bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-Term Opioid Use Following Surgery for Symptomatic Neuroma
Authors: Lans Jonathan , Westenberg Ritsaart F. , Gottlieb Rachel E. , Valerio Ian L. , Chen Neal C. , Eberlin Kyle R.
Published: February 2022

Background Identifying patients at risk for prolonged opioid use following surgery for symptomatic neuroma would be beneficial for perioperative management. The aim of this study is to identify the factors associated with postoperative opioid use of >4 weeks in patients undergoing neuroma surgery.

Methods After retrospective identification, 77 patients who underwent surgery for symptomatic neuroma of the upper or lower extremity were enrolled. Patients completed the Patient-Reported Outcomes Measurement Information System (PROMIS) depression, Numeric Rating Scale (NRS) pain score, and a custom medication questionnaire at a median of 9.7 years (range: 2.5–16.8 years) following surgery. Neuroma excision followed by nerve implantation (n = 39, 51%), nerve reconstruction/repair (n = 18, 23%), and excision alone (n = 16, 21%) were the most common surgical treatments.

Results Overall, 27% (n = 21) of patients reported opioid use of more than 4 weeks postoperatively. Twenty-three patients (30%) reported preoperative opioid use of which 11 (48%) did not report opioid use for >4 weeks, postoperatively. In multivariable logistic regression, preoperative opioid use was independently associated with opioid use of >4 weeks, postoperatively (odds ratio [OR] = 4.4, 95% confidence interval [CI]: 1.36–14.3, p = 0.013).

Conclusion Neuroma surgery reduces opioid use in many patients but patients who are taking opioids preoperatively are at risk for longer opioid use. Almost one-third of patients reported opioid use longer than 4 weeks, postoperatively.
Topic modelling exposes disciplinary divergence in research on the nexus between human mobility and the environment
Authors: Zander Kerstin K. , Garnett Stephen T. , Sterly Harald , Ayeb-Karlsson Sonja , Šedová Barbora , Lotze-Campen Hermann , Richerzhagen Carmen , Baggen Hunter S.
Published: February 2022

Human mobility is increasingly associated with environmental and climatic factors. One way to explore how mobility and the environment are linked is to review the research on different aspects of the topic. However, so many relevant articles are published that analysis of the literature using conventional techniques is becoming prohibitively arduous. To overcome this constraint, we have applied automated textual analysis. Using unsupervised topic modelling on 3197 peer-reviewed articles on the nexus between mobility and the environment published over the last 30 years, we identify 37 major topics. Based on their language use, the topics were deeply branched into two categories of focus: Impact and Adaptation. The Impact theme is further clustered into sub-themes on vulnerability and residential mobility, while articles within the Adaptation theme are clustered into governance, disaster management and farming. The analysis revealed opportunities for greater collaboration within environmental mobility research, particularly improved integration of adaptation and impact research. The topic analysis also revealed that, in the last 30 years, very little research appears to have been undertaken in migration destinations or on the fate of environmentally influenced migrants during their migration process and after arriving in a new location. There are also research gaps in gender and Indigenous issues within the Impact theme, as well as on adaptive capacity and capacity-building.
Examining scattering dynamics in a state of strong rotational non-equilibrium
Authors: Thompson Avery
Published: February 2022

Numerical model explores the behaviors of rapidly rotating molecules scattering off a crystalline surface.
Measure valued solution to the spatially homogeneous Boltzmann equation with inelastic long-range interactions
Authors: Qi Kunlun
Published: February 2022

This paper aims at studying the inelastic Boltzmann equation without Grad’s angular cutoff assumption, where the well-posedness theory of the Cauchy problem is established for the Maxwellian molecules in a space of probability measure defined by Cannone and Karch [Commun. Pure Appl. Math. 63, 747–778 (2010)] via Fourier transform and the infinite energy solutions are not a priori excluded. The key strategy is to construct a brand new geometric relation of the inelastic collision mechanism to extend the result of Cannone and Karch from moderate singularity of the non-cutoff collision kernels to strong singularity and simultaneously handle more general restitution coefficients. Moreover, we extend the self-similar solution to the Boltzmann equation with infinite energy shown by Bobylev and Cercignani [J. Stat. Phys. 106, 1039–1071 (2002)] to the inelastic case by using a constructive approach, which is also proved to be the large-time asymptotic steady solution with the help of an asymptotic stability result in a certain sense.
An alternate approach to simulate the dynamics of perturbed liquid drops
Authors: Singla Tanu , Roy Tanushree , Parmananda P. , Rivera M.
Published: February 2022

Liquid drops when subjected to external periodic perturbations can execute polygonal oscillations. In this work, a simple model is presented that demonstrates these oscillations and their characteristic properties. The model consists of a spring–mass network such that masses are analogous to liquid molecules and the springs correspond to intermolecular links. Neo-Hookean springs are considered to represent these intermolecular links. The restoring force of a neo-Hookean spring depends nonlinearly on its length such that the force of a compressed spring is much higher than the force of the spring elongated by the same amount. This is analogous to the incompressibility of liquids, making these springs suitable to simulate the polygonal oscillations. It is shown that this spring–mass network can imitate most of the characteristic features of experimentally reported polygonal oscillations. Additionally, it is shown that the network can execute certain dynamics, which so far have not been observed in a perturbed liquid drop. The characteristics of dynamics that are observed in the perturbed network are polygonal oscillations, rotation of network, numerical relations (rational and irrational) between the frequencies of polygonal oscillations and the forcing signal, and that the shape of the polygons depends on the parameters of perturbation.
Multiphysics simulation of microscale copper printing by confined electrodeposition using a nozzle array
Authors: Burlison Scott , Minary-Jolandan Majid
Published: February 2022

3D printing of metals at the microscale and nanoscale is crucial to produce high-density interconnects and intricate structures in electronic devices. Conventional melting and sintering processes are not suitable for these scales due to a reliance on individual metal particles in the size range of tens of micrometers. Confined electrodeposition (CED) is an established alternative to conventional metal 3D printing processes in which an electrolyte is used to selectively induce deposition of the metal on the printing surface. However, commercialization and efficiency of this process have been limited due to a reliance on sub-micrometer nozzles to achieve desirable deposition rates and single nozzle to achieve uniformity of printed structures. Here, we address these challenges by computationally analyzing an array of microscale nozzles. We tailor the convection within the electrolyte to alter both deposition rate and geometric uniformity of the printed structures. The results show that for large nozzles the evaporation alone is not sufficient to obtain high deposition rates, yet an external pressure can be used to increase deposition and alter uniformity (thickness) of printed structures. Our results can be used to design and analyze new experiments toward parallel multi-nozzle deposition using CED toward high-throughput metal printing.
Step-like resistance changes in VO2 thin films grown on hexagonal boron nitride with in situ optically observable metallic domains
Authors: Genchi Shingo , Yamamoto Mahito , Iwasaki Takuya , Nakaharai Shu , Watanabe Kenji , Taniguchi Takashi , Wakayama Yutaka , Tanaka Hidekazu
Published: February 2022

Vanadium dioxide (VO2) thin films grown on hexagonal boron nitride (hBN) flakes show three orders of magnitude resistance change due to metal–insulator transition (MIT). The MIT property of VO2 thin films is strongly dependent on the metallic domain size, which should be identified to derive the resistance change owing to the single metallic domain. In this study, we investigated the relationship between the metallic domain size and the device-size-dependent MIT property of VO2 thin films grown on hBN. We observed by temperature-dependent Raman spectroscopy and optical microscopy the emergence of the metallic domains and determined the metallic domain size in VO2 thin films grown on hBN. The metallic domain size of the VO2 thin films grown on hBN was determined to be ∼500 nm on average in length and up to sub-micrometer scale. Electric transport measurements revealed that VO2/hBN microwires exhibit multi-level step-like resistivity changes that change by one to two orders when the length and width are ∼2 μm owing to the confined metallic domains in the micrometer scale. Our results open a way for VO2 devices, showing a steep and large resistance change even in the micrometer scale.
Efficient and accurate phase-measurement method for core-loss characterization
Authors: Huang Anfeng , Fan Jun , Hwang Chulsoon
Published: February 2022

Accurate core-loss characterization is essential to push the power density of power converters to their limits. However, existing core-loss measurement methods still have some limitations, such as a slow test speed and a complex probe calibration procedure. In particular, accurate phase-difference measurement is time-consuming because a fast Fourier transform analysis with a kHz-range frequency interval is typically applied to reduce the influence of noise. An automated measurement system for magnetic core-loss characterization is described in this paper. An accurate phase-detection block with programmable attenuators is developed to measure the phase difference between voltage and current waveforms. The proposed system considerably improves the test speed while providing comparable accuracy to the existing method.
Rotary table wobble error analysis and correction of a rotating accelerometer gravity gradiometer
Authors: Chen P. , Yu M. , Deng Z. , Zhang M. , Liu J. , Fan J. , Hu C. , Tu L.
Published: February 2022

In a rotating accelerometer gravity gradiometer (RAGG), rotary table wobble refers to the shift in the direction of the spin axis during operation. This motion causes errors in the output of the RAGG, but the mechanism is not clear. The purpose of this paper is to analyze the relationship between rotary table wobble and RAGG errors and to propose a method for rejecting these errors. We consider the influence of attitude changes, angular velocity, and angular acceleration caused by the wobble on the specific force, and we describe the error transmission process based on the accelerometer configuration and its measurement principle. Furthermore, we show through a simulated experiment that when the angular velocity noise caused by the wobble is 1 μrad/s, this will produce errors of tens of E. We propose a post-error correction method that is based on the higher-precision RAGG model and motion measurement. The errors in the two channels of the RAGG are reduced to 3.69 E and 1.85 E after error correction. The error analysis of the effects of wobble on a RAGG and the proposed error correction method are of great significance for the development of high-precision gradiometers.
Plasma–neutral coupling allows electrostatic ion cyclotron waves to propagate below ion cyclotron frequency
Authors: Terasaka K. , Yoshimura S.
Published: February 2022

The effect of ion–neutral collisions on the propagation characteristics of electrostatic ion cyclotron (EIC) waves in a partially ionized plasma is investigated. The dispersion relation of EIC waves is derived using a fluid model taking neutral dynamics into account. The propagation properties of EIC modes, including the damping factor, are examined for various ionization degrees and collision frequencies, which determine the momentum transferred from ions to neutral particles. It is found that the motion of neutral particles driven by plasma–neutral coupling leads to an increase in the effective ion mass, and consequently, EIC waves can propagate even below the ion cyclotron frequency. In a hot neutral gas, the gas-thermal mode can also propagate as well as the EIC mode. The possibility of observing in the laboratory and the Earth's ionosphere is discussed.
On the validity of the guiding-center approximation in a magnetic dipole field
Authors: Brizard Alain J. , Markowski Danielle G.
Published: February 2022

The problem of the charged-particle motion in an axisymmetric magnetic-dipole geometry is used to assess the validity of Hamiltonian guiding-center theory, which includes higher-order corrections associated with guiding-center polarization induced by magnetic-field nonuniformity. When a magnetically confined charged-particle orbit is regular (i.e., its guiding-center magnetic moment is adiabatically invariant), the guiding-center approximation, which conserves both energy and azimuthal canonical angular momentum, is shown to be faithful to the particle orbit when guiding-center polarization effects are taken into account.
Reversible optical control of Fano resonance and domain configuration at room temperature in BaTiO3
Authors: Dwij Vivek , De Binoy Krishna , Gupta M. K. , Mittal R. , Lalla N. P. , Sathe Vasant
Published: February 2022

Despite the ubiquitous nature, control of the Fano resonance in insulators has remained unexplored. We have achieved reversible control of Fano resonance using optical control in BaTiO3 at room temperature. Raman spectroscopic signatures and first-principle calculations suggest that the Fano line shape arises from the coupling of the discrete phonons [A(TO1)] comprising oscillations of Ba against TiO6 octahedra and broad phonons A(TO2) arising from oscillations of Ti against O6. Modifications of the A(TO2) phonons by lattice strain under different light polarizations change the resonance condition, which alters the spectral line shape. Domain reconfiguration accompanied by lattice strain is verified using x-ray diffraction experiments carried out under laser light with different polarization.
Numerical analysis of the effect of train length on train aerodynamic performance
Authors: Chen Guang , Li Xiaobai , Zhang Lei , Liang Xifeng , Meng Shi , Zhou Dan
Published: February 2022

The improved delayed detached eddy simulation is adopted in the present study to investigate the influence of the train length on its aerodynamic performance. The low y+ wall treatment and the cubic constitutive relation are adopted to resolve the viscous flows and model the anisotropic turbulence within the boundary layer. The analysis implied that the distribution region and intensity of velocity fluctuation are strengthened, resulting in a larger turbulence kinetic energy distribution and a higher boundary layer thickness as the train length increases. A reduction in the streamwise velocity and the negative pressure with the increasing train length on the tail train is observed, resulting in lower drag and lift coefficients. As the length of the train increases, both the mean and instantaneous slipstream velocities are increased. The boundary layer thickness and the skin friction coefficient are compared with flat plate theory, reduced-scale, and full-scale experiments, proving the ability of numerical simulation to model the boundary layer velocity profile and skin friction coefficient distribution correctly. The wake structures are identified by the Spectral Proper Orthogonal Decomposition method, the dominant mode frequency decreases, and the wavelength becomes larger as the length of the train becomes longer due to the thickening boundary layer.
Relaxation of multi-ion plasmas in an internal conductor
Authors: Gondal S. M.
Published: February 2022

The possibility of the formation and characteristics of the relaxed structures in the multi-ion magnetized plasmas consisting of heavy ions, light ions, and inertia-less electrons have been explored. Using the vortex dynamic equations with the current density, the system is relaxed to triple Beltrami states. Solutions of the relaxed states are determined in two different cases: (i) simple slab geometry and (ii) slab geometry with an internal conductor. The impact of Beltrami parameters and density ratios of the plasma components on the formation of equilibrium structures in both geometries has been studied. Moreover, we also highlight the equivalences of both geometries (simple slab geometry and a slab geometry with an internal conductor). This investigation will be useful for studying and understanding the relaxed structures in different astrophysical objects such as solar wind, Earth’s ionosphere, near-Earth plasmasheet, upper ionosphere, and Saturn and in the laboratory plasmas having two positively charged ions of different masses. Moreover, this work will be helpful in describing the underlying physics of the relaxed structures. These structures are developed in different astrophysical bodies that revolve around the planet such as Jupiter magnetosphere.
Two-faced ions form a promising battery material
Authors: Miller Johanna L.
Published: February 2022

Electrolyte molecules that have both positive and negative charges stay in place while lithium ions move among them.
DOE medical isotope campaign nears completion
Authors: Kramer David
Published: February 2022

The US Department of Energy says it has provided enough support to get a domestic industry off the ground without weapons-usable material.
Impact of hot weather on animal performance and genetic strategies to minimise the effect
Authors: Pryce Jennie E. , Nguyen T. T. T. , Cheruiyot E. K. , Marett L. , Garner J. B. , Haile-Mariam M.
Published: February 2022

Dairy cows in Australia and New Zealand are generally kept outdoors, making them susceptible to weather variability and in particular heat stress. In this paper, we review (1) exploiting genetic variability to improve heat tolerance, (2) genotype by environment interactions, i.e. suitability of high merit cows to weather variability and (3) how novel phenotyping and genomics can help improve heat tolerance. Selection for heat tolerance is a permanent and cumulative strategy and especially useful in grazing situations where management practices, such as cooling mechanisms, are sometimes impractical. Australia was the first country in the world to release breeding values for heat tolerance in dairy cattle nationally in 2017. The breeding value captures genetic variation in the reduction of milk production traits with rising temperature and humidity. The breeding values have been validated in independent studies (in Victoria, Australia, and California, USA), showing that thermotolerant cows maintain a lower core body temperature under hot and humid conditions. Genotype by environment interactions for traits sensitive to heat is only a concern for farms in very extreme conditions and therefore affect only a small proportion of individuals (those in the extreme 5th percentile). Heat tolerance is a complex trait in that in addition to milk traits, health and fertility may also be affected. Next-generation heat tolerance breeding values may include sensor device information in addition to changes in milk composition, or other measurable biomarkers. This is especially useful when measured in genotyped female populations. Research into novel ways of measuring heat tolerance could transform the way we select for this trait and capture more of the complexity of this trait. To be successful in this area, multi-disciplinary collaboration among animal scientists is likely to facilitate this goal. Combining genomics, traditional and novel measures of heat tolerance with intermediate metabolic biomarkers and prioritised genetic variants could be a way to capture the complexity of thermotolerance in future heat tolerance breeding values. Finally, selecting cows that are resilient to variability in weather is feasible and heat tolerance is a good example of this.
Contribution of K solubilising bacteria (
Authors: Zhang Xianchen , Wang Ningning , Hou Mengmeng , Wu Honghong , Jiang Hong , Zhou Ziwen , Chang Na , Wang Qianqian , Wan Xiaochun , Jiang Jiayue , Shen Zhougao , Li Yeyun
Published: February 2022

K+ availability is important for growth and quality of tea (Camellia sine sis L.). K solubilising bacteria convert insoluble K to available K. This study was conducted to screen K solubilising bacteria isolated from tea rhizosphere soil in Qimen county, Anhui province, China. The maximum K solubilisation colony (the ratio of diameter halo/colony was 2.54) was identified as Burkholderia sp. (storage number: M2021105) by biochemistry and molecular analysis. Pot experiments (Laterite) showed that the inoculation of Burkholderia sp. significantly improved tea plant height (Zhongcha108, 1 year old) and total polyphenols content by 21.14% and 21.58% compared with the control, respectively. Higher polyphenol level promoted the formation of theaflavin in the fermentation experiments. Further experiments showed that tartaric acid and pryuvic acid produced by Burkholderia sp. are important components associated with K solubilisation in vitro. Burkholderia sp. significantly increased soil available K by 15.12%; however, there was no significant difference in available N and P, and Cu, Mg, Zn and Ca compared with the control. K content in inoculated tea roots and leaves was significantly higher (50% and 10%, respectively) than the control. Compared with the control, exogenous supply of 60 mg kg−1 K significantly increased levels of polyphenol (53.97%), theaflavin (16.31%), theaflavin-3-gallate (20%), theaflavin 3′-gallic acid ester (32.24%) and theaflavin 3,3′-gallic acid ester (40.95%). Due to its ability to enable higher available soil K, ur study indicated that Burkholderia sp. have potential to increase total polyphenols content be a bio-inoculant for biofortification of tea.
Factors associated with choice of health service delivery for after-hours, urgent, non-life-threatening conditions: a patient survey
Authors: Adie John William , Graham Wayne , Wallis Marianne
Published: February 2022

The objective of this study was to determine factors associated with patient or carer choice of presentation to an emergency department, an urgent care clinic and an after-hours general practice on Sundays in south-east Queensland. The design of the study was a cross-sectional survey of patients or carers. The study setting was an emergency department, an urgent care clinic and an after-hours general practice. Patients or carers of patients were invited to take part in the study while they were waiting to consult the doctor. Patients were more likely to present to community clinics (i.e. urgent care clinic and an after-hours general practice) if they usually came to the facility (P < 0.001), were concerned about cost (P < 0.001), were influenced by the perceived severity of the sickness (P < 0.001), were unable to get an appointment elsewhere (P < 0.001), thought that there would be less waiting time (P < 0.001) and thought there was better doctor explanation (P = 0.007). This research was limited to 337 surveys. Larger studies could further explore insights gained from this study. The results suggest that public health campaigns could focus on promoting community clinic care for urgent non-life-threatening conditions. These campaigns should include information on waiting times, need for referral, conditions safely managed, range of services provided and quality of service. Designing community facilities for hospital avoidance of patients with non-life-threatening urgent conditions could involve public health campaigns, facility upgrades, and subsidies for transport and attendance.
High-value decisions are fast and accurate, inconsistent with diminishing value sensitivity
Authors: Shevlin Blair R. K. , Smith Stephanie M. , Hausfeld Jan , Krajbich Ian
Published: February 2022

Significance

What information about economic value is incorporated into decision-makers’ choices? Across the decision sciences, several prominent models ignore average value, assuming that only value differences are incorporated into the decision-making process, while others assume diminishing sensitivity to value, suggesting that it should be more difficult to choose between high-value options. Other models suggest that high-value decisions should, if anything, be treated as less important (holding value difference constant). Across three experiments with very different types of choices (food, art, and learned stimuli), we find violations of these predictions. Contrary to expectations, the presence of high-value options makes decisions easier while also inducing more effort to get them right.
BRD4-directed super-enhancer organization of transcription repression programs links to chemotherapeutic efficacy in breast cancer
Authors: Liu Beibei , Liu Xinhua , Han Lulu , Chen Xing , Wu Xiaodi , Wu Jiajing , Yan Dong , Wang Yue , Liu Shumeng , Shan Lin , Zhang Yu , Shang Yongfeng
Published: February 2022

Significance

We found that BRD4 interacts with the LSD1/NuRD complex and colocalizes with this repressive complex on super-enhancers and that decommissioning BRD4-directed super-enhancer organization of transcription repression programs inflicts widespread drug resistance in breast cancer. The study uncovers a functional duality of BRD4 in super-enhancer organization of transcription activation and repression linking to oncogenesis and chemoresistance, respectively, supporting the pursuit of a combined targeting of BRD4 and PELI1 in effective treatment of breast cancer.
Economic barriers to green innovations in Morocco: the case of a zero-energy house
Authors: Youssef E , Zaid R , Mohamed E K
Published: February 2022

Building with a reduced ecological footprint has become a major topic in the energy and economic debate in Morocco. This article aims at analyzing the economic barriers facing the integration and diffusion of environmental innovations in the building sector in Morocco. The concept of environmental innovation is taken as a conceptual framework for our analysis. We present a case study of the integration of innovative technical solutions: it concerns the use of a bio-sourced material “hempcrete” (as a green input) and an innovative system (Curved Solar Panels) for the construction and the energy production of a zero-energy building. The results show that these innovative solutions cannot easily be adopted and generalized given the fact that their cost remains high compared to conventional solutions. In addition, at the macroeconomic level, several barriers can hamper the generalization of these solutions in Morocco.
Individualized everolimus treatment for tuberous sclerosis-related angiomyolipoma promotes treatment adherence and response
Authors: Chung Noelle K X , Metherall Peter , McCormick Janet A , Simms Roslyn J , Ong Albert C M
Published: February 2022

Background

Everolimus is a potential alternative to embolization and nephrectomy for managing tuberous sclerosis complex (TSC)-associated renal angiomyolipoma (AML). In 2016, National Health Service England approved its use through regional centres for renal AML ≥30 mm showing interval growth. Evidence of lesion stabilization or reduction after 6 months is mandated for continuation of long-term treatment.

Methods

From November 2016 to June 2021, all potentially eligible adult TSC patients with AML across Yorkshire and Humber were referred for assessment and monitoring. Eligible patients underwent baseline renal magnetic resonance imaging (MRI) assessment and a follow-up MRI scan after 6 months on everolimus. Dose titration was guided by trough levels and lesion responsiveness using a new 3D MRI volumetric protocol.

Results

Of 28 patients commencing treatment, 19 tolerated everolimus for >3 months. Overall, 11 patients (40%) discontinued treatment, mostly due to recurrent infections (42%) and allergic reactions (25%). Sixty-eight percent required dose adjustments from the initiating dose (10 mg) due to sub-optimal trough levels (38%), minimal AML response (15%) or adverse events (47%). 3D volumetric assessment confirmed a reduction in AML volume of a pre-selected index lesion in all treatment-naïve cases (n = 14), showing superiority over 2D measurements of lesion diameter.

Conclusion

In this cohort, everolimus promoted AML regression in all patients who tolerated the drug for >6 months with stabilization observed over 3 years. Trough levels enabled individual dose titration to maximize responsiveness and minimize side effects. The use of 3D MRI assessment of lesion volume was superior to 2D measurements of lesion diameter in monitoring treatment response.
Genome-wide association study reveals novel genetic loci: a new polygenic risk score for mitral valve prolapse
Authors: Roselli Carolina , Yu Mengyao , Nauffal Victor , Georges Adrien , Yang Qiong , Love Katie , Weng Lu Chen , Delling Francesca N , Maurya Svetlana R , Schrölkamp Maren , Tfelt-Hansen Jacob , Hagège Albert , Jeunemaitre Xavier , Debette Stéphanie , Amouyel Philippe , Guan Wyliena , Muehlschlegel Jochen D , Body Simon C , Shah Svati , Samad Zainab , Kyryachenko Sergiy , Haynes Carol , Rienstra Michiel , Le Tourneau Thierry , Probst Vincent , Roussel Ronan , Wijdh-Den Hamer Inez J , Siland Joylene E , Knowlton Kirk U , Jacques Schott Jean , Levine Robert A , Benjamin Emelia J , Vasan Ramachandran S , Horne Benjamin D , Muhlestein Joseph B , Benfari Giovanni , Enriquez-Sarano Maurice , Natale Andrea , Mohanty Sanghamitra , Trivedi Chintan , Shoemaker Moore B , Yoneda Zachary T , Wells Quinn S , Baker Michael T , Farber-Eger Eric , Michelena Hector I , Lundby Alicia , Norris Russell A , Slaugenhaupt Susan A , Dina Christian , Lubitz Steven A , Bouatia-Naji Nabila , Ellinor Patrick T , Milan David J
Published: February 2022

Aims

Mitral valve prolapse (MVP) is a common valvular heart disease with a prevalence of >2% in the general adult population. Despite this high incidence, there is a limited understanding of the molecular mechanism of this disease, and no medical therapy is available for this disease. We aimed to elucidate the genetic basis of MVP in order to better understand this complex disorder.

Methods and results

We performed a meta-analysis of six genome-wide association studies that included 4884 cases and 434 649 controls. We identified 14 loci associated with MVP in our primary analysis and 2 additional loci associated with a subset of the samples that additionally underwent mitral valve surgery. Integration of epigenetic, transcriptional, and proteomic data identified candidate MVP genes including LMCD1, SPTBN1, LTBP2, TGFB2, NMB, and ALPK3. We created a polygenic risk score (PRS) for MVP and showed an improved MVP risk prediction beyond age, sex, and clinical risk factors.

Conclusion

We identified 14 genetic loci that are associated with MVP. Multiple analyses identified candidate genes including two transforming growth factor-β signalling molecules and spectrin β. We present the first PRS for MVP that could eventually aid risk stratification of patients for MVP screening in a clinical setting. These findings advance our understanding of this common valvular heart disease and may reveal novel therapeutic targets for intervention.
Co-Inoculation with Beneficial Soil Microorganisms Promoted Growth and Quality of Tabebuia rosea Seedlings
Authors: Higuita-Aguirre María Isabel , Osorio-Vega Walter , León-Peláez Juan D
Published: February 2022

Poor seedling quality is a major limiting factor for the success of commercial afforestation and ecological restoration in the tropics. This is commonly due to poor nutrient availability of soil-based substrates used for seedling growth. Currently, the use of biofertilizers has gained attention as a biotechnological tool to overcome plant malnutrition and enhance seedling quality from the nursery. The aim of this study was to evaluate the effects of individual and combined inoculation with selected beneficial soil microorganisms on plant growth of Tabebuia rosea (Bertol.) Bertero ex A.DC. in the nursery stage. For this purpose, individual, dual, and triple inoculations were conducted with Rhizoglomus fasciculatum (arbuscular mycorrhizal fungus: AMF), Mortierella sp. (mineral-solubilizing fungus: MSF), and Azospirillum brasilense (plant growth-promoting bacteria: PGPB). After six months, the inoculation with PGPB significantly promoted plant growth over the uninoculated control. Dual inoculation with AMF+MSF and AMF+PGPB had lower but significant effects over the control. The results showed that biofertilization is an effective alternative to promote plant growth and quality of this species in the nursery and thus to produce better plants for forestry and ecological restoration in tropical areas.
Insights into Moho depth beneath the northwestern Andean region from gravity data inversion
Authors: Avellaneda-Jiménez D S , Monsalve G , León S , Gómez-García A M
Published: February 2022

The complex Moho topography beneath the northwestern Andes is the result of multiple geodynamic processes during the Cenozoic. To contribute to our understanding of the Moho depth distribution beneath this region, we inverted gravity data from two widely used satellite-derived data sets (EGM2008 and EIGEN-6C4) and one regional airborne Bouguer gravity anomaly map (ANH2010). Their inversion allowed choosing the ANH2010, based on lower residual gravity and a higher agreement with seismic estimations, as the most suitable data set to gain insights into the Moho depth beneath the northwestern Andes and its relationship with previously identified tectonic features. The inverted Moho argues for a 40–50 km depth beneath the Central and Eastern cordilleras, reaching depths beyond 50 km below the Eastern Cordillera, and shallower depths between 30 and 40 km mainly along the foreland region to the east, the Western Cordillera and the coastal plains. Three main thickened crust features of regional extent were identified: (1) a deep Moho expression with a crustal thickness greater than 40 km in the northwesternmost foreland region, which we consider a direct consequence of the adjacent thickened Eastern Cordillera involving the fold and thrust deformation migration from the range towards the foreland, and the flexural deformation proposed for the eastern foothills; (2) a regional deep Moho expression (50–60 km) along the axis of the Eastern Cordillera, related to its shortening history including multiple phases of Cenozoic thick-skinned deformation and magmatic underplating; and (3) a Moho deeper than 60 km in a southern latitude (1°S–1°N) beneath the modern magmatic arc, whose interpretation is more complex, likely a combined result of mafic addition to the base of the crust, foundering tectonics, and lateral displacement of the lower crust prompted by the subducting Carnegie ridge.
Differential Recruitment of the Infralimbic Cortex in Recent and Remote Retrieval and Extinction of Aversive Memory in Post-Weanling Rats
Authors: Awad Walaa , Kritman Milly , Ferreira Guillaume , Maroun Mouna
Published: February 2022

Background

We previously showed that the infralimbic medial prefrontal cortex (IL-mPFC) plays an important role in recent and remote memory retrieval and extinction of conditioned odor aversion (COA) and contextual fear conditioning (CFC) in adult rats. Because the mPFC undergoes maturation during post-weaning, here, we aimed to explore (1) whether post-weanling rats can form recent and remote COA and CFC memory, and (2) the role of the IL-mPFC in mediating these processes.

Methods

To investigate the retrieval process, we transiently inactivated the IL-mPFC with lidocaine prior to the retrieval test at either recent or remote time points. To target the consolidation process, we applied the protein synthesis inhibitor after the retrieval at recent or remote time points.

Results

Our results show that the post-weanling animals were able to develop both recent and remote memory of both COA and CFC. IL-mPFC manipulations had no effect on retrieval or extinction of recent and remote COA memory, suggesting that the IL has no effect in COA at this developmental stage. In contrast, the IL-mPFC played a role in (1) the extinction of recent, but not remote, CFC memory, and (2) the retrieval of remote, but not recent, CFC memory. Moreover, remote, but not recent, CFC retrieval enhanced c-Fos protein expression in the IL-mPFC.

Conclusions

Altogether, these results point to a differential role of the IL-mPFC in recent and remote CFC memory retrieval and extinction and further confirm the differences in the role of IL-mPFC in these processes in post-weanling and adult animals.
On directional accuracy of some methods to forecast time series of cybersecurity aggregates
Authors: Carriegos Miguel V , Fernández Díaz Ramón Ángel , Trobajo M T , De Zaballa Diego Asterio
Published: February 2022

Cybersecurity aggregates are numerical data obtained by aggregation on features along a database of cybersecurity reports. These aggregates are obtained by integration of time-stamped tables using some recent results of non-standard calculus. Time-series of aggregates are shown to contain relevant information about the concrete system dealt with. Trend time series is also forecasted using known data-driven methods. Although absolute forecasting of trend time series is not obtained, a directional forecasting of trend time series is achieved thence validated by means of a rolling cross validation scheme on a public database of Scareware reports.
Persistent fecal occult blood due to the small intestinal metastasis of pleomorphic lung carcinoma
Authors: Suzuki Takaya , Noda Masafumi , Yamamura Akihiro , Ohishi Hisashi , Notsuda Hirotsugu , Eba Shunsuke , Tanaka Ryota , Tanaka Naoki , Kamei Takashi , Unno Michiaki , Okada Yoshinori
Published: February 2022

The gastrointestinal tract is one of the locations that lung cancers cause metastasis. A 70-year-old male underwent right lower lobectomy while presenting fecal occult blood with a preoperative colonoscopy showing colon polyps as the cause. The pathological diagnosis was pleomorphic carcinoma of the lung, with stage pT3N0M0. Seven months after the lung surgery, the patient presented with sudden-onset abdominal pain and severe anemia. Computed tomography scanning revealed a large mass in the abdominal cavity, and subsequent intestinal endoscopy demonstrated jejunum tumors. Partial jejunum resection was successfully performed. The patient developed multiple peritoneal nodules suggesting metastatic tumors but well responded to an immune checkpoint inhibitor. It can be challenging to diagnose gastrointestinal metastasis in routine radiography; therefore, endoscopic examination, including the small intestine, might be an important option when a lung cancer patient with advanced clinical stage presents with abdominal symptoms, including fecal occult blood.
Emerging and future strategies in the management of recalcitrant Candida auris
Authors: Bandara Nihal , Samaranayake Lakshman
Published: February 2022

Candida auris is an emerging, multi drug resistant fungal pathogen that has caused infectious outbreaks in over 45 countries since its first isolation over a decade ago, leading to in-hospital crude mortality rates as high as 72%. The fungus is also acclimated to disinfection procedures and persists for weeks in nosocomial ecosystems. Alarmingly, the outbreaks of C. auris infections in Coronavirus Disease-2019 (COVID-19) patients have also been reported. The pathogenicity, drug resistance and global spread of C. auris have led to an urgent exploration of novel, candidate antifungal agents for C. auris therapeutics. This narrative review codifies the emerging data on the following new/emerging antifungal compounds and strategies: antimicrobial peptides, combinational therapy, immunotherapy, metals and nano particles, natural compounds, and repurposed drugs. Encouragingly, a vast majority of these exhibit excellent anti- C. auris properties, with promising drugs now in the pipeline in various stages of development. Nevertheless, further research on the modes of action, toxicity, and the dosage of the new formulations are warranted. Studies are needed with representation from all five C. auris clades, so as to produce data of grater relevance, and broader significance and validity.

Lay Summary

Elimination of Candida auris that causes deadly infections to susceptible individuals is extremely challenging due to the lack of effective treatment options. Promising, new antifungal agents and strategies are being developed and further refinement will facilitate their clinical use in the near future.
The impact of the first galaxies on cosmic dawn and reionization
Authors: Muñoz Julian B , Qin Yuxiang , Mesinger Andrei , Murray Steven G , Greig Bradley , Mason Charlotte
Published: February 2022

The formation of the first galaxies during cosmic dawn and reionization (at redshifts z = 5–30), triggered the last major phase transition of our universe, as hydrogen evolved from cold and neutral to hot and ionized. The 21-cm line of neutral hydrogen will soon allow us to map these cosmic milestones and study the galaxies that drove them. To aid in interpreting these observations, we upgrade the publicly available code 21cmFAST. We introduce a new, flexible parametrization of the additive feedback from: an inhomogeneous, H2-dissociating (Lyman–Werner; LW) background; and dark matter – baryon relative velocities; which recovers results from recent, small-scale hydrodynamical simulations with both effects. We perform a large, ‘best-guess’ simulation as the 2021 installment of the Evolution of 21-cm Structure (EOS) project. This improves the previous release with a galaxy model that reproduces the observed UV luminosity functions (UVLFs), and by including a population of molecular-cooling galaxies. The resulting 21-cm global signal and power spectrum are significantly weaker, primarily due to a more rapid evolution of the star formation rate density required to match the UVLFs. Nevertheless, we forecast high signal-to-noise detections for both HERA and the SKA. We demonstrate how the stellar-to-halo mass relation of the unseen, first galaxies can be inferred from the 21-cm evolution. Finally, we show that the spatial modulation of X-ray heating due to relative velocities provides a unique acoustic signature that is detectable at z ≈ 10–15 in our fiducial model. Ours are the first public simulations with joint inhomogeneous LW and relative-velocity feedback across the entire cosmic dawn and reionization, and we make them available at this link https://scholar.harvard.edu/julianbmunoz/eos-21.
Interstellar hydrocarbons: degradation chemistry in diffuse clouds
Authors: Awad Zainab , Viti Serena
Published: February 2022

Observations of diffuse clouds showed that they contain a number of simple hydrocarbons [e.g. CH, C2H, (l- and c-)C3H2, and C4H] in abundances that may be difficult to understand on the basis of conventional gas-phase chemical models. Recent experimental results revealed that the photodecomposition mechanisms of hydrogenated amorphous carbon (HAC) and solid hexane release a range of hydrocarbons into the gas, containing up to six C-atoms for the case of HAC decomposition. These findings motivated us to introduce a new potential input to interstellar chemistry: the ‘top-down’ or degradation scheme, as opposed to the conventional ‘build-up’ or synthesis scheme. In this work, we demonstrate the feasibility of the top-down approach in diffuse clouds using gas–grain chemical models. In order to examine this scheme, we derived an expression to account for the formation of hydrocarbons when HACs are photodecomposed after their injection from grain mantles. Then, we calculated the actual formation rate of these species by knowing their injected fraction (from experimental work) and the average rate of mantle carbon injection into the interstellar medium (from observations). Our preliminary results are promising and reveal that the degradation scheme can be considered as an efficient mechanism for the formation of some simple hydrocarbons in diffuse clouds. However, an actual proof of the efficiency of this process and its rate constants would require comprehensive experimental determination.
Intrinsic alignments of the extended radio continuum emission of galaxies in the EAGLE simulations
Authors: Hill Alexander D , Crain Robert A , McCarthy Ian G , Brown Shaun T
Published: February 2022

We present measurements of the intrinsic alignments (IAs) of the star-forming gas of galaxies in the EAGLE simulations. Radio continuum imaging of this gas enables cosmic shear measurements complementary to optical surveys. We measure the orientation of star-forming gas with respect to the direction to, and orientation of, neighbouring galaxies. Star-forming gas exhibits a preferentially radial orientation–direction alignment that is a decreasing function of galaxy pair separation, but remains significant to $\gtrsim 1\, {\rm Mpc}$ at z = 0. The alignment is qualitatively similar to that exhibited by the stars, but is weaker at fixed separation. Pairs of galaxies hosted by more massive subhaloes exhibit stronger alignment at fixed separation, but the strong alignment of close pairs is dominated by ∼L⋆ galaxies and their satellites. At fixed comoving separation, the radial alignment is stronger at higher redshift. The orientation–orientation alignment is consistent with random at all separations, despite subhaloes exhibiting preferential parallel minor axis alignment. The weaker IA of star-forming gas than for stars stems from the former’s tendency to be less well aligned with the dark matter (DM) structure of galaxies than the latter, and implies that the systematic uncertainty due to IA may be less severe in radio continuum weak lensing surveys than in optical counterparts. Alignment models equating the orientation of star-forming gas discs to that of stellar discs or the DM structure of host subhaloes will therefore overestimate the impact of IAs on radio continuum cosmic shear measurements.
Primordial black holes and lepton flavor violation with scotogenic dark matter
Authors: Kitabayashi Teruyuki
Published: February 2022

We show that if the lepton flavor-violating μ → eγ process is observed in the MEG II experiment, the initial density of primordial black holes (PBHs) can be constrained with scotogenic dark matter. As a benchmark case, if PBH evaporation occurs in the radiation-dominated era, the initial density may be 2 × 10−17 ≲ β ≲ 3 × 10−16 for the $\mathcal {O}$(TeV)-scale dark sector in the scotogenic model, where β is the ratio of the PBH density ρPBH to the radiation density ρrad at the time of PBH formation. As another benchmark case, if PBHs evaporate in the PBH-dominated era, the initial density may be 1 × 10−8 ≲ β ≲ 3 × 10−7 for $\mathcal {O}$(GeV)-scale dark matter, with other $\mathcal {O}$(TeV)-scale particles in the scotogenic model.