Comparison of Short- and Long-Term Effectiveness between Anti-TNF and Ustekinumab after Vedolizumab Failure as First-Line Therapy in Crohn's Disease: A Multi-Center Retrospective Cohort Study

BACKGROUND The effectiveness of anti-TNF or ustekinumab (UST) as a second-line biologic after vedolizumab (VDZ) failure has not yet been described. AIMS AND METHODS In this retrospective multicenter cohort study, We aim to investigate the effectiveness of anti-TNF and UST as second-line therapy in patients with Crohn's disease (CD) who failed VDZ as a first-line treatment. The primary outcome was clinical response at week 16-22. Secondary outcomes included the rates of clinical remission, steroid-free clinical remission, CRP normalization, and adverse events. RESULTS Fifty-nine patients who failed on VDZ as a first-line treatment for CD were included; 52.8% patients received anti-TNF and 47.2% UST as a second-line therapy. In initial period (Week 16-22), the clinical response and remission rate was similar between both groups: 61.2% vs. 68%, p = 0.8 and 48.3% vs. 56%, p = 0.8 on anti-TNF and UST therapy, respectively. Furthermore, in the maintenance period the rate was similar: 75% vs. 82.3%, p = 0.8 and 62.5% vs. 70.5%, p = 0.8, respectively. Of the patients, 12 out of the 59 stopped the therapy, without a significant difference between the two groups (p = 0.6). CONCLUSION Second-line biological therapy after VDZ failure therapy was effective in >60% of the patients with CD. No differences in effectiveness were detected between the use of anti-TNF and UST as a second line

Effectiveness of third-class biologic treatment in crohn’s disease : A multi-center retrospective cohort study

Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Background: Multiple studies have described the effectiveness of ustekinumab (UST) and vedolizumab (VDZ) in patients with Crohn’s disease (CD) failing anti-Tumor necrosis factors (TNFs); however, the effectiveness of VDZ or UST as a third-class biologic has not yet been described. Aims and Methods: In this retrospective multicenter cohort study, we aimed to investigate the effectiveness of VDZ and UST as a third-class biologic in patients with CD. Results: Two-hundred and four patients were included; 156/204 (76%) patients received VDZ as a second-and UST as a third-class therapy (group A); the remaining 48/204 (24%) patients received UST as a second-and VDZ as a third-class therapy (group B). At week 16–22, 87/156 (55.5%) patients and 27/48 (56.2%) in groups A and B, respectively, responded to treatment (p = 0.9); 41/156 (26.2%) and 15/48 (31.2%) were in clinical remission (p = 0.5). At week 52; 89/103 (86%) patients and 25/29 (86.2%) of the patients with available data had responded to third-class treatment in groups A and B, respectively (p = 0.9); 31/103 (30%) and 47/29 (24.1%) were in clinical remission (p = 0.5). Conclusion: Third-class biological therapy was effective in more than half of the patients with CD. No differences in effectiveness were detected between the use of VDZ and UST as a third-class agent.Peer reviewe

Fine‑mapping of angular leaf spot resistance gene Phg‑2 in common bean and development of molecular breeding tools

Common bean (Phaseolus vulgaris L.) is an important food legume in Latin America, Asia and Africa. It is an important source of protein, carbohydrates and micro-minerals, particularly for smallholder farmers. Common bean productivity is affected by angular leaf spot (ALS) disease caused by the pathogenic fungus Pseudocercospora griseola, resulting in significant yield losses, particularly in low-input smallholder farming systems in the tropics. The ALS resistance gene Phg-2, which was found in several highly resistant common bean genotypes, was investigated in crosses between Mesoamerican pre-breeding lines and elite Andean breeding lines. Next-generation sequencing (NGS) data sets were used to design new SNP-based molecular markers. The Phg-2 locus was confirmed to be the major locus providing ALS resistance in these crosses. The locus was fine-mapped to a 409-Kbp region on chromosome 8. Two clusters of highly related LRR genes were identified in this region, which are the best candidate genes for Phg-2. Molecular markers were identified that are closely linked to the Phg-2 resistance gene and also highly specific to the donor germplasm. Marker-assisted selection (MAS) was used to introgress the Phg-2 resistance locus into Andean breeding germplasm using MAB lines. The usefulness of molecular markers in MAS was confirmed in several field evaluations in complex breeding crosses, under inoculation with different ALS pathotypes. This project demonstrates that NGS data are a powerful tool for the characterization of genetic loci and can be applied in the development of breeding tools

GZI index for the file with copy number variation events relative to the bean reference genome v2.1

GZI index for the file with copy number variation events relative to the bean reference genome v2.1. This file was generated using the bgzip tool (http://www.htslib.org/doc/tabix.html

Data from: Resequencing of common bean identifies regions of inter-gene pool introgression and provides comprehensive resources for molecular breeding

Common bean is the most important grain legume for human consumption and a main nutrition source in the tropics. Because bean production is reduced by both abiotic and biotic constraints, current breeding efforts are focused on the development of improved varieties with tolerance to these stresses. We characterized materials from different breeding programs spanning three continents to understand their sequence diversity and advance the development of molecular breeding tools. For this, 37 varieties belonging to P. vulgaris, P. acutifolius, and P. coccineus were sequenced by whole-genome sequencing (WGS), identifying more than 40 million genomic variants. Evaluation of nuclear DNA content and analysis of copy number variation revealed important differences in genomic content not only between P. vulgaris and two other domesticated Phaseolus species, but also within P. vulgaris, affecting hundreds of protein-coding genomic regions. A large number of inter-gene-pool introgressions were identified. Furthermore, interspecific introgressions for disease resistance in breeding lines were mapped. Evaluation of newly developed SNP markers within previously discovered QTL for common bacterial blight and angular leaf spot provide improved specificity to tag sources of resistance to these diseases. We expect that this dataset will provide a deeper molecular understanding of breeding germplasm and deliver molecular tools for germplasm development, aiming to increase the efficiency of bean breeding programs

Data from: Resequencing of common bean identifies regions of inter-gene pool introgression and provides comprehensive resources for molecular breeding

Common bean is the most important grain legume for human consumption and a main nutrition source in the tropics. Because bean production is reduced by both abiotic and biotic constraints, current breeding efforts are focused on the development of improved varieties with tolerance to these stresses. We characterized materials from different breeding programs spanning three continents to understand their sequence diversity and advance the development of molecular breeding tools. For this, 37 varieties belonging to P. vulgaris, P. acutifolius, and P. coccineus were sequenced by whole-genome sequencing (WGS), identifying more than 40 million genomic variants. Evaluation of nuclear DNA content and analysis of copy number variation revealed important differences in genomic content not only between P. vulgaris and two other domesticated Phaseolus species, but also within P. vulgaris, affecting hundreds of protein-coding genomic regions. A large number of inter-gene-pool introgressions were identified. Furthermore, interspecific introgressions for disease resistance in breeding lines were mapped. Evaluation of newly developed SNP markers within previously discovered QTL for common bacterial blight and angular leaf spot provide improved specificity to tag sources of resistance to these diseases. We expect that this dataset will provide a deeper molecular understanding of breeding germplasm and deliver molecular tools for germplasm development, aiming to increase the efficiency of bean breeding programs