bluuebunny/crossref_metadata_2025_split huggingface dataset:
The optimal second-line therapy for older adults with type 2 diabetes mellitus: protocol for a systematic review and network meta-analysis using individual participant data (IPD)
Authors: Wang Jingya , Nirantharakumar Krishnarajah , Sainsbury Christopher , Moore David J. , Sinclair Alan , Thomas G. Neil , Hanif Wasim , Singh Megha , Tan Luyuan , Wang Zhaonan , Simms-Williams Nikita , Yao Mi , Gunathilaka M. Niluka , Singh Pushpa , Toulis Konstantinos , Tsapas Apostolos , Coomar Dyuti , Price Malcolm James 
Published: June 2024

Abstract
Background
Due to increasing life expectancy, almost half of people with type 2 diabetes are aged 65 years or over worldwide. When metformin alone does not control blood sugar, the choice of which second-line therapy to prescribe next is not clear from currently available evidence. The existence of frailty and comorbidities in older adults further increases the complexity of medical decision-making. As only a relatively small proportion of trials report results separately for older adults, the relative efficacy and safety of second-line therapies in older adults with type 2 diabetes mellitus are unknown and require further investigation. This individual participant data (IPD) network meta-analysis evaluates the relative efficacy and safety of second-line therapies on their own or in combination in older adults with type 2 diabetes mellitus.

Methods
All relevant published and unpublished trials will be identified. Studies published prior to 2015 will be identified from two previous comprehensive aggregate data network meta-analyses. Searches will be conducted in CENTRAL, MEDLINE, and EMBASE from 1st January 2015 onwards, and in clinicaltrials.gov from inception. Randomised controlled trials with at least 100 estimated older adults (≥ 65 years) receiving at least 24 weeks of intervention that assess the effects of glucose-lowering drugs on mortality, glycemia, vascular and other comorbidities outcomes, and quality of life will be eligible. The screening and data extraction process will be conducted independently by two researchers. The quality of studies will be assessed using the Cochrane risk of bias tool 2. Anonymised IPD of all eligible trials will be requested via clinical trial portals or by contacting the principal investigators or sponsors. Received data will be reanalysed where necessary to standardise outcome metrics. Network meta-analyses will be performed to determine the relative effectiveness of therapies.

Discussion
With the increasing number of older adults with type 2 diabetes worldwide, an IPD network meta-analysis using data from all eligible trials will provide new insights into the optimal choices of second-line antidiabetic drugs to improve patient management and reduce unnecessary adverse events and the subsequent risk of comorbidities in older adults.

Systematic review registration
PROSPERO CRD42021272686.
Tapping the alphabets of learning-oriented assessment: self-assessment, classroom climate, mindsets, trait emotional intelligence, and academic engagement are in focus
Authors: Namaziandost Ehsan , Kargar Behbahani Hossein , Heydarnejad Tahereh 
Published: June 2024

AbstractThis study investigates the role of self-assessment (SA), classroom climate (CC), and psychological variables in learning-oriented assessment (LOA) within English as a foreign language (EFL) education. Utilizing a mixed-methods approach, data was collected through surveys and semi-structured interviews from EFL learners and instructors. Findings reveal that SA plays a pivotal role in promoting learner autonomy, self-regulated learning, and academic engagement (AE). By actively involving students in the assessment process and providing opportunities for reflection and feedback, educators can empower learners to take ownership of their learning journey and enhance their overall learning outcomes. Moreover, the study underscores the importance of creating a supportive CC characterized by mutual respect, collaboration, and inclusivity. Positive teacher-student relationships and inclusive learning environments contribute significantly to students’ academic and socioemotional development. Additionally, the study highlights the influence of psychological variables such as growth mindset and emotional intelligence (EI) on student learning outcomes. Learners who adopt a growth-oriented mindset and possess high levels of EI are more likely to persevere in the face of challenges and actively engage in the learning process. The implications of this study suggest the importance of adopting a holistic approach to assessment and instruction in EFL education, with stakeholders urged to incorporate strategies to promote SA, create supportive CC, and foster psychological variables for enhanced student learning and well-being.
Protection of Guizhou Miao batik culture based on knowledge graph and deep learning
Authors: Quan Huafeng , Li Yiting , Liu Dashuai , Zhou Yue 
Published: June 2024

Abstract
In the globalization trend, China’s cultural heritage is in danger of gradually disappearing. The protection and inheritance of these precious cultural resources has become a critical task. This paper focuses on the Miao batik culture in Guizhou Province, China, and explores the application of knowledge graphs, natural language processing, and deep learning techniques in the promotion and protection of batik culture. We propose a dual-channel mechanism that integrates semantic and visual information, aiming to connect batik pattern features with cultural connotations. First, we use natural language processing techniques to automatically extract batik-related entities and relationships from the literature, and construct and visualize a structured batik pattern knowledge graph. Based on this knowledge graph, users can textually search and understand the images, meanings, taboos, and other cultural information of specific patterns. Second, for the batik pattern classification, we propose an improved ResNet34 model. By embedding average pooling and convolutional operations into the residual blocks and introducing long-range residual connections, the classification performance is enhanced. By inputting pattern images into this model, their categories can be accurately identified, and then the underlying cultural connotations can be understood. Experimental results show that our model outperforms other mainstream models in evaluation metrics such as accuracy, precision, recall, and F1-score, achieving 94.46%, 94.47%, 93.62%, and 93.8%, respectively. This research provides new ideas for the digital protection of batik culture and demonstrates the great potential of artificial intelligence technology in cultural heritage protection.
Correlation-based outlier detection for ships’ in-service datasets
Authors: Gupta Prateek , Rasheed Adil , Steen Sverre 
Published: June 2024

AbstractWith the advent of big data, it has become increasingly difficult to obtain high-quality data. Solutions are required to remove undesired outlier samples from massively large datasets. Ship operators rely on high-frequency in-service datasets recorded onboard the ships for monitoring the performance of their fleet. The large in-service datasets are known to be highly unbalanced, making it difficult to adopt ordinary outlier detection techniques, as they would also result in the removal of rare but quite valuable data samples. Thus, the current work proposes to establish a correlation-based outlier detection scheme for ships’ in-service datasets using two well-known dimensionality reduction methods, namely, Principal Component Analysis (PCA) and Autoencoders. The correlation-based approach detects samples which do not fit the prominent correlations present in the dataset and avoids misidentifying the rare but correlation-following samples in the sparse regions of data domain. The study also attempts to provide the physical meaning of the latent variables obtained using PCA. The effectiveness of the proposed methodology is proven using an actual dataset recorded onboard a ship.
Ambient air pollution and the risk of violence in primary and secondary school settings: a cross-sectional study
Authors: Rau Austin T. , Harding Alyson B. , Ryan Andy , Ramirez Marizen R. , Renner Lynette M. , Berman Jesse D. 
Published: June 2024

Abstract
Background
Individual and social characteristics are attributed to violent behavior in schools, yet environmental hazards may play an understudied role. Ambient air pollution has been linked to neurological dysfunction that inhibits decision-making and may result in violent behavior in adult populations. However, little is known on how air pollution may be associated with violent behaviors in children.

Methods
A cross-sectional ecologic study was designed to estimate the associations between air pollution (fine particulate matter, carbon monoxide, and nitrogen dioxide) with the occurrence of violent incidents and incidents involving a weapon among a cohort of children in Minnesota schools (2008–2012). Differences by urban and rural status of schools were also explored. Negative binomial regression models were developed to estimate incidence rate ratios (IRR) and incidence rate differences (IRD) to describe associations between air pollution and violent incidents in school settings.

Results
Our results indicate that the highest levels of carbon monoxide, nitrogen dioxide and fine particulate matter concentrations were associated with increased violent disciplinary incidents. Among the total student population, the 4th quartile of carbon monoxide exposure was associated with an IRD of 775.62 (95% CI 543.2, 1008.05) violent incidents per 100,000 students per school year compared to schools in the lowest quartile of exposure. Comparing the 4th to the 1st quartiles of exposure, nitrogen dioxide and fine particulate matter had an IRD of 629.16 (95% CI 384.87, 873.46), and 510.49 (95% CI 274.92, 746.05) violent incidents per 100,000 students per school year respectively. Schools in urban settings shared a larger burden of violent incidents associated with air pollution compared to rural schools.

Conclusions
Modifying environmental pollutants surrounding school environments, particularly for high exposure communities, may be a novel tool for reducing violence and subsequent injuries in schools.
Appendiceal neoplasms derived from appendiceal tip remnants following appendectomy: a report of two cases
Authors: Fujii Yusuke , Hida Koya , Sugimoto Akihiko , Nishijima Ryohei , Fujimoto Masakazu , Hoshino Nobuaki , Maekawa Hisatsugu , Okamura Ryosuke , Itatani Yoshiro , Obama Kazutaka 
Published: June 2024

Abstract
Background
Neoplasms derived from remnant appendix are rarely described, with most cases arising from the appendiceal “stump”. Here, we present two surgical cases of appendiceal neoplasms derived from appendiceal “tip” remnants.

Case presentation
The first patient was a 71-year-old man who had undergone laparoscopic appendectomy for acute appendicitis 12 years prior. During appendectomy, the appendiceal root was ligated, but the appendix was not completely removed due to severe inflammation. At the most recent presentation, computed tomography (CT) was performed to examine choledocholithiasis, which incidentally revealed a cystic lesion of approximately 90 mm adjacent to the cecum. A retrospective review revealed that the cystic lesion had increased in size over time, and laparoscopic ileocecal resection was performed. Pathology revealed no continuity from the appendiceal orifice to the cyst, and a diagnosis of low-grade appendiceal mucinous neoplasm (LAMN) was made from the appendiceal tip remnant. The patient was discharged without complications. The second patient was a 65-year-old man who had undergone surgery for peritonitis due to severe appendicitis 21 years prior. During this operation, the appendix could not be clearly identified due to severe inflammation; consequently, cecal resection was performed. He was referred to our department with a chief complaint of general fatigue and loss of appetite and a cystic lesion of approximately 85 mm close to the cecum that had increased over time. CT showed irregular wall thickening, and malignancy could not be ruled out; therefore, laparoscopic ileocecal resection with D3 lymph node dissection was performed. The pathological diagnosis revealed mucinous adenocarcinoma (TXN0M0) arising from the remnant appendiceal tip. The patient is undergoing follow-up without postoperative adjuvant chemotherapy, with no evidence of pseudomyxoma peritonei or cancer recurrence for 32 months postoperatively.

Conclusions
If appendicitis-associated inflammation is sufficiently severe that accurate identification of the appendix is difficult, it may remain on the apical side of the appendix, even if the root of the appendix is ligated and removed. If the appendectomy is terminated incompletely, it is necessary to check for the presence of a residual appendix postoperatively and provide appropriate follow-up.
Elevated IRF9 raised cell apoptosis and tissue damages through suppressing SIRT1 in hyperlipidemia acute pancreatitis with liver injury
Authors: Pan Jin-Ge , Qin Ru-Xue , Ma Xue-Ying , Han Zi-Yu , Lu Zhong-Hua , Sun Yun , Yu Wei-Li 
Published: June 2024

Abstract
Background
Hyperlipidemia is a vital etiology of acute pancreatitis (AP), 12 to 20% of which have a history of hyperlipidemia. Multiple organ failure is the major cause of the high mortality rate of AP. Liver injury has been discovered in 80% of AP patients. The relationship and role of IRF9 and SIRT1 have not been presented in AP and hyperlipidemia AP (HLAP) with liver injury. This investigation was designed to explore the function and relationship of IRF9 and SIRT1.

Methods
HLAP model in vivo was performed by feeding high-fat forage and induced by peritoneal injection with 20% L-arginine. The severity of pancreas and liver tissues was assessed. Cell apoptosis in the liver was determined by the TUNEL experiment. IRF9, SIRT1, p53, and acetylated p53 (Ac-p53) expression levels in liver tissues were detected by qRT-PCR and Western blot. The association of IRF9 expression with SIRT1 levels was evaluated. The relevance of triglyceride level to tissue damage was analyzed.

Results
Our observation exhibited more distinct liver damage, a large number of hepatic cell apoptosis, marked raised IRF9, Ac-p53, and sharply dropped SIRT1 in the AP and HLAP groups. Compared with other groups, HLAP showed the most significant changes in liver injury, hepatic cell apoptosis, protein, and mRNA levels. The declined expression of SIRT1 was correlated with the elevated expression of IRF9. The damage of the pancreas and liver exacerbated with the increase in triglyceride levels.

Conclusion
Elevated IRF9 in pancreatitis with liver injury raised cell apoptosis and tissue damage by decreasing SIRT1 expression.
Reshaping the tumor microenvironment of cold soft-tissue sarcomas with anti-VEGFR targeted therapy: A Phase 2 Trial of Regorafenib combined with avelumab.
Authors: Italiano Antoine , Guegan Jean-Philippe , Valentin Thibaud , Bahleda Rastilav , Metges Jean Philippe , Cassier Philippe Alexandre , Toulmonde Maud , spalato-Ceruso Mariella , Peyraud Florent , Palussière Jean , Kind Michèle , Cantarel Coralie , Bellera Carine A. , Bessede Alban 
Published: June 2024

11516 Background: Vascular Endothelial Growth Factor (VEGF)-driven angiogenesis is a pivotal factor in creating an immunosuppressive tumor microenvironment. Approximately 80% of Soft Tissue Sarcomas (STS) are characterized by a 'cold' microenvironment, lacking tertiary lymphoid structures (TLS). While the efficacy of VEGF pathway and PD-1/PD-L1 axis blockade has been established in various tumor types, their impact on 'cold' STS remains unexplored. This study aims to evaluate the synergistic effect of anti-angiogenesis and PD-1 blockade in altering the microenvironment of cold STS, potentially enhancing immune response and therapeutic efficacy. Methods: In this phase II, single-arm, open-label, multicentric trial, we explored the efficacy and safety of combining regorafenib (R) and avelumab (A) in advanced TLS-negative STS patients. Patients were administered 160 mg of R daily for 3 weeks in a 4-week cycle, alongside 10 mg/kg of A biweekly. Endpoints included high-throughput analysis of tumor and plasma samples, response rate, progression-free survival (PFS), overall survival (OS), and safety, as per the NCI-CTCAE v5.0 guidelines. Results: From May 2019 to August 2021, 49 TLS-negative STS patients were enrolled, including leiomyosarcoma (45%), synovial sarcoma (18%), and other subtypes. The median age was 57.1 years, with patients having undergone an average of 2 prior treatment lines. High-throughput analysis of sequential plasma samples indicated an upregulation of immune-inducing protein biomarkers such as CXCL10 and soluble CD8 antigen. Multiplex immunofluorescence analysis of sequential tumor samples revealed significant increase in CD8 T cell infiltration on-treatment. The most common severe adverse events were grade 1 or 2 palmar-plantar erythrodysesthesia, fatigue, and diarrhea. The median follow-up was 7.1 months, with 32.6% of patients experiencing tumor shrinkage, and a clinical benefit rate of 48.8%. The 6-month PFS was 22.1%, with a median OS of 15.1 months. Conclusions: The combination of regorafenib and avelumab demonstrates a marked mobilization of antitumor immunity in patients with TLS-negative STS. The observed efficacy appears superior to that of single-agent immune checkpoint inhibition in 'cold' STS, and higher than the 6-month PFS benchmark of 14% set by EORTC. This indicates the potential effectiveness of this treatment combination in managing advanced cold STS, marking a significant stride in precision immunotherapy for this group of tumors. Clinical trial information: NCT03475953 .
Immune infiltrate analysis to reveal distinct immune classes for leiomyosarcomas.
Authors: Gingrich Alicia , Beird Hannah , Lazcano Segura Rossana , Denu Ryan , Nakazawa Michael , Ratan Ravin , Livingston J. Andrew , Zarzour Maria Alejandra , Conley Anthony Paul , Somaiah Neeta , Araujo Dejka M. , Patel S Shreyaskumar , Roland Christina Lynn , Futreal Andrew , Lazar Alexander J. , Keung Emily Zhi-Yun , Nassif Haddad Elise F ,   Rare Tumor Initiative Team, Patient Mosaic Team
Published: June 2024

11546 Background: Leiomyosarcomas (LMS) are aggressive malignancies of smooth-muscle origin. Few targeted molecular options exist and immunotherapy (IO) agents against T cells have been disappointing. In this study, we examine the immune infiltrate of LMS tumors by immunohistochemistry (IHC) and gene expression. Our objective was to identify actionable targets for immunotherapy in patients with LMS. Methods: Tumor samples from a series of LMS patients were prospectively collected and banked for DNA and RNA sequencing as part of the MD Anderson Patient Mosaic. Associated clinical data for the patients were collected and maintained. IHC was performed on available separate tissue microarrays. Differential gene expression (DGE) analysis was done using the DESeq2 package for R and the Benjamini-Hochberg procedure used to control for false discovery rate. Immune cell fractions were estimated using the MCPcounter package. All gene expression analyses were repeated on The Cancer Genome Atlas (TCGA) dataset as an independent dataset. Results: A total of 104 TCGA samples and 72 samples from Mosaic from 53 patients with uterine or soft tissue LMS were included in the analysis. Tumors in the TCGA group were treatment naive. Of the samples in the Mosaic group, 61 (85%) had been previously treated with chemotherapy, 8 (11%) had been radiated, and 5 (7.5%) had been previously treated with immunotherapy. Thirty-one (43%) tumors were metastatic. Fifty-one (70%) were soft tissue LMS and 21 (30%) were uterine LMS. Four distinct immune classes were seen in both the TGCA and Mosaic: a predominantly B-cell group, a monocyte/macrophage group, a mixed infiltrate group and a group with a neutrophil signature. DGE performed between the subgroups revealed a unique gene expression pattern for tumors in the B cell and monocyte/macrophage subgroups. Interrogation of specific immune-associated genes revealed low levels of expression in the neutrophil group, suggesting this may be the most immunologically “cold” subset. Some of these results were reproduced by IHC using a TMA: the presence of a cluster of samples with B-cells and higher expression of immune checkpoints, a macrophage driven cluster, and an immunologically cold cluster. Conclusions: Analyses of LMS samples across two large datasets demonstrate the existence of 4 distinct immune classes of tumors that persist despite variation in clinical and treatment conditions: B cell, monocytic/macrophage, mixed-infiltrate and neutrophil rich. The B cell and monocytic groups have increased expression of immune markers which may be amenable to targeted therapies.
Do patients with myxofibrosarcoma and undifferentiated pleomorphic sarcoma have different clinical outcomes to immune checkpoint blockade-based therapy?
Authors: Rosenbaum Evan , Seier Kenneth , Bradic Martina , Desir Rhoena , Kelly Ciara Marie , Movva Sujana , Avutu Viswatej , Banks Lauren Baker , Chan Jason Earl , Chi Ping , Dickson Mark Andrew , Keohan Mary Louise , Gounder Mrinal M. , Maki Robert G. , Singer Samuel , Qin Li-Xuan , Antonescu Cristina R. , Tap William D. , D'Angelo Sandra P. 
Published: June 2024

11567 Background: Myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS) are distinct histologic subtypes of soft tissue sarcoma that exist on a spectrum of dedifferentiation. Molecular analyses have found MFS and UPS to be indistinguishable, except for a higher expression of matrix-associated genes in MFS. While immune checkpoint blockade (ICB) is a recognized treatment option for UPS patients according to the National Comprehensive Cancer Network guidelines, clinical outcomes to ICB-based therapy in MFS have not been well described. Methods: The objectives of this study were to compare the overall response rate (ORR), progression free survival (PFS), and overall survival (OS) of MFS and UPS patients treated with ICB-based therapy. We retrospectively searched our clinical trial database for MFS and UPS patients treated at our Center with ICB-based therapy. Given the low number of MFS patients identified, we included any MFS patient treated with ICB-based therapy off-label. To determine whether MFS patients treated off-label differed from those treated on a study, a sensitivity analysis was performed comparing PFS and OS between these two groups. Kaplan Meier methods were used to analyze OS and PFS and log rank test was used to compare between groups. ORR were compared using Fisher’s exact test. Results: A total of 70 patients were included, 43 (61%) with UPS and 27 (39%) with MFS. All UPS patients and 13 MFS patients were treated on one of 8 different clinical trials, two utilized ICB alone and 6 combined ICB with another agent. Eleven of 14 (79%) MFS patients treated off-label received ICB alone; 3 (21%) received ICB plus another agent. Fifty-five patients treated on trials were assessed by RECIST 1.1 (12 MFS and 43 UPS). The median age of MFS patients was higher than UPS (69.5 and 57.2, respectively). Both cohorts were predominantly male (55.6% in MFS and 60.5% in UPS) and had a median of 1 prior line of therapy (range: 0 – 6 in MFS and 0 - 7 in UPS). The median myxoid component of baseline MFS tumors was 30% (range: 10 – 90%). Median PFS and OS (in months) and ORR (%) are outlined (Table). A sensitivity analysis within MFS did not find a significant difference between MFS patients treated off or on a clinical trial. Conclusions: In this retrospective analysis, clinical outcomes to ICB-based therapy did not differ between MFS and UPS patients. Based on these data, it may be reasonable to (a) consider ICB as a treatment option for unresectable or metastatic MFS refractory to standard chemotherapy and (b) group UPS and MFS together onto a single cohort in clinical studies of ICB-based therapy. [Table: see text]