bluuebunny/crossref_metadata_2025 huggingface dataset:
Humanized Anti-CD19 CAR-T Cell Therapy and Sequential Allogeneic Hematopoietic Stem Cell Transplantation Achieved Long-Term Survival in Refractory and Relapsed B Lymphocytic Leukemia: A Retrospective Study of CAR-T Cell Therapy
Authors: Chen Wei , Ma Yuhan , Shen Ziyuan , Chen Huimin , Ma Ruixue , Yan Dongmei , Shi Ming , Wang Xiangmin , Song Xuguang , Sun Cai , Cao Jiang , Cheng Hai , Zhu Feng , Sun Haiying , Li Depeng , Li Zhenyu , Zheng Junnian , Xu Kailin , Sang Wei
Published: October 2021

Early response could be obtained in most patients with relapsed or refractory B cell lymphoblastic leukemia (R/R B-ALL) treated with chimeric antigen receptor T-cell (CAR-T) therapy, but relapse occurs in some patients. There is no consensus on treatment strategy post CAR-T cell therapy. In this retrospective study of humanized CD19-targeted CAR-T cell (hCART19s) therapy for R/R B-ALL, we analyzed the patients treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT) or received a second hCART19s infusion, and summarized their efficacy and safety. We retrospectively studied 28 R/R B-ALL patients treated with hCART19s in the Affiliated Hospital of Xuzhou Medical University from 2016 to 2020. After the first hCART19s infusion, 10 patients received allo-HSCT (CART+HSCT group), 7 patients received a second hCART19s infusion (CART2 group), and 11 patients did not receive HSCT or a second hCART19s infusion (CART1 group). The safety, efficacy, and long-term survival were analyzed. Of the 28 patients who received hCART19s treatment, 1 patient could not be evaluated for efficacy, and 25 (92.6%) achieved complete remission (CR) with 20 (74.7%) achieving minimal residual disease (MRD) negativity. Seven (25%) patients experienced grade 3-4 CRS, and one died from grade 5 CRS. No patient experienced ≥3 grade ICANS. The incidence of second CR is higher in the CART+HSCT group compared to the CART2 group (100% vs. 42.9%, p=0.015). The median follow-up time was 1,240 days (range: 709–1,770). Significantly longer overall survival (OS) and leukemia-free survival (LFS) were achieved in the CART+HSCT group (median OS and LFS: not reached, p=0.006 and 0.001, respectively) compared to the CART2 group (median OS: 482; median LFS: 189) and the CART1 group (median OS: 236; median LFS: 35). In the CART+HSCT group, the incidence of acute graft-versus-host disease (aGVHD) was 30% (3/10), and transplantation-related mortality was 30% (3/10). No chronic GVHD occurred. Multivariate analysis results showed that blasts ≥ 20% in the bone marrow and MRD ≥ 65.6% are independent factors for inferior OS and LFS, respectively, while receiving allo-HSCT is an independent factor associated with both longer OS and LFS. In conclusion, early allo-HSCT after CAR-T therapy can achieve long-term efficacy, and the adverse events are controllable.
Anti-BCMA CAR-T Cell Therapy in Relapsed/Refractory Multiple Myeloma Patients With Extramedullary Disease: A Single Center Analysis of Two Clinical Trials
Authors: Que Yimei , Xu Menglei , Xu Yanjie , Almeida Varlene Daniela Fernandes , Zhu Li , Wang Zhiqiong , Wang Ying , Liu Xian , Jiang Lijun , Wang Di , Li Chunrui , Zhou Jianfeng
Published: October 2021

Background

The prognosis of relapsed/refractory multiple myeloma (RRMM) patients with the extramedullary disease was significantly poor. Extramedullary multiple myeloma (EMM) patients gained limited benefits from traditional drugs. Anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy seems to be a promising approach to treat RRMM patients. However, very few clinical studies are designed for EMM. Our study aimed to compare and assess the safety, efficacy, and pharmacokinetics of anti-BCMA CAR-T cell therapy in EMM and non-EMM.

Methods

The results from published anti-BCMA CAR-T clinical trials, in which raw data of EMM patients were available, were reviewed and summarized. Two trials conducted in our clinical centers were analyzed and presented with detailed data.

Results

According to published anti-BCMA CAR-T clinical trials, the ORR of EMM ranged from 57% to 100%, with the complete remission (CR) rate of 29% to 60%. Between February 22, 2017, and September 26, 2019, a total of 61 subjects (EMM 25; non-EMM 36) received anti-BCMA CAR-T cell infusion. The data-cutoff date was April 1, 2021. There were no statistical differences between EMM and non-EMM groups in adverse events (AEs), including cytokine release syndrome (CRS). The most common AEs of grade ≥ 3 in both groups were hematologic toxicities. There was no significant difference in the objective response rate (ORR) and ≥ complete remission (CR) rate between both groups. However, the ≥ CR rate of the EMM group was lower than the non-EMM group receiving the fully human anti-BCMA CAR-T cell therapy (p = 0.026). The median progression-free survival (PFS) for EMM and the non-EMM group was 121 days and 361 days, respectively (p = 0.001). The median overall survival (OS) for EMM and the non-EMM group was 248 days and 1024 days, respectively (p = 0.005). The Cmax and AUC0-28d for EMM group were lower than non-EMM group (Cmax, p = 0.016; AUC0-28d, p = 0.016). Extramedullary disease was an independent prognostic risk factor for PFS (hazard ratio, 2.576; 95% CI, 1.343 to 4.941; p = 0.004) and OS (hazard ratio, 2.312; 95% CI, 1.165 to 4.592; p = 0.017) in RRMM patients receiving anti-BCMA CAR-T cell therapy.

Conclusions

Based on our results, EMM patients could benefit from the two anti-BCMA CAR products, although they had a shorter PFS and OS compared with non-EMM patients.

Clinical Trial Registration

http://www.chictr.org.cn, identifier ChiCTR-OPC-16009113 and ChiCTR1800018137.
T-Cell Metabolism in Graft Versus Host Disease
Authors: Karl Franziska , Hudecek Michael , Berberich-Siebelt Friederike , Mackensen Andreas , Mougiakakos Dimitrios
Published: October 2021

Allogeneic-hematopoietic stem cell transplantation (allo-HSCT) represents the only curative treatment option for numerous hematological malignancies. Elimination of malignant cells depends on the T-cells’ Graft-versus-Tumor (GvT) effect. However, Graft-versus-Host-Disease (GvHD), often co-occurring with GvT, remains an obstacle for therapeutic efficacy. Hence, approaches, which selectively alleviate GvHD without compromising GvT activity, are needed. As already explored for autoimmune and inflammatory disorders, immuno-metabolic interventions pose a promising option to address this unmet challenge. Being embedded in a complex regulatory framework, immunological and metabolic pathways are closely intertwined, which is demonstrated by metabolic reprograming of T-cells upon activation or differentiation. In this review, current knowledge on the immuno-metabolic signature of GvHD-driving T-cells is summarized and approaches to metabolically interfere are outlined. Furthermore, we address the metabolic impact of standard medications for GvHD treatment and prophylaxis, which, in conjunction with the immuno-metabolic profile of alloreactive T-cells, could allow more targeted interventions in the future.
Optimizing the Clinical Impact of CAR-T Cell Therapy in B-Cell Acute Lymphoblastic Leukemia: Looking Back While Moving Forward
Authors: Safarzadeh Kozani Pouya , Safarzadeh Kozani Pooria , Rahbarizadeh Fatemeh
Published: October 2021

Chimeric antigen receptor T-cell (CAR-T) therapy has been successful in creating extraordinary clinical outcomes in the treatment of hematologic malignancies including relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). With several FDA approvals, CAR-T therapy is recognized as an alternative treatment option for particular patients with certain conditions of B-ALL, diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, or multiple myeloma. However, CAR-T therapy for B-ALL can be surrounded by challenges such as various adverse events including the life-threatening cytokine release syndrome (CRS) and neurotoxicity, B-cell aplasia-associated hypogammaglobulinemia and agammaglobulinemia, and the alloreactivity of allogeneic CAR-Ts. Furthermore, recent advances such as improvements in media design, the reduction of ex vivo culturing duration, and other phenotype-determining factors can still create room for a more effective CAR-T therapy in R/R B-ALL. Herein, we review preclinical and clinical strategies with a focus on novel studies aiming to address the mentioned hurdles and stepping further towards a milestone in CAR-T therapy of B-ALL.
Self-Organizing Maps for Cellular In Silico Staining and Cell Substate Classification
Authors: Yuan Edwin , Matusiak Magdalena , Sirinukunwattana Korsuk , Varma Sushama , Kidziński Łukasz , West Robert
Published: October 2021

Cellular composition and structural organization of cells in the tissue determine effective antitumor response and can predict patient outcome and therapy response. Here we present Seg-SOM, a method for dimensionality reduction of cell morphology in H&E-stained tissue images. Seg-SOM resolves cellular tissue heterogeneity and reveals complex tissue architecture. We leverage a self-organizing map (SOM) artificial neural network to group cells based on morphological features like shape and size. Seg-SOM allows for cell segmentation, systematic classification, and in silico cell labeling. We apply the Seg-SOM to a dataset of breast cancer progression images and find that clustering of SOM classes reveals groups of cells corresponding to fibroblasts, epithelial cells, and lymphocytes. We show that labeling the Lymphocyte SOM class on the breast tissue images accurately estimates lymphocytic infiltration. We further demonstrate how to use Seq-SOM in combination with non-negative matrix factorization to statistically describe the interaction of cell subtypes and use the interaction information as highly interpretable features for a histological classifier. Our work provides a framework for use of SOM in human pathology to resolve cellular composition of complex human tissues. We provide a python implementation and an easy-to-use docker deployment, enabling researchers to effortlessly featurize digitalized H&E-stained tissue.
The Impact of Immune Microenvironment on the Prognosis of Pancreatic Ductal Adenocarcinoma Based on Multi-Omics Analysis
Authors: Yang Bing , Zhou Mingyao , Wu Yunzi , Ma Yuanyuan , Tan Qin , Yuan Wei , Ma Jie
Published: October 2021

Pancreatic ductal adenocarcinoma (PDAC) is a malignant tumor characterized by rapid progression, early metastasis, high recurrence, and limited responsiveness to conventional therapies. The 5-year survival rate of PDAC is extremely low (<8%), which lacks effective prognostic evaluation indicators. In this study, we used xCell to analyze infiltrating immune cells in a tumor and through the univariate and multivariate Cox analyses screened out two prognosis-related immune cells, CD4+TN and common lymphoid progenitor (CLP), which were used to construct a Cox model and figure out the risk-score. It was found that the constructed model could greatly improve the sensitivity of prognostic evaluation, that the higher the risk-score, the worse the prognosis. In addition, the risk-score could also identify molecular subtypes with poor prognosis and immunotherapy sensitivity. Through transcriptome and whole-exome sequencing analysis of PDAC dataset from The Cancer Genome Atlas (TCGA), it was found that copy number deletion and low expression of CCL19 might be crucial factors to affect the risk-score. Lastly, validation of the above findings was confirmed not only in Gene Expression Omnibus (GEO) datasets but also in our PDAC patient samples, Peking2020 cohort.
Spatial Profiles of Intratumoral PD-1+ Helper T Cells Predict Prognosis in Head and Neck Squamous Cell Carcinoma
Authors: Yoshimura Kanako , Tsujikawa Takahiro , Mitsuda Junichi , Ogi Hiroshi , Saburi Sumiyo , Ohmura Gaku , Arai Akihito , Shibata Saya , Thibault Guillaume , Chang Young Hwan , Clayburgh Daniel R. , Yasukawa Satoru , Miyagawa-Hayashino Aya , Konishi Eiichi , Itoh Kyoko , Coussens Lisa M. , Hirano Shigeru
Published: October 2021

Background

Functional interactions between immune cells and neoplastic cells in the tumor immune microenvironment have been actively pursued for both biomarker discovery for patient stratification, as well as therapeutic anti-cancer targets to improve clinical outcomes. Although accumulating evidence indicates that intratumoral infiltration of immune cells has prognostic significance, limited information is available on the spatial infiltration patterns of immune cells within intratumoral regions. This study aimed to understand the intratumoral heterogeneity and spatial distribution of immune cell infiltrates associated with cell phenotypes and prognosis in head and neck squamous cell carcinoma (HNSCC).

Methods

A total of 88 specimens of oropharyngeal squamous cell carcinoma, categorized into discovery (n = 38) and validation cohorts (n = 51), were analyzed for immune contexture by multiplexed immunohistochemistry (IHC) and image cytometry-based quantification. Tissue segmentation was performed according to a mathematical morphological approach using neoplastic cell IHC images to dissect intratumoral regions into tumor cell nests versus intratumoral stroma.

Results

Tissue segmentation revealed heterogeneity in intratumoral T cells, varying from tumor cell nest-polarized to intratumoral stroma-polarized distributions. Leukocyte composition analysis revealed higher ratios of TH1/TH2 in tumor cell nests with higher percentages of helper T cells, B cells, and CD66b+granulocytes within intratumoral stroma. A discovery and validation approach revealed a high density of programmed death receptor-1 (PD-1)+helper T cells in tumor cell nests as a negative prognostic factor for short overall survival. CD163+tumor-associated macrophages (TAM) provided the strongest correlation with PD-1+helper T cells, and cases with a high density of PD-1+helper T cells and CD163+TAM had a significantly shorter overall survival than other cases.

Conclusion

This study reveals the significance of analyzing intratumoral cell nests and reports that an immune microenvironment with a high density of PD-1+helper T cells in tumoral cell nests is a poor prognostic factor for HNSCC.
Dysregulated Inflammation During Obesity: Driving Disease Severity in Influenza Virus and SARS-CoV-2 Infections
Authors: Hulme Katina D. , Noye Ellesandra C. , Short Kirsty R. , Labzin Larisa I.
Published: October 2021

Acute inflammation is a critical host defense response during viral infection. When dysregulated, inflammation drives immunopathology and tissue damage. Excessive, damaging inflammation is a hallmark of both pandemic influenza A virus (IAV) infections and Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) infections. Chronic, low-grade inflammation is also a feature of obesity. In recent years, obesity has been recognized as a growing pandemic with significant mortality and associated costs. Obesity is also an independent risk factor for increased disease severity and death during both IAV and SARS-CoV-2 infection. This review focuses on the effect of obesity on the inflammatory response in the context of viral respiratory infections and how this leads to increased viral pathology. Here, we will review the fundamentals of inflammation, how it is initiated in IAV and SARS-CoV-2 infection and its link to disease severity. We will examine how obesity drives chronic inflammation and trained immunity and how these impact the immune response to IAV and SARS-CoV-2. Finally, we review both medical and non-medical interventions for obesity, how they impact on the inflammatory response and how they could be used to prevent disease severity in obese patients. As projections of global obesity numbers show no sign of slowing down, future pandemic preparedness will require us to consider the metabolic health of the population. Furthermore, if weight-loss alone is insufficient to reduce the risk of increased respiratory virus-related mortality, closer attention must be paid to a patient’s history of health, and new therapeutic options identified.
Multifunctional, TNF-α and IFN-γ-Secreting CD4 and CD8 T Cells and CD8High T Cells Are Associated With the Cure of Human Visceral Leishmaniasis
Authors: Rodrigues Lorranny Santana , Barreto Aline Silva , Bomfim Lays Gisele Santos , Gomes Marcos Couto , Ferreira Nathalia Luisa Carlos , da Cruz Geydson Silveira , Magalhães Lucas Sousa , de Jesus Amélia Ribeiro , Palatnik-de-Sousa Clarisa B. , Corrêa Cristiane Bani , de Almeida Roque Pacheco
Published: October 2021

Visceral leishmaniasis (VL) is a chronic and often fatal disease caused by protozoans of the genus Leishmania that affects millions of people worldwide. Patients with symptomatic VL have an impaired anti-Leishmania-specific CD4+ T-cell response, which is reversed after clinical cure. In contrast, the quality of the CD4+ and CD8+ T-cell responses involved in resistance and/or cure of VL relies on the capability of these cells to activate polyfunctional and memory responses, which are associated with the simultaneous production of three cytokines: IFN-γ, IL-2, and TNF-α. Models for the development of CD4 and CD8 T-cell quality in memory and protection to leishmaniasis have been described previously. We aimed to assess the functionality of the T cells involved in the recovery of the immune suppression throughout the VL treatment. Therefore, we cultured peripheral blood mononuclear cells (PBMCs) from VL patients and healthy controls in vitro with soluble Leishmania antigen (SLA). Cell surface markers and intracellular cytokine production were determined on days 7, 14, 21, 30, 60, 90, and 180 after the beginning of chemotherapy. We observed that the frequencies of CD4+TNF-α+IFN-γ+ and the multifunctional CD4+IL-2+TNF-α+IFN-γ+, together with CD4+TNF-α+ and CD4+IFN-γ+ T cells, increased throughout and at the end of the treatment, respectively. In addition, enhanced frequencies of CD8+IL-2+TNF-α+IFN-γ+ and CD8+TNF-α+IFN-γ T cells were also relevant in the healing process. Noteworthy, the frequencies of the CD4+ and CD8 central-memory T cells, which produce IL-2, TNF-α, and IFN-γ and ensure the memory response against parasite reinfection, are significantly enhanced in cured patients. In addition, the subset of the non-functional CD8Low population is predominant in VL untreated patients and decreases along the chemotherapy treatment. In contrast, a CD8High subset increased towards the cure. Furthermore, the cure due to treatment with meglumine antimoniate or with liposomal amphotericin B was associated with the recovery of the T-cell immune responses. We described the evolution and participation of functional T cells during the treatment of patients with VL. Our results disclosed that the clinical improvement of patients is significantly associated with the participation of the CD4+ and CD8+ cytokine-secreting T cells.
Erosion Dynamics of Cultivated Kelp, Saccharina latissima, and Implications for Environmental Management and Carbon Sequestration
Authors: Fieler Reinhold , Greenacre Michael , Matsson Sanna , Neves Luiza , Forbord Silje , Hancke Kasper
Published: October 2021

A growing trend of interest for the cultivation of kelp is driven by predictions for high global demands of important commodities, which require the development of alternative supplies of natural resources. In this study the dynamics of loss of biomass from cultivated Saccharina latissima were studied from February to August 2018 at two kelp farms in Northern (69°45.26′N/019°02.18′E) and in Mid-Norway (63°42.28′N/08°52.23′E). Kelp fronds at each farm were individually followed throughout the growing season. Sectional regression was applied for conversion of measured frond lengths to estimated dry weights. The study shows that between 40 and 100% of all individuals in the studied kelp population constantly eroded slightly from their distal ends. However, until June the accumulated loss was only 8% of produced dry weight. Due to dislodgement of whole sporophytes this picture changed in July and August to heavy losses in Mid-Norway. Thus, the overall losses of kelp in terms of accumulated dry weight were only 8–13% of the gross growth until harvest in June in Mid-Norway and August in Northern Norway. Losses increased significantly in Mid-Norway during July and reached 49.4% of the annual production in August. The rates of losses were separated into specific erosion and dislodgement rates. Erosion rates over the whole experimental period for the two sites were not significantly different, while differences in dislodgement rates between farm sites proved to be highly significant. The exported annual amount of carbon was estimated on the basis of lost and measured carbon content in the tissue. From these data a scenario was built for a commercial Norwegian kelp farm growing S. latissima showing a carbon export of 63–88 g C m–2y–1. This is eight times less than has been reported from scenarios for kelp farms in China. This study confirms that optimal timing of harvest is the most important management tool for avoidance of heavy losses from kelp farms. In conclusion, an industry with early harvest will likely have a low carbon export, while a late-harvested bulk production could export four to six times as much carbon with an increased potential for carbon sequestration.
Seabird Migration Strategies: Flight Budgets, Diel Activity Patterns, and Lunar Influence
Authors: Bonnet-Lebrun Anne-Sophie , Dias Maria P. , Phillips Richard A. , Granadeiro José P. , Brooke M. de L. , Chastel Olivier , Clay Thomas A. , Fayet Annette L. , Gilg Olivier , González-Solís Jacob , Guilford Tim , Hanssen Sveinn A. , Hedd April , Jaeger Audrey , Krietsch Johannes , Lang Johannes , Le Corre Matthieu , Militão Teresa , Moe Børge , Montevecchi William A. , Peter Hans-Ulrich , Pinet Patrick , Rayner Matt J. , Reid Tim , Reyes-González José Manuel , Ryan Peter G. , Sagar Paul M. , Schmidt Niels M. , Thompson David R. , van Bemmelen Rob , Watanuki Yutaka , Weimerskirch Henri , Yamamoto Takashi , Catry Paulo
Published: October 2021

Every year, billions of birds undertake extensive migrations between breeding and non-breeding areas, facing challenges that require behavioural adjustments, particularly to flight timing and duration. Such adjustments in daily activity patterns and the influence of extrinsic factors (e.g., environmental conditions, moonlight) have received much more research attention in terrestrial than marine migrants. Taking advantage of the widespread deployment in recent decades of combined light-level geolocator-immersion loggers, we investigated diel organisation and influence of the moon on flight activities during the non-breeding season of 21 migrant seabird species from a wide taxonomic range (6 families, 3 orders). Migrant seabirds regularly stopped (to either feed or rest) during migration, unlike some terrestrial and wetland birds which fly non-stop. We found an overall increase for most seabird species in time in flight and, for several species, also in flight bout duration, during migration compared to when resident at the non-breeding grounds. Additionally, several nocturnal species spent more of the day in flight during migration than at non-breeding areas, and vice versa for diurnal species. Nocturnal time in flight tended to increase during full moon, both during migration and at the non-breeding grounds, depending on species. Our study provides an extensive overview of activity patterns of migrant seabirds, paving the way for further research on the underlying mechanisms and drivers.
Pan-European Satellite-Derived Coastal Bathymetry—Review, User Needs and Future Services
Authors: Cesbron Guillaume , Melet Angélique , Almar Rafael , Lifermann Anne , Tullot Damien , Crosnier Laurence
Published: October 2021

Low-lying coastal zones are home to around 10% of the world’s population and to many megacities. Coastal zones are largely vulnerable to the dynamics of natural and human-induced changes. Accurate large-scale measurements of key parameters, such as bathymetry, are needed to understand and predict coastal changes. However, nearly 50% of the world’s coastal waters remain unsurveyed and for a large number of coastal areas of interest, bathymetric information is unavailable or is often decades old. This lack of information is due to the high costs in time, money and safety involved in collecting these data using conventional echo sounder on ships or LiDAR on aircrafts. Europe is no exception, as European seas are not adequately surveyed according to the International Hydrographic Organisation. Bathymetry influences ocean waves and currents, thereby shaping sediment transport which may alter coastal morphology over time. This paper discusses state-of-the-art coastal bathymetry retrieval methods and data, user requirements and key drivers for many maritime sectors in Europe, including advances in Satellite-Derived Bathymetry (SDB). By leveraging satellite constellations, cloud services and by combining complementary methods, SDB appears as an effective emerging tool with the best compromise in time, coverage and investment to map coastal bathymetry and its temporal evolution.
Photosensitivity of the Bacterial Pigment Cycloprodigiosin Enables Settlement in Coral Larvae—Light as an Understudied Environmental Factor
Authors: Petersen Lars-Erik , Kellermann Matthias Y. , Nietzer Samuel , Schupp Peter J.
Published: October 2021

The survival of coral reefs largely depends among other factors on the recruitment of a new generation of coral individuals that are more adapted to a rapidly changing climate and other anthropogenic stressors (e.g., pollution, sedimentation). Therefore, a better understanding of the coral settlement process, the molecules involved as well as crucial environmental drivers that control settlement success are needed. In this study, we identified a novel settlement inducer for the brooding scleractinian coral Leptastrea purpurea and highlight the importance of light for the settlement process. Crude extract of the red-pigmented bacterium Pseudoalteromonas rubra reliably triggered attachment and metamorphosis in L. purpurea larvae in less than 24 h. Prodigiosin (II) and the two derivatives, cycloprodigiosin (I) and 2-methyl-3-hexyl prodiginine (III) were isolated and structurally elucidated from the crude extract of P. rubra. We demonstrated that the photosensitive pigment cycloprodigiosin (I) was the responsible compound for attachment and metamorphosis in L. purpurea larvae. Under the tested light regimes (i.e., darkness, constant light and a dark-light alternation), cycloprodigiosin (I) triggered approximately 90% settlement at a concentration of 0.2 μg mL–1 under a 12 h alternating dark-light cycle, mimicking the light-flooded coral reef environment. Our findings enable for the first time a mechanistic understanding of the light-dependent larva to polyp transformation by discovering the novel bacterial settlement cue cycloprodigiosin and its photosensitivity as a determining factor for coral settlement.
Phytoplankton Fuel Fish Food Webs in a Low-Turbidity Temperate Coastal Embayment: A Stable Isotope Approach
Authors: Kundu Goutam Kumar , Kim Changseong , Kim Dongyoung , Bibi Riaz , Kim Heeyong , Kang Chang-Keun
Published: October 2021

Trophic contributions of diverse OM sources to estuarine and coastal food webs differ substantially across systems around the world, particularly for nekton (fish, cephalopods, and crustaceans), which utilize basal resources from multiple sources over space and time because of their mobility and feeding behaviors at multiple trophic levels. We investigated the contributions of putative OM sources to fish food webs and assessed the spatiotemporal patterns, structures, and trophic connectivity in fish food webs across four seasons from three closely spaced (10–15 km) sites: an estuarine channel (EC), a deep bay (DB), and an offshore (OS) region in Gwangyang Bay, a high-productivity, low-turbidity estuarine embayment off the Republic of Korea. While nearly all previous studies have focused on few representative species, we examined δ13C and δ15N values of whole nekton communities along with dominant benthic macro-invertebrates, zooplankton, and their putative primary food sources. The δ13C and δ15N values coupled with MixSIAR, a Bayesian mixing model, revealed that these communities utilized multiple primary producers, but phytoplankton comprised the primary trophic contributor (46.6–69.1%). Microphytobenthos (15.8–20.4%) and the seagrass Zostera marina (8.6–19.8%) made substantial contributions, but the role of river-borne terrestrial organic matter was negligible. Spatially different species composition and stable isotope values, but higher utilization of coastal phytoplankton by estuarine fish, indicated disparate food webs structures between the EC and DB/OS coastal areas, with considerable trophic connectivity. Greater overlaps in fish and cephalopod isotopic niches than among other consumers and a higher estimated carbon trophic enrichment factor for EC nekton confirmed feeding migration-mediated biological transport of coastal OM sources to the estuary. Further, the seasonally consistent structures and resource utilization patterns indicate that fish food webs are resilient to changes at lower trophic levels. Our results contrast with those for other highly turbid coastal systems depending highly on diversified basal sources, including exported terrestrial and wetland detritus alongside autochthonous phytoplankton. Finally, this study provides a novel perspective on the role of OM sources in such low turbidity and highly productive coastal embayments and enhances our understanding of marine ecosystems.
A Review of Biofouling of Ships’ Internal Seawater Systems
Authors: Davidson Ian , Cahill Patrick , Hinz Arne , Kluza Daniel , Scianni Chris , Georgiades Eugene
Published: October 2021

Internal seawater systems (ISS) are critical to the proper functioning of maritime vessels. Sea water is pumped on board ships for a broad array of uses, primarily for temperature control (e.g., engine and electrical systems), cooling capacity (e.g., air conditioners and refrigeration), and water provision (e.g., drinking, firefighting, steam, and ballast). Although sea water may spend only a brief period within ISS of a vessel, it can carry microorganisms and larval stages of macroorganisms throughout the system leading to biofouling accumulation that can impair system function or integrity. ISS can also act as a sub-vector of species translocations, potentially facilitating biological invasions. This review describes ships’ ISS with a focus on operational impacts of biofouling and current drivers and barriers associated with ISS biofouling management. As ISS internal components are difficult to access, reports and studies of ISS biofouling are uncommon and much of the dedicated literature is decades old. The impact of biofouling on ISS and vessel operations is based on increased surface roughness of pipework and equipment, restricted water flow, corrosion and subsequent component impingement, reduced surface functional efficiency, and potential contamination by pathogens that can affect human and aquatic animal health. Biofouling management is primarily achieved using antifouling coatings and marine growth prevention systems, but independent and accessible data on their efficacy in ISS remain limited. Further research is required to resolve the extent to which biofouling occurs in ISS of the modern commercial fleet and the efficacy of preventive systems. Such information can ultimately inform decisions to improve operational efficiency for vessel operators and ensure any biosecurity risks are appropriately managed.
Resolving Chemical Gradients Around Seagrass Roots—A Review of Available Methods
Authors: Scholz Vincent V. , Brodersen Kasper E. , Kühl Michael , Koren Klaus
Published: October 2021

Steep geochemical gradients surround roots and rhizomes of seagrass and protect the plants against the harsh conditions in anoxic sediment, while enabling nutrient uptake. Imbalance of these gradients, due to e.g., low plant performance and/or changing sediment biogeochemical conditions, can lead to plant stress and large-scale seagrass meadow die-off. Therefore, measuring and mapping the dynamic gradients around seagrass roots and rhizomes is needed to better understand plant responses to human impact and environmental changes. Historically, electrochemical microsensors enabled the first measurements of important chemical species like O2, pH or H2S with high sensitivity and spatial resolution giving important insights to the seagrass rhizosphere microenvironment; however, such measurements only provide information in one dimension at a time. In recent years, the use of reversible optical sensors (in the form of planar optodes or nanoparticles) and accumulative gel sampling methods like Diffusive Gradients in Thin films (DGT) have extended the array of analytes and allowed 2-D mapping of chemical gradients in the seagrass rhizosphere. Here, we review and discuss such microscale methods from a practical angle, discuss their application in seagrass research, and point toward novel experimental approaches to study the (bio)geochemistry around seagrass roots and rhizomes using a combination of available techniques, both in the lab andin situ.
The Cellular Composition of the Uveal Immune Environment
Authors: Reekie Ian R. , Sharma Srilakshmi , Foers Andrew , Sherlock Jonathan , Coles Mark C. , Dick Andrew D. , Denniston Alastair K. , Buckley Christopher D.
Published: October 2021

The uveal tract consists of the iris, the ciliary body and the choroid; these three distinct tissues form a continuous layer within the eye. Uveitis refers to inflammation of any region of the uveal tract. Despite being grouped together anatomically, the iris, ciliary body and choroid are distinct functionally, and inflammatory diseases may affect only one part and not the others. Cellular structure of tissues direct their function, and understanding the cellular basis of the immune environment of a tissue in health, the “steady state” on which the perturbations of disease are superimposed, is vital to understanding the pathogenesis of those diseases. A contemporary understanding of the immune system accepts that haematopoietic and yolk sac derived leukocytes, though vital, are not the only players of importance. An array of stromal cells, connective tissue cells such as fibroblasts and endothelial cells, may also have a role in the inflammatory reaction seen in several immune-mediated diseases. In this review we summarise what is known about the cellular composition of the uveal tract and the roles these disparate cell types have to play in immune homeostasis. We also discuss some unanswered questions surrounding the constituents of the resident leukocyte population of the different uveal tissues, and we look ahead to the new understanding that modern investigative techniques such as single cell transcriptomics, multi-omic data integration and highly-multiplexed imaging techniques may bring to the study of the uvea and uveitis, as they already have to other immune mediated inflammatory diseases.
Implementation of the ABCDEF Bundle for Critically Ill ICU Patients During the COVID-19 Pandemic: A Multi-National 1-Day Point Prevalence Study
Authors: Liu Keibun , Nakamura Kensuke , Katsukawa Hajime , Nydahl Peter , Ely Eugene Wesley , Kudchadkar Sapna R. , Takahashi Kunihiko , Elhadi Muhammed , Gurjar Mohan , Leong Be Kim , Chung Chi Ryang , Balachandran Jayachandran , Inoue Shigeaki , Lefor Alan Kawarai , Nishida Osamu
Published: October 2021

Background: Data regarding delivery of evidence-based care to critically ill patients in Intensive Care Units (ICU) during the COVID-19 pandemic is crucial but lacking. This study aimed to evaluate the implementation rate of the ABCDEF bundle, which is a collection of six evidence-based ICU care initiatives which are strongly recommended to be incorporated into clinical practice, and ICU diaries for patients with and without COVID-19 infections in ICUs, and to analyze the impact of COVID-19 on implementation of each element of the bundle and independent associated factors.

Methods: A world-wide 1-day point prevalence study investigated the delivery of the ABCDEF bundle and ICU diary to patients without or with COVID-19 infections on 27 January 2021 via an online questionnaire. Multivariable logistic regression analysis with adjustment for patient demographics evaluated the impact of COVID-19 and identified factors in ICU administrative structures and policies independently associated with delivery.

Results: From 54 countries and 135 ICUs, 1,229 patients were eligible, and 607 (49%) had COVID-19 infections. Implementation rates were: entire bundle (without COVID-19: 0% and with COVID-19: 1%), Element A (regular pain assessment: 64 and 55%), Element B (both spontaneous awakening and breathing trials: 17 and 10%), Element C (regular sedation assessment: 45 and 61%), Element D (regular delirium assessment: 39 and 35%), Element E (exercise: 22 and 25%), Element F (family engagement/empowerment: 16 and 30%), and ICU diary (17 and 21%). The presence of COVID-19 was not associated with failure to implement individual elements. Independently associated factors for each element in common between the two groups included presence of a specific written protocol, application of a target/goal, and tele-ICU management. A lower income status country and a 3:1 nurse-patient ratio were significantly associated with non-implementation of elements A, C, and D, while a lower income status country was also associated with implementation of element F.

Conclusions: Regardless of COVID-19 infection status, implementation rates for the ABCDEF bundle, for each element individually and an ICU diary were extremely low for patients without and with COVID-19 infections during the pandemic. Strategies to facilitate implementation of and adherence to the complete ABCDEF bundle should be optimized and addressed based on unit-specific barriers and facilitators.
The Population Genetics, Virulence, and Public Health Concerns of Escherichia coli Collected From Rats Within an Urban Environment
Authors: Pettengill J. B. , Kase J. A. , Murray M. H.
Published: October 2021

The co-existence of rats and humans in urban environments has long been a cause for concern regarding human health because of the potential for rats to harbor and transmit disease-causing pathogens. Here, we analyze whole-genome sequence (WGS) data from 41 Escherichia coli isolates collected from rat feces from 12 locations within the city of Chicago, IL, United States to determine the potential for rats to serve as a reservoir for pathogenic E. coli and describe its population structure. We identified 25 different serotypes, none of which were isolated from strains containing significant virulence markers indicating the presence of Shiga toxin-producing and other disease-causing E. coli. Nor did the E. coli isolates harbor any particularly rare stress tolerant or antimicrobial resistance genes. We then compared the isolates against a public database of approximately 100,000 E. coli and Shigella isolates of primarily food, food facility, or clinical origin. We found that only one isolate was genetically similar to genome sequences in the database. Phylogenetic analyses showed that isolates cluster by serotype, and there was little geographic structure (e.g., isolation by distance) among isolates. However, a greater signal of isolation by distance was observed when we compared genetic and geographic distances among isolates of the same serotype. This suggests that E. coli serotypes are independent lineages and recombination between serotypes is rare.
Innate Resistance to Leishmania amazonensis Infection in Rat Is Dependent on NOS2
Authors: Chen Yun-Fu , Yu Si-Fei , Wu Chang-You , Wu Na , Shen Jia , Shen Juan , Gao Jiang-Mei , Wen Yan-Zi , Hide Geoff , Lai De-Hua , Lun Zhao-Rong
Published: October 2021

Leishmaniainfection causes diverse clinical manifestations in humans. The disease outcome is complicated by the combination of many host and parasite factors. Inbred mouse strains vary in resistance toLeishmania majorbut are highly susceptible toLeishmania amazonensisinfection. However, rats are highly resistant toL. amazonensisinfection due to unknown mechanisms. We use the inducible nitric oxide synthase (Nos2)gene knockout rat model (Nos2−/−rat) to investigate the role of NOS2 against leishmania infection in rats. Our results demonstrated that diversion toward the NOS2 pathway is the key factor explaining the resistance of rats againstL. amazonensisinfection. Rats deficient in NOS2 are susceptible toL. amazonensisinfection even though their immune response to infection is still strong. Moreover, adoptive transfer of NOS2 competent macrophages intoNos2−/−rats significantly reduced disease development and parasite load. Thus, we conclude that the distinct L-arginine metabolism, observed in rat macrophages, is the basis of the strong innate resistance toLeishmania. These data highlight that macrophages from different hosts possess distinctive properties and produce different outcomes in innate immunity toLeishmaniainfections.
Transcriptomic Responses of Rhizobium phaseoli to Root Exudates Reflect Its Capacity to Colonize Maize and Common Bean in an Intercropping System
Authors: Aguirre-Noyola José Luis , Rosenblueth Mónica , Santiago-Martínez Michel Geovanni , Martínez-Romero Esperanza
Published: October 2021

Corn and common bean have been cultivated together in Mesoamerica for thousands of years in an intercropping system called “milpa,” where the roots are intermingled, favoring the exchange of their microbiota, including symbionts such as rhizobia. In this work, we studied the genomic expression of Rhizobium phaseoli Ch24-10 (by RNA-seq) after a 2-h treatment in the presence of root exudates of maize and bean grown in monoculture and milpa system under hydroponic conditions. In bean exudates, rhizobial genes for nodulation and degradation of aromatic compounds were induced; while in maize, a response of genes for degradation of mucilage and ferulic acid was observed, as well as those for the transport of sugars, dicarboxylic acids and iron. Ch24-10 transcriptomes in milpa resembled those of beans because they both showed high expression of nodulation genes; some genes that were expressed in corn exudates were also induced by the intercropping system, especially those for the degradation of ferulic acid and pectin. Beans grown in milpa system formed nitrogen-fixing nodules similar to monocultured beans; therefore, the presence of maize did not interfere with Rhizobium–bean symbiosis. Genes for the metabolism of sugars and amino acids, flavonoid and phytoalexin tolerance, and a T3SS were expressed in both monocultures and milpa system, which reveals the adaptive capacity of rhizobia to colonize both legumes and cereals. Transcriptional fusions of the putA gene, which participates in proline metabolism, and of a gene encoding a polygalacturonase were used to validate their participation in plant–microbe interactions. We determined the enzymatic activity of carbonic anhydrase whose gene was also overexpressed in response to root exudates.
Characterization of Structural and Physicochemical Properties of an Exopolysaccharide Produced by Enterococcus sp. F2 From Fermented Soya Beans
Authors: Jiang Guangyang , Gan Longzhan , Li Xiaoguang , He Juan , Zhang Shihao , Chen Jia , Zhang Ruoshi , Xu Zhe , Tian Yongqiang
Published: October 2021

The present study sought to isolate a novel exopolysaccharide (EPS-F2) from Enterococcus sp. F2 through ethanol precipitation, anion-exchange, and gel-filtration chromatography and characterize the physicochemical properties by spectral techniques. EPS-F2 was identified as a neutral homo-exopolysaccharide composed of only glucose with a high molecular weight of 1.108 × 108 g/mol. It contained →6)-α-D-Glcp-(1→ linkage in the main chain and →3, 6)-α-D-Glcp-(1→ branch chain). Moreover, EPS-F2 possessed excellent thermal stability (266.6°C), water holding capacity (882.5%), oil holding capacity (1867.76%), and emulsifying activity against various edible oils. The steady shear experiments exhibited stable pseudo plasticity under various conditions (concentrations, temperatures, and pHs). The dynamic oscillatory measurements revealed that EPS-F2 showed a liquid-like behavior at a low concentration (2.5%), while a solid-like behavior at high concentrations (3.0 and 3.5%). Overall, these results suggest that EPS-F2 could be a potential alternative source of functional additives and ingredients and be applied in food industries.
Geobiology of Andean Microbial Ecosystems Discovered in Salar de Atacama, Chile
Authors: Vignale Federico A. , Kurth Daniel , Lencina Agustina I. , Poiré Daniel G. , Chihuailaf Elizabeth , Muñoz-Herrera Natalia C. , Novoa Fernando , Contreras Manuel , Turjanski Adrián G. , Farías María E.
Published: October 2021

The Salar de Atacama in the Chilean Central Andes harbors unique microbial ecosystems due to extreme environmental conditions, such as high altitude, low oxygen pressure, high solar radiation, and high salinity. Combining X-ray diffraction analyses, scanning electron microscopy and molecular diversity studies, we have characterized twenty previously unexplored Andean microbial ecosystems in eight different lakes and wetlands from the middle-east and south-east regions of this salt flat. The mats and microbialites studied are mainly formed by calcium carbonate (aragonite and calcite) and halite, whereas the endoevaporites are composed predominantly of gypsum and halite. The carbonate-rich mats and microbialites are dominated byBacteroidetesandProteobacteriaphyla. Within the phylumProteobacteria, the most abundant classes areAlphaproteobacteria,GammaproteobacteriaandDeltaproteobacteria. While in the phylumBacteroidetes, the most abundant classes areBacteroidiaandRhodothermia.Cyanobacteria,Chloroflexi,Planctomycetes, andVerrucomicrobiaphyla are also well-represented in the majority of these systems. Gypsum endoevaporites, on the contrary, are dominated byProteobacteria,Bacteroidetes, andEuryarchaeotaphyla. TheCyanobacteriaphylum is also abundant in these systems, but it is less represented in comparison to mats and microbialites. Regarding the eukaryotic taxa, diatoms are key structural components in most of the microbial ecosystems studied. The genera of diatoms identified wereAchnanthes,Fallacia,Halamphora,Mastogloia,Navicula,Nitzschia, andSurirella. Normally, in the mats and microbialites, diatoms form nano-globular carbonate aggregates with filamentous cyanobacteria and other prokaryotic cells, suggesting their participation in the mineral precipitation process. This work expands our knowledge of the microbial ecosystems inhabiting the extreme environments from the Central Andes region, which is important to ensure their protection and conservation.