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  1. Article ; Online: Tissue Mass Spectrometry: How Solid Is Our Future?

    Unsihuay, Daisy / Phipps, William S / Paulovich, Amanda G / Chapman, Jessica R / Ducret, Axel / Eberlin, Livia S / Spraggins, Jeffrey M / Goodwin, Richard J A

    Clinical chemistry

    2023  Volume 69, Issue 7, Page(s) 676–683

    MeSH term(s) Humans ; Tandem Mass Spectrometry ; Solid Phase Extraction
    Language English
    Publishing date 2023-06-07
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
    ZDB-ID 80102-1
    ISSN 1530-8561 ; 0009-9147
    ISSN (online) 1530-8561
    ISSN 0009-9147
    DOI 10.1093/clinchem/hvad061
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Unexpected Presence of an Unusual Opioid in a Patient with Chronic Pain.

    Phipps, William S / Bradley, Benjamin / Love, Jason E / Hoofnagle, Andrew N

    Clinical chemistry

    2021  Volume 67, Issue 4, Page(s) 596–599

    MeSH term(s) Analgesics, Opioid/adverse effects ; Chronic Pain/drug therapy ; Humans
    Chemical Substances Analgesics, Opioid
    Language English
    Publishing date 2021-03-31
    Publishing country England
    Document type Journal Article
    ZDB-ID 80102-1
    ISSN 1530-8561 ; 0009-9147
    ISSN (online) 1530-8561
    ISSN 0009-9147
    DOI 10.1093/clinchem/hvaa317
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Clinical Proteomics for Solid Organ Tissues.

    Phipps, William S / Kilgore, Mark R / Kennedy, Jacob J / Whiteaker, Jeffrey R / Hoofnagle, Andrew N / Paulovich, Amanda G

    Molecular & cellular proteomics : MCP

    2023  Volume 22, Issue 11, Page(s) 100648

    Abstract: The evaluation of biopsied solid organ tissue has long relied on visual examination using a microscope. Immunohistochemistry is critical in this process, labeling and detecting cell lineage markers and therapeutic targets. However, while the practice of ... ...

    Abstract The evaluation of biopsied solid organ tissue has long relied on visual examination using a microscope. Immunohistochemistry is critical in this process, labeling and detecting cell lineage markers and therapeutic targets. However, while the practice of immunohistochemistry has reshaped diagnostic pathology and facilitated improvements in cancer treatment, it has also been subject to pervasive challenges with respect to standardization and reproducibility. Efforts are ongoing to improve immunohistochemistry, but for some applications, the benefit of such initiatives could be impeded by its reliance on monospecific antibody-protein reagents and limited multiplexing capacity. This perspective surveys the relevant challenges facing traditional immunohistochemistry and describes how mass spectrometry, particularly liquid chromatography-tandem mass spectrometry, could help alleviate problems. In particular, targeted mass spectrometry assays could facilitate measurements of individual proteins or analyte panels, using internal standards for more robust quantification and improved interlaboratory reproducibility. Meanwhile, untargeted mass spectrometry, showcased to date clinically in the form of amyloid typing, is inherently multiplexed, facilitating the detection and crude quantification of 100s to 1000s of proteins in a single analysis. Further, data-independent acquisition has yet to be applied in clinical practice, but offers particular strengths that could appeal to clinical users. Finally, we discuss the guidance that is needed to facilitate broader utilization in clinical environments and achieve standardization.
    MeSH term(s) Proteomics/methods ; Reproducibility of Results ; Mass Spectrometry ; Proteins ; Antibodies
    Chemical Substances Proteins ; Antibodies
    Language English
    Publishing date 2023-09-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2075924-1
    ISSN 1535-9484 ; 1535-9476
    ISSN (online) 1535-9484
    ISSN 1535-9476
    DOI 10.1016/j.mcpro.2023.100648
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Amino and organic acid analysis: Essential tools in the diagnosis of inborn errors of metabolism.

    Phipps, William S / Jones, Patti M / Patel, Khushbu

    Advances in clinical chemistry

    2019  Volume 92, Page(s) 59–103

    Abstract: Inborn errors of metabolism (IEMs) are a large class of genetic disorders that result from defects in enzymes involved in energy production and metabolism of nutrients. For every metabolic pathway, there are defects that can occur and potentially result ... ...

    Abstract Inborn errors of metabolism (IEMs) are a large class of genetic disorders that result from defects in enzymes involved in energy production and metabolism of nutrients. For every metabolic pathway, there are defects that can occur and potentially result in an IEM. While some defects can go undetected in one's lifetime, some have moderate to severe clinical consequences. In the latter case, the biochemical defect leads to accumulation of metabolites and byproducts that are toxic or interfere with normal biological function. Disorders of amino acid metabolism, organic acid metabolism and the urea cycle comprise a large portion of IEMs. Two essential tools required for the diagnosis of these categories of disorders are amino acid and organic acid profiling. Most all clinical laboratories offering metabolic testing perform amino acid analysis, while organic acid profiling is restricted to more specialized pediatric hospitals and reference laboratories. In this chapter, we will provide an overview of various methodologies employed for amino acid and organic acid profiling as well as specific examples to demonstrate how these techniques are applied in clinical laboratories for the diagnosis of IEMs.
    MeSH term(s) Amino Acids/analysis ; Carboxylic Acids/analysis ; Humans ; Metabolism, Inborn Errors/diagnosis ; Metabolism, Inborn Errors/metabolism
    Chemical Substances Amino Acids ; Carboxylic Acids
    Language English
    Publishing date 2019-06-08
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 210505-6
    ISSN 2162-9471 ; 0065-2423
    ISSN (online) 2162-9471
    ISSN 0065-2423
    DOI 10.1016/bs.acc.2019.04.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Tandem Mass Spectrometry-Based Amyloid Typing Using Manual Microdissection and Open-Source Data Processing.

    Phipps, William S / Smith, Kelly D / Yang, Han-Yin / Henderson, Clark M / Pflaum, Hannah / Lerch, Melissa L / Fondrie, William E / Emrick, Michelle A / Wu, Christine C / MacCoss, Michael J / Noble, William S / Hoofnagle, Andrew N

    American journal of clinical pathology

    2022  Volume 157, Issue 5, Page(s) 748–757

    Abstract: Objectives: Standard implementations of amyloid typing by liquid chromatography-tandem mass spectrometry use capabilities unavailable to most clinical laboratories. To improve accessibility of this testing, we explored easier approaches to tissue ... ...

    Abstract Objectives: Standard implementations of amyloid typing by liquid chromatography-tandem mass spectrometry use capabilities unavailable to most clinical laboratories. To improve accessibility of this testing, we explored easier approaches to tissue sampling and data processing.
    Methods: We validated a typing method using manual sampling in place of laser microdissection, pairing the technique with a semiquantitative measure of sampling adequacy. In addition, we created an open-source data processing workflow (Crux Pipeline) for clinical users.
    Results: Cases of amyloidosis spanning the major types were distinguishable with 100% specificity using measurements of individual amyloidogenic proteins or in combination with the ratio of λ and κ constant regions. Crux Pipeline allowed for rapid, batched data processing, integrating the steps of peptide identification, statistical confidence estimation, and label-free protein quantification.
    Conclusions: Accurate mass spectrometry-based amyloid typing is possible without laser microdissection. To facilitate entry into solid tissue proteomics, newcomers can leverage manual sampling approaches in combination with Crux Pipeline and related tools.
    MeSH term(s) Amyloid/analysis ; Amyloidogenic Proteins ; Amyloidosis/diagnosis ; Humans ; Microdissection ; Tandem Mass Spectrometry/methods
    Chemical Substances Amyloid ; Amyloidogenic Proteins
    Language English
    Publishing date 2022-03-21
    Publishing country England
    Document type Journal Article
    ZDB-ID 2944-0
    ISSN 1943-7722 ; 0002-9173
    ISSN (online) 1943-7722
    ISSN 0002-9173
    DOI 10.1093/ajcp/aqab185
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Dietary Quality and Perceived Barriers to Weight Loss among Older Overweight Veterans with Dysmobility.

    Parker, Elizabeth A / Perez, William J / Phipps, Brian / Ryan, Alice S / Prior, Steven J / Katzel, Leslie / Serra, Monica C / Addison, Odessa

    International journal of environmental research and public health

    2022  Volume 19, Issue 15

    Abstract: Healthier diets are associated with higher muscle mass and physical performance which may reduce the risk of developing frailty and disability later in life. This study examined the dietary quality and self-reported weight loss barriers among older (>60 ... ...

    Abstract Healthier diets are associated with higher muscle mass and physical performance which may reduce the risk of developing frailty and disability later in life. This study examined the dietary quality and self-reported weight loss barriers among older (>60 years), overweight (BMI ≥ 25 kg/m2) Veterans with dysmobility (low gait speed, impaired mobility diagnosis, or a comorbidity that results in impaired mobility). Habitual dietary intake and healthy eating index (HEI-2015) were assessed using 24-h recalls and compared to US nationally representative dietary intake data and national recommendations. The “MOVE!11” Patient Questionnaire assessed weight loss barriers. The sample (n = 28) was primarily male (93%), black (54%) and obese (BMI = 35.5 ± 5.4 kg/m2) adults aged 69.5 ± 7.0 years with two or more comorbidities (82%); 82% were prescribed four or more medications. Daily intakes (mean ± SD) were calculated for total energy (2184 ± 645 kcals), protein (0.89 ± 0.3 g/kg), fruits (0.84 ± 0.94 cup·eq.), vegetables (1.30 ± 0.87 cup·eq.), and HEI-2015 (52.8 ± 13.4). Veterans consumed an average of 11% less protein than the recommendation for older adults (1.0 g/kg/d) and consumed fewer fruits and vegetables than comparisons to national averages (18% and 21%, respectively). Mean HEI-2015 was 17% below the national average for adults >65 years, suggesting poor dietary quality among our sample. Top weight loss barriers were not getting enough physical activity, eating too much and poor food choices. This data suggests that dietary quality is suboptimal in older, overweight Veterans with disability and highlights the need to identify strategies that improve the dietary intake quality of older Veterans who may benefit from obesity and disability management.
    MeSH term(s) Aged ; Body Mass Index ; Diet ; Energy Intake ; Humans ; Male ; Obesity/epidemiology ; Overweight/epidemiology ; Vegetables ; Veterans ; Weight Loss
    Language English
    Publishing date 2022-07-27
    Publishing country Switzerland
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2175195-X
    ISSN 1660-4601 ; 1661-7827
    ISSN (online) 1660-4601
    ISSN 1661-7827
    DOI 10.3390/ijerph19159153
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Multidisciplinary collaborative consensus guidance statement on the assessment and treatment of neurologic sequelae in patients with post-acute sequelae of SARS-CoV-2 infection (PASC).

    Melamed, Esther / Rydberg, Leslie / Ambrose, Anne Felicia / Bhavaraju-Sanka, Ratna / Fine, Jeffrey S / Fleming, Talya K / Herman, Eric / Phipps Johnson, Jamie L / Kucera, Jennifer Ryan / Longo, Michele / Niehaus, William / Oleson, Christina V / Sampsel, Sarah / Silver, Julie K / Smith, Martha M / Verduzco-Gutierrez, Monica

    PM & R : the journal of injury, function, and rehabilitation

    2023  Volume 15, Issue 5, Page(s) 640–662

    MeSH term(s) Humans ; Post-Acute COVID-19 Syndrome ; COVID-19 ; Consensus ; SARS-CoV-2 ; Disease Progression
    Language English
    Publishing date 2023-05-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2608988-9
    ISSN 1934-1563 ; 1934-1482
    ISSN (online) 1934-1563
    ISSN 1934-1482
    DOI 10.1002/pmrj.12976
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: A reduced aperture allows for transcranial focus localization at lower pressure.

    Phipps, M Anthony / Jonathan, Sumeeth / Yang, Pai-Feng / Chen, Li Min / Grissom, William / Caskey, Charles F

    JASA express letters

    2022  Volume 2, Issue 6, Page(s) 62001

    Abstract: Localizing the focus during transcranial focused ultrasound procedures is important to ensure accurate targeting of specific brain regions and interpretation of results. Magnetic resonance acoustic radiation force imaging uses the displacement induced by ...

    Abstract Localizing the focus during transcranial focused ultrasound procedures is important to ensure accurate targeting of specific brain regions and interpretation of results. Magnetic resonance acoustic radiation force imaging uses the displacement induced by the ultrasound focus in the brain to localize the beam, but the high pressure required to displace brain tissue may cause damage or confounds during subsequent neuromodulatory experiments. Here, reduced apertures were applied to a phased array transducer to generate comparable displacement to the full aperture but with 20% lower free field pressure.
    Language English
    Publishing date 2022-06-28
    Publishing country United States
    Document type Journal Article
    ISSN 2691-1191
    ISSN (online) 2691-1191
    DOI 10.1121/10.0011695
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Quantitative amino acid analysis by liquid chromatography-tandem mass spectrometry using low cost derivatization and an automated liquid handler.

    Phipps, William S / Crossley, Eric / Boriack, Richard / Jones, Patricia M / Patel, Khushbu

    JIMD reports

    2019  Volume 51, Issue 1, Page(s) 62–69

    Abstract: Amino acid analysis is central to newborn screening and the investigation of inborn errors of metabolism. Ion-exchange chromatography with ninhydrin derivatization remains the reference method for quantitative amino acid analysis but offers slow ... ...

    Abstract Amino acid analysis is central to newborn screening and the investigation of inborn errors of metabolism. Ion-exchange chromatography with ninhydrin derivatization remains the reference method for quantitative amino acid analysis but offers slow chromatography and is susceptible to interference from other co-eluting compounds. Liquid-chromatography tandem mass spectrometry (LC-MS/MS) provides a rapid and highly specific alternative, but sample preparation is frequently laborious and sometimes cost prohibitive. To address these limitations, we validated an LC-MS/MS method using the aTRAQ Reagents Application Kit with a modified protocol consuming only half reagents. Adequate performance for clinical specimen measurement of 26 amino acids with high clinical relevance was achieved. An automated liquid handler and modified calibration and normalization approaches were used to ensure reproducible assay performance. Linear measurement between 5 and 2000 μM was achieved for most analytes despite use of a small, 10 μl sample size. Overall the method achieved near substantially improved throughput and enabled use of smaller samples volumes for batched analyses of clinical samples.
    Language English
    Publishing date 2019-11-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2672872-2
    ISSN 2192-8312 ; 2192-8304
    ISSN (online) 2192-8312
    ISSN 2192-8304
    DOI 10.1002/jmd2.12080
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  10. Article ; Online: Diagnostic evaluation of upper tract urothelial carcinoma: can we safely omit diagnostic ureteroscopy?

    Trail, Matthew / Rahman, Muhammad Sajid Waheed / Broadhurst, William J / Blackmur, James P / Sharma, Abhishek / Chew, Etienne / O'Donnell, Marie / Keanie, Julian Y / Brush, John / Taylor, John / Phipps, Simon / Thomas, Ben / Mains, Edward A A / McNeill, S Alan / Leung, Steve / Cutress, Mark L / Laird, Alexander

    BJU international

    2023  Volume 131, Issue 6, Page(s) 755–762

    Abstract: Objective: To identify clinicopathological or radiological factors that may predict a diagnosis of upper urinary tract urothelial cell carcinoma (UTUC) to inform which patients can proceed directly to radical nephroureterectomy (RNU) without the delay ... ...

    Abstract Objective: To identify clinicopathological or radiological factors that may predict a diagnosis of upper urinary tract urothelial cell carcinoma (UTUC) to inform which patients can proceed directly to radical nephroureterectomy (RNU) without the delay for diagnostic ureteroscopy (URS).
    Patients and methods: All consecutive patients investigated for suspected UTUC in a high-volume UK centre between 2011 and 2017 were identified through retrospective analysis of surgical logbooks and a prospectively maintained pathology database. Details on clinical presentation, radiological findings, and URS/RNU histopathology results were evaluated. Multivariate regression analysis was performed to evaluate predictors of a final diagnosis of UTUC.
    Results: In all, 260 patients were investigated, of whom 230 (89.2%) underwent URS. RNU was performed in 131 patients (50.4%), of whom 25 (9.6%) proceeded directly without URS - all of whom had a final histopathological diagnosis of UTUC - and 15 (11.5%) underwent RNU after URS despite no conclusive histopathological confirmation of UTUC. Major surgery was avoided in 77 patients (33.5%) where a benign or alternative diagnosis was made on URS, and 14 patients (6.1%) underwent nephron-sparing surgery. Overall, 178 patients (68.5%) had a final diagnosis of UTUC confirmed on URS/RNU histopathology. On multivariate logistic regression analysis, a presenting complaint of visible haematuria (hazard ratio [HR] 5.17, confidence interval [CI] 1.91-14.0; P = 0.001), a solid lesion reported on imaging (HR 37.8, CI = 11.7-122.1; P < 0.001) and a history of smoking (HR 3.07, CI 1.35-6.97; P = 0.007), were predictive of a final diagnosis of UTUC. From this cohort, 51 (96.2%) of 53 smokers who presented with visible haematuria and who had a solid lesion on computed tomography urogram had UTUC on final histopathology.
    Conclusion: We identified specific factors which may assist clinicians in selecting which patients may reliably proceed to RNU without the delay of diagnostic URS. These findings may inform a prospective multicentre analysis including additional variables such as urinary cytology.
    MeSH term(s) Humans ; Urinary Bladder Neoplasms ; Carcinoma, Transitional Cell/diagnosis ; Carcinoma, Transitional Cell/surgery ; Ureteroscopy/methods ; Hematuria/etiology ; Retrospective Studies ; Prospective Studies ; Ureteral Neoplasms/diagnosis ; Ureteral Neoplasms/surgery ; Ureteral Neoplasms/pathology ; Kidney Neoplasms/diagnosis ; Kidney Neoplasms/surgery
    Language English
    Publishing date 2023-01-23
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1462191-5
    ISSN 1464-410X ; 1464-4096 ; 1358-8672
    ISSN (online) 1464-410X
    ISSN 1464-4096 ; 1358-8672
    DOI 10.1111/bju.15945
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