The Adaptive Immune Landscape of the Colorectal Adenoma–Carcinoma Sequence

Background. The tumor immune microenvironment exerts a pivotal influence in tumor initiation and progression. The aim of this study was to analyze the immune context of sporadic and familial adenomatous polyposis (FAP) lesions along the colorectal adenoma–carcinoma sequence (ACS). Methods. We analyzed immune cell counts (CD3+, CD4+, CD8+, Foxp3+, and CD57+), tumor mutation burden (TMB), MHC-I expression and PD-L1 expression of 59 FAP and 74 sporadic colorectal lesions, encompassing adenomas with low-grade dysplasia (LGD) (30 FAP; 30 sporadic), adenomas with high-grade dysplasia (22 FAP; 30 sporadic), and invasive adenocarcinomas (7 FAP; 14 sporadic). Results. The sporadic colorectal ACS was characterized by (1) a stepwise decrease in immune cell counts, (2) an increase in TMB and MHC-I expression, and (3) a lower PD-L1 expression. In FAP lesions, we observed the same patterns, except for an increase in TMB along the ACS. FAP LGD lesions harbored lower Foxp3+ T cell counts than sporadic LGD lesions. A decrease in PD-L1 expression occurred earlier in FAP lesions compared to sporadic ones. Conclusions. The colorectal ACS is characterized by a progressive loss of adaptive immune infiltrate and by the establishment of a progressively immune cold microenvironment. These changes do not appear to be related with the loss of immunogenicity of tumor cells, or to the onset of an immunosuppressive tumor microenvironment.     

Optimizing PSMA Radioligand Therapy for Patients with Metastatic Castration-Resistant Prostate Cancer. A Systematic Review and Meta-Analysis

The aim of the review was to evaluate patient and treatment characteristics for patients with metastatic castration-resistant prostate cancer (mCRPC) treated with PSMA radioligand therapy (PRLT) associated with above-average outcome. The systematic review and meta-analysis followed recommendations by the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA). We searched for publications in PubMed, Embase, and ClinicalTrials.gov up to 31 September 2020. Thirty-six publications and four duplicates reported 2346 patients. Nearly two-thirds of the patients had bone metastases. Median overall survival (OS) was 16 months. Asymptomatic patients and patients with only lymph node metastases lived longer than symptomatic patients and patients with more extensive metastases. Patients treated with an intensified schedule of ¹⁷⁷Lu PRLT lived longer than those treated with a conventional schedule. Half of the patients obtained a PSA decline ≥ 50% and these patients lived longer than those with less PSA decline. Approximately 10% of the patients developed hematologic toxicity with anemia grade 3 as the most severe adverse effect. Characteristics for patients, cancer, restaging, and PRLT predict above average overall survival following treatment with PRLT.     

A2B Adenosine Receptors: When Outsiders May Become an Attractive Target to Treat Brain Ischemia or Demyelination

Adenosine is a signaling molecule, which, by activating its receptors, acts as an important player after cerebral ischemia. Here, we review data in the literature describing A_2BR-mediated effects in models of cerebral ischemia obtained in vivo by the occlusion of the middle cerebral artery (MCAo) or in vitro by oxygen-glucose deprivation (OGD) in hippocampal slices. Adenosine plays an apparently contradictory role in this receptor subtype depending on whether it is activated on neuro-glial cells or peripheral blood vessels and/or inflammatory cells after ischemia. Indeed, A_2BRs participate in the early glutamate-mediated excitotoxicity responsible for neuronal and synaptic loss in the CA1 hippocampus. On the contrary, later after ischemia, the same receptors have a protective role in tissue damage and functional impairments, reducing inflammatory cell infiltration and neuroinflammation by central and/or peripheral mechanisms. Of note, demyelination following brain ischemia, or autoimmune neuroinflammatory reactions, are also profoundly affected by A_2BRs since they are expressed by oligodendroglia where their activation inhibits cell maturation and expression of myelin-related proteins. In conclusion, data in the literature indicate the A_2BRs as putative therapeutic targets for the still unmet treatment of stroke or demyelinating diseases.     

Stability Is Not Everything: The Case of the Cyclisation of a Thrombin-Binding Aptamer

With the aim of developing a new approach to obtain improved aptamers, a cyclic thrombin-binding aptamer (TBA) analogue (cycTBA) has been prepared by exploiting a copper(I)-assisted azide–alkyne cycloaddition. The markedly increased serum resistance and exceptional thermal stability of the G-quadruplex versus TBA were associated with halved thrombin inhibition, which suggested that some flexibility in the TBA structure was necessary for protein recognition.     

Development and characterization of bionanocomposites based on poly(3‐hydroxybutyrate) and cellulose nanocrystals for packaging applications

Poly(3‐hydroxybutyrate) (PHB)‐based bionanocomposites were prepared using various percentages of cellulose nanocrystals (CNCs) by a solution casting method. CNCs were prepared from microcrystalline cellulose using sulfuric acid hydrolysis. The influence of CNCs on PHB properties was evaluated using differential scanning calorimetry, Fourier transform infrared spectroscopy, X‐ray diffraction, thermogravimetry and tensile testing. Vapor permeation and light transmission of the materials were also measured. Differential scanning calorimetric tests demonstrated that CNCs were effective PHB nucleation agents. Tensile strength and Young's modulus of PHB increased with increasing CNC concentration. Moreover, the PHB/CNC bionanocomposites exhibited reduced water vapor permeation compared to neat PHB and had better UV barrier properties than commodity polymers such as polypropylene. It was found that nanocomposites with 6 wt% of CNCs had the optimum balance among thermal, mechanical and barrier properties. © 2016 Society of Chemical Industry     

Vocal learning in the grey parrot (Psittacus erithacus): Effects of species identity and number of trainers.

Grey parrots (Psittacus erithacus) learn referential English labels when they view and interact with 2 humans who model vocal labeling and who demonstrate referentiality and functionality of a label (I. M. Pepperberg, 1990a). To test if both trainers are necessary, the authors contrasted 2-trainer modeling with training by 1 human who presented targeted labels to a bird in concert with appropriate items, who asked questions, and who would reward attempts at the label with the item. The bird was also tutored by either 1 or 2 interactive humans in conjunction with a conspecific who already used referential labels. Referential labels were learned from multiple live tutors but not a single trainer. Presence of a conspecific enhanced learning compared with single-trainer sessions but did not affect acquisition in 2-human sessions. Specific aspects of paired tutoring seem critical for acquiring referential vocal labels. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A rejoinder to "Psychotherapy research ethics: Continuing the debate on controlled clinical trials."

Responds to C. A. Heflinger's (1987) critique of the present authors (1986) by reiterating their concern for the principle of autonomy. The present authors note that all patients were fully informed about the research plan and their right to withdraw. Nonetheless, the ethical criticism offered by Heflinger regarding randomization cannot be entirely dismissed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ethnicity and psychopathology: A meta-analytic review of 31 years of comparative MMPI/MMPI-2 research.

Meta-analyses were performed on 25 comparative Minnesota Multiphasic Personality Inventory (MMPI) and MMPI-2 studies of 1,428 male African Americans versus 2,837 male European Americans, 12 studies of 1,053 female African Americans versus 1,470 female European Americans, and 13 studies of 500 male Latino Americans and 1,345 male European Americans. Aggregate effect sizes suggest higher scores for ethnic minority groups than for European Americans on some MMPI/MMPI-2 scales and lower scores on others. However, none of the aggregate effect sizes suggest substantive differences from either a statistical or clinical perspective. The MMPI and MMPI-2 apparently do not unfairly portray African Americans and Latinos as pathological. Effect sizes across studies generally did not vary as a function of sociodemographic variables, research setting, or use of the MMPI versus MMPI-2. It is recommended that additional between- and within-ethnic groups psychopathology research continue. (PsycINFO Database Record (c) 2010 APA, all rights reserved)