bluuebunny/crossref_metadata_2025 huggingface dataset:
Hardwood spent mushroom substrate–based activated biochar as a sustainable bioresource for removal of emerging pollutants from wastewater
Authors: Grimm Alejandro , dos Reis Glaydson Simões , Dinh Van Minh , Larsson Sylvia H. , Mikkola Jyri-Pekka , Lima Eder Claudio , Xiong Shaojun
Published: April 2022

Hardwood spent mushroom substrate was employed as a carbon precursor to prepare activated biochars using phosphoric acid (H3PO4) as chemical activator. The activation process was carried out using an impregnation ratio of 1 precursor:2 H3PO4; pyrolysis temperatures of 700, 800, and 900 °C; heating rate of 10 °C min−1; and treatment time of 1 h. The specific surface area (SSA) of the biochars reached 975, 1031, and 1215 m2 g−1 for the samples pyrolyzed at 700, 800, and 900 °C, respectively. The percentage of mesopores in their structures was 75.4%, 78.5%, and 82.3% for the samples pyrolyzed at 700, 800, and 900 °C, respectively. Chemical characterization of the biochars indicated disordered carbon structures with the presence of oxygen and phosphorous functional groups on their surfaces. The biochars were successfully tested to adsorb acetaminophen and treat two simulated pharmaceutical effluents composed of organic and inorganic compounds. The kinetic data from adsorption of acetaminophen were fitted to the Avrami fractional-order model, and the equilibrium data was well represented by the Liu isotherm model, attaining a maximum adsorption capacity of 236.8 mg g−1 for the biochar produced at 900 °C. The adsorption process suggests that the pore-filling mechanism mainly dominates the acetaminophen removal, although van der Walls forces are also involved. The biochar produced at 900 °C removed up to 84.7% of the contaminants in the simulated effluents. Regeneration tests using 0.1 M NaOH + 20% EtOH as eluent showed that the biochars could be reused; however, the adsorption capacity was reduced by approximately 50% after three adsorption–desorption cycles.
Evaluating current practice and knowledge about antibiotic stewardship principles in paediatric tertiary hospitals to identify target areas for future teaching activities
Authors: Kolberg Laura , Buschbeck Judith , Wagner Annabelle , Jonat Susanne , Wolf Gerhard , Peters Jochen , Behrends Uta , Steinhauser Maximilian , Huebner Johannes , von Both Ulrich
Published: April 2022

Purpose

Antibiotic exposure among hospitalized children is very high. With inappropriate antimicrobial use resulting in increased rates of antimicrobial resistance, the implementation of antibiotic stewardship programs is critically needed. This survey study aimed to identify current practice and knowledge about antibiotic stewardship and infection control among paediatricians in tertiary care paediatric hospitals in and around Munich, Germany.

Methods

A prospective cross-sectional study based on an anonymous questionnaire, structured into different sub-sections regarding antibiotic use, antimicrobial resistance, antibiotic stewardship and infection control, was conducted between 1st of May and 30th of June 2016 in five paediatric hospitals.

Results

In total, 111 paediatricians across all grades were eligible for participation. The overall proportion of correct answers for all sub-sections of the survey ranged from 54.1% correct answers in the antibiotic handling and bacterial resistance section to 72.9% correct answers in the hospital hygiene/infection control section. In general, knowledge across all categories was similar for junior doctors, middle-grade doctors or consultants. Advocating empiric use of narrow-spectrum instead of broad-spectrum antibiotics was considered to be the most difficult measure to implement in daily practice (36.9%). De-escalation from broad-spectrum empirical therapy to targeted treatment was considered the easiest measure to achieve (43.2%).

Conclusion

Our results demonstrate that principles of antimicrobial stewardship and aspects of hospital hygiene/infection control are not satisfactorily known among hospital-based paediatricians in and around Munich. We identified four important target areas for future educational interventions that should play a more prominent role in both pre- and postgraduate medical training.
2D SPH simulation of an anaerobic digester
Authors: Kumar Prashant , Dabiri Soroush , Rauch Wolfgang
Published: April 2022

Understanding the hydrodynamics within the anaerobic digester tank of a wastewater treatment plant is of high importance to ensure sufficient mixing and subsequently a homogeneous distribution of the substrates. In this paper, we demonstrate a two-dimensional computational fluid dynamics simulation of a real-world case study focusing on both, the methodology and the operation of mixing. For this work, DualSPHysics, a Lagrangian solver, has been explored as an alternative to the more commonly used Eulerian solvers in studying the slow-moving dynamics inside a digester tank. This choice of a Lagrangian solver is primarily due to the inherent accounting for advection within the formulation, thus allowing for subsequent modelling of anaerobic digestion processes. A comparison has been made between the simulations from the two methods (Eulerian and Lagrangian), highlighting the benefits and the shortcomings of using smoothed particle hydrodynamics. Concerning operational mixing, the case relies on a draft tube, the effect of which on the velocity profiles has been studied based on the presence of low-velocity zones and Lagrangian coherent structures. Removing the draft tube results in an increase in low-velocity zones by 21.38% while the amount of dead volume increases from 0.52 to 1.2%.
Erectile dysfunction as a marker of endocrine and glycemic disorders
Authors: Mazzilli R. , Zamponi V. , Olana S. , Mikovic N. , Cimadomo D. , Defeudis G. , Faggiano A.
Published: April 2022

Purpose

The aim of this study was to evaluate in a population of patients with erectile dysfunction (ED): (a) the prevalence of a previously unknown endocrine/glycemic disorders; (b) the correlation between ED severity and endocrine/glycemic disorders.

Methods

1332 patients referred for ED from 2013 to 2020 were included. The ED diagnosis was made using the International-Erectile-Function-Index-5 questionnaire. ED severity was considered according to presence/absence of spontaneous erections, maintenance/achievement deficiency. All patients were subjected to search for sociodemographic and clinical characteristics: age, ethnicity, marital status, previous use of PDE5i, previous prostatectomy, diabetes mellitus (DM), prediabetes, endocrine dysfunctions.

Results

The mean ± SD age was 54.3 ± 13.7 years. The 19.1% (255/1332) of patients were already in treatment for prediabetes/diabetes or endocrine dysfunctions. Among the remaining 1077, the prevalence of previously unknown endocrine and glycemic disorders was 30% (323/1077). Among them, 190/323 subjects (58.8%) were affected by hypogonadism, with high estradiol level observed in 8/190 (4.2%). The prevalence of new glycemic alterations was 17.3% (56/323) [specifically, 32/56 (57.1%) DM, and 24/56 (42.9%) prediabetes]. A thyroid dysfunction was observed in 40/323 subjects (12.3%) and hyperprolactinemia in 37/323 (11.5%). Patients with new diagnosis of DM showed more severe form of ED compared to the total group {difficulty in the achievement of erection: 46/56 [82.2%, vs 265/1332 (19.9%), p < 0.05]; absence of spontaneous erection 23/56 [41.1%, vs 321/1332 (24.1%), p < 0.05]}.

Conclusion

ED is an early marker of endocrine/glycemic disorder, and a previously unknown dysfunction was found in more than a quarter of patients. A newly diagnosed DM is associated with ED severity, especially in elderly man and in presence of hypertension.
Peripheral artery disease and all-cause and cardiovascular mortality in patients with NAFLD
Authors: Ciardullo S. , Bianconi E. , Cannistraci R. , Parmeggiani P. , Marone E. M. , Perseghin G.
Published: April 2022

Purpose

Cardiovascular disease (CVD) is the first cause of death in patients with non-alcoholic fatty liver disease (NAFLD) and risk stratification is recommended by current guidelines. The aim of this study is to assess the prevalence of peripheral arterial disease (PAD) in patients with NAFLD and its association with all-cause and cardiovascular disease (CVD) mortality.

Methods

9145 participants 40 years or older attended a mobile examination center visit in the 1999–2004 cycles of the National Health and Nutrition Examination Survey. PAD was defined as an ankle-brachial index (ABI) < 0.90 in either of the legs and mortality data through December 2015 were obtained from the National Death Index. NAFLD was defined by a fatty liver index ≥ 60 in the absence of other liver conditions, leading to a final sample of 3094 subjects.

Results

The overall prevalence of PAD was 5.9% (95% CI 5.0–6.9). Over a median follow-up of 13 years, 876 participants died, 208 of cardiovascular causes. Incidence rates of all-cause mortality (for 1000 person-years) were 20.2 (95% CI 18.7–21.7) and 70.0 (95% CI 60.1–81.6) for participants without and with PAD, respectively. Multivariable-adjusted Cox proportional hazard models showed that PAD was associated with a higher risk of all-cause (1.8, 95% CI 1.4–2.4) and cardiovascular mortality (HR 2.5, 95% CI 1.5–4.3) after adjustment for potential confounders including prevalent CVD.

Conclusion

Current guidelines strongly encourage the screening of CVD in patients with NAFLD and the use of the simple and inexpensive measurement of ABI in routine clinical practice may find indication.
Uncertainty as a Swiss army knife: new adversarial attack and defense ideas based on epistemic uncertainty
Authors: Tuna Omer Faruk , Catak Ferhat Ozgur , Eskil M. Taner
Published: April 2022

Although state-of-the-art deep neural network models are known to be robust to random perturbations, it was verified that these architectures are indeed quite vulnerable to deliberately crafted perturbations, albeit being quasi-imperceptible. These vulnerabilities make it challenging to deploy deep neural network models in the areas where security is a critical concern. In recent years, many research studies have been conducted to develop new attack methods and come up with new defense techniques that enable more robust and reliable models. In this study, we use the quantified epistemic uncertainty obtained from the model’s final probability outputs, along with the model’s own loss function, to generate more effective adversarial samples. And we propose a novel defense approach against attacks like Deepfool which result in adversarial samples located near the model’s decision boundary. We have verified the effectiveness of our attack method on MNIST (Digit), MNIST (Fashion) and CIFAR-10 datasets. In our experiments, we showed that our proposed uncertainty-based reversal method achieved a worst case success rate of around 95% without compromising clean accuracy.
Adaptive k-center and diameter estimation in sliding windows
Authors: Pellizzoni Paolo , Pietracaprina Andrea , Pucci Geppino
Published: April 2022

In this paper we present novel streaming algorithms for the k-center and the diameter estimation problems for general metric spaces under the sliding window model. The key idea behind our algorithms is to maintain a small coreset which, at any time, allows to compute a solution to the problem under consideration for the current window, whose quality can be made arbitrarily close to the one of the best solution attainable by running a polynomial-time sequential algorithm on the entire window. Remarkably, the size of our coresets is independent of the window length and can be upper bounded by a function of the target number of centers (for the k-center problem), of the desired accuracy, and of the characteristics of the current window, namely its doubling dimension and aspect ratio. One of the major strengths of our algorithms is that they adapt obliviously to these two latter characteristics. We also provide experimental evidence of the practical viability of the algorithms and their superiority over the current state of the art.
Observer-based anti-windup robust PID controller for performance enhancement of damped outrigger structure
Authors: Kavyashree B. G. , Patil Shantharam , Rao Vidya S.
Published: April 2022

This study presents an observer-based anti-windup robust proportional–integral–derivative controller with state estimator method for damped outrigger structure using magneto-rheological damper to mitigate the seismic response. In this approach, full-order Kalman observer is designed for estimating the states of the damped outrigger system from the feedback of the system output with optimum observer gain. However, due to the computational complexity, the integral windup is observed in the loop; therefore, integral anti-windup is introduced for the internal stability in the loop to produce the desired output. The semi-active magneto-rheological damper is integrated with the proposed system, to produce the required force by the system that ranges between the maximum and minimum values as regulated by the voltages produced by the controller in action for every instant of the seismic energy. The proposed strategy is designed in MATLAB and Simulink to find the adequacy of the damped outrigger system in terms of mitigating the following seismic responses like displacement, velocity, and acceleration. The dynamic analysis of the damped outrigger structure with the proposed control strategy shows enhanced performance in reducing the response of the structure as observed in peak response values. The evaluation criteria show a significant reduction in the vibration of the structure.
The novel C5 protein from tomato yellow leaf curl virus is a virulence factor and suppressor of gene silencing
Authors: Zhao Siwen , Gong Pan , Ren Yanxiang , Liu Hui , Li Hao , Li Fangfang , Zhou Xueping
Published: April 2022

Tomato yellow leaf curl virus (TYLCV) is known to encode 6 canonical viral proteins. Our recent study revealed that TYLCV also encodes some additional small proteins with potential virulence functions. The fifth ORF of TYLCV in the complementary sense, which we name C5, is evolutionarily conserved, but little is known about its expression and function during viral infection. Here, we confirmed the expression of the TYLCV C5 by analyzing the promoter activity of its upstream sequences and by detecting the C5 protein in infected cells by using a specific custom-made antibody. Ectopic expression of C5 using a potato virus X (PVX) vector resulted in severe mosaic symptoms and higher virus accumulation levels followed by a burst of reactive oxygen species (ROS) in Nicotiana benthamiana plants. C5 was able to effectively suppress local and systemic post-transcriptional gene silencing (PTGS) induced by single-stranded GFP but not double-stranded GFP, and reversed the transcriptional gene silencing (TGS) of GFP. Furthermore, the mutation of C5 in TYLCV inhibited viral replication and the development of disease symptoms in infected plants. Transgenic overexpression of C5 could complement the virulence of a TYLCV infectious clone encoding a dysfunctional C5. Collectively, this study reveals that TYLCV C5 is a pathogenicity determinant and RNA silencing suppressor, hence expanding our knowledge of the functional repertoire of the TYLCV proteome.
Wood in Archaeology
Authors: Newsom Lee A.
Published: April 2022

In this book, Lee A. Newsom offers an overview of wood in archaeology --how and where it is preserved and analyzed, its relevance to paleoecological and paleoenvironmental questions, as well as its role as an important source of information in modern archaeological science and related historical disciplines. Her book addresses a range of questions about wood reliance practices, sustainability, and the overall relevance of forest ecosystems to past cultures and cultural evolution. Newsom provides a step-by-step treatment of archaeological analysis with clear explanations and examples from various corners of the world. She also shows how the study of archaeological wood is relevant to modern restoration ecology and conservation biology that tracks long-term ancient ecosystems, including questions of global change. Demonstrating the vital role of wood and timber resources to past human societies, her book will interest scholars and students of archaeology, historical ecology, paleoecology, and wood science.
Observed Linkages Between the Atmospheric Circulation and Oceanic‐Forced Sea‐Surface Temperature Variability in the Western North Pacific
Authors: Patrizio Casey R. , Thompson David W. J.
Published: April 2022

Previous research suggests the extratropical atmospheric circulation responds to that sea‐surface temperature (SST) variability in the western North Pacific. However, the relative roles of oceanic and atmospheric processes in driving the SST anomalies that, in turn, seemingly influence the atmospheric circulation are unclear. Here, we exploit a simple stochastic climate model to subdivide the SST variability in the Kuroshio‐Oyashio Extension region into components forced by oceanic and atmospheric processes. We then probe the lead/lag relationships between the atmospheric circulation and both components of the SST variability. Importantly, only the oceanic‐forced SST variability is associated with robust atmospheric anomalies that lag the SSTs by 1 month. The results are consistent with the surface heat fluxes associated with atmospheric and oceanic‐forced components of the SST variability. Overall, the findings suggest that ocean dynamical processes in the western North Pacific play an important role in influencing the variability of the extratropical circulation.
Severe Cold Winters in East Asia Linked to First Winter of La Niña Events and in North America Linked to Second Winter
Authors: Nishihira Gaku , Sugimoto Shusaku
Published: April 2022

La Niña often persists for two years, unlike El Niño. Five single‐year and 8 multi‐year La Niña events occurred over 71 boreal winters (1950/51–2020/21). Atmospheric reanalysis data show a marked increase in diabatic heating over the tropical northwestern Pacific (TNWP) in first winters of La Niña events in addition to a decrease in diabatic heating over the tropical eastern Pacific, common to first and second winters. Linear baroclinic model experiments indicate that combinations of the heating form different atmospheric teleconnections in the mid‐latitudes; first winters with the increased heating over the TNWP form teleconnection across the North Pacific, leading to cold winters in Japan. In second winters with the reduced heating over the TNWP (∼50% of first winters), teleconnection shifts east, resulting in severe cold winters in northwestern North America, whereas there is no impact on Japan.
Ocean Surface Flux Algorithm Effects on Tropical Indo‐Pacific Intraseasonal Precipitation
Authors: Hsu Chia‐Wei , DeMott Charlotte A. , Branson Mark D. , Reeves Eyre Jack , Zeng Xubin
Published: April 2022

Surface latent heat fluxes help maintain tropical intraseasonal precipitation. We develop a latent heat flux diagnostic that depicts how latent heat fluxes vary with the near‐surface specific humidity vertical gradient (Δq) and surface wind speed (|V|). Compared to fluxes estimated from |V| and Δq measured at tropical moorings and the Coupled Ocean Atmosphere Response Experiment 3.0 (COARE3.0) algorithm, tropical latent heat fluxes in the National Center for Atmospheric Research CEMS2 and Department of Energy E3SMv1 models are significantly overestimated at |V| and Δq extrema. Madden–Julian oscillation (MJO) sensitivity to surface flux algorithm is tested with offline and inline flux corrections. The offline correction adjusts model output fluxes toward mooring‐estimated fluxes; the inline correction replaces the original bulk flux algorithm with the COARE3.0 algorithm in atmosphere‐only simulations of each model. Both corrections indicate reduced latent heat flux feedback to intraseasonal precipitation, in better agreement with observations, suggesting that model‐simulated fluxes are overly supportive for maintaining MJO convection.
Weakening Trend of Luzon Strait Overflow Transport in the Past Two Decades
Authors: Zhu Yaohua , Yao Jingxin , Xu Tengfei , Li Shujiang , Wang Yonggang , Wei Zexun
Published: April 2022

The Luzon Strait overflow is a deep current of dense water flowing persistently into the South China Sea (SCS) from the Pacific. It is the primary driving force of the deep SCS circulation and potentially influenced by ocean mass changes. Limited by the lengths of in situ observations, long‐term changes in the Luzon Strait overflow transport (LSOT) have not been ascertained. Based on 14 years of satellite‐based ocean bottom pressure (OBP) time series, here we provide an evidence of a weakening of the LSOT by −0.43 Sv decade−1 between 2003 and 2016. Moreover, both OBP data and mooring time series reveal a large annual cycle in the LSOT. The weakening trend in the LSOT may profoundly influence the deep SCS circulation, as well as heat and mass fluxes between the SCS and surrounding oceans.
Load‐Balancing Intense Physics Calculations to Embed Regionalized High‐Resolution Cloud Resolving Models in the E3SM and CESM Climate Models
Authors: Peng Liran , Pritchard Michael , Hannah Walter M. , Blossey Peter N. , Worley Patrick H. , Bretherton Christopher S.
Published: April 2022

We design a new strategy to load‐balance high‐intensity sub‐grid atmospheric physics calculations restricted to a small fraction of a global climate simulation's domain. We show why the current parallel load balancing infrastructure of Community Earth System Model (CESM) and Energy Exascale Earth Model (E3SM) cannot efficiently handle this scenario at large core counts. As an example, we study an unusual configuration of the E3SM Multiscale Modeling Framework (MMF) that embeds a binary mixture of two separate cloud‐resolving model grid structures that is attractive for low cloud feedback studies. Less than a third of the planet uses high‐resolution (MMF‐HR; sub‐km horizontal grid spacing) relative to standard low‐resolution (MMF‐LR) cloud superparameterization elsewhere. To enable MMF runs with Multi‐Domain cloud resolving models (CRMs), our load balancing theory predicts the most efficient computational scale as a function of the high‐intensity work's relative overhead and its fractional coverage. The scheme successfully maximizes model throughput and minimizes model cost relative to precursor infrastructure, effectively by devoting the vast majority of the processor pool to operate on the few high‐intensity (and rate‐limiting) high‐resolution (HR) grid columns. Two examples prove the concept, showing that minor artifacts can be introduced near the HR/low‐resolution CRM grid transition boundary on idealized aquaplanets, but are minimal in operationally relevant real‐geography settings. As intended, within the high (low) resolution area, our Multi‐Domain CRM simulations exhibit cloud fraction and shortwave reflection convergent to standard baseline tests that use globally homogenous MMF‐LR and MMF‐HR. We suggest this approach can open up a range of creative multi‐resolution climate experiments without requiring unduly large allocations of computational resources.
Ice Towers May Hold Promise—and Water—for Some Cold, Dry Places
Authors: Wilke Carolyn
Published: April 2022

A new study that cues into the formation of ice cones for storing glacial meltwater reveals how the structures can be built more efficiently and which climatic conditions work best.
Mars’s Dust Cycle Controls Its Polar Vortex and Snowfall
Authors: Cartier Kimberly
Published: April 2022

On Earth, the water cycle is a dominant climate force. On Mars, it’s the dust.
The Malawi Active Fault Database: An Onshore‐Offshore Database for Regional Assessment of Seismic Hazard and Tectonic Evolution
Authors: Williams Jack N. , Wedmore Luke N. J. , Scholz Christopher A. , Kolawole Folarin , Wright Lachlan J. M. , Shillington Donna J. , Fagereng Åke , Biggs Juliet , Mdala Hassan , Dulanya Zuze , Mphepo Felix , Chindandali Patrick R. N. , Werner Maximilian J.
Published: April 2022

We present the Malawi Active Fault Database (MAFD), an open‐access (https://doi.org/10.5281/zenodo.5507190) geospatial database of 113 fault traces in Malawi and neighboring Tanzania and Mozambique. Malawi is located within the East African Rift's (EAR) Western Branch where active fault identification is challenging because chronostratigraphic data are rare, and/or faults are buried and so do not have a surface expression. The MAFD therefore includes any fault that has evidence for displacement during Cenozoic East African rifting or is buried beneath the rift valley and is favorably oriented to the regional stresses. To identify such faults, we consider a multidisciplinary data set: high‐resolution digital elevation models, previous geological mapping, field observations, seismic reflection surveys from offshore Lake Malawi, and aeromagnetic and gravity data. The MAFD includes faults throughout Malawi, where seismic risk is increasing because of population growth and its seismically vulnerable building stock. We also investigate the database as a sample of the normal fault population in an incipient continental rift. We cannot reject the null hypothesis that the distribution of fault lengths in the MAFD is described by a power law, which is consistent with Malawi's relatively thick seismogenic layer (30–40 km), low (<8%) regional extensional strain, and regional deformation localization (50%–75%) across relatively long hard‐linked border faults. Cumulatively, we highlight the importance of integrating onshore and offshore geological and geophysical data to develop active fault databases along the EAR and similar continental settings both to understand the regional seismic hazard and tectonic evolution.
1.2 Myr Band of Earth‐Mars Obliquity Modulation on the Evolution of Cold Late Miocene to Warm Early Pliocene Climate
Authors: Qin Jie , Zhang Rui , Kravchinsky Vadim A. , Valet Jean‐Pierre , Sagnotti Leonardo , Li Jianxing , Xu Yong , Anwar Taslima , Yue Leping
Published: April 2022

The climatic transitions during the Miocene‐Pliocene epochs had significant impacts on the worldwide biological diversity and were associated with large turnovers of continental vegetation and fauna. Previous studies have shown that late Miocene cooling and continental aridification which was initiated 7 Ma reversed to warm conditions across the Miocene‐Pliocene Boundary ∼5.3 Ma. Here, we present detailed orbital pacing of Asian monsoon deposits to constrain further the global climate change during this period. We produce high‐resolution magnetic susceptibility records which reveal that the 1.2 Myr obliquity modulation would have been the main driving factor of the cooling and warming that occurred ∼7  and 5.3 Ma, respectively. The Tibetan rise and closures of the Panama and Indonesian seaways enhanced the impact of the 405 Kyr eccentricity cycles to an oscillatory climatic state while the Northern Hemisphere glaciations were increasing from 4 to 2.5 Ma.
Identification of a c-MYB-directed therapeutic for acute myeloid leukemia
Authors: Clesham Katherine , Walf-Vorderwülbecke Vanessa , Gasparoli Luca , Virely Clemence , Cantilena Sandra , Tsakaneli Alexia , Inglott Sarah , Adams Stuart , Samarasinghe Sujith , Bartram Jack , Williams Gareth , de Boer Jasper , Williams Owen
Published: April 2022

A significant proportion of patients suffering from acute myeloid leukemia (AML) cannot be cured by conventional chemotherapy, relapsed disease being a common problem. Molecular targeting of essential oncogenic mediators is an attractive approach to improving outcomes for this disease. The hematopoietic transcription factor c-MYB has been revealed as a central component of complexes maintaining aberrant gene expression programs in AML. We have previously screened the Connectivity Map database to identify mebendazole as an anti-AML therapeutic targeting c-MYB. In the present study we demonstrate that another hit from this screen, the steroidal lactone withaferin A (WFA), induces rapid ablation of c-MYB protein and consequent inhibition of c-MYB target gene expression, loss of leukemia cell viability, reduced colony formation and impaired disease progression. Although WFA has been reported to have pleiotropic anti-cancer effects, we demonstrate that its anti-AML activity depends on c-MYB modulation and can be partially reversed by a stabilized c-MYB mutant. c-MYB ablation results from disrupted HSP/HSC70 chaperone protein homeostasis in leukemia cells following induction of proteotoxicity and the unfolded protein response by WFA. The widespread use of WFA in traditional medicines throughout the world indicates that it represents a promising candidate for repurposing into AML therapy.
Infectious complications of targeted drugs and biotherapies in acute leukemia. Clinical practice guidelines by the European Conference on Infections in Leukemia (ECIL), a joint venture of the European Group for Blood and Marrow Transplantation (EBMT), the European Organization for Research and Treatment of Cancer (EORTC), the International Immunocompromised Host Society (ICHS) and the European Leukemia Net (ELN)
Authors: Maschmeyer Georg , Bullinger Lars , Garcia-Vidal Carolina , Herbrecht Raoul , Maertens Johan , Menna Pierantonio , Pagano Livio , Thiebaut-Bertrand Anne , Calandra Thierry
Published: April 2022

The 9th web-based European Conference on Infections in Leukemia (ECIL-9), held September 16-17, 2021, reviewed the risk of infections and febrile neutropenia associated with more recently approved immunotherapeutic agents and molecular targeted drugs for the treatment of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Novel antibody based treatment approaches (inotuzumab ozogamicin, gemtuzumab ozogamicin, flotetuzumab), isocitrate dehydrogenases inhibitors (ivosidenib, enasidenib, olutasidenib), FLT3 kinase inhibitors (gilteritinib, midostaurin, quizartinib), a hedgehog inhibitor (glasdegib) as well as a BCL2 inhibitor (venetoclax) were reviewed with respect to their mode of action, their immunosuppressive potential, their current approval and the infectious complications and febrile neutropenia reported from clinical studies. Evidence-based recommendations for prevention and management of infectious complications and specific alerts regarding the potential for drug-drug interactions were developed and discussed in a plenary session with the panel of experts until consensus was reached. The set of recommendations was posted on the ECIL website for a month for comments from members of EBMT, EORTC, ICHS and ELN before final approval by the panelists. While a majority of these agents are not associated with a significantly increased risk when used as monotherapy, caution is required with combination therapy such as venetoclax plus hypomethylating agents, gemtuzumab ozogamicin plus cytotoxic drugs or midostaurin added to conventional AML chemotherapy.
MRI radiomics independent of clinical baseline characteristics and neoadjuvant treatment modalities predicts response to neoadjuvant therapy in rectal cancer
Authors: Song Maxiaowei , Li Shuai , Wang Hongzhi , Hu Ke , Wang Fengwei , Teng Huajing , Wang Zhi , Liu Jin , Jia Angela Y. , Cai Yong , Li Yongheng , Zhu Xianggao , Geng Jianhao , Zhang Yangzi , Wan XiangBo , Wang Weihu
Published: April 2022

Background

To analyse the performance of multicentre pre-treatment MRI-based radiomics (MBR) signatures combined with clinical baseline characteristics and neoadjuvant treatment modalities to predict complete response to neoadjuvant (chemo)radiotherapy in locally advanced rectal cancer (LARC).

Methods

Baseline MRI and clinical characteristics with neoadjuvant treatment modalities at four centres were collected. Decision tree, support vector machine and five-fold cross-validation were applied for two non-imaging and three radiomics-based models’ development and validation.

Results

We finally included 674 patients. Pre-treatment CEA, T stage, and histologic grade were selected to generate two non-imaging models: C model (clinical baseline characteristics alone) and CT model (clinical baseline characteristics combining neoadjuvant treatment modalities). The prediction performance of both non-imaging models were poor. The MBR signatures comprising 30 selected radiomics features, the MBR signatures combining clinical baseline characteristics (CMBR), and the CMBR incorporating neoadjuvant treatment modalities (CTMBR) all showed good discrimination with mean AUCs of 0.7835, 0.7871 and 0.7916 in validation sets, respectively. The three radiomics-based models had insignificant discrimination in performance.

Conclusions

The performance of the radiomics-based models were superior to the non-imaging models. MBR signatures seemed to reflect LARC’s true nature more accurately than clinical parameters and helped identify patients who can undergo organ preservation strategies.
Ultrastructural and proteomic profiling of mitochondria-associated endoplasmic reticulum membranes reveal aging signatures in striated muscle
Authors: Lu Xue , Gong Yingchao , Hu Wanyu , Mao Yankai , Wang Ting , Sun Zeyu , Su Xiaoling , Fu Guosheng , Wang Yanpeng , Lai Dongwu
Published: April 2022

Aging is a major risk for developing cardiac and skeletal muscle dysfunction, yet the underlying mechanism remains elusive. Here we demonstrated that the mitochondria-associated endoplasmic reticulum membranes (MAMs) in the rat heart and skeletal muscle were disrupted during aging. Using quantitative morphological analysis, we showed that the mitochondria-endoplasmic reticulum contacts (MERCs) were reduced by half over the lifespan with an early onset of accelerated thickening in the clefts. The ultrastructural changes were further validated by proteomic profiling of the MAM fractions. A combination of subcellular fractionation and quantitative mass spectrometry identified 1306 MAM-enriched proteins in both heart and skeletal muscle, with a catalog of proteins dysregulated with aging. Functional mapping of the MAM proteome suggested several aging signatures to be closely associated with the ER-mitochondria crosstalk, including local metabolic rewiring, calcium homeostasis imbalance, and impaired organelle dynamics and autophagy. Moreover, we identified a subset of highly interconnected proteins in an ER-mitochondria organization network, which were consistently down-regulated with aging. These decreased proteins, including VDAC1, SAMM50, MTX1 and MIC60, were considered as potential contributors to the age-related MAM dysfunction. This study highlights the perturbation in MAM integrity during the striated muscle aging process, and provides a framework for understanding aging biology from the perspective of organelle interactions.
The RBPJ/DAPK3/UBE3A signaling axis induces PBRM1 degradation to modulate the sensitivity of renal cell carcinoma to CDK4/6 inhibitors
Authors: Liu Wentao , Zhang Bin , Zhang Dan , Guo Feng , Ye Kun , Zhu Liang , Jin Xin
Published: April 2022

Renal cell carcinoma (RCC) is a kind of malignant tumor originating from the renal tubular epithelium. Approximately 30% of patients with renal cancer are found to have metastasis when first diagnosed. Exploring other effective treatment methods in addition to surgery is an urgent need in the research field of renal cell carcinoma. Polybromo 1 (PBRM1) is the second most mutated gene in RCC, with a mutation rate of ~40%. Notably, the posttranscriptional modification of PBRM1 in RCC is unclear. In this study, we performed unbiased mass spectrometry of PBRM1 and identified ubiquitin-protein ligase E3A (UBE3A), an extensively studied E3 ligase that can bind with PBRM1 and regulate the stability of PBRM1 in renal cancer cells. We further found that RBPJ/DAPK3 modulated the E3 ligase activity of UBE3A by interfering with the PKA phosphorylation of UBE3A. Finally, we demonstrated that the RBPJ/DAPK3/UBE3A/PBRM1/p21 axis contributed to the sensitivity of renal cancer cells to CDK4/6 inhibitors. In addition, in combination with RBPJ inhibitors, CDK4/6 inhibitors showed synergistically enhanced effects on renal cancer cells. In summary, we not only revealed a novel RBPJ/DAPK3/UBE3A/PBRM1/p21 signaling axis but also identified a combination strategy for overcoming the resistance of renal cancer cells to CDK4/6 inhibitors.
CircRPAP2 regulates the alternative splicing of PTK2 by binding to SRSF1 in breast cancer
Authors: Yu Yunhe , Fang Lin
Published: April 2022

Breast cancer is the most commonly diagnosed malignant tumor and the second-highest cause of cancer-related deaths in women worldwide. Circular RNAs (circRNAs) are associated with the development of numerous cancers, including breast cancer. Here, we present the first report that circRPAP2 (hsa_circ_0000091) is downregulated in breast cancer tissue samples and cell lines. Furthermore, the expression level of circRPAP2 in breast cancer tissues was correlated with axillary lymph node metastasis and TNM stage. Biological function studies demonstrated that circRPAP2 inhibited the proliferation and migration of breast cancer in vivo and in vitro. The mechanistic evaluation indicated that circRPAP2 can bind to the oncoprotein SRSF1, likely competing with the binding between SRSF1 and PTK2 pre-mRNA, thereby attenuating SRSF1-mediated alternate splicing of PTK2, an effector of SRSF1 oncogenic activity, resulting in the reduction of PTK2 mRNA and protein expression. Overall, our findings suggest that circRPAP2 plays a tumor suppressor role and may serve as a biomarker in breast cancer. In addition, the identification of the circRPAP2/SRSF1/PTK2 axis provides new insights into the pathogenesis of breast cancer and highlights a novel target for the development of oncotherapeutics.
Impaired sense of agency and associated confidence in psychosis
Authors: Krugwasser Amit Regev , Stern Yonatan , Faivre Nathan , Harel Eiran Vadim , Salomon Roy
Published: April 2022

The Sense of Agency (SoA), our sensation of control over our actions, is a fundamental mechanism for delineating the Self from the environment and others. SoA arises from implicit processing of sensorimotor signals as well as explicit higher-level judgments. Psychosis patients suffer from difficulties in the sense of control over their actions and accurate demarcation of the Self. Moreover, it is unclear if they have metacognitive insight into their aberrant abilities. In this pre-registered study, we examined SoA and its associated confidence judgments using an embodied virtual reality paradigm in psychosis patients and controls. Our results show that psychosis patients not only have a severely reduced ability for discriminating their actions but they also do not show proper metacognitive insight into this deficit. Furthermore, an exploratory analysis revealed that the SoA capacities allow for high levels of accuracy in clinical classification of psychosis. These results indicate that SoA and its metacognition are core aspects of the psychotic state and provide possible venues for understanding the underlying mechanisms of psychosis, that may be leveraged for novel clinical purposes.
PPP6C, a serine-threonine phosphatase, regulates melanocyte differentiation and contributes to melanoma tumorigenesis through modulation of MITF activity
Authors: Maskin Carolyn R. , Raman Renuka , Houvras Yariv
Published: April 2022

It is critical to understand the molecular mechanisms governing the regulation of MITF, a lineage specific transcription factor in melanocytes and an oncogene in melanoma. We identified PPP6C, a serine/threonine phosphatase, as a key regulator of MITF in melanoma. PPP6C is the only recurrently mutated serine/threonine phosphatase across all human cancers identified in sequencing studies and the recurrent R264C mutation occurs exclusively in melanoma. Using a zebrafish developmental model system, we demonstrate that PPP6C expression disrupts melanocyte differentiation. Melanocyte disruption was rescued by engineering phosphomimetic mutations at serine residues on MITF. We developed an in vivo MITF promoter assay in zebrafish and studied the effects of PPP6C(R264C) on regulating MITF promoter activity. Expression of PPP6C(R264C) cooperated with oncogenic NRAS(Q61K) to accelerate melanoma initiation in zebrafish, consistent with a gain of function alteration. Using a human melanoma cell line, we examined the requirement for PPP6C in proliferation and MITF expression. We show that genetic inactivation of PPP6C increases MITF and target gene expression, decreases sensitivity to BRAF inhibition, and increases phosphorylated MITF in a BRAF(V600E) mutant melanoma cell line. Our data suggests that PPP6C may be a relevant drug target in melanoma and proposes a mechanism for its action.
Mathematical modelling identifies conditions for maintaining and escaping feedback control in the intestinal epithelium
Authors: Fischer Matthias M. , Herzel Hanspeter , Blüthgen Nils
Published: April 2022

The intestinal epithelium is one of the fastest renewing tissues in mammals. It shows a hierarchical organisation, where intestinal stem cells at the base of crypts give rise to rapidly dividing transit amplifying cells that in turn renew the pool of short-lived differentiated cells. Upon injury and stem-cell loss, cells can also de-differentiate. Tissue homeostasis requires a tightly regulated balance of differentiation and stem cell proliferation, and failure can lead to tissue extinction or to unbounded growth and cancerous lesions. Here, we present a two-compartment mathematical model of intestinal epithelium population dynamics that includes a known feedback inhibition of stem cell differentiation by differentiated cells. The model shows that feedback regulation stabilises the number of differentiated cells as these become invariant to changes in their apoptosis rate. Stability of the system is largely independent of feedback strength and shape, but specific thresholds exist which if bypassed cause unbounded growth. When dedifferentiation is added to the model, we find that the system can recover faster after certain external perturbations. However, dedifferentiation makes the system more prone to losing homeostasis. Taken together, our mathematical model shows how a feedback-controlled hierarchical tissue can maintain homeostasis and can be robust to many external perturbations.
Contextual associations represented both in neural networks and human behavior
Authors: Aminoff Elissa M. , Baror Shira , Roginek Eric W. , Leeds Daniel D.
Published: April 2022

Contextual associations facilitate object recognition in human vision. However, the role of context in artificial vision remains elusive as does the characteristics that humans use to define context. We investigated whether contextually related objects (bicycle-helmet) are represented more similarly in convolutional neural networks (CNNs) used for image understanding than unrelated objects (bicycle-fork). Stimuli were of objects against a white background and consisted of a diverse set of contexts (N = 73). CNN representations of contextually related objects were more similar to one another than to unrelated objects across all CNN layers. Critically, the similarity found in CNNs correlated with human behavior across multiple experiments assessing contextual relatedness, emerging significant only in the later layers. The results demonstrate that context is inherently represented in CNNs as a result of object recognition training, and that the representation in the later layers of the network tap into the contextual regularities that predict human behavior.
Spata7 is required for maintenance of the retinal connecting cilium
Authors: Lu Jiaxiong , Xiong Kaitlyn , Qian Xinye , Choi Jongsu , Shim Yoon-Kyung , Burnett Jacob , Mardon Graeme , Chen Rui
Published: April 2022

SPATA7, an early onset LCA3 retinal disease gene, encodes a putative scaffold protein that is essential for the proper assembly of the connecting cilium (CC) complex in photoreceptors. Previous studies have shown that SPATA7 interacts with other photoreceptor-specific ciliary proteins, such as RPGR and RPGRIP1, and maintains the integrity of CC integrity. However, although it is known that Spata7 is required for early formation of the CC, it is unclear if Spata7 is also required for the maintenance of the CC. To investigate Spata7 function in the retina at the adult stage, loss of function was induced in the adult retina upon tamoxifen induction of an inducible Spata7 knockout allele (Spata7flox/−; UbcCreERT2/+). The phenotype of mutant retina was characterized by a combination of histology, immunobiochemistry, and electroretinography (ERG). Our results demonstrated that Spata7 is also essential for maintaining the integrity of the mature retinal CC. Loss of Spata7 in adults caused phenotypes similar to those seen in germline mutant mice, including photoreceptor cell degeneration and defective ERG responses. Close examination of the CC revealed significantly shortened NPHP1 length as a result of Spata7 deletion. Furthermore, mislocalization of rhodopsin, leading to ER stress-mediated apoptosis, was observed in the retinal layers. Our results indicate that Spata7 is required not only for the establishment but also for the maintenance of the CC of photoreceptors.
Detection of volatile organic compounds using mid-infrared silicon nitride waveguide sensors
Authors: Zhou Junchao , Al Husseini Diana , Li Junyan , Lin Zhihai , Sukhishvili Svetlana , Coté Gerard L. , Gutierrez-Osuna Ricardo , Lin Pao Tai
Published: April 2022

Mid-infrared (mid-IR) sensors consisting of silicon nitride (SiN) waveguides were designed and tested to detect volatile organic compounds (VOCs). SiN thin films, prepared by low-pressure chemical vapor deposition (LPCVD), have a broad mid-IR transparent region and a lower refractive index (nSiN = 2.0) than conventional materials such as Si (nSi = 3.4), which leads to a stronger evanescent wave and therefore higher sensitivity, as confirmed by a finite-difference eigenmode (FDE) calculation. Further, in-situ monitoring of three VOCs (acetone, ethanol, and isoprene) was experimentally demonstrated through characteristic absorption measurements at wavelengths λ = 3.0–3.6 μm. The SiN waveguide showed a five-fold sensitivity improvement over the Si waveguide due to its stronger evanescent field. To our knowledge, this is the first time SiN waveguides are used to perform on-chip mid-IR spectral measurements for VOC detection. Thus, the developed waveguide sensor has the potential to be used as a compact device module capable of monitoring multiple gaseous analytes for health, agricultural and environmental applications.
A sensitive and simple competitive nanozyme-linked apta-sorbent assay for the dual-mode detection of ochratoxin A
Authors: Li Min , Wang Hao , Yu Xiaodi , Jia Xindi , Zhu Chao , Liu Jiahui , Zhang Fan , Chen Zilei , Yan Mengmeng , Yang Qinzheng
Published: April 2022

Pd–Pt NRs bound with capture probes catalyzed the conversion of colorless TMB to blue TMB2+. The TMB not only had a distinguishable change in the color but also had a strong SERS signal.
Tunable Dirac states in doped B2S3 monolayers
Authors: Li Xiaoteng , Zuo Xi , Cui Bin , Zhao Wenkai , Xu Yuqing , Zou Dongqing , Yang Chuanlu
Published: April 2022

The Dirac cone of the Sn-doped B2S3 monolayer is just located on the EF, and the typical kagome bands arise. When the SOC is considered, the Dirac cone on the K point is opened, leading to a direct band-gap of about 90 meV.
Protective role of bayberry extract: associations with gut microbiota modulation and key metabolites
Authors: Tu Pengcheng , Tang Qiong , Wang Meng , Chen Wen , Ye Xiang , Zheng Xiaodong
Published: April 2022

We aimed to investigate the metabolic impact of bayberry extract cyanidin-3-O-glucoside and its associations with changes in the gut microbiota.
Bottom-up synthesized crystalline boron quantum dots with nonvolatile memory effects through one-step hydrothermal polymerization of ammonium pentaborane and boric acid
Authors: Wang Huiqi , Han Jiacheng , Wang Mei , Wang Liyong , Jia Suping , Cao Honghong , Hu Shengliang , He Yan-Bing
Published: April 2022

Crystalline BQDs are synthesized through a bottom-up strategy and used to fabricate a BQD–PVP memory device with nonvolatile rewritable memory effects.