The Utility of Spectroscopic MRI in Stereotactic Biopsy and Radiotherapy Guidance in Newly Diagnosed Glioblastoma.

Current diagnostic and therapeutic approaches for gliomas have limitations hindering survival outcomes. We propose spectroscopic magnetic resonance imaging as an adjunct to standard MRI to bridge these gaps. Spectroscopic MRI is a volumetric MRI technique capable of identifying tumor infiltration based on its elevated choline (Cho) and decreased N-acetylaspartate (NAA). We present the clinical translatability of spectroscopic imaging with a Cho/NAA ≥ 5x threshold for delineating a biopsy target in a patient diagnosed with non-enhancing glioma. Then, we describe the relationship between the undertreated tumor detected with metabolite imaging and overall survival (OS) from a pilot study of newly diagnosed GBM patients treated with belinostat and chemoradiation. Each cohort (control and belinostat) were split into subgroups using the median difference between pre-radiotherapy Cho/NAA ≥ 2x and the treated T1-weighted contrast-enhanced (T1w-CE) volume. We used the Kaplan-Meier estimator to calculate median OS for each subgroup. The median OS was 14.4 months when the difference between Cho/NAA ≥ 2x and T1w-CE volumes was higher than the median compared with 34.3 months when this difference was lower than the median. The T1w-CE volumes were similar in both subgroups. We find that patients who had lower volumes of undertreated tumors detected via spectroscopy had better survival outcomes.

A Fully Automated Post-Surgical Brain Tumor Segmentation Model for Radiation Treatment Planning and Longitudinal Tracking.

Glioblastoma (GBM) has a poor survival rate even with aggressive surgery, concomitant radiation therapy (RT), and adjuvant chemotherapy. Standard-of-care RT involves irradiating a lower dose to the hyperintense lesion in T2-weighted fluid-attenuated inversion recovery MRI (T2w/FLAIR) and a higher dose to the enhancing tumor on contrast-enhanced, T1-weighted MRI (CE-T1w). While there have been several attempts to segment pre-surgical brain tumors, there have been minimal efforts to segment post-surgical tumors, which are complicated by a resection cavity and postoperative blood products, and tools are needed to assist physicians in generating treatment contours and assessing treated patients on follow up. This report is one of the first to train and test multiple deep learning models for the purpose of post-surgical brain tumor segmentation for RT planning and longitudinal tracking. Post-surgical FLAIR and CE-T1w MRIs, as well as their corresponding RT targets (GTV1 and GTV2, respectively) from 225 GBM patients treated with standard RT were trained on multiple deep learning models including: Unet, ResUnet, Swin-Unet, 3D Unet, and Swin-UNETR. These models were tested on an independent dataset of 30 GBM patients with the Dice metric used to evaluate segmentation accuracy. Finally, the best-performing segmentation model was integrated into our longitudinal tracking web application to assign automated structured reporting scores using change in percent cutoffs of lesion volume. The 3D Unet was our best-performing model with mean Dice scores of 0.72 for GTV1 and 0.73 for GTV2 with a standard deviation of 0.17 for both in the test dataset. We have successfully developed a lightweight post-surgical segmentation model for RT planning and longitudinal tracking.

Spectroscopic MRI-Based Biomarkers Predict Survival for Newly Diagnosed Glioblastoma in a Clinical Trial.

Despite aggressive treatment, glioblastoma has a poor prognosis due to its infiltrative nature. Spectroscopic MRI-measured brain metabolites, particularly the choline to N-acetylaspartate ratio (Cho/NAA), better characterizes the extent of tumor infiltration. In a previous pilot trial (NCT03137888), brain regions with Cho/NAA ≥ 2x normal were treated with high-dose radiation for newly diagnosed glioblastoma patients. This report is a secondary analysis of that trial where spectroscopic MRI-based biomarkers are evaluated for how they correlate with progression-free and overall survival (PFS/OS). Subgroups were created within the cohort based on pre-radiation treatment (pre-RT) median cutoff volumes of residual enhancement (2.1 cc) and metabolically abnormal volumes used for treatment (19.2 cc). We generated Kaplan-Meier PFS/OS curves and compared these curves via the log-rank test between subgroups. For the subgroups stratified by metabolic abnormality, statistically significant differences were observed for PFS (p = 0.019) and OS (p = 0.020). Stratification by residual enhancement did not lead to observable differences in the OS (p = 0.373) or PFS (p = 0.286) curves. This retrospective analysis shows that patients with lower post-surgical Cho/NAA volumes had significantly superior survival outcomes, while residual enhancement, which guides high-dose radiation in standard treatment, had little significance in PFS/OS. This suggests that the infiltrating, non-enhancing component of glioblastoma is an important factor in patient outcomes and should be treated accordingly.

Applying a Radiation Therapy Volume Analysis Pipeline to Determine the Utility of Spectroscopic MRI-Guided Adaptive Radiation Therapy for Glioblastoma.

Accurate radiation therapy (RT) targeting is crucial for glioblastoma treatment but may be challenging using clinical imaging alone due to the infiltrative nature of glioblastomas. Precise targeting by whole-brain spectroscopic MRI, which maps tumor metabolites including choline (Cho) and N-acetylaspartate (NAA), can quantify early treatment-induced molecular changes that other traditional modalities cannot measure. We developed a pipeline to determine how spectroscopic MRI changes during early RT are associated with patient outcomes to provide insight into the utility of adaptive RT planning. Data were obtained from a study (NCT03137888) where glioblastoma patients received high-dose RT guided by the pre-RT Cho/NAA twice normal (Cho/NAA ≥ 2x) volume, and received spectroscopic MRI scans pre- and mid-RT. Overlap statistics between pre- and mid-RT scans were used to quantify metabolic activity changes after two weeks of RT. Log-rank tests were used to quantify the relationship between imaging metrics and patient overall and progression-free survival (OS/PFS). Patients with lower Jaccard/Dice coefficients had longer PFS (p = 0.045 for both), and patients with lower Jaccard/Dice coefficients had higher OS trending towards significance (p = 0.060 for both). Cho/NAA ≥ 2x volumes changed significantly during early RT, putting healthy tissue at risk of irradiation, and warranting further study into using adaptive RT planning.

Spectroscopic MRI-Guided Proton Therapy in Non-Enhancing Pediatric High-Grade Glioma.

Radiation therapy (RT) is a critical part of definitive therapy for pediatric high-grade glioma (pHGG). RT is designed to treat residual tumor defined on conventional MRI (cMRI), though pHGG lesions may be ill-characterized on standard imaging. Spectroscopic MRI (sMRI) measures endogenous metabolite concentrations in the brain, and Choline (Cho)/N-acetylaspartate (NAA) ratio is a highly sensitive biomarker for metabolically active tumor. We provide a preliminary report of our study introducing a novel treatment approach of whole brain sMRI-guided proton therapy for pHGG. An observational cohort (c1 = 10 patients) receives standard of care RT; a therapeutic cohort (c2 = 15 patients) receives sMRI-guided proton RT. All patients undergo cMRI and sMRI, a high-resolution 3D whole-brain echo-planar spectroscopic imaging (EPSI) sequence (interpolated resolution of 12 µL) prior to RT and at several follow-up timepoints integrated into diagnostic scans. Treatment volumes are defined by cMRI for c1 and by cMRI and Cho/NAA ≥ 2x for c2. A longitudinal imaging database is used to quantify changes in lesion and metabolite volumes. Four subjects have been enrolled (c1 = 1/c2 = 3) with sMRI imaging follow-up of 4-18 months. Preliminary data suggest sMRI improves identification of pHGG infiltration based on abnormal metabolic activity, and using proton therapy to target sMRI-defined high-risk regions is safe and feasible.

A Novel Approach to Determining Tumor Progression Using a Three-Site Pilot Clinical Trial of Spectroscopic MRI-Guided Radiation Dose Escalation in Glioblastoma.

Glioblastoma (GBM) is a fatal disease, with poor prognosis exacerbated by difficulty in assessing tumor extent with imaging. Spectroscopic MRI (sMRI) is a non-contrast imaging technique measuring endogenous metabolite levels of the brain that can serve as biomarkers for tumor extension. We completed a three-site study to assess survival benefits of GBM patients when treated with escalated radiation dose guided by metabolic abnormalities in sMRI. Escalated radiation led to complex post-treatment imaging, requiring unique approaches to discern tumor progression from radiation-related treatment effect through our quantitative imaging platform. The purpose of this study is to determine true tumor recurrence timepoints for patients in our dose-escalation multisite study using novel methodology and to report on median progression-free survival (PFS). Follow-up imaging for all 30 trial patients were collected, lesion volumes segmented and graphed, and imaging uploaded to our platform for visual interpretation. Eighteen months post-enrollment, the median PFS was 16.6 months with a median time to follow-up of 20.3 months. With this new treatment paradigm, incidence rate of tumor recurrence one year from treatment is 30% compared to 60-70% failure under standard care. Based on the delayed tumor progression and improved survival, a randomized phase II trial is under development (EAF211).

An autopsy based descriptive study of the spectrum of pulmonary lesions encountered in fetal deaths at a tertiary care center.

BACKGROUND: : Fetal autopsy has been an indispensable tool in evaluating the cause of death. The most common cause for fetal deaths is associated with respiratory disorders accounting for around 60%. This study was undertaken to evaluate the gross and microscopic features of lungs in fetal autopsies and estimate the incidence of deaths attributable to pulmonary causes. MATERIALS AND METHODS: : All fetuses received for autopsy at our institute were included in the study with prior consent. Gross and microscopic findings along with relevant clinical data were recorded. RESULTS: A total of 426 autopsies were conducted from January 2011 to August 2016. Of those, 184 had abnormal pulmonary findings constituting 43.19%. Aspiration pneumonia was the most common finding with 67 cases (36.4%), followed by atelectasis 54 cases (29.3%), congenital cystic adenomatoid malformation in 13 cases (7.1%), lung hypoplasia 12 cases (6.5%), pulmonary hemorrhage 21 (11.4%), 15 cases (8.15%) of hyaline membrane disease, one case (0.5%) of heterotaxy, and one case of extralobar pulmonary sequestration (0.5%). Congenital malformations of lungs were seen in 27 (14.67%) cases and 38 cases (20.65%) had other associated anomalies. CONCLUSION: Pulmonary pathology is the most common finding in fetal deaths with aspiration pneumonitis being the most common avoidable cause. Accurate fetal autopsy along with clinical data are important in evaluating fetal deaths and can help in reduction of unexplained stillbirths.

A Comparative Evaluation of Surgical, Electrosurgery and Diode Laser in the Management of Maxillofacial Nevus.

PURPOSE: To compare the post-operative wound healing of patients treated for excision of the nevus/mole from maxillofacial region with surgical, electrosurgery and diode laser. MATERIALS AND METHODS: Forty-five clinically confirmed cases of benign nevus were included in the study and randomly divided into three groups according to the technique used for excision, i.e. Group A-surgical excision, Group B-diode laser and Group C-electrosurgery. Post-operative wound evaluation was done using Stony Brook scar evaluation scale on post-operative photographs taken on days 7, 21 and 90 (3 months). RESULTS: Statistically, there was no significant difference between the three techniques on post-operative day 90. Clinically, hypopigmentation was noted with diode laser and electrosurgical excision of benign nevus. CONCLUSION: Since all three techniques yielded statistically comparable results, the patients can be given a choice of technique to undergo surgery. Surgical excision being the most cost effective and nil post-operative hypopigmentation may be the treatment of choice for majority of the patients.

Expression of p16INK4A Protein in Cervical Intraepithelial Neoplasia and Invasive Carcinoma of Uterine Cervix.

INTRODUCTION: Cervical cancer still ranks as the most frequent cancer among women in India. Infection with Human Papilloma Virus (HPV) results in precancerous lesions and invasive cervical cancer. Interaction of HPV oncogenic proteins with cellular regulatory proteins leads to upregulation of p16INK4A, a cyclin dependent kinase inhibitor. Therefore, p16INK4A overexpression is a surrogate biomarker of HPV infection making it useful in evaluating HPV associated premalignant and malignant lesions of gynaecological tract. AIM: This study was conducted to evaluate the usefulness of p16INK4A as a biomarker in dysplastic and malignant alteration of cervical epithelium.Materials and Methods: A total of 57 specimens diagnosed histopathologically as cervical dysplasia or malignancy were included in this prospective study of two year duration. Immunohistochemical (IHC) study of p16INK4A expression was performed on normal cervical tissue samples, Cervical Intraepithelial Neoplasia (CIN) 1, CIN 2, CIN 3, squamous cell carcinoma, adenocarcinoma. Expression was scored by two methods. One was simple positive versus negative p16INK4A staining and the other method was a semi-quantitative IHC scoring (0 to 8 points) according to the intensity of staining and the proportion of stained cells. The collected data was entered in excel sheet and analysed using Statistical Package For Social Science (SPSS) 16.0 software and the descriptive statistics, Chi-square test. The p-value of <0.05 was considered statistically significant. RESULTS: Nuclear and/or cytoplasmic p16INK4A immunoreactivity was absent in normal cervical tissue, while immunopositivity was 25% in CIN 1, 50% in CIN 2, 75% in CIN 3, 75% and 100% in squamous cell carcinoma and adenocarcinoma respectively. All normal cervical samples had low scores (0 to 2 points), while number of cases with high scores was proportional to the degree of cervical dysplasia or invasive carcinoma. p16INK4A immunostaining with higher expression (score>5) was observed in 75% cases of carcinoma cervix. CONCLUSION: IHC expression of p16INK4A is related to degree of histological dysplasia and malignancy, suggesting its prognostic and predictive value in the management of cervical cancers.

Antioxidants: Friend or foe?

Reactive oxygen species are the intermediates that are formed during the normal metabolic process which are effectively neutralized by the antioxidant system of the body. Any imbalance in this neutralization process causes oxidative stress which has been implicated as one of the cause in diseases such as Alzheimer's disease, cardiovascular disorders, cancer etc. Research has enabled the use of antioxidants as therapeutic agents in the treatment of various diseases. Literature also puts forth the negative effects of using antioxidants in the treatment of diseases. This review is a compilation of both the beneficial and detrimental effects of use of antioxidants in the treatment of diseases such as cancer, cardiovascular diseases, diabetes and oral diseases.

Effect of aromatic ring fluorination on CHπ interactions: microwave spectrum and structure of the 1,2-difluorobenzeneacetylene dimer.

Rotational spectra for the normal isotopic species and for six additional isotopologues of the 1,2-difluorobenzeneacetylene (C6H4F2HCCH) weakly bound dimer have been assigned in the 6-18 GHz region using chirped-pulse Fourier-transform microwave spectroscopy. This is the third complex in a series of fluorinated benzeneacetylene dimers. In 1,2-difluorobenzeneHCCH, the Hπ distance (2.725(28) Å) is longer by about 0.23 Å, and the estimated binding energy (EB = 2.3(6) kJ mol(-1)) is weaker by about 1.8 kJ mol(-1), than in the previously studied fluorobenzeneHCCH complex. In addition, in 1,2-difluorobenzeneacetylene, HCCH tips ∼46(3)° away from perpendicular to the aromatic ring, with the H nearest the ring moving away from the fluorine atoms along the C2 axis of the monomer, while in the fluorobenzene and benzene complexes HCCH is perpendicular (benzeneHCCH) or nearly perpendicular (fluorobenzeneHCCH, ∼7° tilt) to the ring plane. Results from ab initio and DFT calculations will be compared to an experimental structure determined from rotational constants for the DCCD and five unique (13)C substituted isotopologues.

The baffling human body and the boundless nanomaterial boon-a trap for cancer crab.

Life is a balance of infinite physiochemical balanced harmonies and the basic unit cell is responsible in maintaining it. Cardiovascular diseases and Cancer are the prime causes of death worldwide. Cancerous cells break the harmonious balance and result in uncontrolled growth and spread. Emerging among the existing modalities for management of cancer, as a ray of hope is Nanotechnology based treatment. Dendrimers, Quantum dots and nanobubbles contribute significantly as part of nano based diagnosis and treatment in the management of cancer. Dendrimers are nanoparticles which employ the principle of Trojan horse strategy in that encapsulation and conjugation of anti cancer agents helps in targeting the cancerous cells specifically without affecting the adjacent healthy cells. Quantum dots are cadmium based nanoparticles which when exposed to UV light glow and help in destroying the cancerous cells in the incipient stage. Nanobubbles are generated with short pulses of laser, which helps in identifying the individual cancerous cells and explodes them. Apart from them other technologies such as liposomes, fullerenes, carbon nanotubes, nanoshells, paramagnetic nanoparticles, nanoburrs, respirocytes, microbiovores, nanopores, smart coating and nano bandaid contribute a great lot as boundless nanomaterial boon for the management of cancer, cardiovascular problems and overall systemic health.

4-Fluoro-N-(4-hy-droxy-benzyl-idene)aniline.

In the title compound, C13H10FNO, the benzene ring planes are inclined at an angle of 50.52 (8)°. A characteristic of aromatic Schiff bases with N-aryl substituents is that the terminal phenyl rings are twisted relative to the plane of the HC=N link between them. In this case, the HC=N unit makes dihedral angles of 10.6 (2) and 40.5 (2)° with the hy-droxy-benzene and fluro-benzene rings, respectively. In the crystal, O-H⋯N and C-H⋯F hydrogen bonds lead to the formation of chains along the c- and b-axis directions, respectively. C-H⋯π contacts link mol-ecules along a and these contacts combine to generate a three-dimensional network with mol-ecules stacked along the b-axis direction.

Achievements and prospects of genomics-assisted breeding in three legume crops of the semi-arid tropics.

Advances in next-generation sequencing and genotyping technologies have enabled generation of large-scale genomic resources such as molecular markers, transcript reads and BAC-end sequences (BESs) in chickpea, pigeonpea and groundnut, three major legume crops of the semi-arid tropics. Comprehensive transcriptome assemblies and genome sequences have either been developed or underway in these crops. Based on these resources, dense genetic maps, QTL maps as well as physical maps for these legume species have also been developed. As a result, these crops have graduated from 'orphan' or 'less-studied' crops to 'genomic resources rich' crops. This article summarizes the above-mentioned advances in genomics and genomics-assisted breeding applications in the form of marker-assisted selection (MAS) for hybrid purity assessment in pigeonpea; marker-assisted backcrossing (MABC) for introgressing QTL region for drought-tolerance related traits, Fusarium wilt (FW) resistance and Ascochyta blight (AB) resistance in chickpea; late leaf spot (LLS), leaf rust and nematode resistance in groundnut. We critically present the case of use of other modern breeding approaches like marker-assisted recurrent selection (MARS) and genomic selection (GS) to utilize the full potential of genomics-assisted breeding for developing superior cultivars with enhanced tolerance to various environmental stresses. In addition, this article recommends the use of advanced-backcross (AB-backcross) breeding and development of specialized populations such as multi-parents advanced generation intercross (MAGIC) for creating new variations that will help in developing superior lines with broadened genetic base. In summary, we propose the use of integrated genomics and breeding approach in these legume crops to enhance crop productivity in marginal environments ensuring food security in developing countries.

3-Benzyl-5-methyl-1,2-benzoxazole 2-oxide.

In the title compound, C(15)H(13)NO(2), the isoxazole unit and the attached benzene ring are almost coplanar, making a dihedral angle of 1.42 (8)°. The benzyl ring is inclined to the isoxazole ring by 74.19 (8)° and is in a +sc conformation with respect to the benzisoxazole unit. In the crystal, C-H⋯O hydrogen bonds link the mol-ecules, forming zigzag chains propagating along the b axis. There are also π-π inter-actions present involving the isoxazole and benzyl rings [centroid-centroid distance = 3.5209 (10) Å], and C-H⋯π inter-actions involving the benzene ring of the benzoisoxazole unit and the methyl-ene bridging group.

Development and characterization of microsatellite markers (SSR) in Sesamum (Sesamum indicum L.) species.

Microsatellites, also known as simple sequence repeats (SSRs), are the class of repetitive DNA sequences present throughout the genome of many plant and animal species. Recent advances in molecular genetics had been the introduction of microsatellite markers to investigate the genetic structuring of natural plant populations. We have employed an enrichment strategy for microsatellite isolation by using multi-enzymes digestion, microsatellite oligoprobes, and streptavidin magnetic beads in Sesamum (Sesamum indicum L.). More than 200 SSR motifs were detected (SSR motifs ≥2 repeat units or 6 bp); 80 % of the clones contained SSR motifs. When regarding SSRs with four or more repeat units and a minimum length of 10 bp, 132 of them showed repeats. Eighteen SSR markers were initially characterized for optimum annealing temperature using a gradient PCR technique. Among the 18 SSR markers characterized, five were found to be polymorphic and used to analyze 60 Sesamum germplasm accessions. The maximum number of alleles detected was four with a single primer and the least number of two alleles with three primers with an average PIC value of 0.77. SSRs are a valuable tool for estimating genetic diversity and analyzing the evolutionary and historical development of cultivars at the genomic level in sesame breeding programs.

4-(4-Meth-oxy-pheneth-yl)-3,5-diphenyl-4H-1,2,4-triazole.

In the title compound, C(23)H(21)N(3)O, the dihedral angles formed by the mean plane of the triazole ring [maximum deviation = 0.007 (1) Å] and the three phenyl rings are 51.13 (8), 52.84 (8) and 47.04 (8)°. In the crystal, mol-ecules are linked by weak C-H⋯N inter-actions, forming infinite chains propagating along the b-axis direction.

Foveal neovascularisation in diabetic retinopathy: case report and review of literature.

To report a rare case of unilateral foveal neovascularisation in an asymptomatic patient with 15-year history of insulin-dependent diabetes mellitus and bilateral proliferative diabetic retinopathy and diabetic macular edema. Fundus fluorescein angiography and optical coherence tomography scan confirmed the presence of foveal neovascularisation. There was complete regression of the foveal neovascularisation after pan retinal laser photocoagulation. We review the literature on foveal neovascularisation in diabetic retinopathy and propose a possible pathogenic mechanism for development of foveal neovascularisation in diabetic retinopathy and the reason for the response to pan retinal laser photocoagulation.

Gender role orientation and anxiety symptoms among African american adolescents.

The present study evaluated gender role theory as an explanation for the observed gender differences in anxiety symptoms among adolescents. Specifically, the relation between gender, gender role orientation (i.e., masculinity and femininity), self-esteem, and anxiety symptoms was examined in a community sample of 114 African Americans aged 14 to 19 (mean age 15.77; 57 girls). Results revealed that masculinity was negatively associated with anxiety symptoms whereas femininity was positively associated with anxiety symptoms. Gender role orientation accounted for unique variance in anxiety scores above biological gender and self-esteem, and self-esteem moderated the relation between femininity (but not masculinity) and overall anxiety symptoms. Consistent with research on children and Caucasians, findings supported gender role theory as a partial explanation for the observed gender disparity in anxiety symptoms among African American adolescents.

Immunolocalization and functional role of Sclerotium rolfsii lectin in development of fungus by interaction with its endogenous receptor.

Many fungi are known to secrete lectins, but their functional roles are not clearly understood. Sclerotium rolfsii, a soilborne plant pathogenic fungus capable of forming fruiting bodies called sclerotial bodies, secrete a cell wall-associated Thomsen-Friedenreich antigen-specific lectin. To understand the functional role of this lectin, we examined its occurrence and expression during development of the fungus. Furthermore, putative endogenous receptors of the lectin were examined to substantiate the functional role of the lectin. Immunolocalization studies using FITC-labeled lectin antibodies revealed discrete distribution of lectin sites at the branching points of the developing mycelia and uniformly occurring lectin sites on the mature sclerotial bodies. During development of the fungus the lectin is expressed in small amounts on the vegetative mycelia and reaching very high levels in mature sclerotial bodies with a sudden spurt in secretion at the maturation stage. Capping of the lectin sites on the sclerotial bodies by lectin antibodies or haptens inhibit strongly the germination of these bodies, indicating functional significance of the lectin. At the maturation stage the lectin interacts with the cell wall-associated putative endogenous receptor leading to the aggregation of mycelium to form sclerotial bodies. The lectin-receptor complex probably acts as signaling molecule in the germination process of sclerotial bodies. Using biotinylated lectin, the receptors were identified by determining the specific lectin binding to lipid components, extracted from sclerotial bodies, and separated on thin-layer chromatograms. Preliminary characterization studies indicated that the receptors are glycosphingolipids and resemble inositolphosphoceramides. These findings together demonstrate the importance of lectin-receptor interactions to explain hitherto speculated functional role of the lectins and also the glycosphingolipids of fungi.