BreakTrans: Uncovering the genomic architecture of gene fusions

Producing gene fusions through genomic structural rearrangements is a major mechanism for tumor evolution. Therefore, accurately detecting gene fusions and the originating rearrangements is of great importance for personalized cancer diagnosis and targeted therapy. We present a tool, BreakTrans, that systematically maps predicted gene fusions to structural rearrangements. Thus, BreakTrans not only validates both types of predictions, but also provides mechanistic interpretations. BreakTrans effectively validates known fusions and discovers novel events in a breast cancer cell line. Applying BreakTrans to 43 breast cancer samples in The Cancer Genome Atlas identifies 90 genomically validated gene fusions. BreakTrans is available at http://bioinformatics.mdanderson.org/main/BreakTran

A Reconfigurable Quantum Local Area Network Over Deployed Fiber

Practical quantum networking architectures are crucial for scaling the connection of quantum resources. Yet quantum network testbeds have thus far underutilized the full capabilities of modern lightwave communications, such as flexible-grid bandwidth allocation. In this work, we implement flex-grid entanglement distribution in a deployed network for the first time, connecting nodes in three distinct campus buildings time-synchronized via the Global Positioning System (GPS). We quantify the quality of the distributed polarization entanglement via log-negativity, which offers a generic metric of link performance in entangled bits per second. After demonstrating successful entanglement distribution for two allocations of our eight dynamically reconfigurable channels, we demonstrate remote state preparation -- the first realization on deployed fiber -- showcasing one possible quantum protocol enabled by the distributed entanglement network. Our results realize an advanced paradigm for managing entanglement resources in quantum networks of ever-increasing complexity and service demands

Toward understanding and exploiting tumor heterogeneity

The extent of tumor heterogeneity is an emerging theme that researchers are only beginning to understand. How genetic and epigenetic heterogeneity affects tumor evolution and clinical progression is unknown. The precise nature of the environmental factors that influence this heterogeneity is also yet to be characterized. Nature Medicine, Nature Biotechnology and the Volkswagen Foundation organized a meeting focused on identifying the obstacles that need to be overcome to advance translational research in and tumor heterogeneity. Once these key questions were established, the attendees devised potential solutions. Their ideas are presented here

Microcalcification crystallography as a potential marker of DCIS recurrence

Ductal carcinoma in-situ (DCIS) accounts for 20-25% of all new breast cancer diagnoses. DCIS has an uncertain risk of progression to invasive breast cancer and a lack of predictive biomarkers may result in relatively high levels (~ 75%) of overtreatment. To identify unique prognostic biomarkers of invasive progression, crystallographic and chemical features of DCIS microcalcifications have been explored. Samples from patients with at least 5-years of follow up and no known recurrence (174 calcifications in 67 patients) or ipsilateral invasive breast cancer recurrence (179 microcalcifications in 57 patients) were studied. Significant differences were noted between the two groups including whitlockite relative mass, hydroxyapatite and whitlockite crystal maturity and, elementally, sodium to calcium ion ratio. A preliminary predictive model for DCIS to invasive cancer progression was developed from these parameters with an AUC of 0.797. These results provide insights into the differing DCIS tissue microenvironments, and how these impact microcalcification formation. [Abstract copyright: © 2023. The Author(s).

2022 Roadmap on integrated quantum photonics

AbstractIntegrated photonics will play a key role in quantum systems as they grow from few-qubit prototypes to tens of thousands of qubits. The underlying optical quantum technologies can only be realized through the integration of these components onto quantum photonic integrated circuits (QPICs) with accompanying electronics. In the last decade, remarkable advances in quantum photonic integration have enabled table-top experiments to be scaled down to prototype chips with improvements in efficiency, robustness, and key performance metrics. These advances have enabled integrated quantum photonic technologies combining up to 650 optical and electrical components onto a single chip that are capable of programmable quantum information processing, chip-to-chip networking, hybrid quantum system integration, and high-speed communications. In this roadmap article, we highlight the status, current and future challenges, and emerging technologies in several key research areas in integrated quantum photonics, including photonic platforms, quantum and classical light sources, quantum frequency conversion, integrated detectors, and applications in computing, communications, and sensing. With advances in materials, photonic design architectures, fabrication and integration processes, packaging, and testing and benchmarking, in the next decade we can expect a transition from single- and few-function prototypes to large-scale integration of multi-functional and reconfigurable devices that will have a transformative impact on quantum information science and engineering

Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Tumor Evolution in Response to Chemotherapy: Phenotype versus Genotype

In this issue of Cell Reports, Almendro et al. report one of the first comprehensive studies on the intratumor heterogeneity of cell phenotypes and genotypes before and after chemotherapy in breast cancer. These data challenge the concept of genetic population bottlenecks and suggest that cellular phenotypes play an important role in developing resistance to therapy