Faculty Bibliography

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease, necessitating approaches to improve prognosis. As the mediator of allergic process, mast cells have been found in various cancers and are associated with survival. However, the biological behaviors of tumor-associated mast cells (TAMCs) remain unclear. Herein, an excessive infiltration of TAMCs in PDAC is demonstrated, which apparently associated with poor survival in PDAC patients. PDAC cells are found to recruit CXCR2⁺ MCs into TME, and then inhibited MCs ferroptosis, and maintained their proliferation. Concomitantly, the tumor-derived exosome miR-188-5p activated the PTEN/AKT/GSK3β signaling, further stabilized transcriptional factor ERG by inhibiting its ubiquitin degradation, and finally enhanced the transcription of cxcl10 within TAMCs. In reverse, TAMCs-derived CXCL10 reversely promoted tumor epithelial-mesenchymal transition and induced immunosuppressive tumor microenvironment by recruiting CXCR3⁺ Tregs. Sodium cromoglycate (SCG) is a membrane stabilizer for MCs and confirmed as an effective and widely used agent to block TAMCs-derived CXCL10 and further sensitize the therapeutic efficacy of anti-PD-1 antibody plus gemcitabine for PDAC. These findings illuminate a critical and innovative crosstalk between TAMCs and PDAC cells that promote PDAC progression, and SCG sensitizes PDAC to the current immuno-chemotherapy, which reveals its potential to be a valuable adjuvant for PDAC patients.

Our brains integrate sensory, cognitive and internal state information with memories to extract behavioral relevance. Cortico-hippocampal interactions likely mediate this interplay, but underlying circuit mechanisms remain elusive. Unlike the entorhinal cortex-to-hippocampus pathway, we know little about the organization and function of the hippocampus-to-cortex feedback circuit. Here we report in mice, two functionally distinct parallel hippocampus-to-entorhinal cortex feedback pathways: the canonical disynaptic route via layer 5 and a novel monosynaptic input to layer 2/3. Circuit mapping reveals that hippocampal input predominantly drives excitation in layer 5 but feed-forward inhibition in layer 2/3. Upon repetitive pairing with cortical layer 1 inputs, hippocampal inputs undergo homosynaptic potentiation in layer 5, but induce heterosynaptic plasticity and spike output in layer 2/3. Behaviorally, hippocampal inputs to layer 5 and layer 2/3 support object memory encoding versus recall, respectively. Two-photon imaging during navigation reveals hippocampal suppression reduces spatially tuned cortical axonal activity. We present a model, where hippocampal feedback could iteratively shape ongoing cortical processing.

Seizures associated with low-grade tumors in pediatric patients can be drug resistant and associated with significant morbidity. There are several low-grade tumor types associated with epilepsy in this population with the majority localized to the temporal lobe and some extra-temporal locations (frontal, parietal, and occipital lobes). The primary treatment of low-grade epilepsy-associated tumors is surgical resection, though the surgical approach and the use of intraoperative techniques remain controversial. Newer treatments are under investigation as primary and/or adjunctive therapy, including non-invasive surgical options and gene-targeted therapy. A multimodal approach to treatment may improve long-term outcomes and quality of life.

Most offspring are born helpless, requiring intense caregiving from parents especially during the first few days of neonatal life. For many species, infant cries are a primary signal used by parents to provide caregiving. Previously we and others documented how maternal left auditory cortex rapidly becomes sensitized to pup calls over hours of parental experience, enabled by oxytocin. The speed and robustness of this maternal plasticity suggests cortical pre-tuning or initial bias for pup call stimulus features. Here we examine the circuit basis of left-lateralized tuning to vocalization features with whole-cell recordings in brain slices. We found that layer 2/3 pyramidal cells of female left auditory cortex show selective suppression of inhibitory inputs with repeated stimulation at the fundamental pup call rate (inter-stimulus interval ∼150 msec) in pup-naïve females and expanded with maternal experience. However, optogenetic stimulation of cortical inhibitory cells showed that inputs from somatostatin-positive and oxytocin-receptor-expressing interneurons were less suppressed at these rates. This suggested that disynaptic inhibition rather than monosynaptic depression was a major mechanism underlying pre-tuning of cortical excitatory neurons, confirmed with simulations. Thus cortical interneuron specializations can augment neuroplasticity mechanisms to ensure fast appropriate caregiving in response to infant cries.

The optimal treatment of patients with diffuse large B-cell lymphoma (DLBCL) or Hodgkin lymphoma (HL) with preexisting cardiomyopathy is uncertain. An anonymous, electronic survey was distributed by e-mail to three US lymphoma cooperative groups, two community hospitals, and twelve academic medical systems, and distributed at one international lymphoma meeting. Fifty hematology-oncology providers caring for patients with lymphoma were included. In response to a vignette of a 67-yo with Stage III DLBCL with LVEF of 40-45%, 15 (30%) would use non-anthracycline regimens, 13 (26%) R-CHOP with liposomal doxorubicin instead of doxorubicin, 11 (22%) R-CHOP without modification and 6 (12%) R-CHOP with a continuous doxorubicin infusion. In a second vignette of a patient with HL in remission after frontline treatment with doxorubicin cumulative dose 300 mg/m², 16 (32%) would order an echocardiogram after treatment. There was substantial variability in preferred treatment regimens with preexisting cardiomyopathy and in cardiac monitoring after anthracycline.

COVID-19 has tragically taken the lives of more than 6.5 million people globally, significantly challenging healthcare systems and service delivery, especially in low-and middle-income countries (LMICs). This systematic review aims to: (1) evaluate the feasibility of telemedicine interventions for COVID-19 management; (2) assess the adoption of telemedicine interventions during the COVID-19 pandemic; (3) examine the cost-effectiveness of telemedicine implementation efforts and (4) analyze the sustainability of telemedicine interventions for COVID-19 disease management within LMIC service settings. We reviewed studies from selected public health and health science databases, focusing on those conducted in countries classified as low and middle-income by the World Bank, using telemedicine for confirmed COVID-19 cases, and adhering to Proctor's framework for implementation outcomes. Of the 766 articles identified and 642 screened, only 3 met all inclusion criteria. These studies showed reduced reliance on antibiotics, prescription drugs, and emergency department referrals among telemedicine patients. Statistical parity was observed in the length of stay, diagnostic test ordering rates, and International Classification of Diseases (ICD)-10 diagnoses between telemedicine and in-person visits. Telemedicine interventions designed for post-COVID physical rehabilitation demonstrated safety, sustainability, and enhanced quality of life for patients without requiring specialized equipment, proving adaptable across contexts with appropriate technology. These interventions were also economically sustainable and cost-effective for healthcare systems as a whole. Proposed strategies to bridge implementation gaps include community-level assessments, strategic planning, multisectoral partnerships of local hospital administration and lawmakers, legal consultations, and healthcare informatics improvements. Increased investment in telemedicine research focusing on infectious disease management is crucial for the continued development and refinement of effective strategies tailored to resource-constrained regions.

Pediatric Long COVID has been associated with a wide variety of symptoms, conditions, and organ systems, but distinct clinical presentations, or subphenotypes, are still being elucidated. In this exploratory analysis, we identified a cohort of pediatric (age <21) patients with evidence of Long COVID and no pre-existing complex chronic conditions using electronic health record data from 38 institutions and used an unsupervised machine learning-based approach to identify subphenotypes. Our method, an extension of the Phe2Vec algorithm, uses tens of thousands of clinical concepts from multiple domains to represent patients' clinical histories to then identify groups of patients with similar presentations. The results indicate that cardiorespiratory presentations are most common (present in 54% of patients) followed by subphenotypes marked (in decreasing order of frequency) by musculoskeletal pain, neuropsychiatric conditions, gastrointestinal symptoms, headache, and fatigue.

OBJECTIVE:To confirm feasibility and safety of the Da Vinci Single-Port (SP) System to perform pulmonary lobectomy procedures utilizing a subcostal, uniportal approach. METHODS:We performed a prospective, multicenter, single arm, clinical study evaluating performance and safety of the da Vinci SP Surgical System for pulmonary lobectomy. RESULTS:Nineteen subjects (benign, n=1; malignant, n=18) were enrolled at six academic medical centers in the United States and underwent robotic-assisted SP subcostal lobectomy. All SP lobectomy procedures were completed without conversion to multiport thoracoscopic/robotic or open approaches. No intraoperative adverse events or unanticipated adverse device effects were observed; 13 postoperative adverse events (AEs) commonly experienced after lobectomy were reported, 4 of which were Clavien-Dindo grade III. Rate of complete (R0) resection was 100%. The median (interquartile (IQR)) number nodal stations sampled was 6.5 (6.0-8.0) with a median of 17.5 (7.0-34.0) nodes resected per patient. CONCLUSIONS:Robotic SP subcostal lobectomy is feasible and is associated with acceptable perioperative and oncologic quality outcomes. Additional clinical experience and research is necessary to determine whether this alternative single incision approach has clinical benefit compared to standard transthoracic, multiport robotic lobectomy.

Occupational therapy practice addressing functional cognition reduces hospital readmission rates. But no widely accepted performance-based functional cognition screen exists for inpatient rehabilitation. The aim was to determine how occupational therapy practitioners perceive the Menu Task's (MT's) utility for addressing functional cognition impairment. This study is a qualitative interpretive constructionist design with a phenomenological approach using semi-structured interviews with nine inpatient rehabilitation occupational therapy practitioners. Three themes emerged: (a) the screen's focus on ability, highlighting what the patient can do; (b) convenient administration, emphasizing the screen's ease of use; and (c) room to grow, focusing on areas for screen improvement. The Menu Task is convenient to administer and informs occupational therapy practice by revealing functional cognition ability. Although needing improvement, the Menu Task aligns with occupational therapy practice tenets by highlighting occupational participation. Occupational therapy practitioners indicated that inclusion of the Menu Task enhanced their clinical practice in inpatient rehabilitation, addressing functional cognition.