Plant-based milk: unravel the changes of the antioxidant index during processing and storage - a review.

As a nutrient rich emulsion extracted from plant materials, plant-based milk (PBM) has been the latest trend and hot topic in the food industry due to the growing awareness of consumers toward plant-based products in managing the environmental (carbon footprint and land utility), ethical (animal well-fare) and societal (health-conscious) issues. There have been extensive studies and reviews done to discuss the distinct perspective of PBM including its production, health effects and market acceptance. However, not much has been emphasized on the valuable antioxidants present in PBM which is one of the attributes making them stand apart from dairy milk. The amounts of antioxidants in PBM are important. They offered tremendous health benefits in maintaining optimum health and reducing the risk of various health disorders. Therefore, enhancing the extraction of antioxidants and preserving their activity during production and storage is important. However, there is a lack of a comprehensive review of how these antioxidants changes in response to different processing steps involved in PBM production. Presumably, antioxidants in PBM could be potentially lost due to thermal degradation, oxidation or leaching into processing water. Hence, this paper aims to fill the gaps by addressing an extensive review of how different production steps (germination, roasting, soaking, blanching, grinding and filtration, and microbial inactivation) affect the antioxidant content in PBM. In addition, the effect of different microbial inactivation treatments (thermal or non-thermal processing) on the alteration of antioxidant in PBM was also highlighted. This paper can provide useful insight for the industry that aims in selecting suitable processing steps to produce PBM products that carry with them a health declaration.

Ammonium-free medium is critical for regeneration of shoot tips of the endangered species Pogostemon yatabeanus cryopreserved using droplet-vitrification.

BACKGROUND: Pogostemon yatabeanus, synonym Dysophylla yatabeana, (Labiatae) is an endangered wild species in Korea. It has has a limited natural habitat and requires urgent conservation measures. OBJECTIVE: To develop an efficient cryopreservation protocol using in vitro shoot tips to complement traditional conservation approaches in case seeds are unavailable, or insufficient in number for conservation programs. MATERIALS AND METHODS: Node-cutting induced shoot tips of in vitro plants were produced and cryopreserved using a droplet-vitrification method following improvements in preculture, osmoprotection, vitrification solution (VS) and regrowth treatments. The starting protocol included preculture with 10% sucrose for 31 h, followed by osmoprotection with C4-35% (17.5% glycerol + 17.5% sucrose) for 40 min, and cryoprotection with A3-80% (33.3% glycerol + 13.3% DMSO + 13.3% EG + 20.1% sucrose) for 60 min on ice, cooling and warming using aluminum foil strips, and regrowth in MS hormone-free medium. RESULTS: Shoot tips of Pogostemon yatabeanus were sensitive to the osmotic stress evidenced by low survival after step-wise preculture with 17.5% sucrose and cryopreservation without osmoprotection. Among VS tested, including PVS2, PVS3 and their alternatives, A3-80% on ice for 60 min resulted in the highest post-cryopreservation survival (80%) and regeneration (20%). Post-cryopreservation regeneration significantly improved (up to 73%) by incubation of cryopreserved shoot tips on ammonium-free medium followed by GA X3-containing medium and medium without growth regulators. CONCLUSION: Cryopreservation of in vitro shoot tips using droplet-vitrification was developed as a complementary conservation approach for D. yatabeana. Adjustment of medium composition during the recovery stage was important for regeneration of healthy plants from both cryoprotected-control and cryopreserved shoot tips.

The risk of developing major depression among individuals with subthreshold depression: a systematic review and meta-analysis of longitudinal cohort studies.

BACKGROUND: Studies have consistently shown that subthreshold depression is associated with an increased risk of developing major depression. However, no study has yet calculated a pooled estimate that quantifies the magnitude of this risk across multiple studies. METHODS: We conducted a systematic review to identify longitudinal cohort studies containing data on the association between subthreshold depression and future major depression. A baseline meta-analysis was conducted using the inverse variance heterogeneity method to calculate the incidence rate ratio (IRR) of major depression among people with subthreshold depression relative to non-depressed controls. Subgroup analyses were conducted to investigate whether IRR estimates differed between studies categorised by age group or sample type. Sensitivity analyses were also conducted to test the robustness of baseline results to several sources of study heterogeneity, such as the case definition for subthreshold depression. RESULTS: Data from 16 studies (n = 67 318) revealed that people with subthreshold depression had an increased risk of developing major depression (IRR = 1.95, 95% confidence interval 1.28-2.97). Subgroup analyses estimated similar IRRs for different age groups (youth, adults and the elderly) and sample types (community-based and primary care). Sensitivity analyses demonstrated that baseline results were robust to different sources of study heterogeneity. CONCLUSION: The results of this study support the scaling up of effective indicated prevention interventions for people with subthreshold depression, regardless of age group or setting.

Prevalence of Clostridium difficile infection and colonization in a tertiary hospital and elderly community of North-Eastern Peninsular Malaysia.

Little is known about Clostridium difficile infection (CDI) in Asia. The aims of our study were to explore (i) the prevalence, risk factors and molecular epidemiology of CDI and colonization in a tertiary academic hospital in North-Eastern Peninsular Malaysia; (ii) the rate of carriage of C. difficile among the elderly in the region; (iii) the awareness level of this infection among the hospital staffs and students. For stool samples collected from hospital inpatients with diarrhea (n = 76) and healthy community members (n = 138), C. difficile antigen and toxins were tested by enzyme immunoassay. Stool samples were subsequently analyzed by culture and molecular detection of toxin genes, and PCR ribotyping of isolates. To examine awareness among hospital staff and students, participants were asked to complete a self-administered questionnaire. For the hospital and community studies, the prevalence of non-toxigenic C. difficile colonization was 16% and 2%, respectively. The prevalence of CDI among hospital inpatients with diarrhea was 13%. Out of 22 C. difficile strains from hospital inpatients, the toxigenic ribotypes 043 and 017 were most common (both 14%). In univariate analysis, C. difficile colonization in hospital inpatients was significantly associated with greater duration of hospitalization and use of penicillin (both P < 0·05). Absence of these factors was a possible reason for low colonization in the community. Only 3% of 154 respondents answered all questions correctly in the awareness survey. C. difficile colonization is prevalent in a Malaysian hospital setting but not in the elderly community with little or no contact with hospitals. Awareness of CDI is alarmingly poor.

Role of the dorsolateral prefrontal cortex in context-dependent motor performance.

Context-dependent motor performance is a phenomenon in which people perform better in the environmental context where they originally practised a task. Some animal and computer simulation studies have suggested that context-dependent performance may be associated with neural activation of the dorsolateral prefrontal cortex (DLPFC). This study aimed to determine the role of the DLPFC in context-dependent motor performance by perturbing the neural processing of the DLPFC with repetitive transcranial magnetic stimulation (rTMS) in healthy adults. Thirty healthy adults were recruited into the Control, rTMS DLPFC and rTMS Vertex groups. The participants practised three finger sequences associated with a specific incidental context (a coloured circle and a location on the computer screen). One day following practice, the rTMS groups received 1 Hz rTMS prior to the testing conditions in which the sequence-context associations remained the same as practice (SAME) or changed (SWITCH). All three groups improved significantly over practice on day 1. The second day testing results showed that the DLPFC group had a significantly lower decrease in motor performance under the SWITCH condition than the Control and Vertex groups. This finding suggests a specific role of the DLPFC in context-dependent motor performance.

Preventing depression and anxiety in young people: a review of the joint efficacy of universal, selective and indicated prevention.

Depression and anxiety (internalizing disorders) are the largest contributors to the non-fatal health burden among young people. This is the first meta-analysis to examine the joint efficacy of universal, selective, and indicated preventive interventions upon both depression and anxiety among children and adolescents (5-18 years) while accounting for their co-morbidity. We conducted a systematic review of reviews in Medline, PsycINFO and the Cochrane Library of Systematic Reviews, from 1980 to August 2014. Multivariate meta-analysis examined the efficacy of preventive interventions on depression and anxiety outcomes separately, and the joint efficacy on both disorders combined. Meta-regressions examined heterogeneity of effect according to a range of study variables. Outcomes were relative risks (RR) for disorder, and standardized mean differences (Cohen's d) for symptoms. One hundred and forty-six randomized controlled trials (46 072 participants) evaluated universal (children with no identified risk, n = 54) selective (population subgroups of children who have an increased risk of developing internalizing disorders due to shared risk factors, n = 45) and indicated prevention (children with minimal but detectable symptoms of an internalizing disorder, n = 47), mostly using psychological-only strategies (n = 105). Reductions in internalizing disorder onset occurred up to 9 months post-intervention, whether universal [RR 0.47, 95% confidence interval (CI) 0.37-0.60], selective (RR 0.61, 95% CI 0.43-0.85) or indicated (RR 0.48, 95% CI 0.29-0.78). Reductions in internalizing symptoms occurred up to 12 months post-intervention for universal prevention; however, reductions only occurred in the shorter term for selective and indicated prevention. Universal, selective and indicated prevention interventions are efficacious in reducing internalizing disorders and symptoms in the short term. They might be considered as repeated exposures in school settings across childhood and adolescence. (PROSPERO registration: CRD42014013990.).

A novel HLA-B*27 allele, B*27:138, identified by sequence-based typing.

HLA-B*27:138 differs from B*27:06 by two nucleotide changes in exon 3.

Stevens-Johnson syndrome and toxic epidermal necrolysis in patients with malignancies.

BACKGROUND: Malignancy is known to be associated with an increased mortality rate in patients with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, risk factors contributing to the poor prognosis of patients with SJS/TEN with malignancies remain undefined. OBJECTIVES: To explore the potential involvement of malignancy and its related factors contributing to the poor outcome of SJS/TEN, in a retrospective study. METHODS: In total 517 patients with SJS/TEN were enrolled. Forty-seven who sustained various types of malignancies were analysed for numerous malignancy-related factors, including cancer types, clinical stages and chemotherapies given or not before the onset of SJS/TEN. RESULTS: We found that the mortality rate of patients with SJS/TEN with malignancies was higher than that of patients without malignancies (32%, 15/47 vs. 8·5%, 40/470, respectively) (P < 0·001). The use of phenytoin was significantly higher in the malignancy group. The presence of hepatocellular carcinoma (80%, four of five; P < 0·001; odds ratio 43) and colorectal cancer (67%, two of three; P = 0·022; odds ratio 21·5) significantly increased the death rate of patients with SJS/TEN, whereas lung cancer and urothelial carcinoma did not. Patients who had received ongoing or recent chemotherapy showed higher mortality than those without chemotherapy (P = 0·022; odds ratio 4·95). Furthermore, among the 47 patients with SJS/TEN with malignancies, lower serum albumin, haemoglobin and platelet count were detected in the deceased patients than in the surviving patients before the onset of SJS/TEN. CONCLUSIONS: Our results suggest that several factors related to malignancies, such as specific cancer types, chemotherapy and malnutrition, may contribute to poor prognosis in patients with malignancies developing SJS/TEN.

Systemic lupus erythematosus is not a risk factor for poor outcomes after total hip and total knee arthroplasty.

OBJECTIVES: Historically, arthroplasty in systemic lupus erythematosus (SLE) patients has been less successful than for patients with osteoarthritis (OA). It is not known if SLE remains an independent risk factor for poor arthroplasty outcomes or if other factors, such as avascular necrosis (AVN), continue to play a role. METHODS: A case-control study using data from a single-institution arthroplasty registry compared SLE total hip arthroplasty (THA) and total knee arthroplasty (TKA) with OA controls matched by age, gender and presence of AVN. Baseline, two-year administrative and self-report data, and diagnosis leading to arthroplasty were evaluated. RESULTS: A total of 54 primary SLE THA and 45 primary SLE TKA were identified from May 2007 through June 2011. AVN was present in 32% of SLE THA and no TKA. SLE THA had worse preoperative WOMAC pain (42.5 vs. 52.7; p = 0.01) and function (38.8 vs. 48.0; p = 0.05) compared with OA. However, at two years there was no difference in WOMAC pain (91.1 vs. 92.1; p = 0.77) or WOMAC function (86.4 vs. 90.8; p = 0.28). SLE TKA were similar to OA in both preoperative pain (42.6 vs. 48.4; p = 0.14) and function (42.1 vs. 46.8; p = 0.30) and two-year pain (85.7 vs. 88.6; p = 0.50) and function (83.7 vs. 85.1; p = 0.23). Compared to OA, SLE THA and TKA patients had more renal failure (14% vs. 1%; p = 0.007) and hypertension (52% vs. 29%; p = 0.009). In a multivariate linear regression, SLE was not predictive of either poor pain or poor function. CONCLUSIONS: While SLE patients have more comorbidities than OA, and SLE THA have worse preoperative pain and function compared with OA controls, SLE was not an independent risk factor for poor short-term pain or function after either hip or knee arthroplasty.

Variation in hospital caesarean section rates and obstetric outcomes among nulliparae at term: a population-based cohort study.

OBJECTIVE: To explore the variation in hospital caesarean section (CS) rates for nulliparous women, to determine whether different case-mix, labour and delivery, and hospital factors can explain this variation and to examine the association between hospital CS rates and outcomes. DESIGN: Population-based cohort study. SETTING: New South Wales, 2009-2010. POPULATION: Nulliparous women with singleton cephalic live births at term. METHODS: Random effect multilevel logistic regression models using linked hospital discharge and birth data. MAIN OUTCOME MEASURES: Prelabour and intrapartum CS rates following spontaneous labour or labour induction; maternal and neonatal severe morbidity rates. RESULTS: Of 67 239 nulliparous women, 4902 (7.3%) had a prelabour CS, 39 049 (58.1%) laboured spontaneously, and 23 288 (34.6%) had labour induced. Overall, there were 18 875 (28.1%) CSs, with labour inductions twice as likely to result in an intrapartum CS compared with women with a spontaneous onset of labour (34.0% versus 15.5%). After adjusting for differences in case-mix, labour and delivery, and hospital factors, the overall variation in CS rates decreased by 78% for prelabour CSs, 52% for intrapartum CSs following spontaneous labour and 9% following labour induction. Adjusting for labour and delivery practices increased the unexplained variation in intrapartum CSs. The adjusted rates of severe maternal and neonatal morbidity were not significantly different across CS rate quintile groups, except for women in spontaneous labour, where the hospitals in the lowest CS quintile had the lowest neonatal morbidity rate. CONCLUSIONS: Differences in clinical practice were substantial contributors to variation in intrapartum CS rates. Our findings suggest that CS rates in some hospitals could be lowered without adversely affect pregnancy outcomes.

Disruption of the gastroesophageal junction by central obesity and waist belt: role of raised intra-abdominal pressure.

Obesity is a major reason for the recent increase in incidence of reflux disease and cancers at the distal esophagus and gastroesophageal junction (GOJ) and is mediated through a rise in the intra-abdominal pressure (IAP) but the exact mechanisms are unclear. Raised IAP from obesity and with application of waist belt produces mechanical distortion of the GOJ through formation of partial hiatus hernia. Even though there is no trans-sphincteric acid reflux, there is increased ingress of acid into the lower sphincter (intra-sphincteric reflux) as a consequence of raised IAP. In addition, short segment acid reflux is more evident in obese subjects with a belt on. Acid pocket is also enlarged in hiatus hernia, and acts as a reservoir of acid available to reflux whenever the sphincter fails. Above mechanisms may explain the common occurrence of cardiac lengthening and inflammation found in asymptomatic obese subjects. The inflamed cardia is also immunohistochemically similar to non-intestinal Barrett's mucosa, which is of etiological importance for cancers at the GOJ. Interventions that can reduce the mechanical distortion and acid exposure at the GOJ, including diet, exercise, drugs, sphincter augmentation therapy, and surgery, are clinically relevant in the treatment of gastroesophageal reflux disease but more data are needed whether if these strategies are also effective in preventing cancer. As a conclusion, raised IAP produces silent mechanical disruption of the GOJ, which may explain the high occurrence of cancers in this region and it is potentially reversible with early interventions.

Age and gender differences in the relationship between hepatitis C infection and all stages of Chronic kidney disease.

Chronic kidney disease (CKD) is a worldwide health issue with heavy economic burden. Chronic hepatitis C virus (HCV) infection is a common cause of CKD, which can significantly impact the progression and mortality among patients with CKD. The prevalence of both illnesses is high in Taiwan. A multicentre and population-based cross-sectional study including 24 642 subjects was conducted to explore the association of HCV infection with the prevalence and severity of CKD. The measurements of metabolic parameters, eGFR and CKD stages were compared between subjects with HCV seropositivity and seronegativity. The analyses of association between HCV infection with CKD stages and evaluation of potential risk factors of CKD were performed by gender and age (≤ and >45 years). HCV-seropositive subjects accounted for 6.9% and had a significantly older age. The prevalence of CKD increased in those with HCV seropositivity (16.5%). Significantly higher prevalence of CKD stages ≥3 in HCV-seropositive subjects was noticed (7.8%). Age (>45 year), male gender, alcohol drinking, hypertension, creatinine and HCV infection were the significant factors associated with the presence of CKD. HCV seropositivity was an independent risk factor of developing CKD and associated with an increased risk of having CKD of all stages. The higher prevalence of earlier stage of CKD warrants longitudinal studies with frequent testing on renal function and sufficient duration to determine the changes of eGFR over time. Implementation of effective treatment intervention is also required for these subjects to prevent the progression of CKD to late stages.

Association between waist-to-height ratio and chronic kidney disease in the Taiwanese population.

BACKGROUND: Obesity, metabolic syndrome (MS) and chronic kidney disease (CKD) are all becoming increasingly prevalent worldwide. Body mass index (BMI) has traditionally been employed to identify overweight or obese individuals, yet multiple studies have yielded conflicting results when BMI was used to evaluate the association between obesity and CKD. AIMS: The purpose of this large, population-based, multicentre study was to evaluate the associations of BMI and waist-to-height ratio (WHtR) with CKD. METHODS: A retrospective study of 41,600 subjects who had physical examinations from January 2010 to December 2011 was performed. Data such as life style and habits were collected by interviews, and systolic and diastolic blood pressure (SBP and DBP), height, body weight, waist circumference, total cholesterol (TC), high-density lipoproteins (HDL), triglycerides (TG), fasting blood glucose and creatinine levels were measured. The association of these factors with CKD was analysed by use of SPSS 15.0 software. RESULTS: The key findings of this study were that WHtR but not BMI was an independent predictor of CKD. Additionally, SBP was a predictor of CKD in males and females, and TG and TC were independent predictors of CKD in females. Such measures are components of MS, which may also be associated with the development of CKD. CONCLUSION: WHtR appears to be a better measure of central obesity than BMI, and is an easy-to-use, noninvasive tool for identifying individuals at risk of developing obesity-related CKD, and potentially also MS-related CKD.

Alopecia associated with strontium ranelate use in a 62-year-old woman.

Strontium ranelate is an effective drug that was developed for treating osteoporosis. Here, we report the case of a 62-year-old woman who developed headache and diffuse scalp hair loss 1 week after receiving strontium ranelate treatment for osteoporosis. The treatment was subsequently stopped because of the intractable headache. Nevertheless, the patient continued to lose hair for 6 weeks following treatment discontinuation. Histopathological analysis of scalp tissues revealed anagen effluvium. The patient's hair started regrowing slowly 2 months after treatment with strontium ranelate was discontinued.

School-based socio-emotional learning programs to prevent depression, anxiety and suicide among adolescents: a global cost-effectiveness analysis.

AIMS: Preventing the occurrence of depression/anxiety and suicide during adolescence can lead to substantive health gains over the course of an individual person's life. This study set out to identify the expected population-level costs and health impacts of implementing universal and indicated school-based socio-emotional learning (SEL) programs in different country contexts. METHODS: A Markov model was developed to examine the effectiveness of delivering universal and indicated school-based SEL programs to prevent the onset of depression/anxiety and suicide deaths among adolescents. Intervention health impacts were measured in healthy life years gained (HLYGs) over a 100-year time horizon. Country-specific intervention costs were calculated and denominated in 2017 international dollars (2017 I$) under a health systems perspective. Cost-effectiveness findings were subsequently expressed in terms of I$ per HLYG. Analyses were conducted on a group of 20 countries from different regions and income levels, with final results aggregated and presented by country income group - that is, low and lower middle income countries (LLMICs) and upper middle and high-income countries (UMHICs). Uncertainty and sensitivity analyses were conducted to test model assumptions. RESULTS: Implementation costs ranged from an annual per capita investment of I$0.10 in LLMICs to I$0.16 in UMHICs for the universal SEL program and I$0.06 in LLMICs to I$0.09 in UMHICs for the indicated SEL program. The universal SEL program generated 100 HLYGs per 1 million population compared to 5 for the indicated SEL program in LLMICs. The cost per HLYG was I$958 in LLMICS and I$2,006 in UMHICs for the universal SEL program and I$11,123 in LLMICs and I$18,473 in UMHICs for the indicated SEL program. Cost-effectiveness findings were highly sensitive to variations around input parameter values involving the intervention effect sizes and the disability weight used to estimate HLYGs. CONCLUSIONS: The results of this analysis suggest that universal and indicated SEL programs require a low level of investment (in the range of I$0.05 to I$0.20 per head of population) but that universal SEL programs produce significantly greater health benefits at a population level and therefore better value for money (e.g., less than I$1,000 per HLYG in LLMICs). Despite producing fewer population-level health benefits, the implementation of indicated SEL programs may be justified as a means of reducing population inequalities that affect high-risk populations who would benefit from a more tailored intervention approach.

Definitive Stereotactic Body Radiation Therapy in Early-Stage Solitary Hepatocellular Carcinoma: An Australian Multi-Institutional Review of Outcomes.

AIMS: Standard curative options for early-stage, solitary hepatocellular carcinoma (HCC) are often unsuitable due to liver dysfunction, comorbidities and/or tumour location. Stereotactic body radiation therapy (SBRT) has shown high rates of local control in HCC; however, limited data exist in the treatment-naïve, curative-intent setting. We report the outcomes of patients with solitary early-stage HCC treated with SBRT as first-line curative-intent therapy. MATERIALS AND METHODS: A multi-institutional retrospective study of treatment-naïve patients with Barcelona Clinic Liver Cancer stage 0/A, solitary ≤5 cm HCC, Child-Pugh score (CPS) A liver function who underwent SBRT between 2010 and 2019 as definitive therapy. The primary end point was freedom from local progression. Secondary end points were progression-free survival, overall survival, rate of treatment-related clinical toxicities and change in CPS >1. RESULTS: In total, 68 patients were evaluated, with a median follow-up of 20 months (range 3-58). The median age was 68 years (range 50-86); 54 (79%) were men, 62 (91%) had cirrhosis and 50 (74%) were Eastern Cooperative Oncology Group 0. The median HCC diameter was 2.5 cm (range 1.3-5) and the median prescription biologically effective dose with a tumour a/b ratio of 10 Gy (BED10) was 93 Gy (interquartile range 72-100 Gy). Two-year freedom from local progression, progression-free survival and overall survival were 94.3% (95% confidence interval 86.6-100%), 59.5% (95% confidence interval 46.3-76.4%) and 88% (95% confidence interval 79.2-97.6%), respectively. Nine patients (13.2%) experienced grade ≥2 treatment-related clinical toxicities. A rise >1 in CPS was observed in six cirrhotic patients (9.6%). CONCLUSION: SBRT is an effective and well-tolerated option to consider in patients with solitary, early-stage HCC. Prospective, randomised comparative studies are warranted to further refine its role as a first-line curative-intent therapy.

Identification of differentially expressed genes according to chemosensitivity in advanced ovarian serous adenocarcinomas: expression of GRIA2 predicts better survival.

BACKGROUND: The purpose of this study was to identify genes that are differentially expressed in chemosensitive serous papillary ovarian carcinomas relative to those expressed in chemoresistant tumours. METHODS: To identify novel candidate biomarkers, differences in gene expression were analysed in 26 stage IIIC/IV serous ovarian adenocarcinomas (12 chemosensitive tumours and 14 chemoresistant tumours). We subsequently investigated the immunohistochemical expression of GRIA2 in 48 independent sets of advanced ovarian serous carcinomas. RESULTS: Microarray analysis revealed a total of 57 genes that were differentially expressed in chemoresistant and chemosensitive tumours. Of the 57 genes, 39 genes were upregulated and 18 genes were downregulated in chemosensitive tumours. Five differentially expressed genes (CD36, LIFR, CHL1, GRIA2, and FCGBP) were validated by quantitative real-time PCR. The expression of GRIA2 was validated at the protein level by immunohistochemistry, and patients with GRIA2 expression showed a longer progression-free and overall survival (P=0.051 and P=0.031 respectively). CONCLUSIONS: We found 57 differentially expressed genes to distinguish between chemosensitive and chemoresistant tumours. We also demonstrated that the expression of GRIA2 among the differentially expressed genes provides better prognosis of patients with advanced serous papillary ovarian adenocarcinoma.