bluuebunny/crossref_metadata_2025 huggingface dataset:
Community Empowerment Through Homegrown Medicinal Plants and The "Wedang Uwuh" Herbal Beverage Cultivation in Seketi Hamlet
Authors: Pudjowati Juliani , Abdurrahman Thariq , Pratiwi Enjelita Putri , Baqi Rizky Nugraha , Syafitri Anggun Kumala
Published: December 2021

Rural community empowerment is an effort to develop independence and community welfare through the improvement of knowledge, attitudes, skills, behaviour, abilities, awareness, and resource utilization. This is carried out by establishing policies, programs, activities and assisting with the problems related to the priority needs of the community to increase community activities through the cultivation of homegrown medicinal plants. The homegrown medicinal plants (TOGA) are traditional medicinal plants. These medicinal plants are used for making Wedang Uwuh. The ingredients consist of various types of spices namely: ginger, cloves, nutmeg, lemongrass, cardamom, cinnamon, sappanwood, and rosella. The method of implementation used is through the diffusion of knowledge and direct practice. These activities were carried out for the residents of Seketi Hamlet. The results of the activities that have been carried out in Seketi Hamlet are as follows: the community gets insight into TOGA plants; people acquire skills in how to process TOGA into Wedang Uwuh herbal beverage which can help increase endurance (immunomodulators) to protect against Covid-19 pandemic; adding or increasing community activities through the use of house yards as TOGA growing media. Therefore, it is necessary for the Head of Seketi Hamlet to consider doing several things, namely the provision of advanced programs via entrepreneurship training to produce superior products from TOGA yields, and community cooperation in the continuous care of the “Seketi Hamlet Health Garden” for long term benefits.
COMPUTER VISION BASED TRAFFIC RULE BREACH DETECTION
Authors: Acharya Sunim , Poudel Sujan , Dangol Shreeya , Subedi Saragam
Published: December 2021

This paper is about the detection of traffic rule
breach via computer vision which takes the feed from the
traffic surveillance system, processes the video feed, detects
the breach and alerts the traffic police. The number of
traffic accidents is on the rise with the increasing number
of vehicles. Traffic breach is the biggest cause of accidents.
So, to mitigate this problem our system processes the CCTV
camera feed in real-time, detects the traffic rule breach
events and sends the push notification to the android based
application of the traffic police stationed nearby; so, further
actions can be taken. As this system detects breach faster
than humans, the concerned authoritarian department will
be at ease in implementing safe roads accurately. This
system acts as an add-on to the current video surveillance
system rather than building new infrastructure. Thus, the
output of this system can be used not only or safety and
security purposes but as well as for analytical purposes with
effective traffic monitoring at a lower cost. Hence, this
system aids law enforcement agencies in implementing road
safety efficiently and effectively ensuring smooth traffic
flow.
RAILWAY TRACK – CRACK DETECTION SYSTEM BY USING ARDUINO MICROCONTROLLER
Authors: Bhojwani N L , Ansari A S , Jirge S S , Baviskar M B , Pawar D N
Published: December 2021

- In India railways transportation service is
the cheapest and most convenient mode of passenger
transport as well as for long distance and suburban
traffic. Almost 80% of the transport in India is being
carried out by railway network. The main cause of the
accidents happened in railways are railway track
crossing and unidentified crack in rail tracks. About
60% accidents are happened at railway track crossing
and due to crack in railway tracks resulting in loss of
precious life of passengers and loss of economy.
Therefore, there is a need to have new technology
which will be robust, efficient and stable for both crack
detection in railway track as well as object detection.
This project discusses a Railway track crack detection
using sensors and is a dynamic approach which
combines the use of GPS tracking system and GSM
module to send alert messages and the geographical
coordinate of location. An Arduino Microcontroller is
used to control and coordinate the activities of this
device.
Causes of Hypermagnesaemia: A Literature Review
Authors: Qazi Moarij , Qazi Huma , Nakhoul Georges , Provenzano Laura Ferreira
Published: December 2021

Magnesium is one of the commonly overlooked electrolytes, yet it plays a vital role in many of the processes in the human body. The balance of magnesium can translate into subtle changes in a person’s daily life, causing fatigue and confusion, to extreme cases that can end up causing central nervous system depression, respiratory failure, or cardiac arrhythmias.

It is vital to be familiar with the physiology of magnesium regulation and knowledgeable regarding the causes that can lead to its toxicity to ensure the prevention of the possibly fatal condition.

Magnesium balance can be summarised as the difference between magnesium intake and its excretion. Any factor overwhelming either of the two factors can cause pathological levels of the electrolyte. In addition to learning preventive measures to help patients against effects of magnesium toxicity, it is also important that the medical community trains to be able to treat cases of hypermagnesaemia.

This review assesses the latest advancements in knowledge of magnesium metabolism, examines the case reports of hypermagnesaemia in an attempt to list the causes of magnesium toxicity, and enumerates management advances for the condition.
Stroke in a Patient with Recurrent Meningeal Tuberculosis and HIV Coinfection
Authors: Fontalvo-Rivera Dilia , Mora-García Gustavo , Jiménez-Borré Gustavo , Segovia-Fuentes Javier , Gómez-Camargo Doris
Published: December 2021

Recurrent tuberculous meningitis can have a non-specific clinical presentation when it presents as a co-infection with HIV and can resemble other causes of subacute and chronic meningitis, leading to unwanted outcomes; for this reason, timely diagnoses are required. The most widely used microbiological diagnostic methods can be of low sensitivity or have delayed results.

The aim of this article is to present a clinical case of recurrent tuberculous meningitis with a clinical presentation of stroke due to a basal cistern ischaemic lesion in a patient co-infected with HIV, who had a microbiological confirmation and a drug sensitivity study with phenotypic and molecular tests.
Optimising Response to Advanced Therapies in Rheumatoid Arthritis – Using
Prehabilitation to Improve Success?
Authors: Mason Alice , Malik Mariam
Published: December 2021

In recent years, a new concept of prehabilitation, enhancing an individual’s functional capacity ahead of a medical intervention, has begun to be explored in the fields of surgery and oncology, with positive results. This article explores applying the principle of prehabilitation to patients with rheumatoid arthritis prior to starting advanced therapies, including biologic disease-modifying antirheumatic drugs and targeted synthetic disease-modifying antirheumatic drugs. In this article, the literature is reviewed and the existing evidence is summarised, and the suggestion is that this approach could improve a patient’s chance of achieving low disease activity or remission.

There are a number of opportunities for improving the likelihood of patients with rheumatoid arthritis having a good response to therapy. Research shows that smokers starting TNF inhibitors are less likely to achieve a good response compared to non-smokers. Obese patients are also less likely to achieve a good response with TNF inhibitors; female patients with obesity may be less likely to achieve a good response with tocilizumab and early real-world data suggest there may be a reduced response to JAK inhibitors. Rheumatoid arthritis patients experiencing depression are less likely to respond to TNF inhibitors. Increased physical activity is potentially beneficial for all rheumatoid arthritis patients, although the effect on response to specific drugs has been less widely explored.

Prehabilitation approaches could include targeting smoking cessation, improving physical activity, providing psychological support, optimising BMI, and dietary changes. A number of studies have shown that each of these interventions can lead to significant improvements in disease activity scores, with some patients potentially benefitting from more than one intervention. The authors identify principles for delivering prehabilitation in practice and suggest that this is an exciting area for ongoing research.
3D Bioprinting of Pectin-Cellulose Nanofibers Multicomponent Bioinks
Authors: Pitton Matteo , Fiorati Andrea , Buscemi Silvia , Melone Lucio , Farè Silvia , Contessi Negrini Nicola
Published: December 2021

Pectin has found extensive interest in biomedical applications, including wound dressing, drug delivery, and cancer targeting. However, the low viscosity of pectin solutions hinders their applications in 3D bioprinting. Here, we developed multicomponent bioinks prepared by combining pectin with TEMPO-oxidized cellulose nanofibers (TOCNFs) to optimize the inks’ printability while ensuring stability of the printed hydrogels and simultaneously print viable cell-laden inks. First, we screened several combinations of pectin (1%, 1.5%, 2%, and 2.5% w/v) and TOCNFs (0%, 0.5%, 1%, and 1.5% w/v) by testing their rheological properties and printability. Addition of TOCNFs allowed increasing the inks’ viscosity while maintaining shear thinning rheological response, and it allowed us to identify the optimal pectin concentration (2.5% w/v). We then selected the optimal TOCNFs concentration (1% w/v) by evaluating the viability of cells embedded in the ink and eventually optimized the writing speed to be used to print accurate 3D grid structures. Bioinks were prepared by embedding L929 fibroblast cells in the ink printed by optimized printing parameters. The printed scaffolds were stable in a physiological-like environment and characterized by an elastic modulus of E = 1.8 ± 0.2 kPa. Cells loaded in the ink and printed were viable (cell viability >80%) and their metabolic activity increased in time during the in vitro culture, showing the potential use of the developed bioinks for biofabrication and tissue engineering applications.
Advances of Glycometabolism Engineering in Chinese Hamster Ovary Cells
Authors: Zhang Huan-Yu , Fan Zhen-Lin , Wang Tian-Yun
Published: December 2021

As the most widely used mammalian cell line, Chinese hamster ovary (CHO) cells can express various recombinant proteins with a post translational modification pattern similar to that of the proteins from human cells. During industrial production, cells need large amounts of ATP to support growth and protein expression, and since glycometabolism is the main source of ATP for cells, protein production partly depends on the efficiency of glycometabolism. And efficient glycometabolism allows less glucose uptake by cells, reducing production costs, and providing a better mammalian production platform for recombinant protein expression. In the present study, a series of progresses on the comprehensive optimization in CHO cells by glycometabolism strategy were reviewed, including carbohydrate intake, pyruvate metabolism and mitochondrial metabolism. We analyzed the effects of gene regulation in the upstream and downstream of the glucose metabolism pathway on cell’s growth and protein expression. And we also pointed out the latest metabolic studies that are potentially applicable on CHO cells. In the end, we elaborated the application of metabolic models in the study of CHO cell metabolism.
Laser Additively Manufactured Iron-Based Biocomposite: Microstructure, Degradation, and In Vitro Cell Behavior
Authors: Yang Youwen , Cai Guoqing , Yang Mingli , Wang Dongsheng , Peng Shuping , Liu Zhigang , Shuai Cijun
Published: December 2021

A too slow degradation of iron (Fe) limits its orthopedic application. In this study, calcium chloride (CaCl2) was incorporated into a Fe-based biocomposite fabricated by laser additive manufacturing, with an aim to accelerate the degradation. It was found that CaCl2 with strong water absorptivity improved the hydrophilicity of the Fe matrix and thereby promoted the invasion of corrosive solution. On the other hand, CaCl2 could rapidly dissolve once contacting the solution and release massive chloride ion. Interestingly, the local high concentration of chloride ion effectively destroyed the corrosion product layer due to its strong erosion ability. As a result, the corrosion product layer covered on the Fe/CaCl2 matrix exhibited an extremely porous structure, thus exhibiting a significantly reduced corrosion resistance. Besides, in vivo cell testing proved that the Fe/CaCl2 biocomposite also showed favorable cytocompatibility.
Carbon-Coated Magnetic Nanoparticle Dedicated to MRI/Photoacoustic Imaging of Tumor in Living Mice
Authors: Li Yujing , Ye Fei , Zhang Shanxiang , Ni Wenjun , Wen Liewei , Qin Huan
Published: December 2021

Multimodality imaging can reveal complementary anatomic and functional information as they exploit different contrast mechanisms, which has broad clinical applications and promises to improve the accuracy of tumor diagnosis. Accordingly, to attain the particular goal, it is critical to exploit multimodal contrast agents. In the present work, we develop novel cobalt core/carbon shell–based nanoparticles (Cobalt at carbon NPs) with both magnetization and light absorption properties for dual-modality magnetic resonance imaging (MRI) and photoacoustic imaging (PAI). The nanoparticle consists of ferromagnetic cobalt particles coated with carbon for biocompatibility and optical absorption. In addition, the prepared Cobalt at carbon NPs are characterized by transmission electron microscope (TEM), visible–near-infrared spectra, Raman spectrum, and X-ray powder diffraction for structural analysis. Experiments verify that Cobalt at carbon NPs have been successfully constructed and the designed Cobalt at carbon NPs can be detected by both MRI and PAI in vitro and in vivo. Importantly, intravenous injection of Cobalt at carbon NPs into glioblastoma-bearing mice led to accumulation and retention of Cobalt at carbon NPs in the tumors. Using such a multifunctional probe, MRI can screen rapidly to identify potential lesion locations, whereas PAI can provide high-resolution morphological structure and quantitative information of the tumor. The Cobalt at carbon NPs are likely to become a promising candidate for dual-modality MRI/PAI of the tumor.
Novel BMP4 Truncations Resulted in Opposite Ocular Anomalies: Pathologic Myopia Rather Than Microphthalmia
Authors: Jiang Yi , Ouyang Jiamin , Li Xueqing , Wang Yingwei , Zhou Lin , Li Shiqiang , Jia Xiaoyun , Xiao Xueshan , Sun Wenmin , Wang Panfeng , Zhang Qingjiong
Published: December 2021

BMP4 variants have been reported to be associated with syndromic microphthalmia (MCOPS6, OMIM 607932). This study aims to describe BMP4 truncation mutations contributing to a novel phenotype in eight patients from four Chinese families. In this study, BMP4 variants were collected from a large dataset from in-house exome sequencing. Candidate variants were filtered by multiple in silico tools as well as comparison with data from multiple databases. Potential pathogenic variants were further confirmed by Sanger sequencing and cosegregation analysis. Four novel truncation variants in BMP4 were detected in four out of 7,314 unrelated probands with different eye conditions. These four mutations in the four families solely cosegregated in all eight patients with a specific form of pathologic myopia, characterized by significantly extended axial length, posterior staphyloma, macula patchy, chorioretinal atrophy, myopic optic neuropathy or glaucoma, vitreous opacity, and unique peripheral snow-grain retinopathy. The extreme rarity of the truncations in BMP4 (classified as intolerant in the gnomAD database, pLI = 0.96), the exclusive presence of these variants in the four families with pathologic myopia, variants fully co-segregated with the same specific phenotypes in eight patients from the four families, and the association of the pathogenicity of truncations with syndromic microphthalmia in previous studies, all support a novel association of BMP4 truncations with a specific form of pathologic myopia. The data presented in this study demonstrated that heterozygous BMP4 truncations contributed to a novel phenotype: pathologic myopia rather than microphthalmia. Mutations in the same gene resulting in both high myopia and microphthalmia have been observed for a few other genes like FZD5 and PAX6, suggesting bidirectional roles of these genes in early ocular development. Further studies are expected to elucidate the molecular mechanism of the bidirectional regulation.
A Novel Insight Into the Fate of Cardiomyocytes in Ischemia-Reperfusion Injury: From Iron Metabolism to Ferroptosis
Authors: Li Jing-yan , Liu Shuang-qing , Yao Ren-qi , Tian Ying-ping , Yao Yong-ming
Published: December 2021

Ischemia-reperfusion injury (IRI), critically involved in the pathology of reperfusion therapy for myocardial infarction, is closely related to oxidative stress the inflammatory response, and disturbances in energy metabolism. Emerging evidence shows that metabolic imbalances of iron participate in the pathophysiological process of cardiomyocyte IRI [also termed as myocardial ischemia-reperfusion injury (MIRI)]. Iron is an essential mineral required for vital physiological functions, including cellular respiration, lipid and oxygen metabolism, and protein synthesis. Nevertheless, cardiomyocyte homeostasis and viability are inclined to be jeopardized by iron-induced toxicity under pathological conditions, which is defined as ferroptosis. Upon the occurrence of IRI, excessive iron is transported into cells that drive cardiomyocytes more vulnerable to ferroptosis by the accumulation of reactive oxygen species (ROS) through Fenton reaction and Haber–Weiss reaction. The increased ROS production in ferroptosis correspondingly leads cardiomyocytes to become more sensitive to oxidative stress under the exposure of excess iron. Therefore, ferroptosis might play an important role in the pathogenic progression of MIRI, and precisely targeting ferroptosis mechanisms may be a promising therapeutic option to revert myocardial remodeling. Notably, targeting inhibitors are expected to prevent MIRI deterioration by suppressing cardiomyocyte ferroptosis. Here, we review the pathophysiological alterations from iron homeostasis to ferroptosis together with potential pathways regarding ferroptosis secondary to cardiovascular IRI. We also provide a comprehensive analysis of ferroptosis inhibitors and initiators, as well as regulatory genes involved in the setting of MIRI.
Catalytic Functionalized Structured Monolithic Micro-/Mesoreactors: Engineering, Properties, and Performance in Flow Synthesis: An Overview and Guidelines
Authors: Szymańska Katarzyna , Ciemięga Agnieszka , Maresz Katarzyna , Pudło Wojciech , Malinowski Janusz , Mrowiec-Białoń Julita , Jarzębski Andrzej B.
Published: December 2021

In this review article, we first discussed the development of silica monoliths with hierarchical macro-/mesopore structure and their potential figures of merit as continuous-flow micro-/mesoreactors of up to 30 ml working volume. Making use of the flow hindrance of different pore structures seen from the Darcy law perspective, we discriminated four structures of the monoliths (M1–M4). We then summarized the most important results, mainly from our studies of continuous-flow structured monolithic reactors and rotating bed reactors (RBRs) filled with structured pellets, activated with various catalytic entities and enzymes. The results show that an increase in the flow rate and thus velocity in reactors activated with more conventional catalytic sites has no or a minor positive effect on the apparent reaction rate. On the contrary, in those with the most open structure (M1) and functionalized with enzymes, it could increase by more than two orders of magnitude even at low overpressures. The production systems worked stably for at least 200 h. To conclude, the synthetic system made of the hierarchically structured monoliths, or RBRs filled with structured catalytic pellets, lay the foundation for a new platform for the high-yield production of a wide variety of specialty chemicals, even on a multikilogram scale, in a safe and sustained manner.
Ultrafine MoS2 Nanosheets Vertically Patterned on Graphene for High-Efficient Li-Ion and Na-Ion Storage
Authors: Wei Chunguang , Hou Zhidong , Sun Huanhuan , Wang Jian-Gan
Published: December 2021

Hierarchically two-dimensional (2D) heteroarchitecture with ultrafine MoS2 nanosheets vertically patterned on graphene is developed by using a facile solvothermal method. It is revealed that the strong interfacial interaction between acidic Mo precursors and graphene oxides allows for uniform and tight alignment of edge-oriented MoS2 nanosheets on planar graphene. The unique sheet-on-sheet architecture is of grand advantage in synergistically utilizing the highly conductive graphene and the electroactive MoS2, thus rendering boosted reaction kinetics and robust structural integrity for energy storage. Consequently, the heterostructured MoS2@graphene exhibits impressive Li/Na-ion storage properties, including high-capacity delivery and superior rate/cycling capability. The present study will provide a positive impetus on rational design of 2D metal sulfide/graphene composites as advanced electrode materials for high-efficient alkali–metal ion storage.
HO-3867 Induces ROS-Dependent Stress Response and Apoptotic Cell Death in Leishmania donovani
Authors: Das Amrita , Kamran Mohd. , Ali Nahid
Published: December 2021

Lack of vaccine and increasing chemotherapeutic toxicities currently necessitate the development of effective and safe drugs against various forms of leishmaniases. We characterized the cellular stress induced by a novel curcumin analogue, HO-3867, encapsulated within the phosphatidylcholine-stearylamine (PC-SA) liposome for the first time against Leishmania. The liposomal formulation of HO-3867 (i.e., PC-SA/HO-3867) initiated oxidative stress-induced apoptosis in L. donovani, revealed by altered cell morphology, phosphatidylserine externalization, mitochondrial depolarization, intracellular lipid accumulation, and cell cycle arrest in promastigotes. Liposomal HO-3867 was observed to be a strong apoptosis inducer in L. donovani and L. major in a dose-dependent manner, yet completely safe for normal murine macrophages. Moreover, PC-SA/HO-3867 treatment induced L. donovani metacaspase and PARP1 activation along with downregulation of the Sir2 gene. PC-SA/HO-3867 arrested intracellular L. donovani amastigote burden in vitro, with reactive oxygen species (ROS) and nitric oxide (NO)-mediated parasite killing. These data suggest that liposomal HO-3867 represents a highly promising and non-toxic nanoparticle-based therapeutic platform against leishmaniasis inspiring further preclinical developments.
Bacterial Quorum-Sensing Molecules as Promising Natural Inhibitors of Candida albicans Virulence Dimorphism: An In Silico and In Vitro Study
Authors: Jothi Ravi , Hari Prasath Nagaiah , Gowrishankar Shanmugaraj , Pandian Shunmugiah Karutha
Published: December 2021

Farnesol, a self-secreted quorum-sensing molecule (QSM) of Candida albicans, has been known to limit yeast-to-hyphal transition by blocking the RAS1–cAMP–PKA pathway. In a similar fashion, certain bacterial QSMs have also been reported to be successful in attenuating C. albicans biofilm and hyphal formation at relatively high cell density. This prompted us to investigate the antihyphal efficacy of certain bacterial QSMs through virtual docking against seminal drug targets, viz., CYCc and RAS1, that have been reported to be the hallmark players in C. albicans dimorphic virulence cascade. Against this backdrop, 64 QSMs belonging to five different bacterial QS signaling systems were subjected to initial virtual screening with farnesol as reference. Data of the virtual screening unveiled QSMs belonging to diketopiperazines (DKPs), i.e., 3-benzyl-6-isobutylidene-2,5-piperazinedione (QSSM 1157) and cyclo(l-Pro-l-Leu) (QSSM 1112), as potential inhibitors of CYCc and RAS1 with binding energies of −8.2 and −7.3 kcal mol−1, respectively. Further, the molecular dynamics simulations (for 50 ns) of CYCc-QSSM 1157 and RAS1-QSSM 1112 complexes revealed the mean ligand root mean square deviation (RMSD) values of 0.35 and 0.27 Å, respectively, which endorsed the rigid nature, less fluctuation in binding stiffness, and conformation of binding complexes. Furthermore, the identified two QSMs were found to be good in solubility, absorption, and permeation and less toxic in nature, as revealed by pharmacokinetics and toxicity analyses. In addition, the in vitro antihyphal assays using liquid and solid media, germ-tube experiment, and microscopic analysis strongly validated DKP-QSSM 1112 as a promising inhibitor of hyphal transition. Taken together, the present study unequivocally proves that DKPs can be used as potent inhibitors of C. albicans virulence dimorphism.
Short-Chain Fatty Acid and FFAR2 Activation – A New Option for Treating Infections?
Authors: Schlatterer Katja , Peschel Andreas , Kretschmer Dorothee
Published: December 2021

The human innate immune system is equipped with multiple mechanisms to detect microbe-associated molecular patterns (MAMPs) to fight bacterial infections. The metabolite short-chain fatty acids (SCFAs) acetate, propionate and butyrate are released by multiple bacteria or are food ingredients. SCFA production, especially acetate production, is usually essential for bacteria, and knockout of pathways involved in acetate production strongly impairs bacterial fitness. Because host organisms use SCFAs as MAMPs and alter immune reactions in response to SCFAs, interventions that modulate SCFA levels can be a new strategy for infection control. The interaction between SCFAs and host cells has been primarily investigated in the intestinal lumen because of the high local levels of SCFAs released by bacterial microbiome members. However, members of not only the intestinal microbiome but also the skin microbiome produce SCFAs, which are known ligands of the seven-transmembrane G-protein-coupled receptor FFAR2. In addition to enterocytes, FFAR2 is expressed on other human cell types, including leukocytes, especially neutrophils. This finding is in line with other research that determined that targeted activation of FFAR2 diminishes susceptibility toward various types of infection by bacteria such as Klebsiella pneumonia, Citrobacter rodentium, and Staphylococcus aureus but also by viruses such as respiratory syncytial and influenza viruses. Thus, our immune system appears to be able to use FFAR2-dependent detection of SCFAs for perceiving and even averting severe infections. We summarize recent advances in understanding the role of SCFAs and FFAR2 in various infection types and propose the manipulation of this receptor as an additional therapeutic strategy to fight infections.
Ischemic Heart Disease Selectively Modifies the Right Atrial Appendage Transcriptome
Authors: Mulari Severi , Eskin Arda , Lampinen Milla , Nummi Annu , Nieminen Tuomo , Teittinen Kari , Ojala Teija , Kankainen Matti , Vento Antti , Laurikka Jari , Kupari Markku , Harjula Ari , Tuncbag Nurcan , Kankuri Esko
Published: December 2021

Background: Although many pathological changes have been associated with ischemic heart disease (IHD), molecular-level alterations specific to the ischemic myocardium and their potential to reflect disease severity or therapeutic outcome remain unclear. Currently, diagnosis occurs relatively late and evaluating disease severity is largely based on clinical symptoms, various imaging modalities, or the determination of risk factors. This study aims to identify IHD-associated signature RNAs from the atrial myocardium and evaluate their ability to reflect disease severity or cardiac surgery outcomes.

Methods and Results: We collected right atrial appendage (RAA) biopsies from 40 patients with invasive coronary angiography (ICA)-positive IHD undergoing coronary artery bypass surgery and from 8 patients ICA-negative for IHD (non-IHD) undergoing valvular surgery. Following RNA sequencing, RAA transcriptomes were analyzed against 429 donors from the GTEx project without cardiac disease. The IHD transcriptome was characterized by repressed RNA expression in pathways for cell–cell contacts and mitochondrial dysfunction. Increased expressions of the CSRNP3, FUT10, SHD, NAV2-AS4, and hsa-mir-181 genes resulted in significance with the complexity of coronary artery obstructions or correlated with a functional cardiac benefit from bypass surgery.

Conclusions: Our results provide an atrial myocardium-focused insight into IHD signature RNAs. The specific gene expression changes characterized here, pave the way for future disease mechanism-based identification of biomarkers for early detection and treatment of IHD.
Uric Acid Variability as a Predictive Marker of Newly Developed Cardiovascular Events in Type 2 Diabetes
Authors: Kim Hae Kyung , Lee Minyoung , Lee Yong-ho , Lee Byung-Wan , Cha Bong-Soo , Kang Eun Seok
Published: December 2021

Background: Cardiovascular disease (CVD) is associated with morbidity and mortality in patients with type 2 diabetes mellitus (T2D). However, the role of serum uric acid as a risk factor for developing cardiovascular disease is controversial. This study investigated whether uric acid variability was associated with new-onset symptomatic CVD in patients with T2D, requiring percutaneous coronary intervention.

Methods: A total of 1,071 patients were enrolled in this retrospective cross-sectional study after propensity score matching. Patients with T2D and new-onset symptomatic CVD who received percutaneous coronary intervention for the first time, and with at least three consecutive 6-monthly measurements of serum uric acid were recruited from Severance Hospital between January 2015 and December 2019. Uric acid variability was measured by average successive variability (ASV) and analyzed to evaluate a possible correlation with the risk of developing CVD.

Results: The patients were divided into quartiles based on the uric acid variability. Patients in the highest quartile were older and presented lower renal function and a higher mortality from CVD. There was a linear association between a high uric acid variability and the development of CVD. Compared to the lowest quartile, patients in the higher quartiles had a higher risk of CVD [quartile 3: adjusted odds ratio (aOR) = 1.76; 95% confidence interval (CI), 1.20–2.82; P = 0.019; quartile 4 aOR = 2.89; 95% CI, 1.74–4.80; P < 0.001].

Conclusion: High uric acid variability is independently associated with an increased risk of new-onset symptomatic CVD requiring percutaneous coronary intervention in patients with T2D. Thus, maintaining serum uric acid in a narrow range by prescribing effective medications is essential to prevent new-onset CVD in patients with T2D. Nonetheless, the potential use of uric acid variability as a predictive marker of CVD in patients with T2D needs further validation.
Case Report: Key Role of the Impella Device to Achieve Complete Revascularization in a Patient With Complex Multivessel Disease and Severely Depressed Left Ventricular Function
Authors: Monizzi Giovanni , Grancini Luca , Olivares Paolo , Bartorelli Antonio L.
Published: December 2021

Background: Left ventricle (LV) assist devices may be required to stabilize hemodynamic status during complex, high-risk, and indicated procedures (CHIP). We present a case in which elective hemodynamic support with the Impella CP device was essential to achieve complete revascularization with PCI in a patient with complex multivessel disease and severely depressed LV function.

Case Summary: A 45-year-old male with no previous history of cardiovascular disease presented to the emergency department for new onset exertional dyspnoea. Echocardiography showed severely depressed LV function (EF 27%) that was confirmed with cardiac magnetic resonance. Two chronic total occlusions (CTOs) of the proximal right coronary artery (RCA) and left circumflex coronary artery (LCx) were found at coronary angiography. After Heart Team evaluation, PCI with Impella hemodynamic support was planned. After crossing and predilating the CTO of the LCx, ventricular fibrillation (VF) occurred. No direct current (DC) shock was performed because the patient was conscious thanks to the support provided by the Impella pump. About 1 min later, spontaneous termination of VF occurred. Afterwards, the two CTOs were successfully treated with good result and no complications. Recovery of LV function was observed at discharge. At 9 months, the patient had no symptoms and echocardiography showed an EF of 60%.

Discussion: In this complex high-risk patient, hemodynamic support was essential to allow successful PCI. It is remarkable that the patient remained conscious and hemodynamically stable during VF that spontaneously terminated after 1 min, likely because the Impella pump provided preserved coronary perfusion and LV unloading. This case confirms the pivotal role of Impella in supporting CHIP, particularly in patients with multivessel disease and depressed LV function.
Accurate Estimation of Heart and Respiration Rates Based on an Optical Fiber Sensor Using Adaptive Regulations and Statistical Classifications Spectrum Analysis
Authors: Zhao Rongjian , Du Lidong , Zhao Zhan , Chen Xianxiang , Sun Jie , Man Zhenzhen , Cao Baogeng , Fang Zhen
Published: December 2021

The aim of this work is to present a method for accurately estimating heart and respiration rates under different actual conditions based on a mattress which was integrated with an optical fiber sensor. During the estimation, a ballistocardiogram (BCG) signal, which was obtained from the optical fiber sensor, was used for extracting the heart rate and the respiration rate. However, due to the detrimental effects of the differential detector, self-interference, and variation of installation status of the sensor, the ballistocardiogram (BCG) signal was difficult to detect. In order to resolve the potential concerns of individual differences and body interferences, adaptive regulations and statistical classifications spectrum analysis were used in this paper. Experiments were carried out to quantify heart and respiration rates of healthy volunteers under different breathing and posture conditions. From the experimental results, it could be concluded that (1) the heart rates of 40–150 beats per minute (bpm) and respiration rates of 10–20 breaths per minute (bpm) were measured for individual differences; (2) for the same individuals under four different posture contacts, the mean errors of heart rates were separately 1.60 ± 0.98 bpm, 1.94 ± 0.83 bpm, 1.24 ± 0.59 bpm, and 1.06 ± 0.62 bpm, in contrast, the mean errors of the polar beat device were 1.09 ± 0.96 bpm, 1.44 ± 0.99 bpm, and 1.78 ± 0.94 bpm. Furthermore, the experimental results were validated by conventional counterparts which used skin-contacting electrodes as their measurements. It was reported that the heart rate was 0.26 ± 2.80 bpm in 95% confidence intervals (± 1.96SD) in comparison with Philips sure-signs VM6 medical monitor, and the respiration rate was 0.41 ± 1.49 bpm in 95% confidence intervals (± 1.96SD) in comparison with ECG-derived respiratory (EDR) measurements for respiration rates. It was indicated that the developed system using adaptive regulations and statistical classifications spectrum analysis performed better and could easily be used under complex environments.
High-Resolution Petrographic Evidence Confirming Detrital and Biogenic Magnetites as Remanence Carriers for Zongpu Carbonates in the Gamba Area, South Tibet
Authors: Zhao Qian , Huang Baochun , Yi Zhiyu , Xue Pengfei
Published: December 2021

Paleocene carbonates from the Gamba area of South Tibet provide the largest paleomagnetic dataset for constraining the paleogeography of the India-Asia collision in the early stage. Previous studies argued that the characteristic remanences (ChRMs) obtained from this unit were remagnetized via orogenic fluids. This study carries out a high-resolution petrographic study on the Paleocene carbonates from Gamba aiming to test the nature of the ChRMs. Electron microscopic observation on magnetic extracts identified a large amount of detrital magnetite that are multi- to single domain in sizes and nanoscale biogenic magnetite. Minor framboidal iron oxides were also identified, which were previously interpreted as authigenic magnetite that substitutes pyrite. However, our scanning and transmission electron microscopic (SEM/TEM) observations, along with optical microscope and Raman spectrum investigations further suggest that these magnetic minerals are pigmentary hematite and goethite that are incapable of carrying a stable primary magnetization. We therefore argue that the ChRMs of the limestones from the Zongpu Formation in the Gamba area are carried by detrital and biogenic magnetites rather than authigenic magnetite. The paleomagnetic data from the Gamba area are interpreted as primary origin and can thus be used for tectonic reconstructions. We emphasize that magnetic extraction, integrated with advanced mineralogic studies (e.g., electron backscatter diffraction and electron diffraction) are effective approaches for investigating the origin of magnetic carriers in carbonate rocks.
Mechanism of Rock Bursts Induced by the Synthetic Action of “Roof Bending and Rock Pillar Prying” in Subvertical Extra-Thick Coal Seams
Authors: Wu Zhenhua , Pan Peng-Zhi , Chen Jianqiang , Liu Xudong , Miao Shuting , Yu Peiyang
Published: December 2021

When studying the rock burst mechanism in subvertical extra-thick coal seams in the Wudong coal mine in Xinjiang, China, most studies focus on rock pillars, while the effect of the roof on rock bursts is usually ignored. In this paper, a rock burst mechanism in subvertical extra-thick coal seams under the control of a “roof-rock pillar” is proposed. A theoretical analysis is first performed to explain the effect of roof-rock pillar combinations on rock bursts in coal seams. Numerical modeling and microseismic analysis are implemented to further study the mechanism of rock burst. The main conclusions are as follows: 1) During the mining of the B3+6 coal seam, an obvious microseismic concentration phenomenon is found in both the roof and rock pillar of B3+6. The rock bursts exhibited obvious directionality, and its main failure characteristics are floor heave and sidewall heave, but there will also be some failures such as shoulder socket subsidence in some parts. 2) The stress transfer caused by rock pillar prying is the main reason for the large difference in rock burst occurrence near the vertical and extra thick adjacent coal seams under the same mining depth. 3) Under the same cantilever length, the elastic deformation energy of the roof is much greater than that of the rock pillar, which makes it easier to produce high-energy microseismic events. With an increasing mining depth, the roof will become the dominant factor controlling the occurrence of rock bursts. 4) The high-energy event produced by the rock mass fracture near the coal rock interface easily induces rock bursts, while the high-energy event produced by the fracture at the far end of the rock mass is less likely to induce rock burst. 5) Roof deformation extrusion and rock pillar prying provide high static stress conditions for the occurrence of rock bursts in the B3+6 coal seam. The superposition of the dynamic disturbance caused by roof and rock pillar failure and the high static stress of the coal seam is the main cause of rock burst in the B3+6 coal seam.
Characterizing Concealed Fault Systems by Integrating Field Data Mapping and Laboratory Experiments: A Case Study of the Huawa Area in East China
Authors: Hu Huiting , Hu Shuang , Zhang Rui , Fu Xiaofei , Ren Chongyu , Liu Qidong , Yu Wenquan , Yang Yuchen
Published: December 2021

Concealed faults can be important for understanding the regional structural geology and the subsurface fluid distribution. However, such faults are usually difficult to identify and characterize because of their small size and complex mechanism. To address this issue, we present an integrated approach of three-dimensional seismic data mapping and physical modeling experiments to examine the geometrical and kinematic characteristics of concealed faults and their relationship with the main faults in the Huawa area, east China. Three series of experiments were designed to characterize the differences in the scale of concealed faults and main faults, which also allowed us to examine how the concealed faults grow with the main faults in the area. Through this integrated study, we have demonstrated that: 1) NE-SW-striking concealed faults are below the resolution of the available seismic datasets and not easily recognized in seismic sections and that most of them grew later than the E-W-striking main faults, with some of them having grown at the same time; 2) pre-existing faults, rather than asymmetry of the basin structure, affect the faults that develop during subsequent episodes of extension; 3) E-W-striking pre-existing faults under a NW-SE stress direction of extension are most likely the formation mechanism of concealed faults. This study is of reference value in the interpretation of concealed faults in other regions.
Translating Embodied Cognition for Embodied Learning in the Classroom
Authors: Macrine Sheila L. , Fugate Jennifer M. B.
Published: December 2021

In this perspective piece, we briefly review embodied cognition and embodied learning. We then present a translational research model based on this research to inform teachers, educational psychologists, and practitioners on the benefits of embodied cognition and embodied learning for classroom applications. While many teachers already employ the body in teaching, especially in early schooling, many teachers’ understandings of the science and benefits of sensorimotor engagement or embodied cognition across grades levels and the content areas is little understood. Here, we outline seven goals in our model and four major “action” steps. To address steps 1 and 2, we recap previously published reviews of the experimental evidence of embodied cognition (and embodied learning) research across multiple learning fields, with a focus on how both simple embodied learning activities—as well as those based on more sophisticated technologies of AR, VR, and mixed reality—are being vetted in the classroom. Step 3 of our model outlines how researchers, teachers, policy makers, and designers can work together to help translate this knowledge in support of these goals. In the final step (step 4), we extract generalized, practical embodied learning principles, which can be easily adopted by teachers in the classroom without extensive training. We end with a call for educators and policy makers to use these principles to identify learning objectives and outcomes, as well as track outcomes to assess whether program objectives and competency requirements are met.
The miR-4739/DLX3 Axis Modulates Bone Marrow-Derived Mesenchymal Stem Cell (BMSC) Osteogenesis Affecting Osteoporosis Progression
Authors: Li Ding , Yuan Qi , Xiong Liang , Li Aoyu , Xia Yu
Published: December 2021

Osteoporosis is a complex multifactorial disorder linked to various risk factors and medical conditions. Bone marrow-derived mesenchymal stem cell (BMSC) dysfunction potentially plays a critical role in osteoporosis pathogenesis. Herein, the study identified that miR-4739 was upregulated in BMSC cultures harvested from osteoporotic subjects. BMSCs were isolated from normal and osteoporotic bone marrow tissues and identified for their osteogenic differentiation potential. In osteoporotic BMSCs, miR-4739 overexpression significantly inhibited cell viability, osteoblast differentiation, mineralized nodule formation, and heterotopic bone formation, whereas miR-4739 inhibition exerted opposite effects. Through direct binding, miR-4739 inhibited distal-less homeobox 3 (DLX3) expression. In osteoporotic BMSCs, DLX3 knockdown also inhibited BMSC viability and osteogenic differentiation. Moreover, DLX3 knockdown partially attenuated the effects of miR-4739 inhibition upon BMSCs. Altogether, the miR-4739/DLX3 axis modulates the capacity of BMSCs to differentiate into osteoblasts, which potentially plays a role in osteoporosis pathogenesis. The in vivo and clinical functions of the miR-4739/DLX3 axis require further investigation.
Iterative Forecasting Improves Near-Term Predictions of Methane Ebullition Rates
Authors: McClure Ryan P. , Thomas R. Quinn , Lofton Mary E. , Woelmer Whitney M. , Carey Cayelan C.
Published: December 2021

Near-term, ecological forecasting with iterative model refitting and uncertainty partitioning has great promise for improving our understanding of ecological processes and the predictive skill of ecological models, but to date has been infrequently applied to predict biogeochemical fluxes. Bubble fluxes of methane (CH4) from aquatic sediments to the atmosphere (ebullition) dominate freshwater greenhouse gas emissions, but it remains unknown how best to make robust near-term CH4 ebullition predictions using models. Near-term forecasting workflows have the potential to address several current challenges in predicting CH4 ebullition rates, including: development of models that can be applied across time horizons and ecosystems, identification of the timescales for which predictions can provide useful information, and quantification of uncertainty in predictions. To assess the capacity of near-term, iterative forecasting workflows to improve ebullition rate predictions, we developed and tested a near-term, iterative forecasting workflow of CH4 ebullition rates in a small eutrophic reservoir throughout one open-water period. The workflow included the repeated updating of a CH4 ebullition forecast model over time with newly-collected data via iterative model refitting. We compared the CH4 forecasts from our workflow to both alternative forecasts generated without iterative model refitting and a persistence null model. Our forecasts with iterative model refitting estimated CH4 ebullition rates up to 2 weeks into the future [RMSE at 1-week ahead = 0.53 and 0.48 loge(mg CH4 m−2 d−1) at 2-week ahead horizons]. Forecasts with iterative model refitting outperformed forecasts without refitting and the persistence null model at both 1- and 2-week forecast horizons. Driver uncertainty and model process uncertainty contributed the most to total forecast uncertainty, suggesting that future workflow improvements should focus on improved mechanistic understanding of CH4 models and drivers. Altogether, our study suggests that iterative forecasting improves week-to-week CH4 ebullition predictions, provides insight into predictability of ebullition rates into the future, and identifies which sources of uncertainty are the most important contributors to the total uncertainty in CH4 ebullition predictions.