bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors impacting the access and use of formal health and social services by caregivers of stroke survivors: an interpretive description study
Authors: Garnett Anna , Ploeg Jenny , Markle-Reid Maureen , Strachan Patricia H. 
Published: April 2022

Abstract
Background
Evidence has shown that family and friend caregivers of stroke survivors are significantly and negatively impacted by caregiving. The negative effects of caregiving may persist over time suggesting that caregivers might benefit from ongoing engagement with supportive services. However, little is known about caregivers’ use of formally funded health and social services, or the factors influencing their access to and use of these services. The aim of this study is to increase understanding of the factors that influence stroke caregivers’ access and use of formal health and social services, from the perspective of stroke caregivers and healthcare providers.

Methods
A qualitative study was conducted with stroke caregivers and health providers in Ontario, Canada using interpretive description. In-depth interviews were conducted with caregivers of survivors who experienced a stroke between six months to five years previous and healthcare providers who support caregivers and stroke survivors. All participants provided written informed consent. Interview data were analyzed using constant comparison to identify codes and develop key thematic constructs.

Results
A total of 40 interviews were conducted with 22 stroke caregivers at an average 30-months post-stroke and 18 health providers. Factors that influenced stroke caregivers’ access and use of services included: finances and transportation; challenges caregivers faced in caring for their health; trust that they could leave their family member and trust in health providers; limited information pertaining to services and a lack of suitable services; and the response of their social networks to their caregiving situation.

Conclusion
Stroke caregivers experience significant challenges in accessing and using formal health and social services. These challenges could be addressed by increasing availability of subsidized community-based supports such as respite and counselling tailored to meet the ongoing needs of caregivers. Systemic change is needed by the health system that readily includes and supports caregivers throughout the stroke recovery continuum, particularly in the community setting.
Expression status of p53 and organic cation transporter 1 is correlated with poor response to preoperative chemotherapy in esophageal squamous cell carcinoma
Authors: Izutsu Masahiro , Domoto Takanori , Kamoshida Shingo , Ohsaki Hiroyuki , Matsuoka Hiroshi , Umeki Yusuke , Shiogama Kazuya , Hirayama Masaya , Suda Koichi , Uyama Ichiro 
Published: April 2022

Abstract
Background
Esophageal squamous cell carcinoma (ESCC) is a highly malignant neoplasm. DNA-damaging drugs, such as cisplatin (CDDP) and 5-fluorouracil (5-FU), are most frequently used in preoperative chemotherapy for ESCC. However, the response to preoperative chemotherapy varies among patients. p53, encoded by TP53, participates in apoptotic pathways following chemotherapy with DNA-damaging drugs, and mutation of TP53 contributes to chemoresistance. Organic cation transporter 1 (OCT1) participates in the uptake of CDDP, and its reduced expression is associated with CDDP resistance. The aim of this study was to evaluate the predictive impact of the expression status of p53 and OCT1 in response to preoperative chemotherapy in ESCC.

Methods
We retrospectively assessed 66 ESCC patients who received preoperative chemotherapy with CDDP/5-FU (CF) or docetaxel/CDDP/5-FU (DCF). p53 and OCT1 expression in pretreatment biopsy specimens was immunohistochemically determined and correlated with histological response to preoperative chemotherapy.

Results
p53 with wild-type (p53WT-ex) and mutant-type (p53MT-ex) expression patterns was identified in 40.9% and 59.1% of patients, respectively. High expression of OCT1 (OCT1High) was detected in 45.5%, and the remaining 54.5% showed low expression (OCT1Low). In a univariate analysis of the entire cohort, p53MT-ex was significantly correlated with poor response (P = 0.026), whereas OCT1Low showed marginal significance (P = 0.091). In a combined analysis, tumors with either p53MT-ex or OCT1Low showed a significant correlation with poor response compared with tumors with both p53WT-ex and OCT1High (P < 0.001). The sensitivity, specificity, and accuracy of combined p53/OCT1 were 93.9%, 47.1%, and 81.8%, respectively. Multivariate analysis identified p53 (P = 0.017), OCT1 (P = 0.032), and combined p53/OCT1 (P < 0.001) as independent predictors of histological response. When samples were stratified according to chemotherapy regimen in the univariate analysis, combined p53/OCT1 was the only significant factor for poor response in the CF (P = 0.011) and DCF (P = 0.021) groups, whereas p53 showed no statistical significance.

Conclusions
Our results suggest that either p53MT-ex or OCT1Low expression in pretreatment biopsy specimens may be a potential predictor of poor response to preoperative chemotherapy with the CF-based regimens in ESCC, although the specificity needs to be improved.
Proteolysis dependent cell cycle regulation in Caulobacter crescentus
Authors: Fatima Nida I , Fazili Khalid Majid , Bhat Nowsheen Hamid 
Published: April 2022

AbstractCaulobacter crescentus, a Gram-negative alpha-proteobacterium, has surfaced as a powerful model system for unraveling molecular networks that control the bacterial cell cycle. A straightforward synchronization protocol and existence of many well-defined developmental markers has allowed the identification of various molecular circuits that control the underlying differentiation processes executed at the level of transcription, translation, protein localization and dynamic proteolysis. The oligomeric AAA+ protease ClpXP is a well-characterized example of an enzyme that exerts post-translational control over a number of pathways. Also, the proteolytic pathways of its candidate proteins are reported to play significant roles in regulating cell cycle and protein quality control. A detailed evaluation of the impact of its proteolysis on various regulatory networks of the cell has uncovered various significant cellular roles of this protease in C. crescentus. A deeper insight into the effects of regulatory proteolysis with emphasis on cell cycle progression could shed light on how cells respond to environmental cues and implement developmental switches. Perturbation of this network of molecular machines is also associated with diseases such as bacterial infections. Thus, research holds immense implications in clinical translation and health, representing a promising area for clinical advances in the diagnosis, therapeutics and prognosis.
Evaluating the impact of possible interobserver variability in CBCT-based soft-tissue matching using TCP/NTCP models for prostate cancer radiotherapy
Authors: Zhang Xiangbin , Wang Xin , Li Xiaoyu , Zhou Li , Nie Shihong , Li Changhu , Wang Xuetao , Dai Guyu , Deng Zhonghua , Zhong Renming 
Published: April 2022

Abstract
Background
Prostate alignment is subject to interobserver variability in cone-beam CT (CBCT)-based soft-tissue matching. This study aims to analyze the impact of possible interobserver variability in CBCT-based soft-tissue matching for prostate cancer radiotherapy.

Methods
Retrospective data, consisting of 156 CBCT images from twelve prostate cancer patients with elective nodal irradiation were analyzed in this study. To simulate possible interobserver variability, couch shifts of 2 mm relative to the resulting patient position of prostate alignment were assumed as potential patient positions (27 possibilities). For each CBCT, the doses of the potential patient positions were re-calculated using deformable image registration-based synthetic CT. The impact of the simulated interobserver variability was evaluated using tumor control probabilities (TCPs) and normal tissue complication probabilities (NTCPs).

Results
No significant differences in TCPs were found between prostate alignment and potential patient positions (0.944 ± 0.003 vs 0.945 ± 0.003, P = 0.117). The average NTCPs of the rectum ranged from 5.16 to 7.29 (%) among the potential patient positions and were highly influenced by the couch shift in the anterior–posterior direction. In contrast, the average NTCPs of the bladder ranged from 0.75 to 1.12 (%) among the potential patient positions and were relatively negligible.

Conclusions
The NTCPs of the rectum, rather than the TCPs of the target, were highly influenced by the interobserver variability in CBCT-based soft-tissue matching. This study provides a theoretical explanation for daily CBCT-based image guidance and the prostate-rectum interface matching procedure.
Trial registration: Not applicable.
The association between lymphocyte-monocyte ratio and postoperative acute kidney injury in patients with acute type A aortic dissection
Authors: Chen Wenxiu , Song Xiaochun , Hong Liang , Xu Huan , Qian Yan , Zhang Wenhao , Sun Jiakui , Shen Xiao , Liu Ying , Wang Xiang , Shi Qiankun , Liu Han , Mu Xinwei , Zhang Cui 
Published: April 2022

Abstract
Background
The aim of this study was to investigate the relationship between baseline lymphocyte-monocyte ratio (LMR) and postoperative acute kidney injury (AKI) in patients with acute type A aortic dissection (ATAAD).

Methods
ATAAD patients undergoing surgery in Nanjing First Hospital were enrolled from January 2019 to April 2021. Lymphocyte and monocyte were measured on admission. Multivariable logistic regression analyses were performed to explore the relationship between LMR and postoperative AKI. We also used receiver operating characteristic (ROC), net reclassification index (NRI) and integrated discrimination improvement (IDI) analyses to assess the predictive ability of LMR.

Results
Among the 159 recruited patients, 47 (29.6%) were diagnosed with AKI. Univariate logistic regression analysis indicated that ATAAD patients with higher levels of LMR were prone to have lower risk to develop AKI (odds ratio [OR], 0.493; 95% confidence interval [CI] 0.284–0.650, P = 0.001). After adjustment for the potential confounders, LMR remained an independent related factor with postoperative AKI (OR 0.527; 95% CI 0.327–0.815, P = 0.006). The cutoff value for LMR to predict AKI was determined to be 2.67 in the ROC curve analysis (area under curve: 0.719). NRI and IDI further confirmed the predictive capability of LMR in postoperative AKI.

Conclusion
Elevated baseline LMR levels were independently associated with lower risk of postoperative AKI in ATAAD patients.
Safety and effectiveness of taliglucerase alfa in patients with Gaucher disease: an interim analysis of real-world data from a multinational drug registry (TALIAS)
Authors: Titievsky Lina , Schuster Tilman , Wang Ronnie , Younus Muhammad , Palladino Andrew , Quazi Kabir , Wajnrajch Michael P. , Hernandez Betina , Becker Pamela S. , Weinreb Neal J. , Chambers Christina , Mansfield Roy , Taylor Louise , Tseng Li-Jung , Kaplan Paige 
Published: April 2022

Abstract
Background
Limited real-world data from routine clinical care are available on the safety and effectiveness of treatment with taliglucerase alfa in patients with Gaucher disease (GD).

Methods
Taliglucerase Alfa Surveillance (TALIAS), a multinational prospective Drug Registry of patients with GD, was established to evaluate the long-term safety (primary objective) and effectiveness (secondary objective) of taliglucerase alfa. We present an interim analysis of the data from the Drug Registry collected over the 5-year period from September 2013 to January 2019.

Results
A total of 106 patients with GD (15.1% children aged < 18 years; 53.8% females) treated with taliglucerase alfa have been enrolled in the Drug Registry, as of January 7, 2019. The median duration of follow-up was 795 days with quartiles (Q1, Q3) of 567 and 994 days. Fifty-three patients (50.0%) were from Israel, 28 (26.4%) were from the United States, and 25 (23.6%) were from Albania. At the time of enrollment, most patients (87.7%) had received prior enzyme replacement therapy (ERT). Thirty-nine of the 106 patients had treatment-emergent adverse events (AEs). Twelve of the 106 patients experienced serious AEs; two patients experienced four treatment-related serious AEs. Four patients died, although none of the deaths was considered to be related to taliglucerase alfa treatment by the treating physicians. Nine patients discontinued from the study, including the four who died. At baseline, patients with prior ERT had a higher mean hemoglobin concentration and platelet counts than treatment-naïve patients, likely reflecting the therapeutic effects of prior treatments. During follow-up, the hemoglobin concentration and platelet counts increased in the treatment-naïve patients and remained relatively constant or increased slightly in patients with prior ERT. Spleen and liver volumes decreased in treatment-naïve patients.

Conclusions
The interim data showed no new or emergent safety signals. The overall interim data are consistent with the clinical program experience and known safety and effectiveness profile of taliglucerase alfa.
How we teach children with asthma to use their inhaler: a scoping review
Authors: McCrossan Patrick , Mallon Orla , Shields Michael D. , Russell Catherine , Kennedy Lesley , O’Donoghue Dara 
Published: April 2022

Abstract
Background
One reason that asthma remains poorly controlled in children is poor inhaler technique. Guidelines recommend checking inhaler technique at each clinical visit. However, they do not specify how best to train children to mastery of correct inhaler technique. Many children are simply shown how to use inhalers which results in less than 50% with correct inhaler technique. The aim of this scoping review is to explore published literature on teaching methods used to train children to master correct inhaler technique.

Methods
We searched (from inception onwards): Medline, Embase, Scopus, Web of Science, CINAHL and the Cochrane library. We included quantitative studies, (e.g. randomised controlled trials, cohort studies and case-control studies), published from 1956 to present, on teaching inhaler technique to children with asthma. Data was extracted onto a data charting table to create a descriptive summary of the results. Data was then synthesised with descriptive statistics and visual mapping.

Results
Thirty-three papers were identified for full text analysis. Educational interventions were found to be taking place in a variety of clinical areas and by a range of healthcare professional disciplines. ‘Brief-Instruction’ and ‘Teach-Back’ were identified as two primary methods of providing inhaler technique training in the majority of papers. Secondary themes identified were; use of written instruction, physical demonstration, video demonstrations and/or use of inhaler devices to augment inhaler technique training.

Conclusion
There are a variety of means by which inhaler technique has been taught to children. These methods are likely applicable to all inhaler types and often involve some form of physical demonstration. Children of all ages can be trained to use their inhaler correctly and by a range of healthcare professionals. We have not analysed the effectiveness of these different interventions, but have described what has been trialled before in an attempt to focus our attentions on what may potentially work best. The majority of these methods can be dichotomised to either ‘Brief-Intervention’ or ‘Teach-Back’. Based on our analysis of this scoping review, we consider the following as areas for future research; how many times does a given intervention have to be done in order to have the desired effect? For what duration does the intervention need to continue to have a long-lasting effect? And, what is the best outcome measure for inhaler technique?.

Trial registration
Systematic review registration: Open Science Framework (osf.io/n7kcw).
De novo mutation of CYBB gene in a boy presenting as intra-abdominal infection of Burkholderia contaminans: a case report
Authors: Zhao Qianqian , Yin Jing , Ma Jijun , Liu Xiaoxue , Wu Jiawen , Li Chongwei 
Published: April 2022

Abstract
Background
Chronic granulomatous disease (CGD) is an inborn error of immunity. It is characterized by recurrent bacterial or fungal infections, including infections by Burkholderia species. This is due to respiratory burst dysfunction of phagocytes. Currently, there is no report on Burkholderia contaminans (B. Contaminans) infection in children with CGD.

Case presentation
We present a previously healthy, 17-month-old Chinese boy infected with B. Contaminans in the intra-abdominal regions. Immunological screening, including assessment of cellular immunity and humoral immunity did not yield conclusive results. The level of nicotinamide adenine dinucleotide phosphatase (NADPH) activity was decreased and whole-exome sequencing identified a de novo mutation in the CYBB gene.

Conclusions
For specific pathogens such as B. Contaminans, immune assessment should be carried out even if there is no positive medical history or specificity in basic immunity screening.
Targeting SHP2 phosphatase in breast cancer overcomes RTK-mediated resistance to PI3K inhibitors
Authors: Heynen Guus J. J. E. , Lisek Kamil , Vogel Regina , Wulf-Goldenberg Annika , Alcaniz Joshua , Montaudon Elodie , Marangoni Elisabetta , Birchmeier Walter 
Published: April 2022

AbstractBackgroundPI3K signaling is frequently activated in breast cancer and is targeted by PI3K inhibitors. However, resistance of tumor cells to PI3K inhibition, often mediated by activated receptor tyrosine kinases, is commonly observed and reduces the potency of PI3K inhibitors. Therefore, new treatment strategies to overcome resistance to PI3K inhibitors are urgently needed to boost their efficacy. The phosphatase SHP2, which plays a crucial role in mediating signal transduction between receptor tyrosine kinases and both the PI3K and MAPK pathways, is a potential target for combination treatment.MethodsWe tested combinations of PI3K and SHP2 inhibitors in several experimental breast cancer models that are resistant to PI3K inhibition. Using cell culturing, biochemical and genetic approaches, we evaluated tumor cell proliferation and signaling output in cells treated with PI3K and SHP2 inhibitors.ResultsCombination treatment with PI3K and SHP2 inhibitors counteracted both acquired and intrinsic breast cancer cell resistance to PI3K inhibition that is mediated by activated receptor tyrosine kinases. Dual PI3K and SHP2 inhibition blocked proliferation and led to sustained inactivation of PI3K and MAPK signaling, where resistant cells rapidly re-activated these pathways upon PI3K inhibitor monotreatment. In addition, we demonstrate that overexpression of SHP2 induced resistance to PI3K inhibition, and that SHP2 was frequently activated during the development of PI3K inhibitor resistance after prolonged treatment of sensitive cells.ConclusionsOur results highlight the importance of SHP2 as a player in resistance to PI3K inhibitors. Combination treatment with PI3K and SHP2 inhibitors could pave the way for significant improvements in therapies for breast cancer.
Application of magnetic nanoparticles in cell therapy
Authors: Chen Yuling , Hou Shike 
Published: April 2022

AbstractFe3O4 magnetic nanoparticles (MNPs) are biomedical materials that have been approved by the FDA. To date, MNPs have been developed rapidly in nanomedicine and are of great significance. Stem cells and secretory vesicles can be used for tissue regeneration and repair. In cell therapy, MNPs which interact with external magnetic field are introduced to achieve the purpose of cell directional enrichment, while MRI to monitor cell distribution and drug delivery. This paper reviews the size optimization, response in external magnetic field and biomedical application of MNPs in cell therapy and provides a comprehensive view.
The therapeutic potential of stem cell-derived exosomes in the ulcerative colitis and colorectal cancer
Authors: Guo Gang , Tan Zhaobang , Liu Yaping , Shi Feiyu , She Junjun 
Published: April 2022

Abstract
Background
Mesenchymal stem cells (MSCs) therapy is a novel treatment strategy for cancer and a wide range of diseases with an excessive immune response such as ulcerative colitis (UC), due to its powerful immunomodulatory properties and its capacity for tissue regeneration and repair. One of the promising therapeutic options can focus on MSC-secreted exosomes (MSC-Exo), which have been identified as a type of paracrine interaction. In light of a wide variety of recent experimental studies, the present review aims to seek the recent research advances of therapies based on the MSC-Exo for treating UC and colorectal cancer (CRC).

Methods
A systematic literature search in MEDLINE, Scopus, and Google Scholar was performed from inception to December 2021 using the terms [(“colorectal cancer” OR “bowel cancer” OR “colon cancer” OR “rectal cancer”) AND (exosome) AND (stem cell) AND (“inflammatory bowel disease” OR “Crohn's disease” OR “colitis”)] in titles and abstracts.

Findings
Exosomes derived from various sources of MSCs, including human umbilical cord-derived MSCs (hUC-MSCs), human adipose-derived MSCs (hAD-MSCs), human bone marrow-derived MSCs (hBM-MSCs), and olfactory ecto-MSCs (OE-MSCs), have shown the protective role against UC and CRC. Exosomes from hUC-MSCs, hBM-MSCs, AD-MSCs, and OE-MSCs have been found to ameliorate the experimental UC through suppressing inflammatory cells including macrophages, Th1/Th17 cells, reducing the expression of proinflammatory cytokines, as well as inducing the anti-inflammatory function of Treg and Th2 cells and enhancing the expression of anti-inflammatory cytokines. In addition, hBM-MSC-Exo and hUC-MSC-Exo containing tumor-suppressive miRs (miR-3940-5p/miR-22-3p/miR‐16‐5p) have been shown to suppress proliferation, migration, and invasion of CRC cells via regulation of RAP2B/PI3K/AKT signaling pathway and ITGA2/ITGA6.

Key messages
The MSC-Exo can exert beneficial effects on UC and CRC through two different mechanisms including modulating immune responses and inducing anti-tumor responses, respectively.
Enhancement of pacing function by HCN4 overexpression in human pluripotent stem cell-derived cardiomyocytes
Authors: Saito Yukihiro , Nakamura Kazufumi , Yoshida Masashi , Sugiyama Hiroki , Akagi Satoshi , Miyoshi Toru , Morita Hiroshi , Ito Hiroshi 
Published: April 2022

Abstract
Background
The number of patients with bradyarrhythmia and the number of patients with cardiac pacemakers are increasing with the aging population and the increase in the number of patients with heart diseases. Some patients in whom a cardiac pacemaker has been implanted experience problems such as pacemaker infection and inconvenience due to electromagnetic interference. We have reported that overexpression of HCN channels producing a pacemaker current in mouse embryonic stem cell-derived cardiomyocytes showed enhanced pacing function in vitro and in vivo. The aim of this study was to determine whether HCN4 overexpression in human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) can strengthen the pacing function of the cells.

Methods
Human HCN4 was transduced in the AAVS1 locus of human induced pluripotent stem cells by nucleofection and HCN4-overexpressing iPSC-CMs were generated. Gene expression profiles, frequencies of spontaneous contraction and pacing abilities of HCN4-overexpressing and non-overexpressing iPSC-CMs in vitro were compared.

Results
HCN4-overexpressing iPSC-CMs showed higher spontaneous contraction rates than those of non-overexpressing iPSC-CMs. They responded to an HCN channel blocker and β adrenergic stimulation. The pacing rates against parent iPSC line-derived cardiomyocytes were also higher in HCN4-overexpressing iPSC-CMs than in non-overexpressing iPSC-CMs.

Conclusions
Overexpression of HCN4 showed enhancement of If current, spontaneous firing and pacing function in iPSC-CMs. These data suggest this transgenic cell line may be useful as a cardiac pacemaker.