bluuebunny/crossref_metadata_2025 huggingface dataset:
GSK-126 Protects CA1 Neurons from H3K27me3-Mediated Apoptosis in Cerebral Ischemia
Authors: Wang Zhongcheng , Su Yaxin , Zhang Lei , Lan Ting , Li Li , Qi Suhua
Published: February 2022

Epigenetics, including histone modifications, play a significant role in central nervous system diseases, but the underlying mechanism remains to be elucidated. The aim of this study was to evaluate the role of H3K27me3 in regulating transcriptomic and pathogenic mechanisms following global ischemic stroke. Here, we found that in vivo ischemic/reperfusion (I/R) injury induced marked upregulation of H3K27me3 in the hippocampus. The administration of GSK-126 to rat brains decreased the levels of H3K27me3 in the hippocampus and reduced neuronal apoptosis after experimental stroke. Furthermore, ChIP-seq data demonstrated that the primary role of GSK-126 in the ischemic brain is to reduce H3K27me3 enrichment, mediating negative regulation of the execution phase of apoptosis and the MAPK signaling pathway. Further study suggested that the protective role of GSK-126 in ischemic rats was antagonized by U0126, an inhibitor of ERK1/2. Collectively, we demonstrated the potential of H3K27me3 as a novel stroke therapeutic target, and GSK-126 exerted a neuroprotective function in ischemic brain injury, which might be associated with activation of the MAPK/ERK pathway.

Graphical Abstract
Expert consensus to optimize the treatment of elderly patients with luminal metastatic breast cancer
Authors: Torregrosa-Maicas M. D. , del Barco-Berrón S. , Cotes-Sanchís A. , Lema-Roso L. , Servitja-Tormo S. , Gironés-Sarrió R.
Published: February 2022

Most patients diagnosed with luminal metastatic breast cancer (MBC) who are seen in oncology consultations are elderly. MBC in elderly patients is characterized by a higher percentage of hormone receptor (HR) expression and a lower expression of human epidermal growth factor receptor 2 (HER2). The decision regarding which treatment to administer to these patients is complex due to the lack of solid evidence to support the decision-making process. The objective of this paper is to review the scientific evidence on the treatment of elderly patients with luminal MBC. For this purpose, the Oncogeriatrics Section of the Spanish Society of Medical Oncology (SEOM), the Spanish Breast Cancer Research Group (GEICAM) and the SOLTI Group appointed a group of experts who have worked together to establish consensus recommendations to optimize the treatment of this population. It was concluded that the chronological age of the patient alone should not guide therapeutic decisions and that a Comprehensive Geriatric Assessment (CGA) should be performed whenever possible before establishing treatment. Treatment selection for the elderly population should consider the patient’s baseline status, the expected benefit and toxicity of each treatment, and the impact of treatment toxicity on the patient’s quality of life and functionality.
Near-Adult Heights and Adult Height Predictions Using Automated and Conventional Greulich–Pyle Bone Age Determinations in Children with Chronic Endocrine Diseases
Authors: Choukair Daniela , Hückmann Annette , Mittnacht Janna , Breil Thomas , Schenk Jens Peter , Alrajab Abdulsattar , Uhlmann Lorenz , Bettendorf Markus
Published: February 2022

Objectives

To validate adult height predictions (BX) using automated and Greulich–Pyle bone age determinations in children with chronic endocrine diseases.

Methods

Heights and near-adult heights were measured in 82 patients (48 females) with chronic endocrinopathies at the age of 10.45 ± 2.12 y and at time of transition to adult care (17.98 ± 3.02 y). Further, bone age (BA) was assessed using the conventional Greulich–Pyle (GP) method by three experts, and by BoneXpert™. PAH were calculated using conventional BP tables and BoneXpert™.

Results

The conventional and the automated BA determinations revealed a mean difference of 0.25 ± 0.72 y (p = 0.0027). The automated PAH by BoneXpert™ were 156.26 ± 0.86 cm (SDS − 2.01 ± 1.07) in females and 171.75 ± 1.6 cm (SDS − 1.29 ± 1.06) in males, compared to 153.95 ± 1.12 cm (SDS − 2.56 ± 1.5) in females and 169.31 ± 1.6 cm (SDS − 1.66 ± 1.56) in males by conventional BP, respectively and in comparison to near-adult heights 156.38 ± 5.84 cm (SDS − 1.91 ± 1.15) in females and 168.94 ± 8.18 cm (SDS − 1.72 ± 1.22) in males, respectively.

Conclusion

BA ratings and adult height predictions by BoneXpert™ in children with chronic endocrinopathies abolish rater-dependent variability and enhance reproducibility of estimates thereby refining care in growth disorders. Conventional methods may outperform automated analyses in specific cases.
Expected Centre of Mass of the Random Kodaira Embedding
Authors: Hashimoto Yoshinori
Published: February 2022

Let$$X \subset \mathbb {P}^{N-1}$$X⊂PN-1be a smooth projective variety. To each$$g \in SL (N , \mathbb {C})$$g∈SL(N,C)which induces the embedding$$g \cdot X \subset \mathbb {P}^{N-1}$$g·X⊂PN-1given by the ambient linear action we can associate a matrix$$\bar{\mu }_X (g)$$μ¯X(g)called the centre of mass, which depends nonlinearly ong. With respect to the probability measure on$$SL (N , \mathbb {C})$$SL(N,C)induced by the Haar measure and the Gaussian unitary ensemble, we prove that the expectation of the centre of mass is a constant multiple of the identity matrix for any smooth projective variety.
Soil Amendments and Biostimulants from the Hydrothermal Processing of Spent Coffee Grounds
Authors: Massaya Jackie , Mills-Lamptey Ben , Chuck Christopher J.
Published: February 2022

Purpose

Use of spent coffee grounds (SCG) in horticulture has deleterious effects on plant health and yields, suggesting that processing of SCG is necessary prior to field application. To this end, two products of an SCG based biorefinery were investigated: primary chars from the hydrothermal carbonisation (HTC) of SCG and enzymatic protein hydrolysates.

Methods

Primary chars were produced under various HTC regimes from raw SCG, and alkaline pre-treated SCG. Primary chars were evaluated in germination toxicity tests and under soil stress conditions using Arabidopsis thaliana (Arabidopsis). Proteolytic enzymes were screened in production of SCG protein hydrolysates; biostimulant activity in the growth of Saccharomyces Cerevisiae, germination of Arabidopsis thaliana under normal and cold conditions and auxin-like activity was assessed.

Results

Toxicity assays of primary chars with land cress (Barbarea verna L.) showed a maximum 35% increase in root length, relative to the control. In Arabidopsis growth trials, outstanding performances were recorded at 100 t/ha for primary chars produced from alkaline pre-treated SCG: rosette diameter and dry weight increased by 531 and 976%, respectively, relative to the control. SCG protein hydrolysate from Bacillus lichenformis proteolysis (glycine present at 47% of total) gave 140% increase in Arabidopsis seeds with expanded cotyledons, relative to the control. Auxin-like activity was also measured in the extracts.

Conclusion

Cascade process design was used to valorise a major waste stream. Removal of phytotoxic components from SCG hydrochars enhanced plant growth, while biostimulant activity of SCG protein hydrolysates was observed.

Graphical Abstract
Applicability of classifier to discovery knowledge for future prediction modelling
Authors: Chauhan Ritu , Yafi Eiad
Published: February 2022

The immense growth of new technological interventions has forced researchers and scientists around the globe to adopt the widely anticipated technology of Machine Learning (ML) and Artificial Intelligence (AI). ML and AI have generously prospected itself from the past decade in the discovery of knowledge from databases. Several ML and AI based adoptive technologies have emerged in varied application domains, and are thus widely opening a new era of knowledge in decision making. Moreover, ML and AI are techniques that can improve the treatment and diagnosis of diseases. In the current study, we have designed and deployed a “PROCLAVE”. The tool was designed in varied layers of structure, where each layer plays a significant role in determining the patterns. We have applied several libraries for the processing of a prototype to develop a visualization interface. The tool forecasts health vulnerability, makes a comparison among variable classifiers and visualize the results for end users. Moreover, the proposed architecture is based on the concepts of conceptualization and visualization to detect the overall dashboard. Furthermore, the current approach was synthesized and populated with a database that allows the end users to select the variable features and relatively determine the interactive patterns for the number of cases. The database was collected from the National Institute of Health Stroke (NIHS) in the United States. Data was gathered for stroke patients who were diagnosed with stroke from 1950 to 2015. The study was based on several attributes which included causes of death, sex, race, Hispanic origin and others to discover unknown patterns for future decision making.
Glycemic control after switching to faster aspart in adults with type 1 diabetes
Authors: Fadini G. P. , Boscari F. , Falaguasta D. , Ferretto S. , Maran A. , Avogaro A. , Bruttomesso D.
Published: February 2022

Aims

Post-prandial hyperglycemia remains an unmet need in the management of type 1 diabetes (T1D). In randomized trials, faster insulin aspart (FIA) showed modest but significant reductions of glycemic spikes after meals. Whether such benefit is evident in routine clinical practice is unclear.

Methods

We analyzed data of patients with T1D at the time they switched from a prior bolus insulin to FIA and at the first available follow-up. The primary endpoint was the change in the time spent in hyperglycemia > 250 mg/dl during daytime from flash glucose monitoring (FGM). Secondary outcomes included the change in HbA1c, body weight, insulin dose and other FGM metrics.

Results

We included 117 patients with T1D on multiple daily injections who switched to FIA, 57 of whom had data from FGM. Patients were 41-year-old, 51.3% men, with 19.3 years diabetes duration and a baseline HbA1c of 7.7% (60 mmol/mol). Mean observation time was 4.3 months. After switching to FIA, HbA1c declined by 0.1% (1 mmol/mol) only in patients with baseline HbA1c > 7.0% (53 mmol/mol). Time spent in hyperglycemia > 250 mg/dl during daytime was significantly reduced from 14.8 to 11.9% (p = 0.006). Time in range improved from 48.3 to 51.0% (p = 0.028). Results were consistent across various patient characteristics.

Conclusions

Under routine care, patients with T1D who switched to FIA experienced a reduction in the time spent in hyperglycemia > 250 mg/dl during daytime and an increase in time in range. These improvements may be due to better control of post-prandial hyperglycemia, as observed in trials.
Voters’ Distance, Information Bias and Politicians’ Salary
Authors: Bartolini David , Sacchi Agnese , Scalera Domenico , Zazzaro Alberto
Published: February 2022

This paper presents a theoretical model exploring the role of institutional distance between voters and politicians in the provision of public goods and citizens’ welfare. Proximity eases access to information about public policies, increasing political accountability. However, rent-seeking politicians can bias information reducing citizens’ welfare. We show that the optimal distance depends on the pool of politicians, voters’ political awareness and the cost of distorting information. As these elements differ across regions, a one-size-fits-all institutional reform may be beneficial for some jurisdictions and detrimental for others. A mechanism based on politicians’ remuneration can mitigate possible welfare-decreasing effects of voter-politician proximity.
Wie bleiben Pflegende gesund
Authors: Ledtermann Ivonne
Published: February 2022

Was ist zu diesem Thema bereits bekannt?

Die Salutogenese und die Resilienz haben jeweils eine positive Wirkung auf die Gesundheit Pflegender. Diese beiden Gesundheitsmodelle werden einzeln erforscht und in Einrichtungen einzeln angewendet.

Was ist neu, wie wird eine neue Perspektive eingebracht?

Um eine umfassendere Gesundheitsförderung zu erzielen, könnten die Salutogenese und die Resilienz miteinander verknüpft werden.

Was sind die Auswirkungen für die Praxis?

Es könnten gezieltere Maßnahmen und Konzepte entwickelt werden, um die Gesundheit psychiatrisch Pflegender zu erhalten und zu fördern.
In‐Depth Evaluation of MiRS Total Precipitable Water From NOAA‐20 ATMS Using Multiple Reference Data Sets
Authors: Lee Yong‐Keun , Grassotti Christopher , Liu Quanhua (Mark) , Liu Shu‐Yan , Zhou Yan
Published: February 2022

The National Oceanic and Atmospheric Administration (NOAA) Microwave Integrated Retrieval System (MiRS) algorithm has been producing retrieval products from NOAA‐20 Advanced Technology Microwave Sounder (ATMS) data since shortly after launch in late 2017. Retrieval products from the Suomi National Polar‐orbiting Partnership (SNPP) ATMS data have been similarly available since 2012. Among the products routinely generated is Total Precipitable Water (TPW), based on the vertical integral of the MiRS retrieved water vapor profile. In this study, TPW data from NOAA‐20 ATMS have been the subject of an in‐depth evaluation. The evaluation included characterization of dependence on orbital node (ascending/descending), season, surface type, scan angle, and meridional (zonally averaged) variation. Due to the similarity between NOAA‐20 and SNPP derived TPW, the emphasis here is on the NOAA‐20 evaluation. The globally averaged values of TPW for 2019 are 25.41 and 25.39 mm from NOAA‐20 and SNPP ATMS, respectively, for combined orbits (ascending and descending). For combined orbits, the bias and standard deviation of MiRS NOAA‐20 ATMS TPW with respect to European Centre for Medium‐Range Weather Forecasts/Global Data Assimilation System (ECMWF/GDAS) analyses are 0.79/1.76 mm and 3.65/3.55 mm, respectively, at 10°N where part of annual mean Intertropical Convergence Zone (ITCZ) is located, while at 40°N, corresponding bias and standard deviation values are 0.84/0.67 mm and 3.00/2.55 mm, respectively. The yearly averaged horizontal distribution of MiRS TPW retrieved from NOAA‐20 ATMS is highly correlated with that of ECMWF and GDAS analyses data, with a correlation coefficient of ∼1.
Three‐Dimensional Surface Downwelling Longwave Radiation Clear‐Sky Effects in the Upper Colorado River Basin
Authors: Feldman D. R. , Worden M. , Falco N. , Dennedy‐Frank P. J. , Chen J. , Dafflon B. , Wainwright H.
Published: February 2022

In complex terrain, non‐parallel surfaces receive emitted radiation from adjacent surfaces. Qualitatively, where surface skin temperatures and lower tropospheric temperature and humidity are not uniform, the downwelling longwave radiation (DLR) will be determined not just by radiation from the atmosphere above a given location, but also by adjacent surface temperatures. We quantify this three‐dimensional longwave radiative effect over the Upper Colorado River Basin in clear‐sky conditions by calculating surface DLR with observed land‐surface temperatures from ECOSTRESS. We find that this effect is due to terrain‐subtended sky‐view and represents ∼22% of the surface longwave flux, rising to ∼28% and ∼24% in the East and Southeast of the Basin, respectively, and can be >50% in extreme cases. The common omission of this effect in atmospheric radiation models leads to an underestimation of DLR in complex terrain, especially at higher elevations, which has significant implications for mountainous ecohydrology simulations.
Do More Frequent Temperature Inversions Aggravate Haze Pollution in China?
Authors: Bai Kaixu , Li Ke , Guo Jianping , Cheng Wei , Xu Xiaofeng
Published: February 2022

By using twice daily high‐resolution radiosonde observations, here we assessed spatiotemporal variability of temperature inversion (TI) and its impact on PM2.5 pollution levels in China from 2014 to 2020. It was found that both surface‐based inversion (SBI) and elevated inversion (EI) became increasingly frequent across China, at a rate of 1.42% a−1 (1.15% a−1) and 2.82% a−1 (3.23% a−1) at 0800 (2000) Beijing time (BJT), respectively. However, the intensity of SBI and EI at 0800 (2000) BJT decreased at −0.17 (−0.43) and −0.07 (−0.05) °C 100m−1 decade−1, making annual mean PM2.5 increment induced by TI dip by 52.5% (73.2%) for the whole study period. Still positive TI induced PM2.5 increments demonstrate an offsetting effect between TI and emission control on haze pollution, underscoring the importance of fully considering TI contribution when assessing the emission control effect on haze reduction.
Potential Link Between Ice Nucleation and Climate Model Spread in Arctic Amplification
Authors: Tan Ivy , Barahona Donifan , Coopman Quentin
Published: February 2022

Arctic amplification (AA) is simulated by all global climate models, however the spread in the degree of projected warming is large and the underlying mechanisms driving it are poorly understood. The impact of the temperature dependence of immersion freezing on cloud feedbacks and AA is studied using NASA's GEOS‐5 model. Parameterizations that exhibit low ice‐nucleating particle (INP) concentrations in the high Arctic during summer are found to weaken the cloud‐phase feedback. This allows sunlight to readily melt sea‐ice in the summer, which decreases the stability of the lower troposphere, causing a decrease in wintertime cloud fraction over open ocean. Arctic amplification was found to span from ∼1.4 to >2.6, which spans 30% of the spread in AA in the coupled model intercomparison project models, depending on the temperature dependence of immersion freezing. These results suggest that summertime INP concentrations may provide an observational constraint on AA.
Evolution of Short‐Term Seismic Hazard in Alberta, Canada, From Induced and Natural Earthquakes: 2011–2020
Authors: Reyes Canales Mauricio , Yusifbayov Javad , van der Baan Mirko
Published: February 2022

We generate short‐term seismic hazard maps for the province of Alberta, Canada, from 2011 through 2020. First, we describe the required adaptations to probabilistic seismic hazard analysis to generate short‐term seismic hazard maps, following the Monte Carlo simulation approach. Second, we identify the natural and induced seismic source areas in Alberta and estimate their earthquake recurrence parameters revealing considerable spatio‐temporal variations in the ‐ and ‐values in the different seismic clusters in the province. Areas with the highest short‐term seismic hazard during the last decade in Alberta are related to cases of induced seismicity, including hydraulic fracturing activities in the Duvernay Fm., near Fox Creek, and waste‐water disposal activities near the Musreau Lake. These maps provide a valuable tool to quantify the short‐term evolution in the seismic hazard, which is particularly important considering past and emerging cases of induced seismicity related to the energy sector in Alberta. Furthermore, using parameters from the previous year, we make a seismic hazard forecast for the year 2021. Our analysis provides a baseline of expected short‐term seismic hazard, with inheren uncertainty due to the assumption of unchanged recurrence parameters from the previous year; yet our study reveals pertinent seismicity patterns in line with changing human activities.
A Coupled Dynamic System Inversion Model for Higher Accuracy in Flood Forecasting
Authors: Huang Yixin , Liang Zhongmin , Singh Vijay P. , Hu Yiming , Li Binquan , Wang Jun
Published: February 2022

Flood routing is a critical component of real‐time flood forecasting and plays a pivotal role in reducing economic and life losses due to flooding. However, flood routing always possesses errors because it is affected by various sources of uncertainty, which are transmitted and accumulated in the routing process from upstream to downstream, particularly for long or complex river systems. Thus, a real‐time error correction is rapidly becoming a key measure for reducing errors and improving flood forecasting accuracy. In this study, a dynamic system inversion (DSI) model was developed as a new correction method to update forecasting errors for long river systems. The new method utilizes all observed, forecasted, and corrected information at upstream stations and couples the matrix‐based Muskingum routing method with an error‐inversed updating technique to form the DSI equation. Multisource spatiotemporal errors of the river system are simultaneously combined into the DSI equation, and the discharges at the downstream station are reforecasted, thereby providing error correction in flood routing. Based on a case study on the Le'an River (China), the DSI model performed better than the traditional autoregressive (AR) model based on five metrics for both small and large flood events. Moreover, with an increase in lead time, the metrics of AR deteriorated rapidly, whereas that of DSI deteriorated slightly. In conclusion, the proposed DSI model is a sophisticated and robust method for flood routing and provides a new alternative for error correction in flood routing simulations of complex river systems.
Genetic variants in eleven central and peripheral chemoreceptor genes in sudden infant death syndrome
Authors: Neubauer Jacqueline , Forst Anna-Lena , Warth Richard , Both Christian Peter , Haas Cordula , Thomas Jörg
Published: February 2022

Background

Sudden infant death syndrome (SIDS) is still one of the leading causes of postnatal infant death in developed countries. The occurrence of SIDS is described by a multifactorial etiology that involves the respiratory control system including chemoreception. It is still unclear whether genetic variants in genes involved in respiratory chemoreception might play a role in SIDS.

Methods

The exome data of 155 SIDS cases were screened for variants within 11 genes described in chemoreception. Pathogenicity of variants was assigned based on the assessment of variant types and in silico protein predictions according to the current recommendations of the American College of Medical Genetics and Genomics.

Results

Potential pathogenic variants in genes encoding proteins involved in respiratory chemoreception could be identified in 5 (3%) SIDS cases. Two of the variants (R137S/A188S) were found in the KNCJ16 gene, which encodes for the potassium channel Kir5.1, presumably involved in central chemoreception. Electrophysiologic analysis of these KCNJ16 variants revealed a loss-of-function for the R137S variant but no obvious impairment for the A188S variant.

Conclusions

Genetic variants in genes involved in respiratory chemoreception may be a risk factor in a fraction of SIDS cases and may thereby contribute to the multifactorial etiology of SIDS.

Impact

What is the key message of your article?

Gene variants encoding proteins involved in respiratory chemoreception may play a role in a minority of SIDS cases.

What does it add to the existing literature?

Although impaired respiratory chemoreception has been suggested as an important risk factor for SIDS, genetic variants in single genes seem to play a minor role.

What is the impact?

This study supports previous findings, which indicate that genetic variants in single genes involved in respiratory control do not have a dominant role in SIDS.
Comprehensive metabolomics expands precision medicine for triple-negative breast cancer
Authors: Xiao Yi , Ma Ding , Yang Yun-Song , Yang Fan , Ding Jia-Han , Gong Yue , Jiang Lin , Ge Li-Ping , Wu Song-Yang , Yu Qiang , Zhang Qing , Bertucci François , Sun Qiuzhuang , Hu Xin , Li Da-Qiang , Shao Zhi-Ming , Jiang Yi-Zhou
Published: February 2022

Metabolic reprogramming is a hallmark of cancer. However, systematic characterizations of metabolites in triple-negative breast cancer (TNBC) are still lacking. Our study profiled the polar metabolome and lipidome in 330 TNBC samples and 149 paired normal breast tissues to construct a large metabolomic atlas of TNBC. Combining with previously established transcriptomic and genomic data of the same cohort, we conducted a comprehensive analysis linking TNBC metabolome to genomics. Our study classified TNBCs into three distinct metabolomic subgroups: C1, characterized by the enrichment of ceramides and fatty acids; C2, featured with the upregulation of metabolites related to oxidation reaction and glycosyl transfer; and C3, having the lowest level of metabolic dysregulation. Based on this newly developed metabolomic dataset, we refined previous TNBC transcriptomic subtypes and identified some crucial subtype-specific metabolites as potential therapeutic targets. The transcriptomic luminal androgen receptor (LAR) subtype overlapped with metabolomic C1 subtype. Experiments on patient-derived organoid and xenograft models indicate that targeting sphingosine-1-phosphate (S1P), an intermediate of the ceramide pathway, is a promising therapy for LAR tumors. Moreover, the transcriptomic basal-like immune-suppressed (BLIS) subtype contained two prognostic metabolomic subgroups (C2 and C3), which could be distinguished through machine-learning methods. We show that N-acetyl-aspartyl-glutamate is a crucial tumor-promoting metabolite and potential therapeutic target for high-risk BLIS tumors. Together, our study reveals the clinical significance of TNBC metabolomics, which can not only optimize the transcriptomic subtyping system, but also suggest novel therapeutic targets. This metabolomic dataset can serve as a useful public resource to promote precision treatment of TNBC.
Systemic adjuvant chemotherapy for advanced malignant ocular medulloepithelioma
Authors: Sheriff Ibrahim H. N. , Karaa Esin K. , Chowdhury Tanzina , Scheimberg Irene , Duncan Catriona , Reddy M. Ashwin , Sagoo Mandeep S.
Published: February 2022

Background

Ocular medulloepithelioma (diktyoma) is a rare and potentially malignant paediatric tumour of the non-pigmented ciliary epithelium. Adjuvant chemotherapy can be given in advanced cases, but the indications and regimens remain to be defined. The aim was to identify whether adjuvant chemotherapy offers treatment benefit in advanced ocular medulloepithelioma.

Methods

This was a retrospective case series of subjects referred to a single specialist ocular oncology centre for advanced ocular medulloepithelioma subsequently treated with enucleation, including those needing adjuvant systemic vincristine, etoposide and carboplatin. A case-note review was performed for included subjects meeting referral criteria. The outcomes were histopathology characteristics, recurrence, metastases and survival.

Results

Between March 2010 and June 2017, four male patients (mean age 31 months) underwent enucleation for ocular medulloepithelioma. Adjuvant chemotherapy was commenced in 3 patients (75%) due to malignant histopathological features. With a mean follow-up time of 81.5 months (median 71 months, range 49–135 months) none of the patients have had recurrence, metastases or death from the tumour.

Conclusions

This series is unique in reporting the management of advanced malignant ocular medulloepithelioma with adjuvant systemic vincristine, etoposide and carboplatin for advanced tumours with malignant features. This regimen appears to be safe and may be effective in preventing metastatic spread.
Large planets may not form fractionally large moons
Authors: Nakajima Miki , Genda Hidenori , Asphaug Erik , Ida Shigeru
Published: February 2022

One of the unique aspects of Earth is that it has a fractionally large Moon, which is thought to have formed from a Moon-forming disk generated by a giant impact. The Moon stabilizes the Earth’s spin axis at least by several degrees and contributes to Earth’s stable climate. Given that impacts are common during planet formation, exomoons, which are moons around planets in extrasolar systems, should be common as well, but no exomoon has been confirmed. Here we propose that an initially vapor-rich moon-forming disk is not capable of forming a moon that is large with respect to the size of the planet because growing moonlets, which are building blocks of a moon, experience strong gas drag and quickly fall toward the planet. Our impact simulations show that terrestrial and icy planets that are larger than ~1.3−1.6R⊕ produce entirely vapor disks, which fail to form a fractionally large moon. This indicates that (1) our model supports the Moon-formation models that produce vapor-poor disks and (2) rocky and icy exoplanets whose radii are smaller than ~1.6R⊕ are ideal candidates for hosting fractionally large exomoons.
Automatic mapping of multiplexed social receptive fields by deep learning and GPU-accelerated 3D videography
Authors: Ebbesen Christian L. , Froemke Robert C.
Published: February 2022

Social interactions powerfully impact the brain and the body, but high-resolution descriptions of these important physical interactions and their neural correlates are lacking. Currently, most studies rely on labor-intensive methods such as manual annotation. Scalable and objective tracking methods are required to understand the neural circuits underlying social behavior. Here we describe a hardware/software system and analysis pipeline that combines 3D videography, deep learning, physical modeling, and GPU-accelerated robust optimization, with automatic analysis of neuronal receptive fields recorded in interacting mice. Our system (“3DDD Social Mouse Tracker”) is capable of fully automatic multi-animal tracking with minimal errors (including in complete darkness) during complex, spontaneous social encounters, together with simultaneous electrophysiological recordings. We capture posture dynamics of multiple unmarked mice with high spatiotemporal precision (~2 mm, 60 frames/s). A statistical model that relates 3D behavior and neural activity reveals multiplexed ‘social receptive fields’ of neurons in barrel cortex. Our approach could be broadly useful for neurobehavioral studies of multiple animals interacting in complex low-light environments.
Room-temperature optically detected magnetic resonance of single defects in hexagonal boron nitride
Authors: Stern Hannah L. , Gu Qiushi , Jarman John , Eizagirre Barker Simone , Mendelson Noah , Chugh Dipankar , Schott Sam , Tan Hoe H. , Sirringhaus Henning , Aharonovich Igor , Atatüre Mete
Published: February 2022

Optically addressable solid-state spins are important platforms for quantum technologies, such as repeaters and sensors. Spins in two-dimensional materials offer an advantage, as the reduced dimensionality enables feasible on-chip integration into devices. Here, we report room-temperature optically detected magnetic resonance (ODMR) from single carbon-related defects in hexagonal boron nitride with up to 100 times stronger contrast than the ensemble average. We identify two distinct bunching timescales in the second-order intensity-correlation measurements for ODMR-active defects, but only one for those without an ODMR response. We also observe either positive or negative ODMR signal for each defect. Based on kinematic models, we relate this bipolarity to highly tuneable internal optical rates. Finally, we resolve an ODMR fine structure in the form of an angle-dependent doublet resonance, indicative of weak but finite zero-field splitting. Our results offer a promising route towards realising a room-temperature spin-photon quantum interface in hexagonal boron nitride.
ΔNp63 regulates a common landscape of enhancer associated genes in non-small cell lung cancer
Authors: Napoli Marco , Wu Sarah J. , Gore Bethanie L. , Abbas Hussein A. , Lee Kyubum , Checker Rahul , Dhar Shilpa , Rajapakshe Kimal , Tan Aik Choon , Lee Min Gyu , Coarfa Cristian , Flores Elsa R.
Published: February 2022

Distinct lung stem cells give rise to lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC). ΔNp63, the p53 family member and p63 isoform, guides the maturation of these stem cells through the regulation of their self-renewal and terminal differentiation; however, the underlying mechanistic role regulated by ∆Np63 in lung cancer development has remained elusive. By utilizing a ΔNp63-specific conditional knockout mouse model and xenograft models of LUAD and LUSC, we found that ∆Np63 promotes non-small cell lung cancer by maintaining the lung stem cells necessary for lung cancer cell initiation and progression in quiescence. ChIP-seq analysis of lung basal cells, alveolar type 2 (AT2) cells, and LUAD reveals robust ∆Np63 regulation of a common landscape of enhancers of cell identity genes. Importantly, one of these genes, BCL9L, is among the enhancer associated genes regulated by ∆Np63 in Kras-driven LUAD and mediates the oncogenic effects of ∆Np63 in both LUAD and LUSC. Accordingly, high BCL9L levels correlate with poor prognosis in LUAD patients. Taken together, our findings provide a unifying oncogenic role for ∆Np63 in both LUAD and LUSC through the regulation of a common landscape of enhancer associated genes.
Relative effects of land conversion and land-use intensity on terrestrial vertebrate diversity
Authors: Semenchuk Philipp , Plutzar Christoph , Kastner Thomas , Matej Sarah , Bidoglio Giorgio , Erb Karl-Heinz , Essl Franz , Haberl Helmut , Wessely Johannes , Krausmann Fridolin , Dullinger Stefan
Published: February 2022

Land-use has transformed ecosystems over three quarters of the terrestrial surface, with massive repercussions on biodiversity. Land-use intensity is known to contribute to the effects of land-use on biodiversity, but the magnitude of this contribution remains uncertain. Here, we use a modified countryside species-area model to compute a global account of the impending biodiversity loss caused by current land-use patterns, explicitly addressing the role of land-use intensity based on two sets of intensity indicators. We find that land-use entails the loss of ~15% of terrestrial vertebrate species from the average 5 × 5 arcmin-landscape outside remaining wilderness areas and ~14% of their average native area-of-habitat, with a risk of global extinction for 556 individual species. Given the large fraction of global land currently used under low land-use intensity, we find its contribution to biodiversity loss to be substantial (~25%). While both sets of intensity indicators yield similar global average results, we find regional differences between them and discuss data gaps. Our results support calls for improved sustainable intensification strategies and demand-side actions to reduce trade-offs between food security and biodiversity conservation.
Catalytic trajectory of a dimeric nonribosomal peptide synthetase subunit with an inserted epimerase domain
Authors: Wang Jialiang , Li Dandan , Chen Lu , Cao Wei , Kong Liangliang , Zhang Wei , Croll Tristan , Deng Zixin , Liang Jingdan , Wang Zhijun
Published: February 2022

Nonribosomal peptide synthetases (NRPSs) are modular assembly-line megaenzymes that synthesize diverse metabolites with wide-ranging biological activities. The structural dynamics of synthetic elongation has remained unclear. Here, we present cryo-EM structures of PchE, an NRPS elongation module, in distinct conformations. The domain organization reveals a unique “H”-shaped head-to-tail dimeric architecture. The capture of both aryl and peptidyl carrier protein-tethered substrates and intermediates inside the heterocyclization domain and l-cysteinyl adenylate in the adenylation domain illustrates the catalytic and recognition residues. The multilevel structural transitions guided by the adenylation C-terminal subdomain in combination with the inserted epimerase and the conformational changes of the heterocyclization tunnel are controlled by two residues. Moreover, we visualized the direct structural dynamics of the full catalytic cycle from thiolation to epimerization. This study establishes the catalytic trajectory of PchE and sheds light on the rational re-engineering of domain-inserted dimeric NRPSs for the production of novel pharmaceutical agents.
Inhibition of base editors with anti-deaminases derived from viruses
Authors: Liu Zhiquan , Chen Siyu , Lai Liangxue , Li Zhanjun
Published: February 2022

Cytosine base editors (CBEs), combining cytidine deaminases with the Cas9 nickase (nCas9), enable targeted C-to-T conversions in genomic DNA and are powerful genome-editing tools used in biotechnology and medicine. However, the overexpression of cytidine deaminases in vivo leads to unexpected potential safety risks, such as Cas9-independent off-target effects. This risk makes the development of deaminase off switches for modulating CBE activity an urgent need. Here, we report the repurpose of four virus-derived anti-deaminases (Ades) that efficiently inhibit APOBEC3 deaminase-CBEs. We demonstrate that they antagonize CBEs by inhibiting the APOBEC3 catalytic domain, relocating the deaminases to the extranuclear region or degrading the whole CBE complex. By rationally engineering the deaminase domain, other frequently used base editors, such as CGBE, A&CBE, A&CGBE, rA1-CBE and ABE8e, can be moderately inhibited by Ades, expanding the scope of their applications. As a proof of concept, the Ades in this study dramatically decrease both Cas9-dependent and Cas9-independent off-target effects of CBEs better than traditional anti-CRISPRs (Acrs). Finally, we report the creation of a cell type-specific CBE-ON switch based on a microRNA-responsive Ade vector, showing its practicality. In summary, these natural deaminase-specific Ades are tools that can be used to regulate the genome-engineering functions of BEs.
Attenuated fusogenicity and pathogenicity of SARS-CoV-2 Omicron variant
Authors: Suzuki Rigel , Yamasoba Daichi , Kimura Izumi , Wang Lei , Kishimoto Mai , Ito Jumpei , Morioka Yuhei , Nao Naganori , Nasser Hesham , Uriu Keiya , Kosugi Yusuke , Tsuda Masumi , Orba Yasuko , Sasaki Michihito , Shimizu Ryo , Kawabata Ryoko , Yoshimatsu Kumiko , Asakura Hiroyuki , Nagashima Mami , Sadamasu Kenji , Yoshimura Kazuhisa ,   The Genotype to Phenotype Japan (G2P-Japan) Consortium, Suganami Mai , Oide Akiko , Chiba Mika , Ito Hayato , Tamura Tomokazu , Tsushima Kana , Kubo Haruko , Ferdous Zannatul , Mouri Hiromi , Iida Miki , Kasahara Keiko , Tabata Koshiro , Ishizuka Mariko , Shigeno Asako , Tokunaga Kenzo , Ozono Seiya , Yoshida Isao , Nakagawa So , Wu Jiaqi , Takahashi Miyoko , Kaneda Atsushi , Seki Motoaki , Fujiki Ryoji , Nawai Bahityar Rahmutulla , Suzuki Yutaka , Kashima Yukie , Abe Kazumi , Imamura Kiyomi , Shirakawa Kotaro , Takaori-Kondo Akifumi , Kazuma Yasuhiro , Nomura Ryosuke , Horisawa Yoshihito , Nagata Kayoko , Kawai Yugo , Yanagida Yohei , Tashiro Yusuke , Takahashi Otowa , Kitazato Kazuko , Hasebe Haruyo , Motozono Chihiro , Toyoda Mako , Tan Toong Seng , Ngare Isaac , Ueno Takamasa , Saito Akatsuki , Butlertanaka Erika P. , Tanaka Yuri L. , Morizako Nanami , Sawa Hirofumi , Ikeda Terumasa , Irie Takashi , Matsuno Keita , Tanaka Shinya , Fukuhara Takasuke , Sato Kei
Published: February 2022

The emergence of the Omicron variant of SARS-CoV-2 is an urgent global health concern1. In this study, our statistical modelling suggests that Omicron has spread more rapidly than the Delta variant in several countries including South Africa. Cell culture experiments showed Omicron to be less fusogenic than Delta and than an ancestral strain of SARS-CoV-2. Although the spike (S) protein of Delta is efficiently cleaved into two subunits, which facilitates cell–cell fusion2,3, the Omicron S protein was less efficiently cleaved compared to the S proteins of Delta and ancestral SARS-CoV-2. Furthermore, in a hamster model, Omicron showed decreased lung infectivity and was less pathogenic compared to Delta and ancestral SARS-CoV-2. Our multiscale investigations reveal the virological characteristics of Omicron, including rapid growth in the human population, lower fusogenicity and attenuated pathogenicity.
RETRACTED ARTICLE: The Hopewell airburst event, 1699–1567 years ago (252–383 CE)
Authors: Tankersley Kenneth Barnett , Meyers Stephen D. , Meyers Stephanie A. , Jordan James A. , Herzner Louis , Lentz David L. , Zedaker Dylan
Published: February 2022

Meteorites, Fe and Si-rich microspherules, positive Ir and Pt anomalies, and burned charcoal-rich Hopewell habitation surfaces demonstrate that a cosmic airburst event occurred over the Ohio River valley during the late Holocene. A comet-shaped earthwork was constructed near the airburst epicenter. Twenty-nine radiocarbon ages establish that the event occurred between 252 and 383 CE, a time when 69 near-Earth comets were documented. While Hopewell people survived the catastrophic event, it likely contributed to their cultural decline. The Hopewell airburst event expands our understanding of the frequency and impact of cataclysmic cosmic events on complex human societies.
Tetrahydroxy stilbene glycoside attenuates endothelial cell premature senescence induced by H2O2 through the microRNA-34a/SIRT1 pathway
Authors: Zhang Lixuan , Guo Yan , Shi Shennan , Zhuge Yani , Chen Nipi , Ding Zhishan , Jin Bo
Published: February 2022

Numerous studies have demonstrated that endothelial cell senescence plays a decisive role in the development and progression of cardiovascular diseases (CVD). Our previous results confirmed that Tetrahydroxy stilbene glycoside (TSG) can alleviate the human umbilical vein endothelial cells (HUVECs) senescence induced by H2O2 through SIRT1. It has been reported that miR-34a is a translational suppressor of SIRT1. In this study, we aimed to explore whether TSG regulates SIRT1 through miR-34a to ameliorate HUVECs senescence. H2O2 was used to induce premature senescence in HUVECs, and miR-34a mimic or inhibitor were transfected to over-express or suppress the expression level of miR-34a. Results revealed that TSG apparently decreased the miR-34a expression level in H2O2-induced premature senescence of HUVECs. When SIRT1 expression was inhibited by EX527, the attenuation of TSG on the expression level of miR-34a were abolished. When miR-34a expression was knockdown, the effect of TSG on HUVECs senescence could be enhanced. While miR-34a mimic could reverse the effect of TSG on HUVECs senescence. In conclusion, we demonstrated that TSG could attenuated endothelial cell senescence by targeting miR-34a/SIRT1 pathway.
Effect of mass variation on vibration properties of the tooth in drilling operation
Authors: Vujkov Sanja , Cveticanin Livija
Published: February 2022

Dental cavity represent one of the widespread illness of the tooth. Method for treating of the tooth is to drill the cavity and to fill the hole with suitable material. Measurements show that during drilling the tooth vibrates with increasing mass that causes unpleasant feeling for patient. The aim of the paper is to give the theoretical explanation for this phenomena and to give suggestion for vibration elimination. During drilling, mass of the tooth is decreasing and the so called ‘reactive force’ occurs. Drilling and reactive force cause tooth vibration. The system is modeled as a nonlinear time variable system. An analytical procedure for solving of the equation of vibration is developed. The solution is assumed in the form of the generalized trigonometric function with time variable amplitude and phase. It is obtained that not only the amplitude but also the frequency of tooth vibration in drilling are increased. In addition to reactive force the drilling velocity, diameter of the drill tool and spindle speed affect the vibration level. The appropriate values of these parameters would eliminate or decrease the patient bad feeling.
Self-catalyzed tumor ferroptosis based on ferrocene conjugated reactive oxygen species generation and a responsive polymer
Authors: Li Jisi , Zong Qingyu , Liu Ye , Xiao Xuan , Zhou Jielian , Zhao Zhongyi , Yuan Youyong
Published: February 2022

In this work, PTAF functions as a ferroptosis self-catalyst, through synergistic actions of self-catalyzed ˙OH accumulation and GPX4 indirect inactivation based on the ROS self-catalytic loop, effectively induced tumor ferroptosis.
The depletion thickness in solutions of semi-flexible polymers near colloidal surfaces: analytical approximations
Authors: Martens C. M. , van Leuken S. H. M. , Opdam J. , Vis M. , Tuinier R.
Published: February 2022

The depletion thickness of a solution of semi-flexible polymers reaches a maximum as a function of chain stiffness in the semidilute concentration regime.
Mass transfer of toluene in a series of metal–organic frameworks: molecular clusters inside the nanopores cause slow and step-like release
Authors: Li Chun , Zhang Zejun , Heinke Lars
Published: February 2022

Toluene forms dimers in sufficiently large pores of MOFs of UiO-type. During the release process, the dimer break-up rather than the diffusion is rate limiting, causing a step-like desorption kinetics with a local maximum of the release rate.
Biocompatible hypocrellin A-Fe(iii) nanoparticles exhibiting efficient photo-activated CDT in vitro and in vivo
Authors: Wang Zhanhua , Gao Chuan , Da Xuwen , Jian Yao , Zhang Chao , Yao Yishan , Wang Xuesong , Zhou Qianxiong
Published: February 2022

Biocompatible hypocrellin A-Fe(iii) nanoparticles had little cytotoxicity in the dark, but exhibited efficient photo-activated CDT activity both in vitro and in vivo upon red light irradiation.
Cation modulated spin state and near room temperature transition within a family of compounds containing the same [FeL2]2− center
Authors: Liu Jia-Hui , Guo Xiao-Qing , Wang Zi-Cheng , Cai Li-Xuan , Zhou Li-Peng , Tian Chong-Bin , Sun Qing-Fu
Published: February 2022

A series of solvent-free FeII compounds with the same anionic [FeL2]2− center were synthesized and characterized. The tuning of the spin states, SCO profiles and critical temperatures was realized by the organic cations change.
A self-regulated gradient interphase for dendrite-free solid-state Li batteries
Authors: Wang Tengrui , Duan Jian , Zhang Bao , Luo Wei , Ji Xiao , Xu Henghui , Huang Ying , Huang Liqiang , Song Zhenyou , Wen Jiayun , Wang Chunsheng , Huang Yunhui , Goodenough John B.
Published: February 2022

A functional gradient lithium anode (FGLA), where a LiF-rich layer faces garnet side and gradually changes to a LiAl-rich layer facing Li side, effectively prevents solid-state electrolytes from dendrite penetration at high current densities.
Incorporating nitrogen vacancies in exfoliated B-doped g-C3N4 towards improved photocatalytic ciprofloxacin degradation and hydrogen evolution
Authors: Acharya Lopamudra , Mishra Bhagyashree Priyadarshini , Pattnaik Sambhu Prasad , Acharya Rashmi , Parida Kulamani
Published: February 2022

The e-BCN fabricated from the double calcination process exhibited significant photocatalytic activity towards photocatalytic ciprofloxacin degradation and hydrogen generation.
Polycyclic heteroaromatics via hydrazine-catalyzed ring-closing carbonyl–olefin metathesis
Authors: Cho Eun Kee , Quach Phong K. , Zhang Yunfei , Sim Jae Hun , Lambert Tristan H.
Published: February 2022

Hydrazine catalysis enables the ring-closing carbonyl–olefin metathesis (RCCOM) to form polycyclic heteroaromatics, especially those with basic functionality.
Unraveling the reactivity of the azo bridge in 3,3′-(5-dinitromethyl-1,2,4-oxadiazolyl)-4,4′-azofurazanate in the synthesis of energetic compounds
Authors: Chen Peng , Qiu Lili , Yin Ping , He Chunlin , Pang Siping , Shreeve Jean’ne M.
Published: February 2022

The introduction of an azo bridge into an energetic compound is an efficient strategy to improve its nitrogen content, heat of formation and detonation performances.
Enantioselective crossed intramolecular [2+2] photocycloaddition reactions mediated by a chiral chelating Lewis acid
Authors: Rigotti Thomas , Schwinger Daniel P. , Graßl Raphaela , Jandl Christian , Bach Thorsten
Published: February 2022

An enantioselective crossed [2+2] photocycloaddition is presented which proceeds under visible light irradiation in the presence of a chiral Lewis acidic metal complex. Chelation of two oxygen atoms to the metal centre accounts for the observed enantioface differentiation.