bluuebunny/crossref_metadata_2025 huggingface dataset:
A healthy lifestyle during adolescence was inversely associated with fatty liver indices in early adulthood: findings from the DONALD cohort study
Authors: Schnermann Maike Elena , Schulz Christina-Alexandra , Perrar Ines , Herder Christian , Roden Michael , Alexy Ute , Nöthlings Ute
Published: May 2022

A healthy lifestyle during adolescence is associated with insulin sensitivity or liver enzyme levels and thus might contribute to the prevention of non-alcoholic fatty liver disease (NAFLD). Therefore, we examined the association between adherence to a hypothesis-based lifestyle score including dietary intake, physical activity, sedentary behaviour, sleep duration and BMI in adolescence and fatty liver indices in early adulthood. Overall, 240 participants of the DOrtmund Nutritional and Anthropometric Longitudinally Designed study completed repeated measurements of lifestyle score factors during adolescence (females: 8·5–15·5 years, males: 9·5–16·5 years). Multivariable linear regression models were used to investigate the association between adolescent lifestyle scores and NAFLD risk (hepatic steatosis index (HSI) and fatty liver index (FLI)) in early adulthood (18–30 years). Participants visited the study centre 4·9 times during adolescence and achieved on average 2·8 (min: 0·6, max: 5) out of five lifestyle score points. Inverse associations were observed between the lifestyle score and fatty liver indices (HSI: ß=−5·8 % (95 % CI −8·3, −3·1), P < 0·0001, FLI: ß=−32·4 % (95 % CI −42·9, −20·0), P < 0·0001) in the overall study population. Sex-stratified analysis confirmed these results in men, while inverse but non-significant associations were observed in women (P > 0·05). A higher lifestyle score was associated with lower HSI and FLI values, suggesting that a healthy lifestyle during adolescence might contribute to NAFLD prevention, predominantly in men. Our findings on repeatedly measured lifestyle scores in adolescents and their association with NAFLD risk in early adulthood warrant confirmation in larger study populations.
Crop–livestock systems transformation in the semiarid zones of North Africa over a decade: approach and case-study in Southern Tunisia
Authors: Alary V. , Frija A.
Published: May 2022

Understanding and representing the transformation of agricultural production systems has attracted increasing interest due to its importance for identifying drivers of changes and coping mechanisms in response to global challenges. These challenges are all the most pressing in North African countries exposed to a dramatic reduction in rainfall and increasing temperatures that affect sustainability in more than half of this semi-arid territory. This paper describes an improved way to understand such transformations through a cross-cutting analysis of crop–livestock system indicators over a period of 10 years in one community in Southern Tunisia. Our methodology is divided into four steps: (i) systems identification, (ii) indicator-based assessment of system crop–livestock sustainability, (iii) hierarchical clustering to identify sustainable intensification (SI)-based farm types and, finally, (iv) analysis of trajectories of these farm types. Results showed that the sustainability of the systems studied increasingly depends on diversification rather than intensification, which dominated in the 2000s. However, diversification has not necessarily improved socio-economic viability. Over the 10-year period, results revealed a dramatic increase of almost 50% in the population of small-scale farms whose viability depends on a range of on- and off-farm activities to meet the short-term needs that correspond to a buffer strategy. Additionally, the dominant SI processes were shown to be mostly based on diversification to livestock activities with both milking and fattening. Our holistic and timeline approach to system transformation makes it possible to account for sustainability between (systems) generations, which will be highly needed in future discussions about sustainability.
Gender-specific co-developmental trajectories of internalizing and externalizing problems from middle childhood to early adolescence: Environmental and individual predictors
Authors: Gong Xue , Guo Nan , Huebner E. Scott , Tian Lili
Published: May 2022

This study aimed to identify gender-specific co-developmental trajectories of internalizing and externalizing problems from middle childhood to early adolescence, along with key environmental and individual predictors among Chinese youth. A total of 1653 Chinese elementary school students (Mage= 9.40;SD= 0.51; 54.57% boys) participated in assessments at six time points, using 6-month assessment intervals. Parallel process latent class growth modeling identified four trajectories for boys: Congruent-low (65.74%), moderate-decreasing internalizing and moderate-stable externalizing problems (18.40%), high increasing-internalizing and low-stable externalizing problems (8.20%), and high decreasing-internalizing and low-stable externalizing problems (7.65%). Three trajectories were identified for girls: Congruent-low (81.09%), moderate co-occurring (7.19%), and high increasing-internalizing and low-stable externalizing problems (11.72%). Multivariate logistic regression analyses revealed that peer victimization served as an environmental risk predictor for the adverse co-developmental trajectories of internalizing and externalizing problems for boys and girls. High sensation-seeking and low self-control served as individual risk variables predicting the trajectories ofhigh increasing-internalizing and low-stable externalizing problems, and low self-control also predicted the trajectories ofhigh decreasing-internalizing and low-stable externalizing problemsfor boys. The findings highlight the importance of gender differences in understanding the progression of internalizing and externalizing problems and inform effective strategies for prevention and intervention.
Mind-mindedness and preschool children’s behavioral difficulties: The moderating role of maternal parenting distress
Authors: Hobby Lucy , Bird Amy L. , Townsend Michelle L. , Barnes Jacqueline
Published: May 2022

Mind-mindedness (MM) is a caregiver’s tendency to appreciate their infant’s internal mental states. This longitudinal study investigated whether maternal MM (10 months) was linked with children’s later behavioral problems (51 months) and the moderating role of maternal parenting distress (PD; 36 months) in a sample of 91 mother–infant dyads. Appropriate MM comments were coded from video-recorded, semi-structured play interactions between mothers and their infants; PD was obtained from maternal completion of the PD subscale of the Parenting Stress Index – Short Form (PSI-SF); and child internalizing and externalizing behavior problems were gathered from maternal report on the Strengths and Difficulties Questionnaire (SDQ). Moderated regression analyses revealed higher early appropriate MM was associated with significantly fewer internalizing emotional problems at 51 months among mothers with lower PD at 36 months, and higher early appropriate MM was associated with lower conduct problems at 51 months in mothers with higher PD at 36 months. Findings demonstrated the importance of considering nuanced contexts such as at-risk mothers and differential presentations of child difficulties in the analysis of the relationship between MM and child behavioral difficulties and the development of MM interventions.
The Takarazuka Opera Company? On the Persistent Ties between the Takarazuka Revue and Opera
Authors: Solander Tove
Published: May 2022

Although the Takarazuka Revue is technically a musical company, its founder's ambition was to create a uniquely Japanese form of opera or operetta, merging elements from Western and Japanese forms. Like opera, and unlike musicals in general, trouser roles play a central part in the all-female Takarazuka Revue, and are typically cited as its main appeal. Research from a Japanese-studies perspective tends to discuss the Takarazuka Revue trouser roles, otokoyaku, as a gender-reversal of all-male kabuki, or put them in the context of androgynous or cross-dressing Japanese idols. This article addresses their connection to trouser roles in non-Japanese music theatre, specifically opera. It does so through three lenses: first, the Takarazuka Revue's opera loans and adaptations; second, the shared aesthetic appeal of trouser roles in these two theatre forms; and finally, the singing styles employed in the Takarazuka Revue, including their change over time and relation to classical singing.
Differential expression of FSHR and LHR genes and proteins during development of rabbit ovarian follicles
Authors: Khalil Eman , Metwally Mohamed , Bahgaat Hatem , Kassab Ahmed , El-Shafey Anwar
Published: May 2022

The development of an ovarian follicle is a complex process at the cellular and molecular level that is mainly regulated by follicle-stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHR). To elucidate the contribution of these receptors to ovarian follicle development, it is necessary to determine their expression profiles during this biological process. Therefore, this study aimed to investigate the relationship between ovarian development pattern and the differential ovarian expression pattern ofFSHRandLHRgenes as well as proteins at different developmental stages. Ovaries were collected from 30 New Zealand rabbits at day 0 (birth), week 2 (neonate), week 4 (cub), week 16 (maturity), and day 18 pregnancy. Ovarian histology, and gene as well as protein expression were determined using light microscopy, real-time PCR and western blotting, respectively. The results showed that the expression levels ofFSHRmRNA and protein increased coincidently with age and the growth of ovarian follicles. The levels ofLHRmRNA and protein remained low from the day of birth until week 4 and became significantly higher by week 16 coinciding with appearance of growing and antral follicles, which have a defined thecal layer. FSHR gene and protein expression decreased with pregnancy, whereas LHR increased, reaching a peak level during pregnancy. It can be concluded that changes in FSHR and LHR gene and protein expression could be related to the growth and development of follicles, indicating the regulatory role for these receptors in rabbit folliculogenesis.
Lodewyk H.S. van Mierop (March 31, 1927–October 17, 2021): a true giant
Authors: Anderson Robert H. , Bleiweis Mark S. , Fricker F.J. , Saidi Arwa , Chandran Arun , Fudge James C. , Gupta Dipankar , Peek Giles J. , Spicer Diane E. , Jacobs Jeffrey P.
Published: May 2022

We honour a great man and a true giant. Lodewyk H.S. van Mierop (March 31, 1927 – October 17, 2021), known as Bob, was not only a Paediatric Cardiologist but also a dedicated Scientist. He made many significant and ground-breaking contributions to the fields of cardiac anatomy and embryology. He was devoted as a teacher, spending many hours with medical students, Residents, and Fellows, all of whom appreciated his regularly scheduled educational sessions. Those of us who were fortunate to know and spend time with him will always remember his great mind, his willingness to share his knowledge, and his ability to encourage spirited and fruitful discussions. His life was most productive, and he will long be remembered by many through his awesome and exemplary scientific contributions.

His legacy continues to influence the current and future generations of surgeons and all providers of paediatric and congenital cardiac care through the invaluable archive he established at University of Florida in Gainesville: The University of Florida van Mierop Heart Archive. Undoubtedly, with these extraordinary contributions to the fields of cardiac anatomy and embryology, which were way ahead of his time, Professor van Mierop was a true giant in Paediatric Cardiology. The invaluable archive he established at University of Florida in Gainesville, The University of Florida van Mierop Heart Archive, has been instrumental in teaching medical students, Residents, Medical Fellows, and Surgical Fellows. Only a handful of similar archives exist across the globe, and these archives are the true legacy of giants such as Dr. van Mierop. We have an important obligation to leave no stone unturned to continue to preserve these archives for the future generations of surgeons, physicians, all providers of paediatric and congenital cardiac care, and, most importantly, our patients.
The role of neutrophil-to-lymphocyte ratio in predicting mortality after bidirectional Glenn procedure
Authors: Ukil Isildak Fatma , Yavuz Yasemin
Published: May 2022

This study aimed to address the role of various inflammation-related blood indices for the assessment of in-hospital outcomes in subjects undergoing Glenn procedure. Subjects who underwent the Glenn procedure for hypoplastic left heart syndrome were analysed retrospectively. Subjects were divided into two groups: Group 1 consisted of 78 patients who were discharged, and Group 2 included 12 patients who died after surgery. Post-operative third-day neutrophil count and neutrophil-to-lymphocyte ratio value were significantly higher in the exitus group compared to the discharged group (p = 0.006 and p = 0.003, respectively). Third-day neutrophil-to-lymphocyte ratio was positively correlated with duration of intubation (r = 0.253, p = 0.018), length of stay in ICU (r = 0.296, p = 0.006) and length of hospital stay (r = 0.297, p = 0.005). Multiple logistic regression analysis revealed that patients with high third-day neutrophil-to-lymphocyte ratio (≥6) had 14.227-fold higher risk of death compared to those with lower values. In addition, higher pulmonary arterial pressure was associated with increased risk of death. Receiver operating characteristics analysis revealed that neutrophil-to-lymphocyte ratio had 66.67% sensitivity, 84% specificity, 81.61% accuracy, 40.00% positive predictive value and 94.03% negative predictive value with a cut-off point of ≥6 to predict mortality. Third-day neutrophil-to-lymphocyte ratio and increased post-operative pulmonary arterial pressure are significant predictors for in-hospital mortality in Glenn procedure recipients. A cut-off value of ≥6 for third-day neutrophil-to-lymphocyte ratio predicts mortality with 66.67% sensitivity and 84% specificity. Given its simplicity and availability, post-operative neutrophil-to-lymphocyte ratio should be monitored on a daily basis to identify patients with high risk for mortality after Glenn procedure.
How to Balance Green and Grain in Marginal Mountainous Areas?
Authors: Zeng Yi , Ran Lishan , Fang Nufang , Wang Zhen , Xu Zhenci , Lu Xixi , Yu Qiang , Wang Ling , Yu Shuxia , Shi Zhihua
Published: May 2022

China has implemented the world's largest‐ever vegetation restoration program in marginal mountainous areas to sustain life on land. However, land competition between the demand for grain and the need for green has threatened sustainable vegetation restoration. Here, focusing on China's marginal mountainous areas with the highest density of slope cropland, we explore the optimal solution in the trade‐offs between green and grain. We find that current vegetation restoration strategies are not sufficiently optimized, which may threaten the survival and development of local farmers and in turn destroy existing vegetation restoration achievements. Through adjusting vegetation restoration objectives carefully tailored to local conditions, the population experiencing grain shortages can be greatly reduced by 51–66% (from 18.26 million to 6.29–8.90 million) compared with the current scheme. The optimal design will alleviate the conflict between grain and green, thereby promoting sustainable ecological restoration in China. Our research provides an important reference for the world's mountainous areas to achieve a win‐win situation between green and grain.
Arctic – Atlantic Exchange of the Dissolved Micronutrients Iron, Manganese, Cobalt, Nickel, Copper and Zinc With a Focus on Fram Strait
Authors: Krisch Stephan , Hopwood Mark J. , Roig Stéphane , Gerringa Loes J. A. , Middag Rob , Rutgers van der Loeff Michiel M. , Petrova Mariia V. , Lodeiro Pablo , Colombo Manuel , Cullen Jay T. , Jackson Sarah L. , Heimbürger‐Boavida Lars‐Eric , Achterberg Eric P.
Published: May 2022

The Arctic Ocean is considered a source of micronutrients to the Nordic Seas and the North Atlantic Ocean through the gateway of Fram Strait (FS). However, there is a paucity of trace element data from across the Arctic Ocean gateways, and so it remains unclear how Arctic and North Atlantic exchange shapes micronutrient availability in the two ocean basins. In 2015 and 2016, GEOTRACES cruises sampled the Barents Sea Opening (GN04, 2015) and FS (GN05, 2016) for dissolved iron (dFe), manganese (dMn), cobalt (dCo), nickel (dNi), copper (dCu) and zinc (dZn). Together with the most recent synopsis of Arctic‐Atlantic volume fluxes, the observed trace element distributions suggest that FS is the most important gateway for Arctic‐Atlantic dissolved micronutrient exchange as a consequence of Intermediate and Deep Water transport. Combining fluxes from FS and the Barents Sea Opening with estimates for Davis Strait (GN02, 2015) suggests an annual net southward flux of 2.7 ± 2.4 Gg·a−1 dFe, 0.3 ± 0.3 Gg·a−1 dCo, 15.0 ± 12.5 Gg·a−1 dNi and 14.2 ± 6.9 Gg·a−1 dCu from the Arctic toward the North Atlantic Ocean. Arctic‐Atlantic exchange of dMn and dZn were more balanced, with a net southbound flux of 2.8 ± 4.7 Gg·a−1 dMn and a net northbound flux of 3.0 ± 7.3 Gg·a−1 dZn. Our results suggest that ongoing changes to shelf inputs and sea ice dynamics in the Arctic, especially in Siberian shelf regions, affect micronutrient availability in FS and the high latitude North Atlantic Ocean.
Calcium Isotopic Constraints on the Transition From Aragonite Seas to Calcite Seas in the Cambrian
Authors: Wei Guang‐Yi , Hood Ashleigh v. S. , Planavsky Noah J. , Li Da , Ling Hong‐Fei , Tarhan Lidya G.
Published: May 2022

The primary mineralogy of marine carbonates has varied over geological time in concert with the secular evolution of global climate and seawater chemistry. Here, we employed a multi‐proxy geochemical and petrographic approach, including measuring the Ca isotope (δ44Ca) and Sr content of Ediacaran–Cambrian carbonates, to provide new insights into the timing of the transition from a “dolomite‐aragonite sea” to a “calcite sea” across the Ediacaran‐Cambrian transition. We find robust evidence for the persistence of an aragonite sea well into Cambrian Age 2 (and potentially up through Age 4). Together with an updated petrographic compilation of abiotic carbonate precipitates (i.e., ooids and cements), these new δ44Ca and Sr data provide further evidence that there was a protracted transition from aragonite seas to calcite seas in the Cambrian. We propose that this transition was mediated, in part, by changes in seawater Mg/Ca ratios potentially regulated by the global marine redox state and extents of authigenic clay precipitation.
Investigating Parametric Dependence of Climate Feedbacks in the Atmospheric Component of CNRM‐CM6‐1
Authors: Peatier S. , Sanderson B. M. , Terray L. , Roehrig R.
Published: May 2022

We sample 30 calibration parameters of the CNRM‐CM6‐1 atmospheric component to produce a perturbed parameter ensemble. An error score aggregating four annual‐averaged metrics is used here as an example to represent the model performance. We propose a method using statistical emulators of climatic fields and feedback parameters to produce model candidates spanning the maximal range of net feedback while minimizing the error score. Optimal candidates are found for a range of climate sensitivity chosen to span 3.8–10.1 K. The candidates show large errors in the extremes of the climate sensitivity range and none of them have better scores than the released version of CNRM‐CM6. However, 65% of the optimal candidates have errors within the inter‐model standard deviation of the seven models participating in the Cloud Feedback Model Intercomparison Project, spanning and ECS range of (4.14–7.22 K). These optimal calibrations will be used to assess feedback diversity in coupled experiments.
Causal Links Between Arctic Sea Ice and Its Potential Drivers Based on the Rate of Information Transfer
Authors: Docquier D. , Vannitsem S. , Ragone F. , Wyser K. , Liang X. S.
Published: May 2022

Arctic sea ice has substantially changed over the past four decades, with a large decrease in sea‐ice area and volume. The exact causes of these changes are not entirely known. In our study, we make use of the Swedish Meteorological and Hydrological Institute Large Ensemble. This ensemble consists of 50 members realized with the EC‐Earth3 global climate model and covers the period 1970‐2100. We apply for the first time the Liang‐Kleeman information flow method to analyze the cause‐effect relationships between Arctic sea ice and its potential drivers. We show that recent and future changes in Arctic sea ice are mainly driven by air and sea‐surface temperatures and ocean heat transport. Conversely, changes in Arctic sea ice also considerably impact temperature and ocean heat transport. Finally, we find a progressive decrease in the influence of sea‐ice area and volume on air temperature and ocean heat transport through the twenty‐first century.
Cordilleran Ice Sheet Stability During the Last Deglaciation
Authors: Darvill C. M. , Menounos B. , Goehring B. M. , Lesnek A. J.
Published: May 2022

We report 20 10Be exposure ages from glacial erratics and bedrock on the west coast of British Columbia, Canada, which add to existing chronologies of Cordilleran Ice Sheet retreat along ∼600 km of coastal North America. Collectively, these data show the western ice limit reached the present coast by 18–16 ka then retreat slowed for ∼4,000 years until 14–13 ka. We attribute initial retreat to destabilization and grounding line retreat resulting from rising sea level and/or ocean warming in the northern Pacific. Subsequent stability of the ice sheet at the present coastal margin was likely due to the transition from marine to terrestrial margins despite increasing temperatures that may have driven ice sheet thinning. Our findings demonstrate the importance of understanding both climatic and nonclimatic drivers of ice sheet change through time.
Denudation Process of Crystalline Nappes in a Continental Collision Zone Constrained by Inversion of Fission‐Track Data and Thermokinematic Forward Modeling: An Example From Eastern Nepalese Himalaya
Authors: Nakajima Toru , Kawakami Tetsuo , Iwano Hideki , Danhara Tohru , Sakai Harutaka
Published: May 2022

Thermochronological methods were applied to the Higher Himalayan Crystalline (HHC) nappe and the underlying Lesser Himalayan Sequences (LHS) to elucidate the denudation process for the middle‐ and upper‐crust of eastern Nepal over millions of years. Thermochronological inverse modeling was undertaken for new results of fission‐track (FT) age and FT length data of zircon and apatite in order to reconstruct the time‐temperature (t‐T) paths in the temperature range of 60–350°C. Eight t‐T paths calculated along the across‐strike section show that the cooling process of the HHC nappe in this study area is characterized by the following three aspects: (a) gradual cooling followed by rapid cooling and subsequent gradual cooling, (b) northward‐younging of the timing of the rapid cooling, and (c) gradual cooling followed by <2 Myr rapid cooling in the frontmost part of the HHC nappe. The observed FT ages and t‐T paths were then compared with those predicted by forwarding thermokinematic modeling. The results of the thermokinematic modeling for the “Flat‐Ramp‐Flat MHT model”, in which the HHC and the underlying LHS are denudated in direct proportion to the uplift of rocks transported along the Main Himalayan Thrust (MHT), reproduced the observed t‐T paths and FT ages in eastern Nepal. This indicates that the observed FT ages and t‐T paths reflect a denudation process driven by the movement of the MHT with a flat‐ramp‐flat geometry and that the denudation rate and its spatial distribution have roughly been constant in eastern Nepal since ca. 9 Ma.
Reconstructing Pyroclastic Currents' Source and Flow Parameters From Deposit Characteristics and Numerical Modeling: The Pozzolane Rosse Ignimbrite Case Study (Colli Albani, Italy)
Authors: Calabrò Laura , Esposti Ongaro Tomaso , Giordano Guido , de’ Michieli Vitturi Mattia
Published: May 2022

In this study, we apply a two‐dimensional, transient depth‐averaged model to simulate the inertial flow dynamics of caldera‐forming pyroclastic currents, using the available data about the Pozzolane Rosse ignimbrite (Colli Albani, Italy) eruption (460 ka, 63 km3 DRE). By performing an extensive set of numerical simulations, we test the effects of the initial parameters of the pyroclastic current (Richardson number, mass flow rate, initial flow density) on simulated deposit characteristics which can be compared with selected ignimbrite field observables, including the deposit dispersal along topography, the maximum distance from source, the deposit thickness, the grain size distribution at different distances, and the emplacement temperature. Results permit us to quantify the first‐order dependency of the flow runout on the mass flow rate, and of the deposit thickness decay pattern on the initial mixture density. By using the results of the parametric study we reconstruct the source parameters of the Pozzolane Rosse ignimbrite constrained by the ignimbrite depositional characteristics, including the mass partition into the co‐ignimbrite cloud. Despite uncertainties associated with the complex, non‐linear interplay between the flow variables, the single‐layer, depth‐averaged model demonstrates to be suitable for simulating inertial pyroclastic currents, such as those generating large‐scale caldera‐forming ignimbrites, providing a tool for reconstructing the eruption source parameters from deposits characteristics, and to assess pyroclastic currents' hazard for future eruptions.
Identifying Efficient Ensemble Perturbations for Initializing Subseasonal‐To‐Seasonal Prediction
Authors: Demaeyer Jonathan , Penny Stephen G. , Vannitsem Stéphane
Published: May 2022

The prediction of the weather at subseasonal‐to‐seasonal (S2S) timescales is dependent on both initial and boundary conditions. An open question is how to best initialize a relatively small‐sized ensemble of numerical model integrations to produce reliable forecasts at these timescales. Reliability in this case means that the statistical properties of the ensemble forecast are consistent with the actual uncertainties about the future state of the geophysical system under investigation. In the present work, a method is introduced to construct initial conditions that produce reliable ensemble forecasts by projecting onto the eigenfunctions of the Koopman or the Perron‐Frobenius operators, which describe the time‐evolution of observables and probability distributions of the system dynamics, respectively. These eigenfunctions can be approximated from data by using the Dynamic Mode Decomposition (DMD) algorithm. The effectiveness of this approach is illustrated in the framework of a low‐order ocean‐atmosphere model exhibiting multiple characteristic timescales, and is compared to other ensemble initialization methods based on the Empirical Orthogonal Functions (EOFs) of the model trajectory and on the backward and covariant Lyapunov vectors (CLVs) of the model dynamics. Projecting initial conditions onto a subset of the Koopman or Perron‐Frobenius eigenfunctions that are characterized by time scales with fast‐decaying oscillations is found to produce highly reliable forecasts at all lead times investigated, ranging from one week to two months. Reliable forecasts are also obtained with the adjoint CLVs, which are the eigenfunctions of the Koopman operator in the tangent space. The advantages of these different methods are discussed.
Magnetic Biosignatures of Magnetosomal Greigite From Micromagnetic Calculation
Authors: Bai Fan , Chang Liao , Pei Zhaowen , Harrison Richard J. , Winklhofer Michael
Published: May 2022

Greigite magnetosomes produced by magnetotactic bacteria (MTB) are widely distributed in natural environments, but large uncertainties remain regarding their magnetic biosignatures. Here, we have constructed micromagnetic models with realistic biogenic greigite particles to quantify the magnetic properties and magnetotaxis efficiency of greigite‐producing MTB cells. Our calculations suggest coercivity (Bc) of ∼15–21 mT for intact greigite‐producing rod‐shaped MTB and many‐celled magnetotactic prokaryotes, with Bc decreasing to ∼11 mT for greigite magnetofossils with clumped particles. These magnetic signatures make biogenic greigite distinguishable from typical biogenic magnetite and inorganic greigite, providing reliable magnetic criteria to detect biogenic greigite in a wide range of environmental and geological settings. Our numerical calculations suggest that rod‐shaped greigite‐producing MTB have a similar magnetotaxis efficiency to magnetite MTB, likely by biomineralizing more greigite crystals to compensate for the lower saturation magnetization of greigite and less ordered chains in greigite MTB cells, demonstrating biological‐controlled optimization of their magnetic nanostructure.
Comparative metabolomic analysis in plasma and cerebrospinal fluid of humans and in plasma and brain of mice following antidepressant-dose ketamine administration
Authors: Moaddel Ruin , Zanos Panos , Farmer Cristan A. , Kadriu Bashkim , Morris Patrick J. , Lovett Jacqueline , Acevedo-Diaz Elia E. , Cavanaugh Grace W. , Yuan Peixiong , Yavi Mani , Thomas Craig J. , Park Lawrence T. , Ferrucci Luigi , Gould Todd D. , Zarate Carlos A.
Published: May 2022

Subanesthetic-dose racemic (R,S)-ketamine (ketamine) produces rapid, robust, and sustained antidepressant effects in major depressive disorder (MDD) and bipolar disorder (BD) and has also been shown to effectively treat neuropathic pain, complex regional pain syndrome, and post-traumatic stress disorder (PTSD). However, to date, its mechanism of action remains unclear. Preclinical studies found that (2 R,6 R;2 S,6 S)-hydroxynorketamine (HNK), a major circulating metabolite of ketamine, elicits antidepressant effects similar to those of ketamine. To help determine how (2 R,6 R)-HNK contributes to ketamine’s mechanism of action, an exploratory, targeted, metabolomic analysis was carried out on plasma and CSF of nine healthy volunteers receiving a 40-minute ketamine infusion (0.5 mg/kg). A parallel targeted metabolomic analysis in plasma, hippocampus, and hypothalamus was carried out in mice receiving either 10 mg/kg of ketamine, 10 mg/kg of (2 R,6 R)-HNK, or saline. Ketamine and (2 R,6 R)-HNK both affected multiple pathways associated with inflammatory conditions. In addition, several changes were unique to either the healthy human volunteers and/or the mouse arm of the study, indicating that different pathways may be differentially involved in ketamine’s effects in mice and humans. Mechanisms of action found to consistently underlie the effects of ketamine and/or (2 R,6 R)-HNK across both the human metabolome in plasma and CSF and the mouse arm of the study included LAT1, IDO1, NAD+, the nitric oxide (NO) signaling pathway, and sphingolipid rheostat.
Hypomethylating agent and venetoclax with FLT3 inhibitor “triplet” therapy in older/unfit patients with FLT3 mutated AML
Authors: Yilmaz Musa , Kantarjian Hagop , Short Nicholas J. , Reville Patrick , Konopleva Marina , Kadia Tapan , DiNardo Courtney , Borthakur Gautam , Pemmaraju Naveen , Maiti Abhishek , Jabbour Elias , Jain Nitin , Issa Ghayas , Takahashi Koichi , Sasaki Koji , Ohanian Maro , Pierce Sherry , Tang Guillin , Loghavi Sanam , Patel Keyur , Wang Sa A. , Garcia-Manero Guillermo , Andreeff Michael , Ravandi Farhad , Daver Naval
Published: May 2022

In older/unfit newly diagnosed patients with FLT3 mutated acute myeloid leukemia (AML), lower intensity chemotherapy (LIC) in combination with either a FLT3 inhibitor or with venetoclax results in poor overall survival (median 8 to 12.5 months). We performed a retrospective analysis of 87 newly diagnosed FLT3 mutated AML patients treated on triplet (LIC + FLT3 inhibitor + Venetoclax, [N = 27]) and doublet (LIC + FLT3 inhibitor, [N = 60]) regimens at our institution. Data were collected from prospective clinical trials in 75% (N = 65) and 25% (N = 22) who received the same treatment regimens outside of a clinical trial. Triplet therapy was associated with significantly higher rates of complete remission (CR) (67% versus 32%, P = 0.002), CR/CRi (93% versus 70%, P = 0.02), FLT3-PCR negativity (96% versus 54%, P < 0.01), and flow-cytometry negativity (83% versus 38%, P < 0.01) than doublets. At the end of the first cycle, the median time to ANC > 0.5 (40 versus 21 days, P = 0.15) and platelet > 50 K (29 versus 25 days, P = 0.6) among responders was numerically longer with triplets, but 60-day mortality was similar (7% v 10%). With a median follow-up of 24 months (median 12 months for triplet arm, and 63 months for doublet arm), patients receiving a triplet regimen had a longer median overall survival (not reached versus 9.5 months, P < 0.01). LIC combined with FLT3 inhibitor and venetoclax (triplet) may be an effective frontline regimen for older/unfit FLT3 mutated AML that should be further validated prospectively.
The dual role of glioma exosomal microRNAs: glioma eliminates tumor suppressor miR-1298-5p via exosomes to promote immunosuppressive effects of MDSCs
Authors: Qi Yanhua , Jin Chuandi , Qiu Wei , Zhao Rongrong , Wang Shaobo , Li Boyan , Zhang Zongpu , Guo Qindong , Zhang Shouji , Gao Zijie , Zhao Shulin , Pan Ziwen , Fan Yang , chen Zihang , Wang Huizhi , Xu Jianye , Deng Lin , Ni Shilei , Wang Jian , Xue Hao , Xue Fuzhong , Li Gang
Published: May 2022

Clear evidence shows that tumors could secrete microRNAs (miRNAs) via exosomes to modulate the tumor microenvironment (TME). However, the mechanisms sorting specific miRNAs into exosomes are still unclear. In order to study the biological function and characterization of exosomal miRNAs, we performed whole-transcriptome sequencing in 59 patients’ whole-course cerebrospinal fluid (CSF) small extracellular vesicles (sEV) and matched glioma tissue samples. The results demonstrate that miRNAs could be divided into exosome-enriched miRNAs (ExomiRNAs) and intracellular-retained miRNAs (CLmiRNAs), and exosome-enriched miRNAs generally play a dual role. Among them, miR-1298-5p was enriched in CSF exosomes and suppressed glioma progression in vitro and vivo experiments. Interestingly, exosomal miR-1298-5p could promote the immunosuppressive effects of myeloid-derived suppressor cells (MDSCs) to facilitate glioma. Therefore, we found miR-1298-5p had different effects on glioma cells and MDSCs. Mechanically, downstream signaling pathway analyses showed that miR-1298-5p plays distinct roles in glioma cells and MDSCs via targeting SETD7 and MSH2, respectively. Moreover, reverse verification was performed on the intracellular-retained miRNA miR-9-5p. Thus, we confirmed that tumor-suppressive miRNAs in glioma cells could be eliminated through exosomes and target tumor-associated immune cells to induce tumor-promoting phenotypes. Glioma could get double benefit from it. These findings uncover the mechanisms that glioma selectively sorts miRNAs into exosomes and modulates tumor immunity.
A novel SRSF3 inhibitor, SFI003, exerts anticancer activity against colorectal cancer by modulating the SRSF3/DHCR24/ROS axis
Authors: Zhang Yawen , Wang Mengmeng , Meng Fanyi , Yang Man , Chen Yinshuang , Guo Xuqin , Wang Weiwei , Zhu Yifan , Guo Yundi , Feng Chunlai , Tian Shen , Zhang Hongjian , Li Huanqiu , Sun Jing , Wang Weipeng
Published: May 2022

As the modulation of serine/arginine-rich splicing factor 3 (SRSF3) may be therapeutically beneficial to colorectal cancer (CRC) treatment, the identification of novel SRSF3 inhibitors is highly anticipated. However, pharmaceutical agents targeting SRSF3 have not yet been discovered. Here, we propose a functional SRSF3 inhibitor for CRC therapy and elucidate its antitumor mechanisms. We found high expression of SRSF3 in 70.6% CRC tissues. Silencing SRSF3 markedly inhibits the proliferation and migration of CRC cells through suppression of its target gene 24-dehydrocholesterol reductase (DHCR24). This is evidenced by the links between SRSF3 and DHCR24 in CRC tissues. The novel SRSF3 inhibitor SFI003 exhibits potent antitumor efficacy in vitro and in vivo, which drives apoptosis of CRC cells via the SRSF3/DHCR24/reactive oxygen species (ROS) axis. Moreover, SFI003 is druggable with suitable pharmacokinetic properties, bioavailability, and tumor distribution. Thus, SRSF3 is a novel potential therapeutic target for CRC. Its inhibitor SFI003 may be developed as an anticancer therapeutic.
The 4D Nucleome Data Portal as a resource for searching and visualizing curated nucleomics data
Authors: Reiff Sarah B. , Schroeder Andrew J. , Kırlı Koray , Cosolo Andrea , Bakker Clara , Mercado Luisa , Lee Soohyun , Veit Alexander D. , Balashov Alexander K. , Vitzthum Carl , Ronchetti William , Pitman Kent M. , Johnson Jeremy , Ehmsen Shannon R. , Kerpedjiev Peter , Abdennur Nezar , Imakaev Maxim , Öztürk Serkan Utku , Çamoğlu Uğur , Mirny Leonid A. , Gehlenborg Nils , Alver Burak H. , Park Peter J.
Published: May 2022

The 4D Nucleome (4DN) Network aims to elucidate the complex structure and organization of chromosomes in the nucleus and the impact of their disruption in disease biology. We present the 4DN Data Portal (https://data.4dnucleome.org/), a repository for datasets generated in the 4DN network and relevant external datasets. Datasets were generated with a wide range of experiments, including chromosome conformation capture assays such as Hi-C and other innovative sequencing and microscopy-based assays probing chromosome architecture. All together, the 4DN data portal hosts more than 1800 experiment sets and 36000 files. Results of sequencing-based assays from different laboratories are uniformly processed and quality-controlled. The portal interface allows easy browsing, filtering, and bulk downloads, and the integrated HiGlass genome browser allows interactive visualization and comparison of multiple datasets. The 4DN data portal represents a primary resource for chromosome contact and other nuclear architecture data for the scientific community.
Physical realization of topological Roman surface by spin-induced ferroelectric polarization in cubic lattice
Authors: Liu Guangxiu , Pi Maocai , Zhou Long , Liu Zhehong , Shen Xudong , Ye Xubin , Qin Shijun , Mi Xinrun , Chen Xue , Zhao Lin , Zhou Bowen , Guo Jia , Yu Xiaohui , Chai Yisheng , Weng Hongming , Long Youwen
Published: May 2022

Topology, an important branch of mathematics, is an ideal theoretical tool to describe topological states and phase transitions. Many topological concepts have found their physical entities in real or reciprocal spaces identified by topological invariants, which are usually defined on orientable surfaces, such as torus and sphere. It is natural to investigate the possible physical realization of more intriguing non-orientable surfaces. Herein, we show that the set of spin-induced ferroelectric polarizations in cubic perovskite oxides AMn3Cr4O12 (A = La and Tb) reside on the topological Roman surface—a non-orientable two-dimensional manifold formed by sewing a Möbius strip edge to that of a disc. The induced polarization may travel in a loop along the non-orientable Möbius strip or orientable disc, depending on the spin evolution as controlled by an external magnetic field. Experimentally, the periodicity of polarization can be the same or twice that of the rotating magnetic field, which is consistent with the orientability of the disc and the Möbius strip, respectively. This path-dependent topological magnetoelectric effect presents a way to detect the global geometry of a surface and deepens our understanding of topology in both mathematics and physics.
The barley leaf rust resistance gene Rph3 encodes a predicted membrane protein and is induced upon infection by avirulent pathotypes of Puccinia hordei
Authors: Dinh Hoan X. , Singh Davinder , Gomez de la Cruz Diana , Hensel Goetz , Kumlehn Jochen , Mascher Martin , Stein Nils , Perovic Dragan , Ayliffe Michael , Moscou Matthew J. , Park Robert F. , Pourkheirandish Mohammad
Published: May 2022

Leaf rust, caused by Puccinia hordei, is an economically significant disease of barley, but only a few major resistance genes to P. hordei (Rph) have been cloned. In this study, gene Rph3 was isolated by positional cloning and confirmed by mutational analysis and transgenic complementation. The Rph3 gene, which originated from wild barley and was first introgressed into cultivated Egyptian germplasm, encodes a unique predicted transmembrane resistance protein that differs from all known plant disease resistance proteins at the amino acid sequence level. Genetic profiles of diverse accessions indicated limited genetic diversity in Rph3 in domesticated germplasm, and higher diversity in wild barley from the Eastern Mediterranean region. The Rph3 gene was expressed only in interactions with Rph3-avirulent P. hordei isolates, a phenomenon also observed for transcription activator-like effector-dependent genes known as executors conferring resistance to Xanthomonas spp. Like known transmembrane executors such as Bs3 and Xa7, heterologous expression of Rph3 in N. benthamiana induced a cell death response. The isolation of Rph3 highlights convergent evolutionary processes in diverse plant-pathogen interaction systems, where similar defence mechanisms evolved independently in monocots and dicots.
A spin promotion effect in catalytic ammonia synthesis
Authors: Cao Ang , Bukas Vanessa J. , Shadravan Vahid , Wang Zhenbin , Li Hao , Kibsgaard Jakob , Chorkendorff Ib , Nørskov Jens K.
Published: May 2022

The need for efficient ammonia synthesis is as urgent as ever. Over the past two decades, many attempts to find new catalysts for ammonia synthesis at mild conditions have been reported and, in particular, many new promoters of the catalytic rate have been introduced beyond the traditional K and Cs oxides. Herein, we provide an overview of recent experimental results for non-traditional promoters and develop a comprehensive model to explain how they work. The model has two components. First, we establish what is the most likely structure of the active sites in the presence of the different promoters. We then show that there are two effects dictating the catalytic activity. One is an electrostatic interaction between the adsorbed promoter and the N-N dissociation transition state. In addition, we identify a new promoter effect for magnetic catalysts giving rise to an anomalously large lowering of the activation energy opening the possibility of finding new ammonia synthesis catalysts.
Comparative effectiveness over time of the mRNA-1273 (Moderna) vaccine and the BNT162b2 (Pfizer-BioNTech) vaccine
Authors: Islam Nazmul , Sheils Natalie E. , Jarvis Megan S. , Cohen Kenneth
Published: May 2022

Real-world analysis of the incidence of SARS-CoV-2 infection post vaccination is important in determining the comparative effectiveness of the available vaccines. In this retrospective cohort study using deidentified administrative claims for Medicare Advantage and commercially insured individuals in a research database we examine over 3.5 million fully vaccinated individuals, including 8,848 individuals with SARS-CoV-2 infection, with a follow-up period between 14 and 151 days after their second dose. Our primary outcome was the rate of Covid-19 infection occurring at 30, 60, and 90 days at least 14 days after the second dose of either the mRNA-1273 vaccine or the BNT162b2 vaccine. Sub-analyses included the incidence of hospitalization, ICU admission, and death/hospice transfer. Separate analysis was conducted for individuals above and below age 65 and those without a prior diagnosis of Covid-19. We show that immunization with mRNA-1273, compared to BNT162b2, provides slightly more protection against SARS-CoV-2 infection that reaches statistical significance at 90 days with a number needed to vaccinate of >290. There are no differences in vaccine effectiveness for protection against hospitalization, ICU admission, or death/hospice transfer (aOR 1.23, 95% CI (0.67, 2.25)).
Neuronal pentraxin 2 is required for facilitating excitatory synaptic inputs onto spinal neurons involved in pruriceptive transmission in a model of chronic itch
Authors: Kanehisa Kensho , Koga Keisuke , Maejima Sho , Shiraishi Yuto , Asai Konatsu , Shiratori-Hayashi Miho , Xiao Mei-Fang , Sakamoto Hirotaka , Worley Paul F. , Tsuda Makoto
Published: May 2022

An excitatory neuron subset in the spinal dorsal horn (SDH) that expresses gastrin-releasing peptide receptors (GRPR) is critical for pruriceptive transmission. Here, we show that glutamatergic excitatory inputs onto GRPR+ neurons are facilitated in mouse models of chronic itch. In these models, neuronal pentraxin 2 (NPTX2), an activity-dependent immediate early gene product, is upregulated in the dorsal root ganglion (DRG) neurons. Electron microscopy reveals that NPTX2 is present at presynaptic terminals connected onto postsynaptic GRPR+ neurons. NPTX2-knockout prevents the facilitation of synaptic inputs to GRPR+ neurons, and repetitive scratching behavior. DRG-specific NPTX2 expression rescues the impaired behavioral phenotype in NPTX2-knockout mice. Moreover, ectopic expression of a dominant-negative form of NPTX2 in DRG neurons reduces chronic itch-like behavior in mice. Our findings indicate that the upregulation of NPTX2 expression in DRG neurons contributes to the facilitation of glutamatergic inputs onto GRPR+ neurons under chronic itch-like conditions, providing a potential therapeutic target.
Cascade reaction networks within audible sound induced transient domains in a solution
Authors: Dhasaiyan Prabhu , Ghosh Tanwistha , Lee Hong-Guen , Lee Yeonsang , Hwang Ilha , Mukhopadhyay Rahul Dev , Park Kyeng Min , Shin Seungwon , Kang In Seok , Kim Kimoon
Published: May 2022

Spatiotemporal control of chemical cascade reactions within compartmentalized domains is one of the difficult challenges to achieve. To implement such control, scientists have been working on the development of various artificial compartmentalized systems such as liposomes, vesicles, polymersomes, etc. Although a considerable amount of progress has been made in this direction, one still needs to develop alternative strategies for controlling cascade reaction networks within spatiotemporally controlled domains in a solution, which remains a non-trivial issue. Herein, we present the utilization of audible sound induced liquid vibrations for the generation of transient domains in an aqueous medium, which can be used for the control of cascade chemical reactions in a spatiotemporal fashion. This approach gives us access to highly reproducible spatiotemporal chemical gradients and patterns, in situ growth and aggregation of gold nanoparticles at predetermined locations or domains formed in a solution. Our strategy also gives us access to nanoparticle patterned hydrogels and their applications for region specific cell growth.