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Article ; Online: Culex Tarsalis Mosquitoes as Vectors of Highlands J Virus.

Borland, Erin M / Ledermann, Jeremy P / Powers, Ann M

Vector borne and zoonotic diseases (Larchmont, N.Y.)

2016 Volume 16, Issue 8, Page(s) 558–565

Abstract: Highlands J virus (HJV) is an alphavirus closely related to western equine encephalitis virus (WEEV ...

Abstract	Highlands J virus (HJV) is an alphavirus closely related to western equine encephalitis virus (WEEV) and eastern equine encephalitis virus (EEEV). HJV is an avian pathogen with the potential for disruption of poultry operations, but is not known to cause human or equine disease. HJV has only been identified in the eastern United States and is thought to have a transmission cycle similar to that of EEEV involving Culiseta melanura mosquitoes and birds. However, HJV is more genetically similar to WEEV and it remains unclear if it may be transmitted by Culex species mosquitoes like WEEV. Seven strains of HJV were characterized to assess this potential. Phylogenetic analysis of whole genome sequences revealed four distinct HJV lineages (lineages 1-4), and vector competence studies in Cx. tarsalis with four of the HJV strains from different lineages yielded two distinct infection patterns. Lineage 1 strains had low infection rates, while lineages 2 and 4 had significantly higher infection rates similar to those previously published for WEEV. The average mosquito body viral titer was highest at 8 dpi (6.60-7.26 log10 pfu equivalents/body), and head titers at all time points ranged between 6.01 and 6.80 log10 pfu equivalents/head. Nearly 45% of mosquitoes infected with strain AB-80-9 were able to transmit virus in saliva with an average titer of 5.02 log10 pfu equivalents/saliva. A single amino acid difference between high and low infectivity phenotypes was identified at genome position 8605, in the E2 gene. A nonpolar glycine was present in the low infectivity lineage 1 strains, while an acidic glutamic acid was present in the higher infectivity lineage 2 and 4 strains. This study demonstrates HJV transmission by Cx. tarsalis mosquitoes and clearly identifies the potential for transmission in the western United States. Two infection phenotypes were exhibited, indicating the need for further studies to understand Culex species transmission patterns.
MeSH term(s)	Alphavirus/genetics ; Alphavirus/isolation & purification ; Animals ; Culex/virology ; Genome, Viral ; Mosquito Vectors/virology ; Phylogeny ; Saliva/virology
Language	English
Publishing date	2016-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2047199-3
ISSN	1557-7759 ; 1530-3667
ISSN (online)	1557-7759
ISSN	1530-3667
DOI	10.1089/vbz.2015.1907
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Article ; Online: Ovarian cancer recurrence: is the definition of platinum resistance modified by PARPi and other intervening treatments? The evolving landscape in the management of platinum-resistant ovarian cancer.

Flynn, Michael J / Ledermann, Jonathan A

Cancer drug resistance (Alhambra, Calif.)

2022 Volume 5, Issue 2, Page(s) 424–435

Abstract: Definitions of platinum resistance have been questioned and changed over the last five years, even though no predictive biomarker of resistance exists. These have sculpted how we approach platinum retreatment and, consequently, how we devise new ... ...

Abstract	Definitions of platinum resistance have been questioned and changed over the last five years, even though no predictive biomarker of resistance exists. These have sculpted how we approach platinum retreatment and, consequently, how we devise new treatment strategies for those patients with tumour progression on platinum therapy. Platinum-non-eligible ovarian cancer is treated with single-agent non-platinum drugs. When bevacizumab can be added to chemotherapy, progression-free survival improves significantly. For patients with a BRCA mutation, PARP inhibitor monotherapy is an option compared to chemotherapy. There is currently no clearly identified role for immune-checkpoint inhibition in this patient population. This review describes some of the challenges in treating patients with platinum resistance and suggests refinements in the selection of patients most likely to benefit from targeting a DNA damage response, angiogenesis or immune modulation. It also describes novel agents of interest and possible mechanisms of the synergy of therapeutic combinations.
Language	English
Publishing date	2022-05-12
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2578-532X
ISSN (online)	2578-532X
DOI	10.20517/cdr.2022.13
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Article ; Online: Updated treatment recommendations for newly diagnosed epithelial ovarian carcinoma from the ESMO Clinical Practice Guidelines.

Colombo, N / Ledermann, J A

Annals of oncology : official journal of the European Society for Medical Oncology

2021 Volume 32, Issue 10, Page(s) 1300–1303

MeSH term(s)	Carcinoma, Ovarian Epithelial/diagnosis ; Carcinoma, Ovarian Epithelial/therapy ; Female ; Humans ; Neoplasms, Glandular and Epithelial/diagnosis ; Neoplasms, Glandular and Epithelial/therapy ; Ovarian Neoplasms/diagnosis ; Ovarian Neoplasms/drug therapy ; Practice Guidelines as Topic
Language	English
Publishing date	2021-07-21
Publishing country	England
Document type	Letter
ZDB-ID	1025984-3
ISSN	1569-8041 ; 0923-7534
ISSN (online)	1569-8041
ISSN	0923-7534
DOI	10.1016/j.annonc.2021.07.004
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Article: Consecutive four-component synthesis of trisubstituted 3-iodoindoles by an alkynylation-cyclization-iodination-alkylation sequence.

Ledermann, Nadia / Moubsit, Alae-Eddine / Müller, Thomas J J

Beilstein journal of organic chemistry

2023 Volume 19, Page(s) 1379–1385

Abstract: A library of 19 differently substituted 3-iodoindoles is generated by a consecutive four-component reaction starting ... ...

Abstract	A library of 19 differently substituted 3-iodoindoles is generated by a consecutive four-component reaction starting from
Language	English
Publishing date	2023-09-14
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2192461-2
ISSN	1860-5397
ISSN	1860-5397
DOI	10.3762/bjoc.19.99
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Article ; Online: El médico como personaje literario en la Edad Moderna.

Ledermann D, Walter

Revista chilena de infectologia : organo oficial de la Sociedad Chilena de Infectologia

2020 Volume 37, Issue 3, Page(s) 304–310

Abstract: ... in the sixteenth century until. A. J. Cronin in the twentieth, shows the evolution of the doctor as a literary ...

Title translation	The doctor as a literary character in the Modern Age.
Abstract	The doctor has been from de Antiquity a victim of the people's affective ambivalence, who loves and hates him accord his success or failures. Some rant against the medical guild, but are proud to be patients of one or another doctor, more o less celebrated, referring familiarly to him as Tony or Jim. A certain envy hurts the doctor's image, countered by gratitude, but finally, as times goes by, the continuous progress of medicine has been improving the public perception about the medical work. A quick review of the Modern Age literature, personal, whimsical and may be imperfect, from Michel de Montaigne, in the sixteenth century until. A. J. Cronin in the twentieth, shows the evolution of the doctor as a literary character, first as a tricky ignorant, after like a clown, later fighting epidemics and ending as a self-sacrificing medical researcher.
MeSH term(s)	Physicians
Language	Spanish
Publishing date	2020-08-27
Publishing country	Chile
Document type	Journal Article
ZDB-ID	2048815-4
ISSN	0717-6341 ; 0716-1018
ISSN (online)	0717-6341
ISSN	0716-1018
DOI	10.4067/s0716-10182020000300304
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Article ; Online: Front-line therapy of advanced ovarian cancer: new approaches.

Ledermann, J A

Annals of oncology : official journal of the European Society for Medical Oncology

2017 Volume 28, Issue suppl_8, Page(s) viii46–viii50

Abstract: Background: The 5-year survival of ovarian cancer has slowly increased but to date much of this has been due to the use of more lines of treatment rather than better first-line therapy. In this setting, there has been little improvement over the past 15 ...

Abstract	Background: The 5-year survival of ovarian cancer has slowly increased but to date much of this has been due to the use of more lines of treatment rather than better first-line therapy. In this setting, there has been little improvement over the past 15 years. The introduction of new treatments to extend time to first progression and overall survival remains a key objective of clinical research. Design: The focus of research in the previous decade has been on the incorporation of anti-angiogenic therapy or dose-dense scheduling of paclitaxel (Taxol) to improve outcome. The new trials being conducted build on the knowledge gained and are focussing on two new areas of research, the use of PARP (poly-ADP ribose polymerase) inhibitors and immunotherapy. Results: Ongoing randomised trials using PARP inhibitors or immune checkpoint inhibits are reviewed and the potential benefits and challenges of using these agents are discussed. Conclusions: Improvements in outcome from some of the many open trials may present challenges; interpretation of the outcome data needs to be taken in the context of clinical benefit and a health-economic assessment. The latter is becoming ever-more important as the cost of trials with combinations of targeted therapy is very great.
MeSH term(s)	Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Bevacizumab/administration & dosage ; Carboplatin/administration & dosage ; Cisplatin/administration & dosage ; Clinical Trials, Phase III as Topic ; Female ; Humans ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/enzymology ; Ovarian Neoplasms/immunology ; Paclitaxel/administration & dosage ; Poly(ADP-ribose) Polymerase Inhibitors/administration & dosage ; Randomized Controlled Trials as Topic
Chemical Substances	Poly(ADP-ribose) Polymerase Inhibitors ; Bevacizumab (2S9ZZM9Q9V) ; Carboplatin (BG3F62OND5) ; Paclitaxel (P88XT4IS4D) ; Cisplatin (Q20Q21Q62J)
Language	English
Publishing date	2017-12-20
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1025984-3
ISSN	1569-8041 ; 0923-7534
ISSN (online)	1569-8041
ISSN	0923-7534
DOI	10.1093/annonc/mdx452
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Article ; Online: PARP inhibitors in ovarian cancer.

Ledermann, J A

Annals of oncology : official journal of the European Society for Medical Oncology

2016 Volume 27 Suppl 1, Page(s) i40–i44

Abstract: Background: Slow progress in improving the outcome of ovarian cancer with chemotherapy over the last decade has stimulated research into molecularly targeted therapy. Poly(ADP-ribose) polymerase (PARP) inhibitors target DNA repair and are specifically ... ...

Abstract	Background: Slow progress in improving the outcome of ovarian cancer with chemotherapy over the last decade has stimulated research into molecularly targeted therapy. Poly(ADP-ribose) polymerase (PARP) inhibitors target DNA repair and are specifically active in cells that have impaired repair of DNA by the homologous recombination (HR) pathway. Cells with mutated BRCA function have HR deficiency (HRD), which is also present in a significant proportion of non-BRCA-mutated ovarian cancer. Design: In the last decade, olaparib, the first and most-investigated oral PARP inhibitor, has undergone phase I-III trials as a single agent, in comparison with and in addition to chemotherapy, and as a maintenance therapy following chemotherapy. Results: The greatest benefit to-date has been in the maintenance setting, prolonging the progression-free survival of high-grade serous ovarian cancer with a BRCA1/2 mutation. In this group of patients, olaparib has received approval as maintenance following chemotherapy from the EMA, and accelerated approval as a single agent in women who have had three or more lines of therapy. Olaparib can be given for a prolonged period with few significant side-effects in most patients. Similar trials with other PARP inhibitors (rucaparib, niraparib and veliparib) are in progress and include non-BRCA-mutated ovarian cancer. Second-generation studies are exploring the combination of PARP inhibitors with anti-angiogenic drugs. Conclusions: PARP inhibitors represent a step change in the management of ovarian cancer. BRCA mutations are the first genotypic predictive markers in ovarian cancer and can be used to select patients who will most likely benefit from PARP inhibitors. BRCA testing is now becoming a routine part of the evaluation of women with ovarian cancer, and tests for HRD are being used to evaluate PARP inhibitors in an extended population of non-BRCA-mutated ovarian cancer.
MeSH term(s)	Drug Discovery ; Drug Synergism ; Female ; Humans ; Mutation ; Ovarian Neoplasms/drug therapy ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use
Chemical Substances	Poly(ADP-ribose) Polymerase Inhibitors
Language	English
Publishing date	2016-05-03
Publishing country	England
Document type	Journal Article
ZDB-ID	1025984-3
ISSN	1569-8041 ; 0923-7534
ISSN (online)	1569-8041
ISSN	0923-7534
DOI	10.1093/annonc/mdw094
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Article ; Online: The interplay between mindfulness and caring for bliss on later student burnout.

Rudaz, Myriam / Ledermann, Thomas / Fincham, Frank D

Journal of American college health : J of ACH

2022 Volume 72, Issue 1, Page(s) 188–194

Abstract: Objectives: ...

Abstract	Objectives:
MeSH term(s)	Humans ; Mindfulness ; Students ; Universities ; Burnout, Psychological ; Burnout, Professional/prevention & control ; Surveys and Questionnaires
Language	English
Publishing date	2022-01-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	604907-2
ISSN	1940-3208 ; 0744-8481
ISSN (online)	1940-3208
ISSN	0744-8481
DOI	10.1080/07448481.2021.2024549
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Article: Chest CT findings of early and progressive phase COVID-19 infection from a US patient.

Adair, Luther B / Ledermann, Eric J

Radiology case reports

2020 Volume 15, Issue 7, Page(s) 819–824

Abstract: The SARS-CoV-2 infection (COVID-19), originally reported in Wuhan, China, has rapidly proliferated throughout several continents and the first case in the United States was reported on January 19, 2020. According to the ACR guidelines issued shortly ... ...

Abstract	The SARS-CoV-2 infection (COVID-19), originally reported in Wuhan, China, has rapidly proliferated throughout several continents and the first case in the United States was reported on January 19, 2020. According to the ACR guidelines issued shortly after this disease was declared a pandemic, radiologists are expected to familiarize themselves with the CT appearance of COVID-19 infection in order to be able to identify specific findings of this entity. This case report discusses the relevant imaging findings of one of the first cases in the mid-western United States. It involves a 60-year-old man who presented with fever, dyspnea, and cough for 1 week and subsequently tested positive for COVID-19. The utility of the noncontrast CT chest in the diagnosis of COVID-19 has been controversial, but there are specific imaging findings that have been increasingly associated with this virus in the appropriate clinical context. The stages of imaging findings in COVID-19 are considered along with the implications of fibrosis throughout the stages. Future considerations include using artificial intelligence algorithms to distinguish between community acquired pneumonias and COVID-19 infection.
Keywords	covid19
Language	English
Publishing date	2020-04-20
Publishing country	Netherlands
Document type	Case Reports
ZDB-ID	2406300-9
ISSN	1930-0433
ISSN	1930-0433
DOI	10.1016/j.radcr.2020.04.031
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Article: Immune checkpoint inhibitors in ovarian cancer: where do we stand?

Leary, Alexandra / Tan, David / Ledermann, Jonathan

Therapeutic advances in medical oncology

2021 Volume 13, Page(s) 17588359211039899

Abstract: Numerous retrospective studies have demonstrated that the density of intra-tumoral immune cell infiltration is prognostic in epithelial ovarian cancer (OC). These observations together with reports of programmed death ligand-1 (PD-L1) expression in ... ...

Abstract	Numerous retrospective studies have demonstrated that the density of intra-tumoral immune cell infiltration is prognostic in epithelial ovarian cancer (OC). These observations together with reports of programmed death ligand-1 (PD-L1) expression in advanced OC provided the rationale for investigating the benefit of programmed death-1 (PD1) or PD-L1 inhibition in OC. Unfortunately clinical trials to date evaluating PD1/PD-L1 inhibition in patients with relapsed OC have been disappointing. In this review we will discuss early results from single agent PD1/PD-L1 inhibitors and the strategies to enhance benefit from immune-oncology agents in OC, including proposing anti-PD-L1 in combination with other agents (cytotoxics, anti-angiogenics, poly(ADP-ribose) polymerase. (PARP) inhibitors, targeted therapies or other immunotherapies), as well as evaluating these agents earlier in the disease course, or in biomarker selected patients.
Language	English
Publishing date	2021-08-18
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2503443-1
ISSN	1758-8359 ; 1758-8340
ISSN (online)	1758-8359
ISSN	1758-8340
DOI	10.1177/17588359211039899
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