bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current management of neurotrophic receptor tyrosine kinase fusion-positive sarcoma: an updated review
Authors: Kubota Yuta , Kawano Masanori , Iwasaki Tatsuya , Itonaga Ichiro , Kaku Nobuhiro , Ozaki Toshifumi , Tanaka Kazuhiro 
Published: February 2025

Abstract
In recent years, pembrolizumab has demonstrated significant efficacy in treating tumors characterized by a high tumor mutational burden and high microsatellite instability. Tropomyosin receptor kinase (TRK) inhibitors have shown considerable efficacy against tumors harboring neurotrophic receptor tyrosine kinase (NTRK) fusion genes, highlighting the growing importance of personalized medicine in cancer treatment. Advanced sequencing technologies enable the rapid analysis of numerous genetic abnormalities in tumors, facilitating the identification of patients with positive biomarkers. These advances have increased the likelihood of providing effective, tailored treatments. NTRK fusion genes are present in various cancer types, including sarcomas, and the TRK inhibitors larotrectinib and entrectinib have been effectively used for these malignancies. Consequently, the treatment outcomes for NTRK fusion-positive tumors have improved significantly, reflecting a shift toward more personalized therapeutic approaches. This review focuses on NTRK fusion-positive sarcomas and comprehensively evaluates their epidemiology, clinical features, and radiological and histological characteristics. We also investigated the treatment landscape, including the latest methodologies involving TRK inhibitors, and discussed the long-term efficacy of these inhibitors, and their optimal order of use. Notably, larotrectinib has demonstrated a high response rate in infantile fibrosarcoma, and its efficacy has been confirmed even in advanced cases. However, further research is warranted to optimize treatment duration and subsequent management strategies. The accumulation of clinical cases worldwide will play a pivotal role in refining the treatment approaches for tumors associated with NTRK fusion genes.
Analysis of medical practices used as indicators in the fourth basic plan for the promotion of cancer control in Japan
Authors: Takahashi Richi , Nakazawa Yoko , Miyashita Mitsunori , Wada Saho , Matsuoka Yutaka 
Published: February 2025

Abstract

Background
In the Fourth Basic Plan to Promote Cancer Control Programs, the number of medical practices using claims data from the National Database (NDB) is measured as a clinical indicator. This study aimed to clarify the characteristics of patients who received care as an indicator of medical practices using more manageable claims data.

Methods
We used the claims data collected by the DeSC Healthcare, Inc., and included patients diagnosed with cancer between 2017 and 2022 in this study. We compared age and cancer type distributions between the study population and population estimates, as well as cancer-specific medical practices with the NDB open data. We also described the number of medical practices, patients, and the percentage of patients receiving care by age and region. The percentage of female patients who underwent treatment was also calculated.

Results
A total of 1 251 850 patients was included. The distribution of cancer types was similar to the estimated prevalence, and the number of medical practices resembled the NDB open data; however, the age distribution was skewed. The highest median number of medical procedures per patient was six for specialized palliative care, whereas the others were one medical procedure per patient. The percentage of patients receiving care according to age was classified into three groups: increased with age, decreased with age, and peaked in their 40s. The percentage of patients receiving care varied by region depending on the type of medical practice. Of the patients who received care for lymphedema, 93.8% were female.

Conclusion
The background information of cancer patients who received designated care may help interpret the total number of medical practices used as clinical indicators in cancer control programs.
Chondrosarcoma in Japan: an analytic study using population-based National Cancer Registry
Authors: Kondo Hiroya , Ogura Koichi , Morizane Chigusa , Satake Tomoyuki , Iwata Shintaro , Toda Yu , Muramatsu Shudai , Takemori Toshiyuki , Kobayashi Eisuke , Higashi Takahiro , Kawai Akira 
Published: February 2025

Abstract

Background
Chondrosarcoma (CS) is a rare malignant bone tumor exhibiting diverse histological features and clinical behaviors. This study aimed to investigate the epidemiological characteristics, clinical features, prognostic factors, and subtype-specific differences of CS in Japan using National Cancer Registry data.

Methods
We analyzed data from CS cases diagnosed between 2016 and 2019, calculating age-adjusted incidence, estimating overall survival, and identifying prognostic factors through multivariate analysis.

Results
The study identified 1015 CS cases with an age-adjusted incidence of 0.159 per 100 000 population and a mean overall survival of 1205.2 days. Multivariate analysis revealed that female sex, younger age (15–39 years), histological subtypes other than dedifferentiated CS, localized disease, and surgical treatment were associated with better prognoses. Conversely, male sex, older age (≥75 years), dedifferentiated subtype, advanced stage, and non-surgical treatment were linked to a higher risk of death. Significant differences in sex distribution, age at diagnosis, tumor location, disease stage, and tumor differentiation were observed among CS subtypes.

Conclusion
This comprehensive analysis provides valuable insights into CS epidemiology, prognostic factors, and subtype-specific characteristics in Japan. The identification of high-risk groups emphasizes the need for improved therapeutic strategies and supportive care. The observed heterogeneity among CS subtypes underscores the importance of individualized management approaches in treating this complex malignancy.
Novel association of ocular myasthenia gravis with Brown syndrome in an adult
Authors: Wang Amy Tianyi , Goodwin Todd 
Published: February 2025

Abstract
Brown syndrome is an ocular misalignment disorder affecting the superior oblique tendon-trochlea complex. We report a case of a 45-year-old woman with protracted symptoms of presumed idiopathic Brown syndrome later diagnosed as ocular myasthenia gravis. Acquired Brown syndrome secondary to ocular myasthenia gravis has not previously been reported in the literature. Ocular myasthenia gravis should be considered a differential in any patient presenting with vertical strabismus presenting as Brown syndrome.
A rare case of granular cell tumor of gall bladder
Authors: Dhakal Sunil , Bhandari Sapana , Kandangwa Avinam H 
Published: February 2025

Abstract
Granular cell tumor is common over skin and subcutaneous and oral cavity. However, lesion is rare in biliary tract and ever more uncommon in gall bladder. These lesions are often misdiagnosed until proven by histology and immunohistochemistry where tumor is positive for CD 68, S 100 which points them toward neural origin of tumor. We report a case of 69-year-old male referred with a suspected gall bladder mass in Computed tomographic scan of abdomen. Laparotomy was done through Kocher’s incision and extended cholecystectomy was performed. Histopathology and immunohistochemical study helped in determining gall bladder lesion to be granular cell tumor. Therefore, granular cell tumor can be considered a possible differential diagnosis of all the gall bladder lesion suspected of cholecystitis and carcinoma. Margin negative excision of the tumor is a curative approach for the patient.
Precise gene expression deconvolution in spatial transcriptomics with STged
Authors: Tu Jia-Juan , Yan Hong , Zhang Xiao-Fei , Lin Zhixiang 
Published: February 2025

Abstract
Spatially resolved transcriptomics (SRT) has transformed tissue biology by linking gene expression profiles with spatial information. However, sequencing-based SRT methods aggregate signals from multiple cell types within capture locations (“spots”), masking cell-type-specific gene expression patterns. Traditional cell-type deconvolution methods estimate cell compositions within spots but fail to resolve cell-type-specific gene expression, limiting their ability to uncover critical biological processes such as cellular interactions and microenvironmental dynamics. Here, we present STged (spatial transcriptomic gene expression deconvolution), a novel computational framework that goes beyond traditional deconvolution by reconstructing cell-type-specific gene expression profiles from mixed spots. STged integrates graph-based spatial correlations and reference-derived gene signatures using a non-negative least-squares regression framework, achieving precise and biologically meaningful deconvolution. Comprehensive simulations show that STged consistently outperforms existing methods in accuracy and robustness. Applications to human pancreatic ductal adenocarcinoma and human squamous cell carcinoma datasets reveal its capacity to identify microenvironment-specific highly variable genes, reconstruct spatial cell–cell communication networks, and resolve tissue architecture at near-single-cell resolution. In mouse kidney tissues, STged uncovers dynamic spatial gene expression patterns and distinct gene programs, advancing our understanding of tissue heterogeneity and cellular dynamics.
Approaching or avoiding? Gender asymmetry in reactions to prior job search outcomes by gig workers in female- versus male-typed job domains
Authors: Yang Tiantian , Bao Jiayi , Leung Ming D 
Published: February 2025

Abstract
Despite recent increases in females entering male-typed job domains, women are more likely to exit these jobs than men, leading to a “leaky-pipeline” phenomenon and contributing to continued occupational gender segregation. Extant work has demonstrated that women are less likely to reapply to employers who previously rejected them for jobs in male-typed job domains. However, these studies leave unexamined whether women will reapply to other employers in those job domains and, if so, whether this pattern differs in female-typed job domains, hampering our confidence in the contribution of these patterns to gender segregation. This paper investigates whether employer rejection dampens women’s job-seeking persistence more than men’s for all employers and across male versus female job domains. Regression analyses of more than 700,000 applications for over 200,000 job postings by roughly 70,000 freelancers in an online contract labor market demonstrate that women are more likely than men to reduce job-seeking activity from all employers following rejections in the male-typed IT and programming job domain. Women are also more likely than men to seek jobs in other domains outside IT and programming following job-seeking rejection. By contrast, female freelancers in female-typed writing and translation jobs do not exhibit similar gendered behavior patterns. Implications for research on gender segregation, careers, and hiring are discussed.
Comprehensive Analysis of Class III Peroxidase Genes Revealed PePRX2 Enhanced Lignin Biosynthesis and Drought Tolerance in Phyllostachys edulis
Authors: Jia Yuhan , Li Mengyun , Xu Jing , Chen Shuxin , Han Xiaojiao , Qiu Wenmin , Lu Zhuchou , Zhuo Renying , Qiao Guirong 
Published: February 2025

Abstract
Class III peroxidase (PRX) is the key enzyme in lignin biosynthesis and critical for maintaining the redox balance in plants to respond to stress. In moso bamboo (Phyllostachys edulis), a globally significant non-timber forestry species, the potential roles of PRX genes remain largely unknown. In this research, a total of 179 PePRXs was identified on a genome-wide scale in moso bamboo. Phylogenic relationship, conserved motifs, gene structure, collinearity, and cis-acting elements were investigated. Analysis of gene expression indicated that PePRXs exhibited tissue-specific expression and different response patterns to hormones and abiotic stresses. Based on the transcriptome data, ten PePRXs with positive correlations between expression levels and lignification degree were screened out. Among them, PePRX2 was selected as a candidate gene according to the co-expression network. Y1H and Dual-Luc assays demonstrated that PeMYB61 could bind to the promoter of PePRX2 and enhance its transcription. The result of in situ hybridization showed that PePRX2 was specifically expressed in the vascular bundle sheath cells of bamboo shoot. As a secreted protein, PePRX2 was located on the cell wall. Overexpression of PePRX2 led to a significant increase in lignin content in transgenic poplar, indicating that PePRX2 could promote lignin polymerization. In comparison to the wild type, the PePRX2-OE poplar lines exhibited increased peroxidase activity and decreased levels of MDA, O2−, and H2O2 under drought stress, indicating enhanced drought resistance. This thorough analysis of the PRX family in moso bamboo provided new insight into the roles of PePRXs in lignin biosynthesis and drought adaptation.
Prediction of Palatoplasty Timing for Infants With Cleft Lip and Palate Using Machine Learning Algorithm
Authors: Jeon Sungmi , Jang Jiwoo , Chakraborty Sabyasachi , Kim So Hee , Oh Seoyoung , Kim Sukwha , Moon Jin Soo , Chung Jee Hyeok , Baek Seung-Hak 
Published: February 2025

This study aims to predict the timing of palatoplasty in infants with cleft lip and palate (CLP) using a machine learning (ML) algorithm. The study included 111 patients with nonsyndromic CLP. Patient subgroups were classified based on birth weight (criterion: -1 SD, low birth weight versus normal birth weight) and cheiloplasty timing (criterion: 5 mo, early cheiloplasty versus late cheiloplasty). Growth trajectories at T2 were compared using T0-weight z-scores between the birth weight subgroups. Changes in the z-scores of weight and height from T1 to T2 were compared between the cheiloplasty timing subgroups. After training the tree-based ML models using cleft type, age, height, and weight at T0, T1, and T2, the palatoplasty timing was predicted with cleft type, weight at T0, and age, height, and weight at T1. The low-birth weight subgroup showed significant catch-up growth during T0-T1 and T0-T2 (all P<0.0001), resulting in no significant difference from the normal birth weight subgroup at T2. Compared with the late cheiloplasty subgroup, the early cheiloplasty subgroup underwent palatoplasty earlier (13.1 versus 14.3 mo; P<0.0001) and showed higher growth rates of weight and height and a greater increase in weight z-scores from T1 to T2 (all P<0.001). The CatBoost algorithm, with a root mean square error of 1.6 months, accurately predicted the palatoplasty timing (mean: actual, 12.8±1.8 mo versus prediction, 12.8±1.0 mo). Use of ML-assisted prediction method may help clinicians decide the timing of personalized palatoplasty in infants with CLP.
Medications used among Non-Hospitalized Pregnant Women with COVID-19: a Prospective Individual Patient Data Meta-analysis in Europe and North America
Authors: de Bruin Odette , Maisonneuve Emeline , Hurley Eimir , Nordeng Hedvig ME , Bérard Anick , Sheehy Odile , Kaul Padma , Shinde Mayura U , Cosgrove Austin , Lyons Jennifer G , Messenger-Jones Elizabeth , Kempner Maria E , Toh Sengwee , Hua Wei , Hernández-Muñoz José J , Sahin Leyla , Cesta Carolyn E , Hägg David , Gini Rosa , Paoletti Olga , Poblador-Plou Beatriz , Jordan Sue , Thayer Daniel , Rodríguez-Bernal Clara L , Sánchez-Sáez Francisco , Lassalle Régis , Bernard Marie-Agnès , Alsina Ema , Ahmadizar Fariba , Favre Guillaume , Panchaud Alice , Bloemenkamp Kitty WM , Plueschke Kelly , de Vries Corinne , Siiskonen Satu J , Sturkenboom Miriam CJM 
Published: February 2025

ABSTRACTAimTo estimate the prevalence of medication use in non-hospitalized pregnant women with COVID-19MethodsA prospective two-stage individual patient meta-analysis across 10 data sources in Europe and North America studied medication use among non-hospitalized pregnant women with COVID-19 between January 2020 to December 2022. Comparisons were made between medication use within 30 days pre- and post-COVID-19 diagnosis in this cohort and two comparator groups: pregnant women without COVID-19, and non-pregnant women with COVID-19. Prevalence estimates were pooled using a random-effects model stratified by trimester.Results50,335 non-hospitalized pregnant women with COVID-19 were identified. The pooled prevalence of antibacterial use in 3rdtrimester was higher post-COVID-19 diagnosis (6.8%, 95%CI 5.5-8.4, I2=94%) compared with the same women pre-COVID-19 (3.9%, 95%CI 3.1-4.9, I2=89%). Overall, pregnant women with COVID-19 had higher medication use compared to pregnant women without COVID-19, although these differences were not statistically significant. Post-COVID-19, antithrombotics prevalence was 4.5% (95%CI 1.1-16.5, I2=100%) among pregnant women with COVID-19 in 3rdtrimester, compared to 2.1% (95%CI 1.2-3.6, I2=99%) among those without COVID-19 in 3rdtrimester. Compared to non-pregnant women with COVID-19, pregnant women with COVID-19 were less likely to be prescribed analgesics, antiprotozoals, corticosteroids, psychoanaleptics and psycholeptics, and more likely to be prescribed antithrombotics, cough and cold and nasal preparations across all trimesters. High heterogeneity existed in nearly all analyses.ConclusionThis international meta-analysis reveals low medication use and country-specific variations, enhancing insight into the management of COVID-19 in non-hospitalized pregnant women. Higher antithrombotics use post-COVID-19 suggests prophylactic treatment in this population.
Survival benefits of cytoreductive nephrectomy in patients with metastatic renal cell carcinoma: evidence from a SEER-based retrospective cohort study
Authors: Peng Xiongwu , Duan Lingxing , Shi Runlin 
Published: February 2025

AbstractBackgroundMetastatic renal cell carcinoma (mRCC) is associated with poor prognosis, with a 5-year survival rate of less than 15%. Cytoreductive nephrectomy (CN) has historically played a critical role in mRCC management, potentially enhancing systemic therapy efficacy by reducing tumor burden. However, its relevance in the era of targeted therapies and immune checkpoint inhibitors (ICIs) has been questioned.ObjectiveThis study evaluates the survival benefits of CN in mRCC patients using real-world, population-based data from the SEER database.MethodsA retrospective cohort analysis of 6,030 mRCC patients was performed using data from 2010 to 2017. Propensity score matching (PSM) minimized selection bias, yielding 1,350 matched patients. Kaplan-Meier survival curves and multivariate Cox proportional hazards models assessed the impact of CN on overall survival (OS) and RCC-specific survival (CSS), stratified by demographic and clinical characteristics.ResultsCN was associated with a 71% reduction in all-cause mortality (HR = 0.29, 95% CI = 0.25–0.33) and RCC-specific mortality (HR = 0.29, 95% CI = 0.25–0.34). Five-year OS rates were 31.5% in the CN group versus 3.6% in the non-CN group. Survival benefits were consistent across subgroups, including patients with high-grade or advanced-stage tumors, underscoring the role of CN within multimodal treatment strategies.ConclusionCN confers significant survival advantages in mRCC, even in challenging clinical scenarios. These findings reinforce the importance of integrating CN into multimodal therapeutic frameworks, particularly alongside modern systemic therapies. Further prospective studies are warranted to optimize patient selection and treatment sequencing.
Interparticle Crosslinked Ion-responsive Microgels for 3D and 4D (Bio)printing Applications
Authors: Pal Vaibhav , Gupta Deepak , Liu Suihong , Namli Ilayda , Rizvi Syed Hasan Askari , Yilmaz Yasar Ozer , Haugh Logan , Gerhard Ethan Michael , Ozbolat Ibrahim T. 
Published: February 2025

AbstractMicrogels offer unique advantages over bulk hydrogels due to their improved diffusion limits for oxygen and nutrients. Particularly, stimuli-responsive microgels with inherently bioactive and self-supporting properties emerge as highly promising biomaterials. This study unveils the development of interparticle-crosslinked, self-supporting, ion-responsive microgels tailored for 3D and 4D (bio)printing applications. A novel strategy was proposed to develop microgels that enabled interparticle crosslinking, eliminating the need for filler hydrogels and preserving essential microscale void spaces to support cell migration and vascularization. Additionally, these microgels possessed unique, ion-responsive shrinking behavior primarily by the Hofmeister effect, reversible upon the removal of the stimulus. Two types of microgels, spherical (µS) and random-shaped (µR), were fabricated, with µR exhibiting superior mechanical properties and higher packing density. Fabricated microgel-based constructs supported angiogenesis with tunable vessel size based on interstitial void spaces while demonstrating excellent shear-thinning and self-healing properties and high print fidelity. Various bioprinting techniques were employed and validated using these microgels, including extrusion-based, embedded, intraembedded, and aspiration-assisted bioprinting, facilitating the biofabrication of scalable constructs. Multi-material 4D printing was achieved by combining ion-responsive microgels with non-responsive microgels, enabling programmable shape transformations upon exposure to ionic solutions. Utilizing 4D printing, complex, dynamic structures were generated such as coiling filaments, grippers, and folding sheets, providing a foundation for the development of advanced tissue models and devices for regenerative medicine and soft robotics, respectively.
Repurposing statins and phenothiazines to treat chemoresistant neuroblastoma
Authors: Radke Katarzyna , Aaltonen Kristina , Muciño-Olmos Erick A. , Esfandyari Javanshir , Mañas Adriana , Seger Alexandra , Adamska Aleksandra , Hansson Karin , Rogova Oksana , Mason Daniel J. , O’Donovan Daniel J. , Roberts Ian , Lock Antonia , Brennan Jane , Davies Emma J. , Spégel Peter , Bedoya-Reina Oscar C. , Brown David , Thompson Neil T. , Spadoni Cesare , Bexell Daniel 
Published: February 2025

AbstractRelapse and treatment resistance are common in children with high-risk neuroblastoma, and novel therapies are needed. Conventional drug discovery is slow, expensive, often fails in practice, and consequently falls short in addressing pediatric and rare conditions. In such instances, drug repurposing is a promising strategy. Here, we used two independentin silicoprediction tools including machine learning to identify approved drugs for repurposing against neuroblastoma. The combination of statins and phenothiazines showed strong synergistic effects in human neuroblastoma organoids, decreased tumor growth and prolonged survival inMYCN-amplified neuroblastoma patient-derived xenografts. The drug combination altered cholesterol metabolism through a dual-hit mechanism and induced a phenotypic switch towards an adrenergic cell state accompanied by increased sensitivity to chemotherapy. Integration of the drug combination into standard-of-care chemotherapy regressed tumors and prolonged survival in chemoresistant patient-derived xenografts. Thus, a combination of safe and approved medications added to standard-of-care chemotherapy outperforms chemotherapy alone in chemoresistant neuroblastoma.TeaserUsingin silicoprediction tools we repurposed statins and phenothiazines as a combination with translational potential in high-risk neuroblastoma.