bluuebunny/crossref_metadata_2025 huggingface dataset:
Leaf architecture and functional traits for 122 species at the University of California Botanical Garden at Berkeley
Authors: Matos Ilaine Silveira , Boakye Mickey , Antonio Monica , Carlos Sonoma , Chu Ashley , Duarte Miguel A. , Echevarria Andrea , Fontao Adrian , Garcia Lisa , Huang LeeAnn , Johnson Breanna Carrillo , Joshi Shama , Kalantar Diana , Madhavan Srinivasan , McDonough Samantha , Niewiadomski Izzi , Nguyen Nathan , Park Hailey Jiyoon , Pechuzal Caroline , Rohde James , Sahu Roshni , Scudder Meg , Sharma Satvik , Sneor LeeDar , To Jason , Vu Bradley , Vuong Natalie , Yokota Nicole , Aparecido Luiza M. T. , Forbes Holly , Fricker Mark , Blonder Benjamin
Published: October 2024

The dataset contains leaf venation architecture and functional traits for a phylogenetically diverse set of 122 plant species (including ferns, basal angiosperms, monocots, basal eudicots, asterids, and rosids) collected from the living collections of the University of California Botanical Garden at Berkeley (37.87° N, 122.23° W; CA, USA) from February to September 2021. The sampled species originated from all continents, except Antarctica, and are distributed in different growth forms (aquatic, herb, climbing, tree, shrub). The functional dataset comprises 31 traits (mechanical, hydraulic, anatomical, physiological, economical, and chemical) and describes six main leaf functional axes (hydraulic conductance, resistance and resilience to damages caused by drought and herbivory, mechanical support, and construction cost). It also describes how architecture features vary across venation networks. Our trait dataset is suitable for (1) functional and architectural characterization of plant species; (2) identification of venation architecture‐function trade‐offs; (3) investigation of evolutionary trends in leaf venation networks; and (4) mechanistic modeling of leaf function. Data are made available under the Open Data Commons Attribution License.
Assessing electronic structure modulation strategies toward the development of low‐cost oxygen evolution reaction catalysts
Authors: Zhang Zhen , Han Shaobo , Li Cheng , Cai Chao , Gu Meng Danny
Published: October 2024

Oxygen evolution reactions (OER) are critical to electrochemical synthesis reactions, including hydrogen production and organic hydrogenation. However, the high cost of existing OER catalysts (primarily Ir/Ru and its derived oxides) limits their practical application for electrochemical synthesis. To develop a low‐cost, high‐efficiency alternative, we need a deeper understanding of both the mechanisms that drive OER and the relationship between the catalyst's electronic structure and active sites. Here, we summarized recent developments of catalysts, especially focusing on the electronic structure modulation strategies and their subsequent activity enhancement. Most importantly, we pointed out the study directions for further work.
Non‐Electron Withdrawing Unit Copolymerization to Enhance Photo‐Stability of Thiophene‐Based Organic Solar Cells
Authors: Mohammed Yissa A. , Hone Fekadu G. , Mola Genene T. , Tegegne Newayemedhin A.
Published: October 2024

The impact of non‐electron withdrawing unit copolymerization on photostability of fullerene‐based organic solar cells is investigated using two donor polymers namely: benzodithiophene‐4,8‐dione (BDD) unit copolymerized with α‐quaterthiophene (4 T) unit (PBDD4T) and poly‐3‐hexyl‐thiophene (P3HT). The optical and electrochemical properties of the polymers reveal a deeper highest occupied molecular orbital (HOMO) and broader absorption in PBDD4T in comparison to P3HT owing to the BDD copolymerization. The copolymer achieves a higher power conversion efficiency (PCE) compared to the P3HT‐based device due to its higher VOC and Jsc that resulted from its deeper HOMO level and broader absorption. The photostability study reveals that PBDD4T‐based devices lost 14% of its initial PCE relative to the 48% reduction in PCE for P3HT‐based devices after 7 h of irradiation. Further investigation into the reasons behind the difference in the photostability suggests that photooxidation and recombination induced by irradiation in PBDD4T‐based devcie are suppressed by BDD‐copolymerization, maintaining better stability. In contrast, P3HT:PC71BM‐based solar absorber shows bimolecular recombination due to photoaging processes, which have negatively impacted the device stability. The reduction in stability of both devices is evident by lower photogenerated current attributed to reduced charge mobility and increased surface roughness.
Simple Smoothing of the Bottom Silicon Surface Using Wet Chemical Etching Methods for Epitaxial III‐V/Silicon Tandem Manufacturing
Authors: Chu Mengmeng , Bae Junhan , Khokhar Muhammad Quddamah , Alamgeer  , Aida Maha Nur , Dao Vinh‐Ai , Pham Duy Phong , Park Sangheon , Yi Junsin
Published: October 2024

The implementation of diverse technologies has recently facilitated the production of cost‐effective and highly efficient solar cells. High‐efficiency solar cells with III‐V compounds tandem crystalline silicon cells have achieved photovoltaic efficiency of higher than 39%. Etching silicon wafers plays a vital role in the deposition of epitaxial layers, neutralizing dangling bonds, and surface passivation for tandem solar cells. The wafers are polished using a solution of HF–HNO3–CH3COOH (HNA) and 20% KOH to smoothen the wafer surface. When HNA wet etching is performed for 3.5 min and the 20% KOH etching lasts for 6 min, the microroughness of the wafer is 1.9 nm with a measurement area of 10 × 10 μm2 and 0.816 nm within an area of 1 × 1 μm2. Compared with the as‐cut wafer, the reflectance increases from 31.7% to 34.7%, and the effective minority carrier lifetime, with 30 nm Al2O3 passivation after 450 °C activated, increases from 1.4 to 1.8 ms in a carrier density of 1.0 × 1015 cm−3.
A codifiable methodology for estimating pallet sliding displacements on steel racking systems
Authors: Tsarpalis Dimitrios , Vamvatsikos Dimitrios
Published: October 2024

To facilitate the logistic processes within a modern warehouse, the contents of steel racking systems are not mechanically connected to the supporting beams, allowing a content‐sliding mechanism to develop when static friction is exceeded. Given that the mass of contents is dominant, this is beneficial for limiting the apparent inertia. On the other hand, pallet fall‐off may occur during strong seismic excitations, which is a failure mode that is not addressed by current seismic design processes and guidelines for racks. Along these lines, a codifiable methodology is proposed for estimating sliding displacements on steel racking systems, based on the statistical interpretation of a large set of response history analyses, using different rack configurations and ground motions. Firstly, a multi‐parametric analysis is conducted using simplified rack models to (i) select the intensity measure and engineering demand parameter that can best describe the problem of pallet sliding and (ii) identify the salient rack characteristics that dominate sliding behavior. Thereafter, a series of multi‐stripe analyses are performed using 180 rack realizations with different feature combinations to derive a so‐called, Empirical Sliding Prediction Equation (ESPE) by following a three‐step procedure: (a) perform regression on maximum sliding, (b) perform regression on the normalized sliding profile, and (c) combine steps a‐b to derive the denormalized profile at a given confidence level. The proposed empirical relationships are then validated through a comparison between the observed and fitted sliding displacements in three rack case studies.
Effects of Resveratrol on Nonmelanoma Skin Cancer (NMSC): A Comprehensive Review
Authors: Zamanian Mohammad Yasin , Shahbazi Taha , Kazmi Syeda Wajida , Hussien Beneen M. , Sharma Abhishek , Qasim Maytham T. , Hjazi Ahmed , Sapaev Ibrohim B. , Nouri Danesh Ayda , Taheri Niloofar , Golmohammadi Maryam
Published: October 2024

Nonmelanoma skin cancer (NMSC) represents the most prevalent form of skin cancer globally, with basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) being the most common types. The search for effective chemopreventive and therapeutic agents has led to the exploration of natural compounds, among which resveratrol (RES), a polyphenolic phytoalexin found in grapes, berries, peanuts, and red wine, has garnered significant attention. This comprehensive review aims to elucidate the effects of RES on NMSC, focusing on its mechanisms of action, efficacy in preclinical studies, and potential as a chemopreventive and therapeutic agent. RES exhibits promising chemopreventive and antineoplastic capabilities against NMSC through various mechanisms, including the induction of apoptosis, inhibition of cell proliferation, modulation of oxidative stress, and anti‐inflammatory activities. Studies have demonstrated that RES can significantly enhance the effectiveness of traditional chemotherapeutic agents, such as 5‐fluorouracil (5‐FU), by inhibiting cellular proliferation and inducing apoptosis in cancerous cells. Furthermore, resveratrol's antioxidant properties may mitigate the impact of reactive oxygen species (ROS) triggered by UV exposure, thus reducing DNA damage and mutations associated with skin cancer development. In vitro and in vivo experiments have shown that RES can effectively hinder the growth and spread of various tumor cell types, including human cutaneous SCC A431 cells, and induce apoptosis. The development of advanced delivery systems, such as nanostructured lipid carriers and liposomes, has been recognized for their potential to enhance the therapeutic effects of RES, particularly its anticancer properties. In conclusion, RES presents a viable candidate for the prevention and treatment of NMSC, owing to its multifaceted mechanisms of action, including its ability to regulate oxidative stress, trigger apoptosis, and inhibit proliferation. However, further clinical studies are required to fully understand its effectiveness and safety in humans, as well as to optimize delivery methods for improved bioavailability and therapeutic outcomes.
The effects of supervisory negative feedback and coaching on employees' responses to feedback: The moderating role of mindset
Authors: Zyberaj Jetmir
Published: October 2024

Feedback is a vital human resource development (HRD) practice, extensively researched and used to regulate employee behavior and performance. However, despite a century of research and immense significance and use, we still do not fully know why some accept feedback while others reject it. Critics blame both providers and recipients, as well as feedback message format, for this failure. In this study, I investigated whether the focus of the supervisory feedback (negative vs. negative and facilitative) could enhance employees' responses to feedback (e.g., acceptance and use). I also examined whether employees' mindset (i.e., fixed vs. growth) would moderate these relationships. I proposed that employee coaching (i.e., negative and facilitative) would be more accepted than negative feedback alone. In addition, I expected a positive moderating role of the growth mindset between supervisory feedback and employees' responses. To test these assumptions, I conducted a laboratory experimental vignette study (N = 69). In line with propositions, employee coaching had a larger effect on the employees' responses to feedback (e.g., feedback acceptance; M = 4.95, SD = 1.24) than negative feedback alone (M = 4.08, SD = 1.35). In addition, simple slope results showed that employee coaching was significantly higher than negative feedback for growth mindset (i.e., +1 SD). Finally, path analysis revealed that the interaction between negative feedback, employee coaching, and mindset yielded the strongest positive effect on employees' responses to feedback. Overall, findings add to and endorse calls for more future‐focused HRD practices during feedback interventions. In addition, for effective feedback, this study calls for HRD practitioners to account for all critical factors involved in feedback exchanges, from provider to recipient and feedback message.
A Novel Metric for Corporate Environmental Responsibility and Its Impact on Investment Inefficiency
Authors: Wang Yadong , Albitar Khaldoon , Chbib Imad
Published: October 2024

This study aims to establish a new measurement standard for quantifying Corporate Environmental Responsibility (CER) information and activities disclosed by enterprises and to examine the relationship between CER and investment inefficiency (IIE), with a specific focus on the mediating role of information asymmetry (IA). By analysing how CER influences IIE through information asymmetry, the study provides insights into how transparency and responsible environmental practices can enhance investment decisions and overall corporate performance. Regression analysis of 22,413 firm‐year observations from China A‐shares (2011–2021) shows that active CER disclosure effectively reduces IIE by mitigating information asymmetry, particularly moral hazard (MH) and adverse selection (AS). Robustness tests, including instrumental variable analysis, the Heckman self‐selection model, and Propensity Score Matching (PSM), consistently support these findings. The study also reveals that CER disclosures by non‐state‐owned enterprises (non‐SOEs) and enterprises less sensitive to environmental concerns (NES) significantly diminish IIE by addressing information asymmetry. This research underscores the need for enterprises to embrace environmental responsibility actively, encouraging proactive engagement and transparent disclosure of environmental activities and information.
Patient‐reported pregnancy loss and maternal complications: Insights from the sickle cell disease implementation consortium
Authors: Mathias Joacy G. , Masese Rita V. , King Allison A. , Bulgin Dominique , Stevenson Eleanor , Hankins Jane S. , Glassberg Jeffrey A. , Kanter Julie , Preiss Liliana , Treadwell Marsha , Knisely Mitchell R. , Tanabe Paula J. , Gibson Robert , Gordeuk Victor R. , Shah Nirmish R.
Published: October 2024

Objective

Sickle cell disease (SCD) is associated with complications during pregnancy and can negatively influence maternal outcomes. Our study aimed to determine the prevalence and predictors of maternal morbidity among participants enrolled in an eight‐site SCD Implementation Consortium (SCDIC) registry.

Methods

We conducted a cross‐sectional analysis of female registry participants, aged 15–45 years, with a confirmed diagnosis of SCD. Participants completed a survey of self‐reported pregnancies and outcomes.

Results

Seven hundred and thirty‐eight individuals had at least one pregnancy event, with 1076 live births. Twenty percent reported a pregnancy loss or fetal demise. Of the 1076 live births, 75% involved at least one complication. The most prevalent complications were pain crises (61.1%) and pregnancy requiring blood transfusion(s) (33.0%).

Multiparous individuals with a prior occurrence of a complication in a previous pregnancy had higher odds of recurrence of the same complication in subsequent pregnancies (i.e., previous acute crisis was associated with subsequent acute pain events odds ratio [OR]: 3.13; 95% confidence interval [CI]: 2.06–4.76) and prior transfusion requiring another transfusion (OR: 3.22; 95% CI: 2.01–5.16).

Conclusion

Individuals reported a high prevalence of pregnancy loss and maternal complications. Our findings underscore the importance of preconception counseling and early initiation of perinatal care in SCD.
Handling client financial insolvency in maternity services: An occurrence, experience and policy gap qualitative analysis among healthcare stakeholders in North‐Central Nigeria
Authors: Adeniran Abiodun S. , Fasiku Mojirola M. , Jimoh Maryam A. , Adesiyun Omotayo O. , Adetiloye Oniyire , Okoli Ugo , Chukwu Elizabeth , Ayoola Olusola S. , Oyeniyi Samuel , Orjingene Obinna , Akande Tanimola M.
Published: October 2024

Objective

To assess the occurrence of client financial insolvency, experiences of key healthcare stakeholders, and policy gaps on handling the situation during maternity services.

Methods

A qualitative study was conducted in North‐Central Nigeria. Participants were key healthcare stakeholders including healthcare workers from private, primary, secondary, and tertiary facilities, healthcare administrators/facility‐heads, program managers and policy makers at local and state government levels through In‐depth and Key Informant interviews. Identified themes were occurrence, experiences of stakeholders, and prevention of client financial insolvency. Data were analyzed with the Nvivo statistical package.

Results

Participants confirmed the occurrence of client financial insolvency. Clients' inability to pay hospital bills was due to being indigent, awaiting support from relations, or clients who were uncommitted to the payment. Health facilities lack guiding policy documents; potential cases are referred from private to public or from primary to secondary/tertiary facilities. Methods of handling financial insolvency included healthcare worker‐related (staff scavenging for needed consumables, fund‐raising among facility staff), facility‐related (revolving fund, medical social welfare, welfare committee, discharge with re‐payment plan, fee‐waiver), community‐related (ward development committee, religious organizations/philanthropists) interventions, or hospital detention of insolvent clients. Although clients' bills did not increase during detention, many clients did not honor post‐discharge re‐payment agreements. Participants suggested a client‐friendly billing system, early initiation of birth preparedness, partner involvement, and a rapid scale‐up of health insurance for pregnant women to curb financial insolvency.

Conclusion

Tackling client financial insolvency requires policy documents, support to private facilities, effective debt‐recovery mechanisms, and scale up of health insurance for pregnant women.
Adeno‐associated virus vectors for gene therapy—focusing on melanoma
Authors: Wang Xingyue , Wei Miao , Miao Rui , Hao Xiujing , Li Min , Wang Wenxin , He Zhonglei
Published: October 2024

Adeno‐Associated Virus (AAV) vectors have been found to have great potential in the field of gene therapy due to their unique properties. These nonpathogenic vectors exhibit high tissue specificity, low immunogenicity, and sustained gene expression, enhancing their efficacy for targeted delivery. This review explores the application of AAV vectors in gene therapy. It introduces the application and development of AAV in hemophilia and Duchenne Muscular Dystrophy. The review also highlights the use of AAV vectors in melanoma gene therapy, focusing on four key areas: cancer growth intervention, targeting cancer cells, mediating immune responses, and modulating key signaling pathways. However, despite its many advantages, rAAV faces significant challenges, including host immune responses and biological barriers that limit its effectiveness. Such complexities need to be addressed; therefore, this review also discusses the application of several polymers, such as hydrogels, nanoparticles, and solid scaffolds, in the controlled delivery of AAV.
A novel artificial intelligence‐based antenna designing model for optimizing 5G mobile communication
Authors: B Vasudevan , V Vaithianathan , V Akshaya
Published: October 2024

Antenna designing involves the creation of devices to transmit or receive electromagnetic signals for various applications. It encompasses optimizing parameters such as size, shape, and frequency response to achieve desired performance characteristics, including signal strength, bandwidth, and efficiency, across diverse communication systems and frequencies. In this research, we intend to establish a novel artificial intelligence (AI)‐based antenna designing model for optimizing 5th generation (5G) mobile communication. We proposed Multi‐Objective Zebra Optimization (MOZO) to enhance 5G antenna design, aiming to minimize return loss () and maximize gain (G) concurrently. MOZO efficiently explores design space, offering Pareto‐optimal solutions that balance objectives. This approach ensures optimal antenna performance across the desired frequency range, advancing 5G communication efficiency. Our model enhances the functionality of a small, rectangular patch antenna designed for the 5G band, specifically operating at 30 GHz. Additionally, we conducted a comparative analysis between the performance of our optimized rectangular 5G antenna and several recently employed 5G‐millimeter wave (mmWave) antennas. This comparison sheds light on the efficacy and competitiveness of our optimized design within the 5G‐mmWave antenna landscape.
What Deters Earnings Management? A Benford's Law Comparison Between Publicized Detection Methods and Increased Regulations
Authors: Tran Arthur M.
Published: October 2024

This paper examines the impact of public awareness and regulatory changes on earnings management over time. Despite scrutiny from regulators, auditors, and investors, the deterrents of earnings management remain unclear. I explore whether public awareness, through the dissemination of research, can influence market behaviors and reduce earnings management activities due to increased detection and penalties. Alternatively, I investigate if stricter regulation plays a role in curbing earnings manipulation. Using Benford's Law, I apply Thomas’ (1989) approach and compare data from 1950 to 1985, 1990 to 2002, and 2003 to 2020. My findings indicate that while public awareness alone does not deter earnings management, heightened regulation, particularly post‐Sarbanes‐Oxley Act (SOX), significantly reduces such practices. This study contributes to the literature by highlighting the comparative impact of public awareness and regulatory changes on earnings management.
Association between nasogastric tube feeding and discharge outcomes in patients aged 80 and older with aspiration pneumonia: A propensity score‐matched retrospective cohort study
Authors: Kitamura Misa , Nishizawa Toshinori , Yanai Atsushi , Taguchi Masako , Matsumoto Noriko , Hayashi Kuniyoshi , Arioka Hiroko
Published: October 2024

Background

This study investigated the association between nasogastric tube feeding (NGF) and discharge rate to previous residences with oral intake in patients aged 80+ with aspiration pneumonia.

Methods

A retrospective cohort study included 256 hospitalized patients with aspiration pneumonia from 2012 to 2022, which could not start oral intake within 48 h due to dysphagia. Using 1:2 matched‐pair analysis, the association of interest was examined using logistic regression analysis.

Results

NGF was associated with a lower discharge rate (odds ratio: 0.15; 95% CI: 0.05–0.46).

Conclusion

Patients with NGF had a lower discharge rate to previous residences with oral intake.
Exploring RNA therapeutics for urea cycle disorders
Authors: Richard Eva , Martínez‐Pizarro Ainhoa , Desviat Lourdes R.
Published: October 2024

RNA has triggered a significant shift in modern medicine, providing a promising way to revolutionize disease treatment methods. Different therapeutic RNA modalities have shown promise to replace, supplement, correct, suppress, or eliminate the expression of a targeted gene. Currently, there are 22 RNA‐based drugs approved for clinical use, including the COVID‐19 mRNA vaccines, whose unprecedented worldwide success has meant a definitive boost in the RNA research field. Urea cycle disorders (UCD), liver diseases with high mortality and morbidity, may benefit from the progress achieved, as different genetic payloads have been successfully targeted to liver using viral vectors, N‐acetylgalactosamine (GalNAc) conjugations or lipid nanoparticles (LNP). This review explores the potential of RNA‐based medicines for UCD and the ongoing development of applications targeting specific gene defects, enzymes, or transporters taking part in the urea cycle. Notably, LNP‐formulated mRNA therapy has been assayed preclinically for citrullinemia type I (CTLN1), adolescent and adult citrin deficiency, argininosuccinic aciduria, arginase deficiency and ornithine transcarbamylase deficiency, in the latter case has progressed to the clinical trials phase.
Study on the relationship between surface tension and dilational visco‐elasticity with foam stability
Authors: Zhao Tingting , Zhang Xianzhong , Chen Yang , Jing Lishuai , Bao Zhiming
Published: October 2024

The replacement of fluorine‐free foam is imminent, but to date, no fluorine‐free foam has reached comparable fire extinguishing performance to AFFF (aqueous film forming foam). The stability of firefighting foam significantly affects its extinguishing performance. In order to better understand the influence of foam formulation physical properties on foam stability, we correlate the foam stability with surface tension and dilational visco‐elasticity based on the AFFF formulation. The results show that, the foam stability rising steadily with the decrease of surface tension, which indicates that low surface tension favors the improvement of foam stability. However, when at the studied highest surface tension, the foam stability elevates slightly instead, demonstrating the surface tension is not the determinant of foam stability. By contrast, the dilational visco‐elasticity shows a closer correlation with foam stability for the consistent tendency. In the case of constantly changing disturbance frequency, the interface dilational elasticity shows a trend of first increasing and then decreasing with the rise of disturbance frequency, whereas the interface dilational viscosity is completely opposite. Different relaxation processes show up for different samples. More attention can be paid to the regulation of dilational visco‐elasticity in the development of fluorine‐free foams, so as to improve their extinguishing ability.
Association between the number of individuals injured in a traumatic event and posttraumatic stress disorder among hospitalized trauma patients
Authors: Talmy Tomer , Bulis Shir , Radomislensky Irina , Bushinsky Shir , Tsur Nir , Gelman Daniel , Paulman Omer ,   Israel Trauma Group, Gendler Sami , Tsur Avishai M. , Almog Ofer , Benov Avi
Published: October 2024

Posttraumatic stress disorder (PTSD) often occurs following mass casualty events, yet the connection between the number of individuals injured in an event and PTSD risk in smaller‐scale events (i.e., involving one or several injured persons) remains unclear. We conducted a registries‐based study cross‐referencing three databases across the continuum of care for military trauma patients hospitalized for traumatic injuries. The study population was categorized into three groups based on the number of injured individuals involved (i.e., single injured person, two to four [2–4] injured people, and five or more [≥ 5] injured people), and PTSD prevalence was assessed using long‐term disability claim diagnoses. Overall, 4,030 military personnel were included (age at injury: Mdn = 20 years), and 18.3% were subsequently diagnosed with PTSD, with the highest prevalence in events involving ≥ 5 injured individuals (35.8%). Regression analyses adjusted for potential confounders revealed that being injured in an event with 2–4 injured persons, OR = 1.68, 95% CI [1.31, 2.15], or ≥ 5 injured persons, OR = 2.36, 95% CI [1.79, 3.13], was associated with increased odds of developing PTSD compared to being the sole injured person. The findings suggest a direct association between the number of injured individuals in an event and PTSD prevalence among traumatic injury survivors. The results underscore the importance of early diagnosis and interventions to prevent PTSD in individuals injured in multicasualty and mass casualty events.
Update on the treatment of BRAFmut metastatic melanoma and future perspectives
Authors: Mohr Peter , Nakouri Inès , Pfersch Sylvie , Denjean François , Lebbé Celeste
Published: October 2024

v‐Raf murine sarcoma viral oncogene homolog B (BRAF) mutations were first identified in melanoma in 2002, leading to increased cell division and proliferation, and resultant tumour growth. The identification and characterisation of BRAF mutations (BRAFmut) led to the development of several highly specific, BRAF‐, then mitogen‐activated kinase enzyme (MEK)‐targeted therapies that have enabled rapid tumour responses and improved treatment outcomes in most patients with metastatic BRAFmut melanoma. The combination of these two drug classes (BRAF inhibitors and MEK inhibitors) has demonstrated improved response rates, progression‐free survival, and overall survival (OS), along with a more tolerable safety profile, compared with BRAF inhibition alone. In parallel, improved knowledge of the immune system has enabled the development of immune checkpoint inhibitors (ICIs), although immune‐related adverse events with ICIs may prove to be problematic in some patients and require careful management. While targeted therapy appears to provide rapid disease control in a relatively high proportion of patients, the development of secondary resistance may limit the overall duration of responses. Acquired resistance, along with primary resistance, has also been reported for ICIs, with a lower overall response rate to that with targeted therapy, although durable responses have been reported in some responding patients. A combination strategy of targeted therapy with ICIs has demonstrated modest increases in efficacy compared with targeted therapy combinations, although data significance varies across studies, there is increased risk of toxicity, and triple combination therapy has not yet received clinical approval in Europe. Thus, there is an ongoing need to establish optimal sequencing of these treatments in patients with advanced BRAFmut melanoma, and this has become the focus of current research. The aim of this narrative review was to provide an update on the treatment of BRAFmut metastatic melanoma, current guideline recommendations, and future clinical perspectives.
Aspergillus otitis externa: A retrospective study of predisposing factors, treatment, and complications
Authors: Viljanen Milla , Saarinen Riitta , Hafrén Lena
Published: October 2024

Objectives

To study the predisposing factors, treatment, and complications of Aspergillus otitis externa.

Methods

A retrospective analysis of patients diagnosed with Aspergillus otitis externa at the Department of Otorhinolaryngology, Helsinki University Hospital, between January 2010 and December 2018 was performed.

Results

Of the 269 Aspergillus otitis externa (OE) patients, 96 developed otitis media (OM) and 7 developed mastoiditis. Antibiotic and steroid treatment and otological history were risk factors for Aspergillus OE. Systemic diseases and immunocompromising states were more common in mastoiditis patients. Repetitive ear cleaning and topical drugs are primary treatments, but systemic drugs and surgery were needed in resistant and invasive cases. Forty‐five novel tympanic membrane (TM) perforations were reported. A strong association between Aspergillus species and final infection types was found; A. niger was the dominant species in OM and in novel TM perforations, whereas A. flavus and A. fumigatus caused mastoiditis. Some of the TM perforations persisted despite treatment. Permanent hearing impairment was associated with OM and mastoiditis.

Conclusion

As Aspergillus OE has the potential to cause acute and chronic complications, fungal OE should be suspected early on if the infection persists after conventional treatment. The identification of Aspergillus species could aid in spotting patients at risk for more severe disease and complications. Intensive local treatment is sufficient in most cases of OE and OM but effective topical antifungals are limited. Patients with Aspergillus OM and mastoiditis should be followed up for hearing impairment and permanent TM perforations after the infection resolves.

Level of evidence

Level 4 (The Oxford 2011 Levels of Evidence).
Exploring Morphological and Molecular Properties of Different Adipose Cell Models: Monolayer, Spheroids, Gellan Gum‐Based Hydrogels, and Explants
Authors: Albrecht Franziska B. , Schick Ann‐Kathrin , Klatt Annemarie , Schmidt Freia F. , Nellinger Svenja , Kluger Petra J.
Published: October 2024

White adipose tissue (WAT) plays a crucial role in energy homeostasis and secretes numerous adipokines with far‐reaching effects. WAT is linked to diseases such as diabetes, cardiovascular disease, and cancer. There is a high demand for suitable in vitro models to study diseases and tissue metabolism. Most of these models are covered by 2D‐monolayer cultures. This study aims to evaluate the performance of different WAT models to better derive potential applications. The stability of adipocyte characteristics in spheroids and two 3D gellan gum hydrogels with ex situ lobules and 2D‐monolayer culture is analyzed. First, the differentiation to achieve adipocyte‐like characteristics is determined. Second, to evaluate the maintenance of differentiated ASC‐based models, an adipocyte‐based model, and explants over 3 weeks, viability, intracellular lipid content, perilipin A expression, adipokine, and gene expression are analyzed. Several advantages are supported using each of the models. Including, but not limited to, the strong differentiation in 2D‐monolayers, the self‐assembling within spheroids, the long‐term stability of the stem cell‐containing hydrogels, and the mature phenotype within adipocyte‐containing hydrogels and the lobules. This study highlights the advantages of 3D models due to their more in vivo‐like behavior and provides an overview of the different adipose cell models.
Study on the effect of fiber‐matrix interface on mechanical response of carbon fiber fabrics reinforced polyether ether ketone composites
Authors: Wang Yan , Lin Ziyu , Li Ming , Zhang Hongbo , Yang Ting , Zhang Yunhe , Zhang Haibo , Zhang Jinling , Pang Jinhui , Jiang Zhenhua
Published: October 2024

Carbon fiber fabrics reinforced polyether ether ketone (CFF/PEEK) composites show extraordinary mechanical properties which deeply relay on their interfacial properties. Herein, two simple desizing method of acetone and high‐temperature were used to remove sizing agent of CFF. The fiber surface roughness and surface activity increased after desizing, which enhances interfacial wettability between fiber and resin. The interface shear strength (IFSS) measured by micro‐bond test was used to evaluated the interfacial properties. After desizing, the IFSS enhanced from 41.7 to 51.2 MPa, which may be owing to enhanced of interfacial adhesion and mechanical locking between CFF and PEEK. CFF/PEEK laminates were fabricated by a simple film stacking method using hot‐pressing process of CFF and PEEK film. Interlaminar shear strength (ILSS) tested by short‐beam method increased from 62.5 to 71.3 MPa, and flexural strength increased from 754.4 to 805.5 MPa, which indicated the fiber‐matrix interface enhanced. Furthermore, forming quality and microscopic failure modes of CFF/PEEK verified fiber‐matrix interface enhanced after removing sizing agent. The interfacial and mechanical properties of CFF/PEEK composites significantly enhanced by using simple and effective desizing method. This study is expected to provide valuable insights into optimizing fiber surface treatments for enhancing durability and reliability of advanced composite materials.

Highlights

Acetone and high‐temperature desizing were used to remove sizing agent of CFF.

The IFSS of treatment CFF increased over 25% compared with untreated ones.

The ILSS and flexural strength of desizing‐CFF/PEEK enhanced notably.

The fiber‐matrix interface between desizing‐CFF and PEEK resin enhanced.
Feasibility of Hybrid Polyaniline/Pullulan Composites for Photocatalytic and Electrochemical Applications
Authors: Mohamed Isa Eleen Dayana , Che Jusoh Nurfatehah Wahyuny , Omar Nurizan , Rasit Ali Roshafima , Shameli Kamyar
Published: October 2024

Energy and water are essential resources currently facing high demand due to the depletion of fossil fuels and increasing water pollution. Conducting polymers like polyaniline (PANI) have gained attention for addressing these challenges. In this study, polyaniline/pullulan composites (PANI/Pul Cps) are synthesized via oxidative polymerization. The influence of the aniline‐to‐pullulan mass ratio on the composite properties is evaluated using various techniques. XRD analysis showed enhanced crystallinity with the addition of pullulan, while TEM results revealed that the composites exhibited a rod‐like shape, with dimensions of 51–55 nm in width and 131–152 nm in length. The photocatalytic potential of the composites is assessed by testing their ability to degrade Crystal Violet dye, with the highest degradation rate observed at 0.0086 min⁻¹. The electrochemical performance of the PANI/Pul Cps is also evaluated, with specific capacitance values ranging from 92 to 123 F/g. These results suggest that PANI/Pul Cps have potential for both wastewater treatment and energy storage applications.
High‐flow nasal cannulas versus standard oxygen therapy for moderate bronchiolitis: a quasi‐experimental analysis
Authors: Antilici Livia , Vittucci Anna C. , Cristaldi Sebastian , Musolino Anna M. C. , Pisani Mara , Rotondi Aufiero Lelia , Di Maio Chiara V. , Scutari Rossana , Cutrera Renato , Dotta Andrea , Perno Carlo F. , Villani Alberto
Published: October 2024

Background

In the last decades none of the medical therapies investigated have shown clear efficacy in the treatment of bronchiolitis, and literature agrees on a general de‐implementation of pharmacological therapies, recognizing an effective role only to nutritional support and oxygen therapy. High‐flow nasal cannulas (HFNC) has become increasingly popular in the last decade, despite its lack of clear efficacy. Recent randomized controlled trials (RCT) comparing standard oxygen therapy (SOT) and HFNC did not demonstrate significant benefit of HFNC. To acquire more clinical data on HFNC efficacy we performed a retrospective, quasi‐experimental analysis of patients admitted for bronchiolitis in the epidemic seasons 2021–2022 and 2022–2023.

Methods

To assess the efficacy of SOT and HFNC we used a pragmatic approach, a fuzzy regression discontinuity design, which is a quasi‐experimental test. Unlike RCTs, this process is not a true randomization, but may be interpreted as quasi‐randomization in an observational setting.

Results

HFNC did not reduce length of oxygen therapy (LOO) nor length of hospitalization (LOS) (respectively, p: 0.383 and p: 0.454). Treatment failure was not significantly different in the treatment groups (p: 0.354).

Conclusions

It is crucial to perform additional RCTs with uniform protocols to determine the efficacy of HFNC more accurately in the treatment of bronchiolitis. HFNC does not reduce LOO, suggesting that early use of HFNC does not change the course of disease in moderate bronchiolitis. In view of the greater complexity and higher cost, HFNC should not be routinely used as first‐line treatment in children with moderate respiratory distress and mild hypoxemia.
The disappearing lesion in the cricopharynx: A hypopharyngeal cushion
Authors: Balaji Sarath , Thirunavukkarasu Saravanamuthu , Chellakutti Thangaraj , Madhusudan Manoj
Published: October 2024

A 2‐year‐old girl presented to our aero‐digestive clinic with complaints of dysphagia to solids. On awake endoscopy, a bluish, expansile lesion was noticed. posterior to the arytenoids, which became prominent when crying. During the airway evaluation under general anesthesia, the lesion completely disappeared, revealing a normal posterior cricoid region. Upon closer examination, a small venous malformation was noted in the posterior pharyngeal wall. A diagnosis of a “hypopharyngeal cushion” was made.
The preclinical pharmacokinetics of Tolinapant—A dual cIAP1/XIAP antagonist with in vivo efficacy
Authors: Martins Vanessa , Ward George , Smyth Tomoko , Reader Mike , Chessari Gianni , Johnson Chris , Wilsher Nicola
Published: October 2024

AT‐IAP (1‐{6‐[(4‐fluorophenyl)methyl]‐3,3‐dimethyl‐1H,2H,3H‐pyrrolo[3,2‐b]pyridin‐1‐yl}‐2‐[(2R,5R)‐5‐methyl‐2‐{[(3R)‐3‐methylmorpholin‐4‐yl]methyl}piperazin‐1‐yl]ethan‐1‐one) was identified as a novel potent non‐alanine small molecule dual inhibitor of cIAP1/XIAP protein. AT‐IAP was assessed in preclinical species, demonstrating favorable bioavailability in rodent species and oral efficacy at 30 mg/kg in MDA‐MB‐231 mouse xenograft models. The major metabolic route of AT‐IAP was identified to be CYP3A driven, resulting in low oral exposure in non‐human primate (NHP) studies, given the comparatively high expression of equivalent CYP3A. AT‐IAP metabolite identification studies determined ring opening of the morpholino or piperazine moiety. An extensive campaign of optimisation resulted in increased polarity by the addition of a hydroxymethyl, which led to the identification of tolinapant (1‐(6‐[(4‐Fluorophenyl)methyl]‐5‐(hydroxymethyl)‐3,3‐dimethyl‐1 H,2 H,3 H‐pyrrolo[3,2‐ b]pyridin‐1‐yl)‐2‐[(2 R,5 R)‐5‐methyl‐2‐([(3R)‐3‐methylmorpholin‐4‐yl]methyl)piperazin‐1‐yl]ethan‐1‐one) with reduced CYP3A metabolism. Tolinapant showed oral bioavailability in rodents and NHP in the range 12–34% at 5 mg/kg. Non‐linear pharmacokinetics in NHP were observed at oral doses in the range 5–75 mg/kg. Pharmacodynamic modulation and efficacy were demonstrated in A375 mouse xenograft models at dose ranges between 5 and 20 mg/kg. On‐target engagement, as measured by reduction of cIAP 1 protein levels, was confirmed in NHP surrogate tissues and applied to target activity assessments in tolinapant phase1/2 clinical trials.
Dynamic Self‐Triggered Parallel Control of Guidance Intercept Systems With Constrained Inputs via Adaptive Dynamic Programming
Authors: Liu Lu , Song Ruizhuo , Lian Bosen
Published: October 2024

This paper introduces an anti‐saturation optimization algorithm based on dynamic self‐triggered adaptive dynamic programming (ADP) for bounded acceleration guidance interception. By establishing a nonlinear input‐constrained guidance intercept and control system, the smooth bounded function is used to constrain the system input to ensure that the system operates in a controllable range. Subsequently, the appropriate performance function that can accurately reflect the system is designed. In alignment with the advantages of parallel control and ADP, a group of parallel systems are constructed by modeling the derivation of control input. A self‐learning control framework is explored, facilitating virtual‐actual interaction and mutual reinforcement between multiple controllers, optimizing the management of the interception system. Furthermore, event‐triggered control (ETC) policies are devised, which can be updated only when needed by setting trigger conditions, thus saving data resources. The stability proof of the closed‐loop system is given to ensure that the system can keep stable operation when the trigger condition is satisfied. On this basis, a dynamic self‐triggered control (DSTC) with soft computing is put forward, enabling trigger instant calculation without real‐time system monitoring and further extending the trigger interval. Simulation results evidence that the devised guidance scheme can intercept the maneuvering target at a reduced expenditure of communication resources.
A Modified Debiased Inverse‐Variance Weighted Estimator in Two‐Sample Summary‐Data Mendelian Randomization
Authors: Su Youpeng , Xu Siqi , Ma Yilei , Yin Ping , Hao Xingjie , Zhou Jiyuan , Fung Wing Kam , Jiang Hongwei , Wang Peng
Published: October 2024

Mendelian randomization uses genetic variants as instrumental variables to estimate the causal effect of exposure on outcome from observational data. A common challenge in Mendelian randomization is that many genetic variants are only modestly or even weakly associated with the exposure of interest, a setting known as many weak instruments. Conventional methods, such as the popular inverse‐variance weighted (IVW) estimator, could be heavily biased toward zero when the instrument strength is weak. To address this issue, the debiased IVW (dIVW) estimator and the penalized IVW (pIVW) estimator, which are shown to be robust to many weak instruments, were recently proposed. However, we find that the dIVW estimator tends to produce an exaggerated estimate of the causal effect, especially when the effective sample size is small. Although the pIVW estimator has better statistical properties, it is slightly more complex, and the idea behind this method is also a bit less intuitive. Therefore, we propose a modified debiased IVW (mdIVW) estimator that directly multiplies a shrinkage factor with the original dIVW estimator. After this simple modification, we prove that the mdIVW estimator not only has second‐order bias with respect to the effective sample size, but also has smaller variance and mean squared error than the preceding two estimators. We then extend the proposed method to account for the presence of instrumental variable selection and balanced horizontal pleiotropy. We demonstrate the improvement of the mdIVW estimator over the competing ones through extensive simulation studies and real data analysis.
UV Filter NanoCapsule with Broad‐Spectrum UV Protection
Authors: Wang Yali , Chen Hao , Zhang Yun , Cao Yuhua
Published: October 2024

In this study, nanocapsules encapsulating avobenzone (AVB) compounded with isooctyl p‐dimethylaminobenzoate (OD‐PABA) were prepared via miniemulsion polymerization using methyl methacrylate (MMA) as the monomer, ethylene glycol dimethacrylate (EGDMA) as the cross‐linker, and poly(styrene‐co‐methacrylic acid) (P(St‐co‐MAA)) as the polymeric emulsifier. When a solid ultraviolet radiation A (UVA) filter, AVB, was encapsulated in nanocapsules (A‐UVNCs), the encapsulation and loading rates were 67.6% and 9.7%, respectively. When a liquid ultraviolet radiation B (UVB) filter, OD‐PABA, was combined with AVB, the encapsulation and loading rates of the nanocapsules (A/O‐UVNCs) of AVB and OD‐PABA increased to 90.0% and 15.6%, respectively, and 71.5% and 14.0%, respectively. The A/O‐UVNCs realized broad‐spectrum ultraviolet (UV) protection with an SPF value of 46.3. The A/O‐UVNCs have raspberry‐like nanostructures. These submicron particles can scatter and reflect a portion of the UV radiation and synergistically enhance UV protection. After exposure to simulated sunlight for four hours, the UVAPF of a sunscreen containing A‐UVNCs or A/O‐UVNCs decreased to a smaller extent than that of the sunscreen containing free AVB. Cell toxicity experiments showed that the cell viability of A‐UVNCs and A/O‐UVNCs was 85.9% and 83.0%, respectively. Therefore, UVNCs not only enhance UV protection but also improve photostability and safety.