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1.
Dongbing Lai Emma C. Johnson Sarah Colbert Gayathri Pandey Grace Chan Lance Bauer Meredith W. Francis Victor Hesselbrock Chella Kamarajan John Kramer Weipeng Kuang Sally Kuo Samuel Kuperman Yunlong Liu Vivia McCutcheon Zhiping Pang Martin H. Plawecki Marc Schuckit Jay Tischfield Leah Wetherill Yong Zang Howard J. Edenberg Bernice Porjesz Arpana Agrawal Tatiana Foroud 《Alcoholism, clinical and experimental research》2022,46(3):374-383
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Lorena Martin-Morales Sara Manzano Maria Rodrigo-Faus Adrian Vicente-Barrueco Victor Lorca Gonzalo Núñez-Moreno Paloma Bragado Almudena Porras Trinidad Caldes Pilar Garre Alvaro Gutierrez-Uzquiza 《International journal of cancer. Journal international du cancer》2023,152(2):283-297
Matrix metalloproteinase-11 (MMP11) is an enzyme with proteolytic activity against matrix and nonmatrix proteins. Although most MMPs are secreted as inactive proenzymes and are later activated extracellularly, MMP11 is activated intracellularly by furin within the constitutive secretory pathway. It is a key factor in physiological tissue remodeling and its alteration may play an important role in the progression of epithelial malignancies and other diseases. TCGA colon and colorectal adenocarcinoma data showed that upregulation of MMP11 expression correlates with tumorigenesis and malignancy. Here, we provide evidence that a germline variant in the MMP11 gene (NM_005940: c.232C>T; p.(Pro78Ser)), identified by whole exome sequencing, can increase the tumorigenic properties of colorectal cancer (CRC) cells. P78S is located in the prodomain region, which is responsible for blocking MMP11's protease activity. This variant was detected in the proband and all the cancer-affected family members analyzed, while it was not detected in healthy relatives. In silico analyses predict that P78S could have an impact on the activation of the enzyme. Furthermore, our in vitro analyses show that the expression of P78S in HCT116 cells increases tumor cell invasion and proliferation. In summary, our results show that this variant could modify the structure of the MMP11 prodomain, producing a premature or uncontrolled activation of the enzyme that may contribute to an early CRC onset in these patients. The study of this gene in other CRC cases will provide further information about its role in CRC development, which might improve patient treatment in the future. 相似文献
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Alexander C. Egbe Rosalyn Adigun Vidhu Anand Collin P. West Victor M. Montori Hassan M. Murad Emmanuel Akintoye Karim Osman Heidi M. Connolly 《The Canadian journal of cardiology》2019,35(12):1784-1790
BackgroundAlthough there are robust data about the pathophysiology and prognostic implications of left ventricular (LV) systolic dysfunction in patients with acquired heart disease, similar prognostic data about LV systolic dysfunction are sparse in the tetralogy of Fallot (TOF) population. The purpose of this study was to perform a meta-analysis of all studies that assessed the relationship between LV ejection fraction (LVEF) and cardiovascular adverse events (CAEs) defined as death, aborted sudden death, or sustained ventricular tachycardia.MethodsWe used random-effects models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsOf the 1,809 citations, 7 studies with 2,854 patients (age 28 ± 4 years) were included. During 5.6 ± 3.4 years' follow-up, there were 82 deaths, 17 aborted sudden cardiac deaths, and 56 sustained ventricular tachycardia events. Overall, CAEs occurred in 5.1% (144 patients). As a continuous variable, LVEF was a predictor of CAE (HR 1.29, 95% CI, 1.09-1.53, P = 0.001) per 5% decrease in LVEF. Similarly, LVEF < 40% was also a predictor of CAE (HR 3.22, 95% CI, 2.16-4.80, P < 0.001).ConclusionsLV systolic dysfunction was an independent predictor of CAE, and we observed a 30% increase in the risk of CAE for every 5% decrease in LVEF, and a 3-fold increase in the risk of CAE in patients with LVEF <40% compared with other patients. These findings underscore the importance of incorporating LV systolic function in clinical risk stratification of patients with TOF and the need to explore new treatment options to address this problem. 相似文献
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Jos M. Martín Encarnacion Montesinos Pilar Cordero Victor Gonzalez Dolores Ramon 《Pediatric dermatology》2019,36(2):265-267
Trichotillomania is a form of traction alopecia resulting from repetitive and compulsive hair pulling and plucking. Trichotillomania and patchy alopecia areata may have similar clinical and dermoscopic features in some cases. On trichoscopic examination, the presence of black dots, coiled or hook hair, shafts of varying lengths with fraying or split ends (trichoptilosis), and an absence of exclamation mark hairs and yellow dots are suggestive of trichotillomania. 相似文献
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Background Context
Long-term follow-up of patient-reported outcome measures (PROM) is essential in both modern spinal care and research. Lack of time and staff are commonly reported barriers to implementing long-term follow-up of PROM. Automated and digital follow-up systems for PROM collection are seeing widespread use, yet their validity and comparative effectiveness have never been evaluated.Purpose
The present study aimed to assess the validity of digital follow-up systems in comparison with the conventional paper-based follow-up (PB-FU).Study Design
This is a retrospective analysis of prospectively collected double follow-up data.Patient Sample
Patients who underwent lumbar spinal fusion for spondylolisthesis or degenerative disc disease between 2013 and 2016 were included in the study.Outcome Measures
The study determined the Oswestry Disability Index (ODI) and Numeric Rating Scale (NRS) for back and leg pain severity at baseline, 6 weeks, 12 months, and 24 months.Materials and Methods
After lumbar spinal fusion surgery, a double follow-up of PROM was carried out by conventional PB-FU during clinical visits, while simultaneously completing an automatically dispatched digital follow-up questionnaire. As the primary end point, we assessed the intraindividual discrepancy in PROM between PB-FU and automated digital follow-up (AD-FU).Results
Forty patients completed all parts of the dual follow-up trajectory and were analyzed. We detected no discrepancy in ODI or NRS for back and leg pain severity at any of the baseline, 6-week, 12-month, or 24 month follow-ups (all p>.05). This was confirmed in a sensitivity analysis.Conclusions
In an analysis of dual paper-based and digital follow-up after lumbar fusion surgery, patients report highly similar values using either method of follow-up. It appears that AD-FU without incentives produces lower response rates. To reassess the validity of these systems for data collection in spinal patient care, a prospective validation with higher statistical power is warranted. 相似文献9.
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Darren R. Feldman MD Yasser Ged MBBS Chung-Han Lee PhD Andrea Knezevic MS Ana M. Molina MD Ying-Bei Chen PhD Joshua Chaim DO Devyn T. Coskey MS Samuel Murray MS Satish K. Tickoo MD Victor E. Reuter MD Sujata Patil PhD Han Xiao MD Jahan Aghalar MD Arlyn J. Apollo MD Maria I. Carlo MD Robert J. Motzer MD Martin H. Voss MD 《Cancer》2020,126(24):5247-5255