bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring healthcare students’ interprofessional teamwork in primary care simulation scenarios: collaboration to create a shared treatment plan
Authors: Lunde Lene , Moen Anne , Jakobsen Rune B. , Rosvold Elin O. , Brænd Anja M. 
Published: August 2021

Abstract
Background
Primary care providers assume responsibility for patients with increasingly complex problems requiring interprofessional collaboration. Introducing interprofessional education in healthcare curricula prepares healthcare students for this reality. Solving simulation scenarios as an educational strategy is promoted to support interprofessional education in health care, and is mostly used in acute clinical situations. This paper aims to explore how healthcare students’ actions influence interprofessional collaboration and treatment plan identification when they solve common, sub-acute patient scenarios in primary care situations.

Methods
Interaction analysis of video recordings from the simulation scenarios was performed with a focus on the students’ joint actions; specifically how these actions unfold and how productive the students were in terms of developing treatment plans.

Results
We found variation in the groups’ interactions, the paths they followed, and the quality of their knowledge output in their shared treatment plan. The groups with the capacity to collaborate and engage in sharing information, and explain and elaborate on concepts, were more successful in developing comprehensive treatment plans. Furthermore, these groups managed the duality of defining and solving the immediate problem and collaboratively preparing for future care.

Conclusions
Analysis of the activities in our scenarios showed the students’ potential to practice interprofessional collaboration. Our study illustrates that simulation of sub-acute scenarios in primary care is an underexplored but suitable arena to train communication and teamwork in complex situations. The simulation scenarios are also feasible for use on-site in an educational facility or in practice with minimal equipment and resources.
Plasma nesfatin-1 and DDP-4 levels in patients with coronary artery disease: Kozani study
Authors: Kadoglou Nikolaos P. E. , Korakas Emmanouil , Lampropoulos Stylianos , Maratou Eirini , Kassimis George , Patsourakos Nikolaos , Plotas Panagiotis , Moutsatsou Paraskevi , Lambadiari Vaia 
Published: August 2021

Abstract
Background
Nesfatin-1, a novel adipokine and dipeptidyl peptidase-4 (DPP4), a mam malian serine protease, are potent factors of atherosclerosis. In the present cross-sectional study, we investigated whether the plasma nesfatin-1 and DPP4 is associated with the prevalence and severity of coronary artery disease (CAD) with and without diabetes mellitus (DM).

Methods
We consecutively enrolled a total of 240 patients with significant CAD (previous revascularization or angiographically-proven coronary artery stenosis > 50%) presented with either unstable angina (UA, N = 76) or stable chronic CAD (SCAD, N = 165). 85 patients with at least 2 classical cardiovascular risk factors but without significant CAD served as controls. The severity of CAD was assessed using coronary angiography by the Gensini score. Clinical parameters, glycemic and lipid profile, high-sensitivity CRP (hsCRP), nesfatin-1 and DPP4 levels were assayed.

Results
No differences were found for age, sex, hypertension and diabetes distribution between groups. Low nesfatin-1 levels were found in both CAD groups (UA & SCAD) with respect to controls. The difference between UA and SCAD groups was marginally non-significant. There was a significant increase of DPP4 along UA to SCAD and control groups. Differences between groups remained unchanged in non-diabetic participants. Nesfatin-1 significantly correlated to hsCRP (r = − 0.287, p = 0.036), HOMA-IR (r = − 0.587, p = 0.007) and hyperlipidemia (r = − 0.331, p = 0.034). DPP4 was significantly associated with hs-CRP (r = 0.353 p < 0.001) and FPG (r = 0.202, p = 0.020) in univariate analysis, but those correlations were lost in multiple regression analysis. There was a negative correlation between nesfatin-1 and the severity of CAD, quantified by the Gensini score (r = − 0.511, p < 0.001), but no association was found for DPP4.

Conclusions
Serum DPP4 levels are increased in patients with CAD, while serum nesfatin-1 levels have a negative association with both the incidence and the severity of CAD. These results are independent of the presence of diabetes mellitus. In addition, both peptides have a strong association with hsCRP.
Trial registration ClinicalTrials.gov Identifier: NCT00306176
Vanillic acid and methoxyhydroquinone production from guaiacyl units and related aromatic compounds using Aspergillus niger cell factories
Authors: Lubbers Ronnie J. M. , Dilokpimol Adiphol , Nousiainen Paula A. , Cioc Răzvan C. , Visser Jaap , Bruijnincx Pieter C. A. , de Vries Ronald P. 
Published: August 2021

Abstract
Background
The aromatic compounds vanillin and vanillic acid are important fragrances used in the food, beverage, cosmetic and pharmaceutical industries. Currently, most aromatic compounds used in products are chemically synthesized, while only a small percentage is extracted from natural sources. The metabolism of vanillin and vanillic acid has been studied for decades in microorganisms and many studies have been conducted that showed that both can be produced from ferulic acid using bacteria. In contrast, the degradation of vanillin and vanillic acid by fungi is poorly studied and no genes involved in this metabolic pathway have been identified. In this study, we aimed to clarify this metabolic pathway in Aspergillus niger and identify the genes involved.

Results
Using whole-genome transcriptome data, four genes involved in vanillin and vanillic acid metabolism were identified. These include vanillin dehydrogenase (vdhA), vanillic acid hydroxylase (vhyA), and two genes encoding novel enzymes, which function as methoxyhydroquinone 1,2-dioxygenase (mhdA) and 4-oxo-monomethyl adipate esterase (omeA). Deletion of these genes in A. niger confirmed their role in aromatic metabolism and the enzymatic activities of these enzymes were verified. In addition, we demonstrated that mhdA and vhyA deletion mutants can be used as fungal cell factories for the accumulation of vanillic acid and methoxyhydroquinone from guaiacyl lignin units and related aromatic compounds.

Conclusions
This study provides new insights into the fungal aromatic metabolic pathways involved in the degradation of guaiacyl units and related aromatic compounds. The identification of the involved genes unlocks new potential for engineering aromatic compound-producing fungal cell factories.
Tumor cell-imposed iron restriction drives immunosuppressive polarization of tumor-associated macrophages
Authors: Sun Jia-Lei , Zhang Ning-Ping , Xu Ru-Chen , Zhang Guang-Cong , Liu Zhi-Yong , Abuduwaili Weinire , Wang Fu , Yu Xiang-Nan , Shi Xuan , Song Guang-Qi , Wu Hao , Liu Tao-Tao , Shen Xi-Zhong , Deng Bin , Weng Shu-Qiang , Dong Ling , Zhu Ji-Min 
Published: August 2021

Abstract
Background
Tumor-associated macrophages (TAM) are immunosuppressive cells that contribute to impaired anti-cancer immunity. Iron plays a critical role in regulating macrophage function. However, it is still elusive whether it can drive the functional polarization of macrophages in the context of cancer and how tumor cells affect the iron-handing properties of TAM. In this study, using hepatocellular carcinoma (HCC) as a study model, we aimed to explore the effect and mechanism of reduced ferrous iron in TAM.

Methods
TAM from HCC patients and mouse HCC tissues were collected to analyze the level of ferrous iron. Quantitative real-time PCR was used to assess M1 or M2 signature genes of macrophages treated with iron chelators. A co-culture system was established to explore the iron competition between macrophages and HCC cells. Flow cytometry analysis was performed to determine the holo-transferrin uptake of macrophages. HCC samples from The Cancer Genome Atlas (TCGA) were enrolled to evaluate the prognostic value of transferrin receptor (TFRC) and its relevance to tumor-infiltrating M2 macrophages.

Results
We revealed that ferrous iron in M2-like TAM is lower than that in M1-like TAM. In vitro analysis showed that loss of iron-induced immunosuppressive M2 polarization of mouse macrophages. Further experiments showed that TFRC, the primary receptor for transferrin-mediated iron uptake, was overexpressed on HCC cells but not TAM. Mechanistically, HCC cells competed with macrophages for iron to upregulate the expression of M2-related genes via induction of HIF-1α, thus contributing to M2-like TAM polarization. We further clarified the oncogenic role of TFRC in HCC patients by TCGA. TFRC is significantly increased in varieties of malignancies, including HCC, and HCC patients with high TFRC levels have considerably shortened overall survival. Also, TFRC is shown to be positively related to tumor-infiltrating M2 macrophages.

Conclusions
Collectively, we identified iron starvation through TFRC-mediated iron competition drives functional immunosuppressive polarization of TAM, providing new insight into the interconnection between iron metabolism and tumor immunity.
Hepatocyte growth factor pathway expression in breast cancer by race and subtype
Authors: Jones Gieira S. , Hoadley Katherine A. , Olsson Linnea T. , Hamilton Alina M. , Bhattacharya Arjun , Kirk Erin L. , Tipaldos Heather J. , Fleming Jodie M. , Love Michael I. , Nichols Hazel B. , Olshan Andrew F. , Troester Melissa A. 
Published: August 2021

AbstractBackgroundAfrican American women have the highest risk of breast cancer mortality compared to other racial groups. Differences in tumor characteristics have been implicated as a possible cause; however, the tumor microenvironment may also contribute to this disparity in mortality. Hepatocyte growth factor (HGF) is a stroma-derived marker of the tumor microenvironment that may affect tumor progression differentially by race.ObjectiveTo examine whether an HGF gene expression signature is differentially expressed by race and tumor characteristics.MethodsInvasive breast tumors from 1957 patients were assessed for a 38-gene RNA-based HGF gene expression signature. Participants were black (n= 1033) and non-black (n= 924) women from the population-based Carolina Breast Cancer Study (1993–2013). Generalized linear models were used to estimate the relative frequency differences (RFD) in HGF status by race, clinical, and demographic factors.ResultsThirty-two percent of tumors were positive for the HGF signature. Black women were more likely [42% vs. 21%; RFD = + 19.93% (95% CI 16.00, 23.87)] to have HGF-positive tumors compared to non-black women. Triple-negative patients had a higher frequency of HGF positivity [82% vs. 13% in non-triple-negative; RFD = + 65.85% (95% CI 61.71, 69.98)], and HGF positivity was a defining feature of basal-like subtype [92% vs. 8% in non-basal; RFD = + 81.84% (95% CI 78.84, 84.83)]. HGF positivity was associated with younger age, stage, higher grade, and high genomic risk of recurrence (ROR-PT) score.ConclusionHGF expression is a defining feature of basal-like tumors, and its association with black race and young women suggests it may be a candidate pathway for understanding breast cancer disparities.
Rapid spheroid assays in a 3-dimensional cell culture chip
Authors: Teh Jia Lin , Abdul Rahman Siti Fairus , Domnic Gregory , Satiyasilan Lengishwarra , Chear Nelson Jeng Yeou , Singh Darshan , Mohana-Kumaran Nethia 
Published: August 2021

Abstract
Objective
The spheroid model provides a physiological platform to study cancer cell biology and drug sensitivity. Usage of bovine collagen I for spheroid assays is costly especially when experiments are conducted in 24-well plates, as high volume of bovine collagen I is needed. The aim of the study was to downsize spheroid assays to a microfluidic 3D cell culture chip and compare the growth, invasion and response to drug/compound of spheroids embedded in the 3D chip to spheroids embedded in 24-well plates.

Results
Spheroids generated from nasopharyngeal carcinoma cell line HK-1 continuously grew and invaded into collagen matrix in a 24-well plate. Similar observations were noticed with spheroids embedded in the 3D chip. Large spheroids in both 24-well plate and the 3D chip disintegrated and invaded into the collagen matrix. Preliminary drug sensitivity assays showed that the growth and invasion of spheroids were inhibited when spheroids were treated with combination of cisplatin and paynantheine at high concentrations, in a 24-well plate. Comparable findings were obtained when spheroids were treated with the same drug combination in the 3D chip. Moving forward, spheroid assays could be performed in the 3D chip in a more high-throughput manner with minimal time and cost.
Tau-related grey matter network breakdown across the Alzheimer’s disease continuum
Authors: Pelkmans Wiesje , Ossenkoppele Rik , Dicks Ellen , Strandberg Olof , Barkhof Frederik , Tijms Betty M. , Pereira Joana B. , Hansson Oskar 
Published: August 2021

AbstractBackgroundChanges in grey matter covariance networks have been reported in preclinical and clinical stages of Alzheimer’s disease (AD) and have been associated with amyloid-β (Aβ) deposition and cognitive decline. However, the role of tau pathology on grey matter networks remains unclear. Based on previously reported associations between tau pathology, synaptic density and brain structural measures, tau-related connectivity changes across different stages of AD might be expected. We aimed to assess the relationship between tau aggregation and grey matter network alterations across the AD continuum.MethodsWe included 533 individuals (178 Aβ-negative cognitively unimpaired (CU) subjects, 105 Aβ-positive CU subjects, 122 Aβ-positive patients with mild cognitive impairment, and 128 patients with AD dementia) from the BioFINDER-2 study. Single-subject grey matter networks were extracted from T1-weighted images and graph theory properties including degree, clustering coefficient, path length, and small world topology were calculated. Associations between tau positron emission tomography (PET) values and global and regional network measures were examined using linear regression models adjusted for age, sex, and total intracranial volume. Finally, we tested whether the association of tau pathology with cognitive performance was mediated by grey matter network disruptions.ResultsAcross the whole sample, we found that higher tau load in the temporal meta-ROI was associated with significant changes in degree, clustering, path length, and small world values (allp< 0.001), indicative of a less optimal network organisation. Already in CU Aβ-positive individuals associations between tau burden and lower clustering and path length were observed, whereas in advanced disease stages elevated tau pathology was progressively associated with more brain network abnormalities. Moreover, the association between higher tau load and lower cognitive performance was only partly mediated (9.3 to 9.5%) through small world topology.ConclusionsOur data suggest a close relationship between grey matter network disruptions and tau pathology in individuals with abnormal amyloid. This might reflect a reduced communication between neighbouring brain areas and an altered ability to integrate information from distributed brain regions with tau pathology, indicative of a more random network topology across different AD stages.
Dispersants as marine oil spill treating agents: a review on mesoscale tests and field trials
Authors: Merlin Francois , Zhu Zhiwen , Yang Min , Chen Bing , Lee Kenneth , Boufadel Michel C. , Isaacman Lisa , Zhang Baiyu 
Published: August 2021

AbstractThe increasing oil demand and busy waterways highlight the importance of oil spill preparedness and responses. Dispersants attract attention as an effective response tool to manage the impacts of major spill incidents. Despite in-depth laboratory evaluations on the effectiveness of chemical dispersants and their impacts on the transportation and fate of spilled oils, how dispersant works at sea remains a question and calls for the tests with greater realism to validate laboratory results, bring in energy impacts, and evaluate dispersant application equipment. Mesoscale studies and field trials have thus been widely conducted to assist better spill response operations. Such research attempts, however, lack a systematic summary. This study tried to fill the knowledge gaps by introducing the mesoscale facilities developed to advance the understanding of dispersant effectiveness on various sea conditions. An up-to-date overview of mesoscale studies and field trial assessments of dispersant effectiveness has also been conducted. We ended this review by highlighting the importance of public perception and future research needs to promote the approval and application of dispersants in spill incidents.
The prognostic and therapeutic implications of distinct patterns of argininosuccinate synthase 1 (ASS1) and arginase-2 (ARG2) expression by cancer cells and tumor stroma in non-small-cell lung cancer
Authors: Giatromanolaki Alexandra , Harris Adrian L. , Koukourakis Michael I. 
Published: August 2021

Abstract
Background
Arginine (Arg) is essential for cancer cell growth and also for the activation of T cells. Thus, therapies aiming to reduce Arg utilization by cancer may prove detrimental for the immune response.

Methods
We examined the expression of two major enzymes involved in arginine depletion and replenishment, namely arginase ARG2 and argininosuccinate synthase ASS1, respectively, in a series of 98 NSCLCs. Their association with immune infiltrates and the postoperative outcome were also studied.

Results
ARG2 was expressed mainly by cancer-associated fibroblasts (CAFs) (58/98 cases; 59.2%), while ASS1 by cancer cells (75/98 cases; 76.5%). ASS1 and ARG2 expression patterns were not related to hypoxia markers. Auxotrophy, implied by the lack of expression of ASS1 in cancer cells, was associated with high angiogenesis (p < 0.02). ASS1 expression by cancer cells was associated with a high density of iNOS-expressing tumor-infiltrating lymphocytes (iNOS+TILs). ARG2 expression by CAFs was inversely related to the TIL-density and linked with poorer prognosis (p = 0.02). Patients with ASS1 expression by cancer cells had a better prognosis especially when CAFs did not express ARG2 (p = 0.004).

Conclusions
ARG2 and ASS1 enzymes are extensively expressed in NSCLC stroma and cancer cells, respectively. Auxotrophic tumors have a poor prognosis, potentially by utilizing Arg, thus reducing Arg-dependent TIL anti-tumor activity. ASS1 expression in cancer cells would allow Arg fueling of iNOS+TILs and enhance anti-tumor immunity. However, upregulation of ARG2 in CAFs may divert Arg from TILs, allowing immune escape. Identification of these three distinct phenotypes may be useful in the individualization of Arg-targeting therapies and immunotherapy.
The pathogenic role of c-Kit+ mast cells in the spinal motor neuron-vascular niche in ALS
Authors: Kovacs Mariángeles , Alamón Catalina , Maciel Cecilia , Varela Valentina , Ibarburu Sofía , Tarragó Lucas , King Peter H. , Si Ying , Kwon Yuri , Hermine Olivier , Barbeito Luis , Trias Emiliano 
Published: August 2021

AbstractDegeneration of motor neurons, glial cell reactivity, and vascular alterations in the CNS are important neuropathological features of amyotrophic lateral sclerosis (ALS). Immune cells trafficking from the blood also infiltrate the affected CNS parenchyma and contribute to neuroinflammation. Mast cells (MCs) are hematopoietic-derived immune cells whose precursors differentiate upon migration into tissues. Upon activation, MCs undergo degranulation with the ability to increase vascular permeability, orchestrate neuroinflammation and modulate the neuroimmune response. However, the prevalence, pathological significance, and pharmacology of MCs in the CNS of ALS patients remain largely unknown. In autopsy ALS spinal cords, we identified for the first time that MCs express c-Kit together with chymase, tryptase, and Cox-2 and display granular or degranulating morphology, as compared with scarce MCs in control cords. In ALS, MCs were mainly found in the niche between spinal motor neuron somas and nearby microvascular elements, and they displayed remarkable pathological abnormalities. Similarly, MCs accumulated in the motor neuron-vascular niche of ALS murine models, in the vicinity of astrocytes and motor neurons expressing the c-Kit ligand stem cell factor (SCF), suggesting an SCF/c-Kit-dependent mechanism of MC differentiation from precursors. Mechanistically, we provide evidence that fully differentiated MCs in cell cultures can be generated from the murine ALS spinal cord tissue, further supporting the presence of c-Kit+ MC precursors. Moreover, intravenous administration of bone marrow-derived c-Kit+ MC precursors infiltrated the spinal cord in ALS mice but not in controls, consistent with aberrant trafficking through a defective microvasculature. Pharmacological inhibition of c-Kit with masitinib in ALS mice reduced the MC number and the influx of MC precursors from the periphery. Our results suggest a previously unknown pathogenic mechanism triggered by MCs in the ALS motor neuron-vascular niche that might be targeted pharmacologically.
Experience of using home-based fortified diet in rehabilitation of malnourished children at Indus Hospital, Karachi, Pakistan: an institution based retrospective chart review study
Authors: Shahid Saba , Mahesar Marvi , Rahim Anum , Sadiq Yumna 
Published: August 2021

Abstract
Background
Globally, it is estimated that 50 million children under five are wasted. National nutrition survey-2018 has shown that 23.3 and 45.5% of children are wasted and stunted in Pakistan. Many studies have shown that hospital-based management of malnutrition is not practical due to high cost and iatrogenic infections and currently WHO recommends community-based management of malnutrition with provision of therapeutic food. There is limited evidence of community rehabilitation of malnourished children by using home fortified diet in Pakistan. This study explores use of energy dense, home fortified diet in achieving weight gain of malnourished children in Karachi.

Methods
A descriptive, retrospective chart review of pediatric patients (aged 6 month–5 years) seen in Indus Hospital between January 2017 to June 2018 was conducted. A pre-designed data abstraction form was used to record detailed information about demographic characteristics, feeding, anthropometric, micronutrient, and nutritional details at enrollment and on follow-up.

Results
A total of 361 patients were included in the final analysis. The median age (IQR) of children was 15 (14) months. Forty eight percent (n = 172) children had diarrhea and 54% (n = 195) children had respiratory tract infection. The median length of stay in the program was 28 days. The median (IQR) for average weight gain was 4.8 (0–10.3) g/Kg/day, 64.6% (n = 226) children defaulted, 29% (n = 102) were cured and 3% (n = 10) died.

Conclusion
This study showed adequate weight gain and recovery in malnourished children by using home fortified diet in real life situations without using therapeutic food or monetary support. Home fortified diets may serve as effective strategy in community-based rehabilitation of malnourished children.