bluuebunny/crossref_metadata_2025_split huggingface dataset:
Establishment and effect evaluation of a hierarchical pharmacological monitoring model for immune checkpoint inhibitors.
Authors: Zhu Yaning , Zhāng Peng 
Published: August 2023

159 Background: To establish a standardized pharmacy service model for PD-1 monoclonal antibodies through a case study of the practice of full pharmacy service for immune checkpoint inhibitors and to explore the effect of clinical pharmacists' participation in the full pharmacy service for PD-1 monoclonal antibodies. Methods: Patients were graded according to age, pathological stage, Carlson co-morbidity index grading and different treatment stages (preoperative neoadjuvant, postoperative adjuvant and advanced first-line, second-line and third-line or above), whether they had concomitant autoimmune diseases and combination drug use (monotherapy, combination chemotherapy, combination targeted or anti-angiogenic drugs, combination chemotherapy + targeted/anti-angiogenic drugs) to establish PD-1 The effect of this pharmacy service model was evaluated by using the immunotherapy treatment of 132 patients in Shaanxi Provincial People's Hospital who were pharmacologically monitored by clinical pharmacists. Results: 132 patients, 91 males and 41 females, 7 patients aged ≥ 70 years with stage IV tumor and Carlson co-morbidity index ≥ 9 scores were subjected to special grade pharmacological monitoring, 1 patient developed immune myocarditis, 1 patient developed immune pneumonia and reactive capillary hyperplasia, which improved after treatment with methylprednisolone, age < 70 years, stage IV tumor, Carlson Primary pharmacological monitoring was performed in 13 patients with co-morbidity index ≥9 points, of which 10 cases (76.9%) had adverse reactions, 3 cases had pulmonary infections and discontinued, 2 cases had severe thrombosis of grade 3 or higher leading to discontinuation, and the others were hyperthyroidism, hypothyroidism, hypocorticism, etc. Secondary monitoring was performed in the other 112 patients, of which 11 cases (9.8%) had adverse reactions The other cases were immune enteritis, immune encephalitis and immune myocardial injury, and most of the adverse reactions occurred in the 5th cycle after drug administration. Conclusions: By establishing a hierarchical pharmacological monitoring model; patients aged <70 years, stage IV tumors, and Carlson co-morbidity index score ≥9 are at high risk for adverse reactions to immunotherapy, and pretreatment of these patients in advance can ensure the safety of patients' medication, improve medication compliance, and improve patients' quality of life.
Clinical outcomes of soft tissue sarcoma in the Philippines: A single-center experience.
Authors: Maaño Omar Paningbatan , Gorospe Agnes Evangelista , Pascual-Panganiban Anna Marie Mangune 
Published: August 2023

160 Background: Soft-tissue sarcomas (STS) are a heterogeneous group of uncommon tumors that account for less than 1 percent of all adult malignant tumors. Data are scarce in the Asia-Pacific region, especially in the Philippines. This study aims to evaluate the epidemiology and clinical outcomes of STS from a private tertiary hospital in the Philippines. Methods: All adult patients treated at St. Luke’s Medical Center (SLMC), Quezon City and Global City, between January 2010 and December 2020 were reviewed. Continuous variables are described in median and categorical variables are described in count and percentage. Kaplan-Meier curves for OS and RFS were compared by the Log-Rank test. Results: One hundred eighty-seven patients diagnosed with STS were eligible for the study. The median age at diagnosis was 53 years old; the majority were male (54.55%). The most common histologic subtypes were liposarcoma (19.79%), pleomorphic sarcoma, undiff (16.58%), and leiomyosarcoma (11.76%). Most were diagnosed with localized disease (90.9%), with the lower extremities (44.39%) as the most common primary site. The median tumor size was 10.3 cm, primarily high grade (46.52%). Nodal involvement on diagnosis was 4.28%. Twelve patients (6.42%) presented with de novo mets; lung (45%) was the most common site. The majority had surgery (81.82%) on the primary tumor, with 56.86% achieving R0. Eighty patients (42.78%) had radiotherapy; the majority were given post-operatively (N=60). Sixty-three patients (33.68%) received systemic therapy. Out of 170 patients with localized disease, 70 (40%) had disease recurrence, mostly local recurrence (57.14%). The 3-year OS and RFS were 58.67% and 55.20%, respectively, for the entire cohort; for localized disease was 95.06%. There was a statistical difference in OS between distant vs local recurrence (23.28% vs 49.11%) (p<0.001), nodal involvement (p=0.041), surgery (p<0.001), and radiotherapy (p=0.001). Conclusions: Most STS seen in SLMC is localized disease but with lower rates of resection than in other countries in the Asia-Pacific region. The histological subtype and primary anatomical site are similar to other data. The low survival rate may be attributed to the site of recurrence, nodal involvement, and treatment pattern received.
A study on the correlation of GDF15 with cancer cell invasion and poor prognosis in gallbladder cancer.
Authors: Joo Mina , Lee Hyo Jin , Kim Jin Man 
Published: August 2023

167 Background: Growth differentiation factor 15 (GDF15) is a member of the TGF-β superfamily and has been found to be expressed in various human cancers. This study investigated the role of GDF15 in gallbladder cancer and its underlying molecular mechanisms. Methods: We examined immunohistochemical staining to evaluate the expression of GDF15 in 57 cases of gallbladder cancer using a tissue microarray, and clinic-pathological parameters were analyzed. In addition, we established a stable cell line overexpressing GDF15 using NOZ and OCUG-1 gallbladder cancer cell lines. The successful overexpression of GDF15 was confirmed using RT-PCR and western blot analysis. Migration and invasion assays were performed using transwell plates coated with collagen or matrigel, and cell motility was analyzed using a wound healing assay. We also performed western blot analysis to detect the expression levels of various proteins associated with cell proliferation, migration, and invasion. Results: High GDF15 expression was significantly associated with pathologic T stage ( P = 0.063), differentiation ( P = 0.062), perineal invasion ( P = 0.059) and lymphatic invasion ( P = 0.008). High GDF15 expression has also been associated with poor prognosis. Overexpression of GDF15 significantly enhanced wound healing, cell migration, invasion, and motility in comparison to controls and regulated the expression of related proteins. Our results indicate that GDF15 enhances the migratory, invasive, and motility abilities of NOZ and OCUG-1 cells in vitro and is involved in poor prognosis and overall survival of gallbladder cancer patients. Conclusions: This study implies that GDF15 could serve as a potential therapeutic target in gallbladder cancer.
Deep learning based on preoperative MR to differentiate germinomas from nongerminomatous cell tumors.
Authors: Li Yanong 
Published: August 2023

19 Background: Intracranial germ cell tumors (iGCTs) are highly malignant brain tumors that predominantly occur in children. Two types of iGCTs exist: germinomas (GEs) and non-germinomatous germ cell tumors (NGGCTs), each having different treatments and prognoses. However, predictive biomarkers for differentiation are limited. Methods: This multicenter Development-validation set study included patients with iGCTs with pathology-confirmed for the developed dataset (n = 280), which was split into training (n = 200) and testing sets (n= 80), and three independent validation sets (n = 64), respectively. Patients were included between January 2010 and December 2021. We developed a DL model based on 3D nnU-Net and preoperative T2-weighted images to differentiate GE from NGGCT, and we compared the model performance with the diagnoses made by five physicians of different majors and experiences with and without referring to the DL model’s output. Data analysis was performed from February 2021 to May 2022.We calculated the diagnostic performances of the model and physicians using the area under the curve (AUC), accuracy, sensitivity, and specificity. Results: The DL pipeline showed an average AUC of 0.837 in the testing set and three independent validation sets, superior to that using conventional information alone (combine with MR features and clinical information, AUC=0.768, p=0.009). The physicians’ diagnoses showed an average AUC of 0.695 without reference to the DL output and 0.842 concerning the DL output in the testing and prospective internal validation sets, with a 21.15% improvement (p=0.014). Conclusions: We developed and validated a DL model using a large dataset to accurately differentiate GE from NGGCT using preoperative T2-weighted images, which is relatively easily incorporated into the workflow of clinical diagnosis at minimal additional cost, and may enhance precision therapy.
A comprehensive survey of tumor mutation burden (TMB) using the AACR GENIE cbioportal database: Pathogenesis of NTRK and RET fusion (NTRK+/RET+) positive colorectal (CRC).
Authors: Arter Zhaohui , Lee Alexandria TM , Nagasaka Misako , Ou Sai-Hong Ignatius 
Published: August 2023

33 Background: Receptor tyrosine kinase fusion (RTK+) has been identified in colorectal carcinoma (CRC). Tumor agnostic treatment has been approved in NTRK fusion ( NTRK+) and RET fusion ( RET+) positive solid tumor. However, overall response rate (ORR) was the lowest among entrectinib-treated NTRK+ CRC (20%, 2/10) and selpercatinib treated RET+ CRC (20%, 2/10) among all NTRK+ and RET+ solid tumors respectively. Methods: We surveyed all 58 human RTKs to identify RTK fusions in CRC and RET and NTRK fusions in other solid tumors using AACR GENIE cbioportal public version 13.0. We abstracted and compared the tumor mutation burden (TMB) of these fusions from the cbioportal database. Patient and tumor characteristics were also abstracted. Results: Among the 14812 unique CRC patients identified in the AACR GENIE cbioportal, a total of 153 unique RTK fusions were identified (44 with known fusion partners, 109 with intragenic rearrangement) in 27 out of the total 58 human RTKs. The most common RTK fusions in CRC were in FGFR1 (N = 23), EGFR (N = 21), ERBB2, NTRK1, RET, FGFR2 (N = 10 each), FLT1 and FLT3 (N = 9 each), FLT4 and ALK (N = 7 each). Considering only samples with identified fusion partners, the mean TMB was 66.6 +/-15.8 (mt/MB) for NTRK+ CRC (N = 9), and 35 +/-11.5 for RET+ CRC (N = 4), which were significantly higher when compared to mean number of 6.2 +/- 5.4 of TMB for all other RTK+ CRC (ALK, EGFR, FGFR1/2, ERBB4, FLT1/3/4, LMKT2, MET, NTRK2, PDGFR-b, ROS1) (N = 30, P< 0.05). Furthermore, NTRK+ CRC harbored significantly higher TMB than RET+ CRC (P = 0.003). The mean TMB was 4.0 +/- 1.9 for RET+ NSCLC (N = 65), 2.6 +/- 1.6 for RET+ Thyroid cancer (N = 52), which were both significantly lower than RET+ CRC. Mean TMB was 3.1 +/- 1.7 for NTRK+ glioma (N = 21), 3.3 +/- 1.7 for NTRK+ thyroid cancer (N = 21), 6.5+/-5.1 for NTRK+ Melanoma (N = 8), 5.9 +/- 3.4 for NTRK+ NSCLC (N = 7), 5.1 +/- 1.2 for NTRK+ breast cancer (N = 7) all of them were significantly lower than the mean TMB of NTRK+ CRC. 1482 (10.0%) patients with CRC had their MSI status reported. 3 out of 3 NTRK+ CRC patients with known MSI status were all MSI-H (100%). 12 out of 12 non-NTRK/non-RET RTK+ CRC patients were MSI-S. Conclusions: In this comprehensive survey of human RTK fusions in CRC, NRTK+ and RET+ CRC harbor significantly higher TMB compared to other RTK+ CRC or to other NTRK+/RET+ solid tumors. Limited data showed NTRK+ CRC were all MSI-H. NTRK+ and RET+ CRC are distinct molecular subtypes of CRC with unique pathogenesis from all other NTRK+ or RET+ solid tumors. We hypothesize that NTRK+/RET+ CRC may benefit from pembrolizumab that has been approved for histologic agnostic high TMB tumors rather than RET or NTRK tyrosine kinase inhibitors (low ORR in CRC) that also have histological agnostic indications.
Comprehensive analysis of acetylation-related genes for the prognosis and immunotherapy response of gastric cancer.
Authors: Liu Yi , Wang Jianhua 
Published: August 2023

38 Background: Although clinical researchers have made great progress in the treatment of gastric cancer, the overall survival time of gastric cancer patients remains unfavorable,It has been reported that HDAC1 is a prognostic marker for survival. However, the relationship between acetylation modification and the prognosis and treatment of gastric cancer has not been elaborated so far. Therefore, we carried out a systematic study and hope to provide novel therapeutic targets. Methods: We obtained the RNA sequencing data of GC patients and the corresponding clinical features from GEO database. T-test was performed to analyze the difference in expression of acetylation-related genes in normal and tumor samples from TCGA-STAD dataset.Using median expression as the threshold, univariate cox regression was performed to analyze the prognostic differences in overall survival (OS) for each acetylation-related gene. ssGSEA was utilized to analyze the percentage of infiltration of 28 immune cells in different clusters. Subsequently, we performed functional enrichment analysis of the differential genes using DAVID.used TIDE to analyze the effect of immune checkpoint inhibition. In addition, we compared the differences in TIDE scores across scoring subgroups. Results: By comparing 32 normal samples and 362 tumor samples in the TCGA dataset, we found that most acetylation-related genes are differentially expressed.most of the KAT genes were amplified more frequently than the deletion frequency, especially KAT2A and ESC1, while the deletion frequency of HDAC4 was high.CREBBP and KAT6A genes were mutated with high frequency.The results of acetylation-related gene clustering were divided into two subgroups (KAT-KDAC-cluster 1 and KAT-KDAC-cluster 2), Cluster 1 was mainly enriched in processes such as mismatch repair and homologous recombination during DNA replication, and cluster 2 was mainly enriched in calcium signaling, insulin signaling pathway and actin cytoskeleton regulation.We filtered out 9 genes most associated with GC were screened by random forest, and 2 of them were found to be unrelated to patient prognosis by univariate analysis, resulting in 7 genes, including FERMT2, CALD1, TGFBII, PPP1R14A, PPPIR3C, ADAMTS1, and RBPMS2.and KAT-KDAC scores were calculated.KAT-KDAC score group had lower TIDE scores, predicting better immune efficacy for patients in the low-KAT-KDAC score group. Conclusions: Expression of acetylation-related genes affects the prognosis of gastric cancer.
Prognostic analysis of postoperative pathological microvascular invasion in hepatocellular carcinoma and the effect of surgical margin on prognosis.
Authors: Chen Huanwei 
Published: August 2023

52 Background: To analyze the impact of different MVI grades and surgical margins on patient survival through analyzing the presence of microvascular invasion (MVI) after liver resection of hepatocellular carcinoma (HCC). Methods: The clinical and follow-up data of 513 HCC patients who underwent hepatectomy in our department from January 2016 to December 2020 were analyzed retrospectively. All the patients signed the informed consent form, complying with the medical ethics regulations. Risk factors of MVI in patients with HCC were analyzed by univariate and multivariate analysis, and effect of different MVI grades on postoperative complications was explored. The effects of different MVI grades and different surgical margins on tumor-free survival and overall survival were also analyzed. Results: There were 332 cases in M0 group, 123 cases in M1 group and 58 cases in M2 group. Univariate analysis showed that tumor diameter, tumor number, CNCL stage and alpha-fetoprotein were risk factors for MVI in patients with HCC, and multivariate analysis showed that tumor maximum diameter, tumor number and CNLC stage were independent influencing factors for MVI. There was no significant difference in the incidence of postoperative complications among different groups. The 1-year, 2-year, 3-year disease-free survival rate of M0 group was 79.6%, 71.0%, 63.4%, which was significantly higher than that in M1 group (59.6%, 48.0%，43.3%) and M2 group (31.0%, 27.5%, 25.2%). The 1-year, 2-year, 3-year overall survival rate of M0 group was 97.3%, 88.2%, 84.6%, which was significantly higher than that in M1 group (87.0%, 71.5%, 66.1%), and M2 group (79.3%, 61.9%, 52.6%),respectively. In the aspect of surgical margin, in MVI negative group, the disease-free survival rate of wide margin resection for 1-year, 2-year, 3-year was 82.6%, 70.7%, 65.4%, while that of narrow margin resection was 79.4%, 64.7% and 60.5% (p=0.322).The 1-year, 2-year, 3-year overall survival rate of patients who received wide margin resection was 97.5%, 89.6%, 85.2%, while that of patients who received narrow margin resection was 97.1%, 86.0%，82.8%. (p= 0.822). In the MVI positive group, the 1-year, 2-year and 3-year disease-free survival rate was 58.1%, 45.4%, 40.3% in the wide margin group and 42.9%, 37.3%, 36.1% in the narrow margin group (p=0. 044). The 1-year, 2-year, 3-year overall survival rate of the wide margin group was 88.8%, 71.9%, 64.3%, which was higher than that of the narrow margin group, 82.6%, 64.8%, 61.0% (p = 0.032). Conclusions: Tumor size, number and stage are independent risk factors for MVI positive patients.The higher the MVI grade, the worse the prognosis.In patients with MVI, the long-term prognosis of patients with wide margin is better than that of patients with narrow margin. Therefore, for patients with high risk of MVI before operation, wide margin should be selected as far as possible.
Effect of spatial transcriptomics on tumor immune microenvironment resistant to immune checkpoint inhibitors in metastatic urothelial carcinoma.
Authors: Iwasawa Tomohiro , Tanaka Nobuyuki , Itahashi Kota , Matsumoto Kazuhiro , Koyama Shohei , Nishikawa Hiroyoshi , Oya Mototsugu 
Published: August 2023

68 Background: Immune checkpoint inhibitors (ICBs) for metastatic urothelial carcinoma (mUC) are widely used, but their response rates are inadequate, around 20%. Currently, analyzing samples prior to ICB administration has accumulated so far; thereby predicting response to ICBs by high tumor mutation burden levels and PD-L1 positivity. However, little is known about what kind of tumor microenvironment is formed in recurrent or residual tumors post ICBs, and how it contributes to ICB resistance. Therefore, we applied large datasets of spatial transcriptome analysis to mUC samples post ICBs in order to reveal the diversity of the tumor microenvironment after ICB administration. Methods: The Visium spatial transcriptome analysis was performed on FFPE samples from 12 mUC patients with viable tumor resection after ICB administration. Further, 4 FFPE samples of non-metastatic UC treated-surgically were subjected to spatial transcriptome analysis and were used as ICB-naïve tumor controls. First, the tumor and stromal regions were pathologically annotated. We then identified CD4-positive, CD8A-positive, and FOXP3-positive spots in both tumor and stromal regions, respectively, and analyzed changes in differentially expressed genes (DEGs) and pathways in the tumor space where cancer cells survive after ICB treatment. Results: For DEGs and pathway analysis, 8082 spots in the tumor region and 10964 spots in the stromal region were used. In the tumor and stromal areas, 15.4% and 15.1% were CD4 positive, 6.5% and 6.3% were CD8A positive, and 2.9% and 2.0% were FOXP3 positive, respectively. In tumor regions of ICB-treated specimens, the expression of SULF1, an extracellular matrix-related gene, was increased in all CD4-, CD8A-, and FOXP3-positive spots compared to negative spots. In addition, the expression of complement-related genes such as C1QB, C1QC, and C1R was upregulated in CD8A-positive spots in the tumor regions after ICB. Pathway analysis revealed that oxidative phosphorylation was enriched in CD8A-positive spots in tumor regions prior to ICB, while angiogenesis was enriched in CD8A-positive spots after ICB. Conclusions: Spatial transcriptome analysis of a large dataset of UC samples showed distinct features of immune infiltration involved in therapeutic resistance in the tumor microenvironment under immunotherapy. Notably, T-cells may be exhausted by metabolic changes in CD8A-positive spots in ICB-refractory tumor environment spaces.
Effects of supervised exercise and self-managed psychosexual therapy on sexual health in men with prostate cancer: A randomized clinical trial.
Authors: Galvao Daniel Abido , Chambers Suzanne K , Taaffe Dennis R , Cormie Prue , Schumacher Oliver , Gardiner Robert Alexander , Spry Nigel , Lopez Pedro , Joseph David John , Tang Colin , Hayne Dickon , Newton Robert Usher 
Published: August 2023

71 Background: Sexual dysfunction is a common, distressing, and persistent adverse effect of prostate cancer treatment and current management strategies do not adequately address physical and psychological effects. Exercise is emerging as potential therapy in the management of sexual health. The purpose of this study was to investigate the effects of supervised, clinic-based, resistance and aerobic exercise with and without psychosexual therapy self-management on sexual health in men with prostate cancer. Methods: A 3-arm, parallel group, multi-center randomized clinical trial was undertaken between 2014 and 2018. The study was conducted at university-affiliated exercise clinics. Eligible participants were men with prostate cancer who had previously or were currently undergoing treatment and concerned about sexual dysfunction. One-hundred and twelve participants were randomized to: 1) 6 months of supervised, group-based resistance and aerobic exercise (n=39), 2) the same exercise program plus psychosexual therapy (n=36), or 3) usual care (n=37). Exercise was undertaken 3 days per week at university-affiliated exercise clinics. Psychosexual therapy consisted of a brief self-management intervention that addressed psychological and sexual wellbeing. The primary outcome was sexual health assessed with the International Index of Erectile Function. Secondary outcomes included body composition, physical function, and muscle strength. Analyses were undertaken using an intention-to-treat approach. Results: Erectile function increased by 5.1 points (exceeds MICD) with exercise and 1.0 point with usual care (P interaction=.010) while intercourse satisfaction increased by 2.2 points with exercise and 0.2 points with usual care (P interaction=.026). Self-managed psychosexual therapy did not result in additional improvements. Compared with usual care, exercise prevented an increase in fat mass (P interaction=.028) and improved physical function outcomes, as well as upper and lower body muscle strength. Conclusions: Supervised resistance and aerobic exercise improved erectile function and intercourse satisfaction in men with prostate cancer; however, self-managed psychosexual therapy resulted in no additional improvements. Men with prostate cancer concerned about sexual dysfunction should be encouraged to undertake exercise as a potential countermeasure. Clinical trial information: ACTRN12613001179729 .