bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic Analysis of Melanoma Types Using Japanese Genomic Database
Authors: Matsumoto Hayato , Nagano Hiromi , Kyutoku Takayuki , Yamashita Masaru 
Published: August 2024

ObjectivesThe purpose of this study is to compare genetic mutations, tumor mutation burden (TMB), and the effects of molecular targeted drugs and immune checkpoint inhibitors (ICIs) in head and neck mucosal melanoma (HNMUM) with those in skin melanoma (SKM) and ocular melanoma (OM).MethodsData were analyzed for 72 consecutive patients with HNMUM, including 366 with SKM and 31 with OM, registered at the Japan National Cancer Center, Center for Cancer Genomics and Advanced Therapeutics (C‐CAT) between June 2019 and October 2023. Genetic alterations and TMB were determined by FoundationOne CDx next‐generation sequencing.ResultsThe top 10 mutations in HNMUM were RAD21 (47.2%), NBN (45.8%), MYC (40.3%), LYN (31.9%), NRAS (29.1%), IRF4 (23.6%), DAXX (22.2%), KIT (22.2%), NOTCH3 (20.8%), and DDR1 (19.4%), with 16.6 ± 0.8 (mean ± SEM) mutations/individual. In SKM, BRAF (p = 0.04) mutation was associated with a significantly better prognosis. The TMB values were 5.7 ± 2.1 (mean ± SEM) in HNMUM, 4.1 ± 0.2 in SKM, and 3.4 ± 0.9 in OM, with no significant differences among the three groups. The median survival time for patients with distant metastases was 803 (95% confidence interval: 539‐NA) days for HNMUM, 1413 (831–2172) days for SKM, and 1138 (438‐NA) days for OM.ConclusionsThe top 10 mutations in HNMUM are closer to those in OM than those in SKM. There was no significant difference in TMB values or survival rates with regard to the therapeutic effect of ICIs among the diseases, which suggests that current treatment of HNMUM with ICIs is appropriate.Level of Evidence3 Laryngoscope, 2024
Severe Acute Motor Exacerbations (SAME) across Metabolic, Developmental and Genetic Disorders
Authors: Couto Blas , Galosi Serena , Steel Dora , Kurian Manju A. , Friedman Jennifer , Gorodetsky Carolina , Lang Anthony E. 
Published: August 2024

AbstractAcute presentation of severe motor disorders is a diagnostic and management challenge. We define severe acute motor exacerbations (SAME) as acute/subacute motor symptoms that persist for hours‐to‐days with a severity that compromise vital signs (temperature, breath, and heart rate) and bulbar function (swallowing/dysphagia). Phenomenology includes dystonia, choreoathetosis, combined movement disorders, weakness, and hemiplegic attacks. SAME can develop in diverse diseases and can be preceded by triggers or catabolic states. Recent descriptions of SAME in complex neurodevelopmental and epileptic encephalopathies have broadened appreciation of this presentation beyond inborn errors of metabolism. A high degree of clinical suspicion is required to identify appropriately targeted investigations and management. We conducted a comprehensive literature analysis of etiologies. Reported triggers are described and classified as per pathophysiological mechanism. A video of six cases displaying multiple SAME with diverse outcomes is provided. We identified 50 different conditions that manifest SAME, some associated with developmental regression. Etiologies include disorders of metabolism: energy substrate, amino acids, complex molecules, vitamins/cofactors, minerals, and neurotransmitters/synaptic vesicle cycling. Non‐metabolic neurodegenerative and genetic disorders that present with movement disorders and epilepsy can additionally manifest SAME. A limited number of triggers are grouped here, together with an approach to investigations and general management strategies. Several neurogenetic and neurometabolic disorders manifest SAME. Identifying triggers can help in certain cases narrow the differential diagnosis and guide the expeditious application of targeted therapies to minimize adverse developmental and neurological consequences. This process may inform pathogenesis and eventually improve our understanding of the mechanisms that lead to the development of SAME. © 2024 International Parkinson and Movement Disorder Society.
Functional Movement Disorder as a Prodromal Symptom of Parkinson's Disease—Clinical and Pathophysiological Insights
Authors: Matar Elie , Tinazzi Michele , Edwards Mark J. , Bhatia Kailash P. 
Published: August 2024

AbstractFunctional movement disorder (FMD) is a common manifestation of functional neurological disorder. FMD can occur alongside other neurological conditions, but especially in patients with established Parkinson's disease (PD). An interesting observation emerging across cohort studies and case series is that FMD can precede the diagnosis of PD, suggesting that FMD may itself be a prodromal symptom of neurodegeneration. Such a notion would have significant clinical implications for the assessment and management of people with FMD, particularly with respect to decisions around the use of auxiliary investigations, counselling, and follow‐up. In this Viewpoint we review the evidence concerning the temporal relationship between FMD and PD. We discuss the potential explanations and mechanisms for FMD as a prodromal symptom of PD, and highlight clinical considerations and important outstanding questions in the field. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Probabilistic Refinement of Focused Ultrasound Thalamotomy Targeting for Parkinson's Disease Tremor
Authors: Cheyuo Cletus , Germann Jürgen , Yamamoto Kazuaki , Zibly Zion , Krishna Vibhor , Sarica Can , Borges Yuri Ferreira Felloni , Vetkas Artur , Kalia Suneil K. , Hodaie Mojgan , Fasano Alfonso , Schwartz Michael L. , Elias W. Jeffrey , Lozano Andres M. 
Published: August 2024

AbstractBackgroundThere remains high variability in clinical outcomes when the same magnetic resonance image‐guided focused ultrasound (MRgFUS) thalamotomy target is used for both essential tremor (ET) and tremor‐dominant Parkinson's disease (TDPD).ObjectiveOur goal is to refine the MRgFUS thalamotomy target for TDPD versus ET.MethodsWe retrospectively performed voxel‐wise efficacy and structural connectivity mapping using 3‐12‐month post‐procedure hand tremor scores for a multicenter cohort of 32 TDPD patients and a previously published cohort of 79 ET patients, and 24‐hour T1‐weighted post‐MRgFUS brain images. We validated our findings using Unified Parkinson's Disease Rating Scale part III scores for an independent cohort of nine TDPD patients.ResultsThe post‐MRgFUS clinical improvements were 45.9% ± 35.9%, 55.5% ± 36%, and 46.1% ± 18.6% for ET, multicenter TDPD and validation TDPD cohorts, respectively. The TDPD and ET efficacy maps differed significantly (ppermute < 0.05), with peak TDPD improvement (87%) at x = −13.5; y = −15.0; z = 1.5, ~3.5 mm anterior and 3 mm dorsal to the ET target. Discriminative connectivity projections were to the motor and premotor regions in TDPD, and to the motor and somatosensory regions in ET. The disorder‐specific voxel‐wise efficacy map could be used to estimate outcome in TDPD patients with high accuracy (R = 0.8; R2 = 0.64; P < 0.0001). The model was validated using the independent cohort of nine TDPD patients (R = 0.73; R2 = 0.53; P = 0.025—voxel analysis).ConclusionWe demonstrated that the most effective MRgFUS thalamotomy target in TDPD is in the ventral intermediate nucleus/ventralis oralis posterior border region. This finding offers new insights into the thalamic regions instrumental in tremor control, with pivotal implications for improving treatment outcomes. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Speech Quality Perception in Unilateral Cochlear Implant Users With Single‐Sided Deafness
Authors: Kelly Scott , Kuhlmey Megan E. , Despotidis Meghan A. , Alter Isaac L. , Hwa Tiffany P. , Chern Alexander , Lalwani Anil K. 
Published: August 2024

AbstractObjectiveCochlear implant (CI) users frequently complain about speech quality perception (SQP). In patients undergoing cochlear implantation for single‐sided deafness, there is concern that poor SQP from the implanted ear will negatively impact binaural (CI + normal hearing [NH]) SQP. In this study, we investigate if binaural SQP is measurably different than unimplanted NH alone.Study DesignCross‐sectional study.SettingTertiary care center.MethodsFifteen unilateral CI users with NH in the contralateral ear completed the validated Columbia Speech Quality Instrument. This instrument consists of 9 audio clips rated across 14 specific speech qualities using a 10‐point visual analog scale. SQP was assessed in 3 conditions: CI only, NH only, and CI + NH.ResultsMedian speech quality scores were worse in the CI only condition compared to the NH only (50.0 vs 72.6, P = .0003) and binaural (50.0 vs 71.0, P = .007) conditions. Median speech quality scores were not significantly different between the NH only and binaural conditions (72.6 vs 71, P = .8). Compared to NH, CI speech quality sounded less clear, less natural, and more mechanical.ConclusionCompared to NH, SQP is poorer with a CI alone. However, in contrast to expectation, there is no significant difference between NH and binaural SQP. This suggests poorer CI speech perception does not negatively impact binaural SQP in patients undergoing cochlear implantation for single‐sided deafness.
Prenatal Diagnosed Agenesis of the Corpus Callosum: Identifying the Underlying Genetic Etiologies
Authors: Wei Xing , Cai Luyao , Zhang Luye , Chen Jianping , Zhang Yun , Meng Meng , Yang Yingjun , Zhou Xinyao , Zou Gang , Sun Luming 
Published: August 2024

ABSTRACTObjectiveTo assess the genetic etiologies underlying agenesis of the corpus callosum (ACC) and its pregnancy outcomes in the era of next‐generation sequencing.MethodsA retrospective analysis was conducted on prospectively collected prenatal ACC cases in which amniocentesis was performed between January 2016 and December 2022. ACC was divided into non‐isolated and isolated according to the presence or absence of ultrasound abnormalities. Chromosomal microarray analysis (CMA), karyotyping and exome sequencing (ES) were performed after genetic counseling. Pregnancy outcomes were assessed by pediatric neurosurgeons and were followed up by telephone through their parents.ResultsSixty‐eight fetuses with ACC were enrolled in this study. CMA detected eight cases with pathogenic copy number variants (CNVs) and all were non‐isolated ACC, with a detection rate of 11.8% (8/68). Among the CMA abnormalities, the majority (6/8) were detectable by karyotyping. ES was performed in 26 cases with normal CMA, revealing pathogenic or likely pathogenic gene variations in 12 cases (46.2%, 12/26), involving L1CMA, SMARCB1, PPP2R1A, ARID1B, USP34, CDC42, NFIA and DCC genes. The detection rates of ES in isolated and non‐isolated ACC were 40% (6/15) and 54.5% (6/11), respectively. After excluding cases where pregnancy was terminated (56 cases), there were 12 live births, ranging in age from 15 months to 7 years. Of these, 91.7% (11 out of 12) demonstrated normal neurodevelopmental outcomes. Specifically, all five cases with isolated ACC and negative ES results exhibited normal neurodevelopment. The remaining six cases with favorable outcomes were all isolated ACC, among which ES identified variants of DCC and USP34 gene in one each case. The other four cases were CMA‐negative and declined ES.ConclusionsWe highlight the efficacy of prenatal ES in determining the genetic etiology of ACC, whether isolated or not. Favorable neurodevelopmental outcomes were observed when ACC was isolated and with normal ES results.
Towards resource‐efficient forests: Mixing species changes crown biomass allocation and improves growth efficiency
Authors: Hilmers Torben , Mehtätalo Lauri , Bielak Kamil , Brazaitis Gediminas , del Río Miren , Ruiz‐Peinado Ricardo , Schmied Gerhard , Uhl Enno , Pretzsch Hans 
Published: August 2024

Societal Impact StatementForests worldwide face significant challenges due to climate change, impacting their health and productivity. In this study, we examined how European beech and Scots pine influence each other's phenology and growth in mixed forests. Our findings indicate that mixing these complementary tree species can increase resource efficiency within forest ecosystems. By leveraging informed species selection, this research highlights the potential for developing knowledge‐based, resource‐efficient forests. These insights are invaluable for policymakers and forest managers in designing forests that are not only productive but also sustainable and adaptable to evolving environmental conditions.Summary

We investigated the effects of interspecific neighbors on crown morphology and growth efficiency in European temperate forests, specifically focusing on European beech (Fagus sylvatica L.) and Scots pine (Pinus sylvestris L.). Our goal was to determine whether the previously reported overyielding in this mixture is primarily due to improved space‐use efficiency and packing density or enhanced resource‐use efficiency.
Our methodology involved a detailed analysis of 128 individual felled trees. We assessed the effect of intraspecific and interspecific neighbors on stem volume growth, the allometric relationships of tree crowns and their components, and the allocation of branch and leaf biomass along the trees' vertical structure.
Our findings demonstrate that interspecific neighbors significantly influence the allometric relationships of tree crowns, especially altering the vertical biomass distribution in European beech. Additionally, we found that interspecific neighbors can significantly enhance the growth efficiency of European beech but not for Scots pine.
This research provides valuable insights for enhancing forest growth models and guiding forest management practices. By understanding the critical role of crown biomass allocation and growth efficiency in mixed‐species stands, policymakers and forest managers can design forests that are both productive and adaptable to changing environmental conditions. This study emphasizes the importance of species interactions in forest dynamics and bridges theoretical concepts with practical applications.
Confinement of Lauric Acid into the Lumen of Halloysite Nanotubes
Authors: Obele Chizoba M. , Barroso‐Bujans Fabienne 
Published: August 2024

AbstractMolecules confined within nanometer‐scale environments frequently exhibit a distinct physical response in contrast to those found in bulk conditions. In this study, intercalates of lauric acid (LA) are synthesized within halloysite nanotubes (HNT), successfully trapping 12 wt.% of LA within the internal HNT tube, as demonstrated by transmission electron microscopy (TEM), and wide‐angle and small‐angle X‐ray scattering (WAXS/SAXS) techniques. Furthermore, it is noted that the confinement of LA within the HNT lumen resulted in a significant reduction in LA crystallinity, consistent with the impact of geometric constraints on crystallization behavior. The presence of a significant amorphous phase in the intercalates proved beneficial for the gradual release of LA into water, as evidenced by pH changes. Remarkably, the necessity of employing a vacuum method and extended contact time (72 h) for the physical entrapment of LA in ethanol within the HNT lumen is found to be unnecessary, as similar physical characteristics are observed in an intercalate generated without vacuum and with very short contact time (<1 h). Finally, it is observed that the source of HNT is crucial in determining the final properties of the confined material.
Topical and transdermal botanical formulations of the Chinese pharmacopoeia—A review
Authors: Gu Jingyi , Lane Majella E. , Da Silva Sil Dos Santos Bruno , Heinrich Michael 
Published: August 2024

AbstractIn pharmaceutics, ingredients are classified as active ingredients and excipients. In topical/transdermal phytomedicines, an ingredient may serve both functions. Published information on these dual‐purpose ingredients and their pharmacological relevance is limited. An intriguing scenario arises in traditional Chinese medicine (TCM) formulations, where active ingredients and excipients are undifferentiated. This study analyzes ingredients in TCM topical/transdermal formulations, aiming at harmonization of understanding of TCMs. The most commonly recorded ingredients from such formulations in the Chinese pharmacopoeia 2020 (ChP 2020) are reviewed, aiming at developing innovative topical/transdermal phytomedicines. Current editions of Chinese historical documents were reviewed to explore the principles underlying the use of these ingredients. TCM formulations containing botanical drugs for topical/transdermal application were selected from the ChP 2020. The use of botanical materials in TCM formulations is guided by the “Jun‐Chen‐Zuo‐Shi” principle rooted in Yin‐Yang and the five elements' theories. In the ChP 2020, 155 botanical drugs, along with 40 excipients (from the “procedure” section, focusing on processing and technical parameters), were identified from 34 botanical formulations intended for topical/transdermal application. Pungent and aromatic botanical materials were the most frequently recorded. Adhesive plasters were the most commonly recorded TCM dosage form, employing specific matrix blends. This new perspective of study reveals the prevalence of pungent and aromatic botanical materials, the common use of adhesive plasters, multifunctional properties of botanical oils, and formulation adaptability in TCM topical/transdermal products. These insights should inform novel formulation designs for both pharmaceutical and phytopharmacological research.
New potential selective estrogen receptor modulators in traditional Chinese medicine for treating menopausal syndrome
Authors: Song Xintong , Shen Lan , Contreras Janine Micahella , Liu Zhiyuan , Ma Kai , Ma Biao , Liu Xiaoling , Wang Dan Ohtan 
Published: August 2024

AbstractWomen go through several predictable conditions and symptoms during menopause that are caused by age, changes in sex hormone levels, and other factors. Conventional menopause hormone therapy has raised serious concerns about the increased risks of cancers, blood clots, depression, etc. Selective estrogen receptor modulators (SERMs) that can be both agonists and antagonists of estrogen receptors in a tissue‐specific manner are being developed to reduce the health concerns associated with menopause hormone therapy. Here, we have searched the Chinese national traditional Chinese medicine (TCM) patent database to identify potential SERM‐like compounds with reduced health risks. TCM has been widely used for treating complex symptoms associated with menopause syndrome and thus can be a particularly rich source for pharmaceutical alternatives with SERM properties. After extensive literature review and molecular simulation, we conclude that protopanaxatriol, paeoniflorin, astragalin, catalpol, and hyperoside among others may be particularly promising as SERM‐like compounds in treating the menopausal syndrome. Compounds in TCM hold promise in yielding comparable outcomes to hormone therapy but with reduced associated risks, thus presenting promising avenues for their clinical applications.
Increased Physical Activity Promotes Skin Clearance, Improves Cardiovascular and Psychological Health, and Increases Functional Capacity in Patients with Psoriasis
Authors: Sheppard Rory , Gan Weh K. , Onambele-Pearson Gladys L. , Young Helen S. 
Published: August 2024

Abstract

Background
Patients with psoriasis are less physically active compared to age-matched controls, due to psoriasis-specific barriers, which significantly limits their ability to benefit from health-promoting levels of physical activity (PA). In addition, long-term health outcomes for people with psoriasis are poor and include depression, metabolic syndrome and cardiovascular disease (CVD); presenting a significant challenge to healthcare services.

Objectives
We designed a PA intervention in partnership with patients with psoriasis hypothesising this may have therapeutic utility in the management of psoriasis.

Methods
Participants with chronic plaque psoriasis were recruited to a single-centre, 20-week, prospective cohort study. A wrist-worn accelerometer (GENEActiv Original; Activinsights Ltd) and a hip-worn pedometer (Onwalk 900; Decathlon Group) were used objectively measure levels of PA. Our 10-week PA intervention comprised twice weekly 60-min walks within three different greenspaces in Greater Manchester, each led by a Sports and Exercise Scientist to deliver a pre-specified volume/dose of activity. During weeks-11–20 of the study, participants followed independent activities. Clinical evaluation, including assessment of psoriasis severity, cardiometabolic parameters, psychological wellbeing and functional capacity was made at baseline, week-10 and -20.

Results
Sixteen patients with psoriasis completed the study. We observed significantly reduced Psoriasis Area and Severity Index at week-10 (p = 0.01) and -20 (p = 0.001) compared to baseline, with 50% of participants achieving PASI-50 at week-20. Dermatology Life Quality Index (DLQI) was significantly reduced at week-20 (p = 0.04), compared to baseline. Significant reduction in blood pressure at week-10 (systolic: −7.4 mmHg, p = 0.002; diastolic: −4.2 mmHg, p = 0.03) and -20 (systolic: −8.8 mmHg, p = 0.001; diastolic: 4.1 mmHg, p = 0.008) was observed and pulse wave velocity was significantly reduced by week-20 (p = 0.02), suggesting improvement in cardiovascular health. Despite high prevalence of anxiety and depression at baseline, we documented a significant improvement in wellbeing and psychological health. Functional capacity was significantly enhanced following completion of the study.

Conclusion
Increasing PA constitutes a promising therapeutic intervention in the management of psoriasis. Evaluation of our intervention in a clinical trial would help determine clinical utility and establish PA guidelines for patients with psoriasis.
White Organic Light‐Emitting Diodes with External Quantum Efficiency of 20.77% at 10000 cd m−2 and Ultra‐High Color Stability by Controlling Exciton Distribution
Authors: Yang Haoran , Sun Weidong , Sun Yufu , Wang Jingyu , Xia Xiaoyang , Ren Guozhu , Sun Yitong , Zhang Danyang , Xu Yue , Shen Leijun , Zhou Liang 
Published: August 2024

AbstractAlthough brightness and efficiency have been continually improved, the inability to achieve superior efficiency, color stability, and low‐efficiency roll‐off simultaneously in white organic light‐emitting diodes (OLEDs) remains a knotty problem restricting the commercial application. In this paper, emission balance for two different horizontal orientation emitting molecules is maintained by using hole transport materials and bipolar host materials to control carriers’ recombination and exciton diffusion. Impressively, the obtained devices exhibit extremely stable white emission with small chromaticity coordinates variation of (0.0023, 0.0078) over a wide brightness range from 1000 to 50000 cd m−2. Meanwhile, the optimal white OLED realizes the power efficiency, current efficiency, and external quantum efficiency up to 70.68 lm W−1, 85.53 cd A−1, and 24.33%, respectively at the practical brightness of 1000 cd m−2. Owing to reduced heterogeneous interfaces and broadening recombination region, this device exhibits a high EQE over 20% under high luminance of 10000 cd m−2, demonstrating slight efficiency roll‐off. The operating mechanism of the device is analyzed by versatile experimental and theoretical evidences, which concludes precise manipulation of charges and excitons is the key points to achieve these excellent performances. This work provides an effective strategy for the design of high‐performance white OLEDs.