- A Clinical pilot study of Resection Process Map: a novel virtual hepatectomy software to visualize the resection process, Case series. [Journal Article]Int J Surg 2019IJ
- CONCLUSIONS: RPM allows for preoperative simulation of hepatectomy and might be helpful for many surgeons. RPM is also useful for education of medical students.
- Impact of cervical range of motion on the global spinal alignment in ankylosing spondylitis patients with thoracolumbar kyphosis following pedicle subtraction osteotomy. [Journal Article]Spine J 2019SJ
- CONCLUSIONS: OT discordance in AS-related thoracolumbar kyphosis could be caused by the reduced cervical ROM. To maintain global spinal balance, the pelvis rotated further backward in response to the larger SVA COG-C7. Moreover, the larger SVA COG-C7 could be decreased after the lumbar PSO. Although there were radiographic differences between the patients with OT concordance and with OT discordance, there was no difference in clinical outcomes, and that a larger sample size and longer follow-up is needed.
- MCC950/CRID3 potently targets the NACHT domain of wild-type NLRP3 but not disease-associated mutants for inflammasome inhibition. [Journal Article]PLoS Biol 2019; 17(9):e3000354PB
- The nucleotide-binding-domain (NBD)-and leucine-rich-repeat (LRR)-containing (NLR) family, pyrin-domain-containing 3 (NLRP3) inflammasome drives pathological inflammation in a suite of autoimmune, metabolic, malignant, and neurodegenerative diseases. Additionally, NLRP3 gain-of-function point mutations cause systemic periodic fever syndromes that are collectively known as cryopyrin-associated per…
The nucleotide-binding-domain (NBD)-and leucine-rich-repeat (LRR)-containing (NLR) family, pyrin-domain-containing 3 (NLRP3) inflammasome drives pathological inflammation in a suite of autoimmune, metabolic, malignant, and neurodegenerative diseases. Additionally, NLRP3 gain-of-function point mutations cause systemic periodic fever syndromes that are collectively known as cryopyrin-associated periodic syndrome (CAPS). There is significant interest in the discovery and development of diarylsulfonylurea Cytokine Release Inhibitory Drugs (CRIDs) such as MCC950/CRID3, a potent and selective inhibitor of the NLRP3 inflammasome pathway, for the treatment of CAPS and other diseases. However, drug discovery efforts have been constrained by the lack of insight into the molecular target and mechanism by which these CRIDs inhibit the NLRP3 inflammasome pathway. Here, we show that the domain conserved in NAIP, CIITA, HET-E, and TP1 (NACHT) domain of NLRP3 is the molecular target of diarylsulfonylurea inhibitors. Interestingly, we find photoaffinity labeling (PAL) of the NACHT domain requires an intact (d)ATP-binding pocket and is substantially reduced for most CAPS-associated NLRP3 mutants. In concordance with this finding, MCC950/CRID3 failed to inhibit NLRP3-driven inflammatory pathology in two mouse models of CAPS. Moreover, it abolished circulating levels of interleukin (IL)-1β and IL-18 in lipopolysaccharide (LPS)-challenged wild-type mice but not in Nlrp3L351P knock-in mice and ex vivo-stimulated mutant macrophages. These results identify wild-type NLRP3 as the molecular target of MCC950/CRID3 and show that CAPS-related NLRP3 mutants escape efficient MCC950/CRID3 inhibition. Collectively, this work suggests that MCC950/CRID3-based therapies may effectively treat inflammation driven by wild-type NLRP3 but not CAPS-associated mutants.
- Circulating methylated RUNX3 and SFRP1 genes as a noninvasive panel for early detection of colorectal cancer. [Journal Article]Eur J Gastroenterol Hepatol 2019EJ
- CONCLUSIONS: Our results verified the reliability of using serum RUNX3 and SFRP1 methylation status as a noninvasive biomarker for diagnosis of CRC and that combined detection of RUNX3/SFRP1/CEA panel might be a promising strategy for early detection of CRC.
- IAC standardized reporting of breast fine-needle aspiration cytology, Yokohama 2016: A critical appraisal over a 2 year period. [Journal Article]Breast Dis 2019BD
- CONCLUSIONS: FNAC is a simple, reliable, cost effective, first line diagnostic procedure for all breast lumps. In collaboration with physical examination and imaging studies (triple approach), FNAC is a highly sensitive diagnostic tool. Adopting a universally acceptable standardized reporting system for breast cytology can enhance the diagnostic accuracy of FNAC.
- [Concordance between the test of the tuberculin and Interferon Gamma Release Assay-IGRA in patients with immune-mediated inflammatory diseases]. [Journal Article]Rev Esp Quimioter 2019RE
- CONCLUSIONS: The concordance between PT and IGRA is affected in patients with EIMI, and to a greater extent to patients with the inflammatory bowel disease, with the corticotherapy, with the BCG vaccination, or in the ones from endemic countries.
- Comparison of the Genedia MTB/NTM Detection Kit and Anyplex plus MTB/NTM Detection Kit for detection of Mycobacterium tuberculosis complex and nontuberculous mycobacteria in clinical specimens. [Journal Article]J Clin Lab Anal 2019; :e23021JC
- CONCLUSIONS: The Genedia and Anyplex kits demonstrated high sensitivity and specificity for the detection of MTB and NTM. Both kits have a high concordance rate and can be used more widely in clinical laboratories for the early detection of tuberculosis.
- Renal cell cancer treatment: an expert panel recommendation from the Latin American cooperative group-genitourinary and the Latin American renal cancer group: focus on surgery. [Review]Ther Adv Urol 2019 Jan-Dec; 11:1756287219872324TA
- CONCLUSIONS: This review suggests recommendations for the surgical treatment of RCC according to the LACOG-GU/LARCG experts.
- Reactive versus Constitutive: Reconcile the Controversial Results about the Prognostic Value of PD-L1 Expression in cancer. [Journal Article]Int J Biol Sci 2019; 15(9):1933-1941IJ
- The prognostic value of programmed death-ligand 1 (PD-L1) has been controversial in recent studies. PD-L1 is known to play a major role in suppressing the immune response, yet increasing studies have reported that PD-L1 expression has a favorable prognostic value for cancer patients. This raises the concern about how to understand PD-L1 expression: merely an immune inhibitory signal, or more like…
The prognostic value of programmed death-ligand 1 (PD-L1) has been controversial in recent studies. PD-L1 is known to play a major role in suppressing the immune response, yet increasing studies have reported that PD-L1 expression has a favorable prognostic value for cancer patients. This raises the concern about how to understand PD-L1 expression: merely an immune inhibitory signal, or more likely a reactive process to T-cell response that indicates cytotoxic T lymphocyte (CTL) level in a tumor? To solve this dilemma, an integrative investigation is required. We compared the PD-L1 expression between tumor cells and immune cells, and characterized the inter- and intra-tumor correlation between CTL and PD-L1 expression. The prognostic values between PD-L1 and CTL is compared across 15 solid cancers and 11 independent cohorts of ovarian cancer. PD-L1 and PD-L1-adjusted CTL are analyzed in immunotherapy dataset receiving nivolumab. We observed unexpected high concordance between the prognostic value of PD-L1 and CTL across different cancers and cohorts. We found primarily reactive rather than constitutive PD-L1 expression in most tumors. We revealed that PD-L1-adjusted CTL level, rather than the expression of PD-L1, effectively predicts the responders to immune checkpoint inhibitors. This study highlights the importance of PD-L1 expression, as primarily a signature of reacting efficiency of pre-existing anti-tumor immunity, in balancing the tumor microenvironment. Importantly, it suggests that the reactive efficiency of PD-L1 is more useful to predict the response to immunotherapy.
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- Highly Variable Disease Courses in Siblings with Stargardt Disease. [Journal Article]Ophthalmology 2019O
- CONCLUSIONS: Phenotypic discordance between siblings with STGD1 carrying the same ABCA4 variants is a prevalent phenomenon. Although the FAF phenotypes are highly comparable between siblings, functional outcomes differ substantially. This complicates both sibling-based prognosis and genotype-phenotype correlations and has important implications for patient care and management.