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Background FLASH therapy is a treatment technique in which radiation is delivered at ultra-high dose rates ( ≥  40 Gy/s). The first-in-human FAST-01 clinical trial demonstrated the clinical feasibility of proton FLASH in the treatment of extremity bone metastases. The objectives of this investigation are to assess the toxicities of treatment and pain relief in study participants with painful thoracic bone metastases treated with FLASH radiotherapy, as well as workflow metrics in a clinical setting. Methods This single-arm clinical trial is being conducted under an FDA investigational device exemption (IDE) approved for 10 patients with 1–3 painful bone metastases in the thorax, excluding bone metastases in the spine. Treatment will be 8 Gy in a single fraction administered at ≥ 40 Gy/s on a FLASH-enabled proton therapy system delivering a single transmission proton beam. Primary study endpoints are efficacy (pain relief) and safety. Patient questionnaires evaluating pain flare at the treatment site will be completed for 10 consecutive days post-RT. Pain response and adverse events (AEs) will be evaluated on the day of treatment and on day 7, day 15, months 1, 2, 3, 6, 9, and 12, and every 6 months thereafter. The outcomes for clinical workflow feasibility are the occurrence of any device issues as well as time on the treatment table. Discussion This prospective clinical trial will provide clinical data for evaluating the efficacy and safety of proton FLASH for palliation of bony metastases in the thorax. Positive findings will support the further exploration of FLASH radiation for other clinical indications including patient populations treated with curative intent. Registration ClinicalTrials.gov NCT05524064.

Purpose Lacosamide (LCM) is a third-generation anti-seizure medication (ASM) approved for focal onset epilepsy in patients aged ≥ 4.378 Previous studies have reported an efficacy of LCM as add-on treatment in brain tumor-related epilepsy (BTRE). To date, there are no studies in the literature focusing on lacosamide used in monotherapy to treat BTRE. In our retrospective study we investigated efficacy and tolerability of LCM in monotherapy in a multicenter national cohort of primary brain tumor patients. Methods We collected from 12 Italian Centers 132 patients with primary brain tumors who were treated with LCM in monotherapy. For each patient we evaluated seizure freedom at 3 and 6 months (primary endpoints), side effects and drop-out rate (secondary endpoints). Results Overall, LCM led to seizure freedom in 64.4% of patients at 3 months and 55% at 6 months. Patients who used two or more ASMs before LCM had a worse seizure control than patients in monotherapy with LCM as first choice. In 14 patients, we observed seizure control despite tumor progression on magnetic resonance (MRI). Multivariate analysis showed that gross-total resection at diagnosis was significantly associated with higher seizure freedom rate at 6 months. Side effects were mainly mild (grade 1–2 according to CTCAE classification) and drop-out rate was low (1.5%). Main side effects were dizziness and somnolence. Conclusions This is the first study showing a good efficacy and tolerability of LCM when used in monotherapy in BTRE. Further prospective studies are needed to confirm these preliminary data, investigating also quality of life and neurocognitive functions.

In this work, the investigation of the surface strain‐induced electrical changes in two commonly employed solution‐processable organic semiconductors, i.e., 6,13‐bis(triisopropylsilylethynyl)pentacene (TIPS‐Pentacene) and N,N′‐bis‐(2‐ethylhexyl)−1,7‐dicyanoperylene‐3,4:9,10‐bis(dicarboximide) (N1400), is reported. A detailed electromechanical characterization of two sets of flexible organic field‐effect transistors is performed, clearly demonstrating that both systems are affected by mechanical deformation in terms of electrical performance. However, the N1400 system shows a much more stable and reproducible response, even after continuous mechanical stress. XRD and AFM analysis demonstrate that such difference is mainly related to the changes induced on the two thin film morphology by the applied deformations. This work examines the impact of surface strain on the electrical properties of two widely employed organic semiconductors, TIPS‐Pentacene and N1400. Electromechanical tests on flexible transistors reveal that while both materials are affected by mechanical deformation, N1400 demonstrates superior stability. XRD and AFM analyses attribute these differences to strain‐induced changes in thin‐film morphology, offering new insights into material performance.

The mRNA levels of NKCC1, an inwardly directed Na⁺, K⁺-2Cl⁻ cotransporter that facilitates the accumulation of intracellular Cl⁻, and of KCC2, an outwardly directed K⁺-Cl⁻ cotransporter that extrudes Cl⁻, were studied in surgically resected brain specimens from drug-resistant temporal lobe (TL) epilepsy (TLE) patients. Quantitative RT-PCR analyses of the mRNAs extracted from the human TLE-associated brain regions revealed an up-regulation of NKCC1 mRNA and a down-regulation of KCC2 mRNA in the hippocampal subiculum, compared with the hippocampus proper or the TL neocortex, suggesting an abnormal transcription of Cl⁻ transporters in the TLE subiculum. In parallel experiments, cell membranes isolated from the same TLE-associated brain regions were injected into Xenopus oocytes that rapidly incorporated human$GABA_{A}$receptors into their surface membrane. The GABA currents elicited in oocytes injected with membranes from the subiculum had a more depolarized reversal potential ($E_{GABA}$) compared with the hippocampus proper or the neocortex. The NKCC1 blocker bumetanide or a temperature decrease of 10°C shifted the GABA-current$E_{GABA}$more negative in oocytes injected with membranes from TLE hippocampal subiculum, matching the$E_{GABA}$of TL neocortex-injected oocytes. We conclude that the anomalous expression of both Cl⁻ transporters, KCC1 and NKCC2, in TLE hippocampal subiculum probably causes altered Cl⁻ transport in the \"epileptic\" neurons, as revealed in the microtransplanted Xenopus oocytes, and renders GABA aberrantly \"exciting,\" a feature that may contribute to the precipitation of epileptic seizures.

Nowadays, Quality Management tools such as failure mode and effect analysis (FMEA) are widely used throughout the aeronautical, automotive, software, food services, health care and many other industries to sustain and improve quality and safety. The increasing complexity of scientific research makes it more difficult to maintain all activities under control, in order to guarantee validity and reproducibility of results. Even in non-regulated research, scientists need to be supported with management tools that maximize study performance and outcomes, while facilitating the research process. Frequently, steps that involve human intervention are the weak links in the process. Risk analysis therefore gives considerable benefit to analytical validation, assessing and avoiding failures due to human error, potential imprecision in applying protocols, uncertainty in equipment function and imperfect control of materials. This paper describes in detail how FMEA methodology can be applied as a performance improvement tool in the field of non-regulated research, specifically on a basic Life Sciences research process. We chose as “pilot process” the selection of oligonucleotide aptamers for therapeutic purposes, as an example of a complex and multi-step process, suitable for technology transfer. We applied FMEA methodology, seeking every opportunity for error and its impact on process output, and then, a set of improvement actions was generated covering most aspects of laboratory practice, such as equipment management and staff training. We also propose a useful tool supporting the risk assessment of research processes and its outputs and that we named “FMEA strip worksheet.” These tools can help scientists working in non-regulated research to approach Quality Management and to perform risk evaluation of key scientific procedures and processes with the final aim to increase and better control efficiency and efficacy of their research.

The MIllimeter Sardinia radio Telescope Receiver based on Array of Lumped elements KIDs, MISTRAL, is a cryogenic LEKID camera, operating in the W band ( 77 - 103 GHz ) from the Gregorian focus of the 64-m aperture Sardinia Radio Telescope (SRT), in Italy. This instrument features a high angular resolution ( ∼ 12 arcsec ) and a wide instantaneous field of view ( ∼ 4 arcmin ), allowing continuum surveys of the mm-wave sky with many scientific targets, including observations of galaxy clusters via the Sunyaev–Zel’dovich effect. In May 2023, MISTRAL has been installed at SRT for the technical commissioning. In this contribution, we will describe the MISTRAL instrument focusing on the laboratory characterization of its focal plane: a ∼ 400 -pixel LEKID array. We will show the optical performance of the detectors highlighting the procedure for the identification of the pixels on the focal plane, the measurements of the optical responsivity and NEP, and the estimation of the optical efficiency.

We describe the design and performance of the cryostat and the multi-stage sub-K single-shot sorption cooler for the MIllimeter Sardinia Radio Telescope Receiver based on Array of Lumped elements kids (MISTRAL) experiment. MISTRAL is a W-band (77 - 103 GHz) Ti/Al bi-layer Lumped Elements Kinetic Inductance Detectors (LEKIDs) camera working at the Gregorian focus of the 64 m aperture Sardinia Radio Telescope (SRT), located in Sardinia (Italy). The cryogenic system, based on a 1.5 W at 4.2 K Pulse Tube (PT) cryocooler, provides the 4 K base temperature for the sub-K refrigerator, and cools down the cold optics and the filters chain of the instrument. The sub-K sorption cooler consists of two intermediate stages, 4 He and 3 He sorption refrigerators that allow to reduce the heat load on the ultra-cold head, and a twin stage of 3 He sorption refrigerator providing the 0.2 K operation temperature for the 415-pixel array of LEKIDs. MISTRAL experiment was installed at SRT in May 2023, the technical commissioning started in June 2023. We will show the performance of the system in the laboratory.

Galaxy clusters and surrounding medium, can be studied using X-ray bremsstrahlung emission and Sunyaev Zel’dovich (SZ) effect. Both astrophysical probes, sample the same environment with different parameters dependance. The SZ effect is relatively more sensitive in low density environments and thus is useful to study the filamentary structures of the cosmic web. In addition, observations of the matter distribution require high angular resolution in order to be able to map the matter distribution within and around galaxy clusters. MISTRAL is a camera working at 90GHz which, once coupled to the Sardinia Radio Telescope (SRT), can reach 12″ angular resolution over 4′ field of view (f.o.v.). The forecasted sensitivity drives to a Noise Equivalent Flux Density of ≃ 10–15 mJy √ s and the mapping speed is MS = 380′ 2 mJy −2 h −1 . MISTRAL was recently installed at the focus of the SRT and soon will take its first photons.

Pharmacotherapeutic strategies have been difficult to develop for several forms of temporal lobe epilepsy, which are consequently treated by surgical resection. To examine this problem, we have studied the properties of transmitter receptors of tissues removed during surgical treatment. We find that when cell membranes, isolated from the temporal neocortex of patients afflicted with drug-resistant mesial temporal lobe epilepsy (TLE), are injected into frog oocytes they acquire GABA type A receptors (GABAA-receptors) that display a marked rundown during repetitive applications of GABA. In contrast, GABAA-receptor function is stable in oocytes injected with cell membranes isolated from the temporal lobe of TLE patients afflicted with neoplastic, dysgenetic, traumatic, or ischemic temporal lesions (lesional TLE, LTLE). Use-dependent GABAA-receptor rundown is also found in the pyramidal neurons of TLE neocortical slices and is antagonized by BDNF. Pyramidal neurons in cortical slices of a traumatic LTLE patient did not show GABAA-receptor rundown. However, the apparent affinity of GABAA-receptor in oocytes microtransplanted with membranes from all of the epileptic patients studied was smaller than the affinity of receptors transplanted from the nonepileptic brain. We conclude that the use-dependent rundown of neocortical GABAA-receptor represents a TLE-specific dysfunction, whereas the reduced affinity may be a general feature of brains of both TLE and LTLE patients, and we speculate that our findings may help to develop new treatments for TLE and LTLE.

Aim: To test a non-invasive presurgical protocol for temporal lobe epilepsy (TLE) based on “anatomo–electro–clinical correlations”. Methods: All consecutive patients with suspected TLE and seizure history <2 years were entered into the protocol, which included video-electroencephalographic (EEG) monitoring and magnetic resonance imaging (MRI). Three different TLE subsyndromes (mesial, lateral, mesiolateral) were identified by combined anatomical, electrical, and clinical criteria. “Tailored” surgery for each subsyndrome was offered. Patients with seizure history <2 years, MRI evidence of temporal mass lesion, and concordant interictal EEG and clinical data bypassed video-EEG monitoring and were directly scheduled for surgery. Results: Lesionectomy was performed without video-EEG recording in 11 patients with tumorous TLE. Of 146 patients studied with video-EEG, 133 received a TLE diagnosis. Four were excluded for neuropsychological risks, eight refused surgery, and 121 underwent surgery. Of 132 consecutive patients who underwent surgery, 101 had at least one year of follow up. They were divided into a “hippocampal sclerosis/cryptogenic” group (n = 57) and a “tumours/cortical organisation disorders” group (n = 44). In the first group, extensive temporal lobectomy (ETL) was performed in 40 patients, anteromesial temporal lobectomy (AMTL) in 17 patients. At follow up, 47 patients were seizure free. In the second group, lesionectomy plus ETL was performed in 23 patients, lesionectomy plus AMTL in six patients, and lesionectomy alone in 15 patients. Thirty nine patients were seizure free. Conclusions: These findings suggest that different TLE subsyndromes can be identified accurately using non-invasive anatomo–electro–clinical data and can be treated effectively and safely with tailored surgery.