bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seismic Architecture of the Upper Mantle Underlying California and Nevada
Authors: Stanciu A. Christian , Humphreys Eugene D. 
Published: November 2021

AbstractWe present new P and S teleseismic tomography models of the upper mantle beneath California and Nevada. Improved tomographic methods and the incorporation of new data increase image resolution and seismic structure definition. Technical advancements include the use of 3‐D ray tracing, ray weighting and finite‐frequency sensitivity kernels. Together with the incorporation of modern crustal velocity models to account for crustal delay time, these tomographic advancements reveal slightly higher amplitudes and narrower structures beneath prominent tectonic features in California and Nevada. The addition of new data from the southern California Borderland and northwestern California are particularly useful. Based on our imaging results, we discuss the effects of temperature and partial melt on upper mantle seismic velocity beneath California and Nevada. We interpret the major seismically fast structures in our study area to be Juan de Fuca slab and its downward continuation beneath central Nevada and foundered Farallon lithosphere beneath the southern Sierra Nevada and Transverse Ranges. The seismically slow structures beneath the slab‐free window of northern California Coast Range, the Salton Trough extensional basin, and the Cascadia back arc, are all consistent with the presence of partial melting of decompressing mantle. The imaged seismically fast and slow anomalies imply buoyancy variations and melt productivity that ultimately act on the overlying crust.
YORP Effect on Asteroid 162173 Ryugu: Implications for the Dynamical History
Authors: Kanamaru Masanori , Sasaki Sho , Morota Tomokatsu , Cho Yuichiro , Tatsumi Eri , Hirabayashi Masatoshi , Hirata Naru , Senshu Hiroki , Shimaki Yuri , Sakatani Naoya , Tanaka Satoshi , Okada Tatsuaki , Usui Tomohiro , Sugita Seiji , Watanabe Sei‐ichiro 
Published: November 2021

AbstractAsteroid 162173 Ryugu is a carbonaceous asteroid that was visited by Japan's Hayabusa2 spacecraft in 2018. The formation mechanism of the “spinning‐top” shape of Ryugu is a vital clue to the dynamical history of the near‐Earth asteroid. In this study, we address the long‐term evolution of its spin state induced by the Yarkovsky‐O’Keefe‐Radzievskii‐Paddack (YORP) effect, that is, the thermal recoil torque that changes the rotation period and spin‐pole direction. Given the current orbit, spin state, and three‐dimensional shape of Ryugu observed by Hayabusa2, we computed the YORP torque exerted on Ryugu using a simplified thermal model assuming zero thermal conductivity. Despite variations in the meter‐scaled topography, all 20 shape models that we examined indicate that the spin velocity of Ryugu is currently decreasing at a rate of deg/day2. Our findings also suggest that the thermal torque is responsible for maintaining the spin pole upright with respect to the orbital plane. Therefore, the YORP effect may explain the significant spin‐down from an earlier period of 3.5 hr to the present period of 7.6 hr. The corresponding time scale of the spin‐down is estimated to be 0.58–8.7 million years, depending on the input shape models. This time scale is comparable to the formation period of the largest crater, Urashima (5–12 Ma), or the western bulge (2–9 Ma) as derived from previous studies on crater statistics in Ryugu. Thus, its rotation may have started to decelerate as a consequence of major resurfacing events.
Wild-type isocitrate dehydrogenase under the spotlight in glioblastoma
Authors: Alzial Gabriel , Renoult Ophelie , Paris François , Gratas Catherine , Clavreul Anne , Pecqueur Claire 
Published: November 2021

AbstractBrain tumors actively reprogram their cellular metabolism to survive and proliferate, thus offering potential therapeutic opportunities. Over the past decade, extensive research has been done on mutant IDH enzymes as markers of good prognosis in glioblastoma, a highly aggressive brain tumor in adults with dismal prognosis. Yet, 95% of glioblastoma are IDH wild-type. Here, we review current knowledge about IDH wild-type enzymes and their putative role in mechanisms driving tumor progression. After a brief overview on tumor metabolic adaptation, we present the diverse metabolic function of IDH enzymes and their roles in glioblastoma initiation, progression and response to treatments. Finally, we will discuss wild-type IDH targeting in primary glioblastoma.
Water-driven microbial nitrogen transformations in biological soil crusts causing atmospheric nitrous acid and nitric oxide emissions
Authors: Maier S , Kratz A M , Weber J , Prass M , Liu F , Clark A T , Abed R M M , Su H , Cheng Y , Eickhorst T , Fiedler S , Pöschl U , Weber B 
Published: November 2021

Abstract
Biological soil crusts (biocrusts) release the reactive nitrogen gases (Nr) nitrous acid (HONO) and nitric oxide (NO) into the atmosphere, but the underlying microbial process controls have not yet been resolved. In this study, we analyzed the activity of microbial consortia relevant in Nr emissions during desiccation using transcriptome and proteome profiling and fluorescence in situ hybridization. We observed that &lt; 30 min after wetting, genes encoding for all relevant nitrogen (N) cycling processes were expressed. The most abundant transcriptionally active N-transforming microorganisms in the investigated biocrusts were affiliated with Rhodobacteraceae, Enterobacteriaceae, and Pseudomonadaceae within the Alpha- and Gammaproteobacteria. Upon desiccation, the nitrite (NO2−) content of the biocrusts increased significantly, which was not the case when microbial activity was inhibited. Our results confirm that NO2− is the key precursor for biocrust emissions of HONO and NO. This NO2− accumulation likely involves two processes related to the transition from oxygen-limited to oxic conditions in the course of desiccation: (i) a differential regulation of the expression of denitrification genes; and (ii) a physiological response of ammonia-oxidizing organisms to changing oxygen conditions. Thus, our findings suggest that the activity of N-cycling microorganisms determines the process rates and overall quantity of Nr emissions.
A review of functional and structural neuroimaging studies to investigate the inner speech model of auditory verbal hallucinations in schizophrenia
Authors: Barber Liam , Reniers Renate , Upthegrove Rachel 
Published: November 2021

AbstractAlthough the pathophysiology of auditory verbal hallucinations remains uncertain, the inner speech model remains a prominent theory. A systematic review and meta-analyses of both functional and structural neuroimaging studies were performed to investigate the inner speech model. Of the 417 papers retrieved, 26 met the inclusion criteria. Meta-analyses found the left insula to be significantly active during auditory verbal hallucinations and to have a significantly reduced grey matter volume in hallucinators. Dysfunction of the left insula may contribute to the misattribution of inner speech due to its suggested roles in both inner speech production and the salience network. No significant activity was found at Broca’s area or Heschl’s gyrus during auditory verbal hallucinations. Furthermore, no structural abnormalities were found at these sites or in the arcuate fasciculi. Overall, evidence was found to both support and oppose the inner speech model. Further research should particularly include a systematic review of task-based trait studies with a focus on inner speech production and self-referential processing, and analyses of additional language-related white matter tracts.
Multiple time measurements of multidimensional psychiatric states from immediately before the COVID-19 pandemic to one year later: a longitudinal online survey of the Japanese population
Authors: Oka Taiki , Kubo Takatomi , Kobayashi Nao , Nakai Fumiya , Miyake Yuka , Hamamura Toshitaka , Honjo Masaru , Toda Hiroyuki , Boku Shuken , Kanazawa Tetsufumi , Nagamine Masanori , Cortese Aurelio , Takebayashi Minoru , Kawato Mitsuo , Chiba Toshinori 
Published: November 2021

AbstractThe coronavirus disease 2019 (COVID-19) pandemic has profoundly affected the mental health of both infected and uninfected people. Although most psychiatric disorders have highly overlapping genetic and pathogenic backgrounds, most studies investigating the impact of the pandemic have examined only single psychiatric disorders. It is necessary to examine longitudinal trajectories of factors that modulate psychiatric states across multiple dimensions. About 2274 Japanese citizens participated in online surveys presented in December 2019 (before the pandemic), August 2020, Dec 2020, and April 2021. These surveys included nine questionnaires on psychiatric symptoms, such as depression and anxiety. Multidimensional psychiatric time-series data were then decomposed into four principal components. We used generalized linear models to identify modulating factors for the effects of the pandemic on these components. The four principal components can be interpreted as a general psychiatric burden, social withdrawal, alcohol-related problems, and depression/anxiety. Principal components associated with general psychiatric burden and depression/anxiety peaked during the initial phase of the pandemic. They were further exacerbated by the economic burden the pandemic imposed. In contrast, principal components associated with social withdrawal showed a delayed peak, with human relationships as an important risk modulating factor. In addition, being female was a risk factor shared across all components. Our results show that COVID-19 has imposed a large and varied burden on the Japanese population since the commencement of the pandemic. Although components related to the general psychiatric burden remained elevated, peak intensities differed between components related to depression/anxiety and those related to social withdrawal. These results underline the importance of using flexible monitoring and mitigation strategies for mental problems, according to the phase of the pandemic.
Decrease in early mortality for newly diagnosed multiple myeloma patients in the Netherlands: a population-based study
Authors: Brink Mirian , Groen Kaz , Sonneveld Pieter , Minnema Monique C. , Broijl Annemiek , Dinmohamed Avinash G. , van der Spek Ellen , Levin Mark-David , Ypma Paula F. , de Waal Esther , Posthuma Eduardus F. M. Ward , Zweegman Sonja , van de Donk Niels W. C. J. 
Published: November 2021

AbstractIdentification of risk factors for early mortality (EM) in multiple myeloma (MM) patients may contribute to different therapeutic approaches in patients at risk for EM. This population-based study aimed to assess trends in EM and risk factors for EM among MM patients diagnosed in the Netherlands. All MM patients, newly diagnosed between 1989 and 2018, were identified in the Netherlands Cancer Registry. Patients were categorized into three calendar periods (1989–1998, 1999–2008, 2009–2018) and into five age groups (≤65, 66–70, 71–75, 76–80, >80 years). EM was defined as death by any cause ≤180 days post-diagnosis. We included 28,328 MM patients (median age 70 years; 55% males). EM decreased from 22% for patients diagnosed in 1989–1998 to 13% for patients diagnosed in 2009–2018 (P < 0.01) and this decrease was observed among all age groups. Exact causes of death could not be elucidated. Besides patient’s age, we found that features related to a more aggressive disease presentation, and patient characteristics reflecting patients’ physical condition were predictive of EM. In summary, EM decreased from 1999 onwards. Nevertheless, EM remains high, especially for patients aged >70 years. Therefore, novel strategies should be explored to improve the outcome of patients at risk for EM.
Distinct patterns of speech disorder in early-onset and late-onset de-novo Parkinson’s disease
Authors: Rusz Jan , Tykalová Tereza , Novotný Michal , Růžička Evžen , Dušek Petr 
Published: November 2021

AbstractSubstantial variability and severity of dysarthric patterns across Parkinson’s disease (PD) patients may reflect distinct phenotypic differences. We aimed to compare patterns of speech disorder in early-onset PD (EOPD) and late-onset PD (LOPD) in drug-naive patients at early stages of disease. Speech samples were acquired from a total of 96 participants, including two subgroups of 24 de-novo PD patients and two subgroups of 24 age- and sex-matched young and old healthy controls. The EOPD group included patients with age at onset below 51 (mean 42.6, standard deviation 6.1) years and LOPD group patients with age at onset above 69 (mean 73.9, standard deviation 3.0) years. Quantitative acoustic vocal assessment of 10 unique speech dimensions related to respiration, phonation, articulation, prosody, and speech timing was performed. Despite similar perceptual dysarthria severity in both PD subgroups, EOPD showed weaker inspirations (p = 0.03), while LOPD was characterized by decreased voice quality (p = 0.02) and imprecise consonant articulation (p = 0.03). In addition, age-independent occurrence of monopitch (p < 0.001), monoloudness (p = 0.008), and articulatory decay (p = 0.04) was observed in both PD subgroups. The worsening of consonant articulation was correlated with the severity of axial gait symptoms (r = 0.38, p = 0.008). Speech abnormalities in EOPD and LOPD share common features but also show phenotype-specific characteristics, likely reflecting the influence of aging on the process of neurodegeneration. The distinct pattern of imprecise consonant articulation can be interpreted as an axial motor symptom of PD.
Patterns of pre-operative opioid use affect the risk for complications after total joint replacement
Authors: Ravi Bheeshma , Pincus Daniel , Croxford Ruth , Leroux Timothy , Paterson JMichael , Hawker Gillian , Redelmeier Donald A. 
Published: November 2021

AbstractPreoperative opioid use has been shown to increase the risk for complications following total joint arthroplasty (TJA); however, these studies have not always accounted for differences in co-morbidities and socio-demographics between patients that use opioids and those that do not. They have also not accounted for the variation in degree of pre-operative use. The objective of this study was to determine if preoperative opioid use is associated with risk for surgical complications after TJA, and if this association varied by degree of use. Population-based retrospective cohort study. Older adult patients undergoing primary TJA of the hip, knee and shoulder for osteoarthritis between 2002 and 2015 in Ontario, Canada were identified. Using accepted definitions, patients were stratified into three groups according to their preoperative opioid use: no use, intermittent use and chronic use. The primary outcome was the occurrence of a composite surgical complication (surgical site infection, dislocation, revision arthroplasty) or death within a year of surgery. Intermittent and chronic users were matched separately to non-users in a 1:1 ratio, matching on TJA type plus a propensity score incorporating patient and provider factors. Overall, 108,067 patients were included in the study; 10% (N = 10,441) used opioids on a chronic basis before surgery and 35% (N = 37,668) used them intermittently. After matching, chronic pre-operative opioid use was associated with an increased risk for complications after TJA (HR 1.44, p = 0.001) relative to non-users. Overall, less than half of patients undergoing TJA used opioids in the year preceding surgery; the majority used them only intermittently. While chronic pre-operative opioid use is associated with an increased risk for complications after TJA, intermitted pre-operative use is not.
Human stem cell-derived GABAergic neurons functionally integrate into human neuronal networks
Authors: Gonzalez-Ramos Ana , Waloschková Eliška , Mikroulis Apostolos , Kokaia Zaal , Bengzon Johan , Ledri Marco , Andersson My , Kokaia Merab 
Published: November 2021

AbstractGamma-aminobutyric acid (GABA)-releasing interneurons modulate neuronal network activity in the brain by inhibiting other neurons. The alteration or absence of these cells disrupts the balance between excitatory and inhibitory processes, leading to neurological disorders such as epilepsy. In this regard, cell-based therapy may be an alternative therapeutic approach. We generated light-sensitive human embryonic stem cell (hESC)-derived GABAergic interneurons (hdIN) and tested their functionality. After 35 days in vitro (DIV), hdINs showed electrophysiological properties and spontaneous synaptic currents comparable to mature neurons. In co-culture with human cortical neurons and after transplantation (AT) into human brain tissue resected from patients with drug-resistant epilepsy, light-activated channelrhodopsin-2 (ChR2) expressing hdINs induced postsynaptic currents in human neurons, strongly suggesting functional efferent synapse formation. These results provide a proof-of-concept that hESC-derived neurons can integrate and modulate the activity of a human host neuronal network. Therefore, this study supports the possibility of precise temporal control of network excitability by transplantation of light-sensitive interneurons.
Remodeling tumor microenvironment by liposomal codelivery of DMXAA and simvastatin inhibits malignant melanoma progression
Authors: Rauca Valentin-Florian , Patras Laura , Luput Lavinia , Licarete Emilia , Toma Vlad-Alexandru , Porfire Alina , Mot Augustin Catalin , Rakosy-Tican Elena , Sesarman Alina , Banciu Manuela 
Published: November 2021

AbstractAnti-angiogenic therapies for melanoma have not yet been translated into meaningful clinical benefit for patients, due to the development of drug-induced resistance in cancer cells, mainly caused by hypoxia-inducible factor 1α (HIF-1α) overexpression and enhanced oxidative stress mediated by tumor-associated macrophages (TAMs). Our previous study demonstrated synergistic antitumor actions of simvastatin (SIM) and 5,6-dimethylxanthenone-4-acetic acid (DMXAA) on an in vitro melanoma model via suppression of the aggressive phenotype of melanoma cells and inhibition of TAMs-mediated angiogenesis. Therefore, we took the advantage of long circulating liposomes (LCL) superior tumor targeting capacity to efficiently deliver SIM and DMXAA to B16.F10 melanoma in vivo, with the final aim of improving the outcome of the anti-angiogenic therapy. Thus, we assessed the effects of this novel combined tumor-targeted treatment on s.c. B16.F10 murine melanoma growth and on the production of critical markers involved in tumor development and progression. Our results showed that the combined liposomal therapy almost totally inhibited (> 90%) the growth of melanoma tumors, due to the enhancement of anti-angiogenic effects of LCL-DMXAA by LCL-SIM and simultaneous induction of a pro-apoptotic state of tumor cells in the tumor microenvironment (TME). These effects were accompanied by the partial re-education of TAMs towards an M1 phenotype and augmented by combined therapy-induced suppression of major invasion and metastasis promoters (HIF-1α, pAP-1 c-Jun, and MMPs). Thus, this novel therapy holds the potential to remodel the TME, by suppressing its most important malignant biological capabilities.
Targeting CD38 in acute myeloid leukemia interferes with leukemia trafficking and induces phagocytosis
Authors: Farber Meike , Chen Yiyang , Arnold Lucas , Möllmann Michael , Boog-Whiteside Eva , Lin Yu-An , Reinhardt H. Christian , Dührsen Ulrich , Hanoun Maher 
Published: November 2021

AbstractTargeting the interaction between leukemic cells and the microenvironment is an appealing approach to enhance the therapeutic efficacy in acute myeloid leukemia (AML). AML infiltration induces a significant release of inflammatory cytokines in the human bone marrow niche which accelerates leukemogenesis. As the transmembrane glycoprotein CD38 has been shown to regulate cytokine release, we assessed the anti-leukemic potential of CD38 inhibition in AML. CD38 expression in AML cells proved to depend on microenvironmental cues and could be significantly enforced through addition of tretinoin. In fact, the anti-CD38 antibody daratumumab showed significant cytostatic efficacy in a 3D in vitro triple-culture model of AML, but with modest cell-autonomous cytotoxic activity and independent of CD38 expression level. In line with a predominantly microenvironment-mediated activity of daratumumab in AML, CD38 inhibition significantly induced antibody-dependent phagocytosis and showed interference with AML cell trafficking in vivo in a xenograft transplantation model, but overall lacked robust anti-leukemic effects.
Assessing the impact of suppressing Southern Ocean SST variability in a coupled climate model
Authors: Purich Ariaan , Boschat Ghyslaine , Liguori Giovanni 
Published: November 2021

AbstractThe Southern Ocean exerts a strong influence on global climate, regulating the storage and transport of heat, freshwater and carbon throughout the world’s oceans. While the majority of previous studies focus on how wind changes influence Southern Ocean circulation patterns, here we set out to explore potential feedbacks from the ocean to the atmosphere. To isolate the role of oceanic variability on Southern Hemisphere climate, we perform coupled climate model experiments in which Southern Ocean variability is suppressed by restoring sea surface temperatures (SST) over 40°–65°S to the model’s monthly mean climatology. We find that suppressing Southern Ocean SST variability does not impact the Southern Annular Mode, suggesting air–sea feedbacks do not play an important role in the persistence of the Southern Annular Mode in our model. Suppressing Southern Ocean SST variability does lead to robust mean-state changes in SST and sea ice. Changes in mixed layer processes and convection associated with the SST restoring lead to SST warming and a sea ice decline in southern high latitudes, and SST cooling in midlatitudes. These results highlight the impact non-linear processes can have on a model’s mean state, and the need to consider these when performing simulations of the Southern Ocean.