Publications by authors named "Jorge Fernandez"

132 Publications

Do Clinical Trials Meet Current Care Needs? Views of Digestive Oncology Specialists in Galicia (Spain) Using the Delphi Method.

Healthcare (Basel) 2021 Jun 3;9(6). Epub 2021 Jun 3.

Complexo Hospitalario Universitario de Ourense, 32005 Ourense, Spain.

In recent years, abundant scientific evidence has been generated based on clinical trials (CT) in the field of oncology. The general objective of this paper is to find out the extent to which decision making is based on knowledge of the most recent CT. Its specific objectives are to pinpoint difficulties with decision making based on the CT performed and find out the motivations patients and clinicians have when taking part in a CT. Combined, prospective study, based on the Delphi method. A lack of correspondence between the people who take part in CT and patients who come for consultation has been identified. A need for training in analysing and interpreting CT has also been identified and a lack of trust in the results of CT financed by the pharmaceutical industry itself has been perceived. There is a difficulty in selecting oncological treatment due to the lack of correspondence between the patients included in the CT and patients seen in consultation. In this process, real world data studies may be highly useful, as they may provide this group with greater training in interpreting CT and their results.
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http://dx.doi.org/10.3390/healthcare9060665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227221PMC
June 2021

A rapid way of formulation development revealing potential synergic effects on numerous antimicrobial combinations against foodborne pathogens.

Microb Pathog 2021 Jun 12;158:105047. Epub 2021 Jun 12.

Research Laboratories in Sciences Applied to Food, Canadian Irradiation Center, INRS-Institut Armand-Frappier, Institute of Nutraceutical and Functional, Laval, Quebec, Canada. Electronic address:

The interactions between various essential oils (EOs) were evaluated for the development of antimicrobial formulations. A full factorial design was applied for testing eight EOs (Mustard, Thyme, Garlic, Oregano, Chinese cinnamon, Cinnamon bark, Red bergamot, Winter savory) against nine bacteria (E.coli O157:H7 RM1239, E.coli O157:H7 RM 1931, E.coli O157:H7 RM 1933, E.coli O157:H7 RM 1934, E.coli O157:H7 380-94, Listeria monocytogenes LM 1045, Listeria innocua ATCC 51742, Salmonella Typhimurium SL 1344, Salmonella enterica Newport ATCC 6962) and two molds (Penicillium chrysogenum ATCC 10106, Aspergillus niger ATCC 1015). Results showed that combinations of Thyme + Oregano, Oregano + Cinnamon bark, Chinese cinnamon + Cinnamon bark have shown high interactions in Factorial design and validated to be mostly additive effects against tested bacteria. The combination of Mustard + Thyme, Mustard + Garlic, and Thyme + Garlic EOs showed high interactions and also all additive effects against tested molds. The corresponding results of Factorial design and checkerboard render the designation to demonstrate the highly efficient formulations and interactions rapidly among abundant mixtures.
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http://dx.doi.org/10.1016/j.micpath.2021.105047DOI Listing
June 2021

Biophysical and Biochemical Comparison of Extracellular Vesicles Produced by Infective and Non-Infective Stages of .

Int J Mol Sci 2021 May 13;22(10). Epub 2021 May 13.

Grupo de Bioquímica y Parasitología Molecular (CTS 183), Departamento de Parasitología, Campus de Fuentenueva, Instituto de Biotecnología, Universidad de Granada, 18071 Granada, Spain.

Extracellular vesicles (EVs) are small lipid vesicles released by either any prokaryotic or eukaryotic cell, or both, with a biological role in cell-to-cell communication. In this work, we characterize the proteomes and nanomechanical properties of EVs released by tissue-culture cell-derived trypomastigotes (mammalian infective stage; (TCT)) and epimastigotes (insect stage; (E)) of , the etiologic agent of Chagas disease. EVs of each stage were isolated by differential centrifugation and analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS), dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), electron microscopy and atomic force microscopy (AFM). Measurements of zeta-potential were also included. Results show marked differences in the surface molecular cargos of EVs between both stages, with a noteworthy expansion of all groups of -sialidase proteins in trypomastigote's EVs. In contrast, chromosomal locations of -sialidases of EVs of epimastigotes were dramatically reduced and restricted to subtelomeric regions, indicating a possible regulatable expression of these proteins between both stages of the parasite. Regarding mechanical properties, EVs of trypomastigotes showed higher adhesion compared to the EVs of epimastigotes. These findings demonstrate the remarkable surface remodeling throughout the life cycle of , which shapes the physicochemical composition of the extracellular vesicles and could have an impact in the ability of these vesicles to participate in cell communication in completely different niches of infection.
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http://dx.doi.org/10.3390/ijms22105183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153575PMC
May 2021

Smart glasses evaluation during the COVID-19 pandemic: First-use on Neurointerventional procedures.

Clin Neurol Neurosurg 2021 Apr 19;205:106655. Epub 2021 Apr 19.

Interventional Neuroradiology, Clinical Hospital Center "Sisters of Mercy", Zagreb, Croatia.

The COVID-19 pandemic is rapidly transforming the healthcare system, with telemedicine, or virtual health, being one of the key drivers of the change. Smart glasses have recently been introduced to the public and have generated interest with healthcare professionals as demonstrated by their early adoption in clinics and hospitals. Observing procedures is essential for young interventionalist-in-training, but sometimes it is difficult for them to be able to get the volume of exposure to procedures that they need. Here, we report the first experience using smart glasses for Neurointerventional procedures, highlighting potential benefits and limitations during different scenarios including invitro and life cases. This field is novel, innovative, and may have potential to improve both patient care and patient safety in other health care settings.
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http://dx.doi.org/10.1016/j.clineuro.2021.106655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054524PMC
April 2021

California ACEP Firearm Injury Prevention Policy.

West J Emerg Med 2021 Jan 20;22(2):266-269. Epub 2021 Jan 20.

University of California, San Diego, Department of Emergency Medicine, San Diego, California.

Firearm-related deaths and injuries are a serious public health problem in California and the United States. The rate of firearm-related deaths is many times higher in the US than other democratic, industrialized nations, yet many of the deaths and injuries are preventable. The California American College of Emergency Physicians Firearm Injury Prevention Policy was approved and adopted in 2013 as an evidence-based, apolitical statement to promote harm reduction. It recognizes and frames firearm injuries as a public health epidemic requiring allocation of robust resources, including increased governmental funding of high-quality research and the development of a national database system. The policy further calls for relevant legislation to be informed by best evidence and expert consensus, and advocates for legislation regarding the following: mandatory universal background checks; mandatory reporting of firearm loss/theft; restrictions against law-enforcement or military-style assault weapons and high capacity magazines; child-protective safety and storage systems; and prohibitions for high-risk individuals. It also strongly defends the right of physicians to screen and counsel patients about firearm-related risk factors and safety. Based upon best-available evidenced, the policy was recently updated to include extreme risk protection orders, which are also known as gun violence restraining orders.
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http://dx.doi.org/10.5811/westjem.2020.11.50900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972396PMC
January 2021

Teaching Rapid Assessment Skills in Triage for the Emergency Medicine Clerkship.

J Emerg Med 2021 Jul 29;61(1):76-81. Epub 2021 Mar 29.

Department of Emergency Medicine, University of California San Diego, San Diego, California.

Background: Rapidly assessing an undifferentiated patient and developing a gestalt for "sick vs. not sick" is a core component of emergency medicine (EM). Developing this skill requires clinical experience and pattern recognition, which can be difficult to attain during a typical EM clerkship.

Objective: We developed a novel approach to teaching medical students rapid assessment skills in the emergency department (ED) by implementing a teaching shift in triage.

Methods: Fourth-year medical students in our EM clerkship in fall 2019 were scheduled one shift in triage with a dedicated teaching attending. The students evaluated patients under direct supervision, discussed their immediate differential diagnosis, and proposed an initial workup. The attending gave real-time feedback using a standardized direct observation tool. Students completed an electronic pre and post survey (5-point Likert scale) to assess their comfort level in the following areas: performing a rapid triage assessment, determining "sick vs. not sick", performing a focused physical examination, developing a targeted differential diagnosis, and ordering an initial diagnostic workup.

Results: Twenty-one students participated in the triage shifts. There was a significant improvement in self-assessed comfort with performing a rapid triage assessment, mean pre 2.76 and post 4.43 (p < 0.0001). There were also significant improvements in the four other survey areas (p < 0.004 or less).

Conclusions: A teaching shift in triage can increase medical students' self-assessed rapid assessment skills for patients in the ED. Benefits to the teaching attending included the opportunity to perform direct observation, give real-time feedback, and identify real-time teaching moments.
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http://dx.doi.org/10.1016/j.jemermed.2021.02.005DOI Listing
July 2021

COVID-19 Educational Innovation: Hybrid In-Person and Virtual Simulation for Emergency Medicine Trainees.

AEM Educ Train 2021 Mar 1:e10593. Epub 2021 Mar 1.

University of California San Diego Department of Emergency Medicine.

The COVID-19 pandemic has dramatically affected medical education. Emergency medicine (EM) requires excellence in multiple core competencies, including leadership, teamwork and communication skills, as well as procedural experience. To meet these objectives, we developed a hybrid simulation model that accommodated a reduced number of learners in our simulation center to allow for physical distancing, seamlessly integrated with an on-line integrated experience for remote learners. All learners participated or watched one adult and one pediatric simulation case. Fourteen residents participated in live simulation, while six residents and six medical students comprised the remote group. At the end of each case, the live-feed was ended, and separate debriefings were conducted by different EM faculty, in-person and on-line (via Zoom). An electronic survey was then sent to participants to rate the effectiveness of the intervention; 23 survey responses were collected: 52.2% (12) from the live session and 47.2% (11) from the virtual session. Survey results demonstrated that the on-line simulation observation and debriefing had the same, if not better, satisfaction than in-person simulation sessions and debriefings. Due to its success, this new method of hybrid simulation will be our plan for the foreseeable future, at least until COVID-19 abates.
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http://dx.doi.org/10.1002/aet2.10593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995095PMC
March 2021

Atovaquone/Proguanil Resistance in an Imported Malaria Case in Chile.

Am J Trop Med Hyg 2021 Mar 29. Epub 2021 Mar 29.

6Malaria Branch, Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, Georgia.

In November 2018, we diagnosed a cluster of falciparum malaria cases in three Chilean travelers returning from Nigeria. Two patients were treated with sequential intravenous artesunate plus oral atovaquone/proguanil (AP) and one with oral AP. The third patient, a 23-year-old man, presented with fever on day 29 after oral AP treatment and was diagnosed with recrudescent falciparum malaria. The patient was then treated with oral mefloquine, followed by clinical recovery and resolution of parasitemia. Analysis of day 0 and follow-up blood samples, collected on days 9, 29, 34, 64, and 83, revealed that parasitemia had initially decreased but then increased on day 29. Sequencing confirmed Tyr268Cys mutation in the cytochrome b gene, associated with atovaquone resistance, in isolates collected on days 29 and 34 and P. falciparum dihydrofolate reductase mutation Asn51Ile, associated with proguanil resistance in all successfully sequenced samples. Molecular characterization of imported malaria contributes to clinical management in non-endemic countries, helps ascertain the appropriateness of antimalarial treatment policies, and contributes to the reporting of drug resistance patterns from endemic regions.
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http://dx.doi.org/10.4269/ajtmh.20-1095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103435PMC
March 2021

Development of neutralizing antibody responses against SARS-CoV-2 in COVID-19 patients.

J Med Virol 2021 07 25;93(7):4334-4341. Epub 2021 Mar 25.

Sección Virus Oncogénicos y SubDepto. Genética Molecular, Instituto de Salud Pública de Chile, Ñuñoa, Chile.

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) are new global problems. The understanding of the host immune response in COVID-19 and its implications in the development of therapeutic agents are new challenges. Here, we evaluated the development of immunoglobulin G (IgG) and neutralizing (Nt) antibodies in symptomatic hospitalized COVID-19 patients. We followed up 117 COVID-19 confirmed patients from a reference health center for COVID-19 during the epidemic in Santiago de Chile. One and two sequential blood samples from 117 to 68 cases were, respectively, obtained to evaluate the immune response. Immunofluorescence and neutralization assays in Vero E6 cells with a Chilean SARS-CoV-2 strain were performed. Out of the 68 patients, 44% were women and 56% men, and the most frequent comorbidities were hypertension (47.7%) and diabetes (27.4%). The most frequent symptoms or signs related to COVID-19 were dyspnea, cough, fever, myalgia, and headache. In all the study population, 76.1% and 60.7% of patients were positive for IgG and Nt antibodies in the first blood sample. All patients except one were positive for IgG and Nt antibodies in the second sample. IgG and Nt antibodies positivity increased significantly according to the disease evolution periods. Higher Nt antibody titers were observed in the first sample in patients under 60 years of age. Obese and diabetic patients had no increase in Nt antibodies, unlike normal weight and diabetes-free patients. Both hypertensive and normotensive patients showed a significant increase in Nt antibodies. These results show an early and robust immune response against SARS-CoV-2 infection during severe COVID-19.
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http://dx.doi.org/10.1002/jmv.26939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8250623PMC
July 2021

Insights into neutralizing antibody responses in individuals exposed to SARS-CoV-2 in Chile.

Sci Adv 2021 02 12;7(7). Epub 2021 Feb 12.

SARS-CoV-2 Research Group, Virology Program, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, Chile.

Chile has one of the worst numbers worldwide in terms of SARS-CoV-2 positive cases and COVID-19-related deaths per million inhabitants; thus, characterization of neutralizing antibody (NAb) responses in the general population is critical to understanding of immunity at the local level. Given our inability to perform massive classical neutralization assays due to the scarce availability of BSL-3 facilities in the country, we developed and fully characterized an HIV-based SARS-CoV-2 pseudotype, which was used in a 96-well plate format to investigate NAb responses in samples from individuals exposed to SARS-CoV-2 or treated with convalescent plasma. We also identified samples with decreased or enhanced neutralization activity against the D614G spike variant compared with the wild type, indicating the relevance of this variant in host immunity. The data presented here represent the first insights into NAb responses in individuals from Chile, serving as a guide for future studies in the country.
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http://dx.doi.org/10.1126/sciadv.abe6855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880587PMC
February 2021

Phase II clinical trial of nab-paclitaxel plus gemcitabine in elderly patients with previously untreated locally advanced or metastatic pancreatic adenocarcinoma: the BIBABRAX study.

Cancer Chemother Pharmacol 2021 Apr 15;87(4):543-553. Epub 2021 Jan 15.

Medical Oncology Department, Hospital Universitario Cruces, Barakaldo, Spain.

Purpose: To evaluate the health-related quality of life (HRQoL), global health status (GHS), and deterioration-free survival of an elderly population (> 70 years) with unresectable locally advanced (LAPC) or metastatic pancreatic cancer (mPC) treated with nab-paclitaxel in combination with gemcitabine.

Methods: In this open-label, single-arm, multicenter, phase II trial, patients received 4-week cycles of intravenous (i.v.) nab-paclitaxel at a dose of 125 mg/m, followed by i.v. injections of gemcitabine at a dose of 1000 mg/m on days 1, 8 and 15 until disease progression or unacceptable toxicity was observed. The primary outcome was the HRQoL (deterioration-free rate at 3 months as evaluated with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30.

Results: Eighty patients (median age: 74.6 years) were enrolled (56 with mPC, 24 with LAPC). The percentage of patients who had not experienced deterioration at 3 months was 54.3% (95% CI 41.6-67.0%). The median (interquartile range) time until definite deterioration was 1.6 (1.1-3.7) months. The objective response rate and clinical benefit rate were achieved by 11 (13.8%, 95% CI 6.2-21.3%) and 54 patients (67.5%, 95% CI 57.2-77.8%), respectively. The median overall survival was 9.2 months (95% CI 6.9-11.5), and the median progression-free survival was 7.2 months (95% CI 5.8-8.5). Only fatigue and neutropenia demonstrated a grade 3-4 toxicity incidence > 20%.

Conclusions: Our study confirms the clinical benefit of the combination of nab-paclitaxel and gemcitabine in an elderly population with pancreatic cancer in terms of improved survival and clinical response. However, we were unable to confirm a benefit in terms of quality-of-life.
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http://dx.doi.org/10.1007/s00280-020-04214-wDOI Listing
April 2021

Electrical percolation in extrinsically conducting, poly(ε-decalactone) composite neural interface materials.

Sci Rep 2021 01 14;11(1):1295. Epub 2021 Jan 14.

Centre for Research in Medical Devices, National University of Ireland, Newcastle Road, Galway, H91 W2TY, Ireland.

By providing a bidirectional communication channel between neural tissues and a biomedical device, it is envisaged that neural interfaces will be fundamental in the future diagnosis and treatment of neurological disorders. Due to the mechanical mismatch between neural tissue and metallic neural electrodes, soft electrically conducting materials are of great benefit in promoting chronic device functionality. In this study, carbon nanotubes (CNT), silver nanowires (AgNW) and poly(hydroxymethyl 3,4-ethylenedioxythiophene) microspheres (MSP) were employed as conducting fillers within a poly(ε-decalactone) (EDL) matrix, to form a soft and electrically conducting composite. The effect of a filler type on the electrical percolation threshold, and composite biocompatibility was investigated in vitro. EDL-based composites exhibited favourable electrochemical characteristics: EDL/CNT-the lowest film resistance (1.2 ± 0.3 kΩ), EDL/AgNW-the highest charge storage capacity (10.7 ± 0.3 mC cm), and EDL/MSP-the highest interphase capacitance (1478.4 ± 92.4 µF cm). All investigated composite surfaces were found to be biocompatible, and to reduce the presence of reactive astrocytes relative to control electrodes. The results of this work clearly demonstrated the ability of high aspect ratio structures to form an extended percolation network within a polyester matrix, resulting in the formulation of composites with advantageous mechanical, electrochemical and biocompatibility properties.
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http://dx.doi.org/10.1038/s41598-020-80361-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809477PMC
January 2021

Effect of antiangiogenic-based treatment and systemic inflammatory factors on outcomes in patients with BRAF v600-mutated metastatic colorectal cancer: a real-world study in Spain.

BMC Cancer 2021 Jan 14;21(1):64. Epub 2021 Jan 14.

Medical Oncology Department, University Hospital A Coruña, Xubias de Arriba, 84, 15006, A Coruña, Galicia, Spain.

Background: Outcomes are poorer in metastatic colorectal cancer (mCRC) patients with BRAF V600E mutations than those without it, but the effect of these mutations on treatment response is unclear. This real-world study assessed the effects of antiangiogenic-based treatment and systemic inflammatory factors on outcomes in patients with BRAF V600-mutated mCRC.

Methods: This real-world, multicenter, retrospective, observational study included patients with BRAF V600-mutated mCRC treated in eight hospitals in Spain. The primary endpoints were overall survival (OS) and progression-free survival (PFS); overall response rate (ORR) and disease control rate (DCR) were also assessed. The effect of first- and second-line treatment type on OS, PFS, ORR, and DCR were evaluated, plus the impact of systemic inflammatory markers on these outcomes. A systemic inflammation score (SIS) of 1-3 was assigned based on one point each for platelet-lymphocyte ratio (PLR) ≥200, neutrophil-lymphocyte ratio (NLR) ≥3, and serum albumin < 3.6 g/dL.

Results: Of 72 patients, data from 64 were analyzed. After a median of 69.1 months, median OS was 11.9 months and median first-line PFS was 4.4 months. First-line treatment was triplet chemotherapy-antiangiogenic (12.5%), doublet chemotherapy-antiangiogenic (47.2%), doublet chemotherapy-anti-EGFR (11.1%), or doublet chemotherapy (18.1%). Although first-line treatment showed no significant effect on OS, antiangiogenic-based regimens were associated with prolonged median PFS versus non-antiangiogenic regimens. Negative predictors of survival with antiangiogenic-based treatment were NLR, serum albumin, and SIS 1-3, but not PLR. Patients with SIS 1-3 showed significantly prolonged PFS with antiangiogenic-based treatment versus non-antiangiogenic-based treatment, while those with SIS=0 showed no PFS benefit.

Conclusions: Antiangiogenic-based regimens, SIS, NLR, and albumin were predictors of survival in patients with mCRC, while SIS, NLR and serum albumin may predict response to antiangiogenic-based chemotherapy.

Trial Registration: GIT-BRAF-2017-01.
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http://dx.doi.org/10.1186/s12885-020-07758-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807898PMC
January 2021

A Curious Case of Hemoperitoneum.

J Emerg Med 2021 Mar 4;60(3):e57-e58. Epub 2021 Jan 4.

Department of Emergency Medicine, University of California, San Diego, San Diego, California.

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http://dx.doi.org/10.1016/j.jemermed.2020.11.017DOI Listing
March 2021

Geographical Distribution of Genetic Variants and Lineages of SARS-CoV-2 in Chile.

Front Public Health 2020 22;8:562615. Epub 2020 Sep 22.

Molecular Genetics Sub Department, Institute of Public Health of Chile, Santiago, Chile.

The pandemic caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a worldwide public health concern. First confined in China and then disseminated widely across Europe and America, SARS-CoV-2 has impacted and moved the scientific community around the world to working in a fast and coordinated way to collect all possible information about this virus and generate new strategies and protocols to try to stop the infection. During March 2020, more than 16,000 full viral genomes have been shared in public databases that allow the construction of genetic landscapes for tracking and monitoring the viral advances over time and study the genomic variations present in geographic regions. In this work, we present the occurrence of genetic variants and lineages of SARS-CoV-2 in Chile during March to April 2020. Complete genome analysis of 141 viral samples from different regions of Chile revealed a predominance of variant D614G like in Europe and the USA and the major presence of lineage B.1. These findings could help take control measures due to the similarity of the viral variants present in Chile, compared with other countries, and monitor the dynamic change of virus variants in the country.
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http://dx.doi.org/10.3389/fpubh.2020.562615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536338PMC
May 2021

Mother-to-Child Transmission of Andes Virus through Breast Milk, Chile.

Emerg Infect Dis 2020 08;26(8):1885-1888

Andes virus (ANDV) is the only hantavirus transmitted between humans through close contact. We detected the genome and proteins of ANDV in breast milk cells from an infected mother in Chile who transmitted the virus to her child, suggesting gastrointestinal infection through breast milk as a route of ANDV person-to-person transmission.
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http://dx.doi.org/10.3201/eid2608.200204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392419PMC
August 2020

First-line panitumumab plus capecitabine for the treatment of older patients with wild-type RAS metastatic colorectal cancer. The phase II, PANEL study.

J Geriatr Oncol 2020 11 21;11(8):1263-1267. Epub 2020 Jun 21.

Cancer Centre of Galicia, A Coruña, Spain.

Background: Despite the high morbidity and mortality of metastatic colorectal cancer (mCRC) in older patients, they have been underrepresented in clinical trials and their optimal treatment is yet to be determined. This open-label phase II study evaluated the benefits of panitumumab and capecitabine as a first-line chemotherapy regimen in older patients with wild-type [WT] RAS mCRC.

Patients And Methods: Patients (≥70 years; ECOG≤2) received 3-week cycles of panitumumab (9 mg/kg on day 1) plus capecitabine (850 mg/m twice daily on days 1-14) until disease progression or unacceptable toxicity. Response was evaluated every 9 weeks according to RECIST_1.1. Outcome measures were: objective response rate (ORR), duration of response (DoR), time to response (TTR), progression (TTP) and treatment failure (TTF), progression-free survival (PFS), overall survival (OS), and safety.

Results: Twenty-seven patients (11 women; median age: 78 years; ECOG: 0 [26%], 1 [67%], 2 [7%]) were evaluated. Median follow-up was 17.7 months. Confirmed ORR (95%CI) was 44.4% (25.7-63.2), with 25.9% of patients achieving at least stable disease. Median (95%CI) DoR was 8.7 (5.5-10.4) months, and median TTR was 2.2 (1.9-2.8) months. Median TTP was 9.6 (4.8-11.5) months, with a median TTF of 5.2 (2.8-7.2) months. The median PFS was 7.5 (4.4-10.4) months, and the median OS was 23.7 (7.4-27.5) months. Seventeen (63%) patients reported panitumumab and/or capecitabine-related adverse events grade 3-4, with skin toxicity (18.5%) being the most common. Two (7.4%) deaths were treatment-related.

Conclusion: This study suggests that panitumumab plus capecitabine is a safe and effective regimen in older patients with WT RAS mCRC.
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http://dx.doi.org/10.1016/j.jgo.2020.06.003DOI Listing
November 2020

Reply for comment on "on the calculation of lake metabolic rates: Diel O and O technique" by Peeters et al. [Water research 165 2019, 114990].

Water Res 2020 08 25;180:115849. Epub 2020 Apr 25.

Department of Biology, Limnological Institute, University of Konstanz, Germany.

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http://dx.doi.org/10.1016/j.watres.2020.115849DOI Listing
August 2020

Racial and Ethnic Differences in Communication and Care for Children With Advanced Cancer.

J Pain Symptom Manage 2020 10 30;60(4):782-789. Epub 2020 Apr 30.

Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA; Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, Massachusetts, USA.

Context: Racial and ethnic disparities in end-of-life care are well documented among adults with advanced cancer.

Objectives: To examine the extent to which communication and care differ by race and ethnicity among children with advanced cancer.

Methods: We conducted a prospective cohort study at nine pediatric cancer centers enrolling 95 parents (42% racial/ethnic minorities) of children with poor prognosis cancer (relapsed/refractory high-risk neuroblastoma). Parents were surveyed about whether prognosis was discussed; likelihood of cure; intent of current treatment; and primary goal of care. Medical records were used to identify high-intensity medical care since the most recent recurrence. Logistic regression evaluated differences between white non-Hispanic and minority (black, Hispanic, and Asian/other race) parents.

Results: About 26% of parents recognized the child's low likelihood of cure. Minority parents were less likely to recognize the poor prognosis (odds ratio [OR] = 0.19; 95% CI = 0.06-0.63; P = 0.006) and the fact that current treatment was unlikely to offer cure (OR = 0.07; 95% CI = 0.02-0.27; P < 0.0001). Children of minority parents were more likely to experience high-intensity medical care (OR = 3.01; 95% CI = 1.29-7.02; P = 0.01). After adjustment for understanding of prognosis, race/ethnicity was no longer associated with high-intensity medical care (adjusted odds ratio = 2.14; 95% CI = 0.84-5.46; P = 0.11), although power to detect an association was limited.

Conclusion: Parental understanding of prognosis is limited across racial and ethnic groups; racial and ethnic minorities are disproportionately affected. Perhaps as a result, minority children experience higher rates of high-intensity medical care. Work to improve prognostic understanding should include focused work to meet needs of minority populations.
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http://dx.doi.org/10.1016/j.jpainsymman.2020.04.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523916PMC
October 2020

Tracing Listeria monocytogenes contamination in artisanal cheese to the processing environments in cheese producers in southern Chile.

Food Microbiol 2020 Sep 25;90:103499. Epub 2020 Mar 25.

Escuela de Medicina Veterinaria, Facultad de Ciencias de La Vida, Universidad Andres Bello, Santiago, Chile; Millennium Initiative for Collaborative Research on Bacterial Resistance (MICROB-R), Santiago, Chile. Electronic address:

Artisanal cheese from southern Chile is made primarily by rural families who raise dairy cows and produce cheese as a way to add value to their milk. The most common cheese produced is chanco, a semi-hard cheese that is typically sold in unauthorized markets. The methods of chanco production do not always follow good manufacturing practices; however, the presence of Listeria monocytogenes contamination in this cheese has not been previously documented. To better understand production practices and L. monocytogenes contamination, 39 cheese producers were surveyed with regard to infrastructure, cleaning and sanitation, pest control, personal hygiene, training, raw materials, and manufacturing. During four sampling trips in 2016 (March, May, August, and November), 546 samples were collected (468 cheese samples and 78 milk samples). For producers that tested positive for L. monocytogenes, environmental monitoring was also conducted, for which 130 additional samples were collected. Presumptive L. monocytogenes isolates (N = 94) were further characterized and subtyped using standard techniques and qPCR-based species/subtype verification; a subset of 52 isolates were also subtyped by Pulsed Field Gel Electrophoresis (PFGE). L. monocytogenes was found in 19 cheeses (4.1%) from five producers (12.8%). The most frequent serotypes were 1/2b (48.9%), group 4B (4b, 4d, 4e) (45.7%), and serotype 1/2a (5.4%). Although no milk samples tested positive for L. monocytogenes, all cheese samples from two producers tested positive during two of the samplings. Distinct PFGE types were recovered from each facility, demonstrating persistence of certain subtypes of the pathogen that ultimately caused end-product contamination. Environmental monitoring of the five positive producers revealed a prevalence of L. monocytogenes ranging from 0 to 30%, with food contact surfaces having the highest incidence of this organism. The findings of this study contribute to the understanding of L. monocytogenes incidence in artisanal cheese in the region of southern Chile.
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http://dx.doi.org/10.1016/j.fm.2020.103499DOI Listing
September 2020

Phylogenetic analysis of the first four SARS-CoV-2 cases in Chile.

J Med Virol 2020 09 8;92(9):1562-1566. Epub 2020 Apr 8.

Molecular Genetics Sub Department, Institute of Public Health of Chile, Santiago, Chile.

The current pandemic caused by the new coronavirus is a worldwide public health concern. To aboard this emergency, and like never before, scientific groups around the world have been working in a fast and coordinated way to get the maximum of information about this virus when it has been almost 3 months since the first cases were detected in Wuhan province in China. The complete genome sequences of around 450 isolates are available, and studies about similarities and differences among them and with the close related viruses that caused similar epidemics in this century. In this work, we studied the complete genome of the first four cases of the new coronavirus disease in Chile, from patients who traveled to Europe and Southeast Asia. Our findings reveal at least two different viral variants entries to Chilean territory, coming from Europe and Asia. We also sub-classified the isolates into variants according to punctual mutations in the genome. Our work contributes to global information about transmission dynamics and the importance to take control measures to stop the spread of the infection.
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http://dx.doi.org/10.1002/jmv.25797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228331PMC
September 2020

Genetic evolution of influenza viruses among selected countries in Latin America, 2017-2018.

PLoS One 2020 10;15(3):e0227962. Epub 2020 Mar 10.

Pan American Health Organization (PAHO/WHO), Washington, DC, United States of America.

Objective: Since the 2009 influenza pandemic, Latin American (LA) countries have strengthened their influenza surveillance systems. We analyzed influenza genetic sequence data from the 2017 through 2018 Southern Hemisphere (SH) influenza season from selected LA countries, to map the availability of influenza genetic sequence data from, and to describe, the 2017 through 2018 SH influenza seasons in LA.

Methods: We analyzed influenza A/H1pdm09, A/H3, B/Victoria and B/Yamagata hemagglutinin sequences from clinical samples from 12 National Influenza Centers (NICs) in ten countries (Argentina, Brazil, Chile, Colombia, Costa Rica, Ecuador, Mexico, Paraguay, Peru and Uruguay) with a collection date from epidemiologic week (EW) 18, 2017 through EW 43, 2018. These sequences were generated by the NIC or the WHO Collaborating Center (CC) at the U.S Centers for Disease Control and Prevention, uploaded to the Global Initiative on Sharing All Influenza Data (GISAID) platform, and used for phylogenetic reconstruction.

Findings: Influenza hemagglutinin sequences from the participating countries (A/H1pdm09 n = 326, A/H3 n = 636, B n = 433) were highly concordant with the genetic groups of the influenza vaccine-recommended viruses for influenza A/H1pdm09 and influenza B. For influenza A/H3, the concordance was variable.

Conclusions: Considering the constant evolution of influenza viruses, high-quality surveillance data-specifically genetic sequence data, are important to allow public health decision makers to make informed decisions about prevention and control strategies, such as influenza vaccine composition. Countries that conduct influenza genetic sequencing for surveillance in LA should continue to work with the WHO CCs to produce high-quality genetic sequence data and upload those sequences to open-access databases.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0227962PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064222PMC
May 2020

How Well Do Core Faculty Understand The Emergency Medicine Milestones?

West J Emerg Med 2019 Dec 19;21(1):160-162. Epub 2019 Dec 19.

Highland Hospital - Alameda Health System, University of California San Francisco, Department of Emergency Medicine, San Francisco, California.

Introduction: It is unclear how emergency medicine (EM) programs educate core faculty about the use of milestones in competency-based evaluations. We conducted a national survey to profile how programs educate core faculty regarding their use and to assess core faculty's understanding of the milestones.

Methods: Our survey tool was distributed over six months in 2017 via the Council of Emergency Medicine Residency Directors (CORD) listserv. Responses, which were de-identified, were solicited from program directors (PDs), assistant/associate program directors (APDs), and core faculty. A single response from a program was considered sufficient.

Results: Our survey had a 69.7% response rate (n=140/201). 62.9% of programs reported educating core faculty about the EM Milestones via the distribution of physical or electronic media. Although 82.6% of respondents indicated that it was important for core faculty to understand how the EM Milestones are used in competency-based evaluations, respondents estimated that 48.6% of core faculty possess "fair or poor" understanding of the milestones. Furthermore, only 50.7% of respondents felt that the EM Milestones were a valuable tool.

Conclusion: These data suggest there is sub-optimal understanding of the EM Milestones among core faculty and disagreement as to whether the milestones are a valuable tool.
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http://dx.doi.org/10.5811/westjem.2019.11.44289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6948701PMC
December 2019

Editorial SARX-JFMF 2018.

Appl Radiat Isot 2020 03 22;157:109006. Epub 2019 Nov 22.

Laboratory of Montecuccolino, Department of Industrial Engineering (DIN), Alma Mater Studiorum, University of Bologna, via deiColli, 16, Bologna, 40136, Italy.

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http://dx.doi.org/10.1016/j.apradiso.2019.109006DOI Listing
March 2020

[Genetic characterization of Listeria monocytogenes strains isolated during 2007-2014 in Chile].

Rev Chilena Infectol 2019 Oct;36(5):585-590

Instituto de Salud Pública de Chile, Chile.

Background: Listeria monocytogenes is a foodborne pathogen that causes listeriosis, a disease that can present as febrile gastroenteritis or as an invasive form that has high mortality rates. So far, the genetic diversity of strains of L. monocytogenes isolated from patients, foods and environmental sources in Chile has been poorly studied.

Aim: To characterize genetically L. monocytogenes strains received by the Institute of Public Health of Chile (ISP) between 2007 and 2014.

Methods: We selected 94 strains of L. monocytogenes corresponding to 94 different pulsotypes identified by pulsed field gel electrophoresis (PFGE), DNA was extracted and serotyping was performed by polymerase chain reaction (PCR) and multilocus sequence typing (MLST).

Results: The most common serotype was 4b (55.3%), followed by serotypes 1/2a (25.5%), 1/2b (17%) and 1/2c (2.2%). 32 sequence-type (ST) were identified, of which 4 were new, and the predominant ones were ST1 (28.7%) and ST2 (13.8%). All the strains of L. monocytogenes were grouped in Lineages I and II.

Conclusions: A great genetic variability was observed in the strains of L. monocytogenes analyzed, being predominant the ST1 and ST2, both belonging to Lineage I. Our results contribute to know the population structure of this pathogen in Chile and its presence in clinical samples, food and the environment.
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http://dx.doi.org/10.4067/S0716-10182019000500585DOI Listing
October 2019

Transcirculation Approach for Endovascular Embolization of Intracranial Aneurysms, Arteriovenous Malformations, and Dural Fistulas: A Multicenter Study.

World Neurosurg 2020 Feb 20;134:e1015-e1027. Epub 2019 Nov 20.

Department of Neurology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA; Department of Neurosurgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA; Department of Radiology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA. Electronic address:

Background: Unfavorable anatomy can preclude traditional anterograde endovascular interventions. Transcirculation approaches, which consist of primary catheterization of a target artery from the contralateral side or opposite cerebral circulation, can provide alternative pathways for successful treatment of these patients. We aimed to assess the safety, efficacy, and outcomes of endovascular embolization through transcirculation approaches.

Methods: Nine centers provided retrospective data on patients who underwent transcirculation procedures for embolization of intracranial aneurysms (IAs), dural arteriovenous fistulas (dAVFs), and arteriovenous malformations (AVMs). Raymond-Roy Occlusion Classification (RROC) grades and degree of obliteration were used to evaluate treatment success. Minor/major complications and clinical/angiographic outcomes were also assessed. A review of the literature reporting patients who underwent transcirculation embolizations was also performed.

Results: Forty patients were included in the study (34 IAs, 3 AVMs, and 3 dAVFs). Most IAs (22/34, 64.7%) were treated electively. Three AVMs and 2 dAVFs presented ruptured. RROC grade I-II was achieved in 97% of IAs. All AVMs and dAVFs were completely obliterated. One patient developed a transient arterial thrombus that was successfully treated with intravenous tirofiban. The most common indications for a transcirculation approach were difficult access angle of the target lesion (42.5%) and occlusion of the parent artery (27.5%). The review of the literature pooled 152 IAs treated via transcirculation approaches. Most common locations were the basilar tip (27%), posterior inferior cerebellar artery (25%), and internal carotid artery (15.1%). The posterior communicating artery was crossed in 60 (39.5%), anterior communicating artery in 48 (31.6%), and vertebral artery in 37 (24.3%) patients. Primary coiling alone was performed in 22 (14.5%), stent-assisted coiling in 67 (44.1%), balloon-assisted coiling in 36 (23.7%), stent-assisted coiling + balloon-assisted coiling in 20 (13.2%) and flow diversion in 7 (4.6%) patients. After intervention, 142 (93.4%) IAs achieved successful RROC grades I-II. Two major complications (1.3%) leading to death were reported, both of which were intraprocedural aneurysmal ruptures with massive subarachnoid hemorrhage and herniation. After a mean angiographic follow-up of 11.3 months, only 6/108 (5.6%) IAs showed intrasaccular filling/recurrence.

Conclusions: Transcirculation approaches seem to be safe and effective in the treatment of IAs, dAVFs, and AVMs. The most common indication for a transcirculation approach is the presence of a difficult angle to access the target lesion and occlusion of the parent artery.
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http://dx.doi.org/10.1016/j.wneu.2019.11.078DOI Listing
February 2020

Validation of the Spanish version of the Uterine Fibroid Symptom and Quality of Life (UFS-QoL) questionnaire in women with uterine myomatosis.

Med Clin (Barc) 2020 03 2;154(6):207-213. Epub 2019 Nov 2.

Clínica Ginecológica CEOGA Lugo, España.

Aim: To validate the Spanish version of the Uterine Fibroid Symptom and Quality of Life (UFS-QoL) questionnaire in women with uterine myomatosis, in order to assess severity of symptoms, and their impact on health-related quality of life.

Materials And Methods: The participants were recruited in gynaecology clinics. The UFS-QoL questionnaire comprises 37 items, 8 of which assess severity of symptoms, and the remaining 29 assess health-related quality of life in 6 subscales. Internal consistency, concurrent and discriminant validity, test-retest reliability, and the scale's sensitivity to change were evaluated.

Results: A total of 619 patients with uterine myomatosis, and 57 women without myomatosis, took part in the study. Cronbach's alpha was 0.97, and the test-retest reliability was 0.90 for the overall scale. The UFS-QoL not only discriminated between patients and healthy controls but also between patients with different degrees of uterine myomatosis. The scale responded to changes after treatment with an effect size of 1.2.

Conclusions: The Spanish version of the UFS-QoL questionnaire, used in a sample of the Spanish population, proved a valid and reliable tool to differentiate patients with uterine myomatosis and different grades of symptoms, and to evaluate the impact of the severity of these symptoms on health-related quality of life. In addition, the UFS-QoL proved sensitive to the changes generated by myomatosis treatment.
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http://dx.doi.org/10.1016/j.medcli.2019.05.027DOI Listing
March 2020

On the calculation of lake metabolic rates: Diel O and O technique.

Water Res 2019 Nov 14;165:114990. Epub 2019 Aug 14.

Environmental Physics, Department of Biology, Limnological Institute, University of Konstanz, Germany.

Metabolic transformations have a major impact on the development of primary producers in aquatic systems and thus affect the dynamics of the entire aquatic food web. Furthermore, metabolic transformations contribute to the carbon budget and thereby influence CO emissions from aquatic systems. Several techniques have been developed that aim at an easy assessment of metabolic rates over long time periods or in many systems. The O technique, which utilizes the isotopic fractionation between O and O isotopes due to metabolic transformations, is receiving increasing popularity in studies comparing the metabolism in many different lakes and served as basis for the conclusions that production increases with increasing atmospheric CO and that surprisingly little terrestrial carbon is recycled in lakes of the arid circumpolar landscape. However, we demonstrate here that the steady state assumptions underlying the O technique cause large uncertainties in the estimated metabolic rates. This conclusion is based on a sensitivity analysis using a numerical model of dissolved oxygen, DO, and of dissolved O, O, but is also confirmed by published metabolic rates estimated from the O and the diel O techniques. Metabolic rates obtained from the O technique appear unsuited for correlation analyses between lakes but may provide reasonable estimates in systems with low and long-term stable production. In addition we illustrate that the combination of few O measurements with the diel O technique and an inverse fitting procedure can improve estimates of metabolic rates and in particular of respiration rates.
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http://dx.doi.org/10.1016/j.watres.2019.114990DOI Listing
November 2019

Morphology and mechanical properties of poly(ethylene brassylate)/cellulose nanocrystal composites.

Carbohydr Polym 2019 Oct 1;221:137-145. Epub 2019 Jun 1.

Department of Mining-Metallurgy Engineering and Materials Science, POLYMAT, University of The Basque Country (UPV/EHU), School of Engineering, Plaza Ingeniero Torres Quevedo s/n, 48013 Bilbao, Spain.

Poly(ethylene brassylate), a novel inexpensive biodegradable polyester, has been reinforced with cellulose nanocrystals (CNCs) with the aim of improving its thermal stability and mechanical properties. The composites have been characterized through calorimetry, tensile tests, thermogravimetry and electron microscopy. The addition of small amounts of CNCs improves both the stiffness and the ductility of the composites, suggesting the existence of some compatibilizing effect. Adding large CNC amounts increases the Young modulus (e.g., 150% for 50 wt% CNCs), but now the material shows brittle behavior. Degradation of the CNCs starts at lower temperature suggesting mutual reactivity. The SEM analysis of the composites with ductile behavior reveals the formation of a percolating network crossing through the interconnected domains that conform a PEB-rich continuous phase. Processing consisting on reinforcement dispersion by sonication followed by melt processing results in composites in which the improvement of mechanical properties does not involve any trade-off.
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http://dx.doi.org/10.1016/j.carbpol.2019.05.091DOI Listing
October 2019

Genetic variability of human papillomavirus type 66 L1 gene among women presenting for cervical cancer screening in Chile.

Med Microbiol Immunol 2019 Dec 4;208(6):757-771. Epub 2019 Jun 4.

Sección Virus Oncogénicos, Subdepto. de Enfermedades Virales, Instituto de Salud Pública de Chile, Avenida Marathon 1000, Ñuñoa, Santiago, Chile.

The high-risk human papillomaviruses (HR-HPVs) are involved in the development of cervical cancer. Nevertheless, there are differences in the oncogenic potential among them. HPV-16 and HPV-18 are associated with approximately 70% of cancer worldwide, and both types are the most extensively studied HR-HPV. Great variations in the prevalence of HR-HPV have been described in different countries. The impact of these variations on the epidemiology of lesions and cervical cancer is currently unknown. A high prevalence of HPV-66 has been detected in Chile. Here, we have analyzed the genetic variability of the L1 gene from HPV-66-infected Chilean women. Higher order interactions between identified mutations were analyzed by co-variation and cluster analyses. Antigenic-index alterations following L1 mutations and B-cell epitopes were predicted by BcePred algorithm. HPV-66 L1 sequences clustered phylogenetically into two main clades. The genetic variability in the HPV-66 L1 gene involved thirty nucleotide changes. Four of these were for the first time identified in this study. Some of these variants are embedded in the B-cell epitope regions. Amino acid homology in the immunodominant epitopes of HPV-66 L1 protein (DE, FG and H1 loops) was 42.9-59.1% and 28.6-68.9% compared with HPV-16 and HPV-18, respectively. The results of this research suggest that the neutralizing epitopes of HPV-66 are antigenically different compared to HPV-16 and HPV-18. Our findings show the need to perform new structural and immunological studies on HPV-66 L1 protein to evaluate the cross-protection conferred by current HPV vaccines.
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http://dx.doi.org/10.1007/s00430-019-00621-wDOI Listing
December 2019
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