Minimizing preparation time for repeated prolonged deep-inspiration breath holds during breast cancer irradiation using pre-oxygenation with high-flow nasal oxygen and voluntary hyperventilation.

Objectives: Deep inspiration breath-holds (DIBHs) reduce heart and lung toxicity during breast cancer radiotherapy. Consecutive DIBHs are stressful, time-consuming, and leads to position changes. To facilitate the introduction of pre-oxygenation using high-flow nasal oxygen (HFNO) and hyperventilation to prolong DIBHs (L-DIBHs), we examined the effect of hyperventilation time on the duration of L-DIBHs.

Exclusion of non-Involved uterus from the target volume (EXIT-trial): An individualized treatment for locally advanced cervical cancer using modern radiotherapy and imaging techniques followed by completion surgery.

Background And Purpose: Chemoradiotherapy followed by brachytherapy is the standard of care for locally advanced cervical cancer (LACC). In this study, we postulate that omitting an iconographical unaffected uterus (+12 mm distance from the tumour) from the treatment volume is safe and that no tumour will be found in the non-targeted uterus (NTU) leading to reduction of high-dose volumes of surrounding organs at risk (OARs).

Material And Methods: In this single-arm phase 2 study, two sets of target volumes were delineated: one standard-volume (whole uterus) and an EXIT-volume (exclusion of non-tumour-bearing parts of the uterus with a minimum 12 mm margin from the tumour).

Assessing the reliability of point mutation as data augmentation for deep learning with genomic data.

Background: Deep neural networks (DNNs) have the potential to revolutionize our understanding and treatment of genetic diseases. An inherent limitation of deep neural networks, however, is their high demand for data during training. To overcome this challenge, other fields, such as computer vision, use various data augmentation techniques to artificially increase the available training data for DNNs.

Disease Control and Late Toxicity in Adaptive Dose Painting by Numbers Versus Nonadaptive Radiation Therapy for Head and Neck Cancer: A Randomized Controlled Phase 2 Trial.

Purpose: Local recurrence remains the main cause of death in stage III-IV nonmetastatic head and neck cancer (HNC), with relapse-prone regions within high F-fluorodeoxyglucose positron emission tomography (F-FDG-PET)-signal gross tumor volume. We investigated if dose escalation within this subvolume combined with a 3-phase treatment adaptation could increase local (LC) and regional (RC) control at equal or minimized radiation-induced toxicity, by comparing adaptive F-FDG-PET voxel intensity-based dose painting by numbers (A-DPBN) with nonadaptive standard intensity modulated radiation therapy (S-IMRT).

Methods And Materials: This 2-center randomized controlled phase 2 trial assigned (1:1) patients to receive A-DPBN or S-IMRT (+/-chemotherapy).

Incidence and radiotherapy treatment patterns of complicated bone metastases.

Background: Despite the encouraging results of the SCORAD trial, single fraction radiotherapy (SFRT) remains underused for patients with complicated bone metastases with rates as low as 18-39%. We aimed to evaluate the incidence and treatment patterns of these metastases in patients being referred to a tertiary centre for palliative radiotherapy.

Materials And Methods: We performed a retrospective review of all bone metastases treated at our centre from January 2013 until December 2017.

Tryp: a dataset of microscopy images of unstained thick blood smears for trypanosome detection.

Trypanosomiasis, a neglected tropical disease (NTD), challenges communities in sub-Saharan Africa and Latin America. The World Health Organization underscores the need for practical, field-adaptable diagnostics and rapid screening tools to address the negative impact of NTDs. While artificial intelligence has shown promising results in disease screening, the lack of curated datasets impedes progress.

Mutate and observe: utilizing deep neural networks to investigate the impact of mutations on translation initiation.

Motivation: The primary regulatory step for protein synthesis is translation initiation, which makes it one of the fundamental steps in the central dogma of molecular biology. In recent years, a number of approaches relying on deep neural networks (DNNs) have demonstrated superb results for predicting translation initiation sites. These state-of-the art results indicate that DNNs are indeed capable of learning complex features that are relevant to the process of translation.

CRISPR-Cas-Docker: web-based in silico docking and machine learning-based classification of crRNAs with Cas proteins.

Background: CRISPR-Cas-Docker is a web server for in silico docking experiments with CRISPR RNAs (crRNAs) and Cas proteins. This web server aims at providing experimentalists with the optimal crRNA-Cas pair predicted computationally when prokaryotic genomes have multiple CRISPR arrays and Cas systems, as frequently observed in metagenomic data.

Results: CRISPR-Cas-Docker provides two methods to predict the optimal Cas protein given a particular crRNA sequence: a structure-based method (in silico docking) and a sequence-based method (machine learning classification).

In silico optimization of RNA-protein interactions for CRISPR-Cas13-based antimicrobials.

RNA-protein interactions are crucial for diverse biological processes. In prokaryotes, RNA-protein interactions enable adaptive immunity through CRISPR-Cas systems. These defence systems utilize CRISPR RNA (crRNA) templates acquired from past infections to destroy foreign genetic elements through crRNA-mediated nuclease activities of Cas proteins.

Four irradiation and three positioning techniques for whole-breast radiotherapy: Is sophisticated always better?

Purpose: We report on a dosimetrical study of three patient positions (supine, prone dive, and prone crawl) and four irradiation techniques for whole-breast irradiation (WBI): wedged-tangential fields (W-TF), tangential-field intensity-modulated radiotherapy (TF-IMRT), multi-beam IMRT (MB-IMRT), and intensity-modulated arc therapy (IMAT). This is the first study to evaluate prone crawl positioning in WBI and the first study to quantify dosimetrical and anatomical differences with prone dive positioning.

Methods: We analyzed five datasets with left- and right-sided patients (n = 51).

Prone Breast and Lymph Node Irradiation in 5 or 15 Fractions: A Randomized 2 × 2 Design Comparing Dosimetry, Acute Toxicity, and Set-Up Errors.

Purpose: Prone whole breast irradiation results in lower dose to organs at risk compared with supine position, especially lung dose. However, the adoption of prone position for whole breast irradiation + lymph node irradiation remains limited and data on lymph node irradiation in 5 fractions are lacking. Although the study was ended prematurely for the primary endpoint (breast retraction at 2 years), we decided to report acute toxicity for prone and supine positions and 5 and 15 fractions.

MP-Net: Deep learning-based segmentation for fluorescence microscopy images of microplastics isolated from clams.

Environmental monitoring of microplastics (MP) contamination has become an area of great research interest, given potential hazards associated with human ingestion of MP. In this context, determination of MP concentration is essential. However, cheap, rapid, and accurate quantification of MP remains a challenge to this date.

Accelerated radiotherapy in patients over sixty years old after mastectomy: Acute and one-year physician-assessed toxicity and health-related quality of life.

Introduction: Postmastectomy radiotherapy reduces the risk of locoregional recurrence in breast cancer patients. The first results on accelerated radiotherapy in five fractions after breast conserving surgery are promising. The data on postmastectomy radiotherapy in five or six fractions is limited.

Rethinking Protein Drug Design with Highly Accurate Structure Prediction of Anti-CRISPR Proteins.

Protein therapeutics play an important role in controlling the functions and activities of disease-causing proteins in modern medicine. Despite protein therapeutics having several advantages over traditional small-molecule therapeutics, further development has been hindered by drug complexity and delivery issues. However, recent progress in deep learning-based protein structure prediction approaches, such as AlphaFold2, opens new opportunities to exploit the complexity of these macro-biomolecules for highly specialised design to inhibit, regulate or even manipulate specific disease-causing proteins.

Reproducibility of repeated breathhold and impact of breathhold failure in whole breast and regional nodal irradiation in prone crawl position.

In whole breast and regional nodal irradiation (WB + RNI), breathhold increases organ at risk (OAR) sparing. WB + RNI is usually performed in supine position, because positioning materials obstruct beam paths in prone position. Recent advancements allow prone WB + RNI (pWB + RNI) with increased sparing of OARs compared to supine WB + RNI.

Safety of pre- or postoperative accelerated radiotherapy in 5 fractions: A randomized pilot trial.

Objective: Neo-adjuvant radiotherapy (NART) for breast cancer has shown promising survival results in retrospective trials. However, there are some obstacles such as a chemotherapy delay, an increased overall treatment time (OTT) and the risk of increasing surgical morbidity. Accelerated radiotherapy (RT) in 5 fractions allows to deliver NART in a very short time span and minimizes the delay of surgery and chemotherapy.

Delineation guidelines for the lymphatic target volumes in 'prone crawl' radiotherapy treatment position for breast cancer patients.

Our recently developed prone crawl position (PCP) for radiotherapy of breast cancer patients with lymphatic involvement showed promising preliminary data and it is being optimized for clinical use. An important aspect in this process is making new, position specific delineation guidelines to ensure delineation (for treatment planning) is uniform across different centers. The existing ESTRO and PROCAB guidelines for supine position (SP) were adapted for PCP.

Massively parallel interrogation of protein fragment secretability using SECRiFY reveals features influencing secretory system transit.

While transcriptome- and proteome-wide technologies to assess processes in protein biogenesis are now widely available, we still lack global approaches to assay post-ribosomal biogenesis events, in particular those occurring in the eukaryotic secretory system. We here develop a method, SECRiFY, to simultaneously assess the secretability of >10 protein fragments by two yeast species, S. cerevisiae and P.

Safely achieving single prolonged breath-holds of > 5 minutes for radiotherapy in the prone, front crawl position.

Objective: Breast cancer radiotherapy is increasingly delivered supine with multiple, short breath-holds. There may be heart and lung sparing advantages for locoregional breast cancer of both prone treatment and in a single breath-hold. We test here whether single prolonged breath-holds are possible in the prone, front crawl position.

Prolonging deep inspiration breath-hold time to 3 min during radiotherapy, a simple solution.

Background And Purpose: Deep inspiration breath-hold is an established technique to reduce heart dose during breast cancer radiotherapy. However, modern breast cancer radiotherapy techniques with lymph node irradiation often require long beam-on times of up to 5 min. Therefore, the combination with deep inspiration breath-hold (DIBH) becomes challenging.

Effects of deep inspiration breath hold on prone photon or proton irradiation of breast and regional lymph nodes.

We report on a comparative dosimetrical study between deep inspiration breath hold (DIBH) and shallow breathing (SB) in prone crawl position for photon and proton radiotherapy of whole breast (WB) and locoregional lymph node regions, including the internal mammary chain (LN_MI). We investigate the dosimetrical effects of DIBH in prone crawl position on organs-at-risk for both photon and proton plans. For each modality, we further estimate the effects of lung and heart doses on the mortality risks of different risk profiles of patients.

Two-year toxicity of simultaneous integrated boost in hypofractionated prone breast cancer irradiation: Comparison with sequential boost in a randomized trial.

Introduction: A simultaneous integrated boost (SIB) leads to less acute toxicity. Less is known for late toxicity due to SIB. In this first and only randomized trial, two-years toxicity is analysed.

Adoption of single fraction radiotherapy for uncomplicated bone metastases in a tertiary centre.

Background: Single-fraction radiotherapy (SFRT) offers equal pain relief for uncomplicated painful bone metastases as compared to multiple-fraction radiotherapy (MFRT). Despite this evidence, the adoption of SFRT has been poor with published rates of SFRT for uncomplicated bone metastases ranging from <10% to 70%. We aimed to evaluate the adoption of SFRT and its evolution over time following the more formal endorsement of the international guidelines in our centre starting from 2013.