bluuebunny/crossref_metadata_2025 huggingface dataset:
Numerical experiments on thermal convection of highly compressible fluids with variable viscosity and thermal conductivity in 2-D cylindrical geometry: implications for mantle convection of super-Earths
Authors: Kameyama Masanori
Published: July 2022

We conduct a series of numerical experiments of thermal convection of highly compressible fluids in 2-D cylindrical annulus, in order to study the mantle convection on super-Earths. The variations in thermodynamic properties (thermal expansivity and reference density) with depth are taken to be relevant for the super-Earths with 10 times the Earth’s mass, while those in transport properties (viscosity and thermal conductivity) are modelled by an exponential dependence on temperature and/or depth. From our experiments we identified a distinct regime of convecting flow patterns induced by the interplay between the adiabatic temperature change and the spatial variations in viscosity and thermal conductivity. That is, for the cases with strong temperature-dependent viscosity and large increase in thermal conductivity with depth, a ‘deep stratosphere’ of stable thermal stratification is formed at the base of the mantle, in addition to thick stagnant lids at their top surfaces. In the ‘deep stratosphere’, the fluid motion is insignificant particularly in the vertical direction in spite of smallest viscosity owing to its strong dependence on temperature. From the comparison with the experiments with the Cartesian geometry, we also found that the occurrence of ‘deep stratosphere’ tends to be suppressed for the cases with cylindrical geometry, owing to the reduction of the surface area with depth which helps increase the temperature gradient in the lowermost mantle. Our finding may further imply that both the effects of adiabatic compression and those of spherical (or cylindrical) geometry of mantle are of crucial importance in understanding the mantle dynamics of massive super-Earths in the presence of spatial variations in physical properties.
Referring patients with suspected lung cancer: a qualitative study with primary healthcare professionals in Ireland
Authors: Saab Mohamad M , O’Driscoll Michelle , FitzGerald Serena , Sahm Laura J , Leahy-Warren Patricia , Noonan Brendan , Kilty Caroline , O’Malley Maria , Lyons Noreen , Burns Heather E , Kennedy Una , Lyng Áine , Hegarty Josephine
Published: July 2022

Lung cancer is the leading cause of cancer death globally. Most cases are diagnosed late. Primary healthcare professionals are often the first point of contact for symptoms of concern. This study explored primary healthcare professionals’ experience of referring individuals with signs and symptoms suggestive of lung cancer along the appropriate healthcare pathway and explored strategies to help primary healthcare professionals detect lung cancer early. Focus groups and individual interviews were conducted with 36 general practitioners, community pharmacists, practice nurses, and public health nurses. Data were analysed thematically. Participants identified typical lung cancer signs and symptoms such as cough and coughing up blood (i.e., haemoptysis) as triggers for referral. Atypical/non-specific signs and symptoms such as back pain, pallor, and abnormal blood tests were perceived as difficult to interpret. Participants often refrained from using the word ‘cancer’ during conversations with patients. Ireland’s Rapid Access Lung Clinics were perceived as underused, with some general practitioners referring patients to these clinics only when clear and definitive lung cancer signs and symptoms are noted. Lack of communication and the resulting disruption in continuity of care for patients with suspected lung cancer were highlighted as healthcare system flaws. Education on early referral can be in the form of communications from professional organizations, webinars, interdisciplinary meetings, education by lung specialists, and patient testimonials. Lung cancer referral checklists and algorithms should be simple, clear, and visually appealing, either developed as standalone tools or embedded into existing primary care software/programmes.
High Wing-Loading Correlates with Dive Performance in Birds, Suggesting a Strategy to Reduce Buoyancy
Authors: Lapsansky Anthony B , Warrick Douglas R , Tobalske Bret W
Published: July 2022

Diving birds are regarded as a classic example of morphological convergence. Divers tend to have small wings extending from rotund bodies, requiring many volant species to fly with rapid wingbeats, and rendering others flightless. The high wing-loading of diving birds is frequently associated with the challenge of using forelimbs adapted for flight for locomotion in a “draggier” fluid, but this does not explain why species that rely exclusively on their feet to dive should have relatively small wings, as well. Therefore, others have hypothesized that ecological factors shared by wing-propelled and foot-propelled diving birds drive the evolution of high wing-loading. Following a reexamination of the aquatic habits of birds, we tested between hypotheses seeking to explain high wing-loading in divers using new comparative data and phylogenetically informed analyses. We found little evidence that wing-propelled diving selects for small wings, as wing-propelled and foot-propelled species share similar wing-loadings. Instead, our results suggest that selection to reduce buoyancy has driven high wing-loading in divers, offering insights for the development of bird-like aquatic robots.
Optimal pricing and budget decisions in public health systems with delay sensitive patients
Authors: Huang Senlong , Hu Dongbin , Chen Wuhua
Published: July 2022

The congestion of public hospitals for elective treatment in some countries and regions, such as Canada and Hong Kong where the free health policy is implemented, is a serious issue. The main reason is the excessive demand generated by the provision of free service. In response, the government can set appropriate service price and budget for public hospitals to moderate such demand. This is often referred to as the charging policy, implemented in countries such as China. A Stackelberg game is established for a health system consisting of a government, a public health provider and delay sensitive patients. The results show that when the customers' waiting cost is low (e.g., the market demand, the patients delay sensitivity, or the unit capacity cost is low), the free health policy outperforms the charging policy; otherwise, the charging policy is better. Moreover, we find that the equilibrium waiting time and the equilibrium price decrease with the market demand when the funder attaches more importance to patients’ welfare than the budget surplus and the total budget is sufficient.
A novel phased-array transmitting source in controlled-source audio-frequency magnetotellurics
Authors: Fan Haifeng , Zhang Yiming , Wang Xuhong
Published: July 2022

In traditional controlled-source audio-frequency magnetotellurics (CSAMT), the orthogonal magnetic and electric field components in the far-field region are recorded to calculate the apparent resistivity. However, as the distance between the receiver and the transmitter increases, the electromagnetic signal weakens considerably. Moreover, as the location of the transmitter is fixed, the location of the far-field region also is fixed, which limits the exploration range. In this study, a novel phased-array transmitting source was proposed to overcome this limitation. In traditional CSAMT, a grounded single-dipole long-line source is used to transmit the electromagnetic wave. This source has a low gain and no directionality, resulting in a low signal-to-noise ratio (SNR) in the area of interest (AoI). Conversely, by using a phased-array source, beam control and stable directional radiation will be achieved so that the electromagnetic energy should be capable of effectively focusing within the AoI. Without increasing the transmitting power, the SNR should be conveniently enhanced and the size of the AoI can be greatly increased. In this paper, the characteristics of the radiation field of a single-dipole long-line source and its application in traditional CSAMT are analyzed. The design principle and the method of implementation of a novel phased-array source are provided. The feasibility and effectiveness of the proposed source are verified by simulations and experiments, and a prototype is realized.
Numerical study ofin situacoustic emission monitoring for small-scale hydraulic fracturing
Authors: Zhan Tingting , Chen Hao , Li Lei
Published: July 2022

Reservoir monitoring is necessary to achieve safe hydrocarbon extraction. It requires monitoring small acoustic emission (AE) events, assisting in determining the exact location, extension and direction of potential damage as early as possible. However, microcracks cannot be detected by the microseismic monitoring networks due to the limitations of frequency range and sensitivity. In contrast, the in situ AE monitoring system extends the detection range to higher frequencies and can detect very small deformation processes with high resolution and sensitivity. It provides detailed insights into ongoing deformation processes. However, the receivers of an in situ AE monitoring system need to be very close to hydraulic fracturing experiments due to the fast decay of high-frequency signals. In this work, by constructing four in situ AE monitoring models, the imaging effects of the interferometric imaging method for three different kHz-level frequency sources at different distances and orientations relative to the monitoring well are investigated. The numerical results show that: the higher the source frequency, the higher the imaging resolution; when the vertical orientation coverage of the source by the monitoring system is incomplete, the closer the source to the borehole axis, the worse the imaging resolution and location accuracy; when the vertical orientation coverage of the source by the monitoring system is complete, the imaging resolution and location accuracy are both improved, especially when the vertical azimuthal coverage angle is large. The integrity of the orientation coverage of the source by the monitoring system plays a critical role in improving source location accuracy.
A comparison of $A\! -\! \phi $ formulae for three-dimensional geo-electromagnetic induction problems
Authors: Zhou Feng , Chen Huang , Tang Jingtian , Zhang Zhiyong , Yuan Yuan , Wu Qihong
Published: July 2022

Geo-electromagnetic forward modeling problems are ill-posed due to the low signal frequencies being used and electrically insulating air space. To overcome this numerical issue, the $A - \phi $ formula using the magnetic vector potentials ($\bf A$) and electric scalar potentials ($\phi $) was developed. At present, there are two sets of $A - \phi $ formulae being used: one has a curl–curl ($\nabla \times \nabla $) structure and another one has a Laplace (${\nabla ^2}$) structure where the Coulomb gauge is enforced. The question as to which of the two approaches have superior performance for 3D geo-electromagnetic induction problems still remains open. In this study, we systemically compared the performances of these two $A - \phi $ systems in terms of both numerical accuracy and convergence rate. Numerical experiments suggest that for both magnetotelluric and controlled-source electromagnetic problems, the $A - \phi $ system with Laplace structure has better performance than the variant with curl–curl structure in terms of convergence rates.
Elastic characteristics of fault damage zones within superdeep carbonates in Tarim Basin, Northwest China
Authors: Jian Shikai , Fu Li-Yun , Liao Zonghu , Deng Wubing , Du Qizhen
Published: July 2022

Superdeep fault-karst carbonate reservoirs discovered over 7 km deep are controlled by strike-slip fault zones and karst collapses in Tarim Basin, Northwest China. The resulting fracture-cave system provides favorable migration channels and reservoir spaces for hydrocarbon, while the characterization of the internal fault structures remains enigmatic. Based on seismic imaging data, we conducted an integrated study on fault damage zones by seismic curvature attributes, velocity anisotropies, and seismic attenuations. The results show that three typical fault-zone patterns can be identified in the study area, including paratactic multiple fault cores, interactive fault cores and one primary-several subsidiary fault cores. These typical patterns can be clearly characterized via curvature attributes. The elastic characteristics of fault damage zones are significantly affected by seismic frequencies, which are manifested from velocity anisotropies and seismic attenuations. The maximum seismic attenuation occurs along with the orientation of fault cores. There is a strong anisotropic characteristic of P-wave phase velocity with incident angle of three fault-zone models. It appears that seismic attributes associated with geological steering are an effective tool for the subsurface characterization of fault damage zones.
De-aliased high-resolution Radon transform based on the sparse prior information from the convolutional neural network
Authors: Feng Luyu , Xue Yaru , Chen Chong , Guo Mengjun , Shen Hewei
Published: July 2022

The resolution of Radon transform is crucial in seismic data interpolation. The high-frequency components usually suffer from serious aliasing problems while the sampling is insufficient. Constraining high-frequency components with unaliased low-frequency components is an effective method for improving the resolution of seismic data. However, it is difficult to obtain high-resolution low-frequency Radon coefficients by traditional analytical methods due to the strong correlation of basis functions. For this problem, a sparse inversion method using the neural network is proposed. First, the convolution model is deduced between the conjugated Radon solution and its ground truth. Then, a convolutional neural network (CNN), with the conjugate Radon solution as input, is designed to realize the deconvolution from the conjugate solution to the sparse and high-resolution Radon solution. Finally, the obtained sparse solution is regarded as prior knowledge of the iteratively reweighted least-squares algorithm. The proposed strategy has a distinct advantage in improving the resolution of low-frequency components, which helps overcome the aliasing. Interpolation experiments on synthetic and field data demonstrate the de-aliased performance of this CNN-based method.
Radiative relativistic magnetohydrodynamic simulations of neutron star column accretion in Cartesian geometry
Authors: Zhang Lizhong , Blaes Omer , Jiang Yan-Fei
Published: July 2022

High luminosity accretion on to a strongly magnetized neutron star results in a radiation pressure dominated, magnetically confined accretion column. We investigate the dynamics of these columns using 2D radiative relativistic magnetohydrodynamic simulations, restricting consideration to modest accretion rates where the height of the column is low enough that Cartesian geometry can be employed. The column structure is dynamically maintained through high-frequency oscillations of the accretion shock at ≃ 10–25 kHz. These oscillations arise because it is necessary to redistribute the power released at the accretion shock through bulk vertical motions, both to balance the cooling and to provide vertical pressure support against gravity. Sideways cooling always dominates the loss of internal energy. In addition to the vertical oscillations, photon bubbles form in our simulations and add additional spatial complexity to the column structure. They are not themselves responsible for the oscillations, and they do not appear to affect the oscillation period. However, they enhance the vertical transport of radiation and increase the oscillation amplitude in luminosity. The time-averaged column structure in our simulations resembles the trends in standard 1D stationary models, the main difference being that the time-averaged height of the shock front is lower because of the higher cooling efficiency of the 2D column shape.
Blanco DECam Bulge Survey (BDBS) IV: Metallicity distributions and bulge structure from 2.6 million red clump stars
Authors: Johnson Christian I , Rich R Michael , Simion Iulia T , Young Michael D , Clarkson William I , Pilachowski Catherine A , Michael Scott , Marchetti Tommaso , Soto Mario , Kunder Andrea , Koch-Hansen Andreas J , Katherina Vivas A , Joyce Meridith , Shen Juntai , Osmond Alexis
Published: July 2022

We present photometric metallicity measurements for a sample of 2.6 million bulge red clump stars extracted from the Blanco DECam Bulge Survey (BDBS). Similar to previous studies, we find that the bulge exhibits a strong vertical metallicity gradient, and that at least two peaks in the metallicity distribution functions appear at b < −5°. We can discern a metal-poor ([Fe/H] ∼ −0.3) and metal-rich ([Fe/H] ∼ +0.2) abundance distribution that each show clear systematic trends with latitude, and may be best understood by changes in the bulge’s star formation/enrichment processes. Both groups exhibit asymmetric tails, and as a result we argue that the proximity of a star to either peak in [Fe/H] space is not necessarily an affirmation of group membership. The metal-poor peak shifts to lower [Fe/H] values at larger distances from the plane while the metal-rich tail truncates. Close to the plane, the metal-rich tail appears broader along the minor axis than in off-axis fields. We also posit that the bulge has two metal-poor populations – one that belongs to the metal-poor tail of the low latitude and predominantly metal-rich group, and another belonging to the metal-poor group that dominates in the outer bulge. We detect the X-shape structure in fields with |Z| > 0.7 kpc and for stars with [Fe/H] > −0.5. Stars with [Fe/H] < −0.5 may form a spheroidal or ‘thick bar’ distribution while those with [Fe/H] $\gtrsim$ −0.1 are strongly concentrated near the plane.
A slow lopsided bar in the interacting dwarf galaxy IC 3167
Authors: Cuomo V , Corsini E M , Morelli L , Aguerri J A L , Lee Y H , Coccato L , Pizzella A , Buttitta C , Gasparri D
Published: July 2022

We present surface photometry and stellar kinematics of IC 3167, a dwarf galaxy hosting a lopsided weak bar and infalling into the Virgo cluster. We measured the bar radius and strength from broad-band imaging and bar pattern speed by applying the Tremaine–Weinberg method to stellar-absorption integral-field spectroscopy. We derived the ratio of the corotation radius to bar radius (${\cal {R}}=1.7^{+0.5}_{-0.3}$) from stellar kinematics and bar pattern speed. The probability that the bar is rotating slowly is more than twice as likely as that the bar is fast. This allows us to infer that the formation of this bar was triggered by the ongoing interaction rather than the internal processes.
Reithrodontomys microdon(Rodentia: Cricetidae)
Authors: Marines-Macías Tania , Colunga-Salas Pablo , León-Paniagua Livia
Published: July 2022

Reithrodontomys microdon Merriam, 1901 is a cricetid rodent commonly called the small-toothed harvest mouse. It is a small-bodied mouse with deep reddish-fulvous fur, a tail longer than the head–body length, and long, dark, and nearly naked ears. There are distinctive dark rings around the eyes. As 1 of 24 species of the genus Reithrodontomys and among the most arboreal, its populations inhabit cool moist forests of high mountains in isolated pockets across its geographic distribution in central Mexico, Oaxaca (Mexico), Chiapas (Mexico,) and west-central Guatemala. Reithrodontomys microdon is considered “Least Concern” (LC) by the International Union for Conservation of Nature (IUCN), mainly due to habitat loss caused by annual and perennial nontimber crops, as well as logging and wood harvesting.
Cyclic-anion salt for high-voltage stable potassium-metal batteries
Authors: Hu Yanyao , Fan Ling , Rao Apparao M , Yu Weijian , Zhuoma Caixiang , Feng Yanhong , Qin Zhihui , Zhou Jiang , Lu Bingan
Published: July 2022

Electrolyte anions are critical for achieving high-voltage stable potassium-metal batteries (PMBs). However, the common anions cannot simultaneously prevent the formation of ‘dead K’ and the corrosion of Al current collector, resulting in poor cycling stability. Here, we demonstrate cyclic anion of hexafluoropropane-1,3-disulfonimide-based electrolytes that can mitigate the ‘dead K’ and remarkably enhance the high-voltage stability of PMBs. Particularly, even using low salt concentration (0.8 M) and additive-free carbonate-based electrolytes, the PMBs with a high-voltage polyanion cathode (4.4 V) also exhibit excellent cycling stability of 200 cycles with a good capacity retention of 83%. This noticeable electrochemical performance is due to the highly efficient passivation ability of the cyclic anions on both anode and cathode surfaces. This cyclic-anion-based electrolyte design strategy is also suitable for lithium and sodium-metal battery technologies.
Incidence and risk factors for autism spectrum disorder among infants born <29 weeks’ gestation
Authors: Busque Andrée-Anne , Jabbour Elias , Patel Sharina , Couture Élise , Garfinkle Jarred , Khairy May , Claveau Martine , Beltempo Marc
Published: July 2022

Objective

This study was aimed to assess the incidence of and risk factors for autism spectrum disorder (ASD) among preterm infants born <29 weeks’ gestational age (GA).

Methods

A retrospective cohort study of infants born <29 weeks’ GA admitted to two tertiary neonatal intensive care units (2009 to 2017) and followed ≥18 months corrected age (CA) at a neonatal follow-up clinic. The primary outcome was ASD, diagnosed using standardized testing or provisional diagnosis at ≥18 months CA. Patient data and 18-month CA developmental outcomes were obtained from the local Canadian Neonatal Follow Up Network database and chart review. Stepwise logistic regression assessed factors associated with ASD.

Results

Among 300 eligible infants, 26 (8.7%) were diagnosed with confirmed and 21 (7.0%) with provisional ASD for a combined incidence of 15.7% (95% confidence interval [CI] 11.7 to 20.3). The mean follow-up duration was 3.9 ± 1.4 years and the mean age of diagnosis was 3.7 ± 1.5 years. Male sex (adjusted odds ratio [aOR] 4.63, 95% CI 2.12 to 10.10), small for gestational age status (aOR 3.03, 95% CI 1.02 to 9.01), maternal age ≥35 years at delivery (aOR 2.22, 95% CI 1.08 to 4.57) and smoking during pregnancy (aOR 5.67, 95% CI 1.86 to 17.29) were significantly associated with ASD. Among ASD infants with a complete 18-month CA developmental assessment, 46% (19/41) had no neurodevelopmental impairment (Bayley-III<70, deafness, blindness, or cerebral palsy).

Conclusions

ASD is common among infants born <29 weeks’ GA and possibly associated with identified risk factors. Such findings emphasize the importance of ASD evaluation among infants <29 weeks’ GA and for continued reporting of developmental outcomes beyond 18-months of corrected age.
Exercise Intervention in Individuals at Clinical High Risk for Psychosis: Benefits to Fitness, Symptoms, Hippocampal Volumes, and Functional Connectivity
Authors: Damme Katherine S F , Gupta Tina , Ristanovic Ivanka , Kimhy David , Bryan Angela D , Mittal Vijay A
Published: July 2022

Background and Hypothesis

Individuals at clinical high risk for psychosis (CHR-p) are less fit than nonclinical peers and show hippocampal abnormalities that relate to clinical symptoms. Exercise generates hippocampal neurogenesis that may ameliorate these hippocampal abnormalities and related cognitive/clinical symptoms. This study examines the impact of exercise on deficits in fitness, cognitive deficits, attenuated psychotic symptoms, hippocampal volumes, and hippocampal connectivity in individuals at CHR-p.

Study Design

In a randomized controlled trial, 32 individuals at CHR-p participated in either an exercise (n = 17) or waitlist (no exercise) (n = 15) condition. All participants were sedentary at use and absent of current antipsychotic medication, psychosis diagnoses, or a substance use disorder. The participants completed a series of fitness, cognitive tasks, clinical assessments, and an MRI session preintervention and postintervention. The exercise intervention included a high-intensity interval exercise (80% of VO2max) with 1-minute high-intensity intervals (95% of VO2max) every 10 minutes) protocol twice a week over 3 months.

Study Results

The exercise intervention was well tolerated (83.78% retention; 81.25% completion). The exercising CHR-p group showed that improved fitness (pre/post-d = 0.53), increased in cognitive performance (pre/post-d = 0.49), decrease in positive symptoms (pre/post-d = 1.12) compared with the waitlist group. Exercising individuals showed stable hippocampal volumes; waitlist CHR-p individuals showed 3.57% decreased hippocampal subfield volume. Exercising individuals showed that increased exercise-related hippocampal connectivity compared to the waitlist individuals.

Conclusions

The exercise intervention had excellent adherence, and there were clear signs of mechanism engagement. Taken together, evidence suggests that high-intensity exercise can be a beneficial therapeutic tool in the psychosis risk period.
Mapping Retinal Abnormalities in Psychosis: Meta-analytical Evidence for Focal Peripapillary and Macular Reductions
Authors: Gonzalez-Diaz Jairo M , Radua Joaquim , Sanchez-Dalmau Bernardo , Camos-Carreras Anna , Zamora Diana C , Bernardo Miquel
Published: July 2022

Background

Several studies have suggested that the retina structure is affected in schizophrenia spectrum disorders (SSD). We aimed to investigate the location and size of the potential differences between patients and healthy controls (HC) in several thickness and volume measures across the retina

Study Design

We included cross-sectional studies comparing peripapillary retinal nerve fiber layer (pRNFL) thickness, macular volume, macular thickness (MT), foveal thickness, ganglion cell and inner plexiform layer thickness (GCL+IPL), cup volume, and cup/disc ratio (C/D) in the right and/or left eyes and/or the pRNFL and MT quadrants between patients with SSD and HC. Search databases were MEDLINE, Web of Science, PsycINFO, Cochrane Central, and medrxiv.org. Risk of bias was assessed with the Newcastle-Ottawa Scale. Standardized mean differences (SMD), subgroup analysis, and meta-regression with several variables were computed using the dmetar package in R. PROSPERO: CRD42021287873.

Study Results

Data from 22 reports (942 patients, 742 HC) were included. We found a retinal thinning in pRNFL (−0.30; 95% CI: −0.46, −0.14), macula (−0.37; 95% CI: −0.61, −0.13), and GCL+IPL (−0.33; 95% CI: −0.57, −0.10). The retinal thinning was especially pronounced in the superior and inferior quadrants of the inner ring of the macula. We also observed a decrease of macular volume (−0.44; 95% CI: −0.68, −0.20) and an increase in C/D ratio (0.35; 95% CI: 0.03, 0.67).

Conclusions

Current evidence demonstrates retinal thinning in SSD, affecting both axonal and cellular structures, specially focused in the inner ring of the macula.
Patients’ Experiences of Clozapine for Treatment-Resistant Schizophrenia: A Systematic Review
Authors: Parkes Steven , Mantell Bethany , Oloyede Ebenezer , Blackman Graham
Published: July 2022

Background

Clozapine is the most effective antipsychotic for patients with treatment-resistant schizophrenia (TRS), however, it remains widely under-utilized in clinical practice. To date, relatively little attention has been given to patients’ experience of clozapine. By synthesizing the existing literature, we sought to determine the experiences of patients with TRS treated with clozapine.

Methods

A systematic review was conducted on Embase, Medline, PsychInfo, and PubMed databases for studies from 1956 to 2021. English language studies and those based on adult patients prescribed clozapine for TRS were included.

Results

Thirteen studies were included with a total of 1487 patients and a narrative synthesis was performed. Overall, most patients reported positive experiences of clozapine, with generally high levels of satisfaction, alongside symptom improvement and preference over previous medications. Negative experiences of clozapine were less common, but when mentioned, focused on blood tests and common side effects, including hypersalivation and weight gain.

Conclusions

This is the first systematic review exploring patients’ subjective experiences of clozapine for TRS. Findings suggest that patients generally have a favorable experience when being treated with clozapine. However, conclusions are limited by the risk of bias, particularly survivorship bias. High-quality longitudinal studies exploring patients’ experiences of clozapine are indicated for the future.
Low carnitine palmitoyltransferase 1 activity is a risk factor for narcolepsy type 1 and other hypersomnia
Authors: Honda Makoto , Shigematsu Yosuke , Shimada Mihoko , Honda Yoshiko , Tokunaga Katsushi , Miyagawa Taku
Published: July 2022

Study Objectives

Narcolepsy type 1 (NT1) is associated with metabolic abnormalities but their etiology remains largely unknown. The gene for carnitine palmitoyltransferase 1B (CPT1B) and abnormally low serum acylcarnitine levels have been linked to NT1. To elucidate the details of altered fatty acid metabolism, we determined levels of individual acylcarnitines and evaluated CPT1 activity in patients with NT1 and other hypersomnia.

Methods

Blood samples from 57 NT1, 51 other hypersomnia patients, and 61 healthy controls were analyzed. The levels of 25 major individual acylcarnitines were determined and the C0/(t[C16] + t[C18]) ratio was used as a CPT1 activity marker. We further performed transcriptome analysis using independent blood samples from 42 NT1 and 42 healthy controls to study the relevance of fatty acid metabolism. NT1-specific changes in CPT1 activity and in expression of related genes were investigated.

Results

CPT1 activity was lower in patients with NT1 (p = 0.00064) and other hypersomnia (p = 0.0014) than in controls. Regression analysis revealed that CPT1 activity was an independent risk factor for NT1 (OR: 1.68; p = 0.0031) and for other hypersomnia (OR: 1.64; p = 0.0042). There was a significant interaction between obesity (BMI <25, ≥25) and the SNP rs5770917 status such that nonobese NT1 patients without risk allele had better CPT1 activity (p = 0.0089). The expression levels of carnitine-acylcarnitine translocase (CACT) and CPT2 in carnitine shuttle were lower in NT1 (p = 0.000051 and p = 0.00014, respectively).

Conclusions

These results provide evidences that abnormal fatty acid metabolism is involved in the pathophysiology of NT1 and other hypersomnia.
HLA-A*01:01 allele vanishing in COVID-19 patients population associated with non-structural epitope abundance in CD8+ T-cell repertoire
Authors: Shkurnikov Maxim , Nersisyan Stepan , Averinskaya Darya , Chekova Milena , Polyakov Fedor , Titov Aleksei , Doroshenko Dmitriy , Vechorko Valery , Tonevitsky Alexander
Published: July 2022

In mid-2021, the SARS-CoV-2 Delta variant caused the third wave of the COVID-19 pandemic in several countries worldwide. The pivotal studies were aimed at studying changes in the efficiency of neutralizing antibodies to the spike protein. However, much less attention was paid to the T-cell response and the presentation of virus peptides by MHC-I molecules. In this study, we compared the features of the HLA-I genotype in symptomatic patients with COVID-19 in the first and third waves of the pandemic. As a result, we could identify the vanishing of carriers of the HLA-A*01:01 allele in the third wave and demonstrate the unique properties of this allele. Thus, HLA-A*01:01-binding immunoprevalent epitopes are mostly derived from ORF1ab. A set of epitopes from ORF1ab was tested, and their high immunogenicity was confirmed. Moreover, analysis of the results of single-cell phenotyping of T-cells in recovered patients showed that the predominant phenotype in HLA-A*01:01 carriers is central memory T-cells. The predominance of T-lymphocytes of this phenotype may contribute to forming long-term T-cell immunity in carriers of this allele. Our results can be the basis for highly effective vaccines based on ORF1ab peptides.
Measures of Behavior and Life Dynamics from Commonly Available GPS Data (DPLocate): Algorithm Development and Validation
Authors: Rahimi-Eichi Habiballah , Coombs Garth , Onnela Jukka-Pekka , Baker Justin T. , Buckner Randy L.
Published: July 2022

Locations of people moving about their lives are now commonly tracked through smartphones and wearable devices that access the Global Positioning System (GPS). Immediate measures include the estimated locations that identify visited map points and the travel paths between them. Here we introduce DPLocate, an open-source GPS data analysis pipeline designed to derive measures that abstract away from the original locations (and hence the identity of the individuals) and capture dynamics related to social, vocational, sleep, and clinical behaviors. We divide derived measures into primary and secondary. Primarily derived measures stay close to the original location data and extract deidentified metrics, including distance traveled, time spent at the main locations, and estimates of travel activity (entropy). Secondary derived measures estimate life patterns that are captured incidentally by extracting returns to the Points of Interest (POIs) in behaviorally-relevant time-bands. For example, measures of behavioral dynamics and social interactions can be gleaned by estimating the time spent in POIs across day, evening, night, and late-night time-bands. The utility of these derived measures for research is illustrated in college students and for clinical monitoring in individuals living with psychiatric disorders. Captured dynamics included behavioral transitions at the onset of the Covid-19 lockdown. Limitations of derived data are discussed, including the necessity to protect derived data from identification and possible ways in which the derived data might be misinterpreted.
Revised spectral metrics for body surface measurements of gastric electrophysiology
Authors: Schamberg Gabriel , Varghese Chris , Calder Stefan , Waite Stephen , Erickson Jonathan , O’Grady Greg , Gharibans Armen A.
Published: July 2022

Background

Electrogastrography (EGG) non-invasively evaluates gastric function but has not achieved common clinical adoption due to several technical limitations. Body Surface Gastric Mapping (BSGM) has been introduced to overcome these limitations, but pitfalls in traditional metrics used to analyze spectral data remain unaddressed. This study critically evaluates five traditional EGG metrics and introduces improved BSGM spectral metrics, with validation in a large cohort.

Methods

Pitfalls in five EGG metrics were assessed (dominant frequency, percentage time normogastria, amplitude, power ratio, and instability coefficient), leading to four revised BSGM spectral metrics. Traditional and revised metrics were compared to validate performance using a 100 BSGM subject database (30 min baseline; 4-hrs postprandial), recorded using Gastric Alimetry (Alimetry, New Zealand).

Key Results

BMI and amplitude were highly correlated (r=-0.57, p<0.001). We applied a conservative BMI correction to obtain aBMI-adjusted amplitudemetric (r=-0.21, p=0.037). Instability coefficient was highly correlated with both dominant frequency (r=-0.44, p<0.001), and percent bradygastria (r=0.85, p<0.001), in part due to conflation of low frequency transients with gastric activity. This was corrected by introducing distinct gastric frequency and stability metrics (Principal Gastric FrequencyandGastric Alimetry Rhythm Index (GA-RI))that were uncorrelated (r=0.14, p=0.314). Only 28% of subjects showed a maximal averaged amplitude within the first postprandial hour. CalculatingFed:Fasted Amplitude Ratioover a 4-hr postprandial window yielded a median increase of 0.31 (IQR 0-0.64) above the traditional ratio.

Conclusions & Inferences

The revised metrics resolve critical pitfalls impairing the performance of traditional EGG, and should be applied in future BSGM spectral analyses.
Organs-on-a-Chip Database (OOCDB): A Comprehensive, Systematic and Real-time Organs-on-a-chip Database
Authors: Li Jian , Liang Weicheng , Chen Zaozao , Li Xingyu , Gu Pan , Liu Anna , Chen Pin , Li Qiwei , Mei Xueyin , Yang Jing , Liu Jun , Jiang Lincao , Gu Zhongze
Published: July 2022

Organs-on-a-Chip is a microfluidic microphysiological system that uses microfluidic technology to make high-resolution and real-time imaging analysis on the structure and function of living human cells at the level of tissue and organ in vitro. Compared with the traditional two-dimensional cell culture model and animal model, organs-on-a-chip technology can simulate the pathological and toxicological interactions between different organs or tissues more closely and reflect the collaborative response of multiple organs to drugs. Although lots of organs-on-a-chip-related literature have been published, none of current databases have achieved all the following functionalities yet: searching, downloading and analyzing data and results from literature of organs-on-a-chip. To address this need, we established a database named organs-on-a-chip database (OOCDB), as a platform to integrate information related to organs-on-a-chip from various sources: literature, patents, microarray and transcriptome sequencing raw data, many open access data of organs-on-a-chip and organoids, as well as the data generated in our lab. OOCDB comprises dozens of sub databases and analysis tools and each sub database contains a number of data related to organs-on-a-chip, aiming to provide a comprehensive, systematic and convenient search engine for researchers. In addition, it provides functions such as mathematical modeling, three-dimensional model and citation map to meet the needs of researchers and to promote the development of organs-on-a-chip. The organs-on-a-chip database can be visited athttp://www.organchip.cn.
SEPRES: Sepsis prediction via the clinical data integration system in the ICU
Authors: Chen Qiyu , Li Ranran , Lin ChihChe , Lai Chiming , Huang Yaling , Lu Wenlian , Li Lei
Published: July 2022

Background

The lack of information interoperability between different devices and systems in the ICU hinders further utilization of data, especially for early warning of specific diseases in the ICU.

Objectives

We aimed to establish a real-time early warning system for sepsis based on a data integration system that can be implemented at the bedside of the intensive care unit (ICU), named SEPRES.

Methods

Data is collected from bedside devices through the integration hub and uploaded to the integration system through the local area network. The data integration system was designed to integrate vital signs data, laboratory data, ventilator data, demographic data, pharmacy data, nursing data, etc. from multiple medical devices and systems. It integrates, standardizes, and stores information, making the real-time inference of the early warning module possible. The built-in sepsis early warning module can detect the onset of sepsis within 5 hours preceding at most.

Results

Our data integration system has already been deployed in Ruijin Hospital, confirming the effectiveness of our system.

Conclusions

We highlight that SEPRES has the potential to improve ICU management by helping medical practitioners identify at-sepsis-risk patients and prepare for timely diagnosis and intervention.
Homologous Recombination Inquiry Through Ovarian Malignancy Investigations: The Japanese Gynecologic Oncology Group study JGOG3025
Authors: Yoshihara Kosuke , Baba Tsukasa , Shimada Muneaki , Nishino Koji , Sekine Masayuki , Takamatsu Shiro , Matsumura Noriomi , Yoshida Hiroshi , Kajiyama Hiroaki , Kagimura Tatsuo , Oda Katsutoshi , Sasajima Yuko , Okamoto Aikou , Sugiyama Toru , Enomoto Takayuki
Published: July 2022

The Cancer Genome Atlas has clarified that about 50% of high-grade serous ovarian cancer shows homologous recombination deficiency (HRD). However, the frequency of HRD in Japanese patients with ovarian cancer remains unclear. The aim of JGOG3025 study (NCT03159572) is to identify the frequency of HRD in Japanese patients with ovarian cancer. The JGOG3025 study is a multicenter collaborative prospective observational study involving 65 study sites throughout Japan. We recruited 996 patients who were clinically diagnosed with ovarian cancer before surgery from March 2017 to March 2019, and 701 patients were eligible for JGOG3025 criteria. We used frozen tumor tissues to extract DNA and performed targeted sequencing for 51 genes most of which are HR-associated genes in 701 ovarian cancers (298 high-grade serous, 189 clear cell, 135 endometrioid, 12 mucinous, 3 low-grade serous, and 64 others). HRD was defined as positive when at least one HR-associated gene was mutated. The frequencies of HRD and tumor BRCA1/2 mutation were 45.2% (317/701) and 18.5% (130/701) in the full analysis set (FAS), respectively. Next, we performed multivariate Cox proportional hazards regression analysis for progression-free survival (PFS) and overall survival (OS). Advanced-stage ovarian cancer patients with HRD had an adjusted hazard ratio of 0.72 (95%CI, 0.55-0.93) and 0.58 (95%CI, 0.39-0.87) for PFS and OS compared to those without HRD (p = 0.013 and 0.009). Our study demonstrated that mutations in HR-associated genes might be associated with their prognosis. Further study will be needed to investigate prognostic impact of each HR-associated gene in ovarian cancer.
Non-linear Measures of Gait Adaptability in Multiple Sclerosis - Sensitivity and Neurological Correlates
Authors: Panisset MG , Lizama LE Cofré , Peng L , Galea MP
Published: July 2022

Multiple sclerosis (MS) is the leading cause of non-traumatic disability among young and middle-aged adults. People with MS (pwMS) rate walking and mobility as their highest priority for both research and symptom management. Given the importance of early initiation of disease-modifying therapeutics (DMTs) to minimize long-term disability, tools to identify early disease activity are needed. Traditional measures of disability, the Expanded Disability Status Scale (EDSS) and gait speed tests demonstrate poor reliability and responsiveness in cases with minimal disability. Nonlinear measures of gait, Local dynamic stability (LDS), Complexity (sample entropy) and Regularity (autocorrelation), measured in laboratory settings is sensitive to subclinical gait deterioration in people with MS (pwMS). These measures have not been tested in a clinical setting using wearable sensors.

Methods

Gait metrics were calculated in MatLab from inertial data collected from 59 pwMS (EDSS 0-4) and 23 age- and sex-matched healthy controls (HC) during a 5-minute walk. We aimed to provide known-groups validation of non-linear gait measures and compare sensitivity of LDS from sensors placed at sternum and sacrum in pwMS (ROC analysis). Associations of gait metrics with disability, Kurtzke Functional System scores and 3T MRI segmental brain volumes were examined.

Results

Most sternum-derived LDS measures detected significant differences between HC and pwMS (EDSS0-1) with moderate to large effect sizes (η2=.100-305), while the effect sizes for sacrum-derived LDS were lower (η2=.104-.166). Sternum3D best distinuished EDSS0-1 from HC whereas the effect size was lower for gait speed (η2=.104). Sternum Instability-3D showed strongest correlation with pyramidal dysfunction (rs=.455, p<.001). Sensory dysfunction correlated significantly with Regularity in the vertical plane from both sensors, while cerebellar dysfunction was significantly associatesd with sacrum Regularity in the saggital plance (r=-.343, p=.008) and brainstem dysfunction with Complexity in the frontal plane (r=-.343, p=.008).

Conclusion

Sternum-derived LDS measures were more sensitive than Sacrum-derived measures. Correlations with clinical and morphological brain measures support the validity of walking deterioration as reflective of neurodegeneration in subcortical grey matter. The current findings of high sensitivity in non-disabled cases, as well as the clinical feasibility and relatively low costs, support the utility of these measures as a supplementary clinical assessment tool.
Profiling of circulating glial cells allows accurate blood-based diagnosis of glial malignancies
Authors: O’Neill Kevin , Syed Nelofer , Crook Timothy , Dubey Sudhir , Potharaju Mahadev , Limaye Sewanti , Ranade Anantbhushan , Anichini Giulio , Datta Vineet
Published: July 2022

We describe an in vitro test for detection of glial malignancies (GLI-M) based on enrichment and immunostaining of Circulating Glial Cells (CGCs) from peripheral blood sample. Extensive analytical validation studies using U87MG reference cell lines spiked into blood established the analytical performance characteristics of the test. The ability of the test to detect and differentiate GLI-M from non-malignant brain tumors (NBT), non glial type central nervous system (CNS) malignancies (NGCM), brain metastases from primary epithelial malignancies in other organs and healthy individuals were evaluated in four studies. The cumulative performance metrics of the test across all 4 clinical studies were 99.35% Sensitivity (95%CI: 96.44% - 99.98%) and 100% Specificity (95%CI: 99.37% - 100%). The performance characteristics of this test support its clinical utility for diagnostic triaging of individuals presenting with ICSOL.
Subgroups of people with high Autism-Spectrum Quotient scores identified from a large set of personality traits and attributes
Authors: Fujiwara Mao , Numano Shotaro , Tanaka Toshiko , Nakamura Motoaki , Kato Nobumasa , Haruno Masahiko
Published: July 2022

The Autism-Spectrum Quotient (AQ) is a widely used index to quantify autistic traits. Previous studies using clustering analysis have indicated that people showing high AQ and other autism indices may comprise several subtypes. However, those studies mainly focused on Big5 personality traits and analyzed a limited number of samples (participants). The inclusion of a larger set of personality traits and attributes would contribute not only to understanding autism more deeply, but also to characterizing AQ more precisely. In addition, an analysis of larger general populations would give new perspectives on people with high AQ scores. To address these issues, here we conducted a personality traits-based clustering of 1364 subjects who had an AQ score of 33 or higher (high AQ group) collected online. We identified three subclasses (subtypes): Group 1, characterized by emotional instability, low self-esteem, high hostility, anxiety, depressive tendency and schizotypal traits; Group 2, characterized by high BIS for an inhibitory attitude towards novelty, and high Interpersonal Reactivity Index (IRI) and Group 3, characterized by personality traits and attributes consistent of the average of the general population. Thus, this study provides empirical results showing subtypes of the high AQ population.