bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incorporating interactive workshops into bedside teaching: completion of a multi-modal rheumatology rotation significantly increases internal medicine residents’ competency and comfort with comprehensive knee examinations
Authors: Kwiatkowski Alysia , Shakoor Najia , Manadan Augustine , Block Joel A. , Khandelwal Sonali 
Published: May 2022

Abstract
Background
Studies have elucidated the lack of competency in musculoskeletal (MSK) examination skills amongst trainees. Various modalities have been studied, however, there remains a dearth of literature regarding the effectiveness of bedside teaching versus dedicated workshops. Our aim was to determine if incorporating a workshop into a rheumatology rotation would be effective in increasing medicine residents’ competency and comfort with knee examinations when compared to the rotation alone.

Methods
Over 16 months, rotators were randomized to workshop plus rotation versus rotation alone. Participants were tested on their knee examination skills using an objective structured clinical examination (OSCE). Surveys were administered assessing to what degree the rotation was beneficial. Comfort and helpfulness were measured using a 5-point Likert scale. Paired and independent samples t-tests were used for comparisons.

Results
Fifty-seven residents participated. For both groups, there were improvements between pre- and post-OSCE scores (workshop p < 0.001, no workshop p = 0.003), and levels of comfort with examination (workshop p < 0.001, no workshop p < 0.001). When comparing groups, there were differences favoring the workshop in post-OSCE score (p = < 0.001), mean change in OSCE score (p < 0.001) and mean change in comfort with knee examination (p = 0.025).

Conclusion
An elective in rheumatology augmented residents’ MSK competency and comfort. Incorporation of a workshop further increased knowledge, skills and comfort with diagnosis and treatment. Current educational research focuses on alternatives to traditional methods. This study provides evidence that a multi-modal approach, combining traditional bedside and interactive models, is of benefit.
The development and implementation of a guideline-based clinical decision support system to improve empirical antibiotic prescribing
Authors: Akhloufi H. , van der Sijs H. , Melles D. C. , van der Hoeven C. P. , Vogel M. , Mouton J. W. , Verbon A. 
Published: May 2022

Abstract
Background
To describe and evaluate a clinical decision support system (CDSS) for empirical antibiotic therapy using a systematic framework.

Methods
A reporting framework for behavior change intervention implementation was used, which includes several domains: development, evaluation and implementation. Within the development domain a description is given of the engagement of stakeholders, a rationale for how the CDSS may influence antibiotic prescribing and a detailed outline of how the system was developed. Within the evaluation domain a technical validation is performed and the interaction between potential users and the CDSS is analyzed. Within the domain of implementation a description is given on how the CDSS was tested in the real world and the strategies that were used for implementation and adoption of the CDSS.

Results
Development: a CDSS was developed, with the involvement of stakeholders, to assist empirical antibiotic prescribing by physicians. Evaluation: Technical problems were determined during the validation process and corrected in a new CDSS version. A usability study was performed to assess problems in the system-user interaction. Implementation: In 114 patients the antibiotic advice that was generated by the CDSS was followed. For 54 patients the recommendations were not adhered to.

Conclusions
This study describes the development and validation of a CDSS for empirical antibiotic therapy and shows the usefulness of the systematic framework for reporting CDSS interventions. In addition it shows that CDSS recommendations are not always adhered to which is associated with incorrect use of the system.
Hospital nurses’ knowledge about older patients in Turkey: a validation and comparison study
Authors: Harputlu Deniz , Kerstens Sander , Özdemir Funda , Dikken Jeroen 
Published: May 2022

Abstract
Background
In Turkey, nursing care in hospitals has gradually included more older patients, resulting in a need for knowledgeable geriatric nurses. It is unknown, however, whether the nursing workforce is ready for this increase. Therefore, the aim of this study is to validate the Knowledge about Older Patients Quiz (KOPQ) in the Turkish language and culture, to describe Turkish hospital nurses’ knowledge about older patients, and to compare levels of knowledge between Turkish and Dutch hospital nurses.

Method
First, the KOPQ was translated, resulting in the KOPQ-TR. Then, content validity was assessed by 10 geriatric experts using the Lynn method, a pilot test among 10 nurses was conducted, and a Rasch analysis was performed using data from 135 nurses working in two Turkish hospitals. Finally, a comparison between Turkish and Dutch nurses’ levels of knowledge was performed.

Results
The results of the qualitative validation (i.e., content validity by experts and nurses), model fit, item reliability and the item separation index of the KOPQ-TR proved excellent, indicating good content and construct validity. However, the Person Separation Index and Person Reliability of the Rash analysis did not meet the criteria for adequate scale and psychometric validation. The levels of knowledge among Turkish nurses were significantly lower than those of Dutch nurses.

Conclusions
The KOPQ-TR is promising for use in Turkey, although psychometric validation should be repeated using a better targeted sample with a larger ability variance to adequately assess the Person Separation Index and Person Reliability. Currently, education regarding care for older patients is not sufficiently represented in Turkish nursing curricula. However, the need to do so is evident, as the results demonstrate that knowledge deficits and an increase in older patients admitted to the hospital will eventually occur. International comparison and cooperation provides an opportunity to learn from other countries that currently face the challenge of an aging (hospital) population.
Repeat hospital transfers among long stay nursing home residents: a mixed methods analysis of age, race, code status and clinical complexity
Authors: Vogelsmeier Amy , Popejoy Lori , Fritz Elizabeth , Canada Kelli , Ge Bin , Brandt Lea , Rantz Marilyn 
Published: May 2022

Abstract
Background
Nursing home residents are at increased risk for hospital transfers resulting in emergency department visits, observation stays, and hospital admissions; transfers that can also result in adverse resident outcomes. Many nursing home to hospital transfers are potentially avoidable. Residents who experience repeat transfers are particularly vulnerable to adverse outcomes, yet characteristics of nursing home residents who experience repeat transfers are poorly understood. Understanding these characteristics more fully will help identify appropriate intervention efforts needed to reduce repeat transfers.

Methods
This is a mixed-methods study using hospital transfer data, collected between 2017 and 2019, from long-stay nursing home residents residing in 16 Midwestern nursing homes who transferred four or more times within a 12-month timeframe. Data were obtained from an acute care transfer tool used in the Missouri Quality Initiative containing closed- and open-ended questions regarding hospital transfers. The Missouri Quality Initiative was a Centers for Medicare and Medicaid demonstration project focused on reducing avoidable hospital transfers for long stay nursing home residents. The purpose of the analysis presented here is to describe characteristics of residents from that project who experienced repeat transfers including resident age, race, and code status. Clinical, resident/family, and organizational factors that influenced transfers were also described.

Results
Findings indicate that younger residents (less than 65 years of age), those who were full-code status, and those who were Black were statistically more likely to experience repeat transfers. Clinical complexity, resident/family requests to transfer, and lack of nursing home resources to manage complex clinical conditions underlie repeat transfers, many of which were considered potentially avoidable.

Conclusions
Improved nursing home resources are needed to manage complex conditions in the NH and to help residents and families set realistic goals of care and plan for end of life thus reducing potentially avoidable transfers.
Liquid biopsies to occult brain metastasis
Authors: Rehman Asad Ur , Khan Parvez , Maurya Shailendra Kumar , Siddiqui Jawed A. , Santamaria-Barria Juan A. , Batra Surinder K. , Nasser Mohd Wasim 
Published: May 2022

AbstractBrain metastasis (BrM) is a major problem associated with cancer-related mortality, and currently, no specific biomarkers are available in clinical settings for early detection. Liquid biopsy is widely accepted as a non-invasive method for diagnosing cancer and other diseases. We have reviewed the evidence that shows how the molecular alterations are involved in BrM, majorly from breast cancer (BC), lung cancer (LC), and melanoma, with an inception in how they can be employed for biomarker development. We discussed genetic and epigenetic changes that influence cancer cells to breach the blood-brain barrier (BBB) and help to establish metastatic lesions in the uniquely distinct brain microenvironment. Keeping abreast with the recent breakthroughs in the context of various biomolecules detections and identifications, the circulating tumor cells (CTC), cell-free nucleotides, non-coding RNAs, secretory proteins, and metabolites can be pursued in human body fluids such as blood, serum, cerebrospinal fluid (CSF), and urine to obtain potential candidates for biomarker development. The liquid biopsy-based biomarkers can overlay with current imaging techniques to amplify the signal viable for improving the early detection and treatments of occult BrM.
Melanoma cells with diverse invasive potential differentially induce the activation of normal human fibroblasts
Authors: Mazurkiewicz Justyna , Simiczyjew Aleksandra , Dratkiewicz Ewelina , Pietraszek-Gremplewicz Katarzyna , Majkowski Michał , Kot Magdalena , Ziętek Marcin , Matkowski Rafał , Nowak Dorota 
Published: May 2022

AbstractBackgroundThe tumor microenvironment consists of stromal cells, extracellular matrix, and physicochemical properties (e.g., oxygenation, acidification). An important element of the tumor niche are cancer-associated fibroblasts (CAFs). They may constitute up to 80% of the tumor mass and share some features with myofibroblasts involved in the process of wound healing. CAFs can facilitate cancer progression. However, their interaction with melanoma cells is still poorly understood.MethodsWe obtained CAFs using conditioned media derived from primary and metastatic melanoma cells, and via co-culture with melanoma cells on Transwell inserts. Using 2D and 3D wound healing assays and Transwell invasion method we evaluated CAFs’ motile activities, while coverslips with FITC-labeled gelatin, gelatin zymography, and fluorescence-based activity assay were employed to determine the proteolytic activity of the examined cells. Western Blotting method was used for the identification of CAFs’ markers as well as estimation of the mediators of MMPs’ (matrix metalloproteinases) expression levels. Lastly, CAFs’ secretome was evaluated with cytokine and angiogenesis proteomic arrays, and lactate chemiluminescence-based assay.ResultsAcquired FAP-α/IL6-positive CAFs exhibited elevated motility expressed as increased migration and invasion ratio, as well as higher proteolytic activity (area of digestion, MMP2, MMP14). Furthermore, fibroblasts activated by melanoma cells showed upregulation of the MMPs’ expression mediators’ levels (pERK, p-p38, CD44, RUNX), enhanced secretion of lactate, several cytokines (IL8, IL6, CXCL1, CCL2, ICAM1), and proteins related to angiogenesis (GM-CSF, DPPIV, VEGFA, PIGF).ConclusionsObserved changes in CAFs’ biology were mainly driven by highly aggressive melanoma cells (A375, WM9, Hs294T) compared to the less aggressive WM1341D cells and could promote melanoma invasion, as well as impact inflammation, angiogenesis, and acidification of the tumor niche. Interestingly, different approaches to CAFs acquisition seem to complement each other showing interactions between studied cells.
Inhibition of NOS1 promotes the interferon response of melanoma cells
Authors: Chen Xi , Zou Zhiwei , Wang Qianli , Gao Wenwen , Zeng Sisi , Ye Shuangyan , Xu Pengfei , Huang Mengqiu , Li Keyi , Chen Jianping , Zhong Zhuo , Zhang Qianbing , Hao Bingtao , Liu Qiuzhen 
Published: May 2022

Abstract
Background
NOS1 expression predicts poor prognosis in patients with melanoma. However, the molecular function of NOS1 in the type I IFN response and immune escape of melanoma is still unknown.

Methods
The CRISPR/Cas9 system was used to generate NOS1-knockout melanoma cells and the biological characteristics of NOS1-knockout cells were evaluated by MTT assay, clonogenic assay, EdU assay, and flow cytometric assay. The effect on tumor growth was tested in BALB/c-nu and C57BL/6 mouse models. The gene expression profiles were detected with Affymetrix microarray and RNA-seq and KEGG (Kyoto Encyclopedia of Genes and Genomes) and CLUE GO analysis was done. The clinical data and transcriptional profiles of melanoma patients from the public database TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus, GSE32611) were analyzed by Qlucore Omics Explorer.

Results
NOS1 deletion suppressed the proliferation of melanoma A375 cells in culture, blocked cell cycling at the G0/G1 phase, and decreased the tumor growth in lung metastasis nodes in a B16 melanoma xenograft mouse model. Moreover, NOS1 knockout increased the infiltration of CD3+ immune cells in tumors. The transcriptomics analysis identified 2203 differential expression genes (DEGs) after NOS1 deletion. These DEGs indicated that NOS1 deletion downregulated mostly metabolic functions but upregulated immune response pathways. After inhibiting with NOS1 inhibitor N-PLA, melanoma cells significantly increased the response to IFN$$\upalpha $$
α
by upregulation expression of IFN$$\upalpha $$
α
simulation genes (ISGs), especially the components in innate immune signaling, JAK-STAT, and TOLL-LIKE pathway. Furthermore, these NOS1-regulating immune genes (NOS1-ISGs) worked as a signature to predict poor overall survival and lower response to chemotherapy in melanoma patients.

Conclusion
These findings provided a transcriptional evidence of NOS1 promotion on tumor growth, which is correlated with metabolic regulation and immune escape in melanoma cells.
The use of ECMO in pediatric granulomatosis with polyangiitis
Authors: Finkel Rachel , Honig Jesse , Chao Chun P. , Rescoe Erin , Solomon Sonia 
Published: May 2022

Abstract
Background
Granulomatosis with polyangiitis (GPA) vasculitis with pulmonary-renal syndrome rarely presents in children and is associated with high mortality rates.

Case presentation
We present the case of a 13-year-old male with newly diagnosed GPA vasculitis, treated with extracorporeal membrane oxygenation, continuous renal replacement therapy, plasmapheresis, rituximab, cyclophosphamide, and corticosteroids.

Conclusion
This case presentation demonstrates that ECMO can be used as a life supporting therapy in pediatric patients with pulmonary hemorrhage from ANCA vasculitis in conjunction with other therapies.
Copper oxide nanoparticles trigger macrophage cell death with misfolding of Cu/Zn superoxide dismutase 1 (SOD1)
Authors: Gupta Govind , Cappellini Francesca , Farcal Lucian , Gornati Rosalba , Bernardini Giovanni , Fadeel Bengt 
Published: May 2022

Abstract
Background
Copper oxide (CuO) nanoparticles (NPs) are known to trigger cytotoxicity in a variety of cell models, but the mechanism of cell death remains unknown. Here we addressed the mechanism of cytotoxicity in macrophages exposed to CuO NPs versus copper chloride (CuCl2).

Methods
The mouse macrophage cell line RAW264.7 was used as an in vitro model. Particle uptake and the cellular dose of Cu were investigated by transmission electron microscopy (TEM) and inductively coupled plasma mass spectrometry (ICP-MS), respectively. The deposition of Cu in lysosomes isolated from macrophages was also determined by ICP-MS. Cell viability (metabolic activity) was assessed using the Alamar Blue assay, and oxidative stress was monitored by a variety of methods including a luminescence-based assay for cellular glutathione (GSH), and flow cytometry-based detection of mitochondrial superoxide and mitochondrial membrane potential. Protein aggregation was determined by confocal microscopy using an aggresome-specific dye and protein misfolding was determined by circular dichroism (CD) spectroscopy. Lastly, proteasome activity was investigated using a fluorometric assay.

Results
We observed rapid cellular uptake of CuO NPs in macrophages with deposition in lysosomes. CuO NP-elicited cell death was characterized by mitochondrial swelling with signs of oxidative stress including the production of mitochondrial superoxide and cellular depletion of GSH. We also observed a dose-dependent accumulation of polyubiquitinated proteins and loss of proteasomal function in CuO NP-exposed cells, and we could demonstrate misfolding and mitochondrial translocation of superoxide dismutase 1 (SOD1), a Cu/Zn-dependent enzyme that plays a pivotal role in the defense against oxidative stress. The chelation of copper ions using tetrathiomolybdate (TTM) prevented cell death whereas inhibition of the cellular SOD1 chaperone aggravated toxicity. Moreover, CuO NP-triggered cell death was insensitive to the pan-caspase inhibitor, zVAD-fmk, and to wortmannin, an inhibitor of autophagy, implying that this was a non-apoptotic cell death. ZnO NPs, on the other hand, triggered autophagic cell death.

Conclusions
CuO NPs undergo dissolution in lysosomes leading to copper-dependent macrophage cell death characterized by protein misfolding and proteasomal insufficiency. Specifically, we present novel evidence for Cu-induced SOD1 misfolding which accords with the pronounced oxidative stress observed in CuO NP-exposed macrophages. These results are relevant for our understanding of the consequences of inadvertent human exposure to CuO NPs.
Youth mental health and/or addiction concerns and service needs during the COVID-19 pandemic: a qualitative exploration of caregiver experiences and perspectives
Authors: Markoulakis Roula , Da Silva Andreina , Kodeeswaran Sugy , Levitt Anthony 
Published: May 2022

AbstractThe COVID-19 pandemic has undoubtedly had a significant impact on youth mental health and/or addiction concerns and exacerbated pre-existing gaps in access to mental health and/or addiction care. Caregivers can support their youth in seeking and participating in care, however, their experiences in doing so in the pandemic and their perspectives of their youth’s care needs are not well-understood. A descriptive qualitative study was conducted to better understand youth’s and caregivers’ experiences accessing care during the pandemic, from the caregivers’ standpoint. Participants completed semi-structured qualitative interviews that focused on experiences seeking and accessing mental health and/or addiction services, with specific questions regarding their experiences accessing services during the pandemic. A total of 46 interviews were included in the thematic analysis of the data. Study findings highlight the impacts of the pandemic on everyday life, on youth mental health and/or addiction needs, on caregiver’s experiences seeking and accessing services for their youth, and on service access, including perceptions of virtual care modalities. The discussion highlights the importance of focusing on factors that enable youth’s participation in care, to ensure accessibility of appropriate and timely care that meets youth’s and families’ needs. Also highlighted is the frustration and despair experienced by caregivers seeking critical mental health and addictions supports for their youth during the pandemic, as well as the sense of isolation and of being left behind by the system. Identifying caregiver perspectives of youth mental health and addiction needs and service access during the COVID-19 pandemic provided important insights that can help inform approaches to youth mental health and addictions care during the pandemic and beyond.
Trends of COVID-19 incidence in Manitoba and public health measures: March 2020 to February 2022
Authors: Aboulatta Laila , Kowalec Kaarina , Delaney Joseph , Alessi-Severini Silvia , Leong Christine , Falk Jamie , Eltonsy Sherif 
Published: May 2022

Abstract
Objectives
The increasing spread of severe acute respiratory syndrome coronavirus-2 has prompted Canada to take unprecedented measures. The objective of this study was to examine the impact of the implemented public health measures on the incidence of COVID-19 in Manitoba.

Results
Using the COVID-19 dataset, we examined the temporal trends of daily reported COVID-19 cases and the coinciding public health measures implemented from March 12, 2020 to February 28, 2022. We calculated the 7-day moving average and crude COVID-19 infection rate/100,000 Manitobans. Due to the restrictions applied, the infection rate decreased from 2.4 (April 1) to 0.07 infections (May 1, 2020). Between May 4 and July 17, 2020, the reported cases stabilized, and some restrictions were lifted. However, in November, the cases peaked with infection rate of 29. Additional restrictions were implemented, and the rate dropped to 3.6 infections on March 31, 2021. As of August 2021, 62.8% of eligible Manitobans received two vaccine doses. The infection rate increased to 128.3 infections on December 31, 2021 and mitigation measures were implemented. This study describes how physical distancing in conjunction with other containment measures can reduce the COVID-19 burden. Future studies into the extent of the implementation of the restrictions are necessary.
Mouse mesoderm-specific transcript inhibits adipogenic differentiation and induces trans-differentiation into hepatocyte-like cells in 3T3-L1 preadiocytes
Authors: Kadota Yoshito , Kawakami Takashige , Sato Masao , Suzuki Shinya 
Published: May 2022

Abstract
Objective
The mesoderm-specific transcript (Mest) is an imprinted gene that is transcribed from the paternal allele. It is a marker of adipose tissue expansion; however, it is uncertain whether Mest expression promotes or suppresses adipogenic differentiation. To elucidate the effects of Mest expression on adipogenic differentiation, we transfected an expression vector or siRNA for mouse Mest into 3T3-L1 mouse preadipocyte cell line.

Results
In differentiated 3T3-L1 adipocytes, Mest overexpression decreased lipid accumulation. Conversely, gene silencing of Mest increased the accumulation of lipid droplets in adipocytes. These results demonstrate that Mest negatively regulates adipocyte differentiation. Further, Mest induced trans-differentiation of 3T3-L1 cells into hepatocytes, and its overexpression induced the expression of hepatocyte marker genes, including albumin and α-fetoprotein. In the presence of dexamethasone, the forced expression of the Mest caused morphological changes in 3T3-L1 cells. Cells were flat and polygonal shapes, with an increased accumulation of intracellular glycogen and other features that are typical of hepatocytes. Therefore, Mest inhibits adipogenic differentiation of 3T3-L1 preadipocytes by inducing hepatocyte trans-differentiation.