bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multi-center international study to evaluate the safety, functional and oncological outcomes of irreversible electroporation for the ablation of prostate cancer
Authors: Zhang Kai , Stricker Phillip , Löhr Martin , Stehling Michael , Suberville Michel , Cussenot Olivier , Lunelli Luca , Ng Chi-Fai , Teoh Jeremy , Laguna Pilar , de la Rosette Jean 
Published: January 2024

Abstract
Background
Irreversible electroporation (IRE) is a novel technique to treat localized prostate cancer with the aim of achieving oncological control while reducing related side effects. We present the outcomes of localized prostate cancer treated with IRE from a multi-center prospective registry.

Methods
Men with histologically confirmed prostate cancer were recruited to receive IRE. All the patients were proposed for prostate biopsy at 1-year post-IRE ablation. The functional outcomes were measured by the International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF-5) questionnaires. The safety of IRE was graded by the treatment-related adverse events (AEs) according to the Common Terminology Criteria for Adverse Events (CTCAE).

Results
411 patients were recruited in this study from July 2015 to April 2020. The median follow-up time was 24 months (IQR 15–36). 116 patients underwent repeat prostate biopsy during 12–18 months after IRE. Clinically significant prostate cancer (Gleason ≥ 3 + 4) was detected in 24.1% (28/116) of the patients; any grade prostate cancers were found in 59.5% (69/116) of the patients. The IPSS score increased significantly from 7.1 to 8.2 (p = 0.015) at 3 months but decreased to 6.1 at 6 months (p = 0.017). Afterwards, the IPSS level remained stable during follow-up. The IIEF-5 score decreased at 3 months from 16.0 to 12.1 (p < 0.001) and then maintained equable afterwards. The rate of AEs was 1.8% at 3 months and then dropped to less than 1% at 6 months and remained stable until 48 months after IRE. Major AEs (Grade 3 or above) were rare.

Conclusion
For men with localized prostate cancer, IRE could achieve good urinary and sexual function outcomes and a reasonable oncological result. The real-world data are consistent with earlier studies, including recently published randomized controlled studies. The long-term oncological results need further investigation and follow-up.
Med23 deficiency reprograms the tumor microenvironment to promote lung tumorigenesis
Authors: Fu Xiaobo , Liu Siming , Cao Dan , Li Chonghui , Ji Hongbin , Wang Gang 
Published: January 2024

Abstract
Background
Lung cancer is the leading cause of cancer-related death worldwide. We previously found that Mediator complex subunit 23 (MED23) is important for the tumourigenicity of lung cancer cells with hyperactive Ras activity in vitro, although the in vivo function of MED23 in lung tumourigenesis remains to be explored.

Methods
In this study, we utilized well-characterized KrasG12D-driven non-small cell lung cancer mouse model to investigate the role of MED23 in lung cancer. The lung tumour progression was evaluated by H&E and IHC analysis. Western blotting and qRT-PCR assays were performed to detect changes in gene expression. Immune cells were analyzed by FACS technology. RNA-seq and reporter assays were conducted to explore the mechanism.

Results
We observed that lung epithelial Med23 deletion by adeno-Cre resulted in a significant increase in KrasG12D tumour number and size, which was further verified with another mouse model with Med23 specifically deleted in alveolar type II cells. Mice with lung-specific Med23 deficiency also exhibited accelerated tumourigenesis, and a higher proliferation rate for tumour cells, along with increased ERK phosphorylation. Notably, the numbers of infiltrating CD4+ T cells and CD8+ T cells were significantly reduced in the lungs of Med23-deficient mice, while the numbers of myeloid-derived suppressor cells (MDSCs) and Treg cells were significantly increased, suggesting the enhanced immune escape capability of the Med23-deficient lung tumours. Transcriptomic analysis revealed that the downregulated genes in Med23-deficient lung tumour tissues were associated with the immune response. Specifically, Med23 deficiency may compromise the MHC-I complex formation, partially through down-regulating B2m expression.

Conclusions
Collectively, these findings revealed that MED23 may negatively regulate Kras-induced lung tumourigenesis in vivo, which would improve the precise classification of KRAS-mutant lung cancer patients and provide new insights for clinical interventions.
Autoantibodies, antigen-autoantibody complexes and antigens complement CA125 for early detection of ovarian cancer
Authors: Young Han Chae , Bedia Jacob S. , Yang Wei-Lei , Hawley Sarah J. , Bergan Lindsay , Hopper Marika , Celestino Joseph , Guo Jing , Gornet Terrie G. , Soosaipillai Antoninus , Yang Hailing , Doskocil Samantha D. , Lokshin Anna E. , Handy Beverly C. , Diamandis Eleftherios P. , Moore Richard G. , Lu Karen H. , Lu Zhen , Anderson Karen S. , Drescher Charles W. , Skates Steven J. , Bast Robert C. 
Published: January 2024

Abstract
Background
Multiple antigens, autoantibodies (AAb), and antigen-autoantibody (Ag-AAb) complexes were compared for their ability to complement CA125 for early detection of ovarian cancer.

Methods
Twenty six biomarkers were measured in a single panel of sera from women with early stage (I-II) ovarian cancers (n = 64), late stage (III-IV) ovarian cancers (186), benign pelvic masses (200) and from healthy controls (502), and then split randomly (50:50) into a training set to identify the most promising classifier and a validation set to compare its performance to CA125 alone.

Results
Eight biomarkers detected ≥ 8% of early stage cases at 98% specificity. A four-biomarker panel including CA125, HE4, HE4 Ag-AAb and osteopontin detected 75% of early stage cancers in the validation set from among healthy controls compared to 62% with CA125 alone (p = 0.003) at 98% specificity. The same panel increased sensitivity for distinguishing early-stage ovarian cancers from benign pelvic masses by 25% (p = 0.0004) at 95% specificity. From 21 autoantibody candidates, 3 AAb (anti-p53, anti-CTAG1 and annt-Il-8) detected 22% of early stage ovarian cancers, potentially lengthening lead time prior to diagnosis.

Conclusion
A four biomarker panel achieved greater sensitivity at the same specificity for early detection of ovarian cancer than CA125 alone.
TNFα modulates PANX1 activation to promote ATP release and enhance P2RX7-mediated antitumor immune responses after chemotherapy in colorectal cancer
Authors: Huang Kevin Chih-Yang , Chiang Shu-Fen , Lin Pei-Chun , Hong Wei-Ze , Yang Pei-Chen , Chang Hui-Ping , Peng Shin-Lei , Chen Tsung-Wei , Ke Tao-Wei , Liang Ji-An , Chen William Tzu-Liang , Chao K. S. Clifford 
Published: January 2024

AbstractATP and its receptor P2RX7 exert a pivotal effect on antitumor immunity during chemotherapy-induced immunogenic cell death (ICD). Here, we demonstrated that TNFα-mediated PANX1 cleavage was essential for ATP release in response to chemotherapy in colorectal cancer (CRC). TNFα promoted PANX1 cleavage via a caspase 8/3-dependent pathway to enhance cancer cell immunogenicity, leading to dendritic cell maturation and T-cell activation. Blockade of the ATP receptor P2RX7 by the systemic administration of small molecules significantly attenuated the therapeutic efficacy of chemotherapy and decreased the infiltration of immune cells. In contrast, administration of an ATP mimic markedly increased the therapeutic efficacy of chemotherapy and enhanced the infiltration of immune cells in vivo. High PANX1 expression was positively correlated with the recruitment of DCs and T cells within the tumor microenvironment and was associated with favorable survival outcomes in CRC patients who received adjuvant chemotherapy. Furthermore, a loss-of-function P2RX7 mutation was associated with reduced infiltration of CD8+ immune cells and poor survival outcomes in patients. Taken together, these results reveal that TNFα-mediated PANX1 cleavage promotes ATP-P2RX7 signaling and is a key determinant of chemotherapy-induced antitumor immunity.
Use of the CONSIDER statement by eye health researchers when conducting and reporting research involving Indigenous peoples: an online survey
Authors: Samuels Isaac , Hamm Lisa M. , Silva Juan Carlos , Tousignant Benoit , Furtado João M. , Goodman Lucy , Watene Renata , Adams Jaki ,   Indigenous Eye Health Research Consortium, Yashadhana Aryati , Wilkinson Ben , Dimaras Helen , Brea Ilena , Rogers Jaymie , Black Joanna , Foreman Joshua , Arboleda Juan Camilo , Yee Juan Francisco , Trujillo Julián , Keay Lisa , Luque Luisa Casas , Oviedo-Cáceres María del Pilar , Saboya Martha , Alves Monica , Lichter Myrna , Silwal Pushkar , Findlay Rebecca , Barrenechea Rosario , Simkin Samantha , Bentley Sharon , Hopkins Shelley , Salomão Solange Rios , Misra Stuti , Fricke Tim , Reis Tulio , Ramke Jacqueline , Harwood Matire 
Published: January 2024

Abstract
Background
Indigenous peoples experience worse eye health compared to non-Indigenous peoples. Service providers and researchers must avoid perpetuating this inequity. To help achieve this, researchers can use the CONSolIDated critERia for strengthening the reporting of health research involving Indigenous peoples (CONSIDER) statement. This study aimed to identify the degree to which the CONSIDER statement has been used by eye health researchers when conducting and reporting research with an Indigenous component, and how they perceive its relevance in their future research.

Methods
We used purposive sampling to recruit eye health researchers from any country who have undertaken research with an Indigenous component. The online survey collected quantitative and qualitative data and was analysed using descriptive statistics and reflexive thematic analysis. Responses were gathered on a four-point Likert scale (1 to 4), with four being the most positive statement.

Results
Thirty-nine eye health researchers from nine countries completed the survey (Aotearoa New Zealand, Argentina, Australia, Brazil, Canada, Colombia, Guatemala, Panama, Peru); almost two-thirds (n = 24) undertake epidemiological research. On average, participants disclosed only ‘sometimes’ previously reporting CONSIDER items (2.26 ± 1.14), but they thought the items were relevant to eye health research and were motivated to use these guidelines in their future research. Some participants requested clarity about how CONSIDER aligned with existing guidelines, and when and how to apply the statement. Others shared rich experiences of the benefits to their research of Indigenous leadership and collaboration.

Conclusions
The CONSIDER statement is perceived as a valuable tool by these eye health researchers, and there are opportunities to maximise uptake and use, including increasing awareness of the statement, clarity about when it applies, and availability of institutional-level support.
Machine learning prediction of hepatic steatosis using body composition parameters: A UK Biobank Study
Authors: Boncan Delbert Almerick T. , Yu Yan , Zhang Miaoru , Lian Jie , Vardhanabhuti Varut 
Published: January 2024

AbstractNon-alcoholic fatty liver disease (NAFLD) has emerged as the most prevalent chronic liver disease worldwide, yet detection has remained largely based on surrogate serum biomarkers, elastography or biopsy. In this study, we used a total of 2959 participants from the UK biobank cohort and established the association of dual-energy X-ray absorptiometry (DXA)-derived body composition parameters and leveraged machine learning models to predict NAFLD. Hepatic steatosis reference was based on MRI-PDFF which has been extensively validated previously. We found several significant associations with traditional measurements such as abdominal obesity, as defined by waist-to-hip ratio (OR = 2.50 (male), 3.35 (female)), android-gynoid ratio (OR = 3.35 (male), 6.39 (female)) and waist circumference (OR = 1.79 (male), 3.80 (female)) with hepatic steatosis. Similarly, A Body Shape Index (Quantile 4 OR = 1.89 (male), 5.81 (female)), and for fat mass index, both overweight (OR = 6.93 (male), 2.83 (female)) and obese (OR = 14.12 (male), 5.32 (female)) categories were likewise significantly associated with hepatic steatosis. DXA parameters were shown to be highly associated such as visceral adipose tissue mass (OR = 8.37 (male), 19.03 (female)), trunk fat mass (OR = 8.64 (male), 25.69 (female)) and android fat mass (OR = 7.93 (male), 21.77 (female)) with NAFLD. We trained machine learning classifiers with logistic regression and two histogram-based gradient boosting ensembles for the prediction of hepatic steatosis using traditional body composition indices and DXA parameters which achieved reasonable performance (AUC = 0.83–0.87). Based on SHapley Additive exPlanations (SHAP) analysis, DXA parameters that had the largest contribution to the classifiers were the features predicted with significant association with NAFLD. Overall, this study underscores the potential utility of DXA as a practical and potentially opportunistic method for the screening of hepatic steatosis.
Highly efficient capture approach for the identification of diverse inherited retinal disorders
Authors: Kao Hsiao-Jung , Lin Ting-Yi , Hsieh Feng-Jen , Chien Jia-Ying , Yeh Erh-Chan , Lin Wan-Jia , Chen Yi-Hua , Ding Kai-Hsuan , Yang Yu , Chi Sheng-Chu , Tsai Ping-Hsing , Hsu Chih-Chien , Hwang De-Kuang , Tsai Hsien-Yang , Peng Mei-Ling , Lee Shi-Huang , Chau Siu-Fung , Chen Chen Yu , Cheang Wai-Man , Chen Shih-Jen , Kwok Pui-Yan , Chiou Shih-Hwa , Lu Mei-Yeh Jade , Huang Shun-Ping 
Published: January 2024

AbstractOur study presents a 319-gene panel targeting inherited retinal dystrophy (IRD) genes. Through a multi-center retrospective cohort study, we validated the assay’s effectiveness and clinical utility and characterized the mutation spectrum of Taiwanese IRD patients. Between January 2018 and May 2022, 493 patients in 425 unrelated families, all initially suspected of having IRD without prior genetic diagnoses, underwent detailed ophthalmic and physical examinations (with extra-ocular features recorded) and genetic testing with our customized panel. Disease-causing variants were identified by segregation analysis and clinical interpretation, with validation via Sanger sequencing. We achieved a read depth of >200× for 94.2% of the targeted 1.2 Mb region. 68.5% (291/425) of the probands received molecular diagnoses, with 53.9% (229/425) resolved cases. Retinitis pigmentosa (RP) is the most prevalent initial clinical impression (64.2%), and 90.8% of the cohort have the five most prevalent phenotypes (RP, cone-rod syndrome, Usher’s syndrome, Leber’s congenital amaurosis, Bietti crystalline dystrophy). The most commonly mutated genes of probands that received molecular diagnosis are USH2A (13.7% of the cohort), EYS (11.3%), CYP4V2 (4.8%), ABCA4 (4.5%), RPGR (3.4%), and RP1 (3.1%), collectively accounted for 40.8% of diagnoses. We identify 87 unique unreported variants previously not associated with IRD and refine clinical diagnoses for 21 patients (7.22% of positive cases). We developed a customized gene panel and tested it on the largest Taiwanese cohort, showing that it provides excellent coverage for diverse IRD phenotypes.
Cortical thickness and white matter microstructure predict freezing of gait development in Parkinson’s disease
Authors: Lin Fabin , Zou Xinyang , Su Jiaqi , Wan Lijun , Wu Shenglong , Xu Haoling , Zeng Yuqi , Li Yongjie , Chen Xiaochun , Cai Guofa , Ye Qinyong , Cai Guoen 
Published: January 2024

AbstractThe clinical applications of the association of cortical thickness and white matter fiber with freezing of gait (FoG) are limited in patients with Parkinson’s disease (PD). In this retrospective study, using white matter fiber from diffusion-weighted imaging and cortical thickness from structural-weighted imaging of magnetic resonance imaging, we investigated whether a machine learning-based model can help assess the risk of FoG at the individual level in patients with PD. Data from the Parkinson’s Disease Progression Marker Initiative database were used as the discovery cohort, whereas those from the Fujian Medical University Union Hospital Parkinson’s Disease database were used as the external validation cohort. Clinical variables, white matter fiber, and cortical thickness were selected by random forest regression. The selected features were used to train the support vector machine(SVM) learning models. The median area under the receiver operating characteristic curve (AUC) was calculated. Model performance was validated using the external validation cohort. In the discovery cohort, 25 patients with PD were defined as FoG converters (15 men, mean age 62.1 years), whereas 60 were defined as FoG nonconverters (38 men, mean age 58.5 years). In the external validation cohort, 18 patients with PD were defined as FoG converters (8 men, mean age 66.9 years), whereas 37 were defined as FoG nonconverters (21 men, mean age 65.1 years). In the discovery cohort, the model trained with clinical variables, cortical thickness, and white matter fiber exhibited better performance (AUC, 0.67–0.88). More importantly, SVM-radial kernel models trained using random over-sampling examples, incorporating white matter fiber, cortical thickness, and clinical variables exhibited better performance (AUC, 0.88). This model trained using the above mentioned features was successfully validated in an external validation cohort (AUC, 0.91). Furthermore, the following minimal feature sets that were used: fractional anisotropy value and mean diffusivity value for right thalamic radiation, age at baseline, and cortical thickness for left precentral gyrus and right dorsal posterior cingulate gyrus. Therefore, machine learning-based models using white matter fiber and cortical thickness can help predict the risk of FoG conversion at the individual level in patients with PD, with improved performance when combined with clinical variables.
EPAC1 enhances brown fat growth and beige adipogenesis
Authors: Reverte-Salisa Laia , Siddig Sana , Hildebrand Staffan , Yao Xi , Zurkovic Jelena , Jaeckstein Michelle Y. , Heeren Joerg , Lezoualc’h Frank , Krahmer Natalie , Pfeifer Alexander 
Published: January 2024

AbstractBrown adipose tissue (BAT) is a central thermogenic organ that enhances energy expenditure and cardiometabolic health. However, regulators that specifically increase the number of thermogenic adipocytes are still an unmet need. Here, we show that the cAMP-binding protein EPAC1 is a central regulator of adaptive BAT growth. In vivo, selective pharmacological activation of EPAC1 increases BAT mass and browning of white fat, leading to higher energy expenditure and reduced diet-induced obesity. Mechanistically, EPAC1 coordinates a network of regulators for proliferation specifically in thermogenic adipocytes, but not in white adipocytes. We pinpoint the effects of EPAC1 to PDGFRα-positive preadipocytes, and the loss of EPAC1 in these cells impedes BAT growth and worsens diet-induced obesity. Importantly, EPAC1 activation enhances the proliferation and differentiation of human brown adipocytes and human brown fat organoids. Notably, a coding variant ofRAPGEF3(encoding EPAC1) that is positively correlated with body mass index abolishes noradrenaline-induced proliferation of brown adipocytes. Thus, EPAC1 might be an attractive target to enhance thermogenic adipocyte number and energy expenditure to combat metabolic diseases.
Parity–time-symmetric photonic topological insulator
Authors: Fritzsche Alexander , Biesenthal Tobias , Maczewsky Lukas J. , Becker Karo , Ehrhardt Max , Heinrich Matthias , Thomale Ronny , Joglekar Yogesh N. , Szameit Alexander 
Published: January 2024

AbstractTopological insulators are a concept that originally stems from condensed matter physics. As a corollary to their hallmark protected edge transport, the conventional understanding of such systems holds that they are intrinsically closed, that is, that they are assumed to be entirely isolated from the surrounding world. Here, by demonstrating a parity–time-symmetric topological insulator, we show that topological transport exists beyond these constraints. Implemented on a photonic platform, our non-Hermitian topological system harnesses the complex interplay between a discrete coupling protocol and judiciously placed losses and, as such, inherently constitutes an open system. Nevertheless, even though energy conservation is violated, our system exhibits an entirely real eigenvalue spectrum as well as chiral edge transport. Along these lines, this work enables the study of the dynamical properties of topological matter in open systems without the instability arising from complex spectra. Thus, it may inspire the development of compact active devices that harness topological features on-demand.
Health effects associated with exposure to secondhand smoke: a Burden of Proof study
Authors: Flor Luisa S. , Anderson Jason A. , Ahmad Noah , Aravkin Aleksandr , Carr Sinclair , Dai Xiaochen , Gil Gabriela F. , Hay Simon I. , Malloy Matthew J. , McLaughlin Susan A. , Mullany Erin C. , Murray Christopher J. L. , O’Connell Erin M. , Okereke Chukwuma , Sorensen Reed J. D. , Whisnant Joanna , Zheng Peng , Gakidou Emmanuela 
Published: January 2024

AbstractDespite a gradual decline in smoking rates over time, exposure to secondhand smoke (SHS) continues to cause harm to nonsmokers, who are disproportionately children and women living in low- and middle-income countries. We comprehensively reviewed the literature published by July 2022 concerning the adverse impacts of SHS exposure on nine health outcomes. Following, we quantified each exposure–response association accounting for various sources of uncertainty and evaluated the strength of the evidence supporting our analyses using the Burden of Proof Risk Function methodology. We found all nine health outcomes to be associated with SHS exposure. We conservatively estimated that SHS increases the risk of ischemic heart disease, stroke, type 2 diabetes and lung cancer by at least around 8%, 5%, 1% and 1%, respectively, with the evidence supporting these harmful associations rated as weak (two stars). The evidence supporting the harmful associations between SHS and otitis media, asthma, lower respiratory infections, breast cancer and chronic obstructive pulmonary disease was weaker (one star). Despite the weak underlying evidence for these associations, our results reinforce the harmful effects of SHS on health and the need to prioritize advancing efforts to reduce active and passive smoking through a combination of public health policies and education initiatives.