bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intratumoral CD73: An immune checkpoint shaping an inhibitory tumor microenvironment and implicating poor prognosis in Chinese melanoma cohorts
Authors: Gao Zixu , Wang Lu , Song Zhengqing , Ren Ming , Yang Yang , Li Jianrui , Shen Kangjie , Li Yinlam , Ding Yiteng , Yang Yanwen , Zhou Yuhong , Wei Chuanyuan , Gu Jianying 
Published: September 2022

BackgroundAs a novel immune checkpoint, CD73 has been reported to play prominent roles in several malignancies. However, the significance of CD73 in melanoma remains ambiguous. This study sought to reveal the impact of CD73 on the tumor microenvironment (TME) and patients’ prognosis, and to investigate whether CD73 could be a therapeutic target in Chinese melanomas, which were dominated by acral and mucosal subtypes.MethodsTwo independent Chinese cohorts of 194 patients with melanoma were enrolled. CD73 and PD-L1 expression as well as CD8+ and CD56+ cell infiltrations were evaluated by immunohistochemistry in 194 resected melanoma samples. Clinical outcomes of patients were assessed utilizing the Kaplan-Meier plotter and Cox proportional hazard analysis. RNA-seq data was obtained from TCGA database. Gene set functional annotations were performed based on GO, KEGG and GSEA analysis. CIBERSORT, ssGSEA and TIMER were used to explore the association between CD73 and immune infiltration. These findings were validated by establishing tumor xenograft model, and functions of tumor-infiltrating immune cells were examined by flow cytometry and immunofluorescence.ResultsHigh CD73 expression showed poorer clinical outcomes and was identified as an independent prognostic indicator for survival in two cohorts. Expression of CD73 was more prevalent than PD-L1 in Chinese melanoma cohorts (54.6% vs 23.2%). Co-expression of both immune checkpoints was infrequent (12.9%) in melanoma, and 54.4% of PD-L1 negative cases showed elevated expression of CD73. CD73high tumors showed a microenvironment with fewer CD8+ T cells and CD56+ NK cells infiltration, which displayed a dysfunctional phenotype. With the treatment of CD73 inhibitor APCP, the amount of CD8+ T cells and CD56+ NK cells infiltrated in tumors was elevated and the immunosuppressive effect of CD73 was eliminated.ConclusionsHigh CD73 expression was associated with an inhibitory TME and adverse clinical outcomes of melanoma. In comparison to PD-L1, CD73 was more prevalent and possessed more definite prognostic significance. Therefore, it may serve as a prognostic indicator and immunotherapeutic target next to PD-L1 in melanoma for Chinese population.
Cytopenia after chimeric antigen receptor T cell immunotherapy in relapsed or refractory lymphoma
Authors: Zhou Jin , Zhang Ying , Shan Meng , Zong Xiangping , Geng Hongzhi , Li Jiaqi , Chen Guanghua , Yu Lei , Xu Yang , Li Caixia , Wu Depei 
Published: September 2022

BackgroundPatients with relapsed or refractory (R/R) lymphomas have benefited from chimeric antigen receptor (CAR)-T-cell therapy. However, this treatment is linked to a high frequency of adverse events (AEs), such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and hematologic toxicity. There has been increasing interest in hematological toxicity in recent years, as it can result in additional complications, such as infection or hemorrhage, which remain intractable.MethodsWe conducted a retrospective, single-institution study to evaluate the patterns and outcomes of cytopenia following CAR-T-cell infusion and potential associated factors.ResultsOverall, 133 patients with R/R lymphoma who received CAR-T-cell therapy from June, 2017 to April, 2022 were included in this analysis. Severe neutropenia, anemia and thrombocytopenia occurred frequently (71, 30 and 41%, respectively) after CAR-T-cell infusion. A total of 98% of severe neutropenia and all severe thrombocytopenia cases occurred in the early phase. Early severe cytopenia was associated with CRS incidence and severity, as well as peak inflammatory factor (IL-6, C-reactive protein (CRP), and ferritin) levels. In multivariate analysis, prior hematopoietic stem cell transplantation (HSCT), baseline hemoglobin (HB), and lymphodepleting chemotherapy were independent adverse factors associated with early severe cytopenia. In addition, 18% and 35% of patients had late neutrophil- and platelet (PLT)-related toxicity, respectively. In multivariate analysis, lower baseline PLT count was an independent factor associated with late thrombocytopenia. More severe cytopenia was associated with higher infection rates and poorer survival.ConclusionsThis research indicates that improved selection of patients and management of CRS may help to decrease the severity of cytopenias and associated AEs and improve survival following CAR-T-cell therapy.Clinical Trial Registrationhttps://www.clinicaltrials.gov/ct2/show/NCT03196830, identifier NCT03196830.
Common adverse events following immunization with the COVID-19 comirnaty vaccine (Pfizer-BioNTech) among adult population in Hanoi, Vietnam, 2021
Authors: Le Xuan Thi Thanh , Hoang Quan Long , Ta Nhung Thi Kim , Pham Quan Thi , Nguyen Thao Thanh , Phan Huong Thi Mai , Nguyen Thanh Van , Le Ha Thi Thanh , Nguyen Nam Thuy , Hoang Linh Dieu , Luong Phuong Thi Huyen , An Lien Hong , Nguyen Thu Ha , Nguyen Thinh Thi , Nguyen Hien Thuy , Le Huong Thu , Nguyen Doanh Quoc , Nguyen Phuong Viet , Nguyen Tuan Xuan , Do Toan Thi Thanh , Nguyen Thang Huu 
Published: September 2022

RationaleTo prevent and control the COVID-19 pandemic, the biggest immunization campaign in history had been deployed worldwide. Therefore, it is important to inform the adverse events following immunization (AEFI) to populations.ObjectivesTo prevent vaccine hesitancy, this study focused on finding the common AEFI with the COVID-19 Comirnaty vaccine (Pfizer-BioNTech) among participants aged 18 and above and related factors in Hanoi, Vietnam.MethodsA cross-sectional study was carried out to collect participants’ data and AEFI after being vaccinated at Hanoi Medical University, Vietnam, in 2021. Logistic regression was utilized for analyzing the correlated factors of AEFI.ResultsWe recruited a random sample of 820 participants who received both basic doses of Pfizer vaccine in September and October 2021. The proportion of AEFI after the first dose, second dose, and both doses of Pfizer vaccine was 24.4%, 64.2%, and 18.5%, respectively. AEFI mostly appeared within 1 day and lasted for 1 to 2 days. The AEFI were more common in females (OR=1.7; 95%CI=1.25–2.29) and younger age groups (OR=1.9; 95%CI=1.37–2.58). History of allergy, allergic diseases, chronic diseases, and occupations were not statistically significant with AEFI.ConclusionOur findings indicated that the COVID-19 Comirnaty vaccine is safe to be injected. Gender and age group are important factors influencing AEFI.
Toxoplasma gondii seroprevalence in the endangered Australian sea lion (Neophoca cinerea)
Authors: Lindsay Scott A. , Caraguel Charles G. B. , O’Handley Ryan , Šlapeta Jan , Gray Rachael 
Published: September 2022

Toxoplasma gondii is a ubiquitous parasite increasingly detected in marine mammals and suspected to contribute to limited recovery of endangered populations. This study reports on the exposure of the Australian sea lion (Neophoca cinerea) to this protozoon using archived adult and pup sera from three island colonies in South Australia. Modified agglutination testing (MAT) detected a seroprevalence of 30.4% (95% CI 13.2-52.9: n = 23) and high antibody titers (512 to &gt; 2048 IU/ml) in adult females (median age 9.5 y, range 5.5-14.5 y) at Dangerous Reef, a felid-free island. Antibodies weren’t detected in any surveyed pup (97.5% CI 0.0-2.0%, n = 184) at two felid-free islands (Dangerous Reef: n = 21; Olive Island: n = 65), nor at Kangaroo Island (n = 98), which has a high-density feral cat population. Kangaroo Island pups of known age were 7-104 d old, while standard length and bodyweight comparison suggested younger and older pup cohorts at Dangerous Reef and Olive Island, respectively. This study provides the first quantification of disease risk in this endangered species from T. gondii exposure. The absence of detectable pup seroconversion supports the lack of detectable congenital transmission, maternal antibody persistence or early post-natal infection in the sampled cohort yet to commence foraging. An extended serosurvey of N. cinerea colonies is recommended to confirm the hypothesis of predominantly forage-associated exposure to T. gondii in this species. Findings have implications for parasitic disease risk in wildlife inhabiting Australia’s islands and for the feral cat control program on Kangaroo Island.
Effectiveness of therapeutic massage for improving motor symptoms in Parkinson's disease: A systematic review and meta-analysis
Authors: Kang Zhiran , Xing Hua , Lin Qiang , Meng Fanchao , Gong Li 
Published: September 2022

BackgroundParkinson's disease (PD) causes movement disorders [called motor symptoms (MS)], and motor dysfunction poses a great barrier to the quality of life. Although pharmacological therapy like levodopa can relieve the symptoms, it can also cause complications, such as psychosis, nausea, and dyskinesia. A therapy with more minor side effects is needed for PD. Therapeutic massages are the most commonly used forms of complementary and alternative medicine (CAM), but no systematic review and meta-analysis have focused on the efficacy of massage on PD.ObjectiveTo evaluate the quality of evidence and efficacy of therapeutic massage for improving MS in PD.MethodsWe independently searched four electronic databases, including Chinese National Knowledge Infrastructure (CNKI), MEDLINE/PubMed, Embase, and Cochrane Library, for randomized controlled trials (RCTs) about therapeutic massage and other available manual therapies improving MS in PD from January 1, 2012, to December 31, 2021 (recent 10 years). The main outcome measures were total effectiveness and the Unified Parkinson's Disease Rating Scale (UPDRS), including UPDRS total, II, and III. For the statistical analysis, the risk ratio, standard mean difference, and 95% confidence interval (CI) were used to calculate effect sizes between groups. To determine heterogeneity, statistical index I2 was used.ResultsA total of 363 PD participants in seven RCTs and one randomized pilot-control study were included in this meta-analysis. The total effectiveness showed that therapeutic massage was more effective than the intervention of the control group for improving MS [ratio risk (RR): 1.33, 95% CI (1.14–1.55), p = 0.0002]. The UPDRS-III scores showed that massage improves motor function more than the control group [SMD = −0.46, 95% CI (−0.67, −0.24), p &lt; 0.00001]. But we found that massage performed no better than the control group in improving daily life activities [SMD = −0.15, 95% CI (−0.40, 0.10), p = 0.23].ConclusionTherapeutic massage was effective in improving MS in PD. It is suggested to be an appropriate form of CAM in treating PD.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=323182, identifier: CRD42022323182.
The role of metabolites under the influence of genes and lifestyles in bone density changes
Authors: Lv Xuewei , Jiang Yanfeng , Yang Dantong , Zhu Chengkai , Yuan Huangbo , Yuan Ziyu , Suo Chen , Chen Xingdong , Xu Kelin 
Published: September 2022

PurposeOsteoporosis is a complex bone disease influenced by numerous factors. Previous studies have found that some metabolites are related to bone mineral density (BMD). However, the associations between metabolites and BMD under the influence of genes and lifestyle have not been fully investigated.MethodsWe analyzed the effect of metabolites on BMD under the synergistic effect of genes and lifestyle, using the data of 797 participants aged 55–65 years from the Taizhou Imaging Study. The cumulative sum method was used to calculate the polygenic risk score of SNPs, and the healthful plant-based diet index was used to summarize food intake. The effect of metabolites on BMD changes under the influence of genes and lifestyle was analyzed through interaction analysis and mediation analysis.ResultsNineteen metabolites were found significantly different in the osteoporosis, osteopenia, and normal BMD groups. We found two high-density lipoprotein (HDL) subfractions were positively associated with osteopenia, and six very-low-density lipoprotein subfractions were negatively associated with osteopenia or osteoporosis, after adjusting for lifestyles and genetic factors. Tea drinking habits, alcohol consumption, smoking, and polygenic risk score changed BMD by affecting metabolites.ConclusionWith the increased level of HDL subfractions, the risk of bone loss in the population will increase; the risk of bone loss decreases with the increased level of very-low-density lipoprotein subfractions. Genetic factors and lifestyles can modify the effects of metabolites on BMD. Our results show evidence for the precise prevention of osteoporosis.
Association of hypercalciuria with vitamin D supplementation in patients undergoing ketogenic dietary therapy
Authors: Lee Myeongseob , Lee Hae In , Song Kyungchul , Choi Han Saem , Suh Junghwan , Kim Se Hee , Chae Hyun Wook , Kang Hoon-Chul , Lee Joon Soo , Kim Heung Dong , Kim Ho-Seong , Kwon Ahreum 
Published: September 2022

BackgroundKetogenic dietary therapy (KDT) is used as an effective treatment for epilepsy. However, KDT carries the risk of bone health deterioration; therefore, vitamin D supplementation is required. Vitamin D replacement therapy in KDT has not been established because it may be related to hypercalciuria/urolithiasis, which are common adverse effects of KDT. Hence, this study aimed to evaluate the dose-dependent association between vitamin D3 and hypercalciuria/urolithiasis in patients undergoing KDT and dose optimization for renal complications.Materials and methodsOverall, 140 patients with intractable childhood epilepsy started 3:1 KDT (lipid to non-lipid ratio) at the Severance Children’s Hospital from January 2016 to December 2019. Regular visits were recommended after KDT initiation. Participants were assessed for height, weight, serum 25-hydroxyvitamin D (25-OH-D3) level, parathyroid hormone level, and ratio of urinary excretion of calcium and creatinine (Uca/Ucr). Kidney sonography was conducted annually. Patients who already had urolithiasis and were taking hydrochlorothiazide before KDT, failed to maintain KDT for 3 months, did not visit the pediatric endocrine department regularly, did not take prescribed calcium and vitamin D3 properly, or needed hospitalization for &gt; 1°month because of serious medical illness were excluded. Data from patients who started diuretic agents, e.g., hydrochlorothiazide, were excluded from that point because the excretion of calcium in the urine may be altered in these patients.ResultIn total, 49 patients were included in this study. Uca/Ucr ratio significantly decreased with increasing levels of 25-OH-D3 (p = 0.027). The odds ratio for hypercalciuria was 0.945 (95% confidence interval, 0.912–0.979; p = 0.002) per 1.0 ng/mL increment in 25-OH-D3 level. Based on findings of receiver operating characteristic curve analysis and Youden’s J statistic, the cut-off 25-OH-D3 level for preventing hypercalciuria was &gt; 39.1 ng/mL at 6 months. Furthermore, the vitamin D3 supplementation dose cut-off was &gt; 49.5 IU/kg for hypercalciuria prevention.ConclusionAn inverse relationship between Uca/Ucr ratio and 25-OH-D3 level was noted, which means that vitamin D supplementation is helpful for preventing hypercalciuria related to KDT. We suggest that the recommended 25-OH-D3 level is &gt; 40 ng/mL for hypercalciuria prevention and that KDT for children with epilepsy can be optimized by vitamin D3 supplementation at 50 IU/kg.
Cost-effectiveness of palbociclib in early breast cancer patients with a high risk of relapse: Results from the PENELOPE-B trial
Authors: Galactionova Katya , Loibl Sibylle , Salari Paola , Marmé Frederik , Martin Miguel , Untch Michael , Bonnefoi Hervé R. , Kim Sung-Bae , Bear Harry D. , McCarthy Nicole , Gelmon Karen A. , García-Sáenz José A. , Kelly Catherine M. , Reimer Toralf , Toi Masakazu , Rugo Hope S. , Gnant Michael , Makris Andreas , Burchardi Nicole , Schwenkglenks Matthias 
Published: September 2022

BackgroundPatients with hormone receptor-positive, HER2-negative breast cancer who have residual invasive disease after neoadjuvant chemotherapy (NACT) are at a high risk of relapse. PENELOPE-B was a double-blind, placebo-controlled, phase III trial that investigated adding palbociclib (PAL) for thirteen 28-day cycles to adjuvant endocrine therapy (ET) in these patients. Clinical results showed no significant improvement in invasive disease-free survival with PAL.MethodsWe performed a pre-planned cost-effectiveness analysis of PAL within PENELOPE-B from the perspective of the German statutory health insurance. Health-related quality of life scores, collected in the trial using the EQ-5D-3L instrument, were converted to utilities based on the German valuation algorithm. Resource use was valued using German price weights. Outcomes were discounted at 3% and modeled with mixed-level linear models to adjust for attrition, repeated measurements, and residual baseline imbalances. Subgroup analyses were performed for key prognostic risk factors. Scenario analyses addressed data limitations and evaluated the robustness of the estimated cost-effectiveness of PAL to methodological choices.ResultsThe effects of PAL on quality-adjusted life years (QALYs) were marginal during the active treatment phase, increasing thereafter to 0.088 (95% confidence interval: −0.001; 0.177) QALYs gained over the 4 years of follow-up. The incremental costs were dominated by PAL averaging EUR 33,000 per patient; costs were higher in the PAL arm but not significantly different after the second year. At an incremental cost-effectiveness ratio of EUR 380,000 per QALY gained, PAL was not cost-effective compared to the standard-of-care ET. Analyses restricted to Germany and other subgroups were consistent with the main results. Findings were robust in the scenarios evaluated.ConclusionsOne year of PAL added to ET is not cost-effective in women with residual invasive disease after NACT in Germany.
Cancer knowledge and health-consciousness in childhood cancer survivors following transition into adult care—results from the ACCS project
Authors: Otth Maria , Denzler Sibylle , Diesch-Furlanetto Tamara , Scheinemann Katrin 
Published: September 2022

BackgroundKnowledge on chronic medical conditions in childhood cancer survivors (CCSs) is constantly growing and underlines that long-term follow-up (LTFU) care is often mandatory, also in adulthood. However, many CCSs discontinue follow-up care after transition to adult care. One reason might be that the current transition practices do not meet the needs of adolescent and young adult CCSs. We therefore aim to evaluate different transition models for Swiss CCSs by assessing their cancer knowledge, cancer worries, self-management skills, and expectations for LTFU care, following transition in two different hospital-based models.MethodsWithin the Aftercare of Childhood Cancer Survivors (ACCS) study, we performed a questionnaire-based survey with a cross-sectional and longitudinal part. We included 5-year CCSs aged &gt;16 years at recruitment who were transitioned to adult care in two hospitals between 2014 and 2021. Here, we report the results of the cross-sectional part. We compared the survivors’ cancer knowledge with medical record data and assessed cancer worries (6 questions), self-management skills (15 questions), and expectations (12 questions) by validated scales. We used descriptive statistics, chi-squared test, and t-tests to describe the results.ResultsWe analyzed 57 CCSs (response rate 44%), 60% of those were female, had a median age of 9 years at diagnosis and 23 years at the questionnaire. Most CCSs recalled their diagnosis (95%) and exposure to treatment modalities (98%) correctly. CCSs worried the most about potential late effects (47%) and issues with having children in the future (44%). At least 75% of CCSs agreed to 12 of the 15 self-management questions, indicating high self-management skills. The top three expectations included that physicians know the survivors’ cancer history, that visits start on time, and that physicians can always be called in case of questions.ConclusionCCSs receiving hospital-based LTFU care have good cancer knowledge and high self-management skills. The identified worries and expectations will help to improve the LTFU care of CCSs who transition to adult care, to further inform and educate survivors and healthcare professionals about and might be relevant for other countries with a similar healthcare system.
Prognostic value of combined inflammatory and nutritional biomarkers in HCC within the Milan criteria after hepatectomy
Authors: Feng Hanxin , Xu Feng , Zhao Yang , Jin Tianqiang , Liu Jianbo , Li Rui , Zhou Tianyi , Dai Chaoliu 
Published: September 2022

AimsThis study aimed to evaluate the predictive value of the combined prognostic nutritional index (PNI) and GGT/ALT for the postoperative prognosis of patients with hepatocellular carcinoma (HCC) within Milan criteria undergoing radical hepatectomy.MethodsThis single-center retrospective study included 283 patients with HCC within the Milan criteria who underwent hepatectomy. The receiver operating characteristic (ROC) curve was used to calculate the optimal PNI and GGT/ALT cut-off values. Pre-treatment PNI, GGT/ALT, and PNI-GGT/ALT grades were calculated. Overall survival (OS) and recurrence-free survival (RFS) were estimated using the Kaplan–Meier method, and multivariate analysis was used to identify prognostic factors.ResultsMultivariate Cox regression analysis identified that the PNI, GGT/ALT, tumor number were significant prognostic markers for OS, and that the GGT/ALT, tumor number were significant prognostic markers for OS. The survival curves showed that low PNI, high GGT/ALT ratio, and high PNI-GGT/ALT grade were associated with poorer OS and DFS. With an area under the curve (AUC) of 0.690, PNI-GGT/ALT outperformed each individual score.ConclusionPNI-GGT/ALT, a new prognostic scoring model, qualifies as a novel prognostic predictor for patients with HCC within the Milan criteria after curative resection.