bluuebunny/crossref_metadata_2025 huggingface dataset:
Biomimetic Vision for Zoom Object Detection Based on Improved Vertical Grid Number YOLO Algorithm
Authors: Shen Xinyi , Shi Guolong , Ren Huan , Zhang Wu
Published: May 2022

With the development of bionic computer vision for images processing, researchers have easily obtained high-resolution zoom sensing images. The development of drones equipped with high-definition cameras has greatly increased the sample size and image segmentation and target detection are important links during the process of image information. As biomimetic remote sensing images are usually prone to blur distortion and distortion in the imaging, transmission and processing stages, this paper improves the vertical grid number of the YOLO algorithm. Firstly, the light and shade of a high-resolution zoom sensing image were abstracted, and the grey-level cooccurrence matrix extracted feature parameters to quantitatively describe the texture characteristics of the zoom sensing image. The Simple Linear Iterative Clustering (SLIC) superpixel segmentation method was used to achieve the segmentation of light/dark scenes, and the saliency area was obtained. Secondly, a high-resolution zoom sensing image model for segmenting light and dark scenes was established to made the dataset meet the recognition standard. Due to the refraction of the light passing through the lens and other factors, the difference of the contour boundary light and dark value between the target pixel and the background pixel would make it difficult to detect the target, and the pixels of the main part of the separated image would be sharper for edge detection. Thirdly, a YOLO algorithm with an improved vertical grid number was proposed to detect the target in real time on the processed superpixel image array. The adjusted aspect ratio of the target in the remote sensing image modified the number of vertical grids in the YOLO network structure by using 20 convolutional layers and five maximum aggregation layers, which was more accurately adapted to “short and coarse” of the identified object in the information density. Finally, through comparison with the improved algorithm and other mainstream algorithms in different environments, the test results on the aid dataset showed that in the target detection of high spatial resolution zoom sensing images, the algorithm in this paper showed higher accuracy than the YOLO algorithm and had real-time performance and detection accuracy.
Surface Functionalization of SBA-15 for Immobilization of Myoglobin
Authors: Miao Hengmin , Li Maosheng , Wang Fang , Li Jiao , Lin Ying-Wu , Xu Jiakun
Published: May 2022

Mesoporous molecular sieve SBA-15 was successfully modified with 3-aminopropyltriethoxysilane (APTES) and 3-glycidyloxypropyltrimethoxysilane (GPTMS). The functionalized SBA-15 were characterized by small-angle X-ray (SAXRD), thermogravimetric analysis (TG), N2 adsorption, and Fourier transformed infrared spectrum (FT-IR). APTES functionalized SBA-15 (named SBA-15-A) and GPTMS functionalized SBA-15 (named SBA-15-G) were used to immobilize myoglobin (Mb). The loading amounts of Mb by SBA-15-A and SBA-15-G were 511.2 and 547.8 mg/g, respectively, whereas only 359.6 mg/g was achieved by SBA-15. Mb/SBA-15-G and Mb/SBA-15-A demonstrated better reusability than SBA-15, retaining 84.6% and 82.7% of the initial activity after repeated use seven times. The Mb/SBA-15-A and Mb/SBA-15-G also exhibited improved thermal stability and storage stability.
Stimulation of Cardiomyocyte Proliferation Is Dependent on Species and Level of Maturation
Authors: Yücel Dogacan , Garay Bayardo I. , Perlingeiro Rita C. R. , van Berlo Jop H.
Published: May 2022

The heart is one of the least regenerative organs. This is in large part due to the inability of adult mammalian cardiomyocytes to proliferate and divide. In recent years, a number of small molecules and molecular targets have been identified to stimulate cardiomyocyte proliferation, including p38 inhibition, YAP-Tead activation, fibroblast growth factor 1 and Neuregulin 1. Despite these exciting initial findings, a therapeutic approach to enhance cardiomyocyte proliferation in vivo is still lacking. We hypothesized that a more comprehensive in vitro validation using live-cell imaging and assessment of the proliferative effects on various cardiomyocyte sources might identify the most potent proliferative stimuli. Here, we used previously published stimuli to determine their proliferative effect on cardiomyocytes from different species and isolated from different developmental timepoints. Although all stimuli enhanced DNA synthesis and Histone H3 phosphorylation in neonatal rat ventricular cardiomyocytes to similar degrees, these effects varied substantially in mouse cardiomyocytes and human iPSC-derived cardiomyocytes. Our results highlight p21 inhibition and Yap-Tead activation as potent proliferative strategies to induce cultured cardiomyocyte cell cycle activity across mouse, rat and human cardiomyocytes.
LC3-Mediated Mitophagy After CCCP or Vibrio splendidus Exposure in the Pacific Oyster Crassostrea gigas
Authors: Sun Jiejie , Lv Xiaoqian , Leng Jinyuan , Wang Lingling , Song Linsheng
Published: May 2022

Mitochondrial selective autophagy, known as mitophagy, surveils the mitochondrial population by eliminating superfluous and/or impaired organelles to mediate cellular survival and viability in response to injury/trauma and infection. In this study, the components of the mitophagy pathway in the Pacific oyster Crassostrea gigas were screened from NCBI with reference to the protein sequences of the human mitophagy process. A total of 10 mitophagy process–related genes were identified from C. gigas, including NIX, FUNDC1, PHB2, Cardiolipin, P62, VDAC2, MFN2, PARL, MPP, and OPTN. They shared high similarities with their homologs in the human mitophagy pathway and were expressed in various tissues of C. gigas. After CCCP exposure, the fluorescence intensity of the mitochondrial probe JC-1 monomers increased significantly in hemocytes, while the fluorescence intensity of JC-1 aggregates decreased significantly. Meanwhile, the fluorescence of lysosomes was found to be co-localized with that of CgLC3 and mitochondria in CCCP-treated hemocytes. Double- and single-membrane-bound vacuoles resembling autophagic structures were observed in the hemocytes after CCCP exposure. The fluorescence intensity of JC-1 monomers and the abundance of CgLC3Ⅱ in hemocytes both increased after Vibrio splendidus exposure. At the same time, the green signals of CgLC3 were co-localized with red signals of the mitochondria, and the fluorescence intensity of autophagy increased significantly in hemocytes after V. splendidus exposure. The results confirmed the existence of a complete mitophagy pathway in mollusks for the first time, which was helpful for further study on the function of mitochondrial autophagy in mollusks.
Prime Real Estate: Metals, Cofactors and MICOS
Authors: Medlock Amy E. , Hixon J. Catrice , Bhuiyan Tawhid , Cobine Paul A.
Published: May 2022

Metals are key elements for the survival and normal development of humans but can also be toxic to cells when mishandled. In fact, even mild disruption of metal homeostasis causes a wide array of disorders. Many of the metals essential to normal physiology are required in mitochondria for enzymatic activities and for the formation of essential cofactors. Copper is required as a cofactor in the terminal electron transport chain complex cytochrome c oxidase, iron is required for the for the formation of iron-sulfur (Fe-S) clusters and heme, manganese is required for the prevention of oxidative stress production, and these are only a few examples of the critical roles that mitochondrial metals play. Even though the targets of these metals are known, we are still identifying transporters, investigating the roles of known transporters, and defining regulators of the transport process. Mitochondria are dynamic organelles whose content, structure and localization within the cell vary in different tissues and organisms. Our knowledge of the impact that alterations in mitochondrial physiology have on metal content and utilization in these organelles is very limited. The rates of fission and fusion, the ultrastructure of the organelle, and rates of mitophagy can all affect metal homeostasis and cofactor assembly. This review will focus of the emerging areas of overlap between metal homeostasis, cofactor assembly and the mitochondrial contact site and cristae organizing system (MICOS) that mediates multiple aspects of mitochondrial physiology. Importantly the MICOS complexes may allow for localization and organization of complexes not only involved in cristae formation and contact between the inner and outer mitochondrial membranes but also acts as hub for metal-related proteins to work in concert in cofactor assembly and homeostasis.
Toward Elucidating Epigenetic and Metabolic Regulation of Stem Cell Lineage Plasticity in Skin Aging
Authors: Lyu Ying , Ge Yejing
Published: May 2022

Skin is the largest organ in human body, harboring a plethora of cell types and serving as the organismal barrier. Skin aging such as wrinkling and hair graying is graphically pronounced, and the molecular mechanisms behind these phenotypic manifestations are beginning to unfold. As in many other organs and tissues, epigenetic and metabolic deregulations have emerged as key aging drivers. Particularly in the context of the skin epithelium, the epigenome and metabolome coordinately shape lineage plasticity and orchestrate stem cell function during aging. Our review discusses recent studies that proposed molecular mechanisms that drive the degeneration of hair follicles, a major appendage of the skin. By focusing on skin while comparing it to model organisms and adult stem cells of other tissues, we summarize literature on genotoxic stress, nutritional sensing, metabolic rewiring, mitochondrial activity, and epigenetic regulations of stem cell plasticity. Finally, we speculate about the rejuvenation potential of rate-limiting upstream signals during aging and the dominant role of the tissue microenvironment in dictating aged epithelial stem cell function.
Integrated Serum Pharmacochemistry and Network Pharmacology Approach to Explore the Effective Components and Potential Mechanisms of Menispermi Rhizoma Against Myocardial Ischemia
Authors: Wei Jinxia , Yu Yingying , Zhang Yue , Li Lingzhi , Li Xia , Shao Jia , Li Yubo
Published: May 2022

Background: Myocardial ischemia (MI) is a leading cause of death worldwide. Menispermi Rhizoma is a traditional Chinese medicine that exerts a variety of beneficial pharmacological activities in many diseases, including MI.

Purpose: Serum pharmacochemistry and network pharmacology were used to explore the material basis and mechanism of action of Menispermi Rhizoma against MI.

Methods: The absorbed components of Menispermi Rhizoma in rat plasma were analyzed by ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS). The key components, targets, pathways, and interrelated information were obtained by network pharmacology. The potential effective components of Menispermi Rhizoma against MI were screened by methyl-thiazolyl-tetrazolium (MTT) assay, and the cardioprotective effect and mechanism of active components were verified by Western blotting and molecular docking.

Results: In total, 25 absorbed components of Menispermi Rhizoma in plasma were identified. Network pharmacology revealed 81 major targets of Menispermi Rhizoma against MI, mainly involving the regulation of the PI3K/AKT and MAPK pathways. In vitro validation of H9c2 cells revealed that acutumine, daurisoline, dauricoside, and 6-O-demethylmenisporphine are the main bioactive components of Menispermi Rhizoma. The levels of lactate dehydrogenase, creatine kinase, and malondialdehyde (MDA) were significantly decreased by four alkaloids, whereas the activities of superoxide dismutase (SOD) and glutathione (GSH) were significantly increased. Four alkaloids effectively protected H9c2 cells against OGD-induced apoptosis by Hoechst/PI staining and flow cytometry assay. Western blotting results showed that the four alkaloids upregulated the expression ratio of Bcl-2/Bax and downregulated the expression levels of Cyt-C and cleaved caspase 3, which further supported the anti-cardiomyocyte apoptosis and antioxidative stress effect of Menispermi Rhizoma. Molecular docking confirmed that the four compounds were capable of binding to AKT1, MAPK1, EGFR, CASP3, and MAPK8 proteins, suggesting the protective effect of Menispermi Rhizoma on MI via PI3K/AKT, MAPK, and apoptosis pathways.

Conclusion: Menispermi Rhizoma exerted cardioprotective effects through the effect characteristics: multiple-ingredient, multi-target, and multi-pathway. This research provided a reference for further mechanistic research on wider applications of Menispermi Rhizoma for MI treatment.
Phosphonates and Phosphonate Prodrugs in Medicinal Chemistry: Past Successes and Future Prospects
Authors: Krečmerová Marcela , Majer Pavel , Rais Rana , Slusher Barbara S.
Published: May 2022

Compounds with a phosphonate group, i.e., –P(O)(OH)2 group attached directly to the molecule via a P-C bond serve as suitable non-hydrolyzable phosphate mimics in various biomedical applications. In principle, they often inhibit enzymes utilizing various phosphates as substrates. In this review we focus mainly on biologically active phosphonates that originated from our institute (Institute of Organic Chemistry and Biochemistry in Prague); i.e., acyclic nucleoside phosphonates (ANPs, e.g., adefovir, tenofovir, and cidofovir) and derivatives of non-nucleoside phosphonates such as 2-(phosphonomethyl) pentanedioic acid (2-PMPA). Principal strategies of their syntheses and modifications to prodrugs is reported. Besides clinically used ANP antivirals, a special attention is paid to new biologically active molecules with respect to emerging infections and arising resistance of many pathogens against standard treatments. These new structures include 2,4-diamino-6-[2-(phosphonomethoxy)ethoxy]pyrimidines or so-called “open-ring” derivatives, acyclic nucleoside phosphonates with 5-azacytosine as a base moiety, side-chain fluorinated ANPs, aza/deazapurine ANPs. When transformed into an appropriate prodrug by derivatizing their charged functionalities, all these compounds show promising potential to become drug candidates for the treatment of viral infections. ANP prodrugs with suitable pharmacokinetics include amino acid phosphoramidates, pivaloyloxymethyl (POM) and isopropoxycarbonyloxymethyl (POC) esters, alkyl and alkoxyalkyl esters, salicylic esters, (methyl-2-oxo-1,3-dioxol-4-yl) methyl (ODOL) esters and peptidomimetic prodrugs. We also focus on the story of cytostatics related to 9-[2-(phosphonomethoxy)ethyl]guanine and its prodrugs which eventually led to development of the veterinary drug rabacfosadine. Various new ANP structures are also currently investigated as antiparasitics, especially antimalarial agents e.g., guanine and hypoxanthine derivatives with 2-(phosphonoethoxy)ethyl moiety, their thia-analogues and N-branched derivatives. In addition to ANPs and their analogs, we also describe prodrugs of 2-(phosphonomethyl)pentanedioic acid (2-PMPA), a potent inhibitor of the enzyme glutamate carboxypeptidase II (GCPII), also known as prostate-specific membrane antigen (PSMA). Glutamate carboxypeptidase II inhibitors, including 2-PMPA have been found efficacious in various preclinical models of neurological disorders which are caused by glutamatergic excitotoxicity. Unfortunately its highly polar character and hence low bioavailability severely limits its potential for clinical use. To overcome this problem, various prodrug strategies have been used to mask carboxylates and/or phosphonate functionalities with pivaloyloxymethyl, POC, ODOL and alkyl esters. Chemistry and biological characterization led to identification of prodrugs with 44–80 fold greater oral bioavailability (tetra-ODOL-2-PMPA).
Synthesis and Bioactivities of Novel Galactoside Derivatives Containing 1,3,4-Thiadiazole Moiety
Authors: Shu Yafei , Chen Meihang , Lu Daowang , Zhou Zengyan , Yu Jianhong , Hu Xiaoling , Yang Jiaqin , Li Aiqin , Liu Jianglong , Luo Hairong
Published: May 2022

A series of novel galactoside derivatives containing 1,3,4-thiadiazole moiety were synthesized, and the structure of them was verified by spectroscopy of NMR and HRMS, and antifungal and antibacterial activities of them were screened. The results showed that the newly synthesized compounds had good antifungal activities. Among them, Ⅲ16, Ⅲ17, and Ⅲ19 exhibited satisfactory activities against Phytophthora infestans (P. infestans), with EC50 values of 5.87, 4.98, and 6.17 μg/ml, respectively, which were similar to those of dimethomorph (5.52 μg/ml). Meanwhile, the title compounds also possessed certain antibacterial activities.
Structural Characterization, Antimicrobial, Antibiofilm, Antioxidant, Anticancer and Acute Toxicity Properties of N-(2-hydroxyphenyl)-2-phenazinamine From Nocardiopsis exhalans (KP149558)
Authors: Ramalingam Vaikundamoorthy , Rajaram Rajendran , Archunan Govindaraju , Padmanabhan Parasuraman , Gulyás Balázs
Published: May 2022

The present study aimed to isolate and identify potential drugs from marine actinomycete Nocardiopsis exhalans and screen them for biomedical applications. The cell-free culture of N. exhalans was extracted with ethyl acetate and the solvent extract showed six fractions in thin-layer chromatography. The fractions were subjected to column chromatography for purification and evaluated for activity against human clinical pathogens. Fraction 4 showed significant activity and was identified as N-(2-hydroxyphenyl)-2-phenazinamine (NHP) using spectral analyses. Further, NHP showed excellent biofilm inhibitory activity against human clinical pathogens Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. The in vitro antioxidant activity confirmed that NHP is scavenging the oxidative stress-enhancing molecules. The anti-proliferative activity of NHP against human breast cancer cells showed significant activity at 300 µg/ml and less cytotoxic activity against normal cells. Additionally, the toxicity assessment against zebrafish revealed that NHP does not cause any toxicity in the important organs. The results highlight N. exhalans as a promising candidate for the development of antibiotics with potential therapeutic applications.
Molecular Characterization and Phylogenetic Analysis of the 2019 Dengue Outbreak in Wenzhou, China
Authors: Han Axiang , Sun Baochang , Sun Zhewei , Xu Xuelian , Yang Qiongying , Xie Danli , Guan Wanchun , Lou Yongliang
Published: May 2022

In 2019, a dengue outbreak occurred with 290 confirmed cases in Wenzhou, a coastal city in southeast China. To identify the origin of the dengue virus (DENV) from this outbreak, viral RNA was extracted from four serum samples and sequenced for whole genome analysis. Then, phylogenetic analysis, gene mutation, secondary structure prediction, selection pressure analysis, and recombination analysis were performed. DENV strains Cam-03 and Cam-11 were isolated from patients traveling from Cambodia, while ZJWZ-18 and ZJWZ-62 strains were isolated from local patients without a record of traveling abroad. The whole genome sequence of all four strains was 10,735 nucleotides long. Phylogenetic tree analysis showed that the four strains belonged to genotype 1 of DENV-1, but the local Wenzhou strains and imported strains clustered in different branches. ZJWZ-18 and ZJWZ-62 were closely related to strain MF033254-Singapore-2016, and Cam-03 and Cam-11 were closely related to strain AB608788-China : Taiwan-1994. A comparison of the coding regions between the local strains and the DENV-1 standard strain (EU848545-Hawaii-1944) showed 82 amino acid mutations between the two strains. A total of 55 amino acid mutations were found between the coding regions of the local and imported strains. The overall secondary structure of the 3′ UTR of the local strains had changed: apparent changes in the head and tail position were observed when compared to DENV-1 standard strain. Furthermore, selection pressure analysis and recombination detection using the 4 isolates and 41 reference strains showed two credible positive selection sites and eight credible recombination events, which warrant further studies. This study may enhance the understanding of viral replication, infection, evolution, virulence, and pathogenicity of DENV.
FuZhengHuaYuJiangZhuTongLuoFang Prescription Modulates Gut Microbiota and Gut-Derived Metabolites in UUO Rats
Authors: Chen Ziwei , Wu Shaobo , Zeng Yu , Chen Zejun , Li Xueying , Li Jing , He Long , Chen Ming
Published: May 2022

Background

Alteration of intestinal flora and metabolites is closely related to chronic kidney disease (CKD) across early to advanced stages. FuZhengHuaYuJiangZhuTongLuoFang prescription (FZHY) is a Chinese herb that has been proven to effectively treat CKD, but the underlying mechanism is not clear.

Methods

Rats were subjected to intragastric treatment with FZHY 7, 14, and 21 days after unilateral ureteral obstruction (UUO) surgery, and kidney tissue, colon tissue, serum, and stool samples were collected.

Results

FZHY treatment effectively ameliorated UUO-induced renal function loss, renal injury and renal fibrosis, and colon tissue damage and fibrosis on day 7. The results of 16S flora analysis (day 7) showed that, compared with the UUO group, both the FZHY group and the sham group showed decreased levels of g_Monoglobus, g_Papillibacter, g_Eubacterium_nodatum, and g_Family_XIII_AD3011. Additionally, FZHY obviously induced the reduction of serum citrulline, glycoursodeoxycholic acid, 23-nordeoxycholic acid, 7-ketodeoxycholic acid, kahweol, lipoid B4, 4-(3,4-dihydro-2H-1,5-benzodioxepin-7-yl)-2-methyl-1,3-thiazole, taurolithocholic acid sodium salt, indoline-2-carboxylic acid, 5(S),15(S)-diHETE, and others and the increase of bilirubin, asparagine, and others, which were positively associated with the above four candidate bacteria. Moreover, FZHY increased the levels of ZO-1, occludin, and claudin-1 in the colonic mucosa and reduced the levels of CRP, TNF-α, IL-6, and IL-1 in the serum and LN, FN, Col-I, and Col-III in the tubulointerstitium of UUO rats on day 7.

Conclusion

Our study revealed that FZHY reduced kidney damage at the early stage of CKD by regulating the above four candidate bacteria biomarkers and gut-derived harmful metabolites, inhibiting the inflammation response and tubulointerstitial fibrosis, providing deep insight into CKD therapeutic strategy.
Interconnected Clinical and Social Risk Factors in Breast Cancer and Heart Failure
Authors: Sinha Arjun , Bavishi Avni , Hibler Elizabeth A. , Yang Eric H. , Parashar Susmita , Okwuosa Tochukwu , DeCara Jeanne M. , Brown Sherry-Ann , Guha Avirup , Sadler Diego , Khan Sadiya S. , Shah Sanjiv J. , Yancy Clyde W. , Akhter Nausheen
Published: May 2022

Breast cancer and heart failure share several known clinical cardiovascular risk factors, including age, obesity, glucose dysregulation, cholesterol dysregulation, hypertension, atrial fibrillation and inflammation. However, to fully comprehend the complex interplay between risk of breast cancer and heart failure, factors attributed to both biological and social determinants of health must be explored in risk-assessment. There are several social factors that impede implementation of prevention strategies and treatment for breast cancer and heart failure prevention, including socioeconomic status, neighborhood disadvantage, food insecurity, access to healthcare, and social isolation. A comprehensive approach to prevention of both breast cancer and heart failure must include assessment for both traditional clinical risk factors and social determinants of health in patients to address root causes of lifestyle and modifiable risk factors. In this review, we examine clinical and social determinants of health in breast cancer and heart failure that are necessary to consider in the design and implementation of effective prevention strategies that altogether reduce the risk of both chronic diseases
Immune Checkpoint Inhibitor-Associated Cardiotoxicity in Solid Tumors: Real-World Incidence, Risk Factors, and Prognostic Analysis
Authors: Chen Xue , Jiang Aimin , Zhang Rui , Fu Xiao , Liu Na , Shi Chuchu , Wang Jingjing , Zheng Xiaoqiang , Tian Tao , Liang Xuan , Ruan Zhiping , Yao Yu
Published: May 2022

Background

Immune checkpoint inhibitors (ICIs) have achieved acknowledged progress in cancer therapy. However, ICI-associated cardiotoxicity as one of the most severe adverse events is potentially life-threatening, with limited real-world studies reporting its predictive factors and prognosis. This study aimed to investigate the real-world incidence, risk factors, and prognosis of ICI-related cardiotoxicity in patients with advanced solid tumors.

Methods

Electronic medical records from patients with advanced solid tumors receiving ICIs in the First Affiliated Hospital of Xi’an Jiaotong University were retrospectively reviewed. All patients were divided into the cardiotoxicity group and control group, with logistic regression analysis being implemented to identify potential risk factors of ICI-related cardiotoxicity. Furthermore, survival analysis was also performed to investigate the prognosis of patients with ICI-related cardiotoxicity.

Results

A total of 1,047 participants were enrolled in this retrospective study. The incidence of ICI-related cardiotoxicity in our hospital is 7.0%, while grade 3 and above cardiotoxicity was 2.4%. The logistic regression analysis revealed that diabetes mellitus [odds ratio (OR):1.96, 95% confidence Interval (CI): 1.05–3.65, p = 0.034] was an independent risk factor, whereas baseline lymphocyte/monocyte ratio (LMR) (OR: 0.59, 95% CI: 0.36–0.97, p = 0.037) was the protective factor of ICI-related cardiotoxicity. Survival analysis indicated that severe cardiotoxicity (≥grade 3) was significantly correlated with bleak overall survival (OS) than mild cardiotoxicity (≤grade 2) (8.3 months vs. not reached, p = 0.001). Patients with ICI-related overlap syndrome had poorer overall survival than patients with mere cardiotoxicity (9.4 vs. 24.7 months, p = 0.033). However, the occurrence of ICI-related cardiotoxicity was not significantly associated with the OS of overall population with solid tumors. Subgroup analysis showed that lung cancer and PD-L1 usage were significantly correlated with a higher incidence of severe cases.

Conclusion

Immune checkpoint inhibitor-related cardiotoxicity is more common in the real-world setting than the previously published studies. Diabetes mellitus and baseline LMR are the potential predictive biomarkers of ICI-related cardiotoxicity. Although ICI-related cardiotoxicity is not correlated with the prognosis of these patients in our cohort, a systematic and comprehensive baseline examination and evaluation should be performed to avoid its occurrence.
Non-linear Embedding Methods for Identifying Similar Brain Activity in 1 Million iEEG Records Captured From 256 RNS System Patients
Authors: Arcot Desai Sharanya , Tcheng Thomas , Morrell Martha
Published: May 2022

Finding electrophysiological features that are similar across patients with epilepsy may facilitate identifying treatment options for one patient that worked in patients with similar brain activity patterns. Three non-linear iEEG (intracranial electroencephalogram) embedding methods of finding similar cross-patient iEEG records in a large iEEG dataset were developed and compared. About 1 million iEEG records from 256 patients with drug-resistant focal onset seizures who were treated in prospective trials of the RNS System were used for analyses. Data from 200, 25, and 31 patients were randomly selected to be in the train, validation, and test datasets. In method 1, ResNet50 convolutional neural network (CNN) model pre-trained on the ImageNet dataset was used for extracting feature maps from spectrogram images (ImageNet-ResNet) of iEEG records. In method 2, ResNet50 custom trained on an iEEG classification task using ~138,000 manually labeled iEEG records was used as the feature extractor (ESC-ResNet). Feature maps were passed through dimensionality reduction and k nearest neighbors were found in the reduced feature space. In method 3, a 256 dimensional iEEG embedding space was learned via contrastive learning by training a ResNet50 model with triplet training sets generated using within-patient iEEG clustering (CL-ResNet). All three methods had comparable performance when identifying iEEG records from the search dataset similar to test iEEG records of baseline (non-seizure) and interictal spiking activity. Epileptic interictal spikes are represented by vertical (broadband) edges in spectrogram images, and hence even generic features extracted using models trained on everyday images appear to be sufficient to represent iEEG records with similar levels of interictal spiking activity in close proximity. In the case of electrographic seizures, however, the ESC-ResNet model, identified cross-patient iEEG records with electrographic seizure morphology features that were most similar to the test iEEG records. For nuanced electrographic seizure iEEG representation learning, domain specific model training with manually generated labels had the advantage. Finally, representative iEEG records were selected from every patient using an unsupervised clustering method which effectively reduced the number of iEEG records in the search dataset from ~750,000 to 2,148, thus substantially reducing the time required for finding similar cross-patient iEEG records.
New Paleomagnetic Constraints on the Early Cretaceous Paleolatitude of the Lhasa Terrane (Tibet)
Authors: Li Zhenyu , Ding Lin , Laskowski Andrew K. , Burke William B. , Chen Yaofei , Song Peiping , Yue Yahui , Xie Jing
Published: May 2022

New zircon U-Pb dating results from the Zonggei Formation volcanics indicate that the volcanic rocks formed at ∼114–110 Ma. Paleomagnetic data, petrography, and rock magnetism confirm the primary nature of isolated characteristic remanent magnetizations carried by titanomagnetite and hematite. A statistical analysis of the combined results from the Zonggei and Duoni formations reveals a group-mean direction of D±ΔD = 0.4° ± 6.0°, I±ΔI = 22.2° ± 5.6°, α95 = 5.6°, k = 35.2 after bedding correction based on 20 group-mean directions. The corresponding paleopole was calculated to be λp = 70.3°N, φp = 270.5°E with A95 = 5.2°. The interpretation of our data alongside the Cenozoic data from the Tethyan Himalaya indicates that the India–Asia collision initiated by 61.7 ± 3.0 Ma at 13.0° ± 1.8°N, assuming a single-collision model. Intracontinental crustal shortening totaling 1,770 ± 470 km took place on the Asian side since the onset of India–Asia collision. Furthermore, the data show that the Neo-Tethys Ocean reached its maximum N-S width of 7,100 ± 530 km at ∼132 Ma and shrank to 6,400 ± 550 km by ∼115 ± 5 Ma. This is consistent with previous estimates based on the geophysical images of the subducted Neo-Tethyan slab beneath Eurasia.
Automated Hierarchical 3D Modeling of Quaternary Aquifers: The ArchPy Approach
Authors: Schorpp Ludovic , Straubhaar Julien , Renard Philippe
Published: May 2022

When modeling groundwater systems in Quaternary formations, one of the first steps is to construct a geological and petrophysical model. This is often cumbersome because it requires multiple manual steps which include geophysical interpretation, construction of a structural model, and identification of geostatistical model parameters, facies, and property simulations. Those steps are often carried out using different software, which makes the automation intractable or very difficult. A non-automated approach is time-consuming and makes the model updating difficult when new data are available or when some geological interpretations are modified. Furthermore, conducting a cross-validation procedure to assess the overall quality of the models and quantifying the joint structural and parametric uncertainty are tedious. To address these issues, we propose a new approach and a Python module, ArchPy, to automatically generate realistic geological and parameter models. One of its main features is that the modeling operates in a hierarchical manner. The input data consist of a set of borehole data and a stratigraphic pile. The stratigraphic pile describes how the model should be constructed formally and in a compact manner. It contains the list of the different stratigraphic units and their order in the pile, their conformability (eroded or onlap), the surface interpolation method (e.g., kriging, sequential Gaussian simulation (SGS), and multiple-point statistics (MPS)), the filling method for the lithologies (e.g., MPS and sequential indicator simulation (SIS)), and the petrophysical properties (e.g., MPS and SGS). Then, the procedure is automatic. In a first step, the stratigraphic unit boundaries are simulated. Second, they are filled with lithologies, and finally, the petrophysical properties are simulated inside the lithologies. All these steps are straightforward and automated once the stratigraphic pile and its related parameters have been defined. Hence, this approach is extremely flexible. The automation provides a framework to generate end-to-end stochastic models and then the proposed method allows for uncertainty quantification at any level and may be used for full inversion. In this work, ArchPy is illustrated using data from an alpine Quaternary aquifer in the upper Aare plain (southeast of Bern, Switzerland).
Amplifying Flood Risk Across the Lower Yellow River Basin, China, Under Shared Socioeconomic Pathways
Authors: Song Jinbo , Zhang Qiang , Wu Wenhuan , Singh Vijay P. , Shen Zexi , Wang Gang , Xu Chong-Yu
Published: May 2022

The ecological conservation and high-quality development of the Yellow River basin (YRB) has been adopted as a major national strategy of China. However, the YRB is still afflicted by floods. Here, we proposed a flood risk indicator using direct economic loss degree and improved the SNRD (station-based nonlinear regression downscaling model) and simulated extreme precipitation processes. The correlation coefficient of downscaled average extreme precipitation of CMORPH and CMIP6 data reached 0.817. Moreover, we evaluated flood risk and flood hazard across the YRB based on the sixth phase Coupled Model Intercomparison Project (CMIP6) data under different SSPs. Under SSP126, SSP245, and SSP585 scenarios, the areas with increasing flood hazards during 2015–2045 accounted for 65.2, 69.0, and 64.5% of the entire YRB. In the spatial pattern, flood hazards decreased from southeastern to northwestern parts of the YRB. When compared with the spatial pattern of flood risks in 2015, regions with high flood risks expanded slightly and regions with low flood risks shrunk slightly. Higher flood risks can be observed in the middle and lower YRB and particularly in the lower YRB. These findings are critical for the mitigation of flood risk across the YRB under warming climate.
Summer Temperature Reconstruction for the Source Area of the Northern Asian Great River Basins, Northern Mongolian Plateau Since 1190 CE and its Linkage With Inner Asian Historical Societal Changes
Authors: Chen Feng , Chen Youping , Davi Nicole , Zhang Heli
Published: May 2022

Mid-to-high latitudes of Asia and its adjacent Arctic area are some of the most sensitive regions to climate warming in Eurasia, but spatio-temporal temperature variation over this region is still limited by a lack of long-term temperature records. Here, June-July temperature reconstructions are developed from a Larix sibirica composite chronology that presents a stable positive linkage with large-scale recorded temperatures and spans 1190–2019 CE for the source area of the Northern Asian great river Basins, northern Mongolian Plateau, Inner Asia. The warmest reconstructed period and low summer sea ice extent in the Arctic Ocean over the past 830 years was estimated to occur in the late twentieth century (1990s–present), with a mean temperature (15.2°C) higher than the long-term mean (13.9°C) of 1190–2019 CE, which is linked with the rapid increase in global temperature. A relationship also exists between the reconstructed temperature and the AMO index, suggesting that the atmospheric patterns over the Arctic and North Atlantic Oceans influence the temperature variations of northern Mongolian Plateau. In addition, we also propose that the warm climate promoted high vegetation productivity and favored the formation of power of the nomadic tribes in the Mongolian Plateau, such as the warm periods 1210s–1250s and 1400s–1430s. Our temperature reconstruction provides us with an opportunity to understand the regional effects of climate warming from multiple perspectives.
Relational Reasoning in Tertiary Education: What Is Its Value and How Can It Be Assessed and Trained?
Authors: Alexander Patricia A. , Gans Nancy , Maki Alina J. K.
Published: May 2022

The goal of this article is to demonstrate the value of incorporating relational reasoning assessment and training in tertiary education. To accomplish this, the authors organize the article into three sections. The first section overviews the nature of relational reasoning, and its different forms, developmental trajectories, and assessment. How relational reasoning predicts performance in various academic domains and fields of practice is also considered. The second section focuses on the role that relational reasoning plays in the scientific domains that are foundational to tertiary education and professional practice—the natural, social, applied, and formal sciences. In the final section, the authors describe an ongoing design experiment in which relational reasoning assessment and training are integrated into a university course.
Outcomes of a GnRH Agonist Trigger Following a GnRH Antagonist or Flexible Progestin-Primed Ovarian Stimulation Cycle
Authors: Kalafat Erkan , Turkgeldi Engin , Yıldız Sule , Dizdar Merve , Keles Ipek , Ata Baris
Published: May 2022

A suggested explanation for the pituitary-suppressive effects of progestin-primed ovarian stimulation cycles (PPOS) is pituitary luteinizing hormone (LH) depletion with progestin exposure during the follicular phase. The GnRH agonist (GnRHa) trigger releases endogenous LH from the pituitary, and if the LH depletion theory is correct, the response to the agonist trigger would be dampened in PPOS cycles. In this study, we compared the performance of the GnRHa trigger after PPOS and GnRH antagonist ovarian stimulation cycles. All women who underwent ovarian stimulation with the GnRH antagonist or flexible PPOS (fPPOS) and received a GnRH agonist trigger were eligible for inclusion. Outcomes included number of metaphase-II (MII) oocytes retrieved per cycle, rates of empty follicle syndrome, maturation, fertilization, blastulation, and cumulative clinical pregnancy per stimulation cycle. During the screening period, there were 166 antagonists and 58 fPPOS cycles triggered with a GnRH agonist. Groups were matched for potential confounders using propensity score matching. Progestin-downregulated cycles had 19% high mature oocyte yield (median: 14 vs. 19 MII oocytes, P = 0.03). Cumulative ongoing pregnancy or live birth rates were estimated after matching for transferred embryo count, and rates were similar between GnRH antagonist and fPPOS group (57.0% vs. 62.1%, P = 0.68). However, the number of remaining blastocysts was higher in the fPPOS group (median: 5.0 vs. 6.0, P < 0.001). LH levels were higher in fPPOS cycles compared to GnRH antagonist cycles up to the trigger day (P < 0.001). After the GnRHa trigger, fPPOS cycles were associated with a steeper LH surge compared with antagonist cycles (P = 0.02). Higher endogenous gonadotropin levels through the stimulation period and an LH surge of higher magnitude following a GnRHa trigger suggest a milder pituitary suppression by fPPOS, which needs to be confirmed in larger samples. It appears that progestins do not deplete pituitary LH reserves and a GnRHa trigger is usable after PPOS in women with high ovarian reserve.
High Normal Urinary Albumin–Creatinine Ratio Is Associated With Hypertension, Type 2 Diabetes Mellitus, HTN With T2DM, Dyslipidemia, and Cardiovascular Diseases in the Chinese Population: A Report From the REACTION Study
Authors: Wang Jie , Wang Yun , Li Yijun , Hu Ying , Jin Lingzi , Wang Weiqing , Gao Zhengnan , Tang Xulei , Yan Li , Wan Qin , Luo Zuojie , Qin Guijun , Chen Lulu , Gu Weijun , Lyv Zhaohui , Mu Yiming
Published: May 2022

Background

Albuminuria has been widely considered a risk factor for cardiovascular diseases (CVDs), which is associated with hypertension (HTN), type 2 diabetes mellitus (T2DM), HTN with T2DM, and dyslipidemia. However, the associations between albuminuria and HTN, T2DM, HTN with T2DM, dyslipidemia, and CVDs are still unclear. Thus, this study aimed to explore the association of albuminuria thoroughly, especially within the normal range, with the abovementioned diseases in the Chinese population.

Methods

This study included 40,188 participants aged over 40 years from seven centers across China. Urinary albumin–creatinine ratio (UACR) was firstly divided into the ≥30-mg/g group, indicating kidney damage, and <30-mg/g group. Furthermore, UACR was divided into five groups: the <20%, 20%–39%, 40%–59%, 60%–79%, and ≥80% groups, according to the quintile division of participants within the normal range. Propensity score matching was used to reduce bias, and multiple logistic regression models were conducted to examine the association between UACR and HTN, T2DM, HTN with T2DM, dyslipidemia, and CVDs.

Results

Multivariable regression analysis revealed that UACR, even within the normal range, is significantly associated with HTN, T2DM, HTN with T2DM, dyslipidemia, and CVDs, and the association between UACR and HTN with T2DM was the most significant in model 3 even after adjusting for confounding factors (HTN: OR = 1.56 (95% CI = 1.45–1.68), p < 0.0001; T2DM: OR = 1.78 (95% CI = 1.60–1.97), p < 0.0001; HTN with T2DM: OR = 1.76 (95% CI = 1.59–1.95), p < 0.0001; dyslipidemia: OR = 1.08 (95% CI = 1.01–1.14), p = 0.0146; CVDs: OR = 1.12 (95% CI = 1.00–1.25), p = 0.0475). In the stratified analysis, high normal UACR was significantly associated with HTN, T2DM, HTN with T2DM, and dyslipidemia in subgroups.

Conclusions

In summary, we observe a higher prevalence of HTN, T2DM, HTN with T2DM, dyslipidemia, and CVDs in abnormal UACR and reveal a significant association of UACR, even within the normal range, with HTN, T2DM, HTN with T2DM, dyslipidemia, and CVDs.
Transcriptome Analysis Reveals Key miRNA–mRNA Pathways in Ovarian Tissues of Yunshang Black Goats With Different Kidding Numbers
Authors: Liu Yufang , Zhou Zuyang , Guo Siwu , Li Kunyu , Wang Peng , Fan Yekai , He Xiaoyun , Jiang Yanting , Lan Rong , Chen Shuangzhao , Dai Shenghong , Hong Qionghua , Chu Mingxing
Published: May 2022

The granulosa cell (GC) is the basic functional unit of follicles, and it is important for promoting follicle growth and sex hormones, as well as growth factor secretion in the process of reproduction. A variety of factors influence granulocyte proliferation, yet there are still many gaps to be filled in target and non-coding RNA regulation. In our study, the differentially expressed (DE) mRNAs and miRNAs were detected by using RNA-seq, and we constructed a mRNA–miRNA network related to goat prolificacy. Then, the goat primary GCs were isolated from the follicle for the function validation of candidate genes and their regulator miRNAs. A total of 2,968 DE mRNAs and 99 DE miRNAs were identified in the high- and low-prolificacy goat by RNA-seq, of which there were 1,553 upregulated and 1,415 downregulated mRNAs, and 80 upregulated and 19 downregulated miRNAs, respectively. JAK3 was identified as highly expressed in the low-prolificacy goats (3 times higher than high-prolificacy goats), and the integrated analysis showed that chi-miR-493-3p was a potential regulator of JAK3. The analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) showed that JAK3 was involved in the PI3K-Akt signaling pathway, the Jak-STAT signaling pathway, and signaling pathways regulating pluripotency of stem cells. In particular, the PI3K-Akt signaling pathway was a typical pathway for cell proliferation, differentiation, apoptosis, and migration. We found that the chi-miR-493-3p targets JAK3 directly via RT-qPCR, dual fluorescence assays, and Western blot. Furthermore, the expression of JAK3 was significantly decreased by the chi-miR-493-3p mimic and increased by the chi-miR-493-3p inhibitor. The CCK-8 assay showed that overexpression of JAK3 promoted cell proliferation, while inhibiting JAK3 had the opposite effect. The expression of cell proliferation markers CDK4 and cyclin D2 also showed the same results. Moreover, the enzyme-linked immunosorbent assay showed that steroid hormones E2 and PROG were increased by overexpressing JAK3 and decreased by inhibiting JAK3. Therefore, our results identified a chi-miR-439-3p-JAK3 regulatory pathway, which provided a new insight into the GC proliferation and prolificacy of goat.
TEMPI Syndrome: Update on Clinical Features, Management, and Pathogenesis
Authors: Xu Jian , Liu Wenqi , Fan Fengjuan , Zhang Bo , Zhao Fei , Hu Yu , Sun Chunyan
Published: May 2022

TEMPI (telangiectasias, elevated erythropoietin level and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting) syndrome is a rare and newly defined multisystemic disease, which belongs to “monoclonal gammopathy of clinical significances”. Due to its rarity, the etiology, pathogenesis, and clinical features of this disease remain largely unknown. Owing to its hidden and diverse clinical manifestations, missed diagnosis and misdiagnosis are common. In recent years, as more patients (including three fatal cases) were identified, some special clinical manifestations other than the typical pentad of TEMPI syndrome have been reported. Meanwhile, several studies attempting to identify the pathogenesis of TEMPI syndrome were conducted. In this review, we summarize the reported clinical characteristics of TEMPI syndrome and discuss the current and potential treatment options for patients with TEMPI syndrome, including those with relapsed/refractory disease. Furthermore, we provide an overview of current knowledge on the pathophysiology of TEMPI syndrome.