bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hydrological Connectivity Controls Magnitude and Distribution of Sediment Deposition Within the Deltaic Islands of Wax Lake Delta, LA, USA
Authors: Olliver E. A. , Edmonds D. A. 
Published: September 2021

AbstractRelative sea‐level rise in the coming century will increase the risk of flooding and shoreline retreat on most major river deltas. River deltas can counteract flooding and shoreline retreat by depositing sediment on their surface. Yet, it is unclear what processes influence sedimentation and its variability on deltaic surfaces. Towards this end, we conducted a numerical modeling study in Delft3D to understand how floods, tides, and vegetation affect sedimentation rates and their spatial variability on islands in a deltaic system. Our experiments use a fully calibrated and validated hydrodynamic model of Wax Lake Delta, LA, USA. We analyzed eight numerical experiments that include a control simulation with no floods, tides, or vegetation, and seven simulations where we add in floods, tides, and vegetation. Our results clearly show that floods and tides have opposing effects. Compared to the control, floods introduce more sediment and increase the mean sedimentation rate, whereas, tides spread sediment over a larger area and decrease the mean sedimentation rate. Vegetation has a negligible effect on mean sedimentation rates but does shift sedimentation closer to the shoreline and to higher elevations. Overall, the amount of sedimentation on an island depends on its hydrological connectivity with the surrounding distributary channels. These results show that hydrologically well‐connected deltaic islands subject to tidal and riverine flooding aggrade their surfaces more evenly, which may be ideal for preventing inundation from relative sea‐level rise.
The postnatal leptin surge in mice is variable in both time and intensity and reflects nutritional status
Authors: Skowronski Alicja A. , Shaulson Evan D. , Leibel Rudolph L. , LeDuc Charles A. 
Published: September 2021

Abstract
Background/objectives
The murine postnatal leptin surge occurs within the first 4 weeks of life and is critical for neuronal projection development within hypothalamic feeding circuits. Here we describe the influence of nutritional status on the timing and magnitude of the postnatal leptin surge in mice.

Methods
Plasma leptin concentrations were measured 1–3 times per week for the first 4 weeks of life in C57BL/6J pups reared in litters adjusted to 3 (small), 7–8 (normal), or 11–12 (large) pups per dam fed breeder chow or raised in litters of 7–8 by dams fed high-fat diet (HFD) ad libitum starting either prior to conception or at parturition.

Results
Mice raised in small litters become fatter than pups raised in either normal or large litters. The leptin surge in small litter pups starts earlier, lasts longer, and is dramatically larger in magnitude compared to normal litter pups, even when leptin concentrations are normalized to fat mass. In mice reared in large litters, weight gain is diminished and the surge is both significantly delayed and lower in magnitude compared to control pups. Pups reared by HFD-fed dams (starting preconception or at parturition) are fatter and have augmented leptin surge magnitude compared to pups suckled by chow-fed dams. Surge timing varies depending upon nutritional status of the pup; the source of the surge is primarily subcutaneous adipose tissue. At peak leptin surge, within each group, fat mass and plasma leptin are uncorrelated; in comparison with adults, pups overproduce leptin relative to fat mass. Plasma leptin elevation persists longer than previously described; at postnatal day 27 mice continue overproducing leptin relative to fat mass.

Conclusions
In mice, small litter size and maternal HFD feeding during the perinatal period augment the plasma leptin surge whereas large litter size is associated with a delayed surge of reduced magnitude.
Level of systolic blood pressure within the normal range and risk of cardiovascular events in the absence of risk factors in Chinese
Authors: Ji Chunpeng , Wang Na , Shi Jihong , Huang Zhe , Chen Shuohua , Wang Guodong , Wu Shouling , Jonas Jost B. 
Published: September 2021

AbstractThe risk of cardiovascular disease (CVD) at currently defined normal systolic blood pressure (SBP) levels in individuals without CVD risk factors is not well examined. We evaluated whether higher systolic blood pressure within the range considered normal is associated with a higher CVD risk in Chinese without traditional CVD risk factors. The community-based study included 25,529 individuals (mean age:47.3 ± 12.3 years;range:18–95 years) with a baseline SBP of 90–129 mmHg, who were free of CVD and traditional CVD risk factors, and who were re-examined in biennial intervals. During a mean follow-up of 10.6 ± 1.49 years (maximum. 11.5 years), 847 CVD events occurred. CVD incidence per 1000 person-years increased with higher baseline SBP levels (SBP,90–99 mmHg:1.45;100–109 mmHg:2.15;110–119 mmHg:3.06; and 120–129 mmHg:3.80). After adjusting for CVD risk factors, the categorical Cox regression suggested that the CVD risk was not statistically significant for study participants with a baseline SBP level of 100–109 mmHg, 110–119 mmHg, and 120–129 mmHg compared with those with a baseline SBP level of 90–99 mmHg. If CVD risk factors including blood pressure categories which developed during follow-up were included in a time-dependent Cox regression analysis, the normal baseline SBP was still not associated with incident CVDs. A SBP between 90 and 129 mmHg was not associated with an increased CVD risk in a healthy population.
Biomimetic cell-actuated artificial muscle with nanofibrous bundles
Authors: Jang Yongwoo , Kim Sung Min , Kim Eunyoung , Lee Dong Yeop , Kang Tong Mook , Kim Seon Jeong 
Published: September 2021

AbstractBiohybrid artificial muscle produced by integrating living muscle cells and their scaffolds with free movement in vivo is promising for advanced biomedical applications, including cell-based microrobotic systems and therapeutic drug delivery systems. Herein, we provide a biohybrid artificial muscle constructed by integrating living muscle cells and their scaffolds, inspired by bundled myofilaments in skeletal muscle. First, a bundled biohybrid artificial muscle was fabricated by the integration of skeletal muscle cells and hydrophilic polyurethane (HPU)/carbon nanotube (CNT) nanofibers into a fiber shape similar to that of natural skeletal muscle. The HPU/CNT nanofibers provided a stretchable basic backbone of the 3-dimensional fiber structure, which is similar to actin-myosin scaffolds. The incorporated skeletal muscle fibers contribute to the actuation of biohybrid artificial muscle. In fact, electrical field stimulation reversibly leads to the contraction of biohybrid artificial muscle. Therefore, the current development of cell-actuated artificial muscle provides great potential for energy delivery systems as actuators for implantable medibot movement and drug delivery systems. Moreover, the innervation of the biohybrid artificial muscle with motor neurons is of great interest for human-machine interfaces.
C-type lectin receptor Dectin3 deficiency balances the accumulation and function of FoxO1-mediated LOX-1+ M-MDSCs in relieving lupus-like symptoms
Authors: Li Dan , Lu Li , Kong Wei , Xia Xiaoyu , Pan Yuchen , Li Jingman , Wang Jiali , Wang Tingting , Liang Jun , Dou Huan , Hou Yayi 
Published: September 2021

AbstractRecent studies indicate that Toll-like receptors (TLRs) and C-type lectin receptors (CLRs) can function as the signal of pattern recognition receptors, which play a pivotal role in the pathogenesis of the autoimmune disease. Systemic lupus erythematosus (SLE) is a classic autoimmune disease. Previous reports mainly focused on the potential role of TLRs in regulating the development of SLE, but little is known about the role of CLRs in the progression of SLE. Our previous studies showed that the inflammation-mediated accumulation of myeloid-derived suppressor cells (MDSCs) including granulocytic (G-MDSCs) and monocytic (M-MDSCs) participated in the pathogenesis of lupus. Mice deficient in Card9 (the downstream molecule of CLRs) were more susceptible to colitis-associated cancer via promoting the expansion of MDSCs. Whether the abnormal activation of CLRs regulates the expansion of MDSCs to participate in the pathogenesis of lupus remains unknown. In the present study, the expressions of CLRs were examined in both SLE patients and mouse models, revealing the expression of Dectin3 was positively correlated with SLEDAI. Dectin3 deficiency retarded the lupus-like disease by regulating the expansion and function of MDSCs. The mechanistic analysis revealed that Dectin3 deficiency promoted FoxO1-mediated apoptosis of MDSCs. Syk-Akt1-mediated nuclear transfer of FoxO1 increased in Dectin3-deficient MDSCs. Notedly, the accumulation of M-MDSCs mainly decreased in Dectin3−/− lupus mice, and the nuclear transfer of FoxO1 negatively correlated with the expression of LOX-1 on M-MDSCs. The silencing of FoxO1 expression in Dectin3−/− mice promoted the expansion of LOX-1+ M-MDSCs in vivo, and LOX-1+ M-MDSCs increased the differentiation of Th17 cells. Both LOX-1 expression on M-MDSCs and Dectin3 expression on MDSCs increased in patients with SLE. These data indicated that increased LOX-1+ M-MDSCs were related to the exacerbation of SLE development and might be potential target cells for the treatment of SLE.
DUSP6 expression is associated with osteoporosis through the regulation of osteoclast differentiation via ERK2/Smad2 signaling
Authors: Zhang Boya , Yuan Putao , Xu Guang , Chen Zhijun , Li Zhifei , Ye Huali , Wang Jiying , Shi Peihua , Sun Xuewu 
Published: September 2021

AbstractOsteoporosis-related fractures, such as femoral neck and vertebral fractures, are common in aged people, resulting in increased disability rate and health-care costs. Thus, it is of great importance to clarify the mechanism of osteoclast-related osteoporosis and find effective ways to avoid its complication. In this study, gene expression profile analysis and real-time polymerase chain reaction revealed that DUSP6 expression was suppressed in human and mice osteoporosis cases. In vitro experiments confirmed that DUSP6 overexpression prevented osteoclastogenesis, whereas inhibition of DUSP6 by small interference RNA or with a chemical inhibitor, (E/Z)-BCI, had the opposite effect. (E/Z)-BCl significantly accelerated the bone loss process in vivo by enhancing osteoclastogenesis. Bioinformatics analyses and in vitro experiments indicated that miR-181a was an upstream regulator of DUSP6. Moreover, miR-181a positively induced the differentiation and negatively regulated the apoptosis of osteoclasts via DUSP6. Furthermore, downstream signals by ERK2 and SMAD2 were also found to be involved in this process. Evaluation of ERK2-deficiency bone marrow-derived macrophages confirmed the role of ERK2 signaling in the DUSP6-mediated osteoclastogenesis. Additionally, immunoprecipitation assays confirmed that DUSP6 directly modified the phosphorylation status of SMAD2 and the subsequent nuclear transportation of NFATC1 to regulate osteoclast differentiation. Altogether, this study demonstrated for the first time the role of miRNA-181a/DUSP6 in the progression of osteoporosis via the ERK2 and SMAD2 signaling pathway. Hence, DUSP6 may represent a novel target for the treatment of osteoclast-related diseases in the future.
Dendritic cells in cancer immunology
Authors: Murphy Theresa L. , Murphy Kenneth M. 
Published: September 2021

AbstractThe clinical success of immune checkpoint therapy (ICT) has produced explosive growth in tumor immunology research because ICT was discovered through basic studies of immune regulation. Much of the current translational efforts are aimed at enhancing ICT by identifying therapeutic targets that synergize with CTLA4 or PD1/PD-L1 blockade and are solidly developed on the basis of currently accepted principles. Expanding these principles through continuous basic research may help broaden translational efforts. With this mindset, we focused this review on three threads of basic research directly relating to mechanisms underlying ICT. Specifically, this review covers three aspects of dendritic cell (DC) biology connected with antitumor immune responses but are not specifically oriented toward therapeutic use. First, we review recent advances in the development of the cDC1 subset of DCs, identifying important features distinguishing these cells from other types of DCs. Second, we review the antigen-processing pathway called cross-presentation, which was discovered in the mid-1970s and remains an enigma. This pathway serves an essential in vivo function unique to cDC1s and may be both a physiologic bottleneck and therapeutic target. Finally, we review the longstanding field of helper cells and the related area of DC licensing, in which CD4 T cells influence the strength or quality of CD8 T cell responses. Each topic is connected with ICT in some manner but is also a fundamental aspect of cell-mediated immunity directed toward intracellular pathogens.
Efficient CRISPR editing with a hypercompact Cas12f1 and engineered guide RNAs delivered by adeno-associated virus
Authors: Kim Do Yon , Lee Jeong Mi , Moon Su Bin , Chin Hyun Jung , Park Seyeon , Lim Youjung , Kim Daesik , Koo Taeyoung , Ko Jeong-Heon , Kim Yong-Sam 
Published: September 2021

AbstractGene therapy would benefit from a miniature CRISPR system that fits into the small adeno-associated virus (AAV) genome and has high cleavage activity and specificity in eukaryotic cells. One of the most compact CRISPR-associated nucleases yet discovered is the archaeal Un1Cas12f1. However, Un1Cas12f1 and its variants have very low activity in eukaryotic cells. In the present study, we redesigned the natural guide RNA of Un1Cas12f1 at five sites: the 5′ terminus of the trans-activating CRISPR RNA (tracrRNA), the tracrRNA–crRNA complementary region, a penta(uridinylate) sequence, the 3′ terminus of the crRNA and a disordered stem 2 region in the tracrRNA. These optimizations synergistically increased the average indel frequency by 867-fold. The optimized Un1Cas12f1 system enabled efficient, specific genome editing in human cells when delivered by plasmid vectors, PCR amplicons and AAV. As Un1Cas12f1 cleaves outside the protospacer, it can be used to create large deletions efficiently. The engineered Un1Cas12f1 system showed efficiency comparable to that of SpCas9 and specificity similar to that of AsCas12a.
Predictors of COVID-19 epidemics in countries of the World Health Organization African Region
Authors: Zhang Feifei , Karamagi Humphrey , Nsenga Ngoy , Nanyunja Miriam , Karinja Miriam , Amanfo Seth , Chase-Topping Margo , Calder-Gerver Giles , McGibbon Miles , Huber Alexandra , Wagner-Gamble Tara , Guo Chuan-Guo , Haynes Samuel , Morrison Alistair , Ferguson Miranda , Awandare Gordon A. , Mutapi Francisca , Yoti Zabulon , Cabore Joseph , Moeti Matshidiso R. , Woolhouse Mark E. J. 
Published: September 2021

AbstractCountries of the World Health Organization (WHO) African Region have experienced a wide range of coronavirus disease 2019 (COVID-19) epidemics. This study aimed to identify predictors of the timing of the first COVID-19 case and the per capita mortality in WHO African Region countries during the first and second pandemic waves and to test for associations with the preparedness of health systems and government pandemic responses. Using a region-wide, country-based observational study, we found that the first case was detected earlier in countries with more urban populations, higher international connectivity and greater COVID-19 test capacity but later in island nations. Predictors of a high first wave per capita mortality rate included a more urban population, higher pre-pandemic international connectivity and a higher prevalence of HIV. Countries rated as better prepared and having more resilient health systems were worst affected by the disease, the imposition of restrictions or both, making any benefit of more stringent countermeasures difficult to detect. Predictors for the second wave were similar to the first. Second wave per capita mortality could be predicted from that of the first wave. The COVID-19 pandemic highlights unanticipated vulnerabilities to infectious disease in Africa that should be taken into account in future pandemic preparedness planning.
Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: a double-blind, randomized controlled phase 3 trial
Authors: Kyriazopoulou Evdoxia , Poulakou Garyfallia , Milionis Haralampos , Metallidis Simeon , Adamis Georgios , Tsiakos Konstantinos , Fragkou Archontoula , Rapti Aggeliki , Damoulari Christina , Fantoni Massimo , Kalomenidis Ioannis , Chrysos Georgios , Angheben Andrea , Kainis Ilias , Alexiou Zoi , Castelli Francesco , Serino Francesco Saverio , Tsilika Maria , Bakakos Petros , Nicastri Emanuele , Tzavara Vassiliki , Kostis Evangelos , Dagna Lorenzo , Koufargyris Panagiotis , Dimakou Katerina , Savvanis Spyridon , Tzatzagou Glykeria , Chini Maria , Cavalli Giulio , Bassetti Matteo , Katrini Konstantina , Kotsis Vasileios , Tsoukalas George , Selmi Carlo , Bliziotis Ioannis , Samarkos Michael , Doumas Michael , Ktena Sofia , Masgala Aikaterini , Papanikolaou Ilias , Kosmidou Maria , Myrodia Dimitra-Melia , Argyraki Aikaterini , Cardellino Chiara Simona , Koliakou Katerina , Katsigianni Eleni-Ioanna , Rapti Vassiliki , Giannitsioti Efthymia , Cingolani Antonella , Micha Styliani , Akinosoglou Karolina , Liatsis-Douvitsas Orestis , Symbardi Styliani , Gatselis Nikolaos , Mouktaroudi Maria , Ippolito Giuseppe , Florou Eleni , Kotsaki Antigone , Netea Mihai G. , Eugen-Olsen Jesper , Kyprianou Miltiades , Panagopoulos Periklis , Dalekos George N. , Giamarellos-Bourboulis Evangelos J. 
Published: September 2021

AbstractEarly increase of soluble urokinase plasminogen activator receptor (suPAR) serum levels is indicative of increased risk of progression of coronavirus disease 2019 (COVID-19) to respiratory failure. The SAVE-MORE double-blind, randomized controlled trial evaluated the efficacy and safety of anakinra, an IL-1α/β inhibitor, in 594 patients with COVID-19 at risk of progressing to respiratory failure as identified by plasma suPAR ≥6 ng ml−1, 85.9% (n = 510) of whom were receiving dexamethasone. At day 28, the adjusted proportional odds of having a worse clinical status (assessed by the 11-point World Health Organization Clinical Progression Scale (WHO-CPS)) with anakinra, as compared to placebo, was 0.36 (95% confidence interval 0.26–0.50). The median WHO-CPS decrease on day 28 from baseline in the placebo and anakinra groups was 3 and 4 points, respectively (odds ratio (OR) = 0.40, P < 0.0001); the respective median decrease of Sequential Organ Failure Assessment (SOFA) score on day 7 from baseline was 0 and 1 points (OR = 0.63, P = 0.004). Twenty-eight-day mortality decreased (hazard ratio = 0.45, P = 0.045), and hospital stay was shorter.
Systematic evaluation of chromosome conformation capture assays
Authors: Akgol Oksuz Betul , Yang Liyan , Abraham Sameer , Venev Sergey V. , Krietenstein Nils , Parsi Krishna Mohan , Ozadam Hakan , Oomen Marlies E. , Nand Ankita , Mao Hui , Genga Ryan M. J. , Maehr Rene , Rando Oliver J. , Mirny Leonid A. , Gibcus Johan H. , Dekker Job 
Published: September 2021

AbstractChromosome conformation capture (3C) assays are used to map chromatin interactions genome-wide. Chromatin interaction maps provide insights into the spatial organization of chromosomes and the mechanisms by which they fold. Hi-C and Micro-C are widely used 3C protocols that differ in key experimental parameters including cross-linking chemistry and chromatin fragmentation strategy. To understand how the choice of experimental protocol determines the ability to detect and quantify aspects of chromosome folding we have performed a systematic evaluation of 3C experimental parameters. We identified optimal protocol variants for either loop or compartment detection, optimizing fragment size and cross-linking chemistry. We used this knowledge to develop a greatly improved Hi-C protocol (Hi-C 3.0) that can detect both loops and compartments relatively effectively. In addition to providing benchmarked protocols, this work produced ultra-deep chromatin interaction maps using Micro-C, conventional Hi-C and Hi-C 3.0 for key cell lines used by the 4D Nucleome project.
Assessment of avidity related to IgG subclasses in SARS-CoV-2 Brazilian infected patients
Authors: Moura Andrew D. , da Costa Hernan H. M. , Correa Victor A. , de S. Lima Ana K. , Lindoso José A. L. , De Gaspari Elizabeth , Hong Marisa A. , Cunha-Junior Jair P. , Prudencio Carlos R. 
Published: September 2021

AbstractSARS-CoV-2 is considered a global emergency, resulting in an exacerbated crisis in the health public in the world. Although there are advances in vaccine development, it is still limited for many countries. On the other hand, an immunological response that mediates protective immunity or indicates that predict disease outcome in SARS-CoV-2 infection remains undefined. This work aimed to assess the antibody levels, avidity, and subclasses of IgG to RBD protein, in symptomatic patients with severe and mild forms of COVID-19 in Brazil using an adapted in-house RBD-IgG ELISA. The RBD IgG-ELISA showed 100% of specificity and 94.3% of sensibility on detecting antibodies in the sera of hospitalized patients. Patients who presented severe COVID-19 had higher anti-RBD IgG levels compared to patients with mild disease. Additionally, most patients analyzed displayed low antibody avidity, with 64.4% of the samples of patients who recovered from the disease and 84.6% of those who died in this avidity range. Our data also reveals an increase of IgG1 and IgG3 levels since the 8th day after symptoms onset, while IgG4 levels maintained less detectable during the study period. Surprisingly, patients who died during 8–14 and 15–21 days also showed higher anti-RBD IgG4 levels in comparison with the recovered (P < 0.05), suggesting that some life-threatening patients can elicit IgG4 to RBD antibody response in the first weeks of symptoms onset. Our findings constitute the effort to clarify IgG antibodies' kinetics, avidity, and subclasses against SARS-CoV-2 RBD in symptomatic patients with COVID-19 in Brazil, highlighting the importance of IgG antibody avidity in association with IgG4 detection as tool laboratory in the follow-up of hospitalized patients with more significant potential for life-threatening.