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Incidence and Management of De Novo Lower Urinary Tract Symptoms After Pelvic Organ Prolapse Repair.Current Urology Reports Sep 2017Pelvic organ prolapse (POP) is a significant problem with many options for surgical correction. Following prolapse surgery, de novo lower urinary tract symptoms (LUTS)... (Review)
Review
PURPOSE OF REVIEW
Pelvic organ prolapse (POP) is a significant problem with many options for surgical correction. Following prolapse surgery, de novo lower urinary tract symptoms (LUTS) are not uncommon. We review the current literature on de novo lower urinary tract symptoms following POP repair and discuss the role of urodynamics in the evaluation of the prolapse patient.
RECENT FINDINGS
Patients with occult stress urinary incontinence (SUI) appear to be at higher risk of developing de novo SUI after POP repair. Prolapse reduction in patients undergoing urodynamic evaluation is important. Different types of POP repair influence rates of de novo SUI. Also, prophylactic anti-incontinence procedures at time of POP repair appear to lower the incidence of de novo SUI, but at the cost of increased risk of complications and morbidity. Pre-existing overactive bladder (OAB) symptoms may either improve or persist, and de novo OAB can develop. The specific role of urodynamic study testing for POP is still being determined. Increasingly, women are seeking surgical treatment for POP. Aside from complications related to surgery in general, proper patient counseling is important regarding the risk of development of de novo voiding problems following surgery. Despite a growing body of literature looking at de novo voiding symptoms after prolapse repair, more studies are still needed.
Topics: Aged; Female; Humans; Incidence; Lower Urinary Tract Symptoms; Middle Aged; Pelvic Organ Prolapse; Postoperative Complications; Risk Factors; Urinary Bladder, Overactive; Urinary Incontinence, Stress; Urodynamics; Urologic Surgical Procedures
PubMed: 28900856
DOI: 10.1007/s11934-017-0732-5 -
Breast Cancer Research and Treatment Nov 2022This study evaluated whether patients with de novo metastatic breast cancer (MBC) have superior outcomes compared to those with recurrent MBC in a contemporary treatment...
PURPOSE
This study evaluated whether patients with de novo metastatic breast cancer (MBC) have superior outcomes compared to those with recurrent MBC in a contemporary treatment era and examined factors related to outcome differentials.
METHODS
Using an institutional database, we examined patient and tumor characteristics, treatment response, and outcome among 232 patients with de novo and 612 patients with recurrent MBC diagnosed between 2011 and 2017.
RESULTS
De novo MBC had 9-month (m) longer overall survival (OS) than recurrent MBC (36.4 vs 27.4 m, p < 0.001). Contributions to this difference included nearly twofold more HER2-positive (29.3% vs 15.2%) and significantly fewer triple-negative breast cancers (20.3% vs 32.4%, both p < 0.001) in de novo compared with recurrent MBC cohorts. Stratified by clinical subtype, progression-free survival (PFS) on first-line therapy was significantly longer in de novo MBC in all but the triple-negative subtype, 25.5 vs 11.6 m (p < 0.001) among 390 patients with hormone receptor-positive, HER2-negative, 11.4 vs 5.4 m (p = 0.002) among 142 patients with HER2-positive, and 4.0 vs 3.0 m (p = 0.121) among 162 with triple-negative MBC. In multivariable analysis, de novo status remained independently associated with improved OS (hazard ratio 0.63, 95% CI 0.49-0.80), regardless of subtype and other features.
CONCLUSION
Patients with de novo MBC have better outcomes than those with recurrent MBC. Differences in clinical subtype and response to therapy in the metastatic setting contribute to, but do not fully explain, this difference. Longer PFS to first-line therapy in de novo MBC suggests biologic differences compared to recurrent MBC, which may be intrinsic or due to acquired resistance from treatment for prior localized breast cancer in recurrent disease.
Topics: Biological Products; Breast Neoplasms; Female; Humans; Neoplasm Recurrence, Local; Prognosis; Receptor, ErbB-2
PubMed: 36008651
DOI: 10.1007/s10549-022-06700-6 -
Case Reports in Transplantation 2022Allograft membranous glomerulopathy can be a recurrent or de novo disease. Both instead have different underlying immune pathophysiology and disease pattern. While the...
Allograft membranous glomerulopathy can be a recurrent or de novo disease. Both instead have different underlying immune pathophysiology and disease pattern. While the introduction of ANTI-PLAR2 and THS7A brought new insights into the management of Immune/primary MN, the treatment of de novo MN is not clear. Relapsing de novo MN in a kidney transplant was rarely reported. Here, we present a case of relapsing de novo MN without evidence of rejection and a gratifying response to rituximab.
PubMed: 35547830
DOI: 10.1155/2022/6754520 -
PeerJ 2017transcriptome assembly of short reads is now a common step in expression analysis of organisms lacking a reference genome sequence. Several software packages are...
BACKGROUND
transcriptome assembly of short reads is now a common step in expression analysis of organisms lacking a reference genome sequence. Several software packages are available to perform this task. Even if their results are of good quality it is still possible to improve them in several ways including redundancy reduction or error correction. Trinity and Oases are two commonly used transcriptome assemblers. The contig sets they produce are of good quality. Still, their compaction (number of contigs needed to represent the transcriptome) and their quality (chimera and nucleotide error rates) can be improved.
RESULTS
We built a RNA-Seq Assembly Pipeline (DRAP) which wraps these two assemblers (Trinity and Oases) in order to improve their results regarding the above-mentioned criteria. DRAP reduces from 1.3 to 15 fold the number of resulting contigs of the assemblies depending on the read set and the assembler used. This article presents seven assembly comparisons showing in some cases drastic improvements when using DRAP. DRAP does not significantly impair assembly quality metrics such are read realignment rate or protein reconstruction counts.
CONCLUSION
Transcriptome assembly is a challenging computational task even if good solutions are already available to end-users, these solutions can still be improved while conserving the overall representation and quality of the assembly. The RNA-Seq Assembly Pipeline (DRAP) is an easy to use software package to produce compact and corrected transcript set. DRAP is free, open-source and available under GPL V3 license at http://www.sigenae.org/drap.
PubMed: 28224052
DOI: 10.7717/peerj.2988 -
Pathology Oncology Research : POR Oct 2020The clinical significances of de novo and nevus-associated melanomas are controversial. In this study, we investigated the correlations of these forms of melanomas in...
The clinical significances of de novo and nevus-associated melanomas are controversial. In this study, we investigated the correlations of these forms of melanomas in respect to their pathological and clinical features and patient outcomes. The data of 660 pathologically confirmed Turkish-Caucasian melanoma patients, whose tumors were either associated with a pre-existing melanocytic nevus or not, were analyzed retrospectively. They were treated and followed up at a single tertiary referral center. A total of 440 de novo (66.7%) and 220 nevus-associated melanomas (33.3%) were enrolled into the study. The median age of the patients was 51 years. The patients consisted of 341 men (51.7%) and 319 women (48.3%). There were significant correlations between de novo melanomas and advanced age (p = 0.003), tumor thickness greater than 2 mm (p = 0.0001), ulceration (p = 0.01) and high mitotic rate (p = 0.03). On the other hand, nevus-associated melanomas were found significantly associated with histological regression (p = 0.03) and BRAFV600E mutation (p = 0.003). Most of the nevus-associated melanomas were found on trunk and head/neck, whereas extremities were more frequently inflicted by de novo melanomas (p = 0.0001). Furthermore, none of other variables, such as sex, histopathology, lymph node involvement and presence of metastasis, showed statistically significant difference between de novo and nevus-associated melanoma patients (p > 0.05). The 5-year DFS rates were 62.4% and 72.7% for de novo melanoma and for nevus-associated melanoma patients, respectively (p = 0.1). The 5-year OS rate were 72.1% and 76.4% for de novo melanoma and nevus-associated melanoma patients, respectively (p = 0.2). In conclusion, even though de novo melanomas are more significantly correlated with aggressive histopathologic variables, such as tumor depth, ulceration and high mitotic rate, the survival rates of de novo and nevus-associated melanomas are similar.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Disease-Free Survival; Female; Humans; Male; Melanoma; Middle Aged; Nevus, Pigmented; Prognosis; Retrospective Studies; Skin Neoplasms; Young Adult
PubMed: 32572820
DOI: 10.1007/s12253-020-00858-4 -
Frontiers in Neurology 2021Duchenne and Becker muscular dystrophy (DMD/BMD) are X-linked recessively inherited neuromuscular disorders caused by deletions, duplications, or small mutations in the...
Duchenne and Becker muscular dystrophy (DMD/BMD) are X-linked recessively inherited neuromuscular disorders caused by deletions, duplications, or small mutations in the gene. With advances in prenatal diagnosis decreasing the number of affected offspring from carrier mothers, the frequency of variants could increase. Therefore, determining the differences between the carrier and variants of the gene, which are rarely explored, is important for trial planning and genetic diagnosis in the future. A total of 440 patients, 349 of whom had DMD and 91 had BMD, diagnosed in our department between 2012 and 2019, along with their respective mothers, were included in this study. Multiplex ligation-dependent probe amplification was used to detected deletions and duplications in patients and their mothers. Small mutations were detected using next-generation sequencing in the patients, followed by Sanger sequencing in the mothers. Deletions, duplications, and small mutations were identified in 204, 46, and 99 of the 349 patients with DMD and in 50, 10, and 31 of the 91 patients with BMD, respectively. deletions were more concentrated in hotspot regions than carrier deletions of DMD/BMD. No clear bias was observed in the variant distribution between carriers, duplications, and small mutations in DMD/BMD. The carrier frequency of DMD (61.6%) was lower than that of BMD (69.2%), but the difference was not statistically significant. The carrier frequency of deletions of the gene (51.2%) was significantly lower than those of duplications (75%) and small mutations (81.5%). Compared to deletions, deletions from carrier mothers had a wider distribution. Moreover, there was no significant difference between the carrier frequencies of DMD and BMD. Duplications and small mutations were more commonly inherited, while deletions were present .
PubMed: 34421809
DOI: 10.3389/fneur.2021.714677 -
Expert Opinion on Drug Discovery Aug 2019: The development of drug candidates with a defined selectivity profile and a unique molecular structure is of fundamental interest for drug discovery. In contrast to... (Review)
Review
: The development of drug candidates with a defined selectivity profile and a unique molecular structure is of fundamental interest for drug discovery. In contrast to the costly screening of large substance libraries, the targeted design of a drug by using structural information of either the biological target and/or structure-activity relationship data of active modulators offers an efficient and intellectually appealing alternative. : This review provides an overview on the different techniques of drug design (ligand-based drug design, structure-based drug design, and fragment-based drug design) and highlights successful examples of this targeted approach toward selective modulators of therapeutically relevant targets. : drug design has established itself as a very efficient method for the development of potent and selective modulators for a variety of different biological target classes. The ever-growing wealth of structural data on therapeutic targets will certainly further enhance the importance of design for the drug discovery process in the future. However, a consistent use of the terminology of drug design in the scientific literature should be sought.
Topics: Drug Design; Drug Development; Drug Discovery; Humans; Ligands; Molecular Targeted Therapy; Structure-Activity Relationship
PubMed: 31179763
DOI: 10.1080/17460441.2019.1615435 -
Drug Resistance Updates : Reviews and... Mar 2023Nucleotide de novo synthesis is essential to cell growth and survival, and its dysregulation leads to cancers and drug resistance. However, how this pathway is...
AIMS
Nucleotide de novo synthesis is essential to cell growth and survival, and its dysregulation leads to cancers and drug resistance. However, how this pathway is dysregulated in cancer has not been well clarified. This study aimed to identify the regulatory mechanisms of nucleotide de novo synthesis and drug resistance.
METHODS
By combining the ChIP-Seq data from the Cistrome Data Browser, RNA sequencing (RNA-Seq) and a luciferase-based promoter assay, we identified transcription factor FOXK2 as a regulator of nucleotide de novo synthesis. To explore the biological functions and mechanisms of FOXK2 in cancers, we conducted biochemical and cell biology assays in vitro and in vivo. Finally, we assessed the clinical significance of FOXK2 in hepatocellular carcinoma.
RESULTS
FOXK2 directly regulates the expression of nucleotide synthetic genes, promoting tumor growth and cancer cell resistance to chemotherapy. FOXK2 is SUMOylated by PIAS4, which elicits FOXK2 nuclear translocation, binding to the promoter regions and transcription of nucleotide synthetic genes. FOXK2 SUMOylation is repressed by DNA damage, and elevated FOXK2 SUMOylation promotes nucleotide de novo synthesis which causes resistance to 5-FU in hepatocellular carcinoma. Clinically, elevated expression of FOXK2 in hepatocellular carcinoma patients was associated with increased nucleotide synthetic gene expression and correlated with poor prognoses for patients.
CONCLUSION
Our findings establish FOXK2 as a novel regulator of nucleotide de novo synthesis, with potentially important implications for cancer etiology and drug resistance.
Topics: Humans; Carcinoma, Hepatocellular; Cell Proliferation; Liver Neoplasms
PubMed: 36682222
DOI: 10.1016/j.drup.2023.100926 -
Molecules (Basel, Switzerland) Dec 2022Axially chiral heterobiaryl frameworks are privileged structures in many natural products, pharmaceutically active molecules, and chiral ligands. Therefore, a variety of... (Review)
Review
Axially chiral heterobiaryl frameworks are privileged structures in many natural products, pharmaceutically active molecules, and chiral ligands. Therefore, a variety of approaches for constructing these skeletons have been developed. Among them, de novo synthesis, due to its highly convergent and superior atom economy, serves as a promising strategy to access these challenging scaffolds including C-N, C-C, and N-N chiral axes. So far, several elegant reviews on the synthesis of axially chiral heterobiaryl skeletons have been disclosed, however, atroposelective construction of the heterobiaryl subunits by de novo synthesis was rarely covered. Herein, we summarized the recent advances in the catalytic asymmetric synthesis of the axially chiral heterobiaryl scaffold via de novo synthetic strategies. The related mechanism, scope, and applications were also included.
Topics: Biological Products; Catalysis; Skeleton
PubMed: 36500610
DOI: 10.3390/molecules27238517 -
Thyroid : Official Journal of the... Oct 2020The prevalence and clinical significance of detection of anti-thyroglobulin antibodies (TgAbs) during the follow-up of patients with differentiated thyroid cancer...
The prevalence and clinical significance of detection of anti-thyroglobulin antibodies (TgAbs) during the follow-up of patients with differentiated thyroid cancer (DTC) is unknown. We utilized the National Thyroid Cancer Treatment Cooperative Study registry (1987-2012). Patients registered after 1996 ( = 3318) were analyzed. We identified 1545 subjects who had available TgAb status (TgAb cohort) between years 1996 and 2012, of whom 1325 were TgAb negative at first postoperative follow-up testing. From this initial TgAb-negative group, we excluded 513 patients: 423 patients who had less than 3 years of follow-up and/or fewer than three follow-up visits, 86 patients with persistent disease after initial treatment, and 4 patients with data entry errors. The remaining 812 patients were included for analysis, comprising the TgAb persistently negative group (defined as TgAb negative for at least 3 consecutive follow-up visits and at least 3 years of follow-up) ( = 772) and the TgAb-positive group in whom TgAbs became detectable ( = 40). We then assessed whether appearance of TgAb was associated with DTC structural recurrence by using the Kaplan-Meier method. The detection of TgAb occurred in 5% of DTC patients. Recurrence of DTC in the TgAb persistently negative group compared with the TgAb-positive group did not differ significantly (9.6% vs. 15.0%, = 0.23). Baseline characteristics, histology, history of radiation exposure, staging, and median duration of follow-up were similar between the two groups. Interestingly, in all six patients who suffered a recurrence in the TgAb-positive group, the TgAbs were negative at the time of recurrence detection and became positive at a median of 2.1 (0.7-8.7) years after the structural recurrence. Utilizing a large North American DTC registry, we found the prevalence of TgAb detection to be 5% among initially TgAb-negative patients. We did not find a statistically significant association between TgAb development and DTC structural recurrence. Larger prospective studies are required to confirm these findings and further assess the significance of TgAb detection in the follow-up of DTC.
Topics: Adult; Autoantibodies; Cell Differentiation; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; North America; Prospective Studies; Registries; Thyroglobulin; Thyroid Gland; Thyroid Neoplasms
PubMed: 32228151
DOI: 10.1089/thy.2019.0791