bluuebunny/crossref_metadata_2025 huggingface dataset:
Interrelations between relief, vegetation, disturbances, and permafrost in the forest‐steppe of central Mongolia
Authors: Klinge Michael , Schneider Florian , Dulamsuren Choimaa , Arndt Kim , Bayarsaikhan Uudus , Sauer Daniela
Published: March 2021

In semi‐arid central Asia, relief has a strong impact on the distribution of vegetation and discontinuous permafrost. Our aim was to analyse causal chains and inter‐relationships that control the spatial patterns of forest and permafrost in the forest‐steppe of the northern Khangai Mountains in Mongolia. For this purpose, we conducted soil‐profile descriptions, ground‐penetrating radar sounding, and vegetation mapping to gain information about forest and permafrost distribution. We integrated remote‐sensing analysis and field‐mapping data, including soil properties, vegetation cover, forest fires and anthropogenic forest use. We developed and applied a technique for spatial delineation of permafrost distribution, based on the parameters Topographic Wetness Index (TWI), incoming solar radiation and Normalized Difference Vegetation Index (NDVI). Key outcomes of this study are that the occurrence of discontinuous permafrost within 1 m depth is limited to forest stands larger than 100 ha on north‐facing slopes. Dense ground vegetation supports permafrost, whereas sandy soil texture leads to greater depth of the permafrost table. As the seasonal ice in the active layer progressively melts down during summer, meltwater interflow above the permafrost table provides additional soil moisture downslope. This process is reflected in enhanced vitality of the steppe vegetation on toe slopes below forests with permafrost. This effect can in turn be used to indirectly detect permafrost in forest stands by remote sensing. Permafrost mostly disappears after forest fires and other severe disturbances, but it may re‐establish during forest regrowth. However, climate warming is presently leading to a loss of permafrost regeneration potential after disturbance, and to a shift from climate‐induced and ecosystem‐driven permafrost to entirely ecosystem‐protected permafrost. These trends will result in a further decrease of permafrost area after forest disturbance.
Spectral efficiency analysis for massive MIMO orthogonal frequency division multiplexing and filter bank multicarrier in a realistic scenario using signal‐to‐noise‐and‐distortion ratio and interpolation for different modulation coding schemes
Authors: Jose Felipe Kurpiel , Assumpção Lolis Luis Henrique , Mafra Samuel Baraldi , Parente Ribeiro Eduardo
Published: March 2021

The study investigates the self‐equalization effect and its impact on the spectral efficiency (SE) analysis in a massive multiple‐input multiple‐output (MIMO) scenario for 5G wireless networks for filter bank multicarrier (FBMC) and orthogonal frequency division multiplexing (OFDM) modulations. For that the SNR adopted in previous studies is compared to the inverse of the mean squared error (MSE) for multiple users in a single cell environment. In order to incorporate other distortions not correlated to the signal, this work uses the inverse of the MSE as the signal‐to‐noise‐and‐distortion ratio (SNDR) and, that metric is adopted for SE calculation in massive MIMO (MM) uplink setup. Throughout the article, the importance of considering this metric for the SE analysis of the MM system will be noticeable. Previous works dealing with MM focus on the case when the number of antennas is so much higher than the number of users that specific conditions could be applied, however, it was shown throughout this study that some of those assumptions could represent an imprecision, especially for the case when the ratio between the number of antennas and the number of users is less expressive.
Germline sequence analysis of RABL3 in a large series of pancreatic ductal adenocarcinoma patients reveals no evidence of deleterious variants
Authors: Roberts Nicholas J. , Grant Robert C. , Gallinger Steven , Klein Alison P. ,   the Familial Pancreatic Cancer Genome Sequencing Project
Published: March 2021

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with a 5‐year survival rate of less than 10%. Individuals with a pathogenic germline variant in a pancreatic cancer susceptibility gene are at an increased risk of developing pancreatic cancer. Understanding the inherited genetic basis of pancreatic tumor development provides a unique opportunity to improve patient care and outcomes. For example, relatives of a patients with PDAC who have a pathogenic germline variant in a pancreatic cancer susceptibility gene are eligible for disease surveillance where cancers may be detected early, and 5‐year survival greatly improved. Furthermore, for some patients with PDAC and a pathogenic germline variant in a pancreatic cancer susceptibility gene, their tumors may be susceptible to specific anti‐cancer therapies. Recently, RABL3 was identified as a pancreatic cancer susceptibility gene. To validate these findings and inform clinical translation, we determined the prevalence of deleterious RABL3 variants in a large cohort of 1037 patients with PDAC that had undergone either whole genome or whole exome germline sequencing. We identified two synonymous variants and four missense variants classified as variants of unknown significance. We found no pathogenic RABL3 variants, indicating that the maximum prevalence of such variants in patients with PDAC is less than 0.36% (minor allele frequency 0, 97.5% one‐sided confidence interval: 0‐0.0036). This finding has important implications for germline genetic testing of patients with PDAC.
Thematic quality assessment of land surface geospatial data based on confusion matrices: A matrix set for research on measures and procedures
Authors: Ariza‐López Francisco J. , García‐Balboa José L. , Alba‐Fernández María V. , Rodríguez‐Avi José
Published: March 2021

The confusion matrix has long been adopted as the ‘de facto’ and ‘de jure’ standard method of reporting on the thematic accuracy assessment of any land surface geospatial dataset. This type of data supports decision‐making in many different fields, so suitable quality is therefore essential in order to take the best decisions. Nevertheless, the creation and exploitation of the confusion matrix remains as an open topic with issues related to sampling design, quantitative indices derived from the matrix, statistical hypotheses that could be applied, etc. In connection with the latter, a confusion matrix dataset would be useful for a researcher in this matter. We have developed such a dataset retrieving confusion matrices from the literature, mainly research articles published in scientific journals included in WoS. We have collected almost 200 matrices in a database. This allows us to access the complete matrices and query different interesting properties of them and of the project where they were developed such as matrix size, sample size, location, year of data capture, labels of the classes, quality indices used, and extension and location of the project (where available).
Sparse deep neural networks on imaging genetics for schizophrenia case–control classification
Authors: Chen Jiayu , Li Xiang , Calhoun Vince D. , Turner Jessica A. , van Erp Theo G. M. , Wang Lei , Andreassen Ole A. , Agartz Ingrid , Westlye Lars T. , Jönsson Erik , Ford Judith M. , Mathalon Daniel H. , Macciardi Fabio , O'Leary Daniel S. , Liu Jingyu , Ji Shihao
Published: March 2021

Deep learning methods hold strong promise for identifying biomarkers for clinical application. However, current approaches for psychiatric classification or prediction do not allow direct interpretation of original features. In the present study, we introduce a sparse deep neural network (DNN) approach to identify sparse and interpretable features for schizophrenia (SZ) case–control classification. An L0‐norm regularization is implemented on the input layer of the network for sparse feature selection, which can later be interpreted based on importance weights. We applied the proposed approach on a large multi‐study cohort with gray matter volume (GMV) and single nucleotide polymorphism (SNP) data for SZ classification. A total of 634 individuals served as training samples, and the classification model was evaluated for generalizability on three independent datasets of different scanning protocols (N = 394, 255, and 160, respectively). We examined the classification power of pure GMV features, as well as combined GMV and SNP features. Empirical experiments demonstrated that sparse DNN slightly outperformed independent component analysis + support vector machine (ICA + SVM) framework, and more effectively fused GMV and SNP features for SZ discrimination, with an average error rate of 28.98% on external data. The importance weights suggested that the DNN model prioritized to select frontal and superior temporal gyrus for SZ classification with high sparsity, with parietal regions further included with lower sparsity, echoing previous literature. The results validate the application of the proposed approach to SZ classification, and promise extended utility on other data modalities and traits which ultimately may result in clinically useful tools.
Improving the sensitivity of cluster‐based statistics for functional magnetic resonance imaging data
Authors: Geerligs Linda , Maris Eric
Published: March 2021

Because of the high dimensionality of neuroimaging data, identifying a statistical test that is both valid and maximally sensitive is an important challenge. Here, we present a combination of two approaches for functional magnetic resonance imaging (fMRI) data analysis that together result in substantial improvements of the sensitivity of cluster‐based statistics. The first approach is to create novel cluster definitions that optimize sensitivity to plausible effect patterns. The second is to adopt a new approach to combine test statistics with different sensitivity profiles, which we call the min(p) method. These innovations are made possible by using the randomization inference framework. In this article, we report on a set of simulations and analyses of real task fMRI data that demonstrate (a) that the proposed methods control the false‐alarm rate, (b) that the sensitivity profiles of cluster‐based test statistics vary depending on the cluster defining thresholds and cluster definitions, and (c) that the min(p) method for combining these test statistics results in a drastic increase of sensitivity (up to fivefold), compared to existing fMRI analysis methods. This increase in sensitivity is not at the expense of the spatial specificity of the inference.
Glycemic Control Predicts Severity of Hepatocyte Ballooning and Hepatic Fibrosis in Nonalcoholic Fatty Liver Disease
Authors: Alexopoulos Anastasia‐Stefania , Crowley Matthew J. , Wang Ying , Moylan Cynthia A. , Guy Cynthia D. , Henao Ricardo , Piercy Dawn L. , Seymour Keri A. , Sudan Ranjan , Portenier Dana D. , Diehl Anna Mae , Coviello Andrea D. , Abdelmalek Manal F.
Published: March 2021

Background and Aims

Whether glycemic control, as opposed to diabetes status, is associated with the severity of NAFLD is open for study. We aimed to evaluate whether degree of glycemic control in the years preceding liver biopsy predicts the histological severity of NASH.

Approach and Results

Using the Duke NAFLD Clinical Database, we examined patients with biopsy‐proven NAFLD/NASH (n = 713) and the association of liver injury with glycemic control as measured by hemoglobin A1c (HbA1c). The study cohort was predominantly female (59%) and White (84%) with median (interquartile range) age of 50 (42, 58) years; 49% had diabetes (n = 348). Generalized linear regression models adjusted for age, sex, race, diabetes, body mass index, and hyperlipidemia were used to assess the association between mean HbA1c over the year preceding liver biopsy and severity of histological features of NAFLD/NASH. Histological features were graded and staged according to the NASH Clinical Research Network system. Group‐based trajectory analysis was used to examine patients with at least three HbA1c (n = 298) measures over 5 years preceding clinically indicated liver biopsy. Higher mean HbA1c was associated with higher grade of steatosis and ballooned hepatocytes, but not lobular inflammation. Every 1% increase in mean HbA1c was associated with 15% higher odds of increased fibrosis stage (OR, 1.15; 95% CI, 1.01, 1.31). As compared with good glycemic control, moderate control was significantly associated with increased severity of ballooned hepatocytes (OR, 1.74; 95% CI, 1.01, 3.01; P = 0.048) and hepatic fibrosis (HF; OR, 4.59; 95% CI, 2.33, 9.06; P < 0.01).

Conclusions

Glycemic control predicts severity of ballooned hepatocytes and HF in NAFLD/NASH, and thus optimizing glycemic control may be a means of modifying risk of NASH‐related fibrosis progression.
Identification of a MicroRNA-E3 Ubiquitin Ligase Regulatory Network for Hepatocyte Death in Alcohol-Associated Hepatitis
Authors: Fan Xiude , Wu Jianguo , Poulsen Kyle L. , Kim Adam , Wu Xiaoqin , Huang Emily , Miyata Tatsunori , Sanz-Garcia Carlos , Nagy Laura E.
Published: March 2021

We aimed to identify a microRNA (miRNA)-E3 ubiquitin ligase regulatory network for protein substrates enriched in cell death pathways and investigate the underlying molecular mechanisms in alcohol-associated hepatitis (AH). An miRNA-E3 ubiquitin ligase regulatory network for protein substrates enriched in cell death pathways was constructed using integrated bioinformatics analysis. Differentially expressed hub miRNAs (GSE59492) and their validated miRNA target genes (GSE28619) were identified in the liver of patients with AH compared with healthy controls. Liver samples from patients with AH and healthy individuals and mice exposed to Gao-binge (acute on chronic) ethanol were used for experimental validation. Using hub miRNAs identified by weighted correlation network analysis, a miRNA-E3 ubiquitin ligase regulatory network was established based on 17 miRNAs and 7 E3 ligase genes targeted by these miRNAs that were down-regulated in AH. Among the miRNAs in this regulatory network, miR-150-5p was the only miRNA regulating the E3 ligase cytokine-inducible SH2 containing protein (CISH), the E3 ligase that regulates the largest number of substrates among all E3 ligase family members. Therefore, the CISH regulatory pathway for ubiquitinated substrates was selected for subsequent experimental validation. Consistent with the bioinformatics analysis results, expression of miR-150-5p was markedly increased, while CISH was decreased, in the livers of patients with AH and mice exposed to Gao-binge ethanol. Moreover, ubiquitination of Fas-associated protein with death domain, a predicted CISH substrate involved in the regulation of programmed cell death, was reduced in livers from mice after Gao-binge ethanol. Conclusion: Identification of the miRNA-E3 ubiquitin ligase regulatory network for protein substrates enriched in the cell death pathways provides insights into the molecular mechanisms contributing to hepatocyte death in AH.

This study identifies a microRNA-E3 ubiquitin ligase regulatory network for protein substrates enriched in cell death pathways. We report that expression of miR-150-5p was elevated in AH and experimentally verified the changes in the key components in this miR-150-5p-CISH-FADD regulatory network in the liver from both patients with AH and a murine model of acute-on-chronic ethanol exposure.
STE20‐Type Protein Kinase MST4 Controls NAFLD Progression by Regulating Lipid Droplet Dynamics and Metabolic Stress in Hepatocytes
Authors: Caputo Mara , Cansby Emmelie , Kumari Sima , Kurhe Yeshwant , Nair Syam , Ståhlman Marcus , Kulkarni Nagaraj M. , Borén Jan , Marschall Hanns‐Ulrich , Blüher Matthias , Mahlapuu Margit
Published: March 2021

Nonalcoholic fatty liver disease (NAFLD) has emerged as a leading cause of chronic liver disease worldwide, primarily because of the massive global increase in obesity. Despite intense research efforts in this field, the factors that govern the initiation and subsequent progression of NAFLD are poorly understood, which hampers the development of diagnostic tools and effective therapies in this area of high unmet medical need. Here we describe a regulator in molecular pathogenesis of NAFLD: STE20‐type protein kinase MST4. We found that MST4 expression in human liver biopsies was positively correlated with the key features of NAFLD (i.e., hepatic steatosis, lobular inflammation, and hepatocellular ballooning). Furthermore, the silencing of MST4 attenuated lipid accumulation in human hepatocytes by stimulating β‐oxidation and triacylglycerol secretion, while inhibiting fatty acid influx and lipid synthesis. Conversely, overexpression of MST4 in human hepatocytes exacerbated fat deposition by suppressing mitochondrial fatty acid oxidation and triacylglycerol efflux, while enhancing lipogenesis. In parallel to these reciprocal alterations in lipid storage, we detected substantially decreased or aggravated oxidative/endoplasmic reticulum stress in human hepatocytes with reduced or increased MST4 levels, respectively. Interestingly, MST4 protein was predominantly associated with intracellular lipid droplets in both human and rodent hepatocytes. Conclusion: Together, our results suggest that hepatic lipid droplet–decorating protein MST4 is a critical regulatory node governing susceptibility to NAFLD and warrant future investigations to address the therapeutic potential of MST4 antagonism as a strategy to prevent or mitigate the development and aggravation of this disease.
Plateau is a prognostic factor of lenalidomide therapy for previously treated multiple myeloma
Authors: Takakuwa Teruhito , Ohta Kensuke , Nakatani Eiji , Ito Tomoki , Kaneko Hitomi , Fuchida Shin‐Ichi , Shimura Yuji , Yagi Hideo , Shibayama Hirohiko , Kanda Junya , Uchiyama Hitoji , Kosugi Satoru , Tanaka Hirokazu , Kawata Eri , Uoshima Nobuhiko , Ishikawa Jun , Shibano Masaru , Karasuno Takahiro , Shindo Maki , Shimizu Yoshifumi , Imada Kazunori , Kanakura Yuzuru , Kuroda Junya , Hino Masayuki , Nomura Shosaku , Takaori‐Kondo Akifumi , Shimazaki Chihiro , Matsumura Itaru
Published: March 2021

The plateau phase emerging during the treatment of multiple myeloma (MM) is known to last steadily for a certain period, even without treatment. Therefore, the treatment started at plateau phase is expected to be associated with a better outcome. In this study, this hypothesis was evaluated retrospectively for previously treated MM patients in Kansai Myeloma Forum database who received lenalidomide (LEN) with or without dexamethasone for the first time. Disease stability index (DSI) was defined as (maximum – minimum values of M protein during the 90 days before the start of LEN) divided by M‐protein values at the start of LEN. The patients were classified into three groups: stable (S), DSI ≤ 0.25; increasing (I), DSI > 0.25 with increasing M protein; decreasing (D), DSI > 0.25 with decreasing M protein. In univariate analysis of 352 patients, DSI group "I", non‐IgG type, serum albumin<3.5 g/dL, and age≥70 were statistically significant prognostic factors for both progression‐free survival and overall survival. In multivariate analysis, the former 3 risk factors were statistically significant for poor overall survival. Thus, DSI is an independent prognostic factor for the treatment with LEN for previously treated MM.
Diagnostic accuracy of the Gaussian first‐trimester combined screening for pre‐eclampsia to predict small‐for‐gestational‐age neonates
Authors: Mendoza Manel , Serrano Berta , Bonacina Erika , Capote Sira , Garcia‐Manau Pablo , Regincós Laia , Murcia Maria Teresa , Barberan Lidia , Míguez Marta , Carreras Elena
Published: March 2021

Objective

Pre‐eclampsia and delivery of small‐for‐gestational‐age (SGA) neonates can be predicted from the first trimester. A Gaussian model for prediction of PE has recently been described, although its capacity to predict SGA is still unknown.

Methods

This was a secondary analysis of a prospective cohort study conducted at Vall d’Hebron University Hospital (Barcelona) in 2483 single pregnancies from October 2015 to September 2017. Mean arterial blood pressure and mean uterine artery pulsatility index were recorded at the first‐trimester scan. Serum concentrations of placental growth factor and pregnancy‐associated plasma protein‐A were assessed between 8+0 and 13+6 weeks. The predictive capacities of early (<32 weeks) and preterm (<37 weeks) SGA were tested.

Results

For SGA without pre‐eclampsia, detection rates of 25.0% (95% confidence interval [CI] 0–75.0) for early SGA and 14.3% (95% CI 3.6–28.6) for preterm SGA were achieved. For SGA with pre‐eclampsia, the algorithm showed detection rates of 100.0% (95% CI 25.0–100.0) for early SGA and 56.3% (95% CI 31.3–81.3) for preterm SGA.

Conclusion

This algorithm identifies 62.5% of early SGA and 27.3% of preterm SGA. Combined screening for predicting both pre‐eclampsia and SGA by using the Gaussian algorithm is feasible and would simplify clinical practice.
Exploring the intergroup consequences of majority members' perceptions that minority members want majority members to adopt the minority culture
Authors: Moftizadeh Nali , Zagefka Hanna , López‐Rodríguez Lucía , Vázquez Alexandra , Barn Ravinder
Published: March 2021

There remains an obvious gap in the acculturation literature, which relates to cultural change associated with the majority/dominant group. This paper explores how majority members react to a perceived expectation from minority members that majority members should undergo cultural change. A study was conducted exploring how majority members' perceptions of a demand by minority members that the majority should adopt the minority culture affects the majority members' preferences for minority acculturation, and whether effects are mediated by perceptions of symbolic threat. Two hundred sixty‐six participants who self‐reported being white British completed an online survey. A model was hypothesized whereby a perception that minority members demand that the majority takes on the minority culture predicted perceived symbolic threat, which was in turn negatively associated with a desire that minority members should maintain the minority culture, and positively with a desire that minority members should adopt the majority culture. Results supported the hypothesized model, with all individual paths and indirect effects significant in the hypothesized directions. Symbolic threat mediated the effect of perceived demand for minority culture adoption on majority preferences for minority acculturation. Findings are discussed in relation to implications for intergroup relations in culturally plural societies.
Network slicing for 5G edge services
Authors: Kourtis Michail‐Alexandros , Sarlas Thanos , Anagnostopoulos Themis , Kukliński Sławomir , Tomaszewski Lechosław , Wierzbicki Michał , Oikonomakis Andreas , Xilouris George , Chochliouros Ioannis P. , Yi Na , Kostopoulos Alexandros , Koumaras Harilaos
Published: March 2021

In the current 5G technology domain network slicing already plays an important role as a critical enabler. An industry that 5G aims to disrupt is the vehicular one. In this paper the brief scope of the 5G‐DRIVE research project is presented, regarding 5G vehicular research between the EU and China. In the frame of 5G‐DRIVE a set of slicing mechanisms are investigated and evaluated in regard to their performance. Firstly, related to slicing mechanisms in the NFV domain the OSM orchestrator is measured in terms of scalability and performance. In the next experimental set related to RAN slicing, the Katana Slice Manager is evaluated and depicts how different slicing configurations can achieve different performance results. Furthermore, the paper showcases how 5G network slicing can be integrated as a key enabler to the stringent demands of a vehicular network environment. Finally, the paper concludes, setting future directions in the related field.
Role of a cysteine residue in substrate entry and catalysis inMtHIBADH: Analysis by chemical modifications and site‐directed mutagenesis
Authors: Singh Amrita , Badepally Nagendar Goud , Surolia Avadhesha
Published: March 2021

Despite sharing conserved substrate‐binding residues, members of 3‐hydroxyisobutyrate dehydrogenase (HIBADH) superfamily show remarkable differences in substrate preference. Cysteine residues were identified within a radius of 6 Å surrounding both the active site and the substrate entry site of HIBADH enzyme fromMycobacterium tuberculosis(MtHIBADH). Chemical modification with thiol‐modifying reagents, pCMB and DTNB, abrogated the dehydrogenase activity of the enzyme. The loss in activity followed pseudo‐first‐order kinetics as a function of the concentration of pCMB. S‐HIBA (substrate) binding provided partial protection, while NAD (cofactor) binding provided ~70% protection from thiol‐modifying reagent. Site‐directed mutagenesis of cysteine residues present in the MtHIBADH enzyme identified the indispensable role of Cys‐210 residue, located at C‐terminal domain, for its dehydrogenase activity. Cys‐210 mutation to serine reduced the dehydrogenase activity by ~2‐fold while mutation to alanine strikingly reduced the activity by ~140‐fold. C210A mutation did not perturb the state of oligomerization of the enzyme but perturbed the secondary structure content. Structural analysis revealed the involvement of Cys‐210 residue in inter‐chain interaction with Gln‐178, which acts as hydrogen bond donor and coordinates with Cys‐210 and Gly‐208 of the adjacent subunit. The data demonstrate a critical role of Cys‐210 residue in maintaining the conformation and rigidity of loop composed of substrate‐interacting residues involved in the entry of S‐HIBA substrate in MtHIBADH.
Chronic Nonbacterial Osteomyelitis of the Sternocostoclavicular Region in Adults: A Single‐Center Dutch Cohort Study
Authors: Ramautar Ashna IE , Appelman‐Dijkstra Natasha M , Lakerveld Shannon , Schroijen Marielle A , Snel Marieke , Winter Elizabeth M , Hamdy Neveen AT
Published: March 2021

Sternocostoclavicular hyperostosis (SCCH) is a rare autoinflammatory bone disorder caused by chronic nonbacterial osteomyelitis (CNO), which is associated with sclerosis and hyperostosis primarily affecting the sternum, the medial end of the clavicles, and the first ribs. Other areas of the axial skeleton may also be affected. The more severe synovitis–acne–pustulosis–hyperostosis–osteitis (SAPHO) syndrome is additionally associated with dermatoses and joint manifestations. This Dutch retrospective cross‐sectional single‐center cohort study characterizes the spectrum of clinical features in adult CNO/SCCH patients at the time of diagnosis. The only inclusion criteria was the availability of complete sets of clinical and imaging data systematically collected over three decades using in‐house protocols. Data from 213 predominantly female patients (88%) with a median age of 36 years at presentation were studied. The mean diagnostic delay was 5 ± 5 years. The main symptoms were chronic pain (92%), bony swelling (61%), and restricted shoulder girdle function (46%); 32% had palmoplantar pustulosis and 22% had autoimmune disease. The majority (73%) had isolated SCCH; 59 (27%) had additional localizations in vertebrae (19%), the mandible (9%), or both (2%); 4 had SAPHO. The prevalence of current or past smoking was high (58%), particularly for patients with palmoplantar pustulosis (76%). There was a significant relationship between delay in diagnosis and both the extent of affected skeletal sites (p = 0.036) and erythrocyte sedimentation rate levels (p = 0.023). Adult‐onset CNO is characterized by distinctive clinical and radiological features, but diverse aspects of its spectrum are currently not fully captured by a comprehensive classification. Delayed diagnosis is still common and potentially associated with irreversible structural changes and debilitating chronic symptoms, increasing the burden of illness and negatively impacting on quality of life. It is hoped that findings from this study will dispel confusion about nomenclature and classification of adult‐onset CNO and increase awareness of its distinctive clinical and radiological features, and thus facilitate early diagnosis and referral for treatment, which should positively impact prognosis by preventing disease progression, although this remains to be established. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Phyllanthin inhibits MOLT‐4 leukemic cancer cell growth and induces apoptosis through the inhibition of AKT and JNK signaling pathway
Authors: Wang Hui , Chinnathambi Arunachalam , Alahmadi Tahani Awad , Alharbi Sulaiman Ali , Veeraraghavan Vishnu Priya , Krishna Mohan Surapaneni , Hussain Sardar , Ramamoorthy Kavitha , Rengarajan Thamaraiselvan
Published: March 2021

Among cancers, leukemia is a multistep progression that involves genetic modifications of normal hematopoietic progenitor cells to cancerous cells. In recent times, leukemia cases and their mortality rate have increased rapidly. Therefore, the immense need for a therapeutic approach is crucial that can control this type of cancer. Phyllanthin is a lignan compound constituent from the Phyllanthus species and has numerous beneficial effects as a dietary component. The present study aims to determine the impact of phyllanthin on the MOLT‐4 cytotoxic effect. MOLT‐4 cells and MS‐5 cells were cultured at different concentrations of phyllanthin (5, 10, 25, 50, 75, and 100 μM/ml), and the viability was assessed by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide method. The level of reactive oxygen species, the membrane potential of mitochondria, apoptosis by 2',7'‐dichlorofluorescin‐diacetate (DCF‐DA), rhodamine, acridine orange (AO)/ethidium bromide (EB), 4′,6‐diamidino‐2‐phenylindole (DAPI)/propidium iodide (PI) staining, gene expression of signaling molecules, and protein levels were assessed by reverse‐transcription polymerase chain reaction and western blot analysis. Phyllanthin did not show toxicity toward MS‐5 cells and significantly decreased the cell viability of MOLT‐4 cells with an IC50 value of 25 µM/ml. Also, phyllanthin induced the production of reactive oxygen species and led to the loss of mitochondrial membrane potential. AO/EB and DAPI/PI staining fluorescent image confirmed the induction of apoptosis by phyllanthin treatment. The messenger RNA (mRNA) expression of cell cycle regulator cyclin D1, antiapoptotic gene Bcl‐2, NF‐κB, and TNF‐α decreased, but the proapoptotic Bax mRNA expression was increased. The phosphorylated protein levels of p‐PI3K1/2, p‐ERK1/2, and p‐AKT were decreased, whereas the levels of p‐p38 and p‐JNKT1/2 increased. Our results confirmed that phyllanthin inhibits the MOLT‐4 cells, increases apoptosis, and inhibits MOLT‐4 migration and cell invasion. Therefore, phyllanthin can be used as a potential target for leukemia treatment.
Deodorizing the king of fruits: Durian stalk deodorizes the aroma of durian
Authors: Tan Ke Qi , Lim Zhi Kheng , Fang Esther Zi Hui , Pui Carmen Sze Min , Lv Yunbo , Zhang Hua Jun , Chua Chun Kiang
Published: March 2021

Durian fruit is well‐known for its strong aroma due to the presence of esters and sulfur compounds. Although the usage of durian husk as a deodorizing agent of durian aroma has been a known practice, there is a lack of scientific evidence. Here, we investigated the effect of using durian stalk extract to deodorize durian aroma. Static‐headspace gas chromatography–mass spectrometry technique is used to semi‐quantitatively track the variation of 13 esters and sulfur compounds found in durian. Durian stalk extract reduced the amount of esters and sulfur compounds in headspace up to 45 and 55%, respectively. NaCl, CaCl2, and Na2SO4 provided a similar effect on sulfur compounds. In addition, lemon and ginger extracts were evaluated and the latter performed as well as durian stalk extract. This study has implications for the application of durian husk as a biomass feedstock for the development of plant‐based deodorizers.
Recent advances of carbazole‐based nonfullerene acceptors: Molecular design, optoelectronic properties, and photovoltaic performance in organic solar cells
Authors: Chen Tsung‐Wei , Karapala Vamsi Krishna , Chen Jiun‐Tai , Hsu Chain‐Shu
Published: March 2021

In this review, the properties, performance, advantages, and applications of carbazole‐based nonfullerene acceptors (NFAs) are summarized and categorized by fused‐ring number. The recent advances of carbazole‐based NFAs are depicted with their decent photovoltaic performance, enabled by the versatality of elegant molecular design. These literature precedents sufficiently validate that carbazole can be exploited as a promising building block embedded in functional, high‐performance NFAs. The structure‐to‐performance relation of carbazole‐based NFAs is systematically studied, which is believed to facilitate the development of photovoltaic technology.
The biogenetic law and the Gastraea theory: From Ernst Haeckel's discoveries to contemporary views
Authors: Levit Georgy S. , Hoßfeld Uwe , Naumann Benjamin , Lukas Paul , Olsson Lennart
Published: March 2021

More than 150 years ago, in 1866, Ernst Haeckel published a book in two volumes called Generelle Morphologie der Organismen (General Morphology of Organisms) in the first volume of which he formulated his biogenetic law, famously stating that ontogeny recapitulates phylogeny. Here, we describe Haeckel's original idea as first formulated in the Generelle Morphologie der Organismen and later further developed in other publications until the present situation in which molecular data are used to test the “hourglass model,” which can be seen as a modern version of the biogenetic law. We also tell the story about his discovery, while traveling in Norway, of an unknown organism, Magosphaera planula, that was important in that it helped to precipitate his ideas into what was to become the Gastraea theory. We also follow further development and reformulations of the Gastraea theory by other scientists, notably the Russian school. Elias Metchnikoff developed the Phagocytella hypothesis for the origin of metazoans based on studies of a colonial flagellate. Alexey Zakhvatin focused on deducing the ancestral life cycle and the cell types of the last common ancestor of all metazoans, and Kirill V. Mikhailov recently pursued this line of research further.
Ultrasound irradiation in heterocycle synthesis: An overview
Authors: Saranya Salim , Radhika Sankaran , Afsina Abdulla Cheriya Mukkolakkal , Anilkumar Gopinathan
Published: March 2021

The synthesis of heterocyclic compounds has been a hot topic for several decades. Synthetic organic chemists are always in search of new methodologies which are greener for the synthesis of heterocyclic compounds. The ultrasound‐assisted reactions have contributed much to this field. This review focuses on the impact of sonochemistry in the synthesis of heterocyclic compounds and covers the literature from 2009 to 2020.
Estimating HIV transmissions in a large U.S. clinic‐based sample: effects of time and syndemic conditions
Authors: Satyanarayana Satyanand , Safren Steven A , Rogers Brooke G , Bainter Sierra A , Christopoulos Katerina A , Fredericksen Rob J , Mathews William C , Moore Richard D , Mugavero Michael J , Napravnik Sonia , Carrico Adam W , Mimiaga Matthew J , Mayer Kenneth H , Crane Heidi M
Published: March 2021

Introduction

Little is known about onward HIV transmissions from people living with HIV (PLWH) in care. Antiretroviral therapy (ART) has increased in potency, and treatment as prevention (TasP) is an important component of ending the epidemic. Syndemic theory has informed modelling of HIV risk but has yet to inform modelling of HIV transmissions.

Methods

Data were from 61,198 primary HIV care visits for 14,261 PLWH receiving care through the Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS) at seven United States (U.S.) sites from 2007 to 2017. Patient‐reported outcomes and measures (PROs) of syndemic conditions – depressive symptoms, anxiety symptoms, drug use (opiates, amphetamines, crack/cocaine) and alcohol use – were collected approximately four to six months apart along with sexual behaviours (mean = 4.3 observations). Counts of syndemic conditions, HIV sexual risk group and time in care were modelled to predict estimated HIV transmissions resulting from sexual behaviour and viral suppression status (HIV RNA < 400/mL) using hierarchical linear modelling.

Results

Patients averaged 0.38 estimated HIV transmissions/100 patients/year for all visits with syndemic conditions measured (down from 0.83, first visit). The final multivariate model showed that per 100 patients, each care visit predicted 0.05 fewer estimated transmissions annually (95% confidence interval (CI): 0.03 to 0.06; p < 0.0005). Cisgender women, cisgender heterosexual men and cisgender men of undisclosed sexual orientation had, respectively, 0.47 (95% CI: 0.35 to 0.59; p < 0.0005), 0.34 (95% CI: 0.20 to 0.49; p < 0.0005) and 0.22 (95% CI: 0.09 to 0.35; p < 0.005) fewer estimated HIV transmissions/100 patients/year than cisgender men who have sex with men (MSM). Each within‐patient syndemic condition predicted 0.18 estimated transmissions/100 patients/year (95% CI: 0.12 to 0.24; p < 0.0005). Each between‐syndemic condition predicted 0.23 estimated HIV transmissions/100 patients/year (95% CI: 0.17 to 0.28; p < 0.0005).

Conclusions

Estimated HIV transmissions among PLWH receiving care in well‐resourced U.S. clinical settings varied by HIV sexual risk group and decreased with time in care, highlighting the importance of TasP efforts. Syndemic conditions remained a significant predictor of estimated HIV transmissions notwithstanding the effects of HIV sexual risk group and time in care.
The regulatory role of insulin in energy metabolism and leukocyte functions
Authors: Cruz-Pineda Walter David , Parra-Rojas Isela , Rodríguez-Ruíz Hugo Alberto , Illades-Aguiar Berenice , Matia-García Inés , Garibay-Cerdenares Olga Lilia
Published: March 2021

Insulin is the hormone responsible for maintaining glucose homeostasis in the body, in addition to participating in lipid metabolism, protein synthesis, and the inhibition of gluconeogenesis. These functions are well characterized in the classic organ target cells that are responsible for general energy regulation: the liver, skeletal muscle, and adipose tissue. However, these actions are not restricted to these tissues because insulin has been shown to affect most cells in the body. This review describes the role of insulin in leukocyte signaling pathways, metabolism and functions, and how insulin resistance could affect this signaling and deteriorate leukocyte metabolism and function, in addition to showing evidence that suggests leukocytes may substantially contribute to the development of systemic insulin resistance.
Metallothioneins alter macrophage phenotype and represent novel therapeutic targets for acetaminophen-induced liver injury
Authors: Devisscher Lindsey , Van Campenhout Sanne , Lefere Sander , Raevens Sarah , Tilleman Laurentijn , Van Nieuwerburgh Filip , Van Eeckhoutte Hannelore P , Hoorens Anne , Lynes Michael A , Geerts Anja , Laukens Debby , Van Vlierberghe Hans
Published: March 2021

Acetaminophen (APAP) intoxication is the foremost cause of drug-induced liver failure in developed countries. The only pharmacologic treatment option, N-acetylcysteine (NAC), is not effective for patients who are admitted too late and/or who have excessive liver damage, emphasizing the need for alternative treatment options. APAP intoxication results in hepatocyte death and release of danger signals, which further contribute to liver injury, in part by hepatic monocyte/macrophage infiltration and activation. Metallothionein (MT) 1 and 2 have important danger signaling functions and might represent novel therapeutic targets in APAP overdose. Therefore, we evaluated hepatic MT expression and the effect of anti-MT antibodies on the transcriptional profile of the hepatic macrophage population and liver injury following APAP overdose in mice. Hepatic MT expression was significantly induced in APAP-intoxicated mice and abundantly present in human livers. APAP intoxication in mice resulted in increased serum transaminase levels, extended necrotic regions on liver histology and induced expression of proinflammatory markers, which was significantly less pronounced in mice treated with anti-MT antibodies. Anti-MT antibody therapy attenuated proinflammatory macrophage polarization, as demonstrated by RNA sequencing analyses of isolated liver macrophages and in LPS-stimulated bone marrow-derived macrophages. Importantly, NAC and anti-MT antibodies were equally effective whereas administration of anti-MT antibody in combination with NAC exceeded the efficiency of both monotherapies in APAP-induced liver injury (AILI). We conclude that the neutralization of secreted MTs using a monoclonal antibody is a novel therapeutic strategy as mono- or add-on therapy for AILI. In addition, we provide evidence suggesting that MTs in the extracellular environment are involved in macrophage polarization.
An evaluation of patients with a previous endemic coronavirus infection during the COVID‐19 pandemic
Authors: Otlu Baris , Yakupogullari Yusuf , Tanriverdi Elif S. , Bayindir Yasar
Published: March 2021

Few studies exist on the clinical manifestation of coronavirus disease 2019 (COVID‐19) in patients who previously had a common cold due to an endemic coronavirus (eCoV). In a retrospective scan of the data obtained in our microbiology laboratory, 64 patients who were diagnosed with an eCoV infection between 2016 and 2020 were identified. National COVID‐19 surveillance data showed that four (6.2%) of 64 patients were infected with severe acute respiratory syndrome coronavirus 2 by the end of 2020, while, simultaneously, the COVID‐19 prevalence in the city of Malatya ranged from 7.8% (polymerase chain reaction‐based diagnosis) to 9.2% (total diagnosis). The differences were found statistically significant (6.2% vs. 7.8%, p < .01; 6.2% vs. 9.2%, p < .001). Patient interviews and evaluation of medical records revealed that these four patients did not manifest any severe COVID‐19 symptoms despite their substantial comorbidities, and they did not require hospitalization. Consequently, despite a low number of samples, we determined a lower frequency of COVID‐19 among the patients who had a prior eCoV infection, and the results of this study support the previous findings that people with a prior eCoV infection develop a milder case of COVID‐19. Our results may provide some insights for future studies aiming at vaccine development, but detailed investigations are still required.
Hazard assessment of extreme heat during summer maize growing season in Haihe Plain, China
Authors: Zhang Qi , Han Jiahao , Yang Zaiqiang
Published: March 2021

The characteristics of extreme heat events (EHE) are changing under global warming. A comprehensive assessment of extreme heat hazards is important for a better understanding of extreme heat distribution and agricultural mitigation planning. In the present study, an extreme heat hazard assessment model is defined by its probability and severity. Continuous days and accumulative temperatures are used to describe the severity of EHE. Daily maximum temperature data from 26 stations in the Haihe Plain during 1960–2019 are used to identify EHE during the summer maize growing seasons. This region is the main summer maize planting area and suffers from numerous EHE. Copula functions are used to estimate the joint probability distributions of continuous days and the accumulative temperature of EHE. The fitted probabilities are then used in the hazard assessment model. The results reveal that the most severe extreme heat hazard areas are found in the western Haihe Plain, the frequency, average continuous days and accumulative temperature of EHE are the largest in this area. The extreme heat hazards are decreased to the northeastern coast area. Annual variations in extreme heat hazard show two change points near 1968 and 1996 that divide the research period into three main stages: higher, lower, and higher extreme heat hazard stage. These findings provide a comprehensive view of extreme heat over the Haihe Plain, which can be used for better extreme heat management and agriculture planning.
Transvaginal Color Mapping Ultrasound in the First Trimester Predicts Placenta Accreta Spectrum: A Retrospective Cohort Study
Authors: Yule Casey S. , Lewis Matthew A. , Do Quyen N. , Xi Yin , Happe Sarah K. , Spong Catherine Y. , Twickler Diane M.
Published: March 2021

Objectives

Ultrasound (US) prediction of placenta accreta spectrum (PAS) in the first trimester may be aided by postprocessing mechanisms employing color pixel quantification near the bladder–uterine serosal interface. Our objective was to create a postprocessing algorithm of color images to identify findings associated with PAS and compare quantification to sonologist impression in prospectively obtained cine US images.

Methods

Transverse transvaginal (TV) US color cines obtained in the first trimester as part of a prospective study were reviewed. Investigators blinded to clinical outcomes reviewed anonymized cines that were archived and labeled the bladder–uterine serosal interface. Color pixels within 2 cm of the defined bladder–uterine serosal interface were ascertained using a Python‐based plugin in the Horos open‐source DICOM viewer. A sonologist classified the findings as suspicious for invasion, indeterminate, or normal. Statistical analysis was performed using Wilcoxon rank‐sum test, Cochran‐Armitage trend test, and calculation of receiver‐operating characteristic (ROC) curves.

Results

Fifty‐four studies met inclusion criteria. Of those, six (11%) required hysterectomy with pathologic confirmation of PAS. Women requiring hysterectomy had a significantly higher color Doppler pixel area than those not requiring hysterectomy (P = .0205). A significant trend was identified in the sonologist impression of invasion (P = .0003). ROC's comparing sonologist impression to Doppler color imaging areas were comparable (P = .054).

Conclusions

Color Doppler mapping in the first trimester showed an increase in color pixel area near the bladder–uterine serosal interface in women requiring cesarean hysterectomy with histologically confirmed PAS at time of delivery, compared to women without hysterectomy or pathologic evidence of PAS.