bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is there a relationship between end-of-life cancer patients’ dignity-related distress and caregivers’ distress? An exploratory study
Authors: Bovero Andrea , Cotardo Francesca , Lops Chiara , Botto Rossana , Geminiani Giuliano Carlo 
Published: July 2022

AbstractObjectivesThe mutual influence between end-of-life cancer patients and their family caregivers is widely endorsed. The present study aimed to explore the relationship between end-of-life cancer patients’ dignity-related distress and the distress of their caregivers.MethodA cross-sectional approach was used. The sample consisted of 128 patients with a Karnofsky Performance Status (KPS) below 50 and a life expectancy of a few weeks, and their family caregivers. Personal and clinical data were collected and validated rating scales were administered:Patient Dignity Inventory(PDI) to terminal cancer patients;Hospital Anxiety and Depression Scale(HADS),Demoralization Scale(DS),Herth Hope Index(HHI),Caregiver Reaction Assessment(CRA),Short Form Health Survey 36(SF-36), andDistress Thermometer (DT)to caregivers.ResultsFindings highlighted significant correlations between patients’ scores on the Psychological Distress PDI subscale and the PDI Total Score and caregivers’ Emotional Role. Patients’ Psychological Distress, PDI Total Score, and Loss of Purpose and Meaning were associated with caregivers’ Disrupted Schedule. Finally, patients’ Physical Symptoms and Dependency, Loss of Purpose and Meaning, and PDI Total Score were correlated with caregivers’ Disheartenment.Significance of resultsThe results highlighted the key role of dignity as a relational dimension during the end-of-life phase. Therefore, because of caregivers’ distress could affect patients’ dignity-related distress by influencing the interpersonal aspects of patients’ autonomy, it would be important to relieve caregivers’ distress in order to promote patients’ autonomy and minimize their fear of being a burden.
Modification of the Loss Cone for Energetic Particles in the Earth's Inner Magnetosphere
Authors: Borovsky J. E. , Yakymenko K. N. , Delzanno G. L. 
Published: July 2022

AbstractThe behavior of energetic particles in the Earth's dipole and stretched magnetic‐field models is explored with a focus on the shift of the atmospheric loss cone away from the magnetic‐field direction and on non‐adiabatic behavior occurring when the particle gyroradius becomes comparable with the gradient scale length of the local magnetic field. It is shown that the equatorial loss cone is aberrated away from the magnetic‐field direction (pitch angle of 0°) by the perpendicular drift of a charged particle (which is referred to as the “Mozer transform” described in Mozer (1966, https://doi.org/10.1029/JZ071i011p02701). It is found that the Mozer coordinate transformation in pitch‐angle/gyrophase‐angle space better organizes the behavior of bounce times, mirror altitudes, drift speeds, and first adiabatic invariant. It also describes the loss‐cone shift accurately for a certain range of values of the adiabaticity parameter ϵ, defined by the ratio of the particle gyroradius to the local radius of curvature of the magnetic field. For particles with larger ϵ, the Mozer transform (evaluated with the standard gradient‐curvature drift) breaks down and the “central trajectory” theory can be used to calculate the angular shift of the loss cone, which now includes an Earthward shift. When ϵ becomes relatively large, stochastic field line curvature (FLC) scattering occurs: we show the intimate connection between the strength of FLC scattering and the loss‐cone shift. By comparing ion orbits in the dipole and Tsyganenko (Ts89 and Ts04) magnetic fields, we conclude that the loss cone of ring‐current ions is significantly modified during geomagnetically active times.
Role of Particle Resuspension in Maintaining Hypoxic Level in the Pearl River Estuary
Authors: Cui Yongsheng , Wu Jiaxue , Tan Ehui , Kao Shuh‐Ji 
Published: July 2022

AbstractEutrophication‐induced seasonal hypoxia in the coastal ocean has widely been attributed to the excessive oxygen consumption induced by settling and deposition of organic particles on sea floor. However, the role of particle resuspension in maintaining the hypoxic level has seldom been investigated based on field observations. Here, we carefully examined particle resuspension and its contribution to oxygen consumption in the Pearl River Estuary in July 2020. The bottom hypoxia was found to appear over the organic‐rich mudbelt off the estuary. Concentrated particles in suspension near the bottom, which were induced by particle resuspension rather than by particle settling, occurred near the front created by shelf salinity intrusions where bottom hypoxia appeared in the summer. The total dissolved oxygen (DO) depletion responsible for bottom hypoxia can be exclusively estimated from the DO budget during the tidal cycle. The water DO depletion dominated by particle resuspension is larger than or at least comparable to sediment oxygen demand. This highlights that the DO budget in the absence of particle resuspension overestimates the DO level in coastal hypoxia. Overall, our results suggest that particle resuspension play a vital role in maintaining the DO level of bottom hypoxia. This finding will be helpful to understand the impact of particle resuspension on coastal hypoxia, as well as other marine environmental problems in estuary and coastal ocean.
Incomplete Crack Sealing Causes Localization of Fracturing in Hydrothermal Quartz Veins
Authors: Späth Michael , Urai Janos L. , Nestler Britta 
Published: July 2022

AbstractCyclic microfracturing and epitaxial crystal growth have long been recognized in crack‐seal veins, but an understanding of a single crack‐seal cycle is still missing. Here we present a phase‐field model that includes both fracture mechanics of crack propagation, and epitaxial crystal growth on the fracture walls, repeating this cycle multiple times in a polycrystalline, microporous quartz rock. Our simulations have two end members: If a vein completely seals, it is stronger than the host rock, cracking is delocalized, forming many single‐seal microveins. Incomplete sealing makes the vein weaker than the host rock and localizes the new fracture inside the vein, leading to multi‐crack‐seal. We suggest that the sealing degree is a key parameter in hydrothermal systems and multi‐crack‐seal veins are long‐lived, microporous sites of mechanical weakness. We generalize the phase‐field approach to conduct probabilistic simulations in between these two types, and show how systems of microveins and multi‐crack‐seal veins emerge.
Equatorial Plasma Bubble Detection Using Vertical TEC From Altimetry Satellite
Authors: Tang Long , Chen Gefa 
Published: July 2022

AbstractIn this study, we detect the equatorial plasma bubble (EPB) using vertical total electron content (vTEC) from altimetry satellite for the first time. The Jason‐2 vTEC data during the high solar activity year of 2014 are employed to investigate the characteristics of EPB. The latitudinal and temporal variations of EPB are analyzed first and the results are consistent to those of previous reported studies, suggesting the observed EPB events are reliable. Furthermore, due to the features of vTEC, the zonal scale and vertical depth of EPB are also obtained: the zonal scale varies mainly with small scope of 0.5 ∼ 1.5° and seems to be independent of latitude, whereas the vertical depth is related to latitude with large value located in the crest region of the equatorial anomaly. The results show the altimetry satellite vTEC is feasible for EPB detection and can serve as a new tool for EPB monitoring.
Second generation androgen receptor antagonists and challenges in prostate cancer treatment
Authors: Chen Yanhua , Zhou Qianqian , Hankey William , Fang Xiaosheng , Yuan Fuwen 
Published: July 2022

AbstractProstate cancer is a hormone-dependent malignancy, whose onset and progression are closely related to the activity of the androgen receptor (AR) signaling pathway. Due to this critical role of AR signaling in driving prostate cancer, therapy targeting the AR pathway has been the mainstay strategy for metastatic prostate cancer treatment. The utility of these agents has expanded with the emergence of second-generation AR antagonists, which began with the approval of enzalutamide in 2012 by the United States Food and Drug Administration (FDA). Together with apalutamide and darolutamide, which were approved in 2018 and 2019, respectively, these agents have improved the survival of patients with prostate cancer, with applications for both androgen-dependent and castration-resistant disease. While patients receiving these drugs receive a benefit in the form of prolonged survival, they are not cured and ultimately progress to lethal neuroendocrine prostate cancer (NEPC). Here we summarize the current state of AR antagonist development and highlight the emerging challenges of their clinical application and the potential resistance mechanisms, which might be addressed by combination therapies or the development of novel AR-targeted therapies.
Dynamic influences on static measures of metacognition
Authors: Desender Kobe , Vermeylen Luc , Verguts Tom 
Published: July 2022

AbstractHumans differ in their capability to judge choice accuracy via confidence judgments. Popular signal detection theoretic measures of metacognition, such as M-ratio, do not consider the dynamics of decision making. This can be problematic if response caution is shifted to alter the tradeoff between speed and accuracy. Such shifts could induce unaccounted-for sources of variation in the assessment of metacognition. Instead, evidence accumulation frameworks consider decision making, including the computation of confidence, as a dynamic process unfolding over time. Using simulations, we show a relation between response caution and M-ratio. We then show the same pattern in human participants explicitly instructed to focus on speed or accuracy. Finally, this association between M-ratio and response caution is also present across four datasets without any reference towards speed. In contrast, when data are analyzed with a dynamic measure of metacognition, v-ratio, there is no effect of speed-accuracy tradeoff.
Lateral habenula glutamatergic neurons projecting to the dorsal raphe nucleus promote aggressive arousal in mice
Authors: Takahashi Aki , Durand-de Cuttoli Romain , Flanigan Meghan E. , Hasegawa Emi , Tsunematsu Tomomi , Aleyasin Hossein , Cherasse Yoan , Miya Ken , Okada Takuya , Keino-Masu Kazuko , Mitsui Koshiro , Li Long , Patel Vishwendra , Blitzer Robert D. , Lazarus Michael , Tanaka Kenji F. , Yamanaka Akihiro , Sakurai Takeshi , Ogawa Sonoko , Russo Scott J. 
Published: July 2022

AbstractThe dorsal raphe nucleus (DRN) is known to control aggressive behavior in mice. Here, we found that glutamatergic projections from the lateral habenula (LHb) to the DRN were activated in male mice that experienced pre-exposure to a rival male mouse (“social instigation”) resulting in heightened intermale aggression. Both chemogenetic and optogenetic suppression of the LHb-DRN projection blocked heightened aggression after social instigation in male mice. In contrast, inhibition of this pathway did not affect basal levels of aggressive behavior, suggesting that the activity of the LHb-DRN projection is not necessary for the expression of species-typical aggressive behavior, but required for the increase of aggressive behavior resulting from social instigation. Anatomical analysis showed that LHb neurons synapse on non-serotonergic DRN neurons that project to the ventral tegmental area (VTA), and optogenetic activation of the DRN-VTA projection increased aggressive behaviors. Our results demonstrate that the LHb glutamatergic inputs to the DRN promote aggressive arousal induced by social instigation, which contributes to aggressive behavior by activating VTA-projecting non-serotonergic DRN neurons as one of its potential targets.
Engineered biomimetic nanoparticles achieve targeted delivery and efficient metabolism-based synergistic therapy against glioblastoma
Authors: Lu Guihong , Wang Xiaojun , Li Feng , Wang Shuang , Zhao Jiawei , Wang Jinyi , Liu Jing , Lyu Chengliang , Ye Peng , Tan Hui , Li Weiping , Ma Guanghui , Wei Wei 
Published: July 2022

AbstractGlioblastoma multiforme (GBM) is an aggressive brain cancer with a poor prognosis and few treatment options. Here, building on the observation of elevated lactate (LA) in resected GBM, we develop biomimetic therapeutic nanoparticles (NPs) that deliver agents for LA metabolism-based synergistic therapy. Because our self-assembling NPs are encapsulated in membranes derived from glioma cells, they readily penetrate the blood-brain barrier and target GBM through homotypic recognition. After reaching the tumors, lactate oxidase in the NPs converts LA into pyruvic acid (PA) and hydrogen peroxide (H2O2). The PA inhibits cancer cell growth by blocking histones expression and inducing cell-cycle arrest. In parallel, the H2O2 reacts with the delivered bis[2,4,5-trichloro-6-(pentyloxycarbonyl)phenyl] oxalate to release energy, which is used by the co-delivered photosensitizer chlorin e6 for the generation of cytotoxic singlet oxygen to kill glioma cells. Such a synergism ensures strong therapeutic effects against both glioma cell-line derived and patient-derived xenograft models.
Etv2 regulates enhancer chromatin status to initiate Shh expression in the limb bud
Authors: Koyano-Nakagawa Naoko , Gong Wuming , Das Satyabrata , Theisen Joshua W. M. , Swanholm Tran B. , Van Ly Daniel , Dsouza Nikita , Singh Bhairab N. , Kawakami Hiroko , Young Samantha , Chen Katherine Q. , Kawakami Yasuhiko , Garry Daniel J. 
Published: July 2022

AbstractSonic hedgehog(Shh) is essential for limb development, and the mechanisms that govern the propagation and maintenance of its expression has been well studied; however, the mechanisms that govern the initiation ofShhexpression are incomplete. Here we report that ETV2 initiatesShhexpression by changing the chromatin status of the developmental limb enhancer, ZRS.Etv2expression precedesShhin limb buds, andEtv2inactivation prevents the opening of limb chromatin, including the ZRS, resulting in an absence ofShhexpression.Etv2overexpression in limb buds causes nucleosomal displacement at the ZRS, ectopicShhexpression, and polydactyly. Areas of nucleosome displacement coincide with ETS binding site clusters. ETV2 also functions as a transcriptional activator of ZRS and is antagonized by ETV4/5 repressors. Known human polydactyl mutations introduce novel ETV2 binding sites in the ZRS, suggesting that ETV2 dosage regulates ZRS activation. These studies identify ETV2 as a pioneer transcription factor (TF) regulating the onset ofShhexpression, having both a chromatin regulatory role and a transcriptional activation role.
Population genomics of Group B Streptococcus reveals the genetics of neonatal disease onset and meningeal invasion
Authors: Chaguza Chrispin , Jamrozy Dorota , Bijlsma Merijn W. , Kuijpers Taco W. , van de Beek Diederik , van der Ende Arie , Bentley Stephen D. 
Published: July 2022

AbstractGroup B Streptococcus (GBS), or Streptococcus agalactiae, is a pathogen that causes preterm births, stillbirths, and acute invasive neonatal disease burden and mortality. Here, we investigate bacterial genetic signatures associated with disease onset time and meningeal tissue infection in acute invasive neonatal GBS disease. We carry out a genome-wide association study (GWAS) of 1,338 GBS isolates from newborns with acute invasive disease; the isolates had been collected annually, for 30 years, through a national bacterial surveillance program in the Netherlands. After controlling for the population structure, we identify genetic variation within noncoding and coding regions, particularly the capsule biosynthesis locus, statistically associated with neonatal GBS disease onset time and meningeal invasion. Our findings highlight the impact of integrating microbial population genomics and clinical pathogen surveillance, and demonstrate the effect of GBS genetics on disease pathogenesis in neonates and infants.
Assembly of planar chiral superlattices from achiral building blocks
Authors: Cheng Zhihua , Jones Matthew R. 
Published: July 2022

AbstractThe spontaneous assembly of chiral structures from building blocks that lack chirality is fundamentally important for colloidal chemistry and has implications for the formation of advanced optical materials. Here, we find that purified achiral gold tetrahedron-shaped nanoparticles assemble into two-dimensional superlattices that exhibit planar chirality under a balance of repulsive electrostatic and attractive van der Waals and depletion forces. A model accounting for these interactions shows that the growth of planar structures is kinetically preferred over similar three-dimensional products, explaining their selective formation. Exploration and mapping of different packing symmetries demonstrates that the hexagonal chiral phase forms exclusively because of geometric constraints imposed by the presence of constituent tetrahedra with sharp tips. A formation mechanism is proposed in which the chiral phase nucleates from within a related 2D achiral phase by clockwise or counterclockwise rotation of tetrahedra about their central axis. These results lay the scientific foundation for the high-throughput assembly of planar chiral metamaterials.
Water as the often neglected medium at the interface between materials and biology
Authors: Dargaville B. L. , Hutmacher D. W. 
Published: July 2022

AbstractDespite its apparent simplicity, water behaves in a complex manner and is fundamental in controlling many physical, chemical and biological processes. The molecular mechanisms underlying interaction of water with materials, particularly polymer networks such as hydrogels, have received much attention in the research community. Despite this, a large gulf still exists in applying what is known to rationalize how the molecular organization of water on and within these materials impacts biological processes. In this perspective, we outline the importance of water in biomaterials science as a whole and give indications for future research directions towards emergence of a complete picture of water, materials and biology.
Sulfur and chlorine budgets control the ore fertility of arc magmas
Authors: Grondahl Carter , Zajacz Zoltán 
Published: July 2022

AbstractContinental arc magmas supply the ore-forming element budget of most globally important porphyry-type ore deposits. However, the processes enabling certain arc segments to preferentially generate giant porphyry deposits remain highly debated. Here we evaluate the large-scale covariation of key ore-forming constituents in this setting by studying silicate melt inclusions in volcanic rocks from a fertile-to-barren segment of the Andean Southern Volcanic Zone (33–40 °S). We show that the north-to-south, fertile-to-barren gradient is characterized by a northward increase in S and Cl concentrations and a simultaneous decrease in Cu. Consequently, we suggest that the concentration of S and Cl rather than the concentration of ore metals regulates magmatic-hydrothermal ore fertility, and that the loss of volatiles prior to arrival in the upper crust impacts ore-forming potential more than magmatic sulfide saturation-related ore metal scavenging.
Post-translational amino acid conversion in photosystem II as a possible origin of photosynthetic oxygen evolution
Authors: Shimada Yuichiro , Suzuki Takehiro , Matsubara Takumi , Kitajima-Ihara Tomomi , Nagao Ryo , Dohmae Naoshi , Noguchi Takumi 
Published: July 2022

AbstractPhotosynthetic oxygen evolution is performed at the Mn cluster in photosystem II (PSII). The advent of this reaction on ancient Earth changed its environment by generating an oxygenic atmosphere. However, how oxygen evolution originated during the PSII evolution remains unknown. Here, we characterize the site-directed mutants at the carboxylate ligands to the Mn cluster in cyanobacterial PSII. A His residue replaced for D1-D170 is found to be post-translationally converted to the original Asp to recover oxygen evolution. Gln/Asn residues in the mutants at D1-E189/D1-D342 are also converted to Glu/Asp, suggesting that amino-acid conversion is a common phenomenon at the ligand sites of the Mn cluster. We hypothesize that post-translational generation of carboxylate ligands in ancestral PSII could have led to the formation of a primitive form of the Mn cluster capable of partial water oxidation, which could have played a crucial role in the evolutionary process of photosynthetic oxygen evolution.
The trispecific DARPin ensovibep inhibits diverse SARS-CoV-2 variants
Authors: Rothenberger Sylvia , Hurdiss Daniel L. , Walser Marcel , Malvezzi Francesca , Mayor Jennifer , Ryter Sarah , Moreno Hector , Liechti Nicole , Bosshart Andreas , Iss Chloé , Calabro Valérie , Cornelius Andreas , Hospodarsch Tanja , Neculcea Alexandra , Looser Thamar , Schlegel Anja , Fontaine Simon , Villemagne Denis , Paladino Maria , Schiegg Dieter , Mangold Susanne , Reichen Christian , Radom Filip , Kaufmann Yvonne , Schaible Doris , Schlegel Iris , Zitt Christof , Sigrist Gabriel , Straumann Marcel , Wolter Julia , Comby Marco , Sacarcelik Feyza , Drulyte Ieva , Lyoo Heyrhyoung , Wang Chunyan , Li Wentao , Du Wenjuan , Binz H. Kaspar , Herrup Rachel , Lusvarghi Sabrina , Neerukonda Sabari Nath , Vassell Russell , Wang Wei , Adler Julia M. , Eschke Kathrin , Nascimento Mariana , Abdelgawad Azza , Gruber Achim D. , Bushe Judith , Kershaw Olivia , Knutson Charles G. , Balavenkatraman Kamal K. , Ramanathan Krishnan , Wyler Emanuel , Teixeira Alves Luiz Gustavo , Lewis Seth , Watson Randall , Haeuptle Micha A. , Zürcher Alexander , Dawson Keith M. , Steiner Daniel , Weiss Carol D. , Amstutz Patrick , van Kuppeveld Frank J. M. , Stumpp Michael T. , Bosch Berend-Jan , Engler Olivier , Trimpert Jakob 
Published: July 2022

AbstractThe emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with potential resistance to existing drugs emphasizes the need for new therapeutic modalities with broad variant activity. Here we show that ensovibep, a trispecific DARPin (designed ankyrin repeat protein) clinical candidate, can engage the three units of the spike protein trimer of SARS-CoV-2 and inhibit ACE2 binding with high potency, as revealed by cryo-electron microscopy analysis. The cooperative binding together with the complementarity of the three DARPin modules enable ensovibep to inhibit frequent SARS-CoV-2 variants, including Omicron sublineages BA.1 and BA.2. In Roborovski dwarf hamsters infected with SARS-CoV-2, ensovibep reduced fatality similarly to a standard-of-care monoclonal antibody (mAb) cocktail. When used as a single agent in viral passaging experiments in vitro, ensovibep reduced the emergence of escape mutations in a similar fashion to the same mAb cocktail. These results support further clinical evaluation of ensovibep as a broad variant alternative to existing targeted therapies for Coronavirus Disease 2019 (COVID-19).