-
BMC Psychiatry Aug 2023Depression is a common mental health problem among veterans, with high mortality. Despite the numerous conducted investigations, the prediction and identification of...
BACKGROUND
Depression is a common mental health problem among veterans, with high mortality. Despite the numerous conducted investigations, the prediction and identification of risk factors for depression are still severely limited. This study used a deep learning algorithm to identify depression in veterans and its factors associated with clinical manifestations.
METHODS
Our data originated from the National Health and Nutrition Examination Survey (2005-2018). A dataset of 2,546 veterans was identified using deep learning and five traditional machine learning algorithms with 10-fold cross-validation. Model performance was assessed by examining the area under the subject operating characteristic curve (AUC), accuracy, recall, specificity, precision, and F1 score.
RESULTS
Deep learning had the highest AUC (0.891, 95%CI 0.869-0.914) and specificity (0.906) in identifying depression in veterans. Further study on depression among veterans of different ages showed that the AUC values for deep learning were 0.929 (95%CI 0.904-0.955) in the middle-aged group and 0.924(95%CI 0.900-0.948) in the older age group. In addition to general health conditions, sleep difficulties, memory impairment, work incapacity, income, BMI, and chronic diseases, factors such as vitamins E and C, and palmitic acid were also identified as important influencing factors.
CONCLUSIONS
Compared with traditional machine learning methods, deep learning algorithms achieved optimal performance, making it conducive for identifying depression and its risk factors among veterans.
Topics: Middle Aged; Humans; Aged; Deep Learning; Depression; Nutrition Surveys; Veterans; Algorithms
PubMed: 37612646
DOI: 10.1186/s12888-023-05109-9 -
Blood Jun 1987The promising antineoplastic agent diaziquone is associated with prolonged aplasia and rare instances of bone marrow necrosis, but only mild extramedullary toxicity. To...
UNLABELLED
The promising antineoplastic agent diaziquone is associated with prolonged aplasia and rare instances of bone marrow necrosis, but only mild extramedullary toxicity. To explore the drug's potential as a myeloablative agent prior to bone marrow transplantation, we compared its effects on hematopoietic versus marrow stromal cells. After short-term (one to six hours) or prolonged (three to seven days) exposure to the drug, marrow was assayed for hematopoietic (CFU-Mix, BFU-E, CFU-GM) and stromal (CFU-F) colony-forming cells and studied in long-term marrow culture (LTMC). One- and three-hour treatments produced little cytotoxicity, even at 5000 ng/mL. After six-hour treatments with this dose, marrow was depleted of CFU-Mix, BFU-E, and CFU-GM, but produced CFU-GM in LTMCs, indicating an ongoing input of CFU-GM from a surviving pre-CFU-Mix population. In contrast, elimination of the latter may be inferred from the absence of CFU-GM in LTMCs exposed for three to seven days to diaziquone at only 150 ng/mL. Under these conditions, CFU-F recovery was 40% and adherent stromal layers in LTMCs were similar to untreated controls regarding rate of development and cellular composition. Our in vitro pre-CFU-Mix-ablative regimen correlates with clinical data that show prolonged but reversible myelosuppression at steady-state diaziquone plasma levels of 101 +/- 10 ng/mL (mean +/- standard error of mean) during 7-day constant infusions.
IN CONCLUSION
hematopoietic cells are more sensitive than marrow stromal cells to the dose- and highly time-dependent cytotoxicity of diaziquone, a direct drug-induced noxious effect on the marrow microenvironment is an unlikely cause of the isolated episodes of marrow necrosis after the use of diaziquone in vivo, and prolonged infusion of diaziquone represents an attractive means for achieving myeloablation in selected clinical situations.
Topics: Aziridines; Azirines; Benzoquinones; Bone Marrow Cells; Bone Marrow Transplantation; Cells, Cultured; Humans; Stem Cells; Time Factors
PubMed: 3555652
DOI: No ID Found -
The Biochemical Journal Sep 1992DT-diaphorase [NAD(P)H:quinone oxidoreductase; EC 1.6.99.2] catalysed the two-electron reduction of the anti-tumour quinone...
Thiol oxidation coupled to DT-diaphorase-catalysed reduction of diaziquone. Reductive and oxidative pathways of diaziquone semiquinone modulated by glutathione and superoxide dismutase.
DT-diaphorase [NAD(P)H:quinone oxidoreductase; EC 1.6.99.2] catalysed the two-electron reduction of the anti-tumour quinone 2,5-bis-(1-aziridinyl)-3,6-bis(ethoxycarbonylamino)-1,4-benzoquino ne (AZQ) to the hydroquinone form (AZQH2). Although DT-diaphorase catalysis of AZQ was not significantly affected by pH, the hydroquinone product was effectively stabilized by protonation at pH values below 7, whereas, above that pH, hyroquinone autoxidation, evaluated in terms of H2O2 production, increased exponentially. The autoxidation of AZQH2 entailed the formation of diverse radicals, such as O2-.,HO., and the semiquinone form of AZQ (AZQ-.), which contributed to different extents to the e.p.r. spectrum. Superoxide dismutase enhanced the autoxidation of AZQH2 and suppressed the e.p.r. signal ascribed to AZQ-., in agreement with a displacement of the equilibrium of the semiquinone autoxidation reaction (AZQ-.+O2 in equilibrium with AZQ+O2-.) upon enzymic withdrawal of O2-.. GSH increased the steady-state concentration of AZQH2 formed during DT-diaphorase catalysis and inhibited temporarily its autoxidation. This effect was accompanied by oxidation of the thiol to the disulphide within a process involving glutathionyl radical (GS.) formation, the relative contribution of which to the e.p.r. spectrum was enhanced by increasing GSH concentrations. GS. formation in this experimental model can be rationalized as originating from the reaction of GSH with AZQ-., rather than with O2-. or HO., for thiol oxidation was not affected significantly by superoxide dismutase, and GS. formation was insensitive to catalase. In addition, GSH suppressed the e.p.r. signal attributed to AZQ-.. No glutathionyl-quinone conjugate was detected during the DT-diaphorase-catalysed reduction of AZQ; although the chemical requirements for alkylation were partly fulfilled (quinone ring aromatization and acid-assisted aziridinyl ring opening), the negligible dissociation of GSH (GS(-)+H+ in equilibrium with GSH) at low pH prevented any nucleophilic addition to occur. Therefore the redox transitions of AZQ during DT-diaphorase catalysis seemed to be centred on the semiquinone species, the fate of which was inversely affected by catalytic amounts of superoxide dismutase and large amounts of GSH: the former enhanced AZQ-. autoxidation and the latter favoured AZQ-. reduction. Accordingly, superoxide dismutase and GSH suppressed the semiquinone e.p.r. signal. These results are discussed in terms of three interdependent redox transitions (comprising one-electron transfer reactions involving the quinone, oxygen and the thiol) and the thermodynamic and kinetic properties of the reactions involved.
Topics: Aziridines; Benzoquinones; Catalysis; Free Radicals; Glutathione; Hydrogen-Ion Concentration; Kinetics; NAD(P)H Dehydrogenase (Quinone); Oxidation-Reduction; Spectrum Analysis; Sulfhydryl Compounds; Superoxide Dismutase; Thermodynamics
PubMed: 1530580
DOI: 10.1042/bj2860481 -
PloS One 2015Senescence is a terminal growth arrest that functions as a tumor suppressor in aging and precancerous cells and is a response to selected anticancer compounds....
PURPOSE
Senescence is a terminal growth arrest that functions as a tumor suppressor in aging and precancerous cells and is a response to selected anticancer compounds. Lysosomal-β-galactosidase (GLB1) hydrolyzes β-galactose from glycoconjugates and is the origin of senescence-associated β-gal activity (SA-β-gal). Using a new GLB1 antibody, senescence biology was investigated in prostate cancer (PCa) tissues.
EXPERIMENTAL DESIGN
In vitro characterization of GLB1 was determined in primary prostate epithelial cell cultures passaged to replicative senescence and in therapy-induced senescence in PCa lines using chemotherapeutic agents. FFPE tissue microarrays were subjected to immunofluorescent staining for GLB1, Ki67 and HP1γ and automated quantitative imaging initially using AQUA in exploratory samples and Vectra in a validation series.
RESULTS
GLB1 expression accumulates in replicative and induced senescence and correlates with senescent morphology and P16 (CDKN2) expression. In tissue arrays, quantitative imaging detects increased GLB1 expression in high-grade prostatic intraepithelial neoplasia (HGPIN), known to contain senescent cells, and cancer compared to benign prostate tissues (p<0.01) and senescent cells contain low Ki67 and elevated HP1γ. Within primary tumors, elevated GLB1 associates with lower T stage (p=0.01), localized versus metastatic disease (p=0.0003) and improved PSA-free survival (p=0.03). Increased GLB1 stratifies better PSA-free survival in intermediate grade PCa (0.01). Tissues that elaborate higher GLB1 display increased uniformity of expression.
CONCLUSION
Increased GLB1 is a valuable marker in formalin-fixed paraffin-embedded (FFPE) tissues for the senescence-like phenotype and associates with improved cancer outcomes. This protein addresses a lack of senescence markers and should be applicable to study the biologic role of senescence in other cancers.
Topics: Aged; Antineoplastic Agents; Aziridines; Benzoquinones; Biomarkers; Cellular Senescence; Epithelial Cells; Formaldehyde; Gene Expression Regulation, Neoplastic; Humans; Kallikreins; Male; Middle Aged; Neoplasm Grading; Neoplasm Recurrence, Local; Neoplasm Staging; Paraffin Embedding; Primary Cell Culture; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Signal Transduction; Survival Analysis; Tissue Fixation; beta-Galactosidase
PubMed: 25876105
DOI: 10.1371/journal.pone.0124366 -
Blood Jan 1986Diaziquone given as a bolus has not been effective in patients with relapsed or refractory leukemia. Because of in vitro data suggesting enhancement of...
Diaziquone given as a bolus has not been effective in patients with relapsed or refractory leukemia. Because of in vitro data suggesting enhancement of diaziquone-induced cytotoxicity for human and murine leukemia cells with increased duration of drug exposure and the relatively short terminal plasma half-life of diaziquone, 49 patients (34 acute nonlymphocytic leukemia [ANLL], six chronic myelogenous leukemia in blast crisis [CML-B], five acute lymphocytic leukemia [ALL], four 2 degrees ANLL) with leukemia were given diaziquone as a continuous infusion for seven days. The maximum tolerated dose was 28 mg/m2/d for seven days. The dose-limiting toxicity was the duration of bone marrow aplasia (median, 49 days to greater than 500 PMNs in responders; range, 28 to 101 days). Nonhematologic toxicity was minimal. Responses occurred only in patients with relapsed ANLL, of whom 26 were treated at effective doses. There were six complete responses (CR) (23%) and two partial responses (PR) (8%), although five of eight responders never achieved platelet counts greater than 100,000/microL. Thrombocytopenia in these patients was felt to be a manifestation of diaziquone effect, not persistence of leukemia. The median duration of CR was 195 days (range, 88 to 860+). One patient had active CNS leukemia at the start of treatment and has had a durable (28+ month) CR in both sites of disease. Diaziquone produced prolonged aplasia in patients with secondary ANLL and CML-B (five of ten patients died aplastic), whereas patients with ALL all had regrowth of leukemia and two failed to become aplastic. The lack of significant nonhematologic toxicity and the activity in patients with relapsed ANLL render diaziquone of interest as second-line therapy or consolidation therapy in first remission for patients with ANLL.
Topics: Acute Disease; Adolescent; Adult; Aged; Antineoplastic Agents; Aziridines; Azirines; Benzoquinones; Female; Humans; Kinetics; Leukemia; Male; Middle Aged; Platelet Count; Recurrence
PubMed: 3940546
DOI: No ID Found -
Scientific Reports Mar 2023The study aimed to determine the resilience of multi-ethnic, multi-cultural adolescent students in cosmopolitan Singapore, their coping abilities, and the impact on...
The study aimed to determine the resilience of multi-ethnic, multi-cultural adolescent students in cosmopolitan Singapore, their coping abilities, and the impact on their social and physical activities during the COVID-19 pandemic and its association with their resilience. A total of 582 adolescents in post-secondary education institutes completed an online survey from June to November 2021. The survey assessed their sociodemographic status, resilience level using the Brief Resilience Scale (BRS) and Hardy-Gill Resilience Scale (HGRS), the impact of the COVID-19 pandemic on their daily activities, life settings, social life, social interactions, and coping ability in these aspects of life. Poor ability to cope with school life (adjusted beta = - 0.163, 95% CI - 1.928 to 0.639, p < 0.001), staying home (adjusted beta = - 0.108, 95% CI = - 1.611 to - 0.126, p = 0.022), sports (adjusted beta = - 0.116, 95% CI - 1.691 to - 0.197, p = 0.013) and friends (adjusted beta = - 0.143, 95% CI - 1.904 to - 0.363, p = 0.004) were associated with statistically significant low resilience level measured with HGRS. About half and a third of the participants reported normal and low resilience, respectively, based on BRS (59.6%/32.7%) and HGRS (49.0%/29.0%) scores. Adolescents of Chinese ethnicity and low socioeconomic status had comparatively lower resilience scores. Approximately half of the adolescents in this study had normal resilience despite the COVID-19 pandemic. Adolescents with lower resilience tended to have lower coping abilities. The study did not compare changes in the social life and coping behaviour of the adolescents due to COVID-19, as data on these aspects prior to the pandemic was unavailable.
Topics: Humans; Adolescent; COVID-19; Pandemics; Income; Low Socioeconomic Status; Adaptation, Psychological
PubMed: 36906711
DOI: 10.1038/s41598-023-31147-0 -
Radiation Oncology (London, England) Aug 2023Hypothyroidism (HT) and subclinical HT after radiotherapy is frequent in nasopharyngeal carcinoma (NPC) patients, results in negative impact on patients' quality of... (Randomized Controlled Trial)
Randomized Controlled Trial
Thyroid V40 is a good predictor for subclinical hypothyroidism in patients with nasopharyngeal carcinoma after intensity modulated radiation therapy: a randomized clinical trial.
BACKGROUND
Hypothyroidism (HT) and subclinical HT after radiotherapy is frequent in nasopharyngeal carcinoma (NPC) patients, results in negative impact on patients' quality of life. The percentage of thyroid volume receiving more than 40 Gy (V40) ≤ 85% was reported to be a useful dose constraint to adopt during intensity-modulated radiation therapy (IMRT) planning. This study aims to verify whether V40 ≤ 85% can be used as an effective dose constraint in IMRT planning in a randomized clinical trial.
METHODS
This single-center 1:1 randomized clinical trial was conducted in Fujian province hospital between March 2018 and September 2022. All patients were treated with IMRT and randomized to induction chemo followed by concurrent chemo-IMRT or concurrent chemo-IMRT alone. Ninety-two clinically NPC patients were included in this study. The thyroid function tests were performed for all patients before and after radiation at regular intervals. Thyroid dose-constraint was defined as V40 ≤ 85%. The primary outcome in this study was subclinical HT.
RESULTS
Median follow up was 34 months. Significant difference in the incidence of subclinical HT between the thyroid dose-constraint group and unrestricted group was observed (P = 0.023). The risk of subclinical HT in the thyroid dose-constraint group was lower than that in the unrestricted group (P = 0.022). Univariate and multivariate cox regression analysis indicated that thyroid dose-constraint was a protective effect of subclinical HT (HR = 0.408, 95% CI 0.184-0.904; HR = 0.361, 95% CI 0.155-0.841).
CONCLUSION
V40 ≤ 85% can be used as an effective dose constraint in IMRT planning to prevent radiation-induced subclinical HT.
Topics: Humans; Nasopharyngeal Carcinoma; Quality of Life; Radiotherapy, Intensity-Modulated; Hypothyroidism; Nasopharyngeal Neoplasms
PubMed: 37626342
DOI: 10.1186/s13014-023-02329-x -
Annals of Oncology : Official Journal... May 1994The EORTC New Drug Development Office has initiated a multicenter collaborative program to evaluate the use of human tumor xenografts to predict phase II clinical...
BACKGROUND
The EORTC New Drug Development Office has initiated a multicenter collaborative program to evaluate the use of human tumor xenografts to predict phase II clinical activity. A first study confirmed the efficacy of doxorubicin and inactivity of amsacrine against human tumor xenografts (Boven et al., Cancer Res: 52, 5940, 1992). In the follow-up study reported here, the activities of cisplatin, AZQ (diaziquone), pazelliptine and retelliptine have been evaluated against a panel of 40 established tumor lines grown subcutaneously in nude mice.
DESIGN
The xenografts used represent carcinomas of the breast, colon, head+neck, ovary, small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC) and melanoma. Drugs were administered intravenously on days 0 and 7. Doses were for cisplatin 5 mg/kg, AZQ 3-7 mg/kg, pazelliptine 20-80 mg/kg and retelliptine 6-12.5 mg/kg and were selected to give a median loss of about 10%-15% body weight.
RESULTS
When activity was defined as a specific growth delay > 1 and a tumor growth inhibition > 50%, then cisplatin demonstrated activity in 15 of 40 xenografts tested (3 of 5 breast, 1 of 6 colon, 0 of 5 head+neck, 2 of 6 NSCLC, 4 of 7 SCLC, 1 of 5 melanoma and 4 of 6 ovarian cancers); AZQ was active in 23 of 38 xenografts (2 of 3 breast, 2 of 7 colon, 4 of 5 head+neck, 3 of 6 NSCLC, 6 of 6 SCLC, 2 of 5 melanoma, 4 of 6 ovarian cancers); pazelliptine was active in 2 of 38 xenografts (1 of 5 breast cancers, 1 of 5 melanoma) while retelliptine was active in 1 of 39 xenografts (a breast cancer xenograft) tested.
CONCLUSIONS
These results are reasonably consistent with the clinical activity of cisplatin, but overpredict the clinical efficacy of AZQ. Since pazelliptine and retelliptine are investigational compounds, the clinical phase II studies will provide a prospective test for this model. The results of the present study and the previous one indicate that the human tumor xenograft model could be suitable for predicting the activity of novel compounds to be developed for treatment of cancer patients.
Topics: Animals; Antineoplastic Agents; Aziridines; Benzoquinones; Cisplatin; Drug Screening Assays, Antitumor; Ellipticines; Europe; Female; Follow-Up Studies; Humans; Indoles; Isoquinolines; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation
PubMed: 8075048
DOI: 10.1093/oxfordjournals.annonc.a058872 -
Translational Oncology Aug 2012Therapy-induced senescence (TIS), a cytostatic stress response in cancer cells, is induced inefficiently by current anticancer agents and radiation. The mechanisms that...
Therapy-induced senescence (TIS), a cytostatic stress response in cancer cells, is induced inefficiently by current anticancer agents and radiation. The mechanisms that mediate TIS in cancer cells are not well defined. Herein, we characterize a robust senescence response both in vitro and in vivo to the quinone diaziquone (AZQ), previously identified in a high-throughput senescence-induction small-molecule screen. Using AZQ and several other agents that induce senescence, we screened a series of cyclin-dependent kinase inhibitors and found that p27(Kip1) was induced in all investigated prostate cancer cell lines. The ubiquitin-ligase Skp2 negatively regulates p27(Kip1) and, during TIS, is translocated to the cytoplasm before its expression is decreased in senescent cells. Overexpression of Skp2 blocks the effects of AZQ on senescence and p27(Kip1) induction. We also find that stable long-term short hairpin RNA knockdown of Skp2 decreases proliferation but does not generate the complete senescence phenotype. We conclude that Skp2 participates in regulating TIS but, alone, is insufficient to induce senescence in cancer cells.
PubMed: 22937180
DOI: 10.1593/tlo.12181 -
Blood Feb 1997This study evaluated the effect of filgrastim (granulocyte colony-stimulating factor [G-CSF]) on the duration of granulocytopenia and thrombocytopenia after intensive... (Clinical Trial)
Clinical Trial
Granulocyte-colony stimulating factor (filgrastim) accelerates granulocyte recovery after intensive postremission chemotherapy for acute myeloid leukemia with aziridinyl benzoquinone and mitoxantrone: Cancer and Leukemia Group B study 9022.
This study evaluated the effect of filgrastim (granulocyte colony-stimulating factor [G-CSF]) on the duration of granulocytopenia and thrombocytopenia after intensive consolidation therapy with diaziquone (AZO) and mitroxantrone for patients less than 60 years of age with acute myeloid leukemia (AML) in complete remission. Patients less than 60 years of age with AML who achieved complete remission (CR) with daunorubicin and cytarabine induction therapy, were scheduled to receive three sequential courses of high-dose cytarabine, cyclophosphamide/etoposide, AZQ, and mitroxantrone in a pilot study to determine their tolerance of these three sequential consolidation regimens. The initial patients treated with AZQ and mitroxantrone experienced prolonged bone marrow suppression and, therefore, subsequent cohorts were treated with G-CSF, 5 micrograms/kg, beginning the day after completion of the third cycle of chemotherapy. There was a marked decrease in the duration of granulocytopenia less than 500/microL in two groups of patients receiving two different dose levels of AZQ and the same dose of mitoxantrone compared with patients not receiving the G-CSF. There was also a decrease in the need for hospitalization, as well as the duration of hospitalization. There was a trend towards shortening of the duration of thromobocytopenia, as well. The duration of complete remission and overall survival was similar in patients who received or did not receive G-CSF. G-CSF markedly shortened the duration of granulocytopenia in patients with AML receiving intensive postremission consolidation with AZQ and mitoxantrone. There was no adverse effect on CR duration or survival.
Topics: Acute Disease; Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Aziridines; Benzoquinones; Bone Marrow; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Granulocytes; Humans; Leukemia, Myeloid; Leukocyte Count; Male; Middle Aged; Mitoxantrone; Pilot Projects; Platelet Count; Recombinant Proteins; Remission Induction
PubMed: 9028308
DOI: No ID Found