Integrating Modular Pipelines with End-to-End Learning: A Hybrid Approach for Robust and Reliable Autonomous Driving Systems.

Autonomous driving navigation relies on diverse approaches, each with advantages and limitations depending on various factors. For HD maps, modular systems excel, while end-to-end methods dominate mapless scenarios. However, few leverage the strengths of both. This paper innovates by proposing a hybrid architecture that seamlessly integrates modular perception and control modules with data-driven path planning. This innovative design leverages the strengths of both approaches, enabling a clear understanding and debugging of individual components while simultaneously harnessing the learning power of end-to-end approaches. Our proposed architecture achieved first and second place in the 2023 CARLA Autonomous Driving Challenge's SENSORS and MAP tracks, respectively. These results demonstrate the architecture's effectiveness in both map-based and mapless navigation. We achieved a driving score of 41.56 and the highest route completion of 86.03 in the MAP track of the CARLA Challenge leaderboard 1, and driving scores of 35.36 and 1.23 in the CARLA Challenge SENSOR track with route completions of 85.01 and 9.55, for, respectively, leaderboard 1 and 2. The results of leaderboard 2 raised the hybrid architecture to the first position, winning the edition of the 2023 CARLA Autonomous Driving Competition.

Physicochemical Properties of Nanoliposomes Encapsulating Grape Seed Tannins Formed with Ultrasound Cycles.

Grape seeds are an excellent source of flavonoids and tannins with powerful antioxidant properties. However, the astringency of tannins limits their direct incorporation into food. To overcome this challenge, we investigated the encapsulation of grape seed tannins within nanoliposomes formed by ultrasound cycling. We characterized the nanoliposomes' physicochemical properties, including encapsulation efficiency, antioxidant activity, stability, microstructure, and rheological properties. Our findings reveal that the nanoliposomes exhibited excellent stability under refrigerated conditions for up to 90 days with a mean particle size of 228 ± 26 nm, a polydispersity index of 0.598 ± 0.087, and a zeta potential of -41.6 ± 1.30 mV, maintaining a spherical multilamellar microstructure. Moreover, they displayed high antioxidant activity, with encapsulation efficiencies of 79% for epicatechin and 90% for catechin. This innovative approach demonstrates the potential of using ultrasound-assisted nanoliposome encapsulation to directly incorporate grape seed tannins into food matrices, providing a sustainable and efficient method for enhancing their bioavailability and functionality.

Mechanical and Surface Properties of Edible Coatings Elaborated with Nanoliposomes Encapsulating Grape Seed Tannins and Polysaccharides.

Edible composite coatings (ECC) formulated from biopolymers that incorporate antioxidant molecules represent an innovative alternative to improve food texture and provide health benefits. Tannins have aroused great interest due to their ability to stabilize suspensions and counteract the effects of free radicals. The mechanical and surface properties are crucial to establishing its quality and applicability. In this study, the objective was to analyze the mechanical and surface properties of ECC made with nanoliposomes that encapsulate grape seed tannins (TLS) and polysaccharides such as hydroxypropylmethylcellulose (HPMC) and kappa carrageenan (KCG) for their future direct application in foods susceptible to oxidation. The inclusion of HPMC or KCG affected the density, showing values in the range of 1010 to 1050 [kg/m3], evidencing significant changes (p < 0.05) in the surface tension in the TLS/FS-HPMC and TLS/FS mixtures. KCG and in the dispersion coefficients, with values in the range of -2.9 to -17.6 [mN/m] in HPS (S1) and -17.6 to -40.9 [mN/m] in PDMS (S2). The TLS/FS-HPMC coating showed higher stiffness and elastic recovery capacity than the TLS/FS-KCG coating, suggesting that the presence of TLS influenced the stiffness of the polymer. HPMC is recommended as a suitable polymer for coating solids, while KCG is more appropriate for suspensions. These findings provide valuable information for directly applying these ECC compounds to food products, potentially offering better preservation and health benefits.

A Ferritin Nanoparticle-Based Zika Virus Vaccine Candidate Induces Robust Humoral and Cellular Immune Responses and Protects Mice from Lethal Virus Challenge.

The severe consequences of the Zika virus (ZIKV) infections resulting in congenital Zika syndrome in infants and the autoimmune Guillain-Barre syndrome in adults warrant the development of safe and efficacious vaccines and therapeutics. Currently, there are no approved treatment options for ZIKV infection. Herein, we describe the development of a bacterial ferritin-based nanoparticle vaccine candidate for ZIKV. The viral envelope (E) protein domain III (DIII) was fused in-frame at the amino-terminus of ferritin. The resulting nanoparticle displaying the DIII was examined for its ability to induce immune responses and protect vaccinated animals upon lethal virus challenge. Our results show that immunization of mice with a single dose of the nanoparticle vaccine candidate (zDIII-F) resulted in the robust induction of neutralizing antibody responses that protected the animals from the lethal ZIKV challenge. The antibodies neutralized infectivity of other ZIKV lineages indicating that the zDIII-F can confer heterologous protection. The vaccine candidate also induced a significantly higher frequency of interferon (IFN)-γ positive CD4 T cells and CD8 T cells suggesting that both humoral and cell-mediated immune responses were induced by the vaccine candidate. Although our studies showed that a soluble DIII vaccine candidate could also induce humoral and cell-mediated immunity and protect from lethal ZIKV challenge, the immune responses and protection conferred by the nanoparticle vaccine candidate were superior. Further, passive transfer of neutralizing antibodies from the vaccinated animals to naïve animals protected against lethal ZIKV challenge. Since previous studies have shown that antibodies directed at the DIII region of the E protein do not to induce antibody-dependent enhancement (ADE) of ZIKV or other related flavivirus infections, our studies support the use of the zDIII-F nanoparticle vaccine candidate for safe and enhanced immunological responses against ZIKV.

Quality Indicators Compliance and Survival Outcomes in Breast Cancer according to Age in a Certified Center.

Age as a breast cancer (BC) prognostic factor remains debatable. Several studies have investigated clinicopathological features at different ages, but few make an age group direct comparison. The European Society of Breast Cancer Specialists quality indicators (EUSOMA-QIs) allow a standardized quality assurance of BC diagnosis, treatment, and follow-up. Our objective was to compare clinicopathological features, compliance to EUSOMA-QIs and BC outcomes in three age groups (≤45 years, 46-69 years, and ≥70 years). Data from 1580 patients with staged 0-IV BC from 2015 to 2019 were analyzed. The minimum standard and desirable target on 19 mandatory and 7 recommended QIs were studied. The 5-year relapse rate, overall survival (OS), and BC-specific survival (BCSS) were also evaluated. No meaningful differences in TNM staging and molecular subtyping classification between age groups were found. On the contrary, disparities in QIs compliance were observed: 73.1% in ≤45 years and 46-69 years women vs. 54% in older patients. No differences in loco-regional or distant progression were observed between age groups. Nevertheless, lower OS was found in older patients due to concurrent non-oncological causes. After survival curves adjustment, we underscored evidence of undertreatment impacting BCSS in ≥70 years women. Despite a unique exception-more invasive G3 tumors in younger patients-no age-specific differences in BC biology impacting outcome were found. Although increased noncompliance in older women, no outcome correlation was observed with QIs noncompliance in any age group. Clinicopathological features and differences in multimodal treatment (not the chronological age) are predictors of lower BCSS.

Lipid-Encapsuled Grape Tannins Prevent Oxidative-Stress-Induced Neuronal Cell Death, Intracellular ROS Accumulation and Inflammation.

The central nervous system (CNS) is particularly vulnerable to oxidative stress and inflammation, which affect neuronal function and survival. Nowadays, there is great interest in the development of antioxidant and anti-inflammatory compounds extracted from natural products, as potential strategies to reduce the oxidative/inflammatory environment within the CNS and then preserve neuronal integrity and brain function. However, an important limitation of natural antioxidant formulations (mainly polyphenols) is their reduced in vivo bioavailability. The biological compatible delivery system containing polyphenols may serve as a novel compound for these antioxidant formulations. Accordingly, in the present study, we used liposomes as carriers for grape tannins, and we tested their ability to prevent neuronal oxidative stress and inflammation. Cultured catecholaminergic neurons (CAD) were used to establish the potential of lipid-encapsulated grape tannins (TLS) to prevent neuronal oxidative stress and inflammation following an oxidative insult. TLS rescued cell survival after H2O2 treatment (59.4 ± 8.8% vs. 90.4 ± 5.6% H2O2 vs. TLS+ H2O2; p < 0.05) and reduced intracellular ROS levels by ~38% (p < 0.05), despite displaying negligible antioxidant activity in solution. Additionally, TLS treatment dramatically reduced proinflammatory cytokines' mRNA expression after H2O2 treatment (TNF-α: 400.3 ± 1.7 vs. 7.9 ± 1.9-fold; IL-1ß: 423.4 ± 1.3 vs. 12.7 ± 2.6-fold; p < 0.05; H2O2 vs. TLS+ H2O2, respectively), without affecting pro/antioxidant biomarker expression, suggesting that liposomes efficiently delivered tannins inside neurons and promoted cell survival. In conclusion, we propose that lipid-encapsulated grape tannins could be an efficient tool to promote antioxidant/inflammatory cell defense.

Lifelong multilineage contribution by embryonic-born blood progenitors.

Haematopoietic stem cells (HSCs) arise in the embryo from the arterial endothelium through a process known as the endothelial-to-haematopoietic transition (EHT)1-4. This process generates hundreds of blood progenitors, of which a fraction go on to become definitive HSCs. It is generally thought that most adult blood is derived from those HSCs, but to what extent other progenitors contribute to adult haematopoiesis is not known. Here we use in situ barcoding and classical fate mapping to assess the developmental and clonal origins of adult blood in mice. Our analysis uncovers an early wave of progenitor specification-independent of traditional HSCs-that begins soon after EHT. These embryonic multipotent progenitors (eMPPs) predominantly drive haematopoiesis in the young adult, have a decreasing yet lifelong contribution over time and are the predominant source of lymphoid output. Putative eMPPs are specified within intra-arterial haematopoietic clusters and represent one fate of the earliest haematopoietic progenitors. Altogether, our results reveal functional heterogeneity during the definitive wave that leads to distinct sources of adult blood.

Variables related to microwave heating-toasting time and water migration assessment with kernel size approaches of specialty maize types.

BACKGROUND: Three main maize types with specialty kernels are used to make ready-to-eat maize by traditional toasting, and microwave toasting may be an innovative application. However, little is known of the toasting process of these Andean maize types. Therefore, the present study aimed to explore the behavior of a broad scope of variables in these maize types. The kernels were packed in sealed paper envelopes and subjected to six microwave heating-toasting times from 0 to 390 s. Subsequently, with actual kernel size approaches, water content (WC), water ratio (WR), and water loss (WL) were analyzed. RESULTS: In addition to WC, WR, and WL, the surface area (S), volume (V), and geometric mean diameter (GMD) behaved like time-related variables with a high correlation depending on the maize types and kernel dimensions. Thus, the WC, WR, and WL third-order polynomial regression curves computed with the spatial (S/V)2 and distance (GMD/2)2 approaches indicated the water variation at each microwave heating-toasting time with a clear difference among maize types a0, a1, and a2. Regarding their exchange profiles without and with the spatial (S/V)2 approach, the maximum rates showed significant differences between maize types and WC and WL. Likewise, the maximum rates displayed significant differences between the spatial (S/V)2 and distance (GMD/2)2 approaches, revealing a notable lack of consistency with the distance (GMD/2)2 approach. CONCLUSION: The kernel size approaches revealed that water migration rates depended on differences in maize types. Such basic information represents the first insight into more physical-based models of water diffusion during raw microwave maize heating-toasting. © 2022 Society of Chemical Industry.

Wine astringency: more than just tannin-protein interactions.

Red wines are characterized by their astringency, a very important sensory attribute that affects the perceived quality of wines. Three mechanisms have been proposed to explain astringency, and two theories describe how these mechanisms work in an integrated manner to produce tactile sensations such as drying, roughening, shrinking and puckering. The factors involved include not only tannins and salivary proteins, but also anthocyanins, grape polysaccharides and mannoproteins, as well as other wine matrix components that modulate their interactions. These multifactorial interactions could be responsible for different sensory responses and therefore need to be further studied. This review presents the latest advances in astringency perception and its possible origins, with special attention on the interactions of components, their impact on oral perception and the development of astringency sub-qualities. Future research efforts should concentrate on understanding the mechanisms involved as well as on the limiting factors related to the conformation and stability of the tannin-salivary protein complexes. © 2021 Society of Chemical Industry.

Frailty-Independent Undertreatment Negative Impact on Survival in Older Patients With Breast Cancer.

PURPOSE: The management of older adults with breast cancer (BC) remains controversial. The challenging assessment of aging idiosyncrasies and the scarce evidence of therapeutic guidelines can lead to undertreatment. Our goal was to measure undertreatment and assess its impact on survival. METHODS: Consecutive patients with BC aged 70 years or older were prospectively enrolled in 2014. Three frailty screening tools (G8, fTRST, and GFI) and two functional status scales (Karnofsky performance score and Eastern Cooperative Oncology Group Performance Status) were applied. Disease characteristics, treatment options, and causes of mortality were recorded during a 5-year follow-up. In addition, we defined undertreatment and correlated its survival impact with frailty. RESULTS: A total of 92 patients were included in the study. The median age was 77 (range 70-94) years. The prevalence of frailty was discordant (G8, 41.9%; fTRST, 74.2%; GFI, 32.3%). Only 47.8% of the patients had a local disease, probably due to a late diagnosis (73.9% based on self-examination). Thirty-three patients (35.6%) died, of which 15 were from BC. We found a considerably high proportion (53.3%) of undertreatment, which had a frailty-independent negative impact on the 5-year survival (hazard ratio [HR], 5.1; 95% confidence interval [CI], 2.1-12.5). Additionally, omission of surgery had a frailty-independent negative impact on overall survival (HR, 3.9; 95% CI, 1.9-7.9). CONCLUSION: BC treatment in older adults should be individualized. More importantly, assessing frailty (not to treat) is essential to be aware of the risk-benefit profile and the patient's well-informed willingness to be treated. Undertreatment in daily practice is frequent and might have a negative impact on survival, as we report.

Clinical Outcome of Patients Submitted to Liver Resection in the Context of Metastatic Breast Cancer: A Study of a Tertiary Hospital Center.

INTRODUCTION: Breast cancer is the most incident cancer in the world, accounting for 25% of new cancers per year in females. It is the most frequent malignancy in women, being the fifth cause of death from cancer worldwide. Approximately 5 to 10% of patients already present with metastases at diagnosis, and the liver is the site of metastases in half of these cases. Liver metastasis (LM) resection, performed after neoadjuvant systemic treatment, has been reported to increase median overall survival in this population. AIM: The aim of this analysis is to assess the outcomes of patients undergoing breast cancer liver metastasis surgical resection, including impact on survival, compared to patients where metastasectomy was not performed. METHODS: retrospective review of 55 female patients with breast cancer liver metastases, diagnosed and treated in a single tertiary university hospital from January 2011 to December 2016 was performed. RESULTS: In 32/55 patients (58.2%), multi-organ metastases were identified (the most common sites being bone, lungs, and lymph nodes). Of the remaining 23 patients, the liver was the unique metastatic site; thirteen patients had diffuse bilobar hepatic metastases. The remaining ten patients were proposed for surgical treatment; three of them had peritoneal carcinomatosis identified during surgery, and no hepatic metastasectomy was performed. As a result, only seven (12.7%) patients underwent liver metastasectomy. Overall survival was higher in patients who had LM surgery (65 months [Interquartile Range (IQR) 54-120]), in comparison to those diagnosed with diffuse bilobar hepatic metastases (17.5 months [IQR 11-41]), and with those showing concurrent liver and bone metastases (16.5 months [IQR 6-36]) (p = 0.012). In univariable analysis, the latter two groups showed worse overall survival outcomes (Hazard Ratio (HR) = 3.447, 95%CI: 1.218-9.756, p = 0.02 and HR = 3.855, 95% Confidence Interval (CI): 1.475-10.077, p = 0.006, respectively) when compared to patients with LM. CONCLUSION: In our series, patients submitted to metastasectomy had a median overall survival after diagnosis of LM three times greater than the non-operated patients with isolated LM, or concurrent LM and bone metastases (65 vs. 17.5 and 16.5 months, respectively). As is vastly known for colorectal cancer liver metastasis, resection of breast cancer liver metastasis may reduce tumor burden, and therefore may improve patient outcome.

Combining edible coatings technology and nanoencapsulation for food application: A brief review with an emphasis on nanoliposomes.

The use of bioactive compounds within the biopolymer-based Edible Coatings (EC) matrices has certain limitations for their application at the food industry level. Encapsulation has been considered as a strategy that enables protecting and improving the physical and chemical characteristics of the compounds; as a result, it extends the shelf life of coated foods. This review discusses recent progress in combining edible coatings with nanoencapsulation technology. We also described and discussed various works, in which nanoliposomes are used as encapsulation systems to prepare, and subsequently apply the edible coatings in plant products and meat products. The use of nanoliposomes for the encapsulation of phenolic compounds and essential oils provides an improvement in the antioxidant and antimicrobial properties of coatings by extending the shelf life of food matrices. However, when liposomes are stored for a long period of time, they may present some degree of instability manifested by an increase in size, polydispersity index, and zeta potential. This is reflected in an aggregation, fusion, and rupture of the vesicles. This investigation can help researchers and industries to select an appropriate and efficient biopolymer to form EC containing nanoencapsulated active compounds. This work also addresses the use of nanoliposomes to create EC extending markedly the shelf life of fruit, reducing the weight loss, and deterioration due to the action of microorganisms.

Regenerative Reprogramming of the Intestinal Stem Cell State via Hippo Signaling Suppresses Metastatic Colorectal Cancer.

Although the Hippo transcriptional coactivator YAP is considered oncogenic in many tissues, its roles in intestinal homeostasis and colorectal cancer (CRC) remain controversial. Here, we demonstrate that the Hippo kinases LATS1/2 and MST1/2, which inhibit YAP activity, are required for maintaining Wnt signaling and canonical stem cell function. Hippo inhibition induces a distinct epithelial cell state marked by low Wnt signaling, a wound-healing response, and transcription factor Klf6 expression. Notably, loss of LATS1/2 or overexpression of YAP is sufficient to reprogram Lgr5+ cancer stem cells to this state and thereby suppress tumor growth in organoids, patient-derived xenografts, and mouse models of primary and metastatic CRC. Finally, we demonstrate that genetic deletion of YAP and its paralog TAZ promotes the growth of these tumors. Collectively, our results establish the role of YAP as a tumor suppressor in the adult colon and implicate Hippo kinases as therapeutic vulnerabilities in colorectal malignancies.

An Engineered CRISPR-Cas9 Mouse Line for Simultaneous Readout of Lineage Histories and Gene Expression Profiles in Single Cells.

Tracing the lineage history of cells is key to answering diverse and fundamental questions in biology. Coupling of cell ancestry information with other molecular readouts represents an important goal in the field. Here, we describe the CRISPR array repair lineage tracing (CARLIN) mouse line and corresponding analysis tools that can be used to simultaneously interrogate the lineage and transcriptomic information of single cells in vivo. This model exploits CRISPR technology to generate up to 44,000 transcribed barcodes in an inducible fashion at any point during development or adulthood, is compatible with sequential barcoding, and is fully genetically defined. We have used CARLIN to identify intrinsic biases in the activity of fetal liver hematopoietic stem cell (HSC) clones and to uncover a previously unappreciated clonal bottleneck in the response of HSCs to injury. CARLIN also allows the unbiased identification of transcriptional signatures associated with HSC activity without cell sorting.

Effect of lyophilization on the physicochemical and rheological properties of food grade liposomes that encapsulate rutin.

The potential use of liposomes as carriers for food active ingredients can be limited by their physical and chemical instabilities in aqueous dispersions, especially for long-term storage. Lyophilization, a process commonly used in the food industry, can also be applied to stabilize and preserve liposomes and to extend their shelf-life. In this work, liposomes with potential use for designing functional foods were prepared with soy phospholipids and rutin. Homogenization and ultrasound were used for particle size reduction. Liposomal stability was evaluated by Dynamic Light Scattering, microscopy and rheological properties. Spherical and unilamellar liposomes were obtained in this work. Zeta potential (ξ = values were around -40 mV), which indicates a great suspension stability even for more than 30 days of storage. Rutin exerted a protective effect by both preventing damage to the liposome bilayer and maintaining the spherical structure after 56 days of storage. Lyophilization caused an increase in the size of the vesicles, reaching sizes around 419 nm and aggregation of vesicles with probably structural damage after 21 storage days. However, it helped to keep the rutin encapsulated (81.9%) for longer time, when compared to refrigerated liposomes. Rheological measurements showed, in general, that the power law model fitted most of the experimental results and dynamic rheological tests showed a sol-gel phase transition between 35 and 45 °C. Lyophilization caused a significant change in all evaluated rheological parameters. For the in vitro release tests, the liposomal bilayer acted as a barrier for the rutin release to the food simulating medium; therefore, the release rate of the antioxidant from the rutin encapsulated liposome was slow compared to the free rutin release rate.