A multicenter phase Ia study of AbGn-107, a novel antibody-drug conjugate, in patients with advanced gastrointestinal cancer.

AbGn-107 is an antibody-drug conjugate directed against AG-7 antigen, a Lewis A-like glycol-epitope expressed in a variety of gastrointestinal (GI) malignancies. Based on promising antitumor activity of AbGn-107 in both in vitro and in vivo preclinical studies, we performed a GI cancer-specific Phase I trial. Standard 3 + 3 dose escalation was used evaluating intravenous doses ranging from 0.1 mg/kg every 4 weeks to 1.0 mg/kg every 2 weeks. Key eligibility included chemo-refractory locally advanced, recurrent, or metastatic gastric, colorectal, pancreatic, or biliary cancer, with ECOG PS 0-1; positive AG-7 expression was not required during dose escalation phase. Patients were treated until disease progression or unacceptable toxicity, with tumor assessments every 8 weeks. Primary objectives included safety and determination of maximum tolerated dose; secondary objectives included efficacy defined by objective response rate. Thirty-nine patients were enrolled across seven dose levels during dose escalation phase. Based on safety profile and pharmacokinetic data, 1.0 mg/kg Q2W was selected as the dose schedule for cohort expansion phase, in which an additional seven patients were enrolled. Median number of lines of prior therapy was 3 (range 1-7). AbGn-107 was generally well-tolerated, with infections, cytopenias, hyponatremia, fatigue, abdominal pain, and diarrhea representing the most common grade 3 or higher treatment-emergent adverse events. One subject achieved a partial response, while 18 (46.2%) achieved a best response of stable disease. Disease control lasting > 6 months was observed in 6 subjects (13.0%), including 4 of 15 (26.7%) treated at the highest dose level. AbGn-107 showed a reasonable safety profile and modest clinical activity in this highly pretreated patient population. Further evaluation is required to assess the clinical validity of AG-7 as a suitable antigen for therapeutic targeting. Clinical Trial information: NCT02908451.

How often should I meditate? A randomized trial examining the role of meditation frequency when total amount of meditation is held constant.

Meditation apps are the most commonly used mental health apps. However, the optimal dosing of app-delivered meditation practice has not been established. We examined whether the distribution of meditation practices across a day impacted outcomes in a distressed population. We investigated the effects of meditation practice frequency in a 2-week compassion-based meditation intervention delivered via the Healthy Minds Program app. Undergraduates with clinically elevated depression and/or anxiety (N = 351) were randomized to a massed (one 20-min meditation per day) or distributed condition (two 10-min meditations per day). Psychological distress (primary outcome; composite of depression and anxiety), experiential avoidance, fear of missing out, loneliness, and self-compassion were assessed pre- and post-intervention. Psychological distress, loneliness, and informal meditation practice were also assessed daily. Practice time and frequency were assessed using app data. Results support feasibility of the study design, success of the manipulation, and acceptability of the intervention. Pooled across conditions, participants exhibited pre-post improvements on all outcomes (absolute value of ds = 0.12-0.63, p ≤ .010) and trajectories of improvement on daily distress and loneliness (p ≤ .010). No between-group differences were observed on changes in pre-post or daily measures (ps = .158-.729). When total amount of meditation practice per day is held constant, the distribution of practice may not influence outcomes for distressed beginners. Although only a first test of dose frequency effects, findings support flexibility in the distribution of meditation throughout the day, which may increase accessibility. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Autonomy and Firefighting: Perceived Competence and Stress.

OBJECTIVE: In workplace settings, autonomy is implicated in employee motivation as well as supervisor autonomy support. As a profession of risk, firefighters may experience greater levels of stress. METHODS: A self-determination paradigm was applied to the firefighter workplace. Of particular interest were perceived competence (to perform job duties) and the experience of stress. Firefighters' levels of autonomous and controlled regulation were surveyed, along with their perceptions of the autonomy support of their immediate supervisor. RESULTS: Autonomous regulation was positively related to perceived competence, whereas controlled regulation was negatively related. Higher levels of controlled regulation were also connected with greater stress. In contrast, greater perceived autonomy support was associated with decreased stress. CONCLUSIONS: Both perceived competence and stress are related to firefighter motivation and autonomy support. Recommendations are offered to increase autonomy support by chief officers.

Assessment of Parent Orientation towards Autonomy vs. Control in Promoting Children's Healthy Eating and Exercise.

BACKGROUND: Self-determination theory has been widely applied to understanding individuals' health-related behaviors such as eating healthy foods and exercising. Different reasons for engagement are associated with varying levels of personal agency or autonomy. Authority figures in the environment can be supportive of autonomy or, in contrast, controlling. Although researchers have assessed individuals' perceptions of the autonomy-support in their environments, studies have not directly examined the authority figures' orientations to autonomy with respect to health contexts. METHODS: A new scale, Parent Orientations to Health, was created to investigate parent orientation to autonomy and control with respect to healthy eating and exercise in children. One hundred and forty-three parents of elementary school-aged children responded to the scale. RESULTS: Scale validation and reliability results indicate that the scale successfully assessed parent orientation towards autonomy for children in health contexts. Furthermore, parent autonomy orientation varied according to child weight status and the healthiness of the child's diet. CONCLUSIONS: Parent orientation towards autonomy can be evaluated through the use of the Parent Orientations to Health scale. In addition, parent autonomy orientation is associated with both the healthiness of the child's diet (as perceived by the parent) and the child's body mass index.

Children's perceived cost for exercise: application of an expectancy-value paradigm.

Expectancy-value models of motivation have been applied to understanding children's choices in areas such as academics and sports. Here, an expectancy-value paradigm is applied to exercising (defined as engaging in physical activity). The notion of perceived cost is highlighted in particular. Two hundred twenty children in third, fourth, and fifth grades were surveyed on their competence beliefs, perceived importance, interest, and perceived cost of being physically active. Results indicated that perceived cost is empirically distinct from competence beliefs and other types of value, that perceived cost is marginally related to children's self-reported level of physical activity, and children's beliefs and other values are related to their self-reported level of physical activity. Children's perceptions of cost vary depending on grade and gender. Interventions based on these findings are proposed.

A novel apoptosis-inducing anti-PSGL-1 antibody for T cell-mediated diseases.

We previously discovered a hamster monoclonal antibody, TAB4, against mouse PSGL-1/CD162 that can induce death of activated T cells. Here, we further investigated the potential of TAB4 in treating two murine models of T cell-mediated diseases. The results showed that administration of TAB4 suppressed incidence and severity of both GVHD and type I diabetes. Analyses of apoptotic T cells ex vivo shortly after antibody injection revealed a higher percentage of apoptosis among activated T cells in the TAB4-treated group than in the control group. Furthermore, restoration of functional donor T cells was observed in TAB4-treated mice. As TAB4 does not affect the binding of P-selectin to activated T cells, our data suggest that its long-lasting therapeutic effect on inhibiting disease progression is attained by specifically inducing apoptosis of activated T cells. These data hence extend our previous finding of the novel property of PSGL-1 and strongly indicate that the PSGL-1-specific apoptosis-inducing antibody is a new therapeutic agent possessing a great potential for controlling GVHD and other T cell-mediated autoimmune diseases.

Cross-linking of P-selectin glycoprotein ligand-1 induces death of activated T cells.

Increasing evidence has shown that death signaling in T cells is regulated in a complicated way. Molecules other than death receptors can also trigger T-cell death. Here, we demonstrate for the first time that P-selectin glycoprotein ligand-1 (PSGL-1) or CD162 molecules cross-linked by an anti-PSGL-1 monoclonal antibody, TAB4, can trigger a death signal in activated T cells. In contrast to classic cell death, PSGL-1-mediated T-cell death is caspase independent. It involves translocation of apoptosis-inducing factor from mitochondria to nucleus and mitochondrial cytochrome c release. Ultrastructurally, both peripheral condensation of chromatin and apoptotic body were observed in PSGL-1-mediated T-cell death. Collectively, this study demonstrates a novel role for PSGL-1 in controlling activated T-cell death and, thus, advances our understanding of immune regulation.