bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the onset and progression of prostate cancer through a multicellular agent-based model
Authors: Passier Margot , van Genderen Maisa , Zaalberg Anniek , Kneppers Jeroen , Bekers Elise , Bergman Andries M , Zwart Wilbert , Eduati Federica 
Published: February 2023

AbstractOver ten percent of men will be diagnosed with prostate cancer (PCa) during their lifetime. Arising from luminal cells of the prostatic acinus, PCa is influenced by multiple cells in its microenvironment. To expand our knowledge and explore means to prevent and treat the disease, it is important to understand what drives the onset and early stages of PCa. In this study, we developed an agent-based model of a prostatic acinus including its microenvironment, to allow forin silicostudying of PCa development.The model was based on prior reports and in-house data of tumor cells co-cultured with Cancer Associated Fibroblasts (CAFs) and pro-tumor and/or anti-tumor macrophages. Growth patterns depicted by the model were pathologically validated on H&E slide images of human PCa specimens. We identified that stochasticity of interactions between macrophages and tumor cells at early stages strongly affect tumor development. Additionally, we discovered that more systematic deviations in tumor development result from a combinatorial effect of the probability of acquiring mutations and the tumor-promoting abilities of CAFs and macrophages.In silicomodeled tumors were then compared with 494 cancer patients with matching characteristics, showing strong association between predicted tumor load and patients’ clinical outcome. Our findings suggest that the likelihood of tumor formation depends on a combination of stochastic events and systematic characteristics. While stochasticity cannot be controlled, information on systematic effects may aid the development of prevention strategies tailored to the molecular characteristics of an individual patient.
DeXtrusion: Automatic recognition of epithelial cell extrusion through machine learningin vivo
Authors: Villars Alexis , Letort Gaëlle , Valon Léo , Levayer Romain 
Published: February 2023

AbstractEpithelial cell death is highly prevalent during development and in adult tissues. It plays an essential role in the regulation of tissue size, shape, and turnover. Cell elimination relies on the concerted remodelling of cell junctions, so-called cell extrusion, which allows the seamless expulsion of dying cells. The dissection of the regulatory mechanism giving rise to a certain number and pattern of cell death was so far limited by our capacity to generate high-throughput quantitative data on cell death/extrusion number and distribution in various perturbed backgrounds. Indeed, quantitative studies of cell death rely so far on manual detection of cell extrusion events or through tedious systematic error-free segmentation and cell tracking. Recently, deep learning was used to automatically detect cell death and cell division in cell culture mostly using transmission light microscopy. However, so far, no method was developed for fluorescent images and confocal microscopy, which constitute most datasets in embryonic epithelia. Here, we devised DeXtrusion, a pipeline for automatic detection of cell extrusion/cell death events in larges movies of epithelia marked with cell contour and based on recurrent neural networks. The pipeline, initially trained on large movies of theDrosophilapupal notum marked with fluorescent E-cadherin, is easily trainable, provides fast and accurate extrusion/cell death predictions in a large range of imaging conditions, and can also detect other cellular events such as cell division or cell differentiation. It also performs well on other epithelial tissues with markers of cell junctions with reasonable retraining.
Mechanism of germination inhibition ofClostridioides difficilespores by an aniline substituted cholate derivative (CaPA)
Authors: Yip Christopher , Abel-Santos Ernesto 
Published: February 2023

ABSTRACTClostridioides difficileinfection (CDI) is the major identifiable cause of antibiotic-associated diarrhea and has been declared an urgent threat by the CDC.C. difficileforms dormant and resistant spores that serve as infectious vehicles for CDI. To cause disease,C. difficilespores recognize taurocholate and glycine to trigger the germination process. In contrast to other sporulating bacteria,C. difficilespores are postulated to use a protease complex, CspABC, to recognize its germinants. Since spore germination is required for infection, we have developed anti-germination approaches for CDI prophylaxis. Previously, the bile salt analog CaPA (an aniline-substituted cholic acid) was shown to block spore germination and protect rodents from CDI caused by multipleC. difficilestrains.In this study, we found that CaPA is an alternative substrate inhibitor ofC. difficilespore germination. By competing with taurocholate for binding, CaPA delaysC. difficilespore germination and reduces spore viability, thus diminishing the number of outgrowing vegetative bacteria. We hypothesize that the reduction of toxin-producing bacterial burden explains CaPA’s protective activity against murine CDI. Previous data combined with our results suggests that CaPA binds tightly toC. difficilespores in a CspC-dependent manner and irreversibly trap spores in an alternative, time-delayed, and low yield germination pathway. Our results are also consistent with kinetic data suggesting the existence of at least two distinct bile salt binding sites inC. difficilespores.
Smart orchard design improves crop pollination
Authors: Anders Mina , Grass Ingo , Linden Valerie M. G. , Taylor Peter J. , Westphal Catrin 
Published: February 2023

Abstract

More sustainable and environmentally friendly agricultural practices, including ecological intensification, are needed to reduce biodiversity loss and environmental degradation.

We evaluated the potential of ecological intensification through the enhancement of pollination services in an intensively managed and insect‐pollinated crop, Macadamia integrifolia. We compared the effects and importance of agronomic practices that include agronomic input (i.e. irrigation and managed honeybees), orchard design requiring no external inputs (i.e. spatial orchard structure) and landscape factors in 10 South African macadamia orchards.

In comparison to experimental pollinator exclusion, insect pollination increased the initial and final nut set by 304% and 23%, respectively. However, nut set was pollination limited as hand pollination further improved nut set.

Flower visitation rates increased with the cover of semi‐natural habitats in the surrounding landscape (1 km radius). This effect was outperforming the effect of the number of managed honeybee colonies, as agronomic practice.

Initial nut set increased with orchard design and flower visitation rates. Perpendicular orientation of the planted macadamia rows towards the semi‐natural habitats increased initial nut set more than threefold compared to parallel row orientation. The initial nut set was 80% higher at the edge to semi‐natural habitats than in the orchard centre. In contrast, agronomic practices, such as irrigation, did not increase initial nut set. Final nut set depended on the preconditions of the initial nut set, additionally, high altitudes and the position in the centre of the orchard had positive effects.

Synthesis and applications: Pollination services were prerequisites for high yields in macadamia and could be improved without further agronomic input. Especially, the orchard design, that is, spatial arrangement of tree rows and semi‐natural habitats at local and landscape scales, was more important to boost insect pollination and the initial development of macadamia nuts than agronomic practices, such as high levels of irrigation. Considering the urgency to reduce the environmental impacts of agricultural production, we highlight the high potential of ecological intensification by a smart orchard design and the restoration and conservation of semi‐natural habitats in the orchards and their surrounding landscape.
Managing the energy trilemma of reliability, affordability and renewables: Assessing consumer demands with discrete choice experiments
Authors: Tocock Mark , Tinch Dugald , Hatton MacDonald Darla , Rose John M. 
Published: February 2023

AbstractIn response to the looming climate crisis, many countries are adopting technologies to reduce the accumulation of greenhouse gases. However, national energy policies are often multiobjective and resolution deeply divisive. The result is a policy trilemma between the energy mix and the trade‐offs with other policy objectives, including cost and reliability. Utilising a discrete choice experiment (DCE), the objective of this study is to explore Australian household preferences for alternative electricity contracts containing features reflecting changes in future energy policy. The first set of features include investments in renewable generation and community‐based energy storage. The second set of features reflect demand‐side management policies, including installing smart meters and consumption limits being imposed on households during peak demand. Two versions of the DCE were developed to obtain both willingness to pay and willingness to accept estimates for the same features. In line with the literature, differences in the two sets of estimates were observed, with the willingness to accept estimates being statistically larger for some features. These dollar value measures can be used to support public policy decision‐making – the choice of which depending on the context of the policy problem being considered.
Search, learning, and tracking
Authors: Preuss Marcel 
Published: February 2023

AbstractIn many search markets, some consumers search to learn both the price and their willingness‐to‐pay whereas others search only to learn prices. When a seller can track indicators of the likelihood that consumers already know their willingness‐to‐pay, I show that price discrimination reduces profits and welfare relative to uniform pricing if search costs are small, but may increase both if search costs are large. The analysis also applies to sequential search if learning causes the likelihood that consumers know their willingness‐to‐pay to depend on the search history.
Delivery system emergency department capacity and its effect on nonsystem service utilization
Authors: Tenso Kertu , Pizer Steven , Palani Sivagaminathan 
Published: February 2023

AbstractBackgroundEmergency department (ED) use is often seen as a source of excess health care spending, prompting managers to limit ED capacity in their health systems. However, if limited ED capacity in a delivery system leads patients to seek emergency care elsewhere, then health care quality and efficient management may be compromised within the system.ObjectiveThe objective of this study was to explore the effect of the Veterans Health Administration (VHA) in‐house ED clinician capacity on VHA community care (CC) ED claims.MethodsWe used administrative data from the VHA to identify CC ED claims and Department of Veterans Affairs emergency physician (EP) capacity for 2014–2019. We used quasi‐experimental instrumental variables approach with two different instruments: percent weekday federal holidays and VHA EP full‐time equivalents (FTEs). We controlled for VHA ED variables such as ED wait times (door to triage, door to doctor, and door to admission) and demand variables such as alternative insurance coverage, driving time to VHA care, and demographic variables (employment, age, household income, race, gender, and VHA priority status).ResultsAfter instrumenting for capacity with percent weekday federal holidays, we found that one clinic‐day capacity (one 8‐h ED shift) per 10,000 enrollees increase at the VHA ED will result in a reduction of 61 CC ED claims per 10,000 enrollees. After instrumenting for capacity with EP FTE, we found that one clinic‐day capacity (one 8‐h ED shift) per 10,000 enrollees increase at the VHA ED will result in a reduction of 48 CC ED claims per 10,000 enrollees. Both of these results are statistically significant at p < 0.001.ConclusionsOur findings imply that offering more in‐house ED care, in the form of clinician capacity, can substantially reduce out‐of‐system ED use. The results may be of interest to integrated health care system managers who prefer their patients to stay within network.
Chronic ethanol exposure induces mitochondrial dysfunction and alters gene expression and metabolism in human cardiac spheroids
Authors: Hwang Hyun , Liu Rui , Eldridge Ronald , Hu Xin , Forghani Parvin , Jones Dean P. , Xu Chunhui 
Published: February 2023

AbstractBackgroundChronic alcohol consumption in adults can induce various cardiac toxicities such as arrhythmias, cardiomyopathy, and heart failure. Prenatal alcohol exposure can increase the risk of developing congenital heart defects among offspring. Understanding the molecular mechanisms underlying long‐term alcohol exposure‐induced cardiotoxicity can help guide the development of therapeutic strategies.MethodsCardiomyocytes derived from human‐induced pluripotent stem cells (hiPSC‐CMs) were engineered into cardiac spheroids and treated with clinically relevant concentrations of ethanol (17 and 50 mM) for 5 weeks. The cells were then analyzed for changes in mitochondrial features, transcriptomic and metabolomic profiles, and integrated omics outcomes.ResultsFollowing chronic ethanol treatment of hiPSC‐CMs, a decrease in mitochondrial membrane potential and respiration and changes in expression of mitochondrial function‐related genes were observed. RNA‐sequencing analysis revealed changes in various metabolic processes, heart development, response to hypoxia, and extracellular matrix‐related activities. Metabolomic analysis revealed dysregulation of energy metabolism and increased metabolites associated with the upregulation of inflammation. Integrated omics analysis further identified functional subclusters and revealed potentially affected pathways associated with cardiac toxicities.ConclusionChronic ethanol treatment of hiPSC‐CMs resulted in overall decreased mitochondrial function, increased glycolysis, disrupted fatty acid oxidation, and impaired cardiac structural development.
Mid‐term outcomes of laparoscopic vs open colectomy for pathological T4 and/or N2 colon cancer patients: Multicenter study using propensity score matched analysis
Authors: Hashimoto Shintaro , Tominaga Tetsuro , Nonaka Takashi , Shiraishi Toshio , To Kazuo , Takeshita Hiroaki , Fukuoka Hidetoshi , Araki Masato , Tanaka Kenji , Sawai Terumitsu , Nagayasu Takeshi 
Published: February 2023

AbstractObjectivesWe aimed to assess mid‐term outcomes after laparoscopic surgery (LAP) vs open surgery (OP) for pathological T4 (pT4) and/or N2 (pN2) colon cancer.MethodsWe retrospectively reviewed 255 primary tumor resections for pT4 and/or pN2 colon cancer performed from 2015 to 2020 at six hospitals, divided into LAP (n = 204) and OP groups (n = 51). After propensity score matching to minimize selection bias, 47 matched patients per group were assessed.ResultsBefore matching, the rate of males (53.9% vs. 37.3%, P = .042), left sided colon cancer (53.9% vs 37.3%, P = .042), D3 lymph node dissection (90.7% vs 68.6%, P < .001) and body mass index (kg/m2) (22.3 vs 21.8, P = .039) were significantly greater in the LAP group. The rate of pT4b (7.8% vs 40.4%, P < .001) was lower and pN2 was higher (57.4% vs 37.3%, P = .012) in the LAP group. After matching, preoperative characteristics and pathologic status were equivalent between the groups. The LAP and OP groups showed comparable overall survival (OS) (2‐year OS, 84.5% vs 76.8%, P = .055) and recurrence‐free survival (RFS) (2‐year RFS, 73.9% vs 52.8%, P = .359). In the patients with pT4, OS (2‐year OS, 79.4% vs 75.7%, P = .359) and RFS (2‐year RFS, 71.3% vs 58.7%) were comparable. In the patients with pN2, OS (2‐year OS, 83.4% vs 76.3%) and RFS (2‐year RFS, 69.6% vs 36.2%) were also comparable.ConclusionsLAP for pT4 and/or pN2 colon cancer showed comparable mid‐term outcomes compared with OP. LAP was an acceptable surgical approach in this cohort.
Urine supernatant reveals a signature that predicts survival in clear‐cell renal cell carcinoma
Authors: Daza Jorge , Salomé Bérengère , Okhawere Kennedy , Bane Octavia , Meilika Kirolos N. , Korn Talia G. , Qi Jingjing , Xe Hui , Patel Manishkumar , Brody Rachel , Kim‐Schulze Seunghee , Sfakianos John P. , Lewis Sara , Rich Jordan M. , Zuluaga Laura , Badani Ketan K. , Horowitz Amir 
Published: February 2023

ObjectiveTo profile the cell‐free urine supernatant and plasma of a small cohort of clear‐cell renal cell carcinoma (ccRCC) patients by measuring the relative concentrations of 92 proteins related to inflammation. Using The Cancer Genome Atlas (TCGA), we then performed a targeted mRNA analysis of genes encoding the above proteins and defined their effects on overall survival (OS).Subjects/patients and MethodsSamples were collected prospectively from ccRCC patients. A multiplex proximity extension assay was used to measure the concentrations of 92 inflammation‐related proteins in cell‐free urine supernatants and plasma. Transcriptomic and clinical information from ccRCC patients was obtained from TCGA. Unsupervised clustering and differential protein expression analyses were performed on protein concentration data. Targeted mRNA analysis on genes encoding significant differentially expressed proteins was performed using TCGA. Backward stepwise regression analyses were used to build a nomogram. The performance of the nomogram and clinical benefit was assessed by discrimination and calibration, and a decision curve analysis, respectively.ResultsUnsupervised clustering analysis revealed inflammatory signatures in the cell‐free urine supernatant of ccRCC patients. Backward stepwise regressions using TCGA data identified transcriptomic risk factors and risk groups associated with OS. A nomogram to predict 2‐year and 5‐year OS was developed using these risk factors. The decision curve analysis showed that our model was associated with a net benefit improvement compared to the treat‐all/none strategies.ConclusionWe defined four novel biomarkers using proteomic and transcriptomic data that distinguish severity of prognosis in ccRCC. We showed that these biomarkers can be used in a model to predict 2‐year and 5‐year OS in ccRCC across different tumour stages. This type of analysis, if validated in the future, provides non‐invasive prognostic information that could inform either management or surveillance strategies for patients.
Oral contraceptives (OCs) in combination with metformin versus OCs alone on metabolism in nonobese polycystic ovary syndrome: A meta‐analysis and systematic review of randomized controlled trials
Authors: Wu Limei , Liu Ye , Huang Xi , Lin Kaiping , Liu Yang , Li Zhizun , Wei Tianqin , Song Ling , Hua Yuanyuan , Wang Xiaoli 
Published: February 2023

AbstractBackgroundTo compare OCs(oral contraceptives) + metformin and OCs alone for metabolic effects in nonobese polycystic ovary syndrome (PCOS) patients.MethodsThe search was performed in PubMed, EMBASE, the Cochrane Library and clinicaltrials.gov for all published studies up to 30 April 2022 and was limited to English‐language articles. All randomized controlled trials (RCTs) comparing OCs + metformin and OCs alone for reproductive‐age women with PCOS were included. Data were processed using Revman 5.3 software.ResultsOf 396 studies identified, 14 RCTs were included for analysis comprising 707 women. OCs+metformin significantly modified fasting glucose (MD = −0.21 [95% confidence interval (CI) = −0.31, −0.12], p < .00001) and fasting insulin (MD = −2.54 [95%CI = −4.04, −1.04], p = .0009) at study completion compared with OCs alone in nonobese PCOS subjects. There was no statistic difference in the homoeostasis model assessment of insulin resistance (HOMA‐IR), high‐density lipoprotein (HDL), low‐density lipoprotein (LDL), total cholesterol or triglycerides at study end between the two groups.ConclusionsMetformin, via its positive effects on insulin clearance, in combination with OCs, improved glucose metabolism and offered a good treatment alternative in nonobese women with PCOS.
Media reporting on alcohol and other drugs in Australia and the Mindframe guidelines: Baseline data
Authors: Sunderland Matthew , Kershaw Stephanie , Ward Caitlin , Bryant Zachary , Teesson Lily , Whittle Rebecca , Paton Elizabeth , Charnley Janine L. , Skehan Jaelea 
Published: February 2023

AbstractIntroductionThe aim of this study was to generate a baseline database of print media reporting on alcohol and other drug (AOD) issues prior to the release of the Mindframe guidelines in March 2019. Specifically, to: (i) describe the content associated with media entries that focus on AOD use in Australian news media; (ii) determine how the media entries compare to several domains associated with recently developed Mindframe guidelines for publicly reporting on AOD; and (iii) identify content factors associated with different scores.MethodsMedia entries between July 2016 and June 2017 were searched for key AOD‐related terms using the Australian and New Zealand Newsstream database. Two coding schemes were developed to rate a stratified sample of 50% of the media entries against the Mindframe guidelines. Associations between content and total comparison scores were determined using linear regression models.ResultsDetailed coding of the 2007 articles identified as relevant for the current study indicated that a majority (67%) were focused on one of three substances: alcohol, cannabis or methamphetamine. Most of the entries were either law enforcement (22%) or criminal justice related (19%). Entries that focused on methamphetamine scored significantly lower than entries on alcohol when compared to the Mindframe guidelines, similarly entries focused on crime/justice‐related topics scored significantly lower than entries focused on positive outcomes.Discussion and ConclusionsA disproportionate number of print media entries, particularly those related methamphetamine use, focused on crime or justice‐related topics, potentially further contributing to stigma, and emphasising the legal consequences of AOD use.
Consensus on level descriptors for a functional children's eating and drinking activity scale
Authors: Hanks Emily , Stewart Alexandra , Au‐Yeung Claudia Kate , Johnson Emily , Smith Christina H. 
Published: February 2023

AbstractAimTo agree wording of level descriptors for a measure of functional outcome of children's eating and drinking.MethodAn online, modified Delphi method was used to gather feedback on current level descriptor wording and generate rewording suggestions. Thirty speech and language therapists, working in a variety of settings and geographical locations, were invited to be part of the Delphi expert panel. Content analysis was used to evaluate participants' comments and develop consensus level descriptors. Consensus for acceptable wording was set at 80% agreement. Face validity was assessed using 5‐point Likert scales.ResultsNineteen expert speech and language therapists (median experience 18 years) completed round one; 15 out of 19 completed round two. Level descriptor rating reached 80% agreement in two rounds. Additionally, 93% of participants agreed the scale would accurately capture change in their setting, with 87% likely to use the scale in practice.InterpretationThis study has produced agreed wording for a functional measure of eating and drinking activity suitable for use with paediatrics feeding disorders, regardless of disease aetiology, presentation, age, or setting. Potential for widespread use is supported. Further evaluation of the tool's reliability and validity is required.