bluuebunny/crossref_metadata_2025_split huggingface dataset:
The importance of SHBG and calculated free testosterone for the diagnosis of symptomatic hypogonadism in HIV-infected men: a single-centre real-life experience
Authors: Pezzaioli Letizia Chiara , Quiros-Roldan Eugenia , Paghera Simone , Porcelli Teresa , Maffezzoni Filippo , Delbarba Andrea , Degli Antoni Melania , Cappelli Carlo , Castelli Francesco , Ferlin Alberto 
Published: December 2020

Abstract
Purpose
The prevalence of low testosterone and symptoms of hypogonadism in HIV-infected men is still debated. We aimed to estimate the prevalence and type of hypogonadism in HIV-infected males complaining about sexual symptoms, and to evaluate the role of calculated free testosterone (cFT) vs total testosterone (TT) for diagnosis. Furthermore, we evaluated relationship between sex hormone-binding globulin (SHBG), gonadal status and clinical and virologic parameters.

Methods
We retrospectively evaluated 169 HIV-infected men with sexual symptoms, with TT available. Among them, we selected 94 patients with TT, SHBG, cFT, and luteinizing hormone (LH) available, and classified hypogonadism into overt (low TT and/or low cFT) and compensated (high LH, normal TT and cFT). Comparison was performed by non-parametric Kruskal–Wallis test and Spearman’s correlation was calculated to verify the possible associations.

Results
Overt and compensated hypogonadism were found in 20.2% and 13.8% of patients, respectively. With reliance on TT alone, only 10.6% of patients would have met diagnosis. SHBG values were elevated in one third of patients, and higher in men with compensated hypogonadism. Significant positive correlation was found between SHBG and HIV infection duration, TT and LH.

Conclusion
Only a complete hormonal profile can properly diagnose and classify hypogonadism in HIV-infected men complaining about sexual symptoms. TT alone reliance may lead to half of diagnoses missing, while lack of gonadotropin prevents the identification of compensated hypogonadism. This largely comes from high SHBG, which seems to play a central role in the pathogenesis of hypogonadism in this population.
Keeping Up with the Trends: Analyzing the Dynamics of Online Learning and Hiring Platforms in the Software Programming Domain
Authors: Yazdanian Ramtin , West Robert , Dillenbourg Pierre 
Published: December 2020

AbstractThe Fourth Industrial Revolution has considerably sped up the pace of skill changes in many professional domains, with scores of new skills emerging and many old skills moving towards obsolescence. For these domains, identifying the new necessary skills in a timely manner is a difficult task, where existing methods are inadequate. Understanding the process, by which these new skills and technologies appear in and diffuse through a professional domain, could give training providers more time to identify these new skills and react. For this purpose, in the present work, we look at the dynamics between online learning platforms and online hiring platforms in the software programming profession, a rapidly evolving domain. To do so, we fuse four data sources together: Stack Overflow, an online community questions and answers (Q&A) platform; Google Trends, which provides online search trends from Google; Udemy, a platform offering skill-based Massively Open Online Courses (MOOCs) where anyone can create courses; and Stack Overflow Jobs, a job ad platform. We place these platforms along two axes: i) how much expertise it takes, on average, to create content on them, and ii) whether, in general, the decision to create content on them is made by individuals or by groups. Our results show that the topics under study have a systematic tendency to appear earlier on platforms where content creation requires (on average) less expertise and is done more individually, rather than by groups: Stack Overflow is found to be more agile than Udemy, which is itself more agile than Stack Overflow Jobs (Google Trends did not prove usable due to extreme data sparsity). However, our results also show that this tendency is not present for all new skills, and that the software programming profession as a whole is remarkably agile: there are usually only a few months between the first Stack Overflow appearance of a new topic, and its first appearance on Udemy or Stack Overflow Jobs. In addition, we find that Udemy’s agility has dramatically increased over time. Our novel methodology is able to provide valuable insights into the dynamics between online education and job ad platforms, enabling training program creators to look at said dynamics for various topics and to understand the pace of change. This allows them to maintain better awareness of the trends and to prioritize their attention, both on the right topics and on the right platforms.
Effects of dual networks on tax strategies: geography and transaction
Authors: Itoh Ryo , Li Zonghui 
Published: December 2020

AbstractThis study investigates how a revenue-maximizing tax strategy of local and central governments incorporates dual networks, namely, an inter-firm transaction network and an inter-country geography network. We assume a two-stage game in which governments propose discriminatory tax levels for firms, whereas each firm has an incentive to invest in a country near the foreign branch office of its transaction partner. In our model, the centrality index of the Kronecker product of the two networks describes the interplay among the location choices and tax strategies in the equilibrium. A stronger linkage within each network generally increases demand for investment and in turn raises overall tax levels to exploit the high demand. Although more central firms in the inter-firm network are likely to be levied higher taxes because of their high demand for investment, firms in the highest tax bracket differ among countries depending on their geographical location. Finally, we show that a uniform tax in which firms are not discriminated and networks do not matter is the socially optimal tax, which incorporates all inter-country externalities. We also investigate decentralized tax strategies based on the rule of non-discriminatory (uniform) taxation and show, by comparing social welfare under discriminatory and uniform tax regimes, that restricting tax discrimination improves social welfare.
Vascular Necrosis of the Upper Extremity After Self-Treatment for Peyronie's Disease
Authors: Yang David , Savage Joshua , Köhler Tobias , Helo Sevann , Trost Landon , Ziegelmann Matthew 
Published: December 2020

Abstract

Peyronie's disease (PD) is associated with significant psychosocial distress, including anxiety, depression, and negative effects on interpersonal relationships. We report outcomes in a patient who researched an enzymatic supplement intended for oral administration for treatment of PD and subsequently self-injected it intravascularly. The enzyme, a combination of serrapeptase and nattokinase, resulted in vascular necrosis of the upper extremity. Despite attempts to salvage the limb, he ultimately required transhumeral amputation. Although extreme, this case illustrates the potential risks of non–Food and Drug Administration–approved therapies, the significant psychosocial impact that PD can have on patients' emotional well-being, and the extent to which some may go to seek treatment.
Yang D, Savage J, Kohler T, et al. Vascular Necrosis of the Upper Extremity After Self-Treatment for Peyronie's Disease. Sex Med 2021;9:100282.
Transcriptomic Profiling of Human Pluripotent Stem Cell-Derived Retinal Pigment Epithelium over Time
Authors: Lidgerwood Grace E. , Senabouth Anne , Smith-Anttila Casey J.A. , Gnanasambandapillai Vikkitharan , Kaczorowski Dominik C. , Amann-Zalcenstein Daniela , Fletcher Erica L. , Naik Shalin H. , Hewitt Alex W. , Powell Joseph E. , Pébay Alice 
Published: December 2020

Abstract
Human pluripotent stem cell (hPSC)-derived progenies are immature versions of cells, presenting a potential limitation to the accurate modelling of diseases associated with maturity or age. Hence, it is important to characterise how closely cells used in culture resemble their native counterparts. In order to select appropriate time points of retinal pigment epithelium (RPE) cultures that reflect native counterparts, we characterised the transcriptomic profiles of the hPSC-derived RPE cells from 1- and 12-month cultures. We differentiated the human embryonic stem cell line H9 into RPE cells, performed single-cell RNA-sequencing of a total of 16,576 cells to assess the molecular changes of the RPE cells across these two culture time points. Our results indicate the stability of the RPE transcriptomic signature, with no evidence of an epithelial–mesenchymal transition, and with the maturing populations of the RPE observed with time in culture. Assessment of Gene Ontology pathways revealed that as the cultures age, RPE cells upregulate expression of genes involved in metal binding and antioxidant functions. This might reflect an increased ability to handle oxidative stress as cells mature. Comparison with native human RPE data confirms a maturing transcriptional profile of RPE cells in culture. These results suggest that long-term in vitro culture of RPE cells allows the modelling of specific phenotypes observed in native mature tissues. Our work highlights the transcriptional landscape of hPSC-derived RPE cells as they age in culture, which provides a reference for native and patient samples to be benchmarked against.
Probability and Consequence of Postfire Erosion for Treatability of Water in an Unfiltered Supply System
Authors: Nyman Petter , Yeates Peter , Langhans Christoph , Noske Philip J. , Peleg Nadav , Schärer Christine , Lane Patrick N. J. , Haydon Shane , Sheridan Gary J. 
Published: December 2020

AbstractForested catchments are critical to water supply in major cities. Many of these catchments face the threat of postwildfire erosion, which can contaminate reservoir water. The aim of this paper is to determine the probability and duration of disruptions to treatability due to runoff‐generated debris flows in the first year after a wildfire, before substantial vegetation recovery takes place. We combine models of reservoir hydrodynamics, postfire erosion, and stochastic rainfall to determine probability and magnitude of sediment concentration at the reservoir water offtake. Central to the paper is our technique for linking model components into a risk framework that gives probabilities to the number of days that the turbidity threshold for treatment is exceeded. The model is applied to the Upper Yarra reservoir, which is the linchpin of the water supply system for Melbourne in SE Australia. However, the framework is applicable to other unfiltered water supply systems where suspended sediment is a risk to treatability. Results show that postwildfire erosion poses a substantial threat, with a relatively high probability (annual exceedance probability = 0.1–0.3) of water being untreatable for >1 year following a high‐severity wildfire. Important factors that influence the risk include postwildfire runoff potential, reservoir temperature, and the amount of clay‐sized grains in eroding headwaters. Assumptions about spatial‐temporal rainfall attributes, reservoir hydrodynamics, and the catchment erosion potential are all important sources of error in our estimate of risk. Our approach to risk quantification will help support planning, risk management, and strategic investment to mitigate impacts.
Contribution of the Northeast Cold Vortex Index and Multiscale Synergistic Indices to Extreme Precipitation Over Northeast China
Authors: Wu Xianghua , Meng Fangxiu , Liu Peng , Zhou Jieqin , Liu Duanyang , Xie Kang , Zhu Qihao , Hu Jingbiao , Sun Haiyan , Xing Fengjuan 
Published: December 2020

AbstractThe northeast cold vortex (NECV) is one of the major synoptic systems affecting Northeast China. The activity of NECV is an important reason for severe convective storms. However, research on extreme precipitation over Northeast China and their associations with the northeast cold vortex index (NECVI) is limited. Based on nonstationary generalized extreme value models, we analyze and quantify the contribution of the NECVI and the multiscale synergistic indices. Then, we verify the necessity of the NECVI by the likelihood ratio test and the blank control experiment, and further verify the impact of the NECVI on the extreme precipitation over Northeast China in combination with the climate index atmospheric circulation analysis. Results suggest that the models established with East Asian summer monsoon index, Southern Oscillation Index, and NINO3.4 index as covariates the most common. The NECVI and the synergies also make significant contribution and have passed the likelihood ratio test at 80% confidence. Especially in late summer, accounting for 18.69% of the 10 selected best models and 29.41% of the nine selected best nonstationary models. Based on the blank experiments, the models with the NECVI have a maximum reduction of 4.72% than those without the NECVI in the Akaike information criterion values in late summer. In early summer and late summer, the center of the high values of the water vapor anomaly is mainly located in southwestern in the strong NECVI years. These findings help to understand the genetic mechanism of extreme precipitation over Northeast China and provide reference for risk management.
Synergies Among Environmental Science Research and Monitoring Networks: A Research Agenda
Authors: Jones J. A. , Groffman P. M. , Blair J. , Davis F. W. , Dugan H. , Euskirchen E. E. , Frey S. D. , Harms T. K. , Hinckley E. , Kosmala M. , Loberg S. , Malone S. , Novick K. , Record S. , Rocha A. V. , Ruddell B. L. , Stanley E. H. , Sturtevant C. , Thorpe A. , White T. , Wieder W. R. , Zhai L. , Zhu K. 
Published: December 2020

AbstractMany research and monitoring networks in recent decades have provided publicly available data documenting environmental and ecological change, but little is known about the status of efforts to synthesize this information across networks. We convened a working group to assess ongoing and potential cross‐network synthesis research and outline opportunities and challenges for the future, focusing on the US‐based research network (the US Long‐Term Ecological Research network, LTER) and monitoring network (the National Ecological Observatory Network, NEON). LTER‐NEON cross‐network research synergies arise from the potentials for LTER measurements, experiments, models, and observational studies to provide context and mechanisms for interpreting NEON data, and for NEON measurements to provide standardization and broad scale coverage that complement LTER studies. Initial cross‐network syntheses at co‐located sites in the LTER and NEON networks are addressing six broad topics: how long‐term vegetation change influences C fluxes; how detailed remotely sensed data reveal vegetation structure and function; aquatic‐terrestrial connections of nutrient cycling; ecosystem response to soil biogeochemistry and microbial processes; population and species responses to environmental change; and disturbance, stability and resilience. This initial study offers exciting potentials for expanded cross‐network syntheses involving multiple long‐term ecosystem processes at regional or continental scales. These potential syntheses could provide a pathway for the broader scientific community, beyond LTER and NEON, to engage in cross‐network science. These examples also apply to many other research and monitoring networks in the US and globally, and can guide scientists and research administrators in promoting broad‐scale research that supports resource management and environmental policy.
Impact of Quasi‐Idealized Future Land Cover Scenarios at High Latitudes in Complex Terrain
Authors: Mooney P. A. , Lee H. , Sobolowski S. 
Published: December 2020

AbstractAfforestation is gaining popularity as a climate mitigation policy in many countries, including high latitude regions such as Norway. However, the impacts of afforestation on local‐to‐regional climate is poorly understood. This study uses the Weather Research and Forecasting model to investigate the biogeophysical impacts of different forestry scenarios on the local‐to‐regional climate of Norway. The forestry scenarios considered are the conversion of open spaces to either evergreen forest by active afforestation or to mixed forest by natural succession. Results show both forestry scenarios lead to additional warming of surface temperatures in winter and spring (between 1.0°C and 1.5°C) and cooling in summer (between −1.6°C and −1.3°C). A temperature decomposition analysis shows that the warming in winter and spring is driven by surface albedo changes while summer cooling is driven by changes in sensible heat fluxes for afforestation and surface albedo for natural succession. Maximum 2 m air temperature increases considerably in spring in both forestry scenarios (∼0.8°C to 1.0°C). Analysis of precipitation, multiple climate indices and extremes, reveal little or no response to the different forestry scenarios. The largest societally relevant response to the forestry scenarios is the partial mitigation of the reduction in snow days expected from global warming by 10–20 days. This suggests that implementing current afforestation policies for climate mitigation in Norway may adversely exacerbate some effects of global warming locally while mitigating others. As such, the impacts of afforestation on the local‐to‐regional climate at high latitudes are complex and cannot support or dismiss afforestation as a climate mitigation policy.
Dynamics of Fungal and Bacterial Biomass Carbon in Natural Ecosystems: Site‐Level Applications of the CLM‐Microbe Model
Authors: He Liyuan , Lipson David A. , Mazza Rodrigues Jorge L. , Mayes Melanie , Björk Robert G. , Glaser Bruno , Thornton Peter , Xu Xiaofeng 
Published: December 2020

AbstractExplicitly representing microbial processes has been recognized as a key improvement to Earth system models for the realistic projections of soil carbon (C) and climate dynamics. The CLM‐Microbe model builds upon the CLM4.5 and explicitly represents two major soil microbial groups, fungi and bacteria. Based on the compiled time‐series data of fungal (FBC) and bacterial (BBC) biomass C from nine biomes, we parameterized and validated the CLM‐Microbe model, and further conducted sensitivity and uncertainty analysis for simulating C cycling. The model performance was evaluated with mean absolute error (MAE), root mean square error (RMSE), and coefficient of determination (R2) for relative change in FBC and BBC. The CLM‐Microbe model is able to reasonably capture the seasonal dynamics of FBC and BBC across biomes, particularly for tropical/subtropical forest, temperate broadleaf forest, and grassland, with MAE <0.49 for FBC and <0.36 for BBC and RMSE <0.52 FBC and <0.39 for BBC, while R2 values are relatively smaller in some biomes (e.g., shrub) due to small sample sizes. We found good consistencies between simulated and observed FBC (R2 = 0.70, P < 0.001) and BBC (R2 = 0.26, P < 0.05) on average across biomes, but the model is not able to fully capture the large variation in observed FBC and BBC. Sensitivity analysis shows that the most critical parameters are turnover rate and carbon‐to‐nitrogen ratio of fungi and bacteria and microbial assimilation efficiency. This study confirms that the explicit representation of soil microbial mechanisms enhances model performance in simulating C variables such as heterotrophic respiration and soil organic C density. The further application of the CLM‐Microbe model would deepen our understanding of microbial contributions to global C cycle.
CRISPR/Cas9-engineered Gad1 elimination in rats leads to complex behavioral changes: implications for schizophrenia
Authors: Fujihara Kazuyuki , Yamada Kazuo , Ichitani Yukio , Kakizaki Toshikazu , Jiang Weiru , Miyata Shigeo , Suto Takashi , Kato Daiki , Saito Shigeru , Watanabe Masahiko , Kajita Yuki , Ohshiro Tomokazu , Mushiake Hajime , Miyasaka Yoshiki , Mashimo Tomoji , Yasuda Hiroki , Yanagawa Yuchio 
Published: December 2020

AbstractGABAergic dysfunctions have been implicated in the pathogenesis of schizophrenia, especially the associated cognitive impairments. The GABA synthetic enzyme glutamate decarboxylase 67-kDa isoform (GAD67) encoded by the GAD1 gene is downregulated in the brains of patients with schizophrenia. Furthermore, a patient with schizophrenia harboring a homozygous mutation of GAD1 has recently been discovered. However, it remains unclear whether loss of function of GAD1 leads to the symptoms observed in schizophrenia, including cognitive impairment. One of the obstacles faced in experimental studies to address this issue is the perinatal lethality of Gad1 knockout (KO) mice, which precluded characterization at the adult stage. In the present study, we successfully generated Gad1 KO rats using CRISPR/Cas9 genome editing technology. Surprisingly, 33% of Gad1 KO rats survived to adulthood and could be subjected to further characterization. The GABA concentration in the Gad1 KO cerebrum was reduced to ~52% of the level in wild-type rats. Gad1 KO rats exhibited impairments in both spatial reference and working memory without affecting adult neurogenesis in the hippocampus. In addition, Gad1 KO rats showed a wide range of behavioral alterations, such as enhanced sensitivity to an NMDA receptor antagonist, hypoactivity in a novel environment, and decreased preference for social novelty. Taken together, the results suggest that Gad1 KO rats could provide a novel model covering not only cognitive deficits but also other aspects of the disorder. Furthermore, the present study teaches an important lesson: differences between species should be considered when developing animal models of human diseases.
Beyond chemoradiotherapy: improving treatment outcomes for patients with stage III unresectable non-small-cell lung cancer through immuno-oncology and durvalumab (Imfinzi®▼, AstraZeneca UK Limited)
Authors:   on behalf of AstraZeneca UK Limited, Patel Priyanka , Alrifai Doraid , McDonald Fiona , Forster Martin 
Published: December 2020

AbstractThe treatment paradigm of non-small-cell lung cancer (NSCLC) has rapidly changed in recent years following the introduction of immune-checkpoint inhibition (ICI). Pre-clinically, both chemotherapy and radiotherapy modulate the tumour microenvironment, providing the rationale for clinical trials evaluating their role in combination with immunotherapy. Standard-of-care treatment for patients with unresectable stage III disease is concurrent chemoradiotherapy (cCRT); however, only recently, the combination with ICI has been explored. The Phase 3 PACIFIC study randomised 713 patients with confirmed locally advanced, unresectable, stage III NSCLC, whose disease has not progressed following cCRT, to either the anti-programmed death-ligand 1 (PD-L1) agent durvalumab (Imfinzi®▼, AstraZeneca UK Limited) or placebo. Patients with a PD-L1 status ≥1% treated with durvalumab had a significantly longer median progression-free survival compared with placebo (17.2 vs. 5.6 months, respectively; HR: 0.51; 95% CI: 0.41–0.63), prolonged median overall survival (OS) (NR vs. 28.7 months, respectively; HR: 0.68; 99.73% CI: 0.47–0.997;P = 0.0025) and long-term clinical benefit (3-year OS HR: 0.69; 95% CI: 0.55–0.86). Grade 3 or 4 toxicity was marginally greater in the durvalumab cohort versus placebo (30.5% vs. 26.1%). Based on these results, durvalumab has been licensed in this setting, and further clinical trials are exploring the use of ICI in unresectable stage III NSCLC.