tbuckley/cabot-search huggingface dataset:
Acute kidney injury in patients treated with immune checkpoint inhibitors
Authors: Shruti Gupta, Samuel A P Short, Meghan E Sise, Jason M Prosek, Sethu M Madhavan, Maria Jose Soler, Marlies Ostermann, Sandra M Herrmann, Ala Abudayyeh, Shuchi Anand, Ilya Glezerman, Shveta S Motwani, Naoka Murakami, Rimda Wanchoo, David I Ortiz-Melo, Arash Rashidi, Ben Sprangers, Vikram Aggarwal, A Bilal Malik, Sebastian Loew, Christopher A Carlos, Wei-Ting Chang, Pazit Beckerman, Zain Mithani, Chintan V Shah, Amanda D Renaghan, Sophie De Seigneux, Luca Campedel, Abhijat Kitchlu, Daniel Sanghoon Shin, Sunil Rangarajan, Priya Deshpande, Gaia Coppock, Mark Eijgelsheim, Harish Seethapathy, Meghan D Lee, Ian A Strohbehn, Dwight H. Owen, Marium Husain, Clara Garcia-Carro, Sheila Bermejo, Nuttha Lumlertgul, Nina Seylanova, Lucy Flanders, Busra Isik, Omar Mamlouk, Jamie S Lin, Pablo Garcia, Aydin Kaghazchi, Yuriy Khanin, Sheru K Kansal, Els Wauters, Sunandana Chandra, Kai M Schmidt-Ott, Raymond K Hsu, Maria C Tio, Suraj Sarvode Mothi, Harkarandeep Singh, Deborah Schrag, Kenar D Jhaveri, Kerry L Reynolds, Frank B Cortazar, David E Leaf
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer. Methods We collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI. Results ICPi-AKI occurred at a median of 16 weeks (IQR 8–32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3–10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI. Conclusions Patients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery.
624P Prevalence and clinical impact of PTEN status in patients (pts) with de novo metastatic hormone sensitive prostate cancer (mHSPC)
Authors: J. Thouvenin, V. Colinet, P. Barthelemy, S. Sideris, M. Van Eycken, S. Rorive, N. Sirtaine, A.A. Hamid, T. Roumeguere, N. Martinez Chanza
Journal: Annals of Oncology (2021)
Hemochromatosis classification: update and recommendations by the BIOIRON Society
Authors: Domenico Girelli, Fabiana Busti, Pierre Brissot, Ioav Cabantchik, Martina U. Muckenthaler, Graça Porto
Journal: Blood (2021)

Hemochromatosis (HC) is a genetically heterogeneous disorder in which uncontrolled intestinal iron absorption may lead to progressive iron overload (IO) responsible for disabling and life-threatening complications such as arthritis, diabetes, heart failure, hepatic cirrhosis, and hepatocellular carcinoma. The recent advances in the knowledge of pathophysiology and molecular basis of iron metabolism have highlighted that HC is caused by mutations in at least 5 genes, resulting in insufficient hepcidin production or, rarely, resistance to hepcidin action. This has led to an HC classification based on different molecular subtypes, mainly reflecting successive gene discovery. This scheme was difficult to adopt in clinical practice and therefore needs revision. Here we present recommendations for unambiguous HC classification developed by a working group of the International Society for the Study of Iron in Biology and Medicine (BIOIRON Society), including both clinicians and basic scientists during a meeting in Heidelberg, Germany. We propose to deemphasize the use of the molecular subtype criteria in favor of a classification addressing both clinical issues and molecular complexity. Ferroportin disease (former type 4a) has been excluded because of its distinct phenotype. The novel classification aims to be of practical help whenever a detailed molecular characterization of HC is not readily available.
LBA36 Nivolumab (N) + ipilimumab (I) vs EXTREME as first-line (1L) treatment (tx) for recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN): Final results of CheckMate 651
Authors: A. Argiris, K. Harrington, M. Tahara, R.L. Ferris, M. Gillison, J. Fayette, A. Daste, P. Koralewski, R. Mesia Nin, N.F. Saba, M. Mak, M.A. Álvarez Avitia, A. Guminski, U. Müller-Richter, N. Kiyota, M. Roberts, T.A. Khan, K. Miller-Moslin, L. Wei, R. Robert Haddad
Journal: Annals of Oncology (2021)
Time of Death
Authors: Jamie C. Riches
Journal: JAMA (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
621P Efficacy and safety of relugolix vs leuprolide (LEU) in men with advanced prostate cancer (APC): Clinical subgroup analysis from the phase III HERO study
Authors: D.R. Saltzstein, N.D. Shore, F. Saad, D.J. George, M.S. Cookson, R. Tutrone, H. Akaza, A. Bossi, B. Brown, B. Selby, S. Lu, J. Walling, B. Tombal
Journal: Annals of Oncology (2021)
171P Combining tumor-infiltrating lymphocytes and PD-L1 expression can stratify prognosis in early-stage triple-negative breast cancer patients who did not receive adjuvant chemotherapy
Authors: S. Yazaki, T. Shimoi, M. Yoshida, H.S. Okuma, S. Kita, K. Yamamoto, Y. Kojima, T. Nishikawa, M. Tanioka, K. Sudo, E. Noguchi, T. Murata, S. Takayama, A. Suto, K. Yonemori
Journal: Annals of Oncology (2021)
17P PD-1 and LAG-3 immune checkpoints constitutive activators exhibit differential expression phenotypes
Authors: L. Chocarro, E.B. Palmeiro, H. Arasanz, A. Bocanegra, M. Zuazo, M. Echaide, P. Morente, L. Fernández-Rubio, G. Fernández-Hinojal, M. Garnica, P. Ramos, M.J. García-Granda, R. Vera, G. Kochan, D. Escors
Journal: Annals of Oncology (2021)
Gene expression signature as a surrogate marker of microvascular invasion on routine hepatocellular carcinoma biopsies
Authors: Aurélie Beaufrère, Stefano Caruso, Julien Calderaro, Nicolas Poté, Jean-Charles Bijot, Gabielle Couchy, François Cauchy, Valérie Vilgrain, Jessica Zucman-Rossi, Valérie Paradis
Journal: Journal of Hepatology (2021)
A systematic review of blood biomarkers with individual participant data meta-analysis of matrix metalloproteinase-7 in idiopathic pulmonary fibrosis
Authors: Fasihul A. Khan, Iain Stewart, Gauri Saini, Karen A. Robinson, R. Gisli Jenkins
Journal: European Respiratory Journal (2021)

Background Blood-derived biomarkers have been described extensively as potential prognostic markers in idiopathic pulmonary fibrosis (IPF), but studies have been limited by analyses using data-dependent thresholds, inconsistent adjustment for confounders and an array of end-points, thus often yielding ungeneralisable results. Meta-analysis of individual participant data (IPD) is a powerful tool to overcome these limitations. Through systematic review of blood-derived biomarkers, sufficient studies with measurements of matrix metalloproteinase (MMP)-7 were identified to facilitate standardised analyses of the prognostic potential of this biomarker in IPF. Methods Electronic databases were searched on 12 November 2020 to identify prospective studies reporting outcomes in patients with untreated IPF, stratified according to at least one pre-specified biomarker, measured at either baseline, or change over 3 months. IPD were sought for studies investigating MMP-7 as a prognostic factor. The primary outcome was overall mortality according to standardised MMP-7 z-scores, with a secondary outcome of disease progression in 12 months, all adjusted for age, gender, smoking and baseline forced vital capacity. Results IPD was available for nine studies out of 12 identified, reporting outcomes from 1664 participants. Baseline MMP-7 levels were associated with increased mortality risk (adjusted hazard ratio 1.23, 95% CI 1.03–1.48; I 2 =64.3%) and disease progression (adjusted OR 1.27, 95% CI 1.11–1.46; I 2 =5.9%). In limited studies, 3-month change in MMP-7 was not associated with outcomes. Conclusion IPD meta-analysis demonstrated that greater baseline MMP-7 levels were independently associated with an increased risk of poor outcomes in patients with untreated IPF, while short-term changes did not reflect disease progression.
Impact of a 24/7 multiplex-PCR on the management of patients with confirmed viral meningitis
Authors: Gauthier Péan de Ponfilly, Anthony Chauvin, Maud Salmona, Hanaa Benmansour, Béatrice Bercot, Francois Camelena, Virginie Courbin, Xavier Eyer, Emmanuel Lecorche, Faïza Mougari, Anne-Lise Munier, Eric Revue, Jérôme LeGoff, Emmanuelle Cambau, Hervé Jacquier
Journal: Journal of Infection (2021)
815TiP ENGOT/GYN1/NCRI: ATR inhibitor in combination with olaparib in gynaecological cancers with ARID1A loss or no loss (ATARI)
Authors: S. Banerjee, A. Leary, S. Lheureux, J. Stewart, A. Attygalle, K. Vroobel, S. Gill, Z. Ali, J. Tai, C. Toms, R. Natrajan, C.J. Lord, N. Porta, J. Bliss
Journal: Annals of Oncology (2021)
230MO First in human, modular study of samuraciclib (CT7001), a first-in-class, oral, selective inhibitor of CDK7, in patients with advanced solid malignancies
Authors: M.G. Krebs, S. Lord, L. Kenny, R.D. Baird, I. MacPherson, A. Bahl, G. Clack, E. Ainscow, A.G. Barrett, P. Dickinson, M.J. Fuchter, M. Lehnert, S. Ali, S. Mcintosh, R.C. Coombes
Journal: Annals of Oncology (2021)
342O Intracranial administration of CTLA-4 and PD-1 immune checkpoint blocking monoclonal antibodies in recurrent glioblastoma (rGB): A multi-cohort adaptive phase I clinical trial
Authors: B. Neyns, J.K. Schwarze, C. Bertels, W. Geens, J. Tijtgat, G. Awada, F. Vaeyens, L. Cras, A-M. Vanbinst, H. Everaert, A. Michotte, M. Bruneau, R. Forsyth, S. Tuyaerts, J. Duerinck
Journal: Annals of Oncology (2021)
Rethinking Oedipus: an evolutionary perspective of incest avoidance
Authors: M T Erickson
Journal: American Journal of Psychiatry (1993)

The author presents a biological hypothesis of incest avoidance. Pertinent literature from evolutionary biology, ethology, anthropology, and clinical research is reviewed. Secure early bonding to immediate kin predicts later adaptive kin-directed behaviors, including preferential altruism (kin selection) and incest avoidance. Impaired bonding predicts aberrant kin-directed behavior, including diminished altruism, neglect, and an increased incidence of incest. Failed bonding predicts the highest frequency of incest. Secure bonding to kin may function to establish adaptive kin-directed behaviors, including incest avoidance. Bonding is conceived of as the developmental foundation of a form of social attraction, here called "familial attraction," which is evolutionarily distinct from sexual attraction.
372P The prognostic value of liver metastases and how affects the applicability of the lung-molGPA in non-small cell lung cancer patients with brain metastases
Authors: J.R. Veas Rodriguez, S. Morales Murillo, A. Rodriguez Galindo, O. Pallisé Subirats, J.F. Cordoba Ortega
Journal: Annals of Oncology (2021)
発作性夜間血色素尿症(PNH)患者2人における造血のクローン性増殖の分子基礎
Authors: Inoue N, Izui-Sarumaru T, Murakami Y, Endo Y, Nishimura Ji, Kurokawa K, Kuwayama M, Shime H, Machii T, Kanakura Y, Meyers G, Wittwer C, Chen Z, Babcock W, Frei-Lahr D, Parker Cj, Kinoshita T
Journal: Blood (2006)
Rapid Gene Evolution in an Ancient Post-transcriptional and Translational Regulatory System Compensates for Meiotic X Chromosomal Inactivation
Authors: Shengqian Xia, Iuri M Ventura, Andreas Blaha, Annamaria Sgromo, Shuaibo Han, Elisa Izaurralde, Manyuan Long
Journal: Molecular Biology and Evolution (2021)

It is conventionally assumed that conserved pathways evolve slowly with little participation of gene evolution. Nevertheless, it has been recently observed that young genes can take over fundamental functions in essential biological processes, for example, development and reproduction. It is unclear how newly duplicated genes are integrated into ancestral networks and reshape the conserved pathways of important functions. Here, we investigated origination and function of two autosomal genes that evolved recently in Drosophila: Poseidon and Zeus, which were created by RNA-based duplications from the X-linked CAF40, a subunit of the conserved CCR4-NOT deadenylase complex involved in posttranscriptional and translational regulation. Knockdown and knockout assays show that the two genes quickly evolved critically important functions in viability and male fertility. Moreover, our transcriptome analysis demonstrates that the three genes have a broad and distinct effect in the expression of hundreds of genes, with almost half of the differentially expressed genes being perturbed exclusively by one paralog, but not the others. Co-immunoprecipitation and tethering assays show that the CAF40 paralog Poseidon maintains the ability to interact with the CCR4-NOT deadenylase complex and might act in posttranscriptional mRNA regulation. The rapid gene evolution in the ancient posttranscriptional and translational regulatory system may be driven by evolution of sex chromosomes to compensate for the meiotic X chromosomal inactivation (MXCI) in Drosophila.
The Evolving Nexus of Sleep and Depression
Authors: David T. Plante
Journal: American Journal of Psychiatry (2021)

Sleep disturbances and depression are closely linked and share a bidirectional relationship. These interconnections can inform the pathophysiology underlying each condition. Insomnia is an established and modifiable risk factor for depression, the treatment of which offers the critical opportunity to prevent major depressive episodes, a paradigm-shifting model for psychiatry. Identification of occult sleep disorders may also improve outcomes in treatment-resistant depression. Sleep alterations and manipulations may additionally clarify the mechanisms that underlie rapid-acting antidepressant therapies. Both sleep disturbance and depression are heterogeneous processes, and evolving standards in psychiatric research that consider the transdiagnostic components of each are more likely to lead to translational progress at their nexus. Emerging tools to objectively quantify sleep and its disturbances in the home environment offer great potential to advance clinical care and research, but nascent technologies require further advances and validation prior to widespread application at the interface of sleep and depression.
1326P Combination of stereotactic ablative radiotherapy with anti-PD-1 in oligoprogressive disease: Final results of a prospective multicenter study
Authors: J. Zafra, R. Chicas Sett, D. Rodriguez, J. Castilla Martinez, B. Salas, A. Vera, G. Benítez, M. Lloret, J.L. Onieva, I. Barragan, P.C. Lara
Journal: Annals of Oncology (2021)
Oncogenic role of the SOX9-DHCR24-cholesterol biosynthesis axis in <i>IGH-BCL2</i>+ diffuse large B-cell lymphomas
Authors: Yajie Shen, Jingqi Zhou, Kui Nie, Shuhua Cheng, Zhengming Chen, Wenhan Wang, Weiqing Wei, Daiji Jiang, Zijing Peng, Yizhuo Ren, Yirong Zhang, Qiuju Fan, Kristy L. Richards, Yitao Qi, Jinke Cheng, Wayne Tam, Jiao Ma
Journal: Blood (2021)

Abstract Although oncogenicity of the stem cell regulator SOX9 has been implicated in many solid tumors, its role in lymphomagenesis remains largely unknown. In this study, SOX9 was overexpressed preferentially in a subset of diffuse large B-cell lymphomas (DLBCLs) that harbor IGH-BCL2 translocations. SOX9 positivity in DLBCL correlated with an advanced stage of disease. Silencing of SOX9 decreased cell proliferation, induced G1/S arrest, and increased apoptosis of DLBCL cells, both in vitro and in vivo. Whole-transcriptome analysis and chromatin immunoprecipitation–sequencing assays identified DHCR24, a terminal enzyme in cholesterol biosynthesis, as a direct target of SOX9, which promotes cholesterol synthesis by increasing DHCR24 expression. Enforced expression of DHCR24 was capable of rescuing the phenotypes associated with SOX9 knockdown in DLBCL cells. In models of DLBCL cell line xenografts, SOX9 knockdown resulted in a lower DHCR24 level, reduced cholesterol content, and decreased tumor load. Pharmacological inhibition of cholesterol synthesis also inhibited DLBCL xenograft tumorigenesis, the reduction of which is more pronounced in DLBCL cell lines with higher SOX9 expression, suggesting that it may be addicted to cholesterol. In summary, our study demonstrated that SOX9 can drive lymphomagenesis through DHCR24 and the cholesterol biosynthesis pathway. This SOX9-DHCR24-cholesterol biosynthesis axis may serve as a novel treatment target for DLBCLs.
658MO Cisplatin (cis)-related immunomodulation and efficacy with atezolizumab (atezo) + cis- vs carboplatin (carbo)-based chemotherapy (chemo) in metastatic urothelial cancer (mUC)
Authors: M.D. Galsky, X. Guan, R. Banchereau, L. Wang, J. Zhu, H. Yu, D. Rishipathak, E. Hajaj, R.H. Herbst, I.D. Davis, E. Grande, A. Bamias, M. De Santis, J.Á. Arranz, E. Kikuchi, J. Zhang, C. Lee, X. Shen, P.C. Black, S. Mariathasan
Journal: Annals of Oncology (2021)
649TiP PRIMORDIUM: A randomized, international, trial-in-progress of adding apalutamide to radiotherapy and an LHRH agonist in high-risk patients with PSMA-PET-positive hormone-sensitive prostate cancer
Authors: B.A. Hadaschik, S. Fanti, P. Ost, N. Tunariu, C. de Nunzio, L. Antoni, M. Lukac, J. Martin, G. Pissart, R. Wapenaar, N. Mottet
Journal: Annals of Oncology (2021)
1199P Dose modification for the management of CNS adverse events in the phase III CROWN study of lorlatinib in non-small cell lung cancer (NSCLC)
Authors: B.J. Solomon, T.S.K. Mok, H. Hayashi, A. Bearz, K.D. Penkov, Y-L. Wu, O. Arrieta, A.M. Calella, G. Peltz, A. Polli, H. Thurm, T.M. Bauer
Journal: Annals of Oncology (2021)
Toward a productive evolutionary understanding of music
Authors: Samuel A. Mehr, Max M. Krasnow, Gregory A. Bryant, Edward H. Hagen
Journal: Behavioral and Brain Sciences (2021)

We discuss approaches to the study of the evolution of music (sect. R1); challenges to each of the two theories of the origins of music presented in the companion target articles (sect. R2); future directions for testing them (sect. R3); and priorities for better understanding the nature of music (sect. R4).
Cirrhosis regression is associated with improved clinical outcomes in patients with nonalcoholic steatohepatitis
Authors: Arun J. Sanyal, Quentin M. Anstee, Michael Trauner, Eric J. Lawitz, Manal F. Abdelmalek, Dora Ding, Ling Han, Catherine Jia, Ryan S. Huss, Chuhan Chung, Vincent Wai‐Sun Wong, Takeshi Okanoue, Manuel Romero‐Gomez, Andrew J. Muir, Nezam H. Afdhal, Jaime Bosch, Zachary Goodman, Stephen A. Harrison, Zobair M. Younossi, Robert P. Myers
Journal: Hepatology (2021)

Surrogate endpoints that predict complications are necessary for assessment and approval of NASH therapies. We assessed associations between histologic and noninvasive tests (NITs) of fibrosis with liver-related complications in patients with NASH cirrhosis.Patients with compensated cirrhosis due to NASH were enrolled in two placebo-controlled trials of simtuzumab and selonsertib. Liver fibrosis at baseline and week 48 (W48) was staged by NASH Clinical Research Network (CRN) and Ishak classifications and a machine learning (ML) approach, hepatic collagen and alpha-smooth muscle actin (α-SMA) expression were quantified by morphometry, liver stiffness (LS) was measured by transient elastography, and serum NITs (enhanced liver fibrosis [ELF], NAFLD fibrosis score [NFS], and Fibrosis-4 index [FIB-4]) were calculated. Cox regression determined associations between these parameters at baseline and their changes over time with adjudicated liver-related clinical events. Among 1,135 patients, 709 (62%) had Ishak stage 6 fibrosis, and median ELF and LS were 10.66 and 21.1 kPa, respectively. During a median follow-up of 16.6 months, 71 (6.3%) had a liver-related event; associated baseline factors included Ishak stage 6 fibrosis, and higher hepatic collagen, α-SMA expression, ML-based fibrosis parameters, LS, ELF, NFS, and FIB-4. Cirrhosis regression observed in 16% (176/1,135) between BL and W48 was associated with a lower risk of events versus nonregression (1.1% [2/176] vs. 7.2% [69/957]; HR, 0.16; 95% CI, 0.04, 0.65 [p = 0.0104]). Conversely, after adjustment for baseline values, increases in hepatic collagen, α-SMA, ML-based fibrosis parameters, NFS, and LS were associated with an increased risk of events.In patients with compensated cirrhosis due to NASH, regression of fibrosis is associated with a reduction in liver-related complications. These data support the utility of histologic fibrosis regression and NITs as clinical trial endpoints for NASH cirrhosis.
Amplicon Remodeling and Genomic Mutations Drive Population Dynamics after Segmental Amplification
Authors: Andrew B Morgenthaler, Ryan K Fritts, Shelley D Copley
Journal: Molecular Biology and Evolution (2021)

New enzymes often evolve by duplication and divergence of genes encoding enzymes with promiscuous activities that have become important in the face of environmental opportunities or challenges. Amplifications that increase the copy number of the gene under selection commonly amplify many surrounding genes. Extra copies of these coamplified genes must be removed, either during or after evolution of a new enzyme. Here we report that amplicon remodeling can begin even before mutations occur in the gene under selection. Amplicon remodeling and mutations elsewhere in the genome that indirectly increase fitness result in complex population dynamics, leading to emergence of clones that have improved fitness by different mechanisms. In this work, one of the two most successful clones had undergone two episodes of amplicon remodeling, leaving only four coamplified genes surrounding the gene under selection. Amplicon remodeling in the other clone resulted in removal of 111 genes from the genome, an acceptable solution under these selection conditions, but one that would certainly impair fitness under other environmental conditions.