Circulating Tumor DNA as a Minimal Residual Disease Assessment and Recurrence Risk in Patients Undergoing Curative-Intent Resection with or without Adjuvant Chemotherapy in Colorectal Cancer: A Systematic Review and Meta-Analysis.

Emerging data have suggested that circulating tumor DNA (ctDNA) can be a reliable biomarker for minimal residual disease (MRD) in CRC patients. Recent studies have shown that the ability to detect MRD using ctDNA assay after curative-intent surgery will change how to assess the recurrence risk and patient selection for adjuvant chemotherapy. We performed a meta-analysis of post-operative ctDNA in stage I-IV (oligometastatic) CRC patients after curative-intent resection. We included 23 studies representing 3568 patients with evaluable ctDNA in CRC patient post-curative-intent surgery. Data were extracted from each study to perform a meta-analysis using RevMan 5.4. software. Subsequent subgroup analysis was performed for stages I-III and oligometastatic stage IV CRC patients. Results showed that the pooled hazard ratio (HR) for recurrence-free survival (RFS) in post-surgical ctDNA-positive versus -negative patients in all stages was 7.27 (95% CI 5.49-9.62), p < 0.00001. Subgroup analysis revealed pooled HRs of 8.14 (95% CI 5.60-11.82) and 4.83 (95% CI 3.64-6.39) for stages I-III and IV CRC, respectively. The pooled HR for RFS in post-adjuvant chemotherapy ctDNA-positive versus -negative patients in all stages was 10.59 (95% CI 5.59-20.06), p < 0.00001. Circulating tumor DNA (ctDNA) analysis has revolutionized non-invasive cancer diagnostics and monitoring, with two primary forms of analysis emerging: tumor-informed techniques and tumor-agnostic or tumor-naive techniques. Tumor-informed methods involve the initial identification of somatic mutations in tumor tissue, followed by the targeted sequencing of plasma DNA using a personalized assay. In contrast, the tumor-agnostic approach performs ctDNA analysis without prior knowledge of the patient's tumor tissue molecular profile. This review highlights the distinctive features and implications of each approach. Tumor-informed techniques enable the precise monitoring of known tumor-specific mutations, leveraging the sensitivity and specificity of ctDNA detection. Conversely, the tumor-agnostic approach allows for a broader genetic and epigenetic analysis, potentially revealing novel alterations and enhancing our understanding of tumor heterogeneity. Both approaches have significant implications for personalized medicine and improved patient outcomes in the field of oncology. The subgroup analysis based on the ctDNA method showed pooled HRs of 8.66 (95% CI 6.38-11.75) and 3.76 (95% CI 2.58-5.48) for tumor-informed and tumor-agnostic, respectively. Our analysis emphasizes that post-operative ctDNA is a strong prognostic marker of RFS. Based on our results, ctDNA can be a significant and independent predictor of RFS. This real-time assessment of treatment benefits using ctDNA can be used as a surrogate endpoint for the development of novel drugs in the adjuvant setting.

Hybridized Radial and Edge Coupled 3D Plasmon Modes in Self-Assembled Graphene Nanocylinders.

Current graphene-based plasmonic devices are restricted to 2D patterns defined on planar substrates; thus, they suffer from spatially limited 2D plasmon fields. Here, 3D graphene forming freestanding nanocylinders realized by a plasma-triggered self-assembly process are introduced. The graphene-based nanocylinders induce hybridized edge (in-plane) and radial (out-of-plane) coupled 3D plasmon modes stemming from their curvature, resulting in a four orders of magnitude stronger field at the openings of the cylinders than in rectangular 2D graphene ribbons. For the characterization of the 3D plasmon modes, synchrotron nanospectroscopy measurements are performed, which provides the evidence of preservation of the hybridized 3D graphene plasmons in the high precision curved nanocylinders. The distinct 3D modes introduced in this paper, provide an insight into geometry-dependent 3D coupled plasmon modes and their ability to achieve non-surface-limited (volumetric) field enhancements.

Self-Assembled 3D Nanosplit Rings for Plasmon-Enhanced Optofluidic Sensing.

Plasmonic sensors are commonly defined on two-dimensional (2D) surfaces with an enhanced electromagnetic field only near the surface, which requires precise positioning of the targeted molecules within hotspots. To address this challenge, we realize segmented nanocylinders that incorporate plasmonic (1-50 nm) gaps within three-dimensional (3D) nanostructures (nanocylinders) using electron irradiation triggered self-assembly. The 3D structures allow desired plasmonic patterns on their inner cylindrical walls forming the nanofluidic channels. The nanocylinders bridge nanoplasmonics and nanofluidics by achieving electromagnetic field enhancement and fluid confinement simultaneously. This hybrid system enables rapid diffusion of targeted species to the larger spatial hotspots in the 3D plasmonic structures, leading to enhanced interactions that contribute to a higher sensitivity. This concept has been demonstrated by characterizing an optical response of the 3D plasmonic nanostructures using surface-enhanced Raman spectroscopy (SERS), which shows enhancement over a 22 times higher intensity for hemoglobin fingerprints with nanocylinders compared to 2D nanostructures.

Small-Scale Biological and Artificial Multidimensional Sensors for 3D Sensing.

A vast majority of existing sub-millimeter-scale sensors have a planar, 2D geometry as a result of conventional top-down lithographic procedures. However, 2D sensors often suffer from restricted sensing capability, allowing only partial measurements of 3D quantities. Here, nano/microscale sensors with different geometric (1D, 2D, and 3D) configurations are reviewed to introduce their advantages and limitations when sensing changes in quantities in 3D space. This Review categorizes sensors based on their geometric configuration and sensing capabilities. Among the sensors reviewed here, the 3D configuration sensors defined on polyhedral structures are especially advantageous when sensing spatially distributed 3D quantities. The nano- and microscale vertex configuration forming polyhedral structures enable full 3D spatial sensing due to orthogonally aligned sensing elements. Particularly, the cubic configuration leveraged in 3D sensors offers an array of diverse applications in the field of biosensing for micro-organisms and proteins, optical metamaterials for invisibility cloaking, 3D imaging, and low-power remote sensing of position and angular momentum for use in microbots. Here, various 3D sensors are compared to assess the advantages of their geometry and its impact on sensing mechanisms. 3D biosensors in nature are also explored to provide vital clues for the development of novel 3D sensors.

Self-Assembled Three-Dimensional Graphene-Based Polyhedrons Inducing Volumetric Light Confinement.

The ability to transform two-dimensional (2D) materials into a three-dimensional (3D) structure while preserving their unique inherent properties might offer great enticing opportunities in the development of diverse applications for next generation micro/nanodevices. Here, a self-assembly process is introduced for building free-standing 3D, micro/nanoscale, hollow, polyhedral structures configured with a few layers of graphene-based materials: graphene and graphene oxide. The 3D structures have been further modified with surface patterning, realized through the inclusion of metal patterns on their 3D surfaces. The 3D geometry leads to a nontrivial spatial distribution of strong electric fields (volumetric light confinement) induced by 3D plasmon hybridization on the surface of the graphene forming the 3D structures. Due to coupling in all directions, resulting in 3D plasmon hybridization, the 3D closed box graphene generates a highly confined electric field within as well as outside of the cubes. Moreover, since the uniform coupling reduces the decay of the field enhancement away from the surface, the confined electric field inside of the 3D structure shows two orders of magnitude higher than that of 2D graphene before transformation into the 3D structure. Therefore, these structures might be used for detection of target substances (not limited to only the graphene surfaces, but using the entire volume formed by the 3D graphene-based structure) in sensor applications.

Vitamin D: The Missing Nutrient Behind the Two Deadly Pandemics, COVID-19 and Cardiovascular Diseases.

The coronavirus (COVID-19) pandemic is claiming millions of lives and creating an additional burden on health care, which is already affected by the rise of non-communicable diseases (NCDs). The scientific community, on the other side, is enormously engaged with studies to best identify the characteristics of the virus and minimize its effect while supporting the fight to contain NCDs, mainly cardiovascular diseases (CVDs), which are contributing hugely to the global death toll. Hence, the roles of vitamin D in COVID-19 immunity and cardiovascular health are gaining traction recently.  This literature review will mainly focus on summarizing pertinent studies and scientific publications which highlight the association of vitamin D levels with the various outcomes of COVID-19 and CVDs. It will also address how low vitamin D correlates with the epidemiology of CVDs and the inflammatory mechanisms attributed to COVID-19 severity. We believe that our review may open up hindsight perspectives and further discussions among the physicians in tapping the potential of vitamin D supplementation to tackle the morbidity, mortality, and health care cost of the two deadly diseases, COVID-19 and CVDs.

Diagnostic Accuracy of Elastography and Liver Disease: A Meta-Analysis.

Background: Ultrasound-based transient elastography (TE) is a non-invasive alternative to liver biopsy for the staging of hepatic fibrosis due to various chronic liver diseases. This meta-analysis aims to assess the diagnostic accuracy of TE for detecting liver cirrhosis (F4) and severe fibrosis (F3) in patients with chronic liver diseases, in comparison to the gold standard liver biopsy. Methods: A systematic search was performed using PubMed search engine following Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines from inception to May 2021. The meta-analysis studies evaluating the diagnostic accuracy of TE for severe fibrosis and cirrhosis were identified. We conducted a meta-meta-analysis to generate pooled estimates of the sensitivity, specificity, and diagnostic odds ratios (ORs) for F3 and F4 fibrosis stage. Results: We included five studies with a total of 124 sub-studies and 20,341 patients in our analysis. Three studies have reported the diagnostic accuracy of TE in detecting F3/severe fibrosis stage and found 81.9% pooled sensitivity (95% confidence interval (CI): 79.9-83.7%; P < 0.001) (I2 = 0%), 84.7% pooled specificity (95% CI: 81.3-87.6%) (I2 = 81%; P = 0.02). All five studies reported the diagnostic accuracy of TE in detecting F4/liver cirrhosis stage. We found 84.8% pooled sensitivity (95% CI: 81.4-87.7%) (I2 = 86.4%; P < 0.001), 87.5% pooled specificity (95% CI: 85.4-89.3%) (I2 = 90%; P < 0.001) and pooled diagnostic OR (41.8; 95% CI: 3.9 - 56.5) (I2 = 87%; P < 0.001). Conclusions: Ultrasound-based TE has excellent diagnostic accuracy for identifying cirrhosis and liver fibrosis stages 3. Future studies should focus on estimating the diagnostic accuracy of other fibrosis stages in chronic liver disease patients. This will eventually decrease the risk associated with invasive liver biopsy.

Cancer Prevalence in E-Cigarette Users: A Retrospective Cross-Sectional NHANES Study.

Background: It is well known that traditional smoking causes various types of cancer, leading to the current decline in traditional smoking among US adults from 20.9% in 2005 to 14.0% in 2019. Electronic cigarettes (e-cigarettes) are commonly marketed as a safe alternative and gaining popularity especially among never-smokers and adolescents. However, there is limited evidence of effects of e-cigarette on cancer. Hence, we aim to find the prevalence and association of e-cigarette and traditional smoking among cancer respondents. Methods: We conducted a retrospective cross-sectional study using the NHANES database from 2015 to 2018. We assessed history of cancer (MCQ220), type of cancers (MCQ230a), and smoking status (e-cigarette: SMQ900 or SMQ905 and traditional smoking: SMQ020) using questionnaires. We performed multivariable logistic regression models to find the association of e-cigarette use, traditional smoking, and no smoking with cancer after adjusting for confounding variables. Results: A total of 154,856 participants were included, of whom 5% were e-cigarette users, 31.4% were traditional smokers, and 63.6% were nonsmokers. There is a higher prevalence of e-cigarette use among younger participants, females (49 vs. 38) in comparison to traditional smokers (P < 0.0001). The e-cigarette users have lower prevalence of cancer compared to traditional smoking (2.3% vs. 16.8%; P < 0.0001), but they were diagnosed with cancer at a younger age. Among cancer subtypes, cervical cancer (22 vs. 2.6), leukemia (8.5 vs. 1.1), skin cancer (non-melanoma) (15.6 vs. 12.3), skin (other) (28 vs. 10) and thyroid (10.6 vs. 2.4) had higher prevalence of e-cigarette use compared to traditional smokers (P < 0.0001). Our regression analysis showed that e-cigarette users have 2.2 times higher risk of having cancer compared to non-smokers (odds ratio (OR): 2.2; 95% confidence interval (CI): 2.2 - 2.3; P < 0.0001). Similarly, traditional smokers have 1.96 higher odds of having cancer compared to nonsmokers (OR: 1.96; 95% CI: 1.96 - 1.97; P < 0.0001). Conclusion: In our study, e-cigarette users had an early age of cancer onset and higher risk of cancer. Hence, this is stepping stone for future research to evaluate the safety and effects of e-cigarettes in patients with cancer.

Asymptomatic Left Atrial Myxoma Treated With Minimally Invasive Surgical Approach.

Myxomas, being the most common primary benign tumor among all cardiac tumors, occur rarely with a very low incidence rate. Myxomas can cause various clinical manifestations or can be diagnosed incidentally. Some patients with cardiac myxomas are completely asymptomatic. Cardiac myxomas cause life-threatening complications, thus early diagnosis is imperative. We are reporting a case of atrial myxoma in a 38-year-old female without any significant past medical history, who came to our clinic for cardiology evaluation prior to plastic surgery. The elliptical mobile mass, located in the left atrium with its attachment to the interatrial septum, was diagnosed by transthoracic echocardiography. The patient was referred for surgery and a minimally invasive surgical approach was chosen. A histological report confirmed the diagnosis of myxoma. The patient recovered well. Three years of follow-up did not reveal any signs of recurrence of the tumor. We are also analyzing 20 previously published cases of asymptomatic myxomas and myxomas treated with a minimally invasive surgical approach, reported in the PubMed database for the last 20 years (2001-2021) in the adult patient population (age 19 and over). The aim of this study is to highlight the asymptomatic presentation of cardiac myxomas and to underline the advantages of a minimally invasive surgical approach. In summary, asymptomatic cardiac myxomas are rare incidental findings. Attention to subtle symptoms during a physical exam and scrupulous history-taking can provide a clue to this diagnosis. Early diagnosis of cardiac myxomas is crucial to prevent life-threatening complications. Minimally invasive surgery is a promising alternative approach to standard open-heart surgery for treating cardiac myxomas, providing faster recovery and higher patient satisfaction with surgical care.

Nano-Architecture Driven Plasmonic Field Enhancement in 3D Graphene Structures.

The limited spatial coverage of the plasmon enhanced near-field in 2D graphene ribbons presents a major hurdle in practical applications. In this study, diverse self-assembled 3D graphene architectures are explored that induce hybridized plasmon modes by simultaneous in-plane and out-of-plane coupling to overcome the limited coverage in 2D ribbons. While 2D graphene can only demonstrate in-plane, bidirectional coupling through the edges, 3D architectures benefit from fully symmetric 360° coupling at the apex of pyramidal graphene, orthogonal four-directional coupling in cubic graphene, and uniform cross-sectional radial coupling in tubular graphene. The 3D coupled vertices, edges, surfaces, and volume induce corresponding enhancement modes that are highly dependent on the shape and dimensions comprising the 3D geometries. The hybridized modes introduced through the 3D coupling amplify the limited plasmon response in 2D ribbons to deliver nondiffusion limited sensors, high efficiency fuel cells, and extreme propagation length optical interconnects.

Ion-Induced Localized Nanoscale Polymer Reflow for Three-Dimensional Self-Assembly.

Thermal reflow of polymers is a well-established phenomenon that has been used in various microfabrication processes. However, present techniques have critical limitations in controlling the various attributes of polymer reflow, such as the position and extent of reflow, especially at the nanoscale. These challenges primarily result from the reflow heat source supplying heat energy to the entire substrate rather than a specific area. In this work, a focused ion beam (FIB) microscope is used to achieve controllable localized heat generation, leading to precise control over the nanoscale polymer reflow. Through the use of the patterning capability of FIB microscopy, dramatically different reflow performances within nanoscale distances of each other are demonstrated in both discrete periodic and continuous polymer structures. Further, we utilize a self-assembly process induced by nanoscale polymer reflow to realize 3D optical devices, specifically, vertically aligned nanoresonators and graphene-based nanocubes. HFSS and Comsol simulations have been carried out to analyze the advantages of the polymer-based 3D metamaterials as opposed to those fabricated with a metallic hinge. The simulation results clearly demonstrate that the polymer hinges have a dual advantage; first, the removal of any interference from the transmission spectrum leading to strong and distinct resonance peaks and, second, the elimination of parasitic leeching of the enhanced field by the metallic hinge resulting in stronger volumetric enhancement. Thus, the 2-fold advantages existing in 3D polymer-hinge optical metamaterials can open pathways for applications in 3D optoelectronic devices and sensors, vibrational molecular spectroscopy, and other nanoscale 3D plasmonic devices.

MRI Brain Lesions in Eclampsia: A Series of 50 Cases Admitted to HDU of a Tertiary Care Hospital.

Objective: To correlate the Magnetic Resonance Imaging findings and clinical presentation in patients of eclampsia. Materials and methods: This one year prospective study was conducted in the HDU of Department of Obstetrics and Gynecology, PT.B.D.Sharma, PGIMS, Rohtak .A total of 50 women with eclampsia (both antepartum and postpartum) were divided into two groups: a) study group patients with abnormal MRI b) control group: b) control group: patients with normal MRI.Comparison was done using chi-square test and unpaired student 't' test. Results: MRI revealed abnormal findings in 24% of women, commonest diagnosis being CVT without infarct (10%) followed by infarct (8%), PRES (4%) and HLE (2%).Totally 66% (n = 33) of the women presented with postpartum eclampsia while 34% (n = 17) had antepartum eclampsia.96%(n = 48) were unbooked cases. Unconsciousness, altered sensorium, headache, blurring of vision, seizures, GCS < 3 correlated well with MRI findings (p = 0.000, p = 0.027, p = 0.001, p = 0.007, p = 0.005, p = 0.000 respectively) whereas fundoscopic changes did not (p = 0.520). The mean uric acid and serum creatinine levels was higher (0.41 ± 0.11 mmol/ L vs 0.26 ± 0.10 mmol/ L and 80 ± 18 µmol/ L vs 71 ± 9 µmol/ L) in the study group and this was statistically significant (p = 0.003, p = 0.04 respectively).There was no statistically significant difference between blood pressure values of cases with or without MR imaging evidence of brain lesions. There was no maternal mortality among 50 cases. The sensitivity, specificity, positive predictive value and negative predictive value of neurological findings for abnormal MRI in patients with eclampsia was found to be 91.7%, 73.7%, 52.4%, 96.6% respectively. Conclusion: Unconsciousness, altered sensorium, headache, blurring of vision,seizures, GCS < 3, elevated uric acid and serum creatinine levels in the follow-up of pregnant patients with preeclampsia/eclampsia should be a warning for possible brain lesions whereas booking status, mean BP, fundoscopy, platelet, hemoglobin, liver enzymes were not significantly associated with positive MRI findings in patients of eclampsia.

Successful Pregnancy Outcome in Recurrent Ovarian Cancer in a 26 Year Old: A Case Report.

Objective: To report a case of Successful Pregnancy Outcome in Recurrent Ovarian Cancer in a 26 year Old. Case Report: A 26 years old primigravida presented in antenatal clinic at 23 weeks of pregnancy with recurrence of ovarian cancer of mucinous type. Following refusal of surgical management, two courses of single dose carboplatin was administered. However, before third cycle of chemotherapy could be administered ,there was deranged liver functions tests, following which elective Cesarean section with staging laparotomy was planned at 34 weeks for breech presentation with oligohydramnios. A live healthy baby girl 2.3kg was delivered. Total abdominal hysterectomy with right salpingo-oopherectomy, infracolic omentectomy, appendectomy was done. The final diagnosis was recurrent mucinous ovarian adenocarcinoma. Postoperatively, she was given six cycles of chemotherapy (carboplatin and paclitaxel). Conclusion: Chemotherapy and surgery, both are safe beyond first trimester and multidisciplinary treatment must be planned after taking into account the wishes of couple.

Three-Dimensional Anisotropic Metamaterials as Triaxial Optical Inclinometers.

Split-ring resonators (SRRs) present an attractive avenue for the development of micro/nano scale inclinometers for applications like medical microbots, military hardware, and nanosatellite systems. However, the 180° isotropy of their two-dimensional structure presents a major hurdle. In this paper, we present the design of a three-dimensional (3D) anisotropic SRR functioning as a microscale inclinometer enabling it to remotely sense rotations from 0° to 360° along all three axes (X, Y, and Z), by employing the geometric property of a 3D structure. The completely polymeric composition of the cubic structure renders it transparent to the Terahertz (THz) light, providing a transmission response of the tilted SRRs patterned on its surface that is free of any distortion, coupling, and does not converge to a single point for two different angular positions. Fabrication, simulation, and measurement data have been presented to demonstrate the superior performance of the 3D micro devices.

Lateral sliding bridge flap technique along with platelet rich fibrin and guided tissue regeneration for root coverage.

Gingival recession is defined as the apical migration of the gingival margin with exposure of root surfaces. The etiology of the condition is multifactorial. Given the high rate of gingival recession defects among the general population, it is imperative that dental practitioners have an understanding of the etiology, complications and management of the condition. A recent innovation in dentistry is the preparation and use of platelet-rich fibrin (PRF) for recession defects. The article presents a case report, which highlights the use of lateral sliding bridge flap along with PRF in a collagen membrane carrier (guided tissue regeneration) for the treatment of multiple recession defects.