bluuebunny/crossref_metadata_2025 huggingface dataset:
Validity and reliability of the Turkish version of the Sustainable and Healthy Eating Behaviors Scale
Authors: Köksal Eda , Bilici Saniye , Çıtar Dazıroğlu Merve Esra , Erdoğan Gövez Nazlıcan
Published: August 2022

This study was conducted to determine the validity and reliability of the Turkish version of the Sustainable and Healthy Eating (SHE) Behaviors Scale. The original scale included eight factors and thirty-four items related to the SHE behaviors of adults. The research was carried out in three stages with a total of 586 participants aged 19 to 50 years. The Cronbach alpha coefficient was used to evaluate internal consistency reliability and the test–retest method was applied. Exploratory factor analysis (EFA) was performed to determine the factor structure. The model obtained with EFA was evaluated with confirmatory factor analysis (CFA). The Cronbachαcoefficient of the scale was found to be excellent at 0·912, and the intra-class correlation coefficient was found to be good at 0·832 using the test–retest method. Considering the suitability of the data for factor analysis, the Kaiser–Meier–Olkin coefficient was 0·859, and the significance level of the Bartlett test of sphericity was less than 0·05 (χ2=3·803,25; P < 0·05). As a result of EFA, the items of the scale were found to be distributed in seven factor dimensions. The factor loadings of the items were between 0·516 and 0·890, and the factors explained 67 % of the variance. Considering the fit indices obtained as a result of the analysis of this model with CFA, it was seen that the model had an acceptable fit (χ2/sd = 2·593, comparative fit index = 0·915, Tucker–Lewis index=0·902, standardised root mean square error = 0·0754 and root mean square error of approximation = 0·067). In conclusion, the Turkish version of the SHE Behaviors Scale has credible reliability and construct validity to assess the sustainable and healthy eating behaviours of the Turkish adult population.
Determination of latitude by two fixed-altitude sightings
Authors: Villmoare Brian
Published: August 2022

The use of multiple observations near noon with a traditional sextant to determine a fix is common among celestial navigators. A recent invention is the fixed-angle ‘Bris sextant’ that comes with advantages, but imposes constraints due to its invariant nature. We propose a method by which both longitude and latitude can be fixed using only two sightings with such a device, each equidistant from the meridian. By modelling the solution space for the method, we explore some of the potential utility across geography and seasonal variation. Although this method was developed for use with a Bris fixed-angle sextant, it can also be conveniently used with a more traditional marine or level-bubble sextant. Because this method is computationally cumbersome, it is most convenient when used in a computer or tablet application, or with tables.
Lessons for International Small and Medium-Sized Enterprises from Counterfeiting Civil Litigations in China
Authors: Cai Chuanzi
Published: August 2022

This study aims to assess the effect of the 2013 trademark law revision (2013 law revision) on judicial remedies in China. The 2013 law revision increased the remedies Chinese courts can grant to plaintiffs, including small and medium enterprise (SME) plaintiffs, thus leading to higher remedies granted to plaintiffs compared to the past years in prevailing cases. This study finds that right after the law revision, the average amount of judicial remedies granted to plaintiffs increased temporarily. Meanwhile, the detailed judicial reasonings, foreign plaintiffs, and company defendants have stronger positive effects than product types and the year of decisions on the amount of monetary relief. These findings suggest that certain factors in cases may increase the remedies in trademark civil litigation. Therefore, SME plaintiffs should pay attention to core factors for litigation strategies, including preliminary injunctions, choice of defendant, choice of venue, and evidence in remedy collection.
The Role of Water Vapor in the Response of the Extratropical Circulation of Earth‐Like Planets to Obliquity Changes
Authors: Lobo Ana H. , Bordoni Simona
Published: August 2022

In this study, we use idealized aquaplanet simulations of Earth‐like planets to explore the large‐scale atmospheric circulation’s response to changes in shortwave radiation, through changes in the planet obliquity, and in longwave radiation, through changes in the prescribed optical depth. We primarily focus on the extratropical circulation and the counterintuitive weakening of extratropical eddy activity, and associated precipitating storm tracks, with increased obliquity. We show that on high‐obliquity planets with a small surface thermal inertia, net energy deficit during the winter months is primarily balanced by the latent energy component of the atmospheric heat capacity, which buffers any significant atmospheric cooling. As temperatures finally start to decrease, condensational latent heat release of atmospheric moisture further slows down the cooling and keeps the winter pole warmer than the midlatitudes until after the winter solstice. This prevents vigorous baroclinic eddy activity, which lives off the potential energy stored in the sloping isopycnals, as well as the development of a Ferrel cell and storm track. For planets with larger surface heat capacity, we see a similar suppression, with the energy storage in the ocean surface, rather than atmospheric latent energy storage, primarily balancing the net energy loss during the winter months. These results suggest that, regardless of surface thermal inertia, water‐covered high‐obliquity Earth‐like planets would not experience significant extratropical storm activity and highlight the need for a proper characterization of polar properties in planetary modeling and observational investigations.
Spectral Diversity of Rocks and Soils in Mastcam Observations Along the Curiosity Rover's Traverse in Gale Crater, Mars
Authors: Rice Melissa S. , Seeger Christina , Bell Jim , Calef Fred , St. Clair Michael , Eng Alivia , Fraeman Abigail A. , Hughes Cory , Horgan Briony , Jacob Samantha , Johnson Jeff , Kerner Hannah , Kinch Kjartan , Lemmon Mark , Million Chase , Starr Mason , Wellington Danika
Published: August 2022

The Mars Science Laboratory Curiosity rover has explored over 400 m of vertical stratigraphy within Gale crater to date. These fluvio‐deltaic, lacustrine, and aeolian strata have been well‐documented by Curiosity's in situ and remote science instruments, including the Mast Camera (Mastcam) pair of multispectral imagers. Mastcam visible to near‐infrared spectra can broadly distinguish between iron phases and oxidation states, and in combination with chemical data from other instruments, Mastcam spectra can help constrain mineralogy, depositional origin, and diagenesis. However, no traverse‐scale analysis of Mastcam multispectral data has yet been performed. We compiled a database of Mastcam spectra from >600 multispectral observations and quantified spectral variations across Curiosity's traverse through Vera Rubin ridge (sols 0–2302). From principal component analysis and an examination of spectral parameters, we identified nine rock spectral classes and five soil spectral classes. Rock classes are dominated by spectral differences attributed to hematite and other oxides (due to variations in grain size, composition, and abundance) and are mostly confined to specific stratigraphic members. Soil classes fall along a mixing line between soil spectra dominated by fine‐grained Fe‐oxides and those dominated by olivine‐bearing sands. By comparing trends in soil versus rock spectra, we find that locally derived sediments are not significantly contributing to the spectra of soils. Rather, varying contributions of dark, mafic sands from the active Bagnold Dune field is the primary spectral characteristic of soils. These spectral classes and their trends with stratigraphy provide a basis for comparison in Curiosity's ongoing exploration of Gale crater.
Stability Analysis of Submerged Vegetation Patterns in Rivers
Authors: Calvani G. , Carbonari C. , Solari L.
Published: August 2022

Aquatic vegetation in fluvial systems is often characterized by spatial patterning of the plant patches. To investigate the conditions for the formation of vegetation patches, we explore the stability of a uniform flow over a non‐erodible bed with a uniform vegetation cover of submerged plants. The flow model consists of the two‐dimensional shallow water and continuity equations. The hydrodynamic equations are coupled firstly to the classic formulation for vegetation dynamics, and secondly to a modified version of the equation. The revised relationship for vegetation dynamics accounts for the influence of removal, transport, and resettlement of propagules on the growth rate of aquatic vegetation. Linear stability analysis of the eco‐hydrodynamic problem is performed by enforcing the quasi‐steady approximation. We obtain a dispersion relation disclosing the growth rate and the migration rate of the perturbations of vegetation density as a function of the wavenumber and the relevant flow and vegetation parameters. The present theory predicts the onset of vegetation patterns and includes an adequate wavelength selection mechanism. While uprooting initially reduces plant density, the analysis demonstrates that resettled propagules after removal are fundamental for further plant population increases and the development of vegetation patterns. The proposed framework is then validated against data available in the literature. Additionally, the presence of an upper threshold in terms of vegetation density, above which uniform vegetation cover is stable, might explain the absence of any spatial pattern and thus the extremely dense vegetation cover induced by climate change and invasive species in altered ecosystems.
Simulation of Latent Heating Rate From the Microphysical Process Associated With Mesoscale Convective System Over Korean Peninsula
Authors: Madhulatha A. , Dudhia Jimy , Park Rae‐Seol , Rajeevan M.
Published: August 2022

To investigate the structure of latent heating rate during different stages of mesoscale convective system (MCS) over the Korean Peninsula, a four nested domain Weather Research and Forecasting (WRF) model simulation with two‐way nesting method has performed. Advanced physics options from the Korean Integrated model physics are considered for simulation. Latent heating rate associated with condensation, evaporation, deposition, sublimation, freezing and melting process is computed based on different microphysical process using WRF double moment (WDM6) microphysics scheme. During the development/mature stage of the convective system, the warming associated with latent heat release by condensation is dominant below 400 hPa, and deposition above 500 hPa. The maximum contribution of warming processes from condensation, cloud nucleation, graupel accretion, and ice, snow deposition is evident. Cooling processes from rain, cloud evaporation followed by graupel, and snow melting are also noticed. Major updrafts associated with ascent of air parcel and large hydrometeor distribution is apparent along with downdrafts in the lower levels. In the dissipating stage, the cooling due to latent heat absorption by evaporation below 600 hPa and melting around 600 hPa are dominant. Contribution from cooling processes is dominant with major downdraft motion in the lower levels corresponding to the hydrometeor fall velocity. Dominant positive (negative) total latent heating provided (restrained) the energy for convection during developing and dissipating stages of system. Varied distribution of total cloud hydrometeors in different stages is apparent. Consistency between cloud hydrometeors, net heating rates, major upward (downward) motion and corresponding rainfall in developing (dissipating) stages of MCS is noticed. Model simulated latent heating (WDM6) profiles are consistent with computed moisture source and sink terms (ERA5).
Traveling Ionospheric Disturbances in the Vicinity of Storm‐Enhanced Density at Midlatitudes
Authors: Zhang Shun‐Rong , Nishimura Yukitoshi , Erickson Philip J. , Aa Ercha , Kil Hyosub , Deng Yue , Thomas Evan G. , Rideout William , Coster Anthea J. , Kerr Robert , Vierinen Juha
Published: August 2022

This study provides first storm time observations of the westward‐propagating medium‐scale traveling ionospheric disturbances (MSTIDs), particularly, associated with characteristic subauroral storm time features, storm‐enhanced density (SED), subauroral polarization stream (SAPS), and enhanced thermospheric westward winds over the continental US. In the four recent (2017–2019) geomagnetic storm cases examined in this study (i.e., 2018‐08‐25/26, 2017‐09‐07/08, 2017‐05‐27/28, and 2016‐02‐02/03 with minimum SYM‐H index −206, −146, −142, and −58 nT, respectively), MSTIDs were observed from dusk‐to‐midnight local times predominately during the intervals of interplanetary magnetic field (IMF) Bz stably southward. Multiple wavefronts of the TIDs were elongated NW‐SE, 2°–3° longitude apart, and southwestward propagated at a range of zonal phase speeds between 100 and 300 m/s. These TIDs initiated in the northeastern US and intensified or developed in the central US with either the coincident SED structure (especially the SED basis region) or concurrent small electron density patches adjacent to the SED. Observations also indicate coincident intense storm time electric fields associated with the magnetosphere–ionosphere–thermosphere coupling electrodynamics at subauroral latitudes (such as SAPS) as well as enhanced thermospheric westward winds. We speculate that these electric fields trigger plasma instability (with large growth rates) and MSTIDs. These electrified MSTIDs propagated westward along with the background westward ion flow which resulted from the disturbance westward wind dynamo and/or SAPS.
Plasmoids in the Jovian Magnetotail: Statistical Survey of Ion Acceleration Using Juno Observations
Authors: Blöcker A. , Kronberg E. A. , Grigorenko E. E. , Clark G. , Vogt M. F. , Roussos E.
Published: August 2022

Transient magnetic reconnection plays an important role in energetic particle acceleration in planetary magnetospheres. Jupiter's magnetosphere provides a unique natural laboratory to study processes of energy transport and transformation. Strong electric fields in spatially confined structures such as plasmoids can be responsible for ion acceleration to high energies. In this study we focus on the effectiveness of ion energization and acceleration in plasmoids. Therefore, we present a statistical study of plasmoid structures in the predawn magnetotail, which were identified in the magnetometer data of the Juno spacecraft from 2016 to 2018. We additionally use the energetic particle observations from the Jupiter Energetic Particle Detector Instrument which discriminates between different ion species. We are particularly interested in the analysis of the acceleration and energization of oxygen, sulfur, helium, and hydrogen ions. We investigate how the event properties, such as the radial distance and the local time of the observed plasmoids in the magnetotail, affect the ion intensities close to the current sheet center. Furthermore, we analyze if ion acceleration is influenced by magnetic field turbulence inside the plasmoids. We find significant heavy ion acceleration in plasmoids close to the current sheet center which is in line with the previous statistical results based on Galileo observations conducted by Kronberg et al. (2019, https://doi.org/10.1029/2019JA026553). The observed effectiveness of the acceleration is dependent on the position of Juno in the magnetotail during the plasmoid event observation. Our results show no correlation between magnetic field turbulence and nonadiabatic acceleration for heavy ions during plasmoids.
Desilicification Rims of Zircon Xenocrysts Record the Timing of Kimberlite Emplacement
Authors: Melnik Aleksey E. , Li Qiu‐Li , Korolev Nester M. , Li Jiao , Ling Xiao‐Xiao , Liu Yu , Tang Guo‐Qiang , Zinger Tatiana F. , Mao Qian , Wu Shi‐Tou , Xu Jing‐Yao , Li Xian‐Hua
Published: August 2022

Kimberlites are deep and relatively rare mantle‐derived igneous rocks, which provide key insights into the lithospheric mantle composition beneath continents (i.e., from the entrained mantle materials) at the time of magma emplacement. In addition, the temporal distribution of kimberlites throughout Earth's history may reveal secular changes in global geodynamics. However, alteration and abundant exotic material (i.e., xenoliths and xenocrysts) of different ages, both typical of kimberlites, often hinder reliable dating of these rocks. In this study, we investigated zircon xenocrysts and their replacement by desilicification reaction rims (DSRs), which consist mainly of baddeleyite, in the metamorphosed Kimozero kimberlites from the Karelian Craton, Russia. Similar DSRs have been identified previously on mantle‐derived zircons in numerous kimberlites, but the precise timing and location of formation of these rims remain unclear. U–Pb isotope dating of mantle zircon xenocrysts in the Kimozero kimberlites indicates that these rocks were emplaced at ca. 1.97 Ga. DSRs with similar textures and baddeleyite chemistry occur on both the 1.97 Ga mantle and 2.70–2.38 Ga crustal zircon xenocrysts in these kimberlites. Pb–Pb isotope dating of the DSRs yields the same age (i.e., ca. 1.97 Ga) as the mantle zircons. The data constrain the formation of DSRs to crustal levels and, more importantly, indicate that these rims record the timing of kimberlite emplacement. Therefore, we suggest that such baddeleyite reaction rims are a new and promising material for kimberlite geochronology.
Precursory Signals in the Stratospheric Meridional Mass Circulation for Mid‐Latitude Cold Air Outbreak Events of High and Low Sub‐Seasonal Predictability
Authors: Yu Yueyue , Liu Bowen , Ren Rongcai , Guan Zhaoyong , Yang Qinlan , Hu Muxin
Published: August 2022

Using the NCEP reforecast data (1999–2010) and NCEP's CFSv2 real‐time forecast data (2012–2019) from the S2S (Sub‐seasonal to Seasonal) project, we evaluated the sub‐seasonal skill by the CFSv2 model with respect to mid‐latitude cold air outbreak events (CAOs) in winter (November–February) and investigated the distinct features of the anomalies of surface temperature, stratospheric mass circulation, and wave activities between the top 11 “high‐skill” CAO events and the top 10 “low‐skill” events. Results show that the predictability limit tends to be longer for wide‐impact and long‐lasting CAOs occurred in Eurasia or both continents, but such tendency is not very robust. The model possesses a better sub‐seasonal skill when there is generally stronger and longer‐lasting equatorward cold air branch of isentropic meridional mass circulation, which is coupled with a stronger stratospheric poleward warm branch in the 3 weeks prior to the peak time of “high‐skill” CAOs. The largest contrast between “high‐skill” and “low‐skill” CAOs lies in the wavenumber‐1 component of stratospheric poleward warm branch. Both the amplitude in the middle stratosphere and vertically westward‐tilting of wavenumber‐1 waves in the lower stratosphere tend to be stronger (weaker) prior to “high‐skill” (“low‐skill”) CAOs, collaboratively contributing to the stronger (weaker) stratospheric poleward warm branch. The temporal evolution of intensity of stratospheric poleward warm branch, wave amplitude, and westward‐tilting are better captured by CFSv2 model at sub‐seasonal scale in the month before “high‐skill” CAOs. These results reveal the important role of stratosphere–troposphere connection in determining the windows of opportunity for skillful sub‐seasonal forecasts of CAOs.
Emulator For Eroded Beach And Dune Profiles Due To Storms
Authors: Gharagozlou A. , Anderson D. L. , Gorski J. F. , Dietrich J. C.
Published: August 2022

Dunes and beaches are vulnerable to erosion during storm events. Numerical models can predict beach response to storms with fidelity, but their computational costs, the domain‐specific knowledge necessary to use them, and the wide range of potential future storm and beach conditions can hinder their use in forecasting storm erosion for short‐ and long‐term horizons. We develop an emulator, which is an efficient predictive model that behaves like a numerical model, to predict the morphologic response of the subaerial beach to storms. Specific emphasis is placed on providing antecedent beach states as an input to the emulator and predicting the post‐storm profile shape. Training data include beach profiles at multiple stages in a nourishment life cycle to assess if such a framework can be applied in locations that nourish as a coastal defense policy. Development and application of the emulator is focused on Nags Head, North Carolina, which nourishes its beaches to mitigate hazards of storm waves, flooding, and erosion. A high‐fidelity, process‐based morphodynamic model is used to train the emulator with 1250 scenarios of sea‐storms and beach profiles. The post‐storm beach state is emulated with a parameterized power‐law function fit to the eroded portion of the subaerial profile. When the emulator was tested for a sequence of real storms from 2019, the eroded beach profiles were predicted with a skill score of 0.66. This emulator is promising for future efforts to predict storm‐induced beach erosion in hazard warnings or adaptation studies.
The psychiatric risk gene BRD1 modulates mitochondrial bioenergetics by transcriptional regulation
Authors: Paternoster Veerle , Cömert Cagla , Kirk Louise Sand , la Cour Sanne Hage , Fryland Tue , Fernandez-Guerra Paula , Stougaard Magnus , Nyengaard Jens Randel , Qvist Per , Bross Peter , Børglum Anders Dupont , Christensen Jane Hvarregaard
Published: August 2022

Bromodomain containing 1 (BRD1) encodes an epigenetic regulator that controls the expression of genetic networks linked to mental illness. BRD1 is essential for normal brain development and its role in psychopathology has been demonstrated in genetic and preclinical studies. However, the neurobiology that bridges its molecular and neuropathological effects remains poorly explored. Here, using publicly available datasets, we find that BRD1 targets nuclear genes encoding mitochondrial proteins in cell lines and that modulation of BRD1 expression, irrespective of whether it is downregulation or upregulation of one or the other existing BRD1 isoforms (BRD1-L and BRD1-S), leads to distinct shifts in the expression profile of these genes. We further show that the expression of nuclear genes encoding mitochondrial proteins is negatively correlated with the expression of BRD1 mRNA during human brain development. In accordance, we identify the key gate-keeper of mitochondrial metabolism, Peroxisome proliferator-activated receptor (PPAR) among BRD1’s co-transcription factors and provide evidence that BRD1 acts as a co-repressor of PPAR-mediated transcription. Lastly, when using quantitative PCR, mitochondria-targeted fluorescent probes, and the Seahorse XFe96 Analyzer, we demonstrate that modulation of BRD1 expression in cell lines alters mitochondrial physiology (mtDNA content and mitochondrial mass), metabolism (reducing power), and bioenergetics (among others, basal, maximal, and spare respiration) in an expression level- and isoform-dependent manner. Collectively, our data suggest that BRD1 is a transcriptional regulator of nuclear-encoded mitochondrial proteins and that disruption of BRD1’s genomic actions alters mitochondrial functions. This may be the mechanism underlying the cellular and atrophic changes of neurons previously associated with BRD1 deficiency and suggests that mitochondrial dysfunction may be a possible link between genetic variation in BRD1 and psychopathology in humans.
Oxytocin-based therapies for treatment of Prader-Willi and Schaaf-Yang syndromes: evidence, disappointments, and future research strategies
Authors: Althammer Ferdinand , Muscatelli Francoise , Grinevich Valery , Schaaf Christian P.
Published: August 2022

The prosocial neuropeptide oxytocin is being developed as a potential treatment for various neuropsychiatric disorders including autism spectrum disorder (ASD). Early studies using intranasal oxytocin in patients with ASD yielded encouraging results and for some time, scientists and affected families placed high hopes on the use of intranasal oxytocin for behavioral therapy in ASD. However, a recent Phase III trial obtained negative results using intranasal oxytocin for the treatment of behavioral symptoms in children with ASD. Given the frequently observed autism-like behavioral phenotypes in Prader-Willi and Schaaf-Yang syndromes, it is unclear whether oxytocin treatment represents a viable option to treat behavioral symptoms in these diseases. Here we review the latest findings on intranasal OT treatment, Prader-Willi and Schaaf-Yang syndromes, and propose novel research strategies for tailored oxytocin-based therapies for affected individuals. Finally, we propose the critical period theory, which could explain why oxytocin-based treatment seems to be most efficient in infants, but not adolescents.
Patient attrition in Molecular Tumour Boards: a systematic review
Authors: Frost Hannah , Graham Donna M. , Carter Louise , O’Regan Paul , Landers Dónal , Freitas André
Published: August 2022

Background

Molecular Tumour Boards (MTBs) were created with the purpose of supporting clinical decision-making within precision medicine. Though in use globally, reporting on these meetings often focuses on the small percentages of patients that receive treatment via this process and are less likely to report on, and assess, patients who do not receive treatment.

Methods

A literature review was performed to understand patient attrition within MTBs and barriers to patients receiving treatment. A total of 51 papers were reviewed spanning a 6-year period from 11 different countries.

Results

In total, 20% of patients received treatment through the MTB process. Of those that did not receive treatment, the main reasons were no mutations identified (27%), no actionable mutations (22%) and clinical deterioration (15%). However, data were often incomplete due to inconsistent reporting of MTBs with only 55% reporting on patients having no mutations, 55% reporting on the presence of actionable mutations with no treatment options and 59% reporting on clinical deterioration.

Discussion

As patient attrition in MTBs is an issue which is very rarely alluded to in reporting, more transparent reporting is needed to understand barriers to treatment and integration of new technologies is required to process increasing omic and treatment data.
Interaction of LATS1 with SMAC links the MST2/Hippo pathway with apoptosis in an IAP-dependent manner
Authors: García-Gutiérrez Lucía , Fallahi Emma , Aboud Nourhan , Quinn Niall , Matallanas David
Published: August 2022

Metastatic malignant melanoma is the deadliest skin cancer, and it is characterised by its high resistance to apoptosis. The main melanoma driving mutations are part of ERK pathway, with BRAF mutations being the most frequent ones, followed by NRAS, NF1 and MEK mutations. Increasing evidence shows that the MST2/Hippo pathway is also deregulated in melanoma. While mutations are rare, MST2/Hippo pathway core proteins expression levels are often dysregulated in melanoma. The expression of the tumour suppressor RASSF1A, a bona fide activator of the MST2 pathway, is silenced by promoter methylation in over half of melanomas and correlates with poor prognosis. Here, using mass spectrometry-based interaction proteomics we identified the Second Mitochondria-derived Activator of Caspases (SMAC) as a novel LATS1 interactor. We show that RASSF1A-dependent activation of the MST2 pathway promotes LATS1-SMAC interaction and negatively regulates the antiapoptotic signal mediated by the members of the IAP family. Moreover, proteomic experiments identified a common cluster of apoptotic regulators that bind to SMAC and LATS1. Mechanistic analysis shows that the LATS1-SMAC complex promotes XIAP ubiquitination and its subsequent degradation which ultimately results in apoptosis. Importantly, we show that the oncogenic BRAFV600E mutant prevents the proapoptotic signal mediated by the LATS1-SMAC complex while treatment of melanoma cell lines with BRAF inhibitors promotes the formation of this complex, indicating that inhibition of the LATS1-SMAC might be necessary for BRAFV600E-driven melanoma. Finally, we show that LATS1-SMAC interaction is regulated by the SMAC mimetic Birinapant, which requires C-IAP1 inhibition and the degradation of XIAP, suggesting that the MST2 pathway is part of the mechanism of action of Birinapant. Overall, the current work shows that SMAC-dependent apoptosis is regulated by the LATS1 tumour suppressor and supports the idea that LATS1 is a signalling hub that regulates the crosstalk between the MST2 pathway, the apoptotic network and the ERK pathway.
Visual performance following implantation of presbyopia correcting intraocular lenses
Authors: Torky Magda A. , Nokrashy Amgad El , Metwally Heba , Abdelhameed Ameera G.
Published: August 2022

Objective

To compare the visual outcomes following bilateral implantation of 3 presbyopia correcting IOLs.

Methods

Results are reported for patients who underwent phacoemulsification with bilateral implantation of one of the following IOLs: Panoptix IOL, AT LISA tri IOL and Symphony IOL. Six months postoperative examination included monocular UIVA at 80 and 60 cm and monocular UNVA and DCNVA at 40 cm, monocular UDVA and CDVA, Spherical equivalent (SE) refraction, binocular defocus curve, contrast sensitivity, photopic phenomena, and spectacle independence.

Results

UIVA at 80 cm was significantly better in the AT LISA group and the Symfony groups than the Panoptix group, while UIVA at 60 cm was better in the Symfony group and the Panoptix group than the AT LISA group. A worse DCNVA was recorded in the Symfony group. At a defocus of −2.50 D, the near VA was similar in the PanOptix and AT LISA groups (0.05, 0.07 logMAR respectively), which were significantly better than the Symfony group (0.3 LogMAR). Binocular photopic and scotopic contrast sensitivity outcomes were similar among the three groups at all spatial frequencies. In Symphony group, the frequency and the degree of bother of photic phenomena was relatively higher than the other two groups. Higher percentage of patients in symphony group reported their need for reading glasses.

Conclusion

PanOptix IOL and AT LISA IOL would be a good choice for patients aiming for an optimum near vision, while Symfony IOL seems suitable for patients having the priority for good intermediate vision.
Anomalous Ferromagnetism of quasiparticle doped holes in cuprate heterostructures revealed using resonant soft X-ray magnetic scattering
Authors: Ong B. L. , Jayaraman K. , Diao C. , Whitcher T. J. , Jain A. , Hung H. , Breese M. B. H. , Tok E. S. , Rusydi A.
Published: August 2022

We report strong ferromagnetism of quasiparticle doped holes both within the ab-plane and along the c-axis of Cu-O planes in low-dimensional Au/d-La1.8Ba0.2CuO4/LaAlO3(001) heterostructures (d = 4, 8 and 12 unit-cells) using resonant soft X-ray and magnetic scattering together with X-ray magnetic circular dichroism. Interestingly, ferromagnetism is stronger at a hole doped peak and at an upper Hubbard band of O with spin-polarization degree as high as 40%, revealing strong ferromagnetism of Mottness. For in-ab-plane spin-polarizations, the spin of doped holes in O2p–Cu3d–O2p is a triplet state yielding strong ferromagnetism. For out-of-ab-plane spin-polarization, while the spins of doped holes in both O2p–O2p and Cu3d–Cu3d are triplet states, the spin of doped holes in Cu3d–O2p is a singlet state yielding ferrimagnetism. A ferromagnetic-(002) Bragg-peak of the doped holes is observed and enhanced as a function of d revealing strong ferromagnetism coupling between Cu-O layers along the c-axis.
Systematic evidence and gap map of research linking food security and nutrition to mental health
Authors: Sparling Thalia M. , Deeney Megan , Cheng Bryan , Han Xuerui , Lier Chiara , Lin Zhuozhi , Offner Claudia , Santoso Marianne V. , Pfeiffer Erin , Emerson Jillian A. , Amadi Florence Mariamu , Mitu Khadija , Corvalan Camila , Verdeli Helen , Araya Ricardo , Kadiyala Suneetha
Published: August 2022

Connections between food security and nutrition (FSN) and mental health have been analytically investigated, but conclusions are difficult to draw given the breadth of literature. Furthermore, there is little guidance for continued research. We searched three databases for analytical studies linking FSN to mental health. Out of 30,896 records, we characterized and mapped 1945 studies onto an interactive Evidence and Gap Map (EGM). In these studies, anthropometry (especially BMI) and diets were most linked to mental health (predominantly depression). There were fewer studies on infant and young child feeding, birth outcomes, and nutrient biomarkers related to anxiety, stress, and mental well-being. Two-thirds of studies hypothesized FSN measures as the exposure influencing mental health outcomes. Most studies were observational, followed by systematic reviews as the next largest category of study. One-third of studies were carried out in low- and middle-income countries. This map visualizes the extent and nature of analytical studies relating FSN to mental health and may be useful in guiding future research.
Competition between hematopoietic stem and progenitor cells controls hematopoietic stem cell compartment size
Authors: Miao Runfeng , Chun Harim , Feng Xing , Gomes Ana Cordeiro , Choi Jungmin , Pereira João P.
Published: August 2022

Cellular competition for limiting hematopoietic factors is a physiologically regulated but poorly understood process. Here, we studied this phenomenon by hampering hematopoietic progenitor access to Leptin receptor+ mesenchymal stem/progenitor cells (MSPCs) and endothelial cells (ECs). We show that HSC numbers increase by 2-fold when multipotent and lineage-restricted progenitors fail to respond to CXCL12 produced by MSPCs and ECs. HSCs are qualitatively normal, and HSC expansion only occurs when early hematopoietic progenitors but not differentiated hematopoietic cells lack CXCR4. Furthermore, the MSPC and EC transcriptomic heterogeneity is stable, suggesting that it is impervious to major changes in hematopoietic progenitor interactions. Instead, HSC expansion correlates with increased availability of membrane-bound stem cell factor (mSCF) on MSPCs and ECs presumably due to reduced consumption by cKit-expressing hematopoietic progenitors. These studies suggest that an intricate homeostatic balance between HSCs and proximal hematopoietic progenitors is regulated by cell competition for limited amounts of mSCF.
ChAdOx1 nCoV-19 (AZD1222) or nCoV-19-Beta (AZD2816) protect Syrian hamsters against Beta Delta and Omicron variants
Authors: van Doremalen Neeltje , Schulz Jonathan E. , Adney Danielle R. , Saturday Taylor A. , Fischer Robert J. , Yinda Claude Kwe , Thakur Nazia , Newman Joseph , Ulaszewska Marta , Belij-Rammerstorfer Sandra , Saturday Greg , Spencer Alexandra J. , Bailey Dalan , Russell Colin A. , Gilbert Sarah C. , Lambe Teresa , Munster Vincent J.
Published: August 2022

ChAdOx1 nCoV-19 (AZD1222) is a replication-deficient simian adenovirus–vectored vaccine encoding the spike (S) protein of SARS-CoV-2, based on the first published full-length sequence (Wuhan-1). AZD1222 has been shown to have 74% vaccine efficacy against symptomatic disease in clinical trials. However, variants of concern (VoCs) have been detected, with substitutions that are associated with a reduction in virus neutralizing antibody titer. Updating vaccines to include S proteins of VoCs may be beneficial, even though current real-world data is suggesting good efficacy following boosting with vaccines encoding the ancestral S protein. Using the Syrian hamster model, we evaluate the effect of a single dose of AZD2816, encoding the S protein of the Beta VoC, and efficacy of AZD1222/AZD2816 as a heterologous primary series against challenge with the Beta or Delta variant. Minimal to no viral sgRNA could be detected in lungs of vaccinated animals obtained at 3- or 5- days post inoculation, in contrast to lungs of control animals. In Omicron-challenged hamsters, a single dose of AZD2816 or AZD1222 reduced virus shedding. Thus, these vaccination regimens are protective against the Beta, Delta, and Omicron VoCs in the hamster model.
Antibody affinity and cross-variant neutralization of SARS-CoV-2 Omicron BA.1, BA.2 and BA.3 following third mRNA vaccination
Authors: Bellusci Lorenza , Grubbs Gabrielle , Zahra Fatema Tuz , Forgacs David , Golding Hana , Ross Ted M. , Khurana Surender
Published: August 2022

There is limited knowledge on durability of neutralization capacity and antibody affinity maturation generated following two versus three doses of SARS-CoV-2 mRNA vaccines in naïve versus convalescent individuals (hybrid immunity) against the highly transmissible Omicron BA.1, BA.2 and BA.3 subvariants. Virus neutralization titers against the vaccine-homologous strain (WA1) and Omicron sublineages are measured in a pseudovirus neutralization assay (PsVNA). In addition, antibody binding and antibody affinity against spike proteins from WA1, BA.1, and BA.2 is determined using surface plasmon resonance (SPR). The convalescent individuals who after SARS-CoV-2 infection got vaccinated develop hybrid immunity that shows broader neutralization activity and cross-reactive antibody affinity maturation against the Omicron BA.1 and BA.2 after either second or third vaccination compared with naïve individuals. Neutralization activity correlates with antibody affinity against Omicron subvariants BA.1 and BA.2 spikes. Importantly, at four months post-third vaccination the neutralization activity and antibody affinity against the Omicron subvariants is maintained and trended higher for the individuals with hybrid immunity compared with naïve adults. These findings about hybrid immunity resulting in superior immune kinetics, breadth, and durable high affinity antibodies support the need for booster vaccinations to provide effective protection from emerging SARS-CoV-2 variants like the rapidly spreading Omicron subvariants.
Allosteric modulation of GPCR-induced β-arrestin trafficking and signaling by a synthetic intrabody
Authors: Baidya Mithu , Chaturvedi Madhu , Dwivedi-Agnihotri Hemlata , Ranjan Ashutosh , Devost Dominic , Namkung Yoon , Stepniewski Tomasz Maciej , Pandey Shubhi , Baruah Minakshi , Panigrahi Bhanupriya , Sarma Parishmita , Yadav Manish K. , Maharana Jagannath , Banerjee Ramanuj , Kawakami Kouki , Inoue Asuka , Selent Jana , Laporte Stéphane A. , Hébert Terence E. , Shukla Arun K.
Published: August 2022

Agonist-induced phosphorylation of G protein-coupled receptors (GPCRs) is a primary determinant of β-arrestin (βarr) recruitment and trafficking. For several GPCRs such as the vasopressin receptor subtype 2 (V2R), agonist-stimulation first drives the translocation of βarrs to the plasma membrane, followed by endosomal trafficking, which is generally considered to be orchestrated by multiple phosphorylation sites. We have previously shown that mutation of a single phosphorylation site in the V2R (i.e., V2RT360A) results in near-complete loss of βarr translocation to endosomes despite robust recruitment to the plasma membrane, and compromised ERK1/2 activation. Here, we discover that a synthetic intrabody (Ib30), which selectively recognizes activated βarr1, efficiently rescues the endosomal trafficking of βarr1 and ERK1/2 activation for V2RT360A. Molecular dynamics simulations reveal that Ib30 enriches active-like βarr1 conformation with respect to the inter-domain rotation, and cellular assays demonstrate that it also enhances βarr1-β2-adaptin interaction. Our data provide an experimental framework to positively modulate the receptor-transducer-effector axis for GPCRs using intrabodies, which can be potentially integrated in the paradigm of GPCR-targeted drug discovery.
Measuring anion binding at biomembrane interfaces
Authors: Wu Xin , Wang Patrick , Lewis William , Jiang Yun-Bao , Gale Philip A.
Published: August 2022

The quantification of anion binding by molecular receptors within lipid bilayers remains challenging. Here we measure anion binding in lipid bilayers by creating a fluorescent macrocycle featuring a strong sulfate affinity. We find the determinants of anion binding in lipid bilayers to be different from those expected that govern anion binding in solution. Charge-dense anions H2PO4–and Cl–that prevail in dimethyl sulfoxide fail to bind to the macrocycle in lipids. In stark contrast, ClO4–and I–that hardly bind in dimethyl sulfoxide show surprisingly significant affinities for the macrocycle in lipids. We reveal a lipid bilayer anion binding principle that depends on anion polarisability and bilayer penetration depth of complexes leading to unexpected advantages of charge-diffuse anions. These insights enhance our understanding of how biological systems select anions and guide the design of functional molecular systems operating at biomembrane interfaces.
Trastuzumab deruxtecan in HER2-positive breast cancer with brain metastases: a single-arm, phase 2 trial
Authors: Bartsch Rupert , Berghoff Anna Sophie , Furtner Julia , Marhold Maximilian , Bergen Elisabeth Sophie , Roider-Schur Sophie , Starzer Angelika Martina , Forstner Heidrun , Rottenmanner Beate , Dieckmann Karin , Bago-Horvath Zsuzsanna , Haslacher Helmuth , Widhalm Georg , Ilhan-Mutlu Aysegül , Minichsdorfer Christoph , Fuereder Thorsten , Szekeres Thomas , Oehler Leopold , Gruenberger Birgit , Singer Christian F. , Weltermann Ansgar , Puhr Rainer , Preusser Matthias
Published: August 2022

Trastuzumab deruxtecan is an antibody–drug conjugate with high extracranial activity in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. We conducted the prospective, open-label, single-arm, phase 2 TUXEDO-1 trial. We enrolled patients aged ≥18 years with HER2-positive breast cancer and newly diagnosed untreated brain metastases or brain metastases progressing after previous local therapy, previous exposure to trastuzumab and pertuzumab and no indication for immediate local therapy. Patients received trastuzumab deruxtecan intravenously at the standard dose of 5.4 mg per kg bodyweight once every 3 weeks. The primary endpoint was intracranial response rate measured according to the response assessment in neuro-oncology brain metastases criteria. A Simon two-stage design was used to compare a null hypothesis of <26% response rate against an alternative of 61%. Fifteen patients were enrolled in the intention-to-treat population of patients who received at least one dose of study drug. Two patients (13.3%) had a complete intracranial response, nine (60%) had a partial intracranial response and three (20%) had stable disease as the best intracranial response, with a best overall intracranial response rate of 73.3% (95% confidential interval 48.1–89.1%), thus meeting the predefined primary outcome. No new safety signals were observed and global quality-of-life and cognitive functioning were maintained over the treatment duration. In the TUXEDO-1 trial (NCT04752059, EudraCT 2020-000981-41), trastuzumab deruxtecan showed a high intracranial response rate in patients with active brain metastases from HER2-positive breast cancer and should be considered as a treatment option in this setting.
Distribution model transferability for a wide-ranging species, the Gray Wolf
Authors: Gantchoff M. G. , Beyer D. E. , Erb J. D. , MacFarland D. M. , Norton D. C. , Roell B. J. , Price Tack J. L. , Belant J. L.
Published: August 2022

Using existing data can be a reliable and cost-effective way to predict species distributions, and particularly useful for recovering or expanding species. We developed a current gray wolf (Canis lupus) distribution model for the western Great Lakes region, USA, and evaluated the spatial transferability of single-state models to the region. This study is the first assessment of transferability in a wide-ranging carnivore, as well as one of few developed for large spatial extents. We collected 3500 wolf locations from winter surveys in Minnesota (2017–2019), Wisconsin (2019–2020), and Michigan (2017–2020). We included 10 variables: proportion of natural cover, pastures, and crops; distance to natural cover, agriculture, developed land, and water; major and minor road density; and snowfall (1-km res.). We created a regional ensemble distribution by weight-averaging eight models based on their performance. We also developed single-state models, and estimated spatial transferability using two approaches: state cross-validation and extrapolation. We assessed performance by quantifying correlations, receiver operating characteristic curves (ROC), sensitivities, and two niche similarity indices. The regional area estimated to be most suitable for wolves during winter (threshold = maximum sensitivity/specificity) was 106,465 km2 (MN = 48,083 km2, WI = 27,757 km2, MI = 30,625 km2) and correctly predicted 88% of wolf locations analyzed. Increasing natural cover and distance to crops were consistently important for determining regional and single-state wolf distribution. Extrapolation (vs. cross-validation) produced results with the greatest performance metrics, and were most similar to the regional model, yet good internal performance was unrelated to greater extrapolation performance. Factors influencing species distributions are scale-dependent and can vary across areas due to behavioral plasticity. When extending inferences beyond the current occurrence of individuals, assessing variation in ecology such as habitat selection, as well as methodological factors including model performance, will be critical to avoid poor scientific interpretations and develop effective conservation applications. In particular, accurate distribution models for recovering or recovered carnivores can be used to develop plans for habitat management, quantify potential of unoccupied habitat, assess connectivity modeling, and mitigate conflict, facilitating long-term species persistence.
Neutralization activity of sera/IgG preparations from fully BNT162b2 vaccinated individuals against SARS-CoV-2 Alpha, Beta, Gamma, Delta, and Kappa variants
Authors: Amano Masayuki , Otsu Sachiko , Maeda Kenji , Uemura Yukari , Shimizu Yosuke , Omata Kazumi , Matsuoka Masao , Shimada Shinya , Mitsuya Hiroaki
Published: August 2022

In the present prospective study, 225 individuals in Kumamoto General Hospital, Japan, who received two-doses of BNT162b2 vaccine were enrolled/followed up over 150 days and neutralizing activity (NT50) of their sera and antiviral activity (EC50) of IgG purified from sera on day-60 post-1st-dose were determined against wild-type SARS-CoV-2 (SARS-CoV-2Wuhan) (n = 211) and 9 variants (Alpha, Beta, Gamma, Delta, and Kappa) (n = 45). Time-dependent changes of IgG-activity (n = 25) against SARS-CoV-2Wuhan and variants were also examined. Day-60 sera showed reduced NT50 by more than 50% against all variants examined, and greatest reduction was seen with Beta. IgG fractions of high-responders and moderate-responders showed similar fold-changes in EC50 against each variant compared to SARS-CoV-2Wuhan. Evaluation of EC50 of IgG obtained at different time-points (day-28 to -150) revealed time-dependent reduction of activity against all variants. However, against Delta, relatively long-lasting favorable antiviral activity (at least 150 days) was observed. Our data strongly suggest that the successful antecedent scale-up of mRNA-based vaccine administrations in Japan was the primary contributor to the lessening of the otherwise more devastating SARS-CoV-2 pandemic wave caused by the Delta variant. The present data that the effectiveness of vaccine against the then-dominant SARS-CoV-2 variant was likely associated with the moderation of the COVID-19 pandemic wave suggest that as in the case of influenza vaccines, the development of multivalent mRNA-based vaccines represent a generalizable approach to pre-emptively respond pandemic with mutable pathogens.