Patritumab deruxtecan in HER2-negative breast cancer: part B results of the window-of-opportunity SOLTI-1805 TOT-HER3 trial and biological determinants of early response.

Patritumab deruxtecan (HER3-DXd) exhibits promising efficacy in breast cancer, with its activity not directly correlated to baseline ERBB3/HER3 levels. This research investigates the genetic factors affecting HER3-DXd's response in women with early-stage hormone receptor-positive and HER2-negative (HR+/HER2-) breast cancer. In the SOLTI-1805 TOT-HER3 trial, a single HER3-DXd dose was administered to 98 patients across two parts: 78 patients received 6.4 mg/kg (Part A), and 44 received a lower 5.6 mg/kg dose (Part B). The CelTIL score, measuring tumor cellularity and infiltrating lymphocytes from baseline to day 21, was used to assess drug activity. Part A demonstrated increased CelTIL score after one dose of HER3-DXd. Here we report CelTIL score and safety for Part B. In addition, the exploratory analyses of part A involve a comprehensive study of gene expression, somatic mutations, copy-number segments, and DNA-based subtypes, while Part B focuses on validating gene expression. RNA analyses show significant correlations between CelTIL responses, high proliferation genes (e.g., CCNE1, MKI67), and low expression of luminal genes (e.g., NAT1, SLC39A6). DNA findings indicate that CelTIL response is significantly associated with TP53 mutations, proliferation, non-luminal signatures, and a distinct DNA-based subtype (DNADX cluster-3). Critically, low HER2DX ERBB2 mRNA, correlates with increased HER3-DXd activity, which is validated through in vivo patient-derived xenograft  models. This study proposes chemosensitivity determinants, DNA-based subtype classification, and low ERBB2 expression as potential markers for HER3-DXd activity in HER2-negative breast cancer.

Development and Validation of a Sonication-Assisted Dispersive Liquid-Liquid Microextraction Procedure and an HPLC-PDA Method for Quantitative Determination of Zolpidem in Human Plasma and Its Application to Forensic Samples.

The use of z-drugs has increased worldwide since its introduction. Although the prescribing patterns of hypnotics differ among countries, zolpidem is the most widely used z-drug in the world. Zolpidem may be involved in poisoning and deaths. A simple and fast HPLC-PDA method was developed and validated. Zolpidem and the internal standard chloramphenicol were extracted from plasma using a sonication-assisted dispersive liquid-liquid microextraction procedure. The method was validated including selectivity, linearity, precision, accuracy, and recovery. The calibration range (0.15-0.6 µg/mL) covers therapeutic and toxic levels of zolpidem in plasma. The limit of quantification was set at 0.15 µg/mL. Intra- and interday accuracy and precision values were lower than 15% at the concentration levels studied. Excellent recovery results were obtained for all concentrations. The proposed method was successfully applied to ten real postmortem plasma samples. In our series, multiple substances (alcohol and/or other drugs) were detected in most cases of death involving zolpidem. Our analytical method is suitable for routine toxicological analysis.

Determination of lamotrigine in human plasma by HPLC-PDA. Application to forensic samples.

PURPOSE: Therapeutic drug monitoring of plasma lamotrigine (LTG) has customarily been carried out in order to prevent some its adverse effects. For forensic purposes, determination of LTG in plasma is an useful tool in cases of accidental overdose or suicidal attempts. Currently, there are several analytical methods available including some based on LC tandem mass spectrometry techniques, but simple and accessible LC-UV methods still can be useful for the purpose. Here we report on a new high-performance liquid chromatography method for the determination of lamotrigine in human plasma which has been developed and validated including selectivity, sensitivity, accuracy, precision and recovery studies. METHODS: Lamotrigine and the internal standard chloramphenicol were extracted from plasma using liquid-liquid extraction using small volumes of buffer and ethylacetate. Detection was monitored at 305.7 and 276.0 nm for lamotrigine and chloramphenicol, respectively. RESULTS: The method was linear concentration dependence within the range of 0.1-10 µg/ml, with a mean coefficient of correlation r = 0.993. The limit of detection (LOD) was 0.04 µg/ml and the limit of quantification (LOQ) was 0.1 µg/ml. Intra and interday precision values were lower than 9.0% at all concentrations studied. The intra and interday accuracy values ranged from - 7.6 to 10.1%. Recovery was found to be 98.9% or higher. The method here described was successfully applied to 11 postmortem blood samples received at the Forensic Sciences Institute of Santiago de Compostela (Spain). CONCLUSION: A new HPLC method for the determination of lamotrigine in human plasma was developed and validated. A liquid-liquid extraction using small volumes of buffer and ethylacetate was optimized. The proposed method is suitable for forensic toxicological analysis.

Effect of Plasticization/Annealing on Thermal, Dynamic Mechanical, and Rheological Properties of Poly(Lactic Acid).

This study investigates the use of low molecular weight poly(ethylene glycol) (PEG) as a plasticizer for poly(lactic acid) (PLA). PLA/PEG blend films were prepared using the solvent casting method with varying mixing ratios. The films were analyzed using differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), and dynamic rheological analysis. The results indicate that the addition of PEG as a plasticizer affects the thermal and mechanical properties of the PLA/PEG blend films. The study found that the glass transition and cold crystallization temperatures decreased with increasing PEG content up to 20 wt%, while the crystallinity and crystallization rate increased. The blends with up to 20 wt% PEG were miscible, but phase separation occurred when the plasticizer content was increased to 30 wt%. Subsequently, amorphous samples of neat PLA and PLA plasticized with 10 wt% of PEG underwent annealing at various temperatures (Ta = 80-120 °C) for durations ta of 1 and 24 h. The samples were then analyzed using DSC and DMA. The addition of PEG to PLA altered the content of α' and α crystalline forms compared to neat PLA at a given (Ta; ta) and favored the formation of a mixture of α' and α crystals. The crystallinity achieved upon annealing increased with increasing Ta or ta and with the incorporation of PEG.

Evaluation of an Oral Fluid Collection Device and a Solid-Phase Extraction Method for the Determination of Coca Leaf Alkaloids by Gas Chromatography-Mass Spectrometry.

Some South American countries have ancient traditions that may pose legal problems, such as the consumption of coca leaves, as this can provide positive results for cocaine use after the analysis of biological samples. For this reason, it is necessary to find specific markers that help differentiate legal from illegal consumption, such as tropacocaine, cinnamoylcocaine, and especially hygrine and cuscohygrine. In this work, two techniques for collecting biological samples are compared: the Quantisal® Oral Fluid collection device and passive drooling. Once the samples were collected, they were subjected to solid-phase extraction for subsequent injection into GC-MS. Different validation parameters included in international guides have been studied to evaluate whether the proposed method is valid for the defined purpose, placing special emphasis on the study of the matrix effect and little value on GC-MS analyses. With respect to this parameter, an increase in the signal was found for CUS and t-CIN, but it was not significant for the rest of the substances studied. The recoveries have varied significantly depending on the way of working, being higher when working with standardized areas. After carrying out work with the oral fluid samples collected from laboratory volunteers, the method was applied to two real samples. The results obtained support the need for further research to overcome certain limitations presented by the device.

Electron Beam Processing as a Promising Tool to Decontaminate Polymers Containing Brominated Flame Retardants.

Electron Beam (EB) irradiation was utilized to decontaminate model systems of industrial polymers that contain a brominated flame retardant (BFR). Acrylonitrile-butadiene-styrene (ABS) and Polycarbonate (PC) are two types of polymers commonly found in Waste Electrical and Electronic Equipment (WEEE). In this study, these polymers were exposed to EB irradiation to degrade DecaBromoDiphenylEther (DBDE), one of the most toxic BFRs. Fourier-transform infrared spectroscopy analysis demonstrated an 87% degradation rate of DBDE for the ABS-DBDE system and 91% for the PC-DBDE system following an 1800 kGy irradiation dose. Thermal analysis using Differential Scanning Calorimetry revealed the presence of crosslinking in ABS and a minor reduction in the glass transition temperature of PC after EB processing. Polymers exhibited thermal stability after photolysis, as indicated by thermogravimetric analysis. In summary, EB irradiation had no impact on the overall thermal properties of both polymers. High-resolution mass spectrometry analysis has confirmed the debromination of both ABS-DBDE and PC-DBDE systems. Therefore, the results obtained are promising and could offer an alternative approach for removing bromine and other additives from plastic E-waste.

Thermal Degradation Studies of Poly(2-ethyl hexyl acrylate) in the Presence of Nematic Liquid Crystals.

The thermal degradation behavior of Poly(2-ethyl hexyl hcrylate) (Poly(2-EHA)), blended with a commercially available nematic liquid crystal (LC) mixture, was investigated by thermal gravimetric analysis (TGA). Different heating rates, ranging from 5 to 200 °C/min, were applied under an inert atmosphere. Based on the TGA results, activation energies (Eα) at different conversion rates (α) were determined using three integral isoconversion methods: Flynn-Wall-Ozawa (FWO), Tang, and Kissinger-Akahira-Sunose (KAS). It can be noticed that the global evolution of these activation energies was the same for the three models. The coefficient of determination R2 presented values generally higher than 0.97. Using these models, the Eα value for the LC remains constant at 64 kJ/mol for all conversions rates. For the polymer Poly(2-EHA), applying the Tang and FWO models, the activation energy presents a variation ranging from 80 kJ/mol, for conversion α = 0.1, to 170 kJ/mol, for α = 0.9. For the third model (KAS), this energy varies between 80 and 220 kJ/mol in the same range of α.

Pilot study on the effect of supplementation with long-chain ω-3 polyunsaturated fatty acids on body composition in children with acute lymphoblastic leukemia: randomized clinical trial.

BACKGROUND: N-3 polyunsaturated fatty acids (LCPUFA-ω3), particularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) might have beneficial effects on lean mass and fat mass synthesis. OBJECTIVE: To investigate the effect of LCPUFA-ω3 supplementation on body composition changes in children with acute lymphoblastic leukemia (ALL) at remission and three months (3 mo) after supplementation. METHODS: This randomized controlled trial enrolled 72 children (3-13 y) with newly diagnosed ALL (placebo group [500 mg sunflower oil]: 36 patients; LCPUFA-ω3 group [225 mg DHA, 45 mg EPA]: 36 patients). LCPUFA-ω3 was administered at 0.100 g/kg of body weight/day for 3 mo. Both groups were provided with an oral milkshake supplement. MAIN OUTCOMES AND MEASURES: Body composition was measured at diagnosis, remission, and 3 months after supplementation by dual-energy X-ray absorptiometry (DXA). Red blood cell fatty acid analyses were performed with gas chromatography. Student's t test compared the percentage changes in body weight, total body fat percentage (TBFP), and lean body mass (LBM) between the groups. The Mann-Whitney U test was used to compare the groups, and the Friedman range test and Wilcoxon signed rank test were used for intratreatment comparisons. Spearman correlation coefficients were calculated for LBM and erythrocyte LCPUFA-ω3 content. RESULTS: LBM decreased significantly in both groups. This loss was greater in the placebo group than in the LCPUFA-ω3 group at remission (p = 0.044) and at 3 months of supplementation (p = 0.039). There were significant and progressive increases in DHA and EPA concentrations in the LCPUFA-ω3 group (p < 0.001). LBM at remission was directly correlated with increased DHA (r = 0.487, p = 0.034) and EPA (r = 0.499, p = 0.030) erythrocytes in the LCPUFA-ω3 group. CONCLUSION: At ALL diagnosis and during the first three months of treatment, 100 mg/kg of body weight/d DHA and EPA decreased LBM loss and allowed the incorporation of fatty acids into cell membranes (clinicaltriasl.gov #: NCT01051154).

Effect of long-chain omega-3 polyunsaturated fatty acids on cardiometabolic factors in children with acute lymphoblastic leukemia undergoing treatment: a secondary analysis of a randomized controlled trial.

Introduction: Increased triglycerides (TGs) are a major risk factor for cardiovascular disease. Furthermore, hypertriglyceridemia is commonly associated with a reduction of high-density lipoprotein cholesterol (HDL-C) and an increase in atherogenic small-dense low-density lipoprotein (LDL-C) levels. Studies provide support that polyunsaturated omega-3 fatty acids (ω3-LCPUFAs) are cardioprotective and have antithrombotic and anti-inflammatory effects. The potential effects of ω3-LCPUFAs on cardiometabolic factors and anti-inflammatory actions in children with acute lymphoblastic leukemia (ALL) are limited. This is a secondary analysis of a previous clinical trial registered at clinical trials.gov (# NCT01051154) that was conducted to analyze the effect of ω3-LCPUFAs in pediatric patients with ALL who were receiving treatment.Objective: To examine the effect of supplementation with ω3-LCPUFAs on cardiometabolic factors in children with ALL undergoing treatment. Methods: Thirty-four children (placebo group: 20 patients; ω3-LCPUFAs group: 14 patients) aged 6.7 ± 2.7 years who were newly diagnosed with ALL were evaluated. Children were randomized to receive either ω3-LCPUFAs or placebo capsules (sunflower oil). ω3-LCPUFAs were administered in the form of 500-mg soft capsules. The ω3-LCPUFA capsules contained 225 mg of DHA, 45 mg of EPA, and 20 mg of another ω3-LCPUFAs. The omega-3 dose was administered at a rate of 0.100 g/kg of body weight/day for three months. Main outcomes: Fasting cholesterol, HDL-C, very-low-density lipoprotein (VLDL-C), TGs, atherogenic index of plasma (AIP), android/gynoid ratio (A/GR), IL-6, TNF-α, and percentage of fat mass (DXA) were measured in all patients. Fatty acid analyses in red blood cells were performed with gas chromatography. Results: We found significantly lower levels of TGs (p=0.043), VLDL-C (p=0.039), IL-6 (p=0.025), and AIP (p=0.042) in the ω3-LCPUFAs group than in the placebo group at three months. In contrast, the total cholesterol concentration was higher at 3 months in the ω3-LCPUFAs group than in the placebo group (155 mg/dl vs. 129 mg/dl, p=0.009). The number of children with hypertriglyceridemia (85% vs. 50%; p=0.054) tended to be lower between the time of diagnosis and after 3 months of supplementation with ω3-LCPUFAs. Conclusion: These findings support the use of ω3-LCPUFAs to reduce some adverse cardiometabolic and inflammatory risk factors in children with ALL. Clinical trial registration: ClinicalTrials.gov, identifier NCT01051154.

Simple Method for the Determination of THC and THC-COOH in Human Postmortem Blood Samples by Gas Chromatography-Mass Spectrometry.

A simple and sensitive analytical method was developed for qualitative and quantitative analysis of Δ9-tetrahydrocannabinol (Δ9-THC) and its metabolite 11-nor-Δ9-tetrahydrocannabinol-carboxylic acid (Δ9-THC-COOH) in human postmortem blood using gas chromatography/mass spectrometry (GC-MS) in selected ion monitoring (SIM) mode. The method involved a liquid-liquid extraction in two steps, one for Δ9-THC and a second one for Δ9-THC-COOH. The first extract was analyzed using Δ9-THC-D3 as internal standard. The second extract was derivatized and analyzed using Δ9-THC-COOH-D3 as internal standard. The method was shown to be very simple, rapid, and sensitive. The method was validated for the two compounds, including linearity (range 0.05-1.5 µg/mL for Δ9-THC and 0.08-1.5 µg/mL for Δ9-THC-COOH), and the main precision parameters. It was linear for both analytes, with quadratic regression of calibration curves always higher than 0.99. The coefficients of variation were less than 15%. Extraction recoveries were superior to 80% for both compounds. The developed method was used to analyze 41 real plasma samples obtained from the Forensic Toxicology Service of the Institute of Forensic Sciences of Santiago de Compostela (Spain) from cases in which the use of cannabis was involved, demonstrating the usefulness of the proposed method.

Statistical Analysis of Toxicological Data of Victims of Traffic Accidents in Galicia (Spain).

Driving under the influence of alcohol or drugs is a very common behavior in our environment and a serious problem for public health. On the one hand, in 2016, 400,000 people died in the world in traffic accidents in which ethanol was involved. On the other hand, traffic accidents in which the use of drugs of abuse other than ethyl alcohol accounted for more than 160,000 deaths worldwide in 2017. The objective of this work is to carry out a review of the 710 cases of people who died in traffic accidents received at the forensic toxicology service of the Institute of Forensic Sciences of the University of Santiago de Compostela (Galicia-Spain) over a period of 10 years (2009-2019). We performed an observational study of period prevalence, in which the following data were collected: age, sex, year, and analytical results in plasma, in the case of being positive. The data collected was subjected to statistical treatment. Of the 710 cases analyzed, 123 correspond to pedestrians and 587 to occupants of vehicles or motorcycles. A total of 77.6% of the deceased were men. At least one psychotropic substance was found in the blood of almost 40% of the victims. The most frequently found substance was ethyl alcohol, which appeared in 231 cases, more frequently in males. The second place is occupied by benzodiazepines, which appeared in 43 cases, followed by cocaine, which was detected in 25 cases. Polydrug use was found in only 44 cases, with the association of ethanol and cocaine being the most commonly found, followed by that of ethanol and benzodiazepines. Only in 5 of the cases analyzed there were 3 or more substances present. With the data obtained in this study, it is shown that in traffic accidents, the finding of different toxic or medicinal substances is frequent. Ethyl alcohol continues to be very present in road accidents (most detected substance), with the great impact that this implies. Secondly, the presence of benzodiazepines stands out, and cocaine is the third most detected toxic in this study. These results allow to obtain a profile of the substances most frequently involved in traffic accidents. Despite the surveillance, control, and information campaigns that the Spanish Government regularly carries out, the results are far from satisfactory.

Insights into Streptomyces coelicolor A3(2) growth and pigment formation with high-throughput online monitoring.

Streptomyces species are intensively studied for their ability to produce a variety of natural products. However, conditions influencing and leading to product formation are often not completely recognized. Therefore, in this study, high-throughput online monitoring is presented as a powerful tool to gain in-depth understanding of the cultivation of the model organism Streptomyces coelicolor A3(2). Through online measurements of oxygen transfer rate and autofluorescence, valuable information about availability of nutrients and product formation patterns of the pigments actinorhodin and undecylprodigiosin can be obtained and explained. Therefore, it is possible to determine the onset of pigmentation and to study in detail the influencing factors thereof. One factor identified in this study is the filling volume of the cultivation vessel. Slight variations led to varying pigmentation levels. By combining optical and metabolic online monitoring techniques, the correlation of the filling volume with pigmentation could be explained as a result of different growth trajectories caused by varying specific power inputs and their influence on the pellet formation of the filamentous system. Finally, experiments with the addition of supernatant from unpigmented and pigmented cultures could highlight the applicability of the presented approach to study quorum sensing and cell-cell interaction.

Tunable population dynamics in a synthetic filamentous coculture.

Microbial cocultures are used as a tool to stimulate natural product biosynthesis. However, studies often empirically combine different organisms without a deeper understanding of the population dynamics. As filamentous organisms offer a vast metabolic diversity, we developed a model filamentous coculture of the cellulolytic fungus Trichoderma reesei RUT-C30 and the noncellulolytic bacterium Streptomyces coelicolor A3(2). The coculture was set up to use α-cellulose as a carbon source. This established a dependency of S. coelicolor on hydrolysate sugars released by T. reesei cellulases. To provide detailed insight into coculture dynamics, we applied high-throughput online monitoring of the respiration rate and fluorescence of the tagged strains. The respiration rate allowed us to distinguish the conditions of successful cellulase formation. Furthermore, to dissect the individual strain contributions, T. reesei and S. coelicolor were tagged with mCherry and mNeonGreen (mNG) fluorescence proteins, respectively. When evaluating varying inoculation ratios, it was observed that both partners outcompete the other when given a high inoculation advantage. Nonetheless, adequate proportions for simultaneous growth of both partners, cellulase, and pigment production could be determined. Finally, population dynamics were also tuned by modulating abiotic factors. Increased osmolality provided a growth advantage to S. coelicolor. In contrast, an increase in shaking frequency had a negative effect on S. coelicolor biomass formation, promoting T. reesei. This comprehensive analysis fills important knowledge gaps in the control of complex cocultures and accelerates the setup of other tailor-made coculture bioprocesses.

Reliable online measurement of population dynamics for filamentous co-cultures.

Understanding population dynamics is a key factor for optimizing co-culture processes to produce valuable compounds. However, the measurement of independent population dynamics is difficult, especially for filamentous organisms and in presence of insoluble substrates like cellulose. We propose a workflow for fluorescence-based online monitoring of individual population dynamics of two filamentous microorganisms. The fluorescent tagged target co-culture is composed of the cellulolytic fungus Trichoderma reesei RUT-C30-mCherry and the pigment-producing bacterium Streptomyces coelicolor A3(2)-mNeonGreen (mNG) growing on insoluble cellulose as a substrate. To validate the system, the fluorescence-to-biomass and fluorescence-to-scattered-light correlation of the two strains was characterized in depth under various conditions. Thereby, especially for complex filamentous microorganisms, microbial morphologies have to be considered. Another bias can arise from autofluorescence or pigments that can spectrally interfere with the fluorescence measurement. Green autofluorescence of both strains was uncoupled from different green fluorescent protein signals through a spectral unmixing approach, resulting in a specific signal only linked to the abundance of S. coelicolor A3(2)-mNG. As proof of principle, the population dynamics of the target co-culture were measured at varying inoculation ratios in presence of insoluble cellulose particles. Thereby, the respective fluorescence signals reliably described the abundance of each partner, according to the variations in the inocula. With this method, conditions can be fine-tuned for optimal growth of both partners along with natural product formation by the bacterium.

Caregiver perspectives on the everyday medical and social needs of long-term pediatric liver transplant patients.

Using in-depth interviews, we sought to characterize the everyday medical and social needs of pediatric liver transplant caregivers to inform the future design of solutions to improve care processes. Participants (parents/caregivers of pediatric liver transplant recipients) completed a survey (assessing socioeconomic status, economic hardship, health literacy, and social isolation). We then asked participants to undergo a 60-min virtual, semistructured qualitative interview to understand the everyday medical and social needs of the caregiver and their household. We intentionally oversampled caregivers who reported a social or economic hardship on the survey. Transcripts were analyzed using thematic analysis and organized around the Capability, Opportunity, Motivation-Behavior model. A total of 18 caregivers participated. Of the participants, 50% reported some form of financial strain, and about half had less than 4 years of college education. Caregivers had high motivation and capability in executing transplant-related tasks but identified several opportunities for improving care. Caregivers perceived the health system to lack capability in identifying and intervening on specific family social needs. Caregiver interviews revealed multiple areas in which family supports could be strengthened, including (1) managing indirect costs of prolonged hospitalizations (e.g., food, parking), (2) communicating with employers to support families' needs, (3) coordinating care across hospital departments, and (4) clarifying care team roles in helping families reduce both medical and social barriers. This study highlights the caregiver perspective on barriers and facilitators to posttransplant care. Future work should identify whether these themes are present across transplant centers. Caregiver perspectives should help inform future interventions aimed at improving long-term outcomes for children after liver transplantation.

Cultivating cultural capitals in introductory algebra-based physics through reflective journaling.

At a large, diverse, hispanic-serving, master's-granting university, the Alma Project was created to support the rich connections of life experiences of science, technology, engineering, and mathematics (STEM) students that come from racially diverse backgrounds through reflective journaling. Utilizing frameworks in ethnic studies and social psychology, the Alma Project aims to make learning STEM inclusive by affirming the intersectional identities and cultural wealth that students bring into STEM classrooms. Approximately once per month students who participate in the Alma Project spend 5-10 min at the beginning of class responding to questions designed to affirm their values and purpose for studying STEM in college. Students then spend time in class sharing their responses with their peers, to the extent that they feel comfortable, including common struggles and successes in navigating through college and STEM spaces. For this study, we analyze 180 reflective journaling essays of students enrolled in General Physics I, an algebra-based introductory physics course primarily for life science majors. Students were enrolled in a required lab, a self-selected community-based learning program (Supplemental Instruction), or in a small number of instances, both. Using the community cultural wealth framework to anchor our analysis, we identified 11 cultural capitals that students often expressed within these physics spaces. Students in both populations frequently expressed aspirational, attainment, and navigational capital, while expressions of other cultural capitals, such as social capital, differ in the two populations. Our findings suggest that students bring rich and diverse perspectives into physics classrooms when asked to reflect about their lived experiences. Moreover, our study provides evidence that reflective journaling can be used as an asset-based teaching tool. By using reflective journaling in physics spaces, recognizing students' assets has the potential for physics educators to leverage students' lived experiences, goals, and values to make physics learning more meaningful and engaging.

Depletion of essential fatty acids in muscle is associated with shorter survival of cancer patients undergoing surgery-preliminary report.

Emerging studies are reporting associations between skeletal muscle abnormalities and survival in cancer patients. Cancer prognosis is associated with depletion of essential fatty acids in erythrocytes and plasma in humans. However the relationship between skeletal muscle membrane fatty acid composition and survival is unknown. This study investigates the relationship between fatty acid content of phospholipids in skeletal muscle and survival in cancer patients. Rectus abdominis biopsies were collected during cancer surgery from 35 patients diagnosed with cancer. Thin-layer and gas chromatography were used for quantification of phospholipid fatty acids. Cutpoints for survival were defined using optimal stratification. Median survival was between 450 and 500 days when patients had arachidonic acid (AA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in muscle phospholipid below the cut-point compared to 720-800 days for patients above. Cox regression analysis revealed that low amounts of AA, EPA and DHA are risk factors for death. The risk of death remained significant for AA [HR 3.5 (1.11-10.87), p = 0.03], EPA [HR 3.92 (1.1-14.0), p = 0.04] and DHA [HR 4.08 (1.1-14.6), p = 0.03] when adjusted for sex. Lower amounts of essential fatty acids in skeletal muscle membrane is a predictor of survival in cancer patients. These results warrant investigation to restore bioactive fatty acids in people with cancer.

Dielectric Spectroscopy Analysis of Liquid Crystals Recovered from End-of-Life Liquid Crystal Displays.

In the present work, the dielectric properties of recycled liquid crystals (LCs) (non-purified, purified, and doped with diamond nanoparticles at 0.05, 0.1, and 0.2 wt%) were investigated. The studied LC mixtures were obtained from industrial recycling of end-of-life LC displays presenting mainly nematic phases. Dielectric measurements were carried out at room temperature on a frequency range from 0.1 to 106 Hz using an impedance analyzer. The amplitude of the oscillating voltage was fixed at 1 V using cells with homogeneous and homeotropic alignments. Results show that the dielectric anisotropy of all purified samples presents positive values and decreases after the addition of diamond nanoparticles to the LC mixtures. DC conductivity values were obtained by applying the universal law of dielectric response proposed by Jonscher. In addition, conductivity of the doped LC mixtures is lower than that of the undoped and non-purified LC.

SOLTI-1805 TOT-HER3 Study Concept: A Window-of-Opportunity Trial of Patritumab Deruxtecan, a HER3 Directed Antibody Drug Conjugate, in Patients With Early Breast Cancer.

Background: Preclinical data support a key role for the human epidermal growth factor receptor 3 (HER3) pathway in hormone receptor (HR)-positive breast cancer. Recently, new HER3 directed antibody drug conjugates have shown activity in breast cancer. Given the need to better understand the molecular biology, tumor microenvironment, and mechanisms of drug resistance in breast cancer, we designed this window-of-opportunity study with the HER3 directed antibody drug conjugate patritumab deruxtecan (HER3-DXd; U3-1402). Trial Design: Based on these data, a prospective, multicenter, single-arm, window-of-opportunity study was designed to evaluate the biological effect of patritumab deruxtecan in the treatment of naïve patients with HR-positive/HER2-negative early breast cancer whose primary tumors are ≥1 cm by ultrasound evaluation. Patients will be enrolled in four cohorts according to the mRNA-based ERBB3 expression by central assessment. The primary endpoint is a CelTIL score after one single dose. A translational research plan is also included to provide biological information and to evaluate secondary and exploratory objectives of the study. Trial Registration Number: EudraCT 2019-004964-23; NCT number: NCT04610528.

Saliva is a reliable and accessible source for the detection of SARS-CoV-2.

OBJECTIVES: The aim of this study was to investigate the feasibility of saliva sampling as a non-invasive and safer tool to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to compare its reproducibility and sensitivity with nasopharyngeal swab samples (NPS). The use of sample pools was also investigated. METHODS: A total of 2107 paired samples were collected from asymptomatic healthcare and office workers in Mexico City. Sixty of these samples were also analyzed in two other independent laboratories for concordance analysis. Sample processing and analysis of virus genetic material were performed according to standard protocols described elsewhere. A pooling analysis was performed by analyzing the saliva pool and the individual pool components. RESULTS: The concordance between NPS and saliva results was 95.2% (kappa 0.727, p = 0.0001) and 97.9% without considering inconclusive results (kappa 0.852, p = 0.0001). Saliva had a lower number of inconclusive results than NPS (0.9% vs 1.9%). Furthermore, saliva showed a significantly higher concentration of both total RNA and viral copies than NPS. Comparison of our results with those of the other two laboratories showed 100% and 97% concordance. Saliva samples are stable without the use of any preservative, and a positive SARS-CoV-2 sample can be detected 5, 10, and 15 days after collection when the sample is stored at 4 °C. CONCLUSIONS: The study results indicate that saliva is as effective as NPS for the identification of SARS-CoV-2-infected asymptomatic patients. Sample pooling facilitates the analysis of a larger number of samples, with the benefit of cost reduction.