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Dead time is a common instrumental effect of X-ray detectors, which would alter the behaviour of timing properties of astronomical signals, such as distorting the shape of power density spectra (PDS), affecting the root-mean-square of potential quasi-periodic oscillation signals, etc. We revisit the effects of the dead time of Medium Energy X-ray telescope (ME) onboard Insight - HXMT based on the simulation of electronic read-out mechanism that causes the dead time and the real data. We investigate dead time effects on the pulse profile as well as the quasi–periodic oscillation (QPO) signals. The dead time coefficient suggests a linear correlation with the observed count rate in each phase bin of the pulse profile according to the simulation of periodic signal as well as the real data observed on Swift J0243.6+6124. The Fourier-amplitude-difference (FAD) method could well recover the intrinsic shape of the observed PDS in the case that the PDS is from two identical detectors. We apply this technique on ME, by splitting the nine FPGA modules into two groups. The results indicate that the FAD technique suits the case when two groups of detectors are not largely different; and the recovered PDS of Sco X-1 observed by ME slightly enhances the significance of the previously known QPO signal, meanwhile the root-mean-square of QPO is significantly improved. We provide the FAD correction tool implemented in HXMTDAS for users in the future to better analyse QPO signals. [ABSTRACT FROM AUTHOR]

Introduction: The use of robotic systems in the surgical domain has become groundbreaking for patients and surgeons in the last decades. While the annual number of robotic surgical procedures continues to increase rapidly, it is essential to provide the surgeon with innovative training courses along with the standard specialization path. To this end, simulators play a fundamental role. Currently, the high cost of the leading VR simulators limits their accessibility to educational institutions. The challenge lies in balancing highfidelity simulation with cost-effectiveness; however, few cost-effective options exist for robotic surgery training. Methods: This paper proposes the design, development and user-centered usability study of an affordable user interface to control a surgical robot simulator. It consists of a cart equipped with two haptic interfaces, a VR visor and two pedals. The simulations were created using Unity, which offers versatility for expanding the simulator to more complex scenes. An intuitive teleoperation control of the simulated robotic instruments is achieved through a high-level control strategy. Results and Discussion: Its affordability and resemblance to real surgeon consoles make it ideal for implementing robotic surgery training programs in medical schools, enhancing accessibility to a broader audience. This is demonstrated by the results of an usability study involving expert surgeons who use surgical robots regularly, expert surgeons without robotic surgery experience, and a control group. The results of the study, which was based on a traditional Peg-board exercise and Camera Control task, demonstrate the simulator's high usability and intuitive control across diverse user groups, including those with limited experience. This offers evidence that this affordable system is a promising solution for expanding robotic surgery training. [ABSTRACT FROM AUTHOR]

We report a time-resolved analysis of the accreting X-ray pulsar Cen X-3 using observations carried out by NuSTAR, which cover approximately two binary orbits in different intensity states. The pulse profile is relatively stable over the orbital phase and shows energy dependence. It has an obvious double-peaked shape in the energy band below 15 keV –with the second pulse peak decreasing as energy increases– and is gradually dominated by a single peak in higher energy bands. We find that the pulse profile in the energy band of 3–5 keV at high-intensity states shows a subtle triple-peaked shape, with the main peak divided into two subpeaks. We also find a positive correlation between the pulse fraction and both energy and flux. Our spectral analysis reveals that the spectra can be well described by the continuum of Fermi-Dirac cutoff and NPEX models, and the cyclotron line is detected with the centroid energies varying from 26 keV to 29 keV, along with the iron emission line around 6.4 keV. We investigated the dependence between the cyclotron resonant scattering feature (CRSF) centroid energy and luminosity and discuss the theoretical critical luminosity. Although the variation of Ecyc − LX is not distinct, there is a possibility that the critical luminosity lies within the range of ∼(0.5 − 4)×1037 erg s−1 in the band of 4–78 keV. The photon index shows a strong positive correlation with luminosity. Our orbital-phase analysis reveals that the spectral parameters show orbital variability, and the highly variable photoelectric absorption may indicate the existence of clumpy stellar winds. [ABSTRACT FROM AUTHOR]

Autonomic symptoms may be local and general clinical manifestations of both epilepsy and migraine caused by the dysfunction of brain areas best known as the central autonomic network. Despite their prevalence, autonomic signs are often misdiagnosed and their treatment is undervalued. This review aims to describe the autonomic manifestations reported during seizures and migraineur attacks according to their presentation, focusing on the role of the central autonomic network (CAN) and on the parasympathetic outflow that often-induced cranial autonomic symptoms (CAS) during migraineur attacks. Further, our purpose is to analyze the pathophysiological meanings and whether their presence influences the prognosis and therapy of these disorders. [ABSTRACT FROM AUTHOR]

A thorough inspection of known Galactic supernova remnants (SNRs) along the Galactic plane with SRG/eROSITA yielded the detection of the X-ray counterpart of the SNR G279.0+01.1. The SNR is located just 1.5° above the Galactic plane. Its X-ray emission emerges as an incomplete, partial shell of ~3° angular extension. It is strongly correlated to the fragmented shell-type morphology of its radio continuum emission. The X-ray spatial morphology of the SNR seems to be linked to the presence of dust clouds in the surroundings. The majority of its X-ray emission is soft (exhibiting strong O, Ne, and Mg lines), and it occurs in a narrow range of energies between 0.3 and 1.5 keV. Above 2.0 keV the remnant remains undetected. The remnant's X-ray spectrum is purely of a thermal nature. Constraining the X-ray absorption column to values which are consistent with optical extinction data from the remnant's location favors nonequilibrium over equilibrium models. A nonequilibrium two-temperature plasma model of kT ~ 0.3 keV and kT ~ 0.6 keV, as well as an absorption column density of NH ~ 0.3 cm−2 describe the spectrum of the entire remnant well. Significant temperature variations across the remnant have been detected. Employing 14.5 yr of Fermi-LAT data, we carried out a comprehensive study of the extended giga-electronvolt source 4FGL J1000.0-5312e. By refining and properly modeling the giga-electronvolt excess originating from the location of the remnant, we conclude that the emission is likely related to the remnant itself rather than being colocated by chance. The remnant's properties as determined by the X-ray spectra are consistent with the ~2.5 kpc distance estimates from the literature, which implies a source diameter of ~140 pc and an old age of >7 × 105 yr. However, if the source is associated with any of the pulsars previously considered to be associated with the SNR, then the updated nearby pulsar distance estimates from the YMW16 electron density model rather place the SNR at a distance of ~0.4 kpc. This would correspond to a ~20 pc linear size and a younger age of 104− < 7 × 105 yr, which would be more in line with the nonequilibrium state of the plasma. [ABSTRACT FROM AUTHOR]

Recurrent headaches, encompassing migraine and tension-type headaches, represent prevalent conditions affecting individuals across different age groups, exerting a substantial influence on daily functioning and quality of life. Headaches serve as common manifestations of underlying health issues. Among these, celiac disease, an autoimmune disorder activated by gluten consumption, has emerged as a noteworthy concern. Recent research indicates a correlation between celiac disease and heightened susceptibility to headaches, particularly migraines. Celiac disease (CD) is an immune-mediated systemic, widespread disorder presenting a heterogeneous constellation of symptoms with a relatively easy diagnosis and therapy. Among signs and symptoms exhibited in celiac disease patients, headache is one of the most common neurological issues addressed among both adults and children. Headache disorders and CD are highly prevalent in the general population; for this reason, any causal association between these conditions and the role of a gluten-free diet (GFD) has been debated. The aim of this manuscript is to review the current scientific literature regarding the potential association between CD and headaches and the beneficial effects of a GFD. Among the various authors, in our opinion, the current state of the evidence suggests a significant role for the early screening of CD during the initial diagnosis of recurrent headaches, either in adults or children. [ABSTRACT FROM AUTHOR]

We present the results obtained from an X-ray timing study of the new black hole candidate Swift J1727.8−1613. The work is based on Hard X-ray Modulation Telescope (Insight - HXMT) observations carried out during the 2023 outburst. Prominent type-C low-frequency Quasi-periodic Oscillations (LFQPOs) are detected throughout the observations. With the substantial effective area of the Insight - HXMT at high energies, we examine the energy dependence of various parameters, including the centroid frequency, fractional rms, and phase lags of the type-C QPOs. Our findings align closely with those observed in high-inclination systems. During the initial stage of the outburst, a peaked noise component is also detected, the frequency of which is highly correlated with the LFQPO frequency, aligning with the Psaltis–Belloni–van der Klis relation. By assuming that the peaked noise originates from the precession of the accretion disc, the spin of this source can be constrained. Our results suggest that this source may possess a high spin. [ABSTRACT FROM AUTHOR]

The adaptor protein 4 (AP-4) constitutes a conserved hetero-tetrameric complex within the family of adaptor protein (AP) complex, crucial for the signal-mediated trafficking of integral membrane proteins. Mutations affecting all subunits of the AP-4 complex have been linked to autosomal-recessive cerebral palsy and a complex hereditary spastic paraparesis (HSP) phenotype. Our report details the case of a 14-year-old boy born to consanguineous parents, presenting psychomotor delay, severe intellectual disability, microcephaly, and trigonocephaly. Despite a history of febrile seizures, subsequent years were devoid of seizures, with normal EEG. Exome sequencing revealed pathogenic variants in both the AP4B1 and ERF genes. Significantly, the patient exhibited features associated with AP4B1 mutations, including distinctive traits such as cranial malformations. The ERF gene variant, linked to craniosynostosis, likely contributes to the observed trigonocephaly. This case represents the initial documentation of a concurrent mutation in the AP4B1 and ERF genes, underscoring the critical role of exome analysis in unraveling complex phenotypes. Understanding these complex genotypes offers valuable insights into broader syndromic conditions, facilitating comprehensive patient management. [ABSTRACT FROM AUTHOR]

The pathophysiological mechanisms underlying migraine are more difficult to investigate in children than in the adult population. Abnormal cortical excitability turns out to be one of the most peculiar aspects of migraine, accounting for the manifestations of migraine attacks. Recently, visual cortical excitability has been explored effectively in adult migraineurs with a technique based on cross-modal audio-visual illusions (with sound-induced flash illusions (SIFIs) being reduced in migraineurs compared to non-migraineur subjects). On such a basis, in this study, we investigated visual cortical excitability in children with migraine using SIFIs using combinations of visual and sound stimuli presented randomly. We evaluated 26 children with migraine without aura and 16 healthy children. Migraineurs did not differ from the age-matched healthy subjects regarding fission or fusion illusions but perceived more flashes in trials of multiple flashes with or without beeps. The higher number of SIFIs in migraineur children compared to adults may be due to a greater propensity of visual stimulation to be driven by auditory stimuli (i.e., acoustic dominance). The increased ability to perceive flashes reveals a hyperfunctional visual cortex, demonstrating that the use of SIFIs is a valid tool for assessing visual cortical responsiveness even in pediatric migraine. [ABSTRACT FROM AUTHOR]

Background: Plexiform neurofibromas (pNFs) are benign neoplasms, primarily originating from Schwann cells, posing challenges in patients with type 1 neurofibromatosis (NF1) due to pain, disfigurement, compression of vital structures and potential for malignancy. Selumetinib, a MEK1/2 inhibitor, has shown promising results in treating inoperable pNFs, with clinical trials demonstrating tumor volume reduction and improved patient-reported outcomes. Despite its efficacy, dermatologic toxicities may impact the quality of life and treatment adherence. Evaluating the frequency and spectrum of such effects is crucial for effective management. Methods: In a four-year retrospective and prospective study, pediatric NF1 patients with symptomatic, inoperable plexiform neurofibromas (pNFs) were treated with selumetinib. Eligibility criteria included significant morbidity, pNF size exceeding 3 cm or surgical inoperability, and performance status >70%. Hematological, liver, lung and cardiac assessments established baseline health. Selumetinib, orally administered at 25 mg/m2 twice, was administered for two years unless a response warranting extension occurred. Cutaneous AEs were documented and graded by severity according to CTCAE v5.0, with evaluations every three to six months. The impact on symptoms and pNF size was systematically recorded, and biopsies characterized histopathological features in those patients requiring surgery. Results: Twenty patients were enrolled, with an average age at therapy initiation of 11.6 years. Cutaneous side effects were common, with all patients experiencing at least one and a median of two per patient. Xerosis, paronychia and acneiform rash were prevalent. Notably, pre-pubertal individuals were more susceptible to xerosis. Acneiform rash had a higher incidence in older patients and those with skin phototypes II and III. Successful management involved tailored approaches, such as clindamycin for acneiform rash and topical agents for paronychia. Hair abnormalities, including color changes and thinning, occurred, with female patients at higher risk for the latter. Paronychia presented challenges, necessitating various interventions, including surgical approaches. AEs led to treatment suspension in 20% of patients, with tumor rebound observed in 75%. Conclusions: According to our experience, successful management of selumetinib-induced cutaneous AEs requires tailored strategies including surgery. AEs might indirectly determine pNF regrowth due to therapy suspension. We thus emphasize the pivotal role of addressing cutaneous reactions for effective selumetinib management in pediatric patients. [ABSTRACT FROM AUTHOR]

Accretion is a universal astrophysical process that plays a key role in cosmic history, from the epoch of reionization to galaxy and stellar formation and evolution. Accreting stellar-mass black holes in X-ray binaries are one of the best laboratories to study the accretion process and probe strong gravity--and most importantly, to measure the angular momentum, or spin, of black holes, and its role as a powering mechanism for relativistic astrophysical phenomena. Comprehensive characterization of the disk-corona system of accreting black holes, and their co-evolution, is fundamental to measurements of black hole spin. Here, we use simulated data to demonstrate how key unanswered questions in the study of accreting stellar-mass black holes will be addressed by the High Energy X-ray Probe (HEX-P). HEX-P is a probe-class mission concept that will combine high spatial resolution X-ray imaging and broad spectral coverage (0.2-80 keV) with a sensitivity superior to current facilities (including XMM-Newton and NuSTAR) to enable revolutionary new insights into a variety of important astrophysical problems. We illustrate the capability of HEX-P to: 1) measure the evolving structures of black hole binary accretion flows down to low (≲ 0.1%) Eddington-scaled luminosities via detailed X-ray reflection spectroscopy; 2) provide unprecedented spectral observations of the coronal plasma, probing its elusive geometry and energetics; 3) perform detailed broadband studies of stellar mass black holes in nearby galaxies, thus expanding the repertoire of sources we can use to study accretion physics and determine the fundamental nature of black holes; and 4) act as a complementary observatory to a range of future ground and space-based astronomical observatories, thus providing key spectral measurements of the multi-component emission from the inner accretion flows of black hole X-ray binaries. [ABSTRACT FROM AUTHOR]

The ketogenic diet (KD) restricts carbohydrate consumption, leading to an increase in ketone bodies, such as acetoacetate, β-hydroxybutyrate, and acetone, which are utilized as energy substrates. This dietary approach impacts several biochemical processes, resulting in improved clinical management of various disorders, particularly in childhood. However, the exact mechanisms underlying the efficacy of KD remain unclear. Interestingly, KD may also impact the gut microbiota, which plays a pivotal role in metabolism, nutrition, and the development of the immune and nervous systems. KD has gained popularity for its potential benefits in weight loss, blood sugar control, and certain neurological conditions. This narrative review sums up KD-related studies published over 30 years. While short-term studies have provided valuable insights into the effects of KD on the gut microbiota, persistent uncertainties surround its long-term efficacy and potential for inducing dysbiosis. The significant influence of KD on epigenetic mechanisms, intracellular pathways, and gut microbial composition underscores its potential as a therapeutic choice. However, a judicious consideration of the potential risks associated with the strict adherence to a low-carbohydrate, high-fat, and high-protein regimen over prolonged periods is imperative. As KDs gain popularity among the adolescent and young adult demographic for weight management, it becomes imperative to undertake additional research to comprehensively assess their impact on nutritional status and gut microbiota, ensuring a holistic and sustainable approach to medical nutrition. [ABSTRACT FROM AUTHOR]

We report on Imaging X-ray polarimetry explorer (IXPE) observations of the Be-transient X-ray pulsar LS V +44 17/RX J0440.9+4431 made at two luminosity levels during the giant outburst in January–February 2023. Considering the observed spectral variability and changes in the pulse profiles, the source was likely caught in supercritical and subcritical states with significantly different emission-region geometry, associated with the presence of accretion columns and hot spots, respectively. We focus here on the pulse-phase-resolved polarimetric analysis and find that the observed dependencies of the polarization degree and polarization angle (PA) on the pulse phase are indeed drastically different for the two observations. The observed differences, if interpreted within the framework of the rotating vector model (RVM), imply dramatic variations in the spin axis inclination, the position angle, and the magnetic colatitude by tens of degrees within the space of just a few days. We suggest that the apparent changes in the observed PA phase dependence are predominantly related to the presence of an unpulsed polarized component in addition to the polarized radiation associated with the pulsar itself. We then show that the observed PA phase dependence in both observations can be explained with a single set of RVM parameters defining the pulsar's geometry. We also suggest that the additional polarized component is likely produced by scattering of the pulsar radiation in the equatorial disk wind. [ABSTRACT FROM AUTHOR]

Background: Congenital myopathies are a group of clinically, genetically, and histologically heterogeneous diseases caused by mutations in a large group of genes. One of these is CACNA1S, which is recognized as the cause of Dihydropyridine Receptor Congenital Myopathy. Methods: To better characterize the phenotypic spectrum of CACNA1S myopathy, we conducted a systematic review of cases in the literature through three electronic databases following the PRISMA guidelines. We selected nine articles describing 23 patients with heterozygous, homozygous, or compound heterozygous mutations in CACNA1S and we added one patient with a compound heterozygous mutation in CACNA1S (c.1394-2A>G; c.1724T>C, p.L575P) followed at our Institute. We collected clinical and genetic data, muscle biopsies, and muscle MRIs when available. Results: The phenotype of this myopathy is heterogeneous, ranging from more severe forms with a lethal early onset and mild–moderate forms with a better clinical course. Conclusions: Our patient presented a phenotype compatible with the mild–moderate form, although she presented peculiar features such as a short stature, myopia, mild sensorineural hearing loss, psychiatric symptoms, and posterior-anterior impairment gradient on thigh muscle MRI. [ABSTRACT FROM AUTHOR]

In this work, using Neutron star Interior Composition Explorer and Insight - Hard X-ray Modulation Telescope observations, we present a study of the broad-band spectral and timing evolution of the source throughout the first reflare, which occurred about 4-month after the major outburst. Our findings suggest that during the reflare, below a critical luminosity L crit ∼ 2.5 × 1036 (D/2.2 kpc)2 erg s−1, the scale of the corona shrinks in the radial direction, whereas the inner radius of the disc does not change considerably; however, the inner radius of the disc starts to move inward when the source exceeds the critical luminosity. We conclude that at low luminosity the increase in accretion rate only heats up the inner zone of the accretion disc without the transfer of angular momentum which occurs above a certain luminosity. [ABSTRACT FROM AUTHOR]

Poor outcomes are common in individuals with anxiety and depression, and the brain circuits underlying symptoms and treatment responses remain elusive. To elucidate these neural circuits, experimental studies must specifically manipulate them, which is only possible in animals. Here, we used a chemogenetics strategy involving engineered designer receptors exclusively activated by designer drugs (DREADDs) to activate a region of the marmoset brain that is dysfunctional in human patients with major depressive disorder, called the subcallosal anterior cingulate cortex area 25 (scACC-25). Using this DREADDs system, we identified separate scACC-25 neural circuits that underlie specific components of anhedonia and anxiety in marmosets. Activation of the neural pathway connecting the scACC-25 to the nucleus accumbens (NAc) caused blunting of anticipatory arousal (a form of anhedonia) in marmosets in response to a reward-associated conditioned stimulus in an appetitive Pavlovian discrimination test. Separately, activation of the circuit between the scACC-25 and the amygdala increased a measure of anxiety (the threat response score) when marmosets were presented with an uncertain threat (human intruder test). Using the anhedonia data, we then showed that the fast-acting antidepressant ketamine when infused into the NAc of marmosets prevented anhedonia after scACC-25 activation for more than 1 week. These neurobiological findings provide targets that could contribute to the development of new treatment strategies. Dissecting the neural circuitry of depression: There is still much to learn about the brain circuits involved in depression and anxiety. Here, Wood and colleagues demonstrate that specific connections of a brain region called area 25 directly affect anxiety and anhedonia in marmosets. Using a chemogenetics strategy, the authors showed that activation of area 25 connections to the nucleus accumbens resulted in anhedonia, whereas activation of area 25 connections to the amygdala induced anxiety in the animals. Moreover, the nucleus accumbens was a target for the response of marmosets to the fast-acting antidepressant ketamine. These findings may help to elucidate more effective treatment strategies for depression and anxiety. —OS [ABSTRACT FROM AUTHOR]