bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring hospital compliance with the primary nursing care model: validating an inventory using the Delphi method
Authors: Cocchieri Antonello , Magon Giorgio , Cavalletti Manuela , Cristofori Elena , Zega Maurizio
Published: October 2021

Background

The primary nursing care model is considered a personalized model of care delivery based on care continuity and on the relationship between the nurse and patient. Primary nursing checklists are not often mentioned in the literature; however, they represent a valid instrument to develop, implement, and evaluate primary nursing. The aim of this study was to create a structured checklist to explore hospital compliance in primary nursing.

Methods

The Delphi method was used to develop and validate a checklist. The preliminary version was created and sent to three experts for their opinions. Their comments were ultimately used in the first version, which included four components with 19 items regarding primary nursing characteristics. A two-round Delphi process was used to generate consensus items. The Delphi panel consisted of six experts working in primary nursing contexts and/or teaching or studying primary nursing. Data were collected using a structured questionnaire from July 2020 to January 2021. These experts were asked to rate each element for relevance using a 4-point Likert-type scale. Furthermore, the consensus among the panel of experts was set at ≥78%, with selected items being voted “quite relevant” and “highly relevant”. Content validity index (I-CVI) and modified kappa statistic were also calculated. Following expert evaluation, the first version of the checklist was modified, and the new version, constituting 17 items, was sent to the same experts.

Results

The first version of the checklist demonstrated a main relevance score of 3.34 (SD = 0.83; range = 1.3–4; mean I-CVI = 0.84; range: 0.83–1), but three items did not receive an adequate I-CVI score, that is, lower than 0.78. After the second round, the I-CVIs improved. The main score of relevance was 3.61 (SD: 0.35; range = 2.83–4; mean = I-CVI: 0.93). The S-CVI/UA was 0.58, and the S-CVI/Ave was 0.93.

Conclusion

Measuring primary nursing compliance should be implemented to provide continuous feedback to nurses. Moreover, utilizing valid checklists could permit comparing different results from others’ research. Future research should be conducted to compare the results from the checklist with nursing outcomes.
Intensive care nurses’ knowledge and practice of evidence-based recommendations for endotracheal suctioning: a multisite cross-sectional study in Changsha, China
Authors: Chen Wenjun , Hu Shuang , Liu Xiaoli , Wang Nina , Zhao Junqiang , Liu Peng , Chen Kaixia , Hu Jiale
Published: October 2021

Background

Endotracheal suctioning is one of the most frequently performed invasive procedures by intensive care nurses. Nurses should have adequate knowledge and skills to perform endotracheal suctioning based on the best evidence. Little is known about intensive care nurses’ knowledge and practice of evidence-based endotracheal suctioning in Chinese hospitals. The purpose of this study was to investigate intensive care nurses’ knowledge and practice of evidence-based recommendations regarding endotracheal suctioning. Specifically, the study aimed to examine (1) intensive care nurses’ awareness of and adherence to endotracheal suctioning guidelines and (2) factors influencing their level of awareness and adherence.

Methods

A cross-sectional survey of 310 staff nurses working in intensive care units was carried out at Changsha, China. Data on participants’ characteristics, awareness of, and adherence to the endotracheal suctioning guidelines were collected through online questionnaires. Following univariate descriptive statistics, the Mann–Whitney U test and Kruskal–Wallis H test were performed using Software Package Statistical Analysis Version 23.0.

Results

A total of 281 nurses completed and returned the survey (response rate = 90.6 %). One-half to three-quarters of the nurses knew 21 of the 26 evidence-based practices and believed their practices followed the guidelines. Over half of them were unaware of the difference between open and close suctions and the pros and cons of using hyperinflation. Almost 50 % of nurses believed some of their clinical practices did not follow the evidence-based recommendations, such as not routinely using normal saline and using 80–120 mmHg suction pressure during endotracheal suctioning. Nurses with endotracheal suctioning training demonstrated significantly higher awareness of endotracheal suctioning recommendations and higher adherence levels than untrained nurses.

Conclusions

The study findings revealed that Chinese intensive care nurses lacked awareness of several essential evidence-based endotracheal suctioning practices, and there were gaps between their current practice and the guideline recommendations. Further research should emphasize revealing barriers and facilitators of implementing evidence-based endotracheal suctioning practices as well as developing context-suitable interventions for guideline implementation.
Impact of empagliflozin on right ventricular parameters and function among patients with type 2 diabetes
Authors: Sarak Bradley , Verma Subodh , David Mazer C. , Teoh Hwee , Quan Adrian , Gilbert Richard E. , Goodman Shaun G. , Bami Karan , Coelho-Filho Otávio R. , Ahooja Vineeta , Deva Djeven P. , Garg Vinay , Gandhi Sumeet , Connelly Kim A. , Yan Andrew T.
Published: October 2021

Background

Sodium-glucose cotransporter 2 (SGLT2) inhibition reduces cardiovascular events in type 2 diabetes (T2DM) and is associated with a reduction in left ventricular (LV) mass index. However, the impact on right ventricular (RV) remodeling is unknown. Accordingly, the objective of this study was to assess the impact of SGLT2 inhibition on RV parameters and function in T2DM and coronary artery disease (CAD).

Methods

In EMPA-HEART CardioLink-6, 97 patients with T2DM and CAD were randomly assigned to empagliflozin 10 mg (n = 49) once daily or placebo (n = 48). Cardiac magnetic resonance imaging was performed at baseline and after 6 months. RV mass index (RVMi), RV end-diastolic and end-systolic volume index (RVEDVi, RVESVi) and RV ejection fraction (RVEF) were assessed in blinded fashion.

Results

At baseline, mean RVMi (± SD) (11.8 ± 2.4 g/m2), RVEF (53.5 ± 4.8%), RVEDVi (64.3 ± 13.2 mL/m2) and RVESVi (29.9 ± 6.9 mL/m2) were within normal limits and were similar between the empagliflozin and placebo groups. Over 6 months, there were no significant differences in RVMi (− 0.11 g/m2, [95% CI − 0.81 to 0.60], p = 0.76), RVEF (0.54%, [95% CI − 1.4 to 2.4], p = 0.58), RVEDVi (− 1.2 mL/m2, [95% CI − 4.1 to 1.7], p = 0.41) and RVESVi (− 0.81 mL/m2, [95% CI − 2.5 to 0.90], p = 0.35) in the empaglifozin group as compared with the placebo group. In both groups, there was no significant correlation between RVMi and LVMi changes from baseline to 6 months.

Conclusions

In this post-hoc analysis, SGLT2 inhibition with empagliflozin had no impact on RVMi and RV volumes in patients with T2DM and CAD. The potentially differential effect of empagliflozin on the LV and RV warrants further investigation.

Clinical Trial Registration: URL: https://www.clinicaltrials.gov/ct2/show/NCT02998970?cond=NCT02998970&draw=2&rank=1. Unique identifier: NCT02998970.
Malaria parasite species composition of Plasmodium infections among asymptomatic and symptomatic school-age children in rural and urban areas of Kinshasa, Democratic Republic of Congo
Authors: Nundu Sabin S. , Culleton Richard , Simpson Shirley V. , Arima Hiroaki , Muyembe Jean-Jacques , Mita Toshihiro , Ahuka Steve , Yamamoto Taro
Published: October 2021

Background

Malaria remains a major public health concern in the Democratic Republic of Congo (DRC), and school-age children are relatively neglected in malaria prevalence surveys and may constitute a significant reservoir of transmission. This study aimed to understand the burden of malaria infections in school-age children in Kinshasa/DRC.

Methods

A total of 634 (427 asymptomatic and 207 symptomatic) blood samples collected from school-age children aged 6 to 14 years were analysed by microscopy, RDT and Nested-PCR.

Results

The overall prevalence of Plasmodium spp. by microscopy, RDT and PCR was 33%, 42% and 62% among asymptomatic children and 59%, 64% and 95% in symptomatic children, respectively. The prevalence of Plasmodium falciparum, Plasmodium malariae and Plasmodium ovale spp. by PCR was 58%, 20% and 11% among asymptomatic and 93%, 13% and 16% in symptomatic children, respectively. Among P. ovale spp., P. ovale curtisi, P. ovale wallikeri and mixed P. ovale curtisi + P. ovale wallikeri accounted for 75%, 24% and 1% of infections, respectively. All Plasmodium species infections were significantly more prevalent in the rural area compared to the urban area in asymptomatic infections (p < 0.001). Living in a rural as opposed to an urban area was associated with a five-fold greater risk of asymptomatic malaria parasite carriage (p < 0.001). Amongst asymptomatic malaria parasite carriers, 43% and 16% of children harboured mixed Plasmodium with P. falciparum infections in the rural and the urban areas, respectively, whereas in symptomatic malaria infections, it was 22% and 26%, respectively. Few children carried single infections of P. malariae (2.2%) and P. ovale spp. (1.9%).

Conclusion

School-age children are at significant risk from both asymptomatic and symptomatic malaria infections. Continuous systematic screening and treatment of school-age children in high-transmission settings is needed.
In vivo efficacy and safety of artemether–lumefantrine and amodiaquine–artesunate for uncomplicated Plasmodium falciparum malaria in Mozambique, 2018
Authors: Nhama Abel , Nhamússua Lídia , Macete Eusébio , Bassat Quique , Salvador Crizolgo , Enosse Sónia , Candrinho Baltazar , Carvalho Eva , Nhacolo Arsénio , Chidimatembue Arlindo , Saifodine Abuchahama , Zulliger Rose , Lucchi Naomi , Svigel Samaly S. , Moriarty Leah F. , Halsey Eric S. , Mayor Alfredo , Aide Pedro
Published: October 2021

Background

Artemisinin-based combination therapy (ACT) has been the recommended first-line treatment for uncomplicated malaria in Mozambique since 2006, with artemether–lumefantrine (AL) and amodiaquine–artesunate (AS–AQ) as the first choice. To assess efficacy of currently used ACT, an in vivo therapeutic efficacy study was conducted.

Methods

The study was conducted in four sentinel sites: Montepuez, Moatize, Mopeia and Massinga. Patients between 6 and 59 months old with uncomplicated Plasmodium falciparum malaria (2000–200,000 parasites/µl) were enrolled between February and September of 2018, assigned to either an AL or AS–AQ treatment arm, and monitored for 28 days. A Bayesian algorithm was applied to differentiate recrudescence from new infection using genotyping data of seven neutral microsatellites. Uncorrected and PCR-corrected efficacy results at day 28 were calculated.

Results

Totals of 368 and 273 patients were enrolled in the AL and AS–AQ arms, respectively. Of these, 9.5% (35/368) and 5.1% (14/273) were lost to follow-up in the AL and AS–AQ arms, respectively. There were 48 and 3 recurrent malaria infections (late clinical and late parasitological failures) in the AL and AS–AQ arms, respectively. The day 28 uncorrected efficacy was 85.6% (95% confidence interval (CI) 81.3–89.2%) for AL and 98.8% (95% CI 96.7–99.8%) for AS–AQ, whereas day 28 PCR-corrected efficacy was 97.9% (95% CI 95.6–99.2%) for AL and 99.6% (95% CI 97.9–100%) for AS–AQ. Molecular testing confirmed that 87.4% (42/48) and 33.3% (1/3) of participants with a recurrent malaria infection in the AL and AS–AQ arms were new infections; an expected finding in a high malaria transmission area. Adverse events were documented in less than 2% of participants for both drugs.

Conclusion

Both AL and AS–AQ have therapeutic efficacies well above the 90% WHO recommended threshold and remain well-tolerated in Mozambique. Routine monitoring of therapeutic efficacy should continue to ensure the treatments remain efficacious.

Trial registration Clinicaltrials.gov: NCT04370977
Oncogenic KRAS blockade therapy: renewed enthusiasm and persistent challenges
Authors: Tang Daolin , Kroemer Guido , Kang Rui
Published: October 2021

Across a broad range of human cancers, gain-of-function mutations in RAS genes (HRAS, NRAS, and KRAS) lead to constitutive activity of oncoproteins responsible for tumorigenesis and cancer progression. The targeting of RAS with drugs is challenging because RAS lacks classic and tractable drug binding sites. Over the past 30 years, this perception has led to the pursuit of indirect routes for targeting RAS expression, processing, upstream regulators, or downstream effectors. After the discovery that the KRAS-G12C variant contains a druggable pocket below the switch-II loop region, it has become possible to design irreversible covalent inhibitors for the variant with improved potency, selectivity and bioavailability. Two such inhibitors, sotorasib (AMG 510) and adagrasib (MRTX849), were recently evaluated in phase I-III trials for the treatment of non-small cell lung cancer with KRAS-G12C mutations, heralding a new era of precision oncology. In this review, we outline the mutations and functions of KRAS in human tumors and then analyze indirect and direct approaches to shut down the oncogenic KRAS network. Specifically, we discuss the mechanistic principles, clinical features, and strategies for overcoming primary or secondary resistance to KRAS-G12C blockade.
Negative correlation between endoglin levels and coronary atherosclerosis
Authors: Chen Haibin , Wang Yiping , Sun Bing , Bao Xunxia , Tang Yu , Huang Feifei , Zhu Sibo , Xu Jiahong
Published: October 2021

Background

Coronary artery disease (CAD) is a common cardiovascular disease, and abnormal blood lipid metabolism is an important risk factor. Transforming growth factor-ß (TGF-ß) and its receptor (TGF-ßR) can inhibit the release of inflammatory factors through the SMAD pathway-mediated immune response, thereby suppressing the progression of CAD. Endoglin (TGF-ßRIII), a TGF-ßR family homologous receptor protein, is directly involved in the immunoregulatory process, but the exact mechanism is unclear. This study aimed to clarify the pathophysiological effects of endoglin on the development of atherosclerosis and to explore the mechanism of the signalling pathway.

Methods

We downloaded the GEO dataset to perform a functional analysis of SMAD family activity and TGF-ß receptor protein expression in the monocyte expression profiles of patients with familial hyperlipidaemia (FH). The effect of endoglin on endothelial cell proliferation, migration, and apoptosis was examined by disrupting the endoglin gene in human umbilical vein endothelial cells (HUVECs) and validated by western blotting. The related genes and pathways regulated by endoglin were obtained by analysing the sequencing data.

Results

Research has shown that interference with endoglin can promote the proliferation and migration and significantly inhibit the apoptosis of vascular endothelial cells. Interference with endoglin particularly encourages the expression of VEGFB in vascular endothelial cells.

Conclusion

The endoglin gene in vascular endothelial cells regulates the PI3K-Akt, Wnt, TNF, and cellular metabolism pathways by activating the SMAD pathway. RAB26, MR1, CCL2, SLC29A4, IBTK, VEGFB, and GOLGA8B play critical roles. Endoglin interacts closely with 11 proteins such as CCL2 and SEPRINE1, which participate in the vital pathway of plaque formation. Interference with endoglin can alter the course of coronary atherosclerosis.
Lipid droplets and the transcriptome of Mycobacterium tuberculosis from direct sputa: a literature review
Authors: Mekonnen Daniel , Derbie Awoke , Mihret Adane , Yimer Solomon Abebe , Tønjum Tone , Gelaw Baye , Nibret Endalkachew , Munshae Abaineh , Waddell Simon J. , Aseffa Abraham
Published: October 2021

Mycobacterium tuberculosis (Mtb), the main etiology of tuberculosis (TB), is predominantly an intracellular pathogen that has caused infection, disease and death in humans for centuries. Lipid droplets (LDs) are dynamic intracellular organelles that are found across the evolutionary tree of life. This review is an evaluation of the current state of knowledge regarding Mtb-LD formation and associated Mtb transcriptome directly from sputa.

Based on the LD content, Mtb in sputum may be classified into three groups: LD positive, LD negative and LD borderline. However, the clinical and evolutionary importance of each state is not well elaborated. Mounting evidence supports the view that the presence of LD positive Mtb bacilli in sputum is a biomarker of slow growth, low energy state, towards lipid degradation, and drug tolerance. In Mtb, LD may serve as a source of chemical energy, scavenger of toxic compounds, prevent destruction of Mtb through autophagy, delay trafficking of lysosomes towards the phagosome, and contribute to Mtb persistence. It is suggest that LD is a key player in the induction of a spectrum of phenotypic and metabolic states of Mtb in the macrophage, granuloma and extracellular sputum microenvironment. Tuberculosis patients with high proportion of LD positive Mtb in pretreatment sputum was associated with higher rate of poor treatment outcome, indicating that LD may have a clinical application in predicting treatment outcome.

The propensity for LD formation among Mtb lineages is largely unknown. The role of LD on Mtb transmission and disease phenotype (pulmonary TB vs extra-pulmonary TB) is not well understood. Thus, further studies are needed to understand the relationships between LD positivity and Mtb lineage, Mtb transmission and clinical types.
Adult onset egg allergy: a case report
Authors: Cremonte Elisa Maria , Galdi Eugenia , Roncallo Chiara , Boni Elisa , Cremonte Luigi Giovanni
Published: October 2021

Background

Egg allergy is one of the most frequent food allergies in childhood while adult onset of egg allergy is a rare condition.

Case presentation

We report the case of a 30 years old man sent to our center in order to investigate gastrointestinal symptoms occurring since 2 years after egg and derivatives intake. He did not suffer from egg or other food allergies in childhood. He is an active smoker with a contact dermatitis related to nickel and mild allergic rhinoconjunctivitis to grass pollen. Skin prick test and serum specific IgE to egg were performed and revealed sensitization to egg proteins.

Conclusions

Even though IgE-mediated egg allergy affects children, this report witnesses a rare case of adult onset.
Hollow polydopamine nanoparticles loading with peptide RL-QN15: a new pro-regenerative therapeutic agent for skin wounds
Authors: Sun Huiling , Wang Ying , He Tiantian , He Dingwei , Hu Yan , Fu Zhe , Wang Yinglei , Sun Dandan , Wang Junsong , Liu Yixiang , Shu Longjun , He Li , Deng Ziwei , Yang Xinwang
Published: October 2021

Background

Although the treatments of skin wounds have greatly improved with the increase in therapeutic methods and agents, available interventions still cannot meet the current clinical needs. Therefore, the development of new pro-regenerative therapies remains urgent. Owing to their unique characteristics, both nanomaterials and peptides have provided novel clues for the development of pro-regenerative agents, however, more efforts were still be awaited and anticipated.

Results

In the current research, Hollow polydopamine (HPDA) nanoparticles were synthesized and HPDA nanoparticles loading with RL-QN15 (HPDAlR) that was an amphibian-derived peptide with obvious prohealing activities were prepared successfully. The characterization, biodistribution and clearance of both HPDA nanoparticles and HPDAlR were evaluated, the loading efficiency of HPDA against RL-QN15 and the slow-releasing rate of RL-QN15 from HPDAlR were also determined. Our results showed that both HPDA nanoparticles and HPDAlR exerted no obvious toxicity against keratinocyte, macrophage and mice, and HPDA nanoparticles showed no prohealing potency in vivo and in vitro. Interestingly, HPDAlR significantly enhanced the ability of RL-QN15 to accelerate the healing of scratch of keratinocytes and selectively modulate the release of healing-involved cytokines from macrophages. More importantly, in comparison with RL-QN15, by evaluating on animal models of full-thickness injured skin wounds in mice and oral ulcers in rats, HPDAlR showed significant increasing in the pro-regenerative potency of 50 and 10 times, respectively. Moreover, HPDAlR also enhanced the prohealing efficiency of peptide RL-QN15 against skin scald in mice and full-thickness injured wounds in swine.

Conclusions

HPDA obviously enhanced the pro-regenerative potency of RL-QN15 in vitro and in vivo, hence HPDAlR exhibited great potential in the development of therapeutics for skin wound healing.

Graphic Abstract
Translation and psychometric evaluation of the Chinese version of the resilience scale for children with cancer
Authors: Chung Joyce Oi Kwan , Li William Ho Cheung , Wei Xia , Cheung Ankie Tan , Ho Laurie Long Kwan , Chan Godfrey Chi-Fung
Published: October 2021

Background

To test the psychometric properties of a traditional Chinese version of the Resilience Scale for Children (RS-10) and examine its factorial structure via a confirmatory factor analysis (CFA).

Methods

One hundred and eighty-six Hong Kong Chinese children with cancer were recruited in the paediatric oncology units of two public acute-care hospitals in Hong Kong to participate in this cross-sectional study. The psychometric properties of the traditional Chinese version of the RS-10 were assessed, namely its content equivalence, convergent and discriminant validity, construct validity, internal consistency and test–retest reliability.

Results

The newly translated traditional Chinese version of the RS-10 demonstrated adequate internal consistency (Cronbach’s α = .83, McDonald’s Ω = .80), excellent test–retest reliability (.89), good content equivalence (CVI = 96%) and appropriate convergent (r =  − .52, P = .01) and discriminant validity (r = .61, P = .01). The CFA results demonstrated that there was a good fit between the factor structure of the Chinese version of the RS-10 and the observed data (χ2/df = 2.34, TLI = .951, RMSEA = .053, CFI = .962, GFI = .948, SRMR = .052), thereby confirming the construct validity of this instrument.

Conclusions

The traditional Chinese version of the RS-10 was found to be a reliable and valid tool for assessing the resilience of Hong Kong Chinese children with cancer. The newly developed traditional Chinese version of the RS-10 is an appropriate clinical research tool for evaluating the effectiveness of nursing interventions in enhancing the resilience of and promoting mental well-being in children with cancer.

Trial registrationNCT03544190.
Identification of a novel glycolysis-related signature to predict the prognosis of patients with breast cancer
Authors: He Menglin , Hu Cheng , Deng Jian , Ji Hui , Tian Weiqian
Published: October 2021

Background

Breast cancer (BC) has a high incidence and mortality rate in females. Its conventional clinical characteristics are far from accurate for the prediction of individual outcomes. Therefore, we aimed to develop a novel signature to predict the survival of patients with BC.

Methods

We analyzed the data of a training cohort from the Cancer Genome Atlas (TCGA) database and a validation cohort from the Gene Expression Omnibus (GEO) database. After the applications of Gene Set Enrichment Analysis (GSEA) and Cox regression analyses, a glycolysis-related signature for predicting the survival of patients with BC was developed; the signature containedAK3,CACNA1H,IL13RA1,NUP43,PGK1, andSDC1. Furthermore, on the basis of expression levels of the six-gene signature, we constructed a risk score formula to classify the patients into high- and low-risk groups. The receiver operating characteristic (ROC) curve and the Kaplan-Meier curve were used to assess the predicted capacity of the model. Later, a nomogram was developed to predict the outcomes of patients with risk score and clinical features over a period of 1, 3, and 5 years. We further used Human Protein Atlas (HPA) database to validate the expressions of the six biomarkers in tumor and sample tissues, which were taken as control.

Results

We constructed a six-gene signature to predict the outcomes of patients with BC. The patients in the high-risk group showed poor prognosis than those in the low-risk group. The area under the curve (AUC) values were 0.719 and 0.702, showing that the prediction performance of the signature is acceptable. Additionally, Cox regression analysis revealed that these biomarkers could independently predict the prognosis of BC patients with BC without being affected by clinical factors. The expression levels of all six biomarkers in BC tissues were higher than that in normal tissues; however,AK3was an exception.

Conclusion

We developed a six-gene signature to predict the prognosis of patients with BC. Our signature has been proved to have the ability to make an accurate prediction and might be useful in expanding the hypothesis in clinical research.
The experiences of new graduate nurses and midwives going through a virtual interview recruitment process during the COVID-19 crisis: a cross-sectional study
Authors: Holm Doreen , Ohr Se Ok , Giles Michelle
Published: October 2021

Background

The annual recruitment of new graduate nurses and midwives is key to recruiting large numbers of staff with the right attitude, skills and knowledge who are the best fit for the organisation. Virtual interviews were undertaken in 2020 due to the surge worldwide in the COVID-19 crisis. This study evaluates those virtual interviews and explores the sustainability of the model.

Methods

A cross-sectional study was conducted at a large health organisation in New South Wales, Australia. Data were collected over 3 weeks using two online surveys, one for interviewees (n = 512) and the other for interviewers (n = 68). Quantitative data were analysed using descriptive statistics and frequency distributions, and additional free-text comments were analysed using content analysis.

Results

Response rates were 55% (n = 280) interviewees and 54% (n = 37) for interviewers. The majority of interviewees (58%, n = 184) and interviewers (78%, n = 29) stated the interview was seamless or very seamless and 55% (n = 156) of interviewees and 73% (n = 27) of interviewers agreed interviewees conveyed themselves well during interviews. Over half of interviewees (65%, n = 182) and interviewers (51%, n = 18) agreed the virtual interview was fair or very fair for interviewee performance, regardless of age, race, or socio-economic status. However, many expressed a need for better internet access, equipment, and support, and a longer interview time to personally connect. Both new graduate interviewees (60%) and interviewers (75%) agreed virtual interviews are a suitable model for future use. However, some respondents indicated they preferred face-to-face interviews.

Conclusions

The use of virtual interviews to select new graduates is considered acceptable, cost-effective and sustainable, as well as fair by the majority of participants. Study findings inform policy development, future planning, support the use of flexible selection practices and provide other health care professionals with a virtual recruitment model to consider when developing strategies to grow their future health workforce.
Development of a two-circular RNA panel as potential prognostic biomarker for gastric cancer
Authors: Liu Jing , Zhu Xingwu , Yan Meinan , Li Hui
Published: October 2021

Background

Circular RNAs (circRNAs) have attracted increasing attention in recent years for their potential application as disease biomarkers due to their high abundance and stability. In this study, we attempted to screen circRNAs that can be used to predict postoperative recurrence and survival in patients with gastric cancer (GC).

Methods

High-throughput RNA sequencing was used to identify differentially expressed circRNAs in GC patients with different prognoses. The expression level of circRNAs in the training set (n = 136) and validation set (n = 167) was detected by quantitative real-time PCR (qRT-PCR). Kaplan–Meier estimator, receiver operating characteristic (ROC) curve and cox regression analysis were used to evaluate the prognostic value of circRNAs on recurrence-free survival (RFS) and overall survival (OS) in GC patients. CeRNA network prediction, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed for the circRNAs with prognostic significance.

Results

A total of 259 differentially expressed circRNAs were identified in GC patients with different RFS. We found two circRNAs (hsa_circ_0005092 and hsa_circ_0002647) that highly expressed in GC patients with good prognoses, and subsequently established a predictive model for postoperative recurrence and prognosis evaluation, named circPanel. Patients with circPanellow might have shorter recurrence-free survival (RFS) and overall survival (OS). We also performed circRNA-miRNA-mRNA network prediction and functional analysis for hsa_circ_0005092 and hsa_circ_0002647.

Conclusions

CircPanel has the potential to be a prognostic biomarker in GC patients with greater accuracy than a single circRNA and certain traditional tumor markers (e.g., CEA, CA19-9 and CA724).
Antigen-capture ELISA and immunochromatographic test strip to detect the H9N2 subtype avian influenza virus rapidly based on monoclonal antibodies
Authors: Xiao Yixin , Yang Fan , Liu Fumin , Yao Hangping , Wu Nanping , Wu Haibo
Published: October 2021

Background

The H9N2 subtype of avian influenza virus (AIV) has become the most widespread subtype of AIV among birds in Asia, which threatens the poultry industry and human health. Therefore, it is important to establish methods for the rapid diagnosis and continuous surveillance of H9N2 subtype AIV.

Methods

In this study, an antigen-capture enzyme-linked immunosorbent assay (AC-ELISA) and a colloidal gold immunochromatographic test (ICT) strip using monoclonal antibodies (MAbs) 3G4 and 2G7 were established to detect H9N2 subtype AIV.

Results

The AC-ELISA method and ICT strip can detect H9N2 subtype AIV quickly, and do not cross-react with other subtype AIVs or other viruses. The detection limit of AC-ELISA was a hemagglutinin (HA) titer of 4 for H9N2 subtype AIV per 100 μl sample, and the limit of detection of the HA protein of AIV H9N2 was 31.5 ng/ml. The ICT strip detection limit was an HA titer of 4 for H9N2 subtype AIV per 100 μl sample. Moreover, both detection methods exhibited good reproducibility and repeatability, with coefficients of variation < 5%. For detection in 200 actual poultry samples, the sensitivities and specificities of AC-ELISA were determined as 93.2% and 98.1%, respectively. The sensitivities and specificities of the ICT strips were determined as 90.9% and 97.4%, respectively.

Conclusions

The developed AC-ELISA and ICT strips displayed high specificity, sensitivity, and stability, making them suitable for rapid diagnosis and field investigation of H9N2 subtype AIV.
Who influences nutrition policy space using international trade and investment agreements? A global stakeholder analysis
Authors: Garton Kelly , Swinburn Boyd , Thow Anne Marie
Published: October 2021

Background

Regulation of food environments is needed to address the global challenge of poor nutrition, yet policy inertia has been a problem. A common argument against regulation is potential conflict with binding commitments under international trade and investment agreements (TIAs). This study aimed to identify which actors and institutions, in different contexts, influence how TIAs are used to constrain policy space for improving food environments, and to describe their core beliefs, interests, resources and strategies, with the objective of informing strategic global action to preserve nutrition policy space.

Methods

We conducted a global stakeholder analysis applying the Advocacy Coalition Framework, based on existing academic literature and key informant interviews with international experts in trade and investment law and public health nutrition policy.

Results

We identified 12 types of actors who influence policy space in the food environment policy subsystem, relevant to TIAs. These actors hold various beliefs regarding the economic policy paradigm, the nature of obesity and dietary diseases as health problems, the role of government, and the role of industry in solving the health problem. We identified two primary competing coalitions: 1) a ‘public health nutrition’ coalition, which is overall supportive of and actively working to enact comprehensive food environment regulation; and 2) an ‘industry and economic growth’ focussed coalition, which places a higher priority on deregulation and is overall not supportive of comprehensive food environment regulation. The industry and economic growth coalition appears to be dominant, based on its relative power, resources and coordination. However, the public health nutrition coalition maintains influence through individual activism, collective lobbying and government pressure (e.g. by civil society), and expert knowledge generation.

Conclusions

Our analysis suggests that industry and economic growth-focussed coalitions are highly capable of leveraging networks, institutional structures and ideologies to their advantage, and are a formidable source of opposition acting to constrain nutrition policy space globally, including through TIAs. Opportunities for global public health nutrition coalitions to strengthen their influence in the support of nutrition policy space include strategic evidence generation and coalition-building through broader engagement and capacity-building.
Role of radiation therapy in primary tonsil large B cell lymphoma: a SEER-based analysis
Authors: Jia Jing , Chen Wenming
Published: October 2021

Backgroud

Primary tonsil diffuse large B cell lymphoma (PT-DLBCL) is an uncommon disease entity. The role of radiation therapy (RT) in PT-DLBCL is debatable in both the pre- and post- rituximab era. The purpose of this study was to evaluate the treatment outcome and establish a prognostic model in PT-DLBCL based on the Surveillance, Epidemiology, and End Results (SEER) database.

Materials and methods

Data of 1214 PT-DLBCL patients diagnosed between 1975 and 2016 were extracted from SEER 18. The effect of RT was assessed for the entire cohort and subgroups by stages using univariate, multivariate Cox regression analyses and propensity score matching (PSM).

Results

The entire cohort included 1043 patients with early-stage (ES) PT-DLBCL and 171 patients with advanced-stage (AS) disease. A decreasing trend of RT utilization in the ES cohort after 2002 was observed. 47.4% of patients in ES received RT, whereas 25.1% in AS underwent RT. RT significantly improved overall survival in both univariate (P < 0.001) and multivariate (P = 0.002) analyses. PSM analysis further validated the survival advantage of RT (P = 0.002). A nomogram was established to predict the potential survival benefit. Subgroup analysis revealed RT was significantly associated with overall survival in ES patients of PT-DLBCL (P = 0.001) and in the rituximab era (P = 0.001) but not in those with AS disease (P = 0.241).

Conclusions

This population-based study encloses the largest sample of PT-DLBCL to date and demonstrates a favorable survival role of RT in early stages rather than advanced stages. The established nomogram helps to identify high risk patients to improve prognosis.
True abscopal effect in a patient with metastatic non-small cell lung cancer
Authors: Vilinovszki Oliver , Andratschke Nicolaus , Huellner Martin , Curioni-Fontecedro Alessandra , Kroeze Stephanie G. C.
Published: October 2021

Background

Systemic response to local anticancer treatment is a phenomenon called ‘abscopal effect’. The immune system is thought to play a pivotal role in its occurrence. To date, several cases have been reported, particularly in patients receiving combined local treatment and immune checkpoint inhibitors. In such cases, it is impossible to discriminate between the effects of local and systemic treatment. Only a few cases of abscopal effect have been described with radiotherapy alone.

Case presentation

Here, we report on the case of an 81-year-old woman with recurrent metastatic squamous cell carcinoma of the lung with mediastinal tumor bulk, lymph node and bone metastases. The patient refused to undergo systemic treatment, and palliative stereotactic radiotherapy of the mediastinal tumor was performed. At restaging with FDG-PET/CT, the patient presented with a decrease in size and FDG-avidity both of the irradiated site and of the lymph node and bone metastases (which did not receive radiotherapy). At 25 months after radiotherapy, the patient is still in remission at all sites.

Conclusions

This is a rare case of an abscopal effect after radiotherapy as monotherapy. It is one of the few hitherto reported for lung cancer. Several ongoing studies with a combination of radiotherapy and immunotherapy are seeking to exploit a potential synergy to induce abscopal effects.
Short-term response might influence the treatment-related benefit of adjuvant chemotherapy after concurrent chemoradiotherapy for esophageal squamous cell carcinoma patients
Authors: Liu Ao , Wang Yalin , Wang Xin , Zhu Liqiong , Nie Yu , Li Minghuan
Published: October 2021

Background

Whether adjuvant chemotherapy (AC) after concurrent chemoradiotherapy (CCRT) could provide benefit to esophageal squamous cell carcinoma (ESCC) patients is controversial. Therefore, we decided to investigate the potential benefit of AC after CCRT for ESCC and to identify biomarkers predictive of a clinical benefit.

Methods

We retrospectively analysed the clinical data of ESCC patients with clinical stage II–IVa who underwent CCRT. Then, we compared patients who received CCRT and AC (CCRT + AC group) with those who received CCRT alone (CCRT group). Propensity score analysis, subgroup analysis and an additional Cox regression model were conducted to analyse the predictive factors. The overall survival (OS) and progression-free survival (PFS) rates were taken as the endpoints.

Results

From January 2013 to December 2017, 244 patients were recruited (n = 131 for CCRT + AC; n = 113 for CCRT alone) for the analysis. After propensity score matching was performed (1:1 and 99 patients for each group) with consideration of the basic clinical characteristics, no significant differences were found in OS (HR = 1.024; 95% CI 0.737–1.423; P = 0.886) or PFS (HR = 0.809; 95% CI 0.582–1.126; P = 0.197) between the two groups. The good short-term response subgroup showed a better PFS and favoured CCRT + AC treatment (HR = 0.542; 95% CI 0.336–0.876; P = 0.008), the independent predictive role of which was confirmed in additional multivariate Cox regression analysis.

Conclusions

Although AC did not significantly improve PFS and OS for all ESCC patients after CCRT, the short-term response to CCRT might help identify a subgroup that will benefit, which needs further prospective research to confirm.
Shikonin attenuates rheumatoid arthritis by targeting SOCS1/JAK/STAT signaling pathway of fibroblast like synoviocytes
Authors: He Lianhua , Luan Huijie , He Juan , Zhang Miaomiao , Qin Qingxia , Hu Yiping , Cai Yueming , Sun Desheng , Shi Yu , Wang Qingwen
Published: October 2021

Background

Rheumatoid arthritis is a progressive and systemic autoimmune disease seriously compromises human health. Fibroblast like synoviocytes are the major effectors of proliferation and inflammation in rheumatoid arthritis synovial tissue. Shikonin has anti-inflammatory and immunomodulatory activities. But, its role on synovitis of rheumatoid arthritis is unknown.

Methods

The DBA/1 male mice were randomly divided into the following three groups (n = 6): (1) the normal control group of mice, (2) the CIA (collagen-induced arthritis) group in which mice suffered from arthritis induced by collagen, (3) the SKN (shikonin) group of mice which got arthritis and given intragastrically with shikonin 4 mg/kg per day continuously for 20 days,(4) the MTX (methotrexate) group of mice which got arthritis and orally administration with shikonin 0.5  mg/kg once two days continuously for 20 days. The therapeutic effect of shikonin on collagen induced arthritis mice was tested by arthritis incidence rate, arthritis score and inflammatory joint histopathology. The invasion, adhesion and migration of fibroblast like synoviocytes induced by tumor necrosis factor-α were applied to measure the anti-synovitis role of shikonin. The effect of shikonin on expression of interleukin-6, interleukin-1β and tumor necrosis factor-α was measured by enzyme linked immunosorbent assay. The interaction between shikonin and suppressor of cytokine signaling 1 was verified by molecular docking. The signaling pathways activated by shikonin were measured by western blot.

Results

Shikonin decreased the arthritis score and arthritis incidence, and inhibited inflammation of inflamed joints in collagen induced arthritis mice. And shikonin reduced the number of vimentin+cells in collagen induced arthritis mice inflamed joints. Meanwhile, shikonin suppressed tumor necrosis factor-α-induced invasion, adhesion and migration of fibroblast like synoviocytes and reduced the expression of interleukin-6, interleukin-1β and tumor necrosis factor-α. And we found that shikonin targeted suppressor of cytokine signaling 1. More interestingly, shikonin blocked the phosphorylation of Janus kinase 1/signal transducer andactivator of transcription 1/signal transducer andactivator of transcription 6 in synovial tissues and in fibroblast like synoviocytes.

Conclusion

Shikonin represents a promising new anti-rheumatoid arthritis drug candidate that has anti-synovitis effect in collagen induced arthritis mice and inhibits tumor necrosis factor-α-induced fibroblast like synoviocytes by targeting suppressor of cytokine signaling 1/ Janus kinase/signal transducer andactivator of transcription signaling pathway. These findings demonstrate that shikonin has anti-synovitis effect and has great potential to be a new drug for the treatment of rheumatoid arthritis.
Expert opinion on monitoring symptomatic hereditary transthyretin-mediated amyloidosis and assessment of disease progression
Authors: Adams David , Algalarrondo Vincent , Polydefkis Michael , Sarswat Nitasha , Slama Michel S. , Nativi-Nicolau Jose
Published: October 2021

Background

Hereditary transthyretin-mediated amyloidosis, also known as ATTRv amyloidosis (v for variant), is a rare, autosomal dominant, fatal disease, in which systemic amyloid progressively impairs multiple organs, leading to disability and death. The recent approval of disease-modifying therapies offers the hope of stabilization or eventual reversal of disease progression, and yet highlights a lack of disease-management guidance. A multidisciplinary panel of expert clinicians from France and the US came to consensus on monitoring the disease and identifying progression through a clinical opinion questionnaire, a roundtable meeting, and multiple rounds of feedback.

Monitoring disease and progression

A multidisciplinary team should monitor ATTRv amyloidosis disease course by assessing potential target organs at baseline and during follow-up for signs and symptoms of somatic and autonomic neuropathy, cardiac dysfunction and restrictive cardiomyopathy, and other manifestations. Variability in penetrance, symptoms, and course of ATTRv amyloidosis requires that all patients, regardless of variant status, undergo regular and standardized assessment in all these categories. Progression in ATTRv amyloidosis may be indicated by: worsening of several existing quantifiable symptoms or signs; the appearance of a new symptom; or the worsening of a single symptom that results in a meaningful functional impairment.

Conclusions

We suggest that a multisystem approach to monitoring the signs and symptoms of ATTRv amyloidosis best captures the course of the disease. We hope this work will help form the basis of further, consensus-based guidance for the treatment of ATTRv amyloidosis.
Collaborative model for diagnosis and treatment of very rare diseases: experience in Spain with thymidine kinase 2 deficiency
Authors: Domínguez-González Cristina , Madruga-Garrido Marcos , Hirano Michio , Martí Itxaso , Martín Miguel A. , Munell Francina , Nascimento Andrés , Olivé Montse , Quan Joanne , Sardina M. Dolores , Martí Ramon , Paradas Carmen
Published: October 2021

Background

Mitochondrial diseases are difficult to diagnose and treat. Recent advances in genetic diagnostics and more effective treatment options can improve patient diagnosis and prognosis, but patients with mitochondrial disease typically experience delays in diagnosis and treatment. Here, we describe a unique collaborative practice model among physicians and scientists in Spain focused on identifying TK2 deficiency (TK2d), an ultra-rare mitochondrial DNA depletion and deletions syndrome.

Main Body

This collaboration spans research and clinical care, including laboratory scientists, adult and pediatric neuromuscular clinicians, geneticists, and pathologists, and has resulted in diagnosis and consolidation of care for patients with TK2d. The incidence of TK2d is not known; however, the first clinical cases of TK2d were reported in 2001, and only ~ 107 unique cases had been reported as of 2018. This unique collaboration in Spain has led to the diagnosis of more than 30 patients with genetically confirmed TK2d across different regions of the country. Research affiliate centers have led investigative treatment with nucleosides based on understanding of TK2d clinical manifestations and disease mechanisms, which resulted in successful treatment of a TK2d mouse model with nucleotide therapy in 2010. Only 1 year later, this collaboration enabled rapid adoption of treatment with pyrimidine nucleotides (and later, nucleosides) under compassionate use. Success in TK2d diagnosis and treatment in Spain is attributable to two important factors: Spain’s fully public national healthcare system, and the designation in 2015 of major National Reference Centers for Neuromuscular Disorders (CSURs). CSUR networking and dissemination facilitated development of a collaborative care network for TK2d disease, wherein participants share information and protocols to request approval from the Ministry of Health to initiate nucleoside therapy. Data have recently been collected in a retrospective study conducted under a Good Clinical Practice–compliant protocol to support development of a new therapeutic approach for TK2d, a progressive disease with no approved therapies.

Conclusions

The Spanish experience in diagnosis and treatment of TK2d is a model for the diagnosis and development of new treatments for very rare diseases within an existing healthcare system.