Publications by authors named "David Chan"

Low-voltage and efficient optical modulators in the silicon photonic (SiPh) platform are highly desired for realizing high-speed connectivity in chip level interconnects, data center interconnects, and high-performance computing (HPC). With the modulator operating at CMOS compatible voltages, high-voltage modulator drivers are no longer needed, thus reducing driver design complexity and power consumption. We demonstrate a silicon microring modulator (MRM) operating at a driving voltage of 0.

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Background: Neoadjuvant chemotherapy (NAC) can provide improved survival outcomes in pancreatic ductal adenocarcinoma (PDAC) patients who respond to treatment, but currently available biomarkers cannot reliably predict NAC response. This study aimed to determine the potential of a previously identified diagnostic and prognostic biomarker panel (i.e.

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BRAFV600E-mutant metastatic colorectal cancer (mCRC) is associated with poor prognosis. The combination of anti-BRAF/anti-EGFR (encorafenib/cetuximab) treatment for patients with BRAFV600E-mutant mCRC improves clinical benefits; unfortunately, inevitable acquired resistance limits the treatment outcome, and the mechanism has not been validated. Here, we discovered that monoacylglycerol O-acyltransferase 3-mediated (MOGAT3-mediated) diacylglycerol (DAG) accumulation contributed to acquired resistance to encorafenib/cetuximab by dissecting a BRAFV600E-mutant mCRC patient-derived xenograft (PDX) model exposed to encorafenib/cetuximab administration.

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Studies of widely distributed species can inform our understanding of how past demographic events tied to historic glaciation and ongoing population genetic processes interact to shape contemporaneous patterns of biodiversity at a continental scale. In this study, we used whole-genome resequencing to investigate the current population structure and genetic signatures of past demographic events in the widespread migratory American goldfinch (Spinus tristis). Phylogenetic relationships inferred from whole mitochondrial genomes were poorly resolved.

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Article Synopsis
  • Evidence-based treatment for advanced gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) requires personalized decisions that take into account individual patient and cancer characteristics. !* -
  • A multidisciplinary panel reviewed 131 publications to develop a guidance document with 24 recommendations and 5 good clinical practice statements focusing on diagnostic features and biomarkers for managing unresectable or metastatic GEP-NENs. !* -
  • The document emphasizes treatment strategies based on tumor characteristics and specific biomarkers, and it received endorsements from major neuroendocrine tumor organizations. !*
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Infertility is associated with the alteration of the seminal microbiome. However, the onset of dysbiosis remains controversial and the involvement of host factors remains elusive. This study investigates the alterations of the seminal microbiome in male infertility and examines the association and function of DEFB119, a reproductive-tract-specific host antimicrobial peptide, on the seminal microbiome and male fertility.

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Ovarian cancer remains a leading cause of death among gynecological cancers, largely due to its propensity for peritoneal metastasis and the development of drug resistance. This review concentrates on the molecular underpinnings of these two critical challenges. We delve into the role of exosomes, the nano-sized vesicles integral to cellular communication, in orchestrating the complex interactions within the tumor microenvironment that facilitate metastatic spread and thwart therapeutic efforts.

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While the association between migration and deteriorated refugee mental health is well-documented, existing research overwhelmingly centers on adult populations, leaving a discernible gap in our understanding of the factors influencing mental health for forcibly displaced children. This focus is particularly noteworthy considering the estimated 43.3 million children who are forcibly displaced globally.

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Our purpose was to prospectively assess the distribution of NETPET scores in well-differentiated (WD) grade 2 and 3 gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) and to determine the impact of the NETPET score on clinical management. This single-arm, institutional ethics review board-approved prospective study included 40 patients with histologically proven WD GEP NETs. Ga-DOTATATE PET and F-FDG PET were performed within 21 d of each other.

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Background: Peritoneal metastases frequently occur in epithelial ovarian cancer (EOC), resulting in poor prognosis and survival rates. Tumor-associated-macrophages (TAMs) massively infiltrate into ascites spheroids and are multi-polarized as protumoral M2-like phenotype, orchestrating the immunosuppression and promoting tumor progression. However, the impact of omental conditioned medium/ascites (OCM/AS) on TAM polarization and its function in tumor progression remains elusive.

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Barrier islands provide a first line of defense against ocean flooding and storm surge. Biogeomorphic interactions are recognized as important in coastal system processes, but current barrier island models are primarily dominated by physical processes. Recent research has demonstrated different biogeomorphic states that influence response to sea level rise and other disturbance.

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Mitochondria-endoplasmic reticulum contact sites (MERCS) serve as hotspots for important cellular processes, including calcium homeostasis, phospholipid homeostasis, mitochondria dynamics, and mitochondrial quality control. MERCS reporters based on complementation of green fluorescent proteins (GFP) fragments have been designed to visualize MERCS in real-time, but we find that they do not accurately respond to changes in MERCS content. Here, we utilize split LacZ complementing fragments to develop the first MERCS reporter system (termed SpLacZ-MERCS) that continuously integrates the MERCS information within a cell and generates a fluorescent output.

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Background: Time-lapse imaging systems for embryo incubation and selection might improve outcomes of in-vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) treatment due to undisturbed embryo culture conditions, improved embryo selection, or both. However, the benefit remains uncertain. We aimed to evaluate the effectiveness of time-lapse imaging systems providing undisturbed culture and embryo selection, and time-lapse imaging systems providing only undisturbed culture, and compared each with standard care without time-lapse imaging.

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Objective: We investigated metabolic tumor volume (MTV) and total lesion glycolysis (TLG) on pre-treatment FDG-PET as prognostic markers for survival in patients with metastatic neuroendocrine neoplasms (NENs) receiving peptide receptor radionuclide therapy (PRRT).

Methods: A retrospective review of patients with metastatic NENs receiving PRRT was undertaken. Pre-treatment FDG-PET images were analyzed and variables collected included MTV and TLG (dichotomized by median into high vs low).

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Article Synopsis
  • Using CA125 thresholds of 70 U/ml or 35 U/ml in monitoring ovarian cancer may lead to missed relapses, prompting the need for better detection methods.
  • A study involving 162 patients found that using a CA125 level defined as 2×nadir significantly improved the sensitivity and timing of relapse detection compared to the standard threshold of 35 U/ml.
  • The findings suggest that the 2×nadir CA125 level is a more reliable early warning signal for relapse, aiding in timely imaging examinations for women with serous ovarian cancer.
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  • Proteotoxicity contributes to type 2 diabetes (T2D), with a study revealing significant accumulation of misfolded proteins in the mitochondria of human pancreatic islets in T2D patients.
  • Quantitative proteomics indicate that T2D islet protein misfolding resembles mitochondrial issues rather than those from the endoplasmic reticulum (ER), highlighting the role of the protease LonP1 and its chaperone mtHSP70 in this process.
  • Deleting LONP1 in mice leads to mitochondrial dysfunction and β cell death, while enhancing LONP1 function improves mitochondrial protein folding and β cell survival, suggesting potential new therapeutic avenues for treating T2D.
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  • Scientists wanted to find out if germs from sperm and fluid around eggs could contaminate the liquid used to grow embryos during fertility treatments.
  • They collected samples from 61 couples and studied the germs using special techniques, discovering that 82.5% of the cases had germs from the sperm in the growing media.
  • While some germs in sperm were linked to poorer sperm health and certain germs in egg fluid were associated with female infertility, they didn’t find a link between these germs and the success of the fertility treatments.
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Depletion or mutations of key proteins for mitochondrial fusion, like optic atrophy 1 (OPA1) and mitofusins 1 and 2 (Mfn 1 and 2), are known to significantly impact the mitochondrial ultrastructure, suggesting alterations of their membranes' lipid profiles. In order to make an insight into this issue, we used hydrophilic interaction liquid chromatography coupled with electrospray ionization-high resolution MS to investigate the mitochondrial phospholipid (PL) profile of mouse embryonic fibroblasts knocked out for OPA1 and Mfn1/2 genes. One hundred sixty-seven different sum compositions were recognized for the four major PL classes of mitochondria, namely phosphatidylcholines (PCs, 63), phosphatidylethanolamines (55), phosphatidylinositols (21), and cardiolipins (28).

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Background: The widespread interest in male reproductive health (MRH), fueled by emerging evidence, such as the global decline in sperm counts, has intensified concerns about the status of MRH. Consequently, there is a pressing requirement for a strategic, systematic approach to identifying critical questions, collecting pertinent information, and utilizing these data to develop evidence-based strategies. The methods for addressing these questions and the pathways toward their answers will inevitably vary based on the variations in cultural, geopolitical, and health-related contexts.

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Background: As waiting lists for elective surgery grow, there seems to be a disconnect between the public's expectations on the amount of time surgeons spend operating compared with reality. On average, a surgeon in the NHS spends one day a week performing elective surgery. We aimed to investigate the public's perception on the amount of time surgeons spend performing elective surgery and what they would desire.

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Mitophagy plays an important role in the maintenance of mitochondrial homeostasis and can be categorized into two types: ubiquitin-mediated and receptor-mediated pathways. During receptor-mediated mitophagy, mitophagy receptors facilitate mitophagy by tethering the isolation membrane to mitochondria. Although at least five outer mitochondrial membrane proteins have been identified as mitophagy receptors, their individual contribution and interrelationship remain unclear.

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