bluuebunny/crossref_metadata_2025 huggingface dataset:
Universal modulations of large-scale motions on entrainment of turbulent boundary layers
Authors: Long Yanguang , Wang Jinjun , Pan Chong
Published: May 2022

The modulations of high/low-speed large-scale motions (H/L-SMs) on the turbulent/non-turbulent interface (TNTI) and turbulent entrainment are investigated in turbulent boundary layers via both experimental and numerical studies. The spanwise locations of large-scale motions can be locked by the spanwise heterogeneity, so the boundary layers over such a configuration are investigated first as an instructive case. In the engulfment process, it is found that irrotational ‘bubbles’ near the TNTI are more likely to originate from engulfment, while bubbles far from the TNTI could be produced by the local turbulence itself. Additionally, H-SMs are found to enhance the engulfment by the sweep flow. In the nibbling process, a competition relationship is observed: L-SMs induce stronger instantaneous ‘nibbling’ events by transporting more fluids towards the TNTI, while the H-SMs induced a more distorted TNTI. Consequently, the integral nibbling flux is greater above H-SMs. Furthermore, the explored mechanisms are verified to be insensitive to the wall shapes such as smooth and homogeneous roughness walls, which demonstrates that these modulations are universal for turbulent boundary layers. Finally, a conceptual modulation model is proposed to illustrate the entrainment process above the large-scale motions.
14C-AMS TECHNOLOGY AND ITS APPLICATIONS TO AN OIL FIELD TRACER EXPERIMENT
Authors: Shen Hongtao , Shi Shulin , Tang Junsen , Qi Mingli , Wei Siyu , Sasa Kimikazu , Liu Mingji , Wang Li , Zhang Guofeng , Qi Linjie , Chen Dingxiong , Gong Shanhua , Song Guofu , Dong Junyan , Wang Ning , Zhou Houbing , He Ming , Zhao Qingzhang , Wei Mingjun , He Yun
Published: May 2022

Many waterflooding oil fields, injecting water into an oil-bearing reservoir for pressure maintenance, are in their middle to late stages of development. To explore the geological conditions and improve oilfield recovery of the most important well group of the Hu 136 block, located on the border areas of three provinces (Henan, Shandong, and Hebei), Zhongyuan Oilfield, Sinopec, central China, a 14C cross-well tracer monitoring technology was developed and applied in monitoring the development status and recognize the heterogeneity of oil reservoirs. The tracer response in the production well was tracked, and the water drive speed, swept volume of the injection fluid were obtained. Finally, the reservoir heterogeneity characteristics, such as the dilution coefficient, porosity, permeability, and average pore-throat radius, were fitted according to the mathematical model of the heterogeneous multi-layer inter-well theory. The 14C-AMS technique developed in this work is expected to be a potential analytical method for evaluating underground reservoir characteristics and providing crucial scientific guidance for the mid to late oil field recovery process.
Effect of milrinone on the meiosis resumption and cytoplasm maturation of buffalo oocytes
Authors: Bian Guihua , Shi Wen , Duan Linwei , Zhu Yungan , Shafique Laiba , Liu Qingyou , Shi Deshun , Xiao Wenhua
Published: May 2022

Buffalo has many excellent economic traits and it is one of the greatest potential livestock. Compared with cattle, buffalo has poorer reproductivity, it is of great significance to improve the development potential of oocytes. Buffalo oocyte in vitro maturation (IVM) has been widely used in production, but the poor development ability of bovine oocytes IVM limits the development of buffalo reproductivity. Milrinone as a phosphodiesterase inhibitor could affect the maturation of oocytes in goat and mice, but there have been few reported studies in water buffalo. To optimize buffalo oocyte in vitro maturation systems, the effects of phosphodiesterase inhibitor (milrinone) on pre-maturation culture of buffalo oocytes were investigated in this study. Buffalo cumulus–oocyte complexes (COCs) were cultured in medium with different concentrations (0, 12, 25, 50 and 100 mol/l) of milrinone for different times (0, 4, 8, 12, 16, 22 and 24 h). The results showed that the buffalo COCs nuclear maturation process could be inhibited by milrinone (25–100 mol/l) in a dose-dependent manner. The inhibitory effect of milrinone on in vitro maturation of buffalo oocytes did not decrease with the extension of time. This indicated that milrinone can be used as a nuclear maturation inhibitor during the maturation process in buffalo oocytes. In addition, milrinone can inhibit the effect of follicle stimulating hormone (FSH)-induced IVM of buffalo oocytes, but with time FSH partially eliminated the inhibition. Therefore, inhibition of milrinone on the nuclear maturation of buffalo oocytes was reversible, and buffalo oocytes can mature normally after the inhibition is lessened.
CATEGORICAL AND K-THEORETIC HALL ALGEBRAS FOR QUIVERS WITH POTENTIAL
Authors: Pădurariu Tudor
Published: May 2022

Given a quiver with potential
$(Q,W)$
, Kontsevich–Soibelman constructed a cohomological Hall algebra (CoHA) on the critical cohomology of the stack of representations of
$(Q,W)$
. Special cases of this construction are related to work of Nakajima, Varagnolo, Schiffmann–Vasserot, Maulik–Okounkov, Yang–Zhao, etc. about geometric constructions of Yangians and their representations; indeed, given a quiver Q, there exists an associated pair
$(\widetilde{Q}, \widetilde{W})$
whose CoHA is conjecturally the positive half of the Maulik–Okounkov Yangian
$Y_{\text {MO}}(\mathfrak {g}_{Q})$
.

For a quiver with potential
$(Q,W)$
, we follow a suggestion of Kontsevich–Soibelman and study a categorification of the above algebra constructed using categories of singularities. Its Grothendieck group is a K-theoretic Hall algebra (KHA) for quivers with potential. We construct representations using framed quivers, and we prove a wall-crossing theorem for KHAs. We expect the KHA for
$(\widetilde{Q}, \widetilde{W})$
to recover the positive part of quantum affine algebra
$U_{q}(\widehat {\mathfrak {g}_{Q}})$
defined by Okounkov–Smirnov.
Calling for policy actions to increase access to long-acting antipsychotics in low-income and middle-income countries
Authors: Ostuzzi Giovanni , Gastaldon Chiara , Papola Davide , Barbui Corrado
Published: May 2022

Schizophrenia-spectrum disorders are associated with substantial impairment and disability. Lack of treatment adherence is a major issue, especially in low- and middle-income countries (LMICs). Despite growing evidence supporting second-generation long-acting antipsychotics (LAIs) as an effective strategy to ensure continued maintenance treatment in schizophrenia, access to these technologies has been very limited in constrained-resource settings. Including second-generation LAIs in national and international essential medicines lists and evidence-based guidelines, promoting public health-oriented patent pooling and extending their availability to primary health care settings, are key actions that should urgently be implemented to increase access to long-acting technologies. Implementing these policy actions can pragmatically improve treatment adherence, ultimately tackling schizophrenia-related impairment and disability in LMICs, which can be regarded as a global health priority.
Diabetes mellitus and femoropopliteal in-stent	restenosis
Authors: Voll Felix , Wolf Florian , Ingwersen Maja , Kinstner Christian M. , Kufner Sebastian , Ibrahim Tareq , Ott Ilka , Krankenberg Hans , Fusaro Massimiliano , Cassese Salvatore
Published: May 2022

Summary: Background: The influence of diabetes mellitus (DM) on recurrent in-stent restenosis (ISR) of femoropopliteal arteries remains understudied. We investigated whether DM has an impact on recurrent restenosis after femoropopliteal stenting in patients included in the dRug-coatEd balloon angioPlasty for femoropopliteAl In-stent Restenosis (REPAIR) cooperation. Patients and methods: The REPAIR cooperation pooled the patient-level data from 3 randomized trials in which patients with ISR of femoropopliteal arteries received either drug-coated balloon (DCB) or plain balloon angioplasty. For this analysis, patients were divided in two groups based on whether they had or had not a DM diagnosis at the time of enrollment. The primary outcome was target lesion revascularization (TLR). The main secondary outcome was recurrent ISR. Other outcomes of interest were death, Rutherford class improvement and ankle-brachial index at follow-up. Results: 256 patients (DM, n=99 vs. non-DM, n=157) with 12-month follow-up were included in the analysis. Compared to non-DM patients, DM patients displayed no difference in terms of TLR [adjusted hazard ratio (95% Confidence intervals): 0.96 (0.55, 1.69), p=0.89] and recurrent ISR [1.04 (0.61, 1.77), p=0.88], whilst mortality was higher [9.38 (1.06, 83.11), p=0.044]. There were no differences between groups with respect to other secondary outcomes. The percutaneous treatment with DCB as compared to plain balloon angioplasty significantly reduced the risk of TLR and recurrent ISR without an excess risk of death irrespective of DM (p for interaction ≥0.70). Conclusions: In patients with femoropopliteal ISR, diabetes has a neutral effect on the risk of recurrence, but increases mortality at 12-month follow-up. DCB as compared to plain balloon angioplasty is associated with superior efficacy without trade-off in safety, regardless of diabetes.
Machine Learning and Prediction in Psychological Assessment
Authors: Fokkema Marjolein , Iliescu Dragos , Greiff Samuel , Ziegler Matthias
Published: May 2022

Abstract. Modern prediction methods from machine learning (ML) and artificial intelligence (AI) are becoming increasingly popular, also in the field of psychological assessment. These methods provide unprecedented flexibility for modeling large numbers of predictor variables and non-linear associations between predictors and responses. In this paper, we aim to look at what these methods may contribute to the assessment of criterion validity and their possible drawbacks. We apply a range of modern statistical prediction methods to a dataset for predicting the university major completed, based on the subscales and items of a scale for vocational preferences. The results indicate that logistic regression combined with regularization performs strikingly well already in terms of predictive accuracy. More sophisticated techniques for incorporating non-linearities can further contribute to predictive accuracy and validity, but often marginally.
Climate Responses to Tambora‐Size Volcanic Eruption and the Impact of Warming Climate
Authors: Yang Linshan , Gao Yujuan , Gao Chaochao , Liu Fei
Published: May 2022

The climatic consequences of large volcanic eruptions depend on the direct radiative perturbation and the climate variability that amplifies or dampens the initial perturbation. Potential climate responses to future eruptions, however, have been rarely studied. Here we show perturbation of Tambora‐size causes significant but no inter‐scenario different global average climate responses, by using Community Earth System Model simulations under preindustrial and RCP8.5 scenarios. Regionally we find severe reduction in African and Asian‐Australian monsoon rainfall and emerge of El Niño‐like responses, largely due to the land‐ocean thermal contrast mechanism. Global warming significantly amplifies such El Niño‐like responses, which feed on the enhanced climatology atmospheric moisture and cause higher sensitivity of monsoon circulation to radiative forcing in the tropics. We also find prolonged Asian‐Australian monsoon suppression associated with the enhanced westerly anomalies over the Pacific, suggesting the complexity of climate responses and feedbacks to external forcing under future climate.
Hydrological Extremes in the Upper Yangtze River Over the Past 700 yr Inferred From a Tree Ring δ18O Record
Authors: An Wenling , Li Jinjian , Wang Shu , Xu Chenxi , Shao Xuemei , Qin Ningsheng , Guo Zhengtang
Published: May 2022

Ongoing global warming has a strong influence on regional hydrological cycles. The upper reaches of the Yangtze River (UYR) are highly vulnerable to extreme hydrological droughts and floods, but a lack of long‐term streamflow observations has limited our understanding on global warming influences. Here, we establish an annually resolved and absolutely dated tree‐ring oxygen (δ18O) isotope chronology and use it to reconstruct the summer streamflow history of the UYR between 1260 and 2017. The UYR experienced 79 extreme floods and 107 extreme hydrological droughts over this period. We found a trend toward dry conditions in the region with tendencies for an increased drought probability since around 1850s. Especially, the frequency of hydrological droughts in recent decades has been outside the envelope of natural variability of extreme hydrological droughts. The temporal evolution of hydrological extremes is closely linked to variability of the Indian summer monsoon (ISM) at decadal scales. The UYR has experienced more frequent droughts during dry spells and experienced more frequent floods during wet spells of the ISM. The recent increase in the frequency of hydrological droughts is consistent with the observed trend toward a weaker ISM and increasing temperatures. Weaker transport of low‐level moisture and greater evaporation caused by global warming have contributed to the increase in extreme hydrological droughts. Our results thus provide a long‐term context for observed hydrological changes and suggest that the UYR will experience more frequent and severe extreme events as a consequence of increasing greenhouse gas emissions.
An Efficient Estimation of Time‐Varying Parameters of Dynamic Models by Combining Offline Batch Optimization and Online Data Assimilation
Authors: Sawada Yohei
Published: May 2022

It is crucially important to estimate unknown parameters in process‐based models by integrating observation and numerical simulation. For many applications in earth system sciences, a parameter estimation method which allows parameters to temporally change is required. In the present paper, an efficient and practical method to estimate time‐varying parameters of relatively low dimensional models is presented. In the newly proposed method, called Hybrid Offline Online Parameter Estimation with Particle Filtering (HOOPE‐PF), an inflation method to maintain the spread of ensemble members in a Sampling‐Importance‐Resampling Particle Filter (SIRPF) is improved using a non‐parametric posterior probabilistic distribution of time‐invariant parameters obtained by comparing simulated and observed climatology. HOOPE‐PF outperforms the original SIRPF in synthetic experiments with toy models and a real‐data experiment with a conceptual hydrological model when an ensemble size is small. The advantage of HOOPE‐PF is that its performance is not greatly affected by the size of perturbation to be added to ensemble members to maintain their spread while it is important to get the optimal performance in the original particle filter. Since HOOPE‐PF is the extension of the existing particle filter which has been extensively applied to many models in earth system sciences such as land, ecosystem, hydrology, and paleoclimate reconstruction, HOOPE‐PF can be applied to improve the simulation of these process‐based models by considering time‐varying model parameters.
Nighttime Atmospheric Scattering Phase Function Derived From the Scattered Light of a Laser Beam
Authors: Kocifaj M. , Kundracik F. , Bará S. , Barentine J. , Wallner S.
Published: May 2022

Continuous monitoring of the atmospheric scattering phase function is difficult to perform since most observational techniques are limited to daylight hours. Among known aerosol optical properties, only atmospheric optical depth is measured routinely during clear nights at a few ground stations. In this paper we develop theoretical and experimental techniques to retrieve the scattering phase function from radiometry of a laser beam whose light is scattered in the lower nocturnal atmosphere. The field experiment we conducted in a night environment demonstrates the capability of the method to determine in real‐world settings. We show that extracting the scattering phase function from radiance data is realizable over a wide range of angles, which makes possible the use of an analytical extrapolation to approximate across the full range of scattering angles.
Plasmaspheric Pi2 Pulsation Enhancement in Response to Plasma Sheet Pi2 Wave Source: Statistical Study Using Van Allen Probes and THEMIS Conjunctions
Authors: Wang Chih‐Ping , Takahashi Kazue , Xing Xiaoyan , Bortnik Jacob
Published: May 2022

To understand the enhancement of Pi2 pulsations inside the plasmasphere in response to the plasma sheet Pi2 wave source, we conduct a statistical investigation of 208 conjunction events by using simultaneous two‐point measurements with one satellite located in the plasmasphere and the other one located in the plasma sheet. All the events had a Pi2 compressional wave source observed in the plasma sheet as indicated by their association with bursty bulk flows (BBFs), but for about 25% of the events there were no corresponding enhancements in plasmaspheric Pi2 waves. For events with plasmaspheric Pi2 wave enhancements, a cavity or virtual resonance was likely the dominant wave mode, while excitation of field line resonance was also observed. We select two groups of events: strong (weak) group with the plasmaspheric compressional wave enhancements above 75% percentile (below 25% percentile), and conduct a statistical‐significance evaluation of the differences between the two groups. The strong events were observed closer to midnight than the weak events. The plasma sheet wave source that has a larger wave amplification or larger dipolarization associated with BBFs is more likely to excite stronger plasmaspheric wave enhancements. The strong events occurred more often with a pre‐condition of lower Auroral Electrojet (AE)* levels than did weak events. We explain these dependencies as strong events being associated with more favorable conditions that allow the inward‐propagating compressional waves from the plasma sheet wave source to reach the plasmapause and excite the plasmaspheric waves.
Klotho in Osx+-mesenchymal progenitors exerts pro-osteogenic and anti-inflammatory effects during mandibular alveolar bone formation and repair
Authors: Fan Yi , Cui Chen , Rosen Clifford J. , Sato Tadatoshi , Xu Ruoshi , Li Peiran , Wei Xi , Bi Ruiye , Yuan Quan , Zhou Chenchen
Published: May 2022

Maxillofacial bone defects are commonly seen in clinical practice. A clearer understanding of the regulatory network directing maxillofacial bone formation will promote the development of novel therapeutic approaches for bone regeneration. The fibroblast growth factor (FGF) signalling pathway is critical for the development of maxillofacial bone. Klotho, a type I transmembrane protein, is an important components of FGF receptor complexes. Recent studies have reported the presence of Klotho expression in bone. However, the role of Klotho in cranioskeletal development and repair remains unknown. Here, we use a genetic strategy to report that deletion of Klotho in Osx-positive mesenchymal progenitors leads to a significant reduction in osteogenesis under physiological and pathological conditions. Klotho-deficient mensenchymal progenitors also suppress osteoclastogenesis in vitro and in vivo. Under conditions of inflammation and trauma-induced bone loss, we find that Klotho exerts an inhibitory function on inflammation-induced TNFR signaling by attenuating Rankl expression. More importantly, we show for the first time that Klotho is present in human alveolar bone, with a distinct expression pattern under both normal and pathological conditions. In summary, our results identify the mechanism whereby Klotho expressed in Osx+-mensenchymal progenitors controls osteoblast differentiation and osteoclastogenesis during mandibular alveolar bone formation and repair. Klotho-mediated signaling is an important component of alveolar bone remodeling and regeneration. It may also be a target for future therapeutics.
Is it possible to stage schizophrenia? A systematic review
Authors: Martínez-Cao Clara , de la Fuente-Tomás Lorena , García-Fernández Ainoa , González-Blanco Leticia , Sáiz Pilar A. , Garcia-Portilla María Paz , Bobes Julio
Published: May 2022

Introduction

A staging model is a clinical tool used to define the development of a disease over time. In schizophrenia, authors have proposed different theoretical staging models of increasing complexity. Therefore, the aims of our study were to provide an updated and critical view of the proposed clinical staging models for schizophrenia and to review the empirical data that support them.

Methods

Systematic literature review following PRISMA guidelines. From the PubMed database and backward reference search, a total of 141 records were retrieved, but only 20 were selected according to the inclusion criteria: (a) available in English; (b) participants with schizophrenia ≥ 18 years; and (c) theoretical and empirical research studies intended to develop, validate, and/or improve staging models of schizophrenia.

Results

Different clinical staging models for schizophrenia were identified, information about the proposed stages was tabulated and presented in the Results section (Tables 1, 2). Most of which include neuroimaging, functioning, and psychopathology, but only two models add objective biomarkers and none include patient point of view. However, few models have been psychometrically tested or used small samples and thus have been validated only partially. In addition, five studies proposed therapeutic interventions according to the stage of the disorder from a theoretical point of view.

Discussion

In conclusion, it is possible to stage schizophrenia, but the models developed have several limitations. Empirical validation and inclusion of more specific biomarkers and measures of other life areas affected by schizophrenia could help in the development of more valid models.
Intensity of care in cancer patients in the last year of life: a retrospective data linkage study
Authors: Luta Xhyljeta , Diernberger Katharina , Bowden Joanna , Droney Joanne , Hall Peter , Marti Joachim
Published: May 2022

Background

Delivering high-quality palliative and end-of-life care for cancer patients poses major challenges for health services. We examine the intensity of cancer care in England in the last year of life.

Methods

We included cancer decedents aged 65+ who died between January 1, 2010 and December 31, 2017. We analysed healthcare utilisation and costs in the last 12 months of life including hospital-based activities and primary care.

Results

Healthcare utilisation and costs increased sharply in the last month of life. Hospital costs were the largest cost elements and decreased with age (0.78, 95% CI: 0.73–0.72, p < 0.005 for age group 90+ compared to age 65–69 and increased substantially with comorbidity burden (2.2, 95% CI: 2.09–2.26, p < 0.005 for those with 7+ comorbidities compared to those with 1–3 comorbidities). The costs were highest for haematological cancers (1.45, 95% CI: 1.38–1.52, p < 0.005) and those living in the London region (1.10, 95% CI: 1.02–1.19, p < 0.005).

Conclusions

Healthcare in the last year of life for advanced cancer patients is costly and offers unclear value to patients and the healthcare system. Further research is needed to understand distinct cancer populations’ pathways and experiences before recommendations can be made about the most appropriate models of care.
Hexokinase 3 enhances myeloid cell survival via non-glycolytic functions
Authors: Seiler Kristina , Humbert Magali , Minder Petra , Mashimo Iris , Schläfli Anna M. , Krauer Deborah , Federzoni Elena A. , Vu Bich , Moresco James J. , Yates John R. , Sadowski Martin C. , Radpour Ramin , Kaufmann Thomas , Sarry Jean-Emmanuel , Dengjel Joern , Tschan Mario P. , Torbett Bruce E.
Published: May 2022

The family of hexokinases (HKs) catalyzes the first step of glycolysis, the ATP-dependent phosphorylation of glucose to glucose-6-phosphate. While HK1 and HK2 are ubiquitously expressed, the less well-studied HK3 is primarily expressed in hematopoietic cells and tissues and is highly upregulated during terminal differentiation of some acute myeloid leukemia (AML) cell line models. Here we show that expression of HK3 is predominantly originating from myeloid cells and that the upregulation of this glycolytic enzyme is not restricted to differentiation of leukemic cells but also occurs during ex vivo myeloid differentiation of healthy CD34+ hematopoietic stem and progenitor cells. Within the hematopoietic system, we show that HK3 is predominantly expressed in cells of myeloid origin. CRISPR/Cas9 mediated gene disruption revealed that loss of HK3 has no effect on glycolytic activity in AML cell lines while knocking out HK2 significantly reduced basal glycolysis and glycolytic capacity. Instead, loss of HK3 but not HK2 led to increased sensitivity to ATRA-induced cell death in AML cell lines. We found that HK3 knockout (HK3-null) AML cells showed an accumulation of reactive oxygen species (ROS) as well as DNA damage during ATRA-induced differentiation. RNA sequencing analysis confirmed pathway enrichment for programmed cell death, oxidative stress, and DNA damage response in HK3-null AML cells. These signatures were confirmed in ATAC sequencing, showing that loss of HK3 leads to changes in chromatin configuration and increases the accessibility of genes involved in apoptosis and stress response. Through isoform-specific pulldowns, we furthermore identified a direct interaction between HK3 and the proapoptotic BCL-2 family member BIM, which has previously been shown to shorten myeloid life span. Our findings provide evidence that HK3 is dispensable for glycolytic activity in AML cells while promoting cell survival, possibly through direct interaction with the BH3-only protein BIM during ATRA-induced neutrophil differentiation.
Social isolation modulates appetite and avoidance behavior via a common oxytocinergic circuit in larval zebrafish
Authors: Wee Caroline L. , Song Erin , Nikitchenko Maxim , Herrera Kristian J. , Wong Sandy , Engert Florian , Kunes Samuel
Published: May 2022

Animal brains have evolved to encode social stimuli and transform these representations into advantageous behavioral responses. The commonalities and differences of these representations across species are not well-understood. Here, we show that social isolation activates an oxytocinergic (OXT), nociceptive circuit in the larval zebrafish hypothalamus and that chemical cues released from conspecific animals are potent modulators of this circuit’s activity. We delineate an olfactory to subpallial pathway that transmits chemical social cues to OXT circuitry, where they are transformed into diverse outputs simultaneously regulating avoidance and feeding behaviors. Our data allow us to propose a model through which social stimuli are integrated within a fundamental neural circuit to mediate diverse adaptive behaviours.
Immunoprofiling reveals cell subsets associated with the trajectory of cytomegalovirus reactivation post stem cell transplantation
Authors: Stern Lauren , McGuire Helen M. , Avdic Selmir , Fazekas de St Groth Barbara , Gottlieb David , Abendroth Allison , Blyth Emily , Slobedman Barry
Published: May 2022

Human cytomegalovirus reactivation is a major opportunistic infection after allogeneic haematopoietic stem cell transplantation and has a complex relationship with post-transplant immune reconstitution. Here, we use mass cytometry to define patterns of innate and adaptive immune cell reconstitution at key phases of human cytomegalovirus reactivation in the first 100 days post haematopoietic stem cell transplantation. Human cytomegalovirus reactivation is associated with the development of activated, memory T-cell profiles, with faster effector-memory CD4+ T-cell recovery in patients with low-level versus high-level human cytomegalovirus DNAemia. Mucosal-associated invariant T cell levels at the initial detection of human cytomegalovirus DNAemia are significantly lower in patients who subsequently develop high-level versus low-level human cytomegalovirus reactivation. Our data describe distinct immune signatures that emerged with human cytomegalovirus reactivation after haematopoietic stem cell transplantation, and highlight Mucosal-associated invariant T cell levels at the first detection of reactivation as a marker that may be useful to anticipate the magnitude of human cytomegalovirus DNAemia.
Ultra-narrow room-temperature emission from single CsPbBr3 perovskite quantum dots
Authors: Rainò Gabriele , Yazdani Nuri , Boehme Simon C. , Kober-Czerny Manuel , Zhu Chenglian , Krieg Franziska , Rossell Marta D. , Erni Rolf , Wood Vanessa , Infante Ivan , Kovalenko Maksym V.
Published: May 2022

Semiconductor quantum dots have long been considered artificial atoms, but despite the overarching analogies in the strong energy-level quantization and the single-photon emission capability, their emission spectrum is far broader than typical atomic emission lines. Here, by using ab-initio molecular dynamics for simulating exciton-surface-phonon interactions in structurally dynamic CsPbBr3 quantum dots, followed by single quantum dot optical spectroscopy, we demonstrate that emission line-broadening in these quantum dots is primarily governed by the coupling of excitons to low-energy surface phonons. Mild adjustments of the surface chemical composition allow for attaining much smaller emission linewidths of 35−65 meV (vs. initial values of 70–120 meV), which are on par with the best values known for structurally rigid, colloidal II-VI quantum dots (20−60 meV). Ultra-narrow emission at room-temperature is desired for conventional light-emitting devices and paramount for emerging quantum light sources.
PERSIST platform provides programmable RNA regulation using CRISPR endoRNases
Authors: DiAndreth Breanna , Wauford Noreen , Hu Eileen , Palacios Sebastian , Weiss Ron
Published: May 2022

Regulated transgene expression is an integral component of gene therapies, cell therapies and biomanufacturing. However, transcription factor-based regulation, upon which most applications are based, suffers from complications such as epigenetic silencing that limit expression longevity and reliability. Constitutive transgene transcription paired with post-transcriptional gene regulation could combat silencing, but few such RNA- or protein-level platforms exist. Here we develop an RNA-regulation platform we call “PERSIST" which consists of nine CRISPR-specific endoRNases as RNA-level activators and repressors as well as modular OFF- and ON-switch regulatory motifs. We show that PERSIST-regulated transgenes exhibit strong OFF and ON responses, resist silencing for at least two months, and can be readily layered to construct cascades, logic functions, switches and other sophisticated circuit topologies. The orthogonal, modular and composable nature of this platform as well as the ease in constructing robust and predictable gene circuits promises myriad applications in gene and cell therapies.
Asymmetric electron acceptor enables highly luminescent organic solar cells with certified efficiency over 18%
Authors: He Chengliang , Chen Zeng , Wang Tonghui , Shen Ziqiu , Li Yaokai , Zhou Jiadong , Yu Jianwei , Fang Huiyu , Li Yuhao , Li Shuixing , Lu Xinhui , Ma Wei , Gao Feng , Xie Zengqi , Coropceanu Veaceslav , Zhu Haiming , Bredas Jean-Luc , Zuo Lijian , Chen Hongzheng
Published: May 2022

Enhancing the luminescence property without sacrificing the charge collection is one key to high-performance organic solar cells (OSCs), while limited by the severe non-radiative charge recombination. Here, we demonstrate efficient OSCs with high luminescence via the design and synthesis of an asymmetric non-fullerene acceptor, BO-5Cl. Blending BO-5Cl with the PM6 donor leads to a record-high electroluminescence external quantum efficiency of 0.1%, which results in a low non-radiative voltage loss of 0.178 eV and a power conversion efficiency (PCE) over 15%. Importantly, incorporating BO-5Cl as the third component into a widely-studied donor:acceptor (D:A) blend, PM6:BO-4Cl, allows device displaying a high certified PCE of 18.2%. Our joint experimental and theoretical studies unveil that more diverse D:A interfacial conformations formed by asymmetric acceptor induce optimized blend interfacial energetics, which contributes to the improved device performance via balancing charge generation and recombination.
Gasdermin-A3 pore formation propagates along variable pathways
Authors: Mari Stefania A. , Pluhackova Kristyna , Pipercevic Joka , Leipner Matthew , Hiller Sebastian , Engel Andreas , Müller Daniel J.
Published: May 2022

Gasdermins are main effectors of pyroptosis, an inflammatory form of cell death. Released by proteolysis, the N-terminal gasdermin domain assembles large oligomers to punch lytic pores into the cell membrane. While the endpoint of this reaction, the fully formed pore, has been well characterized, the assembly and pore-forming mechanisms remain largely unknown. To resolve these mechanisms, we characterize mouse gasdermin-A3 by high-resolution time-lapse atomic force microscopy. We find that gasdermin-A3 oligomers assemble on the membrane surface where they remain attached and mobile. Once inserted into the membrane gasdermin-A3 grows variable oligomeric stoichiometries and shapes, each able to open transmembrane pores. Molecular dynamics simulations resolve how the membrane-inserted amphiphilic β-hairpins and the structurally adapting hydrophilic head domains stabilize variable oligomeric conformations and open the pore. The results show that without a vertical collapse gasdermin pore formation propagates along a set of multiple parallel but connected reaction pathways to ensure a robust cellular response.
Copper-catalysed asymmetric reductive cross-coupling of prochiral alkenes
Authors: Yoon Wan Seok , Jang Won Jun , Yoon Woojin , Yun Hoseop , Yun Jaesook
Published: May 2022

Asymmetric construction of C(sp3)–C(sp3) bond with good stereocontrol of the two connecting carbon centres retaining all carbon or hydrogen substituents is a challenging target in transition metal catalysis. Transition metal-catalysed reductive coupling of unsaturated π-substrates is considered as a potent tool to expediently develop the molecular complexity with high atom efficiency. However, such an asymmetric and intermolecular process has yet to be developed fully. Herein, we report an efficient strategy to reductively couple two prochiral conjugate alkenes using a copper-catalysed tandem protocol in the presence of diboron. Notably, this transformation incorporates a wide range of terminal and internal enynes as coupling partners and facilitates highly diastereo- and enantioselective synthesis of organoboron derivatives with multiple adjacent stereocentres in a single operation.
TMEM16 scramblases thin the membrane to enable lipid scrambling
Authors: Falzone Maria E. , Feng Zhang , Alvarenga Omar E. , Pan Yangang , Lee ByoungCheol , Cheng Xiaolu , Fortea Eva , Scheuring Simon , Accardi Alessio
Published: May 2022

TMEM16 scramblases dissipate the plasma membrane lipid asymmetry to activate multiple eukaryotic cellular pathways. Scrambling was proposed to occur with lipid headgroups moving between leaflets through a membrane-spanning hydrophilic groove. Direct information on lipid-groove interactions is lacking. We report the 2.3 Å resolution cryogenic electron microscopy structure of the nanodisc-reconstituted Ca2+-bound afTMEM16 scramblase showing how rearrangement of individual lipids at the open pathway results in pronounced membrane thinning. Only the groove’s intracellular vestibule contacts lipids, and mutagenesis suggests scrambling does not require specific protein-lipid interactions with the extracellular vestibule. We find scrambling can occur outside a closed groove in thinner membranes and is inhibited in thicker membranes, despite an open pathway. Our results show afTMEM16 thins the membrane to enable scrambling and that an open hydrophilic pathway is not a structural requirement to allow rapid transbilayer movement of lipids. This mechanism could be extended to other scramblases lacking a hydrophilic groove.
Effect of partial distinguishability on quantum supremacy in Gaussian Boson sampling
Authors: Shi Junheng , Byrnes Tim
Published: May 2022

Gaussian boson sampling (GBS) allows for a way to demonstrate quantum supremacy with the relatively modest experimental resources of squeezed light sources, linear optics, and photon detection. In a realistic experimental setting, numerous effects can modify the complexity of the sampling, in particular loss, partial distinguishability of the photons, and the use of threshold detectors rather than photon counting detectors. In this paper, we investigate GBS with partial distinguishability using an approach based on virtual modes and indistinguishability efficiency. We develop a model using these concepts and derive the probabilities of measuring a specific output pattern from partially distinguishable and lossy GBS for both types of detectors. In the case of threshold detectors, the probability as calculated by the Torontonian is a special case under our framework. By analyzing the expressions of these probabilities we propose an efficient classical simulation algorithm which can be used to calculate the probabilities. Our model and algorithm provide foundations for an approximate method for calculating probabilities. It also allows for a way to design sampling algorithms that are not only compatible with existing algorithms for ideal GBS, but can also reduce their complexity exponentially, depending on the indistinguishability efficiency. Using this we show how the boundary of quantum supremacy in GBS can be affected by partial distinguishability.
Shifts in regional water availability due to global tree restoration
Authors: Hoek van Dijke Anne J. , Herold Martin , Mallick Kaniska , Benedict Imme , Machwitz Miriam , Schlerf Martin , Pranindita Agnes , Theeuwen Jolanda J. E. , Bastin Jean-François , Teuling Adriaan J.
Published: May 2022

Tree restoration is an effective way to store atmospheric carbon and mitigate climate change. However, large-scale tree-cover expansion has long been known to increase evaporation, leading to reduced local water availability and streamflow. More recent studies suggest that increased precipitation, through enhanced atmospheric moisture recycling, can offset this effect. Here we calculate how 900 million hectares of global tree restoration would impact evaporation and precipitation using an ensemble of data-driven Budyko models and the UTrack moisture recycling dataset. We show that the combined effects of directly enhanced evaporation and indirectly enhanced precipitation create complex patterns of shifting water availability. Large-scale tree-cover expansion can increase water availability by up to 6% in some regions, while decreasing it by up to 38% in others. There is a divergent impact on large river basins: some rivers could lose 6% of their streamflow due to enhanced evaporation, while for other rivers, the greater evaporation is counterbalanced by more moisture recycling. Several so-called hot spots for forest restoration could lose water, including regions that are already facing water scarcity today. Tree restoration significantly shifts terrestrial water fluxes, and we emphasize that future tree-restoration strategies should consider these hydrological effects.
Instantaneous tracking of earthquake growth with elastogravity signals
Authors: Licciardi Andrea , Bletery Quentin , Rouet-Leduc Bertrand , Ampuero Jean-Paul , Juhel Kévin
Published: May 2022

Rapid and reliable estimation of large earthquake magnitude (above 8) is key to mitigating the risks associated with strong shaking and tsunamis1. Standard early warning systems based on seismic waves fail to rapidly estimate the size of such large earthquakes2–5. Geodesy-based approaches provide better estimations, but are also subject to large uncertainties and latency associated with the slowness of seismic waves. Recently discovered speed-of-light prompt elastogravity signals (PEGS) have raised hopes that these limitations may be overcome6,7, but have not been tested for operational early warning. Here we show that PEGS can be used in real time to track earthquake growth instantaneously after the event reaches a certain magnitude. We develop a deep learning model that leverages the information carried by PEGS recorded by regional broadband seismometers in Japan before the arrival of seismic waves. After training on a database of synthetic waveforms augmented with empirical noise, we show that the algorithm can instantaneously track an earthquake source time function on real data. Our model unlocks ‘true real-time’ access to the rupture evolution of large earthquakes using a portion of seismograms that is routinely treated as noise, and can be immediately transformative for tsunami early warning.
Supporting the gastrointestinal microenvironment during high-dose chemotherapy and stem cell transplantation by inhibiting IL-1 signaling with anakinra
Authors: Wardill H. R. , de Mooij C. E. M. , Da Silva Ferreira A. R. , Havinga H. , Harmsen H. J. M. , van der Velden W. J. F. M. , van Groningen L. F. J. , Tissing W. J. E. , Blijlevens N. M. A.
Published: May 2022

High-dose chemotherapy causes intestinal inflammation and subsequent breakdown of the mucosal barrier, permitting translocation of enteric pathogens, clinically manifesting as fever. Antibiotics are mainstay for controlling these complications, however, they are increasingly recognized for their detrimental effects, including antimicrobial resistance and dysbiosis. Here, we show that mucosal barrier injury induced by the mucotoxic chemotherapeutic agent, high-dose melphalan (HDM), is characterized by hyper-active IL-1b/CXCL1/neutrophil signaling. Inhibition of this pathway with IL-1RA, anakinra, minimized the duration and intensity of mucosal barrier injury and accompanying clinical symptoms, including diarrhea, weight loss and fever in rats. 16S analysis of fecal microbiome demonstrated a more stable composition in rats receiving anakinra, with reduced pathogen expansion. In parallel, we report through Phase IIA investigation that anakinra is safe in stem cell transplant patients with multiple myeloma after HDM. Ramping-up anakinra (100–300 mg administered intravenously for 15 days) did not cause any adverse events or dose limiting toxicities, nor did it change time to neutrophil recovery. Our results reinforce that strengthening the mucosal barrier may be an effective supportive care strategy to mitigate local and systemic clinical consequences of HDM. We are now conducting a Phase IIB multicenter, placebo-controlled, double-blinded trial to assess clinical efficacy of anakinra (AFFECT-2).

Trial registration: ClinicalTrials.gov identifier: NCT03233776.
Whole-genome sequencing of Mycobacterium tuberculosis from Cambodia
Authors: Edokimov Konstantin , Yamada Yoshiyuki , Dary Chhavarath , Miow Qing Hao , Hsu Li-Yang , Ong Rick Twee-Hee , Saphonn Vonthanak
Published: May 2022

Cambodia has one of the highest tuberculosis (TB) incidence rates in the WHO Western Pacific region. Remarkably though, the prevalence of multidrug-resistant TB (MDR-TB) remains low. We explored the genetic diversity of Mycobacterium tuberculosis (MTB) circulating in this unique setting using whole-genome sequencing (WGS). From October 2017 until January 2018, we collected one hundred sputum specimens from consenting adults older than 21 years of age, newly diagnosed with bacteriologically confirmed TB in 3 districts of Phnom Penh and Takeo provinces of Cambodia before they commence on their TB treatment, where eighty MTB isolates were successfully cultured and sequenced. Majority of the isolates belonged to Lineage 1 (Indo-Oceanic) (69/80, 86.25%), followed by Lineage 2 (East Asian) (10/80, 12.5%) and Lineage 4 (Euro-American) (1/80, 1.25%). Phenotypic resistance to both streptomycin and isoniazid was found in 3 isolates (3/80, 3.75%), while mono-resistance to streptomycin and isoniazid was identical at 2.5% (N = 2 each). None of the isolates tested was resistant to either rifampicin or ethambutol. The specificities of genotypic prediction for resistance to all drugs tested were 100%, while the sensitivities of genotypic resistance predictions to isoniazid and streptomycin were lower at 40% (2/5) and 80% (4/5) respectively. We identified 8 clusters each comprising of two to five individuals all residing in the Takeo province, making up half (28/56, 50%) of all individuals sampled in the province, indicating the presence of multiple ongoing transmission events. All clustered isolates were of Lineage 1 and none are resistant to any of the drugs tested. This study while demonstrating the relevance and utility of WGS in predicting drug resistance and inference of disease transmission, highlights the need to increase the representation of genotype–phenotype TB data from low and middle income countries in Asia and Africa to improve the accuracies for prediction of drug resistance.
COVID-19 infections in infants
Authors: Sobolewska-Pilarczyk Małgorzata , Pokorska-Śpiewak Maria , Stachowiak Anna , Marczyńska Magdalena , Talarek Ewa , Ołdakowska Agnieszka , Kucharek Izabela , Sybilski Adam , Mania Anna , Figlerowicz Magdalena , Mazur-Melewska Katarzyna , Potocka Paulina , Sulik Artur , Hasiec Barbara , Stani Martyna , Frańczak-Chmura Paulina , Szczepańska Barbara , Pałyga-Bysiecka Ilona , Ciechanowski Przemysław , Łasecka-Zadrożna Joanna , Zaleska Izabela , Szenborn Leszek , Dryja Urszula , Kuchar Ernest , Niedźwiecka Sławomira , Kalicki Bolesław , Flisiak Robert , Pawłowska Małgorzata
Published: May 2022

The study aimed to analyse the clinical course of COVID-19 in 300 infants, selected from 1283 children diagnosed with COVID-19 between March and December 2020, registered in the SARSTerPED multicenter database. Most of the infants were registered in October and November 2020. 44% of the group were girls, and 56% were boys. At diagnosis, the most common symptoms were fever in 77% of the children, cough in 40%, catarrh in 37%. Pneumonia associated with COVID-19 was diagnosed in 23% of the children, and gastrointestinal symptoms in 31.3%. In 52% of the infants, elevated levels of D-dimers were observed, and in 40%, elevated levels of IL-6 serum concentration were observed. During the second wave of the pandemic, 6 times more infants were hospitalized, and the children were statistically significantly younger compared to the patients during the first wave (3 months vs 8 months, p < 0.0001 respectively). During the second wave, the infants were hospitalized for longer. COVID-19 in infants usually manifests as a mild gastrointestinal or respiratory infection, but pneumonia is also observed with falls in oxygen saturation, requiring oxygen therapy. Gastrointestinal symptoms are common in infants infected with SARS-CoV-2, and infant appetite disorders may lead to hospitalization. The clinical course of the disease differed significantly between the first and second wave of the pandemic. It seems that infants may play a role in the transmission of SARS-COV-2 infections in households, despite mild or asymptomatic courses; eating disorders in infants should be an indication for COVID-19 testing.