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Background/aimThe 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 methodsOvarian 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/m2 subcutaneously (days 1, 4, 8, and 11), and PLD, 40 mg/m2 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.ResultsThe 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.ConclusionThe combination of bortezomib and PLD was well tolerated; however, antitumor activity was not sufficient to warrant further investigation in ovarian cancer.

BackgroundPreventing 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.MethodsPost-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.ResultsForty-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.ConclusionsPLIÉ 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.

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 = 0.00478). This suggests that the development of these brain networks might be partially associated with the variation in "SETBP1."