bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling Lithium Transport and Electrodeposition in Ionic-Liquid Based Electrolytes
Authors: Li Guanchen , Monroe Charles W.
Published: May 2021

Purely ionic electrolytes—wherein ionic liquids replace neutral solvents—have been proposed to improve lithium-ion-battery performance, on the basis that the unique microscopic characteristics of polarized ionic-liquid/electrode interfaces may improve the selectivity and kinetics of interfacial lithium-exchange reactions. Here we model a “three-ion” ionic-liquid electrolyte, composed of a traditional ionic liquid and a lithium salt with a common anion. Newman's concentrated-solution theory is extended to account for space charging and chemomechanical coupling. We simulate electrolytes in equilibrium and under steady currents. We find that the local conductivity and lithium transference number in the diffuse double layers near interfaces differ considerably from their bulk values. The mechanical coupling causes ion size to play a crucial role in the interface's electrical response. Interfacial kinetics and surface charge on the electrodes both affect the apparent transport properties of purely ionic electrolytes near interfaces. Larger ionic-liquid cations and anions may facilitate interfacial lithium-exchange kinetics.
Investigating the Predictability of Photovoltaic Power Using Approximate Entropy
Authors: Yang Mao , Wang Kaixuan , Cui Yang , Feng Fan , Su Xin , Ma Chenglian
Published: May 2021

The predictability concept of Photovoltaic (PV) power on the time series was presented and the approximate entropy algorithm and predictable coefficient were used to quantificationally analyze the predictability of PV power on time series, then the approximate entropy and predictable coefficient variation at different spatial scale were analyzed. Finally, the measured data of a PV plant in western Ningxia were used for testing and confirming the result. The results of several typical prediction methods show that the proposed method can effectively characterize the predictability of PV power on time series.
Quantifying Cooperation Benefits for New Dams in Transboundary Water Systems Without Formal Operating Rules
Authors: Gonzalez Jose M. , Matrosov Evgenii S. , Obuobie Emmanuel , Mul Marloes , Pettinotti Laetitia , Gebrechorkos Solomon H. , Sheffield Justin , Bottacin-Busolin Andrea , Dalton James , Smith D. Mark , Harou Julien J.
Published: May 2021

New dams impact downstream ecosystems and water infrastructure; without cooperative and adaptive management, negative impacts can manifest. In large complex transboundary river basins without well codified operating rules and extensive historical data, it can be difficult to assess the benefits of cooperating, in particular in relation to new dams. This constitutes a barrier to harmonious development of river basins and could contribute to water conflict. This study proposes a generalised framework to assess the benefits of cooperation on the management of new dams in water resource systems that do not have formal sharing arrangements. Benefits are estimated via multi-criteria comparison of historical reservoir operations (usually relatively uncooperative) vs. adopting new cooperative rules which would achieve the best results for riparian countries as evaluated by a water resources simulator and its performance metrics. The approach is applied to the Pwalugu Multipurpose Dam (PMD), which is being built in Ghana in the Volta river basin. The PMD could impact downstream ecosystems and infrastructure in Ghana and could itself be impacted by how the existing upstream Bagre Dam is managed in Burkina Faso. Results show that with cooperation Ghana and Burkina Faso could both increase energy production although some ecosystem services loss would need to be mitigated. The study confirms that cooperative rules achieve higher overall benefits compared to seeking benefits only for individual dams or countries.
Demystifying Negative Connotations of Hybridization for Less Biased Conservation Policies
Authors: Draper David , Laguna Emilio , Marques Isabel
Published: May 2021

Interspecific hybridization is one of the most controversial—and usually neglected—issues in conservation due to its multiple evolutionary consequences that might include the origin and transfer of adaptations, the blur of distinctive lineages or the formation of maladaptive hybrids. However, despite different outcomes, most conservation laws do not offer any possibility of hybrids being protected since they are perceived as a threat to the survival of pure species. We assessed how much hybridization has contributed to species extinction considering all IUCN Red Data assessments. However, we found that it has been scarcely reported as a threat contributing to extinction: only 11 extinct species out of 120,369 assessments mentioned hybridization. Although the causes that contribute to species extinctions should be controlled, the reasons for not conserving hybrids seem subjective rather than empirically supported. In a genomic era where hybridization is being more frequently detected, the debate involving the conservation of hybrids should be re-opened. Should we conserve hybrids despite the possibility of gene flow with parental species? Should we protect only natural hybrids? The resolution of this debate goes to the heart of what we mean to conserve and the time scale of conservation. But hybridization is part of the evolutionary process and might even increase in the future due to human-induced changes. As such, it becomes clear that we need to move beyond the causes and instead tackle the consequences of hybridization to create environmental policies for the management of hybrids, considering both positive and negative consequences.
Responses of Manx Shearwaters to Handicapping and Its Implications for the Coordination of Care
Authors: Gillies Natasha , Syposz Martyna , Wynn Joe , Vansteenberghe Cécile , Guilford Tim
Published: May 2021

Seabirds care for their offspring in remote breeding colonies where foraging sites are distant and may be unpredictable, and where chicks are left unaccompanied for extended periods during their parents’ foraging trips, leaving them vulnerable to predation or starvation. One way to mitigate this risk is for individuals to coordinate parenting duties with their partner. Many biparental and cooperatively breeding species are now known to coordinate their care, though the mechanisms underlying this are not well understood. In Manx shearwaters (Puffinus puffinus), both parents alternate shifts of incubation in a coordinated manner. To resolve which processes may underlie this routine, we imposed a wing-loading handicap on parents to reduce their foraging efficiency, forcing them to choose between an extended foraging trip or to return to the nest before their condition has recovered to optimal levels. We found that handicapped parents took significantly longer trips than normal, to which their partner responded by lengthening their incubation shift, suggesting shift durations are not pre-determined. However, the duration of foraging trips and the mass at which foraging birds returned to the nest appeared to be mediated by the condition of the partner. These results suggest that while foraging trip duration is largely driven by the need for the foraging bird to recoup its own condition losses, information-transfer between the parents may facilitate a more cooperative mechanism whereby the decisions made by foraging birds still account for the condition of their partner.
Proteomics Landscape of Host-Pathogen Interaction in Acinetobacter baumannii Infected Mouse Lung
Authors: Li Xin , Liu Xiaofen , Horvatovich Peter , Hu Yingwei , Zhang Jing
Published: May 2021

Acinetobacter baumannii is an important pathogen of nosocomial infection worldwide, which can primarily cause pneumonia, bloodstream infection, and urinary tract infection. The increasing drug resistance rate of A. baumannii and the slow development of new antibacterial drugs brought great challenges for clinical treatment. Host immunity is crucial to the defense of A. baumannii infection, and understanding the mechanisms of immune response can facilitate the development of new therapeutic strategies. To characterize the system-level changes of host proteome in immune response, we used tandem mass tag (TMT) labeling quantitative proteomics to compare the proteome changes of lungs from A. baumannii infected mice with control mice 6 h after infection. A total of 6,218 proteins were identified in which 6,172 could be quantified. With threshold p < 0.05 and relative expression fold change > 1.2 or < 0.83, we found 120 differentially expressed proteins. Bioinformatics analysis showed that differentially expressed proteins after infection were associated with receptor recognition, NADPH oxidase (NOX) activation and antimicrobial peptides. These differentially expressed proteins were involved in the pathways including leukocyte transendothelial migration, phagocyte, neutrophil degranulation, and antimicrobial peptides. In conclusion, our study showed proteome changes in mouse lung tissue due to A. baumannii infection and suggested the important roles of NOX, neutrophils, and antimicrobial peptides in host response. Our results provide a potential list of protein candidates for the further study of host-bacteria interaction in A. baumannii infection. Data are available via ProteomeXchange with identifier PXD020640.
Novel Compound Heterozygous Pathogenic Variants in SUOX Cause Isolated Sulfite Oxidase Deficiency in a Chinese Han Family
Authors: Zhao Jiangang , An Yao , Jiang Haoxiang , Wu Haibin , Che Fengyu , Yang Ying
Published: May 2021

Aim

To explore the clinical imaging, laboratory and genetic characteristics of a newborn boy with isolated sulfite oxidase deficiency (ISOD) in a Chinese mainland cohort.

Methods

Homocysteine and uric acid in plasma and cysteine and total homocysteine in the blood spot were assessed in a Chinese newborn patient with progressive encephalopathy, tonic seizures, abnormal muscle tone, and feeding difficulties. Whole exome sequencing and Sanger sequencing facilitated an accurate diagnosis. The pathogenicity predictions and conservation analysis of the identified mutations were conducted by bioinformatics tools.

Results

Low total homocysteine was detected in the blood spot, while homocysteine and uric acid levels were normal in the plasma. S-sulfocysteine was abnormally elevated in urine. A follow-up examination revealed several progressive neuropathological findings. Also, intermittent convulsions and axial dystonia were observed. However, the coordination of sucking and swallowing was slightly improved. A novel paternal nonsense variant c.475G > T (p.Glu159∗) and a novel maternal missense variant c.1201A > G (p.Lys401Glu) in SUOX were identified in this case by co-segregation verification.

Conclusion

This is the second report of early-onset ISOD case in a non-consanguineous Chinese mainland family. Combined with the clinical characteristics and biochemical indexes, we speculated that these two novel pathogenic variants of the SUOX gene underlie the cause of the disease in this patient. Next-generation sequencing (NGS) and Sanger sequencing provided reliable basis for clinical and prenatal diagnoses of this family, it also enriched the mutation spectrum of the SUOX gene.
COL1-Related Disorders: Case Report and Review of Overlapping Syndromes
Authors: Gnoli Maria , Brizola Evelise , Tremosini Morena , Pedrini Elena , Maioli Margherita , Mosca Massimiliano , Bassotti Alessandra , Castronovo Paola , Giunta Cecilia , Sangiorgi Luca
Published: May 2021

Collagen type I mutations are related to wide phenotypic expressions frequently causing an overlap of clinical manifestations, in particular between Osteogenesis Imperfecta (OI) and Ehlers-Danlos syndrome (EDS). Both disorders present inter- and intra-familial clinical variability and several clinical signs are present in both diseases. Recently, after the observation that some individuals first ascertained by a suspicion of EDS resulted then carriers of pathogenic variants of genes known to primarily cause OI, some authors proposed the term “COL1-related overlap disorder” to describe these cases. In this paper, we report clinical, molecular, and biochemical information about an individual with a diagnosis of EDS with severe joint hypermobility who carries a pathogenic heterozygous variant in COL1A2 gene, and a benign variant in COL1A1 gene. The pathogenic variant, commonly ascribed to OI, as well as the benign variant, has been inherited from the individual's mother, who presented only mild signs of OI and the diagnosis of OI was confirmed only after molecular testing. In addition, we reviewed the literature of similar cases of overlapping syndromes caused by COL1 gene mutations. The reported case and the literature review suggest that the COL1-related overlap disorders (OI, EDS and overlapping syndromes) represent a continuum of clinical phenotypes related to collagen type I mutations. The spectrum of COL1-related clinical manifestations, the pathophysiology and the underlying molecular mechanisms support the adoption of the updated proposed term “COL1-related overlap disorder” to describe the overlapping syndromes.
Case Report: Two Novel Frameshift Mutations in SLC20A2 and One Novel Splice Donor Mutation in PDGFB Associated With Primary Familial Brain Calcification
Authors: Shen Yuqi , Shu Shi , Ren Yaqiong , Xia Weibo , Chen Jianhua , Dong Liling , Ge Haijun , Fan Shiqi , Shi Lei , Peng Bin , Zhang Xue
Published: May 2021

Primary familial brain calcification (PFBC, OMIM#213600), also known as Fahr's disease, is characterized by bilateral and symmetric brain calcification in the basal ganglia (globus pallidus, caudate nucleus, and putamen), thalamus, subcortical white matter, and cerebellum. PFBC can be caused by loss-of-function mutations in any of the six known causative genes. The most common clinical manifestations include movement disorders, cognitive impairment, and neuropsychiatric signs that gradually emerge in middle-aged patients. To broaden the PFBC mutation spectrum, we examined nine members of a family with PFBC and two sporadic cases from clinical departments, and sequenced all PFBC-causative genes in the index case. Two novel frameshift mutations in SLC20A2 [NM_001257180.2; c.806delC, p.(Pro269Glnfs*49) and c.1154delG, p.(Ser385Ilefs*70)] and one novel splice donor site mutation (NM_002608.4, c.456+1G>C, r.436_456del) in PDGFB were identified in the patient cohort. c.806delC co-segregated with brain calcification and led to SLC20A2 haploinsufficiency among the affected family members. The c.456+1G>C mutation in PDGFB resulted in aberrant mRNA splicing, thereby forming mature transcripts containing an in-frame 21 base pair (bp) deletion, which might create a stably truncated protein [p.(Val146_Gln152del)] and exert a dominant negative effect on wild-type PDGFB. All three mutations were located in highly conserved regions among multiple species and predicted to be pathogenic, as evaluated by at least eight common genetic variation scoring systems. This study identified three novel mutations in SLC20A2 and PDGFB, which broadened and enriched the PFBC mutation spectrum.
Integrating CAR T-Cell Therapy and Transplantation: Comparisons of Safety and Long-Term Efficacy of Allogeneic Hematopoietic Stem Cell Transplantation After CAR T-Cell or Chemotherapy-Based Complete Remission in B-Cell Acute Lymphoblastic Leukemia
Authors: Zhao Yan-Li , Liu De-Yan , Sun Rui-Juan , Zhang Jian-Ping , Zhou Jia-Rui , Wei Zhi-Jie , Xiong Min , Cao Xing-Yu , Lu Yue , Yang Jun-fang , Zhang Xian , Lu Dao-Pei , Lu Peihua
Published: May 2021

Patients often undergo consolidation allogeneic hematopoietic stem cell transplantation (allo-HSCT) to maintain long-term remission following chimeric antigen receptor (CAR) T-cell therapy. Comparisons of safety and efficacy of allo-HSCT following complete remission (CR) achieved by CAR-T therapy versus by chemotherapy for B-cell acute lymphoblastic leukemia (B-ALL) has not been reported. We performed a parallel comparison of transplant outcomes in 105 consecutive B-ALL patients who received allo-HSCT after achieving CR with CAR-T therapy (n=27) or with chemotherapy (n=78). The CAR-T-allo-HSCT group had more patients in second CR compared to the chemotherapy-allo-HSCT group (78% vs. 37%; p<0.01) and more with complex cytogenetics (44% vs. 6%; p<0.001) but the proportion of patients with pre-transplant minimal residual disease (MRD) was similar. The median follow-up time was 49 months (range: 25-54 months). The CAR-T cohort had a higher incidence of Grade II-IV acute graft-versus-host disease (aGVHD 48.1% [95% CI: 46.1-50.1%] vs. 25.6% [95%CI: 25.2-26.0%]; p=0.016). The incidence of Grade III-IV aGVHD was similar in both groups (11.1% vs.11.5%, p=0.945). The overall incidence of chronic GVHD in the CAR-T group was higher compared to the chemotherapy group (73.3% [95%CI: 71.3-75.3%] vs. 55.0% [95%CI: 54.2-55.8%], p=0.107), but the rate of extensive chronic GVHD was similar (11.1% vs.11.9%, p=0.964). Efficacy measures 4 years following transplant were all similar in the CAR-T vs. the chemotherapy groups: cumulative incidences of relapse (CIR; 11.1% vs.12.8%; p=0.84), cumulative incidences of non-relapse mortality (NRM; 18.7% vs. 23.1%; p=0.641) leukemia-free survival (LFS; 70.2% vs. 64.1%; p=0.63) and overall survival (OS; 70.2% vs. 65.4%; p=0.681). We found that pre-transplant MRD-negative CR predicted a lower CIR and a higher LFS compared with MRD-positive CR. In conclusion, our data indicate that, in B-ALL patients, similar clinical safety outcomes could be achieved with either CD19 CAR T-cell therapy followed by allo-HSCT or chemotherapy followed by allo-HSCT. Despite the inclusion of more patients with advanced diseases in the CAR-T group, the 4-year LFS and OS achieved with CAR T-cells followed by allo-HSCT were as remarkable as those achieved with chemotherapy followed by allo-HSCT. Further confirmation of these results requires larger, randomized clinical trials.
Modeling Virus-Induced Inflammation in Zebrafish: A Balance Between Infection Control and Excessive Inflammation
Authors: Sullivan Con , Soos Brandy-Lee , Millard Paul J. , Kim Carol H. , King Benjamin L.
Published: May 2021

The inflammatory response to viral infection in humans is a dynamic process with complex cell interactions that are governed by the immune system and influenced by both host and viral factors. Due to this complexity, the relative contributions of the virus and host factors are best studied in vivo using animal models. In this review, we describe how the zebrafish (Danio rerio) has been used as a powerful model to study host-virus interactions and inflammation by combining robust forward and reverse genetic tools with in vivo imaging of transparent embryos and larvae. The innate immune system has an essential role in the initial inflammatory response to viral infection. Focused studies of the innate immune response to viral infection are possible using the zebrafish model as there is a 4-6 week timeframe during development where they have a functional innate immune system dominated by neutrophils and macrophages. During this timeframe, zebrafish lack a functional adaptive immune system, so it is possible to study the innate immune response in isolation. Sequencing of the zebrafish genome has revealed significant genetic conservation with the human genome, and multiple studies have revealed both functional conservation of genes, including those critical to host cell infection and host cell inflammatory response. In addition to studying several fish viruses, zebrafish infection models have been developed for several human viruses, including influenza A, noroviruses, chikungunya, Zika, dengue, herpes simplex virus type 1, Sindbis, and hepatitis C virus. The development of these diverse viral infection models, coupled with the inherent strengths of the zebrafish model, particularly as it relates to our understanding of macrophage and neutrophil biology, offers opportunities for far more intensive studies aimed at understanding conserved host responses to viral infection. In this context, we review aspects relating to the evolution of innate immunity, including the evolution of viral pattern recognition receptors, interferons and interferon receptors, and non-coding RNAs.
Lysosome-Dependent LXR and PPARδ Activation Upon Efferocytosis in Human Macrophages
Authors: Mota Ana Carolina , Dominguez Monica , Weigert Andreas , Snodgrass Ryan G. , Namgaladze Dmitry , Brüne Bernhard
Published: May 2021

Efferocytosis is critical for tissue homeostasis, as its deregulation is associated with several autoimmune pathologies. While engulfing apoptotic cells, phagocytes activate transcription factors, such as peroxisome proliferator-activated receptors (PPAR) or liver X receptors (LXR) that orchestrate metabolic, phagocytic, and inflammatory responses towards the ingested material. Coordination of these transcription factors in efferocytotic human macrophages is not fully understood. In this study, we evaluated the transcriptional profile of macrophages following the uptake of apoptotic Jurkat T cells using RNA-seq analysis. Results indicated upregulation of PPAR and LXR pathways but downregulation of sterol regulatory element-binding proteins (SREBP) target genes. Pharmacological inhibition and RNA interference pointed to LXR and PPARδ as relevant transcriptional regulators, while PPARγ did not substantially contribute to gene regulation. Mechanistically, lysosomal digestion and lysosomal acid lipase (LIPA) were required for PPAR and LXR activation, while PPARδ activation also demanded an active lysosomal phospholipase A2 (PLA2G15). Pharmacological interference with LXR signaling attenuated ABCA1-dependent cholesterol efflux from efferocytotic macrophages, but suppression of inflammatory responses following efferocytosis occurred independently of LXR and PPARδ. These data provide mechanistic details on LXR and PPARδ activation in efferocytotic human macrophages.
Immunomodulatory Effects of BRAF, MEK, and CDK4/6 Inhibitors: Implications for Combining Targeted Therapy and Immune Checkpoint Blockade for the Treatment of Melanoma
Authors: Lelliott Emily J. , McArthur Grant A. , Oliaro Jane , Sheppard Karen E.
Published: May 2021

The recent advent of targeted and immune-based therapies has revolutionized the treatment of melanoma and transformed outcomes for patients with metastatic disease. The majority of patients develop resistance to the current standard-of-care targeted therapy, dual BRAF and MEK inhibition, prompting evaluation of a new combination incorporating a CDK4/6 inhibitor. Based on promising preclinical data, combined BRAF, MEK and CDK4/6 inhibition has recently entered clinical trials for the treatment of BRAFV600melanoma. Interestingly, while BRAF- and MEK-targeted therapy was initially developed on the basis of potent tumor-intrinsic effects, it was later discovered to have significant immune-potentiating activity. Recent studies have also identified immune-related impacts of CDK4/6 inhibition, though these are less well defined and can be both immune-potentiating and immune-inhibitory. BRAFV600melanoma patients are also eligible to receive immunotherapy, specifically checkpoint inhibitors against PD-1 and CTLA-4. The immunomodulatory activity of BRAF/MEK-targeted therapies has prompted interest in combination therapies incorporating these with immune checkpoint inhibitors, however recent clinical trials investigating this approach have produced variable results. Here, we summarize the immunomodulatory effects of BRAF, MEK and CDK4/6 inhibitors, shedding light on the prospective utility of this combination alone and in conjunction with immune checkpoint blockade. Understanding the mechanisms that underpin the clinical efficacy of these available therapies is a critical step forward in optimizing novel combination and scheduling approaches to combat melanoma and improve patient outcomes.
Immunometabolism of Tissue-Resident Macrophages – An Appraisal of the Current Knowledge and Cutting-Edge Methods and Technologies
Authors: Zago Giulia , Saavedra Pedro H. V. , Keshari Kayvan R. , Perry Justin S. A.
Published: May 2021

Tissue-resident macrophages exist in unique environments, or niches, that inform their identity and function. There is an emerging body of literature suggesting that the qualities of this environment, such as the types of cells and debris they eat, the intercellular interactions they form, and the length of time spent in residence, collectively what we call habitare, directly inform their metabolic state. In turn, a tissue-resident macrophage’s metabolic state can inform their function, including whether they resolve inflammation and protect the host from excessive perturbations of homeostasis. In this review, we summarize recent work that seeks to understand the metabolic requirements for tissue-resident macrophage identity and maintenance, for how they respond to inflammatory challenges, and for how they perform homeostatic functions or resolve inflammatory insults. We end with a discussion of the emerging technologies that are enabling, or will enable, in situ study of tissue-resident macrophage metabolism.
Peripheral Injection of Tim-3 Antibody Attenuates VSV Encephalitis by Enhancing MHC-I Presentation
Authors: Li Ge , Tang Lili , Hou Chunmei , Wang Zhiding , Gao Yang , Dou Shuaijie , Mo Rongliang , Hao Ying , Gao Zhenfang , Li Yuxiang , Dong Jie , Zhang Jiyan , Shen Beifen , Wang Renxi , Han Gencheng
Published: May 2021

Viral encephalitis is the most common cause of encephalitis. It is responsible for high morbidity rates, permanent neurological sequelae, and even high mortality rates. The host immune response plays a critical role in preventing or clearing invading pathogens, especially when effective antiviral treatment is lacking. However, due to blockade of the blood-brain barrier, it remains unclear how peripheral immune cells contribute to the fight against intracerebral viruses. Here, we report that peripheral injection of an antibody against human Tim-3, an immune checkpoint inhibitor widely expressed on immune cells, markedly attenuated vesicular stomatitis virus (VSV) encephalitis, marked by decreased mortality and improved neuroethology in mice. Peripheral injection of Tim-3 antibody enhanced the recruitment of immune cells to the brain, increased the expression of major histocompatibility complex-I (MHC-I) on macrophages, and as a result, promoted the activation of VSV-specific CD8+ T cells. Depletion of macrophages abolished the peripheral injection-mediated protection against VSV encephalitis. Notably, for the first time, we found a novel post-translational modification of MHC-I by Tim-3, wherein, by enhancing the expression of MARCH9, Tim-3 promoted the proteasome-dependent degradation of MHC-I via K48-linked ubiquitination in macrophages. These results provide insights into the immune response against intracranial infections; thus, manipulating the peripheral immune cells with Tim-3 antibody to fight viruses in the brain may have potential applications for combating viral encephalitis.
Associations of D-Dimer on Admission and Clinical Features of COVID-19 Patients: A Systematic Review, Meta-Analysis, and Meta-Regression
Authors: Zhao Runzhen , Su Zhenlei , Komissarov Andrey A. , Liu Shan-Lu , Yi Guohua , Idell Steven , Matthay Michael A. , Ji Hong-Long
Published: May 2021

Background

Dynamic D-dimer level is a key biomarker for the severity and mortality of COVID-19 (coronavirus disease 2019). How aberrant fibrinolysis influences the clinical progression of COVID-19 presents a clinicopathological dilemma challenging intensivists.

Methods

We performed meta-analysis and meta regression to analyze the associations of plasma D-dimer with 106 clinical variables to identify a panoramic view of the derangements of fibrinolysis in 14,862 patients of 42 studies. There were no limitations of age, gender, race, and country. Raw data of each group were extracted separately by two investigators. Individual data of case series, median and interquartile range, and ranges of median or mean were converted to SDM (standard deviation of mean).

Findings

The weighted mean difference of D-dimer was 0.97 µg/mL (95% CI 0.65, 1.29) between mild and severe groups, as shown by meta-analysis. Publication bias was significant. Meta-regression identified 58 of 106 clinical variables were associated with plasma D-dimer levels. Of these, 11 readouts were negatively related to the level of plasma D-dimer. Further, age and gender were confounding factors. There were 22 variables independently correlated with the D-dimer level, including respiratory rate, dyspnea plasma K+, glucose, SpO2, BUN (blood urea nitrogen), bilirubin, ALT (alanine aminotransferase), AST (aspartate aminotransferase), systolic blood pressure, and CK (creatine kinase).

Interpretation

These findings support elevated D-dimer as an independent predictor for both mortality and complications. The identified D-dimer-associated clinical variables draw a landscape integrating the aggregate effects of systemically suppressive and pulmonary hyperactive derangements of fibrinolysis, and the D-dimer-associated clinical biomarkers, and conceptually parameters could be combined for risk stratification, potentially for tracking thrombolytic therapy or alternative interventions.
Acclimation History of Elevated Temperature Reduces the Tolerance of Coralline Algae to Additional Acute Thermal Stress
Authors: Page Tessa M. , Bergstrom Ellie , Diaz-Pulido Guillermo
Published: May 2021

Increasing atmospheric CO2 is driving major environmental changes in the ocean, such as an increase in average ocean temperature, a decrease in average ocean pH (ocean acidification or OA), and an increase in the number and severity of extreme climatic events (e.g., anomalous temperature events and heatwaves). Uncertainty exists in the capacity for species to withstand these stressors occurring concomitantly. Here, we tested whether an acclimation history of ocean warming (OW) and OA affects the physiological responses of an abundant, reef-building species of crustose coralline algae (CCA), Porolithon cf. onkodes, to chronic and acute thermal stress. To address this, we exposed algae to varying temperature and pH levels for 6 weeks and this chronic treatment experiment was followed by an acute exposure to an anomalous temperature event (+4–6°C from acclimation temperature). Net photosynthetic rate was negatively affected across all treatments by increasing temperature during the acute temperature event, however, algae acclimated to the control temperature were able to maintain photosynthetic rates for +4°C above their acclimation temperature, whereas algae acclimated to elevated temperature were not. Average relative change in O2 produced resulted in a 100–175% decrease, with the largest decrease found in algae acclimated to the combined treatment of elevated temperature and reduced pH. We conclude that acclimation to chronic global change stressors (i.e., OW and OA) will reduce the tolerance of P. cf. onkodes to anomalous increases in temperature, and this may have implications for reef building processes.
Nurses' Ethics in the Care of Patients During the COVID-19 Pandemic
Authors: Alloubani Aladeen , Khater Wejdan , Akhu-Zaheya Laila , Almomani Maysa , Alashram Safa
Published: May 2021

Working during an epidemic can be physically, emotionally, and morally demanding for nurses. In addition to caring for patients, nurses are also responsible for looking after themselves and their families. The current study aimed to explore nurses' ethics in the care of patients during the coronavirus disease 2019 (COVID-19) pandemic. A descriptive qualitative approach was adopted in order to gain an in-depth understanding of nurses' experiences of caring for patients with coronavirus. A purposive sample of 10 nurses working with patients with COVID-19 was recruited. Interviews were held with the nurses, and content analysis of the interviews was conducted. Each interview was transcribed, and the text was coded into manageable categories on the word, word sense, phrase, sentence, and theme levels before analysis. Three major themes related to the nurses' ethical commitments during the COVID-19 crisis emerged during the data analysis. These themes are as follows: the obligation of nurses to provide care for patients regardless of their medical diagnosis; the ethical dilemma faced by nurses of whether to care for patients or protect themselves from the virus; and finally, the responsibility of nurses to care for themselves.
The Human Microbiome, an Emerging Key-Player in the Sex Gap in Respiratory Diseases
Authors: Beauruelle Clémence , Guilloux Charles-Antoine , Lamoureux Claudie , Héry-Arnaud Geneviève
Published: May 2021

The sex gap is well-documented in respiratory diseases such as cystic fibrosis and chronic obstructive pulmonary disease. While the differences between males and females in prevalence, severity and prognosis are well-established, the pathophysiology of the sex difference has been poorly characterized to date. Over the past 10 years, metagenomics-based studies have revealed the presence of a resident microbiome in the respiratory tract and its central role in respiratory disease. The lung microbiome is associated with host immune response and health outcomes in both animal models and patient cohorts. The study of the lung microbiome is therefore an interesting new avenue to explore in order to understand the sex gap observed in respiratory diseases. Another important parameter to consider is the gut-lung axis, since the gut microbiome plays a crucial role in distant immune modulation in respiratory diseases, and an intestinal “microgenderome” has been reported: i.e., sexual dimorphism in the gut microbiome. The microgenderome provides new pathophysiological clues, as it defines the interactions between microbiome, sex hormones, immunity and disease susceptibility. As research on the microbiome is increasing in volume and scope, the objective of this review was to describe the state-of-the-art on the sex gap in respiratory medicine (acute pulmonary infection and chronic lung disease) in the light of the microbiome, including evidence of local (lung) or distant (gut) contributions to the pathophysiology of these diseases.
Novel Cephalosporins in Septic Subjects and Severe Infections: Present Findings and Future Perspective
Authors: Corcione Silvia , Lupia Tommaso , De Rosa Francesco Giuseppe
Published: May 2021

In past decade, cephalosporins have developed significantly, and data regarding novel cephalosporins (i.e., ceftobiprole, ceftaroline, ceftolozane/tazobactam, ceftazidime/avibactam, and cefiderocol) within septic and bacteremic subjects are rising. These compounds generally offer very promising in vitro microbiological susceptibility, although the variability among gram-negative and -positive strains of different cohorts is noticed in the literature. We require further pharmacological data to measure the best dose in order to prevent sub-therapeutic drug levels in critically ill patients. These new compounds in theory are the sparing solution in the Enterobacteriales infection group for different antimicrobial classes such as aminoglycosides notably within endovascular and GNB-bacteremias, as well as colistin and carbapenem-sparing strategies, favoring good safety profile molecules. Moreover, new cephalosporins are the basis for the actual indications to open up new and exciting prospects for serious infections in the future. In future, patients will be addressed with the desirable approach to sepsis and serious infections in terms of their clinical situation, inherent features of the host, the sensitivity profile, and local epidemiology, for which evidence of the use of new cephalosporin in the treatment of severe infections will fill the remaining gaps.
Human-Based Advanced in vitro Approaches to Investigate Lung Fibrosis and Pulmonary Effects of COVID-19
Authors: Kiener Mirjam , Roldan Nuria , Machahua Carlos , Sengupta Arunima , Geiser Thomas , Guenat Olivier Thierry , Funke-Chambour Manuela , Hobi Nina , Kruithof-de Julio Marianna
Published: May 2021

The coronavirus disease 2019 (COVID-19) pandemic has caused considerable socio-economic burden, which fueled the development of treatment strategies and vaccines at an unprecedented speed. However, our knowledge on disease recovery is sparse and concerns about long-term pulmonary impairments are increasing. Causing a broad spectrum of symptoms, COVID-19 can manifest as acute respiratory distress syndrome (ARDS) in the most severely affected patients. Notably, pulmonary infection with Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), the causing agent of COVID-19, induces diffuse alveolar damage (DAD) followed by fibrotic remodeling and persistent reduced oxygenation in some patients. It is currently not known whether tissue scaring fully resolves or progresses to interstitial pulmonary fibrosis. The most aggressive form of pulmonary fibrosis is idiopathic pulmonary fibrosis (IPF). IPF is a fatal disease that progressively destroys alveolar architecture by uncontrolled fibroblast proliferation and the deposition of collagen and extracellular matrix (ECM) proteins. It is assumed that micro-injuries to the alveolar epithelium may be induced by inhalation of micro-particles, pathophysiological mechanical stress or viral infections, which can result in abnormal wound healing response. However, the exact underlying causes and molecular mechanisms of lung fibrosis are poorly understood due to the limited availability of clinically relevant models. Recently, the emergence of SARS-CoV-2 with the urgent need to investigate its pathogenesis and address drug options, has led to the broad application ofin vivoandin vitromodels to study lung diseases. In particular, advancedin vitromodels including precision-cut lung slices (PCLS), lung organoids, 3Din vitrotissues and lung-on-chip (LOC) models have been successfully employed for drug screens. In order to gain a deeper understanding of SARS-CoV-2 infection and ultimately alveolar tissue regeneration, it will be crucial to optimize the available models for SARS-CoV-2 infection in multicellular systems that recapitulate tissue regeneration and fibrotic remodeling. Current evidence for SARS-CoV-2 mediated pulmonary fibrosis and a selection of classical and novel lung models will be discussed in this review.
Improving the Generalizability of Infantile Cataracts Detection via Deep Learning-Based Lens Partition Strategy and Multicenter Datasets
Authors: Jiang Jiewei , Lei Shutao , Zhu Mingmin , Li Ruiyang , Yue Jiayun , Chen Jingjing , Li Zhongwen , Gong Jiamin , Lin Duoru , Wu Xiaohang , Lin Zhuoling , Lin Haotian
Published: May 2021

Infantile cataract is the main cause of infant blindness worldwide. Although previous studies developed artificial intelligence (AI) diagnostic systems for detecting infantile cataracts in a single center, its generalizability is not ideal because of the complicated noises and heterogeneity of multicenter slit-lamp images, which impedes the application of these AI systems in real-world clinics. In this study, we developed two lens partition strategies (LPSs) based on deep learning Faster R-CNN and Hough transform for improving the generalizability of infantile cataracts detection. A total of 1,643 multicenter slit-lamp images collected from five ophthalmic clinics were used to evaluate the performance of LPSs. The generalizability of Faster R-CNN for screening and grading was explored by sequentially adding multicenter images to the training dataset. For the normal and abnormal lenses partition, the Faster R-CNN achieved the average intersection over union of 0.9419 and 0.9107, respectively, and their average precisions are both > 95%. Compared with the Hough transform, the accuracy, specificity, and sensitivity of Faster R-CNN for opacity area grading were improved by 5.31, 8.09, and 3.29%, respectively. Similar improvements were presented on the other grading of opacity density and location. The minimal training sample size required by Faster R-CNN is determined on multicenter slit-lamp images. Furthermore, the Faster R-CNN achieved real-time lens partition with only 0.25 s for a single image, whereas the Hough transform needs 34.46 s. Finally, using Grad-Cam and t-SNE techniques, the most relevant lesion regions were highlighted in heatmaps, and the high-level features were discriminated. This study provides an effective LPS for improving the generalizability of infantile cataracts detection. This system has the potential to be applied to multicenter slit-lamp images.
The Performance of Flexible Tip Bougie™ in Intubating Simulated Difficult Airway Model
Authors: Mahli Nurfadilah , Md Zain Jaafar , Mahdi Siti Nidzwani Mohamad , Chih Nie Yeoh , Chian Yong Liu , Shokri Ahmad Fairuz Abdul , Maaya Muhammad
Published: May 2021

This prospective, randomized, cross-over study compared the performance of the novel Flexible Tip Bougie™ (FTB) with a conventional bougie as an intubation aid in a simulated difficult airway manikin model among anaesthesiology trainees with regards of first pass success rate, time to intubation, number of attempts and ease of use. Sixty-two anesthesiology trainees, novice to the usage of FTB, participated in this study. Following a video demonstration, each participant performed endotracheal intubation on a manikin standardized to a difficult airway view. Each participant performed direct laryngoscopy and intubated the manikin using a conventional bougie and FTB, at least 1 day in between devices, in a randomized order. The first pass success rate was significantly higher with FTB (98.4%) compared to conventional bougie (85.5%), p = 0.008. The median time to intubation was significantly faster when using FTB, median = 32.0 s [Interquartile range (IQR): 23.8–41.3 s] compared to when using conventional bougie, median = 41.5 s (IQR: 31.8–69.5 s), p < 0.001. The FTB required significantly less intubation attempts compared to conventional bougie, p = 0.024. The overall ease of use, scored on a Likert scale from 1 to 5, was significantly higher in the FTB (4.26 ± 0.53) compared to the conventional bougie (3.19 ± 0.83), p < 0.001. This simulated difficult airway manikin study finding suggested that FTB is a useful adjunct for difficult airway intubation. The FTB offered a higher first pass success rate with a faster time to intubation and less required attempts.
Distinct H2O2-Scavenging System in Yersinia pseudotuberculosis: KatG and AhpC Act Together to Scavenge Endogenous Hydrogen Peroxide
Authors: Wan Fen , Feng Xue , Yin Jianhua , Gao Haichun
Published: May 2021

To colonize in the digestive tract of animals and humans, Yersinia pseudotuberculosis has to deal with reactive oxygen species (ROS) produced by host cells and microbiota. However, an understanding of the ROS-scavenging systems and their regulation in this bacterium remains largely elusive. In this study, we identified OxyR as the master transcriptional regulator mediating cellular responses to hydrogen peroxide (H2O2) in Y. pseudotuberculosis through genomics and transcriptomics analyses. OxyR activates transcription of diverse genes, especially the core members of its regulon, including those encoding catalases, peroxidases, and thiol reductases. The data also suggest that sulfur species and manganese may play a particular role in the oxidative stress response of Y. pseudotuberculosis. Among the three H2O2-scavenging systems in Y. pseudotuberculosis, catalase/peroxidase KatE functions as the primary scavenger for high levels of H2O2; NADH peroxidase alkyl hydroperoxide reductase (AhpR) and catalase KatG together are responsible for removing low levels of H2O2. The simultaneous loss of both AhpC (the peroxidatic component of AhpR) and KatG results in activation of OxyR. Moreover, we found that AhpC, unlike its well-characterized Escherichia coli counterpart, has little effect on protecting cells against toxicity of organic peroxides. These findings provide not only novel insights into the structural and functional diversity of bacterial H2O2-scavenging systems but also a basic understanding of how Y. pseudotuberculosis copes with oxidative stress.
Increased Organic Fertilizer and Reduced Chemical Fertilizer Increased Fungal Diversity and the Abundance of Beneficial Fungi on the Grape Berry Surface in Arid Areas
Authors: Wu Linnan , Li Zhiqiang , Zhao Fengyun , Zhao Benzhou , Phillip Fesobi Olumide , Feng Jianrong , Liu Huaifeng , Yu Kun
Published: May 2021

Fertilizer practices can significantly impact the fruit quality and microbial diversity of the orchards. The fungi on the surface of fruits are essential for fruit storability and safety. However, it is not clear whether fertilization affects the fungal diversity and community structure on the surface of grape berries. Here, grape quality and the fungal diversity on the surface of grapes harvested from three fertilizer treatments were analyzed shortly after grape picking (T0) and following 8 days of storage (T1). The study involved three treatments: (1) common chemical fertilizer for 2 years (CH); (2) increased organic fertilizer and reduced chemical fertilizer for 1 year (A.O); and (3) increased organic fertilizer and reduced chemical fertilizer for 2 years (B.O). The application of increased organic fertilizer and reduced chemical fertilizer increased the soluble solids content (SSC) of the grape berries and decreased the pH of the grape juice. A total of 827,947 high-quality fungal sequences were recovered and assigned to 527 operational taxonomic units. Members of the Ascomycota phylum were dominant in all samples and accounted for 94.41% of the total number of detected sequences, followed by the Basidiomycota (5.05%), and unidentified fungi (0.54%). Alpha and beta diversity analyses revealed significantly different fungal populations in the three fertilizer treatments over the two time periods. The fungal diversity and richness on the grape berry surface in the B.O and A.O treatments were higher than those in the CH treatment. Among the detected fungi, the B.O treatments were mainly Pichia, Aureobasidium, and Candida genera, while the CH treatments were Botrytis, Aspergillus, and Penicillium. Moreover, significant differences were revealed between the two assessment times (T0 and T1). The samples from the T0 timepoint had higher fungal richness and diversity than the samples from T1 timepoint. Increasing organic fertilizer usage in grape management could improve grape quality and went on to increase the fungal diversity, as well as the relative abundance (RA) of beneficial fungi on grape berry surfaces. The correlation analysis suggested that the pH of the grape juice was significantly negatively correlated with fungal diversity parameters.
Electrostatic Interaction Between NS1 and Negatively Charged Lipids Contributes to Flavivirus Replication Organelles Formation
Authors: Ci Yali , Yang Yang , Xu Caimin , Qin Cheng-Feng , Shi Lei
Published: May 2021

Flavivirus replication occurs in membranous replication compartments, also known as replication organelles (ROs) derived from the host ER membrane. Our previous study showed that the non-structural (NS) protein 1 (NS1) is the essential factor for RO creation by hydrophobic insertion into the ER membrane. Here, we found that the association of NS1 with the membrane can be facilitated by the electrostatic interaction between NS1 and negatively charged lipids. NS1 binds to a series of negatively charged lipids, including PI4P, and a positively charged residue, R31, located on the membrane-binding face of NS1, plays important roles in this interaction. The NS1 R31E mutation significantly impairs NS1 association with negatively charged membrane and its ER remodeling ability in the cells. To interfere with the electrostatic interaction between NS1 and negatively charged lipids, intracellular phosphatidylinositol phosphates (PIPs) level was downregulated by the overexpression of Sac1 or treatment with PI3K and PI4K inhibitors to attenuate flavivirus replication. Our findings emphasize the importance of electrostatic interaction between NS1 and negatively charged lipids in flavivirus RO formation.