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Background Breast cancer is the leading cause of global cancer incidence. In early-stage disease, standard treatment with breast-conserving surgery followed by whole breast irradiation (WBI) is associated with excellent outcomes. Multiple studies with extensive follow-up periods have demonstrated the comparative efficacy and toxicity outcomes of partial breast irradiation (PBI) in contrast to WBI. Various dose fractionation schedules for PBI have been recommended in clinical practice guidelines. In British Columbia (BC), a dose of 26 Gy in 5 fractions has been adopted. Early studies on single-fraction (SF) radiation for PBI have investigated its safety and effect on cosmetic outcomes, with promising initial results. In the context of the ongoing health care crisis, single-fraction PBI has the potential to reduce wait times and improve access to radiation. This study will therefore investigate a single-fraction PBI dose of 13 Gy. Methods This is a phase II randomized controlled trial, with a primary objective of testing the feasibility of randomizing participants to 1 vs. 5 fractions of PBI for early stage, node negative, breast cancer. The primary endpoint is the ability to accrue 60 participants at 4 of the 6 BC Cancer centres over a 2- year period and to randomize them to 1 vs. 5 fractions of radiotherapy for PBI. Its secondary endpoints are time from CT simulation to partial breast radiotherapy, local control rates, quality of life as measured by Prospective Outcomes and Support Initiative (POSI)-Breast, rates of provider-rated toxicities as measured by Common Terminology Criteria for Adverse Events (CTCAE), rates of participant-reported toxicities as measured by participant reported outcome version of CTCAE (PRO-CTCAE), overall survival, and progression-free survival. Discussion One of the trial’s objectives is testing the feasibility of randomizing participants to single vs. multiple fractions for PBI. If successful, it will lead to a phase III non-inferiority trial with the potential to inform breast cancer treatment guidelines. Ultimately, if found to be non-inferior, a single-fraction PBI can reduce wait times, facilitate access to radiation, and improve patient convenience, particularly for those in rural and remote communities who must travel long distances to receive high-quality cancer care. Trial registration Clinicaltrials.gov identifier: NCT06885671. Date of Registration: 14 March 2025.

This work combines single cell Raman spectroscopy (RS) with group and basis restricted non-negative matrix factorisation (GBR-NMF) to identify individual biochemical changes associated with radiation exposure in three human cancer cell lines. The cell lines analysed were derived from lung (H460), breast (MCF7) and prostate (LNCaP) tissue and are known to display varying degrees of radio sensitivity due to the inherent properties of each cell type. The GBR-NMF approach involves the deconstruction of Raman spectra into component biochemical bases using a library of Raman spectra of known biochemicals present in the cells. Subsequently, scores are obtained on each of these bases which can be directly correlated with the contribution of each chemical to the overall Raman spectrum. We validated GBR-NMF through the correlation of GBR-NMF-derived glycogen scores with scores that were previously observed using principal component analysis (PCA). Phosphatidylcholine, glucose, arginine and asparagine showed a distinct differential score pattern between radio-resistant and radio-sensitive cell types. In summary, the GBR-NMF approach allows for the monitoring of individual biochemical radiation-response dynamics previously unattainable with more traditional PCA-based approaches.

The global spread of SARS-CoV-2 has shaken our health care and economic systems, prompting re-evaluation of long-held views on how best to deliver care. This is especially the case for our global diagnostic strategy. While current laboratory-based centralized RT-qPCR will continue to serve as a gold standard diagnostic into the foreseeable future, the shortcomings of our dependence on this method have been laid bare. It is now clear that a robust diagnostics pandemic response strategy, like any disaster planning, must include adaptive, diverse and de-centralized solutions. Here we look at how the COVID-19 pandemic, and previous outbreaks, have set the stage for a new innovative phase in diagnostics and a re-thinking of pandemic preparedness.

Altered cellular metabolism is a hallmark of tumor cells and contributes to a host of properties associated with resistance to radiotherapy. Detection of radiation-induced biochemical changes can reveal unique metabolic pathways affecting radiosensitivity that may serve as attractive therapeutic targets. Using clinically relevant doses of radiation, we performed label-free single cell Raman spectroscopy on a series of human cancer cell lines and detected radiation-induced accumulation of intracellular glycogen. The increase in glycogen post-irradiation was highest in lung (H460) and breast (MCF7) tumor cells compared to prostate (LNCaP) tumor cells. In response to radiation, the appearance of this glycogen signature correlated with radiation resistance. Moreover, the buildup of glycogen was linked to the phosphorylation of GSK-3β, a canonical modulator of cell survival following radiation exposure and a key regulator of glycogen metabolism. When MCF7 cells were irradiated in the presence of the anti-diabetic drug metformin, there was a significant decrease in the amount of radiation-induced glycogen. The suppression of glycogen by metformin following radiation was associated with increased radiosensitivity. In contrast to MCF7 cells, metformin had minimal effects on both the level of glycogen in H460 cells following radiation and radiosensitivity. Our data demonstrate a novel approach of spectral monitoring by Raman spectroscopy to assess changes in the levels of intracellular glycogen as a potential marker and resistance mechanism to radiation therapy.

Background Radiotherapy delivery regimens can vary between a single fraction (SF) and multiple fractions (MF) given daily for up to several weeks depending on the location of the cancer or metastases. With limited evidence comparing fractionation regimens for oligometastases, there is support to explore toxicity levels to nearby organs at risk as a primary outcome while using SF and MF stereotactic ablative radiotherapy (SABR) as well as explore differences in patient-reported quality of life and experience. Methods This study will randomize 598 patients in a 1:1 ratio between the standard arm (MF SABR) and the experimental arm (SF SABR). This trial is designed as two randomized controlled trials within one patient population for resource efficiency. The primary objective of the first randomization is to determine if SF SABR is non-inferior to MF SABR, with respect to healthcare provider (HCP)-reported grade 3-5 adverse events (AEs) that are related to SABR. Primary endpoint is toxicity while secondary endpoints include lesional control rate (LCR), and progression-free survival (PFS). The second randomization (BC Cancer sites only) will allocate participants to either complete quality of life (QoL) questionnaires only; or QoL questionnaires and a symptom-specific survey with symptom-guided HCP intervention. The primary objective of the second randomization is to determine if radiation-related symptom questionnaire-guided HCP intervention results in improved reported QoL as measured by the EuroQoL-5-dimensions-5levels (EQ-5D-5L) instrument. The primary endpoint is patient-reported QoL and secondary endpoints include: persistence/resolution of symptom reporting, QoL, intervention cost effectiveness, resource utilization, and overall survival. Discussion This study will compare SF and MF SABR in the treatment of oligometastases and oligoprogression to determine if there is non-inferior toxicity for SF SABR in selected participants with 1-5 oligometastatic lesions. This study will also compare patient-reported QoL between participants who receive radiation-related symptom-guided HCP intervention and those who complete questionnaires alone. Trial registration Clinicaltrials.gov identifier: NCT05784428. Date of Registration: 23 March 2023.

Background Oligometastases refer to a state of disease where cancer has spread beyond the primary site, but is not yet widely metastatic, often defined as 1–3 or 1–5 metastases in number. Stereotactic ablative radiotherapy (SABR) is an emerging radiotherapy technique to treat oligometastases that require further prospective population-based toxicity estimates. Methods This is a non-randomized phase II trial where all participants will receive experimental SABR treatment to all sites of newly diagnosed or progressing oligometastatic disease. We will accrue 200 patients to assess toxicity associated with this experimental treatment. The study was powered to give a 95% confidence on the risk of late grade 4 toxicity, anticipating a < 5% rate of grade 4 toxicity. Discussion SABR treatment of oligometastases is occurring off-trial at a high rate, without sufficient evidence of its efficacy or toxicity. This trial will provide necessary toxicity data in a population-based cohort, using standardized doses and organ at risk constraints, while we await data on efficacy from randomized phase III trials. Trial Registration Registered through clinicaltrials.gov NCT02933242 on October 14, 2016 prospectively before patient accrual.

Background Bone metastases in the lower spine and pelvis are effectively palliated with radiotherapy (RT), though this can come with side effects such as radiation induced nausea and vomiting (RINV). We hypothesize that high rates of RINV occur in part because of the widespread use of inexpensive simple unplanned palliative radiotherapy (SUPR), over more complex and resource intensive 3D conformal RT, such as volumetric modulated arc therapy (VMAT). Methods This is a randomized, multi-centre phase III trial of SUPR versus VMAT. We will accrue 250 patients to assess the difference in patient-reported RINV. This study is powered to detect a difference in quality of life between patients treated with VMAT vs. SUPR. Discussion This trial will determine if VMAT reduces early toxicity compared to SUPR and may provide justification for this more resource-intensive and costly form of RT. Trial registration Clinicaltrials.gov identifier: NCT03694015 . Date of registration: October 3, 2018.

Recombinant proteins are of extreme importance globally, comprising therapeutics, diagnostics, research tools, and more. Currently, recombinant proteins are synthesized using living hosts in well-resourced laboratories, then distributed globally – often refrigerated – along sometimes fragile supply chains. This model poses a challenge for low-resource and remote communities, and results in a slow-to-respond system when facing outbreaks and emergencies. Cell-free in vitro protein synthesis systems offer a portable small-scale alternative that can be freeze-dried into a room-temperature stable reaction pellet, then rehydrated at the point of need to initiate production of the protein of interest. While cell-free protein synthesis has been used to express proteins in laboratory settings, expansion into the field requires deployment of companion devices to automate the protein synthesis and purification process. This work reports the design, fabrication, and demonstration of MANGO (MANufacturing on the GO), a purpose-built device for portable small-scale protein production.

Defending from cyberattacks requires practitioners to operate on high-level adversary behavior. Cyberthreat intelligence (CTI) reports on past cyberattack incidents describe the chain of malicious actions with respect to time. To avoid repeating cyberattack incidents, practitioners must proactively identify and defend against recurring chain of actions - which we refer to as temporal attack patterns. Automatically mining the patterns among actions provides structured and actionable information on the adversary behavior of past cyberattacks. The goal of this paper is to aid security practitioners in prioritizing and proactive defense against cyberattacks by mining temporal attack patterns from cyberthreat intelligence reports. To this end, we propose ChronoCTI, an automated pipeline for mining temporal attack patterns from cyberthreat intelligence (CTI) reports of past cyberattacks. To construct ChronoCTI, we build the ground truth dataset of temporal attack patterns and apply state-of-the-art large language models, natural language processing, and machine learning techniques. We apply ChronoCTI on a set of 713 CTI reports, where we identify 124 temporal attack patterns - which we categorize into nine pattern categories. We identify that the most prevalent pattern category is to trick victim users into executing malicious code to initiate the attack, followed by bypassing the anti-malware system in the victim network. Based on the observed patterns, we advocate organizations to train users about cybersecurity best practices, introduce immutable operating systems with limited functionalities, and enforce multi-user authentications. Moreover, we advocate practitioners to leverage the automated mining capability of ChronoCTI and design countermeasures against the recurring attack patterns.

The Rev. Jesse Jackson's quest for the Democratic presidential nomination is not the traditional nutsand-bolts campaign. It is a more stem-winding religious crusade, a civil rights march on the nation's primaries.