bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of a six-item dietary calcium screening tool among HIV patients in China
Authors: Tseng Leslie Yingzhijie , Xie Wenni , Pan Wei , Lyu Hui , Yu Zhangping , Shi Wenyan , He Yun , Chen Wei , Li Taisheng , Hsieh Evelyn
Published: April 2021

Objective:

Individuals with HIV are at increased risk for osteoporosis. A healthy diet with adequate Ca is recommended to promote bone health. However, lengthy nutritional assessments pose barriers to routine screenings in clinical practice. This study aimed to examine the validity and reproducibility of a six-item dietary Ca screening tool among Chinese individuals with HIV.

Design:

We conducted a two time-point study in an outpatient setting. Volunteers self-administered the six-item tool upon enrolment and again at 1-month follow-up. At baseline, participants also completed a validated FFQ and surveys regarding demographic and clinical risk factors.

Setting:

Beijing, China; Shenzhen, Guangdong, China.

Participants:

Upon enrolment, 127 individuals with HIV participated in the study, of whom 83 completed the follow-up screening.

Results:

Mean age of participants was 35·2 (sd 9·3) years, average BMI was 22·8 (sd 3·8) kg/m2 and 89 % were men. Among the participants, 54·7 % reported Ca intake less than 800 mg/d. The six-item tool demonstrated fair-to-moderate relative validity with a correlation of 0·39 and 75·7 % of subjects classified in same/adjacent quartiles as the reference, and moderate-to-good reproducibility with a correlation of 0·60 and 83·1 % of subjects classified in same/adjacent quartiles. Finally, receiver operating characteristic analyses yielded a sensitivity of 87·0 % and a specificity of 39·4 % with optimised cut-off level.

Conclusions:

The six-item tool presented adequate validity and reproducibility to identify individuals with low Ca intake among the target population, providing a convenient instrument for categorising Ca intake in clinical practice, prompting referrals for further assessment, and raising awareness of dietary Ca in bone disease prevention.
Brands with personalities – good for businesses, but bad for public health? A content analysis of how food and beverage brands personify themselves on Twitter
Authors: Greene Tenay , Seet Carla , Rodríguez Barrio Andrea , McIntyre Dana , Kelly Bridget , Bragg Marie A
Published: April 2021

Objective:

To examine the extent to which food and beverage brands exhibit personalities on Twitter, quantify Twitter users’ engagement with posts displaying personality features and determine advertising spending across these brands on Twitter.

Design:

We identified 100 tweets from 10 food and beverage brands that displayed a ‘personality’, and 100 ‘control’ tweets (i.e. a post by that brand on the same day). Our codebook quantified the following personification strategies: (1) humour; (2) trendy language and (3) absence of food product mentions. We used media articles to quantify other personification strategies: (4) referencing trending topics; (5) referencing current events; (6) referencing internet memes and (7) targeting niche audiences. We calculated brands’ number of tweets, re-tweets, ‘likes’, and comments and report the relationship between advertising spending and retweets per follower.

Setting:

Twitter posts.

Participants:

Ten food and beverage brands that were described in media articles (e.g. Forbes) as having distinct personalities.

Results:

Personality tweets earned 123 013 retweets, 732 076 ‘likes’ and 14 806 comments, whereas control tweets earned 61 044 retweets, 256 105 ‘likes’ and 14 572 comments. The strategies used most included humour (n 81), trendy language (n 80) and trending topics (n 47). The three brands that spent the most on advertising had similar or fewer retweets per follower than the four that spent relatively little on advertising.

Conclusions:

Some food and beverage brands have distinct ‘personalities’ on Twitter that generate millions of ‘likes’ and retweets. Some retweets have an inverse relationship with advertising spending, suggesting ‘personalities’ may be a uniquely powerful advertising tool for targeting young adults.
Established diet quality indices are not universally associated with body composition in young adult women
Authors: Zagarins Sofija E , Ronnenberg Alayne G , Bertone-Johnson Elizabeth R
Published: April 2021

Objective:

To determine which established diet quality indices best predict weight-related outcomes in young women.

Design:

In this cross-sectional analysis, we collected dietary information using the Harvard FFQ and measured body fat percentage (BF%) by dual-energy X-ray absorptiometry. We used FFQ data to derive five diet quality indices: Recommended Food Score (RFS), Healthy Eating Index 2015 (HEI-2015), Alternate Healthy Eating Index 2010 (AHEI-2010), alternate Mediterranean Diet Score (aMED) and Healthy Plant-Based Diet Index (HPDI).

Setting:

University of Massachusetts at Amherst.

Participants:

Two hundred sixty healthy women aged 18–30 years.

Results:

The AHEI-2010 and HPDI were associated with BMI and BF%, such that a ten-point increase in either diet score was associated with a 1·2 percentage-point lower BF% and a 0·5 kg/m2lower BMI (P< 0·05). Odds of excess body fat (i.e. BF% > 32 %) were 50 % lower for those in the highestv. lowest tertile of the AHEI-2010 (P= 0·04). Neither the RFS nor HEI-2015 was associated with BMI or BF%; the aMED was associated with BMI but not BF%.

Conclusions:

These results suggest that diet quality tends to be inversely associated with BMI and BF% in young women, but that this association is not observed for all diet quality indices. Diet indices may have limited utility in populations where the specific healthful foods and food groups emphasised by the index are not widely consumed. Future research should aim to replicate these findings in longitudinal studies that compare body composition changes over time across diet indices in young women.
Assessing the patient experience of anal and rectal cancer MR simulation for radiotherapy treatment planning
Authors: Bird David , Pearce Sinead , Teo Mark , Gilbert Alexandra , Casanova Nathalie , Cooper Rachel , Burnett Carole , Sebag-Montefiore David , Speight Richard , Henry Ann M. , Al-Qaisieh Bashar
Published: April 2021

Aim:

The patient experience of radiotherapy magnetic resonance (MR) simulation is unknown. This study aims to evaluate the patient experience of MR simulation in comparison to computed tomography (CT) simulation, identifying the quality of patient experience and pathway changes which could improve patient experience outcomes.

Materials and Methods:

MR simulation was acquired for 46 anal and rectal cancer patients. Patient experience questionnaires were provided directly after MR simulation. Questionnaire responses were assessed after 33 patients (cohort one). Changes to the scanning pathway were identified and implemented. The impact of changes was assessed by cohort two (13 patients).

Results:

Response rates were 85% (cohort one) and 54% (cohort two). 75% of cohort one respondents found the magnetic resonance imaging (MRI) experience to be better or similar to their CT experience. Implemented changes included routine use of blankets, earplugs and headphones, music and feet-first positioning and further MRI protocol optimisation. All cohort two respondents found the MRI experience to be better or similar to the CT experience.

Findings:

MR simulation can be a comfortable and positive experience that is comparable to that of standard radiotherapy CT simulation. Special attention is required due to the fundamental differences between CT and MRI scanning.
A Qualitative Theory of Cognitive Attitudes and their Change
Authors: LORINI EMILIANO
Published: April 2021

Abstarct

We present a general logical framework for reasoning about agents’ cognitive attitudes of both epistemic type and motivational type. We show that it allows us to express a variety of relevant concepts for qualitative decision theory including the concepts of knowledge, belief, strong belief, conditional belief, desire, conditional desire, strong desire, and preference. We also present two extensions of the logic, one by the notion of choice and the other by dynamic operators for belief change and desire change, and we apply the former to the analysis of single-stage games under incomplete information. We provide sound and complete axiomatizations for the basic logic and for its two extensions.
Discordance between the perceptions of clinicians and families about end-of-life trajectories in hospitalized dementia patients
Authors: Moon Felicity , Kissane David W. , McDermott Fiona
Published: April 2021

Background

Due to the unpredictable dementia trajectory, it is challenging to recognize illness progression and the appropriateness of a palliative approach. Further confusion occurs during hospitalization where the presence of comorbid conditions complicates prognostication. This research examined clinicians and families' perceptions of dementia as a terminal condition in relation to end-of-life admissions.

Context

The study was based in the General Medicine units of one Australian public hospital. Medical, nursing, and social work clinicians were recruited to reflect multidisciplinary perspectives. Bereaved caregivers of deceased patients with dementia were interviewed 3 months following death.

Methods

Qualitative research underpinned by a social constructionist epistemology and framed through complex systems theory. Semi-structured interviews generated data that illuminated perceptions of deterioration observed toward the end of life.

Results

Although participants anticipated general cognitive and physical deterioration associated with dementia, the emergence of comorbid illness made it difficult to predict the onset of the end of life. During a hospital admission, clinicians attributed the end of life to the advanced outcomes of dementia, whereas families described new medical crises. End-of-life admissions illuminated intersections between dementia and comorbidities rather than illness progression. In contrast with the perception that people with dementia lose awareness at the end of life, families drew attention to evidence that their loved one was present during the dying phase.

Significance of results

Our findings challenge the dominant understanding of dementia trajectories. Bifurcations between clinicians and families' views demonstrate the difficulties in recognizing end-of-life transitions. Implications for the integration of palliative care are considered.
Rice response to sublethal rates of paraquat, metribuzin, fomesafen, and cloransulam-methyl at different application timings
Authors: Lawrence Benjamin H. , Bond Jason A. , Golden Bobby R. , Allen Tom W. , Reynolds Daniel B. , Bararpour Taghi M.
Published: April 2021

The application of paraquat mixtures with residual herbicides before planting rice is a common treatment in Mississippi, and rice in proximity is susceptible to off-target movement of these applications. Four concurrent studies were conducted in Stoneville, MS, to characterize rice performance following exposure to a sublethal rate of paraquat, metribuzin, fomesafen, and cloransulam-methyl at different application timings. Herbicides were applied to rice at the growth stages of spiking to one-leaf (VEPOST), two- to three-leaf (EPOST), three- to four-leaf (MPOST), 7 d postflood (PFLD), and panicle differentiation (PD). Regardless of application timing, rice injury following exposure to paraquat was ≥45%. Delays in maturity were increased by 0.3 d d−1 following paraquat from emergence through PD. Dry weight, rough rice yield, panicle density, and germination were reduced by 18.7 g, 131.5 kg ha−1, 5.6 m−2, and 0.3%, respectively, per day from application of paraquat at emergence through PD. By 28 d after treatment (DAT), metribuzin injured rice 3% to 6%, and that injury did not translate into a yield reduction. Regardless of application timing, rice injury following fomesafen application ranged from 2% to 5% 28 DAT. Rice exposed to cloransulam-methyl EPOST exhibited the greatest root and foliar injury 21 DAT and 28 DAT, respectively. Additionally, when rice was exposed to cloransulam-methyl EPOST, yield was reduced to 6,540 kg ha−1 compared with a yield of 7,850 kg ha−1 from nontreated rice. Rice yield was negatively affected after paraquat was applied any time after rice emergence. However, applications of paraquat to rice at early reproductive growth stages reduced rough rice yield and seed germination the greatest. Application timing is crucial in determining severity of rice injury. Early-season injury to rice following paraquat application had less effect on yield compared with injury at later stages. Additionally, fields devoted to seed rice production are at risk for reduced seed germination if they are exposed to paraquat during early reproductive growth stages.
Applications of topramezone and SpeedZone®for POST goosegrass (Eleusine indica) control in hybrid bermudagrass
Authors: Carroll Devon E. , Brosnan James T. , Breeden Gregory K.
Published: April 2021

Topramezone and carfentrazone + 2,4-D + mecoprop-p + dicamba (SpeedZone®) are herbicides labeled for POST goosegrass (Eleusine indicaL. Gaertn.) control in hybrid bermudagrass (Cynodon dactylon×C. transvaalensisBurtt Davy). Field research was conducted in Knoxville, TN, during 2019 and 2020 to evaluate goosegrass control and hybrid bermudagrass tolerance to these herbicides applied alone and in mixture. Treatments included topramezone (12.2 g ha–1), SpeedZone® [carfentrazone (33.6 g ha–1) + 2,4-D (1,029 g ha–1) + mecoprop-p (322 g ha–1) + dicamba (91 g ha–1)] and SpeedZone® + topramezone at 12.2, 6.1, 3.6, or 2.4 g ha–1. A nontreated control was included for comparison. Hybrid bermudagrass tolerance was assessed on four cultivars (‘Northbridge’, ‘Tifway’, ‘Tahoma 31’, and ‘TifTuf’) via visual ratings of turfgrass injury and assessments of normalized difference vegetation index (NDVI). At the termination of the experiment, SpeedZone® alone and in mixture with topramezone controlled goosegrass better than or equal to topramezone alone. Mixtures of SpeedZone® + topramezone reduced injury on all cultivars compared to topramezone alone, particularly when mixtures delivered ≤6.1 g ha–1topramezone. Injury subsided on all cultivars by 28 d after treatment regardless of herbicide. Findings suggest that SpeedZone® can be mixed with topramezone at the rates tested herein to minimize hybrid bermudagrass injury from topramezone applications for goosegrass control.
Evaluation of Hourly PWV Products Derived From ERA5 and MERRA‐2 Over the Tibetan Plateau Using Ground‐Based GNSS Observations by Two Enhanced Models
Authors: Huang Liangke , Mo Zhixiang , Liu Lilong , Zeng Zhaoliang , Chen Jun , Xiong Si , He Hongchang
Published: April 2021

Precipitable water vapor (PWV), despite being the key factor for assessing climate change over the Tibetan Plateau (TP), is undersampled in this region due to the complex terrain and climate conditions therein. The fifth‐generation European Center for Medium‐Range Weather Forecasts Reanalysis (ERA5) and Second Modern‐Era Retrospective Analysis for Research and Applications (MERRA‐2) data sets are the two newly released global reanalyzes that provide hourly PWV products with a high spatiotemporal resolution for water vapor research. The accuracies of these two PWV products on the TP require a comprehensive and cautious assessment. In this study, the hourly PWV values derived from ERA5 and MERRA‐2 are systematically assessed by a comparison with 33 Global Navigation Satellite System (GNSS) stations from 2017 to 2018 over the TP. To improve the reliability of this evaluation, an enhanced Tm model and a PWV vertical correction model, namely, TP‐Tm and TP‐PWVC, respectively, are developed, and both models show better performance when compared against other widely used models. The accuracies of the ERA5‐ and MERRA‐2‐derived PWV at the 33 GNSS stations are very high; ERA5 has the smallest mean bias and root mean square (RMS) error of −0.08 and 1.77 mm, respectively, compared to those of 0.53 and 2.12 mm for MERRA‐2. In addition, the biases and RMS errors show significant regional and seasonal differences. The performance of ERA5 is slightly better than MERRA‐2, mainly due to its higher spatial resolution. The spatial distributions of the PWV derived from the two reanalyzes are consistent with the GNSS‐derived PWV distribution. The diurnal PWV variations derived from ERA5 are in good agreement with the diurnal variation of the GNSS‐derived PWV, whereas significant differences are observed for MERRA‐2 at several stations. These results indicate that ERA5 can provide more reliable hourly PWV estimates over the TP, which can help users further understand the strengths and weaknesses of these two PWV products and promote climate change research.
Large‐Scale O+ Depletions Observed by ICON in the Post‐Midnight Topside Ionosphere: Data/Model Comparison
Authors: Huba J. D. , Heelis R. , Maute A.
Published: April 2021

The Ion Velocity Meter instrument on the Ionospheric Connection Explorer (ICON) satellite measured large depletions in the O+ density (but not H+) in the post‐midnight topside ionosphere on December 23, 2019. This phenomenon has been observed previously but has yet to be explained. The authors provide for the first time a physical explanation for this observation based on a simulation study using the first‐principles, ionosphere/plasmasphere code SAMI3 (Sami3 is also a model of the ionosphere) with neutral atmosphere inputs (neutral wind, density, and temperature) from the whole atmosphere model Whole Atmosphere Community Climate Model with thermosphere and ionosphere extension (WACCM‐X). The physical processes responsible for these observations are (1) the nighttime O+/H+ transition altitude is below the ICON orbit and (2) a prolonged downward E × B drift in the post‐midnight/pre‐sunrise time sector. Interestingly, the authors also find that equatorial plasma bubbles develop in the African and Pacific sectors.
The Evolution of Lightning Flash Density, Flash Size, and Flash Energy During Hurricane Dorian's (2019) Intensification and Weakening
Authors: Duran Patrick , Schultz Christopher J. , Bruning Eric C. , Stevenson Stephanie N. , PeQueen David J. , Johnson Nicholas E. , Allen Roger E. , Smith Matthew R. , LaFontaine Frank J.
Published: April 2021

The two most distinct inner‐core lightning outbreaks in Hurricane Dorian (2019) are analyzed using the Geostationary Lightning Mapper (GLM). The first outbreak occurred during Dorian's intensification, including a rapid intensification (RI), and the second occurred during weakening. During RI, inner‐core lightning flash density increased as flashes concentrated inside of the radius of maximum wind (RMW). As weakening commenced, numerous flashes still occurred within the RMW, with a flash rate more than three times that during RI–a signal typically associated with strengthening. These flashes, however, were much smaller and less energetic than those during intensification. Evidence is presented that barotropic mixing and secondary eyewall formation increased the number of small, low‐energy lightning flashes in the inner core while simultaneously weakening the storm. The results suggest that flash area and energy from GLM could help distinguish between lightning outbreaks that correspond to intensification and those that correspond to weakening.
On the Breakdown of ENSO's Relationship With Thermocline Depth in the Central‐Equatorial Pacific
Authors: Zhao Sen , Jin Fei‐Fei , Long Xiaoyu , Cane Mark A.
Published: April 2021

Recent classification of El Nino‐Southern Oscillation (ENSO) into two types, Eastern (EP) and Central (CP) events, has highlighted the importance of the central Pacific. We show here that the local correlation between ENSO subsurface temperatures (Tsub) in the upper 100‐m and thermocline depth anomalies breaks down in the central equatorial Pacific, whereas Tsub remains well correlated with sea surface height anomalies. This observed difference in the central equatorial Pacific is simulated by almost all climate models. It arises from a vertically slanted Tsub anomaly structure that is unique to the central equatorial Pacific. We show that this feature is an adiabatic response to wind‐driving that is even present in a linear dynamic model, as long as the model has enough baroclinic modes to adequately represent the observed vertical complexity. Our findings have implications for better understanding the different importance of thermocline feedback in CP and EP events.
Predicted Sources of Samples Returned From Chang’e−5 Landing Region
Authors: Liu Tiantian , Michael Greg , Zhu Meng‐Hua , Wünnemann Kai
Published: April 2021

China's Chang’e‐5 (CE‐5) has returned 1.731 kg lunar samples from a young mare unit on December 2020. Here, the authors used a spatially resolved numerical model, which considers both impact mixing and volcanic effusion, to estimate the evolving distribution of components over the landing region. Using this model, the age composition of surface scooped and sub‐surface drilled CE‐5 samples and their sources were traced back. The proposed model predicts that local mare material predominates in both surface and sub‐surface samples and the nonlocal mare component is ∼1%. There is ∼40% of nonmare component. The composition of both nonmare components in the surface and sub‐surface samples are similar: Abundant components are basin‐sourced melts, where the Imbrium melt are ∼ 25% among all the melt. The ejecta of Sharp B, Harding, Copernicus, and Aristarchus crater that possess different compositions of basin‐sourced melt may have significantly altered the material composition of the landing surface.
Dependence of Climate Sensitivity on the Given Distribution of Relative Humidity
Authors: Bourdin Stella , Kluft Lukas , Stevens Bjorn
Published: April 2021

We study how the vertical distribution of relative humidity (RH) affects climate sensitivity, even if it remains unchanged with warming. Using a radiative‐convective equilibrium model, we show that the climate sensitivity depends on the shape of a fixed vertical distribution of humidity, tending to be higher for atmospheres with higher humidity. We interpret these effects in terms of the effective emission height of water vapor. Differences in the vertical distribution of RH are shown to explain a large part of the 10%–30% differences in clear‐sky sensitivity seen in climate and storm‐resolving models. The results imply that convective aggregation reduces climate sensitivity, even when the degree of aggregation does not change with warming. Combining our findings with RH trends in reanalysis data shows a tendency toward Earth becoming more sensitive to forcing over time. These trends and their height variation merit further study.
The Principal Hugoniot of Iron‐Bearing Olivine to 1465 GPa
Authors: Chidester B. A. , Millot M. , Townsend J. P. , Spaulding D. K. , Davies E. J. , Root S. , Kalita P. , Fratanduono D. E. , Jacobsen S. B. , Stewart S. T.
Published: April 2021

Shock compression experiments on natural compositions are imperative to accurately model planetary accretion and the interior dynamics of planets. Combining shock compression experiments from the Sandia Z Machine and the OMEGA EP laser facility with density functional theory‐based molecular dynamics calculations, we report the first pressure‐density‐temperature (P‐ρ‐T) relationship of natural iron (Fe)‐bearing olivine ((Mg0.91Fe0.09)2SiO4) on the principal Hugoniot between 166 and 1,465 GPa. Additionally, we report the first reflectivities of natural olivine liquid in this pressure range. Compared to the magnesium‐endmember forsterite (Mg2SiO4), the presence of Fe in typical mantle abundance (∼9 wt% FeO) alters the US‐uP relation of olivine. On the other hand, the shock temperature and reflectivity of olivine are indistinguishable from forsterite where experimental conditions overlap. Both forsterite and olivine increase in reflectivity (and hence optical conductivity) with increasing temperature, with a maximum reflectivity of ∼31% at shock velocities greater than 22 km/s (∼800 GPa).
Double‐Peak Structures of Martian Nightside Total Electron Content in Strong Crustal Magnetic Cusp Regions
Authors: Qin JunFeng , Zou Hong , Futaana Yoshifumi , Ye YuGuang , Hao YongQiang , Nielsen Erling , Wang JinSong
Published: April 2021

With the help of the high‐spatial‐resolution total electron content (TEC) data obtained by Mars Advanced Radar for Subsurface and Ionospheric Sounding on board the Mars Express (MEx) during June 2005 to September 2007, the detailed configurations of the Martian nightside ionosphere in crustal magnetic field cusp regions are researched in this paper. It is found that double‐peak structures of orbital observed TEC values frequently appeared when MEx was crossing through the strong crustal magnetic field cusp regions. This observational result implies that the Martian nightside TECs in the periphery of the cusp regions are generally higher than those in the central areas of the cusp regions, a phenomenon never reported before. By combining the TEC data with the in‐situ electron flux data obtained by the Analyzer of Space Plasma and Energetic Atoms‐3 (ASPERA‐3), it is found that the difference between the fluxes of the electrons precipitating in the central and peripheral areas of the cusp regions can be responsible for the observed TEC double‐peak structures.
Atmospheric Nanoparticle Survivability Reduction Due to Charge‐Induced Coagulation Scavenging Enhancement
Authors: Mahfouz Naser G. A. , Donahue Neil M.
Published: April 2021

New‐particle formation is important to aerosol–cloud interactions and thus climate, but for newly formed particles to become cloud condensation nuclei, they must grow and avoid scavenging by larger background particles. Whereas ion‐induced new‐particle formation and growth have received attention recently, here we study an opposing effect, blunting the enhancement due to ions, that has received less attention: Small charged particles are scavenged more efficiently due to their charge, and thus their survival probability is lower than that of their neutral counterparts. Through simulations, we show that particle survival is reduced, in some cases dramatically, matching updated theoretical predictions. We also show that the survival of charged particles is enhanced if particles lose their charge via neutralization; therefore, for ion‐induced nucleation to be important, the resulting charged particles must become neutral as soon as possible. Overall, the coagulation scavenging enhancement due to charge ought to lessen the influence of ions in new‐particle formation and growth.
Flexural Control of Basal Crevasse Opening Under Ice Shelves
Authors: Buck W. Roger , Lai Ching‐Yao
Published: April 2021

Classical analyses of basal crevasse opening do not account for the free surface of a floating ice layer. We describe a high‐resolution numerical treatment of the opening of a single crevasse in a finite thickness elastic layer floating on an inviscid substrate. For low extensional stress (less than about half of the expected maximum for a freely floating shelf) the resulting crevasse height and width match previous studies. For larger magnitude applied extensional stresses, the new results predict basal crevasse widths an order of magnitude greater than the classical solution. An analysis using the thin‐layer approximation shows that the greatly increased predicted width of basal crevasse opening results from layer bending. Given that the height and width of basal crevasses are non‐linear functions of the stress experienced by an ice shelf, the new model results may enable better estimation of buttressing stresses for different parts of ice shelves.
RNA-sequencing data-driven dissection of human plasma cell differentiation reveals new potential transcription regulators
Authors: Kassambara Alboukadel , Herviou Laurie , Ovejero Sara , Jourdan Michel , Thibaut Coraline , Vikova Veronika , Pasero Philippe , Elemento Olivier , Moreaux Jérôme
Published: April 2021

Plasma cells (PCs) play an important role in the adaptive immune system through a continuous production of antibodies. We have demonstrated that PC differentiation can be modeled in vitro using complex multistep culture systems reproducing sequential differentiation process occurring in vivo. Here we present a comprehensive, temporal program of gene expression data encompassing human PC differentiation (PCD) using RNA sequencing (RNA-seq). Our results reveal 6374 differentially expressed genes classified into four temporal gene expression patterns. A stringent pathway enrichment analysis of these gene clusters highlights known pathways but also pathways largely unknown in PCD, including the heme biosynthesis and the glutathione conjugation pathways. Additionally, our analysis revealed numerous novel transcriptional networks with significant stage-specific overexpression and potential importance in PCD, including BATF2, BHLHA15/MIST1, EZH2, WHSC1/MMSET, and BLM. We have experimentally validated a potent role for BLM in regulating cell survival and proliferation during human PCD. Taken together, this RNA-seq analysis of PCD temporal stages helped identify coexpressed gene modules with associated up/downregulated transcription regulator genes that could represent major regulatory nodes for human PC maturation. These data constitute a unique resource of human PCD gene expression programs in support of future studies for understanding the underlying mechanisms that control PCD.
Telomere length and telomere repeat-binding protein in children with sickle cell disease
Authors: Suliman Mohamed E. , Ansari Mohammed G. A. , Rayis Mohamed A. , Hamza Muaawia A. , Saeed Abdullah A. , Mohammed Abdul Khader , Al-Daghri Nasser M.
Published: April 2021

Background

This study aimed to assess the telomere length and plasma telomere repeat-binding factor 2 (TRF2) levels in addition to other inflammatory markers in children with sickle cell disease (SCD).

Methods

We enrolled 106 children (90 SCD and 26 controls) aged 1–15 years from the Hematology unit of King Fahad Medical City (KFMC), Saudi Arabia. Genomic DNA extracted from blood and leukocyte TL was determined using quantitative reverse transcription PCR, whereas TRF2, C-reactive protein, interleukin-6, and DNA oxidative damage were determined by using respective commercially available assays.

Results

Leukocyte TL was inversely correlated with age in the SCD patients (r = −0.24, P = 0.02) and the controls (r = −0.68, P < 0.0001). In addition, SCD patients had significantly shorter TL (7.74 ± 0.81 kb) (P = 0.003) than controls (8.28 ± 0.73 kb). In contrast, no significant difference in TL among the SCD genotypes (HbSS and HbSβ0) has been observed. A modest, positive correlation was seen between TL and reticulocyte % (r = 0.21; P = 0.06). There were no significant differences in the TL and TRF2 concentrations between subjects with HbSS and HbSβ0 genotypes.

Conclusions

Short leukocyte TL was significantly associated with SCD. An inverse association was observed between TL and hemoglobin. Hydroxyurea treatment revealed no impact on TL.

Impact

This study explored the TL and plasma TRF2 in Saudi children with SCD. This is the first documentation that SCD children have shorter TL than their healthy counterparts, and no association between TL and TRF2 has been observed.

Hydroxyurea treatment showed no impact on TL in children with SCD.

This study is the first of its kind in children with SCD.

It will pave the way for another study with a larger sample size in a diverse population to scrutinize these findings better.
“GrimAge,” an epigenetic predictor of mortality, is accelerated in major depressive disorder
Authors: Protsenko Ekaterina , Yang Ruoting , Nier Brent , Reus Victor , Hammamieh Rasha , Rampersaud Ryan , Wu Gwyneth W. Y. , Hough Christina M. , Epel Elissa , Prather Aric A. , Jett Marti , Gautam Aarti , Mellon Synthia H. , Wolkowitz Owen M.
Published: April 2021

Major depressive disorder (MDD) is associated with premature mortality and is an independent risk factor for a broad range of diseases, especially those associated with aging, such as cardiovascular disease, diabetes, and Alzheimer’s disease. However, the pathophysiology underlying increased rates of somatic disease in MDD remains unknown. It has been proposed that MDD represents a state of accelerated cellular aging, and several measures of cellular aging have been developed in recent years. Among such metrics, estimators of biological age based on predictable age-related patterns of DNA methylation (DNAm), so-called ‘epigenetic clocks’, have shown particular promise for their ability to capture accelerated aging in psychiatric disease. The recently developed DNAm metric known as ‘GrimAge’ is unique in that it was trained on time-to-death data and has outperformed its predecessors in predicting both morbidity and mortality. Yet, GrimAge has not been investigated in MDD. Here we measured GrimAge in 49 somatically healthy unmedicated individuals with MDD and 60 age-matched healthy controls. We found that individuals with MDD exhibited significantly greater GrimAge relative to their chronological age (‘AgeAccelGrim’) compared to healthy controls (p = 0.001), with a median of 2 years of excess cellular aging. This difference remained significant after controlling for sex, current smoking status, and body-mass index (p = 0.015). These findings are consistent with prior suggestions of accelerated cellular aging in MDD, but are the first to demonstrate this with an epigenetic metric predictive of premature mortality.
Transcriptomic signaling pathways involved in a naturalistic model of inflammation-related depression and its remission
Authors: Moisan Marie-Pierre , Foury Aline , Dexpert Sandra , Cole Steve W. , Beau Cédric , Forestier Damien , Ledaguenel Patrick , Magne Eric , Capuron Lucile
Published: April 2021

This study aimed at identifying molecular biomarkers of inflammation-related depression in order to improve diagnosis and treatment. For this, we performed whole-genome expression profiling from peripheral blood in a naturalistic model of inflammation-associated major depressive disorder (MDD) represented by comorbid depression in obese patients. We took advantage of the marked reduction of depressive symptoms and inflammation following bariatric surgery to test the robustness of the identified biomarkers. Depression was assessed during a clinical interview using Mini-International Neuropsychiatric Interview and the 10-item, clinician-administered, Montgomery–Asberg Depression Rating Scale. From a cohort of 100 massively obese patients, we selected 33 of them for transcriptomic analysis. Twenty-four of them were again analyzed 4–12 months after bariatric surgery. We conducted differential gene expression analyses before and after surgery in unmedicated MDD and non-depressed obese subjects. We found that TP53 (Tumor Protein 53), GR (Glucocorticoid Receptor), and NFκB (Nuclear Factor kappa B) pathways were the most discriminating pathways associated with inflammation-related MDD. These signaling pathways were processed in compositez-scores of gene expression that were used as biomarkers in regression analyses. Results showed that these transcriptomic biomarkers highly predicted depressive symptom intensity at baseline and their remission after bariatric surgery. While inflammation was present in all patients, GR signaling over-activation was found only in depressed ones where it may further increase inflammatory and apoptosis pathways. In conclusion, using an original model of inflammation-related depression and its remission without antidepressants, we provide molecular predictors of inflammation-related MDD and new insights in the molecular pathways involved.
ZEB1-induced LINC01559 expedites cell proliferation, migration and EMT process in gastric cancer through recruiting IGF2BP2 to stabilize ZEB1 expression
Authors: Shen Huojian , Zhu Hongyi , Chen Yuanwen , Shen Zhiyong , Qiu Weiqing , Qian Changlin , Zhang Jie
Published: April 2021

Gastric cancer (GC) is a common type of tumor that is characterized with high metastatic rate. In recent years, increasing studies have indicated that lncRNAs are involved in the regulation on cancer cell proliferation and migration. However, the functional role of long intergenic non-protein coding RNA 1559 (LINC01559) in GC is still unclear. In this study, we applied quantitative real-time polymerase chain reaction (RT-qPCR) and examined that LINC01559 expression was significantly enhanced in GC cells. Functional assays such as EdU, colony formation, JC-1 and transwell assays displayed that silencing LINC01559 inhibited cell proliferation and migration while promoted cell apoptosis in GC. Besides, western blot analysis and immunofluorescence assays examined the expression of factors related to epithelial-mesenchymal transition (EMT) and indicated that EMT process was blocked by LINC01559 knockdown in GC cells. Besides, LINC01559 silencing inhibited tumor growth in vivo. In addition, Chromatin immunoprecipitation (ChIP) assays demonstrated that zinc finger E-box binding homeobox 1 (ZEB1) served as a transcription factor to combine with LINC01559 promoter and activated the expression of LINC01559 in GC cells. In return, LINC01559 recruited insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) to stabilize ZEB1 mRNA to up-regulate ZEB1 in GC cells. In short, the findings in this research might provide a novel target for GC treatment.
MLL3 suppresses tumorigenesis through regulating TNS3 enhancer activity
Authors: Zheng Jun-Yi , Wang Chen-Yu , Gao Chuan , Xiao Qiong , Huang Cheng-Wei , Wu Min , Li Lian-Yun
Published: April 2021

MLL3 is a histone H3K4 methyltransferase that is frequently mutated in cancer, but the underlying molecular mechanisms remain elusive. Here, we found that MLL3 depletion by CRISPR/sgRNA significantly enhanced cell migration, but did not elevate the proliferation rate of cancer cells. Through RNA-Seq and ChIP-Seq approaches, we identified TNS3 as the potential target gene for MLL3. MLL3 depletion caused downregulation of H3K4me1 and H3K27ac on an enhancer ~ 7 kb ahead of TNS3. 3C assay indicated the identified enhancer interacts with TNS3 promoter and repression of enhancer activity by dCas9-KRAB system impaired TNS3 expression. Exogenous expression of TNS3 in MLL3 deficient cells completely blocked the enhanced cell migration phenotype. Taken together, our study revealed a novel mechanism for MLL3 in suppressing cancer, which may provide novel targets for diagnosis or drug development.
AMPK activation by ASP4132 inhibits non-small cell lung cancer cell growth
Authors: Xia Ying-chen , Zha Jian-hua , Sang Yong-Hua , Yin Hui , Xu Guo-qiu , Zhen Jie , Zhang Yan , Yu Ben-tong
Published: April 2021

Activation of adenosine monophosphate-activated protein kinase (AMPK) is able to produce significant anti-non-small cell lung cancer (NSCLC) cell activity. ASP4132 is an orally active and highly effective AMPK activator. The current study tested its activity against NSCLC cells. In primary NSCLC cells and established cell lines (A549 and NCI-H1944) ASP4132 potently inhibited cell growth, proliferation and cell cycle progression as well as cell migration and invasion. Robust apoptosis activation was detected in ASP4132-treated NSCLC cells. Furthermore, ASP4132 treatment in NSCLC cells induced programmed necrosis, causing mitochondrial p53-cyclophilin D (CyPD)-adenine nucleotide translocase 1 (ANT1) association, mitochondrial depolarization and medium lactate dehydrogenase release. In NSCLC cells ASP4132 activated AMPK signaling, induced AMPKα1-ACC phosphorylation and increased AMPK activity. Furthermore, AMPK downstream events, including mTORC1 inhibition, receptor tyrosine kinases (PDGFRα and EGFR) degradation, Akt inhibition and autophagy induction, were detected in ASP4132-treated NSCLC cells. Importantly, AMPK inactivation by AMPKα1 shRNA, knockout (using CRISPR/Cas9 strategy) or dominant negative mutation (T172A) almost reversed ASP4132-induced anti-NSCLC cell activity. Conversely, a constitutively active AMPKα1 (T172D) mimicked and abolished ASP4132-induced actions in NSCLC cells. In vivo, oral administration of a single dose of ASP4132 largely inhibited NSCLC xenograft growth in SCID mice. AMPK activation, mTORC1 inhibition and EGFR-PDGFRα degradation as well as Akt inhibition and autophagy induction were detected in ASP4132-treated NSCLC xenograft tumor tissues. Together, activation of AMPK by ASP4132 potently inhibits NSCLC cell growth in vitro and in vivo.
Correction: Cullin-5 neddylation-mediated NOXA degradation is enhanced by PRDX1 oligomers in colorectal cancer
Authors: Xu Shoufang , Ma Yilei , Tong Qingchao , Yang Jun , Liu Jia , Wang Yanzhong , Li Guoli , Zeng Jin , Fang Sining , Li Fengying , Xie Xinyou , Zhang Jun
Published: April 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41419-021-03656-1
CircHIPK3 regulates the autophagy and apoptosis of hypoxia/reoxygenation-stimulated cardiomyocytes via the miR-20b-5p/ATG7 axis
Authors: Qiu Zhimei , Wang Yan , Liu Weiwei , Li Chaofu , Zhao Ranzun , Long Xianping , Rong Jidong , Deng Wengweng , Shen Changyin , Yuan Jinson , Chen Wengming , Shi Bei
Published: April 2021

Autophagy and apoptosis are involved in myocardial ischemia/reperfusion (I/R) injury. Research indicates that circular RNA HIPK3 (circHIPK3) is crucial to cell autophagy and apoptosis in various cancer types. However, the role of circHIPK3 in the regulation of cardiomyocyte autophagy and apoptosis during I/R remains unknown. Our study aimed to examine the regulatory effect of circHIPK3 during myocardial I/R and investigate its mechanism in cardiomyocyte autophagy and apoptosis. Methods and results. The expression of circHIPK3 was upregulated during myocardial I/R injury and hypoxia/reoxygenation (H/R) injury of cardiomyocytes. To study the potential role of circHIPK3 in myocardial H/R injury, we performed gain-of-function and loss-of-function analyses of circHIPK3 in cardiomyocytes. Overexpression of circHIPK3 significantly promoted H/R-induced cardiomyocyte autophagy and cell injury (increased intracellular reactive oxygen species (ROS) and apoptosis) compared to those in the control group, while silencing of circHIPK3 showed the opposite effect. Further research found that circHIPK3 acted as an endogenous miR-20b-5p sponge to sequester and inhibit miR-20b-5p activity, resulting in increased ATG7 expression. In addition, miR-20b-5p inhibitors reversed the decrease in ATG7 induced by silencing circHIPK3. Conclusions. CircHIPK3 can accelerate cardiomyocyte autophagy and apoptosis during myocardial I/R injury through the miR-20b-5p/ATG7 axis. These data suggest that circHIPK3 may serve as a potential therapeutic target for I/R.
Watching a double strand break repair polymerase insert a pro-mutagenic oxidized nucleotide
Authors: Jamsen Joonas A. , Sassa Akira , Shock David D. , Beard William A. , Wilson Samuel H.
Published: April 2021

Oxidized dGTP (8-oxo-7,8-dihydro-2´-deoxyguanosine triphosphate, 8-oxodGTP) insertion by DNA polymerases strongly promotes cancer and human disease. How DNA polymerases discriminate against oxidized and undamaged nucleotides, especially in error-prone double strand break (DSB) repair, is poorly understood. High-resolution time-lapse X-ray crystallography snapshots of DSB repair polymerase μ undergoing DNA synthesis reveal that a third active site metal promotes insertion of oxidized and undamaged dGTP in the canonical anti-conformation opposite template cytosine. The product metal bridged O8 with product oxygens, and was not observed in the syn-conformation opposite template adenine (At). Rotation of At into the syn-conformation enabled undamaged dGTP misinsertion. Exploiting metal and substrate dynamics in a rigid active site allows 8-oxodGTP to circumvent polymerase fidelity safeguards to promote pro-mutagenic double strand break repair.
Normal tissue architecture determines the evolutionary course of cancer
Authors: West Jeffrey , Schenck Ryan O. , Gatenbee Chandler , Robertson-Tessi Mark , Anderson Alexander R. A.
Published: April 2021

Cancer growth can be described as a caricature of the renewal process of the tissue of origin, where the tissue architecture has a strong influence on the evolutionary dynamics within the tumor. Using a classic, well-studied model of tumor evolution (a passenger-driver mutation model) we systematically alter spatial constraints and cell mixing rates to show how tissue structure influences functional (driver) mutations and genetic heterogeneity over time. This approach explores a key mechanism behind both inter-patient and intratumoral tumor heterogeneity: competition for space. Time-varying competition leads to an emergent transition from Darwinian premalignant growth to subsequent invasive neutral tumor growth. Initial spatial constraints determine the emergent mode of evolution (Darwinian to neutral) without a change in cell-specific mutation rate or fitness effects. Driver acquisition during the Darwinian precancerous stage may be modulated en route to neutral evolution by the combination of two factors: spatial constraints and limited cellular mixing. These two factors occur naturally in ductal carcinomas, where the branching topology of the ductal network dictates spatial constraints and mixing rates.
Efficiency stagnation in global steel production urges joint supply- and demand-side mitigation efforts
Authors: Wang Peng , Ryberg Morten , Yang Yi , Feng Kuishuang , Kara Sami , Hauschild Michael , Chen Wei-Qiang
Published: April 2021

Steel production is a difficult-to-mitigate sector that challenges climate mitigation commitments. Efforts for future decarbonization can benefit from understanding its progress to date. Here we report on greenhouse gas emissions from global steel production over the past century (1900-2015) by combining material flow analysis and life cycle assessment. We find that ~45 Gt steel was produced in this period leading to emissions of ~147 Gt CO2-eq. Significant improvement in process efficiency (~67%) was achieved, but was offset by a 44-fold increase in annual steel production, resulting in a 17-fold net increase in annual emissions. Despite some regional technical improvements, the industry’s decarbonization progress at the global scale has largely stagnated since 1995 mainly due to expanded production in emerging countries with high carbon intensity. Our analysis of future scenarios indicates that the expected demand expansion in these countries may jeopardize steel industry’s prospects for following 1.5 °C emission reduction pathways. To achieve the Paris climate goals, there is an urgent need for rapid implementation of joint supply- and demand-side mitigation measures around the world in consideration of regional conditions.
Diurnal Fe(II)/Fe(III) cycling and enhanced O2 production in a simulated Archean marine oxygen oasis
Authors: Herrmann A. J. , Sorwat J. , Byrne J. M. , Frankenberg-Dinkel N. , Gehringer M. M.
Published: April 2021

The oxygenation of early Earth’s atmosphere during the Great Oxidation Event, is generally accepted to have been caused by oceanic Cyanobacterial oxygenic photosynthesis. Recent studies suggest that Fe(II) toxicity delayed the Cyanobacterial expansion necessary for the GOE. This study investigates the effects of Fe(II) on two Cyanobacteria, Pseudanabaena sp. PCC7367 and Synechococcus sp. PCC7336, in a simulated shallow-water marine Archean environment. A similar Fe(II) toxicity response was observed as reported for closed batch cultures. This toxicity was not observed in cultures provided with continuous gaseous exchange that showed significantly shorter doubling times than the closed-culture system, even with repeated nocturnal addition of Fe(II) for 12 days. The green rust (GR) formed under high Fe(II) conditions, was not found to be directly toxic to Pseudanabaena sp. PCC7367. In summary, we present evidence of diurnal Fe cycling in a simulated shallow-water marine environment for two ancestral strains of Cyanobacteria, with increased O2 production under anoxic conditions.