The prognostic impact of tumor deposits in colorectal cancer: More than just N1c.

BACKGROUND: The identification of tumor deposits (TD) currently plays a limited role in staging for colorectal cancer (CRC) aside from N1c lymph node designation. The objective of this study was to determine the prognostic impact, beyond American Joint Committee on Cancer N1c designation, of TDs among patients with primary CRC. METHODS: Patients who had resected stage I-III primary CRC diagnosed between 2010 and 2019 were identified from the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Cancer-specific survival (CSS) stratified by TD status and lymph node (N) status was calculated using the Kaplan-Meier method and multivariable Cox proportional hazards regression analyses. RESULTS: In total, 147,783 patients with primary CRC were identified. TDs were present in 15,444 patients (10.5%). The presence of TDs was significantly associated with adverse tumor characteristics, including advanced pathologic stage, nodal status, and metastasis status. The presence of TDs was associated with worse CSS (hazard ratio [HR], 3.12; 95% confidence interval [CI], 3.02-3.22), as it was for each given N category (e.g., N2a and TD-negative [HR, 2.50; 95% CI, 2.37-2.64] vs. N2a and TD-positive [HR, 3.75; 95% CI, 3.49-4.03]). The presence of multiple TDs was also associated with decreased CSS for each given N category compared with a single TD (e.g. N2a with one TD [HR, 3.09; 95% CI, 2.65-3.61] vs. N2a with two or more TDs [HR, 4.32; 95% CI, 3.87-4.82]). CONCLUSIONS: TDs were identified as an independent predictor of a worse outcome in patients with CRC. The presence of TDs confers distinctly different CSS and provides important prognostic information among patients with CRC and warrants further investigation as a unique variable in future iterations of CRC staging.

Para-aortic Lymph Node Dissection for Colorectal Cancer: Predicting Pathologic Lymph Node Positivity and Optimizing Outcomes.

INTRODUCTION: In colorectal cancer, the presence of para-aortic lymph nodes (PALN) indicates extraregional disease. Appropriately selecting patients for whom PALN dissection will provide oncologic benefit remains challenging. This study identified factors to predict survival among patients undergoing PALN dissection for colorectal cancer. METHODS: An institutional database was queried for patients who underwent curative-intent resection of clinically positive PALN for colorectal cancer between 2007 and 2020. Preoperative radiologic images were reviewed, and patients who did and did not have positive PALN on final pathology were compared. Survival analysis was performed to evaluate the impact of pathologically positive PALN on recurrence-free (RFS) and overall survival (OS). RESULTS: Of 74 patients who underwent PALN dissection, 51 had PALN metastasis at the time of primary tumor diagnosis, whereas 23 had metachronous PALN disease. Preoperative chemotherapy ± radiotherapy was given in 60 cases (81.1%), and 28 (37.8%) had pathologically positive PALN. Independent factors associated with positive PALN pathology included metachronous PALN disease and pretreatment and posttreatment radiographically abnormal PALN. On multivariable analysis, pathologically positive PALN was significantly associated with decreased RFS (hazard ratio 3.90) and OS (HR 4.49). Among patients with pathologically positive PALN, well/moderately differentiated histology was associated with better OS, and metachronous disease trended toward an association with better OS. CONCLUSIONS: Pathologically positive PALN are associated with poorer RFS and OS after PALN dissection for colorectal cancer. Clinicopathologic factors may predict pathologic PALN positivity. Curative-intent surgery may provide benefit, especially in patients with well-to-moderately differentiated primary tumors and possibly metachronous PALN disease.

Single-cell transcriptomics is revolutionizing the improvement of plant biotechnology research: recent advances and future opportunities.

Single-cell approaches are a promising way to obtain high-resolution transcriptomics data and have the potential to revolutionize the study of plant growth and development. Recent years have seen the advent of unprecedented technological advances in the field of plant biology to study the transcriptional information of individual cells by single-cell RNA sequencing (scRNA-seq). This review focuses on the modern advancements of single-cell transcriptomics in plants over the past few years. In addition, it also offers a new insight of how these emerging methods will expedite advance research in plant biotechnology in the near future. Lastly, the various technological hurdles and inherent limitations of single-cell technology that need to be conquered to develop such outstanding possible knowledge gain is critically analyzed and discussed.

MRI for Rectal Cancer: Updates and Controversies-AJR Expert Panel Narrative Review.

Rectal MRI is a critical tool in the care of patients with rectal cancer, having established roles for primary staging, restaging, and surveillance. The comprehensive diagnostic and prognostic information provided by MRI helps to optimize treatment decision-making. However, challenges persist in the standardization and interpretation of rectal MRI, particularly in the context of rapidly evolving treatment paradigms, including growing acceptance of nonoperative management. In this AJR Expert Panel Narrative Review, we address recent advances and key areas of contention relating to the use of MRI for rectal cancer. Our objectives include: to discuss concepts regarding anatomic localization of rectal tumors; review the evolving rectal cancer treatment paradigm and implications for MRI assessment; discuss updates and controversies regarding rectal MRI for locoregional staging, restaging, and surveillance; review current rectal MRI acquisition protocols; and discuss challenges in homogenizing and optimizing acquisition parameters.

Anatomic Basis of Rectal Cancer Staging: Clarifying Controversies and Misconceptions.

Rectal MRI provides a detailed depiction of pelvic anatomy; specifically, the relationship of the tumor to key anatomic structures, including the mesorectal fascia, anterior peritoneal reflection, and sphincter complex. However, anatomic inconsistencies, pitfalls, and confusion exist, which can have a strong impact on interpretation and treatment. These areas of confusion include the definition of the rectum itself, specifically differentiation of the rectum from the anal canal and the sigmoid colon, and delineation of the high versus low rectum. Other areas of confusion include the relative locations of the mesorectal fascia and peritoneum and their significance in staging and treatment, the difference between the mesorectal fascia and circumferential resection margin, involvement of the sphincter complex, and evaluation of lateral pelvic lymph nodes. The impact of these anatomic inconsistencies and sources of confusion is significant, given the importance of MRI in depicting the anatomic relationship of the tumor to critical pelvic structures, to triage surgical resection and neoadjuvant chemoradiotherapy with the goal of minimizing local recurrence. Evolving treatment paradigms also place MRI central in management of rectal cancer. ©RSNA, 2024.

Perioperative and oncological outcomes following robotic en bloc multivisceral resection for colorectal cancer.

AIM: As multidisciplinary treatment strategies for colorectal cancer have improved, aggressive surgical resection has become commonplace. Multivisceral and extended resections offer curative-intent resection with significant survival benefit. However, limited data exist regarding the feasibility and oncological efficacy of performing extended resection via a minimally invasive approach. The aim of this study was to determine the perioperative and long-term outcomes following robotic extended resection for colorectal cancer. METHOD: We describe the population of patients undergoing robotic multivisceral resection for colorectal cancer at our single institution. We evaluated perioperative details and investigated short- and long-term outcomes, using the Kaplan-Meier method to analyse overall and recurrence-free survival. RESULTS: Among the 86 patients most tumours were T3 (47%) or T4 (47%) lesions in the rectum (78%). Most resections involved the anterior compartment (72%): bladder (n = 13), seminal vesicle/vas deferens (n = 27), ureter (n = 6), prostate (n = 15) and uterus/vagina/adnexa (n = 27). Three cases required conversion to open surgery; 10 patients had grade 3 complications. The median hospital stay was 4 days. Resections were R0 (>1 mm) in 78 and R1 (0 to ≤1 mm) in 8, with none being R2. The average nodal yield was 26 and 48 (55.8%) were pN0. Three-year overall survival was 88% and median progression-free survival was 19.4 months. Local recurrence was 6.1% and distant recurrence was 26.1% at 3 years. CONCLUSION: Performance of multivisceral and extended resection on the robotic platform allows patients the benefit of minimally invasive surgery while achieving oncologically sound resection of colorectal cancer.

Restaging MRI of Rectal Adenocarcinoma after Neoadjuvant Chemoradiotherapy: Imaging Findings and Potential Pitfalls.

Rectal adenocarcinoma constitutes about one-third of all colorectal adenocarcinoma cases. Rectal MRI has become mandatory for evaluation of patients newly diagnosed with rectal cancer because it can help accurately stage the disease, impact the choice to give neoadjuvant therapy or proceed with up-front surgery, and even direct surgical dissection planes. Better understanding of neoadjuvant chemoradiotherapy effects on rectal tumors and recognition that up to 30% of patients can have a pathologic complete response have opened the door for the nonsurgical "watch-and-wait" management approach for rectal adenocarcinoma. Candidates for this organ-preserving approach should have no evidence of malignancy on all three components of response assessment after neoadjuvant therapy (ie, digital rectal examination, endoscopy, and rectal MRI). Hence, rectal MRI again has a major role in directing patient management and possibly sparing patients from unnecessary surgical morbidity. In this article, the authors discuss the indications for neoadjuvant therapy in management of patients with rectal adenocarcinoma, describe expected imaging appearances of rectal adenocarcinoma after completion of neoadjuvant therapy, and outline the MRI tumor regression grading system. Since pelvic sidewall lymph node dissection is associated with a high risk of permanent genitourinary dysfunction, it is performed for only selected patients who have radiologic evidence of sidewall lymph node involvement. Therefore, the authors review the relevant lymphatic compartments of the pelvis and describe lymph node criteria for determining locoregional nodal spread. Finally, the authors discuss limitations of rectal MRI, describe several potential interpretation pitfalls after neoadjuvant therapy, and emphasize how these pitfalls may be avoided. © RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Bilateral en coup de sabre morphea in a male child: A rare presentation.

En coup de sabre is a rare subtype of morphea. Only a few bilateral cases have been reported to date. We report a case of a 12-year-old male child with two linear brownish depressed asymptomatic lesions over the forehead with hair loss on the scalp. After thorough clinical, ultrasonography and brain imaging, a diagnosis of bilateral en coup de sabre morphea was made and the patient was treated with oral steroids and weekly methotrexate.

Undergraduate dental students' perception of paediatric dental teaching in an urban and rural Australian dental school.

BACKGROUND: Confidence in performing paediatric dental treatment is important as it ensures better oral health outcomes in the patient's adulthood. AIM: To investigate the confidence and attitudes of final year dentistry students, attending an urban and rural dental programme, towards their paediatric dentistry training. DESIGN: A questionnaire was distributed to final year dentistry students at the urban-based university, The University of Queensland, and at the rural-based university, La Trobe University. The questionnaire collected information using 5-point Likert scale and short-answer questions, which explored the theoretical, observational, preclinical and clinical aspects of students' paediatric dentistry training. Jamovi and GraphPad Prism were used for data analysis and the creation of graphs. RESULTS: The questionnaire was completed by 32 rural students and 47 urban students, with a response rate of 79%. Rural students were found to be less confident with the theory on restorative procedures than urban students. Observations of a dentist performing treatment on child were completed by a significantly larger proportion of urban students (70.2%) than rural students (46.9%). Students from both universities reported to have developed the least confidence in the preclinical training of pulp therapies and expressed the need for additional preclinical sessions for more training. At both universities, students indicated they were the least confident in the clinical practice of pulp therapies and management of traumatic dental injuries. Urban students were found to be more confident than their rural counterparts in the clinical practice of examination, treatment planning and preventative procedures, as well as in restorative procedures. CONCLUSIONS: Both urban and rural students were found to have the least confidence in preclinical and clinical skills related to pulp therapies. Restorative dentistry was an area in which urban students were significantly more confident than rural students in both the theoretical and the clinical aspects.

High Rate of Positive Circumferential Resection Margin in Colon Cancer: A National Appraisal and Call for Action.

OBJECTIVE: To identify rates of positive circumferential resection margin (CRM) for colon cancer surgery in the US. SUMMARY BACKGROUND DATA: CRM is one of the most important determinants of local control in colorectal cancers. The extent to which CRM involvement exists after colon cancer surgery is unknown. METHODS: Colon cancer cases with resection 2010 to 2015 were identified from the National Cancer Data Base. Adjusting for patient and tumor characteristics, comparisons were made between cases with CRM > 1 mm (negative margin) and those with margin involved with tumor or ≤ 1 mm (positive margin, CRM+). Hospital-level analysis was performed, examining observed-to-expected CRM+ rates. RESULTS: In total, 170,022 cases were identified: 150,291 CRM- and 19,731 CRM+ (11.6%). Pathologic T-category was the greatest predictor of CRM+, with higher rates in pT4(25.8%), pT4A(24.7%), and pT4B(31.5%) versus pT1(4.5%), pT2(6.3%) and pT3 (10.9%, P < 0.001). Within pT4 patients, predictors of CRM+ included signet-ring histology (38.1% vs 26.7% nonmucinous, and 26.9% mucinous adenocarcinoma, P < 0.001), removing < 12 lymph nodes (36.5% vs 26.1% >12, P < 0.001), community facilities (32.7%) versus academic/research (23.6%, P < 0.001), year (30.1% 2010 vs 22.6% 2015, P < 0.001), and hospital volume (24.5% highest quartile vs 32.7% lowest, P < 0.001). Across 1288 hospitals, observed-to-expected ratios for CRM+ ranged from 0 to 7.899; 429 facilities had higher than expected rates. CONCLUSIONS: Overall rate of CRM+ in US colon cancer cases is high. Variation exists across hospitals, with higher than expected rates in many facilities. Although biology is a major influencing factor, CRM+ rates represent an area for multidisciplinary improvement in quality of colon cancer care.

Magnetic Resonance Imaging Directed Surgical Decision Making for Lateral Pelvic Lymph Node Dissection in Rectal Cancer After Total Neoadjuvant Therapy (TNT).

OBJECTIVE: Lateral pelvic lymph node (LPLN) metastases are an important cause of preventable local failure in rectal cancer. The aim of this study was to evaluate clinical and oncological outcomes following magnetic resonance imaging (MRI)-directed surgical selection for lateral pelvic lymph node dissection (LPLND) after total neoadjuvant therapy (TNT). METHODS: A retrospective consecutive cohort analysis was performed of rectal cancer patients with enlarged LPLN on pretreatment MRI. Patients were categorized as LPLND or non-LPLND. The main outcomes were lateral local recurrence rate, perioperative and oncological outcomes and factors associated with decision making for LPLND. RESULTS: A total of 158 patients with enlarged pretreatment LPLN and treated with TNT were identified. Median follow-up was 20 months (interquartile range 10-32). After multidisciplinary review, 88 patients (56.0%) underwent LPLND. Mean age was 53 (SD±12) years, and 54 (34.2%) were female. Total operative time (509 vs 429 minutes; P =0.003) was greater in the LPLND group, but median blood loss ( P =0.70) or rates of major morbidity (19.3% vs 17.0%) did not differ. LPLNs were pathologically positive in 34.1%. The 3-year lateral local recurrence rates (3.4% vs 4.6%; P =0.85) did not differ between groups. Patients with LPLNs demonstrating pretreatment heterogeneity and irregular margin (odds ratio, 3.82; 95% confidence interval: 1.65-8.82) or with short-axis ≥5 mm post-TNT (odds ratio 2.69; 95% confidence interval: 1.19-6.08) were more likely to undergo LPLND. CONCLUSIONS: For rectal cancer patients with evidence of LPLN metastasis, the appropriate selection of patients for LPLND can be facilitated by a multidisciplinary MRI-directed approach with no significant difference in perioperative or oncologic outcomes.

Prognosis for Poorly Differentiated, High-Grade Rectal Neuroendocrine Carcinomas.

INTRODUCTION: Rectal neuroendocrine carcinomas (rNECs) are poorly characterized and, given their aggressive nature, optimal management is not well-established. We therefore sought to describe clinicopathologic traits, treatment details, and survival patterns for patients with rNECs. METHODS: Patients captured in the National Cancer Database (NCDB; 2004-2016) with rNECs managed with observation, chemotherapy, or proctectomy ± chemotherapy were considered for analysis. RESULTS: The inclusion criteria were met by 777 patients. Mean age was 62.4 years, 45% were male, 80% were Caucasian, 40% presented with lymph nodes metastases, and 49% presented with distant metastases. Chemotherapy and surgical resection were administered in 72 and 19% of cases, respectively. Median overall survival (OS) was 0.83 years (1 year, 41%; 3 years, 13%; 5 years, 10%). During the study interval, 659 (85%) patients died, with a median follow-up of 0.79 years. On multivariable analysis, age ≥60 years, male sex, and distant metastases were associated with worse survival; surgical resection and administration of chemotherapy were associated with a reduced risk of death. Among non-metastatic patients treated with surgical resection, administration of chemotherapy was protective, while a positive lymph node ratio (LNR) ≥42% (median value) was associated with an increased risk of death. There was no difference in the number of examined lymph nodes between LNR cohorts. CONCLUSIONS: Patients with rNECs experience dismal survival outcomes, including those with non-metastatic disease treated with curative-intent surgical resection. Neoadjuvant therapy can serve as a useful biologic test, and surgical resection should be judiciously employed.

Simultaneous axial and radial swelling studies from 2D stereozoom images of tablet compacts composed of superdisintegrants.

Swelling-based disintegration is considered important for drug release from tablets and can be modified with excipients called tablet disintegrants. Swelling of tablets occurs axially and radially, and most researchers have observed both these events separately using 2D images. In the current work, we have studied these events simultaneously instead of separately under a stereozoom microscope for tablet compacts composed of high proportions of disintegrants (sodium starch glycolate, SSG and croscarmellose sodium, CCS), using water as the disintegrating medium. A hypothesis is proposed for the measurements of radial and axial swellings from a single 2D image, as horizontal lengths based on trigonometric functions for a right-angle triangle. All predicted axial and radial lengths (as per proposed hypothesis) are found validated with respect to vernier calliper measurements for dry-tablet compacts with a minute error of 3.809%. The axial swelling is approximately fivefolds more than that of radial swelling on the basis of normalised lengths. No particular trend can be spotted exclusively in favour of a superdisintegrant; however, the CCS-based tablets have shown higher swelling as compared to SSG-based tablets. From the current studies, it is evident that both axial and radial dimensions are obtainable from single 2D stereozoom images and can be successfully implemented for swelling studies of tablets.

Sugar transporters and their molecular tradeoffs during abiotic stress responses in plants.

Sugars as photosynthates are well known as energy providers and as building blocks of various structural components of plant cells, tissues and organs. Additionally, as a part of various sugar signaling pathways, they interact with other cellular machinery and influence many important cellular decisions in plants. Sugar signaling is further reliant on the differential distribution of sugars throughout the plant system. The distribution of sugars from source to sink tissues or within organelles of plant cells is a highly regulated process facilitated by various sugar transporters located in plasma membranes and organelle membranes, respectively. Sugar distribution, as well as signaling, is impacted during unfavorable environments such as extreme temperatures, salt, nutrient scarcity, or drought. Here, we have discussed the mechanism of sugar transport via various types of sugar transporters as well as their differential response during environmental stress exposure. The functional involvement of sugar transporters in plant's abiotic stress tolerance is also discussed. Besides, we have also highlighted the challenges in engineering sugar transporter proteins as well as the undeciphered modules associated with sugar transporters in plants. Thus, this review provides a comprehensive discussion on the role and regulation of sugar transporters during abiotic stresses and enables us to target the candidate sugar transporter(s) for crop improvement to develop climate-resilient crops.

Chronology of disc degeneration and facet joint arthritis in lumbar spine is variable - A CT based cross-sectional study.

BACKGROUND: The notion that disc degeneration (DD) always precedes facet joint arthritis (FJA) has held sway for many decades. However, it is not always the case. We hypothesized that DD is not always the first offender studied the prevalence of isolated DD and isolated FJA in the lumbar spine. METHODS: Inter-vertebral discs and bilateral facet joints of lumbar spines of 135 participants were graded. The participants were divided into one of the four categories. 'No degeneration,' 'Isolated disc degeneration without facet joint arthritis,' 'Combined disc degeneration and facet joint arthritis,' and 'Isolated facet joint arthritis without disc degeneration.' Multivariate logistic regression analysis was done to evaluate the predictive factors for spinal degeneration using FJA as a dependent variable while age, sex, BMI, smoking history, and DD as predictor variables. RESULTS: The majority of participants had isolated FJA 64 (47.4%). Combined DD and FJA were noted in 32 (23.7%), isolated DD in 8 (5.9%), while 31(23%) had no degeneration. Only age was found to be significantly contributing to the prediction model in multivariate analysis. CONCLUSION: Our study shows that spinal degeneration may begin either in the disc or in the facet joints depending upon the aetiological factors. It is a vicious circle that may be entered at any point, FJA or DD.

Spontaneous Pneumomediastinum in a Patient with Covid-19.

Spontaneous pneumomediastinum is a rare diagnosis. A thirty-five-year-old female who was admitted to our hospital with fever, cough and breathlessness and positive RT-PCR for COVID -19 was diagnosed with spontaneous pneumomediastinum and pneumothorax. She was managed with symptomatic approach and oxygen therapy. Small pneumomediastinum usually requires close monitoring and follows an uneventful course.

Arabidopsis protein l-ISOASPARTYL METHYLTRANSFERASE repairs isoaspartyl damage to antioxidant enzymes and increases heat and oxidative stress tolerance.

Stressful environments accelerate the formation of isoaspartyl (isoAsp) residues in proteins, which detrimentally affect protein structure and function. The enzyme PROTEIN l-ISOASPARTYL METHYLTRANSFERASE (PIMT) repairs other proteins by reverting deleterious isoAsp residues to functional aspartyl residues. PIMT function previously has been elucidated in seeds, but its role in plant survival under stress conditions remains undefined. Herein, we used molecular, biochemical, and genetic approaches, including protein overexpression and knockdown experiments, in Arabidopsis to investigate the role of PIMTs in plant growth and survival during heat and oxidative stresses. We demonstrate that these stresses increase isoAsp accumulation in plant proteins, that PIMT activity is essential for restricting isoAsp accumulation, and that both PIMT1 and PIMT2 play an important role in this restriction and Arabidopsis growth and survival. Moreover, we show that PIMT improves stress tolerance by facilitating efficient reactive oxygen species (ROS) scavenging by protecting the functionality of antioxidant enzymes from isoAsp-mediated damage during stress. Specifically, biochemical and MS/MS analyses revealed that antioxidant enzymes acquire deleterious isoAsp residues during stress, which adversely affect their catalytic activities, and that PIMT repairs the isoAsp residues and thereby restores antioxidant enzyme function. Collectively, our results suggest that the PIMT-mediated protein repair system is an integral part of the stress-tolerance mechanism in plants, in which PIMTs protect antioxidant enzymes that maintain proper ROS homeostasis against isoAsp-mediated damage in stressful environments.

Imperative role of sugar signaling and transport during drought stress responses in plants.

Cellular sugar status is essentially maintained during normal growth conditions but is impacted negatively during various environmental perturbations. Drought presents one such unfavorable environmental cue that hampers the photosynthetic fixation of carbon into sugars and affects their transport by lowering the cellular osmotic potential. The transport of cellular sugar is facilitated by a specific set of proteins known as sugar transporters. These transporter proteins are the key determinant of influx/ efflux of various sugars and their metabolite intermediates that support the plant growth and developmental process. Abiotic stress and especially drought stress-mediated injury results in reprogramming of sugar distribution across the cellular and subcellular compartments. Here, we have reviewed the imperative role of sugar accumulation, signaling, and transport under typical and atypical stressful environments. We have discussed the physiological effects of drought on sugar accumulation and transport through different transporter proteins involved in monosaccharide and disaccharide sugar transport. Further, we have illustrated sugar-mediated signaling and regulation of sugar transporter proteins along with the overall crosstalk of this signaling with the phytohormone module of abiotic stress response under osmotic stress. Overall, the present review highlights the critical role of sugar transport, distribution and signaling in plants under drought stress conditions.

MRI Staging in an Evolving Management Paradigm for Rectal Cancer, From the AJR Special Series on Cancer Staging.

The treatment of rectal cancer centers around the distinct but related goals of management of distant metastases and management of local disease. Optimal local management requires attention to the primary tumor and its anatomic relationship to surrounding pelvic structures, with the goal of minimizing local recurrence (LR). High-resolution MRI is ideally suited for this purpose; application of MRI-based criteria in conjunction with optimized surgical and pathologic techniques has successfully reduced LR rates. This success has led to a shift away from using the TNM-based National Comprehensive Cancer Network (NCCN) guidelines as the sole determinant of whether a patient receives neoadjuvant chemoradiation. The new model uses a hybrid approach for assigning risk categories that combines elements of the TNM staging system with MRI-based anatomic features. These risk categories incorporate tumor proximity to the circumferential resection margin, T category, distance to the anal verge, and presence of extramural venous invasion to classify rectal tumors as low, intermediate, or high risk. This approach has been validated by accumulated data from numerous multiinstitutional studies. This article illustrates key anatomic concepts, depicts common interpretive errors and pitfalls, and discusses ongoing limitations; these insights should guide radiologists in optimal rectal MRI interpretation.

Biotechnological interventions of in vitro propagation and production of valuable secondary metabolites in Stevia rebaudiana.

Plant cell and tissue culture makes provision of a sustainable and nature-friendly strategy for the production of secondary metabolites, and modern progress in gene editing and genome engineering provides novel possibilities to improve both the qualitative and quantitative aspects of such phytochemicals. The ever-expanding quest for plant-based medicine to treat diabetes facilitates large-scale cultivation of Stevia rebaudiana to enhance the yield of its much-coveted low-calorie sweetener glycosides. The potential to process stevia as a "natural" product should enhance the acceptance of steviosides as a natural calorie-free sweetener especially suitable for use in diabetic and weight control drinks and foods. Besides sweetener agents, S. rebaudiana is a potent source of many antioxidant compounds and is used to cure immunodeficiencies, neurologic disorders, inflammation, diabetes mellitus, Parkinson's disease, and Alzheimer's disease. This comprehensive review presents the research outcomes of the many biotechnological interventions implicated to upscale the yield of steviol glycosides and its derivatives in in vitro cell, callus, tissue, and organ cultures with notes on the use of bioreactor and genetic engineering in relation to the production of these valuable compounds in S. rebaudiana. KEY POINTS: • Critical and updated assessment on sustainable production of steviol glycosides from Stevia rebaudiana. • In vitro propagation of S. rebaudiana and elicitation of steviol glycosides production. • Genetic fidelity and diversity assessment of S. rebaudiana using molecular markers.