Faculty Bibliography

Hypertensive disorders of pregnancy (HDP) may account for a considerable and growing clinical burden at rural hospitals which have been providing fewer obstetric services over the past two decades. The objectives of this analysis were to evaluate trends, risk factors, and outcomes associated with HDP during delivery hospitalizations at rural hospitals in the United States.The 2000 to 2020 National Inpatient Sample was used for this repeated-cross sectional analysis. Delivery hospitalizations at rural hospitals to women 15 to 54 years of age with and without HDP (including preeclampsia and gestational hypertension) were identified. Trends in HDP were characterized with joinpoint regression and estimated as the average annual percent change (AAPC) with 95% confidence intervals (CIs). The associations between (i) HDP risk factors and HDP and (ii) HDP and adverse maternal outcomes were estimated with adjusted logistic regression models.Among 8,885,683 deliveries that occurred at rural hospitals, the proportion with a HDP diagnosis increased significantly from 6.0% in 2000 to 11.1% in 2020 (AAPC: 3.1%; 95% CI: 2.8 and 3.4%). Preeclampsia with severe features (AAPC: 5.5%; 95% CI: 4.8 and 6.2%) and superimposed preeclampsia (AAPC: 6.5%; 95% CI: 5.6 and 7.5%) underwent the largest relative increases over the study period. Obesity, pregestational diabetes, chronic hypertension, multiple gestation, and chronic kidney disease were all associated with increased adjusted odds of HDP. HDP diagnoses were significantly associated with severe maternal morbidity (SMM), transfusion, stroke, and disseminated intravascular coagulation. The proportion of overall delivery SMM associated with HDP more than doubled from 11.3% in 2000 to 24.7% in 2020.Among delivery hospitalizations at rural hospitals, HDP, and associated risk factors increased significantly over the study period. Deliveries with HDP accounted for an increasing proportion of population-level SMM. HDP is a major, growing contributor to maternal risk and adverse outcomes during deliveries at rural hospitals. · Hypertensive disorders accounted for an increasing proportion of population-level severe morbidity.. · Hypertensive disorders increased among rural delivery hospitalizations.. · Risk factors associated with hypertensive disorders increased among rural delivery hospitalizations..

OBJECTIVE:To assess variation in inpatient antepartum management strategies for placenta accreta spectrum (PAS) disorder and their association with hospitalization costs in a national sample. METHODS:This retrospective cohort study used the 2016-2021 Nationwide Readmissions Database to identify individuals aged 15-54 years who underwent cesarean hysterectomy for PAS between 23 and 35 weeks of gestation. Patients were categorized into four management groups based on whether they had a separate antepartum hospitalization and their predelivery length of stay (LOS) during the delivery hospitalization. Median total hospitalization costs (inclusive of separate antepartum and delivery hospitalization), adjusted to 2023 dollars, were analyzed as continuous and dichotomized outcomes (above the 90th percentile). Unadjusted and adjusted logistic and median regression models assessed whether inpatient management variation, postpartum LOS, demographic, and clinical factors influenced hospitalization costs. RESULTS:Among 3,237 individuals with PAS, 50.5% had no prior antepartum admission and a predelivery LOS of 2 days or less, 31.9% had no prior antepartum admission and a predelivery LOS of more than 2 days, 11.8% had a prior antepartum admission and a predelivery LOS of 2 days or less, and 5.8% had a prior antepartum admission and a predelivery LOS of more than 2 days. Median total hospitalization costs varied significantly by management group, with mean costs ranging from $21,829 to $51,039. Management variation was associated with nearly 3- to 29-times higher likelihood of high total hospitalization costs and $8,907-29,021 adjusted higher median cost depending on the specific management group. Of evaluated clinical factors, only disseminated intravascular coagulation was associated with an adjusted median cost increase of $12,921. CONCLUSION/CONCLUSIONS:Nearly one in five patients with PAS experienced an all-cause antepartum hospitalization. Variation in inpatient admission for management of PAS was evident in this national sample and was a significant driver of hospitalization costs. Although some antepartum hospitalizations and prolonged predelivery lengths of stay are unavoidable due to the complexity and severity of PAS, efforts to reduce unnecessary variations could reduce total hospitalization costs.

Nuclear depletion and cytoplasmic aggregation of the RNA-binding protein TDP-43 are cellular hallmarks of amyotrophic lateral sclerosis (ALS). TDP-43 nuclear loss causes de-repression of cryptic exons, yet cryptic alternative polyadenylation (APA) events have been largely overlooked. In this study, we developed a bioinformatic pipeline to reliably identify alternative last exons, 3' untranslated region (3'UTR) extensions and intronic polyadenylation APA event types, and we identified cryptic APA sites induced by TDP-43 loss in induced pluripotent stem cell (iPSC)-derived neurons. TDP-43 binding sites are enriched at sites of these cryptic events, and TDP-43 can both repress and enhance APA. All categories of cryptic APA were also identified in ALS and frontotemporal dementia (FTD) postmortem brain tissue. RNA sequencing (RNA-seq), thiol(SH)-linked alkylation for the metabolic sequencing of RNA (SLAM-seq) and ribosome profiling (Ribo-seq) revealed that distinct cryptic APA categories have different downstream effects on transcript levels and that cryptic 3'UTR extensions can increase RNA stability, leading to increased translation. In summary, we demonstrate that TDP-43 nuclear depletion induces cryptic APA, expanding the palette of known consequences of TDP-43.

Active nematic liquid crystals are the main structural phase of gliomas, promoting collective migration and aggression. We establish the existence of nematic order and topological defect lines and loops in 3D in vivo mouse and human glioma brain tumors. As predicted by theory, sections through the disclination lines in 3D appear as ±1/2 topological defects in 2D. In 3D, these defects either persist along disclination lines or twist as they interconvert from -1/2 to +1/2. Cell alignment exhibits quasi-long-range order, spreading throughout the tumor over distances between 300-3000 μm. In vitro -1/2 and +1/2 defects display changes in apoptosis levels, suggesting topological defects regulate glioma cell density. The large scale order of gliomas correlates with tumors' aggressive behavior. The organization of gliomas as active nematic liquid crystals provides a novel physical foundation of complex solid tumors; their deconstruction signposts potential treatments for deadly cancers.

A critical challenge in glioma treatment is detecting tumour infiltration during surgery to achieve safe maximal resection^1-3. Unfortunately, safely resectable residual tumour is found in the majority of patients with glioma after surgery, causing early recurrence and decreased survival^4-6. Here we present FastGlioma, a visual foundation model for fast (<10 s) and accurate detection of glioma infiltration in fresh, unprocessed surgical tissue. FastGlioma was pretrained using large-scale self-supervision (around 4 million images) on rapid, label-free optical microscopy, and fine-tuned to output a normalized score that indicates the degree of tumour infiltration within whole-slide optical images. In a prospective, multicentre, international testing cohort of patients with diffuse glioma (n = 220), FastGlioma was able to detect and quantify the degree of tumour infiltration with an average area under the receiver operating characteristic curve of 92.1 ± 0.9%. FastGlioma outperformed image-guided and fluorescence-guided adjuncts for detecting tumour infiltration during surgery by a wide margin in a head-to-head, prospective study (n = 129). The performance of FastGlioma remained high across diverse patient demographics, medical centres and diffuse glioma molecular subtypes as defined by the World Health Organization. FastGlioma shows zero-shot generalization to other adult and paediatric brain tumour diagnoses, demonstrating the potential for our foundation model to be used as a general-purpose adjunct for guiding brain tumour surgeries. These findings represent the transformative potential of medical foundation models to unlock the role of artificial intelligence in the care of patients with cancer.

Purpose To review published literature on the clinical efficacy, use, and accuracy of the 31-gene expression profiling (31-GEP) test for prognostic information in invasive melanoma. Methods A comprehensive literature search used keywords "31-gene expression profiling," "melanoma," "prognosis," "clinical efficacy," and "clinical utility." A panel of 10 dermatologists with expertise in melanoma management reviewed the articles and created consensus statements. A modified Delphi process approved each statement, requiring supermajority approval through multiple rounds of real-time voting, with strength of recommendation assigned. Results The search produced 150 articles; 26 met inclusion criteria. The panel unanimously voted to adopt 9 consensus statements and recommendations regarding 31-GEP testing: 8 with strength "A" and 1 with strength "C." Conclusion The panel agreed there is strong support for using 31-GEP testing to provide prognostic information for invasive melanoma. The test provides prognostic information when thickness and other traditional factors are unknown, improves prognosis assessment when added to American Joint Committee on Cancer 8th edition staging system, and is associated with improved melanoma-specific mortality and overall survival. The panel concluded that the robust existing literature strongly supports its use as a best practice for appropriate patients with melanoma.

BACKGROUND/UNASSIGNED:Colorectal cancer (CRC) poses a major health challenge worldwide, specifically in developing countries, where late-stage diagnoses lead to substantial mortality rates. This study aims to evaluate CRC knowledge and screening behaviors in Pakistan while identifying barriers that hinder CRC screening uptake. MATERIALS AND METHODS/UNASSIGNED:In this cross-sectional study, a paper questionnaire was distributed to patients and companions in hospitals across all provinces in Pakistan between March 2022 and December 2023. RESULTS/UNASSIGNED:Out of 5,244 participants (68.7% male), only 23.2% claimed knowledge of CRC, while 31.5% had some awareness of it. Merely 20.1% believed CRC to be common in Pakistan. Only 6.6% of those aged 50 and above had undergone CRC screening, with 59.7% reporting no prior screening. Notably, 35.9% expressed interest in colonoscopy at age 45 for CRC screening. Screening intentions were lower in younger, female participants, and residents from Balochistan compared to their counterparts. Widowed/divorced individuals showed higher intentions than married ones. Several barriers, including a lack of screening facilities and fear of results, negatively impacted screening intentions. CONCLUSION/UNASSIGNED:Colorectal cancer awareness and screening uptake remain critically low in Pakistan, with significant barriers including a lack of knowledge, physician recommendation, and access to screening facilities. Sociodemographic factors such as age, gender, education, and region significantly influenced screening intentions. Targeted awareness efforts and improved healthcare provider engagement are essential to enhance CRC screening rates and reduce the disease burden. HOW TO CITE THIS ARTICLE/UNASSIGNED:. Colorectal Cancer Screening Knowledge and Associated Willingness and Barriers to Screening in Nationwide Pakistan Cohort. Euroasian J Hepato-Gastroenterol 2025;15(2):156-163.

Preimplantation genetic testing for aneuploidy (PGT-A) has become a widely adopted component of in vitro fertilization (IVF) practice. However, PGT-A is not a single, uniform test; its predictive value and clinical utility remain highly dependent on test performance and interpretation, both of which vary substantially between laboratories and platforms. This article aims to define the intended goals of PGT-A, evaluate methods for proper test validation, and explore how validation data impacts clinical counseling and decision-making. Particular attention is given to newer diagnostic categories such as mosaicism and segmental aneuploidy, for which clinical validation is limited and inter-laboratory variability is high. While PGT-A can reduce futile embryo transfers and support elective single embryo transfer, misapplication of unvalidated results may reduce IVF success rates. To ensure responsible use of PGT-A, clinicians must demand transparent, assay-specific validation data and use this information to guide evidence-based counseling for embryo transfer, storage, and disposition.

The resolution revolution in single particle cryo-electron microscopy (cryo-EM) has dramatically expanded our structural knowledge of large biomolecular complexes. While high-resolution cryo-EM density maps enable atomic model building, lower-resolution maps can still reveal secondary structures, folds, and domains. When combined with integrative modeling approaches, such data can provide meaningful insights into biomolecular structure and function. Constructing accurate models, however, remains challenging: at low resolutions it is difficult to interpret density maps features reliably, and at high resolutions traditional model-building workflows can become a time-consuming bottleneck. Deep learning, which is transforming problem-solving across scientific domains, offers powerful new tools to automate and accelerate this process. In this review, we discuss deep learning-based methods developed to automate model building in cryo-EM density maps, assessing their impact on streamlining structure determination. Recognizing that biomacromolecular structures exhibit hierarchical organization, we classify these methods according to their ability to model primary, secondary, tertiary, and quaternary structures of biomolecules. Deep learning tools for building atomic models in cryo-EM density maps are further grouped as de novo, where the model is predicted directly from features learned from the cryo-EM density, or hybrid, where it is derived by integrating structural templates with these features. We outline current limitations, including the challenge of obtaining sufficiently large and diverse datasets for training networks to model different types of biomolecules in the cryo-EM density maps, and the open challenge of constructing training sets that capture the conformational heterogeneity often observed in the cryo-EM maps. We conclude by highlighting emerging directions for this rapidly advancing field, which promise to make automated, data-driven model building an integral part of structural biology.

Tamm-Horsfall protein (THP) is the most abundant protein in urine, yet its function remains incompletely understood. It has been hypothesized that THP contributes to the maintenance of urinary homeostasis. We report a case of a 71-year-old male with a history of renal cell carcinoma treated with partial nephrectomy in 2017. He represented 8 years later with an enlarging, enhancing renal mass concerning for recurrence. A radical nephrectomy was performed and revealed a benign specimen with a positive PAS stain, consistent with THP. To our knowledge this is the first report of THP deposition in the renal parenchyma after partial nephrectomy.