: February 2025

This article analyzes the question by John of Naples (d. ca. 1348) as to whether it is licit for a Christian king to hire Muslim mercenaries to defend his country against Christian aggressors. John’s answer employs legal, theological, and philosophical sources intended to justify the view that it is indeed licit to do so. John’s original account modifies the just war tradition to qualify his ambitions better and adapts elements of the legal principle of necessity, which support his argument. His overall ethical thinking builds on the primacy of the common good, which allows the use of imperfect means, such as hiring Muslim mercenaries, to achieve the good of Christian community in a just war.
Adam’s Rib as a Shared Source of Patriarchy in Abbasid Iraq: the Interconnectedness of Jewish and Muslim Exegeses on the Creation of Woman
Authors: von Schöneman Katja
Published: February 2025

The creation of humanity is depicted in both the Bible and the Qurʾān, and its details, such as the creation of woman, are abundantly discussed in subsequent exegetic literature. Applying feminist discourse analysis, I compare the interpretations of the creation of woman in rabbinic literature to those in Qurʾānic commentaries produced in the same cultural and geographical environment, second/eighth–sixth/twelfth-century Iraq under Abbasid rule. I show that in both Jewish and Islamic exegetic discourse the creation of woman from male-dependent material was diversely used to explain female characteristics and the treatment of women as subordinate, secondary beings. In addition to the numerous commonalities, the differences in the interpretive discourses reflect the multifarious encounters between Jewish and Muslim scholars in the vivid intellectual atmosphere of this context. The influence of ideas discussed in Talmudic academies was essential in the formation of distinct Islamic interpretive tradition concerning the matter.
Protecting War’s Unseen Environmental Damage
Authors: Sjöstedt Britta
Published: February 2025

This article explores the evolving legal landscape of environmental protection in armed conflict, emphasizing the critical contributions of the icrc Environmental Guidelines and the principles developed by the International Law Commission’s (ilc) on Protection of the Environment in relation to Armed Conflict (perac principles). By incorporating scientific insights and increasing environmental awareness, these frameworks encourage a broader understanding of environmental damage that includes direct and indirect impacts on ecosystems. In particular, the perac principles’ temporal approach, introduced by Special Rapporteur Marie Jacobsson, marks a significant shift towards recognizing environmental harm as a complex, multi-stage issue spanning before, during, and after armed conflict. Drawing on the jurisprudence of the Special Jurisdiction for Peace (the jep) in the transitional justice context of Colombia, the article underscores how the temporal approach can address also long-lasting environmental consequences on vulnerable populations, particularly Indigenous peoples by being informed by Indigenous law.
The Right of Self-defence and Third State Provision of Arms: Reflections on the Current Debate
Authors: Lehto Marja
Published: February 2025

The article examines the legal implications of third-State military assistance in the context of Ukraine’s self-defence against Russian aggression, focusing on the intersections of jus ad bellum, jus in bello, and the law of neutrality. It evaluates whether military aid, such as weapon provision and intelligence sharing, constitutes an indirect use of force under Article 2(4) of the UN Charter or implicates assisting States as parties to the conflict. The article critiques expanding the notion of indirect force to State-to-State assistance and discusses the implications of collective self-defence and the law of neutrality in light of the UN Charter law and the peremptory norm of prohibition of the use of force, including aggression. The analysis concludes that lawful assistance to a State exercising self-defence does not breach international law, emphasizing the superiority of jus cogens norms over conflicting legal provisions, such as neutrality.
A Systematic Review Comparing the Pre-event Behaviours of Suicide by Mass Violence With Individuals Who Commit Suicide Without Mass Violence
Authors: Williams Thomas James Vaughan
Published: February 2025

Intro: Perpetrators of mass violence and individuals who commit suicide have been discussed in terms of the experiencing similar ideations and tendencies. This has led to the promotion of utilising suicide prevention strategies to aid the reduction of mass violence probability. However, there is minimal research in terms of the identifying differentiation behaviours between potential mass violence and individuals who potentially will commit suicide without mass violence. Method: The present study involves a comparative systematic review of both suicide research and mass violence research, to explore and identify behavioural similarities and differences in pre-event behaviour between the two phenomena. Results: The results showcase key similarities but more notably, six key behavioural differences, especially in terms of externalisation and internalisation. Conclusion: There are potentially six key behavioural pre-event differences between mass violence and individuals who commit suicide without mass violence. Implications and future research are discussed.
Navigating Social Media News Use: Exploring the Impact of Intentional and Incidental News Consumption on Objective and Subjective Political Knowledge
Authors: Dreston Jana H. , Neubaum German
Published: February 2025

Research consistently shows that while social media use does not enhance objective political knowledge, it increases users’ sense of being knowledgeable (subjective knowledge). However, it is unclear which specific modes of social media use lead users to an enhanced feeling of being knowledgeable. This work focuses on two factors that are believed to shape users’ subjective knowledge when using social technologies: (a) the intentionality of social media use (intentional vs. incidental news consumption) and (b) the relevance of the news content. In a pre-registered, two-wave experiment ( N = 921), participants were exposed to either personally relevant or non-relevant topics on social media, either intentionally or incidentally. The results indicated that while intentionality of exposure did not affect subjective knowledge, intentional news search improved objective knowledge more than incidental exposure. The latter can still facilitate objective knowledge and increase subjective knowledge, as long as the news is considered as highly relevant.
Efficacy of ubrogepant and atogepant in males and females with migraine: A secondary analysis of randomized clinical trials
Authors: Goadsby Peter J. , Jürgens Tim P. , Brand-Schieber Elimor , Nagy Krisztian , Liu Yingyi , Boinpally Ramesh , Stodtmann Sven , Trugman Joel M.
Published: February 2025

Background

Published evidence supporting efficacy of calcitonin gene-related peptide receptor antagonists as acute migraine treatments in males is limited.

Methods

To fill the gap, we present male and female data from four ubrogepant and four atogepant randomized, double-blind, placebo-controlled trials for acute and preventive treatment of migraine, respectively. Acute outcomes included 2-h pain freedom and absence of most bothersome symptom (co-primary; headache-phase randomized, double-blind, placebo-controlled trials); absence of moderate-to-severe headache within 24 h (primary; prodrome randomized, double-blind, placebo-controlled trial). Preventive outcome included change from baseline in mean monthly migraine days across 12 weeks (primary).

Results

Pooled data from phase 3 headache-phase ubrogepant randomized, double-blind, placebo-controlled trials showed similar rates of pain freedom (19.4% vs 21.1%) and absence of most bothersome symptom (35.1% vs 39.0%) 2 h post-dose between males and females, respectively. Time course of pain freedom and absence of most bothersome symptom over 48 h was similar between male and female subgroups. Comparable reductions in mean monthly migraine days across 12-week treatment periods were found between males and females treated with atogepant 60 mg once-daily in pooled episodic migraine and chronic migraine randomized, double-blind, placebo-controlled trials.

Conclusion/Interpretation

In ubrogepant and atogepant randomized, double-blind, placebo-controlled trials, although analysis power for males is limited due to small sample sizes, evidence supports similar treatment effects in males and females with migraine.

Trial registration

ClinicalTrials.gov: NCT02828020; NCT02867709; NCT04492020; NCT01613248; NCT02848326; NCT03777059; NCT04740827; NCT03855137
Did wear simulator testing indicate biotribological risk for the ASR hip implant systems prior to market release circa 2004?
Authors: Medley John B
Published: February 2025

The DePuy ASR hip implant systems had exceptionally high Cumulative Percent Revision compared with other implants in Australia. This was likely to be the case worldwide and thus the ASR hip implant systems were voluntarily withdrawn by DePuy on August 24, 2010. To avoid such debacles in future implant systems, it is instructive for biotribologists to examine the warnings provided by hip wear simulator testing prior to market release circa 2004. The ASR hip implants had metal-on-metal bearings that had shown some success in other designs. Based on hip wear simulator studies of these designs (mostly having 28 mm diameter heads), a Safe Zone for Wear Rates versus Implantation Time could be defined. However, some of the earlier metal-on-metal designs were wear simulator tested under some harsher clinically relevant conditions. They missed the Safe Zone thus confirming a biotribological risk for ASR hip implant systems. Subsequent analysis after market release of the ASR implants confirmed that the risk had been underestimated. Biotribological risk for new implant designs should be examined rigorously prior to market release.
“It may Happen Everyday, but It Doesn’t Happen to Me Everyday”: A Phenomenological Understanding of Patients’ and Partners’ Medical Experiences of Perinatal Loss
Authors: Kendrick Jennifer , Baisch Kristin , Harris Lesley
Published: February 2025

This study aimed to investigate patients’ and partners’ lived experiences of miscarriage and stillbirth from initial pregnancy notification to recovering from pregnancy loss. Semistructured interviews were conducted with two partners and ten patients who had experienced miscarriage, stillbirth, or neonatal death from 11 to 26 weeks gestation. Interpretive phenomenological analysis revealed significant medical themes: technology taking the place of care and connection, a lack of patient knowledge, and a lack of mental health services. Findings offer a new perspective on the role of medical providers and procedures in meaning-making surrounding perinatal loss.
Child Maltreatment and Adolescent Dissociative Symptomatology: Moderation by Autonomic Regulation
Authors: Tabilin Derrian , Rudd Kristen L. , Yates Tuppett M.
Published: February 2025

This study drew on the biological sensitivity to context model (Ellis & Boyce, 2008) and polyvagal theory (Porges, 2007) to evaluate the moderating influence of children’s autonomic nervous system (ANS) regulation on pathways from child emotional abuse (CEA) and child physical abuse (CPA) to later dissociative symptoms in adolescence. Participants were 232 youth (50.2% assigned female at birth, 45.9% Latine) who reported on their experiences of CEA and CPA at ages 6, 8, and 10 years. Resting cardiography measures of respiratory sinus arrythmia (RSA) and pre-ejection period (PEP) assessed children’s parasympathetic and sympathetic activation, respectively, at these same ages. Youth reported on their dissociative symptoms at age 17. Parasympathetic activation qualified predictions from CEA to dissociative symptoms with relatively high RSA sensitizing children to CEA effects. Sympathetic activation qualified interactive predictions from both CEA and CPA to dissociative symptoms, but in different directions depending on the level of CPA. These findings suggest that resting ANS regulation may sensitize children to the effects of CEA and/or CPA on later dissociative symptoms in adolescence.
Skin complications between totally implantable venous port and peripherally inserted central catheter in patients with head and neck cancer who received cetuximab-based therapy
Authors: Huang Yuwen , Zhou Wenxia , Ju Houyu , Shen Ping , Lu Jiali , Wang Bei , Ma Sijia , Li Li
Published: February 2025

Objectives:

Cetuximab-based therapy is prone to develop skin complications. Our study aims to identify the impact on the central venous access by cetuximab-based therapy in patients with head and neck squamous cell carcinoma (HNSCC).

Methods:

We conducted a single center retrospective study to explore the prevalence and type of skin complications between totally implantable venous port (TIVP) implanted in the subcutaneous tissue of the anterior chest wall and peripherally inserted central catheter (PICC) for patients with HNSCC who received cetuximab-based therapy.

Results:

In the current study, 34 patients had TIVP and 34 patients had PICC. 32.4% (11/34) patients with TIVP had skin complications, while only 11.8% (4/34) skin complications occurred in patients with PICC. Most patients with skin complications were grade 1. However, two patients with TIVP suffered infection by skin complications and experienced TIVP removal. In the correlation analysis, significant ( p < 0.05) risk factors for skin complications were prophylactic use of topical steroid ointment and male sex.

Conclusion:

TIVP implanted in the anterior chest wall was potentially related with higher incidence of cutaneous complications in patients with R/M HNSCC who received cetuximab based therapy, that requires cancer nurses deep concern and uses evidence-based preventative and treatment strategies.
Processing methods and vulcanization influence on the electrical and mechanical behavior of isoprene rubber/MWCNT composites
Authors: Gonçalves Roger , Tozzi Kaique A , Barbosa Rafael , Fernandes Carlos HM , Saccardo Matheus C , Zuquello Ariel G , Scuracchio Carlos H
Published: February 2025

The burgeoning electronics industry demands flexible and cost-effective electrodes. Despite their inherent insulating nature, conductive rubber composites offer compelling advantages due to their flexibility and resilience. Due to reinforcing properties and high electrical conductivity, these materials can be transformed into viable electrode candidates by incorporating conductive additives like carbon nanotubes (CNTs). This study investigates the influence of dispersion and vulcanization methods on the mechanical and electrical properties of polyisoprene/CNT composites, aiming to optimize their suitability for flexible electrode applications. Two dispersion methods (conventional two-roll mill and latex dispersion) and two vulcanization systems (efficient and conventional) were employed. Comprehensive characterization encompassed electrical (resistivity, impedance spectroscopy), mechanical (tensile tests, rheometry), and interfacial properties (contact angle, zeta potential, linear voltammetry). Results demonstrate that the latex dispersion method significantly outperforms the two-roll mill approach. Latex-dispersed composites exhibited a tenfold increase in electrical conductivity and superior surface properties compared to conventionally dispersed counterparts, from 0.123 to 1.33 mS cm−1. Also, the efficient vulcanization system resulted in a modest decrease in modulus while maintaining tensile strength and significantly improving strain at break, from 1.83 to 6.82 MPa and 82.9 to 607%, respectively. This work provides valuable insights into optimizing dispersion and vulcanization techniques for developing high-performance conductive rubber composites with enhanced electrical and mechanical properties, which are crucial for advancing flexible electrode technologies.
The Role of 3D Printing and Augmented Reality in the Management of Hepatic Malignancies
Authors: Karageorgos Filippos F. , Karolos Ion-Anastasios , Pettas Theodoros , Tsioukas Vassilios , Pikridas Christos , Tsoulfas Georgios
Published: February 2025

Introduction: 3-dimensional (3D) printing and augmented reality (AR) are emerging technologies that are used in a wide variety of scientific fields. Among them, medicine is one of the most promising fields of application since these technologies can benefit not only surgeons, but also medical/surgical trainees, patients and can potentially benefit health care systems with better educated staff working on personalized solutions for the patients. Thus, potentially reducing intra-operative and post operative complications and overall costs for the health care systems. Hepatic malignancy surgeries are some of the most demanding surgeries that could a general surgeon perform. The intra-operative and post-operative risks and complications render them demanding. In literature there are cases of research studies including applications of 3D printing and augmented reality in hepatic malignancies. Methods: For this, a comprehensive literature search was conducted on Scopus and Pubmed databases (latest search September 5, 2024). Research studies that included applications of 3D printing and AR in hepatic malignancies were eligible for the review. Results: Herein, twelve papers have been included and presented, which either include the use of 3D printing or the use of AR. There are some cases where both technologies were used simultaneously. 3D printing technology and AR can be used alone or in combination together to aid in the management of hepatic malignancies. Conclusion: Encouraging results (eg, efforts to reduce cost of 3D printing, proper surgical pre-planning, usefulness in education of medical personnel and patients) from the use of these technologies, not only qualitatively but also quantitatively, show that the medical staff can help patients and improve their part of the health system. Yet much more studies need to validate whether the use of these two technologies provides positive results on the surgeries or not.
The Well-Being Coaching Inventory (WCI): Questionnaire Development and Validation
Authors: Harenberg Sebastian , Sforzo Gary , Hunter Rosie , Jackson Erika , Moore Margaret
Published: February 2025

Objective

The aim of the present study was to psychometrically test and validate the Well-being Coaching Inventory (WCI), a proposed measure of interconnected, whole-person well-being in the context of health and wellness coaching (HWC).

Methods

Initially 49 items, the WCI was conceived with 4 dimensions: Mind, Body, Work, and Life. The inventory was evaluated in 3 sequential studies to test: (a) face validity, (b) convergent validity, and (c) predictive validity. Expert judgment, correlational analyses, and factor analyses were techniques applied to collected WCI data.

Results

After statistical evaluation (n = 261) of fit to each dimension, the WCI was shortened to 20 items that demonstrated convergent validity. Further use of confirmatory factor analyses and exploratory structural equation model in a large sample study (n = 531) provided additional support for the inventory’s convergent validity. Through correlation analyses to theoretically related concepts predictive validity was established.

Conclusions

The WCI is a valid, applicable, and reliable scale for use in HWC research and practice. It is an instrument that will aid HWC practitioners and researchers as a central outcome measure for their practice.
The use of a scarf osteotomy to manage a malunited metacarpal fracture
Authors: Lawrence Owen , Hourston George , Johnston Phillip
Published: February 2025

A scarf osteotomy was used to manage a malunited metacarpal fracture, allowing simultaneous correction of both shortening and angulation.
Advancing the understanding and treatment of lung pathologies associated with alpha 1 antitrypsin deficiency
Authors: Turner Alice M. , Ficker Joachim H. , Vianello Andrea , Clarenbach Christian F. , Janciauskiene Sabina , Chorostowska-Wynimko Joanna , Stolk Jan , McElvaney Noel Gerard
Published: February 2025

Alpha 1 antitrypsin deficiency (AATD) is a genetic disorder that alters the functionality and/or serum levels of alpha 1 antitrypsin (AAT). Dysfunctional forms of AAT, or low levels of serum AAT, predispose affected individuals to pulmonary complications. When AATD-associated lung disease develops, the most common pulmonary pathology is emphysema. The development of emphysema and decline in lung function varies by AATD genotype and is accelerated by risk factors, such as smoking. To improve the understanding and treatment of AATD, emerging knowledge and unresolved questions need to be discussed. Here we focus on developments in the areas of disease pathogenesis, biomarkers, and clinical endpoints for trials in AATD, as well as barriers to treatment. The clinical impact of AATD on lung function is highly variable and highlights the complexity of AATD pathogenesis, in which multiple underlying processes are involved. Reduced levels of functional AAT disrupt the protease-antiprotease homeostasis, leading to a loss of neutrophil elastase inhibition and the breakdown of elastin within the lung interstitium. Inflammatory processes also play a critical role in the development of AATD-associated lung disease, which is not yet fully understood. Biomarkers associated with the disease and its complications may have an important role in helping to address AATD underdiagnosis and evaluating response to treatment. To improve access to treatment, the problem of underdiagnosis needs to be addressed and the provision of therapeutic options needs to become uniform. Patients should also be empowered to play a key role in the self-management of the disease. Advancing our understanding of the disease will ultimately improve the life expectancy and quality of life for patients affected by AATD.
End-of-life care for patients with pancreatic cancer in France: a nationwide population-based cohort study
Authors: Marchese Ugo , Pauly Vanessa , Pellat Anna , Richa Yasmina , Fond Guillaume , Tzedakis Stylianos , Gaillard Martin , Fuchs Basile , Orleans Veronica , Fuks David , El Amrani Mehdi , Boyer Laurent
Published: February 2025

Background:

Pancreatic cancer, a frequently fatal disease with severe symptoms, can require high-intensity end-of-life (HI-EOL) care, posing challenges to patients’ well-being. The examination of HI-EOL care to develop tailored interventions in the management of pancreatic cancer is a critical, yet underexplored area.

Objectives:

The objective of this study was to assess the factors that influence the intensity of end-of-life (EOL) care in France.

Design:

A retrospective study of patients registered in the French Nationwide database who were hospitalized in France for pancreatic adenocarcinoma from January 1, 2014 to December 31, 2019, and subsequently died during the follow-up period.

Methods:

Data on patient demographics, clinical characteristics, hospitalization details, and palliative care were collected. The primary outcome measure was the evaluation of HI-EOL care, defined by indicators such as death in an intensive care unit (ICU), multiple hospitalizations, and chemotherapy administration within the last 30 days of life. Secondary outcomes included indicators of most-intensive EOL (MI-EOL) care and invasive procedures (IP). Univariate and multivariate logistic regression analyses were conducted to identify factors associated with each outcome measure.

Results:

A total of 42,696 patients who died from pancreatic adenocarcinoma were included. Among them, 41.1% experienced HI-EOL, with the most common indicators being multiple hospitalizations and death in an ICU, emergency room, or acute care unit. A smaller proportion (2.8%) received MI-EOL care, while 28.1% underwent IPs in the last 30 days of life. The multivariate analysis revealed that male gender and follow-up in non-cancer specialized care facilities were associated with a higher risk of HI-EOL. Conversely, palliative care involvement and older age at death were identified as protective factors. Male gender, older age at death, and palliative care involvement were associated with lower rates of MI-EOL care and IPs.

Conclusion:

These results underscore the importance of palliative care integration and individualized approaches in improving the EOL quality of care and patient outcomes for individuals with advanced pancreatic cancer.
Deaths from Angioedema–Anaphylaxis and Covid-19
Authors: Gray Austin , Ou Richard , Djabourian Raffi , Augustine J. Daniel , Sathyavagiswaran Lakshmanan
Published: February 2025

Angioedema is non-dependent, non-pitting edema at a variety of sites. Its forms can be divided into histamine-mediated and bradykinin-mediated types. Histamine-mediated forms can present similarly to anaphylaxis with urticaria and itching, while bradykinin-mediated angioedema is slower in onset, presents with greater facial oropharyngeal involvement, and has a higher risk of progression. Bradykinin-mediated angioedema is of particular importance as it will not respond to the usual medications used in histamine-mediated anaphylaxis (steroids, antihistamines, epinephrine, etc). In this report, we present two cases of angioedema-induced death with coexisting COVID-19 infections in two male decedents. The associated gross autopsy, histology, and laboratory values will be discussed in detail. This article will highlight the importance of early detection and adequate treatment for the type of angioedema being evaluated as well as a discussion regarding the relationship between COVID-19 and angioedema.