Miracle-dz/UniFAR-FTUs huggingface dataset:
The KM3NeT Consortium and the northern hemisphere neutrino telescope

The KM3NeT Consortium is currently carrying on a research and development activity to build a cubic kilometerscale neutrino telescope in the deep Mediterranean Sea. The KM3NeT Consortium follows on from the NEMO and NESTOR pilot projects, which have produced several prototypes and the ANTARES collaboration, which has built and is operating a 0.1 cubic kilometer volume deep-sea neutrino telescope. The KM3NeT Mediterranean neutrino telescope will complement the Antarctic Icecube observatory, allowing the complete survey of the sky using neutrinos as a probe. The main physics goals of KM3NeT include the detection of neutrinos from astrophysical sources such as active galactic nuclei, supernova remnants and γ-ray bursts as well as the search for new physics, such as neutrino signals from neutralino annihilation. To achieve the best performance, an extensive optimisation process is underway, looking for the best geometrical configuration of the detector for maximum sensitivity, and evaluating the most reliable.
Ubiquitination of NKCC2 by the cullin-RING E3 ubiquitin ligase family in the thick ascending limb of the loop of Henle

The Na/K/2Cl cotransporter (NKCC2) in the thick ascending limb of the loop of Henle (TAL) mediates NaCl reabsorption. Cyclic guanosine monophosphate (cGMP), the second messenger of nitric oxide and atrial natriuretic peptide, inhibits NKCC2 activity by stimulating NKCC2 ubiquitination and decreasing surface NKCC2 levels. Among the E3-ubiquitin ligase families, the Cullin-RING E3 ubiquitin ligase (CRL) family is the largest. Cullins are molecular scaffold proteins that recruit multiple subunits to form the CRL complex. We hypothesize that a CRL complex mediates the cGMP-dependent increase in NKCC2 ubiquitination in TALs. Cullin-1, -2, -3, -4A, and -5 express at the protein level, while the other members of the cullin family were expressed at the mRNA level in rats TAL. CRL complex activity is regulated by the neuronal precursor cell-expressed developmentally downregulated protein 8 (Nedd8) to cullins, process called neddylation. Inhibition of cullin neddylation blunted the cGMP-dependent increase in ubiquitinated NKCC2, while increasing the expression of cullin-1 by threefold, but this effect was not seen on other cullins. CRL complex activity is also regulated by cullin-associated Nedd8-dissociated 1 (CAND1). CAND1 binds to cullins and promotes the exchange of substrate-recognition proteins to target different proteins for ubiquitination. CAND1 inhibition exacerbated the cGMP-dependent increase in NKCC2 ubiquitination and decreased surface NKCC2 expression. Finally, cGMP increased neddylation of cullins. We conclude that the cGMP-dependent increase in NKCC2 ubiquitination is mediated by a CRL complex. To the best of our knowledge, this is the first evidence that a CRL complex mediates NKCC2 ubiquitination in native TALs.
Patients’ perceived quality of care and their satisfaction with care given for MDR-TB at referral hospitals in Ethiopia

Background There is presently dearth of evidence in Ethiopia on patients’ perception on quality of care given for multi-drug resistant tuberculosis (MDR-TB) and their satisfaction with the care and services they receive for the disease. Moreover, there is no evidence on the experiences and practices of caregivers for MDR-TB regarding the functionality of the programmatic management of MDR-TB at referral hospitals in Ethiopia. Thus, this study was conducted to address these gaps. Evidence in these areas would help to institute interventions that could enhance patient satisfaction and their adherence to the treatment given for MDR-TB. Design and methods This study employed an inductive phenomenological approach to investigate patients’ perception of the quality of care given for MDR-TB, level of their satisfaction with the care they received for MDR-TB and the experiences and practices of caregivers for MDR-TB on the functionality of the programmatic management of MDR-TB at referral hospitals in Ethiopia. The data were analysed manually, and that helped to get more control over the data. Results The majority of the patients were satisfied with the compassionate communication and clinical care they received at hospitals. However, as no doctor was dedicated exclusively for the MDR-TB centre of the hospitals, patients could not get timely medical attention during emergent medical conditions. Patients were dissatisfied with the poor communication and uncaring practice of caregivers found at treatment follow-up centres (TFCs). Patients perceived that socio-economic difficulties are both the cause of MDR-TB and it has also challenged their ability to cope-up with the disease and its treatment. Patients were dissatisfied with the poor quality and inadequate quantity of the socio-economic support they got from the programme. Despite the high MDR-TB and HIV/AIDS co-infection, services for both diseases were not available under one roof. Conclusions Socio-economic challenges, inadequate socio-economic support, absence of integrated care for MDR-TB and HIV/AIDS, and the uncaring practice of caregivers at treatment follow-up centres are found to negatively affect patients’ perceived quality of care and their satisfaction with the care given for MDR-TB. Addressing these challenges is recommended to assist patients’ coping ability with MDR-TB and its treatment.
Effects of Age at Implantation on Outcomes of Cochlear Implantation in Children with Short Durations of Single-Sided Deafness

Objective Children with single-sided deafness (SSD) show reduced language and academic development and report hearing challenges. We aim to improve outcomes in children with SSD by providing bilateral hearing through cochlear implantation of the deaf ear with minimal delay. Study Design Prospective cohort study of 57 children with SSD provided with cochlear implant (CI) between May 13, 2013, and June 25, 2021. Setting Tertiary children’s hospital. Participants Children with early onset (n = 40) or later onset of SSD (n = 17) received CIs at ages 2.47 ± 1.58 years (early onset group) and 11.67 ± 3.91 years (late onset group) (mean ± SD). Duration of unilateral deafness was limited (mean ± SD = 1.93 ± 1.56 yr). Intervention Cochlear implantation of the deaf ear. Main Outcomes/Measures Evaluations of device use (data logging) and hearing (speech perception, effects of spatial release from masking on speech detection, localization of stationary and moving sound, self-reported hearing questionnaires). Results Results indicated that daily device use is variable (mean ± SD = 5.60 ± 2.97, range = 0.0–14.7 h/d) with particular challenges during extended COVID-19 lockdowns, including school closures (daily use reduced by mean 1.73 h). Speech perception with the CI alone improved (mean ± SD = 65.7 ± 26.4 RAU) but, in the late onset group, remained poorer than in the normal hearing ear. Measures of spatial release from masking also showed asymmetric hearing in the late onset group (t13 = 5.14, p = 0.001). Localization of both stationary and moving sound was poor (mean ± SD error = 34.6° ± 16.7°) but slightly improved on the deaf side with CI use (F1,36 = 3.95, p = 0.05). Decreased sound localization significantly correlated with poorer self-reported hearing. Conclusions and Relevance Benefits of CI in children with limited durations of SSD may be more restricted for older children/adolescents. Spatial hearing challenges remain. Efforts to increase CI acceptance and consistent use are needed.
Effects of providing tailored information about e-cigarettes in a digital smoking cessation intervention: randomized controlled trial

Abstract The effectiveness of e-cigarettes in smoking cessation is under debate. Informing smokers who are motivated to quit smoking about e-cigarettes may help them to make an informed decision about their use for smoking cessation, which, however, may also lead to unintended effects such as less quitting. This experimental study assessed the influence of providing tailored information about e-cigarettes in a web-based tailored smoking cessation intervention on participants’ decision-making and smoking behavior. Adult smokers (N = 331) were randomized into a personalized eHealth intervention on (i) smoking cessation (control condition) or (ii) smoking cessation and information about e-cigarettes (intervention condition). Directly postintervention, participants in the intervention condition had more knowledge about e-cigarettes than participants in the control condition. Attitudes toward e-cigarettes were more positive among intervention participants than control participants, but the differences in attitude were less pronounced than the differences in knowledge and not consistent across items. At a 6-month follow-up, no between-condition differences were observed in the use of e-cigarettes as a smoking cessation method, the number of tobacco cigarettes smoked in the past 7 days, or other smoking outcomes.
Design of integral variable structure controller and application to electrohydraulic velocity servosystems

An integral variable structure controller (IVSC) for robust servotracking is proposed. It comprises an integral controller, which is designed for achieving zero steady-state error under step input, and a variable structure controller (VSC) which is designed for enhancing robustness. A procedure is developed for determining the coefi- cients of the switching plane and the integral control gain such that the overall closed-loop system has the desired eigenvalues. Furthermore, a modifed proper continuous function is intro- duced to overcome the chattering problem. An electrohydraulic velocity servocontrol system using the proposed IVSC approach is illustrated. Simulation results show that the proposed IVSC approach can achieve accurate servotracking and is fairly robust to plant parameter variations and external load disturbances.
Social participation and incident disability and mortality among frail older adults: A JAGES longitudinal study

Frailty is the highest risk factor for incident disability and mortality. Social participation is a modifiable factor for reducing adverse outcomes among independent older adults. However, the association between social participation and incident disability and mortality among frail older adults remains unclear. Therefore, we examined the association between various social activities and incident disability and mortality.
Spectral properties of naphthalimide dyes mixed with 4-heptyl-4′-cyanobiphenyl (7CB) in Langmuir-Blodgett films

Langmuir-Blodgett (LB) films formed of some fluorescent dyes, namely derivatives of 4-aminonaphthalimide, and their binary mixtures with the liquid crystal 4-heptyl-4′-cyanobiphenyl (7CB) have been studied. The electronic absorption and fluorescence spectra were recorded. On the basis of these spectra, the spectral properties of the dyes and the intermolecular interactions in ultrathin ordered films were determined. The conclusions about the tendency to the creation of aggregates by dye molecules in LB films have been drawn. The measurements of absorption by using linearly polarised light have allowed us to determine the arrangement of the dye and liquid crystal molecules on the air-solid substrate interface.
Minimum Rim Width and Peripapillary Retinal Nerve Fiber Layer Thickness for Diagnosing Early to Moderate Glaucoma

Précis: In a cross-sectional study from a Brazilian multiracial population, minimum rim width (MRW) and peripapillary retinal nerve fiber layer thickness measurements from OCT showed comparable diagnostic performance in discriminating early to moderate glaucoma from healthy eyes. Purpose: The purpose of this study is to compare the ability of MRW and peripapillary retinal nerve fiber layer thickness (RNFLT) measurements in discriminating early to moderate glaucoma from healthy eyes in a Brazilian population. Methods: A total of 155 healthy controls and 118 patients with mild to moderate glaucoma (mean deviation >−12 dB) underwent MRW and RNFLT measurements with optical coherence tomography. Only 1 eye per patient was included in the analysis. A receiver operating characteristic (ROC) regression model was used to evaluate the diagnostic accuracy of MRW and RNFLT, whereas adjusting for age and Bruch membrane opening area. Sensitivities at fixed specificities of 95% were calculated for each parameter. Results: Global RNFLT and MRW showed comparable area under the ROC curves [0.93 (0.91–0.96) and 0.93 (0.89–0.96), respectively; P=0.973]. Both parameters had similar sensitivities (75% vs. 74%, respectively; P=0.852) at a fixed specificity of 95%. The best sector for diagnosing glaucoma for both parameters was the temporal inferior sector, which showed an area under the ROC curve of 0.93 (0.87–0.96) for RNFLT and 0.91 (0.86–0.95) for MRW (P=0.320). The temporal inferior sector showed similar sensitivities for RNFLT and MRW measurements (83% vs. 77%, respectively) at a fixed specificity of 95% (P=0.230). Conclusions: MRW and RNFLT measurements showed comparable diagnostic performance in discriminating early to moderate glaucoma from healthy eyes in a Brazilian multiracial population.
Acute-on-chronic liver failure before liver transplantation does not impact post-transplant survival in children with biliary atresia

Acute-on-chronic liver failure (ACLF) occurs in children with biliary atresia (BA) awaiting liver transplantation (LT). However, data on transplant outcomes in ACLF are limited. Our aim was to characterize ACLF and determine its effect on transplant outcome and resource utilization. Using a linkage of the Scientific Registry of Transplant Recipients and Pediatric Health Information System, we identified children with BA between 3 months and 18 years at the time of listing who received a transplant from 2003 to 2018 and were hospitalized while waiting. ACLF was defined by the presence of at least 1 extra-hepatic organ failure during a pre-LT hospitalization. In all, 1044 patients (58% female, median age at listing 7.0 months IQR 5.0–14.0) were included. Thirty-four percent (351/1044) of the patients had at least 1 ACLF hospitalization. Patients with ACLF had longer waitlist times (114 [54–231] vs. 81 [35–181] days, p < 0.001), and were more likely to be listed as Status 1 (8% vs. 4%, p = 0.02). Pre-LT resource utilization was significantly higher in ACLF patients. There were no differences in mortality at 30 days (ACLF 3% vs. No ACLF 2%, p = 0.17), 90 days (ACLF 3% vs. No ACLF 2%, p = 0.24), 1 year (ACLF 3% vs. No ACLF 2%, p=0.23), 3 years (ACLF 4% vs. No ACLF 3%, p = 0.58), or 5 years (ACLF 5% vs. No ACLF 4%, p = 0.38) after LT. ACLF status was not associated with increased post-transplant mortality (adjusted HR 1.51, 95% CI 0.76–3.0, p=0.25). ACLF is an important morbidity in children with BA awaiting LT as it is associated with higher resource utilization and longer waitlist times. Further studies are needed to help understand the spectrum of ACLF and better prioritize critically ill children awaiting LT, as our study shows successful post-LT outcomes in children with BA and ACLF.
Quadtree-based reversible integer time-domain lapped transform for progressive lossy-to-lossless images compression

Abstract. Reversible integer time-domain lapped transform (RTDLT) has been proven to be efficient in progressive lossy-to-lossless image compression. We introduced the quadtree-based RTDLT (QRTDLT) to further improve the performance of block-transform methods.Traditional block transforms are usually conducted with a fixed size of 8×8 or 16×16. This is an oversimplified and hardware-friendly implementation, but it is not optimal for different areas of various images. In the proposed QRTDLT method, we first partitioned the image into macroblocks. Then, the macroblocks are iteratively processed using quadtree splitting while abiding by special regulation. These blocks are transformed by RTDLTs with different-length basis functions. With limited complexity increase, the QRTDLT is still suitable for online applications of image compression. Simulation results demonstrated that the proposed method yields more than 0.5-dB performance improvement in lossy compression. At the same time, the QRTDLT also performs better than the RTDLT in lossless compression.
A review of the application of three-dimensional convolutional neural networks for the diagnosis of Alzheimer’s disease using neuroimaging

Abstract Alzheimer’s disease (AD) is a degenerative disorder that leads to progressive, irreversible cognitive decline. To obtain an accurate and timely diagnosis and detect AD at an early stage, numerous approaches based on convolutional neural networks (CNNs) using neuroimaging data have been proposed. Because 3D CNNs can extract more spatial discrimination information than 2D CNNs, they have emerged as a promising research direction in the diagnosis of AD. The aim of this article is to present the current state of the art in the diagnosis of AD using 3D CNN models and neuroimaging modalities, focusing on the 3D CNN architectures and classification methods used, and to highlight potential future research topics. To give the reader a better overview of the content mentioned in this review, we briefly introduce the commonly used imaging datasets and the fundamentals of CNN architectures. Then we carefully analyzed the existing studies on AD diagnosis, which are divided into two levels according to their inputs: 3D subject-level CNNs and 3D patch-level CNNs, highlighting their contributions and significance in the field. In addition, this review discusses the key findings and challenges from the studies and highlights the lessons learned as a roadmap for future research. Finally, we summarize the paper by presenting some major findings, identifying open research challenges, and pointing out future research directions.
Stopping the fat: Repurposing an antidepressant for cancer treatment

In this issue of JEM, Chu and An et al. describe the role of the tricyclic antidepressant nortriptyline in inhibition of fatty acid uptake. Nortriptyline promotes cell acidification and suppresses macropinocytosis, providing a link between fatty acid uptake and tumor progression.
Biomechanics models predict increasing smooth muscle tone as a novel therapeutic target for central arterial dysfunction in hypertension

Introduction: Vasodilation can paradoxically increase arterial stiffness in older, hypertensive adults. This study modeled increasing smooth muscle tone as a therapeutic strategy to improve central arterial dysfunction in hypertension using participant-specific simulations. Methods: Participant-specific models of the carotid artery were parameterized from vascular ultrasound measures of nitroglycerin-induced vasodilation in 18 hypertensive veterans. The acute changes in carotid artery mechanics were simulated for changes of ±2, ±4, and ±6% in smooth muscle tone and ±5, ±10, and ±15 mmHg in mean arterial pressure (MAP). The chronic carotid artery adaptations were simulated based on the hypothesis that the carotid artery will remodel wall-cross sectional area to maintain mechanical homeostasis. Results: A 6% increase in smooth muscle tone acutely decreased carotid pulse wave velocity from 6.89 ± 1.24 m/s to 5.83 ± 1.73 m/s, and a 15 mmHg decrease in MAP decreased carotid pulse wave velocity to 6.17 ± 1.23 m/s. A 6% increase in smooth muscle tone acutely decreased wall stress from 76.2 ± 12.3 to 64.2 ± 10.4 kPa, and a 15 mmHg decrease in MAP decreased wall stress to 60.6 ± 10.7 kPa. A 6% increase in smooth muscle tone chronically decreased wall cross-sectional area from 18.3 ± 5.4 to 15.2 ± 4.9 mm2, and a 15 mmHg decrease in MAP decreased wall cross-sectional area to 14.3 ± 4.6 mm2. Conclusion: In participant-specific simulation, increasing smooth muscle tone can have a stronger or equivalent effect on carotid artery mechanics compared with decreasing blood pressure. Increasing central arterial smooth muscle tone may be a novel therapeutic target to improve central arterial dysfunction in older, hypertensive adults and should be a focus of future research.
Intermediate-term Outcomes in Adolescent Recurrent Ankle Instability Managed With a Modified Broström-Gould Procedure Augmented With Distal Fibular Periosteum Incorporation

Background: Once a child has developed chronic ankle instability with recurrent events despite conservative treatment, then ligamentous repair is warranted. We utilize a modification of the modified Broström-Gould technique that further incorporates the distal fibular periosteum into the construct. The purpose of this study was to describe the intermediate-term outcomes of our modified Broström-Gould technique for chronic lateral ankle instability in childhood athletes. Methods: A retrospective review of children who underwent the surgical technique over a 10-year time period (2010 to 2019) was performed, excluding those with <2 years of follow-up. Demographic, surgical, and clinical data were recorded, as well as outcome scores: (1) the Marx activity scale, (2) University of California, Los Angeles activity score, and (3) foot and ankle outcomes score. Recurrent instability events, repeat surgeries, satisfaction with the surgical experience, and return to sport (if applicable) were also recorded. Results: Forty-six children (43 females) with 1 bilateral ankle met the criteria with a mean age at surgery of 14.8 years, and a mean follow-up duration of 4.9 years. The mean Marx activity score was 9.0±5.1, the mean University of California, Los Angeles score was 8.3±1.8, and the mean total foot and ankle outcomes score was 84.0±15.6. Twenty-six ankles (55.3%) reported having at least 1 recurrent episode of instability and 6 of the ankles (12.8%) underwent revision surgery between 3.5 months and 6.5 years of the index procedure. Thirty-nine (84.8%) patients responded that they would undergo our surgery again. Conclusion: A modified Broström-Gould procedure can be performed in children with the incorporation of the adjacent periosteum, but recurrence of instability is distinctly possible with longer follow-up with a risk for revision surgery despite good subjective outcomes. Level of Evidence: Level IV; retrospective case series.