bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aberrant accumulation of NIK promotes tumor growth by dysregulating translation and post-translational modifications in breast cancer
Authors: Hayashi Yusuke , Nakayama Jun , Yamamoto Mizuki , Maekawa Masashi , Watanabe Shinya , Higashiyama Shigeki , Inoue Jun-ichiro , Yamamoto Yusuke , Semba Kentaro 
Published: April 2023

Abstract
Background
In vivo investigations with cancer cells have powerful tools to discover cancer progression mechanisms and preclinical candidate drugs. Among these in vivo experimental models, the establishment of highly malignancy cell lines with xenograft has been frequently used. However, few previous researches targeted malignancy-related genes whose protein levels translationally changed. Therefore, this study aimed to identify malignancy-related genes which contributed to cancer progression and changed at the protein level in the in vivo selected cancer cell lines.

Methods
We established the high malignancy breast cancer cell line (LM05) by orthotopic xenograft as an in vivo selection method. To explore the altered genes by translational or post-translational regulation, we analyzed the protein production by western blotting in the highly malignant breast cancer cell line. Functional analyses of the altered genes were performed by in vitro and in vivo experiments. To reveal the molecular mechanisms of the regulation with protein level, we evaluated post-translational modification by immunoprecipitation. In addition, we evaluated translational production by click reaction-based purification of nascent protein.

Results
As a result, NF-κB inducing kinase (NIK) increased at the protein level and promoted the nuclear localization of NF-κB2 (p52) and RelB in the highly malignant breast cancer cell line. The functional analyses indicated the NIK upregulation contributed to tumor malignancy via cancer-associated fibroblasts (CAFs) attraction and partially anti-apoptotic activities. Additionally, the immunoprecipitation experiment revealed that the ubiquitination of NIK decreased in LM05 cells. The decline in NIK ubiquitination was attributed to the translational downregulation of cIAP1.

Conclusions
Our study identified a dysregulated mechanism of NIK production by the suppression of NIK post-modification and cIAP1 translation. The aberrant NIK accumulation promoted tumor growth in the highly malignant breast cancer cell line.
A comparison of transmissibility of SARS-CoV-2 variants of concern
Authors: Manathunga S. S. , Abeyagunawardena I. A. , Dharmaratne S. D. 
Published: April 2023

Abstract
Background
The World Health Organization (WHO) has currently detected five Variants of Concern of SARS-CoV-2 having the WHO labels of ‘Alpha’, ‘Beta’, ‘Gamma’, ‘Delta’ and ‘Omicron’. We aimed to assess and compare the transmissibility of the five VOCs in terms of basic reproduction number, time-varying reproduction number and growth rate.

Methods
Publicly available data on the number of analyzed sequences over two-week windows for each country were extracted from covariants.org and GISAID initiative database. The ten countries which reported the highest number of analyzed sequences for each of the five variants were included in the final dataset and was analyzed using R language. The epidemic curves for each variant were estimated utilizing the two-weekly discretized incidence data using local regression (LOESS) models. The basic reproduction number was estimated with the exponential growth rate method. The time-varying reproduction number was calculated for the estimated epidemic curves by the ratio of the number of new infections generated at time step t to the total infectiousness of infected individuals at time t, using the EpiEstim package.

Results
The highest R0 for the variants Alpha (1.22), Beta (1.19), Gamma (1.21), Delta (1.38) and Omicron (1.90) were reported from Japan, Belgium, the United States, France and South Africa, respectively. Nine out of ten epidemic curves with the highest estimated growth rates and reproduction numbers were due to the Omicron variant indicating the highest transmissibility.

Conclusions
The transmissibility was highest in the Omicron variant followed by Delta, Alpha, Gamma and Beta respectively.
The association of long-term calcium and dairy products intake in adolescence with carotid intima media thickness and metabolic syndrome in early adulthood: Tehran Lipid and Glucose Study
Authors: AkbarySedigh Assa , Asghari Golaleh , Mahdavi Maryam , Mirmiran Parvin , Valizadeh Majid , Azizi Fereidoun 
Published: April 2023

Abstract
Background
Calcium could impact on vascular functions and structures and cause atherosclerosis. Thus, we aimed to examine the association of long-term calcium and dairy products intake in adolescence with cIMT and MetS in early adulthood.

Methods
We considered 217 adolescents aged 12–18 years in the frame work of the Tehran Lipid and Glucose Study (2006–2009) and follow-up them to early adulthood (2015–2017). The valid food frequency questionnaire was used to assess dietary intake. Ultrasound examination was used to measure common carotid artery. The joint interim statement and cook et al. criteria were used for adults and adolescents to consider MetS, respectively.

Results
Adolescents’ average calcium intake from dairy and non-dairy sources were 395 mg/d and 1088 mg/d, respectively while adults had 212 mg/d and 1191 mg/d. In addition, the mean of cIMT in adults was 0.54 mm. There was no relationship of non-dairy (β: − 0.03; P = 0.804), and total calcium (β: − 0.001; P = 0.591) intake with cIMT and TG. None of the dairy products had link with cIMT, MetS and its components, except cream with cIMT after full adjustment of potential confounders (β: 0.245; P = 0.009). Also, we found that the intake of non-dairy products could increase DBP after controlling for potential confounders (β: 0.365; P = 0.012). Adolescence with higher quartiles of total calcium intake had no odds ratio of MetS in early adulthood (β: 2.05, P = 0.371).

Conclusions
Adolescence calcium and dairy products intake, with the exception of cream did not increase early adulthood cIMT and MetS and its components.
Analysis of plant cuticles and their interactions with agrochemical surfactants using a 3D printed diffusion chamber
Authors: Vittal Lakshmi Venkatesha Manyu , Rookes James , Boyd Ben , Cahill David 
Published: April 2023

Abstract
Background
Decades of research is available on their effects of single component surfactant on active ingredient diffusion across plant cuticular membranes, but ingredient diffusion is rarely analysed in the presence of commercial surfactants. Also, diffusion studies require expensive or specialized apparatus the fabrication of which often requires skilled labour and specialized facilities. In this research we have addressed both problems where the effects of four commercially available surfactants on a known tracer molecule were investigated using a 3D printed customized diffusion chamber.

Results
As a proof-of-concept a customized 3D printed diffusion chamber was devised using two different thermoplastics and was successfully used in a range of diffusion tests . The effect of various solvents and surfactants on S. lycopersicum cuticular membrane indicated an increased rate of flux of tracer molecules across the membranes. This research has validated the application of 3D printing in diffusion sciences and demonstrated the flexibility and potential of this technique.

Conclusions
Using a 3D printed diffusion apparatus, the effect of commercial surfactants on molecular diffusion through isolated plant membranes was studied. Further, we have included here the steps involved in material selection, design, fabrication, and post processing procedures for successful recreation of the chamber. The customizability and rapid production process of the 3D printing demonstrates the power of additive manufacturing in the design and use of customizable labware.
The effect of flipped approach in teaching critical respiratory care among nurses during the COVID-19 era
Authors: Bazrafkan Leila , Panahian Razieh , Zarifsanaiey Nahid 
Published: April 2023

Abstract
Objectives
This study investigated the efficacy of flipped approach on the nurses’ knowledge and motivation regarding critical respiratory care during the COVID-19 pandemic.

Results
This pretest-posttest quasi-experimental study was performed in a hospital affiliated with Shiraz University of Medical Sciences during March-December 2021. One hundred and twenty eligible nurses selected by convenience sampling underwent a seven-day flipped approach respiratory intensive care training. The nurses’ motivation and knowledge were evaluated using the Students’ Motivation Towards Science Learning (SMTSL) and a 20-researcher-made four-option questionnaire before and two weeks after the intervention, for knowledge assessment respectively. The nurses’ knowledge and learning motivation were significantly higher after the intervention (P < 0.001). The flipped approach can improve learning motivation and nurses’ knowledge of critical respiratory care.
LinChemIn: SynGraph—a data model and a toolkit to analyze and compare synthetic routes
Authors: Pasquini Marta , Stenta Marco 
Published: April 2023

AbstractBackgroundThe increasing amount of chemical reaction data makes traditional ways to navigate itscorpusless effective, while the demand for novel approaches and instruments is rising. Recent data science and machine learning techniques support the development of new ways to extract value from the available reaction data. On the one side, Computer-Aided Synthesis Planning tools can predict synthetic routes in a model-driven approach; on the other side, experimental routes can be extracted from the Network of Organic Chemistry, in which reaction data are linked in a network. In this context, the need to combine, compare and analyze synthetic routes generated by different sources arises naturally.ResultsHere we present LinChemIn, a python toolkit that allows chemoinformatics operations on synthetic routes and reaction networks. Wrapping some third-party packages for handling graph arithmetic and chemoinformatics and implementing new data models and functionalities, LinChemIn allows the interconversion between data formats and data models and enables route-level analysis and operations, including route comparison and descriptors calculation. Object-Oriented Design principles inspire the software architecture, and the modules are structured to maximize code reusability and support code testing and refactoring. The code structure should facilitate external contributions, thus encouraging open and collaborative software development.ConclusionsThe current version of LinChemIn allows users to combine synthetic routes generated from various tools and analyze them, and constitutes an open and extensible framework capable of incorporating contributions from the community and fostering scientific discussion. Our roadmap envisages the development of sophisticated metrics for routes evaluation, a multi-parameter scoring system, and the implementation of an entire “ecosystem” of functionalities operating on synthetic routes. LinChemIn is freely available at https://github.com/syngenta/linchemin.Graphical Abstract
Differences in clinical characteristics and quantitative lung CT features between vaccinated and not vaccinated hospitalized COVID-19 patients in Italy
Authors: Chiumello Davide , Tavelli Alessandro , Serio Lorenzo , De Benedittis Sara , Pozzi Tommaso , Maj Roberta , Velati Mara , Brusatori Serena , D’Albo Rosanna , Zinnato Carmelo , Marchetti Giulia , Camporota Luigi , Coppola Silvia , D’Arminio Monforte Antonella 
Published: April 2023

Abstract
Background
To evaluate the differences in the clinical characteristics and severity of lung impairment, assessed by quantitative lung CT scan, between vaccinated and non-vaccinated hospitalized patients with COVID-19; and to identify the variables with best prognostic prediction according to SARS-CoV-2 vaccination status. We recorded clinical, laboratory and quantitative lung CT scan data in 684 consecutive patients [580 (84.8%) vaccinated, and 104 (15.2%) non-vaccinated], admitted between January and December 2021.

Results
Vaccinated patients were significantly older 78 [69–84] vs 67 [53–79] years and with more comorbidities. Vaccinated and non-vaccinated patients had similar PaO2/FiO2 (300 [252–342] vs 307 [247–357] mmHg; respiratory rate 22 [8–26] vs 19 [18–26] bpm); total lung weight (918 [780–1069] vs 954 [802–1149] g), lung gas volume (2579 [1801–3628] vs 2370 [1675–3289] mL) and non-aerated tissue fraction (10 [7.3–16.0] vs 8.5 [6.0–14.1] %). The overall crude hospital mortality was similar between the vaccinated and non-vaccinated group (23.1% vs 21.2%). However, Cox regression analysis, adjusted for age, ethnicity, age unadjusted Charlson Comorbidity Index and calendar month of admission, showed a 40% reduction in hospital mortality in the vaccinated patients (HRadj = 0.60, 95%CI 0.38–0.95).

Conclusions
Hospitalized vaccinated patients with COVID-19, although older and with more comorbidities, presented a similar impairment in gas exchange and lung CT scan compared to non-vaccinated patients, but were at a lower risk of mortality.
Human liver organoid: modeling liver steatosis and beyond
Authors: Wei Jinsong , Zhang Wen , Zhao Bing 
Published: April 2023

AbstractSteatosis, as the early stage of nonalcoholic fatty acid disease (NAFLD), would progress into nonalcoholic steatohepatitis (NASH) and liver failure without intervention. Despite the development of animal models, there is still a lack of the human-relevant platform for steatosis modeling and drug & target discovery. Hendriks et al., reporting in Nature Biotechnology, leveraged human fetal liver organoids to recapitulate steatosis by introducing nutritional and genetic triggers. Using these engineered liver organoid-derived steatosis models, they screened drugs that alleviate steatosis, and mined common mechanism of effective compounds. Further, inspired by the results of drug screening, the arrayed CRISPR-LOF screening targeting 35 lipid metabolism genes was performed, and FADS2 was identified as a critical regulator of steatosis.
Education on medically unexplained symptoms: a systematic review with a focus on cultural diversity and migrants
Authors: Mariman An , Vermeir Peter , Csabai Marta , Weiland Anne , Stegers-Jager Karen , Vermeir Ruben , Vogelaers Dirk 
Published: April 2023

Abstract
Background
Health care providers often struggle with the management of patients with medically unexplained symptoms (MUS), especially in case of a different ethnicity and/or cultural background. These challenges are insufficiently addressed in their training.

Objectives
A systematic review on education in the field of MUS in a diverse context to improve MUS healthcare provider–patient interaction focused on intercultural communication.

Methods
Screening of PubMed, Web of Science, Cinahl and Cochrane Library on the keywords ‘Medical unexplained (physical) symptoms (MUS)’, ‘Somatoform disorder’, ‘Functional syndrome’, ‘Diversity’, ‘Migrants’, ‘Ethnicity’, ‘Care models’, ‘Medical education’, ‘Communication skills’, ‘Health literacy’.

Results
MUS patients, especially with a different ethnic background, often feel not understood or neglected. Health care providers experience feelings of helplessness, which may provoke medical shopping and resource consumption. Attitudes and perceptions from undergraduate trainees to senior physicians tend to be negative, impacting on the quality of the patient/health care provider relationship and subsequently on health outcomes, patient satisfaction and therapeutic adherence. Current undergraduate, graduate and postgraduate education and training does not prepare health care providers for diagnosing and managing MUS patients in a diverse context. A continuum of training is necessary to achieve a long term and lasting change in attitudes towards these patients and trainers play a key role in this process. Hence, education should pay attention to MUS, requiring a specific competency profile and training, taken into account the variety in patients’ cultural backgrounds.

Conclusions
This systematic review identified significant gaps and shortcomings in education on MUS in a diverse context. These need to be addressed to improve outcomes.
Starburst amacrine cells, involved in visual motion perception, lose their synaptic input from dopaminergic amacrine cells and degenerate in Parkinson’s disease patients
Authors: Sánchez-Sáez Xavier , Ortuño-Lizarán Isabel , Sánchez-Castillo Carla , Lax Pedro , Cuenca Nicolás 
Published: April 2023

Abstract
Background
The main clinical symptoms characteristic of Parkinson’s disease (PD) are bradykinesia, tremor, and other motor deficits. However, non-motor symptoms, such as visual disturbances, can be identified at early stages of the disease. One of these symptoms is the impairment of visual motion perception. Hence, we sought to determine if the starburst amacrine cells, which are the main cellular type involved in motion direction selectivity, are degenerated in PD and if the dopaminergic system is related to this degeneration.

Methods
Human eyes from control (n = 10) and PD (n = 9) donors were available for this study. Using immunohistochemistry and confocal microscopy, we quantified starburst amacrine cell density (choline acetyltransferase [ChAT]-positive cells) and the relationship between these cells and dopaminergic amacrine cells (tyrosine hydroxylase-positive cells and vesicular monoamine transporter-2-positive presynapses) in cross-sections and wholemount retinas.

Results
First, we found two different ChAT amacrine populations in the human retina that presented different ChAT immunoreactivity intensity and different expression of calcium-binding proteins. Both populations are affected in PD and their density is reduced compared to controls. Also, we report, for the first time, synaptic contacts between dopaminergic amacrine cells and ChAT-positive cells in the human retina. We found that, in PD retinas, there is a reduction of the dopaminergic synaptic contacts into ChAT cells.

Conclusions
Taken together, this work indicates degeneration of starburst amacrine cells in PD related to dopaminergic degeneration and that dopaminergic amacrine cells could modulate the function of starburst amacrine cells. Since motion perception circuitries are affected in PD, their assessment using visual tests could provide new insights into the diagnosis of PD.
Sex differences in pre-incarceration mental illness, substance use, injury and sexually transmitted infections and health service utilization: a longitudinal linkage study of people serving federal sentences in Ontario
Authors: Butsang Tenzin , McLuhan Arthur , Keown Leslie A. , Fung Kinwah , Matheson Flora I. 
Published: April 2023

Abstract
Background
People who experience incarceration have poorer health than the general population. Yet, we know little about the health and health service utilization of people during the critical period prior to their incarceration, relative to during incarceration and post-release. In this study, we conducted a longitudinal cohort study of 39,498 adults in Ontario, Canada between January 1, 2002, and December 31, 2011 using linked administrative health and correctional data to describe mental illness, substance use, injury, sexually transmitted infections and health service utilization of men and women in federal prisons in the 3 years prior to their incarceration, compared to a matched group.

Results
We found that, in the 3-year period prior to their incarceration, men (n = 6,134) and women (n = 449) experiencing their first federal sentence had poorer health across all indicators examined (e.g., psychosis, drug/alcohol use, and self-harm) and higher outpatient psychiatric and emergency department visits, compared with the matched group. Women in the pre-incarceration group exhibited a higher prevalence of self-harm and substance use, relative to women in the matched comparison group and higher relative prevalence to that of men in the pre-incarceration group, compared to their matched counterparts.

Conclusions
Disparities in health and health service utilization are gendered and exist prior to incarceration. The gendered nature of these findings, specifically the significantly higher prevalence of poor health among women across several indicators, necessitates a focus on the social and systemic factors that contribute to these disparities. Gender-responsive and trauma-informed primary, secondary, and tertiary prevention strategies, alongside transformative approaches to justice should be considered in addressing the health needs of men and women who experience incarceration.
Tailored exercise management (TEMPO) versus usual care for people aged 80 years or older with hip/knee osteoarthritis: study protocol for a feasibility randomised controlled trial
Authors: Nicolson Philippa J. A. , Holden Melanie A. , Marian Ioana R. , Williamson Esther , Dutton Susan J. , Garrett Angela , Hopewell Sally , Lamb Sarah E. 
Published: April 2023

Abstract
Background
Exercise is recommended for all people with osteoarthritis. However, these recommendations are based on randomised clinical trials including people with an average age between 60 and 70 years, and these findings cannot reliably be generalised to people aged 80 years or older. Rapid loss of muscle occurs after 70 years of age, and older people are more likely to also have other health conditions that contribute to difficulties with daily activities and impact on their response to exercise. To improve care for people aged 80 or older with osteoarthritis, it is thought that a tailored exercise intervention targeting both osteoarthritis and any other health conditions they have, may be needed. The aim of this study will be to test if it is possible to conduct a randomised controlled trial (RCT) for people over 80 years of age with hip/knee osteoarthritis of a tailored exercise intervention.

Methods
A multicentre, parallel, 2-group, feasibility RCT with embedded qualitative study, conducted in ≥ 3 UK NHS physiotherapy outpatient services. Participants (n ≥ 50) with clinical knee and/or hip osteoarthritis and ≥ 1 comorbidity will be recruited by screening referrals to participating NHS physiotherapy outpatient services, via screening of general practice records and via identification of eligible individuals from a cohort study run by our research group. Participants will be randomised (computer-generated: 1:1) to receive either: a 12-week education and tailored exercise intervention (TEMPO); or usual care and written information. The primary feasibility objectives are to estimate: (1) ability to screen and recruit eligible participants; (2) retention of participants, measured by the proportion of participants who provide outcome data at 14-week follow-up. Secondary quantitative objectives are to estimate: (1) participant engagement assessed by physiotherapy session attendance and home exercise adherence; (2) sample size calculation for a definitive RCT. One-to-one semi-structured interviews will explore the experiences of trial participants and physiotherapists delivering the TEMPO programme.

Discussion
Progression criteria will be used to determine whether a definitive trial to evaluate the clinical and cost-effectiveness of the TEMPO programme is considered feasible with or without modifications to the intervention or trial design.

Trial registration
ISRCTN75983430. Registered 3/12/2021. https://www.isrctn.com/ISRCTN75983430.