bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultraprocessed plant‐based foods: Designing the next generation of healthy and sustainable alternatives to animal‐based foods
Authors: McClements David Julian 
Published: June 2023

AbstractNumerous examples of next‐generation plant‐based foods, such as meat, seafood, egg, and dairy analogs, are commercially available. These products are usually designed to have physicochemical properties, sensory attributes, and functional behaviors that match those of the animal‐sourced products they are designed to replace. However, there has been concern about the potential negative impacts of these foods on human nutrition and health. In particular, many of these products have been criticized for being ultraprocessed foods that contain numerous ingredients and are manufactured using harsh processing operations. In this article, the concept of ultraprocessed foods is introduced and its relevance to describe the properties of next‐generation plant‐based foods is discussed. Most commercial plant‐based meat, seafood, egg, and dairy analogs currently available do fall into this category, and so can be classified as ultraprocessed plant‐based (UPB) foods. The nutrient content, digestibility, bioavailability, and gut microbiome effects of UPB foods are compared to those of animal‐based foods, and the potential consequences of any differences on human health are discussed. Some commercial UPB foods would not be considered healthy based on their nutrient profiles, especially those plant‐based cheeses that contain low levels of protein and high levels of fat, starch, and salt. However, it is argued that UPB foods can be designed to have good nutritional profiles and beneficial health effects. Finally, areas where further research are still needed to create a more healthy and sustainable food supply are discussed.
A nozzle simulation chip toward high‐throughput formation of curcumin‐loaded zein nanoparticles with tunable properties
Authors: Lei Yanlin , Kilker Sean , Lee Youngsoo 
Published: June 2023

AbstractSize of nanoparticle (NP) is a crucial factor in determining its applicability to various fields. This study aimed to develop a nozzle chip for the scalable formation of self‐assembled curcumin‐loaded zein NPs with tunable properties. A four‐factor (zein concentration in dispersed phase, ethanol concentration in continuous phase, flow rate ratio, and total flow rate), three‐level Box–Behnken design on the measured responses (particle size and polydispersity index [PDI]) was established. The particle size and PDI, ranging from 194.43 to 420.51 nm, and 0.089 to 0.219, respectively, were readily controlled by adjusting four factors. Under the optimal conditions of 6% zein, 0% EtOH, the flow rate ratio of 7, and a total flow rate of 8 mL/min targeting higher production rate, the particle size of 306.02 ± 1.52 nm (mean ± standard deviation) and the PDI of 0.135 ± 0.001 were obtained. High throughput for zein NP production (86.4 g/day) was reached, which was 200 and 960 times higher than using microfluidic and electrospraying techniques, respectively. Curcumin‐loaded zein NPs under the abovementioned experimental conditions were successfully prepared via the nozzle chip with the encapsulation efficiency of 64.29% ± 0.29%, a loading capacity of 3.06% ± 0.01%, enhanced stability, and improved in vitro antioxidant properties. Curcumin was primarily released from zein NPs in the simulated intestinal phase. This study demonstrated that the property of self‐assembled zein NPs can be tuned by altering the operating parameters using the nozzle simulation chip. The results suggest that this approach has potential for use in the food and pharmaceutical industries, particularly for curcumin encapsulation.Practical ApplicationThe fabricated nozzle chip is a promising technology to obtain zein nanoparticles (NPs) with enhanced productivity and narrow particle size distribution. It can be easily adopted to spray drying process. Besides, the nozzle chip shows the potential for the large‐scale production of bioactive loaded zein NPs in the food or pharmaceutical industries.
Lactate secreted by esophageal cancer cells induces M2 macrophage polarization via the AKT/ERK pathway
Authors: Zhang Chunsheng , Cheng Wei , Yang Tongjin , Fang Hanlin , Zhang Renquan 
Published: June 2023

AbstractBackgroundElevated lactate results in an acidic tumor microenvironment (TME), which stimulates the progression of esophageal cancer (EC). Tumor‐associated macrophages (TAMs) are an essential component of the TME. However, the regulatory mechanisms of lactate secreted by EC on TAMs and the effects of EC advancement are unclear.MethodsProteins and mRNA expression were determined by western blot and RT‐qPCR. Cell metastasis and growth were assessed by scratch assay, transwell and BrdU assays. Lactate in cells was quantified using a lactate kit. A mouse model was constructed for validation in vivo.ResultsFirst, we determined that lactate upgraded the M2‐type polarization marker levels of macrophages. Cell function assays confirmed that lactate‐activated M2 macrophages accelerated EC cell migration and proliferation in vitro. However, the lactate inhibitor – oxamate hampered the level of lactate in TE‐1 cells. Oxamate abolished the facilitation of macrophage polarization by lactate. In addition, we discovered that phosphorylated AKT and phosphorylated ERK was obviously raised in lactate‐stimulated macrophages, and oxamate addition reversed this change, implying that AKT and ERK signaling pathways were involved in macrophage polarization. Response experiments proved that attenuation of AKT/ERK signaling markedly returned the lactate‐induced promotion of EC migration and proliferation by macrophages. Finally, mouse tumor models demonstrated that lactate enhanced EC growth by inducing M2 macrophage polarization.ConclusionEC‐secreted lactate stimulated macrophage M2 polarization via the AKT/ERK pathway thereby boosting the growth of EC.
Silencing of circUSPL1 represses breast cancer progression by targeting miR‐1296‐5p/MTA1 axis
Authors: Wang Peien , Qu Haijiang , Wang Lin , Hu Zhe 
Published: June 2023

AbstractBackgroundThe effect of circular RNAs (circRNAs) is widely studied in various human cancers, including breast cancer (BC). Herein, circUSPL1 has been recognized as a new regulator for BC progression. However, the detailed biological function and molecular mechanism of circUSPL1 in BC remain vague.MethodsThe expression level of circUSPL1, miR‐1296‐5p and metastasis associated 1 (MTA1) was examined by quantitative reverse transcription PCR. BC cell proliferation, migration, invasion, apoptosis and aerobic glycolysis were analyzed by colony formation assay, 5‐ethynyl‐2′‐deoxyuridine assay, wound healing assay, transwell assay, flow cytometry and glycolysis corresponding kits, respectively. The protein level of Bcl‐2, Bax, HK2, GLUT1 and MTA1 was evaluated by western blot analysis. The relationship of miR‐1296‐5p and circUSPL1 or MTA1 was affirmed using dual‐luciferase reporter or RIP assays. A murine xenograft model was conducted to analyze the tumor growth in vivo.ResultsCircUSPL1 and MTA1 expression level was increased, but miR‐1296‐5p was particularly reduced in BC tissues and cells. CircUSPL1 deficiency significantly inhibited BC cell proliferation, migration, invasion, glycolysis, and promoted cell apoptosis. In addition, circUSPL1 directly targeted miR‐1296‐5p, and downregulation of miR‐1296‐5p eliminated the inhibitory action of circUSPL1 knockdown. Additionally, overexpression of miR‐1296‐5p repressed cell malignant properties, while the suppressive effects were overturned by MTA1 elevation. Lastly, silencing of circUSPL1 inhibited tumor growth by sponging miR‐1296‐5p and regulating MTA1.ConclusionCircUSPL1 deficiency repressed BC cell malignant phenotypes through reducing MTA1 via targeting miR‐1296‐5p, which might provide a theoretical basis for BC treatment.
Integrating POLE/POLD1 mutated for immunotherapy treatment planning of advanced stage non‐small cell lung cancer
Authors: Zheng Shuhua , Cao Yenong , Randall James , Yu Haomin , Thomas Tarita O. 
Published: June 2023

AbstractBackgroundIn this study, we evaluated the potential of DNA polymerase epsilon (POLE) and DNA polymerase delta 1 (POLD1) as prognostic biomarkers for immune checkpoint inhibitor (ICI) treatment in patients with advanced stage non‐small cell lung cancer (NSCLC).MethodsDisease stage, PD‐L1 positivity, histological subtypes, POLE/POLD1 mutation status, tumor mutation burden (TMB), and response to ICIs in NSCLC cases were derived from AACR GENIE dataset (n = 24 120), TCGA‐Pan Lung Cancer dataset (n = 1144), AACR GENIE BPC NSCLC v2.0‐public (n = 2004), and Memorial Sloan Kettering‐Integrated Mutation Profiling of Actionable Cancer Targets dataset (n = 350). The smoking history from TCGA and AACR GENIE datasets was grouped into current, former or never‐smokers.ResultsPOLE and POLD1 genetic alterations were identified in 5% and 2.6% of NSCLC patients, respectively. Current smokers had 9% and 4% of POLE/POLD1 mutations, respectively, versus 1.7% for both POLE and POLD1 mutations prevalence in never‐smokers. POLE/POLD1 mutations were associated with elevated mutation counts than those with wild‐type (median mutation counts 16 vs. 7, p < 0.0001), more advanced disease stages (stage I disease 15.19% vs. 29.42%), more prevalent squamous histology subtype (21.69% vs. 9.05%, p = 0.0427), and a higher percentage of PD‐L1 positivity (66.67% vs. 43.87%, p < 0.001). Treatment with ICIs improved survival in patients with both POLE/POLD1 mutated and those with TMB > 18 (p < 0.001).ConclusionCurrent smokers have a five‐fold increased risk of having POLE mutations than never‐smokers. POLE/POLD1 mutation status and TMB > 18 can be a composite biomarker for selecting NSCLC patients with survival benefits to ICI treatment.
Evaluation of appropriate conditions for Oncomine DxTT testing of FFPE specimens for driver gene alterations in non–small cell lung cancer
Authors: Iwama Eiji , Yamamoto Hidetaka , Okubo Fumihiko , Ijichi Kayo , Ibusuki Ritsu , Shiaraishi Yoshimasa , Yoneshima Yasuto , Tanaka Kentaro , Oda Yoshinao , Okamoto Isamu 
Published: June 2023

AbstractBackgroundThe Oncomine Dx Target Test Multi‐CDx System (ODxTT) is a next‐generation sequencing panel approved as a companion diagnostic for drugs targeted to corresponding gene alterations in non–small cell lung cancer. However, appropriate slide conditions for ODxTT have remained unclear.MethodsWe focused on the production of the number of tumor cells on a formalin‐fixed paraffin‐embedded (FFPE) section and the number of prepared slides, designated the TS value, and determined a TS value of ≥4000 as a target slide condition for ODxTT. We evaluated the impact of this condition on ODxTT testing with tumor specimens found to have a TS of <4000 (n = 23) or a TS of ≥4000 (n = 142).ResultsA positive correlation was apparent between the TS value and the concentrations of both DNA and RNA. Among the 142 samples with a TS of ≥4000, a sufficient concentration of DNA or RNA for ODxTT analysis was achieved in 100% and 98% samples, respectively. Among samples explored for driver gene alterations after determination of the target slide condition (TS ≥4000), most (84.9%) had a TS of ≥4000 and were submitted for ODxTT analysis.ConclusionOur findings indicate that a TS of ≥4000 is a feasible and relevant criterion for ODxTT testing, and its adoption should help to improve the success rate of such testing in clinical practice.
Good clinical research practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents III: The 2023 Geneva revision
Authors: Fuchs‐Buder Thomas , Brull Sorin J. , Fagerlund Malin Jonsson , Renew J. Ross , Cammu Guy , Murphy Glenn S. , Warlé Michiel , Vested Matias , Fülesdi Béla , Nemes Reka , Columb Malachy O. , Damian Daniela , Davis Peter J. , Iwasaki Hajime , Eriksson Lars I. 
Published: June 2023

AbstractThe set of guidelines for good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents was developed following an international consensus conference in Copenhagen in 1996 (Viby‐Mogensen et al., Acta Anaesthesiol Scand 1996, 40, 59–74); the guidelines were later revised and updated following the second consensus conference in Stockholm in 2005 (Fuchs‐Buder et al., Acta Anaesthesiol Scand 2007, 51, 789–808). In view of new devices and further development of monitoring technologies that emerged since then, (e.g., electromyography, three‐dimensional acceleromyography, kinemyography) as well as novel compounds (e.g., sugammadex) a review and update of these recommendations became necessary. The intent of these revised guidelines is to continue to help clinical researchers to conduct high‐quality work and advance the field by enhancing the standards, consistency, and comparability of clinical studies.There is growing awareness of the importance of consensus‐based reporting standards in clinical trials and observational studies. Such global initiatives are necessary in order to minimize heterogeneous and inadequate data reporting and to improve clarity and comparability between different studies and study cohorts. Variations in definitions of endpoints or outcome variables can introduce confusion and difficulties in interpretation of data, but more importantly, it may preclude building of an adequate body of evidence to achieve reliable conclusions and recommendations. Clinical research in neuromuscular pharmacology and physiology is no exception.
ABC‐training as a new intervention for hazardous alcohol drinking: Two proof‐of‐principle randomized pilot studies
Authors: Van Dessel Pieter , Cummins Jamie , Wiers Reinout W. 
Published: June 2023

AbstractBackground and AimsABC‐training is a new intervention to encourage health behavior change that targets the automatic activation of adaptive beliefs (i.e. automatic inferences). The aim of this proof‐of‐principle study was to test the effectiveness of web‐based ABC‐training to change outcome expectancies of alcohol drinking in a sample of hazardous drinkers.DesignOne exploratory and one confirmatory experiment with two between‐subject conditions (online ABC‐ and control‐training) and assessments at baseline and 1 week later (after three sessions of training).SettingParticipants recruited on Prolific Academic completed the web‐based study.ParticipantsAdults with self‐reported hazardous alcohol drinking (Experiment 1: 193 adults, United Kingdom, age mean = 46.7 years; Experiment 2: 282 adults, different nationalities, age mean = 38.3 years).Intervention and ComparatorABC‐training involved completing an online task that required choosing personally relevant alternative behaviors to drinking alcohol in personally relevant antecedent contexts to attain personally important outcomes. Comparator was control‐training, in which participants selected both the alternative behaviors and alcohol drinking an equal number of times. Training was completed at baseline, after 3 days and after 1 week.MeasurementsPrimary outcome was change in automatic and self‐reported (negative/positive) outcome expectancies of alcohol drinking from baseline to after 1 week. Secondary outcomes were change in weekly alcohol consumption, self‐efficacy, craving and motivation (and approach‐alcohol associations in Experiment 1). Moderators were baseline outcome scores, motivation, age and alcohol dependency.FindingsFindings of this study are as follows: stronger increase in negative outcome expectancies after ABC‐ than control‐training (Experiment 1: self‐report, 95% confidence interval of difference scores (CIdiff) = [0.04, Inf]; automatic, CIdiff = [0.01, Inf]; Experiment 2: self‐report, CIdiff = [0.16, Inf]; automatic, CIdiff = [0.002, Inf]). Stronger reduction in self‐reported positive outcome expectancies after ABC‐ than control‐training (Experiment 1: CIdiff = [−Inf, −0.01]; Experiment 2: CIdiff = [−Inf, −0.21]) but mixed findings on automatic positive outcome expectancies (Experiment 1: CIdiff = [−Inf, 0.02]; Experiment 2: CIdiff = [−Inf, −0.001]).ConclusionsABC‐training may change outcome expectancies of alcohol consumption, but testing of clinically relevant effects in other samples is warranted.
The role of hyperbaric oxygen in osteoradionecrosis—a prophylactic insight
Authors: Dang B , Gamage S , Sethi S , Jensen ED , Sambrook P , Goss A 
Published: June 2023

AbstractBackgroundOsteoradionecrosis (ORN) is an uncommon and debilitating consequence of head and neck radiotherapy and hyperbaric oxygen therapy (HBOT) has been advocated for prophylaxis prior to performing dentoalveolar procedures. The aim of this study was to evaluate a prophylactic HBOT protocol and describe the outcomes of susceptible individuals.MethodsA retrospective audit of adults who attended the Oral and Maxillofacial Surgery department at the Royal Adelaide Hospital (South Australia) who received dental extractions with a history of radiotherapy to the jaws from 2008 to 2020. Data including demographic information and outcomes of osteoradionecrosis and delayed healing was recorded.ResultsA total of 121 individuals were eligible for case note review; 68.6% of individuals were male and 55.4% were aged over 67 years. Osteoradionecrosis occurred in 9.1% of individuals and delayed healing for 3.3%; fifteen individuals (12.4%) were unable to complete the HBOT protocol. The individuals who were diagnosed with ORN had a significant association with age (P = 0.006) and binary analysis showed alcohol consumption to be a significant predictor.ConclusionsProphylactic HBOT protocol had a lower proportion of individuals diagnosed with ORN and those who were diagnosed were more likely to be younger males and have current alcohol consumption.
Privacy challenges in geodata and open data
Authors: Solymosi Reka , Buil‐Gil David , Ceccato Vania , Kim Eon , Jansson Ulf 
Published: June 2023

AbstractThis article presents a discussion of the emerging ethical issue of geodata privacy in geographical research. The paper highlights the importance of considering challenges to privacy when working with geographically explicit data and explores explicit ways in which researchers and practitioners can be conscious of these issues. Through summarising the key problems in this area and presenting outstanding open research areas and questions from a seminar series on geodata privacy, we highlight important considerations for future research in this field. We focus on the specific topics of appropriate anonymization, responsible data dissemination, the balance between data sharing and privacy, and the challenges posed by working across international contexts. We conclude by recommending approaches to manage various legal and ethical frameworks, raise the importance of the international context, and inspire future research to address the challenges of safeguarding sensitive geodata while promoting openness and transparency.
Comparing the effectiveness of two reciprocal reading comprehension interventions for primary school pupils in disadvantaged schools
Authors: O'Hare Liam , Stark Patrick , Cockerill Maria , Lloyd Katrina , McConnellogue Sheila , Gildea Aideen , Biggart Andy , Bower Christine , Connolly Paul 
Published: June 2023

AbstractBackgroundEffective reading comprehension teaching is an aspiration of education systems across the world. Teaching incorporating reciprocal reading theory and evidence is an internationally popular approach for improving comprehension.AimsThis paper uses two large cluster randomized controlled trials of similar reciprocal reading interventions implemented in different ways to compare their effectiveness.SampleThe two interventions had the same teacher professional development, reciprocal reading activities and dosage/exposure, but varied in their implementation, with one delivered as a whole‐class (‘universal’) version for pupils aged 8–9 years and the other a small group (‘targeted’) version for pupils aged 9–11 years with specific comprehension difficulties.MethodsTwo large‐scale cluster RCTs were conducted in 98 schools with N = 3699 pupils in the universal trial and N = 1523 in the targeted trial.ResultsMulti‐level models showed significant effects for the targeted version of the intervention on pupil reading comprehension (g = .18) and overall reading (g = .14). No significant effects were found for the whole class version. A sub‐group analyses of disadvantaged pupils showed the targeted intervention's effects were even larger on reading comprehension (g = .25).ConclusionsThe evidence suggested that this reciprocal reading intervention worked best when implemented in small groups and targeted for pupils with specific comprehension difficulties and particularly for pupils in disadvantaged circumstances.CommentsThis evaluation shows that even if a reading comprehension intervention is underpinned by strong theory and evidence‐based practice, its effectiveness can still depend on implementation choices.
NFE2L3 drives hepatocellular carcinoma cell proliferation by regulating the proteasome‐dependent degradation of ISGylated p53
Authors: Ren Yonggang , Yang Jing , Ding Zhiran , Zheng Menghua , Qiu Lu , Tang Aifa , Huang Dandan 
Published: June 2023

AbstractNuclear factor erythroid 2‐like 3 (NFE2L3) is a member of the cap ‘n’ collar basic‐region leucine zipper (CNC‐bZIP) transcription factor family that plays a vital role in modulating oxidation–reduction steady‐state and proteolysis. Accumulating evidence suggests that NFE2L3 participates in cancer development; however, little is known about the mechanism by which NFE2L3 regulates hepatocellular carcinoma (HCC) cell growth. Here, we confirmed that NFE2L3 promotes HCC cell proliferation by acting as a transcription factor, which directly induces the expression of proteasome and interferon‐stimulated gene 15 (ISG15) to enhance the proteasome‐dependent degradation of ISGylated p53. Post‐translational ISGylation abated the stability of p53 and facilitated HCC cell growth. In summary, we uncovered the pivotal role of NFE2L3 in promoting HCC cell proliferation during proteostasis. This finding may provide a new target for the clinical treatment of HCC.
Influence of abutment macro‐ and micro‐geometry on morphologic and morphometric features of peri‐implant connective tissue
Authors: Canullo Luigi , Giuliani Alessandra , Furlani Michele , Menini Maria , Piattelli Adriano , Iezzi Giovanna 
Published: June 2023

AbstractObjectivesThe aim of the present human observational study is to provide morphologic and morphometric analysis of peri‐implant connective tissue next to abutments with divergent or convergent macro‐geometry and different surface micro‐characteristics.Materials and MethodsThirty patients were rehabilitated with single implants in the posterior area and one out of three different healing abutments with a one‐stage technique: machined divergent abutment (DIV‐MAC), machined convergent abutment (CONV‐MAC) or convergent abutment with ultrathin threaded surface (CONV‐UTM). At 3 months postimplant insertion, peri‐implant soft tissue was harvested; the following outcomes were investigated: histomorphometry (vertical width of connective and epithelial components) as detected by histology and polarized light; and connective tissue vertical width and 3D organization as detected by synchrotron‐based high‐resolution phase‐contrast‐based tomography (PhC‐μCT).ResultsSignificant differences in connective tissue vertical dimension (aJE‐AM) were found between DIV‐MAC and both CONV‐MAC and CONV‐UTM, both by histology and PhC‐μCT, with significantly higher values for the last two groups. Moreover, 2D histological analysis did not find significant differences in the junctional epithelium vertical dimension (PM‐aJE). Importantly, PhC‐μCT analysis revealed, at 3D level, significant greater amount and density of collagen bundles for CONV‐UTM compared with the other two groups.ConclusionsConvergent abutment profiles, regardless of their surface micro‐geometry, seem to favor axial development of peri‐implant connective tissue. Moreover, ultrathin threaded surfaces seem associated with denser and greater connective tissue organization, which might improve peri‐implant soft tissue seal.