bluuebunny/crossref_metadata_2025 huggingface dataset:
Block Row Kronecker-Structured Linear Systems With a Low-Rank Tensor Solution
Authors: Hendrikx Stijn , De Lathauwer Lieven
Published: March 2022

Several problems in compressed sensing and randomized tensor decomposition can be formulated as a structured linear system with a constrained tensor as the solution. In particular, we consider block row Kronecker-structured linear systems with a low multilinear rank multilinear singular value decomposition, a low-rank canonical polyadic decomposition or a low tensor train rank tensor train constrained solution. In this paper, we provide algorithms that serve as tools for finding such solutions for a large, higher-order data tensor, given Kronecker-structured linear combinations of its entries. Consistent with the literature on compressed sensing, the number of linear combinations of entries needed to find a constrained solution is far smaller than the corresponding total number of entries in the original tensor. We derive conditions under which a multilinear singular value decomposition, canonical polyadic decomposition or tensor train solution can be retrieved from this type of structured linear systems and also derive the corresponding generic conditions. Finally, we validate our algorithms by comparing them to related randomized tensor decomposition algorithms and by reconstructing a hyperspectral image from compressed measurements.
Creation of GMP-Compliant iPSCs From Banked Umbilical Cord Blood
Authors: Tian Pei , Elefanty Andrew , Stanley Edouard G. , Durnall Jennifer C. , Thompson Lachlan H. , Elwood Ngaire J.
Published: March 2022

Many clinical trials are in progress using cells derived from induced pluripotent stem cells (iPSC) for immunotherapies and regenerative medicine. The success of these new therapies is underpinned by the quality of the cell population used to create the iPSC lines, along with the creation of iPSCs in a fully Good Manufacturing Practice (GMP)-compliant environment such that they can be used safely and effectively in the clinical setting. Umbilical cord blood (CB) from public cord blood banks is an excellent source of starting material for creation of iPSCs. All CB units are manufactured under GMP-conditions, have been screened for infectious diseases, with known family and medical history of the donor. Furthermore, the HLA tissue typing is known, thereby allowing identification of CB units with homozygous HLA haplotypes. CB cells are naïve with less exposure to environmental insults and iPSC can be generated with high efficiency. We describe a protocol that can be adopted by those seeking to create clinical-grade iPSC from banked CB. This protocol uses a small volume of thawed CB buffy to first undergo ex-vivo expansion towards erythroid progenitor cells, which are then used for reprogramming using the CytoTune™-iPS 2.0 Sendai Reprogramming Kit. Resultant iPSC lines are tested to confirm pluripotency, genomic integrity, and stability. Cells are maintained in a feeder-free, xeno-free environment, using fully defined, commercially available reagents. Adoption of this protocol, with heed given to tips provided, allows efficient and robust creation of clinical-grade iPSC cell lines from small volumes of cryopreserved CB.
A Role of Caveolae in Trabecular Meshwork Mechanosensing and Contractile Tone
Authors: De Ieso Michael L. , Kuhn Megan , Bernatchez Pascal , Elliott Michael H. , Stamer W. Daniel
Published: March 2022

Polymorphisms in the CAV1/2 gene loci impart increased risk for primary open-angle glaucoma (POAG). CAV1 encodes caveolin-1 (Cav1), which is required for biosynthesis of plasma membrane invaginations called caveolae. Cav1 knockout mice exhibit elevated intraocular pressure (IOP) and decreased outflow facility, but the mechanistic role of Cav1 in IOP homeostasis is unknown. We hypothesized that caveolae sequester/inhibit RhoA, to regulate trabecular meshwork (TM) mechanosensing and contractile tone. Using phosphorylated myosin light chain (pMLC) as a surrogate indicator for Rho/ROCK activity and contractile tone, we found that pMLC was elevated in Cav1-deficient TM cells compared to control (131 ± 10%, n = 10, p = 0.016). Elevation of pMLC levels following Cav1 knockdown occurred in cells on a soft surface (137 ± 7%, n = 24, p < 0.0001), but not on a hard surface (122 ± 17%, n = 12, p = 0.22). In Cav1-deficient TM cells where pMLC was elevated, Rho activity was also increased (123 ± 7%, n = 6, p = 0.017), suggesting activation of the Rho/ROCK pathway. Cyclic stretch reduced pMLC/MLC levels in TM cells (69 ± 7% n = 9, p = 0.002) and in Cav1-deficient TM cells, although not significantly (77 ± 11% n = 10, p = 0.059). Treatment with the Cav1 scaffolding domain mimetic, cavtratin (1 μM) caused a reduction in pMLC (70 ± 5% n = 7, p = 0.001), as did treatment with the scaffolding domain mutant cavnoxin (1 μM) (82 ± 7% n = 7, p = 0.04). Data suggest that caveolae differentially regulate RhoA signaling, and that caveolae participate in TM mechanotransduction. Cav1 regulation of these key TM functions provide evidence for underlying mechanisms linking polymorphisms in the Cav1/2 gene loci with increased POAG risk.
Synthetic Strategies Toward Nitrogen-Rich Energetic Compounds Via the Reaction Characteristics of Cyanofurazan/Furoxan
Authors: Wang Luoluo , Zhai Lianjie , She Weiqing , Wang Minchang , Zhang Junlin , Wang Bozhou
Published: March 2022

The structural units of amino-/cyano-substituted furazans and furoxans played significant roles in the synthesis of nitrogen-rich energetic compounds. This account focused on the synthetic strategies toward nitrogen-rich energetic compounds through the transformations based on cyanofurazan/furoxan structures, including 3-amino-4-cyanofurazan, 4-amino-3-cyano furoxan, 3,4-dicyanofurazan, and 3,4-dicyanofuroxan. The synthetic strategies toward seven kinds of nitrogen-rich energetic compounds, such as azo (azoxy)-bridged, ether-bridged, methylene-bridged, hybrid furazan/furoxan-tetrazole–based, tandem furoxan–based, hybrid furazan-isofurazan–based, hybrid furoxan-isoxazole–based and fused framework–based energetic compounds were fully reviewed, with the corresponding reaction mechanisms toward the nitrogen-rich aromatic frameworks and examples of using the frameworks to create high energetic substances highlighted and discussed. The energetic properties of typical nitrogen-rich energetic compounds had also been compared and summarized.
Cerebral Intraparenchymal Hemorrhage Changes Patients’ Gut Bacteria Composition and Function
Authors: Xiong Zujian , Peng Kang , Song Shaoyu , Zhu Yongwei , Gu Jia , Huang Chunhai , Li Xuejun
Published: March 2022

Gut bacteria consists of 150 times more genes than humans that are vital for health. Several studies revealed that gut bacteria are associated with disease status and influence human behavior and mentality. Whether human brain injury alters the gut bacteria is yet unclear, we tested 20 fecal samples from patients with cerebral intraparenchymal hemorrhage and corresponding healthy controls through metagenomic shotgun sequencing. The composition of patients’ gut bacteria changed significantly at the phylum level; Verrucomicrobiota was the specific phylum colonized in the patients’ gut. The functional alteration was observed in the patients’ gut bacteria, including high metabolic activity for nutrients or neuroactive compounds, strong antibiotic resistance, and less virulence factor diversity. The changes in the transcription and metabolism of differential species were more evident than those of the non-differential species between groups, which is the primary factor contributing to the functional alteration of patients with cerebral intraparenchymal hemorrhage.
When the Phagosome Gets Leaky: Pore-Forming Toxin-Induced Non-Canonical Autophagy (PINCA)
Authors: Herb Marc , Gluschko Alexander , Farid Alina , Krönke Martin
Published: March 2022

Macrophages remove bacteria from the extracellular milieu via phagocytosis. While most of the engulfed bacteria are degraded in the antimicrobial environment of the phagolysosome, several bacterial pathogens have evolved virulence factors, which evade degradation or allow escape into the cytosol. To counter this situation, macrophages activate LC3-associated phagocytosis (LAP), a highly bactericidal non-canonical autophagy pathway, which destroys the bacterial pathogens in so called LAPosomes. Moreover, macrophages can also target intracellular bacteria by pore-forming toxin-induced non-canonical autophagy (PINCA), a recently described non-canonical autophagy pathway, which is activated by phagosomal damage induced by bacteria-derived pore-forming toxins. Similar to LAP, PINCA involves LC3 recruitment to the bacteria-containing phagosome independently of the ULK complex, but in contrast to LAP, this process does not require ROS production by Nox2. As last resort of autophagic targeting, macrophages activate xenophagy, a selective form of macroautophagy, to recapture bacteria, which evaded successful targeting by LAP or PINCA through rupture of the phagosome. However, xenophagy can also be hijacked by bacterial pathogens for their benefit or can be completely inhibited resulting in intracellular growth of the bacterial pathogen. In this perspective, we discuss the molecular differences and similarities between LAP, PINCA and xenophagy in macrophages during bacterial infections.
Neutralization Sensitivity of HIV-1 CRF07_BC From an Untreated Patient With a Focus on Evolution Over Time
Authors: Wang Lijie , Liang Shujia , Huang Jianhua , Ding Yibo , He Lin , Hao Yanling , Ren Li , Zhu Meiling , Feng Yi , Rashid Abdur , Liu Yue , Jiang Shibo , Hong Kunxue , Ma Liying
Published: March 2022

The diversity of HIV-1 envelope (Env) glycoproteins affects the potency and breadth of broadly neutralizing antibodies (bNAbs), a promising alternative to antiretroviral drugs for the prevention and treatment of HIV-1 infection. To facilitate immunogen design and development of therapeutic neutralizing antibodies, we characterized viral evolution and monitored the changes in neutralizing activity/sensitivity of a long-term non-progressor patient with HIV-1 CRF07_BC infection. Fifty-nine full-length Env gene fragments were derived from four plasma samples sequentially harvested from the patient between 2016 and 2020. Sequencing of patient-derived Env genes revealed that potential N-linked glycosylation sites (PNGS) in V1 and V5 significantly increased over time. Further, 24 functional Env-pseudotyped viruses were generated based on Env gene sequences. While all 24 Env-pseudotyped viruses remained sensitive to concurrent and subsequent autologous plasma, as well as bNAbs, including 10E8, VRC01, and 12A21, Env-pseudotyped viruses corresponding to later sampling time were increasingly more resistant to autologous plasma and bNAbs. All 24 Env-pseudotyped viruses were resistant to bNAbs 2G12, PGT121, and PGT135. The neutralization breadth of plasma from all four sequential samples was 100% against the global HIV-1 reference panel. Immune escape mutants resulted in increased resistance to bNAb targeting of different epitopes. Our study identified known mutations F277W in gp41 and previously uncharacterized mutation S465T in V5 which may be associated with increased viral resistance to bNAbs.
Prayer Leads to Advocacy: The Theological Logic in a Bishop's Statement on Comprehensive Immigration Reform
Authors: Vining James W.
Published: March 2022

This article contributes to the scholarly discussions about the role of religion in social and political action rhetoric by revealing the complexities of rhetorical resources found in the logic of theology. To this end, I explored rhetorical functions of theology in Bishop Michael Burbidge's 2013 Statement on Comprehensive Immigration Reform. Close textual analysis of the text allows scholars to identify what I call the textual theology—a mediating level of theology between theological traditions and the rhetoric in a text. Analysis of the textual theology in the Bishop's statement provides insights as to how the more abstract levels of theology animate texts in the real world in ways that have implications that reach beyond the particular text.
An in vitro Assessment of the Haemodynamic Features Occurring Within the True and False Lumens Separated by a Dissection Flap for a Patient-Specific Type B Aortic Dissection
Authors: Morris Liam , Tierney Paul , Hynes Niamh , Sultan Sherif
Published: March 2022

One of the highest mortality rates of cardiovascular diseases is aortic dissections with challenging treatment options. Currently, less study has been conducted in developing in vitro patient-specific Type B aortic dissection models, which mimic physiological flow conditions along the true and false lumens separated by a dissection flap with multiple entry and exit tears. A patient-specific Stanford Type B aortic dissection scan was replicated by an in-house manufactured automatic injection moulding system and a novel modelling technique for creating the ascending aorta, aortic arch, and descending aorta incorporating arterial branching, the true/false lumens, and dissection flap with entry and exit intimal tears. The physiological flowrates and pressure values were monitored, which identified jet stream fluid flows entering and exiting the dissection tears. Pressure in the aorta’s true lumen region was controlled at 125/85 mmHg for systolic and diastolic values. Pressure values were obtained in eight sections along the false lumen using a pressure transducer. The true lumen systolic pressure varied from 122 to 128 mmHg along the length. Flow patterns were monitored by ultrasound along 12 sections. Detailed images obtained from the ultrasound transducer probe showed varied flow patterns with one or multiple jet steam vortices along the aorta model. The dissection flap movement was assessed at four sections of the patient-specific aorta model. The displacement values of the flap varied from 0.5 to 3 mm along the model. This model provides a unique insight into aortic dissection flow patterns and pressure distributions. This dissection phantom model can be used to assess various treatment options based on the surgical, endovascular, or hybrid techniques.
Case Report: Takotsubo Syndrome Induced by Severe Anaphylactic Reaction During Anesthesia Induction and Subsequent High-Dose Epinephrine Resuscitation
Authors: Wei Jiaojiao , Zhang Le , Ruan Xia , He Kai , Yu Chunhua , Shen Le
Published: March 2022

Takotsubo syndrome (TTS) is a type of non-ischemic cardiomyopathy characterized by an acute reversible left ventricular dysfunction with typical apical ballooning, usually with subsequent complete recovery. Early diagnosis and prompt treatment are of great essence. Herein, we described a case of TTS of a patient who was scheduled initially for laparoscopic endometrial cancer staging. The 69-year-old woman presented with cardiogenic shock induced by the severe anaphylactic reaction to the antibiotics during anesthesia induction. Cardiopulmonary resuscitation (CPR) was implemented while several boluses of 1 mg epinephrine were injected. After the return of spontaneous circulation, a large number of orange peel-like rash appeared on the head, face, neck, and trunk of the patient. Transesophageal echocardiography (TEE) revealed diffused decreased left ventricular systolic function. Therefore, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and intra-aortic balloon pump (IABP) were applied in the intensive care unit. Biomarkers like cardiac troponin I (cTnI) subsequently decreased with improved cardiac insufficiency. Finally, the patient was discharged in good condition. This case demonstrated that TTS could be secondary to severe anaphylactic shock and exogenous catecholamines. With the consideration of the reversible condition and predictable recovery of TTS, early vigilance and advanced life support devices should be necessary.
Cardiac ISL1-Interacting Protein, a Cardioprotective Factor, Inhibits the Transition From Cardiac Hypertrophy to Heart Failure
Authors: Yan Youchen , Long Tianxin , Su Qiao , Wang Yi , Chen Ken , Yang Tiqun , Zhao Guangyin , Ma Qing , Hu Xiaoyun , Liu Chen , Liao Xinxue , Min Wang , Li Shujuan , Zhang Dihua , Yang Yuedong , Pu William T. , Dong Yugang , Wang Da-Zhi , Chen Yili , Huang Zhan-Peng
Published: March 2022

Heart failure is characterized by the inability of the heart to pump effectively and generate proper blood circulation to meet the body’s needs; it is a devastating condition that affects more than 100 million people globally. In spite of this, little is known about the mechanisms regulating the transition from cardiac hypertrophy to heart failure. Previously, we identified a cardiomyocyte-enriched gene, CIP, which regulates cardiac homeostasis under pathological stimulation. Here, we show that the cardiac transcriptional factor GATA4 binds the promotor of CIP gene and regulates its expression. We further determined that both CIP mRNA and protein decrease in diseased human hearts. In a mouse model, induced cardiac-specific overexpression of CIP after the establishment of cardiac hypertrophy protects the heart by inhibiting disease progression toward heart failure. Transcriptome analyses revealed that the IGF, mTORC2 and TGFβ signaling pathways mediate the inhibitory function of CIP on pathologic cardiac remodeling. Our study demonstrates GATA4 as an upstream regulator of CIP gene expression in cardiomyocytes, as well as the clinical significance of CIP expression in human heart disease. More importantly, our investigation suggests CIP is a key regulator of the transition from cardiac hypertrophy to heart failure. The ability of CIP to intervene in the onset of heart failure suggests a novel therapeutic avenue of investigation for the prevention of heart disease progression.
Experiment Study of Porous Fiber Material on Infiltration and Runoff of Winter Wheat Farmland in Huaibei Plain, China
Authors: Li Wei , Liu Shanshan , Qin Tianling , Xiao Shangbin , Li Chenhao , Zhang Xin , Wang Kun , Abebe Sintayehu A.
Published: March 2022

Drought and floods frequently occurred in the Huaibei plain, which was the main factor that restricted agricultural development. We conducted rainfall experiments, which aimed to explore the impacts of porous fiber material (PFM) on the farmland water cycle processes and soil water storage capacity. In this study, we designed two types of rainfall intensities, 4 PFM volumes, 4 growth periods of winter wheat, and a total of 8 experimental groups and 32 rainfall events to evaluate the effects. The result showed that PFM had significantly affected the soil water circulation in the grain-filling period, and the peak flow and runoff decreased maximumly compared with other periods. However, the effect of PFM on surface runoff was slighter in the fallow period, and the peak flow or runoff decreased with the PFM volumes increased (R2 = −0.92, −0.99). In the 100 and 50 mm/h rainfall intensities, PFM decreased the average values of runoff by (55.2–59.6%) and (57.2–90.2%), reduced peak flow by (62.2–68%) and (64.2–86%), and increased the stable infiltration rate by (13.4–14.3%) and (26.6–41.3%), respectively. After the rainfall experiments ended for 1 h, the surface soil water rapidly infiltrated into PFM, which made the water-storage capacity of PFM groups higher than the control groups by 0.2–11% Vol. Subsequently, PFM increased the water-holding capacity by 0.3–2.3% Vol in the 10–70 cm depth from the heading period to the fallow period. It had a positive relationship between the PFM volumes and the average values of soil water content (R2 = 0.8, 0.84). In general, PFM could increase infiltration, reduce runoff, and improve the water-storage capacity to alleviate soil water deficit and the risk of farmland drought and floods. It has an excellent application effect in long-duration rainfall.
Natural History of Type II Autosomal Dominant Osteopetrosis: A Single Center Retrospective Study
Authors: Wang Ziyuan , Li Xiang , Wang Ya , Fu Wenzhen , Liu Yujuan , Zhang Zhenlin , Wang Chun
Published: March 2022

Background

Autosomal dominant osteopetrosis II (ADO II, MIM166600) is a sclerosing bone disorder caused by CLCN7 mutation. The main clinical characteristics include minor trauma-related fracture and hip osteoarthritis, whereas cranial nerve palsy and bone marrow failure rarely develop. Although it is generally believed that ADO II has a relatively benign course, the natural course of the disease in Chinese patients remains unclear.

Materials and Methods

Thirty-six patients diagnosed with ADO II in Shanghai Jiao Tong University Affiliated Sixth People’s Hospital from 2008 to 2021 were studied retrospectively. Among them, 15 patients were followed for an average of 6.3 years (1-14 years).

Results

In this study, minor trauma-related fractures of the limb were the most typical clinical manifestations. Visual loss (1/36) and bone marrow failure (2/36), was rare in this study. The condition of ADO II seems to be stable in most patients. There were no correlations between markedly elevated bone mineral density (BMD) and minor trauma-related fractures. In total, 21 diseases causing mutations were detected. Among them, the mutation c.2299C>T (p.Arg767Trp) was the most common (16.67%), and mutation c.937G>A [p.(Glu313Lys)] was associated with severe fractures, haematological defects and cranial palsy.

Conclusions

Minor trauma-related fracture is the most typical clinical manifestation of ADO II and always occurs in. The mutation c.2299C>T (p.Arg767Trp) is in general a relatively common variant, while the mutation c.937G>A [p.(Glu313Lys)] seems to be associated with severe phenotype. In our study, ADO II seems to remain stable over time.
A Model for Predicting Polycystic Ovary Syndrome Using Serum AMH, Menstrual Cycle Length, Body Mass Index and Serum Androstenedione in Chinese Reproductive Aged Population: A Retrospective Cohort Study
Authors: Xu Huiyu , Feng Guoshuang , Alpadi Kannan , Han Yong , Yang Rui , Chen Lixue , Li Rong , Qiao Jie
Published: March 2022

Background

A clinical diagnosis of polycystic ovary syndrome (PCOS) can be tedious with many different required tests and examinations. Furthermore, women with PCOS have increased risks for several metabolic complications, which need long-term health management. Therefore, we attempted to establish an easily applicable model to identify such women at an early stage.

Objective

To develop an easy-to-use tool for screening PCOS based on medical records from a large assisted reproductive technology (ART) center in China.

Materials and Methods

A retrospective observational cohort from Peking University Third Hospital was used in the study. Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression with 10-fold cross-validation was applied to construct the model. The area under the receiver operating characteristic curve (AUC), sensitivity, and specificity values were used to evaluate and compare the models.

Design, Setting, and Participants

This retrospective cohort study included 21,219 ovarian stimulation cycle records from January to December 2019 in Peking University Third Hospital.

Main Outcomes and Measures

The main outcome was whether there was a clinical diagnosis of PCOS. The independent variables included were age, body mass index (BMI), upper limit of menstrual cycle length (UML), basal serum levels of anti-Müllerian hormone (AMH), testosterone androstenedione, antral follicle counts et al.

Results

We have established a new mathematical model for diagnosing PCOS using serum AMH and androstenedione levels, UML, and BMI, with AUC values of 0.855 (0.838–0.870), 0.848 (0.791–0.891), 0.846 (0.812–0.875) in the training, validation, and testing sets, respectively. The contribution of each predictor to this model were: AMH 41.2%; UML 35.2%; BMI 4.3%; and androstenedione 3.7%. The top 10 groups of women most predicted to develop PCOS were demonstrated. An online tool (http://121.43.113.123:8888/) has been developed to assist Chinese ART clinics.

Conclusions

The models and online tool we established here might be helpful for screening and identifying women with undiagnosed PCOS in Asian populations and could assist in the long-term management of related metabolic disorders.
Fuzzy-Weighted Echo State Networks
Authors: Yao Zhao , Li Yingshun
Published: March 2022

A novel echo state network (ESN), referred to as a fuzzy-weighted echo state network (FWESN), is proposed by using the structural information of data sets to improve the performance of the classical ESN. The information is incorporated into the classical ESN via the concept of Takagi–Sugeno (TS) models/rules. We employ the fuzzy c-mean clustering method to extract the information based on the given data set. The antecedent part of the TS model is determined by the information. Then, we obtain new fuzzy rules by replacing the affine models in the consequent part of each TS rule with a classical ESN. Consequently, the output of the proposed FWESN is calculated through inferring these new fuzzy rules by a fuzzy-weighted mechanism. The corresponding reservoir is consisted of the sub-reservoirs of the new fuzzy rules. Furthermore, we prove that the FWESN has an echo state property by setting the largest spectrum radium of all the internal weight matrices in the sub-reservoirs less than one. Finally, a nonlinear dynamic system and five nonlinear time series are employed to validate the FWESN.
Event Detection and Identification in Distribution Networks Based on Invertible Neural Networks and Pseudo Labels
Authors: Yang Fan , Ling Zenan , Zhang Yuhang , He Xing , Ai Qian , Qiu Robert C.
Published: March 2022

Anomalous event detection and identification are important to support situational awareness and security analysis in power grids. Particularly, the distribution network is with complicated topology, variable load behaviors, and integration of nonlinear distributed generators (DGs), which is difficult to implement complete modeling mathematically. With the deployment of advanced measurement devices such as μPMUs in distribution networks, massive data containing rich system status information becomes available. In this paper, a framework for event detection, localization, and classification is studied to extract event features from measurements in distribution networks. Specifically, a method based on an invertible neural network (INN) is employed to model the complex distributions of normal-state measurements offline in a flexible way. It then establishes explicit likelihoods as the indicator to enable real-time event detection. Furthermore, a Jacobian-based method is utilized for spatial localization. Finally, as the events in practical power grids are mostly recorded unlabeled, the pseudo label (PL) based approach, superior in the separating ability for events under a low labeling rate, and is used to implement event classification. Several typical types of events simulated in the IEEE 34-bus system and real-world cases in a low-voltage system verify the effectiveness and superiorities of the framework.
Microstructural and Genetic Insights Into the Formation of the “Winter Diffusion Layer” in Japanese Pearl Oyster Pinctada fucata and Its Relation to Environmental Temperature Changes
Authors: Sato Kei , Setiamarga Davin H. E. , Yonemitsu Hiroshi , Higuchi Keita
Published: March 2022

Phenotypic plasticity in molluscan shell microstructures may be related to environmental changes. The “winter diffusion layer,” a shell microstructure of the Japanese pearl oyster Pinctada fucata, is an example of this phenomenon. In this study, we used P. fucata specimens with shared genetic background to evaluate the seasonal plasticity of shell microstructures, at molecular level. To detect the seasonal changes in shell microstructure and mineral composition, shells of multiple individuals were periodically collected and analyzed using scanning electron microscopy and Raman spectrophotometry. Our observations of the winter diffusion layer revealed that this irregular shell layer, located between the outer and middle shell layers, had a sphenoid shape in radial section. This distinct shape might be caused by the internal extension of the outer shell layer resulting from growth halts. The winter diffusion layer could be distinguished from the calcitic outer shell layer by its aragonitic components and microstructures. Moreover, the components of the winter diffusion layer were irregular simple prismatic (the outer and inner sublayers) and homogeneous structures (the middle sublayer). This irregular formation occurred until April, when the animals resumed their “normal” shell formation after hibernation. To check for a correlation between gene expression and the changes in microstructures, we conducted qPCR of seven major biomineralization-related shell matrix protein-coding genes (aspein, prismalin-14, msi7, msi60, nacrein, n16, and n19) in the shell-forming mantle tissue. Tissue samples were collected from the mantle edge (tissue secreting the outer shell layer) and mantle pallium (where the middle shell layer is constructed) of the same individuals used for microstructural observation and mineral identification that were collected in January (winter growth break period), April (irregular shell formation period), and August (normal shell formation period). Statistically significant differences in gene expression levels were observed between mantle edge and mantle pallium, but no seasonal differences were detected in the seasonal expression patterns of these genes. These results suggest that the formation of the irregular shell layer in P. fucata is caused by a currently unknown genetic mechanism unrelated to the genes targeted in the present study. Further studies using big data (transcriptomics and manipulation of gene expression) are required to answer the questions herein raised. Nevertheless, the results herein presented are essential to unravel the intriguing mystery of the formation of the winter diffusion layer, which may allow us to understand how marine mollusks adapt or acclimate to climate changes.
Drought Impacts on Tree Root Traits Are Linked to Their Decomposability and Net Carbon Release
Authors: Carrillo Yolima , Tissue David T. , Bruna Sophia , Maier Chelsea , Dijkstra Feike A.
Published: March 2022

Root trait plasticity can facilitate plant adjustment to water shortages, but the impact of altered traits on belowground carbon (C) cycling is mostly unknown. While drought and nutrient availability can alter root morphological and chemical traits that may affect root decomposition, direct assessments of drought mediated changes on decomposability are not available. We exposed four tree species contrasting in drought stress tolerance and root traits to three dry-down and recovery periods (over 5 months after 11 months of growth in well-watered conditions) under high and low nutrient conditions. We then assessed early stage root decomposability in relation to their morphology and chemistry as well as implications for CO2 release when accounting for effects on root biomass. While each species showed a unique set of responses, drought generally reduced root diameter and increased nitrogen concentration. We found limited evidence that morphological responses to drought were counteracted by high nutrient supply. Results indicated that the degree of association between morphological and nutrient root trait responses to drought and decomposability varied with different species. However, across these contrasting woody species, drought-induced increases in nitrogen and phosphorus concentrations were associated with drought-induced increases in early stage root decomposability. When accounting for changes in root biomass, estimated overall C loss through root decomposition increased with drought stress. Our experimental results demonstrate that changes in tree root traits with drought can enhance C loss via root decomposition, and with other factors being equal, drought may potentially contribute to a positive feedback to climate change. Our findings contribute empirical evidence to help disentangle the multiple factors involved in root contribution to C balances at the ecosystem level.
Genetic Predispositions Between COVID-19 and Three Cardio-Cerebrovascular Diseases
Authors: Tan Jiang-Shan , Liu Ningning , Guo Ting-Ting , Hu Song , Hua Lu , Qian Qiujin
Published: March 2022

Aims: This study was aimed to apply a Mendelian randomization design to explore the causal association between coronavirus disease 2019 (COVID-19) and three cardio-cerebrovascular diseases, including atrial fibrillation, ischemic stroke, and coronary artery disease.

Methods: Two-sample Mendelian randomization was used to determine the following: 1) the causal effect of COVID-19 on atrial fibrillation (55,114 case participants vs 482,295 control participants), coronary artery disease (34,541 case participants vs 261,984 control participants), and ischemic stroke (34,217 case participants vs 40,611 control participants), which were obtained from the European Bioinformatics Institute, and 2) the causal effect of three cardio-cerebrovascular diseases on COVID-19. The single-nucleotide polymorphisms (SNPs) of COVID-19 were selected from the summary-level genome-wide association study data of COVID-19-hg genome-wide association study (GWAS) meta-analyses (round 5) based on the COVID-19 Host Genetics Initiative for participants with European ancestry. The random-effects inverse-variance weighted method was conducted for the main analyses, with a complementary analysis of the weighted median and Mendelian randomization (MR)-Egger approaches.

Results: Genetically predicted hospitalized COVID-19 was suggestively associated with ischemic stroke, with an odds ratio (OR) of 1.049 [95% confidence interval (CI) 1.003–1.098; p = 0.037] in the COVID-19 Host Genetics Initiative GWAS. When excluding the UK Biobank (UKBB) data, our analysis revealed a similar odds ratio of 1.041 (95% CI 1.001–1.082; p = 0.044). Genetically predicted coronary artery disease was associated with critical COVID-19, with an OR of 0.860 (95% CI 0.760–0.973; p = 0.017) in the GWAS meta-analysis and an OR of 0.820 (95% CI 0.722–0.931; p = 0.002) when excluding the UKBB data, separately. Limited evidence of causal associations was observed between critical or hospitalized COVID-19 and other cardio-cerebrovascular diseases included in our study.

Conclusion: Our findings provide suggestive evidence about the causal association between hospitalized COVID-19 and an increased risk of ischemic stroke. Besides, other factors potentially contribute to the risk of coronary artery disease in patients with COVID-19, but not genetics.
An Effective Hypoxia-Related Long Non-Coding RNA Assessment Model for Prognosis of Lung Adenocarcinoma
Authors: Li Yuanshuai , Sun Xiaofang
Published: March 2022

Background: Lung adenocarcinoma (LUAD) represents one of the highest incidence rates worldwide. Hypoxia is a significant biomarker associated with poor prognosis of LUAD. However, there are no definitive markers of hypoxia-related long non-coding RNAs (lncRNAs) in LUAD.

Methods: From The Cancer Genome Atlas (TCGA) and the Molecular Signatures Database (MSigDB), we acquired the expression of hypoxia-related lncRNAs and corresponding clinical information of LUAD patients. The hypoxia-related prognostic model was constructed by univariable COX regression analysis, least absolute shrinkage and selection operator (LASSO), and multivariable Cox regression analysis. To assess the performance of the model, the Kaplan–Meier (KM) survival and receiver operating characteristic (ROC) curve analyses were performed.

Results: We found seven lncRNAs, AC022613.1, AC026355.1, GSEC, LINC00941, NKILA, HSPC324, and MYO16-AS1, as biomarkers of the potential hypoxia-related prognostic signature. In the low-risk group, patients had a better overall survival (OS). In addition, the results of ROC analysis indicated that the risk score predicted LUAD prognosis exactly. Furthermore, combining the expression of lncRNAs with clinical features, two predictive nomograms were constructed, which could accurately predict OS and had high clinical application value.

Conclusion: In summary, the seven-lncRNA prognostic signature related to hypoxia might be useful in predicting clinical outcomes and provided new molecular targets for the research of LUAD patients.
Hybrid RNA Sequencing Strategy for the Dynamic Transcriptomes of Winter Dormancy in an Evergreen Herbaceous Perennial, Iris japonica
Authors: Li Danqing , Shao Lingmei , Xu Tong , Wang Xiaobin , Zhang Runlong , Zhang Kaijing , Xia Yiping , Zhang Jiaping
Published: March 2022

Japanese iris (Iris japonica) is a popular perennial ornamental that originated in China; it has a long display period and remains green outdoors throughout the year. winter dormancy characteristics contribute greatly to the evergreenness of herbaceous perennials. Thus, it is crucial to explore the mechanism of winter dormancy in this evergreen herbaceous perennial. Here, we used the hybrid RNA-seq strategy including single-molecule real-time (SMRT) and next-generation sequencing (NGS) technologies to generate large-scale Full-length transcripts to examine the shoot apical meristems of Japanese iris. A total of 10.57 Gb clean data for SMRT and over 142 Gb clean data for NGS were generated. Using hybrid error correction, 58,654 full-length transcripts were acquired and comprehensively analysed, and their expression levels were validated by real-time qPCR. This is the first full-length RNA-seq study in the Iris genus; our results provide a valuable resource and improve understanding of RNA processing in this genus, for which little genomic information is available as yet. In addition, our data will facilitate in-depth analyses of winter dormancy mechanisms in herbaceous perennials, especially evergreen monocotyledons.
Genome-Wide Identification and Functional Characterization of the Chloride Channel TaCLC Gene Family in Wheat (Triticum aestivum L.)
Authors: Mao Peijun , Run Yonghang , Wang Hanghui , Han Changdong , Zhang Lijun , Zhan Kehui , Xu Haixia , Cheng Xiyong
Published: March 2022

In plants, chloride channels (CLC) are involved in a series of specific functions, such as regulation of nutrient transport and stress tolerance. Members of the wheat Triticum aestivum L. CLC (TaCLC) gene family have been proposed to encode anion channels/transporters that may be related to nitrogen transportation. To better understand their roles, TaCLC family was screened and 23 TaCLC gene sequences were identified using a Hidden Markov Model in conjunction with wheat genome database. Gene structure, chromosome location, conserved motif, and expression pattern of the resulting family members were then analyzed. Phylogenetic analysis showed that the TaCLC family can be divided into two subclasses (I and II) and seven clusters (-a, -c1, -c2, -e, -f1, -f2, and -g2). Using a wheat RNA-seq database, the expression pattern of TaCLC family members was determined to be an inducible expression type. In addition, seven genes from seven different clusters were selected for quantitative real-time PCR (qRT-PCR) analysis under low nitrogen stress or salt stress conditions, respectively. The results indicated that the gene expression levels of this family were up-regulated under low nitrogen stress and salt stress, except the genes of TaCLC-c2 cluster which were from subfamily -c. The yeast complementary experiments illustrated that TaCLC-a-6AS-1, TaCLC-c1-3AS, and TaCLC-e-3AL all had anion transport functions for NO3− or Cl−, and compensated the hypersensitivity of yeast GEF1 mutant strain YJR040w (Δgef1) in restoring anion-sensitive phenotype. This study establishes a theoretical foundation for further functional characterization of TaCLC genes and provides an initial reference for better understanding nitrate nitrogen transportation in wheat.
Identification of Four Novel COL4A5 Variants and Detection of Splicing Abnormalities in Three Chinese X-Linked Alport Syndrome Families
Authors: Wang Sai , Shao Yingfei , Wang Yixiu , Lu Jingru , Shao Leping
Published: March 2022

Chronic renal disease associated with X-linked Alport syndrome (XLAS) is relatively rare. However, due to the lack of specificity in the pathologic and clinical manifestations of the disease, it is easy to be misdiagnosed. In this study, we included three Chinese families with XLAS and used targeted NGS to find gene variants. In family X1, the 36-year-old male proband had hematuria, massive proteinuria, sensorineural deafness and ESRD at 33. In silico prediction showed the novel c.1424-4C > G variant reduced the score of the normal 3’ splice site from 0.47 to 0.00 (according to BDGP). Transcriptional analysis from his peripheral blood cells indicated that it caused the insertion of an amino acid [p.(Lys474_Gly475insVal)]. In family X2, the proband was a 32-year-old male, who had hematuria, proteinuria, hypertension, hearing loss and progressed into ESRD at 30 years. He carried a novel missense variant c.2777G > T p.(Gly926Val). In family X3, the proband, a 16-year-old male, had hematuria, massive proteinuria, sensorineural deafness and ESRD; the results of renal pathological findings were consistent with AS. He carried a novel variant c.4529-2A > T, so did his mother with ESRD and probable XLAS. Bioinformatic analysis with BDGP showed that it abolished the acceptor site from 0.83 to 0.00. RT-PCR analysis from his kidney tissue indicated that it caused exon 50 skipping and exon 50 skipping along with inserting a cryptic exon derived from intron 49 p.[Gly1510Aspfs*11, Gly1510Alafs*35]. Another novel missense variant c.1552G > A p.(Gly518Arg) was identified in his mother and his aunt. No skewed X-chromosome inactivation was involved in these two female patients. In conclusion, four novel variants in COL4A5 were identified and transcriptional analysis is essential to investigate the pathogenicity of intronic variants. Thus we found a rare event in a female patient with XLAS caused by two COL4A5 variants in trans.
LncRNAs and Chromatin Modifications Pattern m6A Methylation at the Untranslated Regions of mRNAs
Authors: Vaasjo Lee O.
Published: March 2022

New roles for RNA in mediating gene expression are being discovered at an alarming rate. A broad array of pathways control patterning of N6-methyladenosine (m6A) methylation on RNA transcripts. This review comprehensively discusses long non-coding RNAs (lncRNAs) as an additional dynamic regulator of m6A methylation, with a focus on the untranslated regions (UTRs) of mRNAs. Although there is extensive literature describing m6A modification of lncRNA, the function of lncRNA in guiding m6A writers has not been thoroughly explored. The independent control of lncRNA expression, its heterogeneous roles in RNA metabolism, and its interactions with epigenetic machinery, alludes to their potential in dynamic patterning of m6A methylation. While epigenetic regulation by histone modification of H3K36me3 has been demonstrated to pattern RNA m6A methylation, these modifications were specific to the coding and 3′UTR regions. However, there are observations that 5′UTR m6A is distinct from that of the coding and 3′UTR regions, and substantial evidence supports the active regulation of 5′UTR m6A methylation. Consequently, two potential mechanisms in patterning the UTRs m6A methylation are discussed; (1) Anti-sense lncRNA (AS-lncRNA) can either bind directly to the UTR, or (2) act indirectly via recruitment of chromatin-modifying complexes to pattern m6A. Both pathways can guide the m6A writer complex, facilitate m6A methylation and modulate protein translation. Findings in the lncRNA-histone-m6A axis could potentially contribute to the discovery of new functions of lncRNAs and clarify lncRNA-m6A findings in translational medicine.
Addressing Structural Inequities, a Necessary Step Toward Ensuring Equitable Access to Telehealth for Medication Abortion Care During and Post COVID-19
Authors: Thompson Terri-Ann , Northcraft Dana , Carrión Fabiola
Published: March 2022

Telehealth, one of the newest health innovations, has been promoted as a tool to enhance access to health care services in ways that center patient needs. However, integrating telehealth within an inequitable health system undermines its potential. This perspective highlights policies and practices that foster structural inequities and names their impact on the use and acceptability of telehealth for medication abortion among specific communities of color. Communities of color have a higher prevalence of abortion use but face many barriers, including financial and geographic barriers, to abortion access. Preliminary evidence on telehealth for medication abortion shows that it is highly acceptable, accommodating of patient needs, and may allow patients to access abortion care at earlier gestational ages. However, evidence during the COVID-19 pandemic shows that utilization of telehealth is lower among communities of color. We describe how systemic barriers, including regulations on or laws banning telehealth for medication abortion, disinvestments in digital access, and restrictions on public insurance coverage, could perpetuate lower utilization of telehealth for medication abortion care among communities of color. We call for systems changes that will remove these barriers and make this health care innovation available to all who may desire it.
Enterogenous Microbiotic Markers in the Differential Diagnosis of Crohn’s Disease and Intestinal Tuberculosis
Authors: Jiang Mingshan , Zeng Zhen , Chen Kexin , Dang Yuan , Li Lili , Ma Chunxiang , Cheng Rui , Hu Kehan , Li Xi , Zhang Hu
Published: March 2022

Crohn’s disease (CD) is a chronic intestinal disorder characterized by refractory gastrointestinal ulcerations. Intestinal tuberculosis (ITB) is one common intestinal disease in east Asia. The two diseases share similar clinical manifestations and endoscopic characteristics. Thus, it is difficult to establish a definite diagnosis of CD, CD concomitant with ITB (CD-ITB), and ITB in practice. Some enterogeneous microbiotic markers have been applied to differentiate CD and ITB, but it remains unknown how they work for the three groups of patients. The aim of our study was to explore the diagnostic values of these enterogeneous microbiotic markers (ASCA IgG, ASCA IgA, ACCA, Anti-I2 and AMCA) among CD, CD-ITB, and ITB patients. A total of 124 individuals were retrospectively enrolled in this study, namely, 103 CD patients, 10 CD-ITB patients, 9 ITB patients, and 68 healthy controls. The demographic and clinical characteristics of these patients were collected and analyzed. The values of these individual or combined enterogeneous microbiotic markers in diagnosis and classification were assessed in CD, CD-ITB, and ITB patients. ASCA IgG, ASCA IgA, and AMCA could accurately differentiate CD patients from healthy controls with an area under curve (AUC) of 0.688, 0.601, and 0.638, respectively. ASCA IgG was significantly higher in CD patients than in CD-ITB patients (P = 0.0003). The Anti-I2 antibody was appropriate for distinguishing CD-ITB from ITB patients (P = 0.039). In CD patients, ASCA IgG was higher in severe patients than in mild (P <0.0001) and inactive patients (P <0.0001), respectively. AMCA was significantly elevated in severe and moderate patients compared to inactive patients (P = 0.001, P = 0.003, respectively). AMCA was associated with a higher risk of CD-related surgery with a significant P-value of 0.0038. In our cohort, ASCAs and AMCA could accurately distinguish CD from healthy controls with an acceptable AUC. A combination of elevated ASCA IgG and AMCA antibodies established a higher sensitivity in differentiating CD from healthy controls. Elevated ASCA IgG demonstrated a differential diagnostic value between CD and CD-ITB. Anti-I2 could also distinguish CD-ITB from ITB. The level of AMCA was associated with both disease severity and CD-related surgery. Likewise, the level of ASCA IgG was also related to disease severity.