bluuebunny/crossref_metadata_2025 huggingface dataset:
Denoising Method of Nuclear Signal Based on Sparse Representation
Authors: He San-Jun , Sun Na , Su Ling-Ling , Chen Bin , Zhao Xiu-Liang
Published: April 2022

Nuclear signals are sensitive to noise which may affect final monitoring results significantly. In order to suppress the nuclear signal noise, a sparse representation method, which is based on the sparse representation of signals and a matching pursuit algorithm, has been proposed for denoising. Time–frequency matching “atoms” have been selected for building an over-complete library by training atoms matching with the characteristics of nuclear signals regardless of the noise. The best time–frequency matching atoms have been extracted by sparsely representing the noisy signals with an Orthogonal Matching Pursuit (OMP) algorithm and the library. The residual ratio threshold has been chosen as a stopping criterion in the OMP algorithm for avoiding the influence of improper selection of iterations on denoising results. At the end, the pulse matching the atom extracted by each iteration has been optimized by performing effective sparse representation on the original noiseless nuclear signal component in noisy nuclear signals. The proposed method has been used to denoise the simulated and measured signals and has been compared with the nuclear denoising result using traditional wavelet theory. The results show that the proposed method can accurately suppress the noise interference of nuclear signals, and the denoising effect is better than that of the traditional wavelet method.
Forecasting Energy Consumption Based on SVR and Markov Model: A Case Study of China
Authors: Meng Zhaosu , Sun Huike , Wang Xi
Published: April 2022

Forecasting energy demand in emerging nations is a critical policy tool utilized by decision makers worldwide. However, as estimated economic and demographic characteristics frequently diverge from realizations, precise forecast results are difficult to get due to the economic system’s intrinsic complexity. This work proposed a machine learning model for estimating energy consumption in China using the support vector regression model (SVR). Additionally, Markov Chain (MC) is employed to forecast and analyze the evolving energy consumption structure. The results demonstrate that SVR model is more accurate (98.4%) than the linear model (Moving Average model), the nonlinear model (Grey model), and past research in predicting energy usage. Under the current rate of energy consumption, China’s total energy consumption will break through six billion in the next 4 years. Furthermore, it is expected that China’s energy consumption structure will be more rational in 2025, with increased non-fossil energy consumption and decreased coal consumption, while natural gas consumption continues to grow at a low rate. It provides scientific basis for the implementation of carbon emission peak action, energy security and energy development plan during the 14th Five-Year Plan period.
Encounter With a Selfish Virus Sabotages Its Vector to Orient Toward Requisite Host Plant: A Case Study With Chili Leaf Curl Virus-Whitefly
Authors: Yadav Rajeev Kumar , Kambham Madhavi Reddy , Parepally Saravan Kumar , Vyas Meenal , Manem Krishna Reddy , Kamala Jayanthi Pagadala Damodaram
Published: April 2022

Interactions of a virus with its vector and host plant have challenged entomologists, pathologists and biologists alike. Phytophagous insects depend on specific host volatile cues to locate suitable host plants for feeding and oviposition. Several studies have revealed that plant viruses modify their insect vector’s orientation toward specific host plants to facilitate their spread and survival. The ecological and molecular basis of this vector behavior modification remains largely unknown and was therefore explored in this study. Interestingly, host volatile preference for non-viruliferous female whiteflies [Bemisia tabaci (Genn.)] was found to be preferentially oriented toward infected chili plant [with chili leaf curl (ChLCV)] volatiles, while viruliferous whiteflies preferred healthy chili plant (Capsicum annum L.) volatiles in olfactometer. The electrophysiological studies involving electroantennogram (EAG) assays exhibited similar trend in EAG response amplitudes. Gas Chromatography linked electroantennodetection (GC EAD) revealed specific plant volatile cues responsible for altered host orientation behavior of the vector. Transcriptome profiling of the viruliferous and non-viruliferous whiteflies and Realtime qPCR validation showed differential expression of certain odorant binding proteins (OBPs) in viruliferous whiteflies. Our results suggest that there is a plant virus mediated altered chemoecological behavior in the vector with respect to orientation toward its host plant. Based on the findings we speculate that the virus mediates such change in the vector for a continued transmission success to the host.
Respiratory Interventions for Preterm Infants in LMICs: A Prospective Study From Cape Town, South Africa
Authors: Lategan Ilse , Price Caris , Rhoda Natasha Raygaan , Zar Heather J. , Tooke Lloyd
Published: April 2022

Background

Preterm birth is a global public health issue and complications of preterm birth result in the death of approximately 1 million infants each year, 99% of which are in low-and-middle income countries (LMIC). Although respiratory interventions such as continuous positive airway pressure (CPAP) and surfactant have been shown to improve the outcomes of preterm infants with respiratory distress, they are not readily available in low-resourced areas. The aim of this study was to report the respiratory support needs and outcomes of preterm infants in a low-resourced setting, and to estimate the impact of a lack of access to these interventions on neonatal mortality.

Methods

We conducted a six-month prospective observational study on preterm infants <1,801 g admitted at Groote Schuur Hospital and Mowbray Maternity Hospital neonatal units in Cape Town, South Africa. We extrapolated results from the study to model the potential outcomes of these infants in the absence of these interventions.

Results

Five hundred and fifty-two infants (552) <1,801 g were admitted. Three hundred (54.3%) infants received CPAP, and this was the initial respiratory intervention for most cases of respiratory distress syndrome. Surfactant was given to 100 (18.1%) infants and a less invasive method was the most common method of administration. Invasive mechanical ventilation was offered to 105 (19%) infants, of which only 57 (54.2%) survived until discharge from hospital. The overall mortality of the cohort was 14.1% and the hypothetical removal of invasive mechanical ventilation, surfactant and CPAP would result in an additional 157 deaths and increase the overall mortality to 42.5%. A lack of CPAP availability would have the largest impact on mortality and result in the largest number of additional deaths (109).

Conclusion

This study highlights the effect that access to key respiratory interventions has on preterm outcomes in LMICs. CPAP has the largest impact on neonatal mortality and improving its coverage should be the primary goal for low-resourced areas to save newborn lives.
The Invisible Burdens of Burden-Sharing
Authors: Thomson Marnie Jane
Published: April 2022

In the global humanitarian realm, there is much discussion and concern for the burdens that states endure when it comes to refugee populations. The word “burden” appears in the Preamble of the 1951 Refugee Convention in reference to placing “unduly heavy burdens” on specific host countries and compels the international community to intervene in such situations. While there have been attempts to change the language from burden-sharing to responsibility-sharing, the emphasis on states assuming the “burden” of hosting and providing for refugee populations continues. Even as the 2018 Global Compact for Refugees has brought refugees into the discussions of an international response to refugee situations, the language and concerns about burden-sharing remain relatively unchanged. This is clearly demonstrated by the first ever Global Refugee Forum, which was held in December 2019, through its central theme of burden- and responsibility-sharing. In the forum, refugees advocated for their continued and increased inclusion, but while state delegations and humanitarian organizations acknowledged this as a benefit for all, their statements continued to assert their own concerns about their positions as the donor and host countries. This continued privileging of the state, even amidst the added language and practices of inclusion of all humanitarian actors, still renders invisible the burdens that refugees bear, many of which are exacerbated by the language and logic of burden-sharing applied to states. A prime example of this is Trump's anti-immigration policies and rhetoric, which demonstrate how state attempts to lighten their burden have far-reaching effects, including long-lasting everyday burdens for those who have already been resettled. Long-term ethnographic research in refugee camps and with resettled refugees provides empirical evidence to engage in the critical policy analysis and discourse analysis of burden-sharing in this piece.
Comprehensive Oncogenic Features of Coronavirus Receptors in Glioblastoma Multiforme
Authors: Chen Anjing , Zhao Wenguo , Li Xiaolong , Sun Guangyu , Ma Zhaoyin , Peng Lingyu , Shi Zhongyang , Li Xingang , Yan Jie
Published: April 2022

The COVID-19 pandemic caused by SARS-CoV-2 infection has placed health systems under excessive pressure and especially elderly people with cancer. Glioblastoma multiforme (GBM) is a malignant brain tumor with an increasing incidence in elderly individuals, and thereby GBM patients are a vulnerable population during the COVID-19 outbreak. Accumulating studies have implied that SARS-CoV-2 might invade the brain directlyviacoronavirus receptors. However, little is known about SARS-CoV-2 infection in the clinical development of GBM. Here, we explored the oncogenic roles of six coronavirus receptors (ACE2, DPP4, ANPEP, AXL, TMPRSS2, and ENPEP) in GBM using bioinformatics and experimental approaches. We found that ANPEP and ENPEP were significantly increased at both the mRNA and protein levels in GBM compared with normal brain tissue. Kaplan–Meier survival curves and Cox regression analysis demonstrated that high expressions ofANPEPandENPEPare associated with poor prognosis and survival. Moreover, all receptors are positively correlated with the immune infiltration levels of monocyte. Furthermore, we identified 245 genes between COVID-19 and coronavirus receptors–correlated genes in GBM and performed a thorough analysis of their protein–protein interaction network, functional signaling pathway and molecular process. Our work explores for the first time the association of coronavirus receptors with GBM and suggests ANPEP and ENPEP as potential therapeutic targets of GBM irrespective of COVID-19.
Pathogenesis of Autoimmune Cytopenias in Inborn Errors of Immunity Revealing Novel Therapeutic Targets
Authors: Cortesi Manuela , Soresina Annarosa , Dotta Laura , Gorio Chiara , Cattalini Marco , Lougaris Vassilios , Porta Fulvio , Badolato Raffaele
Published: April 2022

Autoimmune diseases are usually associated with environmental triggers and genetic predisposition. However, a few number of autoimmune diseases has a monogenic cause, mostly in children. These diseases may be the expression, isolated or associated with other symptoms, of an underlying inborn error of immunity (IEI). Autoimmune cytopenias (AICs), including immune thrombocytopenic purpura (ITP), autoimmune hemolytic anemia (AIHA), autoimmune neutropenia (AN), and Evans’ syndrome (ES) are common presentations of immunological diseases in the pediatric age, with at least 65% of cases of ES genetically determined. Autoimmune cytopenias in IEI have often a more severe, chronic, and relapsing course. Treatment refractoriness also characterizes autoimmune cytopenia with a monogenic cause, such as IEI. The mechanisms underlying autoimmune cytopenias in IEI include cellular or humoral autoimmunity, immune dysregulation in cases of hemophagocytosis or lymphoproliferation with or without splenic sequestration, bone marrow failure, myelodysplasia, or secondary myelosuppression. Genetic characterization of autoimmune cytopenias is of fundamental importance as an early diagnosis improves the outcome and allows the setting up of a targeted therapy, such as CTLA-4 IgG fusion protein (Abatacept), small molecule inhibitors (JAK-inhibitors), or gene therapy. Currently, gene therapy represents one of the most attractive targeted therapeutic approaches to treat selected inborn errors of immunity. Even in the absence of specific targeted therapies, however, whole exome genetic testing (WES) for children with chronic multilineage cytopenias should be considered as an early diagnostic tool for disease diagnosis and genetic counseling.
Natural Killer Cells in Multiple Sclerosis: Entering the Stage
Authors: Beliën Jarne , Goris An , Matthys Patrick
Published: April 2022

Studies investigating the immunopathology of multiple sclerosis (MS) have largely focused on adaptive T and B lymphocytes. However, in recent years there has been an increased interest in the contribution of innate immune cells, amongst which the natural killer (NK) cells. Apart from their canonical role of controlling viral infections, cell stress and malignancies, NK cells are increasingly being recognized for their modulating effect on the adaptive immune system, both in health and autoimmune disease. From different lines of research there is now evidence that NK cells contribute to MS immunopathology. In this review, we provide an overview of studies that have investigated the role of NK cells in the pathogenesis of MS by use of the experimental autoimmune encephalomyelitis (EAE) animal model, MS genetics or through ex vivo and in vitro work into the immunology of MS patients. With the advent of modern hypothesis-free technologies such as single-cell transcriptomics, we are exposing an unexpected NK cell heterogeneity, increasingly blurring the boundaries between adaptive and innate immunity. We conclude that unravelling this heterogeneity, as well as the mechanistic link between innate and adaptive immune cell functions will lay the foundation for the use of NK cells as prognostic tools and therapeutic targets in MS and a myriad of other currently uncurable autoimmune disorders.
Construction of a Large Size Human Immunoglobulin Heavy Chain Variable (VH) Domain Library, Isolation and Characterization of Novel Human Antibody VH Domains Targeting PD-L1 and CD22
Authors: Sun Zehua , Li Wei , Mellors John W. , Orentas Rimas , Dimitrov Dimiter S.
Published: April 2022

Phage display is a well-established technology for in vitro selection of monoclonal antibodies (mAb), and more than 12 antibodies isolated from phage displayed libraries of different formats have been approved for therapy. We have constructed a large size (10^11) human antibody VH domain library based on thermo-stable, aggregation-resistant scaffolds. This diversity was obtained by grafting naturally occurring CDR2s and CDR3s from healthy donors with optimized primers into the VH library. This phage-displayed library was used for bio-panning against various antigens. So far, panels of binders have been isolated against different viral and tumor targets, including the SARS-CoV-2 RBD, HIV-1 ENV protein, mesothelin and FLT3. In the present study, we discuss domain library construction, characterize novel VH binders against human CD22 and PD-L1, and define our design process for antibody domain drug conjugation (DDC) as tumoricidal reagents. Our study provides examples for the potential applications of antibody domains derived from library screens in therapeutics and provides key information for large size human antibody domain library construction.
The Expansion of a Single Bacteriophage Leads to Bacterial Disturbance in Gut and Reduction of Larval Growth in Musca domestica
Authors: Zhang Xinyu , Wang Shumin , Zhang Qian , Zhang Kexin , Liu Wenjuan , Zhang Ruiling , Zhang Zhong
Published: April 2022

The housefly larvae gut microbiota influences larval health and has become an important model to study the ecology and evolution of microbiota–host interactions. However, little is known about the phage community associated with the housefly larval gut, although bacteriophages are the most abundant members of the microbiota and have the potential to shape gut bacterial communities. Changes to bacteriophage composition are associated with disease, but how phages impact insect health remains unclear. We noticed that treating 1-day-old housefly larvae with ~107, ~109, and ~1011 phage particles per ml of bacteriophages led to changes in the growth and development of housefly larvae. Additionally, treating housefly larvae with bacteriophages led to bacterial composition changes in the gut. Changes in the compositions of these gut bacteria are mainly manifested in the increase in harmful bacteria, including Pseudomonas and Providencia and the decrease in beneficial bacteria, including Enterobacter and Klebsiella, after different growth and development periods. The alterations in gut microbiota further influenced the larval growth and development. Collectively, these results indicate that bacteriophages can perturb the intestinal microbiome and impact insect health.
NLRP3 Inflammasome-Mediated Pyroptosis Pathway Contributes to the Pathogenesis of Candida albicans Keratitis
Authors: Lian Huifang , Fang XiaoLong , Li Qingyu , Liu Shuang , Wei Qiuhong , Hua Xia , Li Wenguang , Liao Chunyang , Yuan Xiaoyong
Published: April 2022

Purpose

Fungal keratitis is a sight-threatening corneal infection caused by fungal pathogens, and the pathogenic mechanisms have not been fully elucidated. The aim of this study was to determine whether NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated pyroptosis contributes to Candida albicans (C. albicans) keratitis and explore the underlying mechanism.

Methods

An in vivo mouse model of C. albicans keratitis and an in vitro culture model of human corneal epithelial cells (HCECs) challenged with heat-killed C. albicans (HKCA) were established in this study. The degree of corneal infection was evaluated by clinical scoring. Gene expression was assessed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis or immunofluorescence staining was performed to evaluate protein expression. TdT-mediated dUTP nick end labeling (TUNEL) staining was performed to examine the pyroptotic cell death. A lactate dehydrogenase (LDH) release assay was performed to assess cytotoxicity.

Results

Compared with the mock-infected group, we observed that the mRNA levels of NLRP3, caspase-1 (CASP1), interleukin (IL)−1β and gasdermin-D (GSDMD) in C. albicans-infected mice cornea was significantly increased. Our data also demonstrated that the protein expression of NLRP3 and the pyroptosis-related markers apoptosis-associated speck-like protein containing a CARD (ASC), cleaved CASP1, N-GSDMD, cleaved IL-1β and cleaved IL-18 as well as pyroptotic cell death were dramatically elevated in the mouse model of C. albicans keratitis. More importantly, NLRP3 knockdown markedly alleviated pyroptosis and consequently reduced corneal inflammatory reaction in C. albicans keratitis. In vitro, the presence of activated NLRP3 inflammasome and pyroptotic cell death were validated in HCECs exposed to HKCA. Furthermore, the potassium (K+) channel inhibitor glyburide decreased LDH release and suppressed NLRP3 inflammasome activation and pyroptosis in HCECs exposed to HKCA.

Conclusion

In conclusion, the current study revealed for the first time that NLRP3 inflammasome activation and pyroptosis occur in C. albicans-infected mouse corneas and HCECs. Moreover, NLRP3 inflammasome-mediated pyroptosis signaling is involved in the disease severity of C. albicans keratitis. Therefore, This NLRP3 inflammasome-dependent pathway may be an attractive target for the treatment of fungal keratitis.
Female Presidents of the “Royal College of Pathologists”: Their Achievements and Contributions
Authors: Coupland Sarah E. , Sandle Lance N. , Osborn Michael
Published: April 2022

The Royal College of Pathologists (RCPath) celebrates its Diamond Jubilee in 2022 since its opening by Her Majesty Queen Elizabeth II in 1962. One of the main remits of RCPath is the overseeing of the training of pathologists and scientists working in pathology’s 17 different specialties within the United Kingdom and across the globe. During its 60 years, three female Presidents have been elected: Dame Barbara Clayton (1984–1987), Dr. Suzannah (Suzy) Lishman CBE (2014–2017), and Prof. Joanne (Jo) Martin (2017–2020). Whilst Clayton specialised in Chemical Pathology and its relevance to public health, both Lishman and Martin are diagnostic cellular histopathologists with differing areas of expertise. This article reviews the contributions of these three distinguished and inspirational female pathologists to Pathology (“the science behind the cure”), to healthcare, public health and education, medical research, and to teaching. It highlights their qualities as leaders and mentors for those not only in medicine but in other career settings.
Amelioration of Chromium-Induced Oxidative Stress by Combined Treatment of Selected Plant-Growth-Promoting Rhizobacteria and Earthworms via Modulating the Expression of Genes Related to Reactive Oxygen Species Metabolism in Brassica juncea
Authors: Sharma Pooja , Chouhan Rekha , Bakshi Palak , Gandhi Sumit G. , Kaur Rupinder , Sharma Ashutosh , Bhardwaj Renu
Published: April 2022

Chromium (Cr) toxicity leads to the enhanced production of reactive oxygen species (ROS), which are extremely toxic to the plant and must be minimized to protect the plant from oxidative stress. The potential of plant-growth-promoting rhizobacteria (PGPR) and earthworms in plant growth and development has been extensively studied. The present study was aimed at investigating the effect of two PGPR (Pseudomonas aeruginosa and Burkholderia gladioli) along with earthworms (Eisenia fetida) on the antioxidant defense system in Brassica juncea seedlings under Cr stress. The Cr toxicity reduced the fresh and dry weights of seedlings, enhanced the levels of superoxide anion (O2•–), hydrogen peroxide (H2O2), malondialdehyde (MDA), and electrolyte leakage (EL), which lead to membrane as well as the nuclear damage and reduced cellular viability in B. juncea seedlings. The activities of the antioxidant enzymes, viz., superoxide dismutase (SOD), guaiacol peroxidase (POD), ascorbate peroxidase (APOX), glutathione peroxidase (GPOX), dehydroascorbate reductase (DHAR), and glutathione reductase (GR) were increased; however, a reduction was observed in the activity of catalase (CAT) in the seedlings under Cr stress. Inoculation of the PGPR and the addition of earthworms enhanced the activities of all other antioxidant enzymes except GPOX, in which a reduction of the activity was observed. For total lipid- and water-soluble antioxidants and the non-enzymatic antioxidants, viz., ascorbic acid and glutathione, an enhance accumulation was observed upon the inoculation with PGPR and earthworms. The supplementation of PGPR with earthworms (combined treatment) reduced both the reactive oxygen species (ROS) and the MDA content by modulating the defense system of the plant. The histochemical studies also corroborated that the combined application of PGPR and earthworms reduced O2•–, H2O2, lipid peroxidation, and membrane and nuclear damage and improved cell viability. The expression of key antioxidant enzyme genes, viz., SOD, CAT, POD, APOX, GR, DHAR, and GST showed the upregulation of these genes at post-transcriptional level upon the combined treatment of the PGPR and earthworms, thereby corresponding to the improved plant biomass. However, a reduced expression of RBOH1 gene was noticed in seedlings supplemented under the effect of PGPR and earthworms grown under Cr stress. The results provided sufficient evidence regarding the role of PGPR and earthworms in the amelioration of Cr-induced oxidative stress in B. juncea.
Circulative Transmission of Cileviruses in Brevipalpus Mites May Involve the Paracellular Movement of Virions
Authors: Tassi Aline Daniele , Ramos-González Pedro Luis , Sinico Thais Elise , Kitajima Elliot Watanabe , Freitas-Astúa Juliana
Published: April 2022

Plant viruses transmitted by mites of the genus Brevipalpus are members of the genera Cilevirus, family Kitaviridae, or Dichorhavirus, family Rhabdoviridae. They produce non-systemic infections that typically display necrotic and/or chlorotic lesions around the inoculation loci. The cilevirus citrus leprosis virus C (CiLV-C) causes citrus leprosis, rated as one of the most destructive diseases affecting this crop in the Americas. CiLV-C is vectored in a persistent manner by the flat mite Brevipalpus yothersi. Upon the ingestion of viral particles with the content of the infected plant cell, virions must pass through the midgut epithelium and the anterior podocephalic gland of the mites. Following the duct from this gland, virions reach the salivary canal before their inoculation into a new plant cell through the stylet canal. It is still unclear whether CiLV-C multiplies in mite cells and what mechanisms contribute to its movement through mite tissues. In this study, based on direct observation of histological sections from viruliferous mites using the transmission electron microscope, we posit the hypothesis of the paracellular movement of CiLV-C in mites which may involve the manipulation of septate junctions. We detail the presence of viral particles aligned in the intercellular spaces between cells and the gastrovascular system of Brevipalpus mites. Accordingly, we propose putative genes that could control either active or passive paracellular circulation of viral particles inside the mites.
Myco-Facilitated Biosynthesis of Nano-Silver From Wasp Nest Fungus, Paecilomyces variotii, and Its Antimicrobial Activity Against MTCC Strains
Authors: Nayak B. K. , Prabhakar V. , Nanda Anima
Published: April 2022

The utility of fungi as stabilizing and reducing agents in the biogenic synthesis of silver nanoparticles is striking due to the production of large quantities of biomolecules of minute toxic residuals. During the current study, sunlight- and dark-assessed silver nanoparticles were synthesized from wasp nest fungus, Paecilomyces variotii, at different pHs. Synthesized silver nanoparticles (AgNPs) at 6 pH were found to be more prominent than at 7 and 8 pHs. AgNPs were within the 20- to 90-nm range and were polygonal and elongated in shape. FTIR spectra of light-mediated AgNPs showed diverse transmittance bands than the silver nanoparticles synthesized in the dark. The synthesized AgNPs were found with diverse antimicrobial activities against pathogenic MTCC bacterial strains, i.e., Staphylococcus aureus, Vibrio parahaemolyticus, Escherichia coli, Shewanella putrefaciens, and fungus, Candida albicans. Aqueous filtrate and filtrate-mediated AgNPs combined with methanol solvent extract of yeast extract manitol broth (YEMB) had more inhibitory effects on all bacteria and Candida albicans. Furthermore, the combined effect of AgNPs and methanol solvent extract from YEMB culture filtrate was found more effective against E. coli, while AgNPs combined with methanol solvent of aqueous filtrate had inhibitory effects on E. coli and Candida albicans.
Ecological and Evolutionary Implications of Microbial Dispersal
Authors: Custer Gordon F. , Bresciani Luana , Dini-Andreote Francisco
Published: April 2022

Dispersal is simply defined as the movement of species across space and time. Despite this terse definition, dispersal is an essential process with direct ecological and evolutionary implications that modulate community assembly and turnover. Seminal ecological studies have shown that environmental context (e.g., local edaphic properties, resident community), dispersal timing and frequency, and species traits, collectively account for patterns of species distribution resulting in either their persistence or unsuccessful establishment within local communities. Despite the key importance of this process, relatively little is known about how dispersal operates in microbiomes across divergent systems and community types. Here, we discuss parallels of macro- and micro-organismal ecology with a focus on idiosyncrasies that may lead to novel mechanisms by which dispersal affects the structure and function of microbiomes. Within the context of ecological implications, we revise the importance of short- and long-distance microbial dispersal through active and passive mechanisms, species traits, and community coalescence, and how these align with recent advances in metacommunity theory. Conversely, we enumerate how microbial dispersal can affect diversification rates of species by promoting gene influxes within local communities and/or shifting genes and allele frequencies via migration or de novo changes (e.g., horizontal gene transfer). Finally, we synthesize how observed microbial assemblages are the dynamic outcome of both successful and unsuccessful dispersal events of taxa and discuss these concepts in line with the literature, thus enabling a richer appreciation of this process in microbiome research.
Substrate Protein Interactions and Methylglyoxal Modifications Reduce the Aggregation Propensity of Human Alpha-A-Crystallin G98R Mutant
Authors: Santhoshkumar Puttur , Sharma Krishna K.
Published: April 2022

The G98R mutation in αA-crystallin is associated with presenile cataract development in humans. Previous studies have indicated that mutant proteins altered structure, decreased stability, increased oligomeric size, loss of chaperone-like activity, and susceptibility to proteolysis could be contributing factors to cataract formation. To evaluate the effect of substrate protein interactions with the mutant protein on cataract formation, we have performed chaperone assays with alcohol dehydrogenase (ADH), citrate synthase (CS), and βB2-crystallin (βB2), and analyzed the reaction mixtures by multi-angle light scattering (MALS) analysis. It appears that αAG98R protein initially gets stabilized upon interaction with substrate proteins. Analysis of the chaperone-client protein complexes revealed that wild-type αA-crystallin interacts with substrate proteins to form compact complexes leading to a slight increase in oligomeric mass, whereas αAG98R forms less compact and high molecular weight complexes with the substrate, and the resulting complexes continue to increase in size over time. As a result, the soluble complexes formed initially by the mutant protein begin to scatter light and precipitate. We found that the stability and chaperone activity of the αAG98R can be improved by modifying the protein with low concentrations (50 µM) of methylglyoxal (MGO). Incubation of αAG98R protein (1 mg/ml) under aseptic conditions for 30 days at 37°C resulted in precipitation of the mutant protein. In contrast, mutant protein incubations carried out with 50 µM MGO remained soluble and transparent. SDS-PAGE analysis showed gradual autolysis of the mutant protein in the absence of MGO. The average molar mass of the mutant protein oligomers changed from 7,258 ± 12 kDa to 3,950 ± 08 kDa within 60 min of incubation with MGO. There was no further significant change in the molar mass of mutant protein when tested on day 7 of MGO treatment. Our data suggest that the initial stabilization of αAG98R by substrate proteins could delay congenital cataracts’ appearance, and the uncontrolled long-term interaction amongst mutant subunits and substrate proteins could be the rationale behind presenile cataracts formation. The results also demonstrate the potential benefit of low concentrations of MGO in stabilizing mutant chaperone protein(s).
Neural Substrates of Poststroke Depression: Current Opinions and Methodology Trends
Authors: Pan Chensheng , Li Guo , Sun Wenzhe , Miao Jinfeng , Qiu Xiuli , Lan Yan , Wang Yanyan , Wang He , Zhu Zhou , Zhu Suiqiang
Published: April 2022

Poststroke depression (PSD), affecting about one-third of stroke survivors, exerts significant impact on patients’ functional outcome and mortality. Great efforts have been made since the 1970s to unravel the neuroanatomical substrate and the brain-behavior mechanism of PSD. Thanks to advances in neuroimaging and computational neuroscience in the past two decades, new techniques for uncovering the neural basis of symptoms or behavioral deficits caused by focal brain damage have been emerging. From the time of lesion analysis to the era of brain networks, our knowledge and understanding of the neural substrates for PSD are increasing. Pooled evidence from traditional lesion analysis, univariate or multivariate lesion-symptom mapping, regional structural and functional analyses, direct or indirect connectome analysis, and neuromodulation clinical trials for PSD, to some extent, echoes the frontal-limbic theory of depression. The neural substrates of PSD may be used for risk stratification and personalized therapeutic target identification in the future. In this review, we provide an update on the recent advances about the neural basis of PSD with the clinical implications and trends of methodology as the main features of interest.
Goal-Directed Intraoperative Fluid Therapy Benefits Patients Undergoing Major Gynecologic Oncology Surgery: A Controlled Before-and-After Study
Authors: Yu Jiawen , Che Lu , Zhu Afang , Xu Li , Huang Yuguang
Published: April 2022

Background

Fluid management during major gynecologic oncology surgeries faces great challenges due to the distinctive characteristics of patients with gynecologic malignancies as well as features of the surgical procedure. Intraoperative goal-directed fluid therapy (GDFT) has been proven to be effective in reducing postoperative complications among major colorectal surgeries; however, the efficacy of GDFT has not been fully studied in gynecologic malignancy surgeries. This study aimed to discuss the influence of GDFT practice in patients undergoing major gynecologic oncology surgery.

Methods

This study was a controlled before-and-after study. From June 2015 to June 2018 in Peking Union Medical College Hospital, a total of 300 patients scheduled for elective laparotomy of gynecological malignancies were enrolled and chronologically allocated into two groups, with the earlier 150 patients in the control group and the latter 150 patients in the GDFT group. The GDFT protocol was applied by Vigileo/FloTrac monitoring of stroke volume and fluid responsiveness to guide intraoperative fluid infusion and the use of vasoactive agents. The primary outcome was postoperative complications within 30 days after surgery. The secondary outcome included length of stay and time of functional recovery.

Results

A total of 249 patients undergoing major gynecologic oncology surgery were analyzed in the study, with 129 in the control group and 120 patients in the GDFT group. Patients in the GDFT group had higher ASA classifications and more baseline comorbidities. GDFT patients received significantly less fluid infusion than the control group (15.8 vs. 17.9 ml/kg/h), while fluid loss was similar (6.9 vs. 7.1 ml/kg/h). GDFT was associated with decreased risk of postoperative complications (OR = 0.572, 95% CI 0.343 to 0.953, P = 0.032), especially surgical site infections (OR = 0.127, 95% CI 0.003 to 0.971, P = 0.037). The postoperative bowel function recovery and length of hospital stay were not significantly different between the two groups.

Conclusion

Goal-directed intraoperative fluid therapy is associated with fewer postoperative complications in patients undergoing major gynecologic oncology surgery.
Establishment of an Ex Vivo Tissue Culture Model for Evaluation of Antitumor Efficacy in Clear Cell Renal Cell Carcinoma
Authors: Hong Shanjuan , Yuan Qing , Xia Haizhui , Dou Yuan , Sun Tiantian , Xie Tian , Zhang Zhiyin , He Wei , Dong Chen , Lu Jian , Guo Li , Ni Ling
Published: April 2022

There are many potential immunotherapeutic targets for cancer immunotherapy, which should be assessed for efficacy before they enter clinical trials. Here we established an ex vivo cultured patient-derived tumor tissue model to evaluate antitumor effectiveness of one VISTA inhibitor, given that our previous study showed that VISTA was selectively highly expressed in human clear cell renal cell carcinoma (ccRCC) tumors. We observed that all the tested patients responded to the anti-VISTA monoclonal antibody as manifested by TNF-α production, but only a small fraction were responders to the anti-PD-1 antibody. Co-blockade of VISTA and PD-1 resulted in a synergistic effect in 20% of RCC patients. Taken together, these findings indicate that this ex vivo tumor slice culture model represents a viable tool to evaluate antitumor efficacies for the inhibitors of immune checkpoints and further supports that VISTA could serve as a promising target for immunotherapy in ccRCC.
LncRNA-AC02278.4 Is a Novel Prognostic Biomarker That Promotes Tumor Growth and Metastasis in Lung Adenocarcinoma
Authors: Chen Xi , Zhou Fan , Ren Wenjun , Guo Jishu , Huang Xiaobin , Pu Jun , Niu Xiaoqun , Jiang Xiulin
Published: April 2022

LncRNA-AC02278.4 (ENSG00000248538) is a long non-coding RNA (lncRNA) found to be highly expressed in multiple human cancers including lung adenocarcinoma (LUAD). However, the underlying biological function and potential mechanisms of AC02278.4 driving the progression of LUAD remain unclear. In this study, we investigated the role of AC02278.4 in LUAD and found that AC02278.4 expression was significantly increased in datasets extracted from The Cancer Genome Atlas. Increased expression of lncRNA-AC02278.4 was correlated with advanced clinical parameters. Receiver operating characteristic (ROC) curve analysis revealed the significant diagnostic ability of AC02278.4 [area under the ROC curve (AUC) = 0.882]. In addition, gene set enrichment analysis (GSEA) enrichment showed that AC02278.4 expression was correlated with immune response-related signaling pathways. Finally, we determined that AC02278.4 regulated cell proliferation and migration of LUAD in vitro. Our clinical sample results also confirmed that AC02278.4 was highly expressed in LUAD and correlated with adverse clinical outcomes. In conclusion, our data demonstrated that AC02278.4 was correlated with progression and immune infiltration and could serve as a prognostic biomarker for LUAD.
Targeting ALK Rearrangements in NSCLC: Current State of the Art
Authors: Peng Ling , Zhu Liping , Sun Yilan , Stebbing Justin , Selvaggi Giovanni , Zhang Yongchang , Yu Zhentao
Published: April 2022

Anaplastic lymphoma kinase (ALK) alterations in non-small cell lung cancer (NSCLC) can be effectively treated with a variety of ALK-targeted drugs. After the approval of the first-generation ALK inhibitor crizotinib which achieved better results in prolonging the progression-free survival (PFS) compared with chemotherapy, a number of next-generation ALK inhibitors have been developed including ceritinib, alectinib, brigatinib, and ensartinib. Recently, a potent, third-generation ALK inhibitor, lorlatinib, has been approved by the Food and Drug Administration (FDA) for the first-line treatment of ALK-positive (ALK+) NSCLC. These drugs have manageable toxicity profiles. Responses to ALK inhibitors are however often not durable, and acquired resistance can occur as on-target or off-target alterations. Studies are underway to explore the mechanisms of resistance and optimal treatment options beyond progression. Efforts have also been undertaken to develop further generations of ALK inhibitors. This review will summarize the current situation of targeting the ALK signaling pathway.
Clinical, Laboratory and Radiographic Features Associated With Prolonged Hospitalization in Children With Complicated Appendicitis
Authors: Bhattacharya Jyotsna , Silver Ellen J. , Blumfield Einat , Jan Dominique M. , Herold Betsy C. , Goldman David L.
Published: April 2022

Objective

In children with appendicitis, rupture of the appendix is associated with a significant increase in morbidity. We sought to characterize the spectrum of illness in children with complicated appendicitis and to define those factors associated with a longer hospital stay.

Study Design

We conducted a retrospective review of 132 children, 18 years of age or younger at a large urban teaching hospital in the Bronx, NY between October 2015 and April 2018 with an intraoperative diagnosis of perforated appendix. Clinical, laboratory and radiologic findings were reviewed, and the primary study outcome was length of stay (LOS) dichotomized at the median, which was 7 days. Statistical analyses were done to characterize morbidity and define variables predictive of longer stay.

Results

Children in the longer LOS group experienced significantly more morbidity, including ICU stay, ileus, and need for multiple drainage procedures. A longer duration of symptoms prior to presentation was associated with a longer stay. Multivariable logistic regression analysis indicated that the presence of abscess and presence of free fluid in the right upper quadrant (RUQ FF) on initial imaging and C-reactive protein (CRP) level >12 at admission, were independently associated with a longer stay.

Conclusion

There is considerable variation in the morbidity of complicated appendicitis. The association between longer stay and the findings of abscess and RUQ FF on initial imaging along with an elevated CRP may provide a useful tool in identifying those children at risk for worse outcomes.
Case Report: A Missense Mutation in Dyskeratosis Congenita 1 Leads to a Benign Form of Dyskeratosis Congenita Syndrome With the Mucocutaneous Triad
Authors: Wang Liqing , Li Jianwei , Xiong Qiuhong , Zhou Yong-An , Li Ping , Wu Changxin
Published: April 2022

Background

Dyskeratosis congenita (DC) is a rare inheritable disorder characterized by bone marrow failure and mucocutaneous triad (reticular skin pigmentation, nail dystrophy, and oral leukoplakia). Dyskeratosis congenita 1 (DKC1) is responsible for 4.6% of the DC with an X-linked inheritance pattern. Almost 70 DKC1 variations causing DC have been reported in the Human Gene Mutation Database.

Results

Here we described a 14-year-old boy in a Chinese family with a phenotype of abnormal skin pigmentation on the neck, oral leukoplakia, and nail dysplasia in his hands and feet. Genetic analysis and sequencing revealed hemizygosity for a recurrent missense mutation c.1156G > A (p.Ala386Thr) in DKC1 gene. The heterozygous mutation (c.1156G > A) from his mother and wild-type sequence from his father were obtained in the same site of DKC1. This mutation was determined as disease causing based on silico software, but the pathological phenotypes of the proband were milder than previously reported at this position (HGMDCM060959). Homology modeling revealed that the altered amino acid was located near the PUA domain, which might affect the affinity for RNA binding.

Conclusion

This DKC1 mutation (c.1156G > A, p.Ala386Thr) was first reported in a Chinese family with mucocutaneous triad phenotype. Our study reveals the pathogenesis of DKC1 c.1156G > A mutation to DC with a benign phenotype, which expands the disease variation database, the understanding of genotype–phenotype correlations, and facilitates the clinical diagnosis of DC in China.
Case Report: Fatal Outcome for a Preterm Newborn With Meningitis Caused by Extended-Spectrum β-Lactamase-Producing Escherichia coli Sequence Type 1193
Authors: Oldendorff Frida , Linnér Agnes , Finder Mikael , Eisenlauer Peter , Kjellberg Malin , Giske Christian G. , Nordberg Viveka
Published: April 2022

Introduction

In this case report, we describe an extended-spectrum beta-lactamase (ESBL) – Escherichia coli (E. coli) strain of sequence type (ST) 1193, a novel, virulent, multidrug-resistant (MDR) clone with a rapid global spread. ST 1193 has been more commonly associated with invasive disease than other ESBL-E. coli STs. To our knowledge, this is the first known case in Sweden where a newborn died of an ESBL-E. coli ST 1193 meningitis. We emphasize that the clinical knowledge about the properties of certain MDR-clones should be increased.

Case Report

A moderately preterm boy was born after preterm prolonged rupture of membranes. The mother had an ESBL-E. coli urinary tract infection during pregnancy. At 36 h of age he developed signs of infection and was given first-line therapy for early onset sepsis. Thereafter he developed seizures. The treatment was changed to cover suspected meningitis. Culture showed growth of the same ESBL- E. coli ST 1193 strain in the child’s blood and cerebrospinal fluid, as well as in the mother’s urine. Antibiotics were adapted. His condition deteriorated and he developed fulminant septic shock with treatment-resistant seizures. The boy passed away at 3 days of age.

Conclusion

This case highlights the risk of delay in diagnosis when a marking for carriage of MDR-bacteria is falsely removed from a medical record of a pregnant women. Further, it demonstrates that ESBL-E. coli ST 1193 infection in neonates can be fatal. Thus, studies regarding virulence factors of ESBL-E. coli infections in pregnant women and their children are needed to understand the association between this infection and severe invasive disease in newborn children.
N-Acetyldopamine Dimer Attenuates DSS-Induced Ulcerative Colitis by Suppressing NF-κB and MAPK Pathways
Authors: Huang Li-Jun , Wang Yu-Mei , Gong Lei-Qiang , Hu Chao , Gui Yu , Zhang Chen , Tan Xue , Yu Xian-Kuo , Liao Yi-Le , Luo Yan , Tang Yu-Qin , Dai Yi-Fei , Deng Yun , Wang Dong , Guo Da-le
Published: April 2022

Ulcerative Colitis (UC) is a major form of chronic inflammatory bowel disease of the colonic mucosa and exhibits progressive morbidity. There is still a substantial need of small molecules with greater efficacy and safety for UC treatment. Here, we report a N-acetyldopamine dimer (NADD) elucidated (2R,3S)-2-(3′,4′-dihydroxyphenyl)-3-acetylamino-7-(N-acetyl-2″-aminoethyl)-1,4-benzodioxane, which is derived from traditional Chinese medicine Isaria cicadae, exhibits significant therapeutic efficacy against dextran sulfate sodium (DSS)-induced UC. Functionally, NADD treatment effectively relieves UC symptoms, including weight loss, colon length shortening, colonic tissue damage and expression of pro-inflammatory factors in pre-clinical models. Mechanistically, NADD treatment significantly inhibits the expression of genes in inflammation related NF-κB and MAPK signaling pathways by transcriptome analysis and western blot, which indicates that NADD inhibits the inflammation in UC might through these two pathways. Overall, this study identifies an effective small molecule for UC therapy.