bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition Studies on Carbonic Anhydrase Isoforms I, II, IX, and XII with a Series of Sulfaguanidines
Authors: Abdoli Morteza , De Luca Viviana , Capasso Clemente , Supuran Claudiu T. , Žalubovskis Raivis
Published: January 2023

Two novel sulfaguanidine series, six N‐(N,N′‐dialkyl/dibenzyl‐carbamimidoyl) benzenesulfonamide derivatives and nine N‐(N‐alkyl/benzyl‐carbamimidoyl) benzenesulfonamide derivatives, were obtained by desulfidative amination of easily accessible dimethyl arylsulfonylcarbonimidodithioates under catalyst‐ and base‐free conditions. The newly synthesized compounds were tested for the inhibition of four different isozymes of human carbonic anhydrase (hCA I, II, IX and XII, EC 4.2.1.1). Both series reported here were inactive against the off‐target isozymes hCA I and II (Ki>100 μM). Interestingly, all investigated compounds inhibited both target isozymes hCA IX and XII in the submicromolar to micromolar ranges in which Ki values spanned from 0.168 to 0.921 μM against hCA IX and from 0.335 to 1.451 μM against hCA XII. The results indicated that N‐(N‐alkyl/benzyl‐carbamimidoyl) benzenesulfonamides were slightly more potent inhibitors than N‐(N,N′‐dialkyl/dibenzyl‐carbamimidoyl) benzenesulfonamides. Among the evaluated compounds, N‐n‐octyl‐substituted N‐carbamimidoylbenzenesulfonamide showed the most significant activity with a Ki value of 0.168 μM against hCA IX, which was four‐fold more selective toward this isozyme versus hCA XII. Again, another derivative from N‐(N‐alkyl/benzyl‐carbamimidoyl) benzenesulfonamide series, N‐p‐methylbenzyl‐substituted N‐carbamimidoylbenzenesulfonamide, demonstrated superior inhibitory activity against hCA XII with a Ki value of 0.335 μM.
AVALON: The Italian cohort study on real‐life efficacy of hypomethylating agents plus venetoclax in newly diagnosed or relapsed/refractory patients with acute myeloid leukemia
Authors: Todisco Elisabetta , Papayannidis Cristina , Fracchiolla Nicola , Petracci Elisabetta , Zingaretti Chiara , Vetro Calogero , Martelli Maria Paola , Zappasodi Patrizia , Di Renzo Nicola , Gallo Susanna , Audisio Ernesta , Griguolo Davide , Cerchione Claudio , Selleri Carmine , Mattei Daniele , Bernardi Massimo , Fumagalli Monica , Rizzuto Giuliana , Facchini Luca , Basilico Claudia Maria , Manfra Ilenia , Borlenghi Erika , Cairoli Roberto , Salutari Prassede , Gottardi Michele , Molteni Alfredo , Martini Vincenza , Lunghi Monia , Fianchi Luana , Cilloni Daniela , Lanza Francesco , Abruzzese Elisabetta , Cascavilla Nicola , Rivellini Flavia , Ferrara Felicetto , Maurillo Luca , Nanni Jacopo , Romano Alessandra , Cardinali Valeria , Gigli Federica , Roncoroni Elisa , Federico Vincenzo , Marconi Giovanni , Volpi Roberta , Sciumè Mariarita , Tarella Corrado , Rossi Giuseppe , Martinelli Giovanni ,   for the AVALON Cooperative Group
Published: January 2023

Background

Venetoclax in combination with hypomethylating agents (HMA) is revolutionizing the therapy of acute myeloid leukemia (AML). However, evidence on large sets of patients is lacking, especially in relapsed or refractory leukemia.

Methods

AVALON is a multicentric cohort study that was conducted in Italy on patients with AML who received venetoclax‐based therapies from 2015 to 2020. The study was approved by the ethics committee of the participating institution and was conducted in accordance with the Declaration of Helsinki. The effectiveness and toxicity of venetoclax + HMA in 190 (43 newly diagnosed, 68 refractory, and 79 relapsed) patients with AML are reported here.

Results

In the newly diagnosed AML, the overall response rate and survival confirmed the brilliant results demonstrated in VIALE‐A. In the relapsed or refractory AML, the combination demonstrated a surprisingly complete remission rate (44.1% in refractory and 39.7% in relapsed evaluable patients) and conferred to treated patients a good expectation of survival. Toxicities were overall manageable, and most incidents occurred in the first 60 days of therapy. Infections were confirmed as the most common nonhematologic adverse event.

Conclusions

Real‐life data show that the combination of venetoclax and HMA offers an expectation of remission and long‐term survival to elderly, newly diagnosed patients, and to relapsed or chemoresistant AML, increasing the chance of cure through a different mechanism of action. The venetoclax + HMA combination is expected to constitute the base for triplet combinations and integration of target therapies. Our data contribute to ameliorate the understanding of venetoclax + HMA effectiveness and toxicities in real life.
Ethnic‐specific predictors of neurotoxicity among patients with pediatric acute lymphoblastic leukemia after high‐dose methotrexate
Authors: Harris Rachel D. , Bernhardt Melanie Brooke , Zobeck Mark C. , Taylor Olga A. , Gramatges Maria Monica , Schafer Eric S. , Lupo Philip J. , Rabin Karen R. , Scheurer Michael E. , Brown Austin L.
Published: January 2023

Background

High‐dose methotrexate (HD‐MTX; 5000 mg/m2) is an important component of curative therapy in many treatment regimens for high‐risk pediatric acute lymphoblastic leukemia (ALL). However, methotrexate therapy can result in dose‐limiting neurotoxicity, which may disproportionately affect Latino children. This study evaluated risk factors for neurotoxicity after HD‐MTX in an ethnically diverse population of patients with ALL.

Methods

The authors retrospectively reviewed the medical records of patients who were diagnosed with ALL and treated with HD‐MTX at Texas Children's Cancer Center (2010–2017). Methotrexate neurotoxicity was defined as a neurologic episode (e.g., seizures or stroke‐like symptoms) occurring within 21 days of HD‐MTX that resulted in methotrexate treatment modifications. Mixed effects multivariable logistic regression was used to estimate the odds ratio (OR) and corresponding 95% confidence interval (CI) for the association between clinical factors and neurotoxicity.

Results

Overall, 351 patients (58.1% Latino) who received 1183 HD‐MTX infusions were evaluated. Thirty‐five patients (10%) experienced neurotoxicity, 71% of whom were Latino. After adjusting for clinical risk factors, the authors observed that serum creatinine elevations ≥50% of baseline were associated with a three‐fold increased odds (OR, 3.32; 95% CI, 0.98–11.21; p = .05) for neurotoxicity compared with creatinine elevation <25%. Notably, predictors of neurotoxicity differed by ethnicity. Specifically, Latino children experienced a nearly six‐fold increase in neurotoxicity odds (OR, 5.80; 95% CI, 1.39–24.17; p = .02) with serum creatinine elevation ≥50% compared with creatinine elevation <25%.

Conclusions

The current findings indicate that serum creatinine elevations ≥50% may be associated with an increased risk for neurotoxicity among Latino children with ALL and may identify potential candidates for therapeutic or supportive care interventions.
Top advances of the year: Head and neck cancer
Authors: Verma Avanti , Burtness Barbara
Published: January 2023

Advances in treatment deintensification for human papillomavirus‐associated oropharyngeal cancer include use of transoral surgery to permit reduction in pathologic risk‐based postoperative therapy after transoral resection. The E3311 cooperative group trial demonstrated 3‐year progression‐free survival (PFS) of 95% for intermediate risk patients treated with 50 Gy radiation alone, with no decrement for those with a smoking history. Favorable risk patients could be observed, with a 3‐year PFS of 93%. Reduction in radiation dose is also feasible for favorable risk patients (low or no smoking history and low stage) treated with chemoradiation on the NRG HN002 trial, where 2‐year PFS was 90.7%. For those favorable risk patients treated with radiation alone, 2‐year PFS was 87.7% and this arm did not meet criteria for further testing. Important phase 3 trials of immunotherapy in first‐line treatment of recurrent and/or metastatic head and neck cancer were also reported in 2022. For patients with nonnasopharyngeal sites of disease, the combination of the programmed death‐1–directed antibody nivolumab plus the anti–CTLA‐4 agent ipilimumab was not superior to chemotherapy plus cetuximab in the Checkmate 651 trial. However, in an important breakthrough for patients with nasopharyngeal cancer, the JUPITER‐02 trial, conducted in China, Singapore, and Taiwan among patients with predominantly Epstein‐Barr virus‐related cancers, demonstrated a significant improvement in PFS (hazard ratio, 0.52) when toripalimab was added to gemcitabine/cisplatin chemotherapy. Immature survival data indicate overall survival will likely also be impacted.
An active defense model based on situational awareness and firewalls
Authors: Li Di , Hu Yikun , Xiao Guoqing , Duan Mingxing , Li Kenli
Published: January 2023

With the rapid development of the internet, cyberspace security issues have become increasingly prominent. The importance of constructing a cyberspace security system is self‐evident, but compared with attackers, defenders in cyberspace are in a castle‐like passive defense state in most cases. Therefore, building a reliable, accurate, timely, and active defense system is challenging. The key is to accurately focus on defense priorities, the anticipation of attackers who will likely succeed, and blocking attacks in a timely manner. In this article, we propose an active defense model based on the interaction of situational awareness and firewalls. First, by biasing the integrity, confidentiality, and availability of assets to get the score of assets, and using the Common Vulnerability Scoring System to assess the threat level of assets, we combine the two to determine the maximum system damage that the asset will suffer if it is lost, and then focus on defense. Meanwhile, log analysis of the network situational awareness platform can predict successful attackers, and then the linked firewall strategy can block these attacks in time before the attackers obtain attack gains. After that, we force the attackers to give up their attacks on the target by increasing the attack cost. We compared our model with iptables auto‐blocking and nginx auto‐blocking, and our model excelled them across the board in terms of comprehensiveness and false positive rate. The experimental results verify thar our active defense model proposed in this article can better reduce the defense cost and increase the attack cost, thus achieving the relatively defense goal.
Landslide identification using water cycle particle swarm optimization‐based deep generative adversarial network
Authors: Lekshmanan Lijesh , George Arockia Selva Saroja
Published: January 2023

A natural vulnerability called a landslide threatens people, property, and infrastructure in many different places all over the world. Various landslide identification techniques are developed to assess the landslide hazard, but accurate identification of landslide occurrence particularly in certain regions remains a challenging issue, due to the complex scale‐dependent processes among geomorphometric features and landslides. To solve the shortcomings of landslide identification, the water cycle particle swarm optimization‐based deep generative adversarial network (WCPSO‐based Deep GAN) hybridization technique is presented. To develop the developed WCPSO, the water cycle algorithm (WCA) and particle swarm optimization (PSO) were hybridized. The landslide rainfall dataset is used as the source of the input data in this instance, and the Manhattan distance approach is then used to do feature selection. After performing data augmentation based on the results of the feature selection, the proposed WCPSO‐based deep GAN approach accurately detects the landslides. The developed WCPSO‐driven deep GAN's performance is also measured using the three metrics accuracy, specificity, and sensitivity, with a maximum accuracy of 0.937, higher specificity of 0.919, and higher sensitivity of 0.952.
Robust malware clustering of windows portable executables using ensemble latent representation and distribution modeling
Authors: Rizvi Syed Khurram Jah , Fraz Muhammad Moazam
Published: January 2023

Malware is a malicious program used for unauthorized access to organizational infrastructure and systems. To overcome challenges of exponential growth of malware, notable research has been made for unsupervised clustering of Windows‐based portable executable (PE). Nevertheless, to the best of our knowledge there has been no research for robust cluster prediction of Windows based PEs using static features. To this end, we proposed an ensemble neural network architecture for unsupervised feature learning and its distribution modeling for robust clustering of PE(s). The novel architecture is a cascaded formation of a deep autoencoder (AE) network and latent distribution modeling (LDM) network. The AE performs feature learning using latent representation and LDM performs the distribution modeling of latent representation using Gaussian approximation. An objective function is also devised for model optimization. The network adjusts the Gaussian components to optimize the distribution modeling. It also performs adjustments for data representations toward related Gaussian centers to make the model behave in adaptive manner. A novel malware dataset has also been collected by employing endpoint security management solution over enterprise network to assess proposed architecture. The dataset contains 21,486 samples including 14,497 malicious and 6989 benign ones. We also performed the evaluation of proposed architecture over publicly available benchmark malware dataset including 138,047 samples comprising 96,742 malicious and 41,323 benign PEs. The experimental results demonstrated that the proposed architecture yielded more than 95% accuracy for cluster prediction. The novel architecture has achieved superior performance and outperformed progressive techniques. The dataset along with implementation are accessible at
bit.ly/3J6ZF8S.
The comparison of machine learning classification algorithms used to diagnose liver cirrhosis disease and a brief review
Authors: Güneş Oguzhan Mehmet , Kasap Pelin , Çorba Zorlu Burcin Seyda
Published: January 2023

Liver cirrhosis disease is an important cause of death worldwide. Therefore, early diagnosis of the disease is very important. Machine learning algorithms are frequently used due to its high performance in the field of health, as in many areas. In this study, Multilayer Perceptron‐Artificial Neural Networks, Decision Trees, Random Forest, Naïve Bayes, Support Vector Machines, K‐Nearest Neighborhood, and Logistic Regression classification algorithms are used to classify the factors affecting liver cirrhosis. The performances of these algorithms are compared according to the accuracy rate, F measure, sensitivity, specificity and Kappa score on real data obtained from 2000 liver cirrhosis patients, and the factors affecting the disease are classified with the most appropriate algorithm. In addition, more than 50 articles covering both liver disease and classification methods are reviewed and the latest developments are presented in the study.
Computational Study on Chemoselective Difunctionalization of Unactivated Alkenes with Radical‐mediated Remote Functional Group Migration
Authors: Lafzi Ferruh , Eşsiz Selçuk
Published: January 2023

A computational study of the radical‐mediated chemoselective difunctionalization of the tertiary alcohol substituted aliphatic alkenes is carried out employing density functional theory (DFT) and high‐level coupled‐cluster methods, such as coupled‐cluster singles and doubles with perturbative triples [DLPNO‐CCSD(T)]. Our results indicate that the cyclic vinyl radical plays an important role in the progression of the reactions. Our computations demonstrated that the chemoselective difunctionalization of unactivated alkenes with radical‐mediated remote functional group migration is suitable for the 5‐ and 6‐exo‐dig cyclization, as opposite to 3‐ and 4‐exo‐dig cyclization suffering from cyclic intermediate with high energy. Our results show that the migration of nitrile group is more preferable than that of alkynyl group for the molecules including both cyano group and alkynyl group. For the 5‐ and 6‐exo‐dig cyclization, the rate‐determining step is the homolysis of the C−C σ‐bond in the cyclic intermediate, which results in the hydroxyl alkyl radical.
Improved Photoactivity Of NiO/ZnO Nanorods Heterostructured Films Relying On Scaffold Surface Cleaning And NiO Deposition Time Optimization
Authors: Periyannan Shanmugapriya , Manceriu Laura , Klein Andreas , Jaegermann Wolfram , Henrist Catherine , Cloots Rudi
Published: January 2023

Herein, a surface cleaning procedure involving vacuum annealing under oxygen was applied for cleaning the zinc oxide nanorod (ZNR) scaffold film's surface before nickel oxide (NiO) deposition for heterostructure formation. The scaffold properties (surface stoichiometry, defects fluctuation, Fermi level shift, carrier concentration) were studied as a function of the vacuum level and the NiO deposition time and correlated to the NiO/ZNR interface (charge transfer resistance, band bending) and photo‐response properties. The surface cleaning under a higher vacuum enabled the adsorbate and surface oxygen vacancy passivation but also influenced the surface doping. Our best performing NiO/ZNR interface in terms of photocatalytic efficiency was composed of a high‐vacuum‐cleaned (0.5 Pa) ZNR scaffold and 40 s sputter deposited NiO layer which was post‐annealed. The high photocatalytic efficiency could be correlated with a maximized near‐band edge emission, effective band bending, low charge transfer resistance (as proven by photoelectrochemical impedance measurements), and optimum light harvesting (maximized photocurrent density). The optimized NiO/ZNR showed about 1.5 times increase in photo‐response and improved photodegradation efficiency compared to the ZNR scaffold.
Chiral separation and quantitation of methylphenidate, ethylphenidate, and ritalinic acid in blood using supercritical fluid chromatography
Authors: Smith Christina , Vikingsson Svante , Kronstrand Robert , Swortwood Madeleine J.
Published: January 2023

Supercritical fluid chromatography (SFC) is a technique that analyzes compounds that are temperature‐labile, have moderately low weight, or are chiral compounds. Methylphenidate (MPH) is a chiral compound with two chiral centers. MPH has two chiral metabolites, ethylphenidate (EPH) and ritalinic acid (RA). MPH is sold as a racemic mixture. The d‐enantiomer of threo‐MPH is responsible for medicinal effects. Due to the differing effects of the enantiomers, it is important to analyze the enantiomers individually to better understand their effects. This method utilizes SFCand solid‐phase extraction (SPE) to separate and analyze the enantiomers of MPH, EPH, and RA in postmortem blood. The objective of this method was to assess a unique approach with SFC for enantiomeric separation of MPH, EPH, and RA. A SPE method was developed and optimized to isolate the analytes in blood and validated as fit‐for‐purpose following international guidelines. The linear range for MPH and EPH was 0.25–25 and 10–1000 ng/mL for RA in blood. Bias was −8.6% to 0.8%, and precision was within 15.4% for all analytes. Following method validation, this technique was applied to the analysis of 49 authentic samples previously analyzed with an achiral method. Quantitative results for RA were comparable to achiral technique, whereas there was loss of MPH and EPH over time. The l:d enantiomer ratio was calculated, and MPH demonstrated greater abundance of the d‐enantiomer. This is the first known method to separate and quantify the enantiomers of all three analytes utilizing SFC and SPE.
Comparison of embryonic development, fromHH21toHH40, between ostrich (Struthio camelus) and chicken (Gallus gallus)
Authors: Bai Shibin , Li Shanshan , Li Xiaoping , Zhu Shiyu , Shan Zhixin , Zhang Junpeng , Irwin David M. , Zhang Shuyi , Wang Zhe
Published: January 2023

Background

The chicken has been a representative model organism to study embryonic development in birds, however important differences exist among this class of species. As a representative of one of oldest existing clades of birds, the African ostrich (Struthio camelus), has the largest body among birds, and has two toes. Our purpose is to establish the corresponding stages in ostrich embryo development that match the well‐established HH system of the chicken to facilitate comparative studies between the ostrich and other birds to better understand differences in development.

Results

Here we describe in detail the middle period of embryonic development using microscopic images and skeletal staining. We found that clear morphological differentiation between the ostrich and the chicken begins at stage 26. Bird limb cartilage first form in stage 25, while the development of the limb skeletons differs after stage 31. Calcification of limb skeletons in the chicken was completed faster. The first and second toes of the ostrich disappear at stages 36 and 38, respectively.

Conclusions

This study should greatly aid ostrich‐related developmental and morphological research and provide a reference for studying the development and evolution of avian limb skeletons, including molecular research. Questions that can now be addressed include studies into the fusion of tarsometatarsal skeleton, ossification, and digit loss.
Generation and characterization of a Ddx4‐iCre transgenic line for deletion in the germline beginning at genital ridge colonization
Authors: Burnet Guillaume , Feng Chun‐Wei Allen , Cheung Ka Man Fiona , Bowles Josephine , Spiller Cassy M.
Published: January 2023

Germline‐specific Cre lines are useful for analyses of primordial germ cell, spermatogonial and oogonial development, but also for whole‐body deletions when transmitted through subsequent generations. Several germ cell specific Cre mouse strains exist, with various degrees of specificity, efficiency, and temporal activation. Here, we describe the CRISPR/Cas9 targeted insertion of an improved Cre (iCre) sequence in‐frame at the 3′ end of the Ddx4 locus to generate the Ddx4‐P2A‐iCre allele. Our functional assessment of this new allele, designated Ddx4iCreJoBo, reveals that Cre activity begins in PGCs from at least E10.5, and that it achieves higher efficiency for early gonadal (E10.5–12.5) germline deletion when compared to the inducible Oct4CreERT2 line. We found the Ddx4iCreJoBo allele to be hypomorphic for Ddx4 expression and homozygous males, but not females, were infertile. Using two reporter lines (R26RLacZ and R26RtdTomato) and a floxed gene of interest (Criptoflox) we found ectopic activity in multiple organs; global recombination (a common feature of germline Cre alleles) varies from 10 to 100%, depending on the particular floxed allele. There is a strong maternal effect, and therefore it is preferable for Ddx4iCreJoBo to be inherited from the male parent if ubiquitous deletion is not desired. With these limitations considered, we describe the Ddx4iCreJoBo line as useful for germline studies in which early gonadal deletion is required.
EVIandNDVIas proxies for multifaceted avian diversity in urban areas
Authors: Benedetti Yanina , Callaghan Corey T. , Ulbrichová Iva , Galanaki Antonia , Kominos Theodoros , Abou Zeid Farah , Ibáñez‐Álamo Juan Diego , Suhonen Jukka , Díaz Mario , Markó Gábor , Bussière Raphaël , Tryjanowski Piotr , Bukas Nikos , Mägi Marko , Leveau Lucas , Pruscini Fabio , Jerzak Leszek , Ciebiera Olaf , Jokimäki Jukka , Kaisanlahti‐Jokimäki Marja‐Liisa , Møller Anders Pape , Morelli Federico
Published: January 2023

Most ecological studies use remote sensing to analyze broad‐scale biodiversity patterns, focusing mainly on taxonomic diversity in natural landscapes. One of the most important effects of high levels of urbanization is species loss (i.e., biotic homogenization). Therefore, cost‐effective and more efficient methods to monitor biological communities' distribution are essential. This study explores whether the Enhanced Vegetation Index (EVI) and the Normalized Difference Vegetation Index (NDVI) can predict multifaceted avian diversity, urban tolerance, and specialization in urban landscapes. We sampled bird communities among 15 European cities and extracted Landsat 30‐meter resolution EVI and NDVI values of the pixels within a 50‐m buffer of bird sample points using Google Earth Engine (32‐day Landsat 8 Collection Tier 1). Mixed models were used to find the best associations of EVI and NDVI, predicting multiple avian diversity facets: Taxonomic diversity, functional diversity, phylogenetic diversity, specialization levels, and urban tolerance. A total of 113 bird species across 15 cities from 10 different European countries were detected. EVI mean was the best predictor for foraging substrate specialization. NDVI mean was the best predictor for most avian diversity facets: taxonomic diversity, functional richness and evenness, phylogenetic diversity, phylogenetic species variability, community evolutionary distinctiveness, urban tolerance, diet foraging behavior, and habitat richness specialists. Finally, EVI and NDVI standard deviation were not the best predictors for any avian diversity facets studied. Our findings expand previous knowledge about EVI and NDVI as surrogates of avian diversity at a continental scale. Considering the European Commission's proposal for a Nature Restoration Law calling for expanding green urban space areas by 2050, we propose NDVI as a proxy of multiple facets of avian diversity to efficiently monitor bird community responses to land use changes in the cities.
Using a demographic model to project the long‐term effects of fire management on tree biomass in Australian savannas
Authors: Murphy Brett P. , Whitehead Peter J. , Evans Jay , Yates Cameron P. , Edwards Andrew C. , MacDermott Harry J. , Lynch Dominique C. , Russell‐Smith Jeremy
Published: January 2023

Tropical savannas are characterized by high primary productivity and high fire frequency, such that much of the carbon captured by vegetation is rapidly returned to the atmosphere. Hence, there have been suggestions that management‐driven reductions in savanna fire frequency and/or severity could significantly reduce greenhouse gas emissions and sequester carbon in tree biomass. However, a key knowledge gap is the extent to which savanna tree biomass will respond to modest shifts in fire regimes due to plausible, large‐scale management interventions. Here, we: (1) characterize relationships between the frequency and severity of fires and key demographic rates of savanna trees, based on long‐term observations in vegetation monitoring plots across northern Australia; (2) use these relationships to develop a process‐explicit demographic model describing the effects of fire on savanna tree populations; and (3) use the demographic model to address the question: to what extent is it feasible, through the strategic application of prescribed burning, to increase tree biomass in Australian tropical savannas? Our long‐term tree monitoring dataset included observations of 12,344 tagged trees in 236 plots, monitored for between 3 and 24 years. Analysis of this dataset showed that frequent high‐severity fires significantly reduced savanna tree recruitment, survival, and growth. Our demographic model suggested that: (1) despite the negative effects of frequent high‐severity fires on demographic rates, savanna tree biomass appears to be suppressed by only a relatively small amount by contemporary fire regimes, characterized by a mix of low‐ to high‐severity fires; and (2) plausible, management‐driven reductions in the frequency of high‐severity fires are likely to lead to increases in tree biomass of about 11.0 t DM ha−1 (95% CI: −1.2–20.8) over a century. Accounting for this increase in carbon storage could generate significant carbon credits, worth, on average, three times those generated annually by current greenhouse gas (methane and nitrous oxide) abatement projects, and has the potential to significantly increase the economic viability of fire/carbon projects, thereby promoting ecologically sustainable management of tropical savannas in Australia and elsewhere. This growing industry has the potential to bring much‐needed economic activity to savanna landscapes, without compromising important natural and cultural values.
Modeling spatial distributions of Amah Mutsun priority cultural plants to support Indigenous cultural revitalization
Authors: Taylor Annalise , Sigona Alexii , Kelly Maggi
Published: January 2023

Along the Central Coast of California, USA, native plant biodiversity has depended on various forms of Indigenous stewardship such as burning, tilling, and gathering. Simultaneously, the Amah Mutsun Tribal Band (the Tribe) depends on these native ecosystems for cultural survivance. However, much of the knowledge related to the location and caretaking of cultural plants has become dormant in the community due to the immediate and ongoing effects of Euro‐American colonization. We identified potential gathering areas by modeling the spatial distributions of 10 culturally important plants throughout the Tribe's stewardship area. We utilized community science datasets with an ensemble modeling approach that combines the results of five machine learning models to predict not only the distribution of each species, but also the relative certainty of those predictions spatially. Our results revealed that 265.2 km2 (2.1%) of the Tribe's stewardship area is predicted habitat for seven or more of these cultural plants, and that the Tribe has potential access to approximately a third of these high‐priority areas. Our findings will directly inform the Tribe's cultural revitalization and ecological stewardship programs. We show how geospatial models can support the revitalization of an Indigenous culture by renewing relationships with cultural plants.
Habitat attributes mediate herbivory and influence community development in algal metacommunities
Authors: Srednick Griffin , Cohen Alyssa , Diehl Olivia , Tyler Kaela , Swearer Stephen E.
Published: January 2023

Understanding the drivers and impacts of spatiotemporal variation in species abundance on community trajectories is key to understanding the factors contributing to ecosystem resilience. Temporal variation in species trajectories across patches can provide compensation for species loss and can influence successional patterns. However, little is known about the underlying mechanisms that lead to patterns of species or spatial compensation and how those patterns may be mediated by consumer–resource relationships. Here we describe an experiment testing whether habitat attributes (e.g., structural complexity and spatial heterogeneity) mediate the effects of herbivory on tropical marine macroalgal communities by reducing accessibility and detectability, respectively, leading to variable trajectories among algal species at community (within patch) and metacommunity (i.e., among patch) scales. Reduced accessibility (greater habitat complexity) decreased the effects of herbivory (i.e., depressed consumption rate, increased algal species richness), and both accessibility and detectability (spatial heterogeneity) influenced algal community structure. Moreover, decreased accessibility at the community scale and a mosaic of accessibility at the metacommunity scale led to variation in community assembly. We suggest that habitat attributes can be important influencers of consumer–resource interactions on coral reefs, which in turn can increase species diversity, promote species succession, and enhance stability in algal metacommunities.
COVID‐19‐associated myocardial injury: A case report
Authors: Tadokoro Tomonori , Ohta‐Ogo Keiko , Ikeda Yoshihiko , Sugiyama Masaya , Katano Harutaka , Hatakeyama Kinta , Matsumoto Masanori , Tashiro Hideki
Published: January 2023

Coronavirus disease 2019 (COVID‐19) is often accompanied by pneumonia and can be fatal. We report a case of COVID‐19‐associated myocardial injury mimicking fulminant myocarditis. Endomyocardial biopsy revealed numerous von Willebrand factor‐rich microthrombi with small myocardial necrotic areas, complement deposits in small vessels/microthrombi, and macrophage‐predominant interstitial infiltration. These findings, distinct from those of typical lymphocytic myocarditis, show diffuse endothelial injury, complement activation, and activated macrophages as characteristic features of COVID‐19‐associated pathogenesis. Dysregulated serum cytokine profiles predicting severe/critical COVID‐19‐associated myocardial injury were also determined. This case emphasizes the occurrence of fatal cardiac manifestation with microthrombotic injury in the early stage of COVID‐19.
Ion transfer voltammetry of amino acids with an all‐solid‐state ion‐selective electrode for non‐destructive phenylalanine sensing
Authors: Gan Ai Wei , Seah Georgina E. K. K. , Kwek Li Hui , Goh Shermin S.
Published: January 2023

Amino acids such as phenylalanine (Phe) are key building blocks of proteins and other biomolecules. Although recent advancements in electrochemical sensors have enabled the rapid detection of Phe, these sensors are often destructive as they irreversibly oxidise Phe. In addition, most of them rely on biorecognition elements, which suffer from limited stability at ambient conditions and sensitivity towards environmental fluctuations. Herein, we report the first example of ion transfer voltammetry of Phe using an all‐solid‐state ion‐selective electrode (ISE). The reversibility of this technique enables both the sensor and the Phe sample to be reused. The optimal voltammetric ISE (VISE) exhibits near Nernstian response (56.8 mV/decade) towards Phe and selectivity against amino acids of all classes (hydrophobic, hydrophilic and charged). Voltammetric interrogation of the ISE significantly enhances sensitivity, linear range, selectivity, and stability as compared to traditional open circuit potential measurements. Phe levels in a commercial nutritional supplement and drinking waters were determined to demonstrate the viability of our sensor in real life applications. This proof‐of‐concept can be applied to develop VISEs for other amino acids and biological ions for healthcare and nutrition sensing.
The geomorphological record of an ice stream to ice shelf transition in Northeast Greenland
Authors: Lane Timothy P. , Darvill Christopher , Rea Brice R. , Bentley Michael J. , Smith James A. , Jamieson Stewart S.R. , Ó Cofaigh Colm , Roberts David H.
Published: January 2023

Understanding ice stream dynamics over decadal to millennial timescales is crucial for improving numerical model projections of ice sheet behaviour and future ice loss. In marine‐terminating settings, ice shelves play a critical role in controlling ice‐stream grounding line stability and ice flux to the ocean, but few studies have investigated the terrestrial lateral geomorphological imprint of ice shelves during deglaciation. Here, we document the terrestrial deglacial landsystem of Nioghalvfjerdsfjorden Glacier (79N) in northeast Greenland, following the Last Glacial Maximum, and the margin's lateral transition to a floating ice shelf. High‐elevation areas are influenced by local ice caps and display autochthonous to allochthonous blockfields that mark the interaction of local ice caps with the ice stream below. A thermal transition from cold‐ to warm‐based ice is denoted by the emplacement of erratics onto allochthonous blockfields. Below ~600 m above sea level (a.s.l.) glacially abraded bedrock surfaces and assemblages of lateral moraines, ‘hummocky’ moraine, fluted terrain, and ice‐contact deltas record the former presence of warm‐based ice and thinning of the grounded ice stream margin through time. In the outer fjord a range of landforms such as ice shelf moraines, dead‐ice topography, and ice marginal glaciofluvial outwash was produced by an ice shelf during deglaciation. Along the mid‐ and inner‐fjord areas this ice shelf signal is absent, suggesting ice shelf disintegration prior to grounding line retreat under tidewater conditions. However, below the marine limit, the geomorphological record along the fjord indicates the expansion of the 79N ice shelf during the Neoglacial, which culminated in the Little Ice Age. This was followed by 20th century recession, with the development of a suite of compressional ice shelf moraines, ice‐marginal fluvioglacial corridors, kame terraces, dead‐ice terrain, and crevasse infill ridges. These mark rapid ice shelf thinning and typify the present‐day ice shelf landsystem in a warming climate.
Acute Toxicity of 6PPD-Quinone to Early Life Stage Juvenile Chinook (Oncorhynchus tshawytscha) and Coho (Oncorhynchus kisutch) Salmon
Authors: Lo Bonnie P. , Marlatt Vicki L. , Liao Xiangjun , Reger Sofya , Gallilee Carys , Ross Andrew R.S. , Brown Tanya M.
Published: January 2023

The breakdown product of the rubber tire antioxidant N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD)-6-PPD-quinone has been strongly implicated in toxic injury and death in coho salmon (Oncorhynchus kisutch) in urban waterways. Whereas recent studies have reported a wide range of sensitivity to 6PPD-quinone in several fish species, little is known about the risks to Chinook salmon (Oncorhynchus tshawytscha), the primary prey of endangered Southern Resident killer whales (Orcinus orca) and the subject of much concern. Chinook face numerous conservation threats in Canada and the United States, with many populations assessed as either endangered or threatened. We evaluated the acute toxicity of 6PPD-quinone to newly feeding (~3 weeks post swim-up) juvenile Chinook and coho. Juvenile Chinook and coho were exposed for 24 h under static conditions to five concentrations of 6PPD-quinone. Juvenile coho were 3 orders of magnitude more sensitive to 6PPD-quinone compared with juvenile Chinook, with 24-h median lethal concentration (LC50) estimates of 41.0 and more than 67 307 ng/L, respectively. The coho LC50 was 2.3-fold lower than what was previously reported for 1+-year-old coho (95 ng/L), highlighting the value of evaluating age-related differences in sensitivity to this toxic tire-related chemical. Both fish species exhibited typical 6PPD-quinone symptomology (gasping, increased ventilation, loss of equilibrium, erratic swimming), with fish that were symptomatic generally exhibiting mortality. The LC50 values derived from our study for coho are below concentrations that have been measured in salmon-bearing waterways, suggesting the potential for population-level consequences in urban waters. The higher relative LC50 values for Chinook compared with coho merits further investigation, including for the potential for population-relevant sublethal effects. Environ Toxicol Chem 2023;42:815–822. © 2023 His Majesty the King in Right of Canada and The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. Reproduced with the permission of the Minister of Fisheries and Oceans Canada.
Deep learning identified genetic variants for COVID‐19‐related mortality among 28,097 affected cases in UK Biobank
Authors: Liu Zihuan , Dai Wei , Wang Shiying , Yao Yisha , Zhang Heping
Published: January 2023

Analysis of host genetic components provides insights into the susceptibility and response to viral infection such as severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), which causes coronavirus disease 2019 (COVID‐19). To reveal genetic determinants of susceptibility to COVID‐19 related mortality, we train a deep learning model to identify groups of genetic variants and their interactions that contribute to the COVID‐19 related mortality risk using the UK Biobank data (28,097 affected cases and 1656 deaths). We refer to such groups of variants as super variants. We identify 15 super variants with various levels of significance as susceptibility loci for COVID‐19 mortality. Specifically, we identify a super variant (odds ratio [OR] = 1.594, p = 5.47 × 10−9) on Chromosome 7 that consists of the minor allele of rs76398985, rs6943608, rs2052130, 7:150989011_CT_C, rs118033050, and rs12540488. We also discover a super variant (OR = 1.353, p = 2.87 × 10−8) on Chromosome 5 that contains rs12517344, rs72733036, rs190052994, rs34723029, rs72734818, 5:9305797_GTA_G, and rs180899355.
In vivo characterization of magnetic resonance imaging‐based T1w/T2w ratios reveals myelin‐related changes in temporal lobe epilepsy
Authors: Jiang Yuchao , Li Wei , Qin Yingjie , Zhang Le , Tong Xin , Xiao Fenglai , Jiang Sisi , Li Yunfang , Gong Qiyong , Zhou Dong , An Dongmei , Yao Dezhong , Luo Cheng
Published: January 2023

Temporal lobe epilepsy (TLE) is the most common type of intractable epilepsy in adults. Although brain myelination alterations have been observed in TLE, it remains unclear how the myelination network changes in TLE. This study developed a novel method in characterization of myelination structural covariance network (mSCN) by T1‐weighted and T2‐weighted magnetic resonance imaging (MRI). The mSCNs were estimated in 42 left TLE (LTLE), 42 right TLE (RTLE) patients, and 41 healthy controls (HCs). The topology of mSCN was analyzed by graph theory. Voxel‐wise comparisons of myelination laterality were also examined among the three groups. Compared to HC, both patient groups showed decreased myelination in frontotemporal regions, amygdala, and thalamus; however, the LTLE showed lower myelination in left medial temporal regions than RTLE. Moreover, the LTLE exhibited decreased global efficiency compared with HC and more increased connections than RTLE. The laterality in putamen was differently altered between the two patient groups: higher laterality at posterior putamen in LTLE and higher laterality at anterior putamen in RTLE. The putamen may play a transfer station role in damage spreading induced by epileptic seizures from the hippocampus. This study provided a novel workflow by combination of T1‐weighted and T2‐weighted MRI to investigate in vivo the myelin‐related microstructural feature in epileptic patients first time. Disconnections of mSCN implicate that TLE is a system disorder with widespread disruptions at regional and network levels.
Ischemic stroke on SARS‐CoV2 vasculitis in a healthy young girl
Authors: Petat Hortense , Hassani Adnan , Dabaj Ivana , Tzaroukian Lucile , Goujard Barbara , Michelet Isabelle , More Rebecca
Published: January 2023

Background and Aims

In France, we noted the fifth wave of SARS‐CoV2 pandemic, characterized by presence of Omicron variant. This variant is very contagious, but less often aggressive, especially in pediatric population.

Methods

We report a case of a 10‐year‐old girl, previously healthy, not yet vaccinated for SARS‐CoV2, presented to our emergency department for left hemiparesis associated with headache and vomiting, without any signs of respiratory tract infection.

Results

Cerebral CT and MRI showed an ischemic stroke of right sylvian artery. Magnetic resonance angiography performed upon resurgence of new symptoms was in favor of vasculitis on the right internal carotid and right sylvian artery. PCR SARS‐CoV2 was positive for Omicron variant. She fully recovered after few days and was treated with acetylsalicylic acid and intravenous corticosteroids.

Conclusion

We report this case to raise awareness on the possible complications related to SARS‐CoV2 infection and we highly recommend vaccination in this age group.
Potential clinical benefits of warfarin in end‐stage cancers: A retrospective analysis
Authors: Imataki Osamu , Arai Takeshi , Uemura Makiko
Published: January 2023

Background and Aims

Coagulopathy and thromboembolism are common comorbidities in cancer, and anticoagulants, such as warfarin, are needed in specific situations. This study aimed to determine the clinical relevance of prothrombin time (PT) monitoring and the clinical usefulness of warfarin in patients with malignancy.

Methods

We retrospectively investigated patients with PT lower than 10% treated in our hospital between April 2006 and March 2013. Cases of false coagulopathy, including those due to technical errors during blood sampling, were excluded. The cause of coagulopathy was determined or estimated by physicians.

Results

This study included 338 cases comprising 155 females and 183 males with a median age was 68 (0–97) years. Among them, 89 (26.3%) had cancer, and 163 (48.2%) received warfarin at a median dose of 2.23 (0.5–8.0) mg/day. PT prolongation caused by warfarin overdose and malignancy exacerbation were observed in 75 (22.2%) and 64 (18.9%) patients, respectively. The leading reasons for warfarin administration were arterial fibrillation, chronic heart failure, and deep vein thrombosis. Univariate analysis revealed that the overall survival was higher in the warfarin and nononcology groups than in the nonwarfarin and oncology groups (both p < 0.001). In multivariate analysis, survival was significantly decreased in older adults (p = 0.049), those with malignancy (p < 0.001), and those without warfarin therapy (p < 0.001). Early mortality (within 3 days after PT prolongation) was observed in 65 patients and was mostly related to emergent diseases (36.9%, 24/65) and end‐stage malignancy (32.3%, 21/65).

Conclusion

Patients with malignancy may experience subclinical PT prolongation upon disease progression. Warfarin treatment mitigates panic PT values in patients with malignancy. Conversely, those not treated with warfarin have poor survival, suggesting that coagulopathy without warfarin treatment can lead to death. Warfarin enhances hemostatic conditions, thereby preventing malignancy‐related lethal hemorrhagic or thromboembolic events.
Managing an extension of screening intervals: Avoiding boom and bust in health care workloads
Authors: Pesola Francesca , Rebolj Matejka , Sasieni Peter
Published: January 2023

Extending screening intervals in ongoing cancer screening programmes can lead to challenging year‐on‐year variations in the number of screening tests. We explored how such variation could be diminished with a managed transition to the extended interval. We defined three extension scenarios: immediate extension for the entire target population; stepped transition by birth cohort; and gradual transition by reducing the number of available screening appointments. These were compared to a situation in which the interval remains unchanged in a demographic model covering a 15‐year period. The model was populated with observed parameters from England, a real‐world setting recommending cervical screening with 3‐year intervals at age 25‐49 and 5‐year intervals at age 50‐64. Informed by typical changes currently considered by several European programmes including the programme in England, we explored the effect on screening test numbers of an extension of the 3‐year interval to 5 years for women younger than 50. All three extension scenarios resulted in similar cumulative numbers of screening tests, which were about 30% lower compared to a situation in which the interval would remain unchanged. However, the year‐on‐year variation in the number of screening tests varied between the scenarios. This variation was around 4‐fold for the immediate scenario. In the stepped scenario, the yearly numbers could differ by around 20%, whereas in the gradual scenario they were virtually constant. A managed interval extension, transitioning different groups of the target population at different times, can substantially reduce the yearly variation in screening workload without increasing the total number of screening tests in the long term.