Publications by authors named "Martin Antonio"

388 Publications

Editorial: Understanding the Cytokine Release Syndrome: Toward Improving Cancer Immunotherapy.

Front Immunol 2021 19;12:666703. Epub 2021 Mar 19.

Department of Experimental Hematology, Instituto de Investigación Sanitaria-Fundación Jiménez Diaz, Madrid, Spain.

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http://dx.doi.org/10.3389/fimmu.2021.666703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017175PMC
March 2021

Molecular diagnostic assays for the detection of common bacterial meningitis pathogens: A narrative review.

EBioMedicine 2021 Mar 12;65:103274. Epub 2021 Mar 12.

Department of Zoology, University of Oxford, South Parks Rd, Oxford OX1 3SY, United Kingdom. Electronic address:

Bacterial meningitis is a major global cause of morbidity and mortality. Rapid identification of the aetiological agent of meningitis is essential for clinical and public health management and disease prevention given the wide range of pathogens that cause the clinical syndrome and the availability of vaccines that protect against some, but not all, of these. Since microbiological culture is complex, slow, and often impacted by prior antimicrobial treatment of the patient, molecular diagnostic assays have been developed for bacterial detection. Distinguishing between meningitis caused by Neisseria meningitidis (meningococcus), Streptococcus pneumoniae (pneumococcus), Haemophilus influenzae, and Streptococcus agalactiae and identifying their polysaccharide capsules is especially important. Here, we review methods used in the identification of these bacteria, providing an up-to-date account of available assays, allowing clinicians and diagnostic laboratories to make informed decisions about which assays to use.
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http://dx.doi.org/10.1016/j.ebiom.2021.103274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957090PMC
March 2021

ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma.

Radiother Oncol 2021 Jan;154:327-353

Department of Radiation Oncology, Leiden University Medical Center, Leiden Netherlands.

A European consensus conference on endometrial carcinoma was held in 2014 to produce multidisciplinary evidence-based guidelines on selected questions. Given the large body of literature on the management of endometrial carcinoma published since 2014, the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy & Oncology (ESTRO) and the European Society of Pathology (ESP) jointly decided to update these evidence-based guidelines and to cover new topics in order to improve the quality of care for women with endometrial carcinoma across Europe and worldwide. ESGO/ESTRO/ESP nominated an international multidisciplinary development group consisting of practicing clinicians and researchers who have demonstrated leadership and expertise in the care and research of endometrial carcinoma (27 experts across Europe). To ensure that the guidelines are evidence-based, the literature published since 2014, identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 191 independent international practitioners in cancer care delivery and patient representatives. The guidelines comprehensively cover endometrial carcinoma staging, definition of prognostic risk groups integrating molecular markers, pre- and intra-operative work-up, fertility preservation, management for early, advanced, metastatic, and recurrent disease and palliative treatment. Principles of radiotherapy and pathological evaluation are also defined.
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http://dx.doi.org/10.1016/j.radonc.2020.11.018DOI Listing
January 2021

A novel closed technique for ultrasound-guided plantar fascia release with a needle: review of 107 cases with a minimum follow-up of 24 months.

J Orthop Surg Res 2021 Feb 24;16(1):153. Epub 2021 Feb 24.

University of Alcalá, Madrid. School of Medicine and Health Sciences, Department of Nursery and Physiotherapy, University of Alcalá, Alcalá de Henares, Spain.

Background: This study aims to analyze the clinical outcome of a new ultrasound-guided surgery for partial plantar fasciotomy performed with a needle for treatment of plantar fasciitis.

Methods: We performed a retrospective review of 107 patients diagnosed with plantar fasciitis who underwent ultrasound-guided release of the plantar fascia. The series included 62 males (57.9%) and 45 females (42.1%) treated between April 2014 and February 2018, with a mean follow-up of 21.05 ± 10.96 months (7-66) and a minimum follow-up of 24 months. The mean age was 48.10 ± 10.27 years (27-72). Clinical assessments and ultrasound examination were carried out before treatment, after 1 week, and then after 1, 3, 12, and 24 months. The clinical assessment was based on a visual analog scale and the Foot and Ankle Disability Index.

Results: Heel pain improved in 92.5% (99) of patients, but not in 7.4% (8 patients). In the group of patients whose heel pain improved, 9 experienced overload on the lateral column and dorsum of the foot, which improved with the use of plantar orthoses and a rehabilitation program. We recorded no nerve complications (e.g., paresthesia), vascular injuries, or wound-related problems.

Conclusion: Ultrasound-guided partial plantar fasciotomy with a needle is safe, since structures are under direct visualization of the surgeon and the risk of damage is minimal. Stitches are not necessary, and recovery is fast. Consequently, costs are low, and the patient can return to work quickly. This technique may represent a valid option for treatment of plantar fasciitis.
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http://dx.doi.org/10.1186/s13018-021-02302-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903032PMC
February 2021

Molecular Epidemiology of Group A Infections in The Gambia.

Vaccines (Basel) 2021 Feb 4;9(2). Epub 2021 Feb 4.

Laboratoire de Génétique et Physiologie Bactérienne, IBMM, Université Libre de Bruxelles, 12 Rue des Professeurs Jenner et Brachet, 6041 Gosselies, Belgium.

Molecular epidemiological data on Group A (GAS) infection in Africa is scarce. We characterized the types and -clusters of 433 stored clinical GAS isolates from The Gambia collected between 2004 and 2018. To reduce the potential for strain mistyping, we used a newly published primer for -typing. There was considerable strain diversity, highlighting the need for vaccine development offering broad strain protection.
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http://dx.doi.org/10.3390/vaccines9020124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913941PMC
February 2021

Phylogenomics of reveals a new lineage and a complex evolutionary history.

Microb Genom 2021 02;7(2)

University of Basel, Basel, Switzerland.

Human tuberculosis (TB) is caused by members of the complex (MTBC). The MTBC comprises several human-adapted lineages known as , as well as two lineages (L5 and L6) traditionally referred to as . Strains of L5 and L6 are largely limited to West Africa for reasons unknown, and little is known of their genomic diversity, phylogeography and evolution. Here, we analysed the genomes of 350 L5 and 320 L6 strains, isolated from patients from 21 African countries, plus 5 related genomes that had not been classified into any of the known MTBC lineages. Our population genomic and phylogeographical analyses showed that the unclassified genomes belonged to a new group that we propose to name MTBC lineage 9 (L9). While the most likely ancestral distribution of L9 was predicted to be East Africa, the most likely ancestral distribution for both L5 and L6 was the Eastern part of West Africa. Moreover, we found important differences between L5 and L6 strains with respect to their phylogeographical substructure and genetic diversity. Finally, we could not confirm the previous association of drug-resistance markers with lineage and sublineages. Instead, our results indicate that the association of drug resistance with lineage is most likely driven by sample bias or geography. In conclusion, our study sheds new light onto the genomic diversity and evolutionary history of , and highlights the need to consider the particularities of each MTBC lineage for understanding the ecology and epidemiology of TB in Africa and globally.
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http://dx.doi.org/10.1099/mgen.0.000477DOI Listing
February 2021

Genomic diversity of from healthy children in rural Gambia.

PeerJ 2021 6;9:e10572. Epub 2021 Jan 6.

Quadram Institute Bioscience, Norwich Research Park, Norfolk, United Kingdom.

Little is known about the genomic diversity of in healthy children from sub-Saharan Africa, even though this is pertinent to understanding bacterial evolution and ecology and their role in infection. We isolated and whole-genome sequenced up to five colonies of faecal from 66 asymptomatic children aged three-to-five years in rural Gambia (n = 88 isolates from 21 positive stools). We identified 56 genotypes, with an average of 2.7 genotypes per host. These were spread over 37 seven-allele sequence types and the phylogroups A, B1, B2, C, D, E, F and cryptic clade I. Immigration events accounted for three-quarters of the diversity within our study population, while one-quarter of variants appeared to have arisen from within-host evolution. Several isolates encode putative virulence factors commonly found in Enteropathogenic and Enteroaggregative and 53% of the isolates encode resistance to three or more classes of antimicrobials. Thus, resident in these children may constitute reservoirs of virulence- and resistance-associated genes. Moreover, several study strains were closely related to isolates that caused disease in humans or originated from livestock. Our results suggest that within-host evolution plays a minor role in the generation of diversity compared to independent immigration and the establishment of strains among our study population. Also, this study adds significantly to the number of commensal genomes, a group that has been traditionally underrepresented in the sequencing of this species.
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http://dx.doi.org/10.7717/peerj.10572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796664PMC
January 2021

Characteristics of Salmonella recovered from stools of children enrolled in the Global Enteric Multicenter Study.

Clin Infect Dis 2021 Jan 25. Epub 2021 Jan 25.

Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.

Background: The Global Enteric Multicenter Study (GEMS) determined the etiologic agents of moderate-to-severe diarrhea (MSD) in children under 5 years old in Africa and Asia. Here, we describe the prevalence and antimicrobial susceptibility of non-typhoidal Salmonella (NTS) serovars in GEMS and examine the phylogenetics of Salmonella Typhimurium ST313 isolates.

Methods: Salmonella isolated from children with MSD or diarrhea-free controls were identified by classical clinical microbiology and serotyped using antisera and/or whole genome sequence data. We evaluated antimicrobial susceptibility using the Kirby-Bauer disk diffusion method. Salmonella Typhimurium sequence types were determined using multi-locus sequence typing and whole genome sequencing was performed to assess the phylogeny of ST313.

Results: Out of 370 Salmonella-positive individuals, 190 (51.4%) were MSD cases and 180 (48.6%) were diarrhea-free controls. The most frequent Salmonella serovars identified were Salmonella Typhimurium, serogroup O:8 (C2-C3), serogroup O:6,7 (C1), Salmonella Paratyphi B Java and serogroup O:4 (B). The prevalence of NTS was low but similar across sites, regardless of age, and was similar amongst both cases and controls except in Kenya, where Salmonella Typhimurium was more commonly associated with cases than controls. Phylogenetic analysis showed that these Salmonella Typhimurium isolates, all ST313, were highly genetically related to isolates from controls. Generally, Salmonella isolates from Asia were resistant to ciprofloxacin and ceftriaxone but African isolates were susceptible to these antibiotics.

Conclusion: Our data confirms that NTS is prevalent, albeit at low levels, in Africa and South Asia. Our findings provide further evidence that multi-drug resistant Salmonella Typhimurium ST313 can be carried asymptomatically by humans in sub-Saharan Africa.
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http://dx.doi.org/10.1093/cid/ciab051DOI Listing
January 2021

Carriage Dynamics of Pneumococcal Serotypes in Naturally Colonized Infants in a Rural African Setting During the First Year of Life.

Front Pediatr 2020 8;8:587730. Epub 2021 Jan 8.

Medical Research Council (MRC) Unit The Gambia at the London School of Hygiene and Tropical Medicine, Fajara, Gambia.

(the pneumococcus) carriage precedes invasive disease and influences population-wide strain dynamics, but limited data exist on temporal carriage patterns of serotypes due to the prohibitive costs of longitudinal studies. Here, we report carriage prevalence, clearance and acquisition rates of pneumococcal serotypes sampled from newborn infants bi-weekly from weeks 1 to 27, and then bi-monthly from weeks 35 to 52 in the Gambia. We used sweep latex agglutination and whole genome sequencing to serotype the isolates. We show rapid pneumococcal acquisition with nearly 31% of the infants colonized by the end of first week after birth and quickly exceeding 95% after 2 months. Co-colonization with multiple serotypes was consistently observed in over 40% of the infants at each sampling point during the first year of life. Overall, the mean acquisition time and carriage duration regardless of serotype was 38 and 24 days, respectively, but varied considerably between serotypes comparable to observations from other regions. Our data will inform disease prevention and control measures including providing baseline data for parameterising infectious disease mathematical models including those assessing the impact of clinical interventions such as pneumococcal conjugate vaccines.
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http://dx.doi.org/10.3389/fped.2020.587730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820366PMC
January 2021

Resilience to maintain quality of intrapartum care in war torn Yemen: a retrospective pre-post study evaluating effects of changing birth volumes in a congested frontline hospital.

BMC Pregnancy Childbirth 2021 Jan 7;21(1):36. Epub 2021 Jan 7.

Global Health Section, Department of Public Health, University of Copenhagen, Copenhagen, Denmark.

Background: Fragile and conflict-affected states contribute with more than 60% of the global burden of maternal mortality. There is an alarming need for research exploring maternal health service access and quality and adaptive responses during armed conflict. Taiz Houbane Maternal and Child Health Hospital in Yemen was established during the war as such adaptive response. However, as number of births vastly exceeded the facility's pre-dimensioned capacity, a policy was implemented to restrict admissions. We here assess the restriction's effects on the quality of intrapartum care and birth outcomes.

Methods: A retrospective before and after study was conducted of all women giving birth in a high-volume month pre-restriction (August 2017; n = 1034) and a low-volume month post-restriction (November 2017; n = 436). Birth outcomes were assessed for all births (mode of birth, stillbirths, intra-facility neonatal deaths, and Apgar score < 7). Quality of intrapartum care was assessed by a criterion-based audit of all caesarean sections (n = 108 and n = 82) and of 250 randomly selected vaginal births in each month.

Results: Background characteristics of women were comparable between the months. Rates of labour inductions and caesarean sections increased significantly in the low-volume month (14% vs. 22% (relative risk (RR) 0.62, 95% confidence interval (CI) 0.45-0.87) and 11% vs. 19% (RR 0.55, 95% CI 0.42-0.71)). No other care or birth outcome indicators were significantly different. Structural and human resources remained constant throughout, despite differences in patient volume.

Conclusions: Assumptions regarding quality of care in periods of high demand may be misguiding - resilience to maintain quality of care was strong. We recommend health actors to closely monitor changes in quality of care when implementing resource changes; to enable safe care during birth for as many women as possible.
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http://dx.doi.org/10.1186/s12884-020-03507-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791801PMC
January 2021

Genomic diversity of isolates from backyard chickens and guinea fowl in the Gambia.

Microb Genom 2021 01 30;7(1). Epub 2020 Nov 30.

Quadram Institute Bioscience, Norwich Research Park, Norwich, Norfolk, UK.

Chickens and guinea fowl are commonly reared in Gambian homes as affordable sources of protein. Using standard microbiological techniques, we obtained 68 caecal isolates of from 10 chickens and 9 guinea fowl in rural Gambia. After Illumina whole-genome sequencing, 28 sequence types were detected in the isolates (4 of them novel), of which ST155 was the most common (22/68, 32 %). These strains span four of the eight main phylogroups of with phylogroups B1 and A being most prevalent. Nearly a third of the isolates harboured at least one antimicrobial resistance gene, while most of the ST155 isolates (14/22, 64 %) encoded resistance to ≥3 classes of clinically relevant antibiotics, as well as putative virulence factors, suggesting pathogenic potential in humans. Furthermore, hierarchical clustering revealed that several Gambian poultry strains were closely related to isolates from humans. Although the ST155 lineage is common in poultry from Africa and South America, the Gambian ST155 isolates belong to a unique cgMLST cluster comprising closely related (38-39 alleles differences) isolates from poultry and livestock from sub-Saharan Africa - suggesting that strains can be exchanged between poultry and livestock in this setting. Continued surveillance of and other potential pathogens in rural backyard poultry from sub-Saharan Africa is warranted.
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http://dx.doi.org/10.1099/mgen.0.000484DOI Listing
January 2021

Natural Killer Cells in Immunotherapy: Are We Nearly There?

Cancers (Basel) 2020 Oct 27;12(11). Epub 2020 Oct 27.

Department of Hematology, Hospital Clinic, IDIBAPS, 08036 Barcelona, Spain.

Natural killer (NK) cells are potent anti-tumor and anti-microbial cells of our innate immune system. They are equipped with a vast array of receptors that recognize tumor cells and other pathogens. The innate immune activity of NK cells develops faster than the adaptive one performed by T cells, and studies suggest an important immunoregulatory role for each population against the other. The association, observed in acute myeloid leukemia patients receiving haploidentical killer-immunoglobulin-like-receptor-mismatched NK cells, with induction of complete remission was the determinant to begin an increasing number of clinical studies administering NK cells for the treatment of cancer patients. Unfortunately, even though transfused NK cells demonstrated safety, their observed efficacy was poor. In recent years, novel studies have emerged, combining NK cells with other immunotherapeutic agents, such as monoclonal antibodies, which might improve clinical efficacy. Moreover, genetically-modified NK cells aimed at arming NK cells with better efficacy and persistence have appeared as another option. Here, we review novel pre-clinical and clinical studies published in the last five years administering NK cells as a monotherapy and combined with other agents, and we also review chimeric antigen receptor-modified NK cells for the treatment of cancer patients. We then describe studies regarding the role of NK cells as anti-microbial effectors, as lessons that we could learn and apply in immunotherapy applications of NK cells; these studies highlight an important immunoregulatory role performed between T cells and NK cells that should be considered when designing immunotherapeutic strategies. Lastly, we highlight novel strategies that could be combined with NK cell immunotherapy to improve their targeting, activity, and persistence.
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http://dx.doi.org/10.3390/cancers12113139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694052PMC
October 2020

The clinical presentation of culture-positive and culture-negative, qPCR-attributable shigellosis in the Global Enteric Multicenter Study and derivation of a Shigella severity score: implications for pediatric Shigella vaccine trials.

Clin Infect Dis 2020 Oct 12. Epub 2020 Oct 12.

Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.

Background: Shigella is a leading cause of childhood diarrhea and target for vaccine development. Microbiologic and clinical case definitions are needed for pediatric field vaccine efficacy trials.

Methods: We compared characteristics of moderate to severe diarrhea (MSD) cases in the Global Enteric Multicenter Study (GEMS) between children with culture positive Shigella to those with culture-negative, qPCR-attributable Shigella (defined by an ipaH gene cycle threshold <27.9). Among Shigella MSD cases, we determined risk factors for death and derived a clinical severity score.

Results: Compared to culture-positive Shigella MSD cases (n=745), culture-negative/qPCR-attributable Shigella cases (n=852) were more likely to be under 12 months, stunted, have a longer duration of diarrhea, and less likely to have high stool frequency or a fever. There was no difference in dehydration, hospitalization, or severe classification from a modified Vesikari score. Twenty-two (1.8%) Shigella MSD cases died within the 14-days after presentation to health facilities, and 59.1% of these deaths were in culture-negative cases. Age < 12 months, diarrhea duration prior to presentation, vomiting, stunting, wasting, and hospitalization were associated with mortality. A model-derived score assigned points for dehydration, hospital admission, and longer diarrhea duration but was not significantly better at predicting 14-day mortality than a modified Vesikari score.

Conclusions: A composite severity score consistent with severe disease or dysentery may be a pragmatic clinical endpoint for severe shigellosis in vaccine trials. Reliance on culture for microbiologic confirmation may miss a substantial number of Shigella cases but is currently required to measure serotype specific immunity.
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http://dx.doi.org/10.1093/cid/ciaa1545DOI Listing
October 2020

Bacterial genome-wide association study of hyper-virulent pneumococcal serotype 1 identifies genetic variation associated with neurotropism.

Commun Biol 2020 Oct 8;3(1):559. Epub 2020 Oct 8.

Parasites and Microbes Programme, Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK.

Hyper-virulent Streptococcus pneumoniae serotype 1 strains are endemic in Sub-Saharan Africa and frequently cause lethal meningitis outbreaks. It remains unknown whether genetic variation in serotype 1 strains modulates tropism into cerebrospinal fluid to cause central nervous system (CNS) infections, particularly meningitis. Here, we address this question through a large-scale linear mixed model genome-wide association study of 909 African pneumococcal serotype 1 isolates collected from CNS and non-CNS human samples. By controlling for host age, geography, and strain population structure, we identify genome-wide statistically significant genotype-phenotype associations in surface-exposed choline-binding (P = 5.00 × 10) and helicase proteins (P = 1.32 × 10) important for invasion, immune evasion and pneumococcal tropism to CNS. The small effect sizes and negligible heritability indicated that causation of CNS infection requires multiple genetic and other factors reflecting a complex and polygenic aetiology. Our findings suggest that certain pathogen genetic variation modulate pneumococcal survival and tropism to CNS tissue, and therefore, virulence for meningitis.
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http://dx.doi.org/10.1038/s42003-020-01290-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545184PMC
October 2020

CAR T cells targeting options in the fight against multiple myeloma.

Panminerva Med 2021 Mar 21;63(1):37-45. Epub 2020 Sep 21.

IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), Meldola, Forlì-Cesena, Italy.

Introduction: Multiple myeloma (MM) is a hematological malignancy in which patients present with bone marrow infiltration of clonal terminally-differentiated plasma cells. Monoclonal protein in the serum and/or urine is frequently detected. Over the past decade, important progress has been made in the comprehension of disease biology and treatment personalization. Much work has been put into the development of chimeric antigen receptor (CAR) gene-modified T-cell therapy thought to be a promising therapeutic option for pluritreated patients with refractory MM.

Evidence Acquisition: We performed an analysis of clinical trials registered at the international repository clinicaltrials.gov using "CAR" OR "CAR T" AND "multiple myeloma" as search terms to understand what were the antigens targeted by CAR T strategies and what was the trade-off of their exploitation. The search retrieved a list of 103 trials that was manually filtered to eliminate follow-up and observational or not-pertinent trials.

Evidence Synthesis: Most studies employed anti-BCMA targeting either alone (62/94; 66%), or in combination with a second target (12/94; 13%). The second target most studied was SLAMF7 (CD319) explored by 4/94 (4%) clinical trials. Other antigens investigated and described here include: CD44v6, CD38, CD138, MUC1, CD56, CD19, Igk light chain, Lewis Y, CD229 and GPRC5D.

Conclusions: Targeting an appropriate antigen(s) is the key to both safety and efficacy of CAR T approaches in MM as there is dearth of tumor-specific antigens. Most antigens tested are merely enriched on MM cells. Working with tumor-enriched antigens requires careful assessment of the balance between harm (toxicity) and benefit (disease eradication) to the patient. This review provides an up-to-date overview of the avenues that are being explored.
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http://dx.doi.org/10.23736/S0031-0808.20.04146-4DOI Listing
March 2021

Genomic diversity of isolates from non-human primates in the Gambia.

Microb Genom 2020 09 14;6(9). Epub 2020 Sep 14.

Quadram Institute Bioscience, Norwich Research Park, Norwich, Norfolk, UK.

Increasing contact between humans and non-human primates provides an opportunity for the transfer of potential pathogens or antimicrobial resistance between host species. We have investigated genomic diversity and antimicrobial resistance in isolates from four species of non-human primates in the Gambia: (=22), (=14), (=6) and (=1). We performed Illumina whole-genome sequencing on 101 isolates from 43 stools, followed by nanopore long-read sequencing on 11 isolates. We identified 43 sequence types (STs) by the Achtman scheme (ten of which are novel), spanning five of the eight known phylogroups of . The majority of simian isolates belong to phylogroup B2 - characterized by strains that cause human extraintestinal infections - and encode factors associated with extraintestinal disease. A subset of the B2 strains (ST73, ST681 and ST127) carry the genomic island, which encodes colibactin, a genotoxin associated with colorectal cancer. We found little antimicrobial resistance and only one example of multi-drug resistance among the simian isolates. Hierarchical clustering showed that simian isolates from ST442 and ST349 are closely related to isolates recovered from human clinical cases (differences in 50 and 7 alleles, respectively), suggesting recent exchange between the two host species. Conversely, simian isolates from ST73, ST681 and ST127 were distinct from human isolates, while five simian isolates belong to unique core-genome ST complexes - indicating novel diversity specific to the primate niche. Our results are of planetary health importance, considering the increasing contact between humans and wild non-human primates.
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http://dx.doi.org/10.1099/mgen.0.000428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643976PMC
September 2020

Metal-Metal Cooperation in the Oxidation of a Flapping Platinum Butterfly by Haloforms: Experimental and Theoretical Evidence.

Inorg Chem 2020 Sep 20;59(17):12586-12594. Epub 2020 Aug 20.

Departamento de Química Inorgánica, Facultad de Ciencias, Instituto de Síntesis Química y Catálisis Homogénea (ISQCH), CSIC-Universidad de Zaragoza, Pedro Cerbuna 12, 50009 Zaragoza, Spain.

The model -DFT for the butterfly complex [{Pt(CC*)(μ-pz)}] (; HCC* = 1-(4-(ethoxycarbonyl)phenyl)-3-methyl-1-imidazol-2-ylidene) shows two minima in the potential energy surface of the ground state in acetone solution: the butterfly-wing-spreading molecules , ( ≈ 3.20 Å) and the wing-folding molecules ( ≤ 3.00 Å). Both minima are very close in energy (Δ° = 1.7 kcal/mol) and are connected through a transition state, which lies only 1.9 kcal/mol above and 0.2 kcal/mol above . These very low barriers support a fast interconversion process, resembling a , and the presence of both conformers in acetone solution. However, the ratio is so low that it is undetectable in the excitation and emission spectra of in 2-MeTHF of diluted solutions (10 M) at 77 K, while it is seen in more concentrated solutions (10 M). In acetone solution, undergoes a [2c, 2e] oxidation by CHX (X = Cl, Br) in the sunlight to render the Pt(III,III) compounds [{Pt(CC*)(μ-pz)X)}] (X = Cl (), Br ()). In concentrated solutions, can react with CHCl under blue light to give and with CHBr in the dark, the latter rendering the compound [BrPt(CC*)(μ-pz)Pt(CC*)CHBr] () or mixtures of and if the reaction is performed under an argon atmosphere or in the air, respectively. Mechanistic studies showed that in concentrated solutions the oxidation processes follow a radical mechanism being the MMLCT-based species , those which trigger the reaction of with CHBr and CHCl. In the ground state (S), it promotes the thermal oxidation of by CHBr and in the first singlet excited state (S) the blue-light-driven photooxidation of by CHCl. Complexes, , , and were selectively obtained and fully characterized, showing Pt-Pt distances (ca. 2.6 Å) shorter than that of the starting complex, . They are, together with the analogous [{Pt(CC*)(μ-pz)I)}] and [IPt(CC*)(μ-pz)Pt(CC*)CHI], the only dinuclear metal-metal-bonded Pt(μ-pz)Pt compounds reported to date.
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http://dx.doi.org/10.1021/acs.inorgchem.0c01701DOI Listing
September 2020

The Aetiology of pneumonia from analysis of Lung aspirate and Pleural fluid samples: Findings from the PERCH study.

Clin Infect Dis 2020 Jul 25. Epub 2020 Jul 25.

Medical Research Council Unit, Basse, The Gambia.

Background: An improved understanding of childhood pneumonia aetiology is required to inform prevention and treatment strategies. Lung aspiration is the gold standard specimen for pneumonia diagnostics. We report findings from analyses of lung and pleural aspirates collected in the Pneumonia Etiology Research for Child Health (PERCH) study.

Methods: The PERCH study enrolled children aged 1-59 months hospitalized with World Health Organization defined severe or very severe pneumonia in 7 countries in Africa and Asia. Percutaneous trans-thoracic lung (LA) and pleural fluid (PF) aspiration was performed on a sample of pneumonia cases with radiological consolidation and/or pleural fluid in 4 countries. Venous blood and nasopharyngeal/oropharyngeal swabs were collected from all cases. Multiplex quantitative PCR and routine microbiologic culture were applied to clinical specimens.

Results: Of 44 LAs performed within 3 days of admission on 622 eligible cases, 13 (30%) had a pathogen identified by either culture (5/44) or by PCR (11/29). A pathogen was identified in 12/14 (86%) PF specimens tested by either culture (9/14) or PCR (9/11). Bacterial pathogens were identified more frequently than viruses. All but one of the cases with a virus identified were co-infected with bacterial pathogens. Streptococcus pneumoniae (9/44 [20%]) and Staphylococcus aureus (7/14 [50%]) were the predominant pathogen identified in LA and PF, respectively.

Conclusions: Bacterial pathogens predominated in this selected subgroup of PERCH participants drawn from those with radiological consolidation or pleural fluid, with S. pneumoniae and S. aureus the leading pathogens identified.
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http://dx.doi.org/10.1093/cid/ciaa1032DOI Listing
July 2020

Electrochemical Reduction of Carbon Dioxide to 1-Butanol on Oxide-Derived Copper.

Angew Chem Int Ed Engl 2020 Nov 9;59(47):21072-21079. Epub 2020 Sep 9.

Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore, 117543, Singapore.

The electroreduction of carbon dioxide using renewable electricity is an appealing strategy for the sustainable synthesis of chemicals and fuels. Extensive research has focused on the production of ethylene, ethanol and n-propanol, but more complex C molecules have been scarcely reported. Herein, we report the first direct electroreduction of CO to 1-butanol in alkaline electrolyte on Cu gas diffusion electrodes (Faradaic efficiency=0.056 %, j =-0.080 mA cm at -0.48 V vs. RHE) and elucidate its formation mechanism. Electrolysis of possible molecular intermediates, coupled with density functional theory, led us to propose that CO first electroreduces to acetaldehyde-a key C intermediate to 1-butanol. Acetaldehyde then undergoes a base-catalyzed aldol condensation to give crotonaldehyde via electrochemical promotion by the catalyst surface. Crotonaldehyde is subsequently electroreduced to butanal, and then to 1-butanol. In a broad context, our results point to the relevance of coupling chemical and electrochemical processes for the synthesis of higher molecular weight products from CO .
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http://dx.doi.org/10.1002/anie.202008289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693243PMC
November 2020

Hybridization of Fossil- and CO -Based Routes for Ethylene Production using Renewable Energy.

ChemSusChem 2020 Dec 10;13(23):6370-6380. Epub 2020 Aug 10.

Institute for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zürich, Vladimir-Prelog-Weg 1, 8093, Zürich, Switzerland.

Carbon capture and utilization (CCU) has recently gained broad interest in the chemical industry. Direct electro- and thermocatalytic technologies are currently the focus of intense research, where the former employs electricity directly to reduce the CO molecule, while the latter comprises hydrogenation of CO in tandem with electrocatalytic water splitting. So far, it remains unclear which of the two is superior, yet this information is considered critical. Focusing on the platform chemical ethylene, the two CCU routes were compared using state-of-the-art performances with the fossil technology considering different power and CO sources. The thermo-route was found to be, at present, economically and environmentally better, yet under the same electrolyzer efficiencies, the electro-route would become superior. CCU routes could substantially improve the carbon footprint of the fossil ethylene (by 236 %) while decreasing at the same time impacts on human health, ecosystem quality, and resources (64, 140, and 80 %, respectively). However, they are economically unattractive even when considering externalities (indirect cost of environmental impacts), that is, 1.7- to 3.9-fold more expensive compared to the current fossil-based analogue. Acknowledging this limitation, the concept of hybridization was applied as a means to smooth the transition towards more sustainable chemicals. Accordingly, it was found that an optimal hybrid plant could produce carbon-neutral (cradle-to-gate) ethylene with a premium of only 30 % over the current market prices by judiciously combining CCU routes with fossil technologies.
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http://dx.doi.org/10.1002/cssc.202001312DOI Listing
December 2020

Within-host microevolution of Streptococcus pneumoniae is rapid and adaptive during natural colonisation.

Nat Commun 2020 07 10;11(1):3442. Epub 2020 Jul 10.

Medical Research Council (MRC) Unit The Gambia at the London School of Hygiene and Tropical Medicine, Fajara, The Gambia.

Genomic evolution, transmission and pathogenesis of Streptococcus pneumoniae, an opportunistic human-adapted pathogen, is driven principally by nasopharyngeal carriage. However, little is known about genomic changes during natural colonisation. Here, we use whole-genome sequencing to investigate within-host microevolution of naturally carried pneumococci in ninety-eight infants intensively sampled sequentially from birth until twelve months in a high-carriage African setting. We show that neutral evolution and nucleotide substitution rates up to forty-fold faster than observed over longer timescales in S. pneumoniae and other bacteria drives high within-host pneumococcal genetic diversity. Highly divergent co-existing strain variants emerge during colonisation episodes through real-time intra-host homologous recombination while the rest are co-transmitted or acquired independently during multiple colonisation episodes. Genic and intergenic parallel evolution occur particularly in antibiotic resistance, immune evasion and epithelial adhesion genes. Our findings suggest that within-host microevolution is rapid and adaptive during natural colonisation.
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http://dx.doi.org/10.1038/s41467-020-17327-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351774PMC
July 2020

Senescence in the Development and Response to Cancer with Immunotherapy: A Double-Edged Sword.

Int J Mol Sci 2020 Jun 18;21(12). Epub 2020 Jun 18.

Department of Hematology, Hospital Clinic, IDIBAPS, 08036 Barcelona, Spain.

Cellular senescence was first described as a physiological tumor cell suppressor mechanism that leads to cell growth arrest with production of the senescence-associated secretory phenotype known as SASP. The main role of SASP in physiological conditions is to attract immune cells to clear senescent cells avoiding tumor development. However, senescence can be damage-associated and, depending on the nature of these stimuli, additional types of senescence have been described. In the context of cancer, damage-associated senescence has been described as a consequence of chemotherapy treatments that were initially thought of as a tumor suppressor mechanism. However, in certain contexts, senescence after chemotherapy can promote cancer progression, especially when immune cells become senescent and cannot clear senescent tumor cells. Moreover, aging itself leads to continuous inflammaging and immunosenescence which are responsible for rewiring immune cells to become defective in their functionality. Here, we define different types of senescence, pathways that activate them, and functions of SASP in these events. Additionally, we describe the role of senescence in cancer and its treatments, including how aging and chemotherapy contribute to senescence in tumor cells, before focusing on immune cell senescence and its role in cancer. Finally, we discuss potential therapeutic interventions to reverse cell senescence.
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http://dx.doi.org/10.3390/ijms21124346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352478PMC
June 2020

Point-Of-Care CAR T-Cell Production (ARI-0001) Using a Closed Semi-automatic Bioreactor: Experience From an Academic Phase I Clinical Trial.

Front Immunol 2020 20;11:482. Epub 2020 Mar 20.

Institut D'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

Development of semi-automated devices that can reduce the hands-on time and standardize the production of clinical-grade CAR T-cells, such as CliniMACS Prodigy from Miltenyi, is key to facilitate the development of CAR T-cell therapies, especially in academic institutions. However, the feasibility of manufacturing CAR T-cell products from heavily pre-treated patients with this system has not been demonstrated yet. Here we report and characterize the production of 28 CAR T-cell products in the context of a phase I clinical trial for CD19+ B-cell malignancies (NCT03144583). The system includes CD4-CD8 cell selection, lentiviral transduction and T-cell expansion using IL-7/IL-15. Twenty-seven out of 28 CAR T-cell products manufactured met the full list of specifications and were considered valid products. cell expansion lasted an average of 8.5 days and had a mean transduction rate of 30.6 ± 13.44%. All products obtained presented cytotoxic activity against CD19+ cells and were proficient in the secretion of pro-inflammatory cytokines. Expansion kinetics was slower in patient's cells compared to healthy donor's cells. However, product potency was comparable. CAR T-cell subset phenotype was highly variable among patients and largely determined by the initial product. T and T were the predominant T-cell phenotypes obtained. 38.7% of CAR T-cells obtained presented a T or T phenotype, in average, which are the subsets capable of establishing a long-lasting T-cell memory in patients. An in-depth analysis to identify individual factors contributing to the optimal T-cell phenotype revealed that cell expansion leads to reduced numbers of T, T, and T cells, while T cells increase, both due to cell expansion and CAR-expression. Overall, our results show for the first time that clinical-grade production of CAR T-cells for heavily pre-treated patients using CliniMACS Prodigy system is feasible, and that the obtained products meet the current quality standards of the field. Reduced expansion may yield CAR T-cell products with increased persistence .
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http://dx.doi.org/10.3389/fimmu.2020.00482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7259426PMC
March 2021

Nectin-2 Expression on Malignant Plasma Cells Is Associated with Better Response to TIGIT Blockade in Multiple Myeloma.

Clin Cancer Res 2020 Sep 8;26(17):4688-4698. Epub 2020 Jun 8.

Department of Hematology, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

Purpose: T-cell immunoreceptor with Ig and ITIM domain (TIGIT) blockade could represent an alternative therapeutic option to release the immune response in patients with multiple myeloma. Here we analyzed the expression of TIGIT and its ligands poliovirus receptor (PVR) and nectin-2 in the bone marrow (BM) of patients with monoclonal gammopathies and the efficacy of TIGIT blockade activating antimyeloma immunity.

Experimental Design: Expression levels of TIGIT and its ligands were characterized by flow cytometry and ELISA. TIGIT blockade was analyzed in functional assays with peripheral T cells. BM cells were studied with NanoString technology, real-time PCR, and patient BM cell models.

Results: TIGIT and its ligands are highly expressed in the BM of patients with multiple myeloma, suggesting that may play a role in restraining immune activation. TIGIT blockade depleted FoxP3 Tregs while increasing proliferation of IFNγ-producing CD4 T cells from patients with multiple myeloma. PVR ligation inhibited CD8 T-cell signaling and cell proliferation which could be overcome with anti-TIGIT mAb. However, BM cells showed a remarkable heterogeneity in immune signature. Accordingly, functional BM assays revealed that only some patients respond to checkpoint blockade. Thus, response to TIGIT blockade correlated with low frequency of TIGIT cells and high nectin-2 expression on malignant plasma cells.

Conclusions: TIGIT blockade efficiently reinvigorated peripheral T cells from patients with multiple myeloma. However, in the BM, the efficacy of blocking anti-TIGIT mAb to achieve tumor cell death may depend on the expression of TIGIT and nectin-2, becoming potential predictive biomarkers for identifying patients who may benefit from TIGIT blockade.
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http://dx.doi.org/10.1158/1078-0432.CCR-19-3673DOI Listing
September 2020

Impact of routine vaccination against type b in The Gambia: 20 years after its introduction.

J Glob Health 2020 Jun;10(1):010416

Medical Research Council Unit The Gambia at the London School of Hygiene & Tropical Medicine, Fajara, The Gambia.

Background: In 1997, The Gambia introduced three primary doses of type b (Hib) conjugate vaccine without a booster in its infant immunisation programme along with establishment of a population-based surveillance on Hib meningitis in the West Coast Region (WCR). This surveillance was stopped in 2002 with reported elimination of Hib disease. This was re-established in 2008 but stopped again in 2010. We aimed to re-establish the surveillance in WCR and to continue surveillance in Basse Health and Demographic Surveillance System (BHDSS) in the east of the country to assess any shifts in the epidemiology of Hib disease in The Gambia.

Methods: In WCR, population-based surveillance for Hib meningitis was re-established in children aged under-10 years from 24 December 2014 to 31 March 2017, using conventional microbiology and Real Time Polymerase Chain Reaction (RT-PCR). In BHDSS, population-based surveillance for Hib disease was conducted in children aged 2-59 months from 12 May 2008 to 31 December 2017 using conventional microbiology only. Hib carriage survey was carried out in pre-school and school children from July 2015 to November 2016.

Results: In WCR, five Hib meningitis cases were detected using conventional microbiology while another 14 were detected by RT-PCR. Of the 19 cases, two (11%) were too young to be protected by vaccination while seven (37%) were unvaccinated. Using conventional microbiology, the incidence of Hib meningitis per 100 000-child-year (CY) in children aged 1-59 months was 0.7 in 2015 (95% confidence interval (CI) = 0.0-3.7) and 2.7 (95% CI = 0.7-7.0) in 2016. In BHDSS, 25 Hib cases were reported. Nine (36%) were too young to be protected by vaccination and five (20%) were under-vaccinated for age. Disease incidence peaked in 2012-2013 at 15 per 100 000 CY and fell to 5-8 per 100 000 CY over the subsequent four years. The prevalence of Hib carriage was 0.12% in WCR and 0.38% in BHDSS.

Conclusions: After 20 years of using three primary doses of Hib vaccine without a booster Hib transmission continues in The Gambia, albeit at low rates. Improved coverage and timeliness of vaccination are of high priority for Hib disease in settings like Gambia, and there are currently no clear indications of a need for a booster dose.
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http://dx.doi.org/10.7189/jogh.10.010416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243067PMC
June 2020

Etiology of Pediatric Meningitis in West Africa Using Molecular Methods in the Era of Conjugate Vaccines against Pneumococcus, Meningococcus, and Type b.

Am J Trop Med Hyg 2020 08 21;103(2):696-703. Epub 2020 May 21.

Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia.

Despite the implementation of effective conjugate vaccines against the three main bacterial pathogens that cause meningitis, , type b (Hib), and serogroup A, the burden of meningitis in West Africa remains high. The relative importance of other bacterial, viral, and parasitic pathogens in central nervous system infections is poorly characterized. Cerebrospinal fluid (CSF) specimens were collected from children younger than 5 years with suspected meningitis, presenting at pediatric teaching hospitals across West Africa in five countries including Senegal, Ghana, Togo, Nigeria, and Niger. Cerebrospinal fluid specimens were initially tested using bacteriologic culture and a triplex real-time polymerase chain reaction (PCR) assay for , , and used in routine meningitis surveillance A custom TaqMan Array Card (TAC) assay was later used to detect 35 pathogens including 15 bacteria, 17 viruses, one fungus, and two protozoans. Among 711 CSF specimens tested, the pathogen positivity rates were 2% and 20% by the triplex real-time PCR (three pathogens) and TAC (35 pathogens), respectively. TAC detected 10 bacterial pathogens, eight viral pathogens, and . Overall, was the most prevalent (4.8%), followed by (3.5%) and (3.5%). Multiple pathogens were detected in 4.4% of the specimens. Children with human immunodeficiency virus (HIV) and detected in CSF had high mortality. Among 220 neonates, 17% had at least one pathogen detected, dominated by gram-negative bacteria. The meningitis TAC enhanced the detection of pathogens in children with meningitis and may be useful for case-based meningitis surveillance.
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http://dx.doi.org/10.4269/ajtmh.19-0566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7410464PMC
August 2020

Visualizing variation within Global Pneumococcal Sequence Clusters (GPSCs) and country population snapshots to contextualize pneumococcal isolates.

Microb Genom 2020 05 29;6(5). Epub 2020 Apr 29.

Parasites and microbes, Wellcome Sanger InstituteHinxton, UK.

Knowledge of pneumococcal lineages, their geographic distribution and antibiotic resistance patterns, can give insights into global pneumococcal disease. We provide interactive bioinformatic outputs to explore such topics, aiming to increase dissemination of genomic insights to the wider community, without the need for specialist training. We prepared 12 country-specific phylogenetic snapshots, and international phylogenetic snapshots of 73 common Global Pneumococcal Sequence Clusters (GPSCs) previously defined using PopPUNK, and present them in Microreact. Gene presence and absence defined using Roary, and recombination profiles derived from Gubbins are presented in Phandango for each GPSC. Temporal phylogenetic signal was assessed for each GPSC using BactDating. We provide examples of how such resources can be used. In our example use of a country-specific phylogenetic snapshot we determined that serotype 14 was observed in nine unrelated genetic backgrounds in South Africa. The international phylogenetic snapshot of GPSC9, in which most serotype 14 isolates from South Africa were observed, highlights that there were three independent sub-clusters represented by South African serotype 14 isolates. We estimated from the GPSC9-dated tree that the sub-clusters were each established in South Africa during the 1980s. We show how recombination plots allowed the identification of a 20 kb recombination spanning the capsular polysaccharide locus within GPSC97. This was consistent with a switch from serotype 6A to 19A estimated to have occured in the 1990s from the GPSC97-dated tree. Plots of gene presence/absence of resistance genes (, , ) across the GPSC23 phylogeny were consistent with acquisition of a composite transposon. We estimated from the GPSC23-dated tree that the acquisition occurred between 1953 and 1975. Finally, we demonstrate the assignment of GPSC31 to 17 externally generated pneumococcal serotype 1 assemblies from Utah via Pathogenwatch. Most of the Utah isolates clustered within GPSC31 in a USA-specific clade with the most recent common ancestor estimated between 1958 and 1981. The resources we have provided can be used to explore to data, test hypothesis and generate new hypotheses. The accessible assignment of GPSCs allows others to contextualize their own collections beyond the data presented here.
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http://dx.doi.org/10.1099/mgen.0.000357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371119PMC
May 2020

potential of human mesenchymal stem cells for corneal epithelial regeneration.

Regen Med 2020 03 30;15(3):1409-1426. Epub 2020 Apr 30.

Barcelona Tissue Bank, Banc de Sang I Teixits (BST), Barcelona, Spain.

To determine the potential of mesenchymal stem cells (MSC) for corneal epithelial regeneration . Bone marrow MSC (BM-MSC) and adipose tissue MSC were analyzed for corneal epithelial and mesenchymal markers, using limbal stem cells and corneal cells as controls. MSC with better potential were cultured with specific mediums for epithelial induction. Transepithelial electric resistance and wound healing assay with human corneal epithelial cells were performed. BM-MSC showed better potential, increased corneal markers, and higher transepithelial electric resistance values when induced with limbal epithelial culture medium. Induced BM-MSC promoted better wound healing of human corneal epithelial cells by paracrine secretion. BM-MSC has potential for corneal epithelial induction in a protocol compatible with human application.
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http://dx.doi.org/10.2217/rme-2019-0067DOI Listing
March 2020

COVID-19 pandemic in west Africa.

Lancet Glob Health 2020 05 1;8(5):e631-e632. Epub 2020 Apr 1.

Medical Research Council Unit in The Gambia at the London School of Hygiene and Tropical Medicine, Fajara, PO Box 273, The Gambia. Electronic address:

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http://dx.doi.org/10.1016/S2214-109X(20)30123-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186549PMC
May 2020

Stable mixed-valence diphenylphosphanido bridged platinum(ii)-platinum(iv) complexes.

Dalton Trans 2020 Apr;49(15):4935-4955

DICATECh, Politecnico di Bari, I-70125 Bari, Italy.

The reaction between [NnBu4][(C6F5)2PtII(μ-PPh2)2PtIV(C^N)(I)2] (C^N = κ2-N,C-benzoquinolinate, 1) and (i) bidentate S^S, N^S and O^O anionic ligands or (ii) monodentate S- N- or O-based anionic ligands was studied in order to investigate the factors that may guarantee the stability of Pt(ii),Pt(iv) mixed-valence dinuclear phosphanido complexes. While reactions of 1 with S^S or N^S ligands afforded stable Pt(ii),Pt(iv) species of general formula [(C6F5)2PtII(μ-PPh2)2PtIV(C^N)(L^S)]x- [(L^S)(x-1) = 2-mercaptopyrimidinate (pymS-), 2-mercaptopyridinate (pyS-), dimethyldithiocarbamate (Me2NCS2-), ethyl xanthogenate (EtOCS2-) and 1,2-benzenedithiolate (PhS22-)], the reaction of 1 with the O^O ligand sodium acetylacetonate gave several products, and no pure Pt(ii),Pt(iv) complex could be isolated. The reaction of monodentate ligands such as PhS-, OH- or N3- with 1 led to a stable Pt(ii),Pt(iv) complex only in the case of N3-. The reaction with OH- afforded the Pt(ii),Pt(ii) complex [(C6F5)2PtII(μ-PPh2)(κ2-O,P-μ-O-PPh2)PtII(C^N)]- (8) deriving from reductive coupling of a diphenylphosphanide and an O-donor ligand coordinated to the Pt(iv) centre, while the reaction with PhS- produced the unstable Pt(ii),Pt(iv) complex [NnBu4][(C6F5)2PtII(μ-PPh2)2PtIV(C^N)(PhS)2] (11) that evolved in solution to the Pt(ii),Pt(ii) species [NnBu4][(C6F5)2PtII(μ-PPh2)2PtII(C^N)] (9) by elimination of diphenyldisulfide. Thus, the stability of mixed valence Pt(ii),Pt(iv) phosphanide complexes is affected by several concurrent factors, including the chelating effect of the ligands and the type of ligating atoms.
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http://dx.doi.org/10.1039/d0dt00712aDOI Listing
April 2020