bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevated expression of CXCL3 in colon cancer promotes malignant behaviors of tumor cells in an ERK-dependent manner
Authors: Cheng Yao , Yang Xinyan , Liang Lichun , Xin Hua , Dong Xinyu , Li Weidong , Li Jie , Guo Xiaoli , Li Yue , Zhang Chunbin , Wang Weiqun
Published: February 2023

Background: CXCL3 is a member of CXC-type chemokine family that is identified as a major regulator in immune and inflammation responses. Recently, numerous evidence indicated that CXCL3 is broadly expressed in various human tumor types, and it is also known to play a critical role in mediating tumor development and progression. However, the expression profile of CXCL3 and the exact molecular mechanism behind the role of CXCL3 in colon adenocarcinoma (COAD) has not been fully elucidated.
Methods: The expression and clinical significance of CXCL3 mRNA and protein in the tissues from COAD patients were estimated using bioinformatics and immunohistochemistry assays. The expression and roles of exogenous administration or overexpression of CXCL3 in HT-29 and SW480 COAD cells were determined using ELISA, CCK-8 and Transwell assays. Mechanically, CXCL3-induced malignant behaviors were elucidated using western blotting assay and ERk1/2 inhibitor PD98059.
Results: TCGA-COAD data analysis revealed that CXCL3 mRNA is highly expressed and has high clinical diagnostic accuracy in COAD. Increased expression of CXCL3 mRNA was associated with patient’s clinical stage, race, gender, age, histological subtype, nodal mestastasis and TP53 mutation status. Similarly, immunohistochemistry assay also exhibited that CXCL3 protein in COAD tissues was significantly up-regulated. Gene expression associated assay implied that CXCL1 and CXCL2 were markedly correlated with CXCL3 in COAD. PPI analysis revealed that CCNB1, MAD2L1, H2AFZ and CXCL2 may be the important molecules involved in CXCL3-related tumor biology. GSEA analysis revealed that CXCL3 was mainly enriched in the cell cycle, DNA replication, NOD-like receptors, NOTCH and TGF-β Signal pathways. In vitro, exogenous administration or overexpression of CXCL3 resulted in increased malignant behaviors of HT-29 and SW480 cells, and overexpression of CXCL3 affected the expression of genes related to extracellular signal regulated kinase (ERK) pathway, including ERK1/2, p-ERK, Bcl-2, Bax and Cyclin D1. In addition, CXCL3-induced malignant behaviors in HT-29 and SW480 cells were obviously attenuated following treatment with ERK inhibitor PD98059.
Conclusion: CXCL3 is upregulated in COAD and plays a crucial role in the control of malignant behaviors of tumor cells, which indicated its involvement in the pathogenesis of COAD.
The value of heart rate variability in predicting long-term poorer outcome in patients undergoing coronary artery bypasses grafting and referring intensive care unit: a prospective cohort study
Authors: Mehrabanian Mohammad Javad , Firoozabadi Mehdi Dehghani , Nooralishahi Behrang , Mortazian Meysam , Kachoueian Naser
Published: February 2023

Background
Heart rate variability (HRV) plays an important role in predicting poor prognosis after acute myocardial infarction, but whether this parameter is able to predict long-term adverse outcomes following revascularization procedures is still not clear. We investigated the value of HRV in predicting post-procedural adverse outcome (mortality and major adverse cardiovascular event or MACE) in patients undergoing coronary artery bypass grafting (CABG) surgery and referred to intensive care unit.
Methods
This prospective cohort study was performed on 258 consecutive patients underwent elective isolated CABG. All patients required intensive care unit referring before discharge from the hospital. All patients were planned for a 3-week cardiac rehabilitation program with a 24-hour electrocardiogram Holter monitoring. HRV was analyzed by computer and over-read manually. Within a follow-up period ranged 1 to 3 years, the patients were asked by phone for long-term outcome including death and MACE (including myocardial infarction, reoperation, or brain stroke).
Results
overall, 4.3% of patients died due to cardiovascular events and 15.1% suffered from long-term MACE. Comparing HRV indicators between non-survived and survived subgroups showed significantly lower mean RR, lower mean SDNN, lower LF and lower HF in former group. However, the comparison of HRV between the subgroups with and without long-term MACE showed no difference in HRV indicators between the two groups. Using Cox proportional hazard analysis, lowering HRV (SDNN) could effectively predict long-term death in patients underwent CABG.
Conclusion
Lower postoperative HRV can effectively predict long-term death after CABG in patients admitted to intensive care unit.
WITHDRAWN: Clinical course and ophthalmologic findings in idiopathic intracranial hypertension and pregnancy: a retrospective cohort study
Authors: Knoche Theresia , Danyel Leon Alexander , Varlet Lisa Justine , Haffner Paula , Alzureiqi Mohammad Salim , Kowski Alexander , Gaus Verena
Published: February 2023

Background:
Idiopathic intracranial hypertension (IIH) has its highest prevalence among women of childbearing age. Therefore, it inevitably coincides with pregnancy. Because of physiological maternal changes during pregnancy and because of limited safety data on the available pharmaceuticals, concerns regarding a potential worsening of the disease during pregnancy arise. The literature background is limited to few retrospective studies. The aim of this study was to explore the impact of pregnancy on the visual outcome and on the management of pregnant women with IIH.
Methods
In this cohort study, IIH patients with documented pregnancies were retrospectively identified by medical database screening. The diagnosis of IIH was based on the revised Friedman criteria. Patient records were reviewed for IIH clinical features, treatment strategy and adherence to therapy. The visual acuity, visual field defects and the grade of papilledema at baseline and after pregnancy were compared. Complications over the course of pregnancy and during delivery were recorded.
Results
The database screening identified 16 IIH patients (26.8 ± 5.7 years, median = 27 years) with 19 documented pregnancies. The clinical presentation of IIH during pregnancy was similar to that of non-pregnant IIH patients with visual disturbances in 100% and headaches in 94.8% of patients. When comparing the overall visual acuity and the visual field mean deviation at baseline and at follow-up, no significant differences were found. The visual acuity at baseline in women who were diagnosed with IIH during pregnancy was significantly lower than in women who had been diagnosed with IIH prior to conception but improved at the time of follow-up. Papilledema grading improved after pregnancy. The adherence to therapy was low with 68.8% of patients discontinuing therapy.
Conclusions
Pregnancy did not lead to lasting visual impairment in our cohort of IIH patients, although many patients discontinued therapy during pregnancy. Further prospective studies are necessary to improve the medical care for IIH patients in pregnancy.
Transforming planning and policy making processes - working differently at the intersections of climate, equity, and decolonization challenges
Authors: Cole Lindsay , Low Maggie
Published: February 2023

Cities are facing increasing pressures to address complex challenges of climate change, equity, and reconciliation with Indigenous Peoples as intersecting issues, and innovation into planning and policy making processes is urgently needed to achieve this. It is no longer good enough to work on these challenges discreetly, or solely within the dominant, western colonial paradigm and practices of governance. There are ongoing harms being caused by climate work that does not embed justice, and there are missed opportunities for synergies across these domains as they have the same systemic root causes. Cities must adapt and transform the processes and practices of planning and policy making in order to work at these problematic roots. Drawing on an empirical study, this article describes how social innovation, systemic design, and decolonizing practices can shape a different approach to planning and policy making processes when working at the intersections of climate, equity, and decolonization.
Direct RNA sequencing coupled with adaptive sampling enriches RNAs of interest in the transcriptome
Authors: Wan Yue , Yang Lin , Wang Jia Xu , Tham Cheng-Yong , de Sessions Paola Florez , Cheng Anthony
Published: February 2023

Abundant cellular transcripts occupy most of the sequencing reads in the transcriptome, making it challenging to assay for low abundant transcripts. Here, we utilize the adaptive sampling function of Oxford Nanopore sequencing to selectively deplete and enrich RNAs of interest without biochemical manipulation before sequencing. Adaptive sampling performed on a pool of in vitro transcribed RNAs resulted in a 3.2-4.6-fold increase in transcripts of interest in the accept-read pool. Enriching and depleting different proportions of the candida albicans transcriptome also resulted in a 3-fold enrichment in the accepted-read pool and an 10% increase in the number of reads, with longer transcripts being more efficiently depleted. Depleting all currently annotated candida albicans transcripts revealed 26 new transcripts and isoforms, 17 of which are antisense to existing transcripts. Further improvements in the adaptive sampling of RNAs will allow the technology to be widely applied to study RNA(s) of interest in diverse transcriptomes.
Impact of Tobacco, Marijuana, and Alcohol use on Overall Survival in Recurrent Metastatic head and neck Cancer Patients Treated with Immune Checkpoint Inhibitors
Authors: Alsavaf Mohammad Bilal , Issa Majd , Klamer Brett G , Husain Marium , Dibs Khaled , Pan Xueliang , Grecula John C , Old Matthew O , Konieczkowski David , Mitchell Darrion L , Baliga Sujith , Carrau Ricardo L , Rocco James W , Bonomi Marcelo , Blakaj Dukagjin M. , Bhateja Priyanka
Published: February 2023

Background:
The response rates to immune checkpoint inhibitors (ICI) remain low (13-20%) in metastatic head and neck cancer patients and better understanding of factors predictive of response to these agents is urgently needed. Here we explore the impact of smoking status, marijuana use and alcohol on treatment outcomes in recurrent-metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with ICI.
Methods:
We performed a retrospective analysis of 201 R/M HNSCC patients treated with ICI between January 15th 2016 and April 9th 2020 at a single institution.

Results:
Gender: 154 male (77%), 47 female (23%). Median age 61 (IQR: 55-68). ICI drug: pembrolizumab 100 (50%), nivolumab 91 (45%), nivolumab+ipilimumab 10 (5%). Line of therapy: first: 98 (49%), second and beyond: 103 (51%). Tumor site: oropharynx 84 (42%), oral cavity 45 (22%), larynx 26 (13%), other sites 46 (23%). p16 tumor status: negative 132 (66%), positive 69 (34%). Smoking status: former 111 (55%), never 54 (27%), current 36 (18%), median pack-year 18 (IQR: 0-37). Alcohol use: yes 110 (55%), no 91 (54%). Marijuana use: yes 47 (23%), no 154 (77%). Overall response rate: 36 (18%). Median OS: 12 months (95% CI: 9.4-14.8). Tobacco: former (HR: 0.75, 95% CI: 0.50, 1.11), current (HR: 0.58, 95% CI: 0.33, 1.02). Marijuana: yes (HR: 0.93, 95% CI: 0.58, 1.49). Alcohol: yes (HR: 1.04, 95% CI: 0.72, 1.49).
Conclusion:
In our cohort, smoking status, marijuana use and alcohol consumption did not have a statistically significant impact on OS in patients with R/M HNSCC treated with ICI.
Trial registration: retrospectively registered.
Comparison of body composition in different dialysis states of end-stage renal disease and analysis of influencing factors
Authors: Li Yuxin , Sun Juan , Wu Hong , Liu Jun , Tang Shiqi , Ouyang Qin , Peng Xinyue , Wang Jianwen
Published: February 2023

Objective:To compare the differences in body composition in end-stage renal disease patients.
Methods:General data, biochemical data, and body composition indexes were collected to compare the differences in body composition indexes in ND, PD, and HD states. Spearman’s correlation and multiple linear stepwise regression analyses were performed to investigate the factors influencing the dependent variables.
Results: (1) Skeletal muscle index and phase angle were higher in the PD group than in the HD group (p < 0.05); total body water was lower in the PD and HD groups than in the CKD5-ND group (p < 0.05). (2) In the CKD5-ND and PD groups, the influencing factors of PHA were age, albumin, and prealbumin.
Conclusion: The patients with this central abdominal dialysis were better than those with HD in terms of nutrition and inflammation. PHA may be used to evaluate the nutritional status of patients with CKD5-ND and PD.
Age-associated risk of sarcopenia, falls and fractures: results of Ukrainian cohort study
Authors: Grygorieva Nataliia , Musiienko Anna , Bystrytska Maryna
Published: February 2023

Background
Nowadays, it is well-known that sarcopenia increases the risk of falls and fractures, and therefore, requires correction in order to improve the quality and duration of life of elderly people. Most of the early performed studies were conducted among community-dwelling subjects without stratification by ethnicity. This research aimed to study the age-related changes in the sarcopenia risk, falls, and fractures in Ukrainian women in the late reproductive and postmenopausal periods.
Materials and Methods
In the one-center cohort study we examined 573 females aged from 40 to 89 years old. For the analysis, the subjects were grouped by age decades and presence of high sarcopenia risk (HSR). The sarcopenia risk was measured by Strength, assistance with walking, rising from a chair, climbing stairs, and falls (SARC-F) questionnaire, the risk of falls using the Desmond Fall Risk Questionnaire, 10-year probability of major osteoporotic and hip fractures was assessed by Fracture Risk Assessment Tool, and daily activity – according to the Instrumental Activities of Daily Living scale. Also, we measured the hand grip strength and performed a five-repetition sit-to-stand test.
Results
The frequency of HSR increased with age from 1.5% in the 40-49-year-old group to 73.7% in the subjects over 80 years old, as well as fracture and fall risks (p ˂ 0.00001 for both indices) that were related to decreasing of independence in subjects everyday life. Also, we revealed age-dependent loss of muscle strength according to the hand grip and the five-repetition sit-to-stand test. After the adjustment of the subjects by age we found that the females with HSR had a higher risk of falls, a lower level of independence, and increased frequency and risk of osteoporotic fractures.
Conclusion
Women with HSR have a higher risk of falls, fractures, and more limitations in daily living activities independently from age and body mass index. These findings request comprehensive management of older women with attention to various parameters for the increase of independence and quality of life.
Exosomes derived from human adipose mesenchymal stem cells inhibits fibrosis and treats oral submucous fibrosis via the miR-181a-5p/Smad2 axis.
Authors: Shao Zifei , Xu Jinhao , Xu Xiaoyang , Wang Xiang , Zhou Yuxi , Li Yiyang , Li Kun
Published: February 2023

Background: Oral submucous fibrosis (OSF) is a chronic disease with carcinogenic tendency that poses a non-negligible threat to human health. Exosomes derived from human adipose mesenchymal stem cells (ADSC-Exo) reduces visceral and cutaneous fibroses, but theirrole in OSF has received little attention. The aim of this studywas to investigate the effects of ADSC-Exo on OSFand elucidate the mechanism.
Methods: In brief, ADSCs were extracted from adipose tissues and subjected to flow cytometry and induction culture. Fibroblasts were isolated from human buccal mucosa and subjected to immunofluorescence. Myofibroblasts were obtained from fibroblasts induced by arecoline and identified. Immunofluorescence assay confirmed that myofibroblasts could take up ADSC-Exo. The effects of ADSC-Exo on the proliferative and migratory capacities of myofibroblasts were examined using the Cell Counting Kit-8 and scratch assay. Real-time quantitative polymerase chain reaction (qPCR) was performed to evaluate mothers against decapentaplegic homolog 2 (Smad2), Smad3, Smad7, collagen type 1 (Col1),Col3, alpha smooth muscle actin (α-SMA), fibronectin, and vimentin. Western blotting was performed to detect phospho (p)-Smad2, Smad2, p-Smad2/3, Smad2/3, Smad7, Col1, Col3, α-SMA, fibronectin, and vimentin. Furthermore, the dual-luciferase reporter assay was performed to prove that miR-181a-5p in ADSC-Exo directly inhibited the expression of Smad2mRNA to regulate the transforming growth factor beta (TGF-β)pathway. We also performed qPCR and western blotting to verify the results.
Results: ADSC-Exo could promote the proliferation and migration of myofibroblasts, reduce the expressions of p-smad2, Smad2, p-smad2/3, Smad2/3, Col1, αSMA, fibronectin, and vimentin and elevated the levels of Smad7 and Col3. In addition, miR-181a-5p was highly expressed in ADSC-Exo and bound to the 3'-untranslated region of Smad2. ADSC-Exo enriched with miR-181a-5p reduced collagen production in myofibroblasts and modulated the TGF-β pathway.
Conclusions: ADSC-Exo promoted the proliferative and migratory capacities of myofibroblasts and inhibited collagen deposition and trans-differentiation of myofibroblasts in vitro. miR-181a-5p in exosomes targets Smad2 to regulate the TGF-β pathway in myofibroblasts. ADSC-Exo perform antifibrotic actions through the miR-181a-5p/Smad2 axis and may be a promising clinical treatment for OSF.
Trial registration: Not applicable
Predicting ‘Brainage’ in the Developmental Period using Structural MRI, Morphometric Similarity, and Machine Learning
Authors: Griffiths-King Daniel J. , Wood Amanda G. , Novak Jan
Published: February 2023

Brain development is regularly studied using structural MRI. Recently, studies have used a combination of statistical learning and large-scale imaging databases of healthy-children to predict an individual’s age from structural MRI. This data-driven, ‘brainage’ typically differs from the subjects chronological age, with this difference a potential measure of individual difference. Few studies have leveraged higher-order or connectomic representations of structural MRI data for this brainage approach. We leveraged morphometric similarity as a network-level approach to structural MRI to generate predictive models of age. We benchmarked these novel brain-age approaches using morphometric similarity against more typical, single feature (i.e. cortical thickness) approaches. We showed that these novel methods did not outperform cortical thickness or cortical volume measures. All models were significantly biased by age, but robust to motion confounds. The main results show that, whilst morphometric similarity mapping may be a novel way to leverage additional information from a T1-weighted structural MRI beyond individual features, in the context of a brain-age framework, morphometric similarity does not explain more variance than individual structural features. Morphometric similarity as a network-level approach to structural MRI may be poorly positioned to study individual differences in brain development in healthy individuals.
Genetic Determinants of Vitamin D Deficiency in the Middle Eastern Qatari Population by a Genome-Wide Association Study
Authors: Nemer Georges , Hindi Nagham , Al-Sarraj Yasser , Umlai Umm-Kulthum , Suhre Karsten , Albagha Omar
Published: February 2023

Epidemiological studies have revealed that Middle Eastern countries have the highest incidence of Vitamin D deficiency with severe complications. However, the impact of Vitamin D polymorphisms and the performance of polygenic models have been studied primarily in European with little knowledge of the Middle Eastern. Here, we conducted the first genome-wide association study to identify genetic determinants of Vitamin D levels in Middle Eastern populations using a whole genome sequencing approach in 6,047 discovery subjects. We discovered a novel variant, rs2298850 (P-value = 1.71 × 10-08, effect size (Beta) = -0.1285), in a region of a known locus for the group-specific component gene (GC). We also confirmed the association of Vitamin D to several variants, including rs11723621 (P-value = 1.93 × 10-08, Beta = -0.12574) and rs4588 (P-value = 8.06 × 10-08, Beta = -0.1188) in the GC. A GWAS meta-analysis combining results from our Qatari cohort and previous European data identified novel variants in known loci, including rs67609747 and rs1945603 on chromosome 11. We found a moderately low heritability of Vitamin D (estimated at 18%) compared to Europeans. Finally, a low predictive performance of European ancestry-derived polygenic scores was observed when applied to the Qatari individuals. These results emphasize the diversity in the genetic architecture and its impact on preventive and precision medicine across different populations. Our findings offer novel perspectives on the physiological mechanisms and genetic factors contributing to the variation of Vitamin D levels in the Qatari population.
Depressive symptoms as a predictor of 5-year subsequent work nonparticipation due to long-term sickness absence, unemployment and early retirement in a cohort of 2,413 employees in Germany
Authors: Rose Uwe , Kersten Norbert , Pattloch Dagmar , Burr Hermann
Published: February 2023

Background: We examined the impact of depressive symptoms on events – and duration thereof – of work nonparticipation (long-term sickness absence, unemployment, early retirement).
Methods: We used a 5-year cohort of the Study on Mental Health at Work (S-MGA) based on a random sample of employees subject to social contributions aged 31–60 years in 2012 (N =2413). Depressive symptoms were assessed at baseline through questionnaires, while employment history was recorded in follow-up interviews. Effects of depressive symptoms on work nonparticipation were examined in two-part models, with events analysed by logistic regressions and their duration by generalized linear models (GLMs).
Results: Medium to severe depressive symptoms increased the risk of events of work nonparticipation (males OR=3.22, 95% CI=1.90–5.45; females OR: 1.92, 1.29–2.87), particularly events of long-term sickness absence in both genders and events of unemployment among males. Mild depressive symptoms increased the risk of events of work nonparticipation (males OR=1.59, 1.19–2.11; females OR = 1.42, 1.10–1.84). Among those experiencing one or more events, the duration of total work nonparticipation was twice as high among males [EXP(B) =2.06; 95% CI: 1.53–2.78] and about one third higher [EXP(B) =1.38; 95% CI: 1.05–1.83] among females with medium to severe depressive symptoms.
Conclusions: The present study takes into account the occurrence of work nonparticipation but also its duration, which are both critical for assessing societal consequences of depressive symptoms. It is important to consider mild depressive symptoms and examine several types of work nonparticipation.
FDS_2D: Rethinking magnitude-phase features for DeepFake Detection
Authors: Yang Gaoming , Wei AnXing , Fang Xianjin , Zhang Ji
Published: February 2023

The detection method based on the frequency domain is one of the essential methods to reduce the harm of forged information. This method mostly uses spectra as clues to identify fake content. However, the current methods tend to use only one of the magnitude and phase spectra for learning. In this paper, we notice that the magnitude and phase spectrum contain different image information. Only one spectrum is easily disturbed by noise, and the robustness of the method is difficult to guarantee. Therefore, we propose the Frequency Domain Separable DeepFake Detection (FDS_2D) to use a multi-branch network to obtain features in different frequency spectra. In FDS_2D, the spectral information is divided into three categories: the magnitude spectrum, the phase spectrum, and the relationship between the two spectra. According to their characteristics, we design independent methods for feature extraction from them. Moreover, to improve the utilization efficiency of multi-features, we propose a multi-input multi-output attention mechanism for information interaction between branches. The experimental results show that each part of FDS_2D effectively extracts and applies spectral information; The comprehensive performance of our model is verified on FaceForensic++, CelebDF, and DFDC. It proves that the ability of FDS_2D to detect DeepFake is not inferior to existing models.
A Calorimetric Study of Phase Behavior of the Methane-Propane-Nonane System
Authors: Buleiko V. M. , Buleiko D. V.
Published: February 2023

The recent results of the accurate calorimetric measurements of phase equilibria internary mixtures of methane, propane, and nonane have been presented. The heat capacity, internal energy, pressure, and temperature derivative of pressure at constant volume were measured in the range 160 – 340 K, up to 30 MPa. The phase transitions were localized by the finite discontinuities in temperature derivatives of the thermodynamic potentials. The phase diagrams for ternary mixtures of methane, propane, and nonane have been plotted based on the experimental data. These data are supplemented with the earlier measurements of two ternary hydrocarbon systems for the low concentration of octane and decane. Our investigations show that hydrocarbon mixture for the low concentration of nonane as well as the hydrocarbon mixtures for the low concentration of octane and decane split into two phases, the nonane-lean macrophase and the microphase formed by nonane. Besides, nonane provokes a split of the liquid part of a ternary mixture into two liquid phases, the nonane-rich phase and the nonane-lean phase.
Inhibition of multipotent ILC2s by JAK3 inhibitor attenuates steroid-resistant asthma
Authors: Kim Hye-Young , Kim Jihyun , Ham Jongho , Kang Hye Ryun , Bae Yong-Soo , Kim Tasesoo
Published: February 2023

The standard treatment for allergic-airway inflammation, which is the dominant asthma endotype, is a steroid. However, steroid-refractory asthma is a significant problem. Innate-lymphoid cells (ILCs) produce type-2 cytokines as Th2 cells and play critical roles in asthma pathogenesis. Limited evidence from the asthma-mouse models and human studies suggests that ILC2s may participate in steroid-resistant asthma. Here, we showed that lung ILC2s, but not Th2 cells, can develop steroid resistance that maintains their survival, cytokine production, and pathogenic activities during steroid treatment. Such steroid-resistant ILC2s are associated with the presence of multiple ILC2-stimulating cytokines and the emergence of multipotent IL-5+IL-13+IL-17A+ ILC2s, and the Janus-kinase (JAK) 3/signal-transducer-and-activator-of-transcription (STAT) 3,5, and 6 pathway participates in the acquisition of steroid-resistant ILC2s. JAK3-inhibitor treatment significantly reduced the survival, proliferation, and cytokine production of multipotent ILC2s in vitro ameliorated ILC2-dependent Alternaria-induced asthma. Moreover, JAK3-inhibitor combined with a steroid strongly inhibited steroid-resistant asthma. Therefore, sustained asthmatic conditions may induce multipotent ILC2s that promote steroid-resistant asthma, and combining JAK3-inhibitor with steroid may be a treatment option for steroid-refractory asthma.
Improving recycling sorting behaviour with human eye nudges
Authors: Lotti Lorenzo , Barile Lory , Manfredi Giovanni
Published: February 2023

This paper aims to test whether visual nudges help improving attention towards existing instructions to increase waste sorting accuracy. The study was conducted in a quasi-experimental setting over a period of 8 weeks in two buildings of a large UK university campus. Two treatments were tested against a control group: one considered the impact of visual nudges in the form of human eyes on recycling behaviour; the other one combined human eye with pre-existing sorting instructions. Results show that the combination of visual and information nudges decreased sorting errors by 7 percentage points. By contrast, visual nudges alone increased sorting error by 4.5 percentage points. These findings prove that, when combined, information and a visual nudge are cost-effective tools to improve sorting behaviour with strong efficacy, bringing new evidence to experiments based on neuroscientific theories.
Behavioural Economics, Recycling, Neuroscience, Nudges
Effects of cardiac glycoside digoxin on dendritic spines and motor learning performance in mice
Authors: Hashimoto Junichi , Fujita Erika , Tanimoto Keisuke , Kondo Suzuo , Matsumoto-Miyai Kazumasa
Published: February 2023

Synapse formation following the generation of postsynaptic dendritic spines is essential for motor learning and functional recovery after brain injury. The C -terminal fragment of agrin cleaved by neurotrypsin induces dendritic spine formation in the adult hippocampus. Since the α3 subunit of sodium-potassium ATPase (Na/K ATPase) is a neuronal receptor for agrin in the central nervous system, cardiac glycosides might facilitate dendritic spine formation and subsequent improvements in learning. This study investigated the effects of the cardiac glycoside digoxin on dendritic spine turnover and learning performance in mice. Golgi-Cox staining revealed that intraperitoneal injection of digoxin less than its IC50 in brain significantly increased the density of long spines (≥2 µm) in cerebral cortex and hippocampus in wild-type mice and neurotrypsin-knockout (NT-KO) mice showing impairment of activity-dependent spine formation. Whereas motor learning performance of NT-KO mice showed significantly lower than control wild-type mice under the control condition, low dose of digoxin enhanced performance to a similar degree in both strains. In NT-KO mice, lower doses of digoxin equivalent to clinical doses also significantly improved performance. These data suggest that lower doses of digoxin could modify dendritic spine formation or recycling and facilitate motor learning in compensation for the neurotrypsin-agrin pathway.
Is it up there? - an MR spectroscopy study of frontal lobes and non-primary-auditory temporal areas in subjective bilateral and unilateral tinnitus
Authors: Wójcik Joanna , Kochański Bartosz , Cieśla Katarzyna , Lewandowska Monika , Karpiesz Lucyna , Niedziałek Iwona , Raj-Koziak Danuta , Skarżyński Piotr Henryk , Wolak Tomasz
Published: February 2023

Subjective tinnitus is a prevalent, though heterogeneous, condition whose pathophysiological mechanisms are still under investigation. Based on animal models, changes in neurotransmission along the auditory pathway have been suggested as co-occurring with tinnitus. It has not, however, been studied whether such effects can also be found in other sites beyond the auditory cortex. Our MR spectroscopy study is the first one to measure composite levels of glutamate and glutamine (Glx; and other central nervous system metabolites) in bilateral medial frontal and non-primary auditory temporal brain areas in tinnitus. We studied two groups of participants with unilateral and bilateral tinnitus and a control group without tinnitus, all three with a similar hearing profile. We found no metabolite level changes as related to tinnitus status in neither region of interest, except for a tendency of an increased concentration of Glx in the left frontal lobe in people with bilateral vs unilateral tinnitus. Slightly elevated depressive and anxiety symptoms are also shown in participants with tinnitus, as compared to healthy individuals, with the bilateral tinnitus group marginally more affected by the condition. We discuss the null effect in the temporal lobes, as well as the role of frontal brain areas in chronic tinnitus, with respect to hearing loss, attention mechanisms and psychological well-being. We furthermore elaborate on the design-related and technical obstacles when using MR spectroscopy to elucidate the role of neurometabolites in tinnitus.
Influence of species invasion, seasonality, and connectivity on fish functional and taxonomic beta-diversity in a Neotropical floodplain
Authors: Aleixo Matheus Henrique Ferreira , Florêncio Fernanda Moreira , Lansac-Toha Fernando Miranda , Quirino Barbara Angélio , Fugi Rosemara
Published: February 2023

Studies that combine functional and taxonomic beta-diversity are essential for explaining some ecological processes, including the process of species invasion. We evaluated whether environmental factors (such as lake connectivity, subsystem and hydrological period) and biological factors (occurrence and richness of non-native and native fish species) affect beta-diversity components (total, richness and replacement) of fish communities living in the Upper Paraná River floodplain in Brazil. For this, a distance-based redundancy analysis (dbRDA) was performed for both taxonomic (BDtax) and functional (BDfunc) approaches. In order to see which variables influence the local contribution to BDtax and BDfunc (LCBD), mixed effects regression models were fitted. Our results indicated a significant influence of environmental and biological factors on the taxonomic patterns of beta diversity and functional beta-diversity of fish between lakes. Environmental factors influenced the replacement component for both taxonomic and functional diversity, while biotic factors (occurrence and richness of non-native species) influenced the richness component. The richness of native and non-native species, the occurrence of non-native species and hidrological period showed significant influence on LCBD values. Although in our study the occurrence and richness of non-native species are related to beta-diversity, in the long term, these species can cause a decrease in functional and taxonomic beta-diversity, altering the ecological multifunctionality of the environment. Our study emphasizes that both changes in environmental factors and species diversity (such as the introduction of a non-native species) can impact the beta-diversity of Neotropical fish.
FRET assay for live-cell high-throughput screening of the cardiac SERCA pump yields multiple classes of small-molecule allosteric modulators
Authors: Roopnarine Osha , Yuen Samantha L. , Thompson Andrew R. , Roelike Lauren N. , Rebbeck Robyn T. , Bidwell Phillip A. , Aldrich Courtney C. , Cornea Razvan L. , Thomas David D.
Published: February 2023

We have used FRET-based biosensors in live cells, in a robust high-throughput screening (HTS) platform, to identify small-molecules that alter the structure and activity of the cardiac sarco/endoplasmic reticulum calcium ATPase (SERCA2a). Our primary aim is to discover drug-like small-molecule activators that improve SERCA’s function for the treatment of heart failure. We have previously demonstrated the use of an intramolecular FRET biosensor, based on human SERCA2a, by screening a small validation library using novel microplate readers that can detect the fluorescence lifetime or emission spectrum with high speed, precision, and resolution. Here we report results from a 50,000-compound screen using the same biosensor, with hit compounds functionally evaluated using Ca2+-ATPase and Ca2+-transport assays. We focused on 18 hit compounds, from which we identified eight structurally unique compounds and four compound classes as SERCA modulators, approximately half of which are activators and half are inhibitors. While both activators and inhibitors have therapeutic potential, the activators establish the basis for future testing in heart disease models and lead development, toward pharmaceutical therapy for heart failure.
Essential oil yield and compositions of Dracocephalum moldavica L. in intercropping with fenugreek and inoculation with mycorrhizal fungi and bacteria
Authors: Chelan Zahra Amiriyan , Amini Rouhollah , Nasab Adel Dabbagh Mohammadi
Published: February 2023

Intercropping is one of the most important components of sustainable production of agricultural products. The effects of chemical fertilizer (CF), arbuscular mycorrhizal fungi (AMF) and the combination of AMF and bacteria (AMF + B) in sole Moldavian balm (Mb) (Dracocephalum moldavica L.) and intercropping with fenugreek (F) (Trigonella foenum-graecum L.), was studied on growth characteristics, essential oil yield and compositions of Moldavian balm. The highest dry herbage yield (6132 kg ha− 1) was obtained in Mb:F(4:2) cropping pattern and CF treatment. The highest values of essential oil content were observed in the Mb:F (2:2) cropping pattern (0.261%) and AMF + B treatment (0.259%). After sole-Moldavian balm, the highest essential oil yield (15.28 kg ha− 1) was obtained in Mb:F (4:2) cropping pattern and AMF + B treatment. Geranial, geranyl acetate, geraniol, neral, and nerol were the main chemical constituents of essential oil. In CF and AMF + B treatments the geranial contents in intercropping patterns of Mb:F (1:1), (2:2) and (100:50), were greater than that of sole-Moldavian balm. The highest LERT values were observed in Mb:F (100:50) cropping pattern in 2021 (1.70 and 1.63 for CF and AMF + B treatments). Generally, it can be concluded that Mb:F (100:50) intercropping and use of AMF + B bio-fertilizer could be recommended to medicinal plant growers in sustainable production systems.
GREM1,LRPPRC and SLC39A4 as Potential Biomarkers of Intervertebral Disc Degeneration:A Bioinformatics Analysis based on Multiple Microarray and Single-cell Sequencing Data
Authors: Zhang ZhaoLiang , Ji XingHua , Wei LinDong , Zhang Jinfeng , Huo JianZhong
Published: February 2023

Background:The issue of low back pain (LBP) has received considerable critical attention and has been a worldwide health problem. Intervertebral disc degeneration (IVDD) is always the subject of many classic studies in this field. The mechanistic basis of IVDD is poorly understood and has produced equivocal results.
Methods: Gene expression profiles (GSE34095,GSE147383) of IVDD patients together with control groups were analyzed in order to identify differentially expressed genes (DEGs) in GEO database.GSE23130 and GSE70362 were applied to validate the obtained key genes from DEGs by means of a best subset selection regression. Four machine-learning models were established to assess their predictive ability. Single-sample gene set enrichment analysis (ssGSEA) was used to profile correlation between overall immune infiltration levels with pfirmann grades and key genes. We also analyzed the upstream targeting miRNAs of key genes (GSE63492).We used single-cell transcriptome sequencing data (GSE160756) to define several cell clusters of nucleus pulposus (NP),annulus fibrosus (AF) and cartilaginous endplate (CEP) of degenerated disc and obtained the distribution of key genes in different cell clusters.
Results: By developing appropriate p-values and logFC values, we obtained a total of 6 DEGs. We validated 3 key genes (LRPPRC, GREM1 and SLC39A4) by an externally validated predictive modeling method. The ssGSEA results indicated that key genes were correlated with the infiltration abundance of multiple immune cells, such as dendritic cells and macrophages. Accordingly these 4 key miRNAs (miR-103a-3p,miR-484,miR-665,miR-107)were identified as upstream regulators targeting key genes using miRNet database and external GEO datasets. Finally, we plotted the spatial distribution of key genes in AF, CEP and NP.
Conclusions: Our study offered a new perspective to identify the creadible and effective gene therapy targets in IVDD.
Effect of ammonium stress on phosphorus solubilization of a novel marine mangrove microorganism Bacillus aryabhattai NM1-A2 as revealed by integrated omics analysis
Authors: Lu Zhaomei , He Sheng , Kashif Muhammad , Zhang Zufan , Mo Shuming , Du Linfang , Jiang Chengjian
Published: February 2023

Background
Phosphorus (P) is one of the essential nutrients for plant growth. Phosphate-solubilizing microorganisms (PSMs) can alleviate P deficiency in an eco-friendly way. Ammonium toxicity is widespread, but is not very well known about the effect of ammonium stress on phosphorus solubilization (PS) of PSMs.
Results
In this study, seven PSMs were isolated from mangrove sediments. Among them, Bacillus aryabhattai NM1-A2 showed a high PS ability under ammonium stress, which reached a maximum of 196.96 mg/L at 250 mM (NH4)2SO4. Whole-genome analysis showed that B. aryabhattai NM1-A2 contained various genes related to ammonium transporter (amt), ammonium assimilation (i.e., gdhA, glnA, and gltD), organic acid synthesis (i.e., ackA, fdhD, and idh), and phosphate transport (i.e., pstB and pstS). Furthermore, transcriptome data showed that the expression level of amt was downregulated. This phenomenon contributed to reducing the intake of external ammonium. For ammonium assimilation under ammonium stress, accompanied by protons efflux, the glutamate dehydrogenase pathway was the main approach. The overall upregulated glycolysis and tricarboxylic acid cycle could provide abundant carbon skeletons. Among them, the upregulated expression of idh indicated that more 2-oxoglutarate (2-OG) was induced under NH4+ stress. High performance liquid chromatography results showed that the concentrations of formic acid and acetic acid were significantly increased under ammonium stress, while succinic acid was significantly decreased.
Conclusions
In conclusion, the secretion of protons and organic acids was related to the high PS ability of B. aryabhattai NM1-A2 under ammonium stress. The accumulation of 2-OG and the inhibition of GS/GOGAT pathway might play a key role in ammonium detoxification. Our work provides new insights into the PS mechanism, which will provide theoretical guidance for the application of PSMs to promote environment-friendly agricultural development.
An optimized UHPLC-MS/MS method for simultaneous determination of erythrocyte methotrexate and polyglutamylated metabolites: Application in pediatric patients with acute lymphoblastic leukemia
Authors: Wang Jian , Guan Yanping , Qian Minlin , Yang San , Guo Chenchen , Liu Songze , Huang Min , Zhang Yating , Fang Jianpei , Zhou Dun-hua , Wang Xueding
Published: February 2023

Methotrexate (MTX), a widely used chemotherapeutic drug, is critical for achieving long-term complete remission in contemporary maintenance therapy of acute lymphoblastic leukemia (ALL). MTX is intracellularly converted into methotrexate polyglutamates (MTXPGn) by folylpolyglutamate synthase after transporting into the cells. The intracellular levels of active MTXPGn regulate the clinical efficacy and drug-related side effects, but it is still challenged by large inter-individual differences and narrow therapeutic index. Therefore, it is of great significance to develop a sensitive and stable method to monitor MTXPGs concentrations in the erythrocyte. To facilitate clinical application, an ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed for the quantification of MTX and MTXPGn in erythrocyte. Solid phase extraction was applied to sample clean-up followed by a gradient chromatographic separation. The elution consisting of methanol/water/2 mM ammonium acetate (flow rate: 0.4 mL/min). Linearity of the assay was assured in the range of 1-500 nM (R2 > 0.99). The co-efficient of variation ranged from 2–11% for intraday precision and 0.4–8% for inter day precision. Recovery ranged from 62.51–99.75%, and the matrix-effect varied from 63.24–96.33%. Blood samples from 89 pediatric ALL patients were detected. The concentrations and distribution of MTXPGn in these samples were basically consistent with the current literatures, which confirmed that the optimized method for quantitative detection of MTXPGn in red blood cells had high sensitivity and accuracy. The sensitive method has been fully validated and successfully applied to determine the erythrocyte MTXPGn in pediatric ALL patients during continuation therapy.
Self-Supervised Approaches to the Classification of Spectra: Application to Phase Transitions in X-ray Diffraction Data
Authors: Sun Yue , Brockhauser Sandor , Hegedűs Péter , Plückthun Christian , Gelisio Luca , de Lima Danilo Enoque Ferreira
Published: February 2023

The ability to detect interesting events is instrumental to effectively steer experiments and maximize their scientific efficiency. To address this, here we introduce and validate three frameworks based on self-supervised learning which are capable of classifying 1D spectral data using a limited amount of labeled data. In particular, in this work we focus on the identification of phase transitions in samples investigated by x-ray diffraction. We demonstrate that the three frameworks, based either on relational reasoning, contrastive learning, or a combination of the two, are capable of accurately identifying phase transitions. Furthermore, we discuss in detail the selection of data augmentations, crucial to ensure that scientifically meaningful information is retained.
A Catchment and Location-Allocation Analysis of Mammography Access in Delaware, US: Implications for disparities in geographic access to breast cancer screening
Authors: Webster Jessica L. , Goldstein Neal D. , Rowland Jennifer R. , Tuite Catherine M. , Siegel Scott D.
Published: February 2023

Background: Despite a 40% reduction in breast cancer mortality over the last 30 years, not all groups have benefited equally from these gains. A consistent link between later stage of diagnosis and disparities in breast cancer mortality has been observed by race, socioeconomic status, and rurality. Therefore, ensuring equitable geographic access to screening mammography represents an important priority for reducing breast cancer disparities. This study conducted a catchment and location-allocation analysis of mammography access in Delaware, a state that is representative of the US in terms of race and urban-rural characteristics and experiences an elevated burden from breast cancer.
Methods: A catchment analysis using the ArcGIS Pro Service Area analytic tool characterized the geographic distribution of mammography sites and Breast Imaging Centers of Excellence (BICOEs). Poisson regression analyses identified census tract-level correlates of access. Next, the ArcGIS Pro Location-Allocation analytic tool identified candidate locations for the placement of additional mammography sites in Delaware according to several sets of breast cancer screening guidelines.
Results: The catchment analysis showed that for each standard deviation increase in the number of Black women in a census tract, there were 64% (95% CI, 0.18-0.66) fewer mammography units and 85% (95% CI, 0.04-0.48) fewer BICOEs. The more rural counties in the state accounted for 41% of the population but only 22% of the BICOEs. The results of the location-allocation analysis depended on which set of screening guidelines were adopted, which included increasing mammography sites in communities with a greater proportion of younger Black women and in rural areas.
Conclusions: The results of this study illustrate how catchment and location-allocation analytic tools can be leveraged to guide the equitable selection of new mammography facility locations as part of a larger strategy to close breast cancer disparities.