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  • Oxford University Press (OUP)  (18)
  • 2020-2024  (18)
  • 1
    In: JNCI Cancer Spectrum, Oxford University Press (OUP), Vol. 7, No. 1 ( 2023-01-03)
    Abstract: Noninvasive detection of early stage cancers with accurate prediction of tumor tissue-of-origin could improve patient prognosis. Because miRNA profiles differ between organs, circulating miRNomics represent a promising method for early detection of cancers, but this has not been shown conclusively. Methods A serum miRNA profile (miRNomes)–based classifier was evaluated for its ability to discriminate cancer types using advanced machine learning. The training set comprised 7931 serum samples from patients with 13 types of solid cancers and 5013 noncancer samples. The validation set consisted of 1990 cancer and 1256 noncancer samples. The contribution of each miRNA to the cancer-type classification was evaluated, and those with a high contribution were identified. Results Cancer type was predicted with an accuracy of 0.88 (95% confidence interval [CI] = 0.87 to 0.90) in all stages and an accuracy of 0.90 (95% CI = 0.88 to 0.91) in resectable stages (stages 0-II). The F1 score for the discrimination of the 13 cancer types was 0.93. Optimal classification performance was achieved with at least 100 miRNAs that contributed the strongest to accurate prediction of cancer type. Assessment of tissue expression patterns of these miRNAs suggested that miRNAs secreted from the tumor environment could be used to establish cancer type–specific serum miRNomes. Conclusions This study demonstrates that large-scale serum miRNomics in combination with machine learning could lead to the development of a blood-based cancer classification system. Further investigations of the regulating mechanisms of the miRNAs that contributed strongly to accurate prediction of cancer type could pave the way for the clinical use of circulating miRNA diagnostics.
    Type of Medium: Online Resource
    ISSN: 2515-5091
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2975772-1
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  • 2
    In: Inflammatory Bowel Diseases, Oxford University Press (OUP), Vol. 26, No. 11 ( 2020-10-23), p. 1669-1681
    Abstract: The therapeutic efficacy and safety of ustekinumab for Crohn’s disease (CD) have been reported from randomized controlled trials and real-world data. However, there are few studies describing the identification of patients most suitable for ustekinumab therapy. The aim of this study was to prospectively evaluate the patients receiving ustekinumab and identify predictors of the treatment efficacy. Methods Patients with moderate to severe active CD scheduled to receive ustekinumab were enrolled. The responders and nonresponders were compared at weeks 0, 8, 24, and 48 by evaluating patient demographics, simple endoscopic scores (SES-CD), ustekinumab and cytokine concentrations, and cellular fractions. Results The clinical response and clinical remission rates in the 22 enrolled patients were 59.1% and 31. 8% at week 8, 68.2% and 45.5% at week 24, and 54.4% and 40.9% at week 48, respectively. There were no significant differences in patients’ demographic and disease characteristics at baseline between responders and nonresponders. A combination of low SES-CD and high serum TNF-α concentration at baseline showed a good correlation with the clinical response. Serum TNF-α concentration was decreased because of the therapy. The ratio of CD4+TNF-α cells at baseline was significantly higher in responders than in nonresponders; however, the ratios of CD45+CD11b+TNF-α and CD45+CD11c+TNF-α cells were not different. The ratio of CD4+ TNF-α cells decreased with the treatment in the responders but not in the nonresponders. Conclusions The combination of 2 factors, namely higher serum TNF-α concentration and lower SES-CD at baseline, may assist clinicians in selecting the appropriate therapy for patients with moderate to severe CD.
    Type of Medium: Online Resource
    ISSN: 1078-0998 , 1536-4844
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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  • 3
    In: Journal of Surgical Case Reports, Oxford University Press (OUP), Vol. 2023, No. 6 ( 2023-06-01)
    Abstract: Klebsiella pneumoniae has the ability to form biofilm; therefore, the treatment of prosthetic joint infection involving K. pneumoniae is often challenging. This report describes the first case of acute hematogenous prosthetic knee joint infection with K. pneumoniae that occurred as a result of an asymptomatic gallbladder abscess. The patient was a 78-year-old man who underwent bilateral total knee arthroplasty 6 years ago. He had pain and swelling in his right knee. The synovial fluid culture of the right knee revealed K. pneumoniae and prosthetic joint infection was diagnosed. Computed tomography revealed a gallbladder abscess in the absence of right upper abdominal pain. The patient underwent simultaneous debridement of the knee and open cholecystectomy. The treatment was successful and the prosthesis was retained. In cases of hematogenous prosthetic joint infection with K. pneumoniae, other sources of infection should be suspected and investigated regardless of whether they are symptomatic.
    Type of Medium: Online Resource
    ISSN: 2042-8812
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2580919-2
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  • 4
    In: Japanese Journal of Clinical Oncology, Oxford University Press (OUP), Vol. 50, No. 5 ( 2020-05-05), p. 586-593
    Abstract: The Japanese Psycho-Oncology Society and Japanese Association of Supportive Care in Cancer recently launched the clinical practice guidelines for delirium in adult cancer patients. The aim of the guidelines was to provide evidence-based recommendations for the clinical assessment and management of delirium in cancer patients. This article reports the process of developing the guideline and summarizes the recommendations made. Methods The guidelines were developed in accordance with the Medical Information Network Distribution Service creation procedures. The guideline development group, consisting of multidisciplinary members, formulated nine clinical questions. A systematic literature search was conducted to identify relevant articles published prior to through 31 May 2016. Each article was reviewed by two independent reviewers. The level of evidence and the strength of the recommendations were graded using the grading system developed by the Medical Information Network Distribution Service, following the concept of The Grading of Recommendations Assessment, Development and Evaluation system. The modified Delphi method was used to validate the recommendation statements. Results This article provides a summary of the recommendations with rationales for each, as well as a short summary. Conclusions These guidelines will support the clinical assessment and management of delirium in cancer patients. However, additional clinical studies are warranted to further improve the management of delirium.
    Type of Medium: Online Resource
    ISSN: 1465-3621
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 1494610-5
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  • 5
    In: International Immunology, Oxford University Press (OUP), Vol. 33, No. 8 ( 2021-07-23), p. 435-446
    Abstract: Regulatory T (Treg) cells, which are essential for maintaining self-tolerance, inhibit anti-tumor immunity, consequently hindering protective cancer immunosurveillance, and hampering effective anti-tumor immune responses in tumor-bearing hosts. Here, we show that depletion of Treg cells via targeting glycoprotein A repetitions predominant (GARP) induces effective anti-tumor immune responses. GARP was specifically expressed by highly suppressive Treg cells in the tumor microenvironment (TME) of multiple cancer types in humans. In the periphery, GARP was selectively induced in Treg cells, but not in effector T cells, by polyclonal stimulation. DS-1055a, a novel afucosylated anti-human GARP monoclonal antibody, efficiently depleted GARP+ Treg cells, leading to the activation of effector T cells. Moreover, DS-1055a decreased FoxP3+CD4+ T cells in the TME and exhibited remarkable anti-tumor activity in humanized mice bearing HT-29 tumors. We propose that DS-1055a is a new Treg-cell-targeted cancer immunotherapy agent with augmentation of anti-tumor immunity.
    Type of Medium: Online Resource
    ISSN: 1460-2377
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1467474-9
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  • 6
    In: International Immunology, Oxford University Press (OUP), ( 2024-01-03)
    Abstract: Foxp3-expressing regulatory T (Treg) cells play essential roles in immune homeostasis, but also contribute to establish a favorable environment for tumor growth by suppressing anti-tumor immune responses. It is thus necessary to specifically target tumor-infiltrating Treg cells to minimize effects on immune homeostasis in cancer immunotherapy. However, molecular features that distinguish tumor-infiltrating Treg cells from those in secondary lymphoid organs remain unknown. Here we characterize distinct features of tumor-infiltrating Treg cells by global analyses of transcriptome and chromatin landscape. They exhibited activated phenotypes with enhanced Foxp3-dependent transcriptional regulation, yet being distinct from activated Treg cells in secondary lymphoid organs. Such differences may be attributed to the extensive clonal expansion of tumor-infiltrating Treg cells. Moreover, we found that TCF7 and LEF1 were specifically down-regulated in tumor-infiltrating Treg cells both in mice and humans. These factors and Foxp3 co-occupied Treg suppressive function-related gene loci in secondary lymphoid organ Treg cells, whereas the absence of TCF7 and LEF1 accompanied altered gene expression and chromatin status at these gene loci in tumor-infiltrating Treg cells. Functionally, overexpression of TCF7 and LEF1 in Treg cells inhibited the enhancement of Treg suppressive function upon activation. Our results thus show the down-regulation of TCF7 and LEF1 as markers of highly suppressive Treg cells in tumors and suggest that their absence controls the augmentation of Treg suppressive function in tumors. These molecules may be potential targets for novel cancer immunotherapy with minimum effects on immune homeostasis.
    Type of Medium: Online Resource
    ISSN: 1460-2377
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2024
    detail.hit.zdb_id: 1467474-9
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  • 7
    In: JBMR Plus, Oxford University Press (OUP)
    Abstract: Atypical femoral fracture (AFF) is generally a rare complication of long-term use of bisphosphonate (BP); glucocorticoid (GC) use and Asian race are also risk factors. Femoral localized periosteal thickening (LPT, also termed “beaking”) of the lateral cortex often precedes AFF. This cohort study investigated the incidence of LPT and AFF and their clinical courses over 10 years in patients with autoimmune inflammatory rheumatic diseases (AIRDs) treated with BP and GC. The study population consisted of 121 patients with AIRDs taking BP and GC. LPT was screened by X-ray, and the LPT shape was evaluated. Prednisolone (PSL) dose was 10 (8–12) mg/day at enrollment and 9 (6–10) mg/day at the last observation. LPT was evident in 10 patients at enrollment and increased linearly to 31 patients (26%) at the last observation. AFF occurred in nine femurs of five patients with LPT. All patients with AFF had bilateral LPT, and the prevalence of pointed type and LPT height were higher in the AFF-positive group than in the AFF-negative group. AFF occurred before BP discontinuation in two patients, 1 year after BP discontinuation in one, after BP discontinuation followed by 7 years of alfacalcidol use in one, and after switching from alfacalcidol to denosumab in one. The prevalence rates of AFF and LPT associated with long-term BP use with concomitant use of GC (mostly PSL ≥ 6 mg/day) in Japanese patients with AIRD increased over time. The selection of long-term osteoporosis treatment for LPT-positive patients is difficult in some cases.
    Type of Medium: Online Resource
    ISSN: 2473-4039
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2024
    detail.hit.zdb_id: 2905710-3
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  • 8
    In: European Heart Journal - Cardiovascular Imaging, Oxford University Press (OUP), ( 2021-02-23)
    Abstract: The ability of optical coherence tomography (OCT) to detect plaques at high risk of developing acute coronary syndrome (ACS) remains unclear. The aim of this study was to evaluate the association between non-culprit plaques characterized as both lipid-rich plaque (LRP) and thin-cap fibroatheroma (TCFA) by OCT and the risk of subsequent ACS events at the lesion level. Methods and results In 1378 patients who underwent OCT, 3533 non-culprit plaques were analysed for the presence of LRP (maximum lipid arc & gt; 180°) and TCFA (minimum fibrous cap thickness & lt; 65 μm). The median follow-up period was 6 years [interquartile range (IQR): 5–9 years]. Seventy-two ACS arose from non-culprit plaques imaged by baseline OCT. ACS was more often associated with lipidic plaques that were characterized as both LRP and TCFA vs. lipidic plaques that did not have these characteristics [33% vs. 2%, hazard ratio 19.14 (95% confidence interval: 11.74–31.20), P  & lt; 0.001]. The sensitivity and specificity of the presence of both LRP and TCFA for predicting ACS was 38% and 97%, respectively. A larger maximum lipid arc [1.01° (IQR: 1.01–1.01°)] , thinner minimum fibrous cap thickness [0.99 μm (IQR: 0.98–0.99 μm)], and smaller minimum lumen area [0.78 mm2 (IQR: 0.67–0.90 mm2), P  & lt; 0.001] were independently associated with ACS. Conclusion Non-culprit plaques characterized by OCT as both LRP and TCFA were associated with an increased risk of subsequent ACS at the lesion level. Therefore, OCT might be able to detect vulnerable plaques.
    Type of Medium: Online Resource
    ISSN: 2047-2404 , 2047-2412
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2042482-6
    detail.hit.zdb_id: 2647943-6
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  • 9
    In: Nephrology Dialysis Transplantation, Oxford University Press (OUP), Vol. 38, No. Supplement_1 ( 2023-06-14)
    Abstract: Frailty is widely acknowledged as an age-related fragile state characterized by physiological vulnerability to stress, and it is prevalent among patients undergoing maintenance hemodialysis therapy. Various factors are interconnected and can be theoretically consolidated into a cycle of frailty, with malnutrition and sarcopenia at the core. These can result in numerous negative health outcomes in patients on hemodialysis and prompt identification and treatment are necessary. However, limited research has investigated the impact of the overlap between malnutrition and sarcopenia on mortality in this patient population. In this study, we examined the association of the overlap between malnutrition and sarcopenia with all-cause mortality in patients undergoing maintenance hemodialysis. Method The present prospective cohort study recruited outpatients on hemodialysis from three facilities in Japan. At the study baseline, data on patients' characteristics including age, gender, body mass index, duration of dialysis, primary kidney diseases, 11 comorbid conditions, and laboratory parameters (including serum albumin level) were collected from medical records. In addition, muscle mass (skeletal muscle index [SMI]), muscle strength (handgrip strength), and physical performance (short physical performance battery [SPPB] ) were measured by physical therapists. A comorbidity index was used to quantify the severity of comorbid illnesses, which was calculated based on primary kidney diseases and the 11 comorbidities. Malnutrition was identified based on geriatric nutritional risk index & lt;98, which was calculated using the serum albumin level and body weight. Sarcopenia was diagnosed when patients had low muscle mass (SMI & lt;7.0 kg/m2 for males and & lt;5.7 kg/m2 for females) and low muscle strength (handgrip strength & lt;28.0kg for males and & lt;18 kg for females) or low physical performance (SPPB ≤9), in accordance with the Asian Working Group for Sarcopenia 2019 criteria. After classifying the study participants into four groups based on the absence or presence of malnutrition and sarcopenia, the mortality risk was evaluated using the Kaplan-Meier method and Cox proportional hazard analysis. This study was approved by the Research Ethics Committee and conducted in accordance with the principles of the Declaration of Helsinki. Results A total of 379 patients on hemodialysis were included in the analysis. The mean age of the patients was 69.5±12.6 years, and 40.2% of the cohort being female. The mean duration of dialysis was 7.9±4.5 years. The most prevalent underlying kidney disease was diabetes mellitus. At baseline, the prevalence rates of malnutrition and sarcopenia were 32.7% and 28.2%, respectively. Over a mean follow-up period of 4.3 years, 23 patients died. The Kaplan-Meier analysis demonstrated a lower cumulative survival rate in patients with malnutrition and/or sarcopenia. After adjustment for the effect of age, gender, duration of dialysis, and comorbidity index, the hazard ratio in patients with both malnutrition and sarcopenia was significantly higher than in patients without both (hazard ratio [HR] 5.78, 95% confidence interval [CI] 1.86-17.94). However, the hazard ratios in patients suffering from either malnutrition or sarcopenia alone were not significantly different (Table 1). Conclusion The present study has demonstrated the strong association of a state of co-occurrence between malnutrition and sarcopenia, which implies starvation and muscle wasting, with a poor prognosis in patients undergoing hemodialysis. The findings of this study have accentuated the significance of addressing both malnutrition and sarcopenia in routine clinical practice for patients undergoing maintenance hemodialysis.
    Type of Medium: Online Resource
    ISSN: 0931-0509 , 1460-2385
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1465709-0
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  • 10
    In: International Immunology, Oxford University Press (OUP), Vol. 32, No. 3 ( 2020-03-07), p. 175-186
    Abstract: Ovarian cancer is the second-most lethal gynecological malignancy and the seventh-commonest cause of cancer-related death in women around the world. Most of the ovarian cancer patients are diagnosed at advanced stages and suffer from recurrence after primary cytoreductive surgery and standard first-line chemotherapy. Thus, the successful management of ovarian cancer patients requires the identification of factors that contribute to progression and relapse. Interleukin-34 (IL-34) is a novel cytokine that acts as a tissue-specific ligand of colony-stimulating factor-1 receptor (CSF-1R). In cancer, IL-34 exerts pro-tumorigenic functions that promote tumor growth, metastasis, angiogenesis, immune suppression and therapeutic resistance. In this study, we evaluate the impact of IL-34 on progression and survival of ovarian cancer patients. First, IL-34 was found to be expressed in several human ovarian cancer cell lines and cancer tissues from patients. The expression of IL-34 was enhanced by cytotoxic chemotherapy in ovarian cancer cell lines and cancer tissues from chemotherapy-treated ovarian cancer patients. Importantly, high IL-34 expression correlated with worse progression-free survival (PFS) and overall survival in different cohorts. The assessment of PFS based on a combination between IL34 expression and other related genes such as CSF1R and CD163 helped further to reach more statistical significance compared with IL34 alone. Furthermore, in the murine ovarian cancer cell HM-1 in vivo model, it was suggested that IL-34-derived tumor cells was correlated with tumor progression and survival by modulating the immune environment. Collectively, these findings indicate a possible correlation between IL-34 expression and disease progression in ovarian cancer patients and the mouse model.
    Type of Medium: Online Resource
    ISSN: 1460-2377
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 1467474-9
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