bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding Rad51 function is a prerequisite for progress in cancer research
Authors: Nordén Bengt , Takahashi Masayuki 
Published: October 2020

AbstractThe human protein Rad51 is double-edged in cancer contexts: on one hand, preventing tumourigenesis by eliminating potentially carcinogenic DNA damage and, on the other, promoting tumours by introducing new mutations. Understanding mechanistic details of Rad51 in homologous recombination (HR) and repair could facilitate design of novel methods, including CRISPR, for Rad51-targeted cancer treatment. Despite extensive research, however, we do not yet understand the mechanism of HR in sufficient detail, partly due to complexity, a large number of Rad51 protein units being involved in the exchange of long DNA segments. Another reason for lack of understanding could be that current recognition models of DNA interactions focus only on hydrogen bond-directed base pair formation. A more complete model may need to include, for example, the kinetic effects of DNA base stacking and unstacking (‘longitudinal breathing’). These might explain how Rad51 can recognize sequence identity of DNA over several bases long stretches with high accuracy, despite the fact that a single base mismatch could be tolerated if we consider only the hydrogen bond energy. We here propose that certain specific hydrophobic effects, recently discovered destabilizing stacking of nucleobases, may play a central role in this context for the function of Rad51.
Quality of life of adult Fontan patients
Authors: Soufi Alexandra , Gouton Marielle , Metton Olivier , Mitchell Julia , Bernard Yvette F. , Bozio Andre , Ninet Jean , Di Filippo Sylvie 
Published: October 2020

AbstractBackground:Progress in the management of complex congenital heart disease (CHD) led to an improvement in survival rates of adults with a Fontan-like circulation. The objective of this study was to assess the subjective health status and quality of life of this population.Methods and results:Patients aged more than 18 years at the time of the study, who underwent a Fontan-like procedure. Subjective health status was assessed by the SF-36 questionnaire and a linear analog scale was used to score patients’ self-perception of their quality of life; cardiac and demographic parameters were collected.Results:Among 65 eligible patients, 60 (23 females; mean ± SD age: 25.7 ± 7.2 years) answered the SF-36 questionnaire and 46 of these were interviewed to evaluate their perceived quality of life. Among them, 20 (33.3%) were working full-time and 21 (35%) experienced arrhythmias. The physical SF-36 scores were lower in patients than in the general population (p ≤ 0.05). The New York Hear Association (NYHA) class and occupation were correlated with SF-36 scores of physical activity (respectively, p = 0.0001 and p = 0.025). SF-36 scores of psychological status were associated with the number of drugs and occupation (respectively, p = 0.0001 and p = 0.02). The mean ± SD quality of life score measured using a linear analog scale was 7.02 ± 1.6 and was linked to education and occupation (p ≤ 0.05) but not with cardiac parameters.Conclusion:Adult Fontan patients perceive an impaired physical health but report a good overall quality of life. Education and occupation impacts significantly on Fontan patients’ quality of life.
Relationship of work-related stress with obesity among Brazilian female shift workers
Authors: da Silva Janaína Cristina , Garcez Anderson , Cibeira Gabriela Herrmann , Theodoro Heloísa , Olinto Maria Teresa Anselmo 
Published: October 2020

AbstractObjectives:To explore the relationship between work-related stress and obesity among female shift workers. Additionally, we also aimed to test the interaction between shift work and work-related stress in this association.Design:A cross-sectional study was conducted among Brazilian female shift workers. Work-related stress was assessed through a demand–control questionnaire (Job Stress Scale). Work-related stress was defined by the presence of high psychological demands and low control at work. The obesity cases were defined as those with a BMI of 30 kg/m2 or more. Multivariate Poisson regression with robust variance was used to obtain the prevalence ratios (PR) and their respective 95 % CI.Setting:A group of industries located in southern Brazil in 2017.Participants:Four hundred and twenty female workers aged 18–59 years.Results:The overall prevalence of obesity was 30 % (95 % CI: 25·6, 34·4), and the presence of work-related stress was identified in 24 % (95 % CI: 19·9, 28·1) of the sample. We found an indication of interaction between work-related stress and night shift work on obesity (P = 0·026). After adjusting for confounding factors, work-related stress was associated with a 71 % greater probability of obesity (PR = 1·71; 95 % CI: 1·02, 2·87; P = 0·042) among female night shift workers.Conclusions:In this study, we revealed that exposure to work-related stress and night shift work were associated with obesity among female shift workers. Furthermore, the prevalence of obesity was high among female shift workers.
Dietary fat intakes in Irish children: changes between 2005 and 2019
Authors: O’Connor Aileen , Buffini Maria , Nugent Anne , Kehoe Laura , Flynn Albert , Walton Janette , Kearney John , McNulty Breige 
Published: October 2020

AbstractObjective:To examine current dietary fat intakes and compliance in Irish children and to examine changes in intakes from 2005 to 2019.Design:Analyses were based on data from the Irish National Children’s Food Survey (NCFS) and the NSFS II, two cross-sectional studies that collected detailed food and beverage intake data through 7-day and 4-day weighed food diaries, respectively.Setting:NCFS and NCFS II, Republic of Ireland.Participants:A nationally representative sample of 594 (NCFS) and 600 (NCFS II) children aged 5–12 years. Current intakes from the NCFS II were compared with those previously reported in the NCFS (www.iuna.net).Results:Current intakes of total fat, SFA, MUFA, PUFA andtransfat as a percentage of total energy are 33·3, 14·0, 13·6, 5·6 and 0·5 %, respectively. Total fat, SFA andtransfat intakes since 2005 remained largely stable over time with all displaying minor decreases of <1 %. Adherence to SFA recommendations remains inadequate, with only 7 % of the population complying. Insufficient compliance with PUFA (71 %) and EPA and DHA (DHA; 16 %) recommendations was also noted.Conclusion:Children in Ireland continue to meet the total fat andtransfat target goals. Adherence to MUFA and PUFA recommendations has also significantly improved. However, deviations for some fats remain, in particular SFA. These findings are useful for the development of dietary strategies to improve compliance with current recommendations.
Variations of Stable Isotopic Composition in Atmospheric Water Vapor and their Controlling Factors—A 6‐Year Continuous Sampling Study in Nanjing, Eastern China
Authors: Li Yaju , An Wenling , Pang Hongxi , Wu Shuang‐Ye , Tang Yanying , Zhang Wangbin , Hou Shugui 
Published: October 2020

AbstractLong‐term continuous monitoring of water vapor isotopes has great potential to improve our understanding of mechanisms that control stable isotope variations in hydrological processes, which is essential for accurate interpretation of isotopic proxy records. Here we presented a 6‐year daily data set of stable isotopes in atmospheric water vapor (δ18Ov, δDv, and d‐excessv) and precipitation (δ18Op, δDp, and d‐excessp) at Nanjing in Eastern China, an area under the influence of the East Asian Monsoon. Based on isotopic variations, we divided a year into three seasons, that is, summer monsoon season (June–September), spring (March–May), and fall‐winter (October–February). During summer monsoon season, the low δ18Ov values were mainly caused by the upstream convective rainout process during the large‐scale water vapor transport, and the d‐excessv values were the lowest due to the weak kinetic isotopic fractionation over its oceanic moisture source. Spring had the highest δ18Ov values, which was related to less distillation of local moisture under relatively high air temperatures. The relatively high d‐excessv values resulted from the kinetic isotopic fractionation due to drier condition. The fall‐winter season has the lowest δ18Ov values because the local distillation was the strongest with low air temperature. The d‐excessv values were highest during this season because of the strongest kinetic isotopic fractionation during the continental moisture recycling under dry climate condition. Using the isotopic composition of both precipitation and water vapor, we found that the annual mean subcloud raindrop evaporation is ~11% of precipitation. These findings improve our understanding of hydrological cycle on the East Asian Monsoon region and will potentially improve our interpretation of numerous isotopic proxy records from this region.
Multibeam Energy Moments of Multibeam Particle Velocity Distributions
Authors: Goldman M. V. , Newman D. L. , Eastwood J. P. , Lapenta G. 
Published: October 2020

AbstractHigh‐resolution electron and ion velocity distributions, f(v), which consist of N effectively disjoint beams, have been measured by NASA's Magnetospheric Multiscale Mission and in reconnection simulations. Commonly used standard velocity moments assume a single mean‐flow velocity for the entire distribution. This can lead to counterintuitive results for a multibeam f(v). An example is the standard thermal energy density moment (at a given space‐time point) of a pair of equal and opposite cold particle beams. This standard moment is nonzero even though each beam has zero thermal energy density. By contrast, a multibeam moment of two or more cold beams at a given position and time has no thermal energy. A multibeam moment is obtained by taking a standard moment of each beam and then summing over beams. In this paper we will generalize these notions, explore their consequences, and apply them to an f(v) which is a sum of tri‐Maxwellians. Both standard and multibeam energy moments have coherent and incoherent pieces. Examples of incoherent moments are the thermal energy density, the pressure, and the thermal energy flux (enthalpy flux plus heat flux). Corresponding coherent moments are the bulk kinetic energy density, the ram pressure, and the bulk kinetic energy flux. The difference between a standard incoherent moment and its multibeam counterpart will be defined as the “pseudothermal part” of the standard moment. The sum of a pair of corresponding coherent and incoherent moments is the undecomposed moment. Undecomposed standard moments are always equal to the corresponding undecomposed multibeam moments.
A Generalized Method for Calculating Atmospheric Ionization by Energetic Electron Precipitation
Authors: Xu Wei , Marshall Robert A. , Tyssøy Hilde Nesse , Fang Xiaohua 
Published: October 2020

AbstractAccurate specification of ionization production by energetic electron precipitation is critical for atmospheric chemistry models to assess the resultant atmospheric effects. Recent model‐observation comparison studies have increasingly highlighted the importance of considering precipitation fluxes in the full range of electron energy and pitch angle. However, previous parameterization methods were mostly proposed for isotropically precipitation electrons with energies up to 1 MeV, and the pitch angle dependence has not yet been parameterized. In this paper, we first characterize and tabulate the atmospheric ionization response to monoenergetic electrons with different pitch angles and energies between ∼3 keV and ∼33 MeV. A generalized method that fully accounts for the dependence of ionization production on background atmospheric conditions, electron energy, and pitch angle has been developed based on the parameterization method of Fang et al. (2010, https://doi.org/10.1029/2010GL045406). Moreover, we validate this method using 100 random atmospheric profiles and precipitation fluxes with monoenergetic and exponential energy distributions, and isotropic and sine pitch angle distributions. In a suite of 6,100 validation tests, the error in peak ionization altitude is found to be within 1 km in 91% of all the tests with a mean error of 2.7% in peak ionization rate and 1.9% in total ionization. This method therefore provides a reliable means to convert space‐measured precipitation energy and pitch angle distributions into ionization inputs for atmospheric chemistry models.
Three‐Dimensional Crustal Structures of the Shanxi Rift Constructed by Rayleigh Wave Dispersion Curves and Ellipticity: Implication for Sedimentation, Intraplate Volcanism, and Seismicity
Authors: Xu Hongrui , Luo Yinhe , Yang Yingjie , Shen Weisen , Yin Xiaofei , Chen Guoxiong , Yang Xiaozhou , Sun Shida 
Published: October 2020

AbstractThe Shanxi Rift is one of the world's largest Cenozoic continental rifts. It is one of the most earthquake prone areas in China and has volcanic activities characterized by small volumes of magma. In order to study continental rifting mechanism, intraplate volcanism, and seismicity of the Shanxi Rift, we construct a high‐resolution 3‐D lithospheric shear velocity (Vs) model with a focus of the crust by jointly inverting Rayleigh wave dispersion curves and ellipticity measurements. Compared with published models, our 3‐D Vs model has improved the resolution for shallow structures. Our model reveals several significant velocity features. (1) The sedimentary layer of the Datong Basin is much thicker than those in the southern Shanxi Rift, implying that the sedimentation rate of the Datong Basin is higher, which could be attributed in part to asthenosphere upwelling beneath the Datong Basin area in the past few Ma in addition to passive rifting. (2) A low‐velocity body is observed in the middle crust beneath the Datong Volcanoes, suggesting the presence of a small amount of partial melting in the middle crust. (3) Lower velocities in the middle and lower crust beneath the Datong Basin are coincident with the shallowing of deep earthquakes from the southern to northern Shanxi Rift in the crust, suggesting that higher temperature may elevate the brittle‐to‐ductile transition zone, leading to the shallowing of focal depths of earthquakes in the Shanxi Rift from south to north.
The Mechanism of the Origin and Development of Lightning From Initiating Event to Initial Breakdown Pulses (v.2)
Authors: Kostinskiy Alexander Yu. , Marshall Thomas C. , Stolzenburg Maribeth 
Published: October 2020

AbstractBased on experimental results of recent years, this article presents a qualitative description of a possible mechanism (termed the Mechanism) covering the main stages of lightning initiation, starting before and including the initiating event, followed by the initial electric field change (IEC), followed by the first few initial breakdown pulses (IBPs). The Mechanism assumes initiation occurs in a region of ~1 km3 with average electric field E > 0.3 MV/(m·atm), which contains, because of turbulence, numerous small “Eth volumes” of ~10−4–10−3 m3 with E ≥ 3 MV/(m·atm). The Mechanism allows for lightning initiation by either of two observed types of events: a high‐power, very high frequency (VHF) event such as a Narrow Bipolar Event or a weak VHF event. According to the Mechanism, both types of initiating events are caused by a group of relativistic runaway electron avalanche particles (where the initial electrons are secondary particles of an extensive air shower) passing through many Eth volumes, thereby causing the nearly simultaneous launching of many positive streamer flashes. Due to ionization‐heating instability, unusual plasma formations (UPFs) appear along the streamers' trajectories. These UPFs combine into three‐dimensional (3‐D) networks of hot plasma channels during the IEC, resulting in its observed weak current flow. The subsequent development and combination of two (or more) of these 3‐D networks of hot plasma channels then causes the first IBP. Each subsequent IBP is caused when another 3‐D network of hot plasma channels combines with the chain of networks caused by earlier IBPs.
Mechanical Forcing of Convection by Cold Pools: Collisions and Energy Scaling
Authors: Meyer Bettina , Haerter Jan O. 
Published: October 2020

AbstractForced mechanical lifting through cold pool gust fronts can trigger new convection and, as previous work highlights, is enhanced when cold pools collide. However, as shown by conceptual models, the organization of the convective cloud field emerging from two versus three colliding cold pools differs strongly. In idealized dry large‐eddy simulations we therefore compare collisions between two and three cold pools. The triggering likelihood is quantified in terms of the cumulative vertical mass flux of boundary layer air and the instantaneous updraft strength, generated at the cold pool gust fronts. We find that cold pool expansion can be well described by initial potential energy alone. Cold pool expansion monotonically slows but shows an abrupt transition between an axisymmetric and a broken‐symmetric state mirrored by a sudden drop in expansion speed. We characterize these two dynamic regimes by two distinct power law exponents and explain the transition by the onset of “lobe‐and‐cleft” instabilities at the cold pool head. Two‐cold pool collisions produce the strongest instantaneous updrafts in the lower boundary layer, which we expect to be important in environments with strong convective inhibition. Three‐cold pool collisions generate weaker but deeper updrafts and the strongest cumulative mass flux and are thus predicted to induce the largest midlevel moistening, which has been identified as a precursor for the transition from shallow to deep convection. Combined, our findings may help decipher the role of cold pools in spatially organizing convection and precipitation.
microRNA-199a-3p inhibits hepatic apoptosis and hepatocarcinogenesis by targeting PDCD4
Authors: Li Zhenyang , Zhou Ye , Zhang Liyuan , Jia Kaiwei , Wang Suyuan , Wang Mu , Li Nan , Yu Yizhi , Cao Xuetao , Hou Jin 
Published: October 2020

AbstractHepatic apoptosis and the initiated liver inflammation play the initial roles in inflammation-induced hepatocarcinogenesis. Molecular mechanisms underlying the regulation of hepatocyte apoptosis and their roles in hepatocarcinogenesis have attracted much attention. A set of microRNAs (miRNAs) have been determined to be dysregulated in hepatocellular carcinoma (HCC) and participated in cancer progression, however, the roles of these dysregulated miRNAs in carcinogenesis are still poorly understood. We previously analyzed the dysregulated miRNAs in HCC using high-throughput sequencing, and found that miR-199a/b-3p was abundantly expressed in human normal liver while markedly decreased in HCC, which promotes HCC progression. Whether miR-199a/b-3p participates in HCC carcinogenesis is still unknown up to now. Hence, we focused on the role and mechanism of miR-199a/b-3p in hepatocarcinogenesis in this study. Hepatic miR-199a/b-3p was determined to be expressed by miR-199a-2 gene in mice, and we constructed miR-199a-2 knockout and hepatocyte-specific miR-199a-2 knockout mice. Diethylnitrosamine (DEN)-induced hepatocarcinogenesis were markedly increased by hepatocyte-specific miR-199a-3p knockout, which is mediated by the enhanced hepatocyte apoptosis and hepatic injury by DEN administration. In acetaminophen (APAP)-induced acute hepatic injury model, hepatocyte-specific miR-199a-3p knockout also aggravated hepatic apoptosis. By proteomic screening and reporter gene validation, we identified and verified that hepatic programed cell death 4 (PDCD4), which promotes apoptosis, was directly targeted by miR-199a-3p. Furthermore, we confirmed that miR-199a-3p-suppressed hepatocyte apoptosis and hepatic injury by targeting and suppressing PDCD4. Thus, hepatic miR-199a-3p inhibits hepatocyte apoptosis and hepatocarcinogenesis, and decreased miR-199a-3p in hepatocytes may aggravate hepatic injury and HCC development.
Heterogeneity in PD-L1 expression in malignant peritoneal mesothelioma with systemic or intraperitoneal chemotherapy
Authors: White Michael G. , Schulte Jefree J. , Xue Lai , Berger Yaniv , Schuitevoerder Darryl , Vining Charles C. , Kindler Hedy L. , Husain Aliya , Turaga Kiran K. , Eng Oliver S. 
Published: October 2020

AbstractProgrammed death-ligand 1 (PD-L1) expression has been described in patients with malignant peritoneal mesothelioma (MPM), but treatment strategies utilising immune checkpoint inhibition are yet to be defined. Here, we examine levels of PD-L1 expression in MPM patients treated with systemic and/or intraperitoneal chemotherapy using tissue from patient tumour biopsies or resections at multiple time points. We found the mean PD-L1 expression was higher in those with a germline mutation and/or those with a higher somatic mutation burden. Moreover, PD-L1 expression was lower in patients who had received prior chemotherapy as compared to the treatment-naive cohort. Twenty patients who received chemotherapy, either systemic and/or peritoneal, between PD-L1 measurements showed marked heterogeneity. Six (30%) patients demonstrated upregulation of PD-L1, while eight (40%) demonstrated downregulation. Heterogeneity in PD-L1 expression in MPM before and after cytotoxic therapies may present an additional consideration when initiating immune checkpoint inhibition in this rare and challenging disease.
Trastuzumab upregulates programmed death ligand-1 expression through interaction with NK cells in gastric cancer
Authors: Yamashita Kohei , Iwatsuki Masaaki , Yasuda-Yoshihara Noriko , Morinaga Takeshi , Nakao Yosuke , Harada Kazuto , Eto Kojiro , Kurashige Junji , Hiyoshi Yukiharu , Ishimoto Takatsugu , Nagai Yohei , Iwagami Shiro , Baba Yoshifumi , Miyamoto Yuji , Yoshida Naoya , Ajani Jaffer A. , Baba Hideo 
Published: October 2020

Abstract
Background
The predictive significance of programmed death ligand 1 (PD-L1) for programmed death 1 (PD-1) inhibitors remains unclear in gastric cancer (GC) due to the dynamic alteration by treatments. We aimed to elucidate the effects of trastuzumab (Tmab) on PD-L1 expression in GC.

Methods
PD-L1 expression was evaluated by multicolour flow cytometry analysis after co-culturing GG cell lines and immune cells with Tmab. IFN-γ in the co-culture experiments was quantified. Immunohistochemistry (IHC) for PD-L1 expression using clinical samples was also performed to confirm PD-L1 alteration by Tmab.

Results
PD-L1 expression was significantly upregulated by Tmab in HER2-amplified GC cell lines co-cultured with peripheral blood mononuclear cells (PBMCs). PD-L1 upregulation by Tmab was also observed in the GC cells co-cultured with NK cells in time-dependent manner, but not with monocytes. IFN-γ concentration in conditioned media from co-cultured PBMCs and NK cells with Tmab was significantly higher and anti-IFN-γ significantly suppress the Tmab-induced PD-L1 upregulation. IHC also suggested PD-L1 upregulation after Tmab treatment.

Conclusions
Tmab can upregulate PD-L1 expression on GC cells through interaction with NK cells. These results suggest clinical implications in the assessment of the predictive significance of PD-L1 expression for PD-1 inhibitors.