Publications by authors named "Andrew Ray"

Article Synopsis
  • Antisense oligonucleotides (ASOs) are important in biology for regulating protein expression by binding to specific RNA sequences, and their stability and specificity are improved through synthetic modifications like phosphorothioate and locked nucleic acid.
  • To study gapmer ASOs, advanced mass spectrometry techniques, such as ultraviolet photodissociation and various fragmentation methods, were employed, providing insights into how the structure affects the cleavage.
  • The analysis process used 2DMS for comprehensive data coverage and a custom Python script to manage modifications and produce mass lists, which enhanced signal quality and identification accuracy.
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Dr. Virginia Apgar was an American anesthesiologist and researcher who heavily influenced the development of neonatal resuscitation in the immediate postpartum period with her simple five-point scoring system. Today, the APGAR scoring system is used around the world in delivery rooms to guide clinicians in the evaluation of newborns and to distinguish which might need urgent resuscitation.

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Background: The association of body composition with epithelial ovarian carcinoma (EOC) mortality is poorly understood. To date, evidence suggests that high adiposity is associated with decreased mortality (an obesity paradox), but the impact of muscle on this association has not been investigated. Herein, we define associations of muscle and adiposity joint-exposure body composition phenotypes with EOC mortality.

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Background: Patients with head and neck cancer (HNC) undergoing radiation therapy (RT) often experience sleep disturbances that may contribute to oral mucositis (OM) and quality of life (QOL).

Methods: Patients with HNC treated with RT at a single institution were examined. Sleep questionnaires were given on the first day of RT to assess for insomnia and obstructive sleep apnea (OSA).

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Proteolysis targeting chimeras (PROTACs) are specialized molecules that bind to a target protein and a ubiquitin ligase to facilitate protein degradation. Despite their significance, native PROTACs have not undergone tandem mass spectrometry (MS) analysis. To address this gap, we conducted a pioneering investigation on the fragmentation patterns of two PROTACs in development, dBET1 and VZ185.

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National parks and other protected areas are important for preserving landscapes and biodiversity worldwide. An essential component of the mission of the United States (U.S.

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Background: Skeletal muscle indices have been associated with improved peri-operative outcomes after surgical resection of non-small-cell lung cancer (NSCLC). However, it is unclear if these indices can predict long term cancer specific outcomes.

Methods: NSCLC patients undergoing lobectomy at our institute between 2009-2015 were included in this analysis (N = 492).

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The fragmentation of oligonucleotides by mass spectrometry allows for the determination of their sequences. It is necessary to understand how oligonucleotides dissociate in the gas phase, which allows interpretation of data to obtain sequence information. Since 2014, a range of fragmentation mechanisms, including a novel internal rearrangement, have been proposed using different ion dissociation techniques.

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Importance: Combined modality therapy, such as chemoradiotherapy, often results in significant morbidity among patients with head and neck cancer. Although the role of body mass index (BMI) varies based on cancer subtypes, its association with treatment response, tumor recurrence, and survival outcomes among patients with head and neck cancer remains unclear.

Objective: To evaluate the role of BMI in treatment response, tumor recurrence, and survival outcomes among patients with head and neck cancer undergoing chemoradiotherapy.

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Article Synopsis
  • The study investigates the lymphocyte-monocyte ratio (LMR) as a potential prognostic biomarker for survival outcomes in North American patients with head and neck cancer undergoing chemoradiation treatment.
  • Researchers analyzed data from 476 patients, revealing that lower LMR scores were linked to worse overall and cancer-specific survival, with higher LMR scores correlating with improved survival outcomes.
  • After properly adjusting for biases, they confirmed that a median LMR value of 3.8 could serve as a critical threshold, where patients with LMRs below this value had significantly lower chances of survival.
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Identity testing is a critical part in the development of a therapeutic synthetic oligonucleotide. Tandem Mass Spectrometry (MS/MS) is commonly used for the analysis of oligonucleotides to obtain structural and sequence information, however there are challenges resulting from chemical modifications introduced to improve their pharmacokinetics and stability. For these structurally complex oligonucleotides, Nuclear Magnetic Resonance (NMR) Spectroscopy has found limited use for characterisation and identity testing, as only partial NMR resonance assignment for oligonucleotides is achieved without isotopic labelling methodologies.

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Ball-milling and harsh manufacturing processes often generate crystal disorder which have practical implications on the physical and chemical stabilities of solid drugs during subsequent storage, transport, and handling. The impact of the physical state of solid drugs, containing different degrees/levels of crystal disorder, on their autoxidative stability under storage has not been widely investigated. This study investigates the impact of differing degrees of crystal disorder on the autoxidation of Mifepristone (MFP) to develop a predictive (semi-empirical) stability model.

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Oxidative degradation of drugs is one of the major routes of drug substance and drug product instability. Among the diverse routes of oxidation, autoxidation is considered to be challenging to predict and control, potentially due to the multi-step mechanism involving free radicals. C-H bond dissociation energy (C-H BDE) is evidenced to be a calculated descriptor shown to predict drug autoxidation.

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The C-H bond dissociation energy (BDE) of drug molecules is often used to estimate their relative propensities to undergo autoxidation. BDE calculations based on electronic structures provide a convenient means to estimate the risk for a given compound to degrade via autoxidation. This study aimed to verify the utility of calculated C-H BDEs of a range of drug molecules in predicting their autoxidation propensities, in the solution state.

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Background: It is unclear if the presence of compartmental brain herniation on neuroimaging should be a prerequisite to the clinical confirmation of death using neurological criteria. The World Brain Death Project has posed this as a research question.

Methods: The final computed tomography of the head scans before death of 164 consecutive patients confirmed dead using neurological criteria and 41 patients with devastating brain injury who died following withdrawal of life sustaining treatment were assessed by a neuroradiologist to compare the incidence of herniation and other features of cerebral swelling.

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Objective: To compare the postoperative outcomes of preoperative respiratory muscle training (RMT) with a device to preoperative aerobic exercise training (AET) in patients undergoing thoracic surgeries (cardiac and lung).

Data Sources: PubMed, EMBASE, Cochrane, and Web of Science were comprehensively searched upon inception to 9/2020.

Study Selection: All randomized control studies, including preoperative RMT and preoperative AET compared with a non-training control group, were included.

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The recent emergence of drug-dendrimer conjugates within pharmaceutical industry research and development introduces a range of challenges for analytical and measurement science. These molecules are very high molecular weight (100-200kDa) with a significant degree of structural complexity. The characteristics and quality attributes that require understanding and definition, and impact efficacy and safety, are diverse.

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Hind limbs undergo dramatic changes in loading conditions during the transition from quadrupedal to bipedal locomotion. For example, the most early diverging bipedal jerboas (Rodentia: Dipodidae) are some of the smallest mammals in the world, with body masses that range between 2-4 g. The larger jerboa species exhibit developmental and evolutionary fusion of the central three metatarsals into a single cannon bone.

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Article Synopsis
  • This study aimed to determine the best hemoglobin (Hgb) threshold for predicting outcomes in head and neck cancer patients undergoing chemoradiation, identifying 11.4 as the critical level.
  • Among 496 patients analyzed, low Hgb levels (below 11.4) correlated with significantly worse overall survival (OS) and progression-free survival (PFS), especially in those with HPV-negative tumors.
  • The findings suggest that while low Hgb is a strong negative prognostic factor for patients with HPV-negative head and neck cancers, it does not significantly impact those with HPV-positive tumors.
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The present study aimed to investigate methods for accelerating autoxidation of crystalline drugs in the solid-state that can potentially predict real-time stability. Solid droperidol (DPD) was selected as the model drug. A common free-radical initiator, 2,2'-azobisisobutyronitrile (AIBN), was used to induce autoxidation in solutions.

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Background: While often life-saving, treatment for head and neck cancer (HNC) can be debilitating resulting in unplanned hospitalization. Hospitalizations in cancer patients may disrupt treatment and result in poor outcomes. Pre-treatment muscle quality and quantity ascertained through diagnostic imaging may help identify patients at high risk of poor outcomes early.

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