bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sedentary time, physical activity, and serum SPARC in a middle‐aged population
Authors: Nishida Yuichiro , Hara Megumi , Higaki Yasuki , Taguchi Naoto , Nakamura Kazuyo , Nanri Hinako , Imaizumi Takeshi , Sakamoto Tatsuhiko , Shimanoe Chisato , Horita Mikako , Shinchi Koichi , Tanaka Keitaro 
Published: August 2021

ABSTRACTThe influence of habitual physical activity (PA) on the circulating levels of secreted protein acidic and rich in cysteine (SPARC) remains unclear. The purpose of the current study was to clarify the effects of sedentary time, light‐intensity PA (LPA), and moderate‐ to vigorous‐intensity PA (MVPA) on the serum SPARC in a general middle‐aged population. The current study is a cross‐sectional study of 4,000 men and 6,040 women (40–69 years). Sedentary time, LPA, and MVPA were objectively measured by an accelerometer. The serum SPARC concentration was measured by enzyme‐linked immunosorbent assay. Using an isotemporal substitution model, cross‐sectional associations of replacing sedentary time with either LPA or MVPA on serum SPARC levels were analysed according to sex. Interactions with subject characteristics, such as the body mass index (BMI), smoking, and alcohol consumption, were also examined. In men, replacing 60 min of sedentary time with 60 min of MVPA was significantly associated with 23 ng/mL lower serum SPARC levels (confidence interval: −43, −2) after adjusting for confounders, including the BMI (P = 0.028). A significant interaction between replacing sedentary behaviour with LPA and the BMI on SPARC was detected in women (P = 0.029), although the stratified associations for each BMI level (<25 or ≥25 kg/m2) did not reach significance. The current study suggests that replacing sedentary time with MVPA is associated with reduced serum SPARC levels in middle‐aged men, but not in women. In addition, a potential interaction between LPA and the BMI on SPARC was also found in women.Highlights
An isotemporal substitution analysis showed that replacing sedentary behaviour with moderate‐ to vigorous‐intensity physical activity (MVPA) is associated with decreased serum SPARC levels in men.
Such an inverse association between replacing sedentary behaviour with MVPA and the SPARC levels was not observed in women.
A potential interaction between replacing sedentary behaviour with light‐intensity PA and the body mass index on the serum SPARC levels was also found in women.
Associations Between Smoking Status and Physical and Mental Health-Related Quality of Life Among Individuals With Mobility Impairments
Authors: Endrighi Romano , Zhao Yihong , Hughes Rosemary B , Kumar Deepak , Borrelli Belinda 
Published: August 2021

AbstractBackgroundIn the general population, quitting smoking is associated with improved health-related quality of life (QoL), but this association has not been examined in smokers with chronic mobility impairments (MIs).PurposeWe examined associations between smoking status and health-related QoL over 6 months, and whether relationships are moderated by depression and MI severity.MethodsThis is a secondary analysis of a smoking cessation induction trial among smokers with MIs (n = 241, 56% female, 36% Black) assessed at baseline, and 4 and 6 months after. Participants were grouped into “Smokers” (smoking at 4 and 6 months), “Abstainers” (quit at 4 and 6 months), “Relapsers” (relapsed at 6 months), and “Late-quitters” (quit at 6 months). Physical and mental health-related QoL was assessed with the Short-Form Health Survey. Depression was defined as scores ≥10 on the Patient Health Questionnaire, and MI severity by the use of skilled care for personal needs. Data were analyzed with linear mixed models.ResultsAggregating across time, among nondepressed participants, compared with “Smokers,” the “Abstainer,” and “Late-quitter” groups improved their physical health scores. “Late-quitters” also improved compared with “Relapsers.” Among the total sample, compared with “Smokers,” “Abstainers” showed improvements in mental health scores overtime, whereas “Relapsers” improved their score at 4 months, and “Late-quitters” improved at 6 months.ConclusionsQuitting smoking is associated with improvements in physical health-related QoL regardless of the severity of MI but only among those without depression at baseline. For mental health-related QoL, associations with quitting smoking were independent of baseline depression and severity of MI.
Preclinical evaluation of MRG002, a novel HER2-targeting antibody-drug conjugate with potent antitumor activity against HER2-positive solid tumors
Authors: Li Hu , Zhang Xiao , Xu Zhenyi , Li Lingrui , Liu Wenchao , Dai Zhenyu , Zhao Zhongrun , Xiao Lili , Li Hongfeng , Hu Chaohong 
Published: August 2021

Abstract

Background
ERBB2 is a proto-oncogene of multiple cancers including breast and gastric cancers with HER2 protein overexpression or gene amplification and has been proven clinically as a valid target for these cancers. HER2-targeting agents such as Herceptin®, Kadcyla® and ENHERTU® have been approved by the FDA for the treatment of breast cancer, but these drugs still face the challenge of acquired resistance and/or severe adverse reactions in clinical use. Therefore, there is significant unmet medical need for developing new agents that are more effective and safer for patients with advanced HER2-positive solid tumors including breast and gastric cancers.

Methods
We report here the making of MRG002, a novel HER2-targeted antibody drug conjugate (ADC), and preclinical characterization including pharmacology, pharmacodynamics and toxicology and discuss its potential as a novel agent for treating patients with HER2-positive solid tumors.

Results
MRG002 exhibited similar antigen binding affinity but much reduced antibody-dependent cellular cytotoxicity (ADCC) activity compared to trastuzumab. In addition to potent in vitro cytotoxicity, MRG002 showed tumor regression in both high- and medium-to-low HER2 expressing in vivo xenograft models. Furthermore, MRG002 showed enhanced antitumor activity when used in combination with an anti-PD-1 antibody. Main findings from toxicology studies are related to the payload and are consistent with literature report of other ADCs with monomethyl auristatinE.

Conclusion
MRG002 has demonstrated a favorable toxicity profile and potent antitumor activities in the breast and gastric PDX models with varying levels of HER2 expression, and/or resistance to trastuzumab or T-DM1. A phase I clinical study of MRG002 in patients with HER2-positive solid tumors is ongoing (CTR20181778).
Disrupting porcine glutaminase does not block preimplantation development and elongation nor decrease mTORC1 activation in conceptuses
Authors: Chen Paula R , Lucas Caroline G , Cecil Raissa F , Pfeiffer Caroline A , Fudge Melissa A , Samuel Melissa S , Zigo Michal , Seo Heewon , Spate Lee D , Whitworth Kristin M , Sutovsky Peter , Johnson Gregory A , Wells Kevin D , Geisert Rodney D , Prather Randall S 
Published: August 2021

Abstract
Elongation of pig conceptuses is a dynamic process, requiring adequate nutrient provisions. Glutamine is used as an energy substrate and is involved in the activation of mechanistic target of rapamycin complex 1 (mTORC1) during porcine preimplantation development. However, the roles of glutamine have not been extensively studied past the blastocyst stage. Therefore, the objective of the current study was to determine if glutaminase (GLS), which is the rate-limiting enzyme in glutamine metabolism, was necessary for conceptus elongation to proceed and was involved in mTORC1 activation. The CRISPR/Cas9 system was used to induce loss-of-function mutations in the GLS gene of porcine fetal fibroblasts. Wild type (GLS+/+) and knockout (GLS−/−) fibroblasts were used as donor cells for somatic cell nuclear transfer, and GLS+/+ and GLS−/− blastocyst-stage embryos were transferred into surrogates. On day 14 of gestation, GLS+/+ conceptuses primarily demonstrated filamentous morphologies, and GLS−/− conceptuses exhibited spherical, ovoid, tubular, and filamentous morphologies. Thus, GLS−/− embryos were able to elongate despite the absence of GLS protein and minimal enzyme activity. Furthermore, spherical GLS−/− conceptuses had increased abundance of transcripts related to glutamine and glutamate metabolism and transport compared to filamentous conceptuses of either genotype. Differences in phosphorylation of mTORC1 components and targets were not detected regarding conceptus genotype or morphology, but abundance of two transcriptional targets of mTORC1, cyclin D1, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha was increased in spherical conceptuses. Therefore, porcine GLS is not essential for conceptus elongation and is not required for mTORC1 activation at this developmental timepoint.
Dissociable effects of age and Parkinson’s disease on instruction-based learning
Authors: Parkin Beth L , Daws Richard E , Das-Neves Ines , Violante Ines R , Soreq Eyal , Faisal A Aldo , Sandrone Stefano , Lao-Kaim Nicholas P , Martin-Bastida Antonio , Roussakis Andreas-Antonios , Piccini Paola , Hampshire Adam 
Published: August 2021

Abstract
The cognitive deficits associated with Parkinson’s disease vary across individuals and change across time, with implications for prognosis and treatment. Key outstanding challenges are to define the distinct behavioural characteristics of this disorder and develop diagnostic paradigms that can assess these sensitively in individuals. In a previous study, we measured different aspects of attentional control in Parkinson’s disease using an established fMRI switching paradigm. We observed no deficits for the aspects of attention the task was designed to examine; instead those with Parkinson’s disease learnt the operational requirements of the task more slowly. We hypothesized that a subset of people with early-to-mid stage Parkinson’s might be impaired when encoding rules for performing new tasks. Here, we directly test this hypothesis and investigate whether deficits in instruction-based learning represent a characteristic of Parkinson’s Disease. Seventeen participants with Parkinson’s disease (8 male; mean age: 61.2 years), 18 older adults (8 male; mean age: 61.3 years) and 20 younger adults (10 males; mean age: 26.7 years) undertook a simple instruction-based learning paradigm in the MRI scanner. They sorted sequences of coloured shapes according to binary discrimination rules that were updated at two-minute intervals. Unlike common reinforcement learning tasks, the rules were unambiguous, being explicitly presented; consequently, there was no requirement to monitor feedback or estimate contingencies. Despite its simplicity, a third of the Parkinson’s group, but only one older adult, showed marked increases in errors, 4 SD greater than the worst performing young adult. The pattern of errors was consistent, reflecting a tendency to misbind discrimination rules. The misbinding behaviour was coupled with reduced frontal, parietal and anterior caudate activity when rules were being encoded, but not when attention was initially oriented to the instruction slides or when discrimination trials were performed. Concomitantly, Magnetic Resonance Spectroscopy showed reduced gamma-Aminobutyric acid levels within the mid-dorsolateral prefrontal cortices of individuals who made misbinding errors. These results demonstrate, for the first time, that a subset of early-to-mid stage people with Parkinson’s show substantial deficits when binding new task rules in working memory. Given the ubiquity of instruction-based learning, these deficits are likely to impede daily living. They will also confound clinical assessment of other cognitive processes. Future work should determine the value of instruction-based learning as a sensitive early marker of cognitive decline and as a measure of responsiveness to therapy in Parkinson's disease.
[18F]-AV-1451 binding in the substantia nigra as a marker of neuromelanin in Lewy body diseases
Authors: Mak Elijah , Kouli Antonina , Holland Negin , Nicastro Nicolas , Savulich George , Surendranathan Ajenthan , Malpetti Maura , Manavaki Roido , Hong Young T , Fryer Tim D , Aigbirhio Franklin , Rowe James B , O’Brien John T , Williams-Gray Caroline H 
Published: August 2021

Abstract
While [18F]-AV-1451 was developed as a PET radiotracer with high affinity for hyperphosphorylated tau, it has been proposed that loss of ‘off-target’ [18F]-AV-1451 binding to neuromelanin in the substantia nigra could be a surrogate marker of Lewy body diseases. [18F]-AV-1451 binding was measured in the substantia nigra of patients with Parkinson’s disease (n = 35), dementia with Lewy bodies (n = 10) and separate control groups (n = 37; n = 14). Associations with motor symptoms, cognition and disease duration were evaluated using linear regression models. The dementia with Lewy bodies group had significantly reduced substantia nigra [18F]-AV-1451 binding compared to controls after adjusting for age (P &lt; 0.05). However, there were no significant differences in substantia nigra [18F]-AV-1451 binding between Parkinson’s disease and controls. Substantia nigra [18F]-AV-1451 binding was not associated with age, disease duration, Movement Disorders Society—Unified Parkinson’s Disease Rating Scale and cognitive scores in dementia with Lewy bodies and Parkinson’s disease groups. Despite the reduction of substantia nigra [18F]-AV-1451 binding in dementia with Lewy bodies, these findings suggest that substantia nigra [18F]-AV-1451 binding has no value as a diagnostic marker in early Parkinson’s disease. Further investigations in longitudinal cohorts are warranted.
Estimating the Latent Period of Coronavirus Disease 2019 (COVID-19)
Authors: Xin Hualei , Li Yu , Wu Peng , Li Zhili , Lau Eric H Y , Qin Ying , Wang Liping , Cowling Benjamin J , Tsang Tim K , Li Zhongjie 
Published: August 2021

Abstract
Using detailed exposure information on COVID-19 cases, we estimated the mean latent period to be 5.5 (95% CI: 5.1–5.9) days, shorter than the mean incubation period (6.9 days). Laboratory testing may allow shorter quarantines since 95% of COVID-19 cases shed virus within 10.6 (95% CI: 9.6–11.6) days of infection.
Novel Vector of Scrub Typhus in Sub-Antarctic Chile: Evidence From Human Exposure
Authors: Weitzel Thomas , Silva-de la Fuente María Carolina , Martínez-Valdebenito Constanza , Stekolnikov Alexandr A , Pérez Caricia , Pérez Ruth , Vial Cecilia , Abarca Katia , Acosta-Jamett Gerardo 
Published: August 2021

Abstract
The exposure of a research team to chigger mites in southern Chile allowed the first identification of a trombiculid species as vector and reservoir of scrub typhus outside the tsutsugamushi triangle, providing unique insights into the ecology and transmission of this recently discovered rickettsial infection in South America.
Adult-onset nephrotic syndrome following coronavirus disease vaccination
Authors: Biradar Vivek , Konnur Abhijit , Gang Sishir , Hegde Umapati , Rajapurkar Mohan , Patel Hardik , Pandey Sachida Nand , Soni Shailesh 
Published: August 2021

ABSTRACT
A 22-year-old healthy man was admitted for oedema 15 days after the first injection of the COVISHIELD coronavirus disease 2019 (COVID-19) vaccine (Oxford AstraZeneca) vaccine. Nephrotic syndrome was diagnosed and a kidney biopsy showed minimal change disease. Oral prednisolone was started at 1 mg/kg/day resulting in complete remission within 1 week.
Bioproducts generation from carboxylate platforms by the non-conventional yeast Yarrowia lipolytica
Authors: Park Young-Kyoung , González-Fernández Cristina , Robles-Iglesias Raúl , Vidal Lea , Fontanille Pierre , Kennes Christian , Tomás Pejó Elia , Nicaud Jean-Marc , Fickers Patrick 
Published: August 2021

ABSTRACT
In recent years, there has been a growing interest in the use of renewable sources for bio-based production aiming at developing sustainable and feasible approaches towards a circular economy. Among these renewable sources, organic wastes (OWs) can be anaerobically digested to generate carboxylates like volatile fatty acids (VFAs), lactic acid, and longer-chain fatty acids that are regarded as novel building blocks for the synthesis of value-added compounds by yeasts. This review discusses on the processes that can be used to create valuable molecules from OW-derived VFAs; the pathways employed by the oleaginous yeast Yarrowia lipolytica to directly metabolize such molecules; and the relationship between OW composition, anaerobic digestion, and VFA profiles. The review also summarizes the current knowledge about VFA toxicity, the pathways by which VFAs are metabolized and the metabolic engineering strategies that can be employed in Y. lipolytica to produce value-added biobased compounds from VFAs.
Internal gravity waves in a stratified layer atop a convecting liquid core in a non-rotating spherical shell
Authors: Bouffard M , Favier B , Lecoanet D , Le Bars M 
Published: August 2021

SUMMARYSeismic and magnetic observations have suggested the presence of a stably stratified layer atop Earth’s core. Such a layer could affect the morphology of the geomagnetic field and the evolution of the core, but the precise impact of this layer depends largely on its internal dynamics. Among other physical phenomena, stratified layers host internal gravity waves (IGW), which can be excited by adjacent convective motions. Internal waves are known to play an important role on the large-scale dynamics of the Earth’s climate and on the long-term evolution of stars. Yet, they have received relatively little attention in the Earth’s outer core so far and deserve detailed investigations in this context. Here, we make a first step in that direction by running numerical simulations of IGW in a non-rotating spherical shell in which a stratified layer lies on top of a convective region. We use a nonlinear equation of state to produce self-consistently such a two-layer system. Both propagating waves and global modes coexist in the stratified layer. We characterize the spectral properties of these waves and find that energy is distributed across a wide range of frequencies and length scales, that depends on the Prandtl number. For the control parameters considered and in the absence of rotational and magnetic effects, the mean kinetic energy in the layer is about 0.1 per cent that of the convective region. IGW produce perturbations in the gravity field that may fall within the sensitivity limit of present-day instruments and could potentially be detected in available data. We finally provide a road map for future, more geophysically realistic, studies towards a more thorough understanding of the dynamics and impact of internal waves in a stratified layer atop Earth’s core.
P-wave picking for earthquake early warning: refinement of aTpdmethod
Authors: Yamada Masumi , Mori Jim 
Published: August 2021

SUMMARYDetecting P-wave onsets for online processing is an important component for real-time seismology. As earthquake early warning systems around the world come into operation, the importance of reliable P-wave detection has increased, since the accuracy of the earthquake information depends primarily on the quality of the detection. In addition to the accuracy of arrival time determination, the robustness in the presence of noise and the speed of detection are important factors in the methods used for the earthquake early warning. In this paper, we tried to improve the P-wave detection method designed for real-time processing of continuous waveforms. We used the new Tpd method, and proposed a refinement algorithm to determine the P-wave arrival time. Applying the refinement process substantially decreases the errors of the P-wave arrival time. Using 606 strong motion records of the 2011 Tohoku earthquake sequence to test the refinement methods, the median of the error was decreased from 0.15 to 0.04 s. Only three P-wave arrivals were missed by the best threshold. Our results show that the Tpd method provides better accuracy for estimating the P-wave arrival time compared to the STA/LTA method. The Tpd method also shows better performance in detecting the P-wave arrivals of the target earthquakes in the presence of noise and coda of previous earthquakes. The Tpd method can be computed quickly, so it would be suitable for the implementation in earthquake early warning systems.
Seismic velocity structure along the North Anatolian Fault beneath the Central Marmara Sea and its implication for seismogenesis
Authors: Yamamoto Yojiro , Kalafat Dogan , Pinar Ali , Takahashi Narumi , Polat Remzi , Kaneda Yoshiyuki , Ozener Haluk 
Published: August 2021

SUMMARYThe offshore part of the North Anatolian Fault (NAF) beneath the Marmara Sea is a well-known seismic gap for future M &gt; 7 earthquakes in the sense that more than 250 yr have passed since the last major earthquake in the Central Marmara region. Although many studies discussed the seismic potential for the future large earthquake in this region on the basis of historical record, geodetic and geological observations, it is difficult to evaluate the actual situation on the seismic activity and structure along the NAF beneath the Marmara Sea due to the lack of ocean bottom seismic observations. Using ocean bottom seismometer observations, an assessment of the location of possible asperities that could host an expected large earthquake is undertaken based on heterogeneities in the microseismicity distribution and seismic velocity structure. Specifically, seismic tomography and precise hypocentre estimations are conducted using offshore seismic data whose recording period is 11 months. About five times more microearthquakes are detected with respect to events recorded in a land-based catalogue. A comparison with previously published results from offshore observation data suggests that the seismicity pattern had not changed from 2014 September to 2017 May. The location accuracy of microearthquakes is greatly improved from only the land-based earthquake catalogue, particularly for depth direction. There are several aseismic and inactive zones of microearthquake, and the largest one is detected using land-based seismic observation, whereas other zones are newly detected via offshore observations. The obtained velocity model shows a strong lateral contrast, with two changing points. The western changing point corresponds to a segmentation boundary, where the dip angle of the NAF segments changed. High-velocity zones from tomographic images are characterized by low seismicity eastward of the segment boundary. To the east of 28.50°E, the high-velocity zone becomes thicker in the depth direction and is characterized by low seismicity. Although the low seismic activity alone could be interpreted as both strong coupling and fully creeping, the high-velocity features at the same can be concluded that these zones are consist of brittle material and strong coupling. From comparison with other geodetic and seismic studies, we interpret these zones as locked zones that had been ruptured by the past large earthquakes and could be ruptured by future ones. These zones might accumulate strain since the main shock rupture associated with the 1766 May Ms 7.3 earthquake, the latest major earthquake in this region.