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1.
Objective: Breast cancer is the second most common cancer in the world. Many metastasis suppressor genes were identified, including the KISS1 gene which encodes for a 145 amino acid protein (kisspeptin-145), which undergoes proteolytic cleavage resulting in kisspeptin-14, -13 and -10. All of these proteins can activate KISS1 receptor (KISS1R). The role of KP/KISS1R signaling in breast cancer remains controversial. The present study aimed to measure mRNA gene expression of KISS1 receptor in healthy and cancerous breast tissue and to evaluate the association of its level with the available molecular subtypes and the traditional clinico-pathological variables. Methods: The study was done on 41 operable primary breast cancer patients. Biopsies from both tumor tissue and surrounding healthy mammary tissue were taken from all patients. KISS1R mRNA expression level was measured using a quantitative real time PCR.   Results: KISS1R mRNA expression was significantly higher in stage III patients compared to stage II patients. At a cut-off value for KISS1R mRNA expression of 1.75, stage II was discriminated from stage III. A significant positive correlation was found between KISS1R mRNA expression and tumor size as well as lymph nodes metastasis. KISS1R mRNA was highly expressed in ER negative cases compared to ER positive ones, and in PR negative cases compared to PR positive ones. There was a statistically significant difference in KISS1R mRNA expression levels and different molecular subtypes being over-expressed in HER2 and triple negative cancer cases. Conclusion: This study supports other studies suggesting that KISS1/KISS1R may not be acting as a metastasis suppressor in breast cancer. KISS1R mRNA is over expressed in advanced stages of breast cancer and hence it can be used as a prognostic marker for aggressiveness of breast cancer. Also being over expressed in triple negative patients, KISS1R could represent a promising therapeutic target in triple negative cases.  相似文献   
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Journal of Clinical Immunology - Coronavirus disease 2019 (COVID-19) exhibits a wide spectrum of clinical manifestations, ranging from asymptomatic to critical conditions. Understanding the...  相似文献   
4.
AIM: To compare the diagnostic ability of glaucoma parameters measured by the optical coherence tomography (OCT) in normal, preperimetric glaucoma (PPG) and perimetric glaucoma (PG) patients. METHODS: This cross-sectional observational study includes 127 eyes of 127 subjects. Patients were divided into PPG (51 eyes), PG (46 eyes), and normal controls (30 eyes) based on clinical optic disc assessment and Humphrey visual field changes. The Heidelberg Spectralis OCT machine using Glaucoma Module Premium Edition software was used to measure the retinal nerve fiber layer (RNFL) and Bruch’s membrane opening-minimum rim width (BMO-MRW) to assess the optic nerve head and ganglion cell layer (GCL) thickness in the macula. RESULTS: RNFL, MRW, and GCL thickness were all significantly thinner in PG compared to PPG and the normal group. The BMO-MRW parameters showed better specificity (>70%) at 90% specificity compared to both RNFL and GCL parameters to discriminate normal, PPG, and PG patients. All BMO-MRW parameters showed higher area under curves (AUC) compared to RNFL and GCL parameters with the highest AUC observed in the superotemporal sector of the BMO-MRW (AUC=0.819 and and 0.897 between normal and PPG and PG groups respectively). CONCLUSION: While the BMO-MRW best discriminates PPG and PG against normal eyes, GCL parameters poorly differentiate the three groups.  相似文献   
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Journal of Clinical Immunology - Inborn errors of immunity (IEI) and autoantibodies to type I interferons (IFNs) underlie critical COVID-19 pneumonia in at least 15% of the patients, while the...  相似文献   
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Background

This study aims at identifying the microbiota in traumatized immature permanent teeth with periapical lesions using Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).

Methods

The study included 16 immature maxillary central incisors with periapical lesions in 13 patients. Field decontamination and negative control samples were performed before and after access cavity preparation. Root canal samples were taken using sterile stainless-steel hand files following field decontamination. In-office inoculation and pure sub-cultures were performed. Bacterial isolates were prepared for MALDI-TOF MS (Bruker, Billerica, MA USA) analysis using the formic acid extraction method. A comparison of the prevalence of isolated microorganisms was done using a one-sample chi-square test. Comparisons between identified microbial species with the, cone beam computed tomography periapical index (CBCT PAI) scores and lesion volume were also conducted. The Chi-square test was applied to investigate the association between the categorical variables .

Results

Out of the forty isolates recovered from the 16 traumatized teeth included in the present study with the mean patients’ age of 10.93 ± 1.77, 37 isolates were reliably identified by MALDI-TOF MS. Twelve teeth (62.5%) were polymicrobial. The recovered bacteria belonged to five phyla, 15 genera and 25 species. Firmicutes were the predominant phylum (P < 0.001) over Bacteroidetes, Proteobacteria, Actinobacteria and Fusobacteria. Gram positive bacteria were significantly more prevalent than Gram negative (p = 0.03). Facultative anaerobes were the most prevalent (P < 0.001) compared to the obligate anaerobes and the obligate aerobes. The latter were the least prevalent. Statistically, significant differences existed in the comparison between CBCT PAI scores according to bacterial gram staining.

Conclusion

Traumatized immature permanent teeth with periapical lesions showed a significant predominance of Gram-positive facultative anaerobes. MALDI-TOF MS provided accurate identification of numerous viable endodontic microbes.

  相似文献   
7.
Clinical and Experimental Medicine - The SARS-CoV-2 virus has spread to all corners of the world. Thrombosis is the cause of organ failure and subsequent death in COVID-19. The pathophysiology of...  相似文献   
8.
PurposeHeritable ectopic mineralization disorders comprise a group of conditions with a broad range of clinical manifestations in nonskeletal connective tissues. We report the genetic findings from a large international cohort of 478 patients afflicted with ectopic mineralization.MethodsSequence variations were identified using a next-generation sequencing panel consisting of 29 genes reported in association with ectopic mineralization. The pathogenicity of select splicing and missense variants was analyzed in experimental systems in vitro and in vivo.ResultsA total of 872 variants of unknown significance as well as likely pathogenic and pathogenic variants were disclosed in 25 genes. A total of 159 distinct variants were identified in 425 patients in ABCC6, the gene responsible for pseudoxanthoma elasticum, a heritable multisystem ectopic mineralization disorder. The interpretation of variant pathogenicity relying on bioinformatic predictions did not provide a consensus. Our in vitro and in vivo functional assessment of 14 ABCC6 variants highlighted this dilemma and provided unambiguous interpretations to their pathogenicity.ConclusionThe results expand the ABCC6 variant repertoire, shed new light on the genetic heterogeneity of heritable ectopic mineralization disorders, and provide evidence that functional characterization in appropriate experimental systems is necessary to determine the pathogenicity of genetic variants.  相似文献   
9.
The EORTC QLU‐C10D is a new multi‐attribute utility instrument derived from the widely used cancer‐specific quality of life questionnaire, EORTC QLQ‐C30. It contains 10 dimensions (physical functioning, role functioning, social functioning, emotional functioning, pain, fatigue, sleep, appetite, nausea, bowel problems), each with four levels. The aim of this study was to provide U.K. general population utility weights for the QLU‐C10D. A U.K. online panel was quota‐sampled to align the sample to the general population proportions of sex and age (≥18 years). The online valuation survey included a discrete choice experiment (DCE). Each participant was asked to complete 16 choice‐pairs, each comprising two QLU‐C10D health states plus duration. DCE data were analysed using conditional logistic regression to generate utility weights. Data from 2,187 respondents who completed at least one choice set were included in the DCE analysis. The final U.K. QLU‐C10D utility weights comprised decrements for each level of each health dimension. For nine of the 10 dimensions (all except appetite), the expected monotonic pattern was observed across levels: Utility decreased as severity increased. For the final model, consistent monotonicity was achieved by merging inconsistent adjacent levels for appetite. The largest utility decrements were associated with physical functioning and pain. The worst possible health state (the worst level of each dimension) is ?0.083, which is considered slightly worse than being dead. The U.K.‐specific utility weights will enable cost–utility analysis (CUA) for the economic evaluation of new oncology therapies and technologies in the United Kingdom, where CUA is commonly used to inform resource allocation.  相似文献   
10.
For advanced and metastatic urothelial carcinomas (UCs), platinum (preferably cisplatin)‐based chemotherapy has been the standard treatment for many years. However, many patients are ineligible for cisplatin‐based chemotherapy because of poor performance status and/or other age‐related conditions. At the other end of the spectrum, patients with localized non‐muscle–invasive bladder cancer who are unresponsive to intravesical Bacillus Calmette‐Guérin (BCG) treatment often face radical cystectomy as the only option. In recent years, the application of immunotherapy in the form of immune‐checkpoint inhibitors has provided viable alternatives in the second‐line postplatinum and first‐line cisplatin‐ineligible settings. Recent and ongoing clinical trials are also assessing the safety and efficacy of immunotherapy for neoadjuvant and adjuvant uses before/after cystectomy, for BCG‐unresponsive cases, and for combination treatments that include the newer indoleamine 2,3‐dioxygenase‐1 inhibitors and/or BCG. This review summarizes recent developments in immunotherapy for UCs.  相似文献   
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