Purpose
To explore the association of clinicopathologic and molecular factors with the occurrence of positive margins after first surgery in breast cancer.
Methods
The clinical and RNA-Seq data for ...951 (75 positive and 876 negative margins) primary breast cancer patients from The Cancer Genome Atlas (TCGA) were used. The role of each clinicopathologic factor for margin prediction and also their impact on survival were evaluated using logistic regression, Fisher’s exact test, and Cox proportional hazards regression models. In addition, differential expression analysis on a matched dataset (71 positive and 71 negative margins) was performed using Deseq2 and LASSO regression.
Results
Association studies showed that higher stage, larger tumor size (T), positive lymph nodes (N), and presence of distant metastasis (M) significantly contributed (
p
≤ 0.05) to positive surgical margins. In case of surgery, lumpectomy was significantly associated with positive margin compared to mastectomy. Moreover, PAM50 Luminal A subtype had higher chance of positive margin resection compared to Basal-like subtype. Survival models demonstrated that positive margin status along with higher stage, higher TNM, and negative hormone receptor status was significant for disease progression. We also found that margin status might be a surrogate of tumor stage. In addition, 29 genes that could be potential positive margin predictors and 8 pathways were identified from molecular data analysis.
Conclusion
The occurrence of positive margins after surgery was associated with various clinical factors, similar to the findings reported in earlier studies. In addition, we found that the PAM50 intrinsic subtype Luminal A has more chance of obtaining positive margins compared to Basal type. As the first effort to pursue molecular understanding of the margin status, a gene panel of 29 genes including 17 protein-coding genes was also identified for potential prediction of the margin status which needs to be validated using a larger sample set.
Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of cancer death among women globally. Despite advances, there is considerable variation in clinical outcomes for ...patients with non-luminal A tumors, classified as difficult-to-treat breast cancers (DTBC). This study aims to delineate the proteogenomic landscape of DTBC tumors compared to luminal A (LumA) tumors.
We retrospectively collected a total of 117 untreated primary breast tumor specimens, focusing on DTBC subtypes. Breast tumors were processed by laser microdissection (LMD) to enrich tumor cells. DNA, RNA, and protein were simultaneously extracted from each tumor preparation, followed by whole genome sequencing, paired-end RNA sequencing, global proteomics and phosphoproteomics. Differential feature analysis, pathway analysis and survival analysis were performed to better understand DTBC and investigate biomarkers.
We observed distinct variations in gene mutations, structural variations, and chromosomal alterations between DTBC and LumA breast tumors. DTBC tumors predominantly had more mutations in TP53, PLXNB3, Zinc finger genes, and fewer mutations in SDC2, CDH1, PIK3CA, SVIL, and PTEN. Notably, Cytoband 1q21, which contains numerous cell proliferation-related genes, was significantly amplified in the DTBC tumors. LMD successfully minimized stromal components and increased RNA-protein concordance, as evidenced by stromal score comparisons and proteomic analysis. Distinct DTBC and LumA-enriched clusters were observed by proteomic and phosphoproteomic clustering analysis, some with survival differences. Phosphoproteomics identified two distinct phosphoproteomic profiles for high relapse-risk and low relapse-risk basal-like tumors, involving several genes known to be associated with breast cancer oncogenesis and progression, including KIAA1522, DCK, FOXO3, MYO9B, ARID1A, EPRS, ZC3HAV1, and RBM14. Lastly, an integrated pathway analysis of multi-omics data highlighted a robust enrichment of proliferation pathways in DTBC tumors.
This study provides an integrated proteogenomic characterization of DTBC vs LumA with tumor cells enriched through laser microdissection. We identified many common features of DTBC tumors and the phosphopeptides that could serve as potential biomarkers for high/low relapse-risk basal-like BC and possibly guide treatment selections.
Purpose
Molecular similarities have been reported between basal-like breast cancer (BLBC) and high-grade serous ovarian cancer (HGSOC). To date, there have been no prognostic biomarkers that can ...provide risk stratification and inform treatment decisions for both BLBC and HGSOC. In this study, we developed a molecular signature for risk stratification in BLBC and further validated this signature in HGSOC.
Methods
RNA-seq data was downloaded from The Cancer Genome Atlas (TCGA) project for 190 BLBC and 314 HGSOC patients. Analyses of differentially expressed genes between recurrent vs. non-recurrent cases were performed using different bioinformatics methods. Gene Signature was established using weighted linear combination of gene expression levels. Their prognostic performance was evaluated using survival analysis based on progression-free interval (PFI) and disease-free interval (DFI).
Results
63 genes were differentially expressed between 18 recurrent and 40 non-recurrent BLBC patients by two different methods. The recurrence index (RI) calculated from this 63-gene signature significantly stratified BLBC patients into two risk groups with 38 and 152 patients in the low-risk (RI-Low) and high-risk (RI-High) groups, respectively (
p
= 0.0004 and 0.0023 for PFI and DFI, respectively). Similar performance was obtained in the HGSOC cohort (
p
= 0.0131 and 0.004 for PFI and DFI, respectively). Multivariate Cox regression adjusting for age, grade, and stage showed that the 63-gene signature remained statistically significant in stratifying HGSOC patients (
p
= 0.0005).
Conclusion
A gene signature was identified to predict recurrence in BLBC and HGSOC patients. With further validation, this signature may provide an additional prognostic tool for clinicians to better manage BLBC, many of which are triple-negative and HGSOC patients who are currently difficult to treat.
Purpose
Universal eye screening of neonates is currently not standard of care. Early detection of abnormalities could offer prompt management and a reduction in visual morbidity. We report a pilot ...study using wide‐field digital imaging to screen all infants at birth to explore its feasibility as a tool for universal screening.
Methods
Consecutively enrolled 1021 term infants in a public hospital were imaged within 72 hr of birth using the Retcam shuttle (Clarity MSI, USA). Anterior and dilated posterior segment images were obtained. Infants with abnormal images were examined clinically, and medical or surgical treatment was given when needed, at no cost to the family.
Results
Of the 1021 healthy full‐term newborns, 48 babies had abnormal findings (4.7%). Retinal haemorrhages were the most common (52.1%) abnormality of which 24% were macular. A ‘ridge’ resembling retinopathy of prematurity in both eyes constituted 18.8% of all abnormalities. Nine infants (18.8% of abnormalities and 0.9% overall) had conditions meriting medical or surgical intervention and would have been missed otherwise. Seven of these nine babies (0.7%) needed medical attention with a systemic work‐up for conditions such as posterior uveitis with linear perivasculitis, salt and pepper retinopathy or posterior synechia. Two of nine babies (0.2%) required surgical intervention for unilateral cataract and retinoblastoma.
Conclusion
Universal eye screening of all neonates using wide‐field digital imaging is possible and safe. Extrapolating our results to the national scenario, we estimate that 226 950 infants requiring treatment would go undiagnosed annually. Universal infant eye imaging strategies must receive serious national consideration.
Abstract
Purpose
Universal eye screening of neonates is currently not standard of care. Early detection of abnormalities could offer prompt management and a reduction in visual morbidity. We report a ...pilot study using wide‐field digital imaging to screen all infants at birth to explore its feasibility as a tool for universal screening.
Methods
Consecutively enrolled 1021 term infants in a public hospital were imaged within 72 hr of birth using the Retcam shuttle (Clarity
MSI
,
USA
). Anterior and dilated posterior segment images were obtained. Infants with abnormal images were examined clinically, and medical or surgical treatment was given when needed, at no cost to the family.
Results
Of the 1021 healthy full‐term newborns, 48 babies had abnormal findings (4.7%). Retinal haemorrhages were the most common (52.1%) abnormality of which 24% were macular. A ‘ridge’ resembling retinopathy of prematurity in both eyes constituted 18.8% of all abnormalities. Nine infants (18.8% of abnormalities and 0.9% overall) had conditions meriting medical or surgical intervention and would have been missed otherwise. Seven of these nine babies (0.7%) needed medical attention with a systemic work‐up for conditions such as posterior uveitis with linear perivasculitis, salt and pepper retinopathy or posterior synechia. Two of nine babies (0.2%) required surgical intervention for unilateral cataract and retinoblastoma.
Conclusion
Universal eye screening of all neonates using wide‐field digital imaging is possible and safe. Extrapolating our results to the national scenario, we estimate that 226 950 infants requiring treatment would go undiagnosed annually. Universal infant eye imaging strategies must receive serious national consideration.
•Ours is the first epidemiological report from India on risk factors of Autism Spectrum Disorder.•We conducted a large population based case-cohort study across India.•Out of 25 factors evaluated, ...advanced maternal age, fetal distress, gestational respiratory infections, labor complications, pre-term birth, neonatal jaundice, delayed birth cry and birth asphyxia were significantly associated with the risk of ASD.•These conditions can independently and collectively exert their effect as risk factors, adding important country specific information to existing literature.
Incidence of Autism Spectrum Disorder (ASD) is increasing across the globe and no data is available from India regarding the risk factors of ASD. In this regard a questionnaire based epidemiological assessment was carried out on prenatal, perinatal and neonatal risk factors of ASD across 8 cities in India. A retrospective cohort of 942 children was enrolled for the study. 471 children with ASD, under age of 10, were analyzed for pre-, peri-, and neonatal factors and were compared with the observations from equal number of controls. The quality control of the questionnaire and data collection was done thoroughly and the observations were computed statistically. A total of 25 factors were evaluated by unadjusted and adjusted analysis in this study. Among the prenatal factors considered, advanced maternal age, fetal distress and gestational respiratory infections were found to be associated with ASD and had an odds ratio of 1.8. Evaluation of perinatal and neonatal risk factors showed labor complications, pre-term birth, neonatal jaundice, delayed birth cry and birth asphyxia to be associated with ASD with an odds ratio greater than 1.5. This important study, first of its kind in Indian population gives a firsthand account of the relation of pre-, peri- and neonatal risk factors on ASD from an ethnically and socially diverse country like India, the impact of which was unknown earlier. This advocates additional focused investigations on physiological and genetic changes contributed by these risk factor inducing environments.
Background
Unlike chemical techniques, the combination of metal oxide nanoparticles utilizing plant concentrate is a promising choice. The purpose of this work was to synthesize magnesium oxide ...nanoparticles (MgO-NPs) utilizing heartwood aqueous extract of
Pterocarpus marsupium
. The heartwood extract of
Pterocarpus marsupium
is rich in polyphenolic compounds and flavonoids that can be used as a green source for large-scale, simple, and eco-friendly production of MgO-NPs. The phytoassisted synthesis of MgO is characterized by UV-Visible spectroscopy, X-ray diffraction (XRD), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) with EDS (energy dispersive X-ray spectroscopy), and transmission electron microscopy (TEM).
Results
The formation of MgO-NPs is confirmed by a visual color change from colorless to dark brown and they displayed a wavelength of 310 nm in UV-Spectrophotometry analysis. The crystalline nature of the obtained biosynthesized nanoparticles are revealed by X-ray diffraction analysis. SEM results revealed the synthesized magnesium oxide nanoparticles formed by this cost-effective method are spherically shaped with an average size of < 20 nm. The presence of magnesium and oxygen were confirmed by the EDS data. TEM analysis proved the spherical shape of the nanoparticles with average particle size of 13.28 nm and SAED analysis confirms the crystalline nature of MgO-NPs. FT-IR investigation confirms the existence of the active compounds required to stabilize the magnesium oxide nanoparticles with hydroxyl and carboxyl and phenolic groups that act as reducing, stabilizing, and capping agent. All the nanoparticles vary in particle sizes between 15 and 25 nm and obtained a polydispersity index value of 0.248. The zeta-potential was measured and found to be − 2.9 mV. Further, MgO-NPs were tested for antibacterial action against
Staphylococcus aureus
(Gram-positive bacteria) and
Escherichia coli
(Gram-negative bacteria) by minimum inhibitory concentration technique were found to be potent against both the bacteria. The blended nanoparticles showed good antioxidant activity examined by the DPPH radical scavenging method, showed good anti-diabetic activity determined by alpha-amylase inhibitory activity, and displayed strong anti-inflammatory activity evaluated by the albumin denaturation method.
Conclusions
The investigation reports the eco-friendly, cost-effective method for synthesizing magnesium oxide nanoparticles from
Pterocarpus marsupium
Rox.b heartwood extract with biomedical applications.
Graphical abstract
Objective This study aimed to investigate the knowledge, attitude, and practices (KAP) of intentional replantation among postgraduate students and endodontists in India, the United States of America, ...and the United Kingdom. Materials and methods The sample size was estimated using G*Power. Based on the pilot study done before with 60 participants, a sample size of 928 was obtained. The survey consisted of 22 questions, which were finalized after content validation by two endodontic experts. It was circulated through multiple online social platforms such as Instagram, Facebook, WhatsApp, and other online dental communities/channels. The respondents were questioned about the case selection, extraction methods, antibiotic therapy, patient acceptance level, operator preference, prognostic indicator, and various other steps in the intentional replantation treatment modality. The data for this KAP survey were organized in an Excel sheet, and statistical analysis was done using the Chi-squared test. Analysis of descriptive and inferential statistics was conducted using SPSS version 20.0 (IBM Inc., Armonk, New York). A p-value of <0.05 was considered significant. Results A strong statistical difference was found in the KAP of the practitioners in different countries. The vast majority (72.7%) considered intentional replantation as an adjunct treatment modality rather than a last resort. A total of 76.5% of the respondents preferred replantation of the tooth into the socket within 15 minutes, and 86.4% of the participants regarded replantation as the most cost-effective treatment modality. Ultrasonics (76.8%) was most commonly chosen for retrograde preparation, and Biodentine (60.1%; Septodont, Saint-Maur-des-Fossés, France) as root-end filling material. Conclusion It can be concluded that a broad majority of practitioners in different countries view intentional replantation as an adjunct treatment modality rather than a last resort. Thus, intentional replantation seems to be a promising option for preserving the natural dentition of teeth with high survival rates and better outcomes.
A Decade of Muricatacin Synthesis and Beyond Fernandes, Rodney A.; Gangani, Ashvin J.; Kumari, Anupama ...
European journal of organic chemistry,
November 30, 2020, Letnik:
2020, Številka:
44
Journal Article
Recenzirano
In this review, we have ed the various syntheses of both enantiomers of muricatacin (a member of a bigger class of acetogenins, ACGs), over the last decade (2010–2020). Developments in the synthesis ...of various epimers, homologues, oxa‐analogues, δ‐lactones, and the furofuranone analogues are also enfolded in this review. Most of the synthesis involve chiral pool and catalytic enantioselective approaches, while a few are hinged on the use of chiral auxiliary and resolution methods. Muricatacin with orthogonally differentiated two oxy‐functions also serve as a start point in the synthesis of higher molecules of the acetogenin family, for example, cis‐solamins, and these have also been covered herein.
Various syntheses of both the muricatacin enantiomers and analogues adopting different strategies in the last decade are described in this review. Additionaly, the strategic use of muricatacin as starting point in synthesis of reticulatacin, cis‐solamins and giganin is covered.
Abstract
Introduction
Refinements in the modern computed tomography (CT) imaging techniques have led to anatomical variations in the fissures of lung being diagnosed more frequently. So far, ...majority of the studies conducted are cadaveric. There is paucity of studies in this aspect based on chest CT images. Hence, we undertook this study to find the anatomical variations in the fissures. Prior detection of anatomical abnormalities is important to reduce postoperative complications in lung resection surgeries.
Materials and Methods
This was a cross-sectional study conducted over a period of 2 years. Data were collected from the patients who underwent CT scan thorax. Patients in whom normal anatomy of lung was distorted and cases where both lungs were not visualized completely were excluded from the study. All the CT images were reviewed by a single radiologist. The presence or absence of the normal and accessory pulmonary fissures, as well as the continuity of each fissure, was recorded by the radiologist. Data were compiled and analyzed.
Results
The study population consisted of 394 (70.4%) males and 166 (29.6%) females, totaling 560 cases. Fissural variations were detected in 22.9% (
n
= 128). Also, 17.5% (
n
= 98) fissural variations were seen in males and 5.4% (
n
= 30) fissural variations were seen in females. Further, 54.7% (
n
= 70) of variations were detected in the right lung and 45.3% (
n
= 58) in the left lung. The most common fissural variation noted was right incomplete oblique fissure with a frequency of 8.4% cases (
n
= 47). The most common accessory fissure detected was inferior accessory fissure. Total 22 cases were detected in both the lungs, 17 cases in male and 5 in female.
Conclusion
Anatomical variations in fissures were found to be more in the right lung than the left lung. Accessory fissures were detected in higher incidence on the right side.
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