Publications by authors named "David Pan"

Optical neural networks (ONNs) are promising hardware platforms for next-generation neuromorphic computing due to their high parallelism, low latency, and low energy consumption. However, previous integrated photonic tensor cores (PTCs) consume numerous single-operand optical modulators for signal and weight encoding, leading to large area costs and high propagation loss to implement large tensor operations. This work proposes a scalable and efficient optical dot-product engine based on customized multi-operand photonic devices, namely multi-operand optical neuron (MOON).

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AMP-activated protein kinase (AMPK) is an energy sensor that regulates cellular functions in response to changes in energy availability. However, whether AMPK activity is spatially regulated, and the implications for cell function, have been unclear. We now report that AMPK associates with the Golgi, and that its activation by two specific pharmacological activators leads to Golgi fragmentation similar to that caused by the antibiotic Golgicide A, an inhibitor of Golgi-specific Brefeldin A resistance factor-1 (GBF1), a guanine nucleotide exchange factor that targets ADP-ribosylation factor 1 (ARF1).

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Optimization methods are frequently exploited in the design of silicon photonic devices. In this paper, we demonstrate that pushing the objective function to its minimum during optimization often results in devices that gradually become more sensitive to perturbations of design variables. The dominant strategy of selecting the design with the smallest objective function can lead to fabrication failure or yield loss due to manufacturing process variations.

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Background: The impact of nucleos(t)ide analogues on intrahepatic viral burden and immune microenvironment in patients with chronic hepatitis B (CHB) is not clear.

Objective: We aimed to characterise the effects of tenofovir disoproxil fumarate (TDF) on intrahepatic viral burden and the liver immune microenvironment in patients with CHB.

Design: Core liver biopsies were collected at baseline and year 3 from patients with CHB with minimally raised serum alanine aminotransferase in a double-blind placebo-controlled trial (NCT01522625).

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Robustness is the invariant development of phenotype despite environmental changes and genetic perturbations. In the Arabidopsis flower bud, four sepals robustly initiate and grow to a constant size to enclose and protect the inner floral organs. We previously characterized the mutant development-related myb-like 1 (drmy1), where 3-5 sepals initiate variably and grow to different sizes, compromising their protective function.

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Purpose: Gamma knife radiosurgery (GKRS) for orbital cavernous hemangioma (OCH) has emerged as a promising method due to its significant clinical improvement and low incidence of complications. This study aimed to evaluate the safety and efficacy of GKRS for the treatment of OCH.

Methods: In accordance with the PRISMA framework, we searched PubMed, Cochrane Central, and Embase for studies reporting outcomes of GKRS for OCH.

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Robustness is the reproducible development of a phenotype despite stochastic noise. It often involves tradeoffs with other performance metrics, but the mechanisms underlying such tradeoffs were largely unknown. An Arabidopsis flower robustly develops four sepals from four precisely positioned auxin maxima.

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Article Synopsis
  • Abdominal obesity is linked to an increased risk of metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD).
  • The study employed advanced genetic analysis methods, including RNA sequencing and Mendelian randomization, to explore how specific genes related to abdominal obesity impact MASLD at the cellular level.
  • The research identified 17 key genes that mediate the effects of abdominal obesity on MASLD, demonstrating significant changes in adipocyte functions and highlighting the importance of these genes in the disease's development.
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Article Synopsis
  • The study aimed to determine if the morphology (compact vs. diffuse) of brain arteriovenous malformations (bAVMs) influences the rate of hemorrhagic events in patients undergoing Stereotactic Radiosurgery (SRS).
  • It analyzed 262 adult patients with unruptured bAVMs, revealing that hemorrhagic events occurred in 5.0% of patients, with a higher risk associated with larger and diffuse bAVMs.
  • Findings suggest that compact and smaller bAVMs, along with a higher prescribed treatment dose, are linked to lower hemorrhage risks, which could inform clinical decision-making regarding SRS treatment plans.
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Robustness is the reproducible development of a phenotype despite stochastic noise. It often involves tradeoffs with other performance metrics, but the mechanisms underlying such tradeoffs were largely unknown. An flower robustly develops four sepals from four precisely positioned auxin maxima.

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Clinical tumor tissues that are preserved as formalin-fixed paraffin-embedded (FFPE) samples result in extensive cross-linking, fragmentation, and chemical modification of RNA, posing significant challenges for RNA-seq-based gene expression profiling. This study sought to define an optimal RNA-seq protocol for FFPE samples. We employed a common RNA extraction method and then compared RNA-seq library preparation protocols including RNAaccess, RiboZero and PolyA in terms of sequencing quality and concordance of gene expression using FFPE and case-matched fresh-frozen (FF) triple-negative breast cancer (TNBC) tissues.

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Objective: The goal of this study was to assess the safety and efficacy of single-session Gamma Knife radiosurgery (GKRS) for orbital cavernous hemangiomas (OCHs).

Methods: Patients who presented with an OCH between September 1999 and May 2022 and were treated with single-session GKRS were included in this single-center cohort study.

Results: There were 23 patients (7 males and 16 females) in this study.

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Purpose: To examine the differential effects of SRS and TKI on EGFR-mutated NSCLC patients with brain metastases (BMs) and outcomes following continuation of the same TKI agent in case of new BMs.

Methods: This study included 608 NSCLC patients (2,274 BMs) while meta-analyses included 1,651 NSCLC patients (> 3,944 BMs). Overall survival (OS) and intracranial progression free survival (iPFS) were estimated using Kaplan-Meier methods.

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Article Synopsis
  • Obesity can lead to inflammation and related health issues due to dysfunction in fat tissue.
  • In this study, researchers examined preadipocytes (fat cells) from identical twins with different BMIs to understand how increased BMI affects chromatin structure and its role in inflammation.
  • Findings reveal that higher BMI alters the accessibility of chromatin in these cells, which is linked to higher levels of systemic inflammation, suggesting a genetic and environmental interaction that contributes to obesity-related issues.
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Background And Objectives: The pathophysiology of vestibular schwannoma (VS) pseudoprogression after Gamma Knife radiosurgery (GKRS) remains unclear. Radiological features in pretreatment magnetic resonance images may help predict VS pseudoprogression. This study used VS radiological features quantified using an automated segmentation algorithm to predict pseudoprogression after GKRS treatment.

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Background: Non-alcoholic fatty liver disease (NAFLD) is a fast-growing, underdiagnosed, epidemic. We hypothesise that obesity-related inflammation compromises adipose tissue functions, preventing efficient fat storage, and thus driving ectopic fat accumulation into the liver.

Methods: To identify adipose-based mechanisms and potential serum biomarker candidates (SBCs) for NAFLD, we utilise dual-tissue RNA-sequencing (RNA-seq) data in adipose tissue and liver, paired with histology-based NAFLD diagnosis, from the same individuals in a cohort of obese individuals.

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Article Synopsis
  • * Researchers used machine learning and advanced analysis of tissue samples from NASH clinical trials to identify a 5-gene expression signature that could predict disease progression in patients with severe liver fibrosis (F3 and F4 stages).
  • * This study found that the Notch signaling pathway, linked to liver diseases, was significantly present in the gene signature, and in a validation cohort, drugs that improved liver conditions also reduced levels of various Notch signaling components.
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Robustness is the invariant development of phenotype despite environmental changes and genetic perturbations. In the Arabidopsis flower bud, four sepals robustly initiate and grow to constant size to enclose and protect the inner floral organs. We previously characterized the mutant ( ), where 3-5 sepals initiate variably and grow to different sizes, compromising their protective function.

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Objective: Stereotactic radiosurgery (SRS) is an effective treatment for brain metastases (BMs) in patients with non-small cell lung cancer (NSCLC). However, factors associated with the development of post-SRS leptomeningeal metastasis (LM) remain unclear. The authors analyzed the incidence and risk factors of LM development in patients with NSCLC and BMs after SRS and examined the survival outcomes and prognostic factors after LM development.

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Purpose: Metastases extending to the pituitary gland and cavernous sinus are extremely rare; however, advances in neuroimaging have increased the reported incidence. Stereotactic radiosurgery (SRS) affords the precise delivery of focused radiation to minimize adverse radiation effects. This study assessed the efficacy and safety of SRS in the treatment of pituitary and cavernous sinus metastases.

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Background: Remdesivir (RDV) is an intravenous antiviral with activity against SARS-CoV-2 for treatment of hospitalized COVID-19 patients with moderate-to-severe disease. Biomarkers associated with clinical outcomes have been identified for COVID-19, but few evaluated in context of antiviral treatment. Here, we assessed baseline (day 1, prior to first RDV dose) biomarkers and the impact of RDV treatment on longitudinal biomarker readouts.

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Article Synopsis
  • Whole brain radiation therapy (WBRT) increases the risk of leukoencephalopathy compared to stereotactic radiosurgery (SRS) alone for treating brain metastases.
  • The study analyzed data from 993 patients and found that factors like older age and larger tumor volume are linked to higher leukoencephalopathy incidence.
  • SRS is deemed safe for oligo-brain metastases, as combining it with WBRT does not significantly raise the risk of leukoencephalopathy.
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Objectives: To report on the usability, safety, symmetry, and effectiveness of hyaluronic acid (HA) injected between the prostate and the rectum for patients undergoing treatment for prostate cancer with external beam radiotherapy (EBRT), and present a novel definition of rectal spacer symmetry that is reproducible and independent of patient anatomy.

Patients And Methods: 102 consecutive patients with clinical stage of T1c-3b prostate cancer underwent general anaesthesia for fiducial marker insertion and injection of HA into the perirectal space before EBRT. HA safety, symmetry, separation, and usability based on user experience were assessed.

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Objective: Tyrosine kinase inhibitors (TKIs) is the first-line treatment for EGFR-positive non-small cell lung cancer (NSCLC); however, its applicability to patients with wild-type NSCLC remains an issue of contention. This study compared the effects of gamma knife radiosurgery (GKRS) alone versus combining GKRS and TKIs in treating two genetic forms of NSCLC.

Methods: This retrospective study examined 479 NSCLC patients with 1982 brain metastases who underwent GKRS and for whom imaging follow-up data or death records were available.

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Background And Aims: Primary sclerosing cholangitis (PSC) is a probable autoimmune liver disease characterized by persistent and progressive biliary inflammation that leads to biliary infection, cirrhosis, or cholangiocarcinoma. Genome-wide omics data are scarce regarding this severe disease.

Methods: MEDLINE database gene prioritization by text mining (biliary inflammation, biliary fibrosis, biliary stasis) was integrated in distinct omics data: (1) PSC liver transcriptome training and validation cohorts, (2) farnesoid X receptor (FXR) mice liver transcriptome subjected to an FXR agonist or FXR knockout mice; (3) liver single-cell transcriptome of the Abcb4-/- mice model of PSC.

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