PD-L1 Expression in Non-Small Cell Lung Cancer Specimens: Association with Clinicopathological Factors and Molecular Alterations

Immune checkpoint inhibitors (ICI) targeting programmed cell death-1 or its ligand (PD-L1) have improved outcomes in non-small cell lung cancer (NSCLC). High tumor PD-L1 expression, detected by immunohistochemistry (IHC) typically on formalin-fixed paraffin-embedded (FFPE) histological specimens, is linked to better response. Following our previous investigation on PD-L1 in cytological samples, the aim of this study was to further explore the potential impacts of various clinicopathological and molecular factors on PD-L1 expression. Two retrospective NSCLC cohorts of 1131 and 651 specimens, respectively, were investigated for PD-L1 expression (<1%/1–49%/≥50%), sample type, sample site, histological type, and oncogenic driver status. In both cohorts, PD-L1 was positive (≥1%) in 55% of the cases. Adenocarcinomas exhibited lower PD-L1 expression than squamous cell carcinomas (p < 0.0001), while there was no difference between sample types, tumor locations, or between the two cohorts in multivariate analysis (all p ≥ 0.28). Mutational status correlated significantly with PD-L1 expression (p < 0.0001), with the highest expression for KRAS-mutated cases, the lowest for EGFR-mutated, and the KRAS/EGFR wild-type cases in between. There was no difference in PD-L1 levels between different prevalent KRAS mutations (all p ≥ 0.44), while mucinous KRAS-mutated adenocarcinomas exhibited much lower PD-L1 expression than non-mucinous (p < 0.0001). Our data indicate that cytological and histological specimens are comparable for PD-L1 evaluation. Given the impact of KRAS mutations and the mucinous growth pattern on PD-L1 expression, these factors should be further investigated in studies on ICI response.     

Molecular Mechanisms of Diabetic Kidney Disease

The inflammatory component of diabetic kidney disease has become of great interest in recent years, with genetic and epigenetic variants playing a fundamental role in the initiation and progression of the disease. Cells of the innate immune system play a major role in the pathogenesis of diabetic kidney disease, with a lesser contribution from the adaptive immune cells. Other components such as the complement system also play a role, as well as specific cytokines and chemokines. The inflammatory component of diabetic kidney disease is of great interest and is an active research field, with the hope to find potential innovative therapeutic targets.     

Melatonin as a Potential Approach to Anxiety Treatment

Anxiety disorders are the most common mental diseases. Anxiety and the associated physical symptoms may disturb social and occupational life and increase the risk of somatic diseases. The pathophysiology of anxiety development is complex and involves alterations in stress hormone production, neurosignaling pathways or free radical production. The various manifestations of anxiety, its complex pathophysiological background and the side effects of available treatments underlie the quest for constantly seeking therapies for these conditions. Melatonin, an indolamine produced in the pineal gland and released into the blood on a nightly basis, has been demonstrated to exert anxiolytic action in animal experiments and different clinical conditions. This hormone influences a number of physiological actions either via specific melatonin receptors or by receptor-independent pleiotropic effects. The underlying pathomechanism of melatonin’s benefit in anxiety may reside in its sympatholytic action, interaction with the renin–angiotensin and glucocorticoid systems, modulation of interneuronal signaling and its extraordinary antioxidant and radical scavenging nature. Of importance, the concentration of this indolamine is significantly higher in cerebrospinal fluid than in the blood. Thus, ensuring sufficient melatonin production by reducing light pollution, which suppresses melatonin levels, may represent an endogenous neuroprotective and anxiolytic treatment. Since melatonin is freely available, economically undemanding and has limited side effects, it may be considered an additional or alternative treatment for various conditions associated with anxiety.     

Mechanistic Insights on the Enantioselective (4+3) Cycloaddition Between Oxyallylcations and Furans Catalyzed by BINOL-Based Phosphoramides

The mechanism of the enantioselective (4+3) cycloaddition between furan derivatives and oxyallylcations, which are generated from the corresponding oxiranes through in situ oxidation of allenamides, has been studied using DFT methods. The research has revealed that, under acid-catalysis by a chiral non-racemic phosphoramide, the epoxide ring-opening proceeds without any energy barrier, while the rate-limiting step is the electrophilic attack of the intermediate enaminium ion on the furan ring. The reaction exhibits low energy barriers when dealing with furan derivatives unsubstituted at C2 and C5. Calculations predict the formation of an achiral regioisomer for 2-substituted furans, a prediction that has been experimentally confirmed. Additionally, the calculations accurately predict the reaction with substituted allenamides.     

Mining frequent generators and closures in data streams with FGC-Stream

Knowledge and Information Systems - Mining frequent itemsets (FIs) from data streams is a challenging task due to the limited resources available w.r.t. the typically large size of the result and...     

Swarming Magnetic Microrobots for Pathogen Isolation from Milk

Bovine mastitis produced by Staphylococcus aureus (S. aureus) causes major problems in milk production due to the staphylococcal enterotoxins produced by this bacterium. These enterotoxins are stable and cannot be eradicated easily by common hygienic procedures once they are formed in dairy products. Here, magnetic microrobots (MagRobots) are developed based on paramagnetic hybrid microstructures loaded with IgG from rabbit serum that can bind and isolate S. aureus from milk in a concentration of 3.42 10⁴ CFU g⁻¹ (allowable minimum level established by the United States Food and Drug Administration, FDA). Protein A, which is present on the cell wall of S. aureus, selectively binds IgG from rabbit serum and loads the bacteria onto the surface of the MagRobots. The selective isolation of S. aureus is confirmed using a mixed suspension of S. aureus and Escherichia coli (E. coli). Moreover, this fuel-free system based on magnetic robots does not affect the natural milk microbiota or add any toxic compound resulting from fuel catalysis. This system can be used to isolate and transport efficiently S. aureus and discriminate it from nontarget bacteria for subsequent identification. Finally, this system can be scaled up for industrial use in food production.     

A High-Rate Li–CO2 Battery Enabled by 2D Medium-Entropy Catalyst

Lithium-air batteries based on CO₂ reactant (Li–CO₂) have recently been of interest because it has been found that reversible Li/CO₂ electrochemistry is feasible. In this study, a new medium-entropy cathode catalyst, (NbTa)_0.5BiS₃, that enables the reversible electrochemistry to operate at high rates is presented. This medium entropy cathode catalyst is combined with an ionic liquid-based electrolyte blend to give a Li–CO₂ battery that operates at high current density of 5000 mA g⁻¹ and capacity of 5000 mAh g⁻¹ for up to 125 cycles, far exceeding reported values in the literature for this type of battery. The higher rate performance is believed to be due to the greater stability of the multi-element (NbTa)_0.5BiS₃ catalyst because of its higher entropy compared to previously used catalysts with a smaller number of elements with lower entropies. Evidence for this comes from computational studies giving very low surface energies (high surface stability) for (NbTa)_0.5BiS₃ and transmission electron microscopystudies showing the structure being retained after cycling. In addition, the calculations indicate that Nb-terminated surface promotes Li–CO₂ electrochemistry resulting in Li₂CO₃ and carbon formation, consistent with the products found in the cell. These results open new direction to design and develop high-performance Li–CO₂ batteries.     

Mechanical and thermal properties of polypropylene/montmorillonite nanocomposites using stearic acid as both an interface and a clay surface modifier

The effects of stearic acid treatment on the crystallization, morphology, thermal, and mechanical properties of polypropylene (PP)/montmorillonite (Mm) nanocomposites were investigated. Stearic acid was used as a new surface modifier for Mm, and also small amounts of this acid were used as a new interface modifier. Nanocomposites containing 1.5, 2.5, 5, and 10% in weight of the unmodified and modified Mm were prepared by melt blending. The tensile and impact properties of nanocomposites were evaluated. Wide‐angle X‐ray diffraction was used to study both the generated PP β crystals and the dispersion state of the nanocomposites. Differential scanning calorimeter was used to detect the melting and crystallization behavior of the samples. The toughness of some nanocomposites was higher than the pure PP. β phase of PP was observed with the addition of Mm. Stearic acid favored the dispersion of the nanocomposites when used as interface modifier. Nanocomposites with better dispersion exhibited crystallization temperatures similar to pure PP. POLYM. COMPOS., 35:1–9, 2014. © 2013 Society of Plastics Engineers