tbuckley/cabot-search huggingface dataset:
Magnesium cationic cue enriched interfacial tissue microenvironment nurtures the osseointegration of gamma-irradiated allograft bone
Authors: Wenhao Wang, Jie Shen, Yuan Meng, Miaoman Ye, Shaozhang Lin, Qi Zhao, Le Wang, Kenneth M.C. Cheung, Shuilin Wu, Yufeng Zheng, Xuanyong Liu, Paul K. Chu, Kelvin W.K. Yeung, Zhi-Yong Zhang
Journal: Bioactive Materials (2021)

Regardless of the advancement of synthetic bone substitutes, allograft-derived bone substitutes still dominate in the orthopaedic circle in the treatments of bone diseases. Nevertheless, the stringent devitalization process jeopardizes their osseointegration with host bone and therefore prone to long-term failure. Hence, improving osseointegration and transplantation efficiency remains important. The alteration of bone tissue microenvironment (TME) to facilitate osseointegration has been generally recognized. However, the concept of exerting metal ionic cue in bone TME without compromising the mechanical properties of bone allograft is challenging. To address this concern, an interfacial tissue microenvironment with magnesium cationc cue was tailored onto the gamma-irradiated allograft bone using a customized magnesium-plasma surface treatment. The formation of the Mg cationic cue enriched interfacial tissue microenvironment on allograft bone was verified by the scanning ion-selective electrode technique. The cellular activities of human TERT-immortalized mesenchymal stem cells on the Mg-enriched grafts were notably upregulated. In the animal test, superior osseointegration between Mg-enriched graft and host bone was found, whereas poor integration was observed in the gamma-irradiated controls at 28 days post-operation. Furthermore, the bony in-growth appeared on magnesium-enriched allograft bone was significant higher. The mechanism possibly correlates to the up-regulation of integrin receptors in mesenchymal stem cells under modified bone TME that directly orchestrate the initial cell attachment and osteogenic differentiation of mesenchymal stem cells. Lastly, our findings demonstrate the significance of magnesium cation modified bone allograft that can potentially translate to various orthopaedic procedures requiring bone augmentation.
Concomitant Transthyretin Amyloidosis and Severe Aortic Stenosis in Elderly Indian Population
Authors: Aayush Kumar Singal, Raghav Bansal, Avinainder Singh, Sharmila Dorbala, Gautam Sharma, Kartik Gupta, Anita Saxena, Balram Bhargava, Ganesan Karthikeyan, Sivasubramanian Ramakrishnan, Akshay Kumar Bisoi, Milind Padmakar Hote, Palleti Rajashekar, Ujjwal Kumar Chowdhury, Velayoudam Devagourou, Chetan Patel, Ruma Ray, Sudheer Kumar Arawa, Sundeep Mishra
Journal: JACC CardioOncology (2021)

BACKGROUND Prevalence of both degenerative severe aortic stenosis (AS) and transthyretin cardiac amyloidosis (ATTR-CA) increases with age.Dual disease (ASþmyocardial ATTR-CA) occurs in significant proportion of patients undergoing surgical aortic valve replacement (SAVR).OBJECTIVES This study aimed to determine the prevalence of ATTR-CA in severe AS in the Indian population, identify noninvasive predictors of its diagnosis, and understand its impact on prognosis.METHODS Symptomatic severe AS patients aged $65 years undergoing SAVR were enrolled.ATTR-CA diagnosis was based on preoperative 99m-technetium pyrophosphate (PYP) scan and intraoperatively obtained basal interventricular septum biopsy for myocardial ATTR-CA, and excised native aortic valve for isolated valvular ATTR-CA.Primary amyloidosis was excluded by serum/urine protein electrophoresis with serum immunofixation.RESULTS SAVR was performed in 46 AS patients (age 70 AE 5 years, 70% men).PYP scan was performed for 32 patients, with significant PYP uptake in 3 (n ¼ 3 of 32, 9.4%), suggestive of myocardial ATTR-CA.On histopathological examination, none of the interventricular septum biopsy specimens had amyloid deposits, whereas 33 (71.7%) native aortic valves showed amyloid deposits, of which 19 (57.6%) had transthyretin deposition suggestive of isolated valvular amyloidosis.Noninvasive markers of dual disease included low myocardial contraction fraction (median [interquartile range], 28.8% [23.8% to 39.1%] vs 15.3% [9.3% to 16.1%]; P ¼ 0.006), deceleration time (215 [144 to 236] ms vs 88 [60 to 106] ms; P ¼ 0.009) and global longitudinal strain (-18.7% [-21.1% to -16.9%] vs -14.2% [-17.0% to -9.7%]; P ¼ 0.030).At 1-year follow-up, 2 patients died (4.3%); 1 each in myocardial ATTR-CA negative and positive groups (3.4% vs 33.3%; P ¼ 0.477).CONCLUSIONS Dual disease is not uncommon in India.Isolated valvular amyloidosis in severe AS is much more common.
Emerging role of tumor-derived extracellular vesicles in T cell suppression and dysfunction in the tumor microenvironment
Authors: Feiya Ma, Jensen Vayalil, Grace Lee, Yuqi Wang, Guangyong Peng
Journal: Journal for ImmunoTherapy of Cancer (2021)

Immunotherapeutic drugs including immune checkpoint blockade antibodies have been approved to treat patients in many types of cancers. However, some patients have little or no reaction to the immunotherapy drugs. The mechanisms underlying resistance to tumor immunotherapy are complicated and involve multiple aspects, including tumor-intrinsic factors, formation of immunosuppressive microenvironment, and alteration of tumor and stromal cell metabolism in the tumor microenvironment. T cell is critical and participates in every aspect of antitumor response, and T cell dysfunction is a severe barrier for effective immunotherapy for cancer. Emerging evidence indicates that extracellular vesicles (EVs) secreted by tumor is one of the major factors that can induce T cell dysfunction. Tumor-derived EVs are widely distributed in serum, tissues, and the tumor microenvironment of patients with cancer, which serve as important communication vehicles for cancer cells. In addition, tumor-derived EVs can carry a variety of immune suppressive signals driving T cell dysfunction for tumor immunity. In this review, we explore the potential mechanisms employed by tumor-derived EVs to control T cell development and effector function within the tumor microenvironment. Especially, we focus on current understanding of how tumor-derived EVs molecularly and metabolically reprogram T cell fates and functions for tumor immunity. In addition, we discuss potential translations of targeting tumor-derived EVs to reconstitute suppressive tumor microenvironment or to develop antigen-based vaccines and drug delivery systems for cancer immunotherapy.
P69.02 Video-Assisted Mediastinoscopic Lymphadenctomy Improves Natural Killer Cytotoxicity in Non-Small Cell Lung Cancer
Authors: A. Turna, F. Esen, A. Engin, M. Ağkoç, G. Deniz, E. Aktaş Çetin
Journal: Journal of Thoracic Oncology (2021)
<i>Notes from the Field:</i> Fatal Anthrax Pneumonia in Welders and Other Metalworkers Caused by <i>Bacillus cereus</i> Group Bacteria Containing Anthrax Toxin Genes — U.S. Gulf Coast States, 1994–2020
Authors: Patrick Dawson, Caroline A. Schrodt, Karl Feldmann, Rita M. Traxler, Jay E. Gee, Cari B. Kolton, Chung K. Marston, Christopher A. Gulvik, James M. Antonini, María E. Negrón, John R. McQuiston, Kate Hendricks, Zachary Weiner, Gary A. Balsamo, Theresa Sokol, Paul Byers, Kathryn Taylor, Saad Zaheer, Stephen Long, Briana O’Sullivan, Marie A. de Perio, Alex R. Hoffmaster, Johanna S. Salzer, William A. Bower
Journal: MMWR Morbidity and Mortality Weekly Report (2021)
Investigating Lipid-Modulating Agents for Prevention or Treatment of COVID-19
Authors: Azita H. Talasaz, Parham Sadeghipour, Maryam Aghakouchakzadeh, Isaac Dreyfus, Hessam Kakavand, Hamid Ariannejad, Aakriti Gupta, Mahesh V. Madhavan, Benjamin W. Van Tassell, David Jimenez, Manuel Monreal, Muthiah Vaduganathan, John Fanikos, Dave L. Dixon, Gregory Piazza, Sahil A. Parikh, Deepak L. Bhatt, Gregory Y.H. Lip, Gregg W. Stone, Harlan M. Krumholz, Peter Libby, Samuel Z. Goldhaber, Behnood Bikdeli
Journal: Journal of the American College of Cardiology (2021)
Abstract 505: Propranolol Block of Human Cardiac Sodium Channels is Enhanced by SCN5A Mutations in Long-QT Syndrome Type 3
Authors: Dao W Wang, Alfred L George
Journal: Circulation (2007)

Propranolol is a widely-used, nonselective β-adrenergic receptor antagonist with proven efficacy in reducing mortality after myocardial infarction and in the congenital long-QT syndrome (LQTS). At ...
Revisiting Complexities in the Pediatric Subspecialty Workforce
Authors: Adam Turner, Thomas Ricketts, Laurel K. Leslie
Journal: JAMA Pediatrics (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Posttransplant blockade of CXCR4 improves leukemia complete remission rates and donor stem cell engraftment without aggravating GVHD
Authors: Long Su, Ming-Hui Fang, Jun Zou, Su-Jun Gao, Xiao-Yi Gu, Xian-Di Meng, Xue Wang, Zheng Hu, Yong-Guang Yang
Journal: Cellular and Molecular Immunology (2021)
The UK government’s covid complacency shows lessons haven’t been learned
Authors: Gareth Iacobucci
Journal: BMJ (2021)

This week, England’s health secretary, Sajid Javid told a Downing Street covid briefing that the government would not “at this point” be implementing its so-called “Plan B” measures to prevent the NHS being overwhelmed—including mandatory face coverings indoors and advising people to work from home.

To repurpose a phrase that Javid himself used in July when justifying his decision to remove almost all covid restrictions in England—“If not now, then when?”1

On 20 October 2021—the day of the briefing—the UK recorded 49 139 new cases of covid-19, 179 deaths, and 869 hospital admissions. Javid warned that rising daily infection rates “could yet go as high as 100,000 a day.” The NHS and the BMA say ministers must implement Plan B now, amid warnings of a …
Why is<i>The BMJ</i>misrepresenting assisted dying?
Authors: Claud Regnard, Rob George, Amy Profitt
Journal: BMJ (2021)

Hurley and colleagues’ promotion of the proposed assisted dying bill in England and Wales ignores the obstacles.1

In last year’s BMA survey, a majority of doctors were unwilling to prescribe the necessary drugs.2 Will we end up like Oregon, where a tiny proportion of doctors prescribe (one writing 31 prescriptions in 2020)?3 Every legislature has shortened or removed cooling off periods and expanded their criteria beyond a …
Correction to: Proteomic landscape of Alzheimer’s Disease: novel insights into pathogenesis and biomarker discovery
Authors: Bing Bai, David Vanderwall, Yuxin Li, Xusheng Wang, Suresh Poudel, Hong Wang, Kaushik Kumar Dey, Ping-Chung Chen, Ka Yang, Junmin Peng
Journal: Molecular Neurodegeneration (2021)
Incidence of Cigarette Smoking Relapse Among Individuals Who Switched to e-Cigarettes or Other Tobacco Products
Authors: John P. Pierce, Ruifeng Chen, Sheila Kealey, Eric C. Leas, Martha M. White, Matthew D. Stone, Sara B. McMenamin, Dennis R. Trinidad, David R. Strong, Tarik Benmarhnia, Karen Messer
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Although e-cigarettes are not approved as a cessation device, many who smoke believe that e-cigarettes will help them quit cigarette smoking successfully. <h3>Objective</h3> To assess whether people who recently quit smoking and who had switched to e-cigarettes or another tobacco product were less likely to relapse to cigarette smoking compared with those who remained tobacco free. <h3>Design, Setting, and Participants</h3> This cohort study analyzed a nationally representative sample of US households that participated in 4 waves of the Population Assessment of Tobacco and Health Study (conducted 2013 through 2017), combining 2 independent cohorts each with 3 annual surveys. Eligible participants were individuals who smoked at baseline, had recently quit at the first follow-up, and completed the second follow-up survey. <h3>Exposures</h3> Use of e-cigarettes or alternate tobacco products at follow-up 1 after recently quitting smoking. <h3>Main Outcomes and Measures</h3> Weighted percentage of participants with over 12 months abstinence by follow-up 2. <h3>Results</h3> Of a total of 13 604 participants who smoked cigarettes at baseline, 9.4% (95% CI, 8.7%-10.0%) recently had quit smoking (mean age, 41.9; 95% CI, 39.7-46.6 years; 641 [43.2%] women) Of these, 22.8% (95% CI, 19.7%-26.0%) had switched to e-cigarettes, with 17.6% (95% CI, 14.8%-20.5%) using them daily. A total of 37.1% (95% CI, 33.7%-40.4%) used a noncigarette tobacco product and 62.9% (95% CI, 59.6%-66.3%) were tobacco free. Rates of switching to e-cigarettes were highest for those who were in the top tertile of tobacco dependence (31.3%; 95% CI, 25.0%-37.7%), were non-Hispanic White (26.4%; 95% CI, 22.3%-30.4%), and had higher incomes (annual income ≥$35 000, 27.5%; 95% CI, 22.5%-32.4% vs &lt;$35 000, 19.3%; 95% CI, 16.3%-22.3%). At follow-up 2, unadjusted relapse rates were similar among those who switched to different tobacco products (for any tobacco product: successfully quit, 41.5%; 95% CI, 36.2%-46.9%; relapsed with significant requit, 17.0%; 95% CI, 12.4%-21.6%; currently smoking, 36.2%; 95% CI, 30.9%-41.4%). Controlled for potential confounders, switching to any tobacco product was associated with higher relapse rate than being tobacco free (adjusted risk difference, 8.5%; 95% CI, 0.3%-16.6%). Estimates for those who switched to e-cigarettes, whether daily or not, were not significant. While individuals who switched from cigarettes to e-cigarettes were more likely to relapse, they appeared more likely to requit and be abstinent for 3 months at follow-up 2 (17.0%; 95% CI, 12.4%-21.6% vs 10.4%; 95% CI, 8.0%-12.9%). <h3>Conclusions and Relevance</h3> This large US nationally representative study does not support the hypothesis that switching to e-cigarettes will prevent relapse to cigarette smoking.
Survival in Young-Onset Metastatic Colorectal Cancer: Findings From Cancer and Leukemia Group B (Alliance)/SWOG 80405
Authors: Marla Lipsyc-Sharf, Sui Zhang, Fang-Shu Ou, Chao Ma, Nadine Jackson McCleary, Donna Niedzwiecki, I-Wen Chang, Heinz-Josef Lenz, Charles D Blanke, Sorbarikor Piawah, Katherine Van Loon, Tiffany M Bainter, Alan P Venook, Robert J Mayer, Charles S Fuchs, Federico Innocenti, Andrew B Nixon, Richard Goldberg, Eileen M O’Reilly, Jeffrey A Meyerhardt, Kimmie Ng
Journal: JNCI Journal of the National Cancer Institute (2021)

The incidence of young-onset colorectal cancer (yoCRC) is increasing. It is unknown if there are survival differences between young and older patients with metastatic colorectal cancer (mCRC).We studied the association of age with survival in 2326 mCRC patients enrolled in the Cancer and Leukemia Group B and SWOG 80405 trial, a multicenter, randomized trial of first-line chemotherapy plus biologics. The primary and secondary outcomes of this study were overall survival (OS) and progression-free survival (PFS), respectively, which were assessed by Kaplan-Meier method and compared among younger vs older patients with the log-rank test. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated based on Cox proportional hazards modeling, adjusting for known prognostic variables. All statistical tests were 2-sided.Of 2326 eligible subjects, 514 (22.1%) were younger than age 50 years at study entry (yoCRC cohort). The median age of yoCRC patients was 44.3 vs 62.5 years in patients aged 50 years and older. There was no statistically significant difference in OS between yoCRC vs older-onset patients (median = 27.07 vs 26.12 months; adjusted HR = 0.98, 95% CI = 0.88 to 1.10; P = .78). The median PFS was also similar in yoCRC vs older patients (10.87 vs 10.55 months) with an adjusted hazard ratio of 1.02 (95% CI = 0.92 to 1.13; P = .67). Patients younger than age 35 years had the shortest OS with median OS of 21.95 vs 26.12 months in older-onset patients with an adjusted hazard ratio of 1.08 (95% CI = 0.81 to 1.44; Ptrend = .93).In this large study of mCRC patients, there were no statistically significant differences in survival between patients with yoCRC and CRC patients aged 50 years and older.
The Impact of Diabetes on Productivity in India
Authors: Khyati K. Banker, Danny Liew, Zanfina Ademi, Alice J. Owen, Afsana Afroz, Dianna J. Magliano, Ella Zomer
Journal: Diabetes Care (2021)

Diabetes increases the risk of premature mortality and considerably impacts on work productivity. We sought to examine the impact of diabetes in India, in terms of excess premature mortality, years of life lost (YLL), productivity-adjusted life years (PALYs) lost, and its associated economic impact.A life table model was constructed to examine the productivity of the Indian working-age population currently aged 20-59 years with diabetes, followed until death or retirement age (60 years). The same cohort was resimulated, hypothetically assuming that they did not have diabetes. The total difference between the two cohorts, in terms of excess deaths, YLL and PALYs lost reflected the impact of diabetes. Data regarding the prevalence of diabetes, mortality, labor force dropouts, and productivity loss attributable to diabetes were derived from published sources.In 2017, an estimated 54.4 million (7.6%) people of working-age in India had diabetes. With simulated follow-up until death or retirement age, diabetes was predicted to cause 8.5 million excess deaths (62.7% of all deaths), 42.7 million YLL (7.4% of total estimated years of life lived), and 89.0 million PALYs lost (23.3% of total estimated PALYs), equating to an estimated Indian rupee 176.6 trillion (U.S. dollars 2.6 trillion; purchasing power parity 9.8 trillion) in lost gross domestic product.Our study demonstrates the impact of diabetes on productivity loss and highlights the importance of health strategies aimed at the prevention of diabetes.
Private management consultants: evaluate their work, but don’t forget to ask why their use in the NHS is so high
Authors: Stephen Black
Journal: BMJ (2021)

There is a widespread populist belief that management consulting is a racket designed to take money from virtuous but naive public bodies. Articles like the editorial by Bruch and colleagues perpetuate that belief while failing to ask why the use of management consultants is apparently so prevalent in the NHS.1

I’ve proposed …
P70.07 Examples of Population Kinetics (PopKin) Assessments of Progression-Free (PFS) and Overall Survival (OS)
Authors: D. Stewart, A. Aljassim Alshareef, A. Robinson, M. Fung-Kee-Fung, M. Ong, A. Awan, A. Ocana
Journal: Journal of Thoracic Oncology (2021)
P62.05 Identifying Risk-Factors for Lung Cancer Diagnosis After Detection of Incidental Lung Nodules
Authors: W. Liao, M. Smeltzer, N. Faris, C. Fehnel, J. Goss, A. Epperson, S. Williams, M. Meadows-Taylor, O. Akinbobola, A. Pacheco, J. Luttrell, D. Mccoy, K. Tonkin, R. Optican, J. Wright, T. Robbins, S. Satpute, P. Harris, M. Ray, R. Osarogiagbon
Journal: Journal of Thoracic Oncology (2021)
IL-12 regulates type 3 immunity through interfollicular keratinocytes in psoriasiform inflammation
Authors: Pascale Zwicky, Florian Ingelfinger, Bruno Marcel Silva de Melo, Fiorella Ruchti, Stefanie Schärli, Nicole Puertas, Mirjam Lutz, Truong San Phan, Thomas M. Kündig, Mitchell P. Levesque, Julia-Tatjana Maul, Christoph Schlapbach, Salomé LeibundGut-Landmann, Sarah Mundt, Burkhard Becher
Journal: Science Immunology (2021)

Psoriasis is a chronic inflammatory skin disorder underpinned by dysregulated cytokine signaling. Drugs neutralizing the common p40 subunit of interleukin-12 (IL-12) and IL-23 represented a therapeutic breakthrough; however, new drugs that block the IL-23p19 subunit and spare IL-12 are more effective, suggesting a regulatory function of IL-12. To pinpoint the cell type and underlying mechanism of IL-12–mediated immune regulation in psoriasis, we generated a conditional Il12rb2-knockout (KO)/reporter mouse strain. We detected Il12rb2 expression in T cells and a specific subset of interfollicular (IF) keratinocytes. Analysis of single-cell RNA-sequencing (scRNAseq) data from patients with psoriasis confirmed a similar expression pattern in the human skin. Deletion of Il12rb2 across the hematopoietic compartment did not alter the development of Aldara-induced psoriasiform inflammation. However, depletion of Il12rb2 in keratinocytes exacerbated disease development, phenocopying the Il12rb2 germline knockout. Protective IL-12 signaling blocked the hyperproliferation of keratinocytes, maintained skin barrier integrity, and diminished disease-driving IL-23/type 3 immune circuits. In line, specific IL-23p19 blockade led to a more profound reduction of psoriatic keratinocyte expression signatures in the skin of patients with psoriasis than combined IL-12/IL-23 inhibition. Collectively, we provide a potential explanation for the superior efficacy of IL-23p19 inhibitors in psoriasis and describe an unperceived role of IL-12 in maintaining skin epithelial cell homeostasis.
Endogenous Oxalate Production in Primary Hyperoxaluria Type 1 Patients
Authors: Sander F. Garrelfs, Dewi van Harskamp, Hessel Peters-Sengers, Chris H.P. van den Akker, Ronald J.A. Wanders, Frits A. Wijburg, Johannes B. van Goudoever, Jaap W. Groothoff, Henk Schierbeek, Michiel J.S. Oosterveld
Journal: Journal of the American Society of Nephrology (2021)

Primary hyperoxaluria type 1 (PH1) is an inborn error of glyoxylate metabolism, characterized by increased endogenous oxalate production. The metabolic pathways underlying oxalate synthesis have not been fully elucidated, and upcoming therapies require more reliable outcome parameters than the currently used plasma oxalate levels and urinary oxalate excretion rates. We therefore developed a stable isotope infusion protocol to assess endogenous oxalate synthesis rate and the contribution of glycolate to both oxalate and glycine synthesis in vivo .Eight healthy volunteers and eight patients with PH1 (stratified by pyridoxine responsiveness) underwent a combined primed continuous infusion of intravenous [1- 13 C]glycolate, [U- 13 C 2 ]oxalate, and, in a subgroup, [D 5 ]glycine. Isotopic enrichment of 13 C-labeled oxalate and glycolate were measured using a new gas chromatography-tandem mass spectrometry (GC-MS/MS) method. Stable isotope dilution and incorporation calculations quantified rates of appearance and synthetic rates, respectively.Total daily oxalate rates of appearance (mean [SD]) were 2.71 (0.54), 1.46 (0.23), and 0.79 (0.15) mmol/d in patients who were pyridoxine unresponsive, patients who were pyridoxine responsive, and controls, respectively ( P =0.002). Mean (SD) contribution of glycolate to oxalate production was 47.3% (12.8) in patients and 1.3% (0.7) in controls. Using the incorporation of [1- 13 C]glycolate tracer in glycine revealed significant conversion of glycolate into glycine in pyridoxine responsive, but not in patients with PH1 who were pyridoxine unresponsive.This stable isotope infusion protocol could evaluate efficacy of new therapies, investigate pyridoxine responsiveness, and serve as a tool to further explore glyoxylate metabolism in humans.