bluuebunny/crossref_metadata_2025_split huggingface dataset:
1‐Sulfonylated 1,2,3,4‐tetrahydroquinoline‐6‐carboxylic acids as simple, readily‐accessible MCL‐1 inhibitors
Authors: Chen Lijia , Chan Alexandria M. , Wilder Paul T. , Fletcher Steven 
Published: October 2022

AbstractMCL‐1 is a member of the BCL‐2 family of proteins that regulates the mitochondrial pathway of apoptosis. Overexpression of MCL‐1 is associated with the development and progression of a range of human cancers, and is also responsible for the onset of resistance to conventional chemotherapies. Although several MCL‐1 inhibitors have now advanced to clinical trials, recent suspensions and terminations reveal the urgency with which new inhibitor chemotypes must be discovered. Building on our previous studies of a chiral, isomeric lead, we report the discovery of a new chemotype to inhibit MCL‐1: 1‐sulfonylated 1,2,3,4‐tetrahydroquinoline‐6‐carboxylic acid. The nature of the sulfonyl moiety contributed significantly to the resulting inhibitory ability. For example, transforming a phenylsulfonyl group into a 4‐chloro‐3,5‐dimethylphenoxy)phenyl)sulfonyl moiety elicited more than a 73‐fold enhancement in inhibiton of MCL‐1, possibly through targeting the p2 pocket in the BH3‐binding groove, and so it is anticipated that further structure‐activity studies here will lead to continued improvements in binding. It should be underscored that this class of MCL‐1 inhibitors is readily accessible in four simple steps, is achiral and offers many avenues for optimization, all factors that are welcomed in the search for safe and effective inhibitors of this driver of cancer cell survival.
Quantitative biogeography: Decreasing and more variable dynamics of critical species in an iconic meta‐ecosystem
Authors: Menge Bruce A. , Robinson Jonathan W. , Poirson Brittany N. , Gravem Sarah A. 
Published: October 2022

AbstractEcosystem stability has intrigued ecologists for decades, and the realization that the global climate was changing has sharpened and focused this interest. One possible early warning signal of decreasing stability is increasing variability in ecosystems over time with increasing climate variability. Determining climate change effects on community stability, however, requires long‐term studies of structure and underlying dynamics, including bottom‐up and top‐down effects in natural ecosystems. Although relevant datasets were rare in the early years of community ecology, such information has increased in recent decades. We investigated spatiotemporal changes in mean and variability of ecological subsidies (nutrients, phytoplankton, prey colonization), performance metrics of a dominant space occupier (mussels) and its primary predator (sea stars), and sea star predation rates on mussels in relation to climatic oscillations, temperature, and disease on rocky shores. The research involved annually repeated multiyear (~1999–2018), multisite (13 sites nested within five regions along ~260 km of the Oregon coast) observations, measurements, and experiments. We analyzed associations between environmental variables and ecological performance of key elements of the sea star‐mussel‐dominated mid intertidal system. We found that upwelling declined in some regions, but became more variable across all study regions. Air and water temperatures oscillated, but their mean and variation increased through time, with peak values coinciding with the 2014–2016 combined El Niño and Marine Heat Wave. Ecological subsidies generally declined during the study period but increased in variability. Excepting growth rate, mussel (Mytilus californianus) performance (condition index, reproductive output) generally decreased and became more variable. Primarily due to a sea star wasting epidemic, reproductive output of the top predator Pisaster ochraceus decreased and became more variable, and predation rate on mussels decreased. Analyses indicated that the primary drivers of these changes were temperature‐related environmental factors. As declining means and increasing variability of ecological performances can typify destabilizing ecosystems, and environmental trends are toward ever more stressful conditions, the outlook for this iconic ecosystem is discouraging. Immediate and rapid action to mitigate and ultimately reverse climate change likely is the only option available to prevent an irreversible shift in the future of this, and most other ecosystems.
Effects of Dietary Copper and Escherichia coli Challenge on the Immune Response and Gill Oxidative Balance in the Freshwater Mussel Diplodon chilensis
Authors: Castro Juan M. , Bianchi Virginia A. , Felici Emiliano , De Anna Julieta S. , Venturino Andrés , Luquet Carlos M. 
Published: October 2022

Abstract
Copper is a water and sediment pollutant that can be biomagnified by phytoplankton, and it often co-occurs with fecal bacteria. We addressed the combined effects of copper and Escherichia coli on the immune response and gill oxidative balance of the freshwater mussel Diplodon chilensis. Bivalves were sorted into four groups fed with 1) control algae, 2) bacteria (E. coli), 3) copper-enriched algae (Cu2+) algae, and 4) copper-enriched algae followed by bacteria (Cu2+ + E. coli). Cellular and humoral immune and cytotoxic variables were analyzed in hemolymph, and detoxifying/antioxidant enzyme activities (glutathione S-transferase [GST] and catalase [CAT]) and lipid peroxidation (thiobarbituric acid reactive substances [TBARS]) were studied in gill tissue. The total hemocyte number increased after Cu2+ exposure, independently of the E. coli challenge. The proportion of hyalinocytes significantly diminished in the E. coli and Cu2+ groups but not in Cu2+ + E. coli groups; granulocytes significantly increased with E. coli but not with Cu2+ + E. coli treatments. Phagocytic activity was higher in all treatments than in control mussels. Acid phosphatase activity was increased by E. coli and inhibited by Cu2+ and Cu2+ + E. coli. Both E. coli and Cu2+ but not Cu2+ + E. coli augmented alkaline phosphatase activity. The Cu2+ and Cu2+ + E. coli treatments reduced the lysosomal membrane stability and cell viability. Humoral bacteriolytic and phenol oxidase activities were not affected by any treatment. The Cu2+ treatment induced gill CAT and GST activities and increased TBARS levels. The Cu2+ + E. coli treatment reversed this CAT and GST stimulation and increased the Cu2+ effect on TBARS. Dietary Cu2+ affects bivalves' immunological and oxidative status and impairs defensive responses against bacteria. In turn, E. coli potentiates the gill oxidative effects of Cu2+. Environ Toxicol Chem 2023;42:154–165. © 2022 SETAC
The impact of the first UK COVID‐19 lockdown on presentations with psychosis to mental health services for older adults: An electronic health records study in South London
Authors: Simkin Lauren , Yung Paul , Greig Flora , Perera Gayan , Tsamakis Konstantinos , Rizos Emmanouil , Stewart Robert , Velayudhan Latha , Mueller Christoph 
Published: October 2022

AbstractObjectivesSocial distancing restrictions in the COVID‐19 pandemic may have had adverse effects on older adults' mental health. Whereby the impact on mood is well‐described, less is known about psychotic symptoms. The aim of this study was to compare characteristics associated with psychotic symptoms during the first UK lockdown and a pre‐pandemic comparison period.MethodsIn this retrospective observational study we analysed anonymised records from patients referred to mental health services for older adults in South London in the 16‐week period of the UK lockdown starting in March 2020, and in the comparable pre‐pandemic period in 2019. We used logistic regression models to compare the associations of different patient characteristics with increased odds of presenting with any psychotic symptom (defined as hallucinations and/or delusion), hallucinations, or delusions, during lockdown and the corresponding pre‐pandemic period.Results1991 referrals were identified. There were fewer referrals during lockdown but a higher proportion of presentations with any psychotic symptom (48.7% vs. 42.8%, p = 0.018), particularly hallucinations (41.0% vs. 27.8%, p < 0.001). Patients of non‐White ethnicity (adjusted odds ratio (OR): 1.83; 95% confidence interval (CI): 1.13–2.99) and patients with dementia (adjusted OR: 3.09; 95% CI: 1.91–4.99) were more likely to be referred with psychotic symptoms during lockdown. While a weaker association between dementia and psychotic symptoms was found in the pre‐COVID period (adjusted OR: 1.55; 95% CI: 1.19–2.03), interaction terms indicated higher odds of patients of non‐White ethnicity or dementia to present with psychosis during the lockdown period.ConclusionsDuring lockdown, referrals to mental health services for adults decreased, but contained a higher proportion with psychotic symptoms. The stronger association with psychotic symptoms in non‐White ethnic groups and patients with dementia during lockdown suggests that barriers in accessing care might have increased during the COVID‐19 pandemic.
Risk factors for cardiovascular disease among individuals with hepatic steatosis
Authors: Karády Julia , Ferencik Maros , Mayrhofer Thomas , Meyersohn Nandini M. , Bittner Daniel O. , Staziaki Pedro V. , Szilveszter Balint , Hallett Travis R. , Lu Michael T. , Puchner Stefan B. , Simon Tracey G. , Foldyna Borek , Ginsburg Geoffrey S. , McGarrah Robert W. , Voora Deepak , Shah Svati H. , Douglas Pamela S. , Hoffmann Udo , Corey Kathleen E. 
Published: October 2022

Abstract
Cardiovascular disease (CVD) is the leading cause of mortality in adults with hepatic steatosis (HS). However, risk factors for CVD in HS are unknown. We aimed to identify factors associated with coronary artery disease (CAD) and incident major adverse cardiovascular events (MACE) in individuals with HS. We performed a nested cohort study of adults with HS detected on coronary computed tomography in the PROspective Multicenter Imaging Study for Evaluation of chest pain (PROMISE) trial. Obstructive CAD was defined as ≥50% coronary stenosis. MACE included hospitalization for unstable angina, nonfatal myocardial infarction, or all‐cause death. Multivariate modeling, adjusted for age, sex, atherosclerotic CVD (ASCVD) risk score and body mass index, identified factors associated with obstructive CAD. Cox regression, adjusted for ASCVD risk score, determined the predictors of MACE. A total of 959 of 3,756 (mean age 59.4 years, 55.0% men) had HS. Obstructive CAD was present in 15.2% (145 of 959). Male sex (adjusted odds ratio [aOR] = 1.83, 95% confidence interval [CI] 1.18–1.2.84; p = 0.007), ASCVD risk score (aOR = 1.05, 95% CI 1.03–1.07; p < 0.001), and n‐terminal pro‐b‐type natriuretic peptide (NT‐proBNP; aOR = 1.90, 95% CI 1.38–2.62; p < 0.001) were independently associated with obstructive CAD. In the 25‐months median follow‐up, MACE occurred in 4.4% (42 of 959). Sedentary lifestyle (adjusted hazard ratio [aHR] = 2.53, 95% CI 1.27–5.03; p = 0.008) and NT‐proBNP (aOR = 1.50, 95% CI 1.01–2.25; p = 0.046) independently predicted MACE. Furthermore, the risk of MACE increased by 3% for every 1% increase in ASCVD risk score (aHR = 1.03, 95% CI 1.01–1.05; p = 0.02). Conclusion: In individuals with HS, male sex, NT‐pro‐BNP, and ASCVD risk score are associated with obstructive CAD. Furthermore, ASCVD, NT‐proBNP, and sedentary lifestyle are independent predictors of MACE. These factors, with further validation, may help risk‐stratify adults with HS for incident CAD and MACE.
Influence of COVID‐19 pandemic on research and fieldwork: Perspectives from Ghana
Authors: Fordjour Fatima Amponsah 
Published: October 2022

AbstractThe insurgence of COVID‐19 has received all attention at the detriment of research on most diseases. Procedures and protocols devised to curb the pandemic continues to affect lives and work. As most countries prepare to tune back to normalcy, working conditions undoubtedly will not be the same as the World Health Organization still urges nations to scale up procedures and strategies against the pandemic. As research groups and projects across the globe and especially in Ghana begins work, these protocols must be fashioned into their study protocol before approval will be granted by ethical institutions. This has led to increase in research cost, with additional responsibilities aside their normal research activities. This perspective clearly points out the impact of the pandemic on research, especially fieldwork.
Flow and thermal analysis of Oldroyd 8 constant fluid in a porous channel
Authors: Soumya D. O. , Venkatesh P. , Gireesha B. J. , Gombi Manohar R. , Krishnamurthy M. R. 
Published: October 2022

AbstractThe present research is based on the thermal and flow properties of the viscoelastic Oldroyd 8 constant fluid in an upright microchannel. The energy and momentum equations were solved with the support of temperature Jump and velocity slip boundary conditions. To measure the irreversibility rate of the flow system, the acquired results of velocity and thermal equations were used. To crack the current mathematical model problem, the numerical Runge–Kutta–Fehlberg method was used. With the aid of graphs, the effect of physical parameters such as thermal radiation, thermal‐dependent heat source, Joule heating, fluid parameters, velocity slip, and temperature Jump parameters on the fluid flow, thermal energy, and system entropy generation was discussed. Fluid parameters have different effects on the velocity profile. The Grashof and Hartmann numbers demonstrate opposite effects on the momentum field. The thermal energy of the system reduces with thermal radiation and temperature Jump factor. The thermal radiation, Hartmann number, and temperature Jump parameters reduce the system's irreversibility rate. With the Brinkman number and temperature Jump parameter, the irreversibility ratio increases.
Water vulnerability to pesticide contamination in a Brazilian semiarid watershed
Authors: Francelino John W. C. , de  Azevedo Francisco R. , de  Oliveira André Henrique B. , Menezes Jorge M. C. , de  Paula Filho Francisco J. 
Published: October 2022

Abstract
This study aimed to prepare an inventory of the main active ingredients of pesticides and estimate the risk of pollution of groundwater and surface water resources in a Brazilian semiarid basin. The inventory was prepared using data from government agency databases. The contamination risk estimate was obtained using the GOSS index, Groundwater Ubiquity Score (GUS), Groundwater Screening Index (GSI), Leachability Index (LIX), US Environmental Protection Agency (USEPA) criteria, Leaching Index (LEACH), and Relative Leaching Potential Index (RLPI). The inventory identified 57 active ingredients commercialized under a well-defined chemical class. Most of these (51.5%) belong to the very dangerous class, while 43.6% belong to the moderately toxic class. The GOSS model showed that 23.7% of the active ingredients have a low potential, 50.85% have a moderate potential, and 13.56% have a high potential for surface water contamination, with its transport being associated with the sediment. The GUS index indicates a low potential for groundwater contamination. However, the GSI points to a high potential for water contamination, the USEPA criteria for a possible contamination of groundwater, and, according to the LIX, most of the pollutants do so by leaching. The information provided contributes to the management of xenobiotic compounds in arid and semiarid basins, adding to the water security effort by providing tools for the assessment of potential pesticide pollution. Integr Environ Assess Manag 2023;19:804–816. © 2022 SETAC
Determination of the optimum number of sample points to classify land cover types and estimate the contribution of trees on ecosystem services using the I-Tree Canopy tool
Authors: Selim Serdar , Dönmez Burçin , Kilçik Ali 
Published: October 2022

Abstract
The process of producing information about dynamic land use and land cover and ecosystem health quickly with high accuracy and low cost is important. This information is one of the basic data used for sustainable land management. For this purpose, remote sensing technologies are generally used, and sampling points are mostly assigned. Determination of the optimum number of sampling points using the I-Tree Canopy tool was the main focus of this study. The I-Tree Canopy tool classifies land cover, revealing the effects of tree cover on ecosystem services, such as carbon (C) sequestration and storage, temperature regulation, air pollutant filtering, and air quality improvement, with numerical data. It is used because it is practical, open source, and user-friendly. This software works based on sampling point assignment, but it is unclear how many sampling points should be assigned. Therefore, determining the optimum number of sample points by statistical methods will increase the effectiveness of this tool and guide users. For this purpose, reference data were created for comparison. Then, 31 I-Tree Canopy reports were created with 100-point increments up to 3100. The data obtained from the reports were compared with the reference data, and statistical analysis based on Gaussian and a second-order polynomial fit was performed. At the end of the analysis, the following results were obtained; the results of this study demonstrated that the optimum number of sample points for a 1-ha area is 760 ± 32 from the comparison of the real area and I-Tree Canopy results. Similar results from the Gaussian fit of annually sequestered and stored C and carbon dioxide (CO2) amounts in trees and the reduction in air pollution in grams were obtained as 714 ± 16. Therefore, we may conclude that taking more than 800 sample points will not be statistically significant. Integr Environ Assess Manag 2023;19:726–734. © 2022 SETAC
Influences of calorie restriction and lipopolysaccharide therapy on inflammation, cytokine response, and cell proliferation in pancreatic adenocarcinoma mouse model
Authors: Beydogan Alisa B. , Coskun Yazici Zeynep M. , Bolkent Sema 
Published: October 2022

AbstractThe study aimed to investigate the effects of lipopolysaccharide (LPS) alone and in combination with calorie restriction (CR) on the pancreatic tissues in C57BL/6 mice modeled with pancreatic ductal adenocarcinoma (PDAC). Forty male C57BL/6 mice (10‐13 weeks old) were divided into five groups; LPS, LPS + CR, PDAC, PDAC + LPS, and PDAC + LPS + CR. Nuclear factor kappa B (NF‐κβ), interleukin‐6 (IL‐6), and c‐Jun N‐terminal kinases (JNK) mRNA expression levels were measured in pancreatic tissues. NF‐κβ, IL‐6, JNK, and proliferating cell nuclear antigen (PCNA) peptide levels were determined by immunohistochemistry. Oxidative stress markers and antioxidant enzyme activities were determined spectrophotometrically. TH1/TH2 cytokine measurements were determined by a flow cytometer. It was detected that the number of PCNA immune + cells in the PDAC + LPS + CR group was significantly lower than in the PDAC and PDAC + LPS groups (p < 0.01, p < 0.05 respectively). PDAC + LPS + CR group's plasma interferon‐gamma (IFN‐γ), IL‐6, IL‐2, tumor necrosis factor‐alpha, IL‐3, and IL‐4 levels were found to be significantly lower than the PDAC group (p < 0.01, p < 0.001, p < 0.01, p < 0.05, p < 0.01, and p < 0.05 respectively). According to our findings, the combination of low‐dose LPS and 40% CR was found to be more effective in PDAC model mice.
Rebuilding ships while at sea—Character individuality, homology, and evolutionary innovation
Authors: Schlosser Gerhard 
Published: October 2022

AbstractHow novel traits originate in evolution is still one of the most perplexing questions in Evolutionary Biology. Building on a previous account of evolutionary innovation, I here propose that evolutionary novelties are those individualized characters that are not homologous to any characters in the ancestor. To clarify this definition, I here provide a detailed analysis of the concepts of “character individuality” and “homology” first, before addressing their role for our understanding of evolutionary innovation. I will argue (1) that functional as well as structural considerations are important for character individualization; and (2) that compositional (structural) and positional homology need to be clearly distinguished to properly describe the evolutionary transformations of hierarchically structured characters. My account will therefore integrate functional and structural perspectives and put forward a new multi‐level view of character identity and transformation.
Photoinduced Amyloid Fibril Degradation for Controlled Cell Patterning
Authors: Kaygisiz Kübra , Ender Adriana M. , Gačanin Jasmina , Kaczmarek L. Alix , Koutsouras Dimitrios A. , Nalakath Abin N. , Winterwerber Pia , Mayer Franz J. , Räder Hans‐Joachim , Marszalek Tomasz , Blom Paul W. M. , Synatschke Christopher V. , Weil Tanja 
Published: October 2022

AbstractAmyloid‐like fibrils are a special class of self‐assembling peptides that emerge as a promising nanomaterial with rich bioactivity for applications such as cell adhesion and growth. Unlike the extracellular matrix, the intrinsically stable amyloid‐like fibrils do not respond nor adapt to stimuli of their natural environment. Here, a self‐assembling motif (CKFKFQF), in which a photosensitive o‐nitrobenzyl linker (PCL) is inserted, is designed. This peptide (CKFK‐PCL‐FQF) assembles into amyloid‐like fibrils comparable to the unsubstituted CKFKFQF and reveals a strong response to UV‐light. After UV irradiation, the secondary structure of the fibrils, fibril morphology, and bioactivity are lost. Thus, coating surfaces with the pre‐formed fibrils and exposing them to UV‐light through a photomask generate well‐defined areas with patterns of intact and destroyed fibrillar morphology. The unexposed, fibril‐coated surface areas retain their ability to support cell adhesion in culture, in contrast to the light‐exposed regions, where the cell‐supportive fibril morphology is destroyed. Consequently, the photoresponsive peptide nanofibrils provide a facile and efficient way of cell patterning, exemplarily demonstrated for A549, Chinese Hamster Ovary, and Raw Dual type cells. This study introduces photoresponsive amyloid‐like fibrils as adaptive functional materials to precisely arrange cells on surfaces.
Fused Deposition Modeling of Polyolefins: Challenges and Opportunities
Authors: Verma Nandishwar , Awasthi Pratiksha , Gupta Akash , Banerjee Shib Shankar 
Published: October 2022

AbstractPolyolefins are the largest class of commercially available synthetic polymers that are extensively used in a variety of applications from commodities to engineering owing to their low cost of production, good physico‐mechanical properties, light weight, good processability, and recyclability. Compared to conventional molding techniques, fused deposition modeling (FDM)‐based 3D printing is a smart manufacturing technology for thermoplastics due to its low cost, ease of production of complex geometrical parts, rapid prototyping, and scalable customization. FDM 3D printing can be an ideal manufacturing technology for polyolefins to manufacture various complex parts. However, FDM 3D‐printing of polyolefins is challenged bycritical printing problems like high warpage, dimensional inaccuracies, poor bed adhesion, and poor layer‐to‐layer adhesion. In this review, a fundamental understanding of polyolefins and their FDM 3D‐printing process is established, and the recent progress of FDM 3D printing of polyolefins is summarized. Furthermore, strategies to overcome warpage and to improve mechanical strength of the 3D‐printed polyolefins are provided. Finally, future prospectives of FDM 3D‐printing of polyolefins are critically discussed to inspire prospective research in this field. It is believed that this review article can be tremendously useful for research work related to FDM of polyolefin‐based materials.