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Pharmacological activation of the Sonic hedgehog pathway with a Smoothened small molecule agonist ameliorates the severity of alcohol-induced morphological and behavioral birth defects in a zebrafish model of fetal alcohol spectrum disorder.

J Neurosci Res 2022 Jan 11. Epub 2022 Jan 11.

Biomanufacturing Research Institute and Technology Enterprise, North Carolina Central University, Durham, North Carolina, USA.

Ethanol exposure during the early stages of embryonic development can lead to a range of morphological and behavioral differences termed fetal alcohol spectrum disorders (FASDs). In a zebrafish model, we have shown that acute ethanol exposure at 8-10 hr postfertilization (hpf), a critical time of development, produces birth defects similar to those clinically characterized in FASD. Dysregulation of the Sonic hedgehog (Shh) pathway has been implicated as a molecular basis for many of the birth defects caused by prenatal alcohol exposure. Read More

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January 2022

Artificial intelligence framework identifies candidate targets for drug repurposing in Alzheimer's disease.

Alzheimers Res Ther 2022 Jan 10;14(1). Epub 2022 Jan 10.

Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.

Background: Genome-wide association studies (GWAS) have identified numerous susceptibility loci for Alzheimer's disease (AD). However, utilizing GWAS and multi-omics data to identify high-confidence AD risk genes (ARGs) and druggable targets that can guide development of new therapeutics for patients suffering from AD has heretofore not been successful.

Methods: To address this critical problem in the field, we have developed a network-based artificial intelligence framework that is capable of integrating multi-omics data along with human protein-protein interactome networks to accurately infer accurate drug targets impacted by GWAS-identified variants to identify new therapeutics. Read More

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January 2022

Brain Health Executives: A Transdisciplinary Workforce Innovation-A Commentary.

Innov Clin Neurosci 2021 Apr-Jun;18(4-6):24-27

Dr. Eyre and Mr. Heinemeyer are co-founders of the PRODEO Institute. Dr. Eyre is with the PRODEO Institute in San Francisco, California; the Institute for Mental and Physical Health and Clinical Translation (IMPACT) and School of Medicine at Deakin University in Geelong, Australia; the Global Brain Health Institute (GBHI) at the University of California, San Francisco; the Department of Psychiatry at Baylor College of Medicine in Houston, Texas; Trinity University in Dublin, Ireland, and Neuroscience-inspired Policy Initiative at the Organisation for Economic Co-Operation and Development (OECD) in Paris, France.

Given the rapidly evolving landscape of technologies, social, health, and consumer trends, the development of effective Brain Health Executives is a key workforce innovation. Convergence Brain Health involves the integration of scientists, clinicians, bioinformaticists, global health experts, social scientists, engineers, technology entrepreneurs, medical educators, caregivers, and consumers. Synergy between government, academia, and industry is also vital. Read More

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January 2022

Development and assessment of a brief screening tool for psychosis in dementia.

Alzheimers Dement (Amst) 2021 7;13(1):e12254. Epub 2021 Dec 7.

Banner Sun Health Research Institute Banner Health Sun City Arizona USA.

Introduction: Hallucinations and delusions (H+D) are common in dementia, but screening for these symptoms-especially in busy clinical practices-is challenging.

Methods: Six subject matter experts developed the DRP3™ screen, a novel valid tool to detect H+D in dementia, assessed its content validity through alignment with DRP reference assessments (Scale for the Assessment of Positive Symptoms-Hallucinations + Delusions, Neuropsychiatric Inventory-Questionnaire, International Psychogeriatric Association Criteria), and retrospectively investigated its ability to detect H+D in HARMONY trial (NCT03325556) enrollees.

Results: All items from three reference assessments demonstrated significant agreement with the DRP3 screen among raters ( < . Read More

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December 2021

A fully integrated SNP genotyping system for hereditary hearing-loss detection.

Lab Chip 2021 Dec 19. Epub 2021 Dec 19.

State Key Laboratory of Membrane Biology, Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China.

Hereditary hearing loss is one of the most common human neurosensory disorders, and there is a great need for early intervention methods such as genetically screening newborns. Single nucleotide polymorphisms (SNPs) are the major genetic targets for hearing-loss screening. In this study, a fully integrated SNP genotyping system was constructed to identify hereditary hearing loss-related genetic markers from human whole blood. Read More

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December 2021

Near infrared light triggered ternary synergistic cancer therapy via L-arginine-loaded nanovesicles with modification of PEGylated indocyanine green.

Acta Biomater 2021 Dec 11. Epub 2021 Dec 11.

Ministry of Education (MOE) Key Laboratory of Macromolecular Synthesis and Functionalization Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China. Electronic address:

L-arginine (L-Arg) is an important nitric oxide (NO) donor, and its exploration in NO gas therapy has received widespread attention. Application of nano-platforms that can efficiently deliver L-Arg and induce its rapid conversion to NO becomes a predominant strategy to achieve promising therapeutic effects in tumor treatment. Herein, an enhanced nano-vesicular system of ternary synergistic treatment combining NO therapy, photodynamic therapy (PDT) along with mild photothermal therapy (MPTT) was developed for cancer therapy. Read More

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December 2021

The power of genetic diversity in genome-wide association studies of lipids.

Nature 2021 Dec 9;600(7890):675-679. Epub 2021 Dec 9.

Department of Clinical Biochemistry, Landspitali-National University Hospital of Iceland, Reykjavik, Iceland.

Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use. Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels, heart disease remains the leading cause of death worldwide. Genome-wideassociation studies (GWAS) of blood lipid levels have led to important biological and clinical insights, as well as new drug targets, for cardiovascular disease. Read More

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December 2021

Development of a model-based clinical trial simulation platform to optimize the design of clinical trials for Duchenne muscular dystrophy.

CPT Pharmacometrics Syst Pharmacol 2021 Dec 8. Epub 2021 Dec 8.

Department of Pharmaceutics, Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, Florida, USA.

Early clinical trials of therapies to treat Duchenne muscular dystrophy (DMD), a fatal genetic X-linked pediatric disease, have been designed based on the limited understanding of natural disease progression and variability in clinical measures over different stages of the continuum of the disease. The objective was to inform the design of DMD clinical trials by developing a disease progression model-based clinical trial simulation (CTS) platform based on measures commonly used in DMD trials. Data were integrated from past studies through the Duchenne Regulatory Science Consortium founded by the Critical Path Institute (15 clinical trials and studies, 1505 subjects, 27,252 observations). Read More

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December 2021

Phymatolithopsis gen. nov. (Hapalidiales, Corallinophycidae, Rhodophyta) based on molecular and morpho-anatomical evidence.

J Phycol 2021 Dec 4. Epub 2021 Dec 4.

Department of Life Science, Chosun University, 309 Pilmun-daero, Dong-gu, Gwangju, 61452, Korea.

A multigene (psbA, rbcL, 18S rDNA) molecular phylogeny of the genus Phymatolithon showed a polyphyletic grouping of two monophyletic clades within the Hapalidiales. DNA sequence data integrated with morpho-anatomical comparisons of type material and of recently collected specimens were used to establish Phymatolithopsis gen. nov. Read More

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December 2021

COVID-19-specific metabolic imprint yields insights into multiorgan system perturbations.

Eur J Immunol 2021 Nov 26. Epub 2021 Nov 26.

Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

Corona disease 2019 (COVID-19) affects multiple organ systems. Recent studies have indicated perturbations in the circulating metabolome linked to COVID-19 severity. However, several questions pertain with respect to the metabolome in COVID-19. Read More

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November 2021

Disease modification is not all - we need symptomatic therapies for Alzheimer disease.

Authors:
Jeffrey Cummings

Nat Rev Neurol 2022 Jan;18(1):3-4

Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas, Las Vegas, NV, USA.

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January 2022

A 3D-Printed Microfluidic Device for qPCR Detection of Macrolide-Resistant Mutations of .

Biosensors (Basel) 2021 Oct 29;11(11). Epub 2021 Oct 29.

State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050, China.

Mycoplasma pneumonia (MP) is a common respiratory infection generally treated with macrolides, but resistance mutations against macrolides are often detected in in China. Rapid and accurate identification of and its mutant type is necessary for precise medication. This paper presents a 3D-printed microfluidic device to achieve this. Read More

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October 2021

The probabilistic model of Alzheimer disease: the amyloid hypothesis revised.

Nat Rev Neurosci 2022 Jan 23;23(1):53-66. Epub 2021 Nov 23.

Institut de la Mémoire et de la Maladie d'Alzheimer, IM2A, Groupe Hospitalier Pitié-Salpêtrière, Sorbonne Université, Paris, France.

The current conceptualization of Alzheimer disease (AD) is driven by the amyloid hypothesis, in which a deterministic chain of events leads from amyloid deposition and then tau deposition to neurodegeneration and progressive cognitive impairment. This model fits autosomal dominant AD but is less applicable to sporadic AD. Owing to emerging information regarding the complex biology of AD and the challenges of developing amyloid-targeting drugs, the amyloid hypothesis needs to be reconsidered. Read More

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January 2022

The Cribrilina annulata" problem and new species of Juxtacribrilina (Bryozoa: Cheilostomata: Cribrilinidae) from the North Pacific.

Zootaxa 2021 Aug 6;5016(3):333-364. Epub 2021 Aug 6.

Department of Invertebrate Zoology, Faculty of Biology, Saint Petersburg State University, Universitetskaja nab. 7/9, Saint Petersburg 199034, Russia. Department of Palaeontology, Faculty of Earth Sciences, Geography and Astronomy, University of Vienna, Althanstr. 14, Vienna 1090, Austria. .

Originally described from Greenland, Juxtacribrilina annulata (Fabricius, 1780) (previously known as Cribrilina annulata) has long been regarded as having a circumpolar, Arctic-boreal distribution. The genus Juxtacribrilina Yang, Seo, Min, Grischenko Gordon, 2018 accommodated J. annulata and three related North Pacific species formerly in Cribrilina Gray, 1848 that lack avicularia, have a reduced (hood-like, cap-like, or vestigial) ooecium closely associated with modified latero-oral spines to form an ooecial complex, and produce frontally or marginally positioned dwarf ovicellate zooids. Read More

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Interfacing droplet microfluidics with antibody barcodes for multiplexed single-cell protein secretion profiling.

Lab Chip 2021 12 7;21(24):4823-4830. Epub 2021 Dec 7.

The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, State Key Laboratory of Physical Chemistry of Solid Surfaces, Key Laboratory for Chemical Biology of Fujian Province, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.

Multiplexed protein secretion analysis of single cells is important to understand the heterogeneity of cellular functions and processes in healthy and disease states. However, current single-cell platforms, such as microwell-, microchamber-, or droplet-based assays, suffer from low single-cell occupancy, waste of reagents, limited sensitivity, or inability to perform necessary operations, To overcome these drawbacks, we present an integrated droplet microfluidic device that interfaces with spatially patterned antibody barcodes for multiplexed single-cell secretome analysis. The trapping array of 100 picoliter-sized isolation chambers could achieve >80% single-cell capture efficiency with >90% viability. Read More

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December 2021

Hybrid constructed wetlands integrated with microbial fuel cells and reactive bed filter for wastewater treatment and bioelectricity generation.

Environ Sci Pollut Res Int 2021 Nov 15. Epub 2021 Nov 15.

Postgraduate Program in Environmental Technology, University of Santa Cruz do Sul (UNISC), Avenida Independência, 2293, Santa Cruz do Sul, Rio Grande do Sul, 96815-900, Brazil.

The present study aimed to develop a pilot-scale integrated system composed of anaerobic biofilter (AF), a floating treatment wetland (FTW) unit, and a vertical flow constructed wetland coupled with a microbial fuel cell (CW-MFC) and a reactive bed filter (RBF) for simultaneously decentralized urban wastewater treatment and bioelectricity generation. The first treatment stage (AF) had 1450 L and two compartments: a settler and a second one filled with plastic conduits. The two CWs (1000 L each) were vegetated with mixed plant species, the first supported in a buoyant expanded polyethylene foam and the second (CW-MFC) filled with pebbles and gravel, whereas the RBF unit was filled with P adsorbent material (light expanded clay aggregate, or LECA) and sand. Read More

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November 2021

Clinical outcomes and bacterial characteristics of carbapenem-resistant Klebsiella pneumoniae complex among patients from different global regions (CRACKLE-2): a prospective, multicentre, cohort study.

Lancet Infect Dis 2021 Nov 9. Epub 2021 Nov 9.

Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a global threat. We therefore analysed the bacterial characteristics of CRKP infections and the clinical outcomes of patients with CRKP infections across different countries.

Methods: In this prospective, multicentre, cohort study (CRACKLE-2), hospitalised patients with cultures positive for CRKP were recruited from 71 hospitals in Argentina, Australia, Chile, China, Colombia, Lebanon, Singapore, and the USA. Read More

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November 2021

The Alzheimer's disease drug development landscape.

Alzheimers Res Ther 2021 11 11;13(1):186. Epub 2021 Nov 11.

Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.

Background: Alzheimer's disease (AD) is a devastating neurodegenerative disease leading to dementia. The field has made significant progress over the last 15 years. AD diagnosis has shifted from syndromal, based on signs and symptoms, to a biomarker construct based on the pathological hallmarks of the disease: amyloid β deposition, pathologic tau, and neurodegeneration. Read More

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November 2021

HIV Infection and HIV-Associated Behaviors Among Persons Who Inject Drugs - 23 Metropolitan Statistical Areas, United States, 2018.

MMWR Morb Mortal Wkly Rep 2021 Oct 22;70(42):1459-1465. Epub 2021 Oct 22.

Division of HIV Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, CDC.

In the United States, 10% of HIV infections diagnosed in 2018 were attributed to unsafe injection drug use or male-to-male sexual contact among persons who inject drugs (PWID) (1). In 2017, among PWID or men who have sex with men and who inject drugs (MSM-ID), 76% of those who received a diagnosis of HIV infection lived in urban areas* (2). To monitor the prevalence of HIV infection and associated behaviors among persons who reported injecting drugs in the past 12 months, including MSM-ID, CDC's National HIV Behavioral Surveillance (NHBS) conducts interviews and HIV testing among populations of persons at high risk for HIV infection (MSM, PWID, and heterosexually active adults at increased risk for HIV infection) in selected metropolitan statistical areas (MSAs) (3). Read More

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October 2021

How can we know what we don't know? An exploration of professionals' engagement with complicated grief.

Patient Educ Couns 2021 Sep 13. Epub 2021 Sep 13.

St Michael's House Intellectual Disability Service, Ballymun Rd, Dublin 9, Ireland. Electronic address:

Objective: Research has shown that complicated grief has the potential to adversely affect bereaved individuals, and in this context, understanding how mental health professionals engage with it in practice is of relevance. Gaining an understanding of professionals' knowledge, attitudes, skills and training in relation to complicated grief could provide insights that will inform their training and professional development. The aim of this study was to consider professionals' engagement with complicated grief, as represented by self-reported knowledge, attitudes, skills and training. Read More

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September 2021

Recent advances in multimodality imaging of the tricuspid valve.

Expert Rev Med Devices 2021 Nov 27;18(11):1069-1081. Epub 2021 Oct 27.

Istituto Auxologico Italiano, IRCCS, Department of Cardiac, Neurological and Metabolic Sciences, San Luca Hospital, Milan, Italy.

Introduction: The tricuspid valve (TV) and the right heart chambers are complex three-dimensional structures that are difficult to assess using tomographic imaging techniques. The progressive aging of the general population and the advancements in treating left-sided heart diseases by transcatheter procedures have contributed to the tricuspid regurgitation (TR) becoming a major public health problem associated with progression to refractory heart failure and poor outcome. Recent advances in multimodality cardiac imaging allow a better understanding of the pathophysiology of TR that may translate in better management of patients. Read More

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November 2021

Enzymatic Synthesis of Sialic Acids in Microfluidics to Overcome Cross-Inhibitions and Substrate Supply Limitations.

ACS Appl Mater Interfaces 2021 Oct 6;13(41):49433-49444. Epub 2021 Oct 6.

Leibniz-Institut für Polymerforschung Dresden e.V., Hohe Straße 6, 01069 Dresden, Germany.

Multienzymatic cascade reactions are a powerful strategy for straightforward and highly specific synthesis of complex materials, such as active substances in drugs. Cross-inhibitions and incompatible reaction steps, however, often limit enzymatic activity and thus the conversion. Such limitations occur, e. Read More

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October 2021

The costs of developing treatments for Alzheimer's disease: A retrospective exploration.

Alzheimers Dement 2021 Sep 28. Epub 2021 Sep 28.

Biogen, Cambridge, Massachusetts, USA.

Introduction: With the exception of the recent accelerated approval of aducanumab, in over 26 years of research and development (R&D) investment in Alzheimer's disease (AD), only five novel drugs-all for symptomatic treatment only-have reached FDA approval. Here, we estimate the costs of AD drug development during this period in the private sector.

Methods: To estimate private R&D funding, we collected information on AD clinical trials (n = 1099; phases 1-4) conducted between January 1, 1995 and June 21, 2021 from various databases. Read More

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September 2021

An internet of things-based point-of-care device for direct reverse-transcription-loop mediated isothermal amplification to identify SARS-CoV-2.

Biosens Bioelectron 2022 Jan 23;195:113655. Epub 2021 Sep 23.

Department of Chemical Engineering (BK21 FOUR Integrated Engineering Program), Kyung Hee University, Yongin, 17104, South Korea. Electronic address:

Rapid and accurate testing tools for SARS-CoV-2 detection are urgently needed to prevent the spreading of the virus and to take timely governmental actions. Internet of things (IoT)-based diagnostic devices would be an ideal platform for point-of-care (POC) screening of COVID-19 and ubiquitous healthcare monitoring for patients. Herein, we present an advanced IoT-based POC device for real-time direct reverse-transcription-loop mediated isothermal amplification assay to detect SARS-CoV-2. Read More

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January 2022

Modular operation of microfluidic chips for highly parallelized cell culture and liquid dosing via a fluidic circuit board.

Microsyst Nanoeng 2020 30;6:107. Epub 2020 Nov 30.

BIOS Lab on Chip Group, MESA+ Institute for Nanotechnology, University of Twente, Enschede, The Netherlands.

Microfluidic systems enable automated and highly parallelized cell culture with low volumes and defined liquid dosing. To achieve this, systems typically integrate all functions into a single, monolithic device as a "one size fits all" solution. However, this approach limits the end users' (re)design flexibility and complicates the addition of new functions to the system. Read More

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November 2020

A microfluidic platform for cultivating ovarian cancer spheroids and testing their responses to chemotherapies.

Microsyst Nanoeng 2020 19;6:93. Epub 2020 Oct 19.

Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905 USA.

There is increasing interest in utilizing in vitro cultures as patient avatars to develop personalized treatment for cancer. Typical cultures utilize Matrigel-coated plates and media to promote the proliferation of cancer cells as spheroids or tumor explants. However, standard culture conditions operate in large volumes and require a high concentration of cancer cells to initiate this process. Read More

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October 2020

A mixed-methods study of multi-level factors influencing mammography overuse among an older ethnically diverse screening population: implications for de-implementation.

Implement Sci Commun 2021 Sep 26;2(1):110. Epub 2021 Sep 26.

Department of Sociomedical Sciences, Columbia University Mailman School of Public Health, 722 W 168th Street, New York, NY, 10032, USA.

Background: There is growing concern that routine mammography screening is overused among older women. Successful and equitable de-implementation of mammography will require a multi-level understanding of the factors contributing to mammography overuse.

Methods: This explanatory, sequential, mixed-methods study collected survey data (n= 52, 73. Read More

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September 2021

Parallelizable Microfluidic Platform to Model and Assess In Vitro Cellular Barriers: Technology and Application to Study the Interaction of 3D Tumor Spheroids with Cellular Barriers.

Biosensors (Basel) 2021 Sep 3;11(9). Epub 2021 Sep 3.

NMI Natural and Medical Sciences Institute, University of Tübingen, Markwiesenstraße 55, 72770 Reutlingen, Germany.

Endothelial and epithelial cellular barriers play a vital role in the selective transport of solutes and other molecules. The properties and function of these barriers are often affected in case of inflammation and disease. Modelling cellular barriers in vitro can greatly facilitate studies of inflammation, disease mechanisms and progression, and in addition, can be exploited for drug screening and discovery. Read More

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September 2021

Electrochemical water softening as pretreatment for nitrate electro bioremediation.

Sci Total Environ 2022 Feb 20;806(Pt 1):150433. Epub 2021 Sep 20.

LEQUiA, Institute of the Environment, University of Girona, C/ Maria Aurèlia Capmany, 69, E-17003 Girona, Spain. Electronic address:

Electro bioremediation is gaining interest as a sustainable treatment for contaminated groundwater. Nevertheless, the investigation is still at the laboratory level, and before their implementation is necessary to overcome important drawbacks. A prevalent issue is the high groundwater hardness that generates scale deposition on electrodes that irreversibly affects the treatment effectiveness and their lifetime. Read More

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February 2022