bluuebunny/crossref_metadata_2025 huggingface dataset:
Analisis Pertimbangan KPPU Terhadap Pelanggaran Persaingan Usaha Tidak Sehat Dilakukan Oleh Perusahaan Penerbangan BUMN (Studi Kasus Putusan No. 15/KPPU-I/2019)
Authors: Fachri Faisal , Joesoef Iwan Erar
Published: April 2021

State-Owned Enterprises (SOEs) has a role to improve the nation's economy is very central, in the implementation of SOEs are excluded to monopolize market share based on the Act based on article 33 Paragraph (2) of the 1945 Act basically can be excluded in certain sectors with the welfare of the people, however, in practice, monopolistic practices are often found that are not in accordance with the stipulated regulations. Aviation companies under the auspices of SOEs are necessary considering that the aviation sector is very much needed by the community. This journal examines business competition in BUMN monopolies. This study aims to understand the concept of monopoly carried out by SOEs in the aviation sector and efforts to overcome it. The method used in this research is a normative juridical approach which in the main data processing uses secondary data, namely data obtained from literature reviews. The approach used in solving problems is per se illegal. A good corporate government can be a reference for KPPU in determining the limits of activities in monopoly carried out by SOEs. The type of research carried out in this research is legal research (legal reseacht), namely research that examines the formulation of the problems contained in the research by examining the relevant regulations that apply.
Keywoard:
Effects of Hyperoxia on Mitochondrial Homeostasis: Are Mitochondria the Hub for Bronchopulmonary Dysplasia?
Authors: Xuefei Yu , Xinyi Zhao , Qing Cai , Dan Zhang , Ziyun Liu , Hejuan Zheng , Xindong Xue , Jianhua Fu
Published: April 2021

Mitochondria are involved in energy metabolism and redox reactions in the cell. Emerging data indicate that mitochondria play an essential role in physiological and pathological processes of neonatal lung development. Mitochondrial damage due to exposure to high concentrations of oxygen is an indeed important factor for simplification of lung structure and development of bronchopulmonary dysplasia (BPD), as reported in humans and rodent models. Here, we comprehensively review research that have determined the effects of oxygen environment on alveolar development and morphology, summarize changes in mitochondria under high oxygen concentrations, and discuss several mitochondrial mechanisms that may affect cell plasticity and their effects on BPD. Thus, the pathophysiological effects of mitochondria may provide insights into targeted mitochondrial and BPD therapy.
Enhancing Oocyte Competence With Milrinone as a Phosphodiesterase 3A Inhibitor to Improve the Development of Porcine Cloned Embryos
Authors: Roy Pantu Kumar , Qamar Ahmad Yar , Tanga Bereket Molla , Fang Xun , Kim Ghangyong , Bang Seonggyu , Cho Jongki
Published: April 2021

The objective of this study was to investigate the effect of milrinone supplementation as a phosphodiesterase 3A inhibitor during in vitro maturation (IVM) to coordinate the cytoplasmic and nuclear maturation of porcine oocytes and subsequent development of porcine cloned embryos. Brilliant cresyl blue (BCB)-stained (BCB +) oocytes, classified as well-developed, and BCB− oocytes were used in parthenogenesis (PA) and cloning, and their preimplantation development was compared. In PA embryos, BCB + oocytes had significantly higher rates of development than BCB− oocytes in terms of maturation (87.5 vs. 71.3%), cleavage (88.6 vs. 76.3%), and blastocyst development (34.3 vs. 25.3%) and also had higher cell numbers (46.9 vs. 38.9%), respectively (p < 0.05). In cloned embryos, the BCB + group also had a significantly higher blastocyst formation rate than the BCB− group (30.6 vs. 20.1%; p < 0.05). Supplementation with 75 μM milrinone during IVM of BCB− oocytes showed improvement in maturation and blastocyst development rates, which may be due to the coordinated maturation of the cytoplasm with the nucleus as an effect of milrinone. Moreover, the analysis of nuclear reprogramming via the examination of the expression levels of the reprogramming-related genes POU5F1, DPPA2, and NDP52IL in milrinone-supplemented BCB− oocytes showed higher expression levels than that in non-treated BCB− oocytes. These findings demonstrate that milrinone is useful in improving developmental competence in less competent oocytes during IVM and for proper nuclear reprogramming in the production of porcine cloned embryos by coordinating cytoplasmic and nucleus maturation.
Transcriptome Analyses Reveal IL6/Stat3 Signaling Involvement in Radial Glia Proliferation After Stab Wound Injury in the Adult Zebrafish Optic Tectum
Authors: Shimizu Yuki , Kiyooka Mariko , Ohshima Toshio
Published: April 2021

Adult zebrafish have many neurogenic niches and a high capacity for central nervous system regeneration compared to mammals, including humans and rodents. The majority of radial glia (RG) in the zebrafish optic tectum are quiescent under physiological conditions; however, stab wound injury induces their proliferation and differentiation into newborn neurons. Although previous studies have functionally analyzed the molecular mechanisms of RG proliferation and differentiation and have performed single-cell transcriptomic analyses around the peak of RG proliferation, the cellular response and changes in global gene expression during the early stages of tectum regeneration remain poorly understood. In this study, we performed histological analyses which revealed an increase in isolectin B4+ macrophages prior to the induction of RG proliferation. Moreover, transcriptome and pathway analyses based on differentially expressed genes identified various enriched pathways, including apoptosis, the innate immune system, cell proliferation, cytokine signaling, p53 signaling, and IL6/Jak-Stat signaling. In particular, we found that Stat3 inhibition suppressed RG proliferation after stab wound injury and that IL6 administration into cerebroventricular fluid activates RG proliferation without causing injury. Together, the findings of these transcriptomic and functional analyses reveal that IL6/Stat3 signaling is an initial trigger of RG activation during optic tectum regeneration.
Species-Specific Differences in Sperm Chromatin Decondensation Between Eutherian Mammals Underlie Distinct Lysis Requirements
Authors: Ribas-Maynou Jordi , Garcia-Bonavila Estela , Hidalgo Carlos O. , Catalán Jaime , Miró Jordi , Yeste Marc
Published: April 2021

Sperm present a highly particular DNA condensation that is acquired during their differentiation. Protamines are key elements for DNA condensation. However, whereas the presence of protamine 1 (P1) is conserved across mammalian species, that of protamine 2 (P2) has evolved differentially, existing only few species that use both protamines for sperm DNA condensation. In addition, altered P1/P2 ratios and alterations in the expression of P1 have previously been associated to infertility and DNA damage disorders. On the other hand, different methods evaluating DNA integrity, such as Sperm Chromatin Dispersion (SCD) and Comet tests, need a previous complete DNA decondensation to properly assess DNA breaks. Related with this, the present study aims to analyze the resilience of sperm DNA to decodensation in different eutherian mammals. Sperm samples from humans, horses, cattle, pigs and donkeys were used. Samples were embedded in low melting point agarose and treated with lysis solutions to induce DNA decondensation and formation of sperm haloes. The treatment consisted of three steps: (1) incubation in SDS + DTT for 30 min; (2) incubation in DTT + NaCl for 30 min; and (3) incubation in DTT + NaCl with or without proteinase K for a variable time of 0, 30, or 180 min. How incubation with the third lysis solution (with or without proteinase K) for 0, 30, and 180 min affected DNA decondensation was tested through analyzing core and halo diameters in 50 sperm per sample. Halo/core length ratio was used as an indicator of complete chromatin decondensation. While incubation time with the third lysis solution had no impact on halo/core length ratios in species having P1 and P2 (human, equine and donkey), DNA decondensation of pig and cattle sperm, which only present P1, significantly (P < 0.05) increased following incubation with the third lysis solution for 180 min. In addition, the inclusion of proteinase K was found to accelerate DNA decondensation. In conclusion, longer incubations in lysis solution including proteinase K lead to higher DNA decondensation in porcine and bovine sperm. This suggests that tests intended to analyze DNA damage, such as halo or Comet assays, require complete chromatin deprotamination to achieve high sensitivity in the detection of DNA breaks.
Mutation of Gemin5 Causes Defective Hematopoietic Stem/Progenitor Cells Proliferation in Zebrafish Embryonic Hematopoiesis
Authors: Liu Xiaofen , Zhang Wenjuan , Jing Changbin , Gao Lei , Fu Cong , Ren Chunguang , Hao Yimei , Cao Mengye , Ma Ke , Pan Weijun , Li Dantong
Published: April 2021

Fate determination and expansion of Hematopoietic Stem and Progenitor Cells (HSPCs) is tightly regulated on both transcriptional and post-transcriptional level. Although transcriptional regulation of HSPCs have achieved a lot of advances, its post-transcriptional regulation remains largely underexplored. The small size and high fecundity of zebrafish makes it extraordinarily suitable to explore novel genes playing key roles in definitive hematopoiesis by large-scale forward genetics screening. Here, we reported a novel zebrafish mutant line gemin5cas008 with a point mutation in gemin5 gene obtained by ENU mutagenesis and genetic screening, causing an earlier stop codon next to the fifth WD repeat. Gemin5 is an RNA-binding protein with multifunction in post-transcriptional regulation, such as regulating the biogenesis of snRNPs, alternative splicing, stress response, and translation control. The mutants displayed specific deficiency in definitive hematopoiesis without obvious defects during primitive hematopoiesis. Further analysis showed the impaired definitive hematopoiesis was due to defective proliferation of HSPCs. Overall, our results indicate that Gemin5 performs an essential role in regulating HSPCs proliferation.
Structure Activity Relationship of N-Substituted Phenyldihydropyrazolones Against Trypanosoma cruzi Amastigotes
Authors: Sijm Maarten , Maes Louis , de Esch Iwan J. P. , Caljon Guy , Sterk Geert Jan , Leurs Rob
Published: April 2021

Current drugs for Chagas disease have long treatment regimens with occurrence of adverse drug effects leading to poor treatment compliance. Novel and efficacious medications are therefore highly needed. We previously reported on the discovery of NPD-0227 (2-isopropyl-5-(4-methoxy-3-(pyridin-3-yl)phenyl)-4,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one) as a potent in vitro inhibitor of Trypanosoma cruzi (pIC50 = 6.4) with 100-fold selectivity over human MRC-5 cells. The present work describes a SAR study on the exploration of substituents on the phenylpyrazolone nitrogen. Modifications were either done directly onto this pyrazolone nitrogen or alternatively by introducing a piperidine linker. Attention was pointed toward the selection of substituents with a cLogP preferably below NPD-0227s cLogP of 3.5. Generally the more apolar compounds showed better activities then molecules with cLogPs <2.0. Several new compounds were identified with potencies that are in the same range as NPD-0227 (pIC50 = 6.4) and promising selectivities. While the potency could not be improved, valuable SAR was obtained. Furthermore the introduction of a piperidine linker offers new opportunities for derivatization as valuable novel starting points for future T. cruzi drug discovery.
Synthesis, Biological Evaluation, and QSAR Studies of 3-Iodochromone Derivatives as Potential Fungicides
Authors: Kaushik Parshant , Shakil Najam A. , Rana Virendra S.
Published: April 2021

Despite the emergence of novel biotechnological and biological solutions, agrochemicals continue to play an important role in crop protection. Fungicide resistance is becoming a major problem; numerous cases of fungicide resistance have occurred worldwide in the last decade, resulting in the loss of several fungicides. The discovery of new molecules has therefore assumed critical importance in crop protection. In our quest for biologically active molecules, we herein report the synthesis of a series of twenty-one 3-Iodochromone derivatives (4a–4u), in a two-step process by condensation of 2-hydroxyacetophenone derivatives (2a–2u) with N,N-dimethylformamidedimethylacetal yielding enaminones (3a–3u), followed by cyclization with iodine to corresponding 3-iodochromones. Characterization of these compounds was done by IR, 1H NMR, 13C NMR, and LC-HRMS techniques. All synthesized compounds were screened for their fungicidal activity against Sclerotium rolfsii. Among these 6,8-Dichloro-3-iodochromone 4r was found to be most active (ED50 = 8.43 mg L−1). 2D-Quantitative Structural Activity Relationship (2D-QSAR) analysis was also performed by generating three different models viz., Multiple Linear Regression (MLR, Model 1), Principal Component Regression (PCR, Model 2), and Partial Least Squares (PLS, Model 3). Predictive power and statistical significance of these models were assessed with external and internal validation and leave one-out cross-validation was used for verification. In QSAR study, MLR (Model 1) was found to be best having correlation coefficient (r2) 0.943, cross-validated correlation coefficient (q2) 0.911 and r2pred 0.837. It was observed that DeltaEpsilonC, T_2_Cl_6, T_2_F_6, T_T_F_3, and ZCompDipole are the major descriptors which influence the fungicidal activity of 3-Iodochromone derivatives. The physicochemical parameters were estimated by the VLifeMDS 4.6 software. The QSAR study results will be helpful for structure optimization to improve the activity.
Macrocycle-Antibiotic Hybrids: A Path to Clinical Candidates
Authors: Surur Abdrrahman Shemsu , Sun Dianqing
Published: April 2021

The tale of abate in antibiotics continued defense mechanisms that chaperone the rise of drug-defying superbugs—on the other hand, the astray in antibacterial drug discovery and development. Our salvation lies in circumventing the genesis of resistance. Considering the competitive advantages of antibacterial chemotherapeutic agents equipped with multiple warheads against resistance, the development of hybrids has rejuvenated. The adoption of antibiotic hybrid paradigm to macrocycles has advanced novel chemical entities to clinical trials. The multi-targeted TD-1792, for instance, retained potent antibacterial activities against multiple strains that are resistant to its constituent, vancomycin. Moreover, the antibiotic conjugation of rifamycins has provided hybrid clinical candidates with desirable efficacy and safety profiles. In 2020, the U.S. FDA has granted an orphan drug designation to TNP-2092, a conjugate of rifamycin and fluoroquinolone, for the treatment of prosthetic joint infections. DSTA4637S is a pioneer antibacterial agent under clinical development and represents a novel class of bacterial therapy, that is, antibody–antibiotic conjugates. DSTA4637S is effective against the notorious persistent S. aureus bacteremia, a revelation of the abracadabra potential of antibiotic hybrid approaches.
Ubiquinone Binding and Reduction by Complex I—Open Questions and Mechanistic Implications
Authors: Galemou Yoga Etienne , Schiller Jonathan , Zickermann Volker
Published: April 2021

NADH: ubiquinone oxidoreductase (complex I) is the first enzyme complex of the respiratory chain. Complex I is a redox-driven proton pump that contributes to the proton motive force that drives ATP synthase. The structure of complex I has been analyzed by x-ray crystallography and electron cryo-microscopy and is now well-described. The ubiquinone (Q) reduction site of complex I is buried in the peripheral arm and a tunnel-like structure is thought to provide access for the hydrophobic substrate from the membrane. Several intermediate binding positions for Q in the tunnel were identified in molecular simulations. Structural data showed the binding of native Q molecules and short chain analogs and inhibitors in the access pathway and in the Q reduction site, respectively. We here review the current knowledge on the interaction of complex I with Q and discuss recent hypothetical models for the coupling mechanism.
A Comparison Study of Age and Colorectal Cancer-Related Gut Bacteria
Authors: Zhang Yu-Kun , Zhang Qian , Wang Yu-Liuming , Zhang Wei-Yuan , Hu Han-Qing , Wu Hong-Yu , Sheng Xiang-Zong , Luo Kang-Jia , Zhang Hao , Wang Meng , Huang Rui , Wang Gui-Yu
Published: April 2021

Intestinal microbiota is gaining increasing interest from researchers, and a series of studies proved that gut bacteria plays a significant role in various malignancies, especially in colorectal cancer (CRC). In this study, a cohort of 34 CRC patients (average age=65 years old), 26 young volunteers (below 30 years old), and 26 old volunteers (over 60 years old) was enrolled. 16S ribosomal RNA gene sequencing was used to explore fecal bacteria diversity. The operational taxonomic unit (OTU) clustering analysis and NMDS (non-metric multidimensional scaling) analysis were used to separate different groups. Cluster of ortholog genes (COG) functional annotation and Kyoto encyclopedia of genes and genomes (KEGG) were used to detect enriched pathways among three groups. Community separations were observed among the three groups of this cohort. Clostridia, Actinobacteria, Bifidobacterium, and Fusobacteria were the most enriched bacteria in the young group, old group, and CRC group respectively. Also, in the young, old, and CRC group, the ratio of Firmicutes/Bacteroidetes was increased sequentially despite no statistical differences. Further, COG showed that transcription, cell wall/membrane/envelope biogenesis, inorganic ion transport and metabolism, and signal transduction mechanisms were differentially expressed among three groups. KEGG pathways associated with ABC transporters, amino sugar and nucleotide sugar metabolism, arginine and proline metabolism, and aminoacyl-tRNA biosynthesis also showed statistical differences among the three groups. These results indicated that the intestinal bacterial community varied as age changed and was related to CRC, and we discussed that specific bacteria enriched in the young and old group may exert a protective function, while bacteria enriched in the CRC group may promote tumorigenesis.
TolCV1 Has Multifaceted Roles During Vibrio vulnificus Infection
Authors: Gong Yue , Guo Rui Hong , Rhee Joon Haeng , Kim Young Ran
Published: April 2021

RtxA1 is a major cytotoxin of Vibrio vulnificus (V. vulnificus) causing fatal septicemia and necrotic wound infections. Our previous work has shown that RpoS regulates the expression and secretion of V. vulnificus RtxA1 toxin. This study was conducted to further investigate the potential mechanisms of RpoS on RtxA1 secretion. First, V. vulnificus TolCV1 and TolCV2 proteins, two Escherichia coli TolC homologs, were measured at various time points by Western blotting. The expression of TolCV1 was increased time-dependently, whereas that of TolCV2 was decreased. Expression of both TolCV1 and TolCV2 was significantly downregulated in an rpoS deletion mutation. Subsequently, we explored the roles of TolCV1 and TolCV2 in V. vulnificus pathogenesis. Western blot analysis showed that RtxA1 toxin was exported by TolCV1, not TolCV2, which was consistent with the cytotoxicity results. Furthermore, the expression of TolCV1 and TolCV2 was increased after treatment of the host signal bile salt and the growth of tolCV1 mutant was totally abolished in the presence of bile salt. A tolCV1 mutation resulted in significant reduction of V. vulnificus induced-virulence in mice. Taken together, TolCV1 plays key roles in RtxA1 secretion, bile salt resistance, and mice lethality of V. vulnificus, suggesting that TolCV1 could be an attractive target for the design of new medicines to treat V. vulnificus infections.
Development of Privacy Features on Anecdata.org, a Free Citizen Science Platform for Collecting Datasets for Climate Change and Related Projects
Authors: Bailey Cait , Farrell Anna , Purty Turam , Taylor Ashley , Disney Jane
Published: April 2021

The Anecdata website and its corresponding mobile app provide unique features to meet the needs of a wide variety of diverse citizen science projects from across the world. The platform has been developed with the help of continuous feedback from community partners, project leaders, and website users and currently hosts more than 200 projects. Over 8,000 registered users have contributed more than 30,000 images and over 50,000 observations since the platform became open to the public in 2014. From its inception, one of the core tenets of Anecdata's mission has been to make data from citizen science projects freely accessible to project participants and the general public, and in the platform's first few years, it followed a completely open data access model. As the platform has grown, hosting ever more projects, we have found that this model does not meet all project needs, especially where endangered species, property access rights, participant safety in the field, and personal privacy are concerned. We first introduced features for data and user privacy as part of “All About Arsenic,” a National Institutes of Health (NIH)/National Institute of General Medical Sciences (NIGMS) Science Education Partnership Award (SEPA)-funded project at MDI Biological Laboratory, which engages middle and high school teachers and students from schools across Maine and New Hampshire in sampling their home well water for analysis of arsenic and other heavy metals. In order to host this project on Anecdata, we developed features for spatial privacy or “geoprivacy” to conceal the coordinates of samplers' homes, partial data redaction tools we call “private fields” to withhold certain sample registration questions from public datasets, and “participant anonymity” to conceal which user account uploaded an observation. We describe the impetus for the creation of these features, challenges we encountered, and our technical approach. While these features were originally developed for the purposes of a public health and science literacy project, they are now available to all project leaders setting up projects on Anecdata.org and have been adopted by a number of projects, including Mass Audubon's Eastern Meadowlark Survey, South Carolina Aquarium's SeaRise, and Coastal Signs of the Seasons (SOS) Monitoring projects.
Case Report: Effective Treatment for Acute Chlorpyrifos Poisoning Complicated by a Non-ST-Segment Elevation Myocardial Infarction
Authors: Ye Changqing , Zhang Qiang , Chao Yongsheng , Yin Chun
Published: April 2021

Background: Acute myocardial infarction (AMI) is a rare complication of acute organophosphorus pesticide poisoning. Although chlorpyrifos has been widely used as an organophosphate insecticide, a few cases of AMI complicated by chlorpyrifos poisoning have been reported thus far. Hence, a suitable treatment strategy remains to be explored.

Case Presentation: Based on the clinical manifestations, medical history, results of an auxiliary examination, and serum biomarkers, a 65-year-old male farmer with complaints of nausea, vomiting, chest tightness, and pain was clearly diagnosed as having a severe chlorpyrifos self-poisoning with acute non-ST-segment elevation MI. Because the patient and his family confirmedly refused a coronary intervention, conservative treatment was used instead. It should be noted that there were some conflicts of the management for chlorpyrifos poisoning and AMI. Although rapid atropinization would contribute to the relief of muscarinic symptoms, it would also lead to an increased heart rate and myocardial oxygen consumption in AMI. Furthermore, the reduction of platelet aggregation, which is necessary for coronary recanalization of an AMI patient, is known to aggravate the gastrointestinal injury caused by poisoning. In this case, these conflicts were properly addressed, which led to an excellent effect and prognosis of the patient.

Conclusions: To our knowledge, this is the first case report of acute chlorpyrifos poisoning with AMI. It is emphasized that patients with chest pain or coronary heart disease should be treated with atropine more cautiously because of the possible AMI. Moreover, proper resolution of conflicts in the management for chlorpyrifos poisoning and AMI played contributing roles in patient improvement.
RETRACTED: Silencing CircHIPK3 Sponges miR-93-5p to Inhibit the Activation of Rac1/PI3K/AKT Pathway and Improves Myocardial Infarction-Induced Cardiac Dysfunction
Authors: Wu Yijin , Wu Min , Yang Jue , Li Ying , Peng Wenying , Wu Meifen , Yu Changjiang , Fang Miaoxian
Published: April 2021

The ceRNA network involving circular RNAs (circRNAs) is essential in the cardiovascular system. We investigated the underlying ceRNA network involving circHIPK3 in myocardial infarction (MI). After an MI model was established, cardiac function was verified, and myocardial tissue damage in mice with MI was evaluated. A hypoxia model of cardiomyocytes was used to simulate MI in vivo, and the expression of and targeting relationships among circHIPK3, miR-93-5p, and Rac1 were verified. The apoptosis of cardiomyocyte was identified. Gain- and loss-of-functions were performed to verify the ceRNA mechanism. The MI-modeled mice showed cardiac dysfunction and enlarged infarct size. CircHIPK3 was highly expressed in mouse and cell models of MI. Silencing circHIPK3 reduced infarct size, myocardial collagen deposition, and myocardial apoptosis rate and improved cardiac function. CircHIPK3 sponged miR-93-5p, and miR-93-5p targeted Rac1. Overexpression of miR-93-5p inhibited MI-induced cardiomyocyte injury and eliminated the harmful effect of circHIPK3. CircHIPK3 acted as ceRNA to absorb miR-93-5p, thus promoting the activation of the Rac1/PI3K/AKT pathway. We highlighted that silencing circHIPK3 can upregulate miR-93-5p and then inhibit the activation of Rac1/PI3K/Akt pathway, which can improve MI-induced cardiac dysfunction.
Effect of Left Atrial Appendage Closure in Combination With Catheter Ablation on Left Atrial Function for Persistent Atrial Fibrillation
Authors: Yang Jing , Liu Yue , Feng Liang , Liu Mingqing , You Ling , Liu Yu , Wu Jinglan , Zhang Guangming , Geng Xue , Xie Ruiqin
Published: April 2021

Background: A single procedure combining left atrial appendage closure (LAAC) plus catheter ablation (CA) has been proven to be safe and feasible for treating atrial fibrillation (AF). However, the influence of treatment modality on left atrial (LA) function is not thoroughly explained.

Objective: We aimed to investigate the changes of LA function in persistent AF patients undergoing concomitant LAAC and CA.

Methods: The study population comprised 65 patients who underwent combined AF ablation and Watchman LAAC (combined therapy group) in our center, and 65 participants of the AF simple ablation group who were matched based on sex, age, CHA2DS2-VASc score and HAS-BLED score using propensity score matching. During the 1-year follow-up period, two-dimensional echocardiography and speckle tracking echocardiography were performed to assess LA reservoir, conduit, and contractile function.

Results: The combined therapy was associated with a significant improvement in the LA reservoir function with increased expansion index and strain indices, including strain and strain rate (SR) during ventricular systole. Conduit function with SR during early ventricular diastole was also improved, as was contractile function with active atrial emptying fraction and SR during atrial systole. Similarly, LA reservoir and contractile function indices all improved continuously during follow-up after catheter ablation alone. At 3 months follow-up LA reservoir and conduit function with strain indices had a tendency to improve only in the simple procedure group. At 1-year follow-up there was no significant difference in either LA volumes or strain indices between the two groups.

Conclusion: Both the combined therapy group and the simple ablation group demonstrated significant improvement in LA function. Based upon the fact that LA function was improved in both groups it might be concluded that most of the effects appeared to result from ablation, not LAAC; furthermore the additional LAAC procedure did not affect the improvement of LA function after CA.
Modern Sedimentation and Authigenic Mineral Formation in the Chew Bahir Basin, Southern Ethiopia: Implications for Interpretation of Late Quaternary Paleoclimate Records
Authors: Gebregiorgis Daniel , Deocampo Daniel M. , Foerster Verena , Longstaffe Fred J. , Delaney Jeremy S. , Schaebitz Frank , Junginger Annett , Markowska Monika , Opitz Stephan , Trauth Martin H. , Lamb Henry F. , Asrat Asfawossen
Published: April 2021

We present new mineralogical and geochemical data from modern sediments in the Chew Bahir basin and catchment, Ethiopia. Our goal is to better understand the role of modern sedimentary processes in chemical proxy formation in the Chew Bahir paleolake, a newly investigated paleoclimatic archive, to provide environmental context for human evolution and dispersal. Modern sediment outside the currently dry playa lake floor have higher SiO2 and Al2O3 (50–70 wt.%) content compared to mudflat samples. On average, mudflat sediment samples are enriched in elements such as Mg, Ca, Ce, Nd, and Na, indicating possible enrichment during chemical weathering (e.g., clay formation). Thermodynamic modeling of evaporating water in upstream Lake Chamo is shown to produce an authigenic mineral assemblage of calcite, analcime, and Mg-enriched authigenic illitic clay minerals, consistent with the prevalence of environments of enhanced evaporative concentration in the Chew Bahir basin. A comparison with samples from the sediment cores of Chew Bahir based on whole-rock MgO/Al2O3, Ba/Sr and authigenic clay mineral δ18O values shows the following: modern sediments deposited in the saline mudflats of the Chew Bahir dried out lake bed resemble paleosediments deposited during dry periods, such as during times of the Last Glacial Maximum and Younger Dryas stadial. Sediments from modern detrital upstream sources are more similar to sediments deposited during wetter periods, such as the early Holocene African Humid Period.
Magnetic Mineralogy of Speleothems From Tropical-Subtropical Sites of South America
Authors: Jaqueto Plinio , Trindade Ricardo I. F. , Feinberg Joshua M. , Carmo Janine , Novello Valdir F. , Stríkis Nicolás M. , Cruz Francisco W. , Shimizu Marília H. , Karmann Ivo
Published: April 2021

Fe-bearing minerals are a tiny fraction of the composition of speleothems. They have their origin in the karst system or are transported from the drainage basin into the cave. Recent studies on the magnetism of speleothems focused on the variations of their magnetic mineralogy in specific time intervals and are usually limited to a single sample. In this study, we describe a database of environmental magnetism parameters built from 22 stalagmites from different caves located in Brazil (South America) at different latitudes, comprising different climates and biomes. The magnetic signal observed in these stalagmites is dominated by low-coercivity minerals (∼20 mT) whose magnetic properties resemble those of the magnetite formed in pedogenic environments. Also, a comparison with few samples from soils and the carbonate from cave’s walls shows a good agreement of the magnetic properties of speleothems with those of soil samples, reinforcing previous suggestions that in (sub-)tropical regimes, the dominant magnetic phase in speleothems is associated with the soil above the cave. Spearman’s rank correlation points to a positive strong correlation between magnetic concentration parameters (mass-normalized magnetic susceptibility, natural remanent magnetization, anhysteretic remanent magnetization, and isothermal remanent magnetization). This implies that ultrafine ferrimagnetic minerals are the dominant phase in these (sub-)tropical karst systems, which extend across a diverse range of biomes. Although the samples are concentrated in the savannah biome (Cerrado) (∼70%), comparison with other biomes shows a higher concentration of magnetic minerals in speleothem underlying savannahs and lower concentration in those underlying moist broadleaf forests (Atlantic and Amazon biome) and dry forests (Caatinga). Thus, rainfall, biome, and epikarst dynamics play an important role in the concentration of magnetic minerals in speleothems in (sub-)tropical sites and indicate they can be an important target for paleoenvironmental research in cave systems.
Interpretation and Reconstruction of Depositional Environment and Petroleum Source Rock Using Outcrop Gamma-ray Log Spectrometry From the Huai Hin Lat Formation, Thailand
Authors: Phujareanchaiwon Chawisa , Chenrai Piyaphong , Laitrakull Kasira
Published: April 2021

Gamma ray logs are most useful in identifying subsurface lithology and interpreting depositional environments. This study highlights the use of outcrop gamma-ray logs along with outcrop observations and total organic carbon (TOC) analysis to provide the stratigraphic framework of the organic-rich rocks of Huai Hin Lat Formation in central Thailand. The study reveals five sedimentary facies including (1) structureless sandstone, (2) structured sandstone, (3) interbedded sandstone and siltstone, (4) interbedded mudstone and siltstone and (5) calcareous mudstone. These facies can be grouped into two facies associations; mudstone-dominated and sandstone-dominated facies associations. The depositional environment was interpreted as lacustrine basin-fill subdivided into deep lacustrine environment and sublacustrine fan associated with the turbidity currents. The total gamma-log characteristics are closely related to the lithologies controlled primarily by clay mineral compositions. Whist, the use of spectral gamma-ray can reveal more details on depositional environments and conditions. In this study, U concentrations is proven to be useful in highlighting organic-rich rocks in low K and Th concentration successions due to its ability to be fixed in clay minerals and organic materials under an anoxic condition. Thus, the U spectral gamma ray is suggested to combine with conventional gamma ray log for depositional environment and recognition of organic-rich rocks.
Seafloor Density Contrast Derived From Gravity and Shipborne Depth Observations: A Case Study in a Local Area of Atlantic Ocean
Authors: Wan Xiaoyun , Han Weipeng , Ran Jiangjun , Ma Wenjie , Annan Richard Fiifi , Li Bing
Published: April 2021

Marine gravity data from altimetry satellites are often used to derive bathymetry; however, the seafloor density contrast must be known. Therefore, if the ocean water depths are known, the density contrast can be derived. This study experimented the total least squares algorithm to derive seafloor density contrast using satellite derived gravity and shipborne depth observations. Numerical tests are conducted in a local area of the Atlantic Ocean, i.e., 34°∼32°W, 3.5°∼4.5°N, and the derived results are compared with CRUST1.0 values. The results show that large differences exist if the gravity and shipborne depth data are used directly, with mean difference exceeding 0.4 g/cm3. However, with a band-pass filtering applied to the gravity and shipborne depths to ensure a high correlation between the two data sets, the differences between the derived results and those of CRUST1.0 are reduced largely and the mean difference is smaller than 0.12 g/cm3. Since the spatial resolution of CRUST1.0 is not high and in many ocean areas the shipborne depths and gravity anomalies are much denser, the method of this study can be an alternative method for providing seafloor density variation information.
Reconstructing Nitrogen Sources to Earth’s Earliest Biosphere at 3.7 Ga
Authors: Stüeken Eva E. , Boocock Toby , Szilas Kristoffer , Mikhail Sami , Gardiner Nicholas J.
Published: April 2021

Earth’s sedimentary record has preserved evidence of life in rocks of low metamorphic grade back to about 3.2–3.5 billion years ago (Ga). These lines of evidence include information about specific biological metabolisms, permitting the reconstruction of global biogeochemical cycles in the early Archean. Prior to 3.5 Ga, the geological record is severely compromised by pervasive physical and chemical alteration, such as amphibolite-granulite facies metamorphic overprinting. Despite this alteration, evidence of biogenic organic matter is preserved in rare localities, including meta-turbidites from the 3.8 to 3.7 Ga Isua Supracrustal Belt, Western Greenland. But detailed insights into metabolic strategies and nutrient sources during the time of deposition of these Eoarchean meta-sedimentary rocks are lacking. Here we revisit the Isua meta-turbidites and provide new data for metal abundances as well as organic carbon and nitrogen isotope values. Our results reveal mixing between authigenic and detrital nitrogen phases with the authigenic phase likely fractionated by metamorphic degassing. Rayleigh fractionation models of these 3.7 Ga samples indicate pre-metamorphic δ15N values of between −1 and −10‰. The most plausible initial values are below −5‰, in agreement with a prior study. While the upper endmember of −1‰ could indicate biological N2 fixation at 3.7 Ga, the more plausible lighter values may point toward a distinct biogeochemical nitrogen cycle at that time, relative to the rest of Earth’s history. In light of recent experimental and phylogenetic data aligned with observations from the modern atmosphere, we tentatively conclude that lightning and/or high-energy photochemical reactions in the early atmosphere may have contributed isotopically light nitrogen to surface environment(s) preserved in the Isua turbidites. In this case, recycling of Eoarchean sediments may have led to the isotopically light composition of the Earth’s upper mantle dating back to at least 3.2 Ga.
Case Report: Complete Necrosis of a Large Adrenocortical Cancer and Liver Metastases Achieved by Selective Arterial Embolization: A Case Study and Review of Literature
Authors: Huszty Gergely , Doros Attila , Farkas Katalin , Kóbori László , Reismann Péter , Tőke Judit , Tóth Miklós , Igaz Peter
Published: April 2021

There is very limited experience regarding the interventional radiological treatment of adrenocortical cancer (ACC). We present the case of a 57-year-old female patient with a large, potentially unresectable left-sided ACC and two hepatic metastases. Both liver tumors were effectively treated by trans-arterial embolization (TAE), followed by TAE of the bulky primary tumor as a life-saving intervention necessitated by severe intratumoral bleeding. Surgical removal of the primary tumor revealed complete necrosis. The patient is considered tumor free after 3.5 years. To the best of our knowledge, this is the first report to show that even a primary ACC may be completely ablated by selective embolization, and the fourth to prove the curative potential of liver TAE for ACC metastases. This case highlights the potential of selective embolization in ACC treatment.
Techno Economic Evaluation and Feasibility Analysis of a Hybrid Net Zero Energy Building in Pakistan: A Case Study of Hospital
Authors: Arif Saba , Taweekun Juntakan , Ali Hafiz Muhammad , Theppaya Thanansak
Published: April 2021

The current study is an economic evaluation and feasibility study of hybrid microgrid Net Zero Energy Buildings in Pakistan. A Net Zero Energy approach is proposed for a two-story hospital building situated in Taxila, Pakistan. Consequently, to design a hybrid Net Zero Energy Building, the solar radiation potential of the subject location and electricity usage of the hospital are estimated. The proposed hybrid microgrid Net Zero Energy Building comprises photovoltaic modules and converters. However, the thermal load is computed as a grid-connected hybrid system. Economic evaluation is performed by using economic indicators of the net present cost and the payback period. Also, initial and operational costs are determined, to determine the profitability of the project. Results show that the analysis is a cost-effective approach and has a payback period of 2.53y. Additionally, the per-unit cost of electricity is reduced to 0.12 USD/kWh. Moreover, the energy produced by a hybrid system is 10.24% more economical than that of the pre-working grid system. Results explain the reduction in the cost of energy and profit margin in electricity generation and the increase in electricity production and feasibility of hybrid Net Zero Energy Buildings in Pakistan. Research will help to develop an approach toward an IEA task 47 in Pakistan with the possible development of simulation-based installations of Net Zero Energy Buildings in the health sector in Pakistan.
Network Analyses Predict Small RNAs That Might Modulate Gene Expression in the Testis and Epididymis of Bos indicus Bulls
Authors: de Lima Andressa O. , Afonso Juliana , Edson Janette , Marcellin Esteban , Palfreyman Robin , Porto-Neto Laercio R. , Reverter Antonio , Fortes Marina R. S.
Published: April 2021

Spermatogenesis relies on complex molecular mechanisms, essential for the genesis and differentiation of the male gamete. Germ cell differentiation starts at the testicular parenchyma and finishes in the epididymis, which has three main regions: head, body, and tail. RNA-sequencing data of the testicular parenchyma (TP), head epididymis (HE), and tail epididymis (TE) from four bulls (three biopsies per bull: 12 samples) were subjected to differential expression analyses, functional enrichment analyses, and co-expression analyses. The aim was to investigate the co-expression and infer possible regulatory roles for transcripts involved in the spermatogenesis of Bos indicus bulls. Across the three pairwise comparisons, 3,826 differentially expressed (DE) transcripts were identified, of which 384 are small RNAs. Functional enrichment analysis pointed to gene ontology (GO) terms related to ion channel activity, detoxification of copper, neuroactive receptors, and spermatogenesis. Using the regulatory impact factor (RIF) algorithm, we detected 70 DE small RNAs likely to regulate the DE transcripts considering all pairwise comparisons among tissues. The pattern of small RNA co-expression suggested that these elements are involved in spermatogenesis regulation. The 3,826 DE transcripts (mRNAs and small RNAs) were further subjected to co-expression analyses using the partial correlation and information theory (PCIT) algorithm for network prediction. Significant correlations underpinned the co-expression network, which had 2,216 transcripts connected by 158,807 predicted interactions. The larger network cluster was enriched for male gamete generation and had 15 miRNAs with significant RIF. The miRNA bta-mir-2886 showed the highest number of connections (601) and was predicted to down-regulate ELOVL3, FEZF2, and HOXA13 (negative co-expression correlations and confirmed with TargetScan). In short, we suggest that bta-mir-2886 and other small RNAs might modulate gene expression in the testis and epididymis, in Bos indicus cattle.
Birth of a Regulatory Long Non-coding RNA/Gene, linc-UR-UB
Authors: Delihas Nicholas
Published: April 2021

The origin of genes has been a major topic of research for many years, albeit in some cases, it has been a difficult process to elucidate. Insightful is a recent publication that experimentally shows how one gene, linc-UR-UB was born. This gene is regulated in a complex manner in male germ cells during spermatogenesis and is believed to participate in the regulation of levels of the ubiquitin specific peptidase 18 (USP18) mRNA. The process of formation of linc-UR-UB appears relatively simple. It involves a transcription read through from an upstream gene to a downstream functional element, the USP18 3' UTR sequence. This small element also shares the same sequence as the 3' ends of the lincRNA FAM247 family genes. In addition to linc-UR-UB, it is possible that other genes formed in a similar fashion that involves a genomic sequence read through to a functional element.
Fetal Cytokine Balance, Erythropoietin and Thalassemia but Not Placental Malaria Contribute to Fetal Anemia Risk in Tanzania
Authors: Kabyemela Edward R. , Fried Michal , Kurtis Jonathan D. , Moses Gwamaka , Gorres J. Patrick , Muehlenbachs Atis , Duffy Patrick E.
Published: April 2021

Fetal anemia is common in malaria-endemic areas and a risk factor for anemia as well as mortality during infancy. Placental malaria (PM) and red cell abnormalities have been proposed as possible etiologies, but the relationship between PM and fetal anemia has varied in earlier studies, and the role of red cell abnormalities has not been studied in malaria-endemic areas. In a Tanzanian birth cohort study designed to elucidate the pathogenesis of severe malaria in young infants, we performed a cross-sectional analysis of risk factors for fetal anemia. We determined PM status, newborn red cell abnormalities, and maternal and cord blood levels of iron regulatory proteins, erythropoietin (EPO), cytokines and cytokine receptors. We examined the relationship between these factors and fetal anemia. Fetal anemia was present in 46.2% of the neonates but was not related to PM. Maternal iron deficiency was common (81.6%), most frequent in multigravidae, and interacted with parity to modify risk of fetal anemia, but it was not directly related to risk. Among offspring of iron-deficient women, the odds of fetal anemia increased with fetal α+-thalassemia, as well as these patterns of cord blood cytokines: increased cord IL-6, decreased TNF-RI, and decreased sTfR. The EPO response to fetal anemia was low or absent and EPO levels were significantly decreased in newborns with the most severe anemia. This study from an area of high malaria transmission provides evidence that 1) fetal α+-thalassemia and cytokine balance, but not PM at delivery, are related to fetal anemia; 2) maternal iron deficiency increases the risk that other factors may cause fetal anemia; and 3) fetal anemia has a multifactorial etiology that may require a variety of interventions, although measures that reduce maternal iron deficiency may be generally beneficial.
Cellular Immune Response to COVID-19 and Potential Immune Modulators
Authors: Zhou Xi , Ye Qing
Published: April 2021

Coronavirus disease 2019 (COVID-19) is a respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Droplets and contacts serve as the main route of transmission of SARS-CoV-2. The characteristic of the disease is rather heterogeneous, ranging from no symptoms to critical illness. The factors associated with the outcome of COVID-19 have not been completely characterized to date. Inspired by previous studies on the relevance of infectious diseases, viral and host factors related to clinical outcomes have been identified. The severity of COVID-19 is mainly related to host factors, especially cellular immune responses in patients. Patients with mild COVID-19 and improved patients with severe COVID-19 exhibit a normal immune response to effectively eliminate the virus. The immune response in patients with fatal severe COVID-19 includes three stages: normal or hypofunction, hyperactivation, and anergy. Eventually, the patients were unable to resist viral infection and died. Based on our understanding of the kinetics of immune responses during COVID-19, we suggest that type I interferon (IFN) could be administered to patients with severe COVID-19 in the hypofunctional stage, intravenous immunoglobulin (IVIG) and glucocorticoid therapy could be administered in the immune hyperactivation stage. In addition, low molecular weight heparin (LMWH) anticoagulation therapy and anti-infective therapy with antibiotics are recommended in the hyperactivation stage.