Faculty Bibliography

OBJECTIVES/OBJECTIVE:Much research has documented disruptions to parent well-being and family functioning because of the COVID-19 pandemic in the United States, but little is known about how parents' provision of cognitive stimulation to young children has been affected. This question is of added importance for families with low incomes, who were disproportionately disadvantaged by the pandemic. The current study examined whether and how provision of cognitive stimulation at home, as measured by the parent-reported StimQ2, changed for parents with low incomes after onset of the COVID-19 pandemic. We examined scores on a total scale and subscales tapping multiple aspects of verbal responsivity and reading. DESIGN/METHODS:Data from 7 cohorts of families with low incomes across 3 US cities were de-identified and combined into a single analytic sample for secondary analysis. Cohorts ranged in timing relative to the onset of the pandemic (i.e., as early as 2015 and as late as April 2023). Each study contributed data from families assessed at multiple timepoints between birth and age 4 years. RESULTS:Total scores on the StimQ2 increased after the onset of the COVID-19 pandemic. Subscales reflecting reading stayed the same (quantity) or declined (quality), whereas subscales reflecting verbal responsivity increased. CONCLUSION/CONCLUSIONS:Relative to prepandemic levels, low-income parents' child-directed speech and responsivity increased postpandemic, but the quantity of parent-child reading was unchanged and its quality declined. Findings suggest the possibility of stability or improvement among parents with low incomes during the pandemic and opportunities for intervention.

Bessel beams are commonly used in two-photon microscopy to extend the depth of field and thereby achieve functional volumetric imaging of the living brain. In practice, this approach suffers from background signals and limited lateral resolution due to the Bessel beam's strong side lobes. We introduce and demonstrate a new approach to side lobe suppression based on non-degenerate two-photon excitation, in which dual wavelength illumination produces an imaging point-spread function that is the product of the two coaxial Bessel beams. This technique can reduce the main side lobe intensity of a Bessel beam by 50% or more. We illustrate the approach conceptually with an analytical paraxial model and use detailed physical simulation to show that the approach is effective in the presence of the symmetry-breaking aberrations that amplify side lobes in high NA systems. We experimentally demonstrated the technique using a refractive axicon and the pump and tunable beams of a femtosecond laser. This work establishes non-degenerate two-photon excitation as a practical and broadly applicable strategy for improving point spread-function quality in high-resolution volumetric microscopy.

INTRODUCTION/BACKGROUND:Cognitive decrements in executive function and processing speed have been found in post-9/11 Veterans who have mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD). Decision making (DM) involves the coordination of cognitive sub-processes involving different brain regions known to be impacted by mTBI and/or PTSD, and so may be expected to be compromised. The ability to incorporate context is important because it plays a role in almost every cognitive and social process. However, DM abilities, including DM that requires taking context into account, are not typically assessed or investigated in Veterans. MATERIALS AND METHODS/METHODS:We prospectively recruited Veterans deployed to Iraq or Afghanistan who had the following characteristics: (1) no TBI before deployment, (2) mTBI because of blast only, (3) current PTSD (diagnosed within 6 months), and (4) ≤49 years of age. Deployed Veterans with no mTBI or PTSD served as the comparison group. Veterans with mTBI and comorbid PTSD (mTBI + PTSD; n = 9) and Veterans without mTBI or PTSD (n = 8) performed the Cognitive Bias Task, a DM task in which participants are asked to make a decision based on preference, and the extent to which choices are influenced by contextual information is measured. To further understand any association between DM and mTBI + PTSD, participants also filled out questionnaires to measure neurobehavioral and PTSD symptoms. Because normality was violated in both groups, Fisher's Exact and Mann-Whitney tests and Spearman's rank order correlations were used. RESULTS:Although Veterans without mTBI + PTSD made context-dependent choices, Veterans with mTBI + PTSD made context-independent choices (p = .034), similar to prior research examining individuals with severe TBI and left lateralized frontal lobe brain lesions. As expected, Veterans with mTBI + PTSD also demonstrated elevated scores on the symptom measures. Symptom measure scores were correlated with Cognitive Bias Task (CBT) scores and revealed a negative correlation between somatic, and marginally cognitive and arousal symptoms, and the extent to which context was incorporated into decisions. CONCLUSIONS:Veterans an average of 4.0 years after blast injury who had active PTSD (mTBI + PTSD) did not incorporate contextual information when making their decisions. Because understanding context is required in many everyday activities, if findings replicate in studies with larger samples, clinical testing for DM difficulties and training for context incorporation may improve everyday function in Veterans with mTBI + PTSD.

The ability of cancer cells to consistently escape therapy highlights their remarkable adaptive potential. A longstanding debate in cancer research concerns whether drug resistance originates primarily from mutational processes or through cellular plasticity. Emerging evidence has suggested that adaptive cellular states arise through phenotypic plasticity triggered by intracellular stress signals. Here we propose a theoretical framework for how such cellular adaptation in cancer drug resistance could be 'learned' by the AP-1 family of transcription factors. We highlight key AP-1 properties, including regulatory combinatorics, stress-induced feedback and cellular memory, and argue that this system constitutes a molecular framework for establishing drug-resistant cellular states. Finally, we discuss the potentially broad relevance of this adaptation mechanism beyond cancer.

RATIONALE & OBJECTIVE/UNASSIGNED:Randomized controlled trials (RCTs) show that integrated palliative care can improve symptoms compared with usual care in many serious illnesses, yet there are no comparable RCTs in chronic kidney disease (CKD). STUDY DESIGN/UNASSIGNED:We conducted a pilot feasibility RCT comparing kidney palliative care (KPC) integrated with CKD care with usual CKD care. SETTING & PARTICIPANTS/UNASSIGNED:English and Spanish speakers aged ≥18 years with CKD stage IV and V, or receiving dialysis, seen at an urban safety-net hospital. EXPOSURES/UNASSIGNED:Participants were randomized to usual CKD care or to usual CKD care plus 6-monthly ambulatory KPC visits. OUTCOMES/UNASSIGNED:Primary outcomes were feasibility of recruitment, retention, intervention delivery, and data collection. Secondary outcomes included change in symptom burden at 6 months, measured by the Integrated Palliative Outcome Scale (IPOS)-Renal (lower scores represent lower burden), quality of life measured by the Kidney Disease Quality of Life 36-item survey, and engagement in advance care planning. ANALYTICAL APPROACH/UNASSIGNED:Feasibility outcomes are reported as proportions and clinical outcomes as descriptive summaries of change in scores. RESULTS/UNASSIGNED:Of the 146 people approached, 84 (56%) consented, 75 (89%) were randomized, and 57 (76%) completed the trial. 56% of participants were Hispanic and 32% were Black, with 49% on Medicaid and 13% uninsured. The mean age of participants was 61 years, and 31% were receiving dialysis. A mean of 4-6 intervention visits was attended. At 6 months, the intervention group had a 4.1-point decrease in IPOS score (standard deviation 13.4), whereas the mean IPOS score of the control group increased by 0.6 points (standard deviation 7.8) from baseline. LIMITATIONS/UNASSIGNED:Small sample size and limited number of providers to assess generalizability. CONCLUSIONS/UNASSIGNED:We demonstrate the feasibility of an RCT comparing integrated KPC with usual CKD care in a safety-net hospital. Although this study was not powered to detect significance in change of clinical outcomes, our findings suggest that there is value in testing KPC in efficacy trials and that these are feasible.

BACKGROUND:Flow diversion is effective for unruptured distal anterior cerebral artery (DACA) aneurysms, yet comparative data between the Silk Vista Baby (SVB) and Pipeline Embolization Device (PED) in this challenging territory remain scarce. METHODS:We conducted a retrospective multicenter study using the CRETA Registry, including consecutive patients with unruptured DACA aneurysms treated with SVB or PED. The primary endpoint was complete angiographic occlusion (O'Kelly-Marotta grade D). Secondary outcomes included procedural characteristics, clinical outcome (modified Rankin Scale), and complications. Overlap weighting was applied to account for non-randomized treatment allocation. Predictors of occlusion were explored using penalized logistic regression. A sensitivity analysis using a reduced five-variable model was performed to assess model robustness. RESULTS:137 patients were included (79 SVB, 58 PED). Within the PED group, devices included Pipeline Flex (n = 34), Pipeline Flex with Shield Technology (n = 14), and Pipeline Vantage with Shield Technology (n = 10). After overlap weighting, baseline characteristics were balanced; the effective sample size was 100.4. SVB procedures more often used a single device; PED frequently required multiple stents. Procedure duration was shorter with SVB. Complete occlusion was achieved in 69.6% (SVB) and 70.7% (PED) of aneurysms, with no significant difference in adjusted analysis (OR 1.32, 95% CI 0.59-2.96). Favorable clinical outcomes were observed in both groups, with acceptable and comparable complication rates. No variable, including device type, independently predicted complete occlusion, a finding confirmed in a reduced five-variable sensitivity analysis (aOR 1.04, 95% CI 0.47-2.31; p = 0.915). CONCLUSIONS:SVB and PED demonstrated comparable angiographic efficacy and clinical safety for unruptured DACA aneurysms. Despite procedural differences, mid-term occlusion rates and outcomes were similar. Device selection in this distal territory may be guided primarily by anatomical considerations and operator preference rather than expectations of differential performance.

BACKGROUND:)-mutant non-small-cell lung cancer (NSCLC). Zongertinib is an oral, irreversible tyrosine kinase inhibitor that selectively inhibits HER2 while sparing wild-type epidermal growth factor receptor (EGFR), thereby minimizing associated toxic effects. METHODS:-mutant NSCLC. Here, we evaluated zongertinib at a dose of 120 mg once daily in patients who had not previously received treatment (cohort 2). The primary end point was objective response as assessed by blinded independent central review. Secondary end points included duration of response and progression-free survival. In addition, zongertinib was evaluated in patients with active brain metastases (exploratory cohort 4). RESULTS:In cohort 2, a total of 74 previously untreated patients received zongertinib at a dose of 120 mg. As of August 21, 2025, the percentage of patients with a confirmed objective response was 76% (95% confidence interval [CI], 65 to 84); the median duration of response was 15.2 months (95% CI, 9.8 to not evaluable), and the median progression-free survival was 14.4 months (95% CI, 11.1 to not evaluable). Adverse events of any grade occurred in 73 patients (99%), including events of grade 3 or higher in 33 patients (45%). Treatment-related adverse events occurred in 67 patients (91%), including events of grade 3 or higher in 14 patients (19%). In cohort 4, a total of 30 patients with active brain metastases received zongertinib at a dose of 120 mg; of these, 47% (95% CI, 30 to 64) had a confirmed intracranial objective response according to Response Assessment in Neuro-Oncology Brain Metastases criteria. In this cohort, treatment-related adverse events of grade 3 or higher occurred in 5 patients (17%). CONCLUSIONS:-mutant NSCLC. Treatment-related adverse events were predominantly low-grade. (Funded by Boehringer Ingelheim; Beamion LUNG-1 ClinicalTrials.gov number, NCT04886804.).

We examined the characteristics of subway- and train-related electrocution deaths in New York City between January 1, 2018 and May 31, 2024. These subway and train systems utilize an electrified third rail between 600V and 750V DC. During this period, there were 61 deaths due to electrocution. Of these, 39 cases occurred in the subway or train systems (NYC subway, Long Island Rail Road, Port Authority Trans-Hudson), 27 of which were due to electrocution only, and 12 due to a combination of electrocution and blunt trauma. The manners of death among these 39 deaths were: 23 accident, 11 undetermined, 4 suicide, and 1 homicide. In 36 of 39 deaths, significant charring of the skin was present on at least one part of the body, with charring present in more than one part of the body in most cases. Many cases also demonstrated a characteristic blistering pattern of electrothermal injury at a different location on the body away from the charring that may correspond to an electrical current "exit site." Notably, in two cases, only relatively minor electrothermal injury was identified.