Five-Fraction Proton Therapy for the Treatment of Skull Base Chordomas and Chondrosarcomas: Early Results of a Prospective Series and Description of a Clinical Trial.

(1) Background: Our purpose is to describe the design of a phase II clinical trial on 5-fraction proton therapy for chordomas and chondrosarcomas of the skull base and to present early results in terms of local control and clinical tolerance of the first prospective series. (2) Methods: A dose of 37.5 GyRBE in five fractions was proposed for chordomas and 35 GyRBE in five fractions for chondrosarcomas. The established inclusion criteria are age ≥ 18 years, Karnofsky Performance Status ≥ 70%, clinical target volume up to 50 cc, and compliance with dose restrictions to the critical organs. Pencil beam scanning was used for treatment planning, employing four to six beams. (3) Results: A total of 11 patients (6 chordomas and 5 chondrosarcomas) were included. The median follow-up was 12 months (9-15 months) with 100% local control. Acute grade I-II headache (64%), grade I asthenia and alopecia (45%), grade I nausea (27%), and grade I dysphagia (18%) were described. Late toxicity was present in two patients with grade 3 temporal lobe necrosis. (4) Conclusions: Hypofractionated proton therapy is showing encouraging preliminary results. However, to fully assess the efficacy of this therapeutic approach, future trials with adequate sample sizes and extended follow-ups are necessary.

Small Fluorogenic Amino Acids for Peptide-Guided Background-Free Imaging.

The multiple applications of super-resolution microscopy have prompted the need for minimally invasive labeling strategies for peptide-guided fluorescence imaging. Many fluorescent reporters display limitations (e.g., large and charged scaffolds, non-specific binding) as building blocks for the construction of fluorogenic peptides. Herein we have built a library of benzodiazole amino acids and systematically examined them as reporters for background-free fluorescence microscopy. We have identified amine-derivatized benzoselenadiazoles as scalable and photostable amino acids for the straightforward solid-phase synthesis of fluorescent peptides. Benzodiazole amino acids retain the binding capabilities of bioactive peptides and display excellent signal-to-background ratios. Furthermore, we have demonstrated their application in peptide-PAINT imaging of postsynaptic density protein-95 nanoclusters in the synaptosomes from mouse brain tissues.

Philadelphia-negative chronic myeloproliferative neoplasm follow-up: when the phone rings. Changes during the COVID-19 pandemic and patient satisfaction. Experience in 30 health centers in Spain.

The SARS-CoV-2 pandemic has favored the expansion of telemedicine. Philadelphia-negative chronic myeloproliferative neoplasms (Ph-MPN) might be good candidates for virtual follow-up. In this study, we aimed to analyze the follow-up of patients with Ph-MPN in Spain during COVID-19, its effectiveness, and acceptance among patients. We present a multicenter retrospective study from 30 centers. Five hundred forty-one patients were included with a median age of 67 years (yr). With a median follow-up of 19 months, 4410 appointments were recorded. The median of visits per patient was 7 and median periodicity was 2.7 months; significantly more visits and a higher frequency of them were registered in myelofibrosis (MF) patients. 60.1% of visits were in-person, 39.5% were by telephone, and 0.3% were videocall visits, with a predominance of telephone visits for essential thrombocythemia (ET) and polycythemia vera (PV) patients over MF, as well as for younger patients (< 50 yr). The proportion of phone visits significantly decreased after the first semester of the pandemic. Pharmacological modifications were performed only in 25.7% of the visits, and, considering overall management, ET patients needed fewer global treatment changes. Telephone contact effectiveness reached 90% and only 5.4% required a complementary in-person appointment. Although 56.2% of the cohort preferred in-person visits, 90.5% of our patients claimed to be satisfied with follow-up during the pandemic, with an 83% of positive comments. In view of our results, telemedicine has proven effective and efficient, and might continue to play a complementary role in Ph-MPN patients' follow-up.

Small Fluorogenic Amino Acids for Peptide-Guided Background-Free Imaging.

The multiple applications of super-resolution microscopy have prompted the need for minimally invasive labeling strategies for peptide-guided fluorescence imaging. Many fluorescent reporters display limitations (e.g., large and charged scaffolds, non-specific binding) as building blocks for the construction of fluorogenic peptides. Herein we have built a library of benzodiazole amino acids and systematically examined them as reporters for background-free fluorescence microscopy. We have identified amine-derivatized benzoselenadiazoles as scalable and photostable amino acids for the straightforward solid-phase synthesis of fluorescent peptides. Benzodiazole amino acids retain the binding capabilities of bioactive peptides and display excellent signal-to-background ratios. Furthermore, we have demonstrated their application in peptide-PAINT imaging of postsynaptic density protein-95 nanoclusters in the synaptosomes from mouse brain tissues.

Radiochromic film dosimetry for protons up to 10 MeV with EBT2, EBT3 and unlaminated EBT3 films.

Passive dosimetry with radiochromic films is widely used in proton radiotherapy, both in clinical and scientific environments, thanks to its simplicity, high spatial resolution and dose-rate independence. However, film under-response for low-energy protons, the so-called linear-energy transfer (LET) quenching, must be accounted and corrected for. We perform a meta-analysis on existing film under-response data with EBT, EBT2 and EBT3 GAFchromic™ films and provide a common framework to integrate it, based on the calculation of dose-averaged LET in the active layer of the films. We also report on direct measurements with the 10 MeV proton beam at the Center for Microanalysis of Materials (CMAM) for EBT2, EBT3 and unlaminated EBT3 films, focusing on the 20-80 keVµm-1LET range, where previous data was scarce. Measured film relative efficiency (RE) values are in agreement with previously reported data from the literature. A model on film RE constructed with combined literature and own experimental values in the 5-80 keVµm-1LET range is presented, supporting the hypothesis of a linear decrease of RE with LET, with no remarkable differences between the three types of films analyzed.

Differences in ex-vivo Chemosensitivity to Anthracyclines in First Line Acute Myeloid Leukemia.

BACKGROUND: Induction schedules in acute myeloid leukemia (AML) are based on combinations of cytarabine and anthracyclines. The choice of the anthracycline employed has been widely studied in multiple clinical trials showing similar complete remission rates. MATERIALS AND METHODS: Using an ex vivo test we have analyzed if a subset of AML patients may respond differently to cytarabine combined with idarubicin, daunorubicin or mitoxantrone. Bone marrow (BM) samples of 198 AML patients were incubated for 48 hours in 96 well plates, each well containing different drugs or drug combinations at different concentrations. Ex vivo drug sensitivity analysis was made using the PharmaFlow platform maintaining the BM microenvironment. Drug response was evaluated as depletion of AML blast cells in each well after incubation. Annexin V-FITC was used to quantify the ability of the drugs to induce apoptosis, and pharmacological responses were calculated using pharmacokinetic population models. RESULTS: Similar dose-respond graphs were generated for the three anthracyclines, with a slight decrease in EC50 with idarubicin (p=1.462E-06), whereas the interpatient variability of either drug was large. To identify those cases of selective sensitivity to anthracyclines, potency was compared, in terms of area under the curve. Differences in anthracycline monotherapy potency greater than 30% from 3 pairwise comparisons were identified in 28.3% of samples. Furthermore, different sensitivity was detected in 8.2% of patients comparing combinations of cytarabine and anthracyclines. DISCUSSION: A third of the patients could benefit from the use of this test in the first line induction therapy selection, although it should be confirmed in a clinical trial specifically designed.

Ethics, Science and Mind Control: J. M. Rodríguez-Delgado's Legacy.

This work analyses the evolution of the scientific visibility of the neurophysiologist José Manuel Rodríguez Delgado. It examines the longitudinal evolution from 1955 to 2013 of an article (Delgado, Roberts, & Miller, 1954) studying the neurological basis of learning and motivation and compares it with a coetaneous article (Olds & Milner, 1954) with a similar subject and methodology. Both studies have been essential in Psychology. This work analyses the number of times each article has been cited between 1955-1984 and 1985-2013. The results show that the visibility of James Olds and Peter Milner's article (expressed in number of citations between 1955-1984 and 1985-2013) has longitudinally increased (p < .001), whereas the number of citations received by José Manuel Rodríguez Delgado et al.'s article has significantly reduced (p < .001). The results are discussed and the low visibility of Delgado's article is explained through historical and social factors, including the growing concern about compliance with bioethical and research guidelines and the controversial media projection of the Spanish scientist, not by the intrinsic value or the scientific repercussion of the compared articles.