bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treating Vaginal Laxity Using Nonablative Er:YAG Laser: A Retrospective Case Series of Patients From 2.5 Years of Clinical Practice
Authors: Mitsuyuki Midori , Štok Ula , Hreljac Irena , Yoda Kikue , Vižintin Zdenko 
Published: February 2020

Abstract

Introduction
Vaginal laxity drastically impairs women’s quality of life, suggesting there is a need for effective noninvasive treatments.

Aim
The aim was to retrospectively assess the effectiveness and safety of a nonablative Er:YAG IntimaLase laser procedure for vaginal laxity in patients treated in our clinical practice during a 2.5-year period.

Methods
Laser treatment for vaginal laxity was performed using an intravaginal nonablative Er:YAG laser. Effectiveness was assessed using a Patient Satisfaction Questionnaire and also by independent evaluation of before and after treatment photographs of the patients’ introitus. The safety and tolerability of the procedure was monitored in all patients.

Main Outcome Measure
The study showed an improvement of sexual gratification and improvement of vaginal tightness, as assessed by patients. The tightness of the introitus was also improved, as assessed by independent evaluators.

Results
As assessed by the Patient Satisfaction Questionnaire, we show that 92.7% of patients experienced improvement of sexual gratification after IntimaLase laser treatment. The results of the visual evaluation of the grade of laxity improvement in the introitus area, when open introitus photos were evaluated, show that 69% (n = 20/29) of patients had an improvement of laxity. Nonablative Er:YAG treatment seems to be an effective and safe treatment for vaginal laxity. As it is a noninvasive procedure, it should be considered before any vaginoplasty surgery. The study included all the patients treated in clinical practice and observed very few adverse effects. The results were comparable with other published data. Because it is a retrospective study, there is a lack of a control group.

Conclusion
The results have confirmed that patients suffering from vaginal laxity can be effectively treated using the nonablative Er:YAG IntimaLase procedure without adverse effects.
Macroeconomic and distributional effects of demographic change in an open economy—the case of Belgium
Authors: Devriendt Willem , Heylen Freddy 
Published: February 2020

AbstractWe construct and parameterize an overlapping generations model for an open economy with individuals who differ in innate ability. Key endogenous variables are hours worked, investment in human and physical capital, and per capita growth. The model replicates important data in Belgium since 1960 remarkably well. Simulating it, we observe that behavioral adjustments by households and firms contribute to reverse the negative arithmetical effect of future demographic change on per capita growth. Individuals work and study more. However, with unchanged policies, there remains a net negative effect on annual per capita growth of almost 0.3%-points on average in the next 25 years. This is mainly due to adverse consequences of reduced fertility and a declining working-age population on (the return to) physical capital investment. Model projections also point to rising income inequality induced by demographic change. Differences in the capacity of individuals to respond to increasing life expectancy by investing in education, and by saving, are key.
Voxel-based morphometry and cortical thickness in combat veterans suffering from impulsive aggression
Authors: Varkevisser Tim , van Lutterveld Remko , Heesink Lieke , van Honk Jack , Geuze Elbert 
Published: February 2020

AbstractBackgroundProblems with impulsive aggression occur in many forms of psychiatric dysfunction, and are a common complaint among combat veterans. The present study sought to examine the neuroanatomical correlates of combat-related impulsive aggression.MethodsT1-weighted magnetic resonance images were acquired from 29 male veterans with impulsive aggression and 30 non-aggressive combat controls. Subcortical volumetry was conducted with the amygdala and hippocampus and their main constituent subdivisions as regions-of-interest (ROIs) (basolateral, centromedial amygdala; head, body, tail of hippocampus). Cortical thickness measurements were extracted for the dorsolateral prefrontal cortex, orbitofrontal cortex, and anterior cingulate cortex. Within-group correlations with psychometric measures were also explored.ResultsNo significant group differences in cortical thickness or subcortical grey matter volumes were observed for any of the ROIs. Also, no significant correlations with any of the psychometric measures were recorded. Exploratory whole-brain analysis of cortical thickness revealed a significant group × anxiety interaction effect in a cluster located in the left lingual gyrus.ConclusionsThe current findings indicate that problems with impulsive aggression may not be directly associated with alterations in cortical thickness or amygdalar/hippocampal (sub)volumes. The observed interplay between impulsive aggression problems and anxiety-related symptoms is consistent with prior work showing the two phenomena may share the same underlying (neural) mechanisms.
Sources of Uncertainty in Regional and Global Terrestrial CO2 Exchange Estimates
Authors: Bastos A. , O'Sullivan M. , Ciais P. , Makowski D. , Sitch S. , Friedlingstein P. , Chevallier F. , Rödenbeck C. , Pongratz J. , Luijkx I. T. , Patra P. K. , Peylin P. , Canadell J. G. , Lauerwald R. , Li W. , Smith N. E. , Peters W. , Goll D. S. , Jain A.K. , Kato E. , Lienert S. , Lombardozzi D. L. , Haverd V. , Nabel J. E. M. S. , Poulter B. , Tian H. , Walker A. P. , Zaehle S. 
Published: February 2020

The Global Carbon Budget 2018 (GCB2018) estimated by the atmospheric CO
growth rate, fossil fuel emissions, and modeled (bottom‐up) land and ocean fluxes cannot be fully closed, leading to a “budget imbalance,” highlighting uncertainties in GCB components. However, no systematic analysis has been performed on which regions or processes contribute to this term. To obtain deeper insight on the sources of uncertainty in global and regional carbon budgets, we analyzed differences in Net Biome Productivity (NBP) for all possible combinations of bottom‐up and top‐down data sets in GCB2018: (i) 16 dynamic global vegetation models (DGVMs), and (ii) 5 atmospheric inversions that match the atmospheric CO
growth rate. We find that the global mismatch between the two ensembles matches well the GCB2018 budget imbalance, with Brazil, Southeast Asia, and Oceania as the largest contributors. Differences between DGVMs dominate global mismatches, while at regional scale differences between inversions contribute the most to uncertainty. At both global and regional scales, disagreement on NBP interannual variability between the two approaches explains a large fraction of differences. We attribute this mismatch to distinct responses to El Niño–Southern Oscillation variability between DGVMs and inversions and to uncertainties in land use change emissions, especially in South America and Southeast Asia. We identify key needs to reduce uncertainty in carbon budgets: reducing uncertainty in atmospheric inversions (e.g., through more observations in the tropics) and in land use change fluxes, including more land use processes and evaluating land use transitions (e.g., using high‐resolution remote‐sensing), and, finally, improving tropical hydroecological processes and fire representation within DGVMs.
The 2019 MW 5.7 Changning Earthquake, Sichuan Basin, China: A Shallow Doublet With Different Faulting Styles
Authors: Liu Junqing , Zahradník Jiří 
Published: February 2020

AbstractThe increased seismic activity of the last ~10 years in Changning county of Sichuan Province comprised just small (mostly ML < 5.0) injection‐induced earthquakes. The MW 5.7 earthquake on June 17, 2019, is the largest event ever reported there. Moment tensor of the mainshock was remarkably dominated by a compensated linear vector dipole. We resolve its fine structure showing it was a doublet, allowing approximation by a thrust‐ and strike‐slip subevent. The mainshock nucleated as thrust faulting, which (together with the largest aftershocks) can be linked with previously known reverse faults, favorably oriented to regional stress field. Contrarily, the strike‐slip segment of the mainshock, less favorably oriented, was probably facilitated by elevated pore pressure due to previous injections. Shallow active strike‐slip faulting, not yet mapped in the region, is a new feature, important for future hazard assessment.
Inward Propagation of Flow‐Generated Pi2 Waves From the Plasma Sheet to the Inner Magnetosphere
Authors: Wang Chih‐Ping , Xing Xiaoyan , Bortnik Jacob , Chu Xiangning 
Published: February 2020

AbstractTo understand the inward propagation of the Pi2 waves generated by bursty bulk flows (BBFs) from the plasma sheet to the inner magnetosphere, we statistically investigate 137 midnight conjunction events with one satellite of the Time History of Events and Macroscale Interactions during Substorms (THEMIS) in the plasma sheet and one satellite of Geostationary Operational Environmental Satellite (GOES) in the inner magnetosphere. All events have Pi2 wave enhancements associated with BBFs at THEMIS. In response, larger Pi2 wave enhancements at GOES are correlated with larger dipolarization associated with each BBF at THEMIS but not with stronger waves and flows at THEMIS. The larger wave enhancements at GOES occur preferentially under stronger solar wind driving. We discuss an explanation considering that BBFs are an earthward moving plasma sheet bubble having relatively lower flux tube entropy compared to that of the background plasma and that Pi2 waves are generated by the slowing down of the bubble. The stronger dipolarization of BBFs suggests a bubble of smaller entropy, while the stronger solar wind driving leads to higher background entropy in the inner magnetosphere, both favorable for a bubble to penetrate deeper, and thus, Pi2 waves generated by the bubble are more likely to propagate to the GOES location with less damping to result in larger wave enhancements. In addition, our analyses using empirical density and magnetic field models suggest that the strong Pi2 wave enhancements at GOES are less likely to be a cavity resonance driven inside the plasmasphere.
Impact Gardening as a Constraint on the Age, Source, and Evolution of Ice on Mercury and the Moon
Authors: Costello E. S. , Ghent R. R. , Hirabayashi M. , Lucey P. G. 
Published: February 2020

AbstractWe update an analytic impact gardening model (Costello et al., 2018, https://doi.org/10.1016/j.icarus.2018.05.023) to calculate the depth gardened by impactors on the Moon and Mercury and assess the implications of our results for the age, extent, and source of water ice deposits on both planetary bodies. We show that if the water presently on the Moon has a primordial origin, it may have been 4–15 m thick. If ice deposits are buried, they may be as shallow as 3 cm or as deep as 10 m and provide a gradient of probability for ice gardened into a column. Our calculations for gardening on Mercury show that thermal lag deposits will be reworked into the background over 200 Myr, and, thus, the most recent large‐scale deposition of ice on Mercury must have occurred no more than 200 Myr ago. We also find that gardening mixes incremental layers of ice with underlying regolith and prevents the growth of pure ice deposits by continuous supply. We conclude that ice deposits on the Moon and Mercury are likely the result of sudden and voluminous deposition.
Is Past Variability a Suitable Proxy for Future Change? A Virtual Catchment Experiment
Authors: Stephens C.M. , Marshall L.A. , Johnson F.M. , Lin L. , Band L.E. , Ajami H. 
Published: February 2020

AbstractTo estimate the robustness of hydrologic models under projected future climate change, researchers test transferability between climatically contrasting observed periods. This approach can only assess the performance changes induced by altered precipitation and related environmental dynamics (e.g., greening under wet conditions), since the instrumental record does not contain temperatures or carbon dioxide levels that are similar to future climate change projections. Additionally, there is an inherent assumption that long‐term persistence of changes in precipitation will not further impact catchment response. In this study, we undertake a series of virtual catchment experiments using an ecohydrologic model that simulates dynamic vegetation growth, nutrient cycling, and subsurface hydrology. These experiments explore a number of climate change scenarios. We compare simulations based on persistent altered climate states against simulations designed to represent historical periods with the same precipitation but limited time for ecohydrologic adaptation. We find that persistence of precipitation changes as well as increased temperature and elevated carbon dioxide levels can all substantially impact streamflow under drier future conditions. For wetter future scenarios, simulated differences in the flow regime were smaller, but there was still notable divergence in modeled low flows and other hydrologic variables. The results suggest that historical periods with equivalent precipitation statistics cannot necessarily be used as proxies for future climate change when examining catchment runoff response and/or model performance. The current literature likely underestimates the potential for nonstationarity in hydrologic assessments, especially for drier future scenarios.
Targeting cancer stem cell pathways for cancer therapy
Authors: Yang Liqun , Shi Pengfei , Zhao Gaichao , Xu Jie , Peng Wen , Zhang Jiayi , Zhang Guanghui , Wang Xiaowen , Dong Zhen , Chen Fei , Cui Hongjuan 
Published: February 2020

AbstractSince cancer stem cells (CSCs) were first identified in leukemia in 1994, they have been considered promising therapeutic targets for cancer therapy. These cells have self-renewal capacity and differentiation potential and contribute to multiple tumor malignancies, such as recurrence, metastasis, heterogeneity, multidrug resistance, and radiation resistance. The biological activities of CSCs are regulated by several pluripotent transcription factors, such as OCT4, Sox2, Nanog, KLF4, and MYC. In addition, many intracellular signaling pathways, such as Wnt, NF-κB (nuclear factor-κB), Notch, Hedgehog, JAK-STAT (Janus kinase/signal transducers and activators of transcription), PI3K/AKT/mTOR (phosphoinositide 3-kinase/AKT/mammalian target of rapamycin), TGF (transforming growth factor)/SMAD, and PPAR (peroxisome proliferator-activated receptor), as well as extracellular factors, such as vascular niches, hypoxia, tumor-associated macrophages, cancer-associated fibroblasts, cancer-associated mesenchymal stem cells, extracellular matrix, and exosomes, have been shown to be very important regulators of CSCs. Molecules, vaccines, antibodies, and CAR-T (chimeric antigen receptor T cell) cells have been developed to specifically target CSCs, and some of these factors are already undergoing clinical trials. This review summarizes the characterization and identification of CSCs, depicts major factors and pathways that regulate CSC development, and discusses potential targeted therapy for CSCs.
Acetylation of XPF by TIP60 facilitates XPF-ERCC1 complex assembly and activation
Authors: Wang Jiajia , He Hanqing , Chen Binbin , Jiang Guixing , Cao Liping , Jiang Haiping , Zhang Guofei , Chen Jianxiang , Huang Jun , Yang Bing , Zhou Chun , Liu Ting 
Published: February 2020

AbstractThe XPF-ERCC1 heterodimer is a structure-specific endonuclease that is essential for nucleotide excision repair (NER) and interstrand crosslink (ICL) repair in mammalian cells. However, whether and how XPF binding to ERCC1 is regulated has not yet been established. Here, we show that TIP60, also known as KAT5, a haplo-insufficient tumor suppressor, directly acetylates XPF at Lys911 following UV irradiation or treatment with mitomycin C and that this acetylation is required for XPF-ERCC1 complex assembly and subsequent activation. Mechanistically, acetylation of XPF at Lys911 disrupts the Glu907-Lys911 salt bridge, thereby leading to exposure of a previously unidentified second binding site for ERCC1. Accordingly, loss of XPF acetylation impairs the damage-induced XPF-ERCC1 interaction, resulting in defects in both NER and ICL repair. Our results not only reveal a mechanism that regulates XPF-ERCC1 complex assembly and activation, but also provide important insight into the role of TIP60 in the maintenance of genome stability.
Glycan repositioning of influenza hemagglutinin stem facilitates the elicitation of protective cross-group antibody responses
Authors: Boyoglu-Barnum Seyhan , Hutchinson Geoffrey B. , Boyington Jeffrey C. , Moin Syed M. , Gillespie Rebecca A. , Tsybovsky Yaroslav , Stephens Tyler , Vaile John R. , Lederhofer Julia , Corbett Kizzmekia S. , Fisher Brian E. , Yassine Hadi M. , Andrews Sarah F. , Crank Michelle C. , McDermott Adrian B. , Mascola John R. , Graham Barney S. , Kanekiyo Masaru 
Published: February 2020

AbstractThe conserved hemagglutinin (HA) stem has been a focus of universal influenza vaccine efforts. Influenza A group 1 HA stem-nanoparticles have been demonstrated to confer heterosubtypic protection in animals; however, the protection does not extend to group 2 viruses, due in part to differences in glycosylation between group 1 and 2 stems. Here, we show that introducing the group 2 glycan at Asn38HA1 to a group 1 stem-nanoparticle (gN38 variant) based on A/New Caledonia/20/99 (H1N1) broadens antibody responses to cross-react with group 2 HAs. Immunoglobulins elicited by the gN38 variant provide complete protection against group 2 H7N9 virus infection, while the variant loses protection against a group 1 H5N1 virus. The N38HA1 glycan thus is pivotal in directing antibody responses by controlling access to group-determining stem epitopes. Precise targeting of stem-directed antibody responses to the site of vulnerability by glycan repositioning may be a step towards achieving cross-group influenza protection.
Statin-induced myopathic changes in primary human muscle cells and reversal by a prostaglandin F2 alpha analogue
Authors: Grunwald Stefanie Anke , Popp Oliver , Haafke Stefanie , Jedraszczak Nicole , Grieben Ulrike , Saar Kathrin , Patone Giannino , Kress Wolfram , Steinhagen-Thiessen Elisabeth , Dittmar Gunnar , Spuler Simone 
Published: February 2020

AbstractStatin-related muscle side effects are a constant healthcare problem since patient compliance is dependent on side effects. Statins reduce plasma cholesterol levels and can prevent secondary cardiovascular diseases. Although statin-induced muscle damage has been studied, preventive or curative therapies are yet to be reported. We exposed primary human muscle cell populations (n = 22) to a lipophilic (simvastatin) and a hydrophilic (rosuvastatin) statin and analyzed their expressome. Data and pathway analyses included GOrilla, Reactome and DAVID. We measured mevalonate intracellularly and analyzed eicosanoid profiles secreted by human muscle cells. Functional assays included proliferation and differentiation quantification. More than 1800 transcripts and 900 proteins were differentially expressed after exposure to statins. Simvastatin had a stronger effect on the expressome than rosuvastatin, but both statins influenced cholesterol biosynthesis, fatty acid metabolism, eicosanoid synthesis, proliferation, and differentiation of human muscle cells. Cultured human muscle cells secreted ω-3 and ω-6 derived eicosanoids and prostaglandins. The ω-6 derived metabolites were found at higher levels secreted from simvastatin-treated primary human muscle cells. Eicosanoids rescued muscle cell differentiation. Our data suggest a new aspect on the role of skeletal muscle in cholesterol metabolism. For clinical practice, the addition of omega-n fatty acids might be suitable to prevent or treat statin-myopathy.
Plasma FABP4 is associated with liver disease recovery during treatment-induced clearance of chronic HCV infection
Authors: Gorin Jean-Baptiste , Malone David F. G. , Strunz Benedikt , Carlsson Tony , Aleman Soo , Björkström Niklas K. , Falconer Karolin , Sandberg Johan K. 
Published: February 2020

AbstractDirect-acting antivirals (DAAs) have dramatically improved the management of chronic hepatitis C (CHC). In this study, we investigated the effects of hepatitis C virus clearance on markers of systemic inflammation measured in plasma samples from CHC patients before, during and after DAA therapy. We identified a plasma soluble protein profile associated with CHC. Successful DAA therapy rapidly normalised the plasma inflammatory milieu, with the notable exception of soluble (s)CD163, a marker of macrophage activation, which remained elevated after viral clearance and segregated patients with high and low levels of cirrhosis. Patients who received DAA in combination with Ribavirin maintained elevated levels of CXCL10, consistent with an immune-stimulatory role of Ribavirin. As anticipated, DAA-treated patients experienced durable improvement in liver fibrosis measurements. Interestingly, pre-treatment levels of fatty acid-binding protein 4 (FABP4) were inversely associated with reduction of APRI and FIB-4 scores during treatment. Together, these results support the notion of a rapid restoration of many aspects of the inflammatory state in CHC patients in response to DAA therapy. Furthermore, the associations with sCD163 and FABP4 warrant further investigation into the role of macrophages in residual liver disease and fibrosis resolution after viral clearance.
Assembly and Folding Properties of Cytosolic IgG Intrabodies
Authors: Seo Youngsil , Lee Yeonjin , Kim Minjae , Park Hyunjoon , Kwon Myung-Hee 
Published: February 2020

AbstractIntrabodies, antibodies expressed within cells, offer an interesting way to target intracellular molecules, making them potentially useful for biotechnology and medicine. However, it remains controversial whether full-size IgG intrabodies expressed in the reducing environment of the cytosol of mammalian cells are workable and structurally sound. Herein, we settle this issue with a systematic investigation of the structure and functionality of four chimeric IgG1s with distinct variable (V) domains but identical constant (C) domains. Full-size IgGs expressed in the cytosol of HEK293 cells were either assembly-competent or -incompetent, depending on the intrinsic properties of the V regions. Structural integrity of the C region is required for H:L association and the formation of a functional antigen-binding site. Partial intrachain disulfide bond formation occurs in both H and L chains of cytosolic IgG intrabodies, whereas interchain disulfide bond formation was absent and dispensable for functional assembly. IgG1s expressed in the cytosol and via the ER were shown to assemble differently. Our findings provide insight into the features and possible utilization of full-size IgGs as cytosolic antibodies in biotechnological and medical applications.