THE IMPACT OF ROUTINE CARDIAC TROPONIN I-BASED CARDIOTOXICITY SCREENING ON CLINICAL OUTCOMES IN PATIENTS ON CANCER IMMUNOTHERAPY.

Purpose: Immune checkpoint inhibitors (ICI) used as cancer therapy have been associated with a range of cardiac immune-related adverse events (irAEs), including fulminant myocarditis with a high case fatality rate. Early detection through cardiotoxicity screening by biomarker monitoring can lead to prompt intervention and improved patient outcomes. In this study, we investigate the association between cardiotoxicity screening with routine serial troponin I monitoring in asymptomatic patients receiving ICI, cardiovascular adverse event (CV AE) detection, and overall survival (OS). Methods: We instituted a standardized troponin I screening protocol at baseline and with each ICI dose (every 2-4 weeks) in all patients receiving ICI at our center starting Jan 2019. We subsequently collected data in 825 patients receiving ICI at our institution from January 2018 to October 2021. Of these patients, 428 underwent cardiotoxicity screening with serial troponin I monitoring during ICI administration (Jan 2019-Oct 2021) and 397 patients were unmonitored (Jan 2018-Dec 2018). We followed patients for nine months following their first dose of ICI and compared outcomes of CV AEs and OS between monitored and unmonitored patients. Additionally, we investigated rates of CV AEs, all-cause mortality, and oncologic time-to-treatment failure (TTF) between patients with an elevated troponin I value during the monitoring period versus patients without elevated troponin I. Results: We found a lower rate of severe (grades 4-5) CV AEs, resulting in critical illness or death, in patients who underwent troponin monitoring (0.5%) compared to patients who did not undergo monitoring (1.8%), (HR 0.17, 95% CI 0.02-0.79, p = 0.04). There was no difference in overall CV AEs (grades 3-5) or OS between monitored and unmonitored patients. In the entire cohort, patients with at least one elevated troponin I during the follow up period, during routine monitoring or unmonitored, had a higher risk of overall CV AEs (HR 10.96, 95% CI 4.65-25.85, p<0.001) as well as overall mortality (HR 2.67, 95% CI 1.69 - 4.10, p<0.001) compared to those without elevated troponin. Oncologic time-to-treatment failure (TTF) was not significantly different in a sub-cohort of monitored vs. unmonitored patients. Conclusions: Patients undergoing cardiotoxicity screening with troponin I monitoring during ICI therapy had a lower rate of severe (grade 4-5) CV AEs compared patients who were not screened. Troponin I elevation in screened and unscreened patients was significantly associated with increased CV AEs as well as increased mortality. Troponin I monitoring did not impact oncologic time-to-treatment-failure in a sub-cohort analysis of patients treated with ICI. These results provide preliminary evidence for clinical utility of cardiotoxicity screening with troponin I monitoring in patients receiving ICI therapy.

Characterization and biological evaluation of a novel flavonoid-collagen antioxidant hydrogel with cytoprotective properties.

Reactive oxygen species (ROS) play a critical and important role during wound healing but excess ROS at the wound site can lead to cellular damage and sub-optimal healing. Minimizing oxidative damage to the wound site and any supplemental therapeutic cells can be achieved by delivering exogenous antioxidants. Collagen hydrogels are ideal wound care materials due to their biocompatibility, high water content, and porous, three-dimensional architecture. Yet, they lack the inherent antioxidant activity that could help mitigate excess ROS at a wound site. This work formulates and evaluates the in vitro biocompatibility and antioxidant capabilities of collagen-fibroblast hydrogels combined with the polyphenolic antioxidant luteolin. Collagen solutions mixed with luteolin readily assembled into robust hydrogels with increasing gel strength due to increasing concentrations of luteolin. SEM images confirmed a mean pore size of 2.2 µm and a drastically different macromolecular ultrastructure with extensive fine crosslinking relative to collagen. Adequate cell viability and metabolic activity of dermal fibroblasts cultured within the gels were measured across all formulations, resulting in higher antioxidant activity and more than double the protection to cells from oxidative damage than traditional collagen hydrogels. Given these results, luteolin-collagen hydrogels demonstrate the potential for superior wound-healing properties when compared to collagen alone.

Interacting collagen and tannic acid Particles: Uncovering pH-dependent rheological and thermodynamic behaviors.

HYPOTHESIS: Biomaterials such as collagen and tannic acid (TA) particles are of interest in the development of advanced hybrid biobased systems due to their beneficial therapeutic functionalities and distinctive structural properties. The presence of numerous functional groups makes both TA and collagen pH responsive, enabling them to interact via non-covalent interactions and offer tunable macroscopic properties. EXPERIMENT: The effect of pH on the interactions between collagen and TA particles is explored by adding TA particles at physiological pH to collagen at both acidic and neutral pH. Rheology, isothermal titration calorimetry (ITC), turbidimetric analysis and quartz crystal microbalance with dissipation monitoring (QCM-D) are used to study the effects. FINDINGS: Rheology results show significant increase in elastic modulus with an increase in collagen concentration. However, TA particles at physiological pH provide stronger mechanical reinforcement to collagen at pH 4 than collagen at pH 7 due to the formation of a higher extent of electrostatic interaction and hydrogen bonding. ITC results confirm this hypothesis, with larger changes in enthalpy, |ΔH|, observed when collagen is at acidic pH and |ΔH| > |TΔS| indicating enthalpy-driven collagen-TA interactions. Turbidimetric analysis and QCM-D help to identify structural differences of the collagen-TA complexes and their formation at both pH conditions.

A Scalable Microstructure Photonic Coating Fabricated by Roll-to-Roll "Defects" for Daytime Subambient Passive Radiative Cooling.

The deep space's coldness (∼4 K) provides a ubiquitous and inexhaustible thermodynamic resource to suppress the cooling energy consumption. However, it is nontrivial to achieve subambient radiative cooling during daytime under strong direct sunlight, which requires rational and delicate photonic design for simultaneous high solar reflectivity (>94%) and thermal emissivity. A great challenge arises when trying to meet such strict photonic microstructure requirements while maintaining manufacturing scalability. Herein, we demonstrate a rapid, low-cost, template-free roll-to-roll method to fabricate spike microstructured photonic nanocomposite coatings with Al2O3 and TiO2 nanoparticles embedded that possess 96.0% of solar reflectivity and 97.0% of thermal emissivity. When facing direct sunlight in the spring of Chicago (average 699 W/m2 solar intensity), the coatings show a radiative cooling power of 39.1 W/m2. Combined with the coatings' superhydrophobic and contamination resistance merits, the potential 14.4% cooling energy-saving capability is numerically demonstrated across the United States.

Trends and correlates of low HIV knowledge among ever-married women of reproductive age: Evidence from cross-sectional Bangladesh Demographic and Health Survey 1996-2014.

BACKGROUND: The human immunodeficiency virus (HIV) burden has frequently been changing over time due to epidemiological and demographic transitions. To safeguard people, particularly women of reproductive age, who can be exposed to transmitting this burden to the next generation, knowledge regarding this life-threatening virus needs to be increased. This research intends to identify the trends and associated correlates of "low" HIV knowledge among ever-married women of reproductive age in Bangladesh from 1996 to 2014. METHODS: We analyzed data derived from six surveys of Bangladesh Demographic and Health Surveys conducted in 1996, 1999, 2004, 2007, 2011, and 2014. Analyses were primarily restricted to ever-married women aged 15-49 years who had ever heard of HIV. The correlates of "low" HIV knowledge were investigated using multiple binary logistic regression models. RESULTS: The study found that the proportion of women with "low" HIV knowledge decreased from 72% in 1996 to 58% in 2014. In adjusted models, age at first marriage, level of education, wealth quintile, and place of residence (except in the survey year 2011) were found to be potential correlates of "low" HIV knowledge in all survey years. In the pooled analysis, we found lower odds of "low" HIV knowledge in the survey years 1999 (Adjusted Odds Ratio: 0.67; 95% CI: 0.57, 0.78), 2004 (AOR: 0.60; 95% CI: 0.52, 0.70), 2007 (AOR: 0.51; 95% CI: 0.44, 0.60), 2011 (AOR: 0.36; 95% CI: 0.32, 0.42) and 2014 (AOR: 0.47; 95% CI: 0.41, 0.54) compared to the survey year 1996. CONCLUSION: The proportion of "low" HIV knowledge has declined over time, although the proportion of women with "low" HIV knowledge still remains high. The prevention of early marriage, the inclusion of HIV-related topics in the curricula, reduction of disparities between urban-rural and the poorest-richest groups may help to improve the level of HIV knowledge among ever-married Bangladeshi women.

Association between Multiple Myeloma and Ulcerative Colitis: A Cross-Sectional Analysis.

BACKGROUND AND AIMS: Multiple myeloma (MM) is a plasma cell dyscrasia that is common among patients with autoimmune diseases. However, the association between ulcerative colitis (UC) and multiple myeloma (MM) is yet to be established. We aimed to evaluate the prevalence of MM among patients with UC in the United States. METHODS: This cross-sectional cohort analysis used the National Inpatient Sample from 2015-2018 to assess the overall MM prevalence among patients with and without UC, and within specific demographic subgroups. Prevalences were compared using a logistic regression model controlling for sex and age. RESULTS: The crude prevalence of MM among patients with UC (n = 1750) compared with patients without UC (n = 366,265) was 0.44% vs. 0.37%, respectively. Patients with UC had increased overall odds of having MM (odds ratio (OR), 1.26). Males with UC had higher prevalence of MM (53.7% vs. 46.3%, respectively) than females. Patients with UC and MM were more likely to be African American than White (15.6% vs. 9.2%, respectively). Patients with UC age >64 had a higher prevalence of MM than those aged below 65 (70.9% vs. 29.1%, respectively). Patients with UC who were obese (BMI > 30) had a higher prevalence of MM than those who were non-obese (12.6% vs. 8.3%). CONCLUSIONS: Overall, UC appears to be associated with MM. This association can be particularly observed in specific demographic groups, such as obese, African American males, or patients >64 years of age. Thus, a high degree of clinical suspicion for MM is warranted, even with minimal symptomatology, in patients with UC, in particular among elder, obese, and African American males.

Plant-biomass-based hybrid seed wraps mitigate yield and post-harvest losses among smallholder farmers in sub-Saharan Africa.

Sustainable practices that reduce food loss are essential for enhancing global food security. We report a 'wrap and plant' seed treatment platform to protect crops from soil-borne pathogens. Developed from the abundantly available wastes of banana harvest and recycled old, corrugated cardboard boxes via chemical-free pulping, these paper-like biodegradable seed wraps exhibit tunable integrity and bioavailability of loaded moieties. These wraps were used for nematode control on yam (Dioscorea cayenensis-rotundata) seed pieces in Benin, a major producer of this staple crop in the sub-Saharan African 'yam belt'. Our seed wraps loaded with ultra-low-volume abamectin (1/100 ≤ commercial formulation) consistently controlled yam nematode (Scutellonema bradys) populations while considerably increasing the yield at various locations over 2015-2018. Substantial reduction in post-harvest tuber weight loss and cracking was observed after 3 and 5 months of storage, contributing to increased value, nutrition and stakeholders' preference for the wrap and plant treatment.

Linear and nonlinear rheology of liberase-treated breast cancer tumors.

Extracellular matrix (ECM) rigidity has been shown to increase the invasive properties of breast cancer cells, promoting transformation and metastasis through mechanotransduction. Reducing ECM stiffness via enzymatic digestion could be a promising approach to slowing breast cancer development by de-differentiation of breast cancer cells to less aggressive phenotypes and enhancing the effectiveness of existing chemotherapeutics via improved drug penetrance throughout the tumor. In this study, we examine the effects of injectable liberase (a blend of collagenase and thermolysin enzymes) treatments on the linear and nonlinear rheology of allograft 4T1 mouse mammary tumors. We perform two sets of in vivo mouse studies, in which either one or multiple treatment injections occur before the tumors are harvested for rheological analysis. The treatment groups in each study consist of a buffer control, free liberase enzyme in buffer, a thermoresponsive copolymer called LiquoGel (LQG) in buffer, and a combined, localized injection of LQG and liberase. All tumor samples exhibit gel-like linear rheological behavior with the elastic modulus significantly larger than the viscous modulus and both independent of frequency. Tumors that receive a single injection of localized liberase have significantly lower tumor volumes and lower tissue moduli at both the center and edge compared to buffer- and free liberase-injected control tumors, while tissue viscoelasticity remains relatively unaffected. Tumors injected multiple times with LQG and liberase also have lower tissue volumes but possess higher tissue moduli and lower viscoelasticities compared to the other treatment groups. We propose that a mechanotransductive mechanism could cause the formation of smaller but stiffer tumors after repeated, localized liberase injections. Large amplitude oscillatory shear (LAOS) experiments are also performed on tissues from the multiple injection study and the results are analyzed using MITlaos. LAOS analysis reveals that all 4T1 tumors from the multiple injection study exhibit nonlinear rheological behavior at high strains and strain rates. Examination of the Lissajous-Bowditch curves, Chebyshev coefficient ratios, elastic moduli, and dynamic viscosities demonstrate that the onset and type of nonlinear behavior is independent of treatment type and elastic modulus, suggesting that multiple liberase injections do not affect the nonlinear viscoelasticity of 4T1 tumors.

Radiotherapy and paclitaxel plus pazopanib or placebo in anaplastic thyroid cancer (NRG/RTOG 0912): a randomised, double-blind, placebo-controlled, multicentre, phase 2 trial.

BACKGROUND: Anaplastic thyroid cancer is a rare and aggressive cancer with no standard radiotherapy-based local treatment. Based on data suggesting synergy between pazopanib and paclitaxel in anaplastic thyroid cancer, NRG Oncology did a double-blind, placebo-controlled, randomised phase 2 clinical trial comparing concurrent paclitaxel and intensity-modulated radiotherapy (IMRT) with the addition of pazopanib or placebo with the aim of improving overall survival in this patient population. METHODS: Eligible patients were aged 18 years or older with a pathological diagnosis of anaplastic thyroid cancer, any TNM stage, Zubrod performance status of 0-2, no recent haemoptysis or bleeding, and no brain metastases. Patients were enrolled from 34 centres in the USA. Initially, a run-in was done to establish safety. In the randomised phase 2 trial, patients in the experimental group (pazopanib) received 2-3 weeks of weekly paclitaxel (80 mg/m2) intravenously and daily pazopanib suspension 400 mg orally followed by concurrent weekly paclitaxel (50 mg/m2), daily pazopanib (300 mg), and IMRT 66 Gy given in 33 daily fractions (2 Gy fractions). In the control group (placebo), pazopanib was replaced by matching placebo. Patients were randomly assigned (1:1) to the two treatment groups by permuted block randomisation by NRG Oncology with stratification by metastatic disease. All investigators, patients, and funders of the study were masked to group allocation. The primary endpoint was overall survival in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This trial is registered with Clinicaltrials.gov, NCT01236547, and is complete. FINDINGS: The safety run-showed the final dosing regimen to be safe based on two out of nine participants having adverse events of predefined concern. Between June 23, 2014, and Dec 30, 2016, 89 patients were enrolled to the phase 2 trial, of whom 71 were eligible (36 in the pazopanib group and 35 in the placebo group; 34 [48%] males and 37 [52%] females). At the final analysis (data cutoff March 9, 2020), with a median follow-up of 2·9 years (IQR 0·002-4·0), 61 patients had died. Overall survival was not significantly improved with pazopanib versus placebo, with a median overall survival of 5·7 months (95% CI 4·0-12·8) in the pazopanib group versus 7·3 months (4·3-10·6) in the placebo group (hazard ratio 0·86, 95% CI 0·52-1·43; one-sided log-rank p=0·28). 1-year overall survival was 37·1% (95% CI 21·1-53·2) in the pazopanib group and 29·0% (13·2-44·8) in the placebo group. The incidence of grade 3-5 adverse events did not differ significantly between the treatment groups (pazopanib 88·9% [32 of 36 patients] and placebo 85·3% [29 of 34 patients]; p=0·73). The most common clinically significant grade 3-4 adverse events in the 70 eligible treated patients (36 in the pazopanib group and 34 in the placebo group) were dysphagia (13 [36%] vs 10 [29%]), radiation dermatitis (8 [22%] vs 13 [38%]), increased alanine aminotransferase (12 [33%] vs none), increased aspartate aminotransferase (eight [22%] vs none), and oral mucositis (five [14%] vs eight [24%]). Treatment-related serious adverse events were reported for 16 (44%) patients on pazopanib and 12 (35%) patients on placebo. The most common serious adverse events were dehydration and thromboembolic event (three [8%] each) in patients on pazopanib and oral mucositis (three [8%]) in those on placebo. There was one treatment-related death in each group (sepsis in the pazopanib group and pneumonitis in the placebo group). INTERPRETATION: To our knowledge, this study is the largest randomised anaplastic thyroid cancer study that has completed accrual showing feasibility in a multicenter NCI National Clinical Trials Network setting. Although no significant improvement in overall survival was recorded in the pazopanib group, the treatment combination was shown to be feasible and safe, and hypothesis-generating data that might warrant further investigation were generated. FUNDING: National Cancer Institute and Novartis.

An Alternative Airway Intervention to Preserve the Surgical Field in Oral and Maxillofacial Surgery.

Background/need. Office-based sedation has become increasingly commonplace in dental offices in recent years, allowing for practitioners to provide broader scope of care for their patients. Maintaining high standards of safety is of utmost importance when sedation is utilized in the office-based setting, especially for patients deemed at a higher-risk for intraoperative airway obstruction. This demographic includes but is not limited to individuals with a medical history significant for obstructive sleep apnea, chronic obstructive pulmonary disease, and morbid obesity. Presently, a wide variety of airway devices exist for use in the event of airway obstruction. However, in the context of oral and maxillofacial surgery, placement of these devices can encroach upon the surgical field, extending the perioperative period and putting the patient at greater long-term risk for maintaining adequate oxygenation. Methodology. The authors describe a preliminary technique trialed in our offices which utilizes a size 5.0 endotracheal tube (5OET) as an adjunct supraglottic airway to help mitigate the issue of oxygen saturation maintenance, as well as unimpeded access to the oral cavity. Implementation of the device requires identifying appropriate candidates during preoperative screening and placing the device through the nare and securing it above the glottis. Device Description. The 'tube kit' is comprised of a standard size straight 5.0 cuffed oral ETT, a 5-mL syringe for inflation of the cuff post insertion, lubricant, flex extension tubing, end tidal sampling line for capnography, tape for securement of the 5OET, and an anesthesia breathing circuit. Optional equipment pieces include an elbow connecter and a foam piece for comfort. Results/Current Status. Preliminary results have demonstrated oxygen saturations maintained above 98% when the 5OET is placed preoperatively. Continued use of the trial device will inform the development of a tube by our clinicians, and its efficacy will be studied in our offices. The next steps will be to start developing a pilot cuff that will be submitted for patent approval after its use in IRB-approved clinical studies.

DNA aerogels and DNA-wrapped CNT aerogels for neuromorphic applications.

Nucleic acids are programmable materials that can self-assemble into defined or stochastic three-dimensional network architectures. Various attributes of self-assembled, cross-linked Deoxyribonucleic acid (DNA) hydrogels have recently been investigated, including their mechanical properties and potential biomedical functions. Herein, for the first time, we describe the successful construction of pure DNA aerogels and DNA-wrapped carbon nanotube (CNT) composite (DNA-CNT) aerogels via a single-step freeze-drying of the respective hydrogels. These aerogels reveal highly porous and randomly branched structures with low density. The electrical properties of pure DNA aerogel mimic that of a simple capacitor; in contrast, the DNA-CNT aerogel displays a fascinating resistive switching behavior in response to an applied bias voltage sweep reminiscent of a volatile memristor. We believe these novel aerogels can serve as a platform for developing complex biomimetic devices for a wide range of applications, including real-time computation, neuromorphic computing, biochemical sensing, and biodegradable functional implants. More importantly, insight obtained here on self-assembling DNA to create aerogels will pave the way to construct novel aerogel-based material platforms from DNA coated or wrapped functional entities.

High-Axial-Aspect Tannic Acid Microparticles Facilitate Gelation and Injectability of Collagen-Based Hydrogels.

Injectable collagen-based hydrogels offer great promise for tissue engineering and regeneration, but their use is limited by poor mechanical strength. Herein, we incorporate tannic acid (TA) to tailor the rheology of the corresponding hydrogels while simultaneously adding the therapeutic benefits inherent to this polyphenolic component. TA in the solution form and needle-shaped TA microparticles are combined with collagen and the respective systems studied for their time-dependent sol-gel transitions (from storage to body temperatures, 4-37 °C) as a function of TA concentration. Compared to systems incorporating TA microparticles, those with dissolved TA, applied at a similar concentration, generate a less significant enhancement of the elastic modulus. Premature gelation at a low temperature and associated colloidal arrest of the system are proposed as a main factor explaining this limited performance. A higher yield stress (elastic stress method) is determined for systems loaded with TA microparticles compared to the system with dissolved TA. These results are interpreted in terms of the underlying interactions of TA with collagen, as probed by spectroscopy and isothermal titration calorimetry. Importantly, hydrogels containing TA microparticles show high cell viability (human dermal fibroblasts) and comparative cellular activity relative to the collagen-only hydrogel. Overall, composite hydrogels incorporating TA microparticles demonstrate a new, simple, and better-performance alternative to cell culturing and difficult implantation scenarios.

A phase II study of tarloxotinib (a hypoxia activated prodrug of a pan-erb tyrosine kinase inhibitor) in patients with recurrent or metastatic squamous cell carcinoma of the head and neck or skin.

BACKGROUND: Tarloxotinib, a hypoxia-activated prodrug of an irreversible pan-ErbB tyrosine kinase inhibitor, represents a novel therapeutic which exploits the tumor-specific hypoxic environment as a mechanism for tumor-specific targeting. This study evaluated the safety and activity of tarloxotinib in recurrent or metastatic (R/M) cutaneous (CSCC) or head and neck squamous cell carcinoma (HNSCC). METHODS: This was a phase II two-stage multi-centre study for patients with R/M HNSCC or CSCC. All patients received tarloxotinib 150 mg/m2 on days 1,8,15 and 22 in a 28-day cycle. Stage 1 enrolled patients in three cohorts: p16-negative HNSCC, p16-positive oropharyngeal SCC, and CSCC. In order for a cohort to proceed to stage 2 a minimum response rate of 5% was required. RESULTS: 30 patients were enrolled: 23% were female with median age of 63.3 years. The median duration of follow-up was 20 weeks. The median progression-free survival was 2.0 months (95%CI 1.8-3.4) and median overall survival 5.7 months (95%CI 3.6-8.0). Treatment was well tolerated. The objective response rate was 3% with one patient with CSCC having a partial response. CONCLUSIONS: Hypoxia-activated prodrugs represent a novel approach to cancer treatment, however, no clinically meaningful benefit for tarloxotinib in R/M HNSCC or CSCC was identified in this study. TRIAL REGISTRATION NUMBER: NCT02449681 (May 20, 2015).

Molecular characterization of Mycobacterium tuberculosis through MPT64 gene polymorphism using next-generation sequencing technology.

Aim: To characterize and analyze polymorphism of the MPT64 gene and evaluate AgMPT64-based immunochromatographic assay (ICA) specificity associated with polymorphism. Materials & methods: A total of 1449 suspected samples were tested for tuberculosis (TB), and the MPT64/rv1980c gene was sequenced using next-generation sequencing for polymorphism analysis. Results: Of the TB-positive individuals, 200 (13.80%), 186 (12.84%) and 129 (8.90%) were positive using the liquid culture, GeneXpert and fluorescence microscopy assays, respectively. Liquid culture medium-based samples were confirmed using ICA, in which 193 (96.5%) were positive while seven (3.5%) were negative. Out of 14 sequenced samples, seven were positive and seven negative; 13 were identical to the reference and just one (ICA positive) showed a C477A point mutation (F159L). Conclusion: The results indicate that AgMPT64 can be considered as a potent vaccine candidate.

Veliparib Plus Carboplatin and Paclitaxel Versus Investigator's Choice of Standard Chemotherapy in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer.

BACKGROUND: This open-label Phase III trial (NCT02264990) evaluated the PARP inhibitor, veliparib, combined with carboplatin/paclitaxel versus chemotherapy alone for first-line treatment of patients with advanced non-squamous non-small cell lung cancers (NSCLC). A 52-gene expression classifier (LP52) previously shown to identify patients more likely to respond to veliparib was evaluated as a planned correlative analysis. MATERIALS AND METHODS: Adult current or former smokers with advanced non-squamous NSCLC were randomized 1:1 to veliparib (120 mg daily for 7 days/cycle) with carboplatin and paclitaxel or to investigators' choice of platinum doublet chemotherapy (up to 6, 21-day cycles), with optional pemetrexed maintenance. Prospective analysis of the LP52 signature was conducted using a clinical Qiagen/HTG assay. The primary endpoint was overall survival (OS) in LP52+ patients. RESULTS: Overall, 595 patients received veliparib + carboplatin/paclitaxel (n = 298) or chemotherapy alone (n = 297); 13% (n = 40) in each arm were LP52+. The primary endpoint was not met; median OS was 11.2 months with veliparib + carboplatin/paclitaxel versus 9.2 months with chemotherapy alone in the LP52+ subgroup (hazard ratio [HR] 0.644, 95% confidence interval [CI]: 0.396-1.048; P = .113). In the overall population, median OS was 12.1 months in both arms (HR 0.986, 95% CI: 0.827-1.176; P = .846). No new safety signals were observed. CONCLUSION: In patients with non-squamous NSCLC, there was no significant improvement in OS with veliparib + carboplatin/paclitaxel versus chemotherapy alone, although a trend toward improved OS in the LP52+ population suggests this subgroup may benefit from veliparib. Statistical power was limited due to the small sample size.

Clinical Role of Positron Emission Tomography/Computed Tomography Imaging in Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) imaging is nearly synonymous with positron emission tomography (PET) scans. Many of the nearly 60,000 newly diagnosed patients with HNSCC in the US-and 900,000 worldwide-will undergo a PET scan, if not multiple, throughout the course of their care. In this review, we describe the clinical utility of PET scans in HNSCC, emphasizing whereby their input is most impactful in improving patient outcomes as well as scenarios whereby PET/CT scans should be avoided. We also describe important considerations for capturing and processing PET scans with a special focus on the important role of tumor volume segmentation, scan timing relative to therapy, and concurrent conditions (eg, COVID-19). In addition, we will illustrate the latest innovations in the management of HNSCC. This article also will delve to exhibit novel potential biomarkers in the management of HNSCC. Finally, we describe future directions for PET imaging, including the advent of novel PET radiotracers as an alternative to 18F-fluorodeoxyglucose (18F-FDG).

Peripheral Neuropathy in Beta-Thalassemia: Corneal Confocal Microscopy-Based Study.

Background Peripheral neuropathy is a controversial but serious complication of beta-thalassemia (ß-Th). Although few studies have reported no relationship between neuropathy and thalassemia, many have linked it with increasing age, iron overload, and iron chelator toxicity. This study aims to investigate the presence of neuropathy in ß-Th using corneal nerve fibers. Methodology A cross-sectional study was conducted using corneal confocal microscopy on individuals with intermediate and major ß-Th who were compared to healthy individuals. The main outcome variables were corneal main nerve and branch nerve densities which were calculated using Image J software. The comparison between groups was done using the independent-samples F-test and Bonferroni post-hoc analysis. Results There was reduced corneal main nerve and branch nerve density in ß-Th intermediate and major patients compared to the control group, and the results were statistically significant (p-value <0.05). However, a significant correlation was not observed between serum ferritin levels and corneal nerve parameters. Conclusions The reduction in corneal nerve parameters in ß-Th patients compared to healthy controls can be an indication of peripheral neuropathy in ß-Th. Further work is needed to confirm these findings.

What makes epoxy-phenolic coatings on metals ubiquitous: Surface energetics and molecular adhesion characteristics.

HYPOTHESIS: Wetting characteristics of epoxy and phenolic resins on metals depend on the molecular interactions between resins' functional groups and metal surface. Those interactions affect the practical adhesion strength of epoxy-phenolic coatings on metals. Estimation of the theoretical adhesion energies can reveal this system's microscopic adhesion mechanisms. EXPERIMENTS: Adhesion is estimated theoretically based on resins' wettability on metals, and experimentally through pull-off adhesion testing of cured coatings. The effect of various functional groups on adhesion is decoupled using epoxy and phenolic resins with different functionalities. To assess the impact of the metal passivation on adhesion, tinplated and tin-free steel substrates are used. Differences in their surface chemical composition and polarity are investigated using XPS. FINDINGS: Theoretical adhesion results reveal a superior adhesion of epoxy compared to phenolic resins. Moreover, epoxy resins having a higher content of epoxide-to-hydroxyl groups show improved theoretical and practical adhesion. The importance of epoxides in driving resins' initial adhesion on metals is attributed to the formation of direct chemical bonds with active hydrogen on metal surfaces. The adhesion of coatings on tin-free steel is found to be higher than on tinplated steel. This is associated to the increased hydroxyl fraction on tin-free steel surface leading to more hydrogen bonds formation.

Local SARS-CoV-2 Peptide-Specific Immune Responses in Lungs of Convalescent and Uninfected Human Subjects.

Multi-specific and long-lasting T cell immunity have been recognized as indicators for long term protection against pathogens including the novel coronavirus SARS-CoV-2, the causative agent of the COVID-19 pandemic. Functional significance of peripheral memory T cells in individuals recovering from COVID-19 (COVID-19 + ) are beginning to be appreciated; but little is known about lung resident memory T cells (lung TRM) in SARS-CoV-2 infection. Here, we utilize a perfused three dimensional (3D) human lung tissue model and identify pre-existing local T cell immunity against SARS-CoV-2 proteins in lung tissues. We report ex vivo maintenance of functional multi-specific IFN-γ secreting lung TRM in COVID-19 + and their induction in lung tissues of vaccinated COVID-19 + . Importantly, we identify SARS-CoV-2 peptide-responding B cells and IgA + plasma cells in lung tissues of COVID-19 + in ex vivo 3D-tissue models. Our study highlights the importance of balanced and local anti-viral immune response in the lung with persistent induction of TRM and IgA + plasma cells for future protection against SARS-CoV-2 infection. Further, our data suggest that inclusion of multiple viral antigens in vaccine approaches may broaden the functional profile of memory T cells to combat the severity of coronavirus infection.

Cellulose-Based Hybrid Aerogels: Strategies toward Design and Functionality.

The brittle nature of early aerogels developed from inorganic precursors fueled the discovery of their organic counterparts. Prominent among these organics are cellulose aerogels because of their natural abundance, biocompatibility, sustainable precursors, and tunable properties. The hierarchical structure of cellulose, from polymers to nano/microfibers, further facilitates fabrication of materials across multiple length scales with added applicability. However, the inherent flammability, structural fragility, and low thermal stability have limited their use. Recently developed cellulose-based hybrid aerogels offer strong potential owing to their tunability and enhanced functionality brought about by combining the inherent properties of cellulose with organic and inorganic components. A survey of the historical background and scientific achievements in the design and development of cellulose-based hybrid aerogel materials is encompassed here. The impacts of incorporating organic and inorganic ingredients with cellulose and the corresponding synergistic effects are discussed in terms of their design and functionality. The underlying principles governing the structural integration and functionality enhancement are also analyzed. The latest developments of cellulose-based hybrid aerogels fabricated from nontraditional incipient aerogels, such as fibrous webs, are also explored. Finally, future opportunities that could make these materials achieve even greater impacts through improved scalability, rationally designed synthesis, and multifunctional properties are discussed.