Cold maceration extraction of wild fruit Terminalia bellirica (Gaertn.) Roxb.: exploring its bioactives for biomedical applications.

Terminalia bellirica (T. bellirica) (Gaertn.) Roxb. is a well-known traditional medicinal plants that show promising treatment because of fewer side effects in humans. In the present study, the total phenol, flavonoid, condensed and hydrolyzable tannins extracted and analyzed from cold macerated (CM) T. bellirica (Gaertn.) Roxb. fruit (TBF) and leaves (TBL) extract with the identification of bioactive compounds using GC-MS/MS technique. The highest amount of bioactive content was found in ethanolic extract than toluene. Current experimental data of TBF extract shows the maximum and significant biological activity like free radical scavenging activity against DPPH and FRAP assays with IC50 values of 51.07 ± 0.52 µg/ml and 63.14 ± 0.59 µg/ml respectively. However, IC50 cytotoxicity values of TBF extract on MCF-7 cells for 24 hrs was found to be 6.34 ± 0.72 µg/ml. Minimum inhibitory concentration (MIC) for infectious pathogens Escherichia coli and Bacillus cereus was >12.5 µg/ml and >100 µg/ml respectively, however, anti-inflammatory activity was demonstrated as an IC50 value of 509.1 ± 1.72 µg/ml. Cold macerated fruit extract revealed threatening inhibitory potential against the α-amylase and α-glucosidase enzymes, with IC50 of 50.98 ± 0.23 µg/ml and 46.70 ± 1.38 µg/ml respectively. Finally, the outcome of this study showed that T. bellirica (Gaertn.) Roxb. fruit extract could be an effective source of bioactives with efficient biomedical properties.

Self-Assembled Lanthanum Oxide Nanoflakes by Electrodeposition Technique for Resistive Switching Memory and Artificial Synaptic Devices.

In recent years, many metal oxides have been rigorously studied to be employed as solid electrolytes for resistive switching (RS) devices. Among these solid electrolytes, lanthanum oxide (La2 O3 ) is comparatively less explored for RS applications. Given this, the present work focuses on the electrodeposition of La2 O3 switching layers and the investigation of their RS properties for memory and neuromorphic computing applications. Initially, the electrodeposited La2 O3 switching layers are thoroughly characterized by various analytical techniques. The electrochemical impedance spectroscopy (EIS) and Mott-Schottky techniques are probed to understand the in situ electrodeposition, RS mechanism, and n-type semiconducting nature of the fabricated La2 O3 switching layers. All the fabricated devices exhibit bipolar RS characteristics with excellent endurance and stable retention. Moreover, the device mimics the various bio-synaptic properties such as potentiation-depression, excitatory post-synaptic currents, and paired-pulse facilitation. It is demonstrated that the fabricated devices are non-ideal memristors based on double-valued charge-flux characteristics. The switching variation of the device is studied using the Weibull distribution technique and modeled and predicted by the time series analysis technique. Based on electrical and EIS results, a possible filamentary-based RS mechanism is suggested. The present results assert that La2 O3 is a promising solid electrolyte for memory and brain-inspired applications.

Perioperative Systemic Therapy for Resectable Non-Small Cell Lung Cancer.

Despite remarkable treatment advancements in patients with advanced non-small cell lung cancer (NSCLC), recurrence rates for those with resectable, early-stage disease remains high. Immune checkpoint inhibitors and targeted therapies are 2 promising treatment modalities that may improve survival outcomes for patients with resected NSCLC when moved from the advanced stage to the curable setting. There are many clinical studies that have evaluated or are currently evaluating immunotherapy or targeted therapy in the perioperative setting, and recent trials such as CheckMate 816, ADAURA, and IMpower010 have led to new approvals and demonstrated the promise of this approach. This review discusses recent and ongoing neoadjuvant and adjuvant systemic therapy trials in NSCLC, and where the field may be going in the near future.

Management of Immunotherapy-Related Toxicities, Version 1.2022, NCCN Clinical Practice Guidelines in Oncology.

The aim of the NCCN Guidelines for Management of Immunotherapy-Related Toxicities is to provide guidance on the management of immune-related adverse events resulting from cancer immunotherapy. The NCCN Management of Immunotherapy-Related Toxicities Panel is an interdisciplinary group of representatives from NCCN Member Institutions, consisting of medical and hematologic oncologists with expertise across a wide range of disease sites, and experts from the areas of dermatology, gastroenterology, endocrinology, neurooncology, nephrology, cardio-oncology, ophthalmology, pulmonary medicine, and oncology nursing. The content featured in this issue is an excerpt of the recommendations for managing toxicities related to CAR T-cell therapies and a review of existing evidence. For the full version of the NCCN Guidelines, including recommendations for managing toxicities related to immune checkpoint inhibitors, visit NCCN.org.

Cases from the Immune-Related Adverse Event Tumor Board: Diagnosis and Management of Immune Checkpoint Blockade-Induced Diabetes.

The addition of immune checkpoint inhibitors to the armamentarium of cancer therapies has resulted in unprecedented improvement in clinical outcomes for a vast range of malignancies. Because they interfere with the physiologic function of immune checkpoints, such as programmed cell death protein 1 or cytotoxic T-lymphocyte-associated protein 4, to promote self-tolerance, these agents are associated with a unique spectrum of immune-related adverse events (irAEs). Immune-mediated endocrinopathies are among the most commonly noted irAEs. Immune-mediated diabetes is an uncommon irAE but can be associated with significant morbidity if it is not recognized and treated in a time-sensitive manner. In this manuscript, we present a case based discussion and review of the literature pertaining to immune-mediated diabetes associated with immune checkpoint blockade. KEY POINTS: Immune checkpoint inhibitor associated diabetes mellitus often resembles type 1 diabetes mellitus (DM) in its pathophysiology and clinical manifestations. However, some patients may present with type 2 DM or worsening hyperglycemia in the setting of pre-existent DM. Early recognition and management is key to preventing life-threatening events such as diabetic ketoacidosis. Endocrinology referral and interdisciplinary management should be considered for every patient to optimize glycemic control and to ensure optimal monitoring for long-term microvascular complications.

An Open-Label Phase II Trial of Bevacizumab plus Docetaxel and Gemcitabine in Advanced, Previously Untreated Nonsquamous Non-Small Cell Lung Cancer.

LESSONS LEARNED: The combination of bevacizumab with docetaxel-gemcitabine resulted in unacceptable toxicity, particularly a high rate of pulmonary toxicity (30%).Despite promising efficacy, excessive toxicity of this regimen does not support its use in patients with advanced nonsquamous non-small cell lung cancer. BACKGROUND: Prior to immunotherapy, standard treatment for advanced non-small cell lung cancer (NSCLC) was platinum doublet chemotherapy. In a previous phase II study, docetaxel-gemcitabine demonstrated comparable efficacy and tolerability to platinum doublets. In this phase II trial, we evaluated the efficacy and tolerability of adding bevacizumab to docetaxel- gemcitabine in patients with advanced nonsquamous NSCLC. METHODS: Patients with untreated advanced nonsquamous NSCLC were treated with up to six cycles of docetaxel-gemcitabine-bevacizumab, followed by bevacizumab until progression. The primary endpoint for this study was 1-year progression-free survival (PFS); secondary endpoints were safety, overall response rate (ORR) and overall survival (OS). The planned sample size was 46 patients. RESULTS: A total of 13 patients were enrolled and received a median of six cycles of chemotherapy and four cycles of bevacizumab. The treatment was poorly tolerated, with five patients requiring dose reduction and four discontinuing treatment for toxicity. Grade 3-5 nonhematologic toxicity was seen in 10 patients, and 4 (30%) were hospitalized with pulmonary toxicity possibly related to study drugs. At this point, enrollment was halted for safety concerns. The 12-month PFS was 8%. In 11 evaluable patients, ORR was 72%, median PFS 6 months, and median OS was 11 months. CONCLUSION: Docetaxel, gemcitabine, and bevacizumab at this dose and schedule resulted in excessive toxicity. Despite promising efficacy, in light of efficacious and safe alternative therapies, this regimen should not be used to treat advanced NSCLC.

Cases from the irAE Tumor Board: A Multidisciplinary Approach to a Patient Treated with Immune Checkpoint Blockade Who Presented with a New Rash.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment paradigms for a broad spectrum of malignancies. Because immune checkpoint inhibitors rely on immune reactivation to eliminate cancer cells, they can also lead to the loss of immune tolerance and result in a wide range of phenomena called immune-related adverse events (irAEs). At our institution, the management of irAEs is based on multidisciplinary input obtained at an irAE tumor board that facilitates expedited opinions from various specialties and allows for a more uniform approach to these patients. In this article, we describe a case of a patient with metastatic urothelial carcinoma who developed a maculopapular rash while being treated with a programmed death-ligand 1 inhibitor. We then describe the approach to management of dermatologic toxicities with ICIs based on the discussion at our irAE Tumor Board. KEY POINTS: Innocuous symptoms such as pruritis or a maculopapular rash may herald potentially fatal severe cutaneous adverse reactions (SCARs); therefore, close attention must be paid to the symptoms, history, and physical examination of all patients.Consultation with dermatology should be sought for patients with grade 3 or 4 toxicity or SCARs and prior to resumption of immune checkpoint inhibitors for patients with grade 3 or higher toxicity.A multidisciplinary immune-related adverse events (irAE) tumor board can facilitate timely input and expertise from various specialties, thereby ensuring a streamlined approach to management of irAEs.

Interplay between the Conformational Flexibility and Photoluminescent Properties of Mononuclear Pyridinophanecopper(I) Complexes.

The macrocyclic ligand conformational behavior in solution, solid-state structures and the photophysical properties of copper(I) cationic and neutral mononuclear complexes supported by tetradentate N, N'-dialkyl-2,11-diaza[3.3](2,6)-pyridinophane ligands RN4 (R = H, Me, iBu, secBu, neoPent, iPr, Ts) were investigated in detail. Steric properties of the alkyl group at the axial amine in the RN4 ligand were found to strongly affect the conformational preferences and dynamic behavior in solution. Several types of conformational exchange processes were revealed by variable-temperature NMR and 2D exchange spectroscopy, including degenerative exchange in a pseudotetrahedral species as well as exchange between two isomers with different conformers of tri- and tetracoordinate RN4 ligands. These exchange processes are slower for the complexes containing bulky alkyl groups at the amine compared to less sterically demanding analogues. A clear correlation is also observed between the steric bulk of the alkyl substituents and the photoluminescent properties of the derived complexes, with less dynamic complexes bearing bulkier alkyl substituents exhibiting higher absolute photoluminescence quantum yield (PLQY) in solution and the solid state: PLQY in solution increases in the order Me < neoPent < iBu < secBu ≈ iPr < tBu. The electrochemical properties of the cationic complexes [(RN4)CuI(MeCN)]X (X = BF4, PF6) were also dependent on the steric properties of the amine substituent.

Surface deterioration and elemental composition of retrieved orthodontic miniscrews.

INTRODUCTION: This study provides insight into surface and elemental analyses of orthodontic retrieved miniscrew implants (MSIs). The sole purpose was to investigate the behavior of MSIs while they are in contact with bone and soft tissues, fluids, and food in the oral cavity. The information thus gathered may help to understand the underlying process of success or failure of MSIs and can be helpful in improving their material composition and design. METHODS: The study was carried out on 28 titanium-alloy MSIs (all from the same manufacturer) split into 3 groups: 18 MSIs were retrieved after successful orthodontic treatment, 5 were failed MSIs, and 5 were as-received MSIs serving as the controls. All MSIs were subjected to energy dispersive x-ray microanalysis to investigate the changes in surface elemental composition and to scanning electron microscopy to analyze their surface topography. Data thus obtained were subjected to suitable statistical analyses. RESULTS: Scanning electron microscope analysis showed surface manufacturing imperfections of the as-received MSIs in the form of stripes. Their elemental composition was confirmed to the specifications of the American Society for Testing of Materials for surgical implants. Retrieved MSIs exhibited generalized surface dullness; variable corrosion; craters in the head, neck, body, and tip regions; and blunting on tips and threads. Energy dispersive x-ray analyses showed deposition of additional elements: calcium had greater significance in its proportion in the body region by 0.056 weight percent; iron was seen in greater proportion in the failed retrieved MSIs compared with the successful miniscrews; cerium was seen in greater proportions in the head region by 0.128 weight percent and in the neck region by 0.147 weight percent than in the body and tip regions of retrieved MSIs. CONCLUSIONS: Retrieved MSIs showed considerable surface and structural alterations such as dullness, corrosion, and blunting of threads and tips. Their surfaces showed interactions and adsorption of several elements, such as calcium, at the body region. A high content of iron was found on the failed MSIs, and cerium was seen in the head and neck regions of retrieved MSIs.

A hydrogen peroxide-inactivated virus vaccine elicits humoral and cellular immunity and protects against lethal West Nile virus infection in aged mice.

West Nile virus (WNV) is an emerging pathogen that is now the leading cause of mosquito-borne and epidemic encephalitis in the United States. In humans, a small percentage of infected individuals develop severe neuroinvasive disease, with the greatest relative risk being in the elderly and immunocompromised, two populations that are difficult to immunize effectively with vaccines. While inactivated and subunit-based veterinary vaccines against WNV exist, currently there is no vaccine or therapy available to prevent or treat human disease. Here, we describe the generation and preclinical efficacy of a hydrogen peroxide (H(2)O(2))-inactivated WNV Kunjin strain (WNV-KUNV) vaccine as a candidate for further development. Both young and aged mice vaccinated with H(2)O(2)-inactivated WNV-KUNV produced robust adaptive B and T cell immune responses and were protected against stringent and lethal intracranial challenge with a heterologous virulent North American WNV strain. Our studies suggest that the H(2)O(2)-inactivated WNV-KUNV vaccine is safe and immunogenic and may be suitable for protection against WNV infection in vulnerable populations.

Green Recipes for Pyrimidine.

Pyrimidines serve as key structural components in chemical frameworks and biological processes. Several pyrimidine analogues have been produced over the years by means of traditional methods that necessitated large amounts of solvents, reagents, and, most importantly, additional time, which has led them to become prohibitive. These procedures are now being replaced with more cost-effective adaptive methodologies that incorporate one-pot synthesis and greener approaches involving various green solvents and catalysts. The current review covers a number of green synthetic techniques, including ultrasound-assisted synthesis, visible light irradiation synthesis, solvent-free synthesis, catalyst-free synthesis, microwave-assisted synthesis, and green catalyst synthesis for the synthesis of pyrimidine derivatives. Accordingly, it integrates different strategies to synthesize heterocyclic pyrimidine analogues in a well-organized manner.

Clinical Outcomes With Pembrolizumab-Based Therapies in Recurrent/Refractory NSCLC After Chemoradiation and Consolidative Durvalumab.

BACKGROUND: Often, patients with NSCLC experience recurrent/refractory (R/R) disease within 2 years of chemoradiation (CRT) and consolidative durvalumab. Despite prior immune checkpoint inhibitor exposure, immunotherapy with or without chemotherapy is typically initiated if a driver-oncogene is absent. However, there remains a paucity of data regarding the efficacy of immunotherapy in this patient population. Here, we present survival outcomes associated with pembrolizumab for R/R NSCLC. MATERIALS AND METHODS: We retrospectively assessed adults with NSCLC who received pembrolizumab for R/R disease between January 2016 to January 2023. Primary objective was to estimate OS and PFS in this cohort compared to historical outcomes. Secondary objective was to compare OS and PFS among subgroups. RESULTS: Fifty patients were evaluated. Median follow-up time was 11.3 months (2.9-38.2). OS was 10.6 months (95% CI, 8.8-19.2); 1-year OS rate 49% (95% CI, 36 - 67%). PFS was 6.1 months (95% CI, 4.7-9.0); 1-year PFS rate 25% (95% CI, 15%-42%). Current smokers had significantly better median OS/PFS as compared to former smokers (NA vs. 10.5 and 9.9 vs. 6.0 months, respectively). The addition of chemotherapy demonstrated an OS benefit (median OS 12.9 vs. 6.0 months) but was not statistically significant. CONCLUSION: Patients with R/R NSCLC represent a distinct cohort with inferior survival outcomes when compared to those with de novo stage IV disease treated with pembrolizumab-based regimens. Based on our findings, we recommend oncologists exercise caution when considering checkpoint inhibitor monotherapy in the front-line setting for R/R NSCLC, regardless of PD-L1 expression.

Digitization in Skin Shade Matching for Maxillofacial Prostheses: A Systematic Review.

Color matching of maxillofacial prostheses for the restoration of maxillofacial defects is an important factor for esthetic results. Various methods have been introduced for the accurate and reliable color matching of prostheses with the skin color of patients. A systematic review was conducted to search the existing literature on color-matching digital techniques for maxillofacial prostheses. An electronic literature search was conducted in PubMed/Medline, Scopus, and Web of Science from January 2000 to December 2022 using Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Two independent reviewers conducted the search. Eight articles that fulfilled the inclusion criteria after a full-text evaluation were included in this review. Most of these studies were published in prosthodontics journals and conducted in various countries around the world. A computerized color formulation system was used in three studies; a non-contact spectroradiometer (PR 705; Photo Research Inc., Chatsworth, CA) with a Xenon arc lamp was used in two studies; a mobile phone colorimeter was used in one study; additive manufacturing of 3D facial skin with a spectrophotometer was used in one study; and a recently introduced computerized method known as e-skin (Spectromatch, Bath, UK) was used in two studies. Most of these methods were accurate in color matching, except for the additive manufacturing system, which showed less accuracy, but good repeatability. Owing to a lack of sufficient studies, no method can be labeled as the best method for color-matching maxillofacial prostheses. The latest computerized method, the e-skin, can be used to achieve better accuracy and good color matching. However, further studies are required to validate the use of e-skin for precise color matching.

Review of Electrochemically Synthesized Resistive Switching Devices: Memory Storage, Neuromorphic Computing, and Sensing Applications.

Resistive-switching-based memory devices meet most of the requirements for use in next-generation information and communication technology applications, including standalone memory devices, neuromorphic hardware, and embedded sensing devices with on-chip storage, due to their low cost, excellent memory retention, compatibility with 3D integration, in-memory computing capabilities, and ease of fabrication. Electrochemical synthesis is the most widespread technique for the fabrication of state-of-the-art memory devices. The present review article summarizes the electrochemical approaches that have been proposed for the fabrication of switching, memristor, and memristive devices for memory storage, neuromorphic computing, and sensing applications, highlighting their various advantages and performance metrics. We also present the challenges and future research directions for this field in the concluding section.

Sealing Ability of Obturation with Different Sealers Applied Over Apically Separated Rotary File - Retrograde Bacterial Leakage Study.

Background and Aims: . Retrieval of separated rotary file may not be possible many times. Then sealing of coronal root canal system depends on sealing ability of root canal sealers. The type of seal to be obtained should be bacterial-tight seal. Hence it is important to evaluate the sealing ability of obturation with different newer sealers with separated file in apical 3rd of root canals with bacterial penetration method using e.fecalis. Methods: Forty six human mandibular molars extracted for periodontal reasons were collected. After Decoronation of teeth Protaper rotary S1 files (Dentsply Maillefer) were intentionally separated in apical third of canal and obturated with gutta-percha (Prime Dental Products, India) along with zinc oxide eugenol sealer (Dental products of India-Mumbai) in Group I, Nano Zinc oxide eugenol (Nano Research Lab, Jharkand, India) in Group II and MTA sealer (Angelus, Londrina, Brazil) in Group III. Samples were assessed for bacterial leakage with E fecalis for 48 hours. The number of colony forming units was assessed. Results: The values obtained were subjected to one way ANOVA test and significance level was set to 0.05. Group I scored the highest mean value of (6.58), followed by Group II (3.91). The lowest Mean value was with Group III (2.91). However there was no statistical significant difference in Mean values among groups with (p-value 0.05). Conclusion: The mean value of colony forming units in Group III was 2.91, in Group II 3.91 and 6.58 in Group I. None of the groups demonstrated complete bacteria-tight seal.

Ethylene binding in mono- and binuclear CuI complexes with tetradentate pyridinophane ligands.

Herein we report a series of CuI complexes supported by tetradentate RN4 pyridinophane ligands that coordinate to ethylene forming either mononuclear complexes with ethylene coordinated in an η2-mode or a binuclear complex where ethylene binds to two Cu atoms in a µ-η2-η2-mode, depending on the steric effects of the RN4 ligand and the reaction conditions. In the binuclear complex with bridging ethylene, the CC bond is significantly elongated, with a bond length of 1.444(8) Å according to X-ray diffraction analysis. This complex represents the only examination a µ-η2-η2-coordinated Cu-olefin complex reported to date, featuring one of the longest reported CC bonds. The spectroscopic characterization, structure, electrochemical properties and solution behavior are analyzed in this study. Coordination of ethylene was found to be reversible in these complexes and more favored in less sterically hindered RN4 ligands, so that ethylene binding is observed in a coordinating solvent (MeCN) environment. In the case of the MeN4 ligand, the ethylene complex is photoluminescent in the solid state. The ethylene binding modes in mono- and binuclear complexes are elucidated through Natural Bond Orbital and QTAIM analyses.

Novel imaging biomarkers predict outcomes in stage III unresectable non-small cell lung cancer treated with chemoradiation and durvalumab.

BACKGROUND: The landmark study of durvalumab as consolidation therapy in NSCLC patients (PACIFIC trial) demonstrated significantly longer progression-free survival (PFS) in patients with locally advanced, unresectable non-small cell lung cancer (NSCLC) treated with durvalumab (immunotherapy, IO) therapy after chemoradiotherapy (CRT). In clinical practice in the USA, durvalumab continues to be used in patients across all levels of programmed cell death ligand-1 (PD-L1) expression. While immune therapies have shown promise in several cancers, some patients either do not respond to the therapy or have cancer recurrence after an initial response. It is not clear so far who will benefit of this therapy or what the mechanisms behind treatment failure are. METHODS: A total of 133 patients with unresectable stage III NSCLC who underwent durvalumab after CRT or CRT alone were included. Patients treated with durvalumab IO after CRT were randomly split into training (D1=59) and test (D2=59) sets and the remaining 15 patients treated with CRT alone were grouped in D3. Radiomic textural patterns from within and around the target nodules were extracted. A radiomic risk score (RRS) was built and was used to predict PFS and overall survival (OS). Patients were divided into high-risk and low-risk groups based on median RRS. RESULTS: RRS was found to be significantly associated with PFS in D1 (HR=2.67, 95% CI 1.85 to 4.13, p<0.05, C-index=0.78) and D2 (HR=2.56, 95% CI 1.63 to 4, p<0.05, C-index=0.73). Similarly, RRS was associated with OS in D1 (HR=1.89, 95% CI 1.3 to 2.75, p<0.05, C-index=0.67) and D2 (HR=2.14, 95% CI 1.28 to 3.6, p<0.05, C-index=0.69), respectively. RRS was found to be significantly associated with PFS in high PD-L1 (HR=3.01, 95% CI 1.41 to 6.45, p=0.0044) and low PD-L1 (HR=2.74, 95% CI 1.8 to 4.14, p=1.77e-06) groups. Moreover, RRS was not significantly associated with OS in the high PD-L1 group (HR=2.08, 95% CI 0.98 to 4.4, p=0.054) but was significantly associated with OS in the low PD-L1 group (HR=1.61, 95% CI 1.14 to 2.28, p=0.0062). In addition, RRS was significantly associated with PFS (HR=2.77, 95% CI 1.17 to 6.52, p=0.019, C-index=0.77) and OS (HR=2.62, 95% CI 1.25 to 5.51, p=0.01, C-index=0.77) in D3, respectively. CONCLUSIONS: Tumor radiomics of pretreatment CT images from patients with stage III unresectable NSCLC were prognostic of PFS and OS to CRT followed by durvalumab IO and CRT alone.

Prediction of future imagery of lung nodule as growth modeling with follow-up computed tomography scans using deep learning: a retrospective cohort study.

Background: Risk prediction models of lung nodules have been built to alleviate the heavy interpretative burden on clinicians. However, the malignancy scores output by those models can be difficult to interpret in a clinically meaningful manner. In contrast, the modeling of lung nodule growth may be more readily useful. This study developed a CT-based visual forecasting system that can visualize and quantify a nodule in three dimensions (3D) in any future time point using follow-up CT scans. Methods: We retrospectively included 246 patients with 313 lung nodules with at least 1 follow-up CT scan. For the manually segmented nodules, we calculated geometric properties including CT value, diameter, volume, and mass, as well as growth properties including volume doubling time (VDT), and consolidation-to-tumor ratio (CTR) at follow-ups. These nodules were divided into growth and non-growth groups by thresholding their VDTs. We then developed a convolutional neural network (CNN) to model the imagery change of the nodules from baseline CT image (combined with the nodule mask) to follow-up CT image with a particular time interval. The model was evaluated on the geometric and radiological properties using either logistic regression or receiver operating characteristic (ROC) curve. Results: The lung nodules consisted of 115 ground glass nodules (GGN) and 198 solid nodules and were followed up for an average of 354 days with 2 to 11 scans. The 2 groups differed significantly in most properties. The prediction of our forecasting system was highly correlated with the ground truth with small relative errors regarding the four geometric properties. The prediction-derived VDTs had an area under the curve (AUC) of 0.857 and 0.843 in differentiating growth and non-growth nodules for GGN and solid nodules, respectively. The prediction-derived CTRs had an AUC of 0.892 in classifying high- and low-risk nodules. Conclusions: This proof-of-concept study demonstrated that the deep learning-based model can accurately forecast the imagery of a nodule in a given future for both GGNs and solid nodules and is worthy of further investigation. With a larger dataset and more validation, such a system has the potential to become a prognostication tool for assessing lung nodules.

Single and double deprotonation/dearomatization of the N,S-donor pyridinophane ligand in ruthenium complexes.

We report a series of ruthenium complexes with a tetradentate N,S-donor ligand, 2,11-dithia[3.3](2,6)pyridinophane (N2S2), that undergo single and double deprotonation in the presence of a base leading to the deprotonation of one or both pyridine rings. Both singly and doubly deprotonated complexes were structurally characterized by single-crystal X-ray diffraction. The NMR spectra are indicative of the dearomatization of one or both pyridine rings upon the deprotonation of the CH2-S arm, similar to the dearomatization of phosphine-containing pincer ligands. The deprotonated (N2S2)Ru complexes did not show appreciable catalytic or stoichiometric reactivity in transfer hydrogenation, hydrogenation and dehydrogenation of alcohols, and attempted activation of H2, CO2, and other substrates. Such a lack of reactivity is likely due to the low stability of the deprotonated species as evident from the structural characterization of one of the decomposition products in which shrinkage of the macrocyclic ring occurs via picolyl arm migration.

A tumor vasculature-based imaging biomarker for predicting response and survival in patients with lung cancer treated with checkpoint inhibitors.

Tumor vasculature is a key component of the tumor microenvironment that can influence tumor behavior and therapeutic resistance. We present a new imaging biomarker, quantitative vessel tortuosity (QVT), and evaluate its association with response and survival in patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitor (ICI) therapies. A total of 507 cases were used to evaluate different aspects of the QVT biomarkers. QVT features were extracted from computed tomography imaging of patients before and after ICI therapy to capture the tortuosity, curvature, density, and branching statistics of the nodule vasculature. Our results showed that QVT features were prognostic of OS (HR = 3.14, 0.95% CI = 1.2 to 9.68, P = 0.0006, C-index = 0.61) and could predict ICI response with AUCs of 0.66, 0.61, and 0.67 on three validation sets. Our study shows that QVT imaging biomarker could potentially aid in predicting and monitoring response to ICI in patients with NSCLC.