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41.
42.
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
43.
Chumakov E. M. Petrova N. N. Limankin O. V. Ashenbrenner Yu. V. 《Neuroscience and behavioral physiology》2022,52(1):45-51
Neuroscience and Behavioral Physiology - Objective. To determine the frequency, structure, and severity of cognitive impairments in patients with bipolar affective disorder (BAD) in remission.... 相似文献
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Accurate diagnosis and recognition of predisposing factors has been shown to be challenging in lower limb cellulitis (LLC). Assessment of 1746 consecutive patients with cellulitis presenting to a UK university hospital showed increasing overdiagnosis, with only 31.9% of patients referred during the period 2015–2018 having the diagnosis of LLC confirmed. Recognition of at least one predisposing factor increased from 61% to 89% following introduction of more specific screening questions. This identified a need for better primary care dermatology education and the benefit of a proforma with specific screening questions for reversible predisposing factors for LLC. 相似文献
46.
Sania Amr Magdy Garas Dina N. K. Boulos Doa’a A. Saleh Irene A. Jillson Christopher A. Loffredo 《Journal of substance use》2019,24(3):341-345
Background: Egyptian street youth use substances including tobacco, illicit drugs, and pharmaceutical drugs. To understand the circumstances, including adverse childhood experiences, that place adolescents at risk for engaging in substance use, we conducted in-depth interviews among a sample of Egyptian street children. Methods: From youth residing at or attending Caritas, a non-profit organization, which provides shelter and education to street youth, seven girls and twelve boys, aged 12–18 years, participated in open-ended, in-depth interviews. Results: Eight out of the 19 participants reported family history (early exposure) to substance use; and seven of them were initiated by either a family member (sibling), friend or coworker. Most of the participants reported a history of conflict with or abuse (verbal or physical) by their parents or siblings, or stressful situations at home; they used substance(s) to alleviate their stress. Few attended school, and some were forced to work and help their family. Conclusions: Among Egyptian youth, adverse childhood experiences, such as poverty, child abuse, and family substance use, challenge somewhat susceptible youths and lead them to the path of substance use and addiction. Prevention intervention should be multifaceted, culturally adaptable, and primarily targeting the social environment during childhood. 相似文献
47.
Joseph F. Levy Rahul Khairnar Alexander V. Louie Timothy N. Showalter C. Daniel Mullins Mark V. Mishra 《Practical radiation oncology》2019,9(2):e172-e179
Purpose
A hydrogel rectal spacer (HRS) is a medical device that is approved by the U.S. Food and Drug Administration to increase the separation between the prostate and rectum. We conducted a cost-effectiveness analysis of HRS use for reduction in radiation therapy (RT) toxicities in patients with prostate cancer (PC) undergoing external beam RT (EBRT).Methods and Materials
A multistate Markov model was constructed from the U.S. payer perspective to examine the cost-effectiveness of HRS in men with localized PC receiving EBRT (EBRT alone vs EBRT + HRS). The subgroups analyzed included site of HRS placement (hospital outpatient, physician office, ambulatory surgery center) and proportion of patients with good baseline erectile function (EF). Data on EF, gastrointestinal and genitourinary toxicities incidence, and potential risks associated with HRS implantation were obtained from a recently published randomized clinical trial. Health utilities and costs were derived from the literature and the 2018 Physician Fee Schedule and were discounted 3% annually. Quality-adjusted life years (QALYs) and costs were modeled for a 5-year period from receipt of RT. Probabilistic sensitivity analysis and value-based threshold analyses were conducted.Results
The per-patient 5-year incremental cost for spacers administered in a hospital outpatient setting was $3578, and the incremental effectiveness was 0.0371 QALYs. The incremental cost-effectiveness ratio was $96,440/QALY for patients with PC undergoing HRS insertion in a hospital and $39,286/QALY for patients undergoing HRS insertion in an ambulatory facility. For men with good baseline EF, the incremental cost-effectiveness ratio was $35,548/QALY and $9627/QALY in hospital outpatient and ambulatory facility settings, respectively.Conclusions
Based on the current Medicare Physician Fee Schedule, HRS is cost-effective at a willingness to pay threshold of $100,000. These results contain substantial uncertainty, suggesting more evidence is needed to refine future decision-making. 相似文献48.
49.
Gordon K. B. Saburov V. O. Koryakin S. N. Gulidov I. A. Fatkhudinov T. Kh. Arutyunyan I. V. Kaprin A. D. Solov’ev A. N. 《Bulletin of experimental biology and medicine》2022,173(2):281-285
Bulletin of Experimental Biology and Medicine - Fast neutron therapy, which previously has demonstrated effective results, but along with a large number of complications, can again be considered a... 相似文献
50.