Publications by authors named "P-W Lee"

Molecular subtypes, such as defined by The Cancer Genome Atlas (TCGA), delineate a cancer's underlying biology, bringing hope to inform a patient's prognosis and treatment plan. However, most approaches used in the discovery of subtypes are not suitable for assigning subtype labels to new cancer specimens from other studies or clinical trials. Here, we address this barrier by applying five different machine learning approaches to multi-omic data from 8,791 TCGA tumor samples comprising 106 subtypes from 26 different cancer cohorts to build models based upon small numbers of features that can classify new samples into previously defined TCGA molecular subtypes-a step toward molecular subtype application in the clinic.

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  • Glioblastoma is described as immunologically "cold," making it resistant to solo immune-checkpoint inhibitors (ICI) like pembrolizumab, although neoadjuvant use may improve survival based on prior studies.
  • A study involving 25 additional patients analyzed tumor tissue for gene signatures and found that neoadjuvant pembrolizumab led to decreased cancer proliferation genes and increased T-cell activity, indicating a specific response to this treatment.
  • Despite observing these molecular changes, the study did not confirm an overall survival benefit from neoadjuvant pembrolizumab, suggesting that some patients may inherently resist ICI and may need additional therapies for effective treatment.
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Background: Percutaneous coronary intervention (PCI) using drug-eluting stents is an established strategy for the treatment of significant obstructive coronary artery disease. Evidence supports that intravascular imaging-guided PCI offers advantages over conventional angiography-guided PCI, though its use is limited, likely due to high costs. Angiography-guided PCI relies on visual estimation, leading to inter- and intra-observer variability and suboptimal outcomes.

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Background: Genomic sequencing technology allows for identification of reproductive couples with an increased chance, as compared with that in the general population, of having a child with an autosomal recessive or X-linked genetic condition.

Methods: We investigated the feasibility, acceptability, and outcomes of a nationwide, couple-based genetic carrier screening program in Australia as part of the Mackenzie's Mission project. Health care providers offered screening to persons before pregnancy or early in pregnancy.

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  • Dual immune checkpoint blockade (ICB) using CTLA4 and PD-(L)1 inhibitors shows improved anti-tumor effectiveness and immune toxicity compared to PD-(L)1 inhibitors alone in advanced non-small-cell lung cancer (NSCLC) patients.
  • Patients with mutations in STK11 and/or KEAP1 genes benefit more from the combination treatment compared to those receiving only PD-(L)1 inhibitors, as shown in the POSEIDON trial.
  • The loss of KEAP1 serves as a strong predictor for the success of dual ICB, as it leads to a more favorable outcome by changing the tumor's immune environment to better engage CD4 and CD8 T cells for anti-tumor activity. *
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Background:  About 7% of patients with cancer-associated venous thromboembolism (CAT) develop a recurrence during anticoagulant treatment. Identification of high-risk patients may help guide treatment decisions.

Aim:  To identify clinical predictors and develop a prediction model for on-treatment recurrent CAT.

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Most Americans exceed the recommended limit for sodium in their diet, a risk factor for hypertension and cardiovascular disease. Efforts have been made by the food industry and government agencies to reduce the sodium content in foods and encourage the consumption of lower sodium diets. Such efforts, however, are not successful in improving public health when consumers do not accept and consume lower sodium foods.

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Background MRI plays a crucial role in restaging locally advanced rectal cancer treated with total neoadjuvant therapy (TNT); however, prospective studies have not evaluated its ability to accurately select patients for nonoperative management. Purpose To evaluate the ability of restaging MRI to predict oncologic outcomes and identify imaging features associated with residual disease (RD) after TNT. Materials and Methods This was a secondary analysis of the Organ Preservation in Rectal Adenocarcinoma (OPRA) trial, which randomized participants from April 2014 to March 2020 with stages II or III rectal adenocarcinoma to undergo either induction or consolidation TNT.

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  • Steroidal mineralocorticoid receptor antagonists help patients with heart failure and reduced ejection fraction, but their effectiveness in those with mildly reduced or preserved ejection fraction is unclear, indicating a need for further research on finerenone.
  • In a double-blind study, patients with heart failure (ejection fraction 40% or greater) were assigned to receive either finerenone or a placebo to assess its impact on heart failure events and cardiovascular death.
  • Results showed that finerenone led to fewer worsening heart failure events and a lower overall rate of primary outcome events compared to placebo, although it also carried a higher risk of hyperkalemia.
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Background: Whether a conservative strategy of medical therapy alone or a strategy of medical therapy plus invasive treatment is more beneficial in older adults with non-ST-segment elevation myocardial infarction (NSTEMI) remains unclear.

Methods: We conducted a prospective, multicenter, randomized trial involving patients 75 years of age or older with NSTEMI at 48 sites in the United Kingdom. The patients were assigned in a 1:1 ratio to a conservative strategy of the best available medical therapy or an invasive strategy of coronary angiography and revascularization plus the best available medical therapy.

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In this paper, we propose the use of punch-through nMOS (PTnMOS) as an alternative to pMOS in complementary metal oxide semiconductor (CMOS) circuits. According to the TCAD simulation results, PTnMOS exhibit sub-threshold characteristics similar to those of pMOS and can be formed by simply changing the doping concentration of the source and drain. Without the need for sizing, which solves the area occupation problem caused by the need to increase the width of pMOS due to insufficient hole mobility.

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Background And Purpose: Patients with brain tumors have high intersubject variation in putative language regions, which may limit the utility of straightforward application of healthy subject brain atlases in clinical scenarios. The purpose of this study was to develop a probabilistic functional brain atlas that consolidates language functional activations of sentence completion and Silent Word Generation language paradigms using a large sample of patients with brain tumors.

Materials And Methods: The atlas was developed using retrospectively collected fMRI data from patients with brain tumors who underwent their first standard-of-care presurgical language fMRI scan at our institution between July 18, 2015, and May 13, 2022.

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  • The study investigates the genetic basis of supraventricular tachycardias, focusing on atrioventricular nodal reentrant tachycardia (AVNRT) and atrioventricular accessory pathways/reciprocating tachycardia (AVAP/AVRT).
  • Through multiancestry meta-analyses of genome-wide association studies, researchers identified significant genetic loci associated with AVNRT and AVAP/AVRT, implicating specific genes in these cardiac conditions.
  • The results suggest that gene regions related to ion channels and cardiac development play crucial roles in susceptibility to supraventricular tachycardias, potentially influencing other cardiovascular issues such as atrial fibrillation
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Single-cell genomics is a powerful tool for studying heterogeneous tissues such as the brain. Yet little is understood about how genetic variants influence cell-level gene expression. Addressing this, we uniformly processed single-nuclei, multiomics datasets into a resource comprising >2.

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  • Cardiomyocyte differentiation is regulated by the modulation of BMP/Wnt signaling pathways, with current research focused on understanding how these pathways remove regulatory obstacles during development.* -
  • A genome-wide CRISPR screen identified NF2 as a critical factor for early cardiomyocyte specification, demonstrating that NF2 is essential for maintaining cardiomyocyte identity during differentiation.* -
  • The study revealed that NF2 works with AMOT to inhibit YAP activation during mesendoderm formation, highlighting their joint role in clearing regulatory barriers necessary for proper cardiac lineage development.*
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Purpose: To evaluate the effectiveness of marrow stimulation (MS) versus biphasic scaffold loaded with autologous cartilage (scaffold) in treating focal osteochondral lesions of the knee.

Methods: In total, 54 patients with symptomatic focal chondral or osteochondral lesion in the knee were randomized to either the scaffold group or the MS group. International Knee Documentation Committee subjective score, the Knee Injury Osteoarthritis Outcome Score, and magnetic resonance imaging (MRI) were assessed preoperatively and at 1 and 2 years after operation to compare treatment outcomes.

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The clinical potential of current FDA-approved chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapy is encumbered by its autologous nature, which presents notable challenges related to manufacturing complexities, heightened costs, and limitations in patient selection. Therefore, there is a growing demand for off-the-shelf universal cell therapies. In this study, we have generated universal CAR-engineered NKT (CAR-NKT) cells by integrating iNKT TCR engineering and HLA gene editing on hematopoietic stem cells (HSCs), along with an ex vivo, feeder-free HSC differentiation culture.

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  • - Single-cell genomics helps us study diverse brain tissues, revealing how genetic variants affect gene expression at the cell level through an analysis of over 2.8 million nuclei from the prefrontal cortex across 388 individuals.
  • - Researchers identified more than 550,000 specific regulatory elements and over 1.4 million expression-quantitative-trait loci linked to various cell types, allowing them to develop networks that illustrate the impact of aging and neuropsychiatric disorders on cellular changes.
  • - An integrative model was created to predict single-cell gene expression and simulate cellular changes, which identified around 250 genes associated with disease risk and relevant drug targets tied to specific cell types.
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Background: HLA class II antigens, DR, DQ, and DP, comprised an α and β chains, which typically combine, within the same isotype, to form the major histocompatibility complex:peptide complex. Interisotypic pairing is not commonly observed. Although reports of DQβ:DRα heterodimers exist, the pairing was reported to be unstable and, therefore, not studied to any extent.

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The intraoperative estimated blood loss (EBL), an essential parameter for perioperative management, has been evaluated by manually weighing blood in gauze and suction bottles, a process both time-consuming and labor-intensive. As the novel EBL prediction platform, we developed an automated deep learning EBL prediction model, utilizing the patch-wise crumpled state (P-W CS) of gauze images with texture analysis. The proposed algorithm was developed using animal data obtained from a porcine experiment and validated on human intraoperative data prospectively collected from 102 laparoscopic gastric cancer surgeries.

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In metastatic urothelial cancer (mUC), cisplatin versus carboplatin leads to durable disease control in a subset of patients. The IMvigor130 trial reveals more favorable effects with atezolizumab combined with gemcitabine and cisplatin (GemCis) versus gemcitabine and carboplatin (GemCarbo). This study investigates the immunomodulatory effects of cisplatin as a potential explanation for these observations.

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Antibodies reactive to human leukocyte antigens (HLA) represent a barrier for patients awaiting transplantation. Based on reactivity patterns in single-antigen bead (SAB) assays, various epitope matching algorithms have been proposed to improve transplant outcomes. However, some antibody reactivities cannot be explained by amino acid motifs, leading to uncertainty about their clinical relevance.

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  • Allogeneic Vγ9Vδ2 T cells show promise for cancer therapy due to their safety and tumor-fighting abilities, but their clinical effectiveness has been limited by donor variability and other factors.
  • Researchers are enhancing these T cells by selecting donors based on a biomarker (CD16), which improves their immune response and functionality, supported by RNA sequencing.
  • Preclinical studies in ovarian cancer models confirm that these engineered CD16 Vδ2 T cells are effective, safe, and persist within the body, making them a potential new therapy for treating cancer.
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Solute carrier organic anion (SLCO) transporters (OATP transporters) are involved in cellular uptake of drugs and hormones. Germline variants in SLCO1B3 and SLCO2B1 have been implicated in prostate cancer progression and therapy response, including to androgen deprivation and statin medications, but results have appeared heterogeneous. We conducted a cohort study of five single-nucleotide polymorphisms (SNPs) in SLCO1B3 and SLCO2B1 with prior evidence among 3208 men with prostate cancer who participated in the Health Professionals Follow-up Study or the Physicians' Health Study, following participants prospectively after diagnosis over 32 years (median, 14 years) for development of metastases and cancer-specific death (lethal disease, 382 events).

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  • - The study aimed to compare computed tomography (CT) with automatic rib unfolding and 3D imaging for detecting rib fractures and flail chest in 130 patients with blunt chest trauma.
  • - Five independent readers evaluated rib fractures using traditional CT, automatic rib unfolding, and 3D images, establishing a consensus for accurate diagnosis.
  • - Automatic rib unfolding reduced reading time significantly (by up to 74.9%) while providing similar diagnostic accuracy and better agreement among readers compared to conventional images.
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