bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid cycle training for non-critical care physicians to meet intensive care unit staff shortage at an academic training center in a developing country during the COVID-19 pandemic
Authors: Bakhsh Abdullah , Asiri Razan , Alotaibi Hadeel , Alsaeedi Rowida , Shahbar Raghad , Boker Abdulaziz 
Published: July 2023

Abstract

Background

The sudden unexpected increase in critically ill COVID-19 patients admitted to Intensive Care Units (ICUs), resulted in an urgent need for expanding the physician workforce. A COVID-19 critical care crash (5C) course was implemented to introduce physicians without formal critical care training to care for critically ill COVID-19 patients. Upon successful completion of the course, physicians were recruited to work in a COVID-19 ICU under the supervision of a board-certified critical care physician. The aim of this study is to describe the methods of a novel course designed specifically to teach the management critically ill COVID-19 patients, while assessing change in knowledge, skill competency, and self-reported confidence.

Methods

The blended focused 5C course is composed of both virtual and practical components. Candidates may register for the practical component only after successful completion of the virtual component. We assessed knowledge acquisition using a multiple-choice question test (pre- and post-test assessment), skill competency, and self-reported confidence levels during simulated patient settings. Paired T-test was used to compare before and after course results.

Results
Sixty-five physicians/trainees from different specialties were included in the analysis. Knowledge significantly increased from 14.92± 3.20 (out of 20 multiple-choice questions) to 18.81± 1.40 (p< 0.01), skill competence during practical stations had a mean minimum of 2 (out of 3), and self-reported confidence during a simulated patient setting increased significantly from 4.98± 1.15 (out of 10) to 8.76± 1.10 (out of 10) (p< 0.01).

Conclusion
We describe our initiative in increasing the ICU physician workforce in the midst of the COVID-19 pandemic. The blended 5C course is a valuable educational program designed by experts from different backgrounds. Future research should be directed at examining outcomes of patients associated with graduates of such program.
Explaining of existing challenges of community-based undergraduate nursing education in Iran: a qualitative study
Authors: Atashzadeh-Shoorideh Foroozan , Zeydani Arezoo , Hosseini Meimanat , Zohari-Anboohi Sima 
Published: July 2023

Abstract
Background
The education of nursing students should be such that the health needs of the community are met, but in Iran, due to some problems, students do not receive such education. Therefore, the present study was conducted to explain the existing challenges of community-based undergraduate nursing education in Iran.

Methods
Ten individual semi-structured interviews were conducted with the faculty members and nursing specialists in this qualitative study. Eight focus group interviews were conducted to the nurses and nursing students using a purpose-based sampling method in 2022. The interviews were recorded and transcribed and then content analysis was done by the Lundman and Granheim method.

Results
Five themes were obtained from the analysis of participants' responses, which include "weakness in community-based nursing education and curriculum", "treatment-oriented health system and education", "defect in the infrastructure and basic structures of community-based nursing education", "weakness in the implementation of community-based nursing education" and "weakness in the stakeholder engagement and cooperation of interested organizations".

Conclusion
Interviews with the participants provided a vision of the challenges of community-based nursing education so that the reviewers of the undergraduate nursing curriculum in the ministry and nursing schools, educators, policymakers and nursing managers can use the results of the present study to improve the quality of education and the effective use of nursing students in responding to the community’s needs and provide a proper context for improving students' learning.
The diversity of providers’ and consumers’ views of virtual versus inpatient care provision: a qualitative study
Authors: Clay-Williams Robyn , Hibbert Peter , Carrigan Ann , Roberts Natalie , Austin Elizabeth , Fajardo Pulido Diana , Meulenbroeks Isabelle , Nguyen Hoa Mi , Sarkies Mitchell , Hatem Sarah , Maka Katherine , Loy Graeme , Braithwaite Jeffrey 
Published: July 2023

Abstract
Background
A broad-based international shift to virtual care models over recent years has accelerated following COVID-19. Although there are increasing numbers of studies and reviews, less is known about clinicians’ and consumers’ perspectives concerning virtual modes in contrast to inpatient modes of delivery.

Methods
We conducted a mixed-methods study in late 2021 examining consumers’ and providers’ expectations of and perspectives on virtual care in the context of a new facility planned for the north-western suburbs of Sydney, Australia. Data were collected via a series of workshops, and a demographic survey. Recorded qualitative text data were analysed thematically, and surveys were analysed using SPSS v22.

Results
Across 12 workshops, 33 consumers and 49 providers from varied backgrounds, ethnicities, language groups, age ranges and professions participated. Four advantages, strengths or benefits of virtual care reported were: patient factors and wellbeing, accessibility, better care and health outcomes, and additional health system benefits, while four disadvantages, weaknesses or risks of virtual care were: patient factors and wellbeing, accessibility, resources and infrastructure, and quality and safety of care.

Conclusions
Virtual care was widely supported but the model is not suitable for all patients. Health and digital literacy and appropriate patient selection were key success criteria, as was patient choice. Key concerns included technology failures or limitations and that virtual models may be no more efficient than inpatient care models. Considering consumer and provider views and expectations prior to introducing virtual models of care may facilitate greater acceptance and uptake.
Using technology to reduce critical deterioration (the DETECT study): a cost analysis of care costs at a tertiary children's hospital in the United Kingdom
Authors: Costa Eduardo , Mateus Céu , Carter Bernie , Saron Holly , Eyton-Chong Chin-Kien , Mehta Fulya , Lane Steven , Siner Sarah , Dean Jason , Barnes Michael , McNally Chris , Lambert Caroline , Hollingsworth Bruce , Carrol Enitan D. , Sefton Gerri 
Published: July 2023

Abstract
Background
Electronic early warning systems have been used in adults for many years to prevent critical deterioration events (CDEs). However, implementation of similar technologies for monitoring children across the entire hospital poses additional challenges. While the concept of such technologies is promising, their cost-effectiveness is not established for use in children. In this study we investigate the potential for direct cost savings arising from the implementation of the DETECT surveillance system.

Methods
Data were collected at a tertiary children’s hospital in the United Kingdom. We rely on the comparison between patients in the baseline period (March 2018 to February 2019) and patients in the post-intervention period (March 2020 to July 2021). These provided a matched cohort of 19,562 hospital admissions for each group. From these admissions, 324 and 286 CDEs were observed in the baseline and post-intervention period, respectively. Hospital reported costs and Health Related Group (HRG) National Costs were used to estimate overall expenditure associated with CDEs for both groups of patients.

Results
Comparing post-intervention with baseline data we found a reduction in the total number of critical care days, driven by an overall reduction in the number of CDEs, however without statistical significance. Using hospital reported costs adjusted for the Covid-19 impact, we estimate a non-significant reduction of total expenditure from £16.0 million to £14.3 million (corresponding to £1.7 million of savings – 11%). Additionally, using HRG average costs, we estimated a non-significant reduction of total expenditure from £8.2 million to £ 7.2 million (corresponding to £1.1 million of savings – 13%).

Discussion and conclusion
Unplanned critical care admissions for children not only impose a substantial burden on patients and families but are also costly for hospitals. Interventions aimed at reducing emergency critical care admissions can be crucial to contribute to the reduction of these episodes’ costs. Even though cost reductions were identified in our sample, our results do not support the hypothesis that reducing CDEs using technology leads to a significant reduction on hospital costs.

Trial registration
Current Controlled Trials ISRCTN61279068, date of registration 07/06/2019, retrospectively registered.
Advances in PD-1 signaling inhibition-based nano-delivery systems for tumor therapy
Authors: Liu Songlin , Wang Haiyang , Shao Xinzhe , Chen Haonan , Chao Shushu , Zhang Yanyan , Gao Zhaoju , Yao Qingqiang , Zhang Pingping 
Published: July 2023

AbstractIn recent years, cancer immunotherapy has emerged as an exciting cancer treatment. Immune checkpoint blockade brings new opportunities for more researchers and clinicians. Programmed cell death receptor-1 (PD-1) is a widely studied immune checkpoint, and PD-1 blockade therapy has shown promising results in a variety of tumors, including melanoma, non-small cell lung cancer and renal cell carcinoma, which greatly improves patient overall survival and becomes a promising tool for the eradication of metastatic or inoperable tumors. However, low responsiveness and immune-related adverse effects currently limit its clinical application. Overcoming these difficulties is a major challenge to improve PD-1 blockade therapies. Nanomaterials have unique properties that enable targeted drug delivery, combination therapy through multidrug co-delivery strategies, and controlled drug release through sensitive bonds construction. In recent years, combining nanomaterials with PD-1 blockade therapy to construct novel single-drug-based or combination therapy-based nano-delivery systems has become an effective mean to address the limitations of PD-1 blockade therapy. In this study, the application of nanomaterial carriers in individual delivery of PD-1 inhibitors, combined delivery of PD-1 inhibitors and other immunomodulators, chemotherapeutic drugs, photothermal reagents were reviewed, which provides effective references for designing new PD-1 blockade therapeutic strategies.
Graphical Abstract
Myofiber directs macrophages IL-10-Vav1-Rac1 efferocytosis pathway in inflamed muscle following CTX myoinjury by activating the intrinsic TGF-β signaling
Authors: Liao Zhaohong , Lan Haiqiang , Jian Xiaoting , Huang Jingwen , Wang Han , Hu Jijie , Liao Hua 
Published: July 2023

Abstract
Background
To explore the role of skeletal muscle specific TGF-β signaling on macrophages efferocytosis in inflamed muscle caused by Cardiotoxin (CTX) injection.

Methods
CTX myoinjury was manipulated in TGF-βr2flox/flox (control) mice or transgenic mice with TGF-β receptor 2 (TGF-βr2) being specifically deleted in skeletal muscle (SM TGF-βr2−/−). Gene levels of TGF-β signal molecules, special inflammatory mediators in damaged muscle or in cultured and differentiated myogenic precursor cells (MPC-myotubes) were monitored by transcriptome microarray or qRT-PCR. TGF-β pathway molecules, myokines and embryonic myosin heavy chain in regenerating myofibers, the phenotype and efferocytosis of macrophages were evaluated by immunofluorescence, immunoblotting, Luminex, or FACS analysis. In vitro apoptotic cells were prepared by UV-irradiation.

Results
In control mice, TGF-β-Smad2/3 signaling were significantly up-regulated in regenerating centronuclear myofibers after CTX-myoinjury. More severe muscle inflammation was caused by the deficiency of muscle TGF-β signaling, with the increased number of M1, but the decreased number of M2 macrophages. Notably, the deficiency of TGF-β signaling in myofibers dramatically affected on the ability of macrophages to conduct efferocytosis, marked by the decreased number of Annexin-V−F4/80+Tunel+ macrophages in inflamed muscle, and the impaired uptake of macrophages to PKH67+ apoptotic cells transferred into damaged muscle. Further, our study suggested that, the intrinsic TGF-β signaling directed IL-10-Vav1-Rac1 efferocytosis signaling in muscle macrophages.

Conclusions
Our data demonstrate that muscle inflammation can be suppressed potentially by activating the intrinsic TGF-β signaling in myofibers to promote IL-10 dependent-macrophages efferocytosis.
Efficacy of low-dose risperidone in combination with sertraline in first-episode drug-naïve patients with schizophrenia: a randomized controlled open-label study
Authors: Lang Xiaoe , Xue Mei , Zang Xiaocui , Wu Fengchun , Xiu Meihong , Zhang Xiangyang 
Published: July 2023

Abstract
Objective
Despite advances in pharmacology, the treatment of schizophrenia (SZ) remains a challenge due to relapse after antipsychotic discontinuation and multiple adverse effects of antipsychotics. We hypothesized that a low dose of risperidone in combination with sertraline would reduce serious adverse effects without decreasing treatment response. This study aimed to examine the efficacy, safety, and tolerability of low-dose risperidone combined with sertraline to reduce risperidone dose and serious adverse effects in first-episode and medication-naive (FEMN) SZ patients.

Methods
A total of 230 patients with FEMN SZ were randomly assigned to receive low-dose risperidone in combination with sertraline (RS group) or regular-dose risperidone (control group). The Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale (HAMD), and Personal and Social Performance Scale (PSP) were assessed at baseline and the end of the first, second, third, and sixth months. In addition, serum prolactin levels and extrapyramidal symptoms were measured at baseline and follow-up.

Results
Repeated measures ANCOVA showed significant interaction effects of treatment by time on psychotic symptoms, as well as HAMD, PSP scores, prolactin levels, and extrapyramidal symptoms (all p < 0.05). Compared with the control group, the RS group had greater decreases in PANSS total score and its subscores and HAMD score (all p < 0.01) and a greater increase in PSP total score (p < 0.01). Notably, side effects were lower in the RS group relative to the control group. Improvements in HAMD and PANSS total scores, changes in prolactin levels and gender predicted improvements in PSP from baseline to month 6.

Conclusions
Our study suggests that low-dose risperidone in combination with sertraline was more effective for psychotic symptoms and psychosocial functioning, with significantly fewer adverse effects in patients with FEMN SZ.
Trial registration number: ClinicalTrials.gov, NCT04076371
Association of impaired sensitivity to thyroid hormones with hyperuricemia through obesity in the euthyroid population
Authors: Wu Zhiyuan , Jiang Yue , Li Pingan , Wang Yutao , Zhang Haiping , Li Zhiwei , Li Xia , Tao Lixin , Gao Bo , Guo Xiuhua 
Published: July 2023

Abstract
Background
Impaired sensitivity to thyroid hormones is a newly proposed clinical entity associated with hyperuricemia in the subclinical hypothyroid population. However, it is unknown whether the association exists in the euthyroid population. This study aimed to explore the association of impaired sensitivity to thyroid hormones (assessed by the thyroid feedback quantile-based index [TFQI], parametric thyroid feedback quantile-based index [PTFQI], thyrotrophic thyroxine resistance index [TT4RI] and thyroid-stimulating hormone index [TSHI]) with hyperuricemia and quantify the mediating effect of body mass index BMI in the euthyroid population.

Methods
This cross-sectional study enrolled Chinese adults aged ≥ 20 years who participated in the Beijing Health Management Cohort (2008–2019). Adjusted logistic regression models were used to explore the association between indices of sensitivity to thyroid hormones and hyperuricemia. Odds ratios [OR] and absolute risk differences [ARD] were calculated. Mediation analyses were performed to estimate direct and indirect effects through BMI.

Results
Of 30,857 participants, 19,031 (61.7%) were male; the mean (SD) age was 47.3 (13.3) years; and 6,515 (21.1%) had hyperuricemia. After adjusting for confounders, individuals in the highest group of thyroid hormone sensitivity indices were associated with an increased prevalence of hyperuricemia compared with the lowest group (TFQI: OR = 1.18, 95% CI 1.04–1.35; PTFQI: OR = 1.20, 95% CI 1.05–1.36; TT4RI: OR = 1.17, 95% CI 1.08–1.27; TSHI: OR = 1.12, 95% CI 1.04–1.21). BMI significantly mediated 32.35%, 32.29%, 39.63%, and 37.68% of the associations of TFQI, PTFQI, TT4RI and TSHI with hyperuricemia, respectively.

Conclusions
Our research revealed that BMI mediated the association between impaired sensitivity to thyroid hormones and hyperuricemia in the euthyroid population. These findings could provide useful evidence for understanding the interaction between impaired sensitivity to thyroid hormone and hyperuricemia in euthyroid individuals and suggest the clinical implications of weight control in terms of impaired thyroid hormones sensitivity.
The promoting effect and mechanism of Nrf2 on cell metastasis in cervical cancer
Authors: Zhang Mengwen , Hong Xiaoling , Ma Ning , Wei Zhentong , Ci Xinxin , Zhang Songling 
Published: July 2023

Abstract
Background
Cervical cancer (CC) has poor prognosis and high mortality rate for its metastasis during the disease progression. Epithelial-mesenchymal transition (EMT) and anoikis are initial and pivotal steps during the metastatic process. Although higher levels of Nrf2 are associated with aggressive tumor behaviors in cervical cancer, the detailed mechanism of Nrf2 in cervical cancer metastasis, especially EMT and anoikis, remains unclear.

Methods
Immunohistochemistry (IHC) was used to examine Nrf2 expression in CC. Wound healing assay and transwell analysis were used to evaluate the migration ability of CC cells. Western blot, qTR-PCR and immunofluorescent staining were used to verify the expression level of Nrf2, the EMT associated markers and anoikis associated proteins. Flow cytometry assays and cell counting were used to detect the apoptosis of cervical cancer cells. The lung and lymph node metastatic mouse model were established for studies in vivo. The interaction between Nrf2 and Snail1 was confirmed by rescue-of-function assay.

Results
When compared with cervical cancer patients without lymph node metastasis, Nrf2 was highly expressed in patients with lymph node metastasis. And Nrf2 was proved to enhance the migration ability of HeLa and SiHa cells. In addition, Nrf2 was positively correlated with EMT processes and negatively associated with anoikis in cervical cancer. In vivo, a xenograft assay also showed that Nrf2 facilitated both pulmonary and lymphatic distant metastasis of cervical cancer. Rescue-of-function assay further revealed the mechanism that Nrf2 impacted the metastasis of CC through Snail1.

Conclusion
Our fundings established Nrf2 plays a crucial role in the metastasis of cervical cancer by enhancing EMT and resistance to anoikis by promoting the expression of Snail1, with potential value as a therapeutic candidate.
Caudal DMN neurons innervate the spleen and release CART peptide to regulate neuroimmune function
Authors: Kobori Nobuhide , Moore Anthony N. , Redell John B. , Dash Pramod K. 
Published: July 2023

Abstract
Background
Inflammation is a fundamental biological response to injury and infection, which if unregulated can contribute to the pathophysiology of many diseases. The vagus nerve, which primarily originates from the dorsal motor nucleus (DMN), plays an important role in rapidly dampening inflammation by regulating splenic function. However, direct vagal innervation of the spleen, which houses the majority of immune and inflammatory cells, has not been established. As an alternative to direct innervation, an anti-inflammatory reflex pathway has been proposed which involves the vagus nerve, the sympathetic celiac ganglion, and the neurotransmitter norepinephrine. Although sympathetic regulation of inflammation has been shown, the interaction of the vagus nerve and the celiac ganglia requires a unique interaction of parasympathetic and sympathetic inputs, making this putative mechanism of brain–spleen interaction controversial.

Body
As neuropeptides can be expressed at relatively high levels in neurons, we reasoned that DMN neuropeptide immunoreactivity could be used to determine their target innervation. Employing immunohistochemistry, subdiaphragmatic vagotomy, viral tract tracing, CRISPR-mediated knock-down, and functional assays, we show that cocaine and amphetamine-regulated transcript (CART) peptide-expressing projection neurons in the caudal DMN directly innervate the spleen. In response to lipopolysaccharide (LPS) stimulation, CART acts to reduce inflammation, an effect that can be augmented by intrasplenic administration of a synthetic CART peptide. These in vivo effects could be recapitulated in cultured splenocytes, suggesting that these cells express the as yet unidentified CART receptor(s).

Conclusion
Our results provide evidence for direct connections between the caudal DMN and spleen. In addition to acetylcholine, these neurons express the neuropeptide CART that, once released, acts to suppress inflammation by acting directly upon splenocytes.
An unusual case of huge fibrotic sac of hematoma at saphenous vein harvest site for coronary artery bypass grafting: a case report
Authors: Lee June , Na Hye Rim , Hong Seok Beom , Kim Do Yeon , Kim Hwan Wook , Kim Yong Han 
Published: July 2023

AbstractGreat saphenous vein is a conduit commonly used for coronary artery bypass grafting. However, several complications could occur at leg wound site for vein harvesting. Here, we describe a huge sac of hematoma as an uncommon complication of saphenous vein harvest for coronary artery bypass grafting.A 62-year-old gentleman was readmitted with swelling at left thigh 30 days after coronary artery bypass grafting. Lower extremity computed tomography was suggestive of an oval and thick sac implying a hematoma or seroma. After using ultrasound scanning for the mass, an incision through the previous surgical wound showed a huge mass. Inspection after incision the mass revealed an old hematoma within the sac.Pathologic findings demonstrated chronic inflammation with the hematoma surrounded by a fibrotic sac. The patient’s postoperative course was uneventful without recurrence.Our experience suggests the possibility of a huge hematoma within a thick fibrotic sac at the previous vein harvest site for coronary artery bypass grafting.