The use of oral nomegestrol acetate/estradiol in rapid and random start preparation of endometrium before office hysteroscopic polypectomies: A multicenter, prospective, randomized controlled trial.

OBJECTIVE: To evaluate the use of oral nomegestrol acetate/estradiol in random start rapid preparation of endometrium before office hysteroscopic polypectomy. STUDY DESIGN: Multicenter, prospective, randomized controlled trial. SETTING: University hospitals. PARTICIPANTS: 80 adult women undergoing office hysteroscopic polypectomy between January 2023 and March 2024 were randomized to intervention (n = 40) or control (n = 40). Exclusion criteria included the presence of endouterine pathology other than endometrial polyps solely. METHODS: Subjects in the intervention group were treated with oral nomegestrol acetate/estradiol 1.5 mg/2.5 mg/day started taking the drug from an indefinite time in the menstrual cycle (random start) for 14 days. Subjects in the control group did not receive any pharmaceutical treatment and underwent polypectomy between days 8 and 11 of the menstrual cycle. RESULTS: On the day of the procedure, the difference in pre- and post-office hysteroscopic polypectomy endometrial ultrasound thickness was statistically significant between the two groups, with endometrial thickness in both measurements being thinner for the intervention group (p < 0.001). In the nomegestrol acetate/estradiol-treated group, compared with the control, there was also a statistically significant difference in the physician's assessment of the quality of endometrial preparation (p < 0.001), the quality of visualization of the uterine cavity (p < 0.001), and satisfaction with the performance of the procedure (p < 0.001). Finally, all surgical outcomes analyzed were better in the treatment group. CONCLUSION: Treatment with nomegestrol acetate/estradiol could provide rapid, satisfactory and low-cost preparation of the endometrium before office polypectomy, thus improving surgical performance and woman's compliance. TRIAL REGISTRATION: ClinicalTrials.gov NCT06316219.

Safety and efficacy of a class II medical device based on highly purified and standardized plant extracts in the management of post-menopausal patients with vulvar and vaginal atrophy: a single-center prospective observational study.

BACKGROUND: Despite the gold standard treatment for genitourinary syndrome of menopause (GSM) is based on the use of local or systemic estrogen-containing products, the typical long-term side effects of hormonal treatments and, most importantly, the contraindications in patients with history of breast and endometrial neoplasms do limit in some extent its use. As hyaluronic acid and some highly purified botanicals have clearly demonstrated their anti-inflammatory and mucosa-protecting properties, we have tested, in women with GSM, a class II vaginal medical device containing hyaluronate gel and a mucoadhesive active enriched with purified alkylamides from Zanthoxylum bungeanum, triterpenes from Centella asiatica and high molecular weight polysaccharides from Tamarindus indica. METHODS: Our single-center, open-label, prospective and observational study was conducted on 50 menopausal women enrolled at the Department of Maternal-Fetal Medicine at Umberto I Polyclinic Hospital in Rome, Italy. Gel administration lasted 150 days and was performed daily for the first 12 days and every 48 hours for the remaining 138 days. Clinical evaluations were performed at baseline and after 12, 57 and 150 days. Besides product safety, main outcomes of our study were: 1) vaginal health (by Vaginal Health Index score [VHI]); 2) sexual quality of life (by Female Sexual Distress Scale [FSDS]); and 3) percentage of women declaring regular sexual activity. RESULTS: The product was safe with no specific adverse events reported. It significantly improved VHI (about 5% after 57 days and 8% after 150 days), FSDS (about 7% after 57 days and 10% after 150 days), and sexual activity (about 20% after 150 days). It also reduced dryness, dyspareunia, burning, itching, and dysuria incidence, respectively by about 18%, 14%, 14%, 27% and 11% after 150 days. CONCLUSIONS: In women with GSM, the intravaginal administration of a hyaluronate-based gel enriched with purified botanical actives endowed with anti-inflammatory and mucosal-protecting properties, reduced painful sensation during sexual acts and increased regular sexual activity.

Large-scale genomic rearrangements boost SCRaMbLE in Saccharomyces cerevisiae.

Synthetic Chromosome Rearrangement and Modification by LoxP-mediated Evolution (SCRaMbLE) is a promising tool to study genomic rearrangements. However, the potential of SCRaMbLE to study genomic rearrangements is currently hindered, because a strain containing all 16 synthetic chromosomes is not yet available. Here, we construct SparLox83R, a yeast strain containing 83 loxPsym sites distributed across all 16 chromosomes. SCRaMbLE of SparLox83R produces versatile genome-wide genomic rearrangements, including inter-chromosomal events. Moreover, when combined with synthetic chromosomes, SCRaMbLE of hetero-diploids with SparLox83R leads to increased diversity of genomic rearrangements and relatively faster evolution of traits compared to hetero-diploids only with wild-type chromosomes. Analysis of the SCRaMbLEd strain with increased tolerance to nocodazole demonstrates that genomic rearrangements can perturb the transcriptome and 3D genome structure and consequently impact phenotypes. In summary, a genome with sparsely distributed loxPsym sites can serve as a powerful tool for studying the consequence of genomic rearrangements and accelerating strain engineering in Saccharomyces cerevisiae.

Toward chemical recycling of PU foams: study of the main purification options.

The recovery of the polyol component, after glycolysis of polyurethane (PU) foams coming from automotive waste, was investigated. Several separation methods such as simple sedimentation, centrifugation and liquid-liquid extraction, eventually preceded by an acid washing step, were tested. The obtained fractions were characterized by infrared spectroscopy and CHN elemental analysis. Furthermore, multivariate data analysis was carried out on the infrared spectra by principal component analysis to classify the fractions based on purity. IR spectroscopy coupled with principal component analysis was able to estimate the success of the separation and eventual culprits such as contaminations, which were then quantified by CHN elemental analysis. This approach addresses some critical limitations associated with classical analytical techniques such as NMR, TGA, GPC, MALDI-TOF that often require an extremely accurate separation of the depolymerized product fractions. Moreover, IR spectroscopy and CHN elemental analysis techniques are cheap and widespread in standard materials science laboratories. At last, based on the results of the analysis of the regenerated polyol fractions, and on the foaming tests, considerations were made to guide the choice of the purification method according to the application specifications and greenness.

Is free nipple grafting necessary in patients undergoing reduction mammoplasty for gigantomastia? A systematic review and meta-analysis.

BACKGROUND: Gigantomastia is a debilitating condition characterised by an excessive breast tissue growth impacting patients' quality of life. Surgically treatment options include the limited-length pedicle (LP) technique with free nipple grafting (FNG) and the elongated pedicle (EP) technique, which maintains continuity of the nipple-areola complex (NAC). Initially, despite the less satisfactory aesthetic outcome, FNG was preferred to treat hypertrophic breasts requiring resections over 1000 g of parenchymal and adipose tissue, due to concerns about NAC perfusion. Recently, many studies have questioned this indication. The aim of this study was therefore to evaluate the safety of the NAC-carrying EP technique in patients with gigantomastia eventually challenging the need for FNG. METHODS: A literature search using PubMed and Cochrane databases was performed, including studies describing the outcome of EP technique for resection exceeding 1000 g of breast tissue. Thereby, a meta-analysis was conducted to evaluate the rate of NAC necrosis, whereas a descriptive statistic was applied to assess all other surgery-associated complications. RESULTS: Twenty-five studies, encompassing 1355 patients (2656 breasts), were included. EP demonstrated an extremely low rate of NAC necrosis. Moreover, the analysis demonstrated a low rate of ischaemia-independent complications and a very high probability of maintaining NAC-sensation equal to the preoperative state. CONCLUSION: Current evidence indicates that the EP technique should be the preferred surgical method to treat gigantomastia with or without massive ptosis whenever indicated. It has proven to be safe. Furthermore, it yields superior aesthetic and functional outcomes, including breast feeding and preservation of NAC-sensation compared to the LP technique.

Use of a Dermal Regeneration Template in a two-stage reconstruction after extensive skin surgery for Bowen's disease of the anterior neck - Case report.

INTRODUCTION: Dermal Regeneration Templates may be used in the reconstruction of large skin defects after cutaneous malignancy excisions. Bowen's disease (BD; squamous cell carcinoma in situ) is a common and persistent condition that can be related to chronic sun damage, and consequently, is usually located on the head and neck area or on the lower limbs. Literature does not provide clear guidelines on the treatment of BD, limiting itself to describing a wide range of different methods that can be used, including surgery, laser therapy or topical options. However, large lesions tend to scar in the post-operative setting and hence are difficult to treat surgically. PRESENTATION OF CASE: In this paper the authors present a case of a male in his 60s, ASA III score, who presented with a history of histopathologically-confirmed squamocellular carcinoma in the neck and supraclavicular region. Due to recurrent carcinomas the patient was treated with an extensive skin excision and a successful reconstruction using a Dermal Regeneration Template. The work has been reported in line with the SCARE criteria. DISCUSSION: The main surgical problem caused by BD is reaching complete oncological resection and, consequently, the need for extensive skin excisions. CONCLUSION: The use of the skin substitute resulted in a satisfactory functional and aesthetic result, with total clearance and no recurrence observed after 16 months.

Building a eukaryotic chromosome arm by de novo design and synthesis.

The genome of an organism is inherited from its ancestor and continues to evolve over time, however, the extent to which the current version could be altered remains unknown. To probe the genome plasticity of Saccharomyces cerevisiae, here we replace the native left arm of chromosome XII (chrXIIL) with a linear artificial chromosome harboring small sets of reconstructed genes. We find that as few as 12 genes are sufficient for cell viability, whereas 25 genes are required to recover the partial fitness defects observed in the 12-gene strain. Next, we demonstrate that these genes can be reconstructed individually using synthetic regulatory sequences and recoded open-reading frames with a "one-amino-acid-one-codon" strategy to remain functional. Finally, a synthetic neochromsome with the reconstructed genes is assembled which could substitute chrXIIL for viability. Together, our work not only highlights the high plasticity of yeast genome, but also illustrates the possibility of making functional eukaryotic chromosomes from entirely artificial sequences.

Effects of negative pressure wound therapy with instillation and dwell time (NPWTi-d) versus NPWT or standard of care in orthoplastic surgery: A systematic review and meta-analysis.

Negative pressure wound therapy (NPWT) is a wound-dressing system that applies sub-atmospheric pressure on the surface of a wound to promote healing. An evolution of this technology, NPWT with solution instillation and dwell time (NPWTi-d), is increasingly being used to maximise wound closure and reduce failure rates. However, there is still a lack of evidence concerning its use in orthoplastic surgery. Therefore, the aim of this study is to compare NPWTi-d with NPWT and standard of care for wound management in orthoplastic surgery. A comprehensive literature search using PubMed, Web of Science, and Cochrane databases up to 15 March 2022 was performed, including studies describing the outcomes of NPWTi-d for traumatic/orthopaedic injuries. A meta-analysis on the number of surgical debridements, as well as the rate of complete wound closure and complications was carried out, although for other outcomes, a descriptive statistic was applied. Risk of bias and quality of evidence were assessed using the Downs& Black's Checklist for Measuring Quality. Thirteen studies with a total number of 871 patients were included, in which NPWTi-d demonstrated significantly higher primary wound closure and lower complication rates (P < .05). No difference in the number of surgical procedures required for final wound healing was observed. Moreover, five out of six studies showed better results for NPWTi-d when the change of the bioburden and bacterial count of the wound were analysed. A singular study investigating the length of the hospital stay of patients treated with NPWTi-d showed a reduction in the latter. The present meta-analysis proves that NPWTi-d is superior to NPTW or conventional dressings in orthoplastic wound care management, in terms of complete wound closure rate and the reduced number of complications. Still, the limited quality of the studies analysed shows that future randomised studies are needed to confirm the benefits and to identify the most appropriate recommendations for using NPWTi-d in orthoplastic surgery, as well as to investigate the cost-effectiveness of this wound-dressing system.

Advances in small molecule maintenance therapies for high-grade serous ovarian cancer.

INTRODUCTION: Ovarian cancer is one of the most lethal gynecological tumors with a lack of effective treatment modalities especially in advanced/recurrent disease. Nevertheless, recently, new small molecules have emerged as an effective approach for the management of ovarian cancer patients, especially in the maintenance setting. AREAS COVERED: This review summarizes the role of small molecules used in the management of high-grade serous ovarian cancer. The authors performed a critical review of current evidence and ongoing studies. Of note, tyrosine kinase inhibitors (TKIs) and poly(ADP-ribose) polymerase (PARP) inhibitors are the most intriguing medications in this setting. EXPERT OPINION: Protein-targeted therapies against tumor tissues have progressed significantly in the last years due to an enhanced knowledge of the biological and molecular processes of carcinogenesis. Treatment with small molecules allows the targeting of specific proteins involved in cancer biology. TKIs seem promising but further data are necessary to assess the pros and cons of adopting this treatment modality. PARP inhibitors represent the new standard of care for ovarian cancer patients harboring either a BRCA mutation or with homologous recombination deficiency (HRD). Interestingly, the accumulation of data has highlighted that PARP inhibitors provide benefits even in patients with HR proficient tumors.

Improvement of Poly(lactic acid)-Poly(hydroxy butyrate) Blend Properties for Use in Food Packaging: Processing, Structure Relationships.

Poly(lactic acid)-poly(hydroxybutyrate) (PLA-PHB)-based nanocomposite films were prepared with bio-based additives (CNCs and ChNCs) and oligomer lactic acid (OLA) compatibilizer using extrusion and then blown to films at pilot scale. The aim was to identify suitable material formulations and nanocomposite production processes for film production at a larger scale targeting food packaging applications. The film-blowing process for both the PLA-PHB blend and CNC-nanocomposite was unstable and led to non-homogeneous films with wrinkles and creases, while the blowing of the ChNC-nanocomposite was stable and resulted in a smooth and homogeneous film. The optical microscopy of the blown nanocomposite films indicated well-dispersed chitin nanocrystals while the cellulose crystals were agglomerated to micrometer-size particles. The addition of the ChNCs also resulted in the improved mechanical performance of the PLA-PHB blend due to well-dispersed crystals in the nanoscale as well as the interaction between biopolymers and the chitin nanocrystals. The strength increased from 27 MPa to 37 MPa compared to the PLA-PHB blend and showed almost 36 times higher elongation at break resulting in 10 times tougher material. Finally, the nanocomposite film with ChNCs showed improved oxygen barrier performance as well as faster degradation, indicating its potential exploitation for packaging applications.

Symptom clusters helping the assessment of SARS-COV-2-infected children: Amiens cohort versus European data.

BACKGROUND: Since December 2019, the novel coronavirus (SARS-CoV-2) pandemic, caused >240 million cases and >5 million deaths. Given the current wider dissemination of pediatric cases, it is important to address questions regarding the clinical picture in children or if there are clinical patterns that may help us identify in an early stage what can be the prognosis and help clinicians with patient management. The study aimed to investigate in a French monocentric cohort and other European cohorts the presence of symptom clusterization and its possible connection to illness categories to help medical first-line screening and orientation in the pediatric emergency department (ED). METHODS: We conducted a retrospective cohort study describing clinical, laboratory, and radiological characteristics of SARS-CoV-2-infected children admitted to pediatric ED to assess the presence of symptom clustering. A scoping review of the literature was performed to further investigate symptom clusters. RESULTS: Of 1086 tested children, 48 tested positive to SARS-CoV-2. The clinical, laboratory, and radiological characteristics of our sample were fully described. Two distinct clusters of clinical phenotypes were identified as well as their potential association with illness categories in SARS-CoV-2-infected children. Comparison with similar European cohorts highlights how symptoms coming from the mucocutaneous-enteric, and the respiratory clusters are associated with a more severe clinical picture. CONCLUSIONS: This study promotes the importance to identify early prognostic patterns to help clinicians in the decision process, especially in COVID-19 pediatric patients.

Oncofertility and Reproductive Counseling in Patients with Breast Cancer: A Retrospective Study.

INTRODUCTION: Improving the prognosis of breast cancer patients is of utmost importance in terms of increasing survival rates. Modern medicine has therefore prioritized better quality of life for patients, even after the disease, through a better management of the potential long-term side effects induced by anticancer treatments. Fertility preservation and family planning are therefore crucial issues to be addressed in all cancer patients of reproductive age. Along those lines, a new branch of medicine with distinct multidisciplinary characteristics has developed over the years: oncofertility. Although both national and international guidelines value reproductive counseling as an essential aspect of the diagnostic-therapeutic pathway, part and parcel of the informed consent process, it is not included within the protocols adopted by the operating units for the care and management of neoplastic diseases. OBJECTIVE: This study aimed to evaluate the activity of the Breast Unit of the Policlinico Umberto I Hospital, Rome, Italy, and the degree of compliance with guidelines. By knowing the strengths and weaknesses of such approaches, the standards of care offered to breast cancer patients can be improved. MATERIALS AND METHODS: A retrospective study based on a review of medical records was conducted between 2014 and 2021. Patients under 40 years of age diagnosed with non-metastatic malignancies were included who received chemotherapy treatment, namely neoadjuvant, adjuvant or adjuvant hormone therapy. RESULTS: The data were extracted from the medical records of 51 patients who met the inclusion criteria, 41% of whom received reproductive counseling, and of these, 43% decided to undertake a path of fertility preservation. Factors such as the absence of children and young age reportedly favored both the interest in counseling proposals by the medical staff and the decision to undertake a path of fertility preservation. CONCLUSIONS: The study shows that there has been growing interest in the topic of oncofertility, especially in light of law 219/2017. Therefore, since 2018, multiple proposals for reproductive counseling have been set forth, but there was not an equally growing demand for fertility preservation practices, which can be explained by the invasive nature of such practices, the patients' concern about their own state of health, and poor or inadequate information. Such impediments highlight the importance of standardized counseling and the need for a multidisciplinary medical team to support the patient in the decision-making process. The study also revealed a drop in the number of patients receiving counseling due to the COVID-19 pandemic, contrary to the positive trend that was recorded prior to the pandemic.

Influence of Chitin Nanocrystals on the Crystallinity and Mechanical Properties of Poly(hydroxybutyrate) Biopolymer.

This study focuses on the use of pilot-scale produced polyhydroxy butyrate (PHB) biopolymer and chitin nanocrystals (ChNCs) in two different concentrated (1 and 5 wt.%) nanocomposites. The nanocomposites were compounded using a twin-screw extruder and calendered into sheets. The crystallization was studied using polarized optical microscopy and differential scanning calorimetry, the thermal properties were studied using thermogravimetric analysis, the viscosity was studied using a shear rheometer, the mechanical properties were studied using conventional tensile testing, and the morphology of the prepared material was studied using optical microscopy and scanning electron microscopy. The results showed that the addition of ChNCs significantly affected the crystallization of PHB, resulting in slower crystallization, lower overall crystallinity, and smaller crystal size. Furthermore, the addition of ChNCs resulted in increased viscosity in the final formulations. The calendering process resulted in slightly aligned sheets and the nanocomposites with 5 wt.% ChNCs evaluated along the machine direction showed the highest mechanical properties, the strength increased from 24 to 33 MPa, while the transversal direction with lower initial strength at 14 MPa was improved to 21 MPa.

Current protocols and clinical efficacy of human fetal liver cell therapy in patients with liver disease: A literature review.

The fetal liver is unique because of the coexistence of cells with endodermal and mesenchymal origins, making it a potential source of hepatic and pancreatic regenerative medicine. The liver appears at about the third week of gestation, growing rapidly from the fifth to the 10th week. We define fetal liver from 10 weeks of gestation, when hematopoietic progenitor cells gradually migrate from the aorta-mesonephros-gonad region to colonize the liver. Indeed, the fetal liver may be the most available source of cell therapy for liver disease. We conducted a review of the literature using Medline and EMBASE (up to May 2021) to identify clinical studies in which patients with liver disease had been given fetal liver cell therapy. This literature review highlighted the heterogeneity of cell isolation and selection protocols, which hinders the ability to pool data and perform a meta-analysis. A limitation of the studies analyzed was the scarcity of reports (n = 8) and the extremely small sample sizes (median sample size of treated patients was two), although there was a fairly long follow-up (median 12 months). The weeks after conception ranged from 16 to 34. There were no randomized controlled trials, and therefore no study was stratified as being of good methodological quality. Cryopreservation may help to circumvent the critical logistic issues that hamper the use of fetal liver cell therapy in clinical practice. To help consolidate the role of the fetal liver in regenerative medicine, good preclinical translational studies are necessary, whereas tracing strategies and biopsy-based endpoints are crucial in the clinic, along with well-designed, large, multicenter, randomized controlled trials using clinically applicable primary outcomes and refined imaging assessment.

Clinical management of hypertensive disorders in postpartum women.

Hypertensive disorders of pregnancy (HDP) could persist post-partum, or appear for the first time after delivery and could require a pharmacological treatment. It was found no evidence in literature about which therapy should be used in puerperal hypertension. The aim of this review is to determine the most effective therapy and best in terms of risk-benefit ratio for the treatment of high postpartum systemic arterial blood pressure in women with pregnancy-induced hypertension (PIH) or in those with de-novo diagnosis of hypertension in the puerperium. Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CCRCT), Embase, Medline, and PubMed were searched. The main inclusion criterion was articles regarding postnatal women with hypertension, therapeutic treatment for the management of hypertension compared with placebo or no therapy, with the exclusion of preeclampsia/eclampsia. Twenty-three studies were included. This review highlights significant evidence gaps, demonstrating that further comparative research is required, particularly to clarify postpartum antihypertensive selection. In conclusion, there is insufficient evidence to recommend a particular therapy or model of care, but calcium channel blockers, beta-blockers, alpha-blockers and angiotensin-converting enzyme inhibitors (ACEIs) appeared variably effective.

Abdominal actinomycosis after reparative surgery for cholecystogastric fistula in an immunosuppressed patient.

A male patient, aged over 75 years, was referred to the emergency room for pain in his right hypochondrium. This pain, which persisted for approximately 3 days, radiated to his right flank and right iliac quadrant and worsened after meals. The patient reported no nausea, vomiting, diarrhoea, fever or recent traumatic events. Blood laboratory tests, ultrasonography, an MRI and a CT scan were performed, leading to the diagnosis of a mass in the Morrison's pouch with ultrasound features of adipose tissue compatible with a liposarcoma, infiltrating the liver and the right kidney. Subsequent CT-guided needle aspiration and a histological examination led to the diagnosis of actinomycosis. The patient was initially treated with a daily dose of 18 million IU of benzylpenicillin for 4 weeks and subsequently prescribed the oral administration of 3 g/day of amoxicillin for 11 months. A monitoring CT scan was performed after 1, 5, 8 and 12 months, and a CT scan re-evaluation confirmed that the mass had completely healed.

Enhanced Impact Strength of Recycled PET/Glass Fiber Composites.

In this paper, we report a study on the effects of different ethylene copolymers in improving the impact strength of a fiber-reinforced composite based on a recycled poly(ethylene terephthalate) (rPET) from post-consumer bottles. Different ethylene copolymers have been selected in order to evaluate the effects of the polar co-monomer chemical structure and content. The composite mixtures were prepared via melt extrusion, and the samples were manufactured by injection molding. Impact strength was evaluated using Izod tests, and a morphological study (FESEM) was performed. As a result, a composite with substantially improved impact properties was designed. This study demonstrates that a post-consumer PET from the municipal waste collection of plastic bottles can be successfully used as a matrix of high-performance, injection-molded composites, suitable for use in the automotive sector, among others, with no compromise in terms of mechanical requirements or thermal stability.

SCRaMbLE: A Study of Its Robustness and Challenges through Enhancement of Hygromycin B Resistance in a Semi-Synthetic Yeast.

Recent advances in synthetic genomics launched the ambitious goal of generating the first synthetic designer eukaryote, based on the model organism Saccharomyces cerevisiae (Sc2.0). Excitingly, the Sc2.0 project is now nearing its completion and SCRaMbLE, an accelerated evolution tool implemented by the integration of symmetrical loxP sites (loxPSym) downstream of almost every non-essential gene, is arguably the most applicable synthetic genome-wide alteration to date. The SCRaMbLE system offers the capability to perform rapid genome diversification, providing huge potential for targeted strain improvement. Here we describe how SCRaMbLE can evolve a semi-synthetic yeast strain housing the synthetic chromosome II (synII) to generate hygromycin B resistant genotypes. Exploiting long-read nanopore sequencing, we show that all structural variations are due to recombination between loxP sites, with no off-target effects. We also highlight a phenomenon imposed on SCRaMbLE termed "essential raft", where a fragment flanked by a pair of loxPSym sites can move within the genome but cannot be removed due to essentiality restrictions. Despite this, SCRaMbLE was able to explore the genomic space and produce alternative structural compositions that resulted in an increased hygromycin B resistance in the synII strain. We show that among the rearrangements generated via SCRaMbLE, deletions of YBR219C and YBR220C contribute to hygromycin B resistance phenotypes. However, the hygromycin B resistance provided by SCRaMbLEd genomes showed significant improvement when compared to corresponding single deletions, demonstrating the importance of the complex structural variations generated by SCRaMbLE to improve hygromycin B resistance. We anticipate that SCRaMbLE and its successors will be an invaluable tool to predict and evaluate the emergence of antibiotic resistance in yeast.