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Sustainability science research conducted with Indigenous collaborators must be Indigenous-led and achieve impacts that are grounded in local values and priorities, both for ethical reasons and to achieve more robust outcomes. However, there has been limited focus on determining how best to evaluate the way research is used, shared and created to adaptively solve complex sustainable issues facing Indigenous lands. In this paper, we outline a collaborative and adaptive approach for conducting Indigenous-led evaluations of sustainability research and show how this approach was applied to evaluate cross-cultural knowledge co-production practice and impact in Australia’s jointly managed and World Heritage-listed Kakadu National Park. As part of an Indigenous-led research project, indicators were co-developed by Indigenous and non-Indigenous research team members to monitor the health of the knowledge-sharing and co-production practices that underpinned the design, management and success of the project’s research activities. The evaluations focused on determining whether research activities were providing negotiated benefits for local Indigenous people; helping to restore and protect agreed values in priority areas; and supporting Indigenous-led collaborative knowledge sharing and research practices. In Kakadu, we show how the Indigenous-led design of the research evaluation empowered the usability and benefits of knowledge which was negotiated, shared and co-created. The approach shows how sustainability science can be evaluated by Indigenous leaders to test if and how research practice and impact is responding to their priorities for their traditional estates.

PurposeDuring the early SARS-CoV-2 (COVID-19) pandemic outbreak, the Center for Disease Control and Prevention (CDC) stated masks “may not protect the wearer, but it may keep the wearer from spreading the virus to others”. Health officials revised mask guidelines to include both the wearer and others, but contradiction became a focal point for online debate and credibility. While revised policies eventually became adopted by the public, there was loss time and lives during this critical stage. This study investigates collectivist messaging on public policy support.Design/methodology/approachCOVID-19 public policy hypocrisy was defined as the gap between supporting community policies while rejecting policies more likely to impact the individual. United States participants (N = 1,605) completed questionnaires. Moderated mediation analysis was conducted using SPSS PROCESS.FindingsThose high on collectivism and high on global personal impact associated with lower COVID-19 public policy hypocrisy. These individuals indicated consistent support for community and individual policies, likely requiring personal sacrifices. Indirect conditional effects of lower conscientiousness associated with higher hypocrisy among those collectivistic.Originality/valueParticipants evaluated preference to original public safety ads, representative of basic societal and individual benefits. Those higher on collectivism preferred societal “we” versus individual “me” public safety ads. Implications discuss benefits of personal and communal public health messaging in an individualistic society so businesses can reopen. Entrepreneurs experienced major economic setbacks that effective public health policies could have mitigated.

The scholarship and practice of responsibly navigating the disruptive possibilities of new technologies has yet to fully consider Indigenous worldviews. We draw on Indigenous-led research in northe...

Background/Aim: The majority of targeted therapies are focused on BRCA mutations, homologous recombination repair deficiency, and BRCA wild-type platinum-sensitive recurrent ovarian cancer. There is a growing need for platinum-resistant patients without BRCA mutations. Herein, we conducted a phase II multicenter study evaluated the efficacy and safety of bortezomib plus pegylated liposomal doxorubicin (PLD) in patients with BRCA wild-type platinum-resistant recurrent ovarian cancer (NCT03509246). Patients and Methods: Ovarian cancer patients with wild-type BRCA who experienced platinum-resistant recurrence after three or less prior treatment cycles from three Institutions were included. All patients received bortezomib, 1.3 mg/m(2) subcutaneously (days 1, 4, 8, and 11), and PLD, 40 mg/m(2) intravenously (day 4), every 4 weeks. The primary endpoint was best objective response rate (ORR), and secondary endpoints included disease control rate, progression-free survival (PFS), overall survival, and safety. Targeted sequencing was performed to evaluate biomarkers and their potential association with response to treatment. Results: The trial was terminated after 23 patients were recruited because of slow accrual. The median follow-up was 29.5 months. The overall ORR was 8.7% (2/23); partial response was observed in two patients. The median duration of response was 10.5 months, and median PFS was 2.9 months. Treatment-related adverse events (TRAEs) of grade 3/4 were reported in 43.5% of patients. One patient who exhibited TRAEs discontinued treatment. However, grade 4/5 TRAEs were not observed. Mutations in TP53 and CDK12 were detected in 67% (14/21) and 24% (12/21) of patients, respectively. Two patients with partial response harbored mutations in genes related to homologous recombination repair deficiency, including BRCA2, ATM, and CDK12. Conclusion: The combination of bortezomib and PLD was well tolerated; however, antitumor activity was not sufficient to warrant further investigation in ovarian cancer.

Political marketing campaigns expend enormous effort each campaign season to influence voter turnout. This cyclical democratic process and nonstop news cycle foster an environment of media malaise. Voter pessimism undercuts participation through increased perceived alikeness among ballot options. Differentiation and consolidation theory describe the voting decision process as reconciling rational and irrational information. Voters seek out differences to decide among presented options. More politically interested voters are more likely to vote. Counterintuitively, higher political organizational avocational interest is related to higher perceived alikeness. Across three studies, higher perceived alikeness of parties, candidates, and issues was related to a lower likelihood to vote (LTV). Conditional voting ineffectual beliefs exacerbated these indirect effects on LTV. In a saturated marketing atmosphere with massive spending during each election cycle, we discuss implications to influence LTV based on results.

We aimed to evaluate the association between days alive and out of hospital (DAOH) and mortality at 15 days after a hip replacement. From March 2010 to June 2020, we identified 5369 consecutive adult patients undergoing hip replacements and estimated DAOH at 15, 30, 60, and 90 days after surgery. After excluding 13 patients who died within 15 days after surgery, receiver operating characteristic (ROC) curves were then generated to evaluate predictabilities for each follow-up period. We compared the mortality risk according to the estimated thresholds of DAOH at 15 days after hip replacement. ROC analysis revealed areas under the curve of 0.862, 0.877, 0.906, and 0.922 for DAOH at 15, 30, 60, and 90 days after surgery, respectively. The estimated threshold of DAOH during the 15 postoperative days was 6.5. Patients were divided according to this threshold, and propensity score matching was conducted. In a propensity score-matched population with 864 patients in each group, the risk of mortality increased in patients with a lower DAOH 15 (2.8% vs. 8.1%; hazard ratio [HR] = 3.96; 95% confidence interval [CI]: 2.24–6.99; p < 0.001 for one-year mortality, 5.2% vs. 13.0%; HR = 3.82; 95% CI: 2.33–6.28; p < 0.001 for three-year mortality, and 5.9% vs. 15.6%; HR = 3.07; 95% CI: 2.04–4.61; p < 0.001 for five-year mortality). In patients undergoing a hip replacement, DAOH at 15 days after surgery was shown to be associated with increased mortality. DAOH at 15 days may be used as a valid outcome measure for hip replacement.

Ovarian cancer is mostly diagnosed at advantaged stages due to the lack of early diagnostic biomarkers. The common metastasis pattern is characterized by peritoneal dissemination with a formation of malignant ascites. Extracellular vesicles (EVs) are emerging as promising clinical biomarkers in liquid biopsy. Here, we aimed to investigate robust liquid biopsy-based EV miRNA biomarkers for ovarian cancer diagnosis and metastasis regulation. EVs were isolated from malignant ascites and plasma of ovarian cancer patients as well as the benign control counterparts of patients with benign gynecologic diseases. EV small RNA sequencing identified a panel of eight miRNAs (miR-1246, miR-1290, miR-483, miR-429, miR-34b-3p, miR-34c-5p, miR-145-5p, miR-449a) based on dysregulated miRNAs overlapped in the ascites and plasma subset. The ovarian cancer EV miRNA (OCEM) signature developed based on these eight miRNAs demonstrated high diagnostic accuracy in our in-house dataset and multiple public datasets across diverse clinical samples (blood, tissue and urine). In addition, malignant ascites-derived EVs could significantly facilitate the aggressive property of ovarian cancer cells and boost the growth of ascites-derived organoids. Notably, miR-1246 and miR-1290 shuttled in malignant ascites-derived EVs were identified to promote the invasion and migration of ovarian cancer cells through regulating a common target RORα.

ObjectiveEvidence on recurrence patterns after bevacizumab in epithelial ovarian cancer is still insufficient. The aim of this study was to evaluate recurrence patterns after treatment with bevacizumab as second-line treatment in patients with platinum-sensitive, recurrent epithelial ovarian cancer.MethodsWe retrospectively identified epithelial ovarian cancer patients who relapsed ≥6 months after primary treatment consisting of surgery and platinum-based chemotherapy between January 2008 and June 2019. Only those who received platinum-based doublet chemotherapy with bevacizumab or without bevacizumab as second-line treatment were included (n=192). To adjust confounders, we conducted 1:2 propensity score matching for platinum-free interval and secondary debulking surgery. Imaging studies were performed to locate newly developed or enlarged pre-existing tumors. Recurrence patterns were compared between bevacizumab users (study group) and non-users (control group).ResultsAfter matching, the study group (n=52) and control group (n=104) showed similar baseline clinicopathologic characteristics including platinum-free interval (median (range) 15.3 (6.2–87.3) vs 14.0 (6.2–143.5) months; p=0.29) and patient age at the time of first recurrence (median (range) 55.5 (33.7–72.4) vs 55.0 (35.7–84.2) years; p=0.56). Initially, FIGO stage III disease was the most common in both two groups (55.8% vs 66.3%; p=0.20). Bevacizumab users were less likely to develop disease recurrence in the retroperitoneal lymph nodes (13.5% vs 34.6%; p=0.005), pelvis (17.3% vs 35.6%; p=0.018), and abdomen (40.4% vs 61.5%; p=0.012). However, no difference in distant metastasis was observed between the groups (23.1% vs 24.0%; p>0.99). Multivariate analyses adjusting for stage, histologic type, grade, platinum-free interval, and secondary debulking surgery revealed that the use of bevacizumab significantly reduced risks of nodal (adjusted HR (aHR) 0.24; 95% CI 0.10 to 0.56; p=0.001), pelvic (aHR 0.32; 95% CI 0.15 to 0.68; p=0.003), and abdominal recurrences (aHR 0.43; 95% CI 0.26 to 0.71; p=0.001). Nevertheless, use of bevacizumab did not influence risk of distant metastasis (aHR 0.70; 95% CI 0.35 to 1.40; p=0.32).ConclusionsIn patients with platinum-sensitive, recurrent epithelial ovarian cancer, second-line chemotherapy with bevacizumab is associated with reduced risks of nodal, pelvic, and abdominal recurrences, but similar risks of distant metastases.

Preoperative high-sensitivity cardiac troponin (hs-cTn) above the 99th-percentile upper reference limit (URL) is associated with mortality after noncardiac surgery. This study aimed to evaluate whether preoperative hs-cTn concentrations above the lowest limit of detection (LOD) but below the 99th-percentile URL can predict mortality after noncardiac surgery.From January 2010 to April 2019, a total of 12,415 noncardiac surgical patients with preoperative hs-cTn I below the 99th-percentile URL were enrolled. The patients were divided into two groups according to preoperative hs-cTn I concentration: (1) [hs-cTn] below the LOD (6 ng/L), and (2) mildly elevated [hs-cTn] but below the 99th-percentile URL (40 ng/L). The primary outcome was 30-day mortality. Of the 12,415 patients enrolled, 7958 (64.1%) were in the LOD group whereas 4457 (35.9%) were in the mild elevation group. The incidence of 30-day mortality was significantly greater in the mild elevation group (2.1% vs. 4.0% hazard ratio [HR] 1.73; 95% confidence interval [CI] 1.39–2.16; p

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Purpose This study aimed to present a single institutional experience with BRCA1/2 gene tests and the effects of pathogenic mutations in epithelial peritoneal, ovarian, and fallopian tube cancer (POFTC) on survival outcomes. Materials and methods We identified patients with epithelial POFTCs who underwent BRCA1/2 gene testing by either germline or somatic methods between March 2007 and March 2020. Based on the BRCA1/2 test results, patients were divided into BRCA mutation and wild-type groups, followed by comparisons of clinicopathologic characteristics and survival outcomes after primary treatment. Results The annual number of POFTC patients who received BRCA1/2 gene tests increased gradually. In total, 511 patients were included and BRCA1/2 mutations were observed in 143 (28.0%). Among 57 patients who received both germline and somatic tests, three (5.3%) showed discordant results from the two tests. Overall, no differences in progression-free survival (PFS; p=0.467) and overall survival (p=0.641) were observed between the BRCA mutation and wild-type groups; however, multivariate analyses identified BRCA1/2 mutation as an independent favorable prognostic factor for PFS (adjusted hazard ratio [aHR], 0.765; 95% confidence interval [CI], 0.593 to 0.987; p=0.040). In 389 patients with International Federation of Gynecology and Obstetrics stage III-IV, different results were shown depending on primary treatment strategy: while BRCA1/2 mutation significantly improved PFS in the subgroup of neoadjuvant chemotherapy (aHR, 0.619; 95% CI, 0.385 to 0.995; p=0.048), it did not affect patient PFS in the subgroup of primary debulking surgery (aHR, 0.759; 95% CI, 0.530 to 1.089; p=0.135). Conclusion BRCA1/2 mutations are frequently observed in patients with epithelial POFTCs, and such patients showed better PFS than did those harboring wild-type BRCA1/2.

Objective To investigate the prognostic significance of programmed cell death ligand-1 (PD-L1) in ovarian cancer. Methods PubMed, Embase, and Cochrane Library databases were searched to identify studies that examined the prognostic significance of immunohistochemically assessed PD-L1 expression in histologically confirmed ovarian cancer. Eleven studies on PD-L1 expression involving 1,296 patients with ovarian cancer were included in this meta-analysis. Pooled hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were analyzed. Relationship between PD-L1 expression, and overall survival (OS) or progression-free survival (PFS) among patients with ovarian cancer was assessed. Subgroup analysis was performed based on the race, histologic type, and tumor International Federation of Gynecology and Obstetrics stage to evaluate the source of heterogeneity. Begg's Funnel plot and Egger's linear test were used to evaluate publication bias. Random-effects model was implemented when significant between-study heterogeneity (I2>50%) was observed. Results We found no correlation between PD-L1 expression, and OS (HR, 1.13; 95% CI, 0.95-1.36; I2=78%) or PFS (HR, 1.07; 95% CI, 0.88-1.30; I2=75%) in ovarian cancer. Subgroup analyses showed that higher PD-L1 expression was associated with poor OS in non-Asian patients with ovarian cancer (HR, 1.26; 95% CI, 1.07-1.481; I2=59%). We found that upregulated PD-L1 expression to be a positive predictor for OS in serous ovarian cancer (HR, 0.98; 95% CI, 0.76-1.26; I2=74%) and a negative predictor for OS in non-serous ovarian cancer (HR, 1.29; 95% CI, 1.03-1.61; I2=64%) Furthermore, high PD-L1 expression was found to be a negative predictor for PFS of patients with non-serous ovarian cancer (HR, 1.12; 95% CI, 0.96-1.29; I2=37%). Conclusion Our meta-analysis suggests that PD-L1 expression is not associated with patient risk for ovarian cancer.

The aim of this study was to report the long-term outcomes after sacrocolpopexy (SCP) with or without transobturator tape (TOT). We conducted a planned secondary analysis of a prospective, observational study comparing urinary outcomes in women who underwent SCP with or without TOT based on the results of a prolapse-reduction stress test. Patients were enrolled between November 2008 and December 2011 and were followed up 5 years after surgery. The primary outcomes were 5-year success rates for stress urinary incontinence (SUI) and pelvic organ prolapse (POP) estimated using the Kaplan–Meier method. SUI success was defined as a negative cough stress test, no bothersome SUI symptoms, and no additional anti-incontinence surgery. POP success was defined as no vaginal bulge symptoms, no apical descent greater than one-third of the total vaginal length or anterior or posterior vaginal wall prolapse beyond the hymen, and no retreatment for prolapse. Of 240 women enrolled, 175 (73%) completed 5 years of follow-up. The estimated SUI success rate was 91.1% in the TOT group and 56.5% in the no TOT group (difference, 34.6%; 95% confidence interval, 24.1 to 45.1). The estimated POP success rate was 90.0% in the TOT group and 92.9% in the no TOT group (difference, −2.9%; 95% confidence interval, −10.7 to 4.9). The advantage of concomitant TOT for SUI after SCP that was seen at 2 years remained at 5 years. Long-term POP failure rates after SCP are low and not affected by concomitant TOT.

The etiological mechanisms of the genetic underpinnings of developmental language disorder (DLD) are unknown, in part due to the behavioral heterogeneity of the disorder's manifestations. In this study, we explored an association between the SETBP1 gene (18q21.1), revealed in a genome-wide association study of DLD in a geographically isolated population, and brain network-based endophenotypes of functional intracortical coherence between major language-related brain areas. We analyzed electroencephalogram (EEG) data from thirty-nine children (twenty-three with, sixteen without DLD) aged 7.17-15.83 years acquired during an auditory picture-word matching paradigm. Variation at a single nucleotide polymorphism in the intronic region of the SETBP1 gene, rs8085464, explained 19% of the variance in intracortical network cohesion (p = .00478). This suggests that the development of these brain networks might be partially associated with the variation in SETBP1.

This chapter introduces a cultural dimension of family life showing the contrast between modern, Western, nuclear families and the multi-generational family patterns that exist in many countries in Asia. In Singapore and Hong Kong, for example, grandparents often care for young children whilst parents work to raise funds for family existence and to buy a home at the same time as building a career. This cultural context gives children opportunities to interact over extended periods of time with grandparents in a natural and authentic way. The mother-tongue language of the family will be learned by children and extended through meaningful language dialogues. The presence of technology and emerging community resources in the selected Asia-Pacific areas of the present chapter (i.e., Australia, Singapore, and Hong Kong) also provide grandparents with wider opportunities to strengthen family bonds and increase chances that some cultural traditions can be carried over into the next generation. In return, children enjoy a close and respectful relationship with grandparents, while grandparents’ physical, psychological, and social well- being are fostered through this reciprocal relationship. Unique stories shared by grandparents and the contemporary trend show that in a rapidly changing world, intergenerational bonds with children may preserve precious cultural traditions in significant ways.

Prior research has identified both the contribution that people make to nature and the contribution that nature makes to people (by enhancing wellbeing) - with clear conceptual models to describe the interactions. Prior research has also made a clear case for incorporating insights from multiple perspectives and knowledge systems when seeking to better understand this interactive system. What is lacking, is guidance on how to operationalise some of these ideas to provide bespoke advice to environmental managers. Arguably, we have an adequate, albeit imperfect, understanding of how to operationalise (measure, value and/or otherwise account for) some parts of the conceptual model. There is, for example, abundant literature that describes different ways of valuing Ecosystem services, and a growing body of literature that describes and quantifies the ecological benefits of various stewardship activities, which will subsequently also generate an indirect benefit to people (since improved ecological conditions will improve Ecosystem services). In comparison, we know relatively little about the way in which stewardship activities directly benefit people - and it is on this gap that our paper focuses. We partially fill that knowledge gap by first reaching out to and learning from some of Australia's First Nations People. Key learnings underscore the inter-connectedness of the system, and the need for resource managers to not only monitor the extent and condition of natural system but also the extent and condition of an inextricably connected human system, in addition to the human-nature interactions. We clearly identify ways in which those insights can be used to improve and extend accounting frameworks, such as SEEA Ecosystem Accounts developed by the United Nations that are often used by natural resource managers. In so doing, we generate new insights about Indigenous stewardship (Caring for Country) and methods of accounting for and monitoring stewardship activities. As such, our work provides a practical illustration of one way to populate conceptual models with 'real world' data that also incorporates different world views, to support decision makers for improved social and environmental outcomes.

High-sensitivity cardiac troponin I (hs-cTnI) is a widely used biomarker to identify ischemic chest pain in the Emergency Department (ED), but the clinical impact on emergency coronary artery bypass grafting (eCABG) remains undetermined. We aimed to evaluate the clinical impact of hs-cTnI measured at the ED by comparing outcomes of eCABG in patients with non–ST-segment–elevation acute coronary syndrome (NSTE-ACS) which comprises unstable angina (UA) and non–ST-segment–elevation myocardial infarction (NSTEMI). From January 2012 to March 2016, 242 patients undergoing eCABG were grouped according to serum hs-cTnI level in the ED. The primary endpoint was major cardiovascular cerebral event (MACCE) defined as a composite of all-cause death, myocardial infarction, repeat revascularization, and stroke. The incidence of each MACCE composite, in addition to postoperative complications such as acute kidney injury, reoperation, atrial fibrillation, and hospital stay duration were also compared. Patients were divided into two groups: UA [p-value = 0.032). In-hospital stay was also longer in the NSTEMI group (9.0 days vs. 15.4 days, p-value = 0.008). ECABG for UA and NSTEMI patients showed comparable outcomes, but hs-cTnI elevation at the ED may be associated with immediate postoperative complications.

Background To determine whether additional chemotherapy after concurrent chemoradiation (CCRT) improves survival outcomes in patients with early cervical cancer who undergo radical hysterectomy (RH). Methods We included high- or intermediate-risk patients from two institutions, with 2009 FIGO stage IB–IIA, who underwent primary RH and pelvic lymphadenectomy between January 2007 and June 2020, and had completed adjuvant CCRT. Survival outcomes were compared between patients who received additional chemotherapy (study group) and those who did not (control group). Results A total of 198 patients were included in this analysis. The study (n = 61) and control groups (n = 137) had similar patient age, histologic cancer type, 2009 FIGO stage, and tumor size. However, minimally invasive surgery was performed less frequently in the study group than in the control group (19.7% vs. 46.0%, P P = 0.001). In survival analyses, no differences in the disease-free survival (DFS; P = 0.539) and overall survival (OS; P = 0.121) were observed between the groups. Multivariate analyses adjusting for surgical approach and other factors revealed that additional chemotherapy was not associated with DFS (adjusted HR, 1.149; 95% CI, 0.552–2.391; P = 0.710) and OS (adjusted HR, 1.877; 95% CI, 0.621–5.673; P = 0.264). The recurrence patterns did not differ with additional chemotherapy. Consistent results were observed in a subset of high-risk patients (n = 139). Conclusions Additional chemotherapy after CCRT might not improve survival outcomes in patients with early cervical cancer who undergo RH.

Background The Laparoscopic Approach to Cervical Cancer trial and Surveillance, Epidemiology, and End Results program database study demonstrated that minimally invasive radical hysterectomy was inferior to abdominal radical hysterectomy in terms of disease recurrence and survival. Among risk factors related to poor prognosis after minimally invasive surgery (MIS), tumour spillage during intracorporeal colpotomy became a significant issue. Thus, we designed this trial to evaluate the efficacy and safety of minimally invasive radical hysterectomy using an endoscopic stapler for early-stage cervical cancer. Methods This trial is a prospective, multi-centre, open-label, single-arm, non-inferiority phase II study. The nine organisations will participate in this trial after the approval of the institutional review board. Major eligibility criteria include women aged 20 years or older with cervical cancer stage IB1 squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma according to the revised 2009 FIGO staging system who will undergo type B2 or C hysterectomy by MIS. The primary endpoint is the 4.5-year disease-free survival (DFS) rate between abdominal radical hysterectomy and MIS using an endoscopic stapler. For calculating the sample size, we hypothesised that the 4.5-year DFS rate after MIS using an endoscopic stapler is assumed to be the same after abdominal radical hysterectomy at 90.9%, and the non-inferiority margin was 7.2%. When we consider a three-year accrual and 4.5-year follow-up, at least 13 events must happen, requiring a total of 111 patients assuming a statistical power of 80% and the one-tailed test of 5% significance. A total of 124 patients is needed, considering a drop-out rate of 10%. Discussion We expect intracorporeal colpotomy using an endoscopic stapler may prevent tumour spillage during MIS for stage IB1 cervical cancer, showing a comparable prognosis with abdominal radical surgery. Trial registration ClinicalTrials.gov; NCT04370496; registration date, May 2020.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is known to show uneven distribution and penetration of agents based on the nozzle position. Thus, this study aimed to investigate the ideal nozzle position for maximizing drug delivery during PIPAC.We created 2 cm-, 4 cm- and 8 cm-ex vivo models according to the distance from the bottom to the nozzle using 21×15×16 cm-sized sealable plastic boxes. After each set of eight normal peritoneal tissues from swine were placed at eight different points (A to H), we performed PIPAC, compared the methylene blue staining areas to investigate the distribution, and estimated the depth of concentrated diffusion (DCD) and the depth of maximal diffusion (DMD) of doxorubicin.In terms of distribution, the 4 cm- and 8 cm-ex vivo models showed more stained faces than the 2 cm-ex vivo model. Regarding the penetration depth, the 4 cm- ex vivo model showed the highest DCD (mean; 244.1 μm, C; 105.1 μm, D; 80.9 μm, E; 250.2 μm, G; 250.2 μm, H) and DMD (mean; 174.8 μm, D; 162.7 μm, E; 511.7 μm, F; 522.2 μm, G; 528.1 μm, H) in the most points corresponding to 62.5%.The ideal nozzle position during PIPAC might be halfway between the nozzle inlet and the bottom in the ex vivo model.

Simple Summary Despite the importance of vaccination against Coronavirus disease 2019 (COVID-19) in cancer patients, general vaccine uptake rates among cancer patients are known to be low. Here, we tried to investigate the attitude and acceptance rates for COVID-19 vaccine in cancer patients and identify predictive factors for vaccination that could be modified to promote vaccine uptake rates. Between February and April 2021, a total of 1001 cancer patients from five institutions participated in a paper-based survey, consisting of 58 items over six domains. Among the respondents, 61.8% were willing to receive the COVID-19 vaccine. Along with the previously reported predictors for COVID-19 vaccination, including male gender, older age, and influenza vaccination history, we distinctively found that patient’s disease status and health status (absence of cancer recurrence, time since cancer diagnosis over 5 years, and higher EuroQol Visual Analogue Scale scores) were associated with higher acceptance rates of vaccination. Furthermore, physician’s recommendations effectively reduced patient’s vaccine hesitancy. Abstract Considering the high morbidity and mortality of Coronavirus disease 2019 (COVID-19) in patients with malignancy, they are regarded as a priority for COVID-19 vaccination. However, general vaccine uptake rates among cancer patients are known to be lower than in their healthy counterparts. Thus, we aimed to investigate the attitude and acceptance rates for the COVID-19 vaccine in cancer patients and identify predictive factors for vaccination that could be modified to increase vaccine uptake rates, via a paper-based survey (58 items over six domains). A total of 1001 cancer patients participated in this nationwide, multicenter survey between February and April 2021. We observed that 61.8% of respondents were willing to receive the COVID-19 vaccine. Positive predictive factors found to be independently associated with vaccination were male gender, older age, obesity, previous influenza vaccination history, absence of cancer recurrence, time since cancer diagnosis over 5 years, and higher EuroQol Visual Analogue Scale scores. Along with the well-known factors that are positively correlated with vaccination, here, we report that patients’ disease status and current health status were also associated with their acceptance of the COVID-19 vaccination. Moreover, 91.2% of cancer patients were willing to be vaccinated if their attending physicians recommend it, indicating that almost 30% could change their decision upon physicians’ recommendation. Unlike other factors, which are unmodifiable, physicians’ recommendation is the single modifiable factor that could change patients’ behavior. In conclusion, we firstly report that Korean cancer patients’ acceptance rate of the COVID-19 vaccination was 61.8% and associated with disease status and current health status. Physicians should play a major role in aiding cancer patients’ decision-making concerning COVID-19 vaccines.

Background To assess the rate of germline BRCA gene tests in epithelial ovarian cancer (EOC) patients and uptake of post-test risk management strategies in BRCA1/2-mutated patients. Methods Institutional databases were searched to identify patients who were diagnosed with epithelial ovarian, fallopian tube, or primary peritoneal cancer (EOC) between 2009 and 2019 in two academic hospitals. Retrospective review on medical records was performed to collect clinico-pathologic variables, including performance of germline BRCA gene test and its results, as well as conduct of breast cancer screening tests and cascade testing. If annual mammography +/− breast ultrasonography was performed, it was considered that regular breast cancer surveillance was done. Results A total of 840 women with EOC were identified during the study period. Of these, 454 patients (54.0%) received BRCA gene testing and 106 patients (106/454, 23.3%) were positive for BRCA1/2 mutations. The rate of BRCA tests has markedly increased from 25.8% in 2009-2012 to 62.7% in 2017-2019. Among the 93 patients with BRCA1/2 mutation without previous personal breast cancer history, 20 patients (21.5%) received annual mammography with or without breast ultrasonography for regular surveillance. Among the 106 BRCA1/2-mutated EOC patients, cascade testing on family members was performed only in 13 patients (12.3%). Conclusion Although BRCA1/2 gene tests have been substantially expanded, the uptake of post-test risk management strategies, including breast cancer screening for BRCA1/2-mutated patients and cascade testing for family members, has remained low. Strategies to increase its uptake and education about the importance of post-test risk managements are needed., Graphical Abstract

Simple Summary An increased risk of relapse and death from minimally invasive radical hysterectomy has been reported in some patients with early cervical cancer. Thus, the development of an intuitive and precise decision-aid tool, which estimates recurrence and mortality rates by surgical approach, is necessary. To develop models predicting survival outcomes according to the surgical approach, we collected clinicopathologic and survival data of patients with 2009 FIGO stage IB cervical cancer who underwent a radical hysterectomy. Using only variables that could be obtained preoperatively, we developed various models predicting the probability of 5-year progression-free survival and overall survival. Among them, hybrid ensemble models, combined with logistic regression and multiple machine learning models, achieved the best predictive performance. The developed models are expected to help physicians’ and patients’ decision making related to the surgical approach for primary radical hysterectomy. Abstract We purposed to develop machine learning models predicting survival outcomes according to the surgical approach for radical hysterectomy (RH) in early cervical cancer. In total, 1056 patients with 2009 FIGO stage IB cervical cancer who underwent primary type C RH by either open or laparoscopic surgery were included in this multicenter retrospective study. The whole dataset consisting of patients’ clinicopathologic data was split into training and test sets with a 4:1 ratio. Using the training set, we developed models predicting the probability of 5-year progression-free survival (PFS) and overall survival (OS) with tenfold cross validation. The developed models were validated in the test set. In terms of predictive performance, we measured the area under the receiver operating characteristic curve (AUC) values. The logistic regression models comprised of preoperative variables yielded AUCs of 0.679 and 0.715 for predicting 5-year PFS and OS rates, respectively. Combining both logistic regression and multiple machine learning models, we constructed hybrid ensemble models, and these models showed much improved predictive performance, with 0.741 and 0.759 AUCs for predicting 5-year PFS and OS rates, respectively. We successfully developed models predicting disease recurrence and mortality after primary RH in patients with early cervical cancer. As the predicted value is calculated based on the preoperative factors, such as the surgical approach, these ensemble models would be useful for making decisions when choosing between open or laparoscopic RH.

Purpose This study investigated the uptake rate of risk-reducing salpingo-oophorectomy (RRSO) and surgical outcomes of germline BRCA1/2 mutation carriers at Seoul National University Hospital (SNUH). Materials and Methods We examined the records of 824 women who underwent germline BRCA1/2 gene testing at SNUH between 2005 and 2020. Among them, we identified women with a pathogenic mutation on either the BRCA1 or the BRCA2 gene, and excluded ovarian cancer patients. Characteristics of participants who underwent RRSO (RRSO group) were compared to those who did not (non-RRSO group). Surgical outcomes and pathologic results were investigated in the RRSO group. Results There were 117 BRCA1/2 mutation carriers included in the analysis. The uptake rate of RRSO was 70.1% (82/117). Older age (mean: 48.8 years vs. 42.1 years; p=0.002) and higher employment rate (65.9% vs. 14.3%; p

Background: This study investigated the uptake rate of risk-reducing salpingo-oophorectomy (RRSO) and surgical outcomes of germline BRCA1/2 mutation carriers at Seoul National University Hospital (SNUH). We examined records of 824 women who underwent germline BRCA1/2 gene testing at SNUH between 2005 and 2020. Among them, we identified women with a pathogenic mutation on either the BRCA1 or the BRCA2 gene and excluded ovarian cancer patients. Characteristics of participants who underwent RRSO (RRSO group) were compared to those who did not (non-RRSO group). Surgical outcomes and pathologic results were investigated in the RRSO group.Results: There were 117 BRCA1/2 mutation carriers included in this analysis. The uptake rate of RRSO was 70.1% (82/117). Older age (mean: 48.8 vs. 42.1 years; P = 0.002) and higher employment rate (65.9% vs. 14.3%; P < 0.001) were observed in the RRSO group than in the non-RRSO group. However, no differences in other factors such as personal and family history of breast cancer were observed between the two groups. In the RRSO group, the median time interval between the genetic test and RRSO was 10.0 months, and there were three (3.7%) incidental cases of high-grade serous carcinoma. However, one patient in the non-RRSO group developed primary peritoneal cancer after 103.8 months of surveillance.Conclusions: The uptake rate of RRSO in BRCA1/2 mutation carriers was about 70%. Considering incidental cancer cases in women without abnormal findings on preoperative evaluation, it would be recommended to perform RRSO soon after the genetic test.

Background Preventing Loss of Independence through Exercise (PLIÉ) is an integrative group movement program developed for adults with mild-to-moderate dementia attending day programs. However, many older adults with dementia ultimately require assistance with their activities of daily living and become residents in nursing homes or other long-term care facilities with their complex comorbidities and unique needs. We conducted a post-implementation evaluation of PLIÉ at a San Francisco Veterans Affairs (VA) nursing home to assess reach and effectiveness among residents, staff, and family members who participated in ≥ 1 PLIÉ class from 9/2018 to 6/2019. Methods Post-implementation number of classes offered and mean attendance; anonymous satisfaction surveys (5-point Likert scales); qualitative content analysis of open-ended survey responses and clinical progress notes. Results Forty-five PLIÉ classes were offered over 9 months. Residents attended an average of 13 ± 12 classes with an average class size of 14 residents, 4 staff members, and 2 family members. Most survey respondents rated the program overall as “very good” or “excellent” (100 % residents, n = 15; 87 % staff, n = 14; 100 % family members, n = 8). Respondents reported improvements in themselves and/or others in four domains: (1) physical, (2) psychological, (3) social, and (4) cognitive. Physical improvements among veterans included mobility, strength, and energy. Psychological improvements included feelings of happiness/well-being, enjoyment, and self-empowerment. Social improvements included connection, social skills, and social support. Cognitive improvements included engagement, communication ability, and focus/attention. Responses were similar among resident, staff, and family member surveys and clinical progress notes. Participants frequently reported improvements in multiple domains (e.g., “The veterans are more alert and engaged, many are smiling and laughing.”). Negative comments were primarily related to logistics, suggesting that the class occur more frequently. Conclusions PLIÉ was successfully implemented in a VA nursing home with high attendance and satisfaction among residents, staff, and family members. Participants reported clinically meaningful physical, psychological, social, and cognitive benefits. Other long-term care facilities could potentially benefit from implementing PLIÉ to increase quality of life in residents with dementia.

High-grade serous ovarian cancer (HGSOC) is one of the deadliest cancers that can occur in women. This study aimed to investigate the molecular characteristics of HGSOC through integrative analysis of multi-omics data. We used fresh-frozen, chemotherapy-naïve primary ovarian cancer tissues and matched blood samples of HGSOC patients and conducted next-generation whole-exome sequencing (WES) and RNA sequencing (RNA-seq). Genomic and transcriptomic profiles were comprehensively compared between patients with germline BRCA1/2 mutations and others with wild-type BRCA1/2. HGSOC samples initially divided into two groups by the presence of germline BRCA1/2 mutations showed mutually exclusive somatic mutation patterns, yet the implementation of high-dimensional analysis of RNA-seq and application of epithelial-to-mesenchymal (EMT) index onto the HGSOC samples revealed that they can be divided into two subtypes, homologous recombination repair (HRR)-activated type and mesenchymal type. Patients with mesenchymal HGSOC, characterized by the activation of the EMT transcriptional program, low genomic alteration and diverse cell-type compositions, exhibited significantly worse overall survival than did those with HRR-activated HGSOC (p = 0.002). In validation with The Cancer Genome Atlas (TCGA) HGSOC data, patients with a high EMT index (≥the median) showed significantly worse overall survival than did those with a low EMT index (&lt, the median) (p = 0.030). In conclusion, through a comprehensive multi-omics approach towards our HGSOC cohorts, two distinctive types of HGSOC (HRR-activated and mesenchymal) were identified. Our novel EMT index seems to be a potential prognostic biomarker for HGSOC.

Pharmacological and genetic evidence support a role for an involvement of the dopamine D2-receptor (D2-R) in the pathophysiology of schizophrenia. Previous molecular imaging studies have suggested lower levels of D2-R in thalamus, but results are inconclusive. The objective of the present study was to use improved methodology to compare D2-R density in whole thalamus and thalamic subregions between first-episode psychosis patients and healthy controls. Differences in thalamocortical connectivity was explored based on the D2-R results. 19 antipsychotic-naive first-episode psychosis patients and 19 age- and sex-matched healthy controls were examined using high-resolution Positron Emission Tomography (PET) and the high-affinity D2-R radioligand [