bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contrasting drivers and trends of ocean acidification in the subarctic Atlantic
Authors: Pérez Fiz F. , Olafsson Jon , Ólafsdóttir Solveig R. , Fontela Marcos , Takahashi Taro 
Published: July 2021

AbstractThe processes of warming, anthropogenic CO2 (Canth) accumulation, decreasing pHT (increasing [H+]T; concentration in total scale) and calcium carbonate saturation in the subarctic zone of the North Atlantic are unequivocal in the time-series measurements of the Iceland (IS-TS, 1985–2003) and Irminger Sea (IRM-TS, 1983–2013) stations. Both stations show high rates of Canth accumulation with different rates of warming, salinification and stratification linked to regional circulation and dynamics. At the IS-TS, advected and stratified waters of Arctic origin drive a strong increase in [H+]T, in the surface layer, which is nearly halved in the deep layer (44.7 ± 3.6 and 25.5 ± 1.0 pmol kg−1 yr−1, respectively). In contrast, the weak stratification at the IRM-TS allows warming, salinification and Canth uptake to reach the deep layer. The acidification trends are even stronger in the deep layer than in the surface layer (44.2 ± 1.0 pmol kg−1 yr−1 and 32.6 ± 3.4 pmol kg−1 yr−1 of [H+]T, respectively). The driver analysis detects that warming contributes up to 50% to the increase in [H+]T at the IRM-TS but has a small positive effect on calcium carbonate saturation. The Canth increase is the main driver of the observed acidification, but it is partially dampened by the northward advection of water with a relatively low natural CO2 content.
Investigating the association of testosterone with survival in men and women using a Mendelian randomization study in the UK Biobank
Authors: Schooling C. M. , Zhao J. V. 
Published: July 2021

AbstractLife expectancy in the developed West is currently stagnated and remains shorter in men than women. Well-established evolutionary biology theory suggests lifespan trades-off against reproductive success, possibly sex-specifically. We examined whether a key driver of reproductive success, testosterone, affected survival using a Mendelian randomization longevity study in the UK Biobank to obtain unbiased estimates, along with control exposures. We applied published genetic instruments for testosterone to obtain inverse variance weighted estimates of associations with survival to (i.e., age at) recruitment, in 167,020 men and 194,174 women. We similarly obtained estimates for a positive control (smoking initiation), and a negative control (absorbate), a marker of vitamin C metabolism. Testosterone was associated with poorer survival (0.10 years younger at recruitment per effect size of testosterone, 95% confidence interval (CI) 0.004 to 0.20). As expected, smoking initiation was also associated with poorer survival (0.37 years younger, 95% CI 0.25 to 0.50), but not absorbate (0.01 years younger, 95% CI − 0.09 to 0.11). Several aspects of a healthy lifestyle (low animal fat diet) and several widely used medications (statins, metformin, dexamethasone and possibly aspirin) may modulate testosterone. Explicitly designing interventions sex-specifically based on these insights might help address stagnating life expectancy and sexual disparities.
Cholesterol-dependent plasma membrane order (Lo) is critical for antigen-specific clonal expansion of CD4+ T cells
Authors: Sengupta Soumini , Karsalia Ritesh , Morrissey Amanda , Bamezai Anil K. 
Published: July 2021

AbstractEarly “T cell activation” events are initiated within the lipid microenvironment of the plasma membrane. Role of lipid membrane order (Lo) in spatiotemporal signaling through the antigen receptor in T cells is posited but remains unclear. We have examined the role of membrane order (Lo)/disorder (Ld) in antigen specific CD4+T cell activation and clonal expansion by first creating membrane disorder, and then reconstituting membrane order by inserting cholesterol into the disordered plasma membrane. Significant revival of antigen specific CD4+T cell proliferative response was observed after reconstituting the disrupted membrane order with cholesterol. These reconstitution experiments illustrate Koch’s postulate by demonstrating that cholesterol-dependent membrane order (Lo) is critical for responses generated by CD4+T cells and point to the importance of membrane order and lipid microenvironment in signaling through T cell membrane antigen receptors.
Antibiotics modulate neoadjuvant therapy efficiency in patients with breast cancer: a pilot analysis
Authors: Zhang Xi , Yu Long , Shi Jiajie , Li Sainan , Yang Shiwei , Gao Wei , Yang Shan , Cheng Meng , Wang Haoqi , Guo Zhanjun , Geng Cuizhi 
Published: July 2021

AbstractMounting evidence suggests that microbiota dysbiosis caused by antibiotic administration is a risk factor for cancer, but few research reports focus on the relationships between antibiotics and chemotherapy efficiency. We evaluated the influence of antibiotic administration on neoadjuvant therapy efficacy in patients with breast cancer (BC) in the present study. BC patients were stratified into two groups: antibiotic-treated and control based on antibiotic administration within 30 days after neoadjuvant therapy initiation. Disease-free survival (DFS) and overall survival (OS) were assessed using the Kaplan–Meier method, and the Cox proportional hazards model was used for multivariate analyses. The pathologic complete response rate of the control group was significantly higher than that of the antibiotic-treated group (29.09% vs. 10.20%, p = 0.017). Further univariate analysis with Kaplan–Meier calculations demonstrated that antibiotic administration was strongly linked with both reduced DFS (p = 0.04) at significant statistical levels and OS (p = 0.088) at borderline statistical levels. Antibiotic administration was identified as a significant independent prognostic factor for DFS [hazard ratio (HR) 3.026, 95%, confidence interval (CI) 1.314–6.969, p = 0.009] and OS (HR 2.836, 95% CI 1.016–7.858, p = 0.047) by Cox proportional hazards model analysis. Antibiotics that initiated reduced efficiency of chemotherapy were more noticeable in the HER2-positive subgroup for both DFS (HR 5.51, 95% CI 1.77–17.2, p = 0.003) and OS (HR 7.0395% CI 1.94–25.53, p = 0.003), as well as in the T3-4 subgroup for both DFS (HR 20.36, 95% CI 2.41–172.07, p = 0.006) and OS (HR 13.45, 95% CI 1.39–130.08, p = 0.025) by stratified analysis. Antibiotic administration might be associated with reduced efficacy of neoadjuvant therapy and poor prognosis in BC patients. As a preliminary study, our research made preparations for further understanding and large-scale analyses of the impact of antibiotics on the efficacy of neoadjuvant therapy.
SoxD transcription factor deficiency in Schwann cells delays myelination in the developing peripheral nervous system
Authors: Ittner Ella , Hartwig Anna C. , Elsesser Olga , Wüst Hannah M. , Fröb Franziska , Wedel Miriam , Schimmel Margit , Tamm Ernst R. , Wegner Michael , Sock Elisabeth 
Published: July 2021

AbstractThe three SoxD proteins, Sox5, Sox6 and Sox13, represent closely related transcription factors with important roles during development. In the developing nervous system, SoxD proteins have so far been primarily studied in oligodendroglial cells and in interneurons of brain and spinal cord. In oligodendroglial cells, Sox5 and Sox6 jointly maintain the precursor state, interfere with terminal differentiation, and thereby ensure the proper timing of myelination in the central nervous system. Here we studied the role of SoxD proteins in Schwann cells, the functional counterpart of oligodendrocytes in the peripheral nervous system. We show that Schwann cells express Sox5 and Sox13 but not Sox6. Expression was transient and ceased with the onset of terminal differentiation. In mice with early Schwann cell-specific deletion of both Sox5 and Sox13, embryonic Schwann cell development was not substantially affected and progressed normally into the promyelinating stage. However, there was a mild and transient delay in the myelination of the peripheral nervous system of these mice. We therefore conclude that SoxD proteins—in stark contrast to their action in oligodendrocytes—promote differentiation and myelination in Schwann cells.
Modelling of crustal composition and Moho depths and their Implications toward seismogenesis in the Kumaon–Garhwal Himalaya
Authors: Mandal Prantik , Srinivas D. , Suresh G. , Srinagesh D. 
Published: July 2021

AbstractWe image the lateral variations in the Moho depths and average crustal composition across the Kumaon–Garhwal (KG) Himalaya, through the H–K stacking of 1400 radial PRFs from 42 three-component broadband stations. The modelled Moho depth, average crustal Vp/Vs, and Poisson’s ratio estimates vary from 28.3 to 52.9 km, 1.59 to 2.13 and 0.17 to 0.36, respectively, in the KG Himalaya. We map three NS to NNE trending transverse zones of significant thinning of mafic crust, which are interspaced by zones of thickening of felsic crust. These mapped transverse zones bend toward the north to form a NE dipping zone of maximum changes in Moho depths, below the region between Munsiari and Vaikrita thrusts. The 1991 Mw6.6 Uttarakashi and 1999 Mw6.4 Chamoli earthquakes have occurred on the main Himalayan thrust (MHT), lying just above the mapped zone of maximum changes in Moho depths. Modelled large values of average crustal Vp/Vs (> 1.85) could be attributed to the high fluid (metamorphic fluids) pressure associated with the mid-crustal MHT. Additionally, the serpentinization of the lowermost crust resulted from the continent–continent Himalayan collision process could also contribute to the increase of the average crustal Vp/Vs ratio in the region.
On the shape and structure of the murine pulmonary heart valve
Authors: Liu Yifei , Feng Xinzeng , Liu Hao , McComb David W. , Breuer Christopher K. , Sacks Michael S. 
Published: July 2021

AbstractMurine animal models are an established standard in translational research and provides a potential platform for studying heart valve disease. To date, studies on heart valve disease using murine models have been hindered by a lack of appropriate methodologies due to their small scale. In the present study, we developed a multi-scale, imaging-based approach to extract the functional structure and geometry for the murine heart valve. We chose the pulmonary valve (PV) to study, due to its importance in congenital heart valve disease. Excised pulmonary outflow tracts from eleven 1-year old C57BL/6J mice were fixed at 10, 20, and 30 mmHg to simulate physiological loading. Micro-computed tomography was used to reconstruct the 3D organ-level PV geometry, which was then spatially correlated with serial en-face scanning electron microscopy imaging to quantify local collagen fiber distributions. From the acquired volume renderings, we obtained the geometric descriptors of the murine PV under increasing transvalvular pressures, which demonstrated remarkable consistency. Results to date suggest that the preferred collagen orientation was predominantly in the circumferential direction, as in larger mammalian valves. The present study represents a first step in establishing organ-level murine models for the study of heart valve disease.
Preoperative nomogram for microvascular invasion prediction based on clinical database in hepatocellular carcinoma
Authors: Mao Shuqi , Yu Xi , Yang Yong , Shan Yuying , Mugaanyi Joseph , Wu Shengdong , Lu Caide 
Published: July 2021

AbstractThe presence of microvascular invasion (MVI) is a critical determinant of early hepatocellular carcinoma (HCC) recurrence and prognosis. We developed a nomogram model integrating clinical laboratory examinations and radiological imaging results from our clinical database to predict microvascular invasion presence at preoperation in HCC patients. 242 patients with pathologically confirmed HCC at the Ningbo Medical Centre Lihuili Hospital from September 2015 to January 2021 were included in this study. Baseline clinical laboratory examinations and radiological imaging results were collected from our clinical database. LASSO regression analysis model was used to construct data dimensionality reduction and elements selection. Multivariate logistic regression analysis was performed to identify the independent risk factors associated with MVI and finally a nomogram for predicting MVI presence of HCC was established. Nomogram performance was assessed via internal validation and calibration curve statistics. Decision curve analysis (DCA) was conducted to determine the clinical usefulness of the nomogram model by quantifying the net benefits along with the increase in threshold probabilities. Survival analysis indicated that the probability of overall survival (OS) and recurrence-free survival (RFS) were significantly different between patients with MVI and without MVI (P < 0.05). Histopathologically identified MVI was found in 117 of 242 patients (48.3%). The preoperative factors associated with MVI were large tumor diameter (OR = 1.271, 95%CI: 1.137–1.420, P < 0.001), AFP level greater than 20 ng/mL (20–400 vs. ≤ 20, OR = 2.025, 95%CI: 1.056–3.885, P = 0.034; > 400 vs. ≤ 20, OR = 3.281, 95%CI: 1.661–6.480, P = 0.001), total bilirubin level greater than 23 umol/l (OR = 2.247, 95%CI: 1.037–4.868, P = 0.040). Incorporating tumor diameter, AFP and TB, the nomogram achieved a better concordance index of 0.725 (95%CI: 0.661–0.788) in predicting MVI presence. Nomogram analysis showed that the total factor score ranged from 0 to 160, and the corresponding risk rate ranged from 0.20 to 0.90. The DCA showed that if the threshold probability was > 5%, using the nomogram to diagnose MVI could acquire much more benefit. And the net benefit of the nomogram model was higher than single variable within 0.3–0.8 of threshold probability. In summary, the presence of MVI is an independent prognostic risk factor for RFS. The nomogram detailed here can preoperatively predict MVI presence in HCC patients. Using the nomogram model may constitute a usefully clinical tool to guide a rational and personalized subsequent therapeutic choice.
Molecular characterization and nutritional regulation of sodium-dependent glucose cotransporter 1 (Sglt1) in blunt snout bream (Megalobrama amblycephala)
Authors: Liang Hualiang , Ge Xianping , Ren Mingchun , Zhang Lu , Xia Dong , Ke Ji , Pan Liangkun 
Published: July 2021

AbstractFish has poor utilization capacity for glucose metabolism. The possible reasons are related to the core regulatory elements of glucose metabolism: transport proteins. Studies on the species and functions of Sglt1 in aquatic animals are scarce, therefore further studies are needed. In this study, the full length of blunt snout bream (Megalobrama amblycephala) sglt1 (Masglt1) was 2965 bp including 5′-UTR region of 168 bp and a 3′-UTR region of 820 bp. Masglt1 have a highest sequence homology in Cypriniformes fish. MaSglt1 protein was identified as a transmembrane protein with 14 α-helix structures locating plasma membrane by the methods of predicted tertiary structure and immunohistochemical staining. MaSglt1 protein has a hollow channel forms which could be specifically coupled with two Na+ ions to recognize glucose and carry out transmembrane transport. High sglt1 mRNA was found in the intestine and kidney. The mRNA levels of intestinal sglt1 had a positive correlation with dietary starch levels at 3 h after feeding, and the mRNA was significantly higher than that at 24 h, however, the mRNA levels of renal sglt1 presented results opposite to those of intestinal sglt1. The mRNA levels of renal sglt1 had a positive correlation with dietary starch levels at 24 h after feeding, and the expression was significantly higher than that at 3 h. These results confirmed that Masglt11 was mainly found in the intestine and kidney and was located in the cell membrane, playing a role in glucose homeostasis.
Three dimensional modeling of biologically relevant fluid shear stress in human renal tubule cells mimics in vivo transcriptional profiles
Authors: Ross Emily J. , Gordon Emily R. , Sothers Hanna , Darji Roshan , Baron Oakley , Haithcock Dustin , Prabhakarpandian Balabhaskar , Pant Kapil , Myers Richard M. , Cooper Sara J. , Cox Nancy J. 
Published: July 2021

AbstractThe kidney proximal tubule is the primary site for solute reabsorption, secretion and where kidney diseases can originate, including drug-induced toxicity. Two-dimensional cell culture systems of the human proximal tubule cells (hPTCs) are often used to study these processes. However, these systems fail to model the interplay between filtrate flow, fluid shear stress (FSS), and functionality essential for understanding renal diseases and drug toxicity. The impact of FSS exposure on gene expression and effects of FSS at differing rates on gene expression in hPTCs has not been thoroughly investigated. Here, we performed RNA-sequencing of human RPTEC/TERT1 cells in a microfluidic chip-based 3D model to determine transcriptomic changes. We measured transcriptional changes following treatment of cells in this device at three different fluidic shear stress. We observed that FSS changes the expression of PTC-specific genes and impacted genes previously associated with renal diseases in genome-wide association studies (GWAS). At a physiological FSS level, we observed cell morphology, enhanced polarization, presence of cilia, and transport functions using albumin reabsorption via endocytosis and efflux transport. Here, we present a dynamic view of hPTCs response to FSS with increasing fluidic shear stress conditions and provide insight into hPTCs cellular function under biologically relevant conditions.
Relative platelet reductions provide better pathophysiologic signatures of coagulopathies in sepsis
Authors: Kasugai Daisuke , Ozaki Masayuki , Nishida Kazuki , Goto Yukari , Takahashi Kunihiko , Matsui Shigeyuki , Matsuda Naoyuki 
Published: July 2021

AbstractIn sepsis-associated coagulopathies and disseminated intravascular coagulation, relative platelet reductions may reflect coagulopathy severity. However, limited evidence supports their clinical significance and most sepsis-associated coagulopathy criteria focus on the absolute platelet counts. To estimate the impact of relative platelet reductions and absolute platelet counts on sepsis outcomes. A multicenter retrospective observational study was performed using the eICU Collaborative Research Database, comprising 335 intensive care units (ICUs) in the United States. Patients with sepsis and an ICU stay > 2 days were included. Estimated effects of relative platelet reductions and absolute platelet counts on mortality and coagulopathy-related complications were evaluated. Overall, 26,176 patients were included. Multivariate mixed-effect logistic regression analysis revealed marked in-hospital mortality risk with larger platelet reductions between days one and two, independent from the resultant absolute platelet counts. The adjusted odds ratio (OR) [95% confidence intervals (CI)] for in-hospital mortality was 1.28[1.23–1.32], 1.86[1.75–1.97], 2.99[2.66–3.36], and 6.05[4.40–8.31] for 20–40%, 40–60%, 60–80%, and > 80% reductions, respectively, when compared with a < 20% decrease in platelets (P < 0.001 for each). In the multivariate logistic regression analysis, platelet reductions ≥ 11% and platelet counts ≤ 100,000/μL on day 2 were associated with high coagulopathy-related complications (OR [95%CI], 2.03 and 1.18; P < 0.001 and P < 0.001), while only platelet reduction was associated with thromboembolic complications (OR [95%CI], 1.43 [1.03–1.98], P < 0.001). The magnitude of platelet reductions represent mortality risk and provides a better signature of coagulopathies in sepsis; therefore, it is a plausible criterion for sepsis-associated coagulopathies.
Global patterns in genomic diversity underpinning the evolution of insecticide resistance in the aphid crop pest Myzus persicae
Authors: Singh Kumar Saurabh , Cordeiro Erick M. G. , Troczka Bartlomiej J. , Pym Adam , Mackisack Joanna , Mathers Thomas C. , Duarte Ana , Legeai Fabrice , Robin Stéphanie , Bielza Pablo , Burrack Hannah J. , Charaabi Kamel , Denholm Ian , Figueroa Christian C. , ffrench-Constant Richard H. , Jander Georg , Margaritopoulos John T. , Mazzoni Emanuele , Nauen Ralf , Ramírez Claudio C. , Ren Guangwei , Stepanyan Ilona , Umina Paul A. , Voronova Nina V. , Vontas John , Williamson Martin S. , Wilson Alex C. C. , Xi-Wu Gao , Youn Young-Nam , Zimmer Christoph T. , Simon Jean-Christophe , Hayward Alex , Bass Chris 
Published: July 2021

AbstractThe aphid Myzus persicae is a destructive agricultural pest that displays an exceptional ability to develop resistance to both natural and synthetic insecticides. To investigate the evolution of resistance in this species we generated a chromosome-scale genome assembly and living panel of >110 fully sequenced globally sampled clonal lines. Our analyses reveal a remarkable diversity of resistance mutations segregating in global populations of M. persicae. We show that the emergence and spread of these mechanisms is influenced by host–plant associations, uncovering the widespread co‐option of a host-plant adaptation that also offers resistance against synthetic insecticides. We identify both the repeated evolution of independent resistance mutations at the same locus, and multiple instances of the evolution of novel resistance mechanisms against key insecticides. Our findings provide fundamental insights into the genomic responses of global insect populations to strong selective forces, and hold practical relevance for the control of pests and parasites.
Towards attosecond imaging at the nanoscale using broadband holography-assisted coherent imaging in the extreme ultraviolet
Authors: Eschen Wilhelm , Wang Sici , Liu Chang , Klas Robert , Steinert Michael , Yulin Sergiy , Meißner Heide , Bussmann Michael , Pertsch Thomas , Limpert Jens , Rothhardt Jan 
Published: July 2021

AbstractNanoscale coherent imaging has emerged as an indispensable modality, allowing to surpass the resolution limit given by classical imaging optics. At the same time, attosecond science has experienced enormous progress and has revealed the ultrafast dynamics in complex materials. Combining attosecond temporal resolution of pump-probe experiments with nanometer spatial resolution would allow studying ultrafast dynamics on the smallest spatio-temporal scales but has not been demonstrated yet. To date, the large bandwidth of attosecond pulses poses a major challenge to high-resolution coherent imaging. Here, we present broadband holography-enhanced coherent imaging, which enables the combination of high-resolution coherent imaging with a large spectral bandwidth. By implementing our method at a high harmonic source, we demonstrate a spatial resolution of 34 nm in combination with a spectral bandwidth of 5.5 eV at a central photon energy of 92 eV. The method is single-shot capable and retrieves the spectrum from the measured diffraction pattern.
Red emissive sulfone-rhodols as mitochondrial imaging agents
Authors: Vygranenko Kateryna V. , Poronik Yevgen M. , Wrzosek Antoni , Szewczyk Adam , Gryko Daniel T. 
Published: July 2021

The controlled hydrolysis of sulfone-rhodamines affords a series of core-modified red-emitting rhodols, the fluorescence of which is sensitive to solvent polarity. After equipping with PPh3+ group they selectively stain mitochondria.