Differentiating radiation necrosis from tumor recurrence: a systematic review and diagnostic meta-analysis comparing imaging modalities.

PURPSOSE: Cerebral radiation necrosis (RN) is often a delayed phenomenon occurring several months to years after the completion of radiation treatment. Differentiating RN from tumor recurrence presents a diagnostic challenge on standard MRI. To date, no evidence-based guidelines exist regarding imaging modalities best suited for this purpose. We aim to review the current literature and perform a diagnostic meta-analysis comparing various imaging modalities that have been studied to differentiate tumor recurrence and RN. METHODS: A systematic search adherent to PRISMA guidelines was performed using Scopus, PubMed/MEDLINE, and Embase. Pooled sensitivities and specificities were determined using a random-effects or fixed-effects proportional meta-analysis based on heterogeneity. Using diagnostic odds ratios, a diagnostic frequentist random-effects network meta-analysis was performed, and studies were ranked using P-score hierarchical ranking. RESULTS: The analysis included 127 studies with a total of 220 imaging datasets, including the following imaging modalities: MRI (n = 10), MR Spectroscopy (MRS) (n = 28), dynamic contrast-enhanced MRI (n = 7), dynamic susceptibility contrast MRI (n = 36), MR arterial spin labeling (n = 5), diffusion-weighted imaging (n = 13), diffusion tensor imaging (DTI) (n = 2), PET (n = 89), and single photon emission computed tomography (SPECT) (n = 30). MRS had the highest pooled sensitivity (90.7%). DTI had the highest pooled specificity (90.5%). Our hierarchical ranking ranked SPECT and MRS as most preferable, and MRI was ranked as least preferable. CONCLUSION: These findings suggest SPECT and MRS carry greater utility than standard MRI in distinguishing RN from tumor recurrence.

Pilot-phase PET/CT study targeting integrin αvß6 in pancreatic cancer patients using the cystine-knot peptide-based 18F-FP-R01-MG-F2.

PURPOSE: A novel cystine-knot peptide-based PET radiopharmaceutical, 18F-FP-R01-MG-F2 (knottin), was developed to selectively bind to human integrin αvß6 which is overexpressed in pancreatic cancer. The purpose of this study is to evaluate the safety, biodistribution, dosimetry, and lesion uptake of 18F-FP-R01-MG-F2 in patients with pancreatic cancer. METHODS: Fifteen patients (6 men, 9 women) with histologically confirmed pancreatic cancer were prospectively enrolled and underwent knottin PET/CT between March 2017 and February 2021 (ClinicalTrials.gov Identifier NCT02683824). Vital signs and laboratory results were collected before and after the imaging scans. Maximum standardized uptake values (SUVmax) and mean SUV (SUVmean) were measured in 24 normal tissues and pancreatic cancer lesions for each patient. From the biodistribution data, the organ doses and whole-body effective dose were calculated using OLINDA/EXM software. RESULTS: There were no significant changes in vital signs or laboratory values that qualified as adverse events or serious adverse events. At 1 h post-injection, areas of high 18F-FP-R01-MG-F2 uptake included the pituitary gland, stomach, duodenum, kidneys, and bladder (average SUVmean: 9.7-14.5). Intermediate uptake was found in the normal pancreas (average SUVmean: 4.5). Mild uptake was found in the lungs and liver (average SUVmean < 1.0). The effective dose was calculated to be 2.538 × 10-2 mSv/MBq. Knottin PET/CT detected all known pancreatic tumors in the 15 patients, although it did not detect small peri-pancreatic lymph nodes of less than 1 cm in short diameter in two of three patients who had lymph node metastases at surgery. Knottin PET/CT detected distant metastases in the lungs (n = 5), liver (n = 4), and peritoneum (n = 2), confirmed by biopsy and/or contrast-enhanced CT. CONCLUSION: 18F-FP-R01-MG-F2 is a safe PET radiopharmaceutical with an effective dose comparable to other diagnostic agents. Evaluation of the primary pancreatic cancer and distant metastases with 18F-FP-R01-MG-F2 PET is feasible, but larger studies are required to define the role of this approach. TRIAL REGISTRATION: NCT02683824.

Principles of Structural Design of Conjugated Polymers Showing Excellent Charge Transport toward Thermoelectrics and Bioelectronics Applications.

Conjugated polymers, especially their second generation with a donor-acceptor alternating structure, have promising properties. These are suitable for two emerging fields, thermoelectrics and bioelectronics, if appropriate structural designs are implemented. This review aims to give a perspective for the potential and challenges of novel conjugated polymers in such applications. In particular, the aspects of synthetic design and the consequences of modifications of the chemical structure on the charge transport in selected second-generation conjugated polymers are reviewed. By understanding the effects of structural motifs on the overall material properties, polymers can be specifically tailored for the respective application. The basics of charge transport measurements are briefly summarized, as the charge transport plays an important role for thermoelectrics as well as for bioelectronics. In particular, the correlation between the reported charge carrier mobility values and the structural design of the polymers is reviewed. Examples of the application of second-generation conducting polymers in thermoelectrics and bioelectronics are shown to demonstrate the current state of research. Finally, the prospect of a purposeful design of new materials for these two emerging fields is discussed.

Evaluation of Total Salivary Secretory Immunoglobulin A and Mi/fans-specific SIgA among Children having Dissimilar Caries Status.

INTRODUCTION: The occurrence of dental caries has become quite a common phenomenon nowadays. The varying levels of salivary secretory immunoglobulin A (SIgA) usually determine the progression of caries. The present study was aimed to determine the correlation between SIgA and mutans-specific antigen SIgA in children having different caries status. Scanning electron microscopic analysis was also completed to correlate the results. MATERIALS AND METHODS: This study comprised 60 subjects, who were divided into three groups depending on caries status. In all, saliva was collected to determine the level of SIgA and mutans-specific antigen SIgA using enzyme linked immunosorbent assay (ELISA). The World Health Organization (WHO) criteria and method were used to evaluate dental caries. Bradford reagent was used to evaluate the levels of protein in the antigen. Furthermore, 20 sections of enamel were randomly obtained to estimate the severity of caries development among groups. RESULTS: Categorical characteristics among all groups were compared by basic statistical analysis and Chi-squared test. Mean age (years) was found to be 9.214 ± 2.28, 9.5 ± 2.51, and 10.2 ± 2.35 in groups I, II, and III respectively. Mutans-specific IgA level (|jg/mL) was 34.63 ± 7.46, 28.24 ± 4.52, and 23.56 ± 1.62 in groups I, II, and III respectively. Total SIgA (jg/mL) was 142.53 ± 22.4, 186.10 ± 24.70, and 214.8 ± 27.56 in groups I, II, and III respectively. Caries index was 6.74 ± 2.16, 2.32 ± 0.86, and 0 ± 0 in groups I, II, and III respectively. CONCLUSION: Immunoglobulin A is dominantly present in saliva and it plays a significant role in prevention of dental caries. Hence, dental caries is more likely to develop in subjects with low level of salivary IgA (high caries index). CLINICAL SIGNIFICANCE: A low level of IgA may be associated with a high risk of developing dental caries. This association may possibly be useful in predicting the future caries status. Accordingly, suitable caries-preventive measures can be selected and employed.

Adult neuro-oncology trials in the United States over 5 decades: Analysis of trials completion rate to guide the path forward.

Background: Clinical trials are important to close the gap between therapeutic unmet needs and scientific advances in neuro-oncology. This study analyzes the landscape of neuro-oncology trials to identify completion rates and guide strategies for the path forward. Methods: US-registered adult neuro-oncology clinical trials were extracted from www.clinicaltrials.gov (1966-2019), including funding source, trial type, scope, phase, and subjects' demographics. Completed trials defined as those that had completed participants' examinations or intervention administration for the purpose of the final collection of data for the primary outcome were dichotomized against those that failed to reach completion. Univariate and multivariate analyses were used to detect differences across factors comparing the last 2 decades (2000-2009, 2010-2019). Results: Our search yielded 4522 trials, of which 1257 are eligible for this study. In 25 US states, neuro-oncology trial availability is <0.85/100,000 population. Comparing the past 2 decades, trial completion rate decreased from 88% to 64% (P < .001) and National Institutes of Health funding decreased from 47% to 24% (P < .001). Inclusion of subjects >65-year-old and women increased, while inclusion of Hispanic subjects decreased (P < .001). The top 2 reasons for lack of completion included accrual and operational difficulties. A larger proportion of women, non-Hispanic subjects, and older adults were enrolled in completed trials than in those that failed completion. Conclusions: Our study is the first report on the neuro-oncology clinical trial landscape in the United States and supports the development of strategies to further improve access to these trials. Additionally, attention is needed to identify and modify other factors contributing to lack of completion.

Retreatment of Classical Tic Douloureux With Stereotactic Radiosurgery: A Scoping Review.

Stereotactic radiosurgery (SRS), also known as gamma knife surgery (GKS), is a noninvasive procedure for treating tic douloureux (TD) or trigeminal neuralgia (TN). Due to a lack of sufficient evidence regarding the indication of SRS for the treatment of recurrent TD, the present scoping review was conducted to assess the effectiveness of repeated SRS procedures for managing recurrent TD. The literature search was performed from January 2012 to December 2022 on the PubMed, Scopus, and Web of Science databases. Of the 215 initial results obtained, 10 articles were finally selected for the review. Three studies used the SRS procedure for the third time in patients with recurrent TD. All studies were retrospective, with a mean maximal dose of 70-90 Gy and a cumulative dose of 120-180 Gy for two SRS treatments and 150-270 Gy for three SRS treatments. The target zone for irradiation was the retrogasserian zone (RGZ). Repeat SRS procedures led to pain relief in 80-90% of patients within one to four months and excellent pain relief in 50-90% of patients. Pain recurrence was noticed after one year in 20-40% of patients. Postoperative complications, such as trigeminal nerve deficits, facial numbness, and mild corneal dryness, were noted in the studies. The review concluded that repeat SRS is an effective and relatively safe procedure for pain management in patients with recurrent TD.

Ameloblastic Fibro-Odontoma of the Posterior Mandible: A Rare Pathological Entity.

Ameloblastic fibro-odontoma (AFO) is a rare, slow-growing neoplastic lesion classified as a benign, epithelial mixed odontogenic tumor with odontogenic mesenchyme. This tumor demonstrates the histological features characteristic of both ameloblastic fibromas and complex odontomas. The clinical manifestation of AFO is typically characterized by asymptomatic enlargement of the jawbones. Radiographically, it presents as a distinct radiolucent region, indicating the presence of radiopaque substances with varying degrees of irregularities in size and morphology. Standard therapeutic intervention involves enucleation. Despite its benign nature, AFO can cause significant morbidity if left untreated. Therefore, prompt diagnosis and appropriate management are essential to ensure optimal patient outcomes. The following case report details the clinical presentation and management of an 18-year-old male with an AFO lesion located in the posterior mandible. This particular case was treated with conservative measures involving surgical enucleation.

Ameloblastic fibro­odontoma in the posterior mandible: A case report.

Ameloblastic fibro-odontoma (AFO) is a rare, slow-growing neoplastic lesion classified as a benign, epithelial odontogenic mesenchymal tumor. This tumor exhibits histological features characteristic of both ameloblastic fibromas and complex odontomas. The clinical manifestation of AFO is typically characterized by the asymptomatic enlargement of the jawbones. Radiographically, it presents as a distinct radiolucent region, indicating the presence of radiopaque substances with varying degrees of irregularities in size and morphology. Standard therapeutic intervention involves enucleation. Despite its benign nature, AFO can cause significant morbidity if left untreated. Therefore, prompt diagnosis and appropriate management are essential to ensure optimal patient outcomes. The present study describes the case (clinical presentation and management) of an 18-year-old male patient with an AFO lesion located in the posterior mandible. This particular case was treated with conservative measures involving surgical enucleation along with the extraction of the impacted tooth and the curettage of residual bone.

C-H/π-interaction-guided self-assembly in π-conjugated oligomers.

We report CH/π hydrogen-bond-driven self-assembly in π-conjugated skeletons based on oligophenylenevinylenes (OPVs) and trace the origin of interactions at the molecular level by using single-crystal structures. OPVs were designed with appropriate pendants in the aromatic core and varied by hydrocarbon or fluorocarbon tails along the molecular axis. The roles of aromatic π-stack, van der Waals forces, fluorophobic effect and CH/π interactions were investigated on the theromotropic liquid crystallinity of OPV molecules. Single-crystal structures of hydrocarbon OPVs provided direct evidence for the existence of CH/π interactions between the π-ring (H-bond acceptor) and alkyl C-H (H-bond donor). The four important crystallographic parameters, d(c-x)=3.79 Å, θ=21.49°, φ=150.25° and d(Hp-x)=0.73 Å, matched in accordance with typical CH/π interactions. The CH/π interactions facilitate the close-packing of mesogens in x-y planes, which were further protruded along the c axis producing a lamellar structure. In the absence of CH/π interactions, van der Waals interactions drove the assembly towards a Schlieren nematic texture. Fluorocarbon OPVs exhibited smectic liquid-crystalline textures that further underwent Smectic A (SmA) to Smectic C (SmC) phase transitions with shrinkage up to 11%. The orientation and translational ordering of mesogens in the liquid-crystalline (LC) phases induced H- and J-type molecular arrangements in fluorocarbon and hydrocarbon OPVs, respectively. Upon photoexcitation, the H- and J-type molecular arrangements were found to emit a blue or yellowish/green colour. Time-resolved fluorescence decay measurements confirmed longer lifetimes for H-type smectic OPVs relative to that of loosely packed one-dimensional nematic hydrocarbon-tailed OPVs.

Herringbone and helical self-assembly of π-conjugated molecules in the solid state through CH/π hydrogen bonds.

Self-organization of organic molecules through weak noncovalent forces such as CH/π interactions and creation of large hierarchical supramolecular structures in the solid state are at the very early stage of research. The present study reports direct evidence for CH/π interaction driven hierarchical self-assembly in π-conjugated molecules based on custom-designed oligophenylenevinylenes (OPVs) whose structures differ only in the number of carbon atoms in the tails. Single-crystal X-ray structures were resolved for these OPV synthons and the existence of long-range multiple-arm CH/π interactions was revealed in the crystal lattices. Alignment of these π-conjugated OPVs in the solid state was found to be crucial in producing either right-handed herringbone packing in the crystal or left-handed helices in the liquid-crystalline mesophase. Pitch- and roll-angle displacements of OPV chromophores were determined to trace the effect of the molecular inclination on the ordering of hierarchical structures. Furthermore, circular dichroism studies on the OPVs were carried out in the aligned helical structures to prove the existence of molecular self-assembly. Thus, the present strategy opens up new approaches in supramolecular chemistry based on weak CH/π hydrogen bonding, more specifically in π-conjugated materials.

Direct Pulp Capping with Mineral Trioxide Aggregate and Biodentine in Cariously Exposed Molar Teeth: 1-Year Follow-up - An In vivo Study.

Aim: To assess and compare the treatment outcome of direct pulp capping with mineral trioxide aggregate (MTA) and Biodentine, after complete excavation of caries in permanent dentition with a 2-visit treatment protocol. Materials and Methods: Direct pulp capping with white MTA was performed in 70 teeth. Direct pulp capping with Biodentine was also done in 72 teeth. In the subsequent visits after 2 weeks, pulp sensibility tests were attempted in both studied groups. All clinical outcomes were categorized as success or failure. Results: The success rate of the pulp capping procedure in the MTA group at the end of 12 months study was 94.3% in the Class I subgroup and 93.3% in the Class II subgroup. Conclusion: Direct pulp capping with MTA and Biodentine, after pulp exposure during excavation of deep caries could maintain pulp vitality in permanent teeth.

HOMO-HOMO Electron Transfer: An Elegant Strategy for p-Type Doping of Polymer Semiconductors toward Thermoelectric Applications.

Unlike the conventional p-doping of organic semiconductors (OSCs) using acceptors, here, an efficient doping concept for diketopyrrolopyrrole-based polymer PDPP[T]2 -EDOT (OSC-1) is presented using an oxidized p-type semiconductor, Spiro-OMeTAD(TFSI)2 (OSC-2), exploiting electron transfer from HOMOOSC-1 to HOMOOSC-2 . A shift of work function toward the HOMOOSC-1 upon doping is confirmed by ultraviolet photoelectron spectroscopy (UPS). Detailed X-ray photoelectron spectroscopy (XPS) and UV-vis-NIR absorption studies confirm HOMOOSC-1 to HOMOOSC-2 electron transfer. The reduction products of Spiro-OMeTAD(TFSI)2 to Spiro-OMeTAD(TFSI) and Spiro-OMeTAD is also confirmed and their relative amounts in doped samples is determined. Mott-Schottky analysis shows two orders of magnitude increase in free charge carrier density and one order of magnitude increase in the charge carrier mobility. The conductivity increases considerably by four orders of magnitude to a maximum of 10 S m-1 for a very low doping ratio of 8 mol%. The doped polymer films exhibit high thermal and ambient stability resulting in a maximum power factor of 0.07 µW m-1  K-2 at a Seebeck coefficient of 140 µV K-1 for a very low doping ratio of 4 mol%. Also, the concept of HOMOOSC-1 to HOMOOSC-2 electron transfer is a highly efficient, stable and generic way to p-dope other conjugated polymers.

Direct evidence for secondary interactions in planar and nonplanar aromatic π-conjugates and their photophysical characteristics in solid-state assemblies.

Direct evidence for non-covalent secondary interactions in planar and nonplanar aromatic π-conjugates and their solid-state assemblies is established. A series of horizontally, vertically, and radially expanded oligo(phenylenevinylene)s (H-OPVs, V-OPVs, and R-OPVs, respectively) were designed with a fixed π-core and variable alkyl chain lengths on the periphery. Single-crystal structures of the OPVs were resolved to trace the secondary interactions that direct the solid-state self-organization and molecular packing of the chromophores. The H-OPVs were found to be planar, and they did not show any secondary interactions in the crystal lattices. The V-OPVs and R-OPVs were found to be nonplanar and to exhibit multiple CH/π hydrogen-bonding interactions among aryl hydrogen donors and acceptors. The enthalpies of the melting and crystallization transitions revealed that the planar H-OPVs are highly crystalline compared with the nonplanar R-OPVs and V-OPVs. Polarized light microscopy studies revealed the formation of one-dimensional nematic mesophases in H-OPVs. The absolute solid-state photoluminescence quantum yields (PLQYs) of the OPVs were determined using an integrating sphere setup. The highly packed H-OPVs showed low PLQYs compared with those of the weakly packed V-OPVs and R-OPVs. Time-resolved fluorescence decay measurements revealed that the excited-state decay dynamics of highly packed H-OPVs was much faster with respect to their low PLQYs. The decay profiles were found to be relatively slow (with higher life time (τ)) in the V-OPVs and R-OPVs. A field-effect transistor (FET) device was constructed for an OPV sample that showed a hole carrier mobility in the range of 10(-5) cm(2) V(-1) s(-1). The present investigation thus provides a new opportunity to trace the role of secondary interactions on π-conjugated mesophase self-assemblies and their solid-state emission and FET devices, more specifically based on OPV chromophores.

Probing the role of chain length on the diffusion dynamics of π-conjugated polymers by fluorescence correlation spectroscopy.

We investigate the role of the chain length and molecular weight distribution on the diffusion dynamics of freshly synthesized MEH-PPV polymer chains. For the above purpose, a new technique based on combination of size exclusion chromatography (SEC) with fluorescence correlation spectroscopy (FCS) is developed to probe the diffusion dynamics of a narrow molecular weight distribution of fractionated samples of 20-500 kDa. The narrow dispersed samples were characterized by absorbance, emission, and time-resolved fluorescence decay techniques. The results revealed that the properties of fractionated samples were almost uniform for a wide range of molecular weights. A maximum entropy based method for FCS data analysis is employed to obtain the correct diffusion coefficients of the polymer chains with heterogeneous dynamics. The FCS experiment on the unfractionated broad molecular weight sample is not enough to establish the correlation between the molecular weight of the chains with diffusion dynamics and emphasized the need for relatively monodispersed π-conjugated polymers. FCS results show that higher molecular weight chains diffuse much faster than shorter ones. Atomic force microscopy revealed that 300 kDa polymers produced 130 nm particles, whereas 50 kDa polymer chains formed micrometer size aggregates. At higher molecular weights, the strong chain interactions promote the formation of globular (or tightly packed) particles which diffuse faster in solution. The low molecular weight chains experience strong interparticle interaction; as a consequence, the diffusion of chains becomes slower. In the present investigation, we demonstrate the need for the narrow polydisperse sample for establishing the correlation between diffusion dynamics and chain length (or molecular weights) of π-conjugated polymers using a single molecule spectroscopy technique such as FCS.

Supramolecular liquid crystalline π-conjugates: the role of aromatic π-stacking and van der Waals forces on the molecular self-assembly of oligophenylenevinylenes.

Here, we report a unique design strategy to trace the role of aromatic π-stacking and van der Waals interactions on the molecular self-organization of π-conjugated building blocks in a single system. A new series of bulky oligophenylenevinylenes (OPVs) bearing a tricyclodecanemethylene (TCD) unit in the aromatic π-core with flexible long methylene chains (n = 0-12 and 16) in the longitudinal position were designed and synthesized. The OPVs were found to be liquid crystalline, and their enthalpies of phase transitions (also entropies) showed odd-even oscillation with respect to the number of carbon atoms in alkyl chains. OPVs with an even number of methylene units in the side chains showed higher enthalpies with respect to their highly packed solid structures compared to odd-numbered ones. Polarized light microscopic analysis confirmed the formation of cholesteric liquid crystalline (LC) phases of fan shaped textures with focal conics in OPVs with 5 ≤ n ≤ 9. OPVs with longer alkyl chains (OPV-10 to OPV-12) produced a birefringence pattern consisting of dark and bright ring-banded suprastructures. The melting temperature followed a sigmoidal trend, indicating the transformation of molecular self-organization in OPVs from solid to ring-banded suprastructures via cholesteric LC intermediates. At longer alkyl chain lengths, the van der Waals interactions among the alkyl chains became predominant and translated the mesogenic effect across the lamellae; as a consequence, the lamellae underwent twisted self-organization along the radial growth direction of the spherulites to produce bright and dark bands. Scanning electron microscope (SEM) analysis of cholesteric LC and ring-banded textures strongly supported the existence of twisted lamellae in the OPVs with ring-banded textures. Variable temperature X-ray diffraction analysis confirmed the reversibility of the molecular self-organization in the solid state and also showed the existence of the higher ordered lamellar structure in ring-banded OPVs. Photophysical characterizations such as excitation, emission, and time resolved fluorescence decay measurements were employed to trace molecular self-organization in their liquid crystalline phases. The emission spectra of the OPV samples showed odd-even oscillation in their emission wavelengths with respect to the length of alkyl chains. Highly packed even-OPVs showed more blue shift compared to that of less crystalline odd-OPVs. Time dependent fluorescence decay of OPVs followed a biexponential fit, and their lifetimes (τ(1) and τ(2) values) revealed that the decay is faster for odd-OPVs compared to even-OPVs. Among all the OPVs, the τ(2) values for OPV-8 and OPV-12 were found to be much higher, indicating their high luminescent characteristics. In a nut shell, bulky liquid crystalline OPV chromophores were cleverly utilized, for the first time, to probe the aromatic π-stacking versus van der Waals interactions on the molecular self-organization of π-conjugated system.