bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic and immunological significance of tertiary lymphoid structures in nasopharyngeal carcinoma.
Authors: Huang Daofeng , Liu Xu , Li Hui , Zheng Zi-Qi , Du Juan , Ma Jun 
Published: August 2024

220 Background: Tertiary lymphoid structures (TLSs) are ectopic lymphoid tissues found in non-lymphoid organs, characterized by the presence of CD20+ B cell follicles adjacent to a T cell zone. Their presence has been associated with improved survival in various tumor types. However, the role of TLSs in nasopharyngeal carcinoma (NPC) remains unclear. In this study, we investigated the prognostic and immunological significance of TLSs in NPC patients. Methods: The investigation involved a discovery cohort (n = 145) comprising NPC patients diagnosed at Sun Yat-sen University Cancer Center between July 2010 and December 2016, with pretreatment primary tumor samples collected. An independent validation cohort included 150 NPC patients with gene expression profiles, among whom Hematoxylin & Eosin (H&E)-stained slides were available for 95 patients. The primary endpoint of this study is overall survival, defined as the duration of time from diagnosis until death from any cause. The presence of TLSs was assessed on H&E and CD20-stained slides. Analyses of tumor-infiltrating immune cell subsets, differentially expressed genes, and BCR/TCR clonotypes were performed to explore the association between TLSs and the anti-tumor immune response. A molecular definition of TLSs was proposed and assessed for its prognostic value across multiple cohorts. Results: The presence of TLSs was independently associated with a favorable overall survival (hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.07-0.94; log-rank p = 0.04), surpassing the significance of B cell density in multivariate analysis (HR, 0.83; 95% CI, 0.38-1.79, log-rank p = 0.63). These findings were corroborated in the independent validation cohort. TLSs positively correlated with multiple immune-related pathways and a higher proportion of functionally mature immune cells. Notably, the counts of BCR and TCR clonotypes showed a significant positive correlation with the TLSs score. We proposed a TLSs gene signature and demonstrated its prognostic relevance across multiple cohorts, including patients treated with immune checkpoint blockade. Conclusions: TLSs exhibit heightened immune activity and indicate improved survival outcomes in NPC patients. A TLSs gene signature was proposed and demonstrated its prognostic relevance across multiple cohorts, indicating potential guidance for treatment decisions in cancer.
Tissue of origin detection for cancer tumor using low-depth cfDNA samples through combination of tumor-specific methylation atlas and genome-wide methylation density in graph convolutional neural networks.
Authors: Doan Nhu Nhat Tan , Nguyen Trong Hieu , Tran Trung Hieu , Nguyen Thi Hue Hanh , Nguyen Van Thien Chi , Giang Hoa , Tran Le Son , Phan Minh Duy 
Published: August 2024

224 Background: Cell free DNA (cfDNA)-based assays hold great potential in detecting early cancer signals yet determining the tissue-of-origin (TOO) for cancer signals remains a challenging task. Here, we investigated the contribution of a methylation atlas to TOO detection in low depth cfDNA samples. Methods: We constructed a tumor-specific methylation atlas (TSMA) using whole-genome bisulfite sequencing (WGBS) data from five types of tumor tissues (breast, colorectal, gastric, liver and lung cancer) and paired white blood cells (WBC). TSMA was used with a non-negative least square matrix factorization (NNLS) deconvolution algorithm to identify the abundance of tumor tissue types in a WGBS sample. We showed that TSMA worked well with tumor tissue but struggled with cfDNA samples due to the overwhelming amount of WBC-derived DNA. To construct a model for TOO, we adopted the multi-modal strategy and used as inputs the combination of deconvolution scores from TSMA with other features of cfDNA. Results: Our final model comprised of a graph convolutional neural network using deconvolution scores and genome-wide methylation density features, which achieved an accuracy of 69% in a held-out validation dataset of 239 low-depth cfDNA samples. Conclusions: In conclusion, we have demonstrated that our TSMA in combination with other cfDNA features can improve TOO detection in low-depth cfDNA samples.
Prognostic value of immuno-nutritional status in patients with cancer treated by immune checkpoint inhibitors.
Authors: Kuo Ming-Chun 
Published: August 2024

226 Background: The treatment efficacy of immune checkpoint inhibitors (ICIs) may relate to tumor factors or host factors, such as systemic inflammation status or nutritional status. In this study, we investigated the prognostic value of immuno-nutritional status in cancer patients treated by ICIs, and develop nomogram models for predicting overall survival (OS). Methods: We used Chang Gung Research Database to retrospectively evaluate cancer patients who received ICIs during January 2015 to December 2021. Patients had double cancer or received only one cycle of ICI were excluded. All patients were divided into a training cohort and a validation cohort. The training cohort was used to analyze the risk factors and develop nomogram models. The models were validated by the validation cohort. The univariate analysis, stepwise multivariate analysis, receiver operator characteristics (ROC) analysis were used to find out the independent risk factors. The calibration plot were used to evaluate the reliability of the models. Results: All patients (3219 cases) could be categorized into lung cancer (22.1%), genitourinary cancer (14.9%), upper gastrointestinal tract cancer (8.1%), colorectal cancer (3.1%), hepatocellular carcinoma (24.6%), pancreatobiliary cancer (3.8%), head and neck cancer (12.9%), melanoma (4.0%), breast cancer (1.9%) and lymphoma (0.5%). 80.2% of patients received anti-PD1, 19.8% of patients received anti-PD-L1. In training cohort, the cut-off value was set for neutrophil-to-lymphocyte ratio (NLR), total lymphocyte count (TLC), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), prognostic nutrition index (PNI) and hemoglobin-albumin-lymphocyte-platelet (HALP) score. The above risk factors showed significant difference in median OS in validation cohort respectively (Table). The multivariate analysis demonstrated that NLR, PNI and HALP score were independent risk factors in predicting OS. The hazard ratio were 1,439 (95% CI 1.149-1.801), 0.689 (95% CI 0.549-0.865) and 0.784 (95% CI 0.626-0.982) respectively. Conclusions: We developed nomogram models to investigate the immuno-nutritional status and predict the OS of cancer patients who received ICIs therapy. High NLR, low PNI and low HALP score were associated with worse OS. [Table: see text]
Unsupervised clustering of brain tumor leukocytes to reveal atypical lymphoid cell subsets.
Authors: Hermelo Ismaïl , Virtanen Tuomo , Salonen Iida , Nätkin Reetta , Keitaanniemi Sofia , Tiihonen Aliisa , Lehtipuro Suvi , Kummola Laura , Nordfors Kristiina , Haapasalo Hannu , Rauhala Minna , Kesseli Juha , Nykter Matti , Haapasalo Joonas , Rautajoki Kirsi 
Published: August 2024

25 Background: The brain tumor immune microenvironment (TiME) is characterised by suppression of tumor-infiltrating leukocytes. The lymphocyte niche activity is particularly downregulated within this TiME milieu. Methods: Here, using data-driven approaches in flow cytometry and RNA sequencing analysis, we aimed at dissecting leukocyte cell types infiltrating human brain tumor TiME. Results: Unsupervised clustering provided T lymphocyte subsets including double-negative (CD3+CD4- CD8-) T cells (DNT). Our DNT phenotype was validated with an independent dataset, suggesting DNT to be compatible with γδ T cell phenotype. In our cohort, myeloid immune cell frequencies were associated with malignancy type as previously reported, while a gliosarcoma notably presented unexpectedly high lymphocyte frequencies. Consistently, double-positive (CD4+ CD8+) T cells (DPT) had higher frequency in the gliosarcoma than other tumors. The flow cytometry results were supported by transcriptome patterns and the activity of immune-related genes in these tumors. Conclusions: Our findings feature the benefit of data-driven approaches for brain TiME lymphocyte analysis, and show that primary brain tumors can entail atypical lymphocyte subsets like DNTs and DPT cells. Unbiased lymphocyte characterisation can potentially outline novel targets for immune checkpoint blockade therapy.
Challenges of liquid panel in genomic profiling of esophageal squamous cell carcinoma (ESCC): Insights from an analysis of over 1000 cases.
Authors: Morita Ryuichi , Ishikawa Takeshi , Itani Junichiro , Sone Daiki , Iwai Naoto , Doi Toshifumi , Iwasaku Masahiro , Inoue Ken , Dohi Osamu , Yoshida Naohisa , Uchiyama Kazuhiko , Takagi Tomohisa , Konishi Hideyuki , Horiguchi Go , Takayama Koichi , Itoh Yoshito 
Published: August 2024

86 Background: Genomic analysis of ctDNA from cancer patients can allow identification of actionable alterations of tumor without an invasive biopsy. ctDNA analysis has been reported to be superior for global summary of tumor heterogeneity and a short turnaround time compared to tissue analysis,however, there are potential issues including the detection sensitivity, threshold to determine TMB-H, and clonal hematopoiesis of indeterminate potential (CHIP). In order to elucidate the impact of ctDNA analysis on personalized cancer treatment, we decided to examine the genetic landscape and clinical outcomes of ESCC cohort registered in the C-CAT database. Methods: We retrospectively analyzed data from 1059 cases of ESCC registered in the C-CAT from June 2019 to February 2024. Clinical characteristics, TMB status, pathological gene variants, and time to treatment failure (TTF) of first-line treatment were examined. Results: The panels applied to eligible patients consisted of 925 tumor tissue panels (87.3%) and 134 liquid panels (12.7%). Pathological gene mutations were detected in 924 cases (99.8%) in tissue panels and 133 cases (99.2%) in liquid panels. The top 10 detected genes were TP53 (93.4%), CDKN2A (57.8%), CDKN2B (45.5%), CCND1 (43.9%), FGF19 (41.0%), PIK3CA (29.0%), NFE2L2 (28.3%), BCL6 (16.5%), NOTCH1 (13.5%), and KMT2D (12.2%). The detection rate for these genes excluding NOTCH1 and KMT2D were significantly higher in tissue panels than in liquid panels (P≤0.01). The median TMB was 5.00 Muts/Mb for both. In first-line treatment, the TTF for immune checkpoint inhibitors (ICIs) and chemotherapy was significantly longer in TMB-H (≧10 Muts/Mb) compared to TMB-L (3.1M vs. 1.9M, P<0.01) in patients evaluated by tissue panels, but it was not proven in patients evaluated by liquid panels (P=0.38). Furthermore, the results suggest that patients with CDKN2A, CCND1, and FGF19 variants benefit more by adding ICIs to chemotherapy than patients without these variants and while the opposite was true for BCL6 and NOTCH1 and KMT2D. Conclusions: In this ESCC cohort, detection rates in the liquid panels were generally lower than in the tissue panels, suggesting that sufficient ctDNA could not be obtained in many cases. The appropriate patient selection for the liquid panels and the timing of blood collection should be discussed. Furthermore, the ideal threshold for determining TMB-H in the liquid panels needs to be further investigated.
Thyroid Arteriovenous Malformation in Hereditary Hemorrhagic Telangiectasia: Insights on Successful Noninvasive Imaging
Authors: Goto Hisanori , Tanimura Iyo , Nakano Yujiro , Takeshita Yumie , Takamura Toshinari 
Published: August 2024

Abstract
Hereditary hemorrhagic telangiectasia (HHT) causes arteriovenous malformations (AVMs) in several organs. This report is the first to document and image a thyroid AVM complication in HHT.
A 72-year-old woman with HHT was referred for thyroid nodule evaluation. Ultrasonography showed a hypervascularized nodule in the right thyroid lobe which was initially suspected to be malignant. However, 3-dimensional computed tomography angiography demonstrated a thyroid AVM with abnormal anastomosis of the superior thyroid artery and the inferior thyroid vein.
In the formation of thyroid AVM, here, chronic thyroiditis and hypothyroidism complications may have been a second hit, due to the predisposing first-hit germline mutation.
This report sheds light on overlooked thyroid lesions in HHT and advocates a noninvasive imaging approach in diagnosing thyroid AVMs. Furthermore, this case suggests a potential mechanism of AVM formation in human HHT, possibly supporting the second-hit hypothesis.
Preliminary Experience With Novel Straight 3-Fr Guiding Sheath for Transradial Access in Endovascular Treatment: Feasibility and Safety
Authors: Fuga Michiyasu , Sano Tohru , Hataoka Shunsuke , Ishibashi Toshihiro , Kan Issei , Aoki Ken , Tachi Rintaro , Kato Naoki , Nagayama Gota , Murayama Yuichi 
Published: August 2024

BACKGROUND AND OBJECTIVES:
Radial artery diameter may limit whether a guiding sheath (GS) can be used via transradial artery access (TRA). A smaller GS may reduce the risk of access site–related complications. This study investigated the feasibility and safety of endovascular treatment (EVT) using a straight-shaped 3-Fr GS (Axcelguide; Medikit).

METHODS:
Patients who underwent EVT with a straight-shaped 3-Fr GS at 3 institutions between April 2022 and March 2024 were retrospectively reviewed. Patient background, anatomic and procedural factors, and complications were recorded.

RESULTS:
Twenty-six pathologies were treated with EVT using a 3-Fr GS. Median radial artery diameter was 1.9 mm, and distal TRA (73.1%) was selected more often than TRA (26.9%) as the access site. The breakdown of target pathologies and the role of the 3-Fr GS were as follows: 12 unruptured cerebral aneurysms for intra-aneurysmal coiling, with 5 dural arteriovenous fistulas, 5 brain or head and neck tumors, 2 chronic subdural hematoma, 1 arteriovenous malformation, and 1 hereditary hemorrhagic telangiectasia for transarterial embolization. A success rate of 96.2% was achieved, with no access site– or non–access site–related complications observed within 30 days.

CONCLUSION:
The straight-shaped 3-Fr GS may be applicable for selected pathologies, allowing access even with RAs <2 mm in diameter and facilitating EVT without complications. Preliminary experience with the 3-Fr GS via TRA demonstrated excellent feasibility and safety.
The FAM114A proteins are adaptors for the recycling of Golgi enzymes
Authors: Welch Lawrence G. , Muschalik Nadine , Munro Sean 
Published: August 2024

ABSTRACT
Golgi-resident enzymes remain in place while their substrates flow through from the endoplasmic reticulum to elsewhere in the cell. COPI-coated vesicles bud from the Golgi to recycle Golgi residents to earlier cisternae. Different enzymes are present in different parts of the stack, and one COPI adaptor protein, GOLPH3, acts to recruit enzymes into vesicles in part of the stack. Here, we used proximity biotinylation to identify further components of intra-Golgi vesicles and found FAM114A2, a cytosolic protein. Affinity chromatography with FAM114A2, and its paralogue FAM114A1, showed that they bind to Golgi-resident membrane proteins, with membrane-proximal basic residues in the cytoplasmic tail being sufficient for the interaction. Deletion of both proteins from U2OS cells did not cause substantial defects in Golgi function. However, a Drosophila orthologue of these proteins (CG9590/FAM114A) is also localised to the Golgi and binds directly to COPI. Drosophila mutants lacking FAM114A have defects in glycosylation of glue proteins in the salivary gland. Thus, the FAM114A proteins bind Golgi enzymes and are candidate adaptors to contribute specificity to COPI vesicle recycling in the Golgi stack.
Conditional Lead-Time Flexibility in an Assemble-to-Order System
Authors: Yu Yi , Deng Tianhu , Song Jing-Sheng 
Published: August 2024

Problem definition: We introduce and formalize a concept termed conditional lead-time flexibility (CLF), which refers to the industry practice where a manufacturer requests that its upstream suppliers dynamically adjust the pipeline orders’ remaining lead times. Over a finite horizon, an assemble-to-order manufacturer makes joint decisions on inventory replenishment and lead-time adjustment to minimize the total discounted expected cost. Methodology/results: The problem is formulated as a multiperiod dynamic programming with an enlarged state space to track the adjustable pipeline orders. The replenishment and lead-time adjustment decisions are made sequentially in each period. The analysis reveals that (i) the optimal cost-to-go function is both convex and additively separable, that (ii) both the optimal replenishment and lead-time adjustment decisions follow general base-stock policies, and that (iii) the convexity and additive separability allow us to perform a derivative analysis on the optimality equations and design an efficient algorithm. Managerial implications: Using real industry data, we numerically find that (i) CLF achieves notable cost savings over a wide range of parameters, that (ii) the value of CLF comes from both the order expediting and deferring, and that (iii) CLF outperforms dual sourcing when the unit adjustment cost is less than 40% of the unit ordering cost from the express source. Our findings underscore the importance of CLF. Funding: T. Deng acknowledges financial support from the National Key Research and Development Program of China [Grant 2022YFB3305602] and the National Natural Science Foundation of China (NSFC) [Grant 72188101]. Supplemental Material: The electronic companion is available at https://doi.org/10.1287/msom.2023.0520 .
Enhancing self-power broadband photodetection performance of Co3O4/ZnCo2O4/ZnO heterojunction via graphene oxide modification
Authors: Wang Hang , Peng Shaolong , Zhou Longjie , Li Lihua , Gu Yongjun , Kim Bok-Hee , Huang Jinliang 
Published: August 2024

In today’s field of optoelectronic devices, high-performance, self-power broadband responsive photodetectors hold significant application prospects and can find wide-ranging utility in areas such as optical communication, biomedical imaging, and environmental monitoring. This study investigates a series of samples with varying graphene oxide (GO) content, obtained through detailed characterization and optoelectronic performance testing. An appropriate amount of GO modification can form a thin film covering the brush-like Co3O4/ZnCo2O4/ZnO heterojunction surface, creating a conductive network. However, excessive content leads to GO aggregation on the heterojunction surface, affecting detection performance. Density functional theory (DFT) calculations elucidate the electron structure and transport mechanism at the interface between ZnO and GO, demonstrating graphene oxide’s efficacy as an electron transfer channel, thus enhancing the material’s optoelectronic detection performance. By employing the most suitable amount of GO modification, the optoelectronic detection performance of the Co3O4/ZnCo2O4/ZnO heterojunction is further improved. The maximum responsivity and detectivity under monochromatic light reach 193.33 mA/W and 3.68×1013 Jones, respectively. This work provides significant insights for the design and manufacturing of optoelectronic devices, with crucial scientific significance and practical value.
Retourenverhinderung durch gezielte Rabatte: Entwicklung eines KI-basierten Prototyps mit Low-Code-Technologie für den Kundendienst
Authors: Stevenson Anthony Boyd , Rieck Julia 
Published: August 2024

ZusammenfassungIn dieser Fallstudie wurde ein Prototyp entwickelt, der den Mitarbeitenden des Kundendienstes Rabatte für die Kundschaft vorschlägt, um Retouren zu verhindern. Durch die gewährten Rabatte sollen die kaufenden Personen angehalten werden, die Produkte zu behalten. Zudem soll die Zufriedenheit der Kundschaft trotz der Qualitätsdefizite oder Leistungseinschränkungen gewährleistet werden. Die Hauptkomponente des Prototyps ist ein KI-basiertes Modell, das auf dem Fallbasierten Schließen beruht und zur verbesserten Nutzbarkeit in eine Webapplikation integriert wurde. Mit Hilfe der Low-Code-Technologie myCBR konnten der Entwicklungsprozess beschleunigt und die Entwicklungskosten gering gehalten werden. Die Evaluierung erfolgte unter realen Bedingungen bei einem kooperierenden Versandhändler für Möbel und Wohnaccessoires und zielte darauf ab, sowohl die Praktikabilität als auch die Ökonomie des Prototyps zu ermitteln. Die Studie belegt, dass der Prototyp in der Lage ist, die Datengrundlage des Kundendienstes systematisch zu nutzen, um effiziente und kostenreduzierte Rabattvorschläge zu generieren. Indem die Rabatte datenbasiert vergeben werden, können Anliegen der kaufenden Personen effektiver gelöst und unnötige Retouren verhindert werden. Durch die Verhinderung von Retouren trägt der Prototyp somit zur Nachhaltigkeit, Kostenreduktion und Ressourceneffizienz bei.
A conceptualization and psychometric evaluation of positive psychological outcome measures used in adolescents and young adults living with HIV: A mixed scoping and systematic review
Authors: Dambi Jermaine M. , Cowan Frances M. , Martin Faith , Sibanda Sharon , Simms Victoria , Willis Nicola , Bernays Sarah , Mavhu Webster 
Published: August 2024

Introduction
Sub-Saharan Africa bears the greatest burden of HIV, with comorbid mental conditions highly prevalent in people living with HIV. It is important to evaluate the mental health of adolescents and young adults living with HIV (AYALHIV) comprehensively by measuring both negative and positive psychological constructs. There has been a proliferation of interest in positive psychological outcome measures, but the evidence of their psychometric robustness is fragmented. This review sought to: 1) Identify positive psychological outcomes and corresponding outcome measures used in AYALHIV in sub-Saharan Africa. 2) Critically appraise the psychometrics of the identified outcome measures.

Methods and analysis
Two reviewers independently searched articles in PubMed, Scopus, Africa-Wide Information, CINAHL, Psych INFO and Google Scholar. Searches were conducted from November 2022 to February 2023. Two separate reviewers independently reviewed retrieved articles. We applied a narrative synthesis to map the key constructs. The risk of bias across studies was evaluated using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. The quality of the psychometric properties was rated using the COSMIN checklist and qualitatively synthesized using the modified Grading of Recommendations Assessment, Development, and Evaluation checklist.

Results
We identified 15 positive psychological constructs: body appreciation, confidence, coping, flourishing, meaningfulness, personal control, positive outlook, resilience, self-management, self-compassion, self-concept, self-efficacy, self-esteem, self-worth and transcendence, that had been used to assess ALHIV. The most measured constructs were resilience, self-concept, self-esteem, coping and self-efficacy. Construct validity and internal consistency were the properties most frequently considered, while content validity and structural validity were assessed less often.

Conclusions
Few studies performed complete validations; thus, evidence for psychometric robustness was fragmented. However, this review shows the initial evidence of the feasibility of using positive psychological outcomes in low-resource settings. Instead of creating new outcome measures, researchers are recommended to leverage the existing measures, adapt them for use and, if appropriate, strive to maintain the factorial structure to facilitate comparisons.

Registration
PROSPERO-CRD42022325172.