bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case report: The effect of second-line vebreltinib treatment on a patient with advanced NSCLC harboring the MET exon 14 skipping mutation after tepotinib treatment
Authors: Huang Siyuan , Li Linlin , Yan Ningning , Zhang Huixian , Guo Qianqian , Guo Sanxing , Geng Di , Liu Xincheng , Li Xingya 
Published: April 2024

BackgroundHighly selective type Ib mesenchymal–epithelial transition gene (MET) tyrosine kinase inhibitors (TKIs) are the standard-of-care (SOC) therapy for previously untreated non-small cell lung cancer (NSCLC) harboring MET exon 14 (METex14) skipping mutations. However, there are rare reports describing effective regimens for patients who fail SOC without identifying resistant mutations or tissue transformation.Case reportWe report the first case of a 74-year-old woman with lung adenocarcinoma (cT1cNxM0) harboring METex14 splice region mutation, which was identified by a next-generation sequencing (NGS)-based assay. The patient was administered two treatments, including first-line tepotinib and second-line vebreltinib. The patient achieved progression-free survival (PFS) of 7.6 months, and then disease progression of tepotinib was observed. A re-biopsy was performed for NGS, which revealed the same mutations as before, with no new gene mutations detected. The woman received subsequent vebreltinib therapy and experienced durable clinical benefits. In the first 6.8 months, chest computed tomography demonstrated stable disease. Then, she achieved partial response (PR). The durable PR lasted for more than 13 months, and the PFS is currently over 20 months, exceeding the prior treatment.ConclusionThis case highlights the importance of considering re-biopsy and reanalysis of genetic profiles in NSCLC patients harboring METex14 skipping mutations after progressive disease in MET TKI treatment. This raises the possibility that vebreltinib may have long-term survival benefits for patients without mutations conferring resistance (funded by Beijing Pearl Biotechnology Co., Ltd; ClinicalTrials.gov number, NCT04258033).
The research advances in Kirsten rat sarcoma viral oncogene homolog (KRAS)-related cancer during 2013 to 2022: a scientometric analysis
Authors: Huang Yujie , Zheng Daitian , Zhou Zhongming , Wang Haiting , Li Yanpo , Zheng Huihui , Tan Jianhui , Wu Jingyao , Yang Qiuping , Tian Huiting , Lin Liuming , Li Zhiyang , Li Tianyu 
Published: April 2024

IntroductionCancer represents a significant global public health concern. In recent years, the incidence of cancer has been on the rise worldwide due to various factors, including diet, environment, and an aging population. Simultaneously, advancements in tumor molecular biology and genomics have led to a shift from systemic chemotherapy focused on disease sites and morphopathology towards precise targeted therapy for driver gene mutations. Therefore, we propose a comprehensive review aimed at exploring the research hotspots and directions in the field of Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutant cancers over the past decade, providing valuable insights for cancer treatment strategies. Specifically, we aim to present an intellectual landscape using data obtained from the Web of Science (WoS) regarding KRAS mutation.MethodsBibliometrix, VOSviewer, CiteSpace, and HistCite were employed to conduct scientometric analyses on national publications, influential authors, highly cited articles, frequent keywords, etc.ResultsA total of 16,609 publications met the screening criteria and exhibited a consistent annual growth trend overall. Among 102 countries/regions, the United States occupied the vast majority share of the published volume. The journal Oncotarget had the highest circulation among all scientific publications. Moreover, the most seminal articles in this field primarily focus on biology and targeted therapies, with overcoming drug resistance being identified as a future research direction.ConclusionThe findings of the thematic analysis indicate that KRAS mutation in lung cancer, the prognosis following B-Raf proto-oncogene, serine/threonine kinase (BRAF) or rat sarcoma (RAS) mutations, and anti-epidermal growth factor receptor (EGFR)-related lung cancer are the significant hotspots in the given field. Considering the significant advancements made in direct targeting drugs like sotorasib, it is anticipated that interest in cancers associated with KRAS mutations will remain steadfast.
Molecular characterization of the evolution of premalignant lesions in the upper aerodigestive tract
Authors: Lechner Axel , Kumbrink Jörg , Walz Christoph , Jung Andreas , Baumeister Philipp , Flach Susanne 
Published: April 2024

IntroductionEarly relapse and development of metastatic disease are some of the primary reasons for the poor prognosis of patients with head and neck squamous cell carcinoma (HNSCC). HNSCC is a heterogeneous disease which may develop in large premalignant fields of genetically altered cells. Yet knowing which individuals will progress and develop clinically significant cancers during their lifetimes remains one of the most important challenges of reducing HNSCC morbidity and mortality. To further elucidate the molecular mechanisms, we performed a focused analysis of the genome and immune microenvironment from multiple, matched normal squamous tissue, premalignant lesions, as well as primary and recurrent tumors from seven patients with p16-negative HNSCC.MethodsWe performed targeted panel Next Generation Sequencing (161 genes) to analyze somatic variants from sequentially collected, matched formalin-fixed paraffin-embedded tissue (normal, premalignant, HNSCC) from two patients. These samples plus samples from five additional patients were analyzed with the Nanostring PanCancer Immune Panel. In addition, we performed shallow whole genome sequencing (0.5x coverage on average) on samples from three of these patients. Patients were, apart from one case, primarily treated with curative-intent surgery, and received subsequent adjuvant treatment, if indicated.ResultsThe most frequently mutated genes were TP53 and NOTCH1. Other mutated genes included NOTCH3 and CDKN2A, among others. A significant number of mutations were private to dysplasia and invasive carcinoma, respectively, however, almost 20% were shared between them. Increasing genomic instability was observed when comparing histologically normal squamous mucosa with higher levels of dysplasia. High-grade dysplasia showed similarly rearranged genomes as invasive carcinoma. Pathways related to interferon alpha and gamma response were upregulated even in moderate dysplastic lesions with increasing expression in higher grades of dysplasia and carcinoma. SPINK5, a known tumor suppressor gene in HNSCC, was already downregulated in low-grade dysplastic lesions, indicating an early deactivation in the evolution of the disease.ConclusionGenomic alterations as well as aberrant immune gene expression can be observed early in the evolution of tumors of the upper aerodigestive tract, highlighting the potential for targeting early mechanisms of disease progression.
The Shehata technique for undescended testes that cannot be brought into the scrotum in one operation—a case series and meta-analysis
Authors: Lin Zhenying , Yu Zhongjing , Li Huanyuan , Wu ri ni Letu , Zhang Baoxin 
Published: April 2024

BackgroundFowler–Stephens orchiopexy is commonly used for testes that cannot be brought into the scrotum in one operation. However, this surgical technique may result in a higher rate of testicular atrophy postoperatively.MethodsDuring the period between 2019 and 2023, we analyzed the cases of 20 patients in whom the Shehata technique was applied for testes that could not be brought into the scrotum in one operation, and we conducted a meta-analysis to explore the incidence of testicular atrophy vis-à-vis the Shehata technique and Fowler–Stephens orchiopexy.ResultsThe average age of the 20 patients was 3.78 (0.76–11.42) years. The blood supply to the testes was satisfactory, with the absence of atrophy, and the testes could be brought into the scrotum in stage II surgery. A postoperative reexamination with ultrasound revealed that the testes were securely positioned within the scrotum, with good blood supply and no atrophy, which was in contrast to their condition before the operation. The volume of the testes postoperatively was significantly greater than that of the preoperative testes (p = 0.009). There were no statistically significant differences in the growth rate of volume of the testes between the surgically treated side and the contralateral side (p = 0.25). The meta-analysis showed that the Shehata technique resulted in a lower incidence of testicular atrophy compared with Fowler–Stephens orchiopexy (p = 0.01).ConclusionsThe Shehata technique preserves the main vessels of the testes with a lower incidence of testicular atrophy, which may be a valid and safe alternative to the Fowler–Stephens technique.
Anti-inflammatory and uric acid lowering effects of Euodiae fructus on hyperuricemia and gout mice
Authors: Wang Zhilei , Liu Jingwen , Mou Yu , Liao Wenhao , Li Yuchen , Liu Juan , Tang Jianyuan 
Published: April 2024

The metabolic disease hyperuricemia (HUA) is caused by presence of excessive serum uric acid (UA), which leads to an increased risk of chronic kidney disease and gout. As a widely used traditional Chinese medicine, Euodiae fructus (ER) has strong anti-inflammatory and analgesic effects, however, its therapeutic effects on HUA and gout have not been investigated. To investigate the potential effects and underlying mechanisms, the effect of ER on proinflammatory cytokines and NLRP3 inflammasome activation was studied in mouse bone marrow macrophages. Moreover, a mouse model of HUA and gouty arthritis was established by coadministration of potassium oxonate (PO) and monosodium urate crystals to mice fed a high-fat diet (HFD) for 37 consecutive days. Oral administration of ER aqueous extract was given 1 hour later after the injection of PO for 10 days. Our study showed that ER is a powerful NLRP3 inhibitor in mouse macrophages. Most importantly, ER (0.75 g/kg) treatment substantially decreased the ankle joint thickness ratio, serum UA, creatinine and blood urea nitrogen levels (p &lt; 0.05). Additionally, ER (0.75 g/kg) dramatically reversed the increases in renal urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) as well as the decreases in organic anion transporter 1 (OAT1) and ATP binding cassette subfamily G member 2 (ABCG2) levels (p &lt; 0.05). Moreover, ER (0.75 g/kg) markedly ameliorated the production of the serum inflammatory cytokines IL-1β and TNF-α (p &lt; 0.01), and improved the activation of NLRP3 inflammasome signaling in the kidneys. Taken together, these data indicate that ER, a powerful and specific NLRP3 inhibitor, has multiple anti-HUA, anti-gout and anti-inflammatory effects. Our investigation is designed to experimentally support the conventional use of ER-containing classical herbal formulas in the treatment of HUA-related disorders and may add a new dimension to the clinical application of ER.
Short-term cutaneous vasodilatory and thermosensory effects of topical methyl salicylate
Authors: Versteeg Ninja , Wellauer Vanessa , Wittenwiler Selina , Aerenhouts Dirk , Clarys Peter , Clijsen Ron 
Published: April 2024

Introduction:Methyl salicylate, the main compound of wintergreen oil, is widely used in topical applications. However, its vascular and thermosensory effects are not fully understood. The primary aim was to investigate the effects of topical methyl salicylate on skin temperature (Tskin), skin microcirculation (MCskin) and muscle oxygen saturation (SmO2) compared to a placebo gel. The secondary aim was to assess thermosensory responses (thermal sensation, thermal comfort) and to explore to which extent these sensations correspond to the physiological responses over time.Methods:21 healthy women (22.2 ± 2.9 years) participated in this single-blind, randomized controlled trial. Custom-made natural wintergreen oil (12.9%), containing methyl salicylate (&gt;99%) and a placebo gel, 1 g each, were applied simultaneously to two paravertebral skin areas (5 cm × 10 cm, Th4-Th7). Tskin (infrared thermal imaging), MCskin (laser speckle contrast imaging) and SmO2 (deep tissue oxygenation monitoring) and thermosensation (Likert scales) were assessed at baseline (BL) and at 5-min intervals during a 45 min post-application period (T0-T45).Results:Both gels caused an initial decrease in Tskin, with Tskin(min) at T5 for both methyl salicylate (BL-T5: Δ-3.36°C) and placebo (BL-T5: Δ-3.90°C), followed by a gradual increase (p &lt; .001). Methyl salicylate gel resulted in significantly higher Tskin than placebo between T5 and T40 (p &lt; .05). For methyl salicylate, MCskin increased, with MCskin(max) at T5 (BL-T5: Δ88.7%). For placebo, MCskin decreased (BL-T5: Δ-17.5%), with significantly lower values compared to methyl salicylate between T0 and T45 (p &lt; .05). Both gels had minimal effects on SmO2, with no significant differences between methyl salicylate and placebo (p &gt; .05). Thermal sensation responses to topical methyl salicylate ranged from “cool” to “hot”, with more intense sensations reported at T5.Discussion:The findings indicate that topical methyl salicylate induces short-term cutaneous vasodilation, but it may not enhance skeletal muscle blood flow. This study highlights the complex sensory responses to its application, which may be based on the short-term modulation of thermosensitive transient receptor potential channels.
Stress phenotyping analysis leveraging autofluorescence image sequences with machine learning
Authors: Das Choudhury Sruti , Guadagno Carmela Rosaria , Bashyam Srinidhi , Mazis Anastasios , Ewers Brent E. , Samal Ashok , Awada Tala 
Published: April 2024

BackgroundAutofluorescence-based imaging has the potential to non-destructively characterize the biochemical and physiological properties of plants regulated by genotypes using optical properties of the tissue. A comparative study of stress tolerant and stress susceptible genotypes of Brassica rapa with respect to newly introduced stress-based phenotypes using machine learning techniques will contribute to the significant advancement of autofluorescence-based plant phenotyping research.MethodsAutofluorescence spectral images have been used to design a stress detection classifier with two classes, stressed and non-stressed, using machine learning algorithms. The benchmark dataset consisted of time-series image sequences from three Brassica rapa genotypes (CC, R500, and VT), extreme in their morphological and physiological traits captured at the high-throughput plant phenotyping facility at the University of Nebraska-Lincoln, USA. We developed a set of machine learning-based classification models to detect the percentage of stressed tissue derived from plant images and identified the best classifier. From the analysis of the autofluorescence images, two novel stress-based image phenotypes were computed to determine the temporal variation in stressed tissue under progressive drought across different genotypes, i.e., the average percentage stress and the moving average percentage stress.ResultsThe study demonstrated that both the computed phenotypes consistently discriminated against stressed versus non-stressed tissue, with oilseed type (R500) being less prone to drought stress relative to the other two Brassica rapa genotypes (CC and VT).ConclusionAutofluorescence signals from the 365/400 nm excitation/emission combination were able to segregate genotypic variation during a progressive drought treatment under a controlled greenhouse environment, allowing for the exploration of other meaningful phenotypes using autofluorescence image sequences with significance in the context of plant science.
From burnout to behavior: the dark side of emotional intelligence on optimal functioning across three managerial levels
Authors: Sariraei Samira A. , Shkoler Or , Giamos Dimitris , Chênevert Denis , Vandenberghe Christian , Tziner Aharon , Vasiliu Cristinel 
Published: April 2024

IntroductionBurnout has been typically addressed as an outcome and indicator of employee malfunctioning due to its profound effects on the organization, its members, and its profitability. Our study assesses its potential as a predictor, delving into how different sources of motivation—autonomous and controlled—act as mediational mechanisms in the association between burnout and behavioral dimensions of functioning (namely, organizational citizenship behaviors and work misbehaviors). Furthermore, the buffering effects of emotional intelligence across three different managerial levels were also examined.MethodsTo this end, a total non-targeted sample of 840 Romanian managers (513 first-, 220 mid-, and 107 top-level managers) was obtained.ResultsBurnout predicted motivation, which predicted work behaviors in a moderated-mediation framework. Contrary to our initial prediction, emotional intelligence augmented the negative association between burnout and motivation, exhibiting a dark side to this intelligence type. These findings are nuanced by the three managerial positions and shed light on the subtle differences across supervisory levels.DiscussionThe current article suggests a relationship between multiple dimensions of optimal (mal)functioning and discusses valuable theoretical and practical insights, supporting future researchers and practitioners in designing burnout, motivation, and emotional intelligence interventions.
When they just don’t sleep: differential impacts of reduced child sleep on depression, anxiety, and stress among caregivers of children with and without neurogenetic syndromes
Authors: Gálvez-Ortega Kimberly , Marceau Kristine , Foti Dan , Kelleher Bridgette 
Published: April 2024

IntroductionChildren with neurogenetic syndromes commonly experience significant and pervasive sleep disturbances, however, associations with caregiver mental health remains unclear. Previous studies have linked sleep disturbances with increased caregiver depression in typically developing populations, and heightened caregiver stress among neurogenetic populations. The present study expands on findings by exploring the longitudinal association between child sleep duration and caregiver mental health (depression, anxiety, stress) throughout development (infancy to school-aged children) in dyads with and without a child affected by a neurogenetic syndrome.MethodsParticipants were drawn from the Purdue Early Phenotype Study, including 193 caregivers (Age: M = 34.40 years, SD = 4.53) of children with neurogenetic syndromes (Age: M = 40.91 months, SD =20.72) and typically developing children (n = 55; Age: M = 36.71 months, SD = 20.68). Children in the neurogenetic group were diagnosed with Angelman (n = 49), Prader Willi (n = 30), Williams (n = 51), and Fragile X (n = 8) syndromes. Caregivers completed assessments every six months up to child age three, and annual assessments thereafter. Child sleep duration was measured using the Brief Infant Sleep Questionnaire, and caregiver internalizing symptoms were assessed using the Depression, Anxiety, Stress Scale. Multilevel models were conducted to examine caregiver depression, anxiety, and stress in relation to child sleep duration at both between- and within-person levels, with child age as a moderator.ResultsResults indicated a between-person effect of child sleep duration on caregiver depression (i.e., differences between families) and a within-person effect on caregiver stress (i.e., change over time) in the full, combined sample. These effects were not maintained when examined separately in neurogenetic and typically developing groups, except for a between-person effect on caregiver stress in the typically developing cohort. Moderating effects of child age were significant for depression and stress only in the typically developing cohort.DiscussionIn summary, persistent child sleep disruptions were linked to exacerbated caregiver depression across the sample, while acute child sleep disruptions exacerbate caregiver stress within dyads over time. These findings emphasize the importance of addressing child sleep to enhance caregiver wellbeing and has potential relevance for a wide range of neurogenetic syndromes.
Drivers of antimicrobial resistance within the communities of Nepal from One Health perspective: a scoping review
Authors: Parajuli Ayuska , Mitchell Jessica , King Natalie , Arjyal Abriti , Latham Sophia , King Rebecca , Baral Sushil 
Published: April 2024

BackgroundA major driver of antimicrobial resistance (AMR) is the inappropriate use of antimicrobials. At the community level, people are often engaged in behaviors that drive AMR within human, animal, and environmental (One Health) impacts. This scoping review consolidates research to determine (a) the community’s knowledge, attitudes, and practices around AMR; (b) existing community-based interventions; and (c) barriers and enablers to addressing AMR in Nepal.MethodsThis scoping review follows the Joanna Briggs Institute scoping review methodology. Literature indexed in PubMed, Scopus, CINAHL, Global Index Medicus, HINARI-SUMMON, Embase (Ovid), Global Health (Ovid), CAB Abstracts (Ovid), Web of Science, and Google Scholar between January 2000 and January 2023 were reviewed for inclusion. Articles were included in the review if they considered the issues of AMR at the community level in Nepal; this excluded clinical and laboratory-based studies. A total of 47 studies met these criteria, were extracted, and analyzed to consolidate the key themes.ResultsA total of 31 (66%) articles exclusively included human health; five (11%) concentrated only on animal health; no studies solely focused on environmental aspects of AMR; and the remaining studies jointly presented human, animal, and environmental aspects. Findings revealed inadequate knowledge accompanied by inappropriate practice in both the human and animal health sectors. Four community interventions improved knowledge and practices on the appropriate use of antimicrobials among community people. However, various social and economic factors were found as barriers to the appropriate use of antimicrobials in the community.ConclusionCommunity engagement and One Health approaches could be key tools to improve awareness of AMR and promote behavioral change related to AM use in communities, as current studies have revealed inadequate knowledge alongside inappropriate practices shared in both human and animal health sectors.Systematic review registrationDOI: 10.17605/OSF.IO/FV326