Faculty Bibliography

Hepatitis B virus (HBV) mother-to-child transmission (MTCT) remains a major challenge in Uganda, where 43% of births occur at home, and access to timely birth dose (BD) vaccination is limited. We evaluated the impact of combining universal three-dose (3D) infant vaccination, targeted BD vaccination, and maternal antiviral treatment for high viral load (HVL) mothers on HBV prevalence among infants. In a prospective 18-month cohort study at five regional maternity hospitals, HIV-negative pregnant women were screened for HBsAg. HBsAg-positive mothers were stratified by HBV DNA into HVL (≥ 20,000 IU/mL), low viral load (LVL), or LVL on treatment. HVL mothers received Tenofovir Disoproxil Fumarate plus Lamivudine in the third trimester. Infants of HBsAg-positive mothers received BD vaccination within 24 h and the 3D pentavalent series; infants of HBsAg-negative mothers received the 3D series only. All infants were tested for HBsAg at nine months. Of 19,053 mothers screened, 3.46% were HBsAg-positive (n = 660). Among HVL mothers (n = 80), 96.3% initiated antivirals; none of their infants who received both BD and 3D tested HBsAg-positive. Among LVL mothers not on treatment (n = 558), the prevalence of infection at nine months was 0.4% despite full vaccination. No infections occurred among LVL mothers on treatment or among infants of HBsAg-negative mothers. Overall infant HBsAg prevalence was 0.19%, with an adjusted national estimate of 0.02%. Integrating maternal antiviral prophylaxis, targeted BD vaccination, and universal 3D vaccination achieved near-elimination of HBV MTCT in this setting. Nationally scaling this strategy could enable Uganda to meet the WHO target of less than 0.1% infant HBV prevalence before 2030 and serve as a model for other high-burden countries with significant rates of home births.

BACKGROUND/UNASSIGNED:Re-recurrent rectal cancer (RRRC) represents a highly complex disease following curative-intent treatment of recurrent rectal cancer (RRC). While management principles for primary and locally recurrent rectal cancer (RRC) have been defined by expert collaborations, no specific guidelines currently outline the perioperative management of RRRC. This systematic review aimed to appraise the reported perioperative strategies and oncological outcomes of patients undergoing curative-intent treatment for RRRC. METHODS/UNASSIGNED:Eligibility criteria, Studies reporting perioperative management and outcomes of adult patients undergoing curative-intent treatment for RRRC were included. Non-English articles, letters, abstracts, and studies lacking surgical or oncological data were excluded. Information sources, The review was conducted according to PRISMA guidelines and registered in PROSPERO (CRD420251244390). MEDLINE (PubMed), Cochrane Library, Web of Science, and Scopus were searched for relevant articles. Risk of bias, Methodological quality was assessed using the Newcastle-Ottawa Scale for cohort studies. Synthesis of results, Given heterogeneity in treatment strategies and outcome reporting, results were synthesized narratively. RESULTS/UNASSIGNED:Included studies, Three retrospective cohort studies comprising 169 patients treated with curative intent surgery for RRRC were included. Synthesis of results, Neoadjuvant therapy was administered in 20-92% of included patients, depending on the previous cumulative radiation dose. Pelvic exenteration was frequently required, with total exenteration performed in 6-20% and sacrectomy in up to 15% of cases; reconstructive procedures were reported in less than 16%. IORT was used in 44-77% of patients in centers where it was available. R0 resection rates ranged from 33% to 62%, with oncological outcomes directly associated with margin status. DISCUSSION/UNASSIGNED:Limitations of evidence, Evidence was limited to retrospective observational studies with small sample sizes, heterogeneous management, and varied institutional resources, precluding meta-analysis. Interpretation, Curative-intent surgery for RRRC is feasible in highly selected patients, with R0 being the principal prognostic determinant of oncological outcome. However, significant variability in perioperative pathways, margin definition, MRI-based classification, and reconstructive strategies underlines the necessity for the development of standardized, consensus-based recommendations to optimize multidisciplinary treatment. SYSTEMATIC REVIEW REGISTRATION/UNASSIGNED:https://www.crd.york.ac.uk/PROSPERO/view/CRD420251244390, identifier CRD420251244390.

PURPOSE/OBJECTIVE:To evaluate the prevalence and clinical relevance of incidental findings detected during pancreatic cyst surveillance and explore their implications for pancreas-focused imaging protocols. METHODS:This single-center retrospective study analyzed abdominal MRI and CT reports for pancreatic cyst surveillance (2005-2025) using a large language model (LLM). Incidental findings were findings unrelated to the clinical indication. Only the earliest surveillance examination per patient was included. Patients were stratified into cyst-only surveillance (cyst-only), cyst surveillance with high-risk pancreatic screening (cyst-HRI), or cyst surveillance with additional clinical indications (cyst-other). Electronic health record (EHR) review evaluated suspected extrapancreatic neoplastic incidental findings and incidental intrapancreatic hyperenhancing lesions. LLM performance was validated against two reviewers in 100 sampled reports. Multivariable logistic regression adjusted for age and sex. RESULTS:6174 patients (mean age, 70.6 ± 12.3 years; 65.7% women) were included; 94.8% underwent MRI. LLM-reviewer agreement was high (Cohen κ = 0.857 and 0.882). Incidental findings were identified in 43.0% of examinations and were predominantly nonneoplastic (98.7%), with most not requiring further action (70.2%). EHR targeted review confirmed 19 extrapancreatic neoplasms, most commonly renal neoplasms (n = 14). Extrapancreatic neoplasms were more frequent in cyst-other than cyst-only patients (14/906 [1.55%] vs. 5/4,822 [0.10%]; aOR, 14.20; 95% CI 5.09-39.61; p < 0.001). No extrapancreatic neoplasms were identified in cyst-HRI patients (0/446; 95% CI 0.00-0.82%). Incidentally detected intrapancreatic hyperenhancing lesions were uncommon (31/6,174, 0.50%); final diagnoses included 25 neuroendocrine tumors and four intrapancreatic splenules. CONCLUSION/CONCLUSIONS:Clinically significant extrapancreatic neoplasms were rare during pancreatic cyst surveillance, particularly among cyst-only and cyst-HRI patients. While this study did not directly assess the diagnostic performance of reduced field-of-view or non-contrast MRI, the low burden of extrapancreatic neoplasms suggests these protocol strategies warrant further evaluation in selected populations.

BACKGROUND/UNASSIGNED:Inflammatory skin diseases, including psoriasis and atopic dermatitis, require long-term management strategies that balance efficacy with safety. The 2025 American Academy of Dermatology guidelines encourage the judicious application of topical corticosteroids when their use is deemed necessary and for short durations of therapy. Recent availability of newer nonsteroidal topical therapies that are effective and safe, including for prolonged durations and on sensitive skin sites, has prompted a need for evidence-based guidance for clinicians in real-world practice. Tapinarof, a first-in-class, nonsteroidal aryl hydrocarbon receptor (AhR) agonist, was approved by the US Food and Drug Administration for the treatment of plaque psoriasis in adults and atopic dermatitis in patients aged 2 years and older in 2022 and 2025, respectively; however, its optimal place in therapy remains to be established. OBJECTIVE/UNASSIGNED:To develop expert consensus statements on the role of AhR agonists in the management of inflammatory skin diseases. METHODS/UNASSIGNED:A literature search produced 31 articles meeting inclusion criteria that were independently reviewed by an 11-member expert panel that convened on January 19, 2026. A modified Delphi process was used to develop 9 consensus statements. CONSENSUS RECOMMENDATIONS/ KEY FINDINGS/UNASSIGNED:AhR agonists represent a distinct therapeutic class with a unique multimodal mechanism involving immune modulation across Th1/Th2/Th17/Th22 pathways, skin barrier normalization, and antioxidant activity; tapinarof demonstrates a favorable safety profile with no restrictions on anatomic site, body surface area, or duration of use; tapinarof may be used concomitantly with systemic therapies; tapinarof is appropriate as both initial and long-term therapy for psoriasis in adults and atopic dermatitis in patients aged 2 years and older; and nonsteroidal topical therapies are preferred for chronic inflammatory skin diseases, particularly on the face and intertriginous areas. CONCLUSION/UNASSIGNED:AhR agonist therapy offers a clinically meaningful, advanced nonsteroidal option that addresses key limitations of traditional topical therapies in inflammatory skin disease management.

Trajectories of age-related neurocognitive decline are nonuniform, and are impacted by numerous environmental and physiological factors. Earlier life phases set the stage for later life neurocognitive function, with midlife marking a critical transition characterized by increasing variability in cognitive, affective, and physiological functioning. Despite its importance, this turbulent period remains underrepresented in open neuroimaging data resources. To address this gap, the Nathan Kline Institute - Rockland Sample (NKI-RS) created 'Mapping Interindividual Variation in the Aging Connectome' (MIVAC), an openly shared, multimodal dataset designed to map brain aging trajectories beginning in midlife and assess the influence of key modifiable factors linked to dementia prevention such as cardiorespiratory fitness, sleep, and mood. This longitudinal investigation includes 348 community-ascertained participants aged 38 to 71 years at baseline, with 219 participants completing 3 annual timepoints. Data collection incorporated deep phenotyping, including detailed assessment of cognitive, behavioral, medical, and cardiorespiratory fitness domains, to compliment multimodal neuroimaging (resting-state fMRI, diffusion MRI, morphometric MRI, and arterial spin labeling) and biospecimen collection. The protocol harmonizes with prior NKI-RS sub studies, enabling lifespan cross-sectional or longitudinal questions, while incorporating age-specific considerations for cognitive and neural aging. The full dataset is openly available.

IMPORTANCE/UNASSIGNED:Limited granular data exist on breast cancer in transgender, nonbinary, and/or gender-diverse (TGD) individuals. OBJECTIVE/UNASSIGNED:To describe patient demographic and tumor clinicopathological variables, clinically relevant risk factors, method of breast cancer detection, treatment characteristics, and locoregional outcomes and to estimate a 5-year breast cancer-specific survival (BCSS). DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cohort study obtained data on patients treated from 1990 to 2023 from 22 US academic medical centers using institutional databases, electronic medical records, and tumor registries. Included participants were TGD individuals 18 years or older with stage 0 to IV breast cancer. A comparative breast cancer cohort was selected from the 2016 to 2021 Surveillance, Epidemiology, and End Results Program (SEER) breast cancer dataset. Data were analyzed from January to October 2025. EXPOSURE/UNASSIGNED:Breast cancer. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Estimated 5-year BCSS and locoregional recurrence rates. Wilcoxon rank sum and χ2 tests were used to compare continuous and categorical variables. Kaplan-Meier analysis was used to estimate 5-year BCSS. RESULTS/UNASSIGNED:A total of 112 TGD persons (median [IQR] age at diagnosis, 42.5 [36.5-51.0] years; 104 individuals [92.9%] were assigned female at birth) with breast cancer and 1 with bilateral disease were included in the analysis. Forty-three patients (38.4%) used gender-affirming hormone therapy before diagnosis. Among the entire cohort, 58 patients (51.8%) detected their own breast cancer, 68 (60.7%) had a familial breast cancer history, and 16 (14.3%) had a pathogenic germline variant. Tumors were predominantly hormone receptor positive (96 [85.7%]) and early stage (29 [25.7%] ductal carcinoma in situ [DCIS]; 51 [45.1%] stage I). The TGD cohort, compared with patients with breast cancer in the SEER dataset (N = 480 915), was younger (median [IQR] age, 42.5 [36.5-51.0] years vs 62.0 [52.0-72.0] years), had a higher proportion of persons assigned male at birth (8 [7.1%] vs 3522 [0.7%]), more often had progesterone receptor-positive disease (89 [79.5%] vs 335 491 [69.8%]), and presented with earlier-stage disease (eg, DCIS: 29 [25.9%] vs 79 604 [16.6%]). With a median (IQR) follow-up time for the TGD cohort of 38 (24-74) months, 5-year BCSS was favorable at 96.2% (95% CI, 85.3%-99.0%). CONCLUSIONS AND RELEVANCE/UNASSIGNED:This cohort study of TGD patients with breast cancer found that this population was young and often detected their own tumors via self-examination, suggesting opportunities to improve early detection through screening for individuals at elevated risk. Although short-term BCSS appeared favorable, prospective research is essential to define evidence-based guidelines and elucidate long-term outcomes.

Radiation therapy (RT) cures many patients with localized prostate cancer, but late urinary toxicity impairs quality of life and can limit dose escalation for better RT efficacy. Understanding the mechanistic bases of radiation toxicity is critical for designing effective treatment strategies to benefit prostate cancer survivors. Genome-wide association studies (GWAS) have shown that genetic susceptibility can influence toxicity risk. A GWAS of reduced urinary stream two years after RT identified rs7720298 tagging a risk locus, but the mechanism through which this SNP acts is unclear. We performed integrative bioinformatics and molecular studies that identified a nearby long non-coding RNA, LncDNAH5, whose expression is influenced by rs7720298 in human tissues, and we hypothesized it mediates RT responses. In cultured cells, LncDNAH5 suppressed the DNA repair factor TP53BP1, thus favoring homologous recombination (HR) over non-homologous end joining (NHEJ). Mechanistically, LncDNAH5 enhanced MDM2-dependent ubiquitination and degradation of TP53BP1 by promoting formation of an MDM2-TP53BP1 complex; MDM2 antagonist Nutlin-3 attenuated these effects. In vivo, a bladder-specific LncDNAH5 overexpression mouse model exhibited exacerbated RT-induced inflammatory and fibrotic responses, consistent with a heightened urothelial radiosensitivity. Together, these data support a rs7720298/LncDNAH5/MDM2/TP53BP1 axis that modulates DNA repair choice and tissue response to radiation. Clinically, LncDNAH5 expression and rs7720298 genotype may serve as complementary biomarkers to identify patients at risk for late urinary toxicity and to guide early intervention and personalized radioprotective strategies for better patient outcomes.

BACKGROUND:Minimally invasive surgical techniques have improved outcomes in colorectal surgery, but comparative data on their use in total abdominal colectomy with end ileostomy for inflammatory bowel disease remain limited. This study aimed to compare postoperative outcomes among patients undergoing robotic, laparoscopic, or open total abdominal colectomy for inflammatory bowel disease. METHODS:We performed a retrospective cohort analysis using propensity score matching to control for baseline differences across patients. Data were obtained from the 2022 American College of Surgeons National Surgical Quality Improvement Program, a national surgical outcomes registry. Adult patients who underwent total abdominal colectomy with end ileostomy for ulcerative colitis or Crohn's disease were included. Patients were treated with robotic-assisted, laparoscopic, or open total abdominal colectomy with end ileostomy. The primary outcome was any postoperative complication within 30 days of surgery. Secondary outcomes included operative time, conversion to open surgery, length of hospital stay, 30-day readmission, and other specific postoperative complications such as surgical site infection and renal insufficiency. RESULTS:A total of 581 matched patients were analyzed, including 83 robotic, 415 laparoscopic, and 83 open cases. There were no significant differences in overall 30-day morbidity across groups. Robotic surgery had significantly longer operative time than laparoscopic but not open surgery. Organ space infections and renal complications were more common in the robotic group compared with laparoscopic. Although robotic surgery was associated with shorter hospital stay, it also had the highest 30-day readmission rate. CONCLUSIONS:Robotic total abdominal colectomy demonstrated similar overall morbidity and conversion rates compared with other approaches but was associated with longer operative time, increased complications, and higher readmissions. Further refinement of perioperative protocols and patient selection may improve outcomes.

The Ca²⁺ release-activated Ca²⁺ (CRAC) channel mediates store-operated calcium entry (SOCE), a ubiquitous pathway essential for many cell types, including immune cells. Three Orai (Orai1/2/3) proteins constitute the plasma membrane pore-forming units of CRAC channels that are activated by the endoplasmic reticulum (ER) Ca²⁺-sensing STIM1/2 proteins when ER Ca²⁺ stores are depleted. Orai1/2/3 are differentially expressed across primary cells with discernible differences in their structures and biophysical properties. Further, Orai1 has two alternatively translated isoforms: long mammalian-specific Orai1α and the 63-residue shorter Orai1β, which is evolutionarily older and conserved across vertebrates. Whether Orai1α/1β/2/3 produce unique cytosolic Ca²⁺ signatures that bias transcriptional responses through effectors like NFAT is unclear. Here, we used HEK293 cells engineered to express one native Orai isoform and show that all Orai isoforms couple to NFAT1/4 induction. The magnitude of NFAT1/4 induction for each Orai isoform matches that of SOCE, with the following profile: Orai1β>Orai1α>>Orai2>Orai3. Near-native re-expression of either Orai1α or Orai1β in primary murine Orai1 ^-/- CD4⁺ T cells restored SOCE, NFAT activation, cytokine production and promoted near identical transcriptional responses enriched for immune activation pathways. An analysis of genetic and clinical data of human individuals showed that homozygous null mutations selectively abolishing Orai1α are not associated with disease resembling CRAC channelopathy. Primary T cells from individuals homozygous or heterozygous for an Orai1α null mutation showed enhanced, rather than impaired, SOCE and NFAT induction. Our data indicate that NFAT activation and transcriptional outputs are primarily driven by the graded strength of SOCE mediated by each isoform of the Orai quartet.