bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival outcomes in patients with chemotherapy-naive metastatic castration-resistant prostate cancer treated with enzalutamide or abiraterone acetate
Authors: Tagawa Scott T. , Ramaswamy Krishnan , Huang Ahong , Mardekian Jack , Schultz Neil M. , Wang Li , Sandin Rickard , Lechpammer Stanislav , George Daniel J. 
Published: February 2021

Abstract
Objective
Evaluation of the comparative effectiveness of enzalutamide and abiraterone in patients with metastatic castration-resistant prostate cancer (mCRPC) is limited to meta-analyses of randomized trials that exclude patients with significant comorbidities. We evaluated overall survival (OS) in patients with chemotherapy-naive mCRPC treated with enzalutamide or abiraterone acetate (abiraterone) in a real-world single payer setting.

Methods
A retrospective analysis (4/1/2014–3/31/2018) of the Veterans Health Administration (VHA) database was conducted. Patients with mCRPC had ≥1 pharmacy claim for enzalutamide or abiraterone (first claim date = index date) following disease progression on surgical/medical castration, without chemotherapy <12 months prior to index date. Patients had continuous VHA enrollment for ≥12 months pre-index date and were followed until death, disenrollment, or end of study. Kaplan–Meier analysis and multivariable Cox proportional hazards regression models examined the OS treatment effect.

Results
Patients with chemotherapy-naive mCRPC (N = 3174; enzalutamide, n = 1229; abiraterone, n = 1945) had mean ages of 74 and 73 years, respectively. Median follow-up was 18.27 and 19.07 months with enzalutamide and abiraterone, respectively. Enzalutamide-treated patients had longer median treatment duration than abiraterone-treated patients (9.93 vs 8.47 months, respectively, p = 0.0008). After baseline comorbidity adjustment, enzalutamide-treated patients had a 16% reduced risk of death (hazard ratio [HR] = 0.84; 95% CI, 0.76–0.94; p = 0.0012). For patients who remained on first line-therapy only, enzalutamide-treated patients had improved OS versus abiraterone-treated patients (HR = 0.71; 95% CI, 0.62–0.82). Enzalutamide-treated patients who crossed over to abiraterone had a comparable risk of death versus abiraterone-treated patients who crossed over to enzalutamide (HR = 1.10; 95% CI, 0.89–1.35). These results were confirmed by sensitivity analysis, which considered prognostic variables.

Conclusions
Retrospective analysis of the VHA database indicated that chemotherapy-naive patients with mCRPC initiating therapy with enzalutamide had improved survival versus abiraterone.
The first Conus genome assembly reveals a primary genetic central dogma of conopeptides in C. betulinus
Authors: Peng Chao , Huang Yu , Bian Chao , Li Jia , Liu Jie , Zhang Kai , You Xinxin , Lin Zhilong , He Yanbin , Chen Jieming , Lv Yunyun , Ruan Zhiqiang , Zhang Xinhui , Yi Yunhai , Li Yanping , Lin Xueqiang , Gu Ruobo , Xu Junmin , Yang Jia’an , Fan Chongxu , Yao Ge , Chen Ji-Sheng , Jiang Hui , Gao Bingmiao , Shi Qiong 
Published: February 2021

AbstractAlthough there are various Conus species with publicly available transcriptome and proteome data, no genome assembly has been reported yet. Here, using Chinese tubular cone snail (C. betulinus) as a representative, we sequenced and assembled the first Conus genome with original identification of 133 genome-widely distributed conopeptide genes. After integration of our genomics, transcriptomics, and peptidomics data in the same species, we established a primary genetic central dogma of diverse conopeptides, assuming a rough number ratio of ~1:1:1:10s for the total genes: transcripts: proteins: post-translationally modified peptides. This ratio may be special for this worm-hunting Conus species, due to the high diversity of various Conus genomes and the big number ranges of conopeptide genes, transcripts, and peptides in previous reports of diverse Conus species. Only a fraction (45.9%) of the identified conotopeptide genes from our achieved genome assembly are transcribed with transcriptomic evidence, and few genes individually correspond to multiple transcripts possibly due to intraspecies or mutation-based variances. Variable peptide processing at the proteomic level, generating a big diversity of venom conopeptides with alternative cleavage sites, post-translational modifications, and N-/C-terminal truncations, may explain how the 133 genes and ~123 transcripts can generate thousands of conopeptides in the venom of individual C. betulinus. We also predicted many conopeptides with high stereostructural similarities to the putative analgesic ω-MVIIA, addiction therapy AuIB and insecticide ImI, suggesting that our current genome assembly for C. betulinus is a valuable genetic resource for high-throughput prediction and development of potential pharmaceuticals.
Widespread increase in dynamic imbalance in the Getz region of Antarctica from 1994 to 2018
Authors: Selley Heather L. , Hogg Anna E. , Cornford Stephen , Dutrieux Pierre , Shepherd Andrew , Wuite Jan , Floricioiu Dana , Kusk Anders , Nagler Thomas , Gilbert Lin , Slater Thomas , Kim Tae-Wan 
Published: February 2021

AbstractThe Getz region of West Antarctica is losing ice at an increasing rate; however, the forcing mechanisms remain unclear. Here we use satellite observations and an ice sheet model to measure the change in ice speed and mass balance of the drainage basin over the last 25-years. Our results show a mean increase in speed of 23.8 % between 1994 and 2018, with three glaciers accelerating by over 44 %. Speedup across the Getz basin is linear, with speedup and thinning directly correlated confirming the presence of dynamic imbalance. Since 1994, 315 Gt of ice has been lost contributing 0.9 ± 0.6 mm global mean sea level, with increased loss since 2010 caused by a snowfall reduction. Overall, dynamic imbalance accounts for two thirds of the mass loss from this region of West Antarctica over the past 25-years, with a longer-term response to ocean forcing the likely driving mechanism.
Emergent vulnerability to climate-driven disturbances in European forests
Authors: Forzieri Giovanni , Girardello Marco , Ceccherini Guido , Spinoni Jonathan , Feyen Luc , Hartmann Henrik , Beck Pieter S. A. , Camps-Valls Gustau , Chirici Gherado , Mauri Achille , Cescatti Alessandro 
Published: February 2021

AbstractForest disturbance regimes are expected to intensify as Earth’s climate changes. Quantifying forest vulnerability to disturbances and understanding the underlying mechanisms is crucial to develop mitigation and adaptation strategies. However, observational evidence is largely missing at regional to continental scales. Here, we quantify the vulnerability of European forests to fires, windthrows and insect outbreaks during the period 1979–2018 by integrating machine learning with disturbance data and satellite products. We show that about 33.4 billion tonnes of forest biomass could be seriously affected by these disturbances, with higher relative losses when exposed to windthrows (40%) and fires (34%) compared to insect outbreaks (26%). The spatial pattern in vulnerability is strongly controlled by the interplay between forest characteristics and background climate. Hotspot regions for vulnerability are located at the borders of the climate envelope, in both southern and northern Europe. There is a clear trend in overall forest vulnerability that is driven by a warming-induced reduction in plant defence mechanisms to insect outbreaks, especially at high latitudes.
Global irrigation contribution to wheat and maize yield
Authors: Wang Xuhui , Müller Christoph , Elliot Joshua , Mueller Nathaniel D. , Ciais Philippe , Jägermeyr Jonas , Gerber James , Dumas Patrice , Wang Chenzhi , Yang Hui , Li Laurent , Deryng Delphine , Folberth Christian , Liu Wenfeng , Makowski David , Olin Stefan , Pugh Thomas A. M. , Reddy Ashwan , Schmid Erwin , Jeong Sujong , Zhou Feng , Piao Shilong 
Published: February 2021

AbstractIrrigation is the largest sector of human water use and an important option for increasing crop production and reducing drought impacts. However, the potential for irrigation to contribute to global crop yields remains uncertain. Here, we quantify this contribution for wheat and maize at global scale by developing a Bayesian framework integrating empirical estimates and gridded global crop models on new maps of the relative difference between attainable rainfed and irrigated yield (ΔY). At global scale, ΔY is 34 ± 9% for wheat and 22 ± 13% for maize, with large spatial differences driven more by patterns of precipitation than that of evaporative demand. Comparing irrigation demands with renewable water supply, we find 30–47% of contemporary rainfed agriculture of wheat and maize cannot achieve yield gap closure utilizing current river discharge, unless more water diversion projects are set in place, putting into question the potential of irrigation to mitigate climate change impacts.
Smoothing the energy transfer pathway in quasi-2D perovskite films using methanesulfonate leads to highly efficient light-emitting devices
Authors: Kong Lingmei , Zhang Xiaoyu , Li Yunguo , Wang Haoran , Jiang Yuanzhi , Wang Sheng , You Mengqing , Zhang Chengxi , Zhang Ting , Kershaw Stephen V. , Zheng Weitao , Yang Yingguo , Lin Qianqian , Yuan Mingjian , Rogach Andrey L. , Yang Xuyong 
Published: February 2021

AbstractQuasi-two-dimensional (quasi-2D) Ruddlesden–Popper (RP) perovskites such as BA2Csn–1PbnBr3n+1 (BA = butylammonium, n > 1) are promising emitters, but their electroluminescence performance is limited by a severe non-radiative recombination during the energy transfer process. Here, we make use of methanesulfonate (MeS) that can interact with the spacer BA cations via strong hydrogen bonding interaction to reconstruct the quasi-2D perovskite structure, which increases the energy acceptor-to-donor ratio and enhances the energy transfer in perovskite films, thus improving the light emission efficiency. MeS additives also lower the defect density in RP perovskites, which is due to the elimination of uncoordinated Pb2+ by the electron-rich Lewis base MeS and the weakened adsorbate blocking effect. As a result, green light-emitting diodes fabricated using these quasi-2D RP perovskite films reach current efficiency of 63 cd A−1 and 20.5% external quantum efficiency, which are the best reported performance for devices based on quasi-2D perovskites so far.
Deep learning enhanced individual nuclear-spin detection
Authors: Jung Kyunghoon , Abobeih M. H. , Yun Jiwon , Kim Gyeonghun , Oh Hyunseok , Henry Ang , Taminiau T. H. , Kim Dohun 
Published: February 2021

AbstractThe detection of nuclear spins using individual electron spins has enabled diverse opportunities in quantum sensing and quantum information processing. Proof-of-principle experiments have demonstrated atomic-scale imaging of nuclear-spin samples and controlled multi-qubit registers. However, to image more complex samples and to realize larger-scale quantum processors, computerized methods that efficiently and automatically characterize spin systems are required. Here, we realize a deep learning model for automatic identification of nuclear spins using the electron spin of single nitrogen-vacancy (NV) centers in diamond as a sensor. Based on neural network algorithms, we develop noise recovery procedures and training sequences for highly non-linear spectra. We apply these methods to experimentally demonstrate the fast identification of 31 nuclear spins around a single NV center and accurately determine the hyperfine parameters. Our methods can be extended to larger spin systems and are applicable to a wide range of electron-nuclear interaction strengths. These results pave the way towards efficient imaging of complex spin samples and automatic characterization of large spin-qubit registers.
Comparing different approaches for operationalizing subjective cognitive decline: impact on syndromic and biomarker profiles
Authors: Diaz-Galvan Patricia , Ferreira Daniel , Cedres Nira , Falahati Farshad , Hernández-Cabrera Juan Andrés , Ames David , Barroso Jose , Westman Eric 
Published: February 2021

AbstractSubjective cognitive decline (SCD) has been proposed as a risk factor for future cognitive decline and dementia. Given the heterogeneity of SCD and the lack of consensus about how to classify this condition, different operationalization approaches still need to be compared. In this study, we used the same sample of individuals to compare different SCD operationalization approaches. We included 399 cognitively healthy individuals from a community-based cohort. SCD was assessed through nine questions about memory and non-memory subjective complaints. We applied four approaches to operationalize SCD: two hypothesis-driven approaches and two data-driven approaches. We characterized the resulting groups from each operationalization approach using multivariate methods on comprehensive demographic, clinical, cognitive, and neuroimaging data. We identified two main phenotypes: an amnestic phenotype characterized by an Alzheimer’s Disease (AD) signature pattern of brain atrophy; and an anomic phenotype, which was mainly related to cerebrovascular pathology. Furthermore, language complaints other than naming helped to identify a subgroup with subclinical cognitive impairment and difficulties in activities of daily living. This subgroup also showed an AD signature pattern of atrophy. The identification of SCD phenotypes, characterized by different syndromic and biomarker profiles, varies depending on the operationalization approach used. In this study we discuss how these findings may be used in clinical practice and research.
A multivalent T-antigen-based vaccine for Group A Streptococcus
Authors: Loh Jacelyn M. S. , Rivera-Hernandez Tania , McGregor Reuben , Khemlani Adrina Hema J. , Tay Mei Lin , Cork Amanda J. , M. Raynes Jeremy , Moreland Nicole J. , Walker Mark J. , Proft Thomas 
Published: February 2021

AbstractPili of Group A Streptococcus (GAS) are surface-exposed structures involved in adhesion and colonisation of the host during infection. The major protein component of the GAS pilus is the T-antigen, which multimerises to form the pilus shaft. There are currently no licenced vaccines against GAS infections and the T-antigen represents an attractive target for vaccination. We have generated a multivalent vaccine called TeeVax1, a recombinant protein that consists of a fusion of six T-antigen domains. Vaccination with TeeVax1 produces opsonophagocytic antibodies in rabbits and confers protective efficacy in mice against invasive disease. Two further recombinant proteins, TeeVax2 and TeeVax3 were constructed to cover 12 additional T-antigens. Combining TeeVax1–3 produced a robust antibody response in rabbits that was cross-reactive to a full panel of 21 T-antigens, expected to provide over 95% vaccine coverage. These results demonstrate the potential for a T-antigen-based vaccine to prevent GAS infections.
Identification of two different coagulation phenotypes in people living with HIV with undetectable viral replication
Authors: Fink Asbjørn , Knudsen Andreas Dehlbæk , Thudium Rebekka Faber , Von Stemann Jakob Hjorth , Afzal Shoaib , Lundgren Jens , Kirkegaard-Klitbo Ditte Marie , Ostrowski Sisse Rye , Nordestgaard Børge G. , Nielsen Susanne Dam 
Published: February 2021

AbstractAltered coagulation has been reported in people living with HIV (PLWH) with ongoing viral replication and may predispose to cardiovascular diseases. However, less is known about coagulation in PLWH with undetectable viral replication. In a cross-sectional observational study, we investigated whether HIV infection with undetectable viral replication is independently associated with activated partial thromboplastin time (APTT) and coagulation factor II–VII–X concentrations out of reference. Logistic regression analyses were used to assess the association of HIV infection with APTT and coagulation factor II–VII–X, after adjusting for age, sex, smoking status, alcohol consumption, BMI, diabetes and hsCRP. 936 PLWH with undetectable viral replication from the Copenhagen Co-morbidity in HIV infection study (COCOMO-study) and 2955 uninfected controls were included. Higher prevalence of short APTT was found in PLWH compared to controls (13.5% vs. 7.6%, P < 0.001). Furthermore, higher prevalence of low coagulation factor II–VII–X was found in PLWH than in controls (9.6% vs. 7.4%, P = 0.022). HIV was independently associated with short APTT (adjusted odds ratio (aOR) 2.3 (95% CI 1.7–2.9), P < 0.001) and low coagulation factor II–VII–X (aOR 1.4 (95% CI 1.0–1.9), P = 0.046). Few participants among PLWH and controls had both short APTT and low coagulation factor II–VII–X, 2.1% vs. 0.8%, respectively. We found evidence of both procoagulant (short APTT) and anticoagulant (low coagulation factor II–VII–X) alterations in PLWH with undetectable viral replication, and our findings suggest that two different coagulation phenotypes exist in participants with treated HIV infection.
Evidence of hydrogen trapping at second phase particles in zirconium alloys
Authors: Jones Christopher , Tuli Vidur , Shah Zaheen , Gass Mhairi , Burr Patrick A. , Preuss Michael , Moore Katie L. 
Published: February 2021

AbstractZirconium alloys are used in safety–critical roles in the nuclear industry and their degradation due to ingress of hydrogen in service is a concern. In this work experimental evidence, supported by density functional theory modelling, shows that the α-Zr matrix surrounding second phase particles acts as a trapping site for hydrogen, which has not been previously reported in zirconium. This is unaccounted for in current models of hydrogen behaviour in Zr alloys and as such could impact development of these models. Zircaloy-2 and Zircaloy-4 samples were corroded at 350 °C in simulated pressurised water reactor coolant before being isotopically spiked with 2H2O in a second autoclave step. The distribution of 2H, Fe and Cr was characterised using nanoscale secondary ion mass spectrometry (NanoSIMS) and high-resolution energy dispersive X-ray spectroscopy. 2H− was found to be concentrated around second phase particles in the α-Zr lattice with peak hydrogen isotope ratios of 2H/1H = 0.018–0.082. DFT modelling confirms that the hydrogen thermodynamically favours sitting in the surrounding zirconium matrix rather than within the second phase particles. Knowledge of this trapping mechanism will inform the development of current understanding of zirconium alloy degradation through-life.
Inflammaging markers characteristic of advanced age show similar levels with frailty and dependency
Authors: Alberro Ainhoa , Iribarren-Lopez Andrea , Sáenz-Cuesta Matías , Matheu Ander , Vergara Itziar , Otaegui David 
Published: February 2021

AbstractThe improvement of life quality and medical advances has resulted in increased life expectancy. Despite this, health status commonly worsens in the last years of life. Frailty is an intermediate and reversible state that often precedes dependency and therefore, its identification may be essential to prevent dependency. However, there is no consensus on the best tools to identify frailty. In this sense, diverse molecules have been proposed as potential biomarkers. Some investigations pointed to an increased chronic inflammation or inflammaging with frailty, while others did not report such differences. In this work, we evaluated the circulating concentration of the inflammaging markers in adults and older adults (aged over 70 years) by ELISA and Luminex techniques. The Barthel Index was applied for the evaluation of dependency and Timed up-and-go, Gait Speed, Short Physical Performance Battery, Tilburg Frailty Indicator and Gerontopole Frailty Screening Tool were used for the identification of frailty. CRP, TNF-α, IL-6 and albumin concentrations were measured, and we found that elevated inflammation is present in older adults, while no differences with frailty and dependency were reported. Our results were consistent for all the evaluated frailty scales, highlighting the need to reconsider increased inflammation as a biomarker of frailty.
A cannabidiol-loaded Mg-gallate metal–organic framework-based potential therapeutic for glioblastomas
Authors: Sharma Anu , Kumar Abhishek , Li Changning , Panwar Hazari Puja , Mahajan Supriya D. , Aalinkeel Ravikumar , Sharma Rakesh Kumar , Swihart Mark T. 
Published: February 2021

Anticancer effects of cannabidiol-loaded magnesium-gallate metal–organic framework were studied in a rat glioma cell line, revealing anti-inflammatory responses and triggering of apoptosis, suggesting promise for glioblastoma therapy.
A Cross-Sectional Survey Evaluating Awareness of Congenital Cytomegalovirus Among Audiologists and Speech-Language Pathologists
Authors: Dedhia Kavita , Fifer Robert C. , Muldoon Kathleen M. , Park Albert 
Published: February 2021

Purpose
Congenital cytomegalovirus (cCMV) is the most common congenital infection worldwide and a leading environmental cause of pediatric hearing loss (HL). The objective of this study was to evaluate audiologists and speech-language pathologists (SLPs) on awareness and knowledge of cCMV.

Method
A multiple-choice survey assessing awareness, knowledge, and practice patterns was sent electronically to audiologists and SLPs of the American Speech-Language-Hearing Association. Results were compared between audiologists and SLPs and within stratified groups of audiologists. Data were collected, and descriptive analysis was performed.

Results

Ninety-four audiologists and 317 SLPs responded. Most audiologists were somewhat or very familiar with cCMV (85.9%), while only 26% of SLPs responded that they were at least somewhat familiar with cCMV (
p
< .0001). When comparing audiologists' and SLPs' knowledge of symptoms, transmission, and diagnostic age for cCMV, audiologists had higher scores in all categories (
p
< .0001). Audiologists were then stratified into subgroups to evaluate the association of the given subgroup with their overall knowledge. The more advanced audiology training, the more knowledgeable the respondent was regarding HL progression (
p
= .002). Audiologists who were more familiar with cCMV scored better in most categories compared to those reporting somewhat or less familiar; these findings were only significant for knowledge of symptoms (
p
< .0001). Audiologists who were sometimes or frequently evaluating children less than 5 years of age had a better understanding of HL presentation among cCMV patients than those who rarely saw this patient population. Those who were in practice for < 20 years frequently knew the time-sensitive age of diagnosis than respondents in practice longer.

Conclusions
As a leading environmental cause of pediatric HL, cCMV is frequently encountered by audiologists and SLPs. This study highlights knowledge gaps and areas where targeted education is needed for both groups.