Psychrobacillus antarcticus sp. nov., a psychrotolerant bioemulsifier producer isolated from King George Island, Antarctica.

A Gram-stain-positive rod, psychrotolerant, aerobic and bioemulsifier-producing strain, denoted as Val9T, was isolated from soil sampled at Vale Ulman, King George Island, Antarctica. The strain grew at up to 30 °C (optimum, 15 °C), at pH 6-9 (optimum, pH 8) and with up to 5 % w/v NaCl (optimum, 3 %). The strain was motile and positive for catalase, oxidase and H2S. It did not hydrolyse starch, casein or gelatin. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain Val9T belonged to the genus Psychrobacillus and was closely related to Psychrobacillus psychrotolerans DSM 11706T (99.9 % similarity), Psychrobacillus psychrodurans DSM 11713T (99.8 %) and Psychrobacillus glaciei PB01T (99.2 %). Digital DNA-DNA hybridization and average nucleotide identity values were lower than 37.3 and 85.5 %, respectively, with the closest phylogenetic neighbours. The DNA G+C content of strain Val9T calculated from the complete genome sequence was 36.6 mol%. The predominant cellular fatty acids were anteiso-C15 : 0, iso-C15 : 0 and anteiso-C17 : 1ω11c. Menaquinone-8 was the major respiratory quinone. The peptidoglycan type was A4ß l-Orn-d-glu. The novel strain contained diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol as predominant polar lipids. Based on 16S rRNA phylogenetic and multilocus sequence analyses (recA, rpoB and gyrB), as well as phylogenomic, chemotaxonomic and phenotypic tests, we demonstrate that strain Val9T represents a novel species of the genus Psychrobacillus, for which the name Psychrobacillus antarcticus sp. nov. is proposed. The type strain is Val9T (=DSM 115096T=CCGB 1952T=NRRL B-65674T).

First Identification of bla NDM-1 Producing Escherichia coli ST 9499 Isolated from Musca domestica in the Urban Center of Rio de Janeiro, Brazil.

The present study presents phenotypic and molecular characterization of a multidrug-resistant strain of Escherichia coli (Lemef26), belonging to sequence type ST9499 carrying a blaNDM-1 carbapenem resistance gene. The bacterium was isolated from a specimen of Musca domestica, collected in proximity to a hospital in Rio de Janeiro City, Brazil. The strain was identified as E. coli by matrix-assisted laser desorption-ionization time of flight mass spectrometry (Maldi-TOF-MS) and via genotypic analysis (Whole-Genome Sequencing-WGS), followed by phylogenetic analysis, antibiotic resistance profiling (using phenotypic and genotypic methods) and virulence genotyping. Interestingly, the blaNDM-1 was the only resistance determinant detected using a panel of common resistance genes, as evaluated by PCR. In contrast, WGS detected genes conferring resistance to aminoglycosides, fluoroquinolones, quinolones, trimethoprim, beta-lactams, chloramphenicol, macrolides, sulfonamide, tetracycline, lincosamide and streptogramin B. Conjugation experiments demonstrated the transfer of carbapenem resistance, via acquisition of the blaNDM-1 sequence, to a sensitive receptor strain of E. coli, indicating that blaNDM-1 is located on a conjugative plasmid (most likely of the IncA/C incompatibility group, in association with the transposon Tn3000). Phylogenetic analyses placed Lemef26 within a clade of strains exhibiting allelic and environment diversity, with the greatest level of relatedness recorded with a strain isolated from a human source suggesting a possible anthropogenic origin. Analysis of the virulome revealed the presence of fimbrial and pilus genes, including a CFA/I fimbriae (cfaABCDE), common pilus (ecpABCDER), laminin-bind fimbrae (elfADG), hemorrhagic pilus (hcpABC) and fimbrial adherence determinants (stjC) indicates the ability of strain Lemef26 to colonize animal hosts. To the best of our knowledge, this study represents the first report of blaNDM-1 carbapenemase gene in an E. coli strain isolated from M. domestica. In concordance with the findings of previous studies on the carriage of MDR bacteria by flies, the data presented herein provide support to the idea that flies may represent a convenient means (as sentinel animals) for the monitoring of environmental contamination with multidrug-resistant bacteria.

The scientific publication of the Memórias do Instituto Oswaldo Cruz (1909-2020): a history of contribution to the biomedical sciences.

BACKGROUND: The Memórias do Instituto Oswaldo Cruz (MIOC) is one of the first scientific journals created in Brazil and currently one of the most important biomedical journals in South America. Knowledge of the main themes disseminated over time and its main contributors can contribute towards a better understanding of its trajectory and future. OBJECTIVES: Map the journal's scientific publication between 1909 and 2020. METHODS: Data from three scientific databases was combined, alongside bibliometrics and network analysis to analyse publication records between 1909 and 2020. FINDINGS: Publications increased substantially since the 1980s. The main publishing organisations are Brazilian. Excluding Brazil, the main publishing countries are the USA, Argentina, and Colombia. During the entire investigated period, the main themes refer to Chagas disease, schistosomiasis, and Leishmaniasis. During some periods, publications followed disease outbreaks in Brazil (e.g., dengue fever and yellow fever). MAIN CONCLUSIONS: Since its foundation in 1909, the MIOC has focused on infectious and parasitic diseases. The editorial changes implemented from the 1980s onwards led MIOC to a relevant growth concerning annual publications and its transformation into an important communication vehicle for researchers from several Brazilian organisations besides Fiocruz, as well as organisations from other countries, especially within Latin America.

Differences in Charge Distribution in Leishmania tarentolae Leishmanolysin Result in a Reduced Enzymatic Activity.

Leishmania tarentolae is a non-pathogenic trypanosomatid isolated from lizards widely used for heterologous protein expression and extensively studied to understand the pathogenic mechanisms of leishmaniasis. The repertoire of leishmanolysin genes was reported to be expanded in L. tarentolae genome, but no proteolytic activity was detected. Here, we analyzed L. tarentolae leishmanolysin proteins from the genome to the structural levels and evaluated the enzymatic activity of the wild-type and overexpressing mutants of leishmanolysin. A total of 61 leishmanolysin sequences were retrieved from the L. tarentolae genome. Five of them were selected for phylogenetic analysis, and for three of them, we built 3D models based on the crystallographic structure of L. major ortholog. Molecular dynamics simulations of these models disclosed a less negative electrostatic potential compared to the template. Subsequently, L. major LmjF.10.0460 and L. tarentolae LtaP10.0650 leishmanolysins were cloned in a pLEXSY expression system into L. tarentolae. Proteins from the wild-type and the overexpressing parasites were submitted to enzymatic analysis. Our results revealed that L. tarentolae leishmanolysins harbor a weak enzymatic activity about three times less abundant than L. major leishmanolysin. Our findings strongly suggest that the less negative electrostatic potential of L. tarentolae leishmanolysin can be the reason for the reduced proteolytic activity detected in this parasite.

Probing expert opinions on the future of kidney replacement therapies.

Patients with kidney failure can only survive with some form of kidney replacement (transplant or dialysis). Unfortunately, innovations in kidney replacement therapy lag behind many other medical fields. This study compiles expert opinions on candidate technologies for future kidney replacement therapies. A worldwide web-based survey was conducted with 1566 responding experts, identified from scientific publications on kidney (renal) replacement therapy, indexed in the Web of Science Core Collection (period 2014-2019). Candidate innovative approaches were categorized in line with the Kidney Health Initiative roadmap for innovative kidney replacement therapies. Most respondents expected a revolution in kidney replacement therapies: 68.59% before 2040 and 24.85% after 2040, while 6.56% expected none. Approaches anticipated as most likely were implantable artificial kidneys (38.6%) and wearable artificial kidneys (32.4%). A majority of experts expect that kidney replacement therapies can be significantly improved by innovative technologies.

Plasmodium vivax metacaspase 1 (PvMCA1) catalytic domain is conserved in field isolates from Brazilian Amazon.

In the present study, we investigated the genetic diversity of Plasmodium vivax metacaspase 1 (PvMCA1) catalytic domain in two municipalities of the main malaria hotspot in Brazil, i.e., the Juruá Valley, and observed complete sequence identity among all P. vivax field isolates and the Sal-1 reference strain. Analysis of PvMCA1 catalytic domain in different P. vivax genomic sequences publicly available also revealed a high degree of conservation worldwide, with very few amino acid substitutions that were not related to putative histidine and cysteine catalytic residues, whose involvement with the active site of protease was herein predicted by molecular modeling. The genetic conservation presented by PvMCA1 may contribute to its eligibility as a druggable target candidate in vivax malaria.

Mapping the tuberculosis scientific landscape among BRICS countries: a bibliometric and network analysis.

BACKGROUND: The five BRICS (Brazil, Russian, Indian, China, and South Africa) countries bear 49% of the world's tuberculosis (TB) burden and they are committed to ending tuberculosis. OBJECTIVES: The aim of this paper is to map the scientific landscape related to TB research in BRICS countries. METHODS: Were combined bibliometrics and social network analysis techniques to map the scientific publications related to TB produced by the BRICS. Was made a descriptive statistical data covering the full period of analysis (1993-2016) and the research networks were made for 2007-2016 (8,366 records). The bubble charts were generated by VantagePoint and the networks by the Gephi 0.9.1 software (Gephi Consortium 2010) from co-occurrence matrices produced in VantagePoint. The Fruchterman-Reingold algorithm provided the networks' layout. FINDINGS: During the period 1993-2016, there were 38,315 peer-reviewed, among them, there were 11,018 (28.7%) articles related by one or more authors in a BRICS: India 38.7%; China 23.8%; South Africa 21.1%; Brazil 13.0%; and Russia 4.5% (The total was greater than 100% because our criterion was all papers with at least one author in a BRICS). Among the BRICS, there was greater interaction between India and South Africa and organisations in India and China had the highest productivity; however, South African organisations had more interaction with countries outside the BRICS. Publications by and about BRICS generally covered all research areas, especially those in India and China covered all research areas, although Brazil and South Africa prioritised infectious diseases, microbiology, and the respiratory system. MAIN CONCLUSIONS: An overview of BRICS scientific publications and interactions highlighted the necessity to develop a BRICS TB research plan to increase efforts and funding to ensure that basic science research successfully translates into products and policies to help end the TB epidemic.

2,3-Butanediol production by the non-pathogenic bacterium Paenibacillus brasilensis.

2,3-Butanediol (2,3-BDO) is of considerable importance in the chemical, plastic, pharmaceutical, cosmetic, and food industries. The main bacterial species producing this compound are considered pathogenic, hindering large-scale productivity. The species Paenibacillus brasilensis is generally recognized as safe (GRAS) and is phylogenetically similar to P. polymyxa, a species widely used for 2,3-BDO production. Here, we demonstrate, for the first time, that P. brasilensis strains produce 2,3-BDO. Total 2,3-BDO concentrations for 15 P. brasilensis strains varied from 5.5 to 7.6 g/l after 8 h incubation at 32 °C in modified YEPD medium containing 20 g/l glucose. Strain PB24 produced 8.2 g/l of 2,3-BDO within a 12-h growth period, representing a yield of 0.43 g/g and a productivity of 0.68 g/l/h. An increase in 2,3-BDO production by strain PB24 was observed using higher concentrations of glucose, reaching 27 g/l of total 2,3-BDO in YEPD containing about 80 g/l glucose within a 72-h growth period. We sequenced the genome of P. brasilensis PB24 and uncovered at least six genes related to the 2,3-BDO pathway at four distinct loci. We also compared gene sequences related to the 2,3-BDO pathway in P. brasilensis PB24 with those of other spore-forming bacteria, and found strong similarity to P. polymyxa, P. terrae, and P. peoriae 2,3-BDO-related genes. Regulatory regions upstream of these genes indicated that they are probably co-regulated. Finally, we propose a production pathway from glucose to 2,3-BDO in P. brasilensis PB24. Although the gene encoding S-2,3-butanediol dehydrogenase (butA) was found in the genome of P. brasilensis PB24, only R,R-2,3- and meso-2,3-butanediol were detected by gas chromatography under the growth conditions tested here. Our findings can serve as a basis for further improvements to the metabolic capabilities of this little-studied Paenibacillus species in relation to production of the high-value chemical 2,3-butanediol.

Mapping the dengue scientific landscape worldwide: a bibliometric and network analysis.

BACKGROUND: Despite the current global trend of reduction in the morbidity and mortality of neglected diseases, dengue's incidence has increased and occurrence areas have expanded. Dengue also persists as a scientific and technological challenge since there is no effective treatment, vaccine, vector control or public health intervention. Combining bibliometrics and social network analysis methods can support the mapping of dengue research and development (R&D) activities worldwide. OBJECTIVES: The aim of this paper is to map the scientific scenario related to dengue research worldwide. METHODS: We use scientific publication data from Web of Science Core Collection - articles indexed in Science Citation Index Expanded (SCI-EXPANDED) - and combine bibliometrics and social network analysis techniques to identify the most relevant journals, scientific references, research areas, countries and research organisations in the dengue scientific landscape. FINDINGS: Our results show a significant increase of dengue publications over time; tropical medicine and virology as the most frequent research areas and biochemistry and molecular biology as the most central area in the network; USA and Brazil as the most productive countries; and Mahidol University and Fundação Oswaldo Cruz as the main research organisations and the Centres for Disease Control and Prevention as the most central organisation in the collaboration network. MAIN CONCLUSIONS: Our findings can be used to strengthen a global knowledge platform guiding policy, planning and funding decisions as well as to providing directions to researchers and institutions. So that, by offering to the scientific community, policy makers and public health practitioners a mapping of the dengue scientific landscape, this paper has aimed to contribute to upcoming debates, decision-making and planning on dengue R&D and public health strategies worldwide.

The evolution of environmental metalloproteomics over the last 15 years through bibliometric techniques.

Metalloproteomic studies in environmental scenarios are of significant value in elucidating metal uptake, trafficking, accumulation and metabolism linked to biomolecules in biological systems. The advent of this field occurred in the early 2000s, and it has since become an interesting and growing area of interdisciplinary research, although the number of publications in Environmental Metalloprotemics is still very low compared to other metallomic areas. In this context, the evolution of Environmental Metalloprotemics in the last decades was evaluated herein through the use of bibliometric techniques, identifying variables that may aid researchers in this area to form collaborative networks with established scientists in this regard, such as main authors, published articles, institutions, countries and established collaborations involved in academic research on this subject. Results indicate a growing trend of publications over time, reflecting the interest of the scientific community in Environmental Metalloprotemics, but also demonstrated that the research interactions in this field are still country- and organization-specific. Higher amounts of publications are observed from the late 2000's onwards, related to the increasing technological advances in the area, such as the development of techniques combining atomic spectroscopy and biochemical or proteomic techniques. The retrieved publications also indicate that the recent advances in genomic, proteomic and metallomic areas have allowed for extended applications of Environmental Metalloprotemics in non-model organisms. The results reported herein indicate that Environmental Metalloprotemics seems to now be reaching a more mature stage, in which analytical techniques are now well established and can be routinely applied in environmental scenarios, benefitting researchers and allowing for further insights into this fascinating field.

Exploring the landscape of adult autism research in psychology: a bibliometric and network analysis.

The global prevalence of autism spectrum disorder (ASD) is increasing. ASD manifests with persistent social communication and interaction challenges, limited interests, and repetitive behaviors. As the scientific literature on ASD in adults varies greatly, mapping the recent global research becomes valuable for enhancing comprehension of this subject. This study aims to map recent global scientific publications on ASD in adults. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, bibliometrics, and network analyses, we assessed 850 articles indexed in the Web of Science Core Collection between 2013 and 2022 assigned to the research area of psychology. Findings indicate an annual average growth of 11.69%. Key keywords include Emotion, Anxiety, and Depression, with Anxiety, Depression, and Mental Health as central nodes in the network. Rehabilitation, Behavioral Sciences, and Psychiatry frequently co-occur, and Psychology, Psychiatry, and 'Neurosciences and Neurology' are central nodes in the network of research areas. The United States of America and the United Kingdom lead in publications, with the United Kingdom being the most central country in the network. King's College London and the University of California are the main research organizations, with King's College London as the central node in the network. The American Psychiatric Association's DSM-5-TR was the most cited reference in the period. This comprehensive analysis contributes to understanding the landscape of ASD research in adults, providing insights for future research and fostering collaborations.

Problem-Based Learning in Medical Education: A Global Research Landscape of the Last Ten Years (2013-2022).

Background: Problem-based learning (PBL) constructs a curriculum that merges theory and practice by employing clinical scenarios or real-world problems. Originally designed for the pre-clinical phase of undergraduate medicine, PBL has since been integrated into diverse aspects of medical education. Therefore, this study aims to map the global scientific landscape related to PBL in medical education in the last ten years. Methods: We combined bibliometrics and network analysis to analyze the metadata of related research articles published between 2013 and 2022 and indexed in the Web of Science Core Collection. Results: Our results show an annual publication rate of 9.42%. The two main journals disseminating research on this subject are BMC Medical Education and Medical Teacher. Education & Educational Research and Health Care Sciences & Services are the two most frequent research areas, and also the two most central nodes of the related network. The USA and China are the most publishing countries, while the Netherlands and Canada are the most collaborative. The Maastricht University holds the position of most publishing and collaborative research organization. The University of California ranks second in publications, while the University of Toronto is the second most central research organization. Conclusions: Our study provides an overview of the last ten years of publications related to PBL and medical education, and we hope it can be of interest to educators, researchers, and students involved with this subject. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-024-02003-1.

Future of Artificial Intelligence Applications in Cancer Care: A Global Cross-Sectional Survey of Researchers.

Cancer significantly contributes to global mortality, with 9.3 million annual deaths. To alleviate this burden, the utilization of artificial intelligence (AI) applications has been proposed in various domains of oncology. However, the potential applications of AI and the barriers to its widespread adoption remain unclear. This study aimed to address this gap by conducting a cross-sectional, global, web-based survey of over 1000 AI and cancer researchers. The results indicated that most respondents believed AI would positively impact cancer grading and classification, follow-up services, and diagnostic accuracy. Despite these benefits, several limitations were identified, including difficulties incorporating AI into clinical practice and the lack of standardization in cancer health data. These limitations pose significant challenges, particularly regarding testing, validation, certification, and auditing AI algorithms and systems. The results of this study provide valuable insights for informed decision-making for stakeholders involved in AI and cancer research and development, including individual researchers and research funding agencies.

A thermophilic chemolithoautotrophic bacterial consortium suggests a mutual relationship between bacteria in extreme oligotrophic environments.

A thermophilic, chemolithoautotrophic, and aerobic microbial consortium (termed carbonitroflex) growing in a nutrient-poor medium and an atmosphere containing N2, O2, CO2, and CO is investigated as a model to expand our understanding of extreme biological systems. Here we show that the consortium is dominated by Carbonactinospora thermoautotrophica (strain StC), followed by Sphaerobacter thermophilus, Chelatococcus spp., and Geobacillus spp. Metagenomic analysis of the consortium reveals a mutual relationship among bacteria, with C. thermoautotrophica StC exhibiting carboxydotrophy and carbon-dioxide storage capacity. C. thermoautotrophica StC, Chelatococcus spp., and S. thermophilus harbor genes encoding CO dehydrogenase and formate oxidase. No pure cultures were obtained under the original growth conditions, indicating that a tightly regulated interactive metabolism might be required for group survival and growth in this extreme oligotrophic system. The breadwinner hypothesis is proposed to explain the metabolic flux model and highlight the vital role of C. thermoautotrophica StC (the sole keystone species and primary carbon producer) in the survival of all consortium members. Our data may contribute to the investigation of complex interactions in extreme environments, exemplifying the interconnections and dependency within microbial communities.

Molecular characterization of Paenibacillus antarcticus IPAC21, a bioemulsifier producer isolated from Antarctic soil.

Paenibacillus antarcticus IPAC21, an endospore-forming and bioemulsifier-producing strain, was isolated from King George Island, Antarctica. As psychrotolerant/psychrophilic bacteria can be considered promising sources for novel products such as bioactive compounds and other industrially relevant substances/compounds, the IPAC21 genome was sequenced using Illumina Hi-seq, and a search for genes related to the production of bioemulsifiers and other metabolic pathways was performed. The IPAC21 strain has a genome of 5,505,124 bp and a G + C content of 40.5%. Genes related to the biosynthesis of exopolysaccharides, such as the gene that encodes the extracellular enzyme levansucrase responsible for the synthesis of levan, the 2,3-butanediol pathway, PTS sugar transporters, cold-shock proteins, and chaperones were found in its genome. IPAC21 cell-free supernatants obtained after cell growth in trypticase soy broth at different temperatures were evaluated for bioemulsifier production by the emulsification index (EI) using hexadecane, kerosene and diesel. EI values higher than 50% were obtained using the three oil derivatives when IPAC21 was grown at 28°C. The bioemulsifier produced by P. antarcticus IPAC21 was stable at different NaCl concentrations, low temperatures and pH values, suggesting its potential use in lower and moderate temperature processes in the petroleum industry.

Desmoid fibroma simulating malignant breast neoplasm: A case report and literature review.

INTRODUCTION: Desmoid fibroma (DF) is a disorder characterized by strong clonal proliferation of myofibroblasts and fibroblasts. We describe a case of DF that mimicked a breast tumor, along with a review of the literature on the clinical manifestation, diagnostic process, and course of therapy for this combative disease. CASE REPORT: A 34-year-old female patient with breast lump at the junction of the upper quadrants of the left breast. After the diagnosis of DF, it was decided to perform a sectorectomy of the left breast associated with post-quadrant reconstruction, with immunohistochemistry and findings compatible with DF. DISCUSSION: Clinically manifests as a solid mass that is often painless and occasionally adherent to the chest wall. A treatment strategy should be idealized for each patient. Thus, there is the possibility of performing radical surgery for resection and/or radiotherapy, and surgery may be followed by radiotherapy.

Antimicrobial activity of Paenibacillus kribbensis POC 115 against the dermatophyte Trichophyton rubrum.

In a search for an antifungal substance with activity against the dermatophyte fungus Trichophyton rubrum, strain POC 115 was chosen among different Paenibacillus strains for its phenotypic and genetic characterization and for preliminary characterization of its antimicrobial substance. Strain POC 115 was identified as belonging to Paenibacillus kribbensis. Physico-chemical characterization of the antimicrobial substance showed that it was not stable during heat and organic solvents treatments, but its activity was preserved at a wide range of pH and after treatment with pronase E, trypsin and DNase I. The crude concentrated supernatant of POC 115 culture was partially purified and the fraction presenting antimicrobial activity was further analyzed by UPLC/Mass Spectrometry. Two peaks were observed at 2.02 (mass 1,207 D) and 2.71 (mass 1,014 D) min in the mass chromatogram. The antimicrobial substance produced by POC 115 was correlated to iturin family compounds based on a set of primers designed for the amplification of PKS operon in the POC 115 genome. As happens with the mode of action of the antibiotics of the iturin group, the AMS produced by POC 115 caused the disruption of cytoplasmic membrane of T. rubrum and the subsequent withdraw of the intracellular material. This is the first report on the production of antimicrobial substances in P. kribbensis, and it may be of great relevance as an alternative or supplementary substance to antifungal drugs currently used against dermatophytes.

Future of genetic therapies for rare genetic diseases: what to expect for the next 15 years?

Introduction: Rare genetic diseases affect millions of people worldwide. Most of them are caused by defective genes that impair quality of life and can lead to premature death. As genetic therapies aim to fix or replace defective genes, they are considered the most promising treatment for rare genetic diseases. Yet, as these therapies are still under development, it is still unclear whether they will be successful in treating these diseases. This study aims to address this gap by assessing researchers' opinions on the future of genetic therapies for the treatment of rare genetic diseases. Methods: We conducted a global cross-sectional web-based survey of researchers who recently authored peer-reviewed articles related to rare genetic diseases. Results: We assessed the opinions of 1430 researchers with high and good knowledge about genetic therapies for the treatment of rare genetic diseases. Overall, the respondents believed that genetic therapies would be the standard of care for rare genetic diseases before 2036, leading to cures after this period. CRISPR-Cas9 was considered the most likely approach to fixing or replacing defective genes in the next 15 years. The respondents with good knowledge believed that genetic therapies would only have long-lasting effects after 2036, while those with high knowledge were divided on this issue. The respondents with good knowledge on the subject believed that non-viral vectors are more likely to be successful in fixing or replacing defective genes in the next 15 years, while most of the respondents with high knowledge believed viral vectors would be more successful. Conclusion: Overall, the researchers who participated in this study expect that in the future genetic therapies will greatly benefit the treatment of patients with rare genetic diseases.

A global survey of researchers on the future of genetic therapies for rare genetic diseases Rare genetic diseases are caused by defective genes that result from one or more mutations in the genome. Today, the therapeutic options for these diseases are limited, and there are approved treatments for about 5% of them. In the future, genetic therapies (a group of techniques developed to correct defective genes) are expected to revolutionize the treatment of rare genetic diseases. Although promising, most of these therapies are currently under development and have a long way to go before their efficacy and safety can be proved. The uncertainty surrounding this topic therefore means the success of genetic therapies in treating or curing rare genetic diseases is not yet assured. To address this knowledge gap, we surveyed 1430 researchers working in rare genetic diseases about the future of genetic therapies for the treatment of these diseases over the next 15 years. Most of them expected gene therapies to be the standard of care for rare genetic diseases before 2036 and to be able to cure them after this date. CRISPR-Cas9 was felt to be the gene editing approach that was most likely to succeed in fixing or replacing defective genes in the next 15 years. The respondents with high knowledge about gene therapies for the treatment of rare diseases believed gene therapies would have long-lasting effects before 2036, while those with good knowledge expected this to be the case only after 2036. The former believed in viral vectors and the latter in non-viral vectors to fix or replace defective genes in the next 15 years.

Anticipating New Treatments for Cystic Fibrosis: A Global Survey of Researchers.

Cystic fibrosis is a life-threatening disease that affects at least 100,000 people worldwide. It is caused by a defect in the cystic fibrosis transmembrane regulator (CFTR) gene and presently, 360 CFTR-causing mutations have been identified. Since the discovery of the CFTR gene, the expectation of developing treatments that can substantially increase the quality of life or even cure cystic fibrosis patients is growing. Yet, it is still uncertain today which developing treatments will be successful against cystic fibrosis. This study addresses this gap by assessing the opinions of over 524 cystic fibrosis researchers who participated in a global web-based survey. For most respondents, CFTR modulator therapies are the most likely to succeed in treating cystic fibrosis in the next 15 years, especially through the use of CFTR modulator combinations. Most respondents also believe that fixing or replacing the CFTR gene will lead to a cure for cystic fibrosis within 15 years, with CRISPR-Cas9 being the most likely genetic tool for this purpose.