Publications by authors named "ONeill A"

Background: Indigenous biocultural knowledge is a vital part of Nepalese environmental management strategies; however, much of it may soon be lost given Nepal's rapidly changing socio-ecological climate. This is particularly true for knowledge surrounding parasitic and mycoheterotrophic plant species, which are well represented throughout the Central-Eastern Himalayas but lack a collated record. Our study addresses this disparity by analyzing parasitic and mycoheterotrophic plant species diversity in Nepal as well as the ethnobotanical knowledge that surrounds them.

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Antibiotic resistance in clinically important bacteria can be mediated by proteins that physically associate with the drug target and act to protect it from the inhibitory effects of an antibiotic. We present here the first detailed structural characterization of such a target protection mechanism mediated through a protein-protein interaction, revealing the architecture of the complex formed between the FusB fusidic acid resistance protein and the drug target (EF-G) it acts to protect. Binding of FusB to EF-G induces conformational and dynamic changes in the latter, shedding light on the molecular mechanism of fusidic acid resistance.

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Background: Newborn infants are endotoxin tolerant which may be responsible for their increased susceptibility to bacterial sepsis. Vitamin D has an immunomodulatory effect and newborn infants are at risk of vitamin D deficiency. We examined the in vitro effect of 1, 25-dihydroxyvitamin D (1,25OHD) on whole blood phagocytic toll-like receptor 4 (TLR4), CD11b, and reactive oxygen intermediates (ROIs) in newborn infants during sepsis.

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nonalcoholic fatty liver disease (NAFLD), an obesity and insulin resistance associated clinical condition - ranges from simple steatosis to nonalcoholic steatohepatitis. To model the human condition, a high-fat Western diet that includes liquid sugar consumption has been used in mice. Even though liver pathophysiology has been well characterized in the model, little is known about the metabolic phenotype (e.

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Background: Blockade of human epidermal growth factor receptor type 2 (HER2) has dramatically improved outcome for patients with HER2-positive breast cancer. Trastuzumab, an anti-HER2 monoclonal antibody, has previously demonstrated improvement in overall survival (OS) in patients with metastatic and early stage HER2-positive breast cancer. However, trastuzumab can cause congestive heart failure (CHF) with an increased frequency for patients who have also received an anthracycline.

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Background: Human papillomavirus (HPV) infection indicates favorable prognosis in oropharyngeal squamous cell carcinoma (SCC). The purpose of this study was for us to assess the impact of HPV in patients treated with sequential therapy versus concomitant chemoradiotherapy (CRT).

Methods: Patients with stage III and IVA and B oropharyngeal SCC were reviewed spanning 10 years.

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Background: Macrophages represent a critical cell type in host defense, development and homeostasis. The ability to image non-invasively pro-inflammatory macrophage infiltrate into a transplanted organ may provide an additional tool for the monitoring of the immune response of the recipient against the donor graft. We therefore decided to image in vivo sialoadhesin (Sn, Siglec 1 or CD169) using anti-Sn mAb (SER-4) directly radiolabelled with (99m)Tc pertechnetate.

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Background: Serum response factor (SRF) is an important transcription factor in castrate-resistant prostate cancer (CRPC). Since CRPC is associated with androgen receptor (AR) hypersensitivity, we investigated the relationship between SRF and AR.

Materials And Methods: Transcriptional activity was assessed by luciferase assay.

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We report subnanometer modification enabled by an ultrafine helium ion beam. By adjusting ion dose and the beam profile, structural defects were controllably introduced in a few-layer molybdenum disulfide (MoS2) sample and its stoichiometry was modified by preferential sputtering of sulfur at a few-nanometer scale. Localized tuning of the resistivity of MoS2 was demonstrated and semiconducting, metallic-like, or insulating material was obtained by irradiation with different doses of He(+).

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Article Synopsis
  • Taxane-induced peripheral neuropathy (TIPN) is a significant concern for cancer patients, and researchers aimed to identify genetic markers that could help predict which patients are at higher risk for developing this condition.
  • A genome-wide association study involving 3,431 patients focused on identifying single nucleotide polymorphisms (SNPs) associated with TIPN, with subsequent validation in another group of patients.
  • The study found that the SNP rs3125923 is significantly linked to severe TIPN, while race, particularly being of African descent, was the most prominent predictor for increased risk of developing TIPN.
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Introduction: Recent advances in molecular genetics have increased the identification of genes and mutations responsible for inherited forms of hearing loss (HL), enabling early detection of these cases. Approximately, 60% of early-onset HL cases are due to genetic causes, of which 70% are non-syndromic. Of these, 75-80% are inherited in an autosomal recessive pattern (DFNB).

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Importance: Blinding patients to treatment regimen is an important component of high-quality randomized clinical trials, although concern exists about how receipt of a placebo will affect participants' views, particularly among patients with cancer.

Objective: To determine whether unblinding of random assignment to placebo vs experimental agent in a large adjuvant breast cancer chemotherapy randomized clinical trial was associated with perception of greater chance of cancer recurrence and lower confidence in the decision to participate in the trial in participants who were randomized to placebo compared with those randomized to experimental therapy.

Design, Setting, And Participants: Serial telephone-based prospective survey substudy of all Eastern Cooperative Oncology Group Protocol 5103 (ECOG5103) participants enrolling between January 5 and June 8, 2010.

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Objective: Small bowel (SB) is the second most common site of gastrointestinal stromal tumours (GISTs). We evaluated clinical presentation, pathology, imaging features and metastatic pattern of SB GIST.

Methods: Imaging and clinicopathological data of 102 patients with jejunal/ileal GIST treated at Dana-Farber Cancer Institute and Brigham and Women's Hospital (Boston, MA) between 2002 and 2013 were evaluated.

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Pre-clinical studies of allogeneic stem cell transplantation suggest that depletion of naive T cells from donor lymphocytes will reduce the risk of GvHD but preserve immunity to infectious pathogens. In this study, we have established a clinical-grade protocol under good manufacturing practice conditions for purging CD62L(+) naive T cells from steady-state leukapheresis products using the CliniMACS system. The efficacy of immunomagnetic CD62L depletion was assessed by analysis of cell composition and functional immune responses.

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Purpose: To study the frequency, timing, and associations of thoracic metastases in advanced (stage III and IV) high-grade serous ovarian cancer (HGSC) to help optimize the use of cross-sectional chest imaging.

Materials And Methods: This institutional review board-approved retrospective study with waived informed consent included 186 consecutive patients with pathologically proven advanced HGSC after primary cytoreduction (mean age ± standard deviation, 60 years ± 9.7) who underwent imaging at our tertiary cancer institution from January 2012 to December 2012 with at least 1 year of follow-up, unless there was thoracic metastasis or death.

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An approach was developed for the verification of method performance of the AOAC 2005.06 LC-fluorescence detector (FLD) method for determination of paralytic shellfish poisoning (PSP) toxins in bivalve shellfish. This was developed following advice published by the Analytical Laboratory Accreditation Criteria Committee and applied to shellfish species that had not been previously subjected to a full single-laboratory validation scheme.

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Objectives: To validate estimated tumour volumetry in primary gastric gastrointestinal stromal tumours (GISTs) using semiautomated volumetry.

Methods: In this IRB-approved retrospective study, we measured the three longest diameters in x, y, z axes on CTs of primary gastric GISTs in 127 consecutive patients (52 women, 75 men, mean age 61 years) at our institute between 2000 and 2013. Segmented volumes (Vsegmented) were obtained using commercial software by two radiologists.

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Introduction: There is limited evidence regarding the impact of alcohol use disorders on long term outcomes from intensive care. The aims of this study were to analyse the nature and complications of alcohol related admissions to intensive care and determine whether alcohol use disorders impact on survival at six months post ICU discharge.

Method: This was an 18 month prospective observational cohort study in a 20 bedded mixed ICU, in a large teaching hospital in Scotland.

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Background: Activated leukocytes and infection are implicated in neonatal brain injury. Leukocyte surface receptors are increased in stroke models and may be targets for future adjunctive therapies.

Methods: Serial blood samples were analyzed from preterm infants (n = 51; <32 wk gestation) on days 0, 1, 2, and 7 of life.

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Robinow syndrome (RS) is a phenotypically and genetically heterogeneous condition that can be caused by mutations in genes encoding components of the non-canonical Wnt signaling pathway. In contrast, germline mutations that act to increase canonical Wnt signaling lead to distinctive osteosclerotic phenotypes. Here, we identified de novo frameshift mutations in DVL1, a mediator of both canonical and non-canonical Wnt signaling, as the cause of RS-OS, an RS subtype involving osteosclerosis, in three unrelated individuals.

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Aim: Circulating immune cell activation is associated with worse outcome in adult and animal models of brain injury. Our aim was to profile the systemic inflammatory response over the first week of life in infants at risk of neonatal encephalopathy and correlate early neutrophil and monocyte endotoxin and activation responses with outcome.

Methods: Prospective observational study in a tertiary referral university hospital including 22 infants requiring resuscitation at birth who had serial (five time points) neutrophil and monocyte CD11b (marker of cell adhesion) (intracellular Reactive oxygen intermediates) ROI (cell activation), and Toll-like receptor (endotoxin recognition) before and after endotoxin stimulation ex vivo compared to neonatal controls.

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