bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics comparison of vardenafil as administered by an intranasal spray formulation vs a 10-mg oral tablet
Authors: Wang Jeffrey , Chow Sheryl L , Chow Moses S S , Paik Amy , Louie Stan G , Dong Fanglong , Sathananthan Airani , White Stephanie 
Published: May 2023

Abstract

Background
Oral vardenafil (VDF) tablet is an effective treatment for erectile dysfunction (ED), but intranasal administration with a suitable formulation can lead to a faster onset of action and offer more convenient planning for ED treatment.

Aim
The primary purpose of the present pilot clinical study was to determine whether intranasal VDF with an alcohol-based formulation can result in more “user-friendly pharmacokinetics” as compared with oral tablet administration.

Methods
This single-dose randomized crossover study was conducted in 12 healthy young volunteers receiving VDF as a 10-mg oral tablet or 3.38-mg intranasal spray. Multiple blood concentrations were obtained, and VDF concentrations were determined with a liquid chromatography–tandem mass spectrometry assay. Pharmacokinetic parameters following each treatment were compared and adverse events assessed.

Outcomes
Pharmacokinetic parameters were obtained: apparent elimination rate constant, elimination half-life, peak concentration, peak time, total area under the curve, and relative bioavailability.

Results
Although mean apparent elimination rate constant, elimination half-life, peak concentration, and total area under the curve were similar between intranasal and oral administration, the median peak time from intranasal was much shorter (10 vs 58 minutes, P &lt; .001, Mann-Whitney U test). The variability of the pharmacokinetic parameters was also less with intranasal than oral administration. The relative bioavailability of intranasal to oral was 1.67. Intranasal VDF caused transient but tolerable local nasal reactions in 50% of subjects. Other adverse events (eg, headache) were similar between the treatments. The incidence of adverse events was, however, significantly less in the second treatment after initial exposure to VDF. No serious adverse events were noted.

Clinical Implications
Intranasal VDF potentially offers a more timely and lower dose for the treatment of ED in patients who can tolerate the transient local adverse reactions.

Strengths and Limitations
The strength of this study is its randomized crossover design. Because the study was conducted in 12 healthy young subjects, the results may not reflect those observed in elderly patients who may be likely taking VDF for ED. Nevertheless, the changes of pharmacokinetic parameters in the present study are likely a reflection of the differences between intranasal and oral administration of the formulations.

Conclusion
Our study indicated that the present VDF formulation, when administered intranasally, can achieve a more rapid but similar plasma concentration with only about one-third dose when compared with the oral administration.
Unsigned magnetic flux proxy from solar optical intensity spectra
Authors: Lienhard F , Mortier A , Cegla H M , Cameron A Collier , Klein B , Watson C A 
Published: May 2023

ABSTRACT
The photospheric unsigned magnetic flux has been shown to be highly correlated with radial velocity (RV) variations caused by solar surface activity. This activity indicator is therefore a prime candidate to unlock the potential of RV surveys to discover Earth twins orbiting Sun-like stars. We show for the first time how a precise proxy of the unsigned magnetic flux (ΔαB2) can be obtained from Sun-as-a-star intensity spectra by harnessing the magnetic information contained in over 4000 absorption lines in the wavelength range from 380 to 690 nm. This novel activity proxy can thus be obtained from the same spectra from which RVs are routinely extracted. We derived  ΔαB2 from 500 randomly selected spectra from the HARPS-N public solar data set, which spans from 2015 to 2018. We compared our estimates with the unsigned magnetic flux values from the Solar Dynamics Observatory (SDO) finding excellent agreement (median absolute deviation: 4.9 per cent). The extracted indicator  ΔαB2 correlates with SDO’s unsigned magnetic flux estimates on the solar rotational time-scale (Pearson correlation coefficient 0.67) and on the 3-yr time-scale of our data set (correlation coefficient 0.91). We find correlations of  ΔαB2 with the HARPS-N solar RV variations of 0.49 on the rotational time-scale and 0.78 on the 3-yr time-scale. The Pearson correlation of  ΔαB2 with the RVs is found to be greater than the correlation of the classical activity indicators with the RVs. For solar-type stars,  ΔαB2 therefore represents the best simultaneous activity proxy known to date.
Fundamental cosmology from ANDES precision spectroscopy
Authors: Marques C M J , Martins C J A P , Alves C S 
Published: May 2023

ABSTRACT
Fundamental cosmology observations, such as the detection of the redshift drift and tests of the universality of physical laws, are key science and design drivers of the ArmazoNes high Dispersion Echelle Spectrograph (ANDES), an Extremely Large Telescope instrument. While separate forecasts for each of them have been reported, we have developed Fisher matrix based forecast tools combining both of these observables. We demonstrate the synergies between the two ANDES data sets, quantifying the improvements in cosmology and fundamental physics parameter constraints for two separate theoretical paradigms. We publicly release this forecast code, which is one of the tools for the optimization of the ANDES observing strategy.
Overmassive central black holes in the cosmological simulations astrid and Illustris TNG50
Authors: Weller Emma Jane , Pacucci Fabio , Natarajan Priyamvada , Di Matteo Tiziana 
Published: May 2023

ABSTRACT
Recent dynamical measurements indicate the presence of a central supermassive black hole (SMBH) with mass ${\sim} 3\times 10^6\, {\rm M_\odot }$ in the dwarf galaxy Leo I, placing the system ∼50 times above the standard, local MBH–M⋆ relation. While a few overmassive central SMBHs are reported in nearby isolated galaxies, this is the first one detected in a Milky Way satellite. We used the ASTRID and Illustris TNG50 lambda cold dark matter (LCDM) cosmological simulations to investigate the assembly history of galaxies hosting overmassive SMBHs. We estimate that, at the stellar mass of Leo I, ${\sim} 15~{{\ \rm per\ cent}}$ of galaxies above the MBH–M⋆ relation lie &gt;10 times above it. Leo I-like systems are rare but exist in LCDM simulations: they occur in ${\sim} 0.005~{{\ \rm per\ cent}}$ of all overmassive systems. Examining the properties of simulated galaxies harbouring overmassive central SMBHs, we find that: (i) stars assemble more slowly in galaxies above the MBH–M⋆ relation; (ii) the gas fraction in these galaxies experiences a significantly steeper decline over time; and (iii) $\gt 95~{{\ \rm per\ cent}}$ of satellite host galaxies in overdense regions are located above the MBH–M⋆ relation. This suggests that massive satellite infall and consequent tidal stripping in a group/dense environment can drive systems away from the MBH–M⋆ relation, causing them to become overmassive. As the merging histories of overmassive and undermassive systems do not differ, we conclude that additional environmental effects, such as being in overdense regions must play a crucial role. In the high-z Universe, central overmassive SMBHs are a signature of heavy BH seeds; we demonstrate, in contrast, that low-z overmassive systems result from complex environmental interactions.
Deviations from spherical shape decrease the growth velocity in granular aggregate collisions – a granular mechanics study
Authors: Bandyopadhyay Rahul , Urbassek Herbert M 
Published: May 2023

ABSTRACT
We used granular mechanics simulations to study collisions between spherical aggregates and axisymmetric ellipsoidal aggregates of equal mass. Non-spherical aggregates may be generated, for example, as the result of previous aggregate collisions, either from the merging of aggregates or from fragmentation processes. Of particular interest is the growth velocity, i.e. the critical collision velocity above which the size of the largest post-collision fragment is smaller than the original aggregate size. We find a systematic decrease of the growth velocity with axis ratio of the ellipsoid. The decrease is caused by the ‘rim peel-off’ effect: grain material close to the rims is more readily ejected from the boundaries of aggregates. When considering collisions with ellipsoids of identical semimajor axis, the growth velocity of oblate ellipsoids surpasses that of prolate ellipsoids. Averaging over the orientation of the ellipsoid and over the impact parameters possible in a collision retains the above-mentioned results. The influence of aggregate shape on collision outcomes is of interest, for instance, for codes describing the evolution of dust clouds under collisions.
The variability of the broad-line Balmer decrement for quasars from the Sloan Digital Sky Survey reverberation mapping
Authors: Ma Yan-Song , Li Shao-Jun , Gu Chen-Sheng , Jiang Jian-Xia , Hou Kai-Li , Qin Shu-Hao , Bian Wei-Hao 
Published: May 2023

ABSTRACT
Based on the spectral decomposition through a code of PrepSpec, the light curves (spanning 6.5 yr in the observed frame) of the broad-line Balmer decrement, i.e. the flux ratio of the broad Hα to the broad Hβ line, are calculated for a sample of 44 Sloan Digital Sky Survey reverberation-mapped quasars (z &lt; 0.53). It is found that the logarithm of the mean broad-line Balmer decrement is 0.62 with a standard deviation of 0.15 dex. The relations between the mean Balmer decrement and the supermassive black hole accretion properties (the luminosity, black hole mass, Eddington ratio, and accretion rate) are investigated and no obvious correlations are found. It is found that there are 27 quasars ($61{{\ \rm per\ cent}}$ ) showing strong negative correlations between the Balmer decrement variance and the continuum variance, i.e. the Balmer decrement would be smaller with larger continuum flux. Assuming that the dust obscuration leads to the variance in the Balmer decrement and the continuum, an expected slope is −1/3, which is not consistent with most of measured slopes. Using the interpolated cross-correlation function, the time delays between the inverse Balmer decrement and the continuum are measured for 14 quasars with the maximum correlation coefficient larger than 0.6. It suggests that the size corresponding to the Balmer decrement lag extends from the broad-line region size to the torus size.
Selenium deficiency causes oxidative stress and activates inflammation, apoptosis, and necroptosis in the intestine of weaned calves
Authors: Lei Lei , Jing Mu , Yingce Zheng , Pei Zhang , Yun Liu 
Published: May 2023

Abstract
Selenium performs a variety of biological functions in organisms, including antioxidant and anti-inflammatory effects. This study investigated how selenium deficiency affects weaned calves' intestines. According to Inductively coupled plasma mass spectrometry (ICP-MS) analysis of intestinal selenium concentrations in calves, the Se-D group had a significantly lower concentration of selenium. Hematoxylin-eosin staining showed that the intestinal epithelial cells were detached, the goblet cells were lost, and the intestinal villi were fragmented and loosely arranged in the Se-D group, along with hyperemia and inflammatory infiltration. Of the 22 selenoprotein genes, 9 were downregulated in response to selenium deficiency in Reverse transcription-PCR (RT-PCR), whereas 6 genes were upregulated. In the Se-D group, oxidative stress was detected by measuring redox levels in the intestines. Furthermore, TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, RT-PCR, and Western blotting (WB) results indicated that both intrinsic and extrinsic apoptosis pathways are activated in the intestine during selenium deficiency. Selenium deficiency also induced necroptosis in the intestine through upregulation of MLKL, RIPK1, and RIPK3 mRNA levels. In addition, according to hematoxylin-eosin staining and ELISA, selenium-deficient calves had severe inflammation in their intestines. As a result of RT-PCR and WB analyses, we found that selenium deficiency was associated with nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Our study suggested that weaned calves' intestines are affected by selenium deficiency, which causes oxidative stress, inflammation, apoptosis, and necroptosis.
The connection of α- and β-domains in mammalian metallothionein-2 differentiates Zn(II) binding affinities, affects folding, and determines zinc buffering properties
Authors: Singh Avinash Kumar , Pomorski Adam , Wu Sylwia , Peris-Díaz Manuel D , Czepczyńska-Krężel Hanna , Krężel Artur 
Published: May 2023

Abstract
Mammalian metallothioneins (MTs) are small Cys-rich proteins involved in Zn(II) and Cu(I) homeostasis. They bind seven Zn(II) ions in two distinct β- and α-domains, forming Zn3Cys9 and Zn4Cys11 clusters, respectively. After six decades of research, their role in cellular buffering of Zn(II) ions has begun to be understood recently. This is because of different affinities of bound ions and the proteins’ coexistence in variously Zn(II)-loaded Zn4-7MT species in the cell. To date, it has remained unclear how these mechanisms of action occur and how the affinities are differentiated despite the Zn(S-Cys)4 coordination environment being the same. Here, we dissect the molecular basis of these phenomena by using several MT2 mutants, hybrid protein, and isolated domains. Through a combination of spectroscopic and stability studies, thiol(ate) reactivity, and steered molecular dynamics, we demonstrate that both protein folding and thermodynamics of Zn(II) ion (un)binding significantly differ between isolated domains and the whole protein. Close proximity reduces the degrees of freedom of separated domains, making them less dynamic. It is caused by the formation of intra- and interdomain electrostatic interactions. The energetic consequence of domains connection has a critical impact on the role of MTs in the cellular environment, where they function not only as a zinc sponge but also as a zinc buffering system keeping free Zn(II) in the right concentrations. Any change of that subtle system affects the folding mechanism, zinc site stabilities, and cellular zinc buffer components.
Intracranial injection of natural killer cells engineered with a HER2-targeted chimeric antigen receptor in patients with recurrent glioblastoma
Authors: Burger Michael C , Forster Marie-Therese , Romanski Annette , Straßheimer Florian , Macas Jadranka , Zeiner Pia S , Steidl Eike , Herkt Stefanie , Weber Katharina J , Schupp Jonathan , Lun Jennifer H , Strecker Maja I , Wlotzka Karolin , Cakmak Pinar , Opitz Corinna , George Rosemol , Mildenberger Iris C , Nowakowska Paulina , Zhang Congcong , Röder Jasmin , Müller Elvira , Ihrig Kristina , Langen Karl-Josef , Rieger Michael A , Herrmann Eva , Bonig Halvard , Harter Patrick N , Reiss Yvonne , Hattingen Elke , Rödel Franz , Plate Karl H , Tonn Torsten , Senft Christian , Steinbach Joachim P , Wels Winfried S 
Published: May 2023

Abstract

Background
Glioblastoma (GB) is incurable at present without established treatment options for recurrent disease. In this phase I first-in-human clinical trial we investigated safety and feasibility of adoptive transfer of clonal chimeric antigen receptor (CAR)-NK cells (NK-92/5.28.z) targeting HER2, which is expressed at elevated levels by a subset of glioblastomas.

Methods
Nine patients with recurrent HER2-positive GB were treated with single doses of 1 × 107, 3 × 107, or 1 × 108 irradiated CAR-NK cells injected into the margins of the surgical cavity during relapse surgery. Imaging at baseline and follow-up, peripheral blood lymphocyte phenotyping and analyses of the immune architecture by multiplex immunohistochemistry and spatial digital profiling were performed.

Results
There were no dose-limiting toxicities, and none of the patients developed a cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. Five patients showed stable disease after relapse surgery and CAR-NK injection that lasted 7 to 37 weeks. Four patients had progressive disease. Pseudoprogression was found at injection sites in 2 patients, suggestive of a treatment-induced immune response. For all patients, median progression-free survival was 7 weeks, and median overall survival was 31 weeks. Furthermore, the level of CD8+ T-cell infiltration in recurrent tumor tissue prior to CAR-NK cell injection positively correlated with time to progression.

Conclusions
Intracranial injection of HER2-targeted CAR-NK cells is feasible and safe in patients with recurrent GB. 1 × 108 NK-92/5.28.z cells was determined as the maximum feasible dose for a subsequent expansion cohort with repetitive local injections of CAR-NK cells.
Direct observation of spreading precursor liquids in a corner
Authors: Miao Weining , Tian Shihao , Yuan Quanzi , Tian Ye , Jiang Lei 
Published: May 2023

ABSTRACT
Precursor liquid is a nanoscale liquid creeping ahead of the macroscopic edge of spreading liquids, whose behaviors tightly correlate with the three-phase reaction efficiency and patterning accuracy. However, the important spatial–temporal characteristic of the precursor liquid still remains obscure because its real-time spreading process has not been directly observed. Here, we report that the spreading ionic liquid precursors in a silicon corner can be directly captured on video using in situ scanning electron microscopy. In situ spreading videos show that the precursor liquid spreads linearly over time (${\rm{\Delta }}L\ \sim\ {\rm{\Delta }}T$) rather than obeying the classic Lucas–Washburn law ($l\ \sim\ {t}^{1/2}$) and possesses a characteristic width of ∼250–310 nm. Theoretical analyses and molecular dynamics simulations demonstrate that the unique behaviors of precursor liquids originate from the competing effect of van der Waals force and surface energy. These findings provide avenues for directly observing liquid/solid interfacial phenomena on a microscopic level.
CSI acquisition in RIS-assisted mobile communication systems
Authors: Han Yu , Tang Wankai , Li Xiao , Matthaiou Michail , Jin Shi 
Published: May 2023

ABSTRACTReconfigurable intelligent surface- (RIS) assisted mobile communication is a promising technological paradigm thanks to the attractive advantages of low cost and flexible control of electromagnetic waves. However, the low-cost features of RISs entail some fundamental challenges to the acquisition of channel state information (CSI), which is essential for the optimal RIS design. To tackle this problem, there have been extensive studies on CSI acquisition in RIS-assisted mobile communication systems, from the perspective of architectural improvement as well as specific mathematical solutions. This article aims to overview the existing works on CSI acquisition in RIS-assisted mobile communication systems.
MYB30 Regulates Submergence Tolerance by Repressing Ethylene Biosynthesis via ACS7 in Arabidopsis
Authors: Zhang Yiyi , Xie Yuanfu , Shi Haifan , Zhuang Yufen , Zheng Yuan , Lin Honghui , Zhou Huapeng 
Published: May 2023

Abstract
Floods impose detrimental effects on natural and agro-ecosystems, leading to a significant loss of worldwide crop production. Global climate change has even worsened this situation. Flooding is a continuous process including two stages of submergence and re-oxygenation, and both are harmful to plant growth and development, resulting in a serious decline in crop yield. Therefore, the understanding of plant flooding tolerance and developing flooding-resistant crops are of great significance. Here, we report that the Arabidopsis thaliana (Arabidopsis) R2R3-MYB transcription factor MYB30 participates in plant submergence response through 1-aminocyclopropane-1-carboxylic acid synthase 7 (ACS7) by repressing ethylene (ET) biosynthesis. The MYB30 loss-of-function mutant exhibits reduced submergence tolerance with a higher level of ET production, whereas the MYB30-overexpressing plant displays enhanced submergence tolerance and repressed ET production. The coding gene of ACS7 might be a direct target of MYB30 during the submergence response. MYB30 binds to the promoter of ACS7 and represses its transcription. The ACS7 loss-of-function mutant with defect in ET biosynthesis displays enhanced submergence tolerance, whereas plants overexpressing ACS7 exhibit a submergence-sensitive phenotype. Genetic analysis shows that ACS7 functions downstream of MYB30 in both ET biosynthesis and submergence response. Taken together, our work revealed a novel transcriptional regulation that modulates submergence response in plants.
Integrated genetic and metabolic characterization of Latin American cassava (Manihot esculenta) germplasm
Authors: Perez-Fons Laura , Ovalle Tatiana Maria , Drapal Margit , Ospina Maria Alejandra , Gkanogiannis Anestis , Bohorquez-Chaux Adriana , Becerra Lopez-Lavalle Luis Augusto , Fraser Paul David 
Published: May 2023

Abstract
Cassava (Manihot esculenta Crantz) is an important staple crop for food security in Africa and South America. The present study describes an integrated genomic and metabolomic approach to the characterization of Latin American cassava germplasm. Classification based on genotyping correlated with the leaf metabolome and indicated a key finding of adaption to specific eco-geographical environments. In contrast, the root metabolome did not relate to genotypic clustering, suggesting the different spatial regulation of this tissue's metabolome. The data were used to generate pan-metabolomes for specific tissues, and the inclusion of phenotypic data enabled the identification of metabolic sectors underlying traits of interest. For example, tolerance to whiteflies (Aleurotrachelus socialis) was not linked directly to cyanide content but to cell wall–related phenylpropanoid or apocarotenoid content. Collectively, these data advance the community resources and provide valuable insight into new candidate parental breeding materials with traits of interest directly related to combating food security.
The effect of IHAPIM program on health perceptions and health responsibilities of immigrant men: a randomized controlled trial
Authors: Korkmaz Mehmet , Avcı Iknur Aydın 
Published: May 2023

Abstract

Background
Health promotion interventions for immigrant health are generally directed toward women and youth. There is no program specific to migrant male in the global and national literature to protect, improve and promote their health. The aim of this study was to examine the effect of the Increasing Health Awareness of Immigrant Men (IHAPIM) program on health perceptions, health responsibilities, perceived stress level, attitudes toward utilizing health care services and the types of coping strategies of immigrant male.

Methods
Researchers applied the short-term IHAPIM program experimental group for 5 weeks. This study was held in the two districts where predominantly immigrants live. The immigrant male’s health perceptions, health responsibilities, perceived stress level, attitudes toward utilizing health care services and the types of coping strategies measured before and after 3 months of the IHAPIM program was performed.

Results
The study results showed that the levels of health perceptions, health responsibilities and the types of coping strategies of immigrant male were significantly different between the two study groups.

Conclusions
At the end of the study, the experimental group showed improvement in measures of the health perceptions, health responsibilities, attitudes toward utilizing health care services, the types of coping strategies and perceived stress level of male decreased. Nursing interventions specific to immigrant male and sensitive to their language have led to positive changes in the health variables of immigrant male.