bluuebunny/crossref_metadata_2025 huggingface dataset:
Deoxyribonuclease 1-Mediated Clearance of Circulating Chromatin Prevents From Immune Cell Activation and Pro-inflammatory Cytokine Production, a Phenomenon Amplified by Low Trap1 Activity: Consequences for Systemic Lupus Erythematosus
Authors: Felux Jasmin , Erbacher Annika , Breckler Magali , Hervé Roxane , Lemeiter Delphine , Mannherz Hans Georg , Napirei Markus , Rammensee Hans-Georg , Decker Patrice
Published: March 2021

Increased concentrations of circulating chromatin, especially oligo-nucleosomes, are observed in sepsis, cancer and some inflammatory autoimmune diseases like systemic lupus erythematosus (SLE). In SLE, circulating nucleosomes mainly result from increased apoptosis and decreased clearance of apoptotic cells. Once released, nucleosomes behave both as an autoantigen and as a damage-associated molecular pattern (DAMP) by activating several immune cells, especially pro-inflammatory cells. Deoxyribonuclease 1 (DNase1) is a major serum nuclease whose activity is decreased in mouse and human lupus. Likewise, the mitochondrial chaperone tumor necrosis factor (TNF) receptor-associated protein-1 (Trap1) protects against oxidative stress, which is increased in SLE. Here, using wild type, DNase1-deficient and DNase1/Trap1-deficient mice, we demonstrate that DNase1 is a major serum nuclease involved in chromatin degradation, especially when the plasminogen system is activated.In vitrodegradation assays show that chromatin digestion is strongly impaired in serum from DNase1/Trap1-deficient mice as compared to wild type mice.In vivo, after injection of purified chromatin, clearance of circulating chromatin is delayed in DNase1/Trap1-deficient mice in comparison to wild type mice. Since defective chromatin clearance may lead to chromatin deposition in tissues and subsequent immune cell activation, spleen cells were stimulatedin vitrowith chromatin. Splenocytes were activated by chromatin, as shown by interleukin (IL)-12 secretion and CD69 up-regulation. Moreover, cell activation was exacerbated when Trap1 is deficient. Importantly, we also show that cytokines involved in lupus pathogenesis down-regulate Trap1 expression in splenocytes. Therefore, combined low activities of both DNase1 and Trap1 lead to an impaired degradation of chromatinin vitro, delayed chromatin clearancein vivoand enhanced activation of immune cells. This situation may be encountered especially, but not exclusively, in SLE by the negative action of cytokines on Trap1 expression.
Experimental Study of Bond Behavior Between Rebar and PVA-Engineered Cementitious Composite (ECC) Using Pull-Out Tests
Authors: Xiao Jie , Long Xiang , Ye Ming , Jiang Haibo , Liu Lingfei , Zhai Keyi
Published: March 2021

As a novel civil engineering material, Engineered Cementitious Composite (ECC) has attracted more and more attention due to its strain-hardening characteristics, good post-cracking resistance and its unique properties. Bonding between Engineered Cementitious Composite (ECC) and rebar has a great effect on the mechanical behavior of structural members. In this paper, direct pull-out tests were conducted to understand the bond behavior between the ECC and rebar. The test parameters included rebar diameter and type, cover layer thickness, embedment length and fiber volume content. Bond-slip curves, failure and cracking pattern and bond strength were compared and discussed. The test results indicated that the bond strength decreased with the increase of embedded length. Through regression analysis with the test data, the functional relationships between bond strength and cover layer thickness and rebar diameter were fitted well. According to the positive and negative signs of the fitting parameters m and n, the relationship between the bond strength and the cover layer thickness and the rebar diameter could be determined. The bond strength increased obviously with the increase of fiber content. When the fiber volume content was 1, 1.5 and 2%, the bond strength of these specimens were 1.5, 2.5 and 3.1 times that of specimens without polyvinyl alcohol (PVA) fiber.
Angiotensin-Converting Enzyme (ACE) Inhibitors and Angiotensin Receptor Blockers (ARB) Are Protective Against ICU Admission and Mortality for Patients With COVID-19 Disease
Authors: ElAbd Rawan , AlTarrah Dana , AlYouha Sarah , Bastaki Hamad , Almazeedi Sulaiman , Al-Haddad Mohannad , Jamal Mohammad , AlSabah Salman
Published: March 2021

Introduction: Corona Virus disease 2019 (COVID-19) caused by the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. The aim of this study was to investigate the impact of being on an Angiotensin-Converting Enzyme Inhibitors (ACEI) and/or Angiotensin Receptor Blockers (ARB) on hospital admission, on the following COVID-19 outcomes: disease severity, ICU admission, and mortality.

Methods: The charts of all patients consecutively diagnosed with COVID-19 from the 24th of February to the 16th of June of the year 2020 in Jaber Al-Ahmed Al-Sabah hospital in Kuwait were checked. All related patient information and clinical data was retrieved from the hospitals electronic medical record system. The primary outcome was COVID-19 disease severity defined as the need for Intensive Care Unit (ICU) admission. Secondary outcome was mortality.

Results: A total of 4,019 COVID-19 patients were included, of which 325 patients (8.1%) used ACEI/ARB, users of ACEI/ARB were found to be significantly older (54.4 vs. 40.5 years). ACEI/ARB users were found to have more co-morbidities; diabetes (45.8 vs. 14.8%) and hypertension (92.9 vs. 13.0%). ACEI/ARB use was found to be significantly associated with greater risk of ICU admission in the unadjusted analysis [OR, 1.51 (95% CI: 1.04–2.19), p = 0.028]. After adjustment for age, gender, nationality, coronary artery disease, diabetes and hypertension, ICU admission was found to be inversely associated with ACEI use [OR, 0.57 (95% CI: 0.34–0.88), p = 0.01] and inversely associated with mortality [OR, 0.56 (95% CI: 0.33–0.95), p = 0.032].

Conclusion: The current evidence in the literature supports continuation of ACEI/ARB medications for patients with co-morbidities that acquire COVID-19 infection. Although, the protective effects of such medications on COVID-19 disease severity and mortality remain unclear, the findings of the present study support the use of ACEI/ARB medication.
Strategies to Overcome Intermediate Accumulation During in situ Nitrate Remediation in Groundwater by Hydrogenotrophic Denitrification
Authors: Duffner Clara , Wunderlich Anja , Schloter Michael , Schulz Stefanie , Einsiedl Florian
Published: March 2021

Bioremediation of polluted groundwater is one of the most difficult actions in environmental science. Nonetheless, the clean-up of nitrate polluted groundwater may become increasingly important as nitrate concentrations frequently exceed the EU drinking water limit of 50 mg L–1, largely due to intensification of agriculture and food production. Denitrifiers are natural catalysts that can reduce increasing nitrogen loading of aquatic ecosystems. Porous aquifers with high nitrate loading are largely electron donor limited and additionally, high dissolved oxygen concentrations are known to reduce the efficiency of denitrification. Therefore, denitrification lag times (time prior to commencement of microbial nitrate reduction) up to decades were determined for such groundwater systems. The stimulation of autotrophic denitrifiers by the injection of hydrogen into nitrate polluted regional groundwater systems may represent a promising remediation strategy for such environments. However, besides high costs other drawbacks, such as the transient or lasting accumulation of the cytotoxic intermediate nitrite or the formation of the potent greenhouse gas nitrous oxide, have been described. In this article, we detect causes of incomplete denitrification, which include environmental factors and physiological characteristics of the underlying bacteria and provide possible mitigation approaches.
CARD-FISH in the Sequencing Era: Opening a New Universe of Protistan Ecology
Authors: Piwosz Kasia , Mukherjee Indranil , Salcher Michaela M. , Grujčić Vesna , Šimek Karel
Published: March 2021

Phagotrophic protists are key players in aquatic food webs. Although sequencing-based studies have revealed their enormous diversity, ecological information onin situabundance, feeding modes, grazing preferences, and growth rates of specific lineages can be reliably obtained only using microscopy-based molecular methods, such as Catalyzed Reporter Deposition-Fluorescencein situHybridization (CARD-FISH). CARD-FISH is commonly applied to study prokaryotes, but less so to microbial eukaryotes. Application of this technique revealed thatParaphysomonasorSpumella-like chrysophytes, considered to be among the most prominent members of protistan communities in pelagic environments, are omnipresent but actually less abundant than expected, in contrast to little known groups such as heterotrophic cryptophyte lineages (e.g., CRY1), cercozoans, katablepharids, or the MAST lineages. Combination of CARD-FISH with tracer techniques and application of double CARD-FISH allow visualization of food vacuole contents of specific flagellate groups, thus considerably challenging our current, simplistic view that they are predominantly bacterivores. Experimental manipulations with natural communities revealed that larger flagellates are actually omnivores ingesting both prokaryotes and other protists. These new findings justify our proposition of an updated model of microbial food webs in pelagic environments, reflecting more authentically the complex trophic interactions and specific roles of flagellated protists, with inclusion of at least two additional trophic levels in the nanoplankton size fraction. Moreover, we provide a detailed CARD-FISH protocol for protists, exemplified on mixo- and heterotrophic nanoplanktonic flagellates, together with tips on probe design, a troubleshooting guide addressing most frequent obstacles, and an exhaustive list of published probes targeting protists.
A Role for the Amygdala in Impairments of Affective Behaviors Following Mild Traumatic Brain Injury
Authors: McCorkle Taylor A. , Barson Jessica R. , Raghupathi Ramesh
Published: March 2021

Mild traumatic brain injury (TBI) results in chronic affective disorders such as depression, anxiety, and fear that persist up to years following injury and significantly impair the quality of life for patients. Although a great deal of research has contributed to defining symptoms of mild TBI, there are no adequate drug therapies for brain-injured individuals. Preclinical studies have modeled these deficits in affective behaviors post-injury to understand the underlying mechanisms with a view to developing appropriate treatment strategies. These studies have also unveiled sex differences that contribute to the varying phenotypes associated with each behavior. Although clinical and preclinical studies have viewed these behavioral deficits as separate entities with unique neurobiological mechanisms, mechanistic similarities suggest that a novel approach is needed to advance research on drug therapy. This review will discuss the circuitry involved in the expression of deficits in affective behaviors following mild TBI in humans and animals and provide evidence that the manifestation of impairment in these behaviors stems from an amygdala-dependent emotional processing deficit. It will highlight mechanistic similarities between these different types of affective behaviors that can potentially advance mild TBI drug therapy by investigating treatments for the deficits in affective behaviors as one entity, requiring the same treatment.
Unsupervised Learning and Clustered Connectivity Enhance Reinforcement Learning in Spiking Neural Networks
Authors: Weidel Philipp , Duarte Renato , Morrison Abigail
Published: March 2021

Reinforcement learning is a paradigm that can account for how organisms learn to adapt their behavior in complex environments with sparse rewards. To partition an environment into discrete states, implementations in spiking neuronal networks typically rely on input architectures involving place cells or receptive fields specified ad hoc by the researcher. This is problematic as a model for how an organism can learn appropriate behavioral sequences in unknown environments, as it fails to account for the unsupervised and self-organized nature of the required representations. Additionally, this approach presupposes knowledge on the part of the researcher on how the environment should be partitioned and represented and scales poorly with the size or complexity of the environment. To address these issues and gain insights into how the brain generates its own task-relevant mappings, we propose a learning architecture that combines unsupervised learning on the input projections with biologically motivated clustered connectivity within the representation layer. This combination allows input features to be mapped to clusters; thus the network self-organizes to produce clearly distinguishable activity patterns that can serve as the basis for reinforcement learning on the output projections. On the basis of the MNIST and Mountain Car tasks, we show that our proposed model performs better than either a comparable unclustered network or a clustered network with static input projections. We conclude that the combination of unsupervised learning and clustered connectivity provides a generic representational substrate suitable for further computation.
Using Oculomotor Features to Predict Changes in Optic Nerve Sheath Diameter and ImPACT Scores From Contact-Sport Athletes
Authors: Rao Hrishikesh M. , Yuditskaya Sophia , Williamson James R. , Vian Trina R. , Lacirignola Joseph J. , Shenk Trey E. , Talavage Thomas M. , Heaton Kristin J. , Quatieri Thomas F.
Published: March 2021

There is mounting evidence linking the cumulative effects of repetitive head impacts to neuro-degenerative conditions. Robust clinical assessment tools to identify mild traumatic brain injuries are needed to assist with timely diagnosis for return-to-field decisions and appropriately guide rehabilitation. The focus of the present study is to investigate the potential for oculomotor features to complement existing diagnostic tools, such as measurements of Optic Nerve Sheath Diameter (ONSD) and Immediate Post-concussion Assessment and Cognitive Testing (ImPACT). Thirty-one high school American football and soccer athletes were tracked through the course of a sports season. Given the high risk of repetitive head impacts associated with both soccer and football, our hypotheses were that (1) ONSD and ImPACT scores would worsen through the season and (2) oculomotor features would effectively capture both neurophysiological changes reflected by ONSD and neuro-functional status assessed via ImPACT. Oculomotor features were used as input to Linear Mixed-Effects Regression models to predict ONSD and ImPACT scores as outcomes. Prediction accuracy was evaluated to identify explicit relationships between eye movements, ONSD, and ImPACT scores. Significant Pearson correlations were observed between predicted and actual outcomes for ONSD (Raw = 0.70; Normalized = 0.45) and for ImPACT (Raw = 0.86; Normalized = 0.71), demonstrating the capability of oculomotor features to capture neurological changes detected by both ONSD and ImPACT. The most predictive features were found to relate to motor control and visual-motor processing. In future work, oculomotor models, linking neural structures to oculomotor function, can be built to gain extended mechanistic insights into neurophysiological changes observed through seasons of participation in contact sports.
Risk Factors for Long-Term Death After Medullary Infarction: A Multicenter Follow-Up Study
Authors: Zhang Dao Pei , Liu Xiang Zhe , Yin Suo , Ma Qian Kun , Yu Meng , Zhang Huai Liang , Wang Xin Zhi , Zhang Jie Wen
Published: March 2021

Background and Purpose: We investigated the risk factors for death in patients with medullary infarction (MI) during a long-term follow-up.

Methods: We retrospectively examined 179 consecutive patients (130 men and 49 women) who had clinical and MRI findings consistent with MI between February 2012 and January 2017 at three university hospitals. Long-term outcomes were assessed by telephonic interview. The clinical and radiological features and risk factors for poor outcomes (modified Rankin scale score ≥ 3, all-cause death) were analyzed.

Results: Mean age of patients was 58.3 ± 12.8 years (range, 25–87); mean follow-up period after stroke onset was 42.7 ± 13.2 months (range, 24–78). Basilar artery (BA) stenosis >50% was more closely related to medial medullary infarction (MMI) than other types. There was greater frequency of ipsilateral vertebral artery hypoplasia (VAH) or V4AH and V4 occlusion in lateral MI than in other types. On rostro-caudal classification, middle (M)+dorsal (D) was most frequent, followed by the ventral (V)+M+D types. 21.2% patients showed poor long-term prognosis. Age ≥ 65 years, recurrent stroke, dysphagia, >50% BA stenosis, and ventral MI were risk factors for poor long-term prognosis. All-cause mortality rate was 10.6%; age ≥ 65 years, recurrent stroke, and dysphagia were risk factors for death in the long-term. Ventral MI and MMI+cerebellar infarction, as well as stroke mechanism of artery-to-artery embolism, were potential risk factors for death in the long-term. Pneumonia and recurrent stroke were major causes of death.

Conclusions: Long-term poor outcomes of MI and all-cause mortality were not infrequent. Older age, recurrent stroke, and dysphagia were common risk factors for poor prognosis and death.
Case Report: Aperiodic Fluctuations of Neural Activity in the Ictal MEG of a Child With Drug-Resistant Fronto-Temporal Epilepsy
Authors: van Heumen Saskia , Moreau Jeremy T. , Simard-Tremblay Elisabeth , Albrecht Steffen , Dudley Roy WR. , Baillet Sylvain
Published: March 2021

Successful surgical treatment of patients with focal drug-resistant epilepsy remains challenging, especially in cases for which it is difficult to define the area of cortex from which seizures originate, the seizure onset zone (SOZ). Various diagnostic methods are needed to select surgical candidates and determine the extent of resection. Interictal magnetoencephalography (MEG) with source imaging has proven to be useful for presurgical evaluation, but the use of ictal MEG data remains limited. The purpose of the present study was to determine whether pre-ictal variations of spectral properties of neural activity from ictal MEG recordings are predictive of SOZ location.We performed a 4 h overnight MEG recording in an 8-year-old child with drug-resistant focal epilepsy of suspected right fronto-temporal origin and captured one ~45-s seizure. The patient underwent a right temporal resection from the anterior temporal neocortex and amygdala to the mid-posterior temporal neocortex, sparing the hippocampus proper. She remains seizure-free 21 months postoperatively. The histopathological assessment confirmed frank focal cortical dysplasia (FCD) type IIa in the MEG-defined SOZ, which was based on source imaging of averaged ictal spikes at seizure onset. We investigated temporal changes (inter-ictal, pre-ictal, and ictal periods) together with spatial differences (SOZ vs. control regions) in spectral parameters of background brain activity, namely the aperiodic broadband offset and slope, and assessed how they confounded the interpretation of apparent variations of signal power in typical electrophysiological bands. Our data show that the SOZ was associated with a higher aperiodic offset and exponent during the seizure compared to control regions. Both parameters increased in all regions from 2 min before the seizure onwards. Regions anatomically closer to the SOZ also expressed higher values compared to contralateral regions, potentially indicating ictal spread. We also show that narrow-band power changes were caused by these fluctuations in the aperiodic component of ongoing brain activity. Our results indicate that the broadband aperiodic component of ongoing brain activity cannot be reduced to background noise of no physiological interest, and rather may be indicative of the neuropathophysiology of the SOZ. We believe these findings will inspire future studies of ictal MEG cases and confirm their significance.
Lateral Habenula Glutamatergic Neurons Modulate Isoflurane Anesthesia in Mice
Authors: Liu Chengxi , Liu Junxiao , Zhou Liang , He Haifeng , Zhang Yu , Cai Shuang , Yuan Chengdong , Luo Tianyuan , Zheng Jijian , Yu Tian , Zhang Mazhong
Published: March 2021

Since their introduction in the 1840s, one of the largest mysteries of modern anesthesia are how general anesthetics create the state of reversible loss of consciousness. Increasing researchers have shown that neural pathways that regulate endogenous sleep–wake systems are also involved in general anesthesia. Recently, the Lateral Habenula (LHb) was considered as a hot spot for both natural sleep–wake and propofol-induced sedation; however, the role of the LHb and related pathways in the isoflurane-induced unconsciousness has yet to be identified. Here, using real-time calcium fiber photometry recordings in vivo, we found that isoflurane reversibly increased the activity of LHb glutamatergic neurons. Then, we selectively ablated LHb glutamatergic neurons in Vglut2-cre mice, which caused a longer induction time and less recovery time along with a decrease in delta-band power in mice under isoflurane anesthesia. Furthermore, using a chemogenetic approach to specifically activate LHb glutamatergic neurons shortened the induction time and prolonged the recovery time in mice under isoflurane anesthesia with an increase in delta-band power. In contrast, chemogenetic inhibition of LHb glutamatergic neurons was very similar to the effects of selective lesions of LHb glutamatergic neurons. Finally, optogenetic activation of LHb glutamatergic neurons or the synaptic terminals of LHb glutamatergic neurons in the rostromedial tegmental nucleus (RMTg) produced a hypnosis-promoting effect in isoflurane anesthesia with an increase in slow wave activity. Our results suggest that LHb glutamatergic neurons and pathway are vital in modulating isoflurane anesthesia.
Freeze-Frame Imaging of Dendritic Calcium Signals With TubuTag
Authors: Perez-Alvarez Alberto , Huhn Florian , Dürst Céline D. , Franzelin Andreas , Lamothe-Molina Paul J. , Oertner Thomas G.
Published: March 2021

The extensive dendritic arbor of neurons is thought to be actively involved in the processing of information. Dendrites contain a rich diversity of ligand- and voltage-activated ion channels as well as metabotropic receptors. In addition, they are capable of releasing calcium from intracellular stores. Under specific conditions, large neurons produce calcium spikes that are locally restricted to a dendritic section. To investigate calcium signaling in dendrites, we introduce TubuTag, a genetically encoded ratiometric calcium sensor anchored to the cytoskeleton. TubuTag integrates cytoplasmic calcium signals by irreversible photoconversion from green to red fluorescence when illuminated with violet light. We used a custom two-photon microscope with a large field of view to image pyramidal neurons in CA1 at subcellular resolution. Photoconversion was strongest in the most distal parts of the apical dendrite, suggesting a gradient in the amplitude of dendritic calcium signals. As the read-out of fluorescence can be performed several hours after photoconversion, TubuTag will help investigating dendritic signal integration and calcium homeostasis in large populations of neurons.
Silencing of PGK1 Promotes Sensitivity to Paclitaxel Treatment by Upregulating XAF1-Mediated Apoptosis in Triple-Negative Breast Cancer
Authors: Sun Shanshan , Wu Hao , Wu Xiaohong , You Zilong , Jiang Yang , Liang Xiaoshuan , Chen Zhuo , Zhang Ye , Wei Wei , Jiang Yongdong , Chen Yanbo , Song Yanni , Pang Da
Published: March 2021

Objective:Triple negative breast cancer (TNBC) is known to have aggressive clinical course and a high risk of recurrence. Given the lack of effective targeted therapy options, paclitaxel-based chemotherapy is still the primary option for TNBC patients. However, patients who fail to achieve a complete response during neoadjuvant chemotherapy may be mainly due to sensitivity and resistance to chemotherapy. Thus, we concentrated the present research on the role of PGK1 in the sensitivity to paclitaxel treatment and the possible underlying mechanisms in TNBC.

Methods:After exposure to paclitaxel, a cell viability analysis was made to investigate the influence of PGK1 silencing on cell death. The effect of PGK1 on apoptosis induced by paclitaxel treatment was examinedin vitroby flow cytometry cell apoptosis assays. Western blotting was performed to examine the impact of PGK1 on paclitaxel-induced apoptosis. The correlation of PGK1 with apoptosis-associated protein X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1) was analyzed in 39 specimens by immunohistochemistry analysis.

Results:We observed that silencing PGK1 sensitized triple-negative breast cancer (TNBC) cell lines to paclitaxel treatment as a result of increased drug-induced apoptosis. Furthermore, mechanistic investigations suggested that XAF1 was increased in PGK1-knockdown cells along with the expression of the apoptotic proteins including cleaved caspase-3 and Bax. Immunohistochemistry analysis showed that PGK1 was negatively related to XAF1. Moreover, we found that downregulation of XAF1 reduced paclitaxel-induced apoptosis in PGK1-silenced triple-negative cell lines.

Conclusion:Our results identified PGK1 as a potential biomarker for the treatment of TNBC, and inhibition of PGK1 expression might represent a novel strategy to sensitize TNBC to paclitaxel treatment.
Long-Term Survival Outcomes and Treatment Experience of 64 Patients With Esthesioneuroblastoma
Authors: Zeng Qian , Tian Yifu , He Yihong , Xie Qiongxuan , Ou Ludi , Wang Min , Chen Wen , Wei Rui
Published: March 2021

Background: Esthesioneuroblastoma (ENB) is a rare sinonasal malignancy, lacking a unified staging system and treatment. Management at a single center was retrospectively evaluated to inform future treatment options and prognostic factors.

Methods: Clinical data of 64 consecutive ENB patients, including prognostic factors and treatment methods, were reviewed retrospectively. Data were collected to calculate overall survival (OS) and progression free survival (PFS).

Results: The majority of tumors 84.4% were within Kadish C stage, 79.7% were within T3 or T4, and 64.0% were within Hyams grade III or IV. A total of 50 (78.1%) patients received surgery and combined radiotherapy with or without chemotherapy, 10 (15.6%) received surgery with or without chemotherapy alone, and 4 (6.3%) received radiotherapy with or without chemotherapy alone. The majority of patients (79.7%) underwent endoscopic resection (endoscopic and endoscopically assisted). Surgery combined with radiotherapy with or without chemotherapy resulted in significantly better OS (84.4 vs. 50.6%, 84.4 vs. 37.5%) compared to surgery alone and radiotherapy alone (P = 0.0064). Endoscopic surgery group (endoscopic and endoscopically assisted) resulted in significantly better 5-year PFS (61.7 vs. 22.2%) compared to the open surgery group (P < 0.001). Although endoscopic surgery group was not a statistically significant predictor of 5-year OS (P = 0.54), the 5-year OS was 79.3% for the endoscopic surgery group and 76.2% for the open surgery group. A Cox regression analysis identified intracranial extension and surgery combined with radiotherapy as independent factors affecting 5-year OS while cervical lymph node metastasis and Hyams grade IV as independent factors affecting 5-year PFS.

Conclusion: Our findings suggest that surgery combined with radiotherapy is the best treatment approach for ENB. For advanced tumors, endoscopic surgery is an effective treatment, and its survival rate is equal to or better than open surgery.
Case Report: Asymmetric Bone Marrow Involvement in Patients With Acute Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Yan Han , Zhou Zhenyang , Wu Yingying , Zhong Zhaodong , You Yong , Yao Junxia , Chen Wanxin , Xia Linghui , Xia Xiaotian , Shi Wei
Published: March 2021

After allogeneic hematopoietic stem cell transplantation (allo-HSCT), acute leukemia relapse is common, and asymmetric bone marrow recurrence hasn't been reported. Because the anatomical distribution of acute leukemia clones in the bone marrow after allo-HSCT is presumed to be diffuse, bone marrow aspirations are performed in single site. The first case was a 20-year-old man who was diagnosed with acute myelomonocytic leukemia and received haploidentical allo-HSCT. Routine bone marrow biopsy of his left posterior iliac bone marrow showed 52% leukemia blasts, while the right side had 0% blasts 10 days later. The second case was a 23-year-old woman who was diagnosed with acute B lymphoblastic leukemia and received HLA-identical sibling allo-HSCT. Although 62% of blasts were found in her left iliac marrow on day +122, 0% of blasts were found on a sample obtained from the right iliac crest on day +128. Bilateral iliac bone marrow pathology and whole-body 18F-FDG PET/CT scans confirmed that the leukemic infiltration in her bone marrow was asymmetric. To our knowledge, these are the first case reports of asymmetric bone marrow infiltration of blasts in acute leukemia patients after allo-HSCT. Bilateral posterior iliac crest aspirations or 18F-FDG-PET/CT scans may help distinguish such involvement.
Clinical Value of ctDNA in Hematological Malignancies (Lymphomas, Multiple Myeloma, Myelodysplastic Syndrome, and Leukemia): A Meta-Analysis
Authors: Tan Xiangyu , Yan Han , Chen Lei , Zhang Yuyang , Sun Chunyan
Published: March 2021

Background: Circulating tumor DNA (ctDNA) has offered a minimally invasive approach for the detection and measurement of cancer. However, its diagnostic and prognostic value in hematological malignancies remains unclear.

Materials and methods: Pubmed, Embase, and Cochrane Library were searched for relating literature. Diagnostic accuracy variables and disease progression prediction data were pooled by the Meta-Disc version 1.4 software. Review Manager version 5.4 software was applied for prognostic data analysis.

Results: A total of 11 studies met our inclusion criteria. In terms of diagnosis, the pooled sensitivity and specificity were 0.51 (95% confidence intervals (CI) 0.38–0.64) and 0.96 (95% CI 0.88–1.00), respectively. The AUSROC (area under the SROC) curve was 0.89 (95%CI 0.75–1.03). When it comes to the prediction of disease progression, the overall sensitivity and specificity was 0.83 (95% CI 0.67–0.94) and 0.98 (95% CI 0.93–1.00), respectively. Moreover, a significant association also existed between the presence of ctDNA and worse progression-free survival (HR 2.63, 95% CI 1.27–5.43, p = 0.009), as well as overall survival (HR 2.92, 95% CI 1.53–5.57, p = 0.001).

Conclusions: The use of ctDNA in clinical practice for hematological malignancies is promising, as it may not only contribute to diagnosis, but could also predict the prognosis of patients so as to guide treatment. In the future, more studies are needed to realize the standardization of sequencing techniques and improve the detection sensitivity of exploration methods.
Clinical and Genetic Spectra of Inherited Liver Disease in Children in China
Authors: Fang Youhong , Yu Jindan , Lou Jingan , Peng Kerong , Zhao Hong , Chen Jie
Published: March 2021

Background: Children presenting with chronic liver disease or acute liver failure often have an underlying genetic disorder. The aim of this study was to analyze the clinical and genetic spectra of inherited liver disease in children in a tertiary hospital.

Methods: A total of 172 patients were classified into three groups according to their clinical presentation: cholestasis (Group A), liver enzyme elevation (Group B), and hepato/splenomegaly (Group C). Next-generation sequencing (NGS) was performed on all patients recruited in this study. The genotypic and phenotypic spectra of disease in these patients were reviewed.

Results: The median age at enrollment of the 172 patients was 12.0 months (IQR: 4.9, 42.5 months), with 52.3% males and 47.7% females. The overall diagnostic rate was 55.8% (96/172) in this group. The diagnostic rates of whole-exome sequencing (WES) and targeted gene panel sequencing (TGPS) were 47.2% and 62.0%, respectively (no significant difference, p = 0.054). We identified 25 genes related to different phenotypes, including 46 novel disease-related pathogenic mutations. The diagnostic rates in the three groups were 46.0% (29/63), 48.6% (34/70), and 84.6% (33/39). ATP7B, SLC25A13, and G6PC were the top three genes related to monogenic liver disease in this study.

Conclusion: WES and TGPS show similar diagnostic rates in the diagnosis of monogenic liver disease. NGS has an important role in the diagnosis of monogenetic liver disease and can provide more precise medical treatment and predict the prognosis of these diseases.
A Meta-Analysis Reveals Opposite Effects of Biotic and Abiotic Stresses on Transcript Levels of Arabidopsis Intracellular Immune Receptor Genes
Authors: Yang Leiyun , Wang Zhixue , Hua Jian
Published: March 2021

Plant intracellular immune receptor NLR (nucleotide-binding leucine-rich repeat) proteins sense the presence of pathogens and trigger strong and robust immune responses. NLR genes are known to be tightly controlled at the protein level, but little is known about their dynamics at the transcript level. In this study, we presented a meta-analysis of transcript dynamics of all 207 NLR genes in the Col-0 accession of Arabidopsis thaliana under various biotic and abiotic stresses based on 88 publicly available RNA sequencing datasets from 27 independent studies. We find that about two thirds of the NLR genes are generally induced by pathogens, immune elicitors, or salicylic acid (SA), suggesting that transcriptional induction of NLR genes might be an important mechanism in plant immunity regulation. By contrast, NLR genes induced by biotic stresses are often repressed by abscisic acid, high temperature and drought, suggesting that transcriptional regulation of NLR genes might be important for interaction between abiotic and biotic stress responses. In addition, pathogen-induced expression of some NLR genes are dependent on SA induction. Interestingly, a small group of NLR genes are repressed under certain biotic stress treatments, suggesting an unconventional function of this group of NLRs. This meta-analysis thus reveals the transcript dynamics of NLR genes under biotic and abiotic stress conditions and suggests a contribution of NLR transcript regulation to plant immunity as well as interactions between abiotic and biotic stress responses.
Historical Analysis Exposes Catastrophic Seagrass Loss for the United Kingdom
Authors: Green Alix E. , Unsworth Richard K. F. , Chadwick Michael A. , Jones Peter J. S.
Published: March 2021

The spatial extent of seagrass is poorly mapped, and knowledge of historical loss is limited. Here, we collated empirical and qualitative data using systematic review methods to provide unique analysis on seagrass occurrence and loss in the United Kingdom. We document 8,493 ha of recently mapped seagrass in the United Kingdom since 1998. This equates to an estimated 0.9 Mt of carbon, which, in the current carbon market represents about £22 million. Using simple models to estimate seagrass declines triangulated against habitat suitability models, we provide evidence of catastrophic seagrass loss; at least 44% of United Kingdom’s seagrasses have been lost since 1936, 39% since the 1980’s. However, losses over longer time spans may be as high as 92%. Based on these estimates, historical seagrass meadows could have stored 11.5 Mt of carbon and supported approximately 400 million fish. Our results demonstrate the vast scale of losses and highlight the opportunities to restore seagrass to support a range of ecosystems services.
Polyploidy on Islands: Its Emergence and Importance for Diversification
Authors: Meudt Heidi M. , Albach Dirk C. , Tanentzap Andrew J. , Igea Javier , Newmarch Sophie C. , Brandt Angela J. , Lee William G. , Tate Jennifer A.
Published: March 2021

Whole genome duplication or polyploidy is widespread among floras globally, but traditionally has been thought to have played a minor role in the evolution of island biodiversity, based on the low proportion of polyploid taxa present. We investigate five island systems (Juan Fernández, Galápagos, Canary Islands, Hawaiian Islands, and New Zealand) to test whether polyploidy (i) enhances or hinders diversification on islands and (ii) is an intrinsic feature of a lineage or an attribute that emerges in island environments. These island systems are diverse in their origins, geographic and latitudinal distributions, levels of plant species endemism (37% in the Galapagos to 88% in the Hawaiian Islands), and ploidy levels, and taken together are representative of islands more generally. We compiled data for vascular plants and summarized information for each genus on each island system, including the total number of species (native and endemic), generic endemicity, chromosome numbers, genome size, and ploidy levels. Dated phylogenies were used to infer lineage age, number of colonization events, and change in ploidy level relative to the non-island sister lineage. Using phylogenetic path analysis, we then tested how the diversification of endemic lineages varied with the direct and indirect effects of polyploidy (presence of polyploidy, time on island, polyploidization near colonization, colonizer pool size) and other lineage traits not associated with polyploidy (time on island, colonizer pool size, repeat colonization). Diploid and tetraploid were the most common ploidy levels across all islands, with the highest ploidy levels (>8x) recorded for the Canary Islands (12x) and New Zealand (20x). Overall, we found that endemic diversification of our focal island floras was shaped by polyploidy in many cases and certainly others still to be detected considering the lack of data in many lineages. Polyploid speciation on the islands was enhanced by a larger source of potential congeneric colonists and a change in ploidy level compared to overseas sister taxa.
Mental Health Impacts in Argentinean College Students During COVID-19 Quarantine
Authors: López Steinmetz Lorena Cecilia , Leyes Candela Abigail , Dutto Florio María Agustina , Fong Shao Bing , López Steinmetz Romina Lucrecia , Godoy Juan Carlos
Published: March 2021

Background:We aimed to: (1) analyze differences in both general (in terms of psychological well-being/discomfort, social functioning and coping, and psychological distress) and specific (depression, trait-anxiety, negative alcohol-related consequences, and suicidal risk) mental health state (MHS) in college students, residing in four different Argentinean regions (center, north, south, and the most populated) exposed to different spread-rates of the COVID-19; (2) analyze between-group differences in both general and specific MHS indicators at four quarantine sub-periods (twice prior, and twice following the first quarantine extension).

Methods:We used a cross-sectional design with a convenience sample including 2,687 college students. Data was collected online during the Argentinean quarantine. We calculated one-way between-groups ANOVA with Tukey'spost hoctest.

Results:Regionally, the center and the most populated area differed in psychological well-being/discomfort and negative alcohol-related consequences, but not in the remaining MHS indicators. According to the quarantine sub-periods, there were differences in psychological well-being/discomfort, social functioning and coping, psychological distress, and negative alcohol-related consequences. Negative alcohol-related consequences were the only MHS indicator improving over time. For all of the remaining MHS indicators, we found a similar deterioration pattern in the course of time, with mean scores decreasing from the first to the 2nd week of the quarantine pre-extensions, then increasing toward the 1st week of the quarantine post-extension (with some MHS indicators reaching mean scores worse than the start), and then continued to increase.

Conclusion:A worsened mean MHS during quarantine suggests that quarantine and its extensions contribute to negative mental health impacts.
Neural Networks Predicting Microbial Fuel Cells Output for Soft Robotics Applications
Authors: Tsompanas Michail-Antisthenis , You Jiseon , Philamore Hemma , Rossiter Jonathan , Ieropoulos Ioannis
Published: March 2021

The development of biodegradable soft robotics requires an appropriate eco-friendly source of energy. The use of Microbial Fuel Cells (MFCs) is suggested as they can be designed completely from soft materials with little or no negative effects to the environment. Nonetheless, their responsiveness and functionality is not strictly defined as in other conventional technologies, i.e. lithium batteries. Consequently, the use of artificial intelligence methods in their control techniques is highly recommended. The use of neural networks, namely a nonlinear autoregressive network with exogenous inputs was employed to predict the electrical output of an MFC, given its previous outputs and feeding volumes. Thus, predicting MFC outputs as a time series, enables accurate determination of feeding intervals and quantities required for sustenance that can be incorporated in the behavioural repertoire of a soft robot.
Undenatured Type II Collagen Ameliorates Inflammatory Responses and Articular Cartilage Damage in the Rat Model of Osteoarthritis
Authors: Orhan Cemal , Juturu Vijaya , Sahin Emre , Tuzcu Mehmet , Ozercan Ibrahim Hanifi , Durmus Ali Said , Sahin Nurhan , Sahin Kazim
Published: March 2021

Osteoarthritis (OA) is an age-related joint disease that includes gradual disruption of the articular cartilage and the resulting pain. The present study was designed to test the effects of undenatured type II collagen (UC-II®) on joint inflammation in the monoiodoacetate (MIA) OA model. We also investigated possible mechanisms underlying these effects. Female Wistar rats were divided into three groups: (i) Control; (ii) MIA-induced rats treated with vehicle; (iii) MIA-induced rats treated with UC-II (4 mg/kg BW). OA was induced in rats by intra-articular injection of MIA (1 mg) after seven days of UC-II treatment. UC-II reduced MIA-induced Kellgren-Lawrence scoring (53.3%, P < 0.05). The serum levels of inflammatory cytokines [IL-1β (7.8%), IL-6 (18.0%), TNF-α (25.9%), COMP (16.4%), CRP (32.4%)] were reduced in UC-II supplemented group (P < 0.0001). In the articular cartilage, UC-II inhibited the production of PGE2 (19.6%) and the expression of IL-1β, IL-6, TNF-a, COX-2, MCP-1, NF-κB, MMP-3, RANKL (P < 0.001). The COL-1 and OPG levels were increased, and MDA decreased in UC-II supplemented rats (P < 0.001). UC-II could be useful to alleviate joint inflammation and pain in OA joints by reducing the expression of inflammatory mediators.
Taxonomic Analysis of Some Edible Insects From the State of Michoacán, Mexico
Authors: Pino Moreno José Manuel , Blasquez Julieta Ramos-Elorduy
Published: March 2021

In the state of Michoacán, Mexico, 49 genera and 69 species of edible insects were registered, and they belong to the following orders: Orthoptera: (families) Pyrgomorphidae (2 species) and Acrididae (5); Hemiptera-Heteroptera: Coreidae (1), Corixidae (2), Pentatomidae (2), Membracidae (2), and Aethalionidae (3); Coleoptera: Cerambycidae (1), Cicendelidae (2), Curculionidae (2), Dytiscidae (1), Noteridae (1), Gyrinidae (1), Passalidae (1), Scarabaeidae (1), Tenebrionidae (2), Bostrichidae (1), Buprestidae (1), and Melolonthidae (1); Lepidoptera: Cossidae (1), Danaidae (1), Megathymidae (1), Pieridae (1), Bombycidae (1), Sessidae (1), Noctuidae (1), and Nymphalidae (1); Diptera: Stratiomydae (2); and Hymenoptera: Diprionidae (2), Apidae (10), Formicidae (4), and Vespidae (12). The order Coleoptera presents the highest number of families (12), but the order Hymenoptera has the highest number of genera (18) and species (28), 12 of which belong to the family Vespidae. Among the genera, 75.52% are monospecific, 14.28% are bispecific, 4.08% are trispecific, 4.08% are tetraspecific, and 2.04% are pentaspecific. Their distribution by locality is indicated, and these localities correspond to the municipalities of the state sampled so far; likewise, we report various forms in which they are prepared and the economic importance of, for example, the grasshoppers of the genusSphenariumthat are widely looked for, collected, accepted as part of the diet, consumed, and marketed.
Preserving Human Perspectives in Cultural Heritage Acoustics: Distance Cues and Proxemics in Aural Heritage Fieldwork
Authors: Kolar Miriam A. , Ko Doyuen , Kim Sungyoung
Published: March 2021

We examine the praxis implications of our working definition of aural heritage: spatial acoustics as physically experienced by humans in cultural contexts; aligned with the aims of anthropological archaeology (the study of human life from materials). Here we report on human-centered acoustical data collection strategies from our project “Digital Preservation and Access to Aural Heritage via a Scalable, Extensible Method,” supported by the National Endowment for the Humanities (NEH) in the USA. The documentation and accurate translation of human sensory perspectives is fundamental to the ecological validity of cultural heritage fieldwork and the preservation of heritage acoustics. Auditory distance cues, which enable and constrain sonic communication, relate to proxemics, contextualized understandings of distance relationships that are fundamental to human social interactions. We propose that source–receiver locations in aural heritage measurements should be selected to represent a comprehensive range of proxemics according to site-contextualized spatial-use scenarios, and we identify and compare acoustical metrics for auditory distance cues from acoustical fieldwork we conducted using this strategy in three contrasting case-study heritage sites. This conceptual shift from architectural acoustical sampling to aural heritage sampling prioritizes culturally and physically plausible human auditory/sound-sensing perspectives and relates them to spatial proxemics as scaled architecturally.
Universal Control of Permanent Magnet Synchronous Motors with Uncertain Dynamics
Authors: Lakhe Rishil Kirankumar , Chaoui Hicham , Alzayed Mohamad , Liu Shichao
Published: March 2021

This paper focuses on the universal control design of permanent magnet synchronous motors (PMSMs) with uncertain system dynamics. In vector control, classical proportional-integral (PI) controllers are used to control d-q axis currents and speed of the PMSM. This paper uses two control methods: conventional field-oriented vector control and simplified control. First, all the control gains are determined for numerous PMSMs with various power ratings using an empirical study and generalized mathematical expressions are derived for each of the gains. Then, these expressions are used for automatic gain calculation for various PMSMs with a wide power-rating range. In vector control, the control gains are determined using only the motor power ratings. In the simplified control, generalized control gain expressions are obtained using the number of pole pairs and the flux linkage. Compared to the vector control, the simplified control method provides much simpler generalized mathematical expressions. Validation is carried out in MATLAB/Simulink environment using various PMSMs from 0.2 HP to 10 HP, and results show accurate tracking of reference speed and d-q axis reference currents. Thus, the proposed gain scheduling approach is effective and can be used for self-commissioning motor drives.