bluuebunny/crossref_metadata_2025_split huggingface dataset:
The protein disulfide isomerase A3 and osteopontin axis promotes influenza‐induced lung remodelling
Authors: Kumar Amit , Mark Zoe F. , Carbajal Morgan P. , DeLima Dhemerson Souza , Chamberlain Nicolas , Walzer Joseph , Ruban Mona , Chandrasekaran Ravishankar , Daphtary Nirav , Aliyeva Minara , Poynter Matthew E. , Janssen‐Heininger Yvonne M. W. , Bates Jason H. , Alcorn John F. , Britto Clemente J. , Dela Cruz Charles S. , Jegga Anil G. , Anathy Vikas 
Published: August 2024

AbstractBackground and PurposeFibrotic lung remodelling after a respiratory viral infection represents a debilitating clinical sequela. Studying or managing viral–fibrotic sequela remains challenging, due to limited therapeutic options and lack of understanding of mechanisms. This study determined whether protein disulfide isomerase A3 (PDIA3) and secreted phosphoprotein 1 (SPP1), which are associated with pulmonary fibrosis, can promote influenza‐induced lung fibrotic remodelling and whether inhibition of PDIA3 or SPP1 can resolve viral‐mediated fibrotic remodelling.Experimental ApproachA retrospective analysis of TriNetX data sets was conducted. Serum from healthy controls and influenza A virus (IAV)‐infected patients was analysed. An inhibitor of PDIA3, punicalagin, and a neutralizing antibody for SPP1 were administered in mice. Macrophage cells treated with macrophage colony‐stimulating factor (M‐CSF) were used as a cell culture model.Key ResultsThe TriNetX data set showed an increase in lung fibrosis and decline in lung function in flu‐infected acute respiratory distress syndrome (ARDS) patients compared with non‐ARDS patients. Serum samples revealed a significant increase in SPP1 and PDIA3 in influenza‐infected patients. Lung PDIA3 and SPP1 expression increased following viral infection in mouse models. Punicalagin administration 2 weeks after IAV infection in mice caused a significant decrease in lung fibrosis and improved oxygen saturation. Administration of neutralizing SPP1 antibody decreased lung fibrosis. Inhibition of PDIA3 decreased SPP1secretion from macrophages, in association with diminished disulfide bonds in SPP1.Conclusion and ImplicationsThe PDIA3–SPP1 axis promotes post‐influenza lung fibrosis in mice and that pharmacological inhibition of PDIA3 or SPP1 can treat virus‐induced lung fibrotic sequela.
Newly developed humanized anti‐CKAP4 antibody suppresses pancreatic cancer growth by inhibiting DKK1‐CKAP4 signaling
Authors: Sada Ryota , Yamamoto Hideki , Matsumoto Shinji , Harada Akikazu , Kikuchi Akira 
Published: August 2024

AbstractCytoskeleton‐associated protein 4 (CKAP4) is a cell surface receptor for Dickkopf 1 (DKK1), a secreted protein. The DKK1–CKAP4 pathway is activated in various malignant tumors, including pancreatic, lung, esophageal, and liver cancers, to promote tumor growth. Thus, CKAP4 has been expected to represent a novel molecular target of cancer therapy. Recombinant mouse anti‐CKAP4 antibodies were generated based on an original mouse antibody (3F11‐2B10) and inhibited DKK1–CKAP4 signaling and xenograft tumor formation induced by pancreatic cancer cells, which was comparable with 3F11‐2B10. From the 3F11‐2B10 nucleotide sequence, humanized anti‐CKAP4 antibody (Hv1Lt1) was subsequently developed. The binding affinity of Hv1Lt1 for CKAP4 was superior to that of 3F11‐2B10. Hv1Lt1 inhibited DKK1 binding to CKAP4, AKT activity, and sphere formation of pancreatic cancer cells, which was comparable with 3F11‐2B10. Hv1Lt1 also suppressed xenograft tumor formation induced by human pancreatic cancer cells and tumor growth in murine cancer models, in which murine pancreatic cancer organoids were orthotopically transplanted into the pancreas. In resected tumor samples from mice treated with Hv1Lt1, anti‐tumor immune reactions were modulated and cytotoxic T cells were highly infiltrated in the tumor microenvironment. Additionally, combination of Hv1Lt1 and other chemotherapy drugs exhibited stronger effects compared with monotherapy. These results suggest that Hv1Lt1 represents a promising anti‐cancer therapy.
Overcoming immunotherapy resistance and inducing abscopal effects with boron neutron immunotherapy (B‐NIT)
Authors: Fujimoto Takuya , Yamasaki Osamu , Kanehira Noriyuki , Matsushita Hirokazu , Sakurai Yoshinori , Kenmotsu Naoya , Mizuta Ryo , Kondo Natsuko , Takata Takushi , Kitamatsu Mizuki , Igawa Kazuyo , Fujimura Atsushi , Otani Yoshihiro , Shirakawa Makoto , Shigeyasu Kunitoshi , Teraishi Fuminori , Togashi Yosuke , Suzuki Minoru , Fujiwara Toshiyoshi , Michiue Hiroyuki 
Published: August 2024

AbstractImmune checkpoint inhibitors (ICIs) are effective against many advanced malignancies. However, many patients are nonresponders to immunotherapy, and overcoming this resistance to treatment is important. Boron neutron capture therapy (BNCT) is a local chemoradiation therapy with the combination of boron drugs that accumulate selectively in cancer and the neutron irradiation of the cancer site. Here, we report the first boron neutron immunotherapy (B‐NIT), combining BNCT and ICI immunotherapy, which was performed on a radioresistant and immunotherapy‐resistant advanced‐stage B16F10 melanoma mouse model. The BNCT group showed localized tumor suppression, but the anti‐PD‐1 antibody immunotherapy group did not show tumor suppression. Only the B‐NIT group showed strong tumor growth inhibition at both BNCT‐treated and shielded distant sites. Intratumoral CD8+ T‐cell infiltration and serum high mobility group box 1 (HMGB1) levels were higher in the B‐NIT group. Analysis of CD8+ T cells in tumor‐infiltrating lymphocytes (TILs) showed that CD62L‐ CD44+ effector memory T cells and CD69+ early‐activated T cells were predominantly increased in the B‐NIT group. Administration of CD8‐depleting mAb to the B‐NIT group completely suppressed the augmented therapeutic effects. This indicated that B‐NIT has a potent immune‐induced abscopal effect, directly destroying tumors with BNCT, inducing antigen‐spreading effects, and protecting normal tissue. B‐NIT, immunotherapy combined with BNCT, is the first treatment to overcome immunotherapy resistance in malignant melanoma. In the future, as its therapeutic efficacy is demonstrated not only in melanoma but also in other immunotherapy‐resistant malignancies, B‐NIT can become a new treatment candidate for advanced‐stage cancers.
A multicenter study on deep learning for glioblastoma auto‐segmentation with prior knowledge in multimodal imaging
Authors: Tian Suqing , Liu Yinglong , Mao Xinhui , Xu Xin , He Shumeng , Jia Lecheng , Zhang Wei , Peng Peng , Wang Junjie 
Published: August 2024

AbstractA precise radiotherapy plan is crucial to ensure accurate segmentation of glioblastomas (GBMs) for radiation therapy. However, the traditional manual segmentation process is labor‐intensive and heavily reliant on the experience of radiation oncologists. In this retrospective study, a novel auto‐segmentation method is proposed to address these problems. To assess the method's applicability across diverse scenarios, we conducted its development and evaluation using a cohort of 148 eligible patients drawn from four multicenter datasets and retrospective data collection including noncontrast CT, multisequence MRI scans, and corresponding medical records. All patients were diagnosed with histologically confirmed high‐grade glioma (HGG). A deep learning‐based method (PKMI‐Net) for automatically segmenting gross tumor volume (GTV) and clinical target volumes (CTV1 and CTV2) of GBMs was proposed by leveraging prior knowledge from multimodal imaging. The proposed PKMI‐Net demonstrated high accuracy in segmenting, respectively, GTV, CTV1, and CTV2 in an 11‐patient test set, achieving Dice similarity coefficients (DSC) of 0.94, 0.95, and 0.92; 95% Hausdorff distances (HD95) of 2.07, 1.18, and 3.95 mm; average surface distances (ASD) of 0.69, 0.39, and 1.17 mm; and relative volume differences (RVD) of 5.50%, 9.68%, and 3.97%. Moreover, the vast majority of GTV, CTV1, and CTV2 produced by PKMI‐Net are clinically acceptable and require no revision for clinical practice. In our multicenter evaluation, the PKMI‐Net exhibited consistent and robust generalizability across the various datasets, demonstrating its effectiveness in automatically segmenting GBMs. The proposed method using prior knowledge in multimodal imaging can improve the contouring accuracy of GBMs, which holds the potential to improve the quality and efficiency of GBMs' radiotherapy.
Cognitive enhancement through technology: A review of transcranial electrical stimulation (TES) interventions in children and adolescents with specific learning disabilities
Authors: Fathi Azar Elahe , Hejazi‐Shirmard Mahnaz , Mirzaie Hooshang 
Published: August 2024

AbstractBackgroundIn recent years, the exploration of innovative interventions for addressing problems of children and adolescents with specific learning disabilities (SLD) has garnered significant attention within the realm of neurocognitive research. Transcranial electrical stimulation (TES) has emerged as a promising tool for enhancing cognitive skills in children, offering a non‐invasive and safe method that may particularly benefit those with learning difficulties. We aimed to appraise the extent and the quality of studies about impact of TES on cognitive skills including academic skills in children and adolescents with SLD.MethodsA literature search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Articles published between January 2000 and January 2024 were searched in PubMed, Embase, Scopus, Web of Science and Google Scholar. The study eligibility criteria were previously established according to the PICO model. The Physiotherapy Evidence Database (PEDro) scale and Cochrane Collaboration tool (ROB2) were used to assess the methodological quality and the risk of bias of the included studies, respectively.ResultsThe initial search yielded 1571 studies among which 30 studies were systematically reviewed. The total number of participants was 224 individuals (intervention: 114; control: 110). Findings showed significant improvements in reading skills such as text reading, high‐frequency word reading speed and efficiency and mathematical skills. Conversely, other cognitive skills such as working memory were not improved in people with dyslexia and dyscalculia.DiscussionTES interventions can positively affect cognitive skills in children and adolescents with SLD; However, due to the small number of studies, medium methodological quality and high risk of bias, caution should be taken when interpreting the results.
The clinical and genetic spectrum of mitochondrial diseases in China: A multicenter retrospective cross‐sectional study
Authors: Zhao Yang , Zhao Xutong , Ji Kunqian , Wang Junling , Zhao Yuying , Lin Jie , Gang Qiang , Yu Meng , Yuan Yun , Jiang Haishan , Sun Chong , Fang Fang , Yan Chuanzhu , Wang Zhaoxia 
Published: August 2024

AbstractMitochondrial diseases (MtDs) present diverse clinical phenotypes, yet large‐scale studies are hindered by their rarity. This retrospective, multicenter study, conducted across five Chinese hospitals' neurology departments from 2009 to 2019, aimed to address this gap. Nationwide, 1351 patients were enrolled, with a median onset age of 14.0 (18.5) years. The predominant phenotype was mitochondrial encephalomyopathy, lactic acidosis, and stroke‐like episodes (MELAS) (45.0%). Mitochondrial DNA (mtDNA) mutations were prevalent (87.4%), with m.3243A>G being the most common locus (48.7%). Meanwhile, POLG mutations in nuclear DNA (nDNA) accounted for 16.5%. Comparative analysis based on age groups (with a cut‐off at 14 years) revealed the highest prevalence of MELAS, with Leigh syndrome (LS) and chronic progressive external ophthalmoplegia (CPEO) being the second most common phenotypes in junior and senior groups, respectively. Notably, the most commonly mutated nuclear genes varied across age groups. In conclusion, MELAS predominated in this Chinese MtD cohort, underscored by m.3243A>G and POLG as principal mtDNA mutations and pathogenic nuclear genes. The phenotypic and genotypic disparities observed among different age cohorts highlight the complex nature of MtDs.
Unraveling multi‐scale neuroimaging biomarkers and molecular foundations for schizophrenia: A combined multivariate pattern analysis and transcriptome‐neuroimaging association study
Authors: Peng Yanmin , Chai Chao , Xue Kaizhong , Tang Jie , Wang Sijia , Su Qian , Liao Chongjian , Zhao Guoshu , Wang Shaoying , Zhang Nannan , Zhang Zhihui , Lei Minghuan , Liu Feng , Liang Meng 
Published: August 2024

AbstractAimsSchizophrenia is characterized by alterations in resting‐state spontaneous brain activity; however, it remains uncertain whether variations at diverse spatial scales are capable of effectively distinguishing patients from healthy controls. Additionally, the genetic underpinnings of these alterations remain poorly elucidated. We aimed to address these questions in this study to gain better understanding of brain alterations and their underlying genetic factors in schizophrenia.MethodsA cohort of 103 individuals with diagnosed schizophrenia and 110 healthy controls underwent resting‐state functional MRI scans. Spontaneous brain activity was assessed using the regional homogeneity (ReHo) metric at four spatial scales: voxel‐level (Scale 1) and regional‐level (Scales 2–4: 272, 53, 17 regions, respectively). For each spatial scale, multivariate pattern analysis was performed to classify schizophrenia patients from healthy controls, and a transcriptome‐neuroimaging association analysis was performed to establish connections between gene expression data and ReHo alterations in schizophrenia.ResultsThe ReHo metrics at all spatial scales effectively discriminated schizophrenia from healthy controls. Scale 2 showed the highest classification accuracy at 84.6%, followed by Scale 1 (83.1%) and Scale 3 (78.5%), while Scale 4 exhibited the lowest accuracy (74.2%). Furthermore, the transcriptome‐neuroimaging association analysis showed that there were not only shared but also unique enriched biological processes across the four spatial scales. These related biological processes were mainly linked to immune responses, inflammation, synaptic signaling, ion channels, cellular development, myelination, and transporter activity.ConclusionsThis study highlights the potential of multi‐scale ReHo as a valuable neuroimaging biomarker in the diagnosis of schizophrenia. By elucidating the complex molecular basis underlying the ReHo alterations of this disorder, this study not only enhances our understanding of its pathophysiology, but also pave the way for future advancements in genetic diagnosis and treatment of schizophrenia.
Based on Cardiopulmonary Exercise Testing to Construct and Validate Nomogram of Long‐Term Prognosis Within 12 Months for NSCLC
Authors: Wang Xinyu , Li Jin , Zhou Jingjie , Gao Min , Wang Bin , Tong Yiman , Cao Yuhan , Chen Wei 
Published: August 2024

ABSTRACTObjectiveConstruction nomogram was to effectively predict long‐term prognosis in patients with non‐small cell lung cancer (NSCLC).Materials and MethodsThe nomogram is developed by a retrospective study of 347 patients with NSCLC who underwent cardiopulmonary exercise testing (CPET) before surgery from May 2019 to February 2022. Cross‐validation divided the data into a training cohort and validation cohort. The discrimination and accuracy ability of the nomogram were proofed by concordance index (C‐index), calibration curve, receiver operating characteristic (ROC) curve, the area under the curve (AUC), and time‐dependent ROC in validation cohort.ResultsAge, intraoperative blood loss, VO2 peak, and VE/VCO2 slope were included in the model of nomogram. The model demonstrated good discrimination and accuracy with C‐index of 0.770 (95% CI: 0.712–0.822). AUC of 6 (AUC: 0.789, 95% CI: 0.726–0.851) and 12 months (AUC: 0.787, 95% CI: 0.724–0.850) were shown in ROC. Time‐independent ROC maintains a good effect within 12 months.ConclusionWe developed a nomogram based on CPET. This model has a good ability of discrimination and accuracy. It could help clinicians to make treatment decision in clinical decision.
Perceptions, attitudes and barriers to effective obesity care among people living with obesity and healthcare professionals in China: The ACTION‐China study
Authors: Ji Linong , Mu Yiming , Chang Cuiqing , Wang Huali , Zhao Di , Liu Dongmei , Shen Zewei , Chen Wei 
Published: August 2024

AbstractAimsTo identify perceptions, attitudes, behaviours and barriers to effective obesity care among people living with obesity (PLwO) and healthcare professionals (HCPs) across mainland China.Materials and MethodsACTION‐China (ClinicalTrials.gov: NCT05428501) was a cross‐sectional, observational, descriptive, online survey‐based study of 7000 PLwO and 1000 HCPs (conducted between August and November 2022).ResultsThe majority of PLwO (76.8% [5374/7000]) and HCPs (94.6% [946/1000]) agreed that obesity is a chronic disease. Only 40.8% of PLwO (2853/7000) had discussed their weight or talked about losing weight with an HCP in the past 5 years. The most frequent reason given by PLwO for not discussing weight management with an HCP was believing it was their responsibility to manage their weight (34.7% [2430/7000]), whereas the most frequent reason HCPs gave for not discussing obesity with their patients with obesity was having more important health issues to discuss (72.1% [721/1000]). A smaller proportion of PLwO (19.1%) than HCPs (53.6%) felt that weight management discussions with an HCP would be very or extremely helpful for the patient, and 30.7% of PLwO experienced negative feelings after their most recent discussion. Overall, 34.8% (2438/7000) of PLwO had been diagnosed with obesity by an HCP, while 30.0% (2101/7000) of PLwO did not recognize that they had obesity.ConclusionsThis large, national survey conducted among PLwO and HCPs highlights key barriers to effective obesity care in China, including underestimation of weight status by PLwO and the need for increased communication between HCPs and PLwO regarding weight management.
Cystic fibrosis‐related diabetes develops from a combination of insulin secretion defects and insulin resistance
Authors: Bolduc Marie‐Ève , Potter Kathryn J. , Olmos Maxime , Bonhoure Anne , Coriati Adèle , Alexandre‐Heymann Laure , Tremblay François , Lavoie Annick , Carricart Maité , Senior Peter A. , Boudreau Valérie , Rabasa‐Lhoret Rémi 
Published: August 2024

AbstractAimThe relative contributions of insulin secretory defects and possible additional contribution of insulin resistance for the development of cystic fibrosis (CF)‐related diabetes (CFRD) are poorly understood. We aimed to (a) determine which indices of insulin resistance predict progression to CFRD, and (b) to model the relative contributions of insulin secretory function and insulin resistance to predict the risk of CFRD.Materials and MethodsThree hundred and three individuals living with CF underwent a 2‐h oral glucose tolerance test with blood sampling every 30 min at 12–24‐month intervals until they developed CFRD or until the end of follow‐up (up to 15 years). Indices of insulin resistance (e.g. Stumvoll) and insulin secretion were calculated from oral glucose tolerance test glucose and insulin measurements. CFRD‐free survival was assessed by survival analysis.ResultsEstimated insulin resistance showed associations with glucose homeostasis and risk of progression to CFRD. The CFRD‐free survival was significantly different between quartiles of insulin resistance (p < 0.0001). When patients were subdivided according to both insulin resistance and insulin secretion (insulinogenic index), CFRD‐free survival was significantly lower in those with combined lowest insulin secretion and highest insulin resistance (Stumvoll) indices (hazard ratio: 11.2; p < 0.0001). There was no significant difference when the same analysis was performed for the nine other indices.ConclusionsInsulin resistance is correlated with glucose homeostasis and the risk of progression to CFRD. Patients combining low insulin secretion and high insulin resistance had the greatest odds of developing CFRD over a 15‐year period.
Activity‐based funding reform and the performance of public hospitals: The case of Queensland, Australia
Authors: Nguyen Bao Hoang , Grosskopf Shawna , Yong Jongsay , Zelenyuk Valentin 
Published: August 2024

AbstractThis study investigates the impact of activity‐based funding (ABF) on the performance of hospitals by exploiting a natural experiment that happened in the state of Queensland, Australia. To examine the outcome of the reform, the performance of hospitals is measured by the technical efficiency estimated from data envelopment analysis (DEA) models. We try to identify the causal effect of ABF on the technical efficiency of hospitals by incorporating difference‐in‐differences approach in the popular two‐stage DEA framework. We find empirical evidence that ABF improves the technical efficiency of hospitals.
Bait type affects the diversity assessment of cetoniid beetles in the Brazilian Cerrado
Authors: Evangelista Juliane , Blassioli‐Moraes Maria Carolina , Laumann Raúl Alberto , Borges Miguel , de Oliveira Charles Martins , Frizzas Marina Regina 
Published: August 2024

AbstractCetoniidae (Coleoptera), known as flower and fruit beetles, form a diverse group, feed on nectar, pollen, plant exudates, and are highly attracted to fermented fruits. To evaluate their diversity in natural and agricultural areas, traps baited with fermented fruits are used. The objective of this study was to compare the effectiveness of various types of fruit used as bait, with or without the addition of sugarcane juice to accelerate fruit fermentation, on the assessment of Cetoniidae diversity in the Brazilian Cerrado. The study was conducted in two conservation units in Brasília (DF, Brazil). Two experiments were conducted, the first aiming to select the most attractive fruits (banana, pineapple, mango, grape, or cagaita), and the second to verify whether there is interference of sugarcane juice in the fruit fermentation process and, consequently, in the attractiveness to Cetoniidae. The chemical profiles of the types of bait were evaluated by identifying and quantifying the main volatile organic compounds released by the fruit traps. Insect collections were conducted weekly using fruit‐baited traps for 1 month, without interruption. We found that the diversity estimate of Cetoniidae was higher for banana‐based baits relative to grape and cagaita fruit, but not relative to pineapple, mango, and sugarcane juice. Additionally, no increase in attractiveness was observed with the addition of sugarcane juice to banana, pineapple, and mango bait. Most compounds in the fruit extracts belong to alcohol, ester, and terpene functional groups. Our results suggest that banana, pineapple, mango, and sugarcane juice, used alone, may be used for Cetoniidae diversity studies, and that banana bait seems to be the most suitable for Cetoniidae collection in the Cerrado, because it enables the collection of a high diversity of species and also of species considered rare.