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Endostatin is a Mr 20,000 COOH-terminal fragment of collagen XVIII that inhibits the growth of several primary tumors. We report here the cloning and expression of mouse endostatin in both prokaryotic and eukaryotic expression systems. Soluble recombinant protein expressed in yeast (15–20 mg/L) inhibited the proliferation and migration of endothelial cells in response to stimulation by basic fibroblast growth factor. A rabbit polyclonal antibody was raised that showed positive immunoreactivity to the recombinant protein expressed from both systems. Importantly, the biological activity of the mouse recombinant protein could be neutralized by this antiserum in both endothelial proliferation and chorioallantoic membrane assays. Systemic administration of endostatin at 10 mg/kg suppressed the growth of renal cell cancer in a nude mouse model. The inhibition of tumor growth with soluble yeast-produced protein was comparable to that obtained with non-refolded precipitated protein expressed from bacteria. In addition, two closely related COOH-terminal deletion mutants of endostatin were also tested and showed strikingly differing activity. Collectively, these findings demonstrate the expression of a biologically active form of mouse endostatin in yeast, define a role for the molecule in inhibiting endothelial cell migration, extend its antitumor effects to renal cell carcinoma, and provide a formal proof (via the neutralizing antiserum experiments and the mutant data) that endostatin (and not a possible contaminant) acts as an antiangiogenic agent. Finally, the high level expression of mouse endostatin in yeast serves as an endotoxin free, soluble source of protein for fundamental studies on the mechanisms of tumor growth suppression by angiogenesis inhibitors.

Endostatin is a Mr 20,000 COOH-terminal fragment of collagen XVIII that inhibits the growth of several primary tumors. We report here the cloning and expression of mouse endostatin in both prokaryotic and eukaryotic expression systems. Soluble recombinant protein expressed in yeast (15–20 mg/L) inhibited the proliferation and migration of endothelial cells in response to stimulation by basic fibroblast growth factor. A rabbit polyclonal antibody was raised that showed positive immunoreactivity to the recombinant protein expressed from both systems. Importantly, the biological activity of the mouse recombinant protein could be neutralized by this antiserum in both endothelial proliferation and chorioallantoic membrane assays. Systemic administration of endostatin at 10 mg/kg suppressed the growth of renal cell cancer in a nude mouse model. The inhibition of tumor growth with soluble yeast-produced protein was comparable to that obtained with non-refolded precipitated protein expressed from bacteria. In addition, two closely related COOH-terminal deletion mutants of endostatin were also tested and showed strikingly differing activity. Collectively, these findings demonstrate the expression of a biologically active form of mouse endostatin in yeast, define a role for the molecule in inhibiting endothelial cell migration, extend its antitumor effects to renal cell carcinoma, and provide a formal proof (via the neutralizing antiserum experiments and the mutant data) that endostatin (and not a possible contaminant) acts as an antiangiogenic agent. Finally, the high level expression of mouse endostatin in yeast serves as an endotoxin free, soluble source of protein for fundamental studies on the mechanisms of tumor growth suppression by angiogenesis inhibitors.

Global plastic production reached a new high in 2019. The high use of plastic leads to a high amount of plastic waste. Thereof, only 33% was collected for recycling in Europe. Plastic production depends on crude oil and energy and has high environmental impacts such as greenhouse gas emissions. The recycling of plastic waste can reduce dependency on fossil resources, help reduce environmental impacts, and achieve sustainability goals. Currently, the chemical recycling of plastic is discussed to complement the existing mechanical recycling. Comparing the recycling technologies is needed to identify and establish the most environmentally and economically promising technology for each waste stream. However, the quality of the recovered material has a high impact on assessment results. This study discusses different assessment metrics for recycling technologies concerning the influence of recovered materials’ quality by material substitution rates and circularity potential. In a case study, mechanical and chemical recycling via pyrolysis of HDPE from lightweight packaging waste from Germany is assessed. Mechanical recycling has a lower climate change impact than chemical recycling for material substitution rates above 0.85. On the other hand, chemical recycling has a higher potential to close the plastic loop and retain plastics within the economy due to the higher secondary material quality. The assessment allows evaluating recycling options for the considered plastics from the German collection systems for packaging.

ADT in combination with external beam radiation therapy (EBRT) is a well-established treatment for prostate cancer, though ADT is known to cause significant side effects impacting patients' quality of life. This study focuses on the lived experiences of prostate cancer patients on ADT, seeking to better understand how these treatment-related side effects impact their overall well-being. By exploring patient perspectives, we aim to provide valuable insights that can inform patient-centered care. Semi-structured qualitative interviews were conducted with patients diagnosed with intermediate-risk prostate cancer and treated with 6 months of ADT and EBRT, and who were enrolled on a larger protocol aiming to develop tailored treatment guidelines for men with intermediate-risk prostate cancer. The interviews explored nuanced experiences with six treatment-related side effects: hot flashes, fatigue, weight gain, loss of libido, erectile dysfunction, and changes in body image. Interviews were audio-recorded and analyzed for themes. Saturation was achieved after interviews with 8 participants; 3 additional interviews were performed for validation. The duration of the interview was a median of 37 minutes [IQR 32-42]. All 11 participants experienced hot flashes, with descriptions ranging from "feeling increases in body temperature" and "heavy sweating" to "big jolts like an electric shock." Notably, men reported the predominance of severe nighttime hot flashes, causing loss of sleep and changes in their daily routines. Most participants did not expect the hot flashes to be as frequent and intense. Fatigue was pervasive, making day-to-day tasks more difficult, with some patients resorting to frequent naps to cope. Strategies to mitigate weight gain included dietary changes including "eating more greens and less sugar" and increased physical activity. Loss of libido and erectile dysfunction were universally reported, with varying emotional responses based on importance of sexual activity in personal relationships prior to diagnosis of prostate cancer. Sexually active men found medication "like Cialis" helpful, stating "it doesn't clear the problem or the issue, but it helps." There were 5 participants who reported changes in body image, including loss of muscle mass and feelings of weakness. While most patients managed ADT side effects, hot flashes were notably burdensome yet accepted as a tradeoff for treatment efficacy. Loss of libido and erectile dysfunction posed significant distress, particularly for sexually active men anticipating full recovery post-treatment. This study provides valuable insights into the nuanced experiences of patients undergoing ADT, emphasizing the need for tailored support in managing treatment-related challenges. [ABSTRACT FROM AUTHOR]

The inner nuclear membrane (INM), a subdomain of the endoplasmic reticulum (ER), sequesters hundreds of transmembrane proteins within the nucleus. We previously found that one INM protein, emerin, can evade the INM by secretory transport to the lysosome, where it is degraded. In this work, we used targeted mutagenesis to identify intrinsic sequences that promote or inhibit emerin's secretory trafficking. By manipulating these sequences across several tag and expression level combinations, we now find that emerin's localization is sensitive to C-terminal GFP tagging. While emerin's long, hydrophobic C-terminal transmembrane domain facilitates trafficking to the lysosome, extending its lumenal terminus with a GFP tag biases the protein toward this pathway. In contrast, we identify a conserved ER retention sequence that stabilizes N- and C-terminally tagged emerin by limiting its lysosomal flux. These findings underscore long-standing concerns about tagging artifacts and reveal novel determinants of tail-anchored INM protein targeting.

Background: Personalized risk (PR) estimates may enhance clinical decision making and risk communication by providing individualized estimates of patient outcomes. We explored stakeholder attitudes toward the utility, acceptability, usefulness and best-practices for integrating PR estimates into patient education and decision making about Left Ventricular Assist Device (LVAD)., Methods and Results: As part of a 5-year multi-institutional AHRQ project, we conducted 40 interviews with stakeholders (physicians, nurse coordinators, patients, and caregivers), analyzed using Thematic Content Analysis. All stakeholder groups voiced positive views towards integrating PR in decision making. Patients, caregivers and coordinators emphasized that PR can help to better understand a patient's condition and risks, prepare mentally and logistically for likely outcomes, and meaningfully engage in decision making. Physicians felt it can improve their decision making by enhancing insight into outcomes, enhance tailored pre-emptive care, increase confidence in decisions, and reduce bias and subjectivity. All stakeholder groups also raised concerns about accuracy, representativeness and relevance of algorithms; predictive uncertainty; utility in relation to physician's expertise; potential negative reactions among patients; and overreliance., Conclusion: Stakeholders are optimistic about integrating PR into clinical decision making, but acceptability depends on prospectively demonstrating accuracy, relevance and evidence that benefits of PR outweigh potential negative impacts on decision making quality., Competing Interests: Declaration of Competing Interest Thank you for your time and consideration. This article has not been published previously and is not under consideration elsewhere. There are no conflicts of interests to report. All authors agree with the content of the manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this study, we investigate the flow dynamics in a fixed bed of hydrogel beads using particle tracking velocimetry to compute the velocity field in the middle of the bed for moderate Reynolds numbers (Re=[124,169,203,211]). We discover that even though the flow is stationary at the larger scales, it exhibits complex multiscale spatial dynamics reminiscent of those observed in classical turbulence. We find evidence of the presence of an inertial range and a direct energy cascade, and are able to obtain a value for a "porous" Kolmogorov constant of C_{2}=3.1±0.3. This analogy with turbulence opens up new possibilities for understanding mixing and global transport properties in porous media.

Chemical recycling of complex plastic waste via pyrolysis can reduce fossil resource dependence of the plastics value chain and greenhouse gas emissions. However, economic viability is crucial for its implementation, especially considering challenging waste streams with high shares of engineering plastics that have lower pyrolysis product quality than standard thermoplastics waste. Thus, this study conducts a techno-economic assessment determining the profitability factors of pyrolysis plants for automotive plastic waste in Germany including different plant capacities and calculating cost-covering minimum sales prices for the resulting pyrolysis oil. Main findings are that due to economies of scale, the cost-covering minimum sales prices vary between 1182 €/Mg pyrolysis oil (3750 Mg input/year) and 418 €/Mg pyrolysis oil (100,000 Mg input/year). The pyrolysis technology employed must be robust and scalable to realize these economies of scale. Large plant capacities face challenges such as feedstock availability at reasonable costs, constant feedstock quality, and pyrolysis oil quality, affecting pyrolysis oil pricing. Due to the limited yield and quality of pyrolysis oil produced from these technically demanding feedstocks, policy implications are that additional revenue streams such as gate fees or subsidies that are essential to ensure a positive business case are necessary. Depending on the assessed plant capacity, additional revenues between 720 and 59 €/Mg pyrolysis oil should be realized to be competitive with the price of the reference product heavy fuel oil. Otherwise, the environmental potential of this technology cannot be exploited., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Patient decision aids are interventions designed to support people making health decisions. At a minimum, patient decision aids make the decision explicit, provide evidence-based information about the options and associated benefits/harms, and help clarify personal values for features of options. This is an update of a Cochrane review that was first published in 2003 and last updated in 2017., Objectives: To assess the effects of patient decision aids in adults considering treatment or screening decisions using an integrated knowledge translation approach., Search Methods: We conducted the updated search for the period of 2015 (last search date) to March 2022 in CENTRAL, MEDLINE, Embase, PsycINFO, EBSCO, and grey literature. The cumulative search covers database origins to March 2022., Selection Criteria: We included published randomized controlled trials comparing patient decision aids to usual care. Usual care was defined as general information, risk assessment, clinical practice guideline summaries for health consumers, placebo intervention (e.g. information on another topic), or no intervention., Data Collection and Analysis: Two authors independently screened citations for inclusion, extracted intervention and outcome data, and assessed risk of bias using the Cochrane risk of bias tool. Primary outcomes, based on the International Patient Decision Aid Standards (IPDAS), were attributes related to the choice made (informed values-based choice congruence) and the decision-making process, such as knowledge, accurate risk perceptions, feeling informed, clear values, participation in decision-making, and adverse events. Secondary outcomes were choice, confidence in decision-making, adherence to the chosen option, preference-linked health outcomes, and impact on the healthcare system (e.g. consultation length). We pooled results using mean differences (MDs) and risk ratios (RRs) with 95% confidence intervals (CIs), applying a random-effects model. We conducted a subgroup analysis of 105 studies that were included in the previous review version compared to those published since that update (n = 104 studies). We used Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to assess the certainty of the evidence., Main Results: This update added 104 new studies for a total of 209 studies involving 107,698 participants. The patient decision aids focused on 71 different decisions. The most common decisions were about cardiovascular treatments (n = 22 studies), cancer screening (n = 17 studies colorectal, 15 prostate, 12 breast), cancer treatments (e.g. 15 breast, 11 prostate), mental health treatments (n = 10 studies), and joint replacement surgery (n = 9 studies). When assessing risk of bias in the included studies, we rated two items as mostly unclear (selective reporting: 100 studies; blinding of participants/personnel: 161 studies), due to inadequate reporting. Of the 209 included studies, 34 had at least one item rated as high risk of bias. There was moderate-certainty evidence that patient decision aids probably increase the congruence between informed values and care choices compared to usual care (RR 1.75, 95% CI 1.44 to 2.13; 21 studies, 9377 participants). Regarding attributes related to the decision-making process and compared to usual care, there was high-certainty evidence that patient decision aids result in improved participants' knowledge (MD 11.90/100, 95% CI 10.60 to 13.19; 107 studies, 25,492 participants), accuracy of risk perceptions (RR 1.94, 95% CI 1.61 to 2.34; 25 studies, 7796 participants), and decreased decisional conflict related to feeling uninformed (MD -10.02, 95% CI -12.31 to -7.74; 58 studies, 12,104 participants), indecision about personal values (MD -7.86, 95% CI -9.69 to -6.02; 55 studies, 11,880 participants), and proportion of people who were passive in decision-making (clinician-controlled) (RR 0.72, 95% CI 0.59 to 0.88; 21 studies, 4348 participants). For adverse outcomes, there was high-certainty evidence that there was no difference in decision regret between the patient decision aid and usual care groups (MD -1.23, 95% CI -3.05 to 0.59; 22 studies, 3707 participants). Of note, there was no difference in the length of consultation when patient decision aids were used in preparation for the consultation (MD -2.97 minutes, 95% CI -7.84 to 1.90; 5 studies, 420 participants). When patient decision aids were used during the consultation with the clinician, the length of consultation was 1.5 minutes longer (MD 1.50 minutes, 95% CI 0.79 to 2.20; 8 studies, 2702 participants). We found the same direction of effect when we compared results for patient decision aid studies reported in the previous update compared to studies conducted since 2015., Authors' Conclusions: Compared to usual care, across a wide variety of decisions, patient decision aids probably helped more adults reach informed values-congruent choices. They led to large increases in knowledge, accurate risk perceptions, and an active role in decision-making. Our updated review also found that patient decision aids increased patients' feeling informed and clear about their personal values. There was no difference in decision regret between people using decision aids versus those receiving usual care. Further studies are needed to assess the impact of patient decision aids on adherence and downstream effects on cost and resource use., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

This data article describes an instance dataset motivated by the problem of scheduling a project with diverging material flows. Such material flows are released during the execution of the project and are subject to limited processing and storage capacities. Typical examples are nuclear dismantling or other deconstruction/demolition projects, where large amounts of material must be classified, scanned for hazardousness, and processed accordingly. The problem setting is mathematically described as a resource-constrained project scheduling problem with cumulative resources (RCPSP/c). The RCPSP/c deals with finding a project schedule with minimal makespan that satisfies temporal, renewable resource, and cumulative resource constraints. In total, the dataset comprises 192 artificially generated instances that are suitable for testing models and solution methods. In addition, we provide our best found solution for each instance and different modeling variants (e.g., for two types of objective functions). These solutions were computed by heuristic solution methods. The dataset serves as a benchmark for researchers evaluating the performance of solution methods for the RCPSP/c or the more general problem class with resources that can be produced and consumed., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Inc.)

Thermal Bridges on Building Rooftops (TBBR) is a multi-channel remote sensing dataset. It was recorded during six separate UAV fly-overs of the city center of Karlsruhe, Germany, and comprises a total of 926 high-resolution images with 6927 manually-provided thermal bridge annotations. Each image provides five channels: three color, one thermographic, and one computationally derived height map channel. The data is pre-split into training and test data subsets suitable for object detection and instance segmentation tasks. All data is organized and structured to comply with FAIR principles, i.e. being findable, accessible, interoperable, and reusable. It is publicly available and can be downloaded from the Zenodo data repository. This work provides a comprehensive data descriptor for the TBBR dataset to facilitate broad community uptake., (© 2023. The Author(s).)

Enterocytes modulate the extent of postprandial lipemia by storing dietary fats in cytoplasmic lipid droplets (cLDs). We have previously shown that the integrin ligand MFGE8 links absorption of dietary fats with activation of triglyceride (TG) hydrolases that catabolize cLDs for chylomicron production. Here, we identify CES1D as the key hydrolase downstream of the MFGE8-αvβ5 integrin pathway that regulates catabolism of diet-derived cLDs. Mfge8 knockout (KO) enterocytes have reduced CES1D transcript and protein levels and reduced protein levels of the transcription factor HNF4γ. Both Ces1d and Hnf4γ KO mice have decreased enterocyte TG hydrolase activity coupled with retention of TG in cLDs. Mechanistically, MFGE8-dependent fatty acid uptake through CD36 stabilizes HNF4γ protein level; HNF4γ then increases Ces1d transcription. Our work identifies a regulatory network that regulates the severity of postprandial lipemia by linking dietary fat absorption with protein stabilization of a transcription factor that increases expression of hydrolases responsible for catabolizing diet-derived cLDs., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Importance: Currently, computed tomography (CT) is used for lung cancer screening (LCS) among populations with various levels of compliance to the eligibility criteria from the US Preventive Services Task Force (USPSTF) recommendations and may represent suboptimal allocation of health care resources., Objective: To evaluate the appropriateness of CT LCS according to the USPSTF eligibility criteria., Design, Setting, and Participants: This cross-sectional study used the 2019 Behavioral Risk Factor Surveillance System (BRFSS) survey. Participants included individuals who responded to the LCS module administered in 20 states and had valid answers to questions regarding screening and smoking history. Data were analyzed between October 2021 and August 2022., Exposures: Screening eligibility groups were categorized according to the USPSTF 2013 recommendations, and subgroups of individuals who underwent LCS were analyzed., Main Outcomes and Measures: Main outcomes included LCS among the screening-eligible population and the proportions of the screened populations according to compliance categories established from the USPSTF 2013 and 2021 recommendations. In addition, the association between respondents' characteristics and LCS was evaluated for the subgroup who were screened despite not meeting any of the 3 USPSTF screening criteria: age, pack-year, and years since quitting smoking., Results: A total of 96 097 respondents were identified for the full study cohort, and 2 subgroups were constructed: (1) 3374 respondents who reported having a CT or computerized axial tomography to check for lung cancer and (2) 33 809 respondents who did not meet any screening eligibility criteria. The proportion of participants who were under 50 years old was 53.1%; between 50 and 54, 9.1%; between 55 and 79, 33.8%; and over 80, 4.0%. A total of 51 536 (50.9%) of the participants were female. According to the USPSTF 2013 recommendation, 807 (12.8%) of the screening-eligible population underwent LCS. Among those who were screened, only 807 (20.9%) met all 3 screening eligibility criteria, whereas 538 (20.1%) failed to meet any criteria. Among respondents in subgroup 2, being of older age and having a history of stroke, chronic obstructive pulmonary disease, kidney disease, or diabetes were associated with higher likelihood of LCS., Conclusions and Relevance: In this cross-sectional study of the BRFSS 2019 survey, the low uptake rate among screening-eligible patients undermined the goal of LCS of early detection. Suboptimal screening patterns could increase health system costs and add financial stress, psychological burden, and physical harms to low-risk patients, while failing to provide high-quality preventive services to individuals at high risk of lung cancer.