Aging in Place and 'The Little Things': Prioritizing Mobile Health and Social Care in Rural Communities.

Older adults are more frequently wanting to age in place. Governments are seeking cost-effective and efficient methods of supporting aging populations. Older adults who want to stay in their homes for as long as possible encounter multiple barriers, including struggling to maintain their homes, inadequate levels of social and healthcare support, and the lack of financial capacity to pay for home support services. The Mobile Seniors' Wellness Network (MSWN), a multi-disciplinary and person-centered mobile health and social support intervention study was designed to investigate and support aging in place for older adults living in rural New Brunswick, Canada. Secondary analysis of case notes and exit interviews using content analysis revealed concerns with the lack of affordable and mobile care services for vulnerable rural older adults. Older adults revealed that their needs include "the little things" rather than grand gestures or sweeping policies to age in place such as assistance with grounds and home maintenance, in addition to relational and person-centered health and social care in the home. Reliance on private service delivery and volunteer organizations can increase the likelihood that older adults will experience a breakdown of social support networks tied together loosely by friends, family, and their communities. When services are unattainable aging in place becomes an unreachable goal.

ACTION: a randomized phase 3 study of ONC201 (dordaviprone) in patients with newly diagnosed H3 K27M-mutant diffuse glioma.

BACKGROUND: H3 K27M-mutant diffuse glioma primarily affects children and young adults, is associated with a poor prognosis, and no effective systemic therapy is currently available. ONC201 (dordaviprone) has previously demonstrated efficacy in patients with recurrent disease. This phase 3 trial evaluates ONC201 in patients with newly diagnosed H3 K27M-mutant glioma. METHODS: ACTION (NCT05580562) is a randomized, double-blind, placebo-controlled, parallel-group, international phase 3 study of ONC201 in newly diagnosed H3 K27M-mutant diffuse glioma. Patients who have completed standard frontline radiotherapy are randomized 1:1:1 to receive placebo, once-weekly dordaviprone, or twice-weekly dordaviprone on 2 consecutive days. Primary efficacy endpoints are overall survival (OS) and progression-free survival (PFS); PFS is assessed by response assessment in neuro-oncology high-grade glioma criteria (RANO-HGG) by blind independent central review. Secondary objectives include safety, additional efficacy endpoints, clinical benefit, and quality of life. Eligible patients have histologically confirmed H3 K27M-mutant diffuse glioma, a Karnofsky/Lansky performance status ≥70, and completed first-line radiotherapy. Eligibility is not restricted by age; however, patients must be ≥10 kg at time of randomization. Patients with a primary spinal tumor, diffuse intrinsic pontine glioma, leptomeningeal disease, or cerebrospinal fluid dissemination are not eligible. ACTION is currently enrolling in multiple international sites.

Segmental Odontomaxillary Dysplasia: A Case Report and Review of the Literature.

Segmental odontomaxillary dysplasia (SOD) is a rare and unusual nonhereditary developmental disorder that affects one side of the maxilla, impacting the hard tissue, soft tissue, and dentition in the affected area. It most frequently presents with enlargement of the gingival and osseous tissue of the affected side and hypodontia of the involved quadrant. Cutaneous irregularities of the impacted area are also common. We report a case of SOD arising in the right maxilla of a three-year-old female. Our report and review of the literature highlight the clinical, radiographic, and histopathologic characteristics of SOD, as well as the management of patients and the proposed etiologies of its pathogenesis.

The oncolytic adenovirus Delta-24-RGD in combination with ONC201 induces a potent antitumor response in pediatric high-grade and diffuse midline glioma models.

BACKGROUND: Pediatric high-grade gliomas (pHGGs), including diffuse midline gliomas (DMGs), are aggressive pediatric tumors with one of the poorest prognoses. Delta-24-RGD and ONC201 have shown promising efficacy as single agents for these tumors. However, the combination of both agents has not been evaluated. METHODS: The production of functional viruses was assessed by immunoblotting and replication assays. The antitumor effect was evaluated in a panel of human and murine pHGG and DMG cell lines. RNAseq, the seahorse stress test, mitochondrial DNA content, and γH2A.X immunofluorescence were used to perform mechanistic studies. Mouse models of both diseases were used to assess the efficacy of the combination in vivo. The tumor immune microenvironment was evaluated using flow cytometry, RNAseq and multiplexed immunofluorescence staining. RESULTS: The Delta-24-RGD/ONC201 combination did not affect the virus replication capability in human pHGG and DMG models in vitro. Cytotoxicity analysis showed that the combination treatment was either synergistic or additive. Mechanistically, the combination treatment increased nuclear DNA damage and maintained the metabolic perturbation and mitochondrial damage caused by each agent alone. Delta-24-RGD/ONC201 cotreatment extended the overall survival of mice implanted with human and murine pHGG and DMG cells, independent of H3 mutation status and location. Finally, combination treatment in murine DMG models revealed a reshaping of the tumor microenvironment to a proinflammatory phenotype. CONCLUSIONS: The Delta-24-RGD/ONC201 combination improved the efficacy compared to each agent alone in in vitro and in vivo models by potentiating nuclear DNA damage and in turn improving the antitumor (immune) response to each agent alone.

Importance of specific vital signs in nurses' recognition and response to deteriorating patients: A scoping review.

AIM(S): To explore the published research related to nurses' documentation and use of vital signs in recognising and responding to deteriorating patients. DESIGN: Scoping review of international, peer-reviewed research studies. DATA SOURCES: Cumulative Index to Nursing and Allied Health Literature Complete, Medline Complete, American Psychological Association PsycInfo and Excerpta Medica were searched on 25 July 2023. REPORTING METHOD: Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. RESULTS: Of 3880 potentially eligible publications, 32 were included. There were 26 studies of nurses' vital sign documentation: 21 adults and five paediatric. The most and least frequently documented vital signs were blood pressure and respiratory rate respectively. Seven studies focused on vital signs and rapid response activation or afferent limb failure. Five studies of vital signs used to trigger the rapid response system showed heart rate was the most frequent and respiratory rate and conscious state were the least frequent. Heart rate was least likely and oxygen saturation was most likely to be associated with afferent limb failure (n = 4 studies). CONCLUSION: Despite high reliance on using vital signs to recognise clinical deterioration and activate a response to deteriorating patients in hospital settings, nurses' documentation of vital signs and use of vital signs to activate rapid response systems is poorly understood. There were 21studies of nurses' vital sign documentation in adult patients and five studies related to children. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: A deeper understanding of nurses' decisions to assess (or not assess) specific vital signs, analysis of the value or importance nurses place (or not) on specific vital sign parameters is warranted. The influence of patient characteristics (such as age) or the clinical practice setting, and the impact of nurses' workflows of vital sign assessment warrants further investigation. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.

ZNF827 is a single-stranded DNA binding protein that regulates the ATR-CHK1 DNA damage response pathway.

The ATR-CHK1 DNA damage response pathway becomes activated by the exposure of RPA-coated single-stranded DNA (ssDNA) that forms as an intermediate during DNA damage and repair, and as a part of the replication stress response. Here, we identify ZNF827 as a component of the ATR-CHK1 kinase pathway. We demonstrate that ZNF827 is a ssDNA binding protein that associates with RPA through concurrent binding to ssDNA intermediates. These interactions are dependent on two clusters of C2H2 zinc finger motifs within ZNF827. We find that ZNF827 accumulates at stalled forks and DNA damage sites, where it activates ATR and promotes the engagement of homologous recombination-mediated DNA repair. Additionally, we demonstrate that ZNF827 depletion inhibits replication initiation and sensitizes cancer cells to the topoisomerase inhibitor topotecan, revealing ZNF827 as a therapeutic target within the DNA damage response pathway.

Safety and pharmacokinetics of ONC201 (dordaviprone) administered two consecutive days per week in pediatric patients with H3 K27M-mutant glioma.

BACKGROUND: This study evaluated the safety and pharmacokinetics (PK) of oral ONC201 administered twice-weekly on consecutive days (D1D2) in pediatric patients with newly diagnosed DIPG and/or recurrent/refractory H3 K27M glioma. METHODS: This phase 1 dose-escalation and expansion study included pediatric patients with H3 K27M-mutant glioma and/or DIPG following ≥1 line of therapy (NCT03416530). ONC201 was administered D1D2 at 3 dose levels (DLs; -1, 1, and 2). The actual administered dose within DLs was dependent on weight. Safety was assessed in all DLs; PK analysis was conducted in DL2. Patients receiving once-weekly ONC201 (D1) served as a PK comparator. RESULTS: Twelve patients received D1D2 ONC201 (DL1, n = 3; DL1, n = 3; DL2, n = 6); no dose-limiting toxicities or grade ≥3 treatment-related adverse events occurred. PK analyses at DL2 (D1-250 mg, n = 3; D1-625 mg, n = 3; D1D2-250 mg, n = 2; D1D2-625 mg, n = 2) demonstrated variability in Cmax, AUC0-24, and AUC0-48, with comparable exposures across weight groups. No accumulation occurred with D1D2 dosing; the majority of ONC201 cleared before administration of the second dose. Cmax was variable between groups but did not appear to increase with D1D2 dosing. AUC0-48 was greater with D1D2 than once-weekly. CONCLUSIONS: ONC201 given D1D2 was well tolerated at all DLs and associated with greater AUC0-48.

Selective DRD2 antagonist and ClpP agonist ONC201 in a recurrent non-midline H3 K27M-mutant glioma cohort.

BACKGROUND: Diffuse midline glioma, H3 K27-altered (H3 K27M-altered DMG) are invariably lethal, disproportionately affecting the young and without effective treatment besides radiotherapy. The 2016 World Health Organization (WHO) Central Nervous System (CNS) Tumors Classification defined H3 K27M mutations as pathognomonic but restricted diagnosis to diffuse gliomas involving midline structures by 2018. Dordaviprone (ONC201) is an oral investigational small molecule, DRD2 antagonist, and ClpP agonist associated with durable responses in recurrent H3 K27M-mutant DMG. Activity of ONC201 in non-midline H3 K27M-mutant diffuse gliomas has not been reported. METHODS: Patients with recurrent non-midline H3 K27M-mutant diffuse gliomas treated with ONC201 were enrolled in 5 trials. Eligibility included measurable disease by Response Assessment in Neuro-Oncology (RANO) high-grade glioma, Karnofsky/Lansky performance score ≥60, and ≥90 days from radiation. The primary endpoint was overall response rate (ORR). RESULTS: Five patients with cerebral gliomas (3 frontal, 1 temporal, and 1 parietal) met inclusion. One complete and one partial response were reported by investigators. Blinded independent central review confirmed ORR by RANO criteria for 2, however, 1 deemed nonmeasurable and another stable. A responding patient also noted improved mobility and alertness. CONCLUSIONS: H3 K27M-mutant diffuse gliomas occasionally occur in non-midline cerebrum. ONC201 exhibits activity in H3 K27M-mutant gliomas irrespective of CNS location.

ONC201 (Dordaviprone) in Recurrent H3 K27M-Mutant Diffuse Midline Glioma.

PURPOSE: Histone 3 (H3) K27M-mutant diffuse midline glioma (DMG) has a dismal prognosis with no established effective therapy beyond radiation. This integrated analysis evaluated single-agent ONC201 (dordaviprone), a first-in-class imipridone, in recurrent H3 K27M-mutant DMG. METHODS: Fifty patients (pediatric, n = 4; adult, n = 46) with recurrent H3 K27M-mutant DMG who received oral ONC201 monotherapy in four clinical trials or one expanded access protocol were included. Eligible patients had measurable disease by Response Assessment in Neuro-Oncology (RANO) high-grade glioma (HGG) criteria and performance score (PS) ≥60 and were ≥90 days from radiation; pontine and spinal tumors were ineligible. The primary end point was overall response rate (ORR) by RANO-HGG criteria. Secondary end points included duration of response (DOR), time to response (TTR), corticosteroid response, PS response, and ORR by RANO low-grade glioma (LGG) criteria. Radiographic end points were assessed by dual-reader, blinded independent central review. RESULTS: The ORR (RANO-HGG) was 20.0% (95% CI, 10.0 to 33.7). The median TTR was 8.3 months (range, 1.9-15.9); the median DOR was 11.2 months (95% CI, 3.8 to not reached). The ORR by combined RANO-HGG/LGG criteria was 30.0% (95% CI, 17.9 to 44.6). A ≥50% corticosteroid dose reduction occurred in 7 of 15 evaluable patients (46.7% [95% CI, 21.3 to 73.4]); PS improvement occurred in 6 of 34 evaluable patients (20.6% [95% CI, 8.7 to 37.9]). Grade 3 treatment-related treatment-emergent adverse events (TR-TEAEs) occurred in 20.0% of patients; the most common was fatigue (n = 5; 10%); no grade 4 TR-TEAEs, deaths, or discontinuations occurred. CONCLUSION: ONC201 monotherapy was well tolerated and exhibited durable and clinically meaningful efficacy in recurrent H3 K27M-mutant DMG.

The Imipridone ONC213 Targets α-Ketoglutarate Dehydrogenase to Induce Mitochondrial Stress and Suppress Oxidative Phosphorylation in Acute Myeloid Leukemia.

Eradication of acute myeloid leukemia (AML) is therapeutically challenging; many patients succumb to AML despite initially responding to conventional treatments. Here, we showed that the imipridone ONC213 elicits potent antileukemia activity in a subset of AML cell lines and primary patient samples, particularly in leukemia stem cells, while producing negligible toxicity in normal hematopoietic cells. ONC213 suppressed mitochondrial respiration and elevated α-ketoglutarate by suppressing α-ketoglutarate dehydrogenase (αKGDH) activity. Deletion of OGDH, which encodes αKGDH, suppressed AML fitness and impaired oxidative phosphorylation, highlighting the key role for αKGDH inhibition in ONC213-induced death. ONC213 treatment induced a unique mitochondrial stress response and suppressed de novo protein synthesis in AML cells. Additionally, ONC213 reduced the translation of MCL1, which contributed to ONC213-induced apoptosis. Importantly, a patient-derived xenograft from a relapsed AML patient was sensitive to ONC213 in vivo. Collectively, these findings support further development of ONC213 for treating AML. SIGNIFICANCE: In AML cells, ONC213 suppresses αKGDH, which induces a unique mitochondrial stress response, and reduces MCL1 to decrease oxidative phosphorylation and elicit potent antileukemia activity. See related commentary by Boët and Sarry, p. 950.

Two-step light gradient boosted model to identify human west nile virus infection risk factor in Chicago.

West Nile virus (WNV), a flavivirus transmitted by mosquito bites, causes primarily mild symptoms but can also be fatal. Therefore, predicting and controlling the spread of West Nile virus is essential for public health in endemic areas. We hypothesized that socioeconomic factors may influence human risk from WNV. We analyzed a list of weather, land use, mosquito surveillance, and socioeconomic variables for predicting WNV cases in 1-km hexagonal grids across the Chicago metropolitan area. We used a two-stage lightGBM approach to perform the analysis and found that hexagons with incomes above and below the median are influenced by the same top characteristics. We found that weather factors and mosquito infection rates were the strongest common factors. Land use and socioeconomic variables had relatively small contributions in predicting WNV cases. The Light GBM handles unbalanced data sets well and provides meaningful predictions of the risk of epidemic disease outbreaks.

Immunohistochemistry Detection of Histone H3 K27M Mutation in Human Glioma Tissue.

The presence of the histone 3 (H3) K27M mutation in diffuse midline glioma has implications for diagnosis, prognosis, and treatment, making rapid and accurate H3 K27M characterization vital for optimal treatment. This study evaluated an immunohistochemical assay using a commercially available monoclonal anti-H3 K27M in human central nervous system tumors. H3 K27M-positive glioma specimens were obtained from clinical sites with prior H3 K27M testing using local methods; negative control glioblastoma tissue was obtained from a tissue library. Specimens were stained with a rabbit anti-H3 K27M monoclonal antibody; slides were evaluated for the proportion of H3 K27M-positive tumor cells and staining intensity by a board-certified pathologist. H-score was calculated for each sample. Sensitivity, specificity, accuracy, repeatability, and reproducibility were evaluated. Fifty-one central nervous system specimens were stained (H3 K27M, n=41; H3 wild type, n=10). All H3 K27M-mutant specimens had positive nuclear staining, and most specimens had an H-score ≥150 (31/40, 77.5%). No nuclear staining occurred in H3 wild-type specimens; all cores in the normal tissue microarray were negative. Results were 100% sensitive, specific, and accurate for H3 K27M detection relative to local methods. Repeatability and reproducibility analyses were 100%, with a high degree of concordance for staining intensity. H3 K27M antigen was stable for at least 12 months at ambient temperature. Immunohistochemistry using a commercially available anti-H3 K27M monoclonal antibody provides a highly sensitive, specific, and stable method of establishing H3 K27M status in human glioma; this method may facilitate diagnosis in cases where sequencing is not feasible or available.

Factors influencing tobacco use behaviour initiation - From the perspective of the Capability, Opportunity, Motivation- Behaviour (COM-B) Model.

Introduction: Non-communicable diseases such as ischemic heart disease, cancer, diabetes, and chronic respiratory diseases are the leading causes of death worldwide, and are associated with tobacco use. The ultimate goal of health professionals and researchers working to combat smoking's extremely harmful health effects is to prevent smoking initiation. Nearly 5500 new smokers are added each day, for a total of almost 2 million new smokers each year. The COM-B model's primary goal is to determine what needs to be done for a behaviour change to occur. Behaviour modification requires an understanding of the factors that drive behaviour. Aim: The current qualitative study intends to explore the factors affecting tobacco use initiation (TUI) using the COM-B model, given the relevance of investigating the factors affecting TUI and the model. Methods: The present qualitative study has used a directed content analysis approach. Seventeen participants who reported having started any kind of tobacco in the last six months were recruited in the study using a purposive sampling method to understand the factors affecting TUI. The data was collected through interviews, and all of the participants were from the Hyderabad-Karnataka region of Karnataka, India (a state which has been reported as having the highest prevalence of cigarette smoking in India). Results: Directed content analysis revealed six categories: psychological capabilities affecting TUI (lack of knowledge about adverse health effects of tobacco, behavioural control, and poor academic performance), physical capabilities affecting TUI (lack of better physical resilience), physical opportunities favouring TUI (tobacco advertisements, easy access of tobacco products, and favourite star smoke on screen), social opportunities favouring TUI (peer influence, tobacco use by parents, tradition of hospitality, tobacco use as a normal behaviour, and toxic masculinity), automatic motivation causal factors of TUI (affect regulation, risk taking behaviours and tobacco use for pleasure) and reflective motivation causal factors of TUI (perceived benefits of tobacco, risk perception, perceived stress, and compensatory health beliefs). Conclusion: Identifying the factors that influence TUI may help to limit or prevent people from smoking their first cigarette. Given the importance of preventing TUI, the findings of this study indicated the factors that influence TUI, which can be valuable in improving behaviour change processes.

Bilateral Exudative Retinal Detachments and Panuveitis in a Patient with Multiple Myeloma.

PURPOSE: To report a case of bilateral exudative retinal detachments and panuveitis in a patient with multiple myeloma (MM). CASE REPORT: A 54-year-old patient with non-proliferative diabetic retinopathy was referred with blurred vision and scotomas in both eyes (OU). Three months prior to the onset of ocular symptoms, he was diagnosed with systemic MM and was receiving chemotherapy. Clinical examination revealed best-corrected visual acuities of 20/80 OU, rare anterior chamber cell, 2+ vitreous cell, diffuse intraretinal hemorrhages, and exudative retinal detachments (RD). Optical coherence tomography of the macula showed central subretinal fluid with cystic intraretinal fluid OU. The findings were consistent with panuveitis and exudative RD in the setting of MM. He reported symptomatic improvement after plasmapheresis and oral prednisone initiation. CONCLUSION: Extensive, bilateral exudative RD and panuveitis are rare but potentially sight-threatening findings in patients with MM.

Variation in oxidative status, but not structural and physiological development, associated with changing ontogenetic environments.

Despite the potential for temporally dependent relationships between trait values and fitness (e.g. as juveniles approach life-stage transitions such as fledging), how developmental stage affects canalization (a measure of robustness to environmental variation) of morphological and physiological traits is rarely considered. To test the sensitivity of morphological and physiological traits to environmental variation in two developmental stages, we manipulated brood size at hatch in European starlings (Sturnus vulgaris) and cross-fostered chicks between enlarged and reduced broods approaching fledging. We measured body size (mass, tarsus, wing length) and physiological state (aerobic capacity, oxidative status) at asymptotic mass on day 15, then cross-fostered chicks between 'high' and 'low' quality environments and assessed the same traits again on day 20, after 5 days of pre-fledging mass recession. Chicks in reduced broods were heavier at asymptotic mass and had lower reactive oxygen metabolites than enlarged broods, whereas structural size, aerobic capacity and antioxidant capacity were unaffected by experimental brood size. The observed canalization of structural and physiological traits during early development was maintained after cross-fostering, during late development. However, in contrast to early development, antioxidant capacity approaching fledging appeared sensitive to environmental conditions, as trajectories varied by cross-fostering treatment. Elevated reactive oxygen metabolites observed after early development in enlarged brood chicks were maintained after cross-fostering, suggesting that canalized development in low-quality environments could produce oxidative costs that carry over between life stages, even when conditions improve. These data reveal trait-specific relationships between environmental conditions and development, and highlight how natal environment effects may vary by developmental stage.

Short-term toxicity studies of thallium (I) sulfate administered in drinking water to Sprague Dawley rats and B6C3F1/N mice.

Thallium is a heavy metal that is known to induce a broad spectrum of adverse health effects in humans including alopecia, neurotoxicity, and mortality following high dose acute poisoning events. Widespread human exposure to thallium may occur via consumption of contaminated drinking water; limited toxicity data are available to evaluate the corresponding public health risk. To address this data gap, the Division of Translational Toxicology conducted short-term toxicity studies of a monovalent thallium salt, thallium (I) sulfate. Thallium (I) sulfate was administered via dosed drinking water to time-mated Sprague Dawley (Hsd:Sprague Dawley® SD®) rats (F0 dams) and their offspring (F1) from gestation day (GD) 6 until up to postnatal day (PND) 28 at concentrations of 0, 3.13, 6.25, 12.5, 25, or 50 mg/L, and adult male and female B6C3F1/N mice for up to 2 weeks at concentrations of 0, 6.25, 12.5, 25, 50, or 100 mg/L. Rat dams in the 50 mg/L exposure group were removed during gestation, and dams and offspring in the 25 mg/L exposure group were removed on or before PND 0 due to overt toxicity. Exposure to thallium (I) sulfate at concentrations ≤ 12.5 mg/L did not impact F0 dam body weights, maintenance of pregnancy, littering parameters, or F1 survival (PND 4-28). However, in F1 pups, exposure to 12.5 mg/L thallium (I) sulfate resulted in decreased body weight gains relative to control rats and onset of whole-body alopecia. Measurement of thallium concentrations in dam plasma, amniotic fluid, fetuses (GD 18), and pup plasma (PND 4) indicated marked maternal transfer of thallium to offspring during gestation and lactation. Mice exposed to 100 mg/L thallium (I) sulfate were removed early due to overt toxicity, and mice exposed to ≥ 25 mg/L exhibited exposure concentration-related decreases in body weight. Lowest-observed-effect levels of 12.5 mg/L (rats) and 25 mg/L (mice) were determined based on the increased incidence of clinical signs of alopecia in F1 rat pups and significantly decreased body weights for both rats and mice.

A novel dopamine receptor D2 antagonist (ONC206) potentiates the effects of olaparib in endometrial cancer.

Poly ADP-ribose polymerase (PARP) inhibitors are effective therapies for cancer patients with homologous recombination (HR) deficient tumors. The imipridone ONC206 is an orally bioavailable dopamine receptor D2 antagonist and mitochondrial protease ClpP agonist that has anti-tumorigenic effects in endometrial cancer via induction of apoptosis, activation of the integrated stress response and modulation of PI3K/AKT signaling. Both PARP inhibitors and imipridones are being evaluated in endometrial cancer clinical trials but have yet to be explored in combination. In this manuscript, we evaluated the effects of the PARP inhibitor olaparib in combination with ONC206 in human endometrioid endometrial cancer cell lines and in a genetically engineered mouse model of endometrial cancer. Our results showed that simultaneous exposure of endometrial cancer cells to olaparib and ONC206 resulted in synergistic anti-proliferative effects and increased cellular stress and apoptosis in both cell lines, compared to either drug alone. The combination treatment also decreased expression of the anti-apoptotic protein Bcl-2 and reduced phosphorylation of AKT and S6, with greater effects compared to either drug alone. In the transgenic model of endometrial cancer, the combination of olaparib and ONC206 resulted in a more significant reduction in tumor weight in obese and lean mice compared to ONC206 alone or olaparib alone, together with a considerably decreased Ki-67 and enhanced H2AX expression in obese and lean mice. These results suggest that this novel dual therapy may be worthy of further exploration in clinical trials.

Multiplexed Long-Range Electrohydrodynamic Transport and Nano-Optical Trapping with Cascaded Bowtie Photonic Crystal Nanobeams.

Photonic crystal cavities with bowtie defects that combine ultrahigh Q and ultralow mode volume are theoretically studied for low-power nanoscale optical trapping. By harnessing the localized heating of the water layer near the bowtie region, combined with an applied alternating current electric field, this system provides long-range electrohydrodynamic transport of particles with average radial velocities of 30 µm/s towards the bowtie region on demand by switching the input wavelength. Once transported to a given bowtie region, synergistic interaction of optical gradient and attractive negative thermophoretic forces stably trap a 10 nm quantum dot in a potential well with a depth of 10 k_{B}T using a mW input power.