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Abstract Background Patients with metastatic colorectal cancer (mCRC) and KRAS mutations have a poor prognosis, seemingly dependent on the location of the mutation. This multicenter, retrospective, cohort study assessed the frequency and prognostic value of specific KRAS mutation codon locations in mCRC patients, and survival outcomes in relation to treatment. Materials and Methods Data from mCRC patients treated in 10 Spanish hospitals between January 2011 and December 2015 were analyzed. The main objective was to investigate (1) the impact of KRAS mutation location on overall survival (OS), and (2) the effect of targeted treatment plus metastasectomy and primary tumor location on OS in patients with KRAS mutations. Results The KRAS mutation location was known for 337/2002 patients. Of these, 177 patients received chemotherapy only, 155 received bevacizumab plus chemotherapy, and 5 received anti-epidermal growth factor receptor therapy plus chemotherapy; 94 patients underwent surgery. The most frequent KRAS mutation locations were G12A (33.8%), G12D (21.4%), and G12V (21.4%). Compared with other locations, patients with a G12S mutation had the shortest median OS (10.3 [95% CI, 2.5-18.0] months). OS was longer in patients who underwent surgery versus those who did not, with a trend toward prolonged survival with bevacizumab (median OS 26.7 [95% CI, 21.8-31.7] months) versus chemotherapy alone (median OS 23.2 [95% CI, 19.4-27.0] months). Conclusion These findings confirm that KRAS mutation location may predict survival outcomes in patients with mCRC, and suggest that pre-/post-operative bevacizumab plus metastasectomy provides survival benefits in patients with KRAS mutations. Patients with metastatic colorectal cancer (mCRC) and KRAS mutations have a poor prognosis, seemingly dependent on the location of the mutation. This study assessed the frequency and prognostic value of specific KRAS mutation codon locations in mCRC and survival outcomes in relation to treatment.

Breast cancer is one of the most prevalent diseases in women. Prevention and treatments have lowered mortality; nevertheless, the impact of the diagnosis and treatment continue to impact all aspects of patients' lives (physical, emotional, cognitive, social, and spiritual). This study seeks to explore the experiences of the different stages women with breast cancer go through by means of a patient journey. This is a qualitative study in which 21 women with breast cancer or survivors were interviewed. Participants were recruited at 9 large hospitals in Spain and intentional sampling methods were applied. Data were collected using a semi-structured interview that was elaborated with the help of medical oncologists, nurses, and psycho-oncologists. Data were processed by adopting a thematic analysis approach. The diagnosis and treatment of breast cancer entails a radical change in patients' day-to-day that linger in the mid-term. Seven stages have been defined that correspond to the different medical processes: diagnosis/unmasking stage, surgery/cleaning out, chemotherapy/loss of identity, radiotherapy/transition to normality, follow-up care/the \"new\" day-to-day, relapse/starting over, and metastatic/time-limited chronic breast cancer. The most relevant aspects of each are highlighted, as are the various cross-sectional aspects that manifest throughout the entire patient journey. Comprehending patients' experiences in depth facilitates the detection of situations of risk and helps to identify key moments when more precise information should be offered. Similarly, preparing the women for the process they must confront and for the sequelae of medical treatments would contribute to decreasing their uncertainty and concern, and to improving their quality-of-life.

The efficacy and safety profiles of vaccines against SARS-CoV-2 in patients with cancer is unknown. We aimed to assess the safety and immunogenicity of the BNT162b2 (Pfizer–BioNTech) vaccine in patients with cancer. For this prospective observational study, we recruited patients with cancer and healthy controls (mostly health-care workers) from three London hospitals between Dec 8, 2020, and Feb 18, 2021. Participants who were vaccinated between Dec 8 and Dec 29, 2020, received two 30 μg doses of BNT162b2 administered intramuscularly 21 days apart; patients vaccinated after this date received only one 30 μg dose with a planned follow-up boost at 12 weeks. Blood samples were taken before vaccination and at 3 weeks and 5 weeks after the first vaccination. Where possible, serial nasopharyngeal real-time RT-PCR (rRT-PCR) swab tests were done every 10 days or in cases of symptomatic COVID-19. The coprimary endpoints were seroconversion to SARS-CoV-2 spike (S) protein in patients with cancer following the first vaccination with the BNT162b2 vaccine and the effect of vaccine boosting after 21 days on seroconversion. All participants with available data were included in the safety and immunogenicity analyses. Ongoing follow-up is underway for further blood sampling after the delayed (12-week) vaccine boost. This study is registered with the NHS Health Research Authority and Health and Care Research Wales (REC ID 20/HRA/2031). 151 patients with cancer (95 patients with solid cancer and 56 patients with haematological cancer) and 54 healthy controls were enrolled. For this interim data analysis of the safety and immunogenicity of vaccinated patients with cancer, samples and data obtained up to March 19, 2021, were analysed. After exclusion of 17 patients who had been exposed to SARS-CoV-2 (detected by either antibody seroconversion or a positive rRT-PCR COVID-19 swab test) from the immunogenicity analysis, the proportion of positive anti-S IgG titres at approximately 21 days following a single vaccine inoculum across the three cohorts were 32 (94%; 95% CI 81–98) of 34 healthy controls; 21 (38%; 26–51) of 56 patients with solid cancer, and eight (18%; 10–32) of 44 patients with haematological cancer. 16 healthy controls, 25 patients with solid cancer, and six patients with haematological cancer received a second dose on day 21. Of the patients with available blood samples 2 weeks following a 21-day vaccine boost, and excluding 17 participants with evidence of previous natural SARS-CoV-2 exposure, 18 (95%; 95% CI 75–99) of 19 patients with solid cancer, 12 (100%; 76–100) of 12 healthy controls, and three (60%; 23–88) of five patients with haematological cancers were seropositive, compared with ten (30%; 17–47) of 33, 18 (86%; 65–95) of 21, and four (11%; 4–25) of 36, respectively, who did not receive a boost. The vaccine was well tolerated; no toxicities were reported in 75 (54%) of 140 patients with cancer following the first dose of BNT162b2, and in 22 (71%) of 31 patients with cancer following the second dose. Similarly, no toxicities were reported in 15 (38%) of 40 healthy controls after the first dose and in five (31%) of 16 after the second dose. Injection-site pain within 7 days following the first dose was the most commonly reported local reaction (23 [35%] of 65 patients with cancer; 12 [48%] of 25 healthy controls). No vaccine-related deaths were reported. In patients with cancer, one dose of the BNT162b2 vaccine yields poor efficacy. Immunogenicity increased significantly in patients with solid cancer within 2 weeks of a vaccine boost at day 21 after the first dose. These data support prioritisation of patients with cancer for an early (day 21) second dose of the BNT162b2 vaccine. King's College London, Cancer Research UK, Wellcome Trust, Rosetrees Trust, and Francis Crick Institute.

Automated depalletizing systems aim to offer continuous and efficient operation in warehouse logistics, reducing cycle times and contributing to worker safety. However, most commercially available depalletizing solutions are designed primarily for highly homogeneous cargo arranged in orthogonal configurations. This paper presents a real-time approach for depalletizing heterogeneous pallets with boxes of varying sizes and arbitrary orientations, including configurations where the topmost surfaces of boxes are not necessarily parallel to each other. To accomplish this, we propose an algorithm that leverages deep learning-based machine vision to determine the size, position, and orientation of boxes relative to the horizontal plane of a robot arm from sparse depth data. Using this information, we implement a path planning method that generates collision-free trajectories to enable precise box grasping and placement onto a production line. Validation through both simulated and real-world experiments demonstrates the feasibility and accuracy of this approach in complex industrial settings, highlighting potential improvements in the efficiency and adaptability of automated depalletizing systems.

Although care and gender mainstreaming are increasingly recognized as key dimensions of sustainable urban planning, an analysis of their implementation in Mexico reveals the conceptual and material limitations of anthropocentric approaches to care within public space projects. In this article, we argue that ecofeminist and posthumanist perspectives on care help foreground the spatial and environmental dimensions of Everyday Care Environments (ECEs), highlighting ecosystemic interdependencies that remain largely overlooked in research focused on domestic, feminized, and family-based aspects of care work. Through qualitative research based on documentary analysis of local urban planning instruments and gender initiatives in Mexico City (CDMX) in the last 25 years, this article identifies persistent gaps in the integration of care work, safety, mobility, and intersectional perspectives into sustainable urban policy and practice. The findings offer insights for developing planning strategies capable of creating ECE that foster More-than-Human socio-environmental understandings of care, while advancing nature-based and ecosystem-oriented approaches to spatial justice.

Dense depth completion is critical for 3D computer vision but remains challenging when depth data are sparse and misaligned with color images due to sensor offsets. We propose a fully convolutional neural network architecture that simultaneously performs depth completion and color image registration, effectively addressing the problem of sparse depth maps and misaligned RGB inputs. Our model is trained with a novel synthetic depth generation strategy that mimics real time-of-flight (ToF) sensor noise and occlusion artifacts, helping to bridge the simulation-to-real gap. In addition, we adopt a staged curriculum learning paradigm that progressively increases task complexity over three training phases, from easy alignment scenarios to full-depth completion with simulated sensor noise. By leveraging shared features between the depth and color tasks, the joint model outperforms separate single-task approaches. At the KITTI Depth Completion benchmark, the proposed approach achieves competitive accuracy while using significantly fewer parameters and achieving faster inference than existing methods, demonstrating its effectiveness and efficiency.

Background/objectiveThe impact a cancer diagnosis and its treatment are affected by psychosocial factors and how these factors interrelate among themselves. The objective of this study was to analyze the relationship between optimism and social support in spiritual wellbeing in cancer patients initiating chemotherapy.MethodsA cross-sectional, multi-center (15 sites), prospective study was conducted with 912 cancer patients who had undergone curative surgery for a stage I–III cancer and were to receive adjuvant chemotherapy. They completed the Functional Assessment of Chronic Illness-Spiritual Well-being Scale (FACIT-Sp), Life Orientation Test-Revised (LOT-R), and the Multidimensional Scale of Perceived Social Support (MSPSS).ResultsSignificant differences on spirituality scales (meaning/peace and faith) were detected depending on age (≤ 65 vs > 65), sex, marital status, employment, and cancer treatment. Married or partnered participants had significantly higher meaning/peace scores compared to their non-partnered counterparts (p = 0.001). Women, > 65 years, unemployed, and patients treated with chemotherapy and radiotherapy had significantly higher faith scores versus men, ≤ 65 years, employed, and subjects only receiving adjuvant chemotherapy (all p < 0.030). Multivariate analyses indicated that meaning/peace and faith correlated positively with optimism and social support.ConclusionDuring oncological treatment, the positive effects of optimism and social support exhibit a positive correlation with spiritual coping. A brief assessment evaluation of these factors can aid in identifying at risk for a worse adaptation to the disease.

Fluoropyrimidine derivatives can cause severe toxicity in patients with DPD deficiency. Regulatory agencies, such as the European Medicines Agency (EMA), recommend pre-emptive genotyping of the HapB3 haplotype, along with other variants. Historically, the two main HapB3 variants, the benign c.1236G>A and the pathogenic c.1129-5923C>G, have been assumed to be in complete linkage disequilibrium. Recent findings contradict this assumption, questioning the reliability of the HapB3 analysis through c.1236G>A, which could directly impact patient safety. The aim of this study is to assess the linkage disequilibrium between the c.1236G>A and c.1129-5923C>G variants, with the ultimate goal of revising genotyping guidelines. A total of 46 patients already heterozygous for the c.1236G>A variant have been carefully reviewed for the c.1129-5923C>G variant. From the 46 patients analyzed, 45 maintain complete linkage disequilibrium between both variants. However, there is one patient where this linkage disequilibrium is not complete, being heterozygous for c.1236G>A and homozygous for c.1129-5923C>G. These findings challenge the validity of c.1236G>A as a surrogate marker for pathogenic variant c.1129-5923C>G. This article highlights the need for a review of the recommendations of the EMA and suggests laboratories to analyze both variants, or at least the pathogenic one, to ensure accurate therapeutic decisions.