Nanoscale spin-wave circuits based on engineered reconfigurable spin-textures

Magnonics is gaining momentum as an emerging technology for information processing. The wave character and Joule heating-free propagation of spin-waves hold promises for highly efficient computing platforms, based on integrated magnonic circuits. The realization of such nanoscale circuitry is crucial, although extremely challenging due to the difficulty of tailoring the nanoscopic magnetic properties with conventional approaches. Here we experimentally realize a nanoscale reconfigurable spin-wave circuitry by using patterned spin-textures. By space and time-resolved scanning transmission X-ray microscopy imaging, we directly visualize the channeling and steering of propagating spin-waves in arbitrarily shaped nanomagnonic waveguides, with no need for external magnetic fields or currents. Furthermore, we demonstrate a prototypic circuit based on two converging nanowaveguides, allowing for the tunable spatial superposition and interference of confined spin-waves modes. This work paves the way to the use of engineered spin-textures as building blocks of spin-wave based computing devices

A new schedule of fotemustine in temozolomide-pretreated patients with relapsing glioblastoma

In the present study we investigated the feasibility and effectiveness of a new biweekly schedule of fotemustine (FTM) in patients with recurrent glioblastoma, after at least one previous treatment. The primary endpoint was progression-free survival at 6 months; secondary objectives were clinical response, overall survival, disease-free survival, and toxicity. Forty patients (median age 52.8 years; median Karnofsky Performance Status at progression 90) underwent second-line chemotherapy with FTM. Selected patients were previously treated with a standard radiotherapy course with concomitant temozolomide (TMZ). After tumor relapse or progression proven by magnetic resonance imaging (MRI), all patients underwent chemotherapy with FTM, given intravenously at dose of 80 mg/m2 every 2 weeks for five consecutive administrations (induction phase), and then every 3 weeks at 100 mg/m2 as maintenance. A total of 329 infusions were administered; the median number of cycles administered was 8. All patients completed the induction phase, and 29 patients received at least one maintenance infusion. Response to treatment was assessed using MacDonald criteria. One complete response [2.5%, 95% confidence interval (CI): 0–10%], 9 partial responses (22.5%, 95% CI: 15–37%), and 16 stable diseases (40%, 95% CI: 32–51%) were observed. Median time to progression was 6.7 months (95% CI: 3.9–9.1 months). Progression-free survival at 6 months was 61%. Median survival from beginning of FTM chemotherapy was 11.1 months. The schedule was generally well tolerated; the main toxicities were hematologic (grade 3 thrombocytopenia in two cases). To the best of our knowledge, this is the first report specifically dealing with the use of a biweekly induction schedule of FTM. The study demonstrates that FTM has therapeutic efficacy as single-drug second-line chemotherapy with a favorable safety profile

Targeting Orexin Receptors for the Treatment of Insomnia: From Physiological Mechanisms to Current Clinical Evidence and Recommendations

After a detailed description of orexins and their roles in sleep and other medical disorders, we discuss here the current clinical evidence on the effects of dual (DORAs) or selective (SORAs) orexin receptor antagonists on insomnia with the aim to provide recommendations for their further assessment in a context of personalized and precision medicine. In the last decade, many trials have been conducted with orexin receptor antagonists, which represent an innovative and valid therapeutic option based on the multiple mechanisms of action of orexins on different biological circuits, both centrally and peripherally, and their role in a wide range of medical conditions which are often associated with insomnia. A very interesting aspect of this new category of drugs is that they have limited abuse liability and their discontinuation does not seem associated with significant rebound effects. Further studies on the efficacy of DORAs are required, especially on children and adolescents and in particular conditions, such as menopause. Which DORA is most suitable for each patient, based on comorbidities and/or concomitant treatments, should be the focus of further careful research. On the contrary, studies on SORAs, some of which seem to be appropriate also in insomnia in patients with psychiatric diseases, are still at an early stage and, therefore, do not allow to draw definite conclusions

Focus on the Complex Interconnection between Cancer, Narcolepsy and Other Neurodegenerative Diseases: A Possible Case of Orexin-Dependent Inverse Comorbidity

Conditions such as Alzheimer’s (AD) and Parkinson’s diseases (PD) are less prevalent in cancer survivors and, overall, cancer is less prevalent in subjects with these neurodegenerative disorders. This seems to suggest that a propensity towards one type of disease may decrease the risk of the other. In addition to epidemiologic data, there is also evidence of a complex biological interconnection, with genes, proteins, and pathways often showing opposite dysregulation in cancer and neurodegenerative diseases. In this narrative review, we focus on the possible role played by orexin signaling, which is altered in patients with narcolepsy type 1 and in those with AD and PD, and which has been linked to β-amyloid brain levels and inflammation in mouse models and to cancer in cell lines. Taken together, these lines of evidence depict a possible case of inverse comorbidity between cancer and neurodegenerative disorders, with a role played by orexins. These considerations suggest a therapeutic potential of orexin modulation in diverse pathologies such as narcolepsy, neurodegenerative disorders, and cancer

Combining Information on Nocturnal Rem Sleep Latency and Atonia to Facilitate Diagnosis of Pediatric Narcolepsy Type 1

the diagnosis of narcolepsy type 1 (NT1) at its onset in children and adolescents is often difficult, with substantial diagnostic delay. We aimed to test and validate the effectiveness of rapid-eye-movement (REM) sleep latency (REML), the REM sleep atonia index (RAI), and their combination for the automatic identification of pediatric patients with NT1 based on the standard scoring of nocturnal polysomnograms

Combining Information on Nocturnal Rem Sleep Latency and Atonia to Facilitate Diagnosis of Pediatric Narcolepsy Type 1

Study objectives: the diagnosis of narcolepsy type 1 (NT1) at its onset in children and adolescents is often difficult, with substantial diagnostic delay. We aimed to test and validate the effectiveness of rapid-eye-movement (REM) sleep latency (REML), the REM sleep atonia index (RAI), and their combination for the automatic identification of pediatric patients with NT1 based on the standard scoring of nocturnal polysomnograms. Methods: a retrospective cohort of 71 pediatric patients with NT1 and 42 controls was subdivided in test and validation cohorts. A novel index (COM) was developed as a nonlinear function of REML and RAI. The effectiveness of REML, RAI, and COM in identifying patients with NT1 was assessed with Receiver Operating Characteristic (ROC) curves. Results: REML, RAI and COM significantly identified patients with NT1 both in the test and validation cohorts. Optimal thresholds that maximized identification accuracy were estimated in the test cohort (REML, 49.5 min; RAI, 0.91; COM, 4.57 AU) and validated in the other cohort. COM performed significantly better in identifying patients with NT1 than either REML or RAI, with ROC area under the curve of 94-100%, sensitivity 85-96%, and specificity 92-100%, and with good night-to-night agreement (Cohen's k = 0.69). Conclusions: the analysis of REML, RAI, and particularly their combination in the COM index may help shorten diagnostic delay of NT1 in children and adolescents based on the standard scoring of nocturnal polysomnography