bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute-phase protein concentrations in serum of clinically healthy and diseased European bison (Bison bonasus) – preliminary study
Authors: Pomorska-Mól Małgorzata , Libera Kacper , Larska Magdalena , Krzysiak Michał K. 
Published: January 2022

Abstract
Background
This is the first report describing levels of APPs in European bison. Serum concentration of acute phase proteins (APPs) may be helpful to assess general health status in wildlife and potentially useful in selecting animals for elimination. Since there is a lack of literature data regarding concentration of APPs in European bisons, establishment of the reference values is also needed.

Methods
A total of 87 European bison from Polish populations were divided into two groups: (1) healthy: immobilized for transportation, placing a telemetry collar and routine diagnostic purposes; and (2) selectively culled due to the poor health condition. The serum concentration of haptoglobin, serum amyloid A and α1-acid-glycoprotein were determined using commercial quantitative ELISA assays. Since none of the variables met the normality assumptions, non-parametric Mann-Whitney U test was used for all comparisons. Statistical significance was set at p < 0.05. Statistical analyses were performed using Statistica 13.3 (Tibco, USA).

Results
The concentration of haptoglobin and serum amyloid A was significantly higher in animals culled (euthanised) due to the poor condition in respect to the clinically healthy European bison. The levels of α1-acid-glycoprotein did not show statistical difference between healthy and sick animals.

Conclusions
Correlation between APPs concertation and health status was proven, therefore the determination of selected APPs may be considered in future as auxiliary predictive tool in assessing European bison health condition.
Monocarboxylate transporter functions and neuroprotective effects of valproic acid in experimental models of amyotrophic lateral sclerosis
Authors: Gyawali Asmita , Latif Sana , Choi Seung-Hye , Hyeon Seung Jae , Ryu Hoon , Kang Young-Sook 
Published: January 2022

Abstract
Background
Amyotrophic lateral sclerosis (ALS) is a devasting neurodegenerative disorder for which no successful therapeutics are available. Valproic acid (VPA), a monocarboxylate derivative, is a known antiepileptic drug and a histone deacetylase inhibitor.

Methods
To investigate whether monocarboxylate transporter 1 (MCT1) and sodium-coupled MCT1 (SMCT1) are altered in ALS cell and mouse models, a cellular uptake study, quantitative real time polymerase chain reaction and western blot parameters were used. Similarly, whether VPA provides a neuroprotective effect in the wild-type (WT; hSOD1WT) and ALS mutant-type (MT; hSOD1G93A) NSC-34 motor neuron-like cell lines was determined through the cell viability assay.

Results
[3H]VPA uptake was dependent on time, pH, sodium and concentration, and the uptake rate was significantly lower in the MT cell line than the WT cell line. Interestingly, two VPA transport systems were expressed, and the VPA uptake was modulated by SMCT substrates/inhibitors in both cell lines. Furthermore, MCT1 and SMCT1 expression was significantly lower in motor neurons of ALS (G93A) model mice than in those of WT mice. Notably, VPA ameliorated glutamate- and hydrogen peroxide-induced neurotoxicity in both the WT and MT ALS cell lines.

Conclusions
Together, the current findings demonstrate that VPA exhibits a neuroprotective effect regardless of the dysfunction of an MCT in ALS, which could help develop useful therapeutic strategies for ALS.
Speed dating for enzymes! Finding the perfect phosphopantetheinyl transferase partner for your polyketide synthase
Authors: Pedersen Tobias Bruun , Nielsen Mikkel Rank , Kristensen Sebastian Birkedal , Spedtsberg Eva Mie Lang , Sørensen Trine , Petersen Celine , Muff Jens , Sondergaard Teis Esben , Nielsen Kåre Lehmann , Wimmer Reinhard , Gardiner Donald Max , Sørensen Jens Laurids 
Published: January 2022

AbstractThe biosynthetic pathways for the fungal polyketides bikaverin and bostrycoidin, from Fusarium verticillioides and Fusarium solani respectively, were reconstructed and heterologously expressed in S. cerevisiae alongside seven different phosphopantetheinyl transferases (PPTases) from a variety of origins spanning bacterial, yeast and fungal origins. In order to gauge the efficiency of the interaction between the ACP-domains of the polyketide synthases (PKS) and PPTases, each were co-expressed individually and the resulting production of target polyketides were determined after 48 h of growth. In co-expression with both biosynthetic pathways, the PPTase from Fusarium verticillioides (FvPPT1) proved most efficient at producing both bikaverin and bostrycoidin, at 1.4 mg/L and 5.9 mg/L respectively. Furthermore, the remaining PPTases showed the ability to interact with both PKS’s, except for a single PKS-PPTase combination. The results indicate that it is possible to boost the production of a target polyketide, simply by utilizing a more optimal PPTase partner, instead of the commonly used PPTases; NpgA, Gsp and Sfp, from Aspergillus nidulans, Brevibacillus brevis and Bacillus subtilis respectively.
miR-133a targets YES1 to reduce cisplatin resistance in ovarian cancer by regulating cell autophagy
Authors: Zhou Yang , Wang Chunyan , Ding Jinye , Chen Yingying , Sun Yaoqi , Cheng Zhongping 
Published: January 2022

Abstract
Background
Accumulating evidence has revealed that aberrant microRNA (miRNA) expression can affect the development of chemotherapy drug resistance by modulating the expression of relevant target proteins. Emerging evidence has demonstrated that miR-133a participates in the tumorigenesis of various cancers. However, whether miR-133a is associated with cisplatin resistance in ovarian cancer remains unclear.

Objective
To investigate the role of miR-133a in the development of cisplatin resistance in ovarian cancer.

Methods
MiR-133a expression in cisplatin-resistant ovarian cancer cell lines was assessed by reverse-transcription quantitative PCR (RT–qPCR). A cell counting kit-8 (CCK-8) assay was used to evaluate the viability of tumour cells treated with cisplatin in the presence or absence of miR-133a. A luciferase reporter assay was used to analyse the binding of miR-133a with the 3′ untranslated region (3′UTR) of YES proto-oncogene 1 (YES1). The YES1 expression level was analysed using a dataset from the International Cancer Genome Consortium (ICGC) and assessed by RT–qPCR and western blotting in vitro. The roles and mechanisms of YES1 in cell functions were further probed via gain- and loss-of-function analysis.

Results
The expression of miR-133a was significantly decreased in cisplatin-resistant ovarian cancer cell lines (A2780-DDP and SKOV3-DDP), and the overexpression of the miR-133a mimic reduced cisplatin resistance in A2780-DDP and SKOV3-DDP cells. Treatment with the miR-133a inhibitor increased cisplatin sensitivity in normal A2780 and SKOV3 cells. MiR-133a binds the 3’UTR of YES1 and downregulates its expression. Bioinformatics analysis revealed that YES1 expression was upregulated in recurrent cisplatin-resistant ovarian cancer tissue, and in vitro experiments also verified its upregulation in cisplatin-resistant cell lines. Furthermore, we discovered that miR-133a downregulated the expression of YES1 and thus inhibited cell autophagy to reduce cisplatin resistance. Yes1 knockdown significantly suppressed the cisplatin resistance of ovarian cancer cells by inhibiting autophagy in vitro. Xenograft tumour implantation further demonstrated that Yes1 overexpression promoted ovarian tumour development and cisplatin resistance.

Conclusions
Our results suggest that the miR-133a/YES1 axis plays a critical role in cisplatin resistance in human ovarian cancer by regulating cell autophagy, which might serve as a promising therapeutic target for ovarian cancer chemotherapy treatment in the future.
“We are not stray leaves blowing about in the wind”: exploring the impact of Family Wellbeing empowerment research, 1998–2021
Authors: Perera Nirukshi , Tsey Komla , Heyeres Marion , Whiteside Mary , Baird Leslie , McCalman Janya , Cadet-James Yvonne , Calabria Bianca , Hamilton Michael , Yan Li , Zuchowski Ines , Sims Kearrin , Udah Hyacinth 
Published: January 2022

Abstract
Background
An Aboriginal-developed empowerment and social and emotional wellbeing program, known as Family Wellbeing (FWB), has been found to strengthen the protective factors that help Indigenous Australians to deal with the legacy of colonisation and intergenerational trauma. This article reviews the research that has accompanied the implementation of the program, over a 23 year period. The aim is to assess the long-term impact of FWB research and identify the key enablers of research impact and the limitations of the impact assessment exercise. This will inform more comprehensive monitoring of research impact into the future.

Methods
To assess impact, the study took an implementation science approach, incorporating theory of change and service utilisation frameworks, to create a logic model underpinned by Indigenous research principles. A research impact narrative was developed based on mixed methods analysis of publicly available data on: 1) FWB program participation; 2) research program funding; 3) program outcome evaluation (nine studies); and 4) accounts of research utilisation (seven studies).

Results
Starting from a need for research on empowerment identified by research users, an investment of $2.3 million in research activities over 23 years produced a range of research outputs that evidenced social and emotional wellbeing benefits arising from participation in the FWB program. Accounts of research utilisation confirmed the role of research outputs in educating participants about the program, and thus, facilitating more demand (and funding acquisition) for FWB. Overall research contributed to 5,405 recorded participants accessing the intervention. The key enablers of research impact were; 1) the research was user- and community-driven; 2) a long-term mutually beneficial partnership between research users and researchers; 3) the creation of a body of knowledge that demonstrated the impact of the FWB intervention via different research methods; 4) the universality of the FWB approach which led to widespread application.

Conclusions
The FWB research impact exercise reinforced the view that assessing research impact is best approached as a “wicked problem” for which there are no easy fixes. It requires flexible, open-ended, collaborative learning-by-doing approaches to build the evidence base over time. Steps and approaches that research groups might take to build the research impact knowledge base within their disciplines are discussed.
Prenatal exposure to organophosphate pesticides and risk-taking behaviors in early adulthood
Authors: Sagiv Sharon K. , Rauch Stephen , Kogut Katherine R. , Hyland Carly , Gunier Robert B. , Mora Ana M. , Bradman Asa , Deardorff Julianna , Eskenazi Brenda 
Published: January 2022

Abstract
Introduction
Previous studies show evidence for associations of prenatal exposure to organophosphate (OP) pesticides with poorer childhood neurodevelopment. As children grow older, poorer cognition, executive function, and school performance can give rise to risk-taking behaviors, including substance abuse, delinquency, and violent acts. We investigated whether prenatal OP exposure was associated with these risk-taking behaviors in adolescence and young adulthood in a Mexican American cohort.

Methods
We measured urinary dialkyl phosphates (DAPs), non-specific metabolites of OPs, twice (13 and 26 weeks gestation) in pregnant women recruited in 1999–2000 in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, a birth cohort set in a primarily Latino agricultural community in the Salinas Valley, California. We followed up children throughout their childhood and adolescence; at the 18-year visit, adolescent youth (n = 315) completed a computer-based questionnaire which included questions about substance use, risky sexual activity, risky driving, and delinquency and police encounters. We used multivariable models to estimate associations of prenatal total DAPs with these risk-taking behaviors.

Results
The prevalence of risk-taking behaviors in CHAMACOS youth ranged from 8.9% for smoking or vaping nicotine to 70.2% for committing a delinquent act. Associations of total prenatal DAPs (geometric mean = 132.4 nmol/L) with risk-taking behavior were generally null and imprecise. Isolated findings included a higher risk for smoking or vaping nicotine within the past 30 days (relative risk [RR] per 10-fold increase in prenatal DAPs = 1.89, 95% CI: 1.00, 3.56) and driving without a license (RR = 1.74, 95% CI: 1.25, 2.42). There were no consistent differences by sex or childhood adversity.

Discussion
We did not find clear or consistent evidence for associations of prenatal OP exposure with risk-taking behaviors in adolescence/early adulthood in the CHAMACOS population. Our small sample size may have prevented us from detecting potentially subtle associations of early life OP exposure with these risk-taking behaviors.
3D hanging spheroid plate for high-throughput CAR T cell cytotoxicity assay
Authors: Chen Zhenzhong , Han Seokgyu , Sanny Arleen , Chan Dorothy Leung-Kwan , van Noort Danny , Lim Wanyoung , Tan Andy Hee-Meng , Park Sungsu 
Published: January 2022

AbstractBackgroundMost high-throughput screening (HTS) systems studying the cytotoxic effect of chimeric antigen receptor (CAR) T cells on tumor cells rely on two-dimensional cell culture that does not recapitulate the tumor microenvironment (TME). Tumor spheroids, however, can recapitulate the TME and have been used for cytotoxicity assays of CAR T cells. But a major obstacle to the use of tumor spheroids for cytotoxicity assays is the difficulty in separating unbound CAR T and dead tumor cells from spheroids. Here, we present a three-dimensional hanging spheroid plate (3DHSP), which facilitates the formation of spheroids and the separation of unbound and dead cells from spheroids during cytotoxicity assays.ResultsThe 3DHSP is a 24-well plate, with each well composed of a hanging dripper, spheroid wells, and waste wells. In the dripper, a tumor spheroid was formed and mixed with CAR T cells. In the 3DHSP, droplets containing the spheroids were deposited into the spheroid separation well, where unbound and dead T and tumor cells were separated from the spheroid through a gap into the waste well by tilting the 3DHSP by more than 20°. Human epidermal growth factor receptor 2 (HER2)-positive tumor cells (BT474 and SKOV3) formed spheroids of approximately 300–350 μm in diameter after 2 days in the 3DHSP. The cytotoxic effects of T cells engineered to express CAR recognizing HER2 (HER2-CAR T cells) on these spheroids were directly measured by optical imaging, without the use of live/dead fluorescent staining of the cells. Our results suggest that the 3DHSP could be incorporated into a HTS system to screen for CARs that enable T cells to kill spheroids formed from a specific tumor type with high efficacy or for spheroids consisting of tumor types that can be killed efficiently by T cells bearing a specific CAR.ConclusionsThe results suggest that the 3DHSP could be incorporated into a HTS system for the cytotoxic effects of CAR T cells on tumor spheroids.Graphical Abstract
Anxiety disorders in patients with noncardiac chest pain: association with health-related quality of life and chest pain severity
Authors: Hamel Stéphanie , Denis Isabelle , Turcotte Stéphane , Fleet Richard , Archambault Patrick , Dionne Clermont E. , Foldes-Busque Guillaume 
Published: January 2022

Abstract
Background
Patients with noncardiac chest pain (NCCP) report more severe symptoms and lowered health-related quality of life when they present with comorbid panic disorder (PD). Although generalized anxiety disorder (GAD) is the second most common psychiatric disorder in these patients, its impact on NCCP and health-related quality of life remains understudied. This study describes and prospectively compares patients with NCCP with or without PD or GAD in terms of (1) NCCP severity; and (2) the physical and mental components of health-related quality of life.

Methods
A total of 915 patients with NCCP were consecutively recruited in two emergency departments. The presence of comorbid PD or GAD was assessed at baseline with the Anxiety Disorder Schedule for DSM-IV. NCCP severity at baseline and at the six-month follow-up was assessed with a structured telephone interview, and the patients completed the 12-item Short-Form Health Survey Version 2 (SF-12v2) to assess health-related quality of life at both time points.

Results
Average NCCP severity decreased between baseline and the six-month follow-up (p < .001) and was higher in the patients with comorbid PD or GAD (p < .001) at both time points compared to those with NCCP only. However, average NCCP severity did not differ between patients with PD and those with GAD (p = 0.901). The physical component of quality of life improved over time (p = 0.016) and was significantly lower in the subset of patients with PD with or without comorbid GAD compared to the other groups (p < .001). A significant time x group interaction was found for the mental component of quality of life (p = 0.0499). GAD with or without comorbid PD was associated with a lower mental quality of life, and this effect increased at the six-month follow-up.

Conclusions
Comorbid PD or GAD are prospectively associated with increased chest pain severity and lowered health-related quality of life in patients with NCCP. PD appears to be mainly associated with the physical component of quality of life, while GAD has a greater association with the mental component. Knowledge of these differences could help in the management of patients with NCCP and these comorbidities.
Accreditation and professional integration experiences of internationally qualified dentists working in the United Kingdom
Authors: Davda Latha S. , Radford David R. , Scambler Sasha , Gallagher Jennifer E. 
Published: January 2022

Abstract
Introduction
Regulatory processes for Oral health care professionals are considered essential for patient safety and to ensure health workforce quality. The global variation in their registration and regulation is under-reported in the literature. Regulatory systems could become a barrier to their national and international movement, leading to loss of skilled human resources. The General Dental Council is the regulatory authority in the UK, one of the nine regulators of health care overseen by the Professional Standards Authority.

Aim
The aim of this paper is to present the professional integration experiences of internationally qualified dentists (IQDs) working in the UK, against the background of regulation and accreditation nationally.

Methods
Registration data were obtained from the General Dental Council to inform the sampling and recruitment of research participants. Semi-structured interviews of 38 internationally qualified dentists working in the United Kingdom were conducted between August 2014 and October 2017. The topic guide which explored professional integration experiences of the dentists was informed by the literature, with new themes added inductively. A phenomenological approach involving an epistemological stance of interpretivism, was used with framework analysis to detect themes.

Results
Internationally qualified dentist’s professional integration was influenced by factors that could be broadly classified as structural (source country training; registration and employment; variation in practising dentistry) and relational (experiences of discrimination; value of networks and support; and personal attributes). The routes to register for work as a dentist were perceived to favour UK dental graduates and those qualifying from the European Economic Area. Dentists from the rest of the world reported experiencing major hurdles including succeeding in the licensing examinations, English tests, proving immigration status and succeeding in obtaining a National Health Service performer number, all prior to being able to practice within state funded dental care.

Conclusion
The pathways for dentists to register and work in state funded dental care in UK differ by geographic type of registrant, creating significant inconsistencies in their professional integration. Professional integration is perceived by an individual IQD as a continuum dictated by host countries health care systems, workforce recruitment policies, access to training, together with their professional and personal skills. The reliance of the UK on internationally qualified dentists has increased in the past two decades, however, it is not known how these trends will be affected by UK’s exit from the European Union and the COVID-19 pandemic.
Immunological status of the olfactory bulb in a murine model of Toll-like receptor 3-mediated upper respiratory tract inflammation
Authors: Kagoya Ryoji , Toma-Hirano Makiko , Yamagishi Junya , Matsumoto Naoyuki , Kondo Kenji , Ito Ken 
Published: January 2022

AbstractBackgroundPostviral olfactory dysfunction (PVOD) following a viral upper respiratory tract infection (URI) is one of the most common causes of olfactory disorders, often lasting for over a year. To date, the molecular pathology of PVOD has not been elucidated.MethodsA murine model of Toll-like receptor 3 (TLR3)-mediated upper respiratory tract inflammation was used to investigate the impact of URIs on the olfactory system. Inflammation was induced via the intranasal administration of polyinosinic–polycytidylic acid (poly(I:C), a TLR3 ligand) to the right nostril for 3 days. Peripheral olfactory sensory neurons (OSNs), immune cells in the olfactory mucosa, and glial cells in the olfactory bulb (OB) were analyzed histologically. Proinflammatory cytokines in the nasal tissue and OB were evaluated using the quantitative real-time polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA).ResultsIn the treated mice, OSNs were markedly reduced in the olfactory mucosa, and T cell and neutrophil infiltration therein was observed 1 day after the end of poly(I:C) administration. Moreover, there was a considerable increase in microglial cells and slight increase in activated astrocytes in the OB. In addition, qPCR and ELISA revealed the elevated expression of interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, and interferon-gamma both in the OB and nasal tissue.ConclusionsTaken together, the decreased peripheral OSNs, OB microgliosis, and elevated proinflammatory cytokines suggest that immunological changes in the OB may be involved in the pathogenesis of PVOD.