bluuebunny/crossref_metadata_2025 huggingface dataset:
Identical IFT140 Variants Cause Variable Skeletal Ciliopathy Phenotypes—Challenges for the Accurate Diagnosis
Authors: Walczak-Sztulpa Joanna , Wawrocka Anna , Doornbos Cenna , van Beek Ronald , Sowińska-Seidler Anna , Jamsheer Aleksander , Bukowska-Olech Ewelina , Latos-Bieleńska Anna , Grenda Ryszard , Bongers Ernie M. H. F. , Schmidts Miriam , Obersztyn Ewa , Krawczyński Maciej R. , Oud Machteld M.
Published: July 2022

Ciliopathies are rare congenital disorders, caused by defects in the cilium, that cover a broad clinical spectrum. A subgroup of ciliopathies showing significant phenotypic overlap are known as skeletal ciliopathies and include Jeune asphyxiating thoracic dysplasia (JATD), Mainzer-Saldino syndrome (MZSDS), cranioectodermal dysplasia (CED), and short-rib polydactyly (SRP). Ciliopathies are heterogeneous disorders with >187 associated genes, of which some genes are described to cause more than one ciliopathy phenotype. Both the clinical and molecular overlap make accurate diagnosing of these disorders challenging. We describe two unrelated Polish patients presenting with a skeletal ciliopathy who share the same compound heterozygous variants in IFT140 (NM_014,714.4) r.2765_2768del; p.(Tyr923Leufs*28) and exon 27–30 duplication; p.(Tyr1152_Thr1394dup). Apart from overlapping clinical symptoms the patients also show phenotypic differences; patient 1 showed more resemblance to a Mainzer-Saldino syndrome (MZSDS) phenotype, while patient 2 was more similar to the phenotype of cranioectodermal dysplasia (CED). In addition, functional testing in patient-derived fibroblasts revealed a distinct cilium phenotyps for each patient, and strikingly, the cilium phenotype of CED-like patient 2 resembled that of known CED patients. Besides two variants in IFT140, in depth exome analysis of ciliopathy associated genes revealed a likely-pathogenic heterozygous variant in INTU for patient 2 that possibly affects the same IFT-A complex to which IFT140 belongs and thereby could add to the phenotype of patient 2. Taken together, by combining genetic data, functional test results, and clinical findings we were able to accurately diagnose patient 1 with “IFT140-related ciliopathy with MZSDS-like features” and patient 2 with “IFT140-related ciliopathy with CED-like features”. This study emphasizes that identical variants in one ciliopathy associated gene can lead to a variable ciliopathy phenotype and that an in depth and integrated analysis of clinical, molecular and functional data is necessary to accurately diagnose ciliopathy patients.
Vitamin D3 Priming of Dendritic Cells Shifts Human Neutrophil-Dependent Th17 Cell Development to Regulatory T Cells
Authors: Hafkamp Florianne M. J. , Taanman-Kueter Esther W. M. , van Capel Toni M. M. , Kormelink Tom Groot , de Jong Esther C.
Published: July 2022

Vitamin D3 (VD3) is a potential adjuvant for use in tolerogenic vaccine formulations that target dendritic cells (DCs) for the treatment of chronic inflammatory disorders, e.g., autoimmune diseases. These disorders are often associated with enhanced activity of IL-17-producing T helper 17 (Th17) cells which develop in a DC-driven and neutrophil-dependent fashion. Here, we investigated the effect of VD3 on Candida albicans-specific human T-cell differentiation, since C. albicans is a model pathogen for Th17 cell development. VD3 priming of DCs restricted neutrophil-dependent Th17 cell development and neutrophil-independent Th1 cell formation from naive CD4+ T cells. In line with this, the production of Th1/Th17-polarizing cytokines IL-12 and IL-23 by DCs was reduced by VD3 priming. Development of both FoxP3+CD127lowCD25+ Tregs and IL-10-producing T cells was significantly enhanced in VD3-primed conditions, even in the presence of neutrophils. ICOS+ Tregs, major IL-10 producers, CD69+FoxP3+, and TIGIT+FoxP3+ Tregs were significantly induced by VD3 priming as well. Our data support the potential use of VD3 as an adjuvant to induce tolerance in the treatment of autoimmune disorders, including those in which neutrophils are involved in pathogenesis, since we show that Treg development is enhanced by VD3 even in the presence of neutrophils, while Th17 cell development is restricted.
Adverse Event Reporting Quality in Cancer Clinical Trials Evaluating Immune Checkpoint Inhibitor Therapy: A Systematic Review
Authors: Wang Yuhong , Chen Chen , Du Wei , Zhou Yixin , He Lina , Hong Shaodong , Zhang Li
Published: July 2022

Background

Immunotherapy has become one of the most important breakthroughs in cancer treatment. Consequently, there have been more immuno-oncology (IO) clinical trials for various cancers in recent decades. However, the quality of such trials in reporting adverse events (AE), especially immune-related AE (irAE), has not been comprehensively evaluated.

Methods

We evaluated the harm reporting quality of IO trials. The PubMed, Embase, Cochrane Library, and Web of Science databases were searched to identify all head-to-head phase II and III clinical trials assessing cancer immunotherapy published between January 1, 2010, and December 31, 2021. Publications were assessed using a 16-point harm reporting quality score (HRQS) derived from the 2004 Consolidated Standards of Reporting Trials (CONSORT) extension. The characteristics associated with improved reporting quality were identified with linear regression.

Results

A total of 123 publications were included. The mean HRQS was 11.1 (range, 5-14). The most common poorly reported items were harms addressed in the title (2%), AE collection methodology (3%), the statistical approach for analyzing harms (11%), and the irAE onset patterns and management (adequately reported in 14% and 33% of publications, respectively). The harm information was well described in the publications’ Results and Discussion sections (89-99%). The multivariable regression model revealed that higher impact factor (IF) (30<IF<60 vs. IF<30, P=0.021) and phase III clinical trial (phase III vs. phase II, P=0.023) were independent predictors of higher quality score.

Conclusion

Our findings show that AE reporting in IO randomized trials is suboptimal. Efforts should be made to improve harm reporting and to standardize reporting practices. Improvements in AE reporting would permit more balanced assessment of interventions and would enhance evidence-based IO practice.
Transcriptome Analysis of Tumor-Infiltrating Lymphocytes Identifies NK Cell Gene Signatures Associated With Lymphocyte Infiltration and Survival in Soft Tissue Sarcomas
Authors: Judge Sean J. , Bloomstein Joshua D. , Sholevar Cyrus J. , Darrow Morgan A. , Stoffel Kevin M. , Vick Logan V. , Dunai Cordelia , Cruz Sylvia M. , Razmara Aryana M. , Monjazeb Arta M. , Rebhun Robert B. , Murphy William J. , Canter Robert J.
Published: July 2022

Purpose

Clinical successes using current T-cell based immunotherapies have been limited in soft tissue sarcomas (STS), while pre-clinical studies have shown evidence of natural killer (NK) cell activity. Since tumor immune infiltration, especially tumor-infiltrating lymphocytes, is associated with improved survival in most solid tumors, we sought to evaluate the gene expression profile of tumor and blood NK and T cells, as well as tumor cells, with the goal of identifying potential novel immune targets in STS.

Experimental Design

Using fluorescence-activated cell sorting, we isolated blood and tumor-infiltrating CD3-CD56+ NK and CD3+ T cells and CD45- viable tumor cells from STS patients undergoing surgery. We then evaluated differential gene expression (DGE) of these purified populations with RNA sequencing analysis. To evaluate survival differences and validate primary DGE results, we also queried The Cancer Genome Atlas (TCGA) database to compare outcomes stratified by bulk gene expression.

Results

Sorted intra-tumoral CD3+ T cells showed significant upregulation of established activating (CD137) and inhibitory genes (TIM-3) compared to circulating T cells. In contrast, intra-tumoral NK cells did not exhibit upregulation of canonical cytotoxic genes (IFNG, GZMB), but rather significant DGE in mitogen signaling (DUSP4) and metabolic function (SMPD3, SLC7A5). Tumors with higher NK and T cell infiltration exhibited significantly increased expression of the pro-inflammatory receptor TLR4 in sorted CD45- tumor cells. TCGA analysis revealed that tumors with high TLR4 expression (P = 0.03) and low expression of STMN1 involved in microtubule polymerization (P < 0.001) were associated with significantly improved survival.

Conclusions

Unlike T cells, which demonstrate significant DGE consistent with upregulation of both activating and inhibiting receptors in tumor-infiltrating subsets, NK cells appear to have more stable gene expression between blood and tumor subsets, with alterations restricted primarily to metabolic pathways. Increased immune cell infiltration and improved survival were positively correlated with TLR4 expression and inversely correlated with STMN1 expression within tumors, suggesting possible novel therapeutic targets for immunotherapy in STS.
Bv8 Blockade Sensitizes Anti-PD1 Therapy Resistant Tumors
Authors: Benguigui Madeleine , Vorontsova Avital , Timaner Michael , Levin Sapir , Haj-Shomaly Jozafina , Deo Abhilash , Menachem Rotem , Manobla Bar , Cooper Tim J. , Raviv Ziv , Shaked Yuval
Published: July 2022

Myeloid-derived suppressor cells (MDSCs) are known to promote tumor growth in part by their immunosuppressive activities and their angiogenesis support. It has been shown that Bv8 blockade inhibits the recruitment of MDSCs to tumors, thereby delaying tumor relapse associated with resistance to antiangiogenic therapy. However, the impact of Bv8 blockade on tumors resistant to the new immunotherapy drugs based on the blockade of immune checkpoints has not been investigated. Here, we demonstrate that granulocytic-MDSCs (G-MDSCs) are enriched in anti-PD1 resistant tumors. Importantly, resistance to anti-PD1 monotherapy is reversed upon switching to a combined regimen comprised of anti-Bv8 and anti-PD1 antibodies. This effect is associated with a decreased level of G-MDSCs and enrichment of active cytotoxic T cells in tumors. The blockade of anti-Bv8 has shown efficacy also in hyperprogressive phenotype of anti-PD1-treated tumors. In vitro, anti-Bv8 antibodies directly inhibit MDSC-mediated immunosuppression, as evidenced by enhanced tumor cell killing activity of cytotoxic T cells. Lastly, we show that anti-Bv8-treated MDSCs secrete proteins associated with effector immune cell function and T cell activity. Overall, we demonstrate that Bv8 blockade inhibits the immunosuppressive function of MDSCs, thereby enhancing anti-tumor activity of cytotoxic T cells and sensitizing anti-PD1 resistant tumors. Our findings suggest that combining Bv8 blockade with anti-PD1 therapy can be used as a strategy for overcoming therapy resistance.
Drosophila Innate Immunity Involves Multiple Signaling Pathways and Coordinated Communication Between Different Tissues
Authors: Yu Shichao , Luo Fangzhou , Xu Yongyi , Zhang Yan , Jin Li Hua
Published: July 2022

The innate immune response provides the first line of defense against invading pathogens, and immune disorders cause a variety of diseases. The fruit flyDrosophila melanogasteremploys multiple innate immune reactions to resist infection. First, epithelial tissues function as physical barriers to prevent pathogen invasion. In addition, macrophage-like plasmatocytes eliminate intruders through phagocytosis, and lamellocytes encapsulate large particles, such as wasp eggs, that cannot be phagocytosed. Regarding humoral immune responses, the fat body, equivalent to the mammalian liver, secretes antimicrobial peptides into hemolymph, killing bacteria and fungi.Drosophilahas been shown to be a powerfulin vivomodel for studying the mechanism of innate immunity and host-pathogen interactions becauseDrosophilaand higher organisms share conserved signaling pathways and factors. Moreover, the ease with whichDrosophilagenetic and physiological characteristics can be manipulated prevents interference by adaptive immunity. In this review, we discuss the signaling pathways activated inDrosophilainnate immunity, namely, the Toll, Imd, JNK, JAK/STAT pathways, and other factors, as well as relevant regulatory networks. We also review the mechanisms by which different tissues, including hemocytes, the fat body, the lymph gland, muscles, the gut and the brain coordinate innate immune responses. Furthermore, the latest studies in this field are outlined in this review. In summary, understanding the mechanism underlying innate immunity orchestration inDrosophilawill help us better study human innate immunity-related diseases.
Multi-Omics Techniques Make it Possible to Analyze Sepsis-Associated Acute Kidney Injury Comprehensively
Authors: Qiao Jiao , Cui Liyan
Published: July 2022

Sepsis-associated acute kidney injury (SA-AKI) is a common complication in critically ill patients with high morbidity and mortality. SA-AKI varies considerably in disease presentation, progression, and response to treatment, highlighting the heterogeneity of the underlying biological mechanisms. In this review, we briefly describe the pathophysiology of SA-AKI, biomarkers, reference databases, and available omics techniques. Advances in omics technology allow for comprehensive analysis of SA-AKI, and the integration of multiple omics provides an opportunity to understand the information flow behind the disease. These approaches will drive a shift in current paradigms for the prevention, diagnosis, and staging and provide the renal community with significant advances in precision medicine in SA-AKI analysis.
The Roles of Neutrophils Linking Periodontitis and Atherosclerotic Cardiovascular Diseases
Authors: Irwandi Rizky A. , Chiesa Scott T. , Hajishengallis George , Papayannopoulos Venizelos , Deanfield John E. , D’Aiuto Francesco
Published: July 2022

Inflammation plays a crucial role in the onset and development of atherosclerosis. Periodontitis is a common chronic disease linked to other chronic inflammatory diseases such as atherosclerotic cardiovascular disease (ASCVD). The mechanistic pathways underlying this association are yet to be fully understood. This critical review aims at discuss the role of neutrophils in mediating the relationship between periodontitis and ASCVD. Systemic inflammation triggered by periodontitis could lead to adaptations in hematopoietic stem and progenitor cells (HSPCs) resulting in trained granulopoiesis in the bone marrow, thereby increasing the production of neutrophils and driving the hyper-responsiveness of these abundant innate-immune cells. These alterations may contribute to the onset, progression, and complications of atherosclerosis. Despite the emerging evidence suggesting that the treatment of periodontitis improves surrogate markers of cardiovascular disease, the resolution of periodontitis may not necessarily reverse neutrophil hyper-responsiveness since the hyper-inflammatory re-programming of granulopoiesis can persist long after the inflammatory inducers are removed. Novel and targeted approaches to manipulate neutrophil numbers and functions are warranted within the context of the treatment of periodontitis and also to mitigate its potential impact on ASCVD.
Fever of Unknown Origin, Wasting Syndrome and Bone Marrow Involvement: A Leprosy Case Report
Authors: Santana Marcela Araujo de Oliveira , da Costa Willian Vargas Tenório , Celestino Isadora Costa , dos Santos Diogo Fernandes , Dornelas Bruno de Carvalho , Pavelka Matthew Martin , Luppi Andrea De Martino , Goulart Isabela Maria Bernardes
Published: July 2022

Mycobacterium leprae, the etiologic agent of leprosy, is an acid-fast-staining and slow-growing bacilli that infect macrophages and Schwann cells individually or through forming globi. The clinical presentation of leprosy is broad and depends on the host immune response. We report a case of a 42-year-old Brazilian man presenting with fever of unknown origin (FUO), anemia, wasting syndrome, and neuropathy. The diagnosis of lepromatous leprosy was made after an extensive investigation revealed the presence of M. leprae in the bone marrow. Bone marrow involvement in leprosy is rare and some authors believe the presence of M. leprae in the bone marrow can act as a reservoir of the disease facilitating future relapses. It is important to investigate bone marrow involvement in leprosy, especially when the patient presents with cytopenias and positive epidemiologic history.
The Potential Predictive Biomarkers for Advanced Hepatocellular Carcinoma Treated With Anti-Angiogenic Drugs in Combination With PD-1 Antibody
Authors: Liu Chenxi , Zhu Sihui , Dong Yanbing , Shao Jie , Liu Baorui , Shen Jie
Published: July 2022

Background

Based on molecular biomarkers, anti-angiogenic drugs in combination with programmed cell death protein 1 (PD-1) antibodies can screen the potentially beneficial populations with hepatocellular carcinoma (HCC) and predict the efficacy after treatment. Therefore, we aimed to study predictive molecular biomarkers to improve the effectiveness of immuno-targeted combination therapy for HCC.

Patients and Methods

Baseline clinical data, blood samples, and imaging data of the first evaluation after two cycles of treatment were collected for 40 patients with advanced HCC who underwent combination therapy, and then these data were compared according to the efficacy. Since 15 patients had complete hematology samples, we additionally tested the T lymphocyte subpopulations of these 15 patients and also compared them according to the efficacy. In addition, we also selected five patients who benefited the most from the combination therapy and five patients with the worst curative effect for gene detection based on survival time and efficacy evaluation. Finally, the relationship between certain clinical characteristics, laboratory indicators, specific T lymphocyte subpopulations, gene mutations and the response of immuno-targeted combination therapy for HCC was evaluated.

Results

The high levels of CD3+CD4+CD279+, CD3+CD8+CD45RO+CD62L+T lymphocytes and tumor mutational burden (TMB) were associated with good efficacy of the combination therapy (P=0.03, P<0.01 and P=0.03). The high levels of CD3+CD4+CD28+ T lymphocytes were associated with poor efficacy of the combination therapy (P=0.02). The high mutation frequency of TP53 and ARID1A appeared in the non-response cohort. In addition, amplification mutation of 11q13-CCND1, FGF3, FGF4, and FGF19 was found in a patient with hyperprogression (HP).

Conclusions

The certain clinical characteristics, laboratory indicators, specific T lymphocyte subpopulations, and gene mutations established in this paper were potential predictive biomarkers for HCC patients treated with combination therapy.
The Impact of Human Microbiotas in Hematopoietic Stem Cell and Organ Transplantation
Authors: Sen Tirthankar , Thummer Rajkumar P.
Published: July 2022

The human microbiota heavily influences most vital aspects of human physiology including organ transplantation outcomes and transplant rejection risk. A variety of organ transplantation scenarios such as lung and heart transplantation as well as hematopoietic stem cell transplantation is heavily influenced by the human microbiotas. The human microbiota refers to a rich, diverse, and complex ecosystem of bacteria, fungi, archaea, helminths, protozoans, parasites, and viruses. Research accumulating over the past decade has established the existence of complex cross-species, cross-kingdom interactions between the residents of the various human microbiotas and the human body. Since the gut microbiota is the densest, most popular, and most studied human microbiota, the impact of other human microbiotas such as the oral, lung, urinary, and genital microbiotas is often overshadowed. However, these microbiotas also provide critical and unique insights pertaining to transplantation success, rejection risk, and overall host health, across multiple different transplantation scenarios. Organ transplantation as well as the pre-, peri-, and post-transplant pharmacological regimens patients undergo is known to adversely impact the microbiotas, thereby increasing the risk of adverse patient outcomes. Over the past decade, holistic approaches to post-transplant patient care such as the administration of clinical and dietary interventions aiming at restoring deranged microbiota community structures have been gaining momentum. Examples of these include prebiotic and probiotic administration, fecal microbial transplantation, and bacteriophage-mediated multidrug-resistant bacterial decolonization. This review will discuss these perspectives and explore the role of different human microbiotas in the context of various transplantation scenarios.
Akkermansia muciniphila and Gut Immune System: A Good Friendship That Attenuates Inflammatory Bowel Disease, Obesity, and Diabetes
Authors: Rodrigues Vanessa Fernandes , Elias-Oliveira Jefferson , Pereira Ítalo Sousa , Pereira Jéssica Assis , Barbosa Sara Cândida , Machado Melissa Santana Gonsalez , Carlos Daniela
Published: July 2022

Akkermansia muciniphila is a Gram-negative anaerobic mucus-layer-degrading bacterium that colonizes the intestinal mucosa of humans and rodents. Metagenomic data have shown an inverse correlation between the abundance of A. muciniphila and diseases such as inflammatory bowel disease (IBD), obesity, and diabetes. Thus, in recent decades, the potential of this bacterium as an immunomodulatory probiotic for autoimmune and chronic inflammatory diseases has been explored in experimental models. Corroborating these human correlation data, it has been reported that A. muciniphila slows down the development and progression of diabetes, obesity, and IBD in mice. Consequently, clinical studies with obese and diabetic patients are being performed, and the preliminary results are very promising. Therefore, this mini review highlights the main findings regarding the beneficial roles of A. muciniphila and its action mechanisms in autoimmune and chronic inflammatory diseases.
Host Manipulation, Gene Editing, and Non-Traditional Model Organisms: A New Frontier for Behavioral Research?
Authors: Doherty Jean-François , Matthews Benjamin J.
Published: July 2022

Insects and parasites dominate the biosphere, in terms of known biodiversity and mode of life, respectively. Consequently, insects play a part in many host-parasite systems, either as parasite, host, or both. Moreover, a lot of these systems involve adaptive parasite-induced changes of host phenotype (typically behavior or morphology), which is commonly known as host manipulation. While many host manipulation systems have been described within the last few decades, the proximate mechanisms that underpin host phenotypic change are still largely unknown. Given the intimate co-evolutionary history of host-parasite systems, teasing apart the intricate network of biochemical reactions involved in host manipulation requires the integration of various complementary technologies. In this perspective, we stress the importance of multidisciplinary research on host manipulation, such as high-throughput sequencing methods (genomics and transcriptomics) to search for candidate mechanisms that are activated during a manipulation event. Then, we argue that gene editing technologies, specifically the CRISPR-Cas9 system, are a powerful way to test for the functional roles of candidate mechanisms, in both the parasite and the host. Finally, given the sheer diversity of unique host-parasite systems discovered to date, there is indeed a tremendous potential to create novel non-traditional model systems that could greatly expand our capacity to test the fundamental aspects of behavior and behavioral regulation.
Advances in the Diagnosis of Leprosy
Authors: Sharma Mukul , Singh Pushpendra
Published: July 2022

Leprosy is a public health issue, and early detection is critical to avert disability. Despite the global attempt to eradicate this disease as a public health problem, it remains an important cause of global neurological disability. India, Brazil and Indonesia share more than 70% of the cases. The reduction of new cases is a priority in the WHO global strategy 2021-2030 which aims to reduce disease transmission in the community by diagnosing cases and identifying subclinical infection. The clinical manifestations of leprosy range from a few to several lesions. The identification remains difficult due to the limited sensitivity of traditional approaches based on bacillary counts of skin smears and histology. To aid in the diagnosis of this disease, molecular biology, and biotechnological technologies have been applied, each with its own set of benefits and downsides despite providing an essential tool to validate the clinical diagnosis of leprosy. Because of this, it is strongly recognized that specific, inexpensive point of care technologies should be developed, particularly to identify asymptomatic M. leprae infections or leprosy nearer to the suspected cases seeking medical attention. Thus, this review will provide an overview of the advancements in leprosy diagnosis over the world. The purpose of this review is to improve our understanding of the outcomes of current tests and technologies used in leprosy diagnosis and to emphasize critical aspects concerning the detection of leprosy bacilli.
Microbial RNA, the New PAMP of Many Faces
Authors: Milillo M. Ayelén , Velásquez Lis N. , Barrionuevo Paula
Published: July 2022

Traditionally, pathogen-associated molecular patterns (PAMPs) were described as structural molecular motifs shared by different classes of microorganisms. However, it was later discovered that the innate immune system is also capable of distinguishing metabolically active microbes through the detection of a special class of viability-associated PAMPs (vita-PAMPs). Indeed, recognition of vita-PAMPs triggers an extra warning sign not provoked by dead bacteria. Bacterial RNA is classified as a vita-PAMP since it stops being synthesized once the microbes are eliminated. Most of the studies in the literature have focused on the pro-inflammatory capacity of bacterial RNA on macrophages, neutrophils, endothelial cells, among others. However, we, and other authors, have shown that microbial RNA also has down-modulatory properties. More specifically, bacterial RNA can reduce the surface expression of MHC class I and MHC class II on monocytes/macrophages and help evade CD8+ and CD4+ T cell-mediated immune surveillance. This phenomenon has been described for several different bacteria and parasites, suggesting that microbial RNA plays a significant immunoregulatory role in the context of many infectious processes. Thus, beyond the pro-inflammatory capacity of microbial RNA, it seems to be a crucial component in the intricate collection of immune evasion strategies. This review focuses on the different facets of the immune modulating capacity of microbial RNA.
Diversity of Free-Living and Particle-Attached Prokaryotes in a River-Influenced Coastal Area of the Northern Adriatic Sea
Authors: Trano Anna Chiara , Piredda Roberta , Balestra Cecilia , Bastianini Mauro , Gasol Josep M. , Casotti Raffaella
Published: July 2022

The Northern Adriatic Sea is a key area of the Mediterranean Sea, strongly affected by freshwater inputs, mainly from the Po River, which bring high amounts of nutrients as well as organic and inorganic particles. Free-living and particle-attached prokaryotes were characterized by 16S rRNA gene amplicon sequencing of size-fractionated samples collected during a diatom bloom in this area. The diversity of free-living and particle-attached prokaryotic assemblages was investigated with the aim to understand how the microbial communities are structured in the two fractions and whether specific microbial groups are associated to one lifestyle or the other. The results highlight a diverse prokaryotic community dominated by Proteobacteria, Bacteroidetes, and, remarkably, Firmicutes. Taxa within Firmicutes and Alphaproteobacteria are identified as the main particle-attached indicators by LEfSe, while members of Bacteroidetes and Gammaproteobacteria were representative of the free-living lifestyle, although they were also usually found as particle-attached. Collectively, the results suggest that both the free-living and the particle-attached lifestyles are a complex combination of specialization and adaptation to local conditions.
Sustainable Chromium Encapsulation: Alkali Activation Route
Authors: Sgarlata Caterina , Leonelli Cristina , Lancellotti Isabella , Mortalò Cecilia , Berrettoni Mario , Fattobene Martina , Zamponi Silvia , Giorgetti Marco
Published: July 2022

This article highlights recent experimental advances in the use of inorganic substances in the encapsulation of pollutants and, in particular, discusses the potential applicability and constraints of the geopolymerization process for the treatment of wastewater containing chromium. A great percentage of waste containing chromium salts is produced by the leather industry during the tannery process. Such industrial waste is in the form of liquor containing almost 40% of the initial chromium combined with many other pollutants. The stabilization/solidification (S/S) treatment of this type of waste must be combined with chromium encapsulation in an economic, environmentally friendly and efficient process to be industrially feasible. Here we present a novel process in which the wastewater is used as a component of the formulation together with a clay by-product and with the addition of NaOH pellets with the goal of a no-water plus no-waste technology approach. The final solidified “ceramic-like” material successfully immobilized the heavy metal cations as well as anions and macromolecules of surfactants, avoiding environmental damages to soil and groundwater. The article is completed by mentioning other S/S processes where wastewater has been treated and the resulting sludge encapsulated. The future of the S/S technologies in the tannery industry should progress in the direction of significantly reducing the amount of wastewater directed to the treatment plants, with associated reductions in transport and their CO2 emissions. This article intends to be a contribution in the direction of preventing waste, aligning circular economy and waste management objectives.
3D Bioprinted Scaffolds for Tissue Repair and Regeneration
Authors: Liu Na , Zhang Xiaopei , Guo Qingxia , Wu Tong , Wang Yuanfei
Published: July 2022

Three-dimensional (3D) printing technology has emerged as a revolutionary manufacturing strategy that could realize rapid prototyping and customization. It has revolutionized the manufacturing process in the fields of electronics, energy, bioengineering and sensing. Based on digital model files, powdered metal, plastic and other materials were used to construct the required objects by printing layer by layer. In addition, 3D printing possesses remarkable advantages in realizing controllable compositions and complex structures, which could further produce 3D objects with anisotropic functions. In recent years, 3D bioprinting technology has been applied to manufacture functional tissue engineering scaffolds with its ability to assemble complicated construction under precise control, which has attracted great attention. Bioprinting creates 3D scaffolds by depositing and assembling biological and/or non-biological materials with an established tissue. Compared with traditional technology, it can create a structure tailored to the patient according to the medical images. This conception of 3D bioprinting draws on 3D printing technology, which could be utilized to produce personalized implants, thereby opening up a new way for bio-manufacturing methods. As a promising tool, 3D bioprinting can create complex and delicate biomimetic 3D structures, simulating extracellular matrix and preparing high precision multifunctional scaffolds with uniform cell distribution for tissue repair and regeneration. It can also be flexibly combined with other technologies such as electrospinning and thermally induced phase separation, suitable for tissue repair and regeneration. This article reviews the relevant research and progress of 3D bioprinting in tissue repair and regeneration in recent years. Firstly, we will introduce the physical, chemical and biological characteristics of biological scaffolds prepared by 3D bioprinting from several aspects. Secondly, the significant effects of 3D bioprinting on nerves, skin, blood vessels, bones and cartilage injury and regeneration are further expounded. Finally, some views on the clinical challenges and future opportunities of 3D bioprinting are put forward.
Sustainable and Repulpable Barrier Coatings for Fiber-Based Materials for Food Packaging: A Review
Authors: Kathuria Ajay , Zhang Shanju
Published: July 2022

Due to the inherent hydrophilic nature and porosity of the paper fibers, hydrophobic polymeric materials, waxes, and inorganic fillers have been widely utilized as coatings and fillers, respectively, on a fiber-based substrate. Coatings also impart oxygen, aroma, and oil barrier properties desirable for food packaging applications. In addition, coatings improve the functional properties and characteristics of paper, including reduced water absorbance, enhanced surface finish, gloss finish, printability, readability, dimensional stability of the substrate, and antimicrobial performance. Such functional properties are highly desirable for consumer packaging applications. However, such coatings may limit the repulpability, recyclability, biodegradability, and compostability of paper and paperboard. In addition, the contamination of the substrate by-product also limits the recyclability of the fiber-based substrates, and the paper, paperboard, or corrugated material ends up in landfill sites. This review focuses on bioderived, biodegradable, compostable, and functional organic, inorganic, and hybrid hydrophobic coatings, which promote the circular economy by improving the repulpability or reduces carbon footprints.
Electric-Field Control of Magnetoresistance Behavior in a Conetic Alloy Thin Film/Pb(Mg1/3Nb2/3)0.7Ti0.3O3 Multiferroic Heterostructure
Authors: Wang Cangmin , Huang Wenyu , Wang Chi , Li Lu , Wei Chong , Sun Yuchen , Ge Weifeng , Mao Xiaoli , Li Qiang , Yang Yuanjun , Jia Cheng , Zhang Hui , Luo Zhenlin , Gao Chen
Published: July 2022

In this work, we investigate the influence of electric fields (E-fields) on the room-temperature magnetotransport behavior of an artificial multiferroic heterostructure, a Conetic alloy (Ni77Fe14Cu5Mo4) thin film/Pb(Mg1/3Nb2/3)0.7Ti0.3O3 (011). When the external magnetic field is parallel to the applied current, the switching field increases from 0.8 to 3.3 Oe at 0 and 8 kV/cm, respectively, and the corresponding magnetoresistance (MR) ratio at 20 Oe respectively decreases from 0.14% to 0.03% at 0 and 8 kV/cm. However, when the external magnetic field is perpendicular to the current, the switching field decreases from 10.1 to 1.7 Oe at 0 and 8 kV/cm, and the MR ratio in such a case decreases from −0.001% to −0.10%, respectively. Consequently, under the parallel and perpendicular modes, the tunabilities of the switching field are approximately +313% and −83%, and the MR ratio tunabilities under E-fields are approximately −79% and +9,900%, respectively. Such a large and anisotropic tunability of both the switching field and MR ratio is attributed to the ultrasoft magnetic property of the Conetic alloy thin film and anisotropic in-plane strain-mediated magnetoelectric coupling. However, the anisotropic MR ratio is approximately 0.15% and does not vary with the applied E-fields owing to the intrinsic property of Conetic thin films using transfer and circle transfer curve measurements, rather than the magnetization rotation caused by E-field-induced magnetoelastic anisotropy. This work demonstrates that multiferroic heterostructures with electrically tunable MR show considerable potential in designing energy-efficient electronic and spintronic devices.
Pathological Findings Associated With SARS-CoV-2 on Postmortem Core Biopsies: Correlation With Clinical Presentation and Disease Course
Authors: Ramos-Rincon Jose-Manuel , Herrera-García Cristian , Silva-Ortega Sandra , Portilla-Tamarit Julia , Alenda Cristina , Jaime-Sanchez Francisco-Angel , Arenas-Jiménez Juan , Fornés-Riera Francisca-Eugenia , Scholz Alexander , Escribano Isabel , Pedrero-Castillo Víctor , Muñoz-Miguelsanz Carlos , Orts-Llinares Pedro , Martí-Pastor Ana , Amo-Lozano Antonio , García-Sevila Raquel , Ribes-Mengual Isabel , Moreno-Perez Oscar , Concepcion-Aramendía Luis , Merino Esperanza , Sánchez-Martínez Rosario , Aranda Ignacio
Published: July 2022

Background

Autopsies can shed light on the pathogenesis of new and emerging diseases.

Aim

To describe needle core necropsy findings of the lung, heart, and liver in decedents with COVID-19.

Material

Cross-sectional study of needle core necropsies in patients who died with virologically confirmed COVID-19. Histopathological analyses were performed, and clinical data and patient course evaluated.

Results

Chest core necropsies were performed in 71 decedents with a median age of 81 years (range 52–97); 47 (65.3%) were men. The median interval from symptoms onset to death was 17.5 days (range 1–84). Samples of lung (n = 62, 87.3%), heart (n = 48, 67.6%) and liver (n = 39, 54.9%) were obtained. Fifty-one lung samples (82.3%) were abnormal: 19 (30.6%) showed proliferative diffuse alveolar damage (DAD), 12 (19.4%) presented exudative DAD, and 10 (16.1%) exhibited proliferative plus exudative DAD. Of the 46 lung samples tested for SARS-CoV-19 by RT-PCR, 39 (84.8%) were positive. DAD was associated with premortem values of lactate dehydrogenase of 400 U/L or higher [adjusted odds ratio (AOR) 21.73; 95% confidence interval (CI) 3.22–146] and treatment with tocilizumab (AOR 6.91; 95% CI 1.14–41.7). Proliferative DAD was associated with an onset-to-death interval of over 15 days (AOR 7.85, 95% CI 1.29–47.80). Twenty-three of the 48 (47.9%) heart samples were abnormal: all showed fiber hypertrophy, while 9 (18.8%) presented fibrosis. Of the liver samples, 29/39 (74.4%) were abnormal, due to steatosis (n = 12, 30.8%), cholestasis (n = 6, 15.4%) and lobular central necrosis (n = 5, 12.8%).

Conclusion

Proliferative DAD was the main finding on lung core needle necropsy in people who died from COVID-19; this finding was related to a longer disease course. Changes in the liver and heart were common.
Using Evolutionary Analyses to Refine Whole-Genome Sequence Match Criteria
Authors: Pightling Arthur W. , Rand Hugh , Pettengill James
Published: July 2022

Whole-genome sequence databases continue to grow. Collection times between samples are also growing, providing both a challenge for comparing recently collected sequence data to historical samples and an opportunity for evolutionary analyses that can be used to refine match criteria. We measured evolutionary rates for 22 Salmonella enterica serotypes. Based upon these measurements, we propose using an evolutionary rate of 1.97 single-nucleotide polymorphisms (SNPs) per year when determining whether genome sequences match.
Discovery, Yield Improvement, and Application in Marine Coatings of Potent Antifouling Compounds Albofungins Targeting Multiple Fouling Organisms
Authors: She Weiyi , Ye Wei , Cheng Aifang , Ye Wenkang , Ma Chunfeng , Wang Ruojun , Cheng Jinping , Liu Xuan , Yuan Yujing , Chik Sin Yu , Limlingan Malit Jessie James , Lu Yanhong , Chen Feng , Qian Pei-Yuan
Published: July 2022

Marine biofouling caused huge economic losses of maritime industries. We aim to develop high-efficient, less-toxic, and cost-effective antifoulants to solve the problems of biofouling. In this study, we described the antifouling compounds albofungin and its derivatives (albofungin A, chrestoxanthone A, and chloroalbofungin) isolated from the metabolites of bacterium Streptomyces chrestomyceticus BCC 24770, the construction of high-yield strains for albofungin production, and application of albofungin-based antifouling coatings. Results showed that these albofungins have potent antibiofilm activities against Gram-positive and Gram-negative bacteria and anti-macrofouling activities against larval settlement of major fouling organisms with low cytotoxicity. With the best antifouling activity and highest yield in bacterial culture, albofungin was subsequently incorporated with hydrolyzable and degradable copolymer to form antifouling coatings, which altered biofilm structures and prevented the settlement of macrofouling organisms in marine environments. Our results suggested that albofungins were promising antifouling compounds with potential application in marine environments.
Rhizosphere and Straw Return Interactively Shape Rhizosphere Bacterial Community Composition and Nitrogen Cycling in Paddy Soil
Authors: Zhao Ya-Hui , Wang Ning , Yu Meng-Kang , Yu Jian-Guang , Xue Li-Hong
Published: July 2022

Currently, how rice roots interact with straw return in structuring rhizosphere communities and nitrogen (N) cycling functions is relatively unexplored. In this study, paddy soil was amended with wheat straw at 1 and 2% w/w and used for rice growth. The effects of the rhizosphere, straw, and their interaction on soil bacterial community composition and N-cycling gene abundances were assessed at the rice maturity stage. For the soil without straw addition, rice growth, i.e., the rhizosphere effect, significantly altered the bacterial community composition and abundances of N-cycling genes, such as archaeal and bacterial amoA (AOA and AOB), nirK, and nosZ. The comparison of bulk soils between control and straw treatments showed a shift in bacterial community composition and decreased abundance of AOA, AOB, nirS, and nosZ, which were attributed to sole straw effects. The comparison of rhizosphere soils between control and straw treatments showed an increase in the nifH gene and a decrease in the nirK gene, which were attributed to the interaction of straw and the rhizosphere. The number of differentially abundant genera in bulk soils between control and straw treatments was 13–23, similar to the number of 16–22 genera in rhizosphere soil between control and straw treatment. However, the number of genera affected by the rhizosphere effect was much lower in soil amended with straw (3–4) than in soil without straw addition (9). Results suggest possibly more pronounced impacts of straw amendments in shaping soil bacterial community composition.
Genomic Investigation of Proteus mirabilis Isolates Recovered From Pig Farms in Zhejiang Province, China
Authors: Qu Xiaoyun , Zhou Jie , Huang Haoqi , Wang Wen , Xiao Yingping , Tang Biao , Liu Hanlin , Xu Chenggang , Xiao Xingning
Published: July 2022

Proteus mirabilis is a common opportunistic zoonotic pathogen, and its ongoing acquisition of antimicrobial resistance genes poses challenges to clinical treatments. Human-sourced whole genomic sequencing of human P. mirabilis isolates has been reported, but pig-sourced isolates have not been thoroughly investigated even though these animals can serve as reservoirs for human infections. In the current study, we report a molecular epidemiological investigation to unravel the antimicrobial and virulence gene risk factors for P. mirabilis contamination in 9 pig farms in 3 different cities in Zhejiang Province, China. We collected 541 swab samples from healthy pigs and 30 were confirmed as P. mirabilis. All 30 isolates were resistant to tetracyclines, macrolides, sulfonamides, β-lactams and chloramphenicol, and all were multiple drug-resistant and 27 were strong biofilm formers. Phylogenetic analyses indicated these 30 isolates clustered together in 2 major groups. Whole genome sequencing demonstrated that the isolates possessed 91 different antimicrobial resistance genes belonging to 30 antimicrobial classes including rmtB, sul1, qnrS1, AAC(6′) − Ib − cr, blaCTX − M − 65 and blaOXA − 1. All isolates contained mobile genetic elements including integrative conjugative elements (ICEs) and integrative and mobilizable elements (IMEs). Minimum inhibitory concentration (MIC) testing indicated direct correlates between cognate genes and antimicrobial resistance. We also identified 95 virulence factors, almost all isolates contained 20 fimbrial and flagellar operons, and this represents the greatest number of these operon types found in a single species among all sequenced bacterial genomes. These genes regulate biofilm formation and represent a confounding variable for treating P. mirabilis infections. Our P. mirabilis isolates were present in healthy animals, and multiple drug resistance in these isolates may serve as a reservoir for other intestinal and environmental Enterobacteriaceae members. This prompts us to more strictly regulate veterinary antibiotic use.
Cerebrospinal Fluid Cortisol and Dehydroepiandrosterone Sulfate, Alzheimer’s Disease Pathology, and Cognitive Decline
Authors: Ouanes Sami , Clark Christopher , Richiardi Jonas , Maréchal Bénédicte , Lewczuk Piotr , Kornhuber Johannes , Kirschbaum Clemens , Popp Julius
Published: July 2022

Introduction

Elevated cortisol levels have been reported in Alzheimer’s disease (AD) and may accelerate the development of brain pathology and cognitive decline. Dehydroepiandrosterone sulfate (DHEAS) has anti-glucocorticoid effects and it may be involved in the AD pathophysiology.

Objectives

To investigate associations of cerebrospinal fluid (CSF) cortisol and DHEAS levels with (1) cognitive performance at baseline; (2) CSF biomarkers of amyloid pathology (as assessed by CSF Aβ levels), neuronal injury (as assessed by CSF tau), and tau hyperphosphorylation (as assessed by CSF p-tau); (3) regional brain volumes; and (4) clinical disease progression.

Materials and Methods

Individuals between 49 and 88 years (n = 145) with mild cognitive impairment or dementia or with normal cognition were included. Clinical scores, AD biomarkers, brain MRI volumetry along with CSF cortisol and DHEAS were obtained at baseline. Cognitive and functional performance was re-assessed at 18 and 36 months from baseline. We also assessed the following covariates: apolipoprotein E (APOE) genotype, BMI, and education. We used linear regression and mixed models to address associations of interest.

Results

Higher CSF cortisol was associated with poorer global cognitive performance and higher disease severity at baseline. Cortisol and cortisol/DHEAS ratio were positively associated with tau and p-tau CSF levels, and negatively associated with the amygdala and insula volumes at baseline. Higher CSF cortisol predicted more pronounced cognitive decline and clinical disease progression over 36 months. Higher CSF DHEAS predicted more pronounced disease progression over 36 months.

Conclusion

Increased cortisol in the CNS is associated with tau pathology and neurodegeneration, and with decreased insula and amygdala volume. Both CSF cortisol and DHEAS levels predict faster clinical disease progression. These results have implications for the identification of patients at risk of rapid decline as well as for the development of interventions targeting both neurodegeneration and clinical manifestations of AD.