bluuebunny/crossref_metadata_2025 huggingface dataset:
β-Glucan-Induced IL-10 Secretion by Monocytes Triggers Porcine NK Cell Cytotoxicity
Authors: Hermans Leen , De Pelsmaeker Steffi , Denaeghel Sofie , Cox Eric , Favoreel Herman W. , Devriendt Bert
Published: February 2021

Beta-glucans are naturally occurring polysaccharides present in cell walls of fungi, yeast, bacteria, cereals, seaweed, and algae. These microbe-associated molecular patterns (MAMPs) possess immunomodulatory properties. In human, it has been suggested that NK cells can be activated by β-glucans. Here, we aimed to elucidate whether β-glucans modulate porcine NK cell responses in vitro and if so, how these effects are mediated. We investigated the effect of two β-glucans, Macrogard and Curdlan, which differ in solubility and structure. Direct addition of β-glucans to purified porcine NK cells did not affect cytotoxicity of these cells against K562 target cells. However, when using PBMC instead of purified NK cells, β-glucan addition significantly increased NK cell-mediated cytotoxicity. This effect depended on factors secreted by CD14+ monocytes upon β-glucan priming. Further analysis showed that monocytes secrete TNF-α, IL-6, and IL-10 upon β-glucan addition. Of these, IL-10 turned out to play a critical role in β-glucan-triggered NK cell cytotoxicity, since depletion of IL-10 completely abrogated the β-glucan-induced increase in cytotoxicity. Furthermore, addition of recombinant IL-10 to purified NK cells was sufficient to enhance cytotoxicity. In conclusion, we show that β-glucans trigger IL-10 secretion by porcine monocytes, which in turn leads to increased NK cell cytotoxicity, and thereby identify IL-10 as a potent stimulus of porcine NK cell cytotoxicity.
SUMOylation Connects Cell Stress Responses and Inflammatory Control: Lessons From the Gut as a Model Organ
Authors: Karhausen Jörn , Ulloa Luis , Yang Wei
Published: February 2021

Conjugation with the small ubiquitin-like modifier (SUMO) constitutes a key post-translational modification regulating the stability, activity, and subcellular localization of its target proteins. However, the vast numbers of identified SUMO substrates obscure a clear view on the function of SUMOylation in health and disease. This article presents a comprehensive review on the physiological relevance of SUMOylation by discussing how global SUMOylation levels—rather than specific protein SUMOylation—shapes the immune response. In particular, we highlight the growing body of work on SUMOylation in intestinal pathologies, because of the unique metabolic, infectious, and inflammatory challenges of this organ. Recent studies show that global SUMOylation can help restrain detrimental inflammation while maintaining immune defenses and tissue integrity. These results warrant further efforts to develop new therapeutic tools and strategies to control SUMOylation in infectious and inflammatory disorders.
Stressful Conditions Give Rise to a Novel and Cryptic Filamentous Form of Caulerpa cylindracea
Authors: Santamaría Jorge , Golo Raül , Cebrian Emma , García María , Vergés Alba
Published: February 2021

Morphological plasticity can enable algae to adapt to environmental change and increase their invasibility when introduced into new habitats. Nevertheless, there is still a lack of knowledge on how such plasticity can affect the invasion process of an invasive species. In this context, the high plasticity in the genus Caulerpa is well documented. However, after an extremely hot summer, a previously unreported filamentous morphology of Caulerpa cylindracea was detected; indeed, this morphology could only be confirmed taxonomically after in-depth morphological characterization and molecular analysis with the genetic marker tufA. We describe an ex situ culture experiment which showed that stressful conditions, such as high temperatures, can trigger this morphological change. Almost all of the thalli maintained at a constant extreme temperature of 29°C died, but after being returned to optimum temperature conditions, the filamentous morphology began to develop from the surviving microscopic tissue. In contrast, thalli at a control temperature of 21°C maintained the regular morphology throughout the experiment. When C. cylindracea develops this filamentous morphology, it may act as a cryptic invader because it is difficult to detect in the field. Furthermore, the filaments likely improve C. cylindracea’s invasive capabilities with regard to resistance, persistence and dispersion and may have an important role in the re-colonization process, after a population disappears following a period of stressful conditions. Possibly, C. cylindracea’s ability to respond plastically to stressful conditions might explain its remarkable success as an invasive species.
Slow Community Development Enhances Abiotic Limitation of Benthic Community Structure in a High Arctic Kelp Bed
Authors: Bonsell Christina , Dunton Kenneth H.
Published: February 2021

We examined the patterns of propagule recruitment to assess the timescale and trajectory of succession and the possible roles of physical factors in controlling benthic community structure in a shallow High Arctic kelp bed in the Beaufort Sea, Alaska. Spatial differences in established epilithic assemblages were evaluated against static habitat attributes (depth, distance from river inputs) and environmental factors (temperature, salinity, current speed, underwater light) collected continuously over 2–6 years. Our measurements revealed that bottom waters remained below freezing (mean winter temperatures ∼−1.8°C) and saline (33–36) with negligible light levels for 8–9 months. In contrast, the summer open water period was characterized by variable salinities (22–36), higher temperatures (up to 8–9°C) and measurable irradiance (1–8 mol photons m–2 day–1). An inshore, near-river site experienced strong, acute, springtime drops in salinity to nearly 0 in some years. The epilithic community was dominated by foliose red algae (47–79%), prostrate kelps (2–19%), and crustose coralline algae (0–19%). Strong spatial distinctions among sites included a positive correlation between cover by crustose coralline algae and distance to river inputs, but we found no significant relationships between multi-year means of physical factors and functional groups. Low rates of colonization and the very slow growth rates of recruits are the main factors that contribute to prolonged community development, which augments the influence of low-frequency physical events over local community structure. Mortality during early succession largely determines crustose coralline algal and invertebrate prevalence in the established community, while kelp seem to be recruitment-limited. On scales > 1 m, community structure varies with bathymetry and exposure to freshwater intrusion, which regulate frequency of primary and physiological disturbance. Colonization rates (means of 3.3–69.9 ind. 100 cm–1 year–1 site–1) were much lower than studies in other Arctic kelp habitats, and likely reflect the nature of a truly High Arctic environment. Our results suggest that community development in the nearshore Beaufort Sea occurs over decades, and is affected by combinations of recruitment limitation, primary disturbance, and abiotic stressors. While seasonality exerts strong influence on Arctic systems, static habitat characteristics largely determine benthic ecosystem structure by integrating seasonal and interannual variability over timescales longer than most ecological studies.
A de novo Transcriptome Assembly of the European Flounder (Platichthys flesus): The Preselection of Transcripts Encoding Active Forms of Enzymes
Authors: Pomianowski Konrad , Burzyński Artur , Kulczykowska Ewa
Published: February 2021

The RNA sequencing data sets available for different fish species show a potentially high variety of forms of enzymes just in teleosts. This is primarily considered an effect of the first round of whole-genome duplication with mutations in duplicated genes (isozymes) and alternative splicing of mRNA (isoforms). However, the abundance of the mRNA transcript variants is not necessarily reflected in the abundance of active forms of proteins. We have investigated the transcriptional profiles of two enzymes, aralkylamine N-acetyltransferase (AANAT: EC 2.3.1.87) and N-acetylserotonin O-methyltransferase (ASMT: EC 2.1.1.4), in the eyeball, brain, intestines, spleen, heart, liver, head kidney, gonads, and skin of the European flounder (Platichthys flesus). High-throughput next-generation sequencing technology NovaSeq6000 was used to generate 500M sequencing reads. These were then assembled and filtered producing 75k reliable contigs. Gene ontology (GO) terms were assigned to the majority of annotated contigs/unigenes based on the results of PFAM, PANTHER, UniProt, and InterPro protein database searches. BUSCOs statistics for metazoa, vertebrata, and actinopterygii databases showed that the reported transcriptome represents a high level of completeness. In this article, we show how to preselect transcripts encoding the active enzymes (isozymes or isoforms), using AANAT and ASMT in the European flounder as the examples. The data can be used as a tool to design the experiments as well as a basis for discussion of diversity of enzyme forms and their physiological relevance in teleosts.
Variance Component Decomposition for Growth Traits of the Bay Scallop (Argopecten irradians irradians)
Authors: Li Hengde , Wang Yangfan , Xing Qiang , Zeng Qifan , Zhao Liang , Zhang Yaqun , Hu Xiaoli , Bao Zhenmin
Published: February 2021

The bay scallop (Argopecten irradians irradians) is one of the most important shellfish species in China. Since their introduction into China, only mass selection has been used in bay scallop breeding. With its gradual expansion and shortage of mate selection, population homozygosity increased, and fitness decreased. To investigate the effects of inbreeding and provide reference for improving breeding strategies and mating management, the variance components of the growth traits of the bay scallop were decomposed with genomic relationship matrices. The results indicated that the genetic variations in shell height and length were mainly accounted for by the additive effects. The genetic variation in shell width was mainly caused by dominance or dominance-by-dominance epistasis. The genetic variation in body weight was accounted for by dominance. No significant directional dominances were detected for all growth traits. Cross-validation for genomic prediction showed that including insignificant inbreeding in the genomic prediction model is not necessary, and we suggest that the genomic prediction model should be optimized with both likelihood ratio tests and cross-validation before utilization in practice.
Insight Into the Strengthening Mechanism of the Al-Induced Cross-Linked Calcium Aluminosilicate Hydrate Gel: A Molecular Dynamics Study
Authors: Zhang Gaozhan , Li Yang , Yang Jun , Ding Qingjun , Sun Daosheng
Published: February 2021

Understanding and controlling the mechanical properties of calcium aluminosilicate hydrate (C-A-S-H) gel is essential to the performance improvement of cementing materials. This study characterizes the mechanical properties and failure mechanism of cross-linked C-A-S-H that have Al/Si ratios ranging from 0 to 0.20 by employing the reactive molecular dynamics simulation. In these constructed C-A-S-H models, the Al-induced cross-linking effect on the aluminosilicate chains is well reproduced. With the incorporation of aluminate species, layered C-S-H structure gradually transforms into three-dimensional C-A-S-H. The uniaxial tensile tests show that Al-induced cross-links significantly increase the cohesive force and stiffness of C-A-S-H along both y- and z-directions. In the C-A-S-H model with the Al/Si ratio equal to 0.2, in which all the bridging sites are cross-linked, the toughness along y-direction significantly improves the interlayer mechanical properties compared to those within the layers. The deformation mechanism of the C-A-S-H structure is also studied. Results show that the depolymerization of the calcium aluminosilicate skeleton is the main route to uptake the loading energy. Both the increase of y- and z-directional strength of the structure can be related to the increasing polymerization of aluminosilicate chains along that direction. This demonstrates the important role of aluminosilicate chains in resisting the external tensile loading. Besides, during the failure process in C-A-S-H elongation, the hydrolysis reactions of calcium silicate skeleton are caused by the coupling effect of loading and interlayer water “attack.” While the Al-O-Si bond breakage results from the protonation of bridging oxygen atom, the hydrolytic reaction of Si-O-Si is initiated by five-coordinate silicon formation. Both pathways weaken the bridging bond and thus result in the breakage of T-O-Si, where T is Al or Si.
Toward Machine-Learning-Based Decision Support in Diabetes Care: A Risk Stratification Study on Diabetic Foot Ulcer and Amputation
Authors: Schäfer Zeinab , Mathisen Andreas , Svendsen Katrine , Engberg Susanne , Rolighed Thomsen Trine , Kirketerp-Møller Klaus
Published: February 2021

Diabetes mellitus is associated with serious complications, with foot ulcers and amputation of limbs among the most debilitating consequences of late diagnosis and treatment of foot ulcers. Thus, prediction and on-time treatment of diabetic foot ulcers (DFU) are of great importance for improving and maintaining patients' quality of life and avoiding the consequent socio-economical burden of amputation. In this study, we use Danish national registry data to understand the risk factors of developing diabetic foot ulcers and amputation among patients with diabetes. We analyze the data of 246,705 patients with diabetes to assess some of the main risk factors for developing DFU/amputation. We study the socioeconomic information and past medical history of the patients. Factors, such as low family disposable income, cardiovascular disorders, peripheral artery, neuropathy, and chronic renal complications are among the important risk factors. Mental disorders and depression, albeit not as pronounced, still pose higher risks in comparison to the group of people without these complications. We further use machine learning techniques to assess the practical usefulness of such risk factors for predicting foot ulcers and amputation. Finally, we outline the limitations of working with registry data sources and explain potentials for combining additional public and private data sources in future applications of artificial intelligence (AI) to improve the prediction of diabetic foot ulcers and amputation.
The Role of Hyperbaric Oxygen Therapy in Pneumatosis Cystoides Intestinalis—A Scoping Review
Authors: Alpuim Costa Diogo , Modas Daniel Pedro , Vieira Branco João
Published: February 2021

Pneumatosis cystoides intestinalis (PCI) is characterized by gas-filled cysts within gastrointestinal tract wall from esophagus to rectum, with preferential involvement of large and small intestine. PCI is rare with an estimated incidence of 0.03 to 0–2% in general population. PCI can be distinguished into idiopathic (15%) or secondary (85%) and the clinical picture ranges from completely asymptomatic to life-threatening intraabdominal complications. Although etiology of PCI appears to be multifactorial, the exact pathophysiology is poorly understood and two main theories have been proposed (mechanical and bacterial). Over the last decades, an enormous therapeutic armamentarium was considered in PCI's management, including hyperbaric oxygen therapy (HBOT). Treatment comprises conservative treatment in mild cases to surgery in highly symptomatic and complicated PCI. In the late 70s, HBOT started to be used in selected cases of PCI not responding to conservative measures. Since then, several case reports, case series, and reviews have been published in the literature with variable outcomes. The overall response rate and complete response were 92.1% (n = 82/89) and 65.2% (n = 58/89), respectively, with a median follow-up of 7 months. Furthermore, HBOT is extremely safe, with few reported complications in the literature when used for PCI. Nevertheless, a randomized, controlled, and double-blind clinical trial is unlikely to occur given the rarity of PCI, logistical issues of HBOT, and methodological considerations related to adequate blinding with a sham-controlled group. HBOT in combination with personalized diet and antibiotics may be beneficial for moderate to severe PCI in patients with no indication for emergency exploratory laparotomy. The purpose of this article is to synthesize the existing data, analyse results of previous studies, identify gaps in knowledge, and discuss PCI' management, including the proposal of an algorithm, with a special focus on HBOT.
The COVID-19 Treatment Landscape: A South African Perspective on a Race Against Time
Authors: Hendricks Candice Laverne , Herd Candice , Nel Marcel , Tintinger Gregory , Pepper Michael Sean
Published: February 2021

The pandemic caused by SARS-CoV-2 has infected more than 94 million people worldwide (as of 17 January 2020). Severe disease is believed to be secondary to the cytokine release syndrome (CRS or “cytokine storm”) which causes local tissue damage as well as multi-organ dysfunction and thrombotic complications. Due to the high mortality rates in patients receiving invasive ventilation, practice has changed from “early-intubation” for acute respiratory distress syndrome (ARDS) to a trial of non-invasive ventilation (NIV) or high flow nasal cannula (HFNC) oxygen. Reports indicating the benefit of NIV and HFNC have been encouraging and have led to more than 20,000 such devices being manufactured and ready for roll-out in South Africa (SA) as of July 2020. The need to identify drugs with clear clinical benefits has led to an array of clinical trials, most of which are repurposing drugs for COVID-19. The treatment landscape reflects the need to target both the virus and its effects such as the CRS and thrombotic complications. Conflicting results have the potential to confuse the implementation of coordinated treatment strategies and guidelines. The purpose of this review is to address pertinent areas in the current literature on the available medical treatment options for COVID-19. Remdesivir, tocilizumab, and dexamethasone are some of the treatment options that have shown the most promise, but further randomized trials are required to particularly address timing and dosages to confidently create standardized protocols. For the SA population, two healthcare sectors exist. In the private sector, patients with medical insurance may have greater access to a wider range of treatment options than those in the public sector. The latter serves >80% of the population, and resource constraints require the identification of drugs with the most cost-effective use for the greatest number of affected patients.
Angiotensin-Converting Enzyme 2 Activator Ameliorates Severe Pulmonary Hypertension in a Rat Model of Left Pneumonectomy Combined With VEGF Inhibition
Authors: Chen I-Chen , Lin Jao-Yu , Liu Yi-Ching , Chai Chee-Yin , Yeh Jwu-Lai , Hsu Jong-Hau , Wu Bin-Nan , Dai Zen-Kong
Published: February 2021

Background: Pulmonary arterial hypertension (PAH) is a life-threatening and deteriorating disease with no promising therapy available currently due to its diversity and complexity. An imbalance between vasoconstriction and vasodilation has been proposed as the mechanism of PAH. Angiotensin-converting enzyme 2 (ACE2), which catalyzes the hydrolysis of the vasoconstrictor angiotensin (Ang) II into the vasodilator Ang-(1-7), has been shown to be an important regulator of blood pressure and cardiovascular diseases. Herein we hypothesized diminazene aceturate (DIZE), an ACE2 activator, could ameliorate the development of PAH and pulmonary vascular remodeling.

Methods: A murine model of PAH was established using left pneumonectomy (PNx) on day 0 followed by injection of a single dose of the VEGF receptor-2 inhibitor SU5416 (25 mg/kg) subcutaneously on day 1. All hemodynamic and biochemical measurements were done at the end of the study on day 42. Animals were divided into 4 groups (n = 6–8/group): (1) sham-operated group, (2) vehicle-treatment group (SuPNx42), (3) early treatment group (SuPNx42/DIZE1−42) with DIZE at 15 mg/kg/day, subcutaneously from day 1 to day 42, and (4) late treatment group (SuPNx42/DIZE29−42) with DIZE from days 29–42.

Results: In both the early and late treatment groups, DIZE significantly attenuated the mean pulmonary artery pressure, pulmonary arteriolar remodeling, and right ventricle brain natriuretic peptide (BNP), as well as reversed the overexpression of ACE while up-regulating the expression of Ang-(1-7) when compared with the vehicle-treatment group. In addition, the early treatment group also significantly decreased plasma BNP and increased the expression of eNOS.

Conclusions: ACE2 activator has therapeutic potentials for preventing and attenuating the development of PAH in an animal model of left pneumonectomy combined with VEGF inhibition. Activation of ACE2 may thus be a useful therapeutic strategy for the treatment of human PAH.
Case Report: Placental Maternal Vascular Malperfusion Affecting Late Fetal Development and Multiorgan Infection Caused by SARS-CoV-2 in Patient With PAI-1 4G/5G Polymorphism
Authors: JAK Behling , Zanirati Gabriele , Rodrigues Felipe V. F. , Grahl Matheus , Krimberg Felipe , Pinzetta Giulia , Borém Larissa , Savi Daniela , Machado Denise Cantarelli , Da Costa Jaderson Costa , Marinowic Daniel Rodrigo
Published: February 2021

Background: Pregnant women are susceptible to the novel coronavirus (SARS-CoV-2), and the consequences for the fetus are still uncertain. Here, we present a case of a pregnant woman with subclinical hypothyroidism and a plasminogen activator inhibitor type 1 (PAI-1) 4G/5G polymorphism who was infected with SARS-CoV-2 at the end of the third trimester of pregnancy, with unexpected evolution of death of the newborn 4 days postpartum.

Methods: Nested PCR was performed to detect the virus, followed by ssDNA sequencing.

Results: Transplacental transmission of SARS-CoV-2 can cause placental inflammation, ischemia, and neonatal viremia, with complications such as preterm labor and damage to the placental barrier in patients with PAI-1 4G/5G polymorphism.

Conclusion: We showed a newborn with several damages potentially caused due to the PAI-1 polymorphisms carried by the mother infected with SARS-CoV-2 during pregnancy.
Liraglutide Protects Nucleus Pulposus Cells Against High-Glucose Induced Apoptosis by Activating PI3K/Akt/ mTOR/Caspase-3 and PI3K/Akt/GSK3β/Caspase-3 Signaling Pathways
Authors: Yao Mingyan , Zhang Jing , Li Zhihong , Bai Xiaoliang , Ma Jinhui , Li Yukun
Published: February 2021

Background and Objective: Diabetes mellitus (DM) is reportedly a significant risk factor for intervertebral disc degeneration (IDD). Incretin system and particularly glucagon-like peptide 1 (GLP-1) because of its glucose-lowering effects has become an important target in therapeutic strategies of type 2 diabetes (T2D). Liraglutide is a GLP-1 receptor (GLP-1R) agonist with glucoregulatory and insulinotropic functions as well as regulatory functions on cell proliferation, differentiation, and apoptosis. However, little is known on the roles and signaling pathways of apoptosis protecting effects of liraglutide in IDD. This study aimed to investigate the potential protective effects of liraglutide against high glucose-induced apoptosis of nucleus pulposus cells (NPCs) and the possible involved signaling pathways.

Methods: The human NPCs were incubated with 100 nM liraglutide alone or in combination with LY294002 (PI3K inhibitor), rapamycin (mTOR inhibitor), and SB216763 (GSK3β inhibitor) in a high glucose culture for 48 h. The four groups were assessed further for apoptosis and genes expressions. The apoptotic effect was evaluated by flow cytometry and further confirmed by cell death detection enzyme-linked immunoassay plus (ELISAPLUS). The gene and protein expression levels were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting techniques. The results were comparatively assessed between the four groups.

Results: The results confirmed the presence of GLP-1R in the NPCs indicating that liraglutide inhibited the high glucose-induced apoptosis, which was blocked by silencing GLP-1R with siRNA. Moreover, liraglutide stimulated the phosphorylation of Akt, mTOR and GSK3β. Treatment with LY294002 significantly increased the apoptosis of NPCs and reduced the levels of their downstream substrates (p-AKT, p-mTOR, and p-GSK3β). Further assessments revealed that activation of mTOR and GSK3β was almost completely inhibited by rapamycin and SB216763, respectively, which significantly increased the caspase-3 levels.

Conclusion: Liraglutide could protect NPCs against high glucose-induced apoptosis by activating the PI3K/AKT/mTOR/caspase-3 and PI3K/AKT/GSK3β/caspase-3 signaling pathways.
Cesarean Section or Vaginal Delivery to Prevent Possible Vertical Transmission From a Pregnant Mother Confirmed With COVID-19 to a Neonate: A Systematic Review
Authors: Cai Jianghui , Tang Mi , Gao Yu , Zhang Hongxi , Yang Yanfeng , Zhang Dan , Wang Han , Liang Hua , Zhang Rui , Wu Bo
Published: February 2021

Background: The impact of delivery mode on the infection rates of Coronavirus disease 2019 (COVID-19) in the newborn remains unknown. We aimed to summarize the existing literature on COVID-19 infection during pregnancy to evaluate which mode of delivery is better for preventing possible vertical transmission from a pregnant mother confirmed with COVID-19 to a neonate.

Methods: We performed a comprehensive literature search of PubMed, Embase, Cochrane Library, Web of Science, Google Scholar, and the Chinese Biomedical Literature database (CBM) from 31 December 2019 to 18 June 2020. We applied no language restrictions. We screened abstracts for relevance, extracted data, and assessed the risk of bias in duplicate. We rated the certainty of evidence using the GRADE approach. The primary outcome was severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test positivity in neonates born to mothers with confirmed COVID-19 following different delivery modes. Secondary outcomes were neonatal deaths and maternal deaths. This study is registered with PROSPERO, CRD42020194049.

Results: Sixty-eight observational studies meeting inclusion criteria were included in the current study, with no randomized controlled trials. In total, information on the mode of delivery, detailed neonatal outcomes, and SARS-CoV-2 status were available for 1,019 pregnant women and 1,035 neonates. Six hundred and eighteen (59.71%) neonates were born through cesarean section and 417(40.29%) through vaginal delivery. Probable congenital SARS-CoV-2 infections were reported in 34/1,035 (3.29%) neonates. Of babies born vaginally, 9/417 (2.16%) were tested positive compared with 25/618 (4.05%) born by cesarean. Of babies born vaginally, 0/417 (0.00%) neonatal deaths were reported compared with 6/618 (0.97%) born by cesarean. Of women who delivered vaginally, 1/416 (0.24%) maternal deaths were reported compared with 11/603 (1.82%) delivered by cesarean. Two women died before delivery. Sensitivity analyses and subgroup analyses showed similar findings.

Conclusions: The rate of neonatal COVID-19 infection, neonatal deaths, and maternal deaths are no greater when the mother gave birth through vaginal delivery. Based on the evidence available, there is no sufficient evidence supporting that the cesarean section is better than vaginal delivery in preventing possible vertical transmission from a pregnant mother confirmed with COVID-19 to a neonate. The mode of birth should be individualized and based on disease severity and obstetric indications. Additional good-quality studies with comprehensive serial tests from multiple specimens are urgently needed.

Study registration: PROSPERO CRD42020194049.
On Naevi and Melanomas: Two Sides of the Same Coin?
Authors: Lee Katie J. , Janda Monika , Stark Mitchell S. , Sturm Richard A. , Soyer H. Peter
Published: February 2021

Benign naevi are closely linked to melanoma, as risk factors, simulators, or sites of melanoma formation. There is a heavy genetic overlap between the two lesions, a shared environmental influence of ultraviolet radiation, and many similar cellular features, yet naevi remain locally situated while melanomas spread from their primary site and may progress systemically to distal organs. Untangling the overlapping contributors and predictors of naevi and melanoma is an ongoing area of research and should eventually lead to more personalized prevention and treatment strategies, through the development of melanoma risk stratification tools and early detection of evolving melanomas. This will be achieved through a range of complementary strategies: risk-adjusted primary prevention counseling; the use of lesion imaging technologies such as sequential 3D total body photography and consumer-performed lesion imaging; artificial intelligence deep phenotyping and clinical assistance; a better understanding of genetic drivers of malignancy, risk variants, clinical genetics, and polygenic effects; and the interplay between genetics, phenotype and the environment.
Distribution Patterns (7B Rule) and Characteristics of Large Congenital Melanocytic Nevi: A Retrospective Cohort Study in China
Authors: Wang Huijing , Wang Wei , Lu Jun , Gu Yihui , Cui Xiwei , Wei Chengjiang , Ren Jieyi , Gu Bin , Wang Zhichao , Li Qingfeng
Published: February 2021

Large congenital melanocytic nevus has a high risk of malignancy. However, few studies have summarized its characteristics, treatments, outcomes and malignancy incidence in Chinese patients. This paper reviews a retrospective cohort study evaluating 1,171 patients from Shanghai Ninth People's Hospital between 1 January 1989 and 31 August 2019 using electronic medical records and phone calls to collect clinical and pathological data in which 133 patients were diagnosed with a large congenital melanocytic nevus. Three patients relapsed, and none developed melanoma among the qualified patients. Besides, a new “7B” rule for distribution patterns of large congenital melanocytic nevi was proposed, including bonce, bolero, back, bathing trunk, breast/belly, body extremity, and body. The most common distribution pattern of large congenital melanocytic nevi was bonce, and all blue nevi distributed as bonce. Statistical analysis showed a significant difference (P = 0.0249) in the “7B” patterns between the melanocytic nevus and the neuronevus. In conclusion, the malignancy rate of large congenital melanocytic nevi is much lower in China than in other regions and people of other races. The pathology of large congenital melanocytic nevus may decide its “7B” distribution pattern.
New Insights Into the Physiopathology of COVID-19: SARS-CoV-2-Associated Gastrointestinal Illness
Authors: Devaux Christian A. , Lagier Jean-Christophe , Raoult Didier
Published: February 2021

Although SARS-CoV-2 is considered a lung-tropic virus that infects the respiratory tract through binding to the ACE2 cell-surface molecules present on alveolar lungs epithelial cells, gastrointestinal symptoms have been frequently reported in COVID-19 patients. What can be considered an apparent paradox is that these symptoms (e.g., diarrhea), sometimes precede the development of respiratory tract illness as if the breathing apparatus was not its first target during viral dissemination. Recently, evidence was reported that the gut is an active site of replication for SARS-CoV-2. This replication mainly occurs in mature enterocytes expressing the ACE2 viral receptor and TMPRSS4 protease. In this review we question how SARS-CoV-2 can cause intestinal disturbances, whether there are pneumocyte-tropic, enterocyte-tropic and/or dual tropic strains of SARS-CoV-2. We examine two major models: first, that of a virus directly causing damage locally (e.g., by inducing apoptosis of infected enterocytes); secondly, that of indirect effect of the virus (e.g., by inducing changes in the composition of the gut microbiota followed by the induction of an inflammatory process), and suggest that both situations probably occur simultaneously in COVID-19 patients. We eventually discuss the consequences of the virus replication in brush border of intestine on long-distance damages affecting other tissues/organs, particularly lungs.
Decision Tree With Only Two Musculoskeletal Sites to Diagnose Polymyalgia Rheumatica Using [18F]FDG PET-CT
Authors: Flaus Anthime , Amat Julie , Prevot Nathalie , Olagne Louis , Descamps Lucie , Bouvet Clément , Barres Bertrand , Valla Clémence , Mathieu Sylvain , Andre Marc , Soubrier Martin , Merlin Charles , Kelly Antony , Chanchou Marion , Cachin Florent
Published: February 2021

Introduction: The aim of this study was to find the best ordered combination of two FDG positive musculoskeletal sites with a machine learning algorithm to diagnose polymyalgia rheumatica (PMR) vs. other rheumatisms in a cohort of patients with inflammatory rheumatisms.

Methods: This retrospective study included 140 patients who underwent [18F]FDG PET-CT and whose final diagnosis was inflammatory rheumatism. The cohort was randomized, stratified on the final diagnosis into a training and a validation cohort. FDG uptake of 17 musculoskeletal sites was evaluated visually and set positive if uptake was at least equal to that of the liver. A decision tree classifier was trained and validated to find the best combination of two positives sites to diagnose PMR. Diagnosis performances were measured first, for each musculoskeletal site, secondly for combination of two positive sites and thirdly using the decision tree created with machine learning.

Results: 55 patients with PMR and 85 patients with other inflammatory rheumatisms were included. Musculoskeletal sites, used either individually or in combination of two, were highly imbalanced to diagnose PMR with a high specificity and a low sensitivity. The machine learning algorithm identified an optimal ordered combination of two sites to diagnose PMR. This required a positive interspinous bursa or, if negative, a positive trochanteric bursa. Following the decision tree, sensitivity and specificity to diagnose PMR were respectively 73.2 and 87.5% in the training cohort and 78.6 and 80.1% in the validation cohort.

Conclusion: Ordered combination of two visually positive sites leads to PMR diagnosis with an accurate sensitivity and specificity vs. other rheumatisms in a large cohort of patients with inflammatory rheumatisms.
Evolutionary Dynamics and Dissemination Pattern of the SARS-CoV-2 Lineage B.1.1.33 During the Early Pandemic Phase in Brazil
Authors: Resende Paola Cristina , Delatorre Edson , Gräf Tiago , Mir Daiana , Motta Fernando Couto , Appolinario Luciana Reis , Paixão Anna Carolina Dias da , Mendonça Ana Carolina da Fonseca , Ogrzewalska Maria , Caetano Braulia , Wallau Gabriel Luz , Docena Cássia , Santos Mirleide Cordeiro dos , de Almeida Ferreira Jessylene , Sousa Junior Edivaldo Costa , Silva Sandro Patroca da , Fernandes Sandra Bianchini , Vianna Lucas Alves , Souza Larissa da Costa , Ferro Jean F. G. , Nardy Vanessa B. , Santos Cliomar A. , Riediger Irina , do Carmo Debur Maria , Croda Júlio , Oliveira Wanderson K. , Abreu André , Bello Gonzalo , Siqueira Marilda M.
Published: February 2021

A previous study demonstrates that most of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Brazilian strains fell in three local clades that were introduced from Europe around late February 2020. Here we investigated in more detail the origin of the major and most widely disseminated SARS-CoV-2 Brazilian lineage B.1.1.33. We recovered 190 whole viral genomes collected from 13 Brazilian states from February 29 to April 31, 2020 and combined them with other B.1.1 genomes collected globally. Our genomic survey confirms that lineage B.1.1.33 is responsible for a variable fraction of the community viral transmissions in Brazilian states, ranging from 2% of all SARS-CoV-2 genomes from Pernambuco to 80% of those from Rio de Janeiro. We detected a moderate prevalence (5–18%) of lineage B.1.1.33 in some South American countries and a very low prevalence (<1%) in North America, Europe, and Oceania. Our study reveals that lineage B.1.1.33 evolved from an ancestral clade, here designated B.1.1.33-like, that carries one of the two B.1.1.33 synapomorphic mutations. The B.1.1.33-like lineage may have been introduced from Europe or arose in Brazil in early February 2020 and a few weeks later gave origin to the lineage B.1.1.33. These SARS-CoV-2 lineages probably circulated during February 2020 and reached all Brazilian regions and multiple countries around the world by mid-March, before the implementation of air travel restrictions in Brazil. Our phylodynamic analysis also indicates that public health interventions were partially effective to control the expansion of lineage B.1.1.33 in Rio de Janeiro because its median effective reproductive number (Re) was drastically reduced by about 66% during March 2020, but failed to bring it to below one. Continuous genomic surveillance of lineage B.1.1.33 might provide valuable information about epidemic dynamics and the effectiveness of public health interventions in some Brazilian states.
Trace Metal Contamination Impacts Predicted Functions More Than Structure of Marine Prokaryotic Biofilm Communities in an Anthropized Coastal Area
Authors: Coclet Clément , Garnier Cédric , D’Onofrio Sébastien , Durrieu Gaël , Pasero Emilie , Le Poupon Christophe , Omanović Dario , Mullot Jean-Ulrich , Misson Benjamin , Briand Jean-François
Published: February 2021

Trace metal (TM) contamination in marine coastal areas is a worldwide threat for aquatic communities. However, little is known about the influence of a multi-chemical contamination on both marine biofilm communities’ structure and functioning. To determine how TM contamination potentially impacted microbial biofilms’ structure and their functions, polycarbonate (PC) plates were immerged in both surface and bottom of the seawater column, at five sites, along strong TM contamination gradients, in Toulon Bay. The PC plates were incubated during 4 weeks to enable colonization by biofilm-forming microorganisms on artificial surfaces. Biofilms from the PC plates, as well as surrounding seawaters, were collected and analyzed by 16S rRNA amplicon gene sequencing to describe prokaryotic community diversity, structure and functions, and to determine the relationships between bacterioplankton and biofilm communities. Our results showed that prokaryotic biofilm structure was not significantly affected by the measured environmental variables, while the functional profiles of biofilms were significantly impacted by Cu, Mn, Zn, and salinity. Biofilms from the contaminated sites were dominated by tolerant taxa to contaminants and specialized hydrocarbon-degrading microorganisms. Functions related to major xenobiotics biodegradation and metabolism, such as methane metabolism, degradation of aromatic compounds, and benzoate degradation, as well as functions involved in quorum sensing signaling, extracellular polymeric substances (EPS) matrix, and biofilm formation were significantly over-represented in the contaminated site relative to the uncontaminated one. Taken together, our results suggest that biofilms may be able to survive to strong multi-chemical contamination because of the presence of tolerant taxa in biofilms, as well as the functional responses of biofilm communities. Moreover, biofilm communities exhibited significant variations of structure and functional profiles along the seawater column, potentially explained by the contribution of taxa from surrounding sediments. Finally, we found that both structure and functions were significantly distinct between the biofilm and bacterioplankton, highlighting major differences between the both lifestyles, and the divergence of their responses facing to a multi-chemical contamination.
E. coli Is a Poor End-Product Criterion for Assessing the General Microbial Risk Posed From Consuming Norovirus Contaminated Shellfish
Authors: Sharp Jasmine H. , Clements Katie , Diggens Mallory , McDonald James E. , Malham Shelagh K. , Jones Davey L.
Published: February 2021

The fecal indicator organism (FIO) Escherichia coli is frequently used as a general indicator of sewage contamination and for evaluating the success of shellfish cleaning (depuration) processes. To evaluate the robustness of this approach, the accumulation, retention, and depuration of non-pathogenic E. coli, pathogenic E. coli O157:H7 and norovirus GII (NoV GII) RNA were evaluated using a combination of culture-based (E. coli) and molecular methods (E. coli, NoV GII) after exposure of mussels (Mytilus edulis) to water contaminated with human feces. We simulated water contamination after a point-source release from a combined sewer overflow (CSO) where untreated wastewater is released directly into the coastal zone. All three microbiological indicators accumulated rapidly in the mussels, reaching close to maximum concentration within 3 h of exposure, demonstrating that short CSO discharges pose an immediate threat to shellfish harvesting areas. Depuration (72 h) in clean water proved partially successful at removing both pathogenic and non-pathogenic E. coli from shellfish tissue, but failed to eradicate NoV GII RNA. We conclude that current EU standards for evaluating microbiological risk in shellfish are inadequate for protecting consumers against exposure to human norovirus GII found in polluted marine waters.
A Molecular Interaction Map of Klebsiella pneumoniae and Its Human Host Reveals Potential Mechanisms of Host Cell Subversion
Authors: Saha Deeya , Kundu Sudip
Published: February 2021

Klebsiella pneumoniae is a leading cause of pneumonia and septicemia across the world. The rapid emergence of multidrug-resistant K. pneumoniae strains necessitates the discovery of effective drugs against this notorious pathogen. However, there is a dearth of knowledge on the mechanisms by which this deadly pathogen subverts host cellular machinery. To fill this knowledge gap, our study attempts to identify the potential mechanisms of host cell subversion by building a K. pneumoniae–human interactome based on rigorous computational methodology. The putative host targets inferred from the predicted interactome were found to be functionally enriched in the host’s immune surveillance system and allied functions like apoptosis, hypoxia, etc. A multifunctionality-based scoring system revealed P53 as the most multifunctional protein among host targets accompanied by HIF1A and STAT1. Moreover, mining of host protein–protein interaction (PPI) network revealed that host targets interact among themselves to form a network (TTPPI), where P53 and CDC5L occupy a central position. The TTPPI is composed of several inter complex interactions which indicate that K. pneumoniae might disrupt functional coordination between these protein complexes through targeting of P53 and CDC5L. Furthermore, we identified four pivotal K. pneumoniae-targeted transcription factors (TTFs) that are part of TTPPI and are involved in generating host’s transcriptional response to K. pneumoniae-mediated sepsis. In a nutshell, our study identifies some of the pivotal molecular targets of K. pneumoniae which primarily correlate to the physiological response of host during K. pneumoniae-mediated sepsis.
Mobile Carbapenemase Genes in Pseudomonas aeruginosa
Authors: Yoon Eun-Jeong , Jeong Seok Hoon
Published: February 2021

Carbapenem-resistantPseudomonas aeruginosais one of the major concerns in clinical settings impelling a great challenge to antimicrobial therapy for patients with infections caused by the pathogen. While membrane permeability, together with derepression of the intrinsic beta-lactamase gene, is the global prevailing mechanism of carbapenem resistance inP. aeruginosa, the acquired genes for carbapenemases need special attention because horizontal gene transfer through mobile genetic elements, such as integrons, transposons, plasmids, and integrative and conjugative elements, could accelerate the dissemination of the carbapenem-resistantP. aeruginosa. This review aimed to illustrate epidemiologically the carbapenem resistance inP. aeruginosa, including the resistance rates worldwide and the carbapenemase-encoding genes along with the mobile genetic elements responsible for the horizontal dissemination of the drug resistance determinants. Moreover, the modular mobile elements including the carbapenemase-encoding gene, also known as theP. aeruginosaresistance islands, are scrutinized mostly for their structures.
Anthropogenic and Environmental Constraints on the Microbial Methane Cycle in Coastal Sediments
Authors: Wallenius Anna J. , Dalcin Martins Paula , Slomp Caroline P. , Jetten Mike S. M.
Published: February 2021

Large amounts of methane, a potent greenhouse gas, are produced in anoxic sediments by methanogenic archaea. Nonetheless, over 90% of the produced methane is oxidized via sulfate-dependent anaerobic oxidation of methane (S-AOM) in the sulfate-methane transition zone (SMTZ) by consortia of anaerobic methane-oxidizing archaea (ANME) and sulfate-reducing bacteria (SRB). Coastal systems account for the majority of total marine methane emissions and typically have lower sulfate concentrations, hence S-AOM is less significant. However, alternative electron acceptors such as metal oxides or nitrate could be used for AOM instead of sulfate. The availability of electron acceptors is determined by the redox zonation in the sediment, which may vary due to changes in oxygen availability and the type and rate of organic matter inputs. Additionally, eutrophication and climate change can affect the microbiome, biogeochemical zonation, and methane cycling in coastal sediments. This review summarizes the current knowledge on the processes and microorganisms involved in methane cycling in coastal sediments and the factors influencing methane emissions from these systems. In eutrophic coastal areas, organic matter inputs are a key driver of bottom water hypoxia. Global warming can reduce the solubility of oxygen in surface waters, enhancing water column stratification, increasing primary production, and favoring methanogenesis. ANME are notoriously slow growers and may not be able to effectively oxidize methane upon rapid sedimentation and shoaling of the SMTZ. In such settings, ANME-2d (Methanoperedenaceae) and ANME-2a may couple iron- and/or manganese reduction to AOM, while ANME-2d and NC10 bacteria (Methylomirabilota) could couple AOM to nitrate or nitrite reduction. Ultimately, methane may be oxidized by aerobic methanotrophs in the upper millimeters of the sediment or in the water column. The role of these processes in mitigating methane emissions from eutrophic coastal sediments, including the exact pathways and microorganisms involved, are still underexplored, and factors controlling these processes are unclear. Further studies are needed in order to understand the factors driving methane-cycling pathways and to identify the responsible microorganisms. Integration of the knowledge on microbial pathways and geochemical processes is expected to lead to more accurate predictions of methane emissions from coastal zones in the future.