This paper aims at investigating phonological representation of negation in Sakizaya, an endangered Formosan language in Taiwan. Defying Yaeger-Dror's “Cognitive prominence principles” (2003), Chiang (2006) examines negators in Saisiyat, a SVO language as English, and finds the sentential subjects are more prominent acoustically rather than negators. Thus, I will adopt Chiang's modal (2006) and analyze phonological representation of six negators in Sakizaya to see where the pitch accent falls. Besides, if falling on the negators, I will see whether it is because of either cognitive prominence properties or its sentence-initial position? Six informants (three male and three female), from 50-74 years old, participated in the experiment, recorded by DAT, analyzed by Praat and digitized at a 22050-Hz sampling rate. Affirmative and negative sentences are asked in Mandarin while the informants are instructed to translate them into Sakizaya. Besides, they are asked to produce iterative -ay sentences since the negator ca'ay is the most frequently used negator with higher prominent syllable -ay. The results show negators are more prominent in Sakizaya compared to sentential subjects. I conclude it is word order that influences the prominence of pitch contour since Saisiyat is an SVO language and Sakizaya a VSO one.
Abstract Aim Buprenorphine is one of the strongest opioids used for the relief of cancer pain. This study aims to evaluate the real‐world clinical experiences of transdermal buprenorphine used in moderate to severe cancer pain in the Asian population. Methods This is an open‐labeled, multicenter, 4‐week observational study. Stable cancer pain patients who decided to switch the previous opioid to transdermal buprenorphine will be enrolled in this study. The safety and effectiveness were observed and collected. Pain assessment was performed using a numerical rating scale by the investigators and the Brief Pain Inventory Short Form (BPI‐SF) by the patient. The safety profiles included concomitant medications and adverse events (AEs). Results A total of 83 patients were enrolled in this study. The global pain scores in the BPI, as well as the four individual pain parameters (worst, least, average, and right now), showed a continued decrease ( p < .05) from week 2 to week 4. Significant improvements were observed in normal work activities, relations with other people, sleep, enjoyment of life, and global BPI pain interference score on week 4. Pain assessments conducted by investigators demonstrated significant, continuous improvements during the study periods. In addition, transdermal buprenorphine demonstrated good safety/tolerability with limited drug‐related AEs in the Asian population with cancer pain. Conclusion This study demonstrated that transdermal buprenorphine in the Asian population has good safety profiles and continued improvements in pain relief, sleep, and pain interferences. Transdermal buprenorphine can be an effective and convenient option as a transdermal opioid for patients with moderate to severe cancer pain in Taiwan. (NCT Number: NCT04315831)
This study aimed to evaluate the effect of Astragalus polysaccharides (PG2) on reducing chemotherapy-induced fatigue (CIF) and toxicity, thereby encouraging compliance to chemotherapy. This was a randomized, placebo-controlled, phase 2 study. Patients with stage II/III early breast cancer planning to undergo adjuvant anthracycline-based chemotherapy were randomly assigned to receive PG2 500 mg or placebo on days 1, 3, and 8 every 21 days. The fatigue global score (FGS) was assessed using the brief fatigue inventory (BFI)-Taiwan. The Breast Cancer-Specific Module of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires-Core30 evaluated the health-related quality of life during the first four cycles of adjuvant chemotherapy. Overall, 66 eligible patients were equally randomized into the PG2 and placebo groups between March 01, 2018, and March 09, 2021. The mean change in the FGS and fatigue intensity did not significantly differ between both groups. However, the FGS and fatigue intensity were less aggravated in the first four cycles in the premenopausal-PG2 group than in the placebo group. Our study concluded PG2 combined with adjuvant chemotherapy can reduce CIF, insomnia, the negative effect on future perspectives, and improve global health status, especially for premenopausal patients with breast cancer. Trial registration number: NCT03314805 registered on 19/10/2017.
Coronary artery disease (CAD) is a global health issue. Lipid peroxidation produces various by-products that associate with CAD, such as 4-hydroxynonenal (HNE) and malondialdehyde (MDA). The autoantibodies against HNE and MDA-modified peptides may be useful in the diagnosis of CAD. This study included 41 healthy controls (HCs) and 159 CAD patients with stenosis rates of <30%, 30−70%, and >70%. The plasma level of autoantibodies against four different unmodified and HNE-modified peptides were measured in this study, including CFAH1211−1230, HPT78−108, IGKC2−19, and THRB328−345. Furthermore, feature ranking, feature selection, and machine learning models have been utilized to exploit the diagnostic performance. Also, we combined autoantibodies against MDA and HNE-modified peptides to improve the models’ performance. The eXtreme Gradient Boosting (XGBoost) model received a sensitivity of 78.6% and a specificity of 90.4%. Our study demonstrated the combination of autoantibodies against oxidative modification may improve the model performance.
Coronary artery disease (CAD) is one of the most common subtypes of cardiovascular disease. The progression of CAD initiates from the plaque of atherosclerosis and coronary artery stenosis, and eventually turns into acute myocardial infarction (AMI) or stable CAD. Alpha-1-antichymotrypsin (AACT) has been highly associated with cardiac events. In this study, we proposed incorporating clinical data on AACT levels to establish a model for estimating the severity of CAD. Thirty-six healthy controls (HCs) and 162 CAD patients with stenosis rates of <30%, 30−70%, and >70% were included in this study. Plasma concentration of AACT was determined by enzyme-linked immunosorbent assay (ELISA). The receiver operating characteristic (ROC) curve analysis and associations were conducted. Further, five machine learning models, including decision tree, random forest, support vector machine, XGBoost, and lightGBM were implemented. The lightGBM model obtained a sensitivity of 81.4%, a specificity of 67.3%, and an area under the curve (AUC) of 0.822 for identifying CAD patients with a stenosis rate of <30% versus >30%. In this study, we provided a demonstration of a monitoring model with clinical data and AACT.
537 Background: Fatigue is one of the most common symptoms of breast cancer (BC) patients who are receiving adjuvant chemotherapy. Astragalus Polysaccharides (PG2) had been proved to relieve cancer-related fatigue in advanced BC patients. The aim of this study is to evaluate the efficacy of PG2 as a complementary treatment among stage II/III BC patients with adjuvant chemotherapy of epirubicin-cyclophosphamide(EC) regimen in reduction of chemotherapy-induced toxicity and encouraging compliance with chemotherapy. Methods: This double blind, multicenter, phase II trial randomized stage II/III BC patients who would receive adjuvant EC at least 4 cycles to either PG2 500 mg or placebo on day1, 3, 8 every 21 days as the combination. Changes in chemotherapy-related fatigue score (CRFS) was evaluated by the Brief Fatigue Inventory-Taiwanese Form and incidence of Grade 3/4 neutropenia were the primary endpoints. Results: A total of 66 eligible patients were enrolled and equally randomized to PG2 and placebo groups, 30 cases in each group completed this trial. In general, there was no significant difference in the mean change of CRFS and fatigue intensity between the groups. But the CRFS and fatigue intensity in premenopausal-PG2 group were less aggravated after 4 cycles of EC than that of postmenopausal-placebo group. Persisted significance difference in CRFSs from cycle 1 day 5 (PG2: 0.6; Placebo: 1.9, P = 0.023) to cycle 4 day 15 (PG2: -0.3; Placebo: 0.7, P = 0.002). In all population, a lower proportion of patients suffered from grade 3/4 neutropenia from cycle 1 to cycle 4 were observed in the PG2 group compared to the placebo group (78.8% vs. 87.9% in intent-to-treat population). Conclusions: PG2 combined with adjuvant EC significantly improved adjuvant EC-induced fatigue in premenopausal BC patients. PG2 assists these patients with maintaining normal daily life and job activities, also less need of family support during chemotherapy. Furthermore, patients treated with PG2 might have better compliance to complete the whole course of adjuvant chemotherapy. Clinical trial information: NCT03314805 .
9545 Background: The combination of ifosfamide, carboplatin, and etoposide (ICE) has previously been demonstrated to be an effective regimen in children with recurrent or refractory solid tumors (Cairo et al JPHO, 2001). Substituting topotecan (a Topoisomerase I inhibitor) for etoposide (a Topoisomerase II inhibitor) may be a more efficacious regimen due to the cytotoxic activity of topotecan in pediatric solid tumor xenografts, as well as its in vitro synergistic activity with platinum and alkylating agents (Houghton et al CCP, 1992). Methods: In this limited institution study, we evaluated the addition of escalating doses of topotecan with fixed doses of ifosfamide and carboplatin. Patients initially received ifosfamide 3,000 mg/m2/day × 3 days, carboplatin dosed to an AUC of 3 mg/ml/min (equivalent to 250 mg/m2/dose) × 3 days, and topotecan × 3 days. 6 patients were enrolled at dose level #1 (topotecan: 0.5 mg/m2/day), with 2 patients having ifosfamide related neurotoxicity (related to the dosing schedule). The schedule was amended to 1,800 mg/m2/day × 5 days with 6 further patients enrolled at dose level #1 and no further reports of neurotoxicity. 3 patients were enrolled at dose level #2 (topotecan: 0.75 mg/m2/day). Results: 14 patients (3-18 yrs) with relapsed/refractory disease and histological verification of their disease at the time of initial diagnosis or relapse were enrolled on this study (Wilms 2; osteosarcoma 2; germ cell tumor 2; high grade glioma 1; rhabdomyosarcoma 1; sarcoma 1; non-Hodgkin's lymphoma 1; neuroblastoma 1; medulloblastoma 1; hepatoblastoma 1; neurocytoma 1). Overall, 2 DLT's (dose level #1: hematologic; dose level #2: hematologic and infection) were observed with a median of 3 cycles being administered (range: 1-3). Disease response showed 4/14 with CR, 2/14 with PR, and 1/14 with SD for an overall response rate (ORR) of 43%. Conclusions: These preliminary results demonstrate that the combination of topotecan, ifosfamide, and carboplatin (TIC) is feasible, induces a ≥40% ORR in relapsed/refractory patients, and warrants further study in children with CNS and solid tumors. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline
The combination of docetaxel and cisplatin has shown promising results in anthracycline-pretreated patients with advanced breast cancer, but with substantial toxicity. The efficacy and safety in anthracycline-naive patients has not been evaluated. Between October 2003 and January 2006, we enrolled 39 patients. None had undergone chemotherapy for metastatic disease or been exposure to adjuvant anthracycline-based regimens earlier. Eligibility criteria included: histologically proven metastatic cancer; WHO performance status (PS) 0-2; and adequate hematological, hepatic and renal function. Docetaxel (70 mg/m) and cisplatin (50 mg/m) were administered every 3 weeks until the patient either refused to continue, or progression, or even unacceptable toxicity occurred. Tumor response was assessed every three cycles. One patient was withdrawn from response analysis because of toxicity. Thirty-eight patients had a complete tumor assessment. Median age was 50 years (range, 28-63); 5.1% had a WHO of PS of 0; 87% a PS of 1; 7.7% a PS of 2; in 69%, two or more organs were involved. A total of 291 cycles (range, 1-9) were administered. Three complete responses and 27 partial responses (intent-to-treat response rate 30/39=76.9%) resulted; disease remained stable in six patients and two had disease progression. Grade III/IV toxicities included diarrhea in 10.2%, asthenia/fatigue in 2.5%, mucositis in 5.1% and neutropenia in 87.3% of patients. Seven patients developed febrile neutropenia (17.9%). The median time to progression was 11.2 months; the timespan was not sufficient to track the median survival. Docetaxel/cisplatin is an active regimen with acceptable toxicity in the first-line treatment of metastatic breast cancer, but it is not sufficiently promising as a standard. Further randomized study is warranted.
Abstract Objective Grief reactions in bereaved caregivers of cancer patients have been identified individually as distinct prolonged grief disorder (PGD)—and major depressive disorder (MDD)—symptom trajectories, but no research has examined whether the patterns of change (trajectories) for PGD and MDD symptoms synchronize during bereavement. We conducted a secondary analysis study to investigate the construct distinctiveness of PGD and MDD by simultaneously identifying and examining similarities and differences between bereaved caregivers' PGD‐ and depressive‐symptom trajectories from immediately post‐loss through 2 years later. Methods PGD and depressive symptoms were measured for 849 cancer patients' caregivers over their first 2 years of bereavement using 11 grief‐symptom items of the prolonged grief‐13 scale (PG‐11) and the center for epidemiologic studies‐depression (CES‐D) scale, respectively. PGD‐ and depressive‐symptom trajectories were identified using latent class growth analysis with continuous latent‐class indicators (total PG‐11 and CES‐D scores). Concordance of caregiver participants' membership in PGD‐ and depressive‐symptom trajectories was examined by a percentage and a kappa value. Results Five distinct symptom trajectories were identified for both PGD and MDD, with four shared trajectories (endurance, transient‐reaction, resilience, and prolonged‐symptomatic) having different prevalence rankings. Nonetheless, unique trajectories were identified for PGD (potential recurrence) and depressive symptoms (chronically distressed), respectively. Concordance between membership in PGD‐ and depressive‐symptom trajectories was moderate (61.3%, kappa [95% CI]: 0.49 [0.44, 0.53]). Conclusion PGD and MDD are related but distinct constructs indicated by the unique trajectories identified for each, different prevalence rankings for PGD‐ and depressive‐symptom trajectories, and moderate concordance between membership in PGD‐ and depressive‐symptom trajectories, respectively.
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