Faculty Bibliography

BACKGROUND/UNASSIGNED:The aging and caregiving population is becoming increasingly diverse in the United States, leading to a growing need for culturally adapted interventions to address the unique needs of underrepresented groups, such as Asian Americans. However, interventions targeting Asian Americans and exploring cultural adaptation strategies remain limited in dementia caregiving research. OBJECTIVE/UNASSIGNED:This study aimed to describe the cultural adaptation process of an evidence-based intervention for Chinese and Korean American dementia caregivers, called the New York University Caregiver Intervention-Enhanced Support. METHODS/UNASSIGNED:We conducted a deductive content analysis and categorized our adaptation strategies into 5 elements: content, context, relationship fidelity and core elements, engagement, and cultural competence. Timing and types of responses to each adaptation strategy were also observed. Two authors conducted the initial analysis, and additional team members finalized the synthesis through discussion. The Template for Intervention Description and Replication (TIDieR) checklist was used to guide the methodological rigor. RESULTS/UNASSIGNED:Twenty-four major adaptations were identified and categorized. For content, we translated materials, used culturally relevant terms, incorporated ethnic-specific surveys and resources, created social media support groups on platforms widely used by the targeted population, and extended the time allocated to complete the 6 counseling sessions. Context adaptation included expanding the range of individuals eligible for family counseling sessions to include fictive kin, using online and social media apps for communication, cultural matching and training of staff, and partnerships with relevant community organizations. Relationship fidelity and core elements involved consulting with community experts, conducting focus group interviews with caregivers, having regular meetings with the developer of the original intervention and an experienced New York University Caregiver Intervention-Enhanced Support clinician as well as experts in Chinese and Korean culture, and continuing regular counseling supervision. To enhance engagement, we provided clear explanations of the study procedure, which emphasized the benefits in participants' native languages and matched participants with social workers who shared the same cultural backgrounds. We also used a step-by-step contact approach and prolonged communication, explained staff roles to build rapport, and offered participant compensation. Finally, cultural competence was reflected in tailoring counseling techniques with respect for cultural beliefs, the use of euphemistic language for taboo subjects, and culturally appropriate refreshments to show respect and build interpersonal relationships. CONCLUSIONS/UNASSIGNED:We systematically adjusted a counseling-based intervention, an approach less familiar among Asian Americans, to fit the cultural characteristics of the target population. A contribution of this study is using an integrated, theory-driven approach that combines 2 cultural adaptation frameworks while also capturing real-time adaptations informed by external feedback and self-reflection. This work provides a practical model for adapting evidence-based interventions to serve Chinese and Korean American dementia caregivers and may inform future adaptations for other East Asian populations.

BACKGROUND/UNASSIGNED:As life expectancy rises, identifying causes and risk factors for incident acute ischemic stroke (AIS) among the oldest-old (≥80 years) is increasingly important. We examined whether the effect of age at stroke on AIS subtype is mediated by embolic risk factors and whether these factors improve AIS prediction. METHODS/UNASSIGNED:-VASc) and compared preinclusion and postinclusion of embolic risk factors. RESULTS/UNASSIGNED:-VASc: C statistics, 0.63 [95% CI, 0.59-0.67]). CONCLUSIONS/UNASSIGNED:These findings suggest that identification and control of embolic risk factors are critical to reduce stroke risk as people age, and better stroke-specific prediction tools are needed.

INTRODUCTION/BACKGROUND:Affiliate stigma may cause depressive symptoms among Asian American dementia caregivers, yet few studies have examined the underlying mechanisms or cross-ethnic differences. METHODS:We analyzed data from 338 older dementia caregivers (176 Chinese Americans, 162 Korean Americans; mean age 68.8 years) who completed measures of affiliate stigma, social isolation, loneliness, and depressive symptoms. RESULTS:for interaction < 0.01). DISCUSSION/CONCLUSIONS:These findings identify affiliate stigma as an important risk factor for dementia caregivers' depressive symptoms, operating through both objective and emotional forms of social disconnection. Culturally sensitive efforts to reduce caregivers' stigma and social disconnection may improve mental health outcomes in Asian American communities.

INTRODUCTION/BACKGROUND:Accurate preoperative evaluation of pancreatic cysts is essential. However, cytology and biochemical analysis are often limited by low cellularity, and risk stratification is critical for management. PancreaSeq Genomic Classifier (GC) analyzes cyst fluid for molecular alterations to aid diagnosis and risk assessment. MATERIALS AND METHODS/METHODS:We retrospectively analyzed 219 pancreatic cysts from 206 patients using PancreaSeq GC, integrating molecular findings with cytology, biochemical, imaging, surgical pathology, and follow-up. RESULTS:PancreaSeq GC successfully analyzed 216/219 cysts (99%) and detected alterations in 182 (83%). Among cases with both cytology and molecular data (n = 201), concordance was high in cytologically mucinous neoplasms (94%) and atypical cases (95%). Notably, among cases reported as negative for malignancy or nondiagnostic on cytology (n = 128), PancreaSeq GC identified mucinous neoplasms in 82 cases (64%), demonstrating added value in limited samples. Surgical pathology correlation (n = 24) showed excellent performance for distinguishing mucinous from nonmucinous cysts (area under the curve [AUC] = 0.94, P < 0.001). Risk stratification for detection of any dysplasia yielded an AUC of 0.78 (P = 0.006), and for high-grade dysplasia an AUC of 0.74 (P = 0.046). PancreaSeq GC reliably predicted neuroendocrine tumors, but the sensitivity for focal high-grade dysplasia in mucinous neoplasms and serous cystadenoma was limited. Compared with carcinoembryonic antigen (CEA), cyst fluid glucose showed higher sensitivity but lower specificity for mucinous cyst detection. CONCLUSIONS:PancreaSeq GC provides significant diagnostic and risk-stratification value that complements cytological evaluation, particularly in indeterminate or nondiagnostic cytology specimens and when biochemical data are unavailable. Integration of molecular findings improves cyst classification and dysplasia risk assessment. Multidisciplinary assessment remains essential, given the assay's limited sensitivity for focal high-grade dysplasia and serous cystadenomas.

AIM/OBJECTIVE:Postoperative delirium (POD) is a frequent neurological complication following surgery, often leading to poor prognoses. The red blood cell distribution width (RDW) to albumin ratio (RAR), an emerging indicator of inflammation and nutrition, was extensively utilized for prognostic evaluation of neurological disorders in elderly patients. However, the relationship between RAR and POD was not evaluated. This study aimed to investigate the independent risk factors for POD and assess the predictive value of preoperative RAR among elderly patients who had gastrointestinal tumors. METHODS:We conducted a retrospective analysis to collect perioperative data on 203 patients aged 65 years or older undergoing gastrointestinal tumor surgery from November 2023 to August 2024. The risk factors for POD were detected through univariate and multivariate logistic regression analyses. Propensity score matching (PSM) was employed to make their clinical characteristics balanced. RESULTS:Out of 203 patients, 30 (14.8%) experienced POD, with a median age of 70 (range 67-76). Hypertension, creatinine, MCH, and RAR were determined as independent risk factors for POD through multivariate logistic regression analysis. In the post-PSM cohort, RAR was still verified as a factor influencing POD. CONCLUSIONS:Hypertension, creatinine, MCH, and RAR were recognized as independent risk factors for postoperative delirium in patients following gastrointestinal tumor surgery. Particularly, the preoperative RAR served as a more efficient index for predicting POD. TRIAL REGISTRATION/BACKGROUND:Chinese Clinical Trial Center: ChiCTR2400094315.

The BRAF inhibitor encorafenib and anti-epidermal growth factor receptor (EGFR) antibody cetuximab modestly improve survival for patients with microsatellite stable (MSS) BRAF^V600E metastatic colorectal cancer (mCRC), characterized by higher immune activation than MSS BRAF^wild-type colorectal cancer (CRC). In this phase 1/2 study (NCT04017650) of 26 participants with MSS BRAF^V600E mCRC who received encorafenib, cetuximab, and anti-PD-1 antibody nivolumab, we report an overall response rate of 50% (95% confidence interval [CI] 29-71) and median progression-free survival of 7.4 months (95% CI, 5.6-9.6). Transcriptomic profiling of pretreatment biopsies and extracellular vesicle RNA (evRNA) isolated from plasma show enrichment of non-canonical mitogen-activated protein kinase (MAPK) signaling and immune activation signatures for responders. Complement pathway activation enriches in non-responder biopsies. On serial evRNA profiling, decreased MAPK signature and increased interferon gamma response signature associate with sustained treatment benefit. MSS BRAF^V600E mCRC with baseline MAPK activation and immune activation signatures may benefit from the triple combination but not with complement pathway activation.

Perineural invasion (PNI) is a well-established factor of poor prognosis in multiple cancer types¹, yet its mechanism remains unclear. Here we provide clinical and mechanistic insights into the role of PNI and cancer-induced nerve injury (CINI) in resistance to anti-PD-1 therapy. Our study demonstrates that PNI and CINI of tumour-associated nerves are associated with poor response to anti-PD-1 therapy among patients with cutaneous squamous cell carcinoma, melanoma and gastric cancer. Electron microscopy and electrical conduction analyses reveal that cancer cells degrade the nerve fibre myelin sheets. The injured neurons respond by autonomously initiating IL-6- and type I interferon-mediated inflammation to promote nerve healing and regeneration. As the tumour grows, the CINI burden increases, and its associated inflammation becomes chronic and skews the general immune tone within the tumour microenvironment into a suppressive and exhaustive state. The CINI-driven anti-PD-1 resistance can be reversed by targeting multiple steps in the CINI signalling process: denervating the tumour, conditional knockout of the transcription factor mediating the injury signal within neurons (Atf3), knockout of interferon-α receptor signalling (Ifnar1^-/-) or by combining anti-PD-1 and anti-IL-6-receptor blockade. Our findings demonstrate the direct immunoregulatory roles of CINI and its therapeutic potential.

BACKGROUND AND OBJECTIVE/OBJECTIVE:Only a minority of renal oncocytic tumors are aggressive. These tumors' behavior is difficult to predict by histopathological evaluation; consequently, many patients experience anxiety upon diagnosis and may undergo unnecessary treatment. Our aim was to derive genomic and epigenomic signatures to distinguish clinically indolent renal oncocytic tumors from aggressive chromophobe renal cell carcinoma (ChRCC). METHODS:We performed molecular profiling of nephrectomies from 68 patients: 44 with indolent renal oncocytic tumors (19 renal oncocytoma, two oncocytic renal neoplasm of low malignant potential, and 23 indolent ChRCC) and 24 with aggressive ChRCC. We performed targeted exome sequencing, gene expression profiling, and whole-genome methylation sequencing of formalin-fixed, paraffin-embedded (FFPE) samples. We also analyzed The Cancer Genome Atlas Kidney Chromophobe data from 66 ChRCC patients in silico. Genomic and epigenomic signatures linked to aggressive ChRCC-obtained from sampling morphologically nonsarcomatoid foci-from both cohorts were derived using the least absolute shrinkage and selection operator method. KEY FINDINGS AND LIMITATIONS/UNASSIGNED:Aggressive ChRCC was distinguished from indolent ChRCC and other indolent renal oncocytic tumors using a focused seven- to 11-gene expression signature (ten-fold cross-validation [CV] area under the curve [AUC] = 0.77-0.85) with an external validation AUC of 0.88, and an eight-CpG methylation signature (ten-fold CV AUC = 0.86) with an external validation AUC of 0.91. TP53 and PTEN mutations substantially increased the probability of aggressive ChRCC. Limitations include the small sample size. CONCLUSIONS AND CLINICAL IMPLICATIONS/CONCLUSIONS:Focused genomic and epigenomic signatures from routinely processed FFPE tumor tissues can help distinguish aggressive ChRCC from indolent renal oncocytic tumors, including indolent ChRCC. This forms the basis for replication studies to inform appropriate patient management, provide reassurance, and guide follow-up.

INTRODUCTION/BACKGROUND:The New York University Caregiver Intervention plus Enhanced Support Project is a randomized controlled trial of a family-based psychosocial intervention to enhance social support and reduce cardiometabolic risk for Chinese and Korean American dementia caregivers, using culturally tailored recruitment strategies. METHODS:We reviewed reflections from research staff, weekly meeting minutes, debriefing sessions, and progress reports, to identify key challenges and approaches to engaging participants. RESULTS:Key challenges included reluctance to involve family members, dementia stigma, and resistance to involving family. In response, we engaged online communities, partnered with local organizations, participated in events, and adapted recruitment messages to cultural norms. For the Chinese community, we focused on practical skills while for the Korean community, we emphasized caregiving strategies and the personal/social benefits of participation, reducing rejection rates. DISCUSSION/CONCLUSIONS:Our findings underscore the importance of culturally tailored recruitment strategies in dementia research. Respectful, sensitive, and culturally informed approaches can significantly enhance engagement and participation. HIGHLIGHTS/CONCLUSIONS:Culturally adapted recruitment strategies improve study engagement with Chinese and Korean American dementia caregivers. Community partnerships with local social services agencies are essential for recruitment success. Culturally relevant social media applications were integrated to increase accessibility for study participants. This study uniquely targets and recruits Chinese and Korean American dementia caregivers with metabolic syndrome-related symptoms, incorporating a psychological intervention alongside biomarker data collection. The iterative adaptation of recruitment methods and tailored messaging to specific ethnic groups ensure the intervention is culturally aligned, enhancing both participation and relevance to the caregivers' unique health and caregiving contexts.

Theories propose that speech production can be approximated as a temporal reversal of speech perception. For example, phonological code is assumed to precede phonetic encoding in the motor system during speech production. However, empirical neural evidence directly testing the temporal order hypothesis remains scarce, mostly because of motor artifacts in non-invasive electrophysiology recordings and the requirements of both temporal and spatial precision. In this study, we investigated the neural dynamics of speech production using stereotactic electroencephalography (sEEG). In both onset latency analysis and representational similarity analysis (RSA), activation in the auditory region of the posterior superior temporal gyrus (pSTG) was observed before articulation, suggesting the availability of auditory phonological code before production. Surprisingly, the activation in the motor region of the inferior frontal gyrus (IFG) preceded that of pSTG, suggesting that the phonological code in the auditory domain may not necessarily be activated before the encoding in the motor domain during speech production.