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The coarse-grained machine-learning derived ML-BOP model [Chan et al., Nature Commun. 10, 379 (2019)] provides a monoatomic representation of the water-water interaction potential in which orientational interactions are included as three-body contributions. Despite its simplicity, the model reproduces the phase diagram of water and its anomalies. Here, we show that a two-state Gibbs free energy expression – fitted simultaneously on the temperature and pressure dependence of the density and internal energy – predicts the existence of a liquid–liquid critical point, with critical parameters consistent with previous estimates. We also show that in this model: (i) while the low density liquid is pre-empted by crystal nucleation, the high-density liquid and its spinodal are accessible in numerical studies down to 100 K; (ii) crystallisation requires the presence of a local low density region. Thus, for densities larger than the critical density, spinodal decomposition (or nucleation of the low-density liquid) is a pre-requisite for ice nucleation. [ABSTRACT FROM AUTHOR]

Wireless sensor networks are composed of many nodes distributed in a region of interest to monitor different environments and physical variables. In many cases, access to nodes is not easy or feasible. As such, the system lifetime is a primary design parameter to consider in the design of these networks. In this regard, for some applications, it is preferable to extend the system lifetime by actively reducing the number of packet transmissions and, thus, the number of reports. The system administrator can be aware of such reporting reduction to distinguish this final phase from a malfunction of the system or even an attack. Given this, we explore different mathematical functions that drastically reduce the number of packet transmissions when the residual energy in the system is low but still allow for an adequate number of transmissions. Indeed, in previous works, where the negative exponential distribution is used, the system reaches the point of zero transmissions extremely fast. Hence, we propose different dampening functions with different decreasing rates that present oscillations to allow for packet transmissions even at the end of the system lifetime. We compare the system performance under these mathematical functions, which, to the best of our knowledge, have never been used before, to find the most adequate transmission scheme for packet transmissions and system lifetime. We develop an analytical model based on a discrete-time Markov chain to show that a moderately decreasing function provides the best results. We also develop a discrete event simulator to validate the analytical results. [ABSTRACT FROM AUTHOR]

Employing the Internet of Things (IoT) in healthcare provides many advantages for patient monitoring and analysis of the patient's health with the help of generated data. The basic role of IoT in healthcare is to ease the patient's life by giving them a monitor over their medical condition. The use of IoT in medical devices requires a focus on the end-user. Medical devices such as glucose meters are designed to record the data of the patient and their vital signs. The generated information can be used to enhance decision-making for the physician. The collected information about the patient can be at risk due to certain security issues during the transferring of information can compromise the identity and social life of the patient. This review explores the IoT regarding its structural requirement and its role in various fields with special emphasis on healthcare. The security and privacy issues than can hinder the utilization of IoT at its potential and ways to overcome these issues are being addressed. [ABSTRACT FROM AUTHOR]

The stability of catalyst layers and membranes in proton exchange membrane water electrolysis (PEMWE) cells represents an ongoing challenge, compounded by the dissolution of components and migration of elements within the catalyst‐coated membrane (CCM). Conventional microscopy methods often struggle to efficiently evaluate large cross‐sections of PEMWE membranes, which is essential for representative analysis of technical scale CCMs. Herein, synchrotron radiation‐based X‐Ray fluorescence microscopy is exploited to analyze the stability of CCMs with around 1 μm resolution and a field of view of ≈200 × 75 μm2. Three application scenarios are investigated: 1) migration of catalyst elements, 2) dissolution of components, and 3) contaminated water supply containing Fe2+$\left(\text{Fe}\right)^{2 +}$ ions. XRF is performed at three different X‐Ray energies (11.7, 11.4, and 11.0 keV), revealing the local elemental composition, including Pt, Ir, Ti, and Fe, under different stressing conditions. Notable observations include the distribution of Ir across the membrane and in the cathode catalyst layer, localization of Pt within the membrane, accumulation of Ti in the cathode catalyst layer, and minimal presence of Fe. XRF has been demonstrated to be a powerful analytical tool for accurate and high throughput imaging of catalyst degradation in PEMWE scenarios, particularly of technical scale devices. [ABSTRACT FROM AUTHOR]

Infantile neuroaxonal dystrophy (INAD) is a rare neurodegenerative disorder affecting 1:1,000,000 children. It results from pathogenic variants in the PLA2G6 gene located on chromosome 22q13.1. The onset of symptoms usually occurs between 6 and 18 months, causing developmental regression leading to debilitating symptoms such as muscle weakness, dementia, and loss of basic skills. Eventually, it progresses to life-threatening symptoms, including breathing difficulties, which limit the life expectancy to 5–10 years. While potential genetic therapies for treatment are being developed, they are yet to be approved for use, and management remains essentially supportive. This case report is about a nine-year-old Pakistani girl with INAD. She presented with recurrent chest infections, developmental regression, loss of speech, paralysis, hypertension, and eventually breathing difficulties. Brain magnetic resonance imaging and genetic testing confirmed the diagnosis. This case posed diagnostic challenges in view of its overlapping clinical presentation. Through this report, we aim to raise awareness about this condition among practitioners, outline the importance of genetic counseling in susceptible couples, and suggest potential areas of further research. [ABSTRACT FROM AUTHOR]

Reversible axonal swelling and brainstem auditory evoked potential (BAEP) changes were observed in standard chronic (9‐month) toxicology studies in dogs treated with ritlecitinib, an oral Janus kinase 3/tyrosine kinase expressed in hepatocellular carcinoma family kinase inhibitor, at exposures higher than the approved 50‐mg human dose. To evaluate the clinical relevance of the dog toxicity finding, this phase 2a, double‐blind study assessed BAEP changes and intraepidermal nerve fiber (IENF) histology in adults with alopecia areata treated with ritlecitinib. Patients were randomized to receive oral ritlecitinib 50 mg once daily (QD) with a 4‐week loading dose of 200 mg QD or placebo for 9 months (placebo‐controlled phase); they then entered the active‐therapy extension and received ritlecitinib 50 mg QD (with a 4‐week loading dose of 200 mg in patients switching from placebo). Among the 71 patients, no notable mean differences in change from baseline (CFB) in Waves I–V interwave latency (primary outcome) or Wave V amplitude on BAEP at a stimulus intensity of 80 dB nHL were observed in the ritlecitinib or placebo group at Month 9, with no notable differences in interwave latency or Wave V amplitude between groups. The CFB in mean or median IENF density and in percentage of IENFs with axonal swellings was minimal and similar between groups at Month 9. Ritlecitinib treatment was also not associated with an imbalanced incidence of neurological and audiological adverse events. These results provide evidence that the BAEP and axonal swelling finding in dogs are not clinically relevant in humans. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this review is to present current scientific reports on the pathophysiology, diagnosis and treatment of pantothenate kinase-associated neurodegeneration (PKAN). Views: The condition is caused by a mutation in the PANK2 gene, which results in iron accumulation in the brain and changes in the functioning of biochemical pathways dependent on coenzyme A. There are two clinical types of PKAN, which differ in the time of onset of symptoms and speed of disease progression. Imaging studies, specifically magnetic resonance (MR), and genetic testing are commonly used in the diagnosis process. The characteristic radiological image seen in T2-MR images is the "eye of the tiger". Patients with PKAN can only receive treatment for symptoms because there are no effective treatment methods available. Pharmacological methods include symptomatic medications, such as pregabalin, gabapentin, or botulinum toxin, and disease-modifying agents, such as iron chelators. Surgical procedures or deep brain stimulation as alternative methods can also be considered. The review presents data from studies published between 2017 and 2024. Conclusions: There are many studies on the pathophysiology and treatment methods for PKAN patients, but the results are still limited. The future of PKAN treatment will be characterized by personalized treatment that is based on the patient's genetic and environmental factors. Further investigation of these is necessary. [ABSTRACT FROM AUTHOR]

Multiple barriers with basal clearance are usually adopted in engineering practice to mitigate large volumes of debris flows. This approach allows for sufficient discharge and minimizes the need for cleaning and maintenance over the service life of the barriers. Despite the effectiveness, the design of basal clearance is still based on empirical methods, which can lead to uncertainty in safety. In this study, a new dimensionless overflow number Nof is proposed for designing dual rigid barriers with basal clearance and validated with physical and numerical results. The physical tests were conducted using a 28 m long flume model. A finite element model calibrated using the physical test results is utilized for numerical parametric study to investigate the effects of basal clearance on debris flow impact force against dual barriers. Physical and numerical results reveal that Nof can serve to determine whether the impact force on the second barrier is governed by basal discharge or overflow from the first barrier. A threshold value of Nof=1 can be used to design dual barriers with basal clearance to achieve the lowest impact force on the second barrier. The proposed Nof also enables engineers to predict the impact force on the second barrier by only considering the impact force from basal discharge. [ABSTRACT FROM AUTHOR]

Takotsubo syndrome (TS), also known as apical ballooning syndrome, is a transient stress-related cardiomyopathy characterised by acute but reversible left ventricular dysfunction. The condition tends to occur in postmenopausal women after a stressful event. At presentation, TS typically mimics acute myocardial infarction (MI) and the incidence of TS has been increasing worldwide. This is likely a consequence of an improved awareness of the existence of this syndrome and easier access to early echocardiography and coronary angiography. However, its aetiology remains poorly understood and it is probably still underdiagnosed. Similar to other countries, TS is being increasingly recognised in New Zealand. In this review, we discuss the demographics, clinical features and outcomes of patients with TS in New Zealand. Doing so informs us not only of the pattern of disease in New Zealand but it also provides insights into the condition itself., (© 2022 Royal Australasian College of Physicians.)

Children and adolescents with SGCE-myoclonus dystonia showed a progression of motor symptoms during a mean follow-up of 4 years. Patients developed a significant increase in the severity of axial and limb myoclonus, as well as dystonia during writing. Consequently, patients reported a marked decline in their speech, writing, and walking abilities. Up to 74% of patients had a psychiatric diagnosis, most commonly anxiety, obsessive-compulsive disorders, and attention-deficit/hyperactivity disorder., (© 2025 Mac Keith Press.)

Aim: To investigate the natural progression of SGCE-associated myoclonus dystonia from symptom onset in childhood to early adulthood., Method: Myoclonus and dystonia were monitored using rating scales in two cohorts of participants from Spain and the Netherlands. Individual annualized rates of change were calculated and longitudinal trends were assessed using Bayesian mixed models. Psychiatric features were evaluated cross-sectionally in the Spanish cohort., Results: Thirty-eight patients (21 males, 17 females) were evaluated at a mean age (SD) of 10 years (4 years 7 months; range 2-21 years) and 14 years 2 months (4 years 8 months; range 4-25 years). We observed a significant worsening of action myoclonus, global dystonia, and dystonia during writing (mean annual increases of 1.356, 0.226, and 0.518 in the Unified Myoclonus, Burke-Fahn-Marsden, and Writer's Cramp Rating Scales respectively). Accordingly, participants perceived a significant worsening in their speech, writing, and walking abilities. Twenty-six of 32 participants suffered from anxiety (n = 13), obsessive-compulsive disorder (n = 9), and attention-deficit/hyperactivity disorder (n = 8)., Interpretation: This study demonstrates that, unlike in the adult population, myoclonus dystonia syndrome in childhood and adolescence follows a progressive course that can be debilitating in the early stages of life. These findings, along with a high prevalence of psychiatric symptoms, highlight the need for early therapeutic interventions to prevent long-term motor and psychological sequelae., (© 2024 The Author(s). Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

Neurodegeneration with brain iron accumulation 5 (NBIA5) is a distinctive type of NBIA phenotype that is caused by mutations in the WDR45 gene. This disorder is inherited in an X-linked manner. Here, we report three Iranian cases affected with this condition. Whole-exome sequencing revealed the following pathogenic variants within WDR45 gene in these cases, respectively: c.697 C > T (p.R233X), c.657_658del (p.F221X) and c.1004_1005del (p.Y335Cfs*5). Hypothyroidism was detected in two cases. Other clinical manifestations did not significantly differ from cases reported in the literature. All cases occurred de novo. Similar mutations have been reported in the literature. The present study broadens the insight about the genetics of this disorder in the mentioned population., Competing Interests: Declarations. Ethics approval and consent to participate: Informed consent has been obtained from legal representatives of patients. Ethical approval for this study has been obtained from the Ethical Committee of Shahid Beheshti University of Medical Sciences (IR.SBMU.MSP.REC.1401.583). All methods were carried out in accordance with relevant guidelines and regulations. Competing interests: The authors declare no competing interests. Conflict of interest: The authors declare they have no competing interests. Consent to publication: Informed consent has been obtained from legal representatives of patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Trio-based whole-exome sequencing (trio-WES) enables identification of pathogenic variants, including copy-number variants (CNVs), in children with unexplained neurodevelopmental delay (NDD) and neurodevelopmental comorbidities (NDCs), including autism spectrum disorder (ASD), epilepsy, and attention deficit hyperactivity disorder. Further phenotypic and genetic analysis on trio-WES-tested NDD-NDCs cases may help to identify key phenotypic factors related to higher diagnostic yield of using trio-WES and novel risk genes associated with NDCs in clinical settings. Methods: In this study, we retrospectively performed phenotypic analysis on 163 trio-WES-tested NDD-NDCs children to determine the phenotypic differences between genetically diagnosed and non-genetically diagnosed groups. Additionally, we conducted genetic analysis of ASD genes with the help of Simons Foundation for Autism Research Institute (SFARI) Gene database to identify novel possible ASD-risk genes underlying genetic NDD conditions. Results: Among these 163 patients, pathogenic variants were identified in 82 cases (82/163, 50.3%), including 20 cases with CNVs. By comparing phenotypic variables between genetically diagnosed group (82 cases) and non-genetically diagnosed group (81 cases) with multivariate binary logistic regression analysis, we revealed that NDD-NDCs cases presenting with severe-profound NDD [53/82 vs 17/81, adjusted-OR (95%CI): 4.865 (2.213 – 10.694), adjusted-P < 0.001] or having multiple NDCs [26/82 vs 8/81, adjusted-OR (95%CI): 3.731 (1.399 – 9.950), adjusted-P = 0.009] or accompanying ASD [64/82 vs 35/81, adjusted-OR (95%CI): 3.256 (1.479 – 7.168), adjusted-P = 0.003] and head circumference abnormality [33/82 vs 11/81, adjusted-OR (95%CI): 2.788 (1.148 – 6.774), adjusted-P = 0.024] were more likely to have a genetic diagnosis using trio-WES. Moreover, 37 genes with monogenetic variants were identified in 48 patients genetically diagnosed with NDD-ASD, and 15 dosage-sensitive genes were identified in 16 individuals with NDD-ASD carrying CNVs. Most of those genes had been proven to be ASD-related genes. However, some of them (9 genes) were not proven sufficiently to correlate with ASD. By literature review and constructing protein-protein interaction networks among these 9 candidate ASD-risk genes and 102 established ASD genes obtained from the SFARI Gene database, we identified CUL4B, KCNH1, and PLA2G6 as novel possible ASD-risk genes underlying genetic NDD conditions. Conclusions: Trio-WES testing is recommended for patients with unexplained NDD-NDCs that have severe-profound NDD or multiple NDCs, particularly those with accompanying ASD and head circumference abnormality, as these independent factors may increase the likelihood of genetic diagnosis using trio-WES. Moreover, NDD patients with pathogenic variants in CUL4B, KCNH1 and PLA2G6 should be aware of potential risks of developing ASD during their disease courses. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Clinical Hepatology / Linchuang Gandanbing Zazhi is the property of Journal of Clinical Hepatology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: As the incidence of traumatic spine injuries has been steadily increasing, especially in the elderly, the ability to categorize patients based on their underlying risk for the adverse outcomes could be of great value in clinical decision making. This study aimed to investigate the association between the Revised Cardiac Risk Index (RCRI) and adverse outcomes in patients who have undergone surgery for traumatic spine injuries. Methods: All adult patients (18 years or older) in the 2013–2019 TQIP database with isolated spine injuries resulting from blunt force trauma, who underwent spinal surgery, were eligible for inclusion in the study. The association between the RCRI and in-hospital mortality, cardiopulmonary complications, and failure-to-rescue (FTR) was determined using Poisson regression models with robust standard errors to adjust for potential confounding. Results: A total of 39,391 patients were included for further analysis. In the regression model, an RCRI ≥ 3 was associated with a threefold risk of in-hospital mortality [adjusted IRR (95% CI): 3.19 (2.30–4.43), p < 0.001] and cardiopulmonary complications [adjusted IRR (95% CI): 3.27 (2.46–4.34), p < 0.001], as well as a fourfold risk of FTR [adjusted IRR (95% CI): 4.27 (2.59–7.02), p < 0.001], compared to RCRI 0. The risk of all adverse outcomes increased stepwise along with each RCRI score. Conclusion: The RCRI may be a useful tool for identifying patients with traumatic spine injuries who are at an increased risk of in-hospital mortality, cardiopulmonary complications, and failure-to-rescue after surgery. [ABSTRACT FROM AUTHOR]

This study investigates the antioxidant potential of over 20 sorghum genotypes, spanning popular lines, inter-specific hybrids, and inter-generic crosses. Parameters such as free radical scavenging, flavonoid and phenolic content, and nitrous oxide (NO) neutralization were meticulously assessed. Leading the pack, ISC2020-C and SPV2612 demonstrated exceptional DPPH and ABTS radical scavenging, highlighting their prowess against oxidative stress. ISC812-C stood out for its highest total phenolic content, linking phenolic abundance to overall antioxidant strength. Positive correlations between NO scavenging, DPPH, ABTS, and total phenolic content emphasized the synergistic role of bioactive components in colored sorghum grains. Principal Component Analysis (PCA) revealed distinct patterns, with ISC202-C, ISC812-W, 27B, and SPV2612 displaying potent antioxidant profiles. UPGMA analysis of solvent extracts unveiled clusters, hinting at untapped diversity in inter-specific and inter-generic crosses. ISC304-C shared similarities with SM2288-G, while ISC812-C formed a unique cluster, suggesting unexplored bioactive profiles. In conclusion, this exploration showcases colored sorghum grains as rich sources of bioactive antioxidants. Utilizing inter-specific and inter-generic hybridization strategies can enhance sorghum's nutritional value, fostering the development of safe and functional food products. The research sets the stage for optimizing sorghum breeding and processing techniques, maximizing antioxidant potential for practical applications in human health and food security. [ABSTRACT FROM AUTHOR]

Background It has previously been reported that there are similar reoperation rates after elective colorectal surgery but higher failure-to-rescue (FTR) rates in low-volume hospitals (LVHs) versus high-volume hospitals (HVHs). This study assessed the effect of hospital volume on reoperation rate and FTR after reoperation following elective colorectal surgery in a matched cohort. Methods Population-based retrospective multicentre cohort study of adult patients undergoing reoperation for a complication after an elective, non-centralized colorectal operation between 2006 and 2017 in 11 hospitals. Hospitals were divided into either HVHs (3 hospitals, median ≥126 resections per year) or LVHs (8 hospitals, <126 resections per year). Patients were propensity score–matched (PSM) for baseline characteristics as well as indication and type of elective surgery. Primary outcome was FTR. Results A total of 6428 and 3020 elective colorectal resections were carried out in HVHs and LVHs, of which 217 (3.4%) and 165 (5.5%) underwent reoperation (P < 0.001), respectively. After PSM, 142 patients undergoing reoperation remained in both HVH and LVH groups for final analyses. FTR rate was 7.7% in HVHs and 10.6% in LVHs (P = 0.410). The median Comprehensive Complication Index was 21.8 in HVHs and 29.6 in LVHs (P = 0.045). There was no difference in median ICU-free days, length of stay, the risk for permanent ostomy or overall survival between the groups. Conclusion The reoperation rate and postoperative complication burden was higher in LVHs with no significant difference in FTR compared with HVHs. [ABSTRACT FROM AUTHOR]

In this study, the graphene field-effect transistor (FET) has been created by depositing a film-forming suspension of reduced graphene oxide (RGO) on the silicon substrate with a SiO2 layer and air-drying at room temperature. The possibility of using the obtained FET for ionizing radiation detection was investigated. The electrical characteristics of the radiation sensor based on the RGO film were studied in modes of direct current and alternating current. The dependencies of the drain current and the resistance of the RGO film on the gate voltage of the obtained FET were analyzed. Linear sections on the dependence of the drain current on the gate voltage, the positions of which are determined by the sign of the drain-source voltage, were detected. A decrease in the conductivity of the FET based on the RGO film near the point of charge neutrality due to irradiation from the 226Ra isotope was established. An increase in resistance and a decrease in capacitance of the investigated FET have been found in the frequency range of 25 Hz – 1 MHz caused by the joint action of alpha and beta particles and gamma quanta. A linear dependence of the electrical characteristics of the proposed sensor on the adsorbed dose determined by the irradiation duration was discovered. Possible mechanisms of the ionizing radiation influence on the conductivity of the obtained structure based on the RGO film are considered. The generation of electron-hole pairs in the silicon substrate and the formation of radiation defects in the insulator layer are probably the main factors affecting the electrical characteristics of the RGO based FET under the action of ionizing radiation. The obtained results expand the perspective of using graphene FETs to create a new type of radiation detectors and diametric devices. [ABSTRACT FROM AUTHOR]

Chronic pancreatitis is a common inflammatory disease that severely impairs patients' quality of life, mainly due to abdominal pain which is the most frequent symptom. Current guidelines suggest medical therapy as the first line intervention based on a stepwise use of analgesics (i.e. NSAIDs followed by weak opioids and later by strong oppioids), which is rarely effective in improving pain and often leads to opioid addiction. Interventional procedures are therefore frequently needed. Endoscopic therapy is suggested as the second line of intervention, aiming at decompressing the main pancreatic duct via structure dilatation and ductal stone removal. Endoscopic therapy is usually effective in reducing pain in the short term, but its effects frequently decrease with time and multiple procedures are often required. Surgery is usually reserved as a last resource when medical and endoscopic therapy have failed. Pancreatic surgery is burdened with non negligible morbidity and mortality but is effective in reducing pain and improving quality of life in chronic pancratitis with long lasting effects. Surgical treatment of chronic pancreatitis is based on resection of inflammatory head mass or decompression of the ductal system, alone or in combination, which can be performed using different techniques. In this paper we reviewed the current evidence on the long-term outcomes of this type of surgery in terms of pain relief, quality of life, exocrine end endocrine function, and long-term mortality. Quality of current evidence on this field is on average poor; a consensus to define clinically significant outcomes is needed in order to correctly design prospective studies that will enable gastroenterologists to understand which patients, and when, will benefit most from surgery and should therefore be referred to surgeons. [ABSTRACT FROM AUTHOR]

Aim: The idiographic case study aimed to explore the trust of a person with chronic pancreatitis in healthcare professionals. Design: An interpretive phenomenological idiographic case study. Methods: Data collection was carried out through a semistructured in-depth interview with a 29-year-old man with chronic pancreatitis. The purposive sampling of the participant was carried out according to feasibility criteria. Interpretative phenomenological analysis was used with the assistance of Atlas.ti 9 for data analysis. Results: Five interconnected personal experiential themes reflecting the trust of the participant in healthcare professionals were identified: Trust in healthcare professionals as an inner feeling; Active and partnership approach of healthcare professionals; Paternalistic approach and lack of interest of healthcare professionals in the patient; Expertise of healthcare professionals; and Linking trust in health professionals with the hospital ward environment, with 22 experiential statements. Conclusion: The participant considered trust to be an internal feeling of expectation that healthcare professionals would help him actively solve his health problems. The findings promote the implementation of patient-centered care and the partnership approach in the care of patients with chronic pancreatitis. The personal experience themes identified provide information for further qualitative research aimed at a deeper understanding of the lived experience of trust for patients with chronic pancreatitis. [ABSTRACT FROM AUTHOR]

It is proven that Boson sampling is a much promising model of optical quantum computation, which is applied to designing quantum computer successfully, such as "Jiuzhang". However, the meaningful randomness of Boson sampling results has not been utilized or exploited. In this research, Boson sampling is applied to design a quantum random number generator (QRNG) by fully exploiting the randomness of Boson sampling results, and its prototype system is constructed with the programmable silicon photonic processor, which can generate unbiased random sequences and overcome the shortcomings of the existing discrete QRNGs such as source‐restricted, high demand for the photon number resolution capability of detector and slow self‐detection generator speed. Boson sampling is implemented as a random entropy source, and random bit strings with satisfactory randomness and uniformity can be obtained after post‐processing the sampling results. It is the first approach for applying the randomness of Boson sampling results to develop a practical prototype system for actual tasks, and the experiment results demonstrate that the designed Boson sampling‐based QRNG prototype system passes 15 tests of the NIST SP 800‐22 statistical test component, which proves that Boson sampling has great potential for practical applications with desirable performance besides quantum advantage. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer is a prevalent disease, often progressing to metastatic stages. A subgroup of patients displaying oligometastases presents a unique opportunity for extended survival due to the advances in multidisciplinary treatment. The imperative goal is complete metastatic eradication, with surgical resection serving as the standard of care. For patients ineligible for surgery, percutaneous ablation or stereotactic body radiotherapy are viable options. Although clinical trial evidence supports perioperative systemic therapy in improving progression-free survival, consistent enhancement in overall survival is not observed. Consequently, tailored treatment strategies, considering various oncological factors, are essential for patients with oligometastatic colorectal cancer. Further prospective trials are crucial to establish a comprehensive framework for defining and optimizing the treatment strategy for oligometastatic colorectal cancer. Colorectal cancer (CRC) is the third most common cancer, and nearly half of CRC patients experience metastases. Oligometastatic CRC represents a distinct clinical state characterized by limited metastatic involvement, demonstrating a less aggressive nature and potentially improved survival with multidisciplinary treatment. However, the varied clinical scenarios giving rise to oligometastases necessitate a precise definition, considering primary tumor status and oncological factors, to optimize treatment strategies. This review delineates the concepts of oligometastatic CRC, encompassing oligo-recurrence, where the primary tumor is under control, resulting in a more favorable prognosis. A comprehensive examination of multidisciplinary treatment with local treatments and systemic therapy is provided. The overarching objective in managing oligometastatic CRC is the complete eradication of metastases, offering prospects of a cure. Essential to this management approach are local treatments, with surgical resection serving as the standard of care. Percutaneous ablation and stereotactic body radiotherapy present less invasive alternatives for lesions unsuitable for surgery, demonstrating efficacy in select cases. Perioperative systemic therapy, aiming to control micrometastatic disease and enhance local treatment effectiveness, has shown improvements in progression-free survival through clinical trials. However, the extension of overall survival remains variable. The review emphasizes the need for further prospective trials to establish a cohesive definition and an optimized treatment strategy for oligometastatic CRC. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Clinical Hepatology / Linchuang Gandanbing Zazhi is the property of Journal of Clinical Hepatology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Sleep patterns are more frequently interrupted in patients with Parkinson's disease (PD), and it is still unclear whether genetic factors are involved in PD-related sleep disorders. In this study, we hypothesize that PD-associated genetic risk affects lipid metabolism, which in turn contributes to different types of sleep disorders. Methods: We used a non-targeted lipidomics to explore the lipid composition of cerebrospinal fluid (CSF) exosomes derived from patients with PD carrying phospholipase A2 Group VI (PLA2G6) and sphingomyelin phosphodiesterase 1 (SMPD1) mutations. Results: PLA2G6 mutations (c.1966C > G, Leu656Val; c.2077C > G, Leu693Val; c.1791delC, His597fx69) significantly increase the exosomal content of glycerophospholipids and lysophospholipids, specifically phosphatidylcholine (PC) and lysophosphatidylcholine (LPC). Exosome surface presence of melatomin receptor 1A (MTNR1A) was detectable only in patients with PLA2G6 mutations. We have further shown that, in patients with PD carrying PLA2G6 mutations, sleep latency was significantly longer compared to those carrying WT PLA2G6, and we speculate that functional PLA2G6 mutations lead to structural changes and lipid deregulation of exosomes, which in turn alters exosomal cargo and affects PD-related sleep disorders. In SMPD1, G508R variant-carrying patients with PD abundance of sphingomyelins was significantly higher and had significantly shorter rapid eye movement sleep. Conclusions: Our study demonstrated that the disturbed composition and function of CSF-derived exosome lipidome during the pathological stage of PD may affect different types of sleep disorder in PD. [ABSTRACT FROM AUTHOR]

In the early stages of Alzheimer–Perusini's disease (AD), individuals often experience vision-related issues such as color vision impairment, reduced contrast sensitivity, and visual acuity problems. As the disease progresses, there is a connection with glaucoma and age-related macular degeneration (AMD) leading to retinal cell death. The retina's involvement suggests a link with the hippocampus, where most AD forms start. A thinning of the retinal nerve fiber layer (RNFL) due to the loss of retinal ganglion cells (RGCs) is seen as a potential AD diagnostic marker using electroretinography (ERG) and optical coherence tomography (OCT). Amyloid beta fragments (Aβ), found in the eye's vitreous and aqueous humor, are also present in the cerebrospinal fluid (CSF) and accumulate in the retina. Aβ is known to cause tau hyperphosphorylation, leading to its buildup in various retinal layers. However, diseases like AD are now seen as mixed proteinopathies, with deposits of the prion protein (PrP) and α-synuclein found in affected brains and retinas. Glial cells, especially microglial cells, play a crucial role in these diseases, maintaining immunoproteostasis. Studies have shown similarities between retinal and brain microglia in terms of transcription factor expression and morphotypes. All these findings constitute a good start to achieving better comprehension of neurodegeneration in both the eye and the brain. New insights will be able to bring the scientific community closer to specific disease-modifying therapies. [ABSTRACT FROM AUTHOR]

HERMES Pathfinder is an in-orbit demonstration consisting of a constellation of six 3U nano-satellites hosting simple but innovative detectors for the monitoring of cosmic high-energy transients. The main objective of HERMES Pathfinder is to prove that accurate position of high-energy cosmic transients can be obtained using miniaturized hardware. The transient position is obtained by studying the delay time of arrival of the signal to different detectors hosted by nano-satellites on low-Earth orbits. In this context, we need to develop novel tools to fully exploit the future scientific data output of HERMES Pathfinder. In this paper, we introduce a new framework to assess the background count rate of a spaceborne, high energy detector; a key step towards the identification of faint astrophysical transients. We employ a neural network to estimate the background lightcurves on different timescales. Subsequently, we employ a fast change-point and anomaly detection technique called Poisson-FOCuS to identify observation segments where statistically significant excesses in the observed count rate relative to the background estimate exist. We test the new software on archival data from the NASA Fermi Gamma-ray Burst Monitor (GBM), which has a collecting area and background level of the same order of magnitude to those of HERMES Pathfinder. The neural network performances are discussed and analyzed over period of both high and low solar activity. We were able to confirm events in the Fermi-GBM catalog, both solar flares and gamma-ray bursts, and found events, not present in Fermi-GBM database, that could be attributed to solar flares, terrestrial gamma-ray flashes, gamma-ray bursts and galactic X-ray flashes. Seven of these are selected and further analyzed, providing an estimate of localisation and a tentative classification. [ABSTRACT FROM AUTHOR]

Background: Neuroaxonal dystrophy (NAD) is a group of inherited neurodegenerative disorders characterized primarily by the presence of spheroids (swollen axons) throughout the central nervous system. In humans, NAD is heterogeneous, both clinically and genetically. NAD has also been described to naturally occur in large animal models, such as dogs. A newly recognized disorder in Miniature American Shepherd dogs (MAS), consisting of a slowly progressive neurodegenerative syndrome, was diagnosed as NAD via histopathology., Objectives: To describe the clinical and pathological phenotype together with the identification of the underlying genetic cause., Methods: Clinical and postmortem evaluations, together with a genome-wide association study and autozygosity mapping approach, followed by whole-genome sequencing., Results: Affected dogs were typically young adults and displayed an abnormal gait characterized by pelvic limb weakness and ataxia. The underlying genetic cause was identified as a 1-bp (base pair) deletion in RNF170 encoding ring finger protein 170, which perfectly segregates in an autosomal recessive pattern. This deletion is predicted to create a frameshift (XM&#95;038559916.1:c.367delG) and early truncation of the RNF170 protein (XP&#95;038415844.1:(p.Ala123Glnfs*11)). The age of this canine RNF170 variant was estimated at ~30 years, before the reproductive isolation of the MAS breed., Conclusions: RNF170 variants were previously identified in human patients with autosomal recessive spastic paraplegia-85 (SPG85); this clinical phenotype shows similarities to the dogs described herein. We therefore propose that this novel MAS NAD could serve as an excellent large animal model for equivalent human diseases, particularly since affected dogs demonstrate a relatively long lifespan, which represents an opportunity for therapeutic trials. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Pathogenic variants in the WDR45 (OMIM: 300,526) gene on chromosome Xp11 are the genetic cause of a rare neurological disorder characterized by increased iron deposition in the basal ganglia. As WDR45 encodes a beta-propeller scaffold protein with a putative role in autophagy, the disease has been named Beta-Propeller Protein-Associated Neurodegeneration (BPAN). BPAN represents one of the four most common forms of Neurodegeneration with Brain Iron Accumulation (NBIA). In the current study, we generated and characterized a whole-body Wdr45 knock-out (KO) mouse model. The model, developed using TALENs, presents a 20-bp deletion in exon 2 of Wdr45. Homozygous females and hemizygous males are viable, proving that systemic depletion of Wdr45 does not impair viability and male fertility in mice. The in-depth phenotypic characterization of the mouse model revealed neuropathology signs at four months of age, neurodegeneration progressing with ageing, hearing and visual impairment, specific haematological alterations, but no brain iron accumulation. Biochemically, Wdr45 KO mice presented with decreased complex I (CI) activity in the brain, suggesting that mitochondrial dysfunction accompanies Wdr45 deficiency. Overall, the systemic Wdr45 KO described here complements the two mouse models previously reported in the literature (PMIDs: 26,000,824, 31,204,559) and represents an additional robust model to investigate the pathophysiology of BPAN and to test therapeutic strategies for the disease., (© 2021. The Author(s).)

The detection module of the ARDESIA spectrometer, an SDD-based, multichannel X-ray detector is presented. The detector design and experimental characterization are discussed. ARDESIA has been optimized for synchrotron radiation applications that require high-rate (>1-Mcps per channel) and high-resolution (better than 200 eV at 6 keV) X-ray detection. The main target applications considered in this development are X-ray fluorescence and X-ray absorption fine structure spectroscopy, in particular for the DAFNE-Light DXR1 beamline at LNF (Frascati, Italy). This detector is based on a compact unit (16 mm $\times16$ mm) that can be replicated and juxtaposed with several units, thus easily covering different detection configurations. The detector consists of a four-channel monolithic array of SDDs, produced by Fondazione Bruno Kessler (Trento, Italy) connected to a four-channel monolithic CUBE preamplifier mounted on the same carrier. The CUBE preamplifier, compatible with both analog and digital pulse processing, enables reaching high count rates (1-Mcps per channel), while keeping good spectroscopic performances. It is extremely low white series noise guarantees good energy resolution, even at short pulse processing times (below 200 ns). [ABSTRACT FROM AUTHOR]

In recent decades, deep brain stimulation (DBS) has been extensively studied due to its reversibility and significantly fewer side effects. DBS is mainly a symptomatic therapy, but the stimulation of subcortical areas by DBS is believed to affect the cytoarchitecture of the brain, leading to adaptability and neurogenesis. The neurological disorders most commonly studied with DBS were Parkinson's disease, essential tremor, obsessive-compulsive disorder, and major depressive disorder. The most precise approach to evaluating the location of the leads still relies on the stimulus-induced side effects reported by the patients. Moreover, the adequate voltage and DBS current field could correlate with the patient's symptoms. Implantable pulse generators are the main parts of the DBS, and their main characteristics, such as rechargeable capability, magnetic resonance imaging (MRI) safety, and device size, should always be discussed with patients. The safety of MRI will depend on several parameters: the part of the body where the device is implanted, the part of the body scanned, and the MRI-tesla magnetic field. It is worth mentioning that drug-resistant individuals may have different pathophysiological explanations for their resistance to medications, which could affect the efficacy of DBS therapy. Therefore, this could explain the significant difference in the outcomes of studies with DBS in individuals with drug-resistant neurological conditions. [ABSTRACT FROM AUTHOR]

Background: Most episodic ataxias (EA) are autosomal dominantly inherited and characterized by recurrent attacks of ataxia and other paroxysmal and non‐paroxysmal features. EA is often caused by pathogenic variants in the CACNA1A, KCNA1, PDHA1, and SLC1A3 genes, listed as paroxysmal movement disorders (PxMD) by the MDS Task Force on the Nomenclature of Genetic Movement Disorders. Little is known about the genotype–phenotype correlation of the different genetic EA forms. Methods: We performed a systematic review of the literature to identify individuals affected by an episodic movement disorder harboring pathogenic variants in one of the four genes. We applied the standardized MDSGene literature search and data extraction protocol to summarize the clinical and genetic features. All data are available via the MDSGene protocol and platform on the MDSGene website (https://www.mdsgene.org/). Results: Information on 717 patients (CACNA1A: 491, KCNA1: 125, PDHA1: 90, and SLC1A3: 11) carrying 287 different pathogenic variants from 229 papers was identified and summarized. We show the profound phenotypic variability and overlap leading to the absence of frank genotype–phenotype correlation aside from a few key 'red flags'. Conclusion: Given this overlap, a broad approach to genetic testing using a panel or whole exome or genome approach is most practical in most circumstances. [ABSTRACT FROM AUTHOR]