bluuebunny/crossref_metadata_2025_split huggingface dataset:
The optimal percutaneous coronary intervention strategy for patients with ST-segment elevation myocardial infarction and multivessel disease: a pairwise and network meta-analysis
Authors: Hu Meng-Jin , Tan Jiang-Shan , Jiang Wen-Yang , Gao Xiao-Jin , Yang Yue-Jin 
Published: March 2022

Objective: To investigate the optimal percutaneous coronary intervention (PCI) strategy in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease. Methods: Trials that randomized patients with STEMI and multivessel coronary artery disease to immediate multivessel PCI, staged multivessel PCI, or culprit-only PCI and prospective observational studies that investigated all-cause death were included. Random effect risk ratio (RR) and 95% confidence interval (CI) were calculated. Results: A total of 13 randomized trials with 7627 patients and 21 prospective observational studies with 60311 patients were included. In the pairwise and network meta-analysis based on randomized trials, immediate or staged multivessel PCI was associated with a lower risk of long-term major adverse cardiac events (MACE; RR: 0.58; 95% CI: 0.45 to 0.74) than culprit-only PCI, which was mainly due to lower risks of myocardial infarction (RR: 0.67; 95% CI: 0.51 to 0.88) and revascularization (RR: 0.38; 95% CI: 0.28 to 0.51), without any significant difference in all-cause death (RR: 0.85; 95% CI: 0.69 to 1.04; I2 = 0.0%). However, short-term outcomes were deficient in randomized trials. The results from real-world prospective observational studies suggested that staged multivessel PCI reduced long-term all-cause death (RR: 0.53; 95% CI: 0.39 to 0.71; I2 = 15.6%), whereas immediate multivessel PCI increased short-term all-cause death (RR: 1.58; 95% CI: 1.22 to 2.05; I2 = 43.8%) relative to culprit-only PCI. Conclusion: For patients in randomized trials, multivessel PCI in an immediate or staged procedure was preferred due to improvements in long-term outcomes. As a supplement, the results in real-world patients derived from prospective observational studies suggested that staged multivessel PCI was superior to immediate multivessel PCI. Therefore, staged multivessel PCI may be the optimal PCI strategy for patients with STEMI and multivessel coronary artery disease.
Are caregivers ready for digital? Caregiver preferences for health technology tools to monitor medication adherence among patients with serious mental illness
Authors: Forma Felicia , Chiu Kevin , Shafrin Jason , Boskovic Dusica Hadzi , Veeranki S Phani 
Published: March 2022

Background Adherence to antipsychotic medication is critical for bipolar disorder (BPD), major depression (MDD) and schizophrenia (SCZ) patients. Digital tools have emerged to monitor medication adherence along with tracking general health. Evidence on physician or patient preferences for such tools exists but is limited among caregivers. The study objective was to assess preferences and willingness-to-pay (WTP) for medication adherence monitoring tools among caregivers of SMI patients. Methods A web-based survey was administered to caregivers of adult SMI patients. Twelve discrete choice questions comparing adherence monitoring tools that varied across two attribute bundles: (1) tool attributes including source of medication adherence information, frequency of information updates, access to adherence information, and physical activity, mood, and rest tracking, and (2) caregiver monthly out-of-pocket cost attribute were administered to caregiver respondents. Attributes were parameterized for both digital and non-digital tools. Random utility models were used to estimate caregivers’ preferences and WTP. Results Among 184 study-eligible caregivers, 57, 61 and 66 participants cared for BPD, MDD, and SCZ patients, respectively. Caregivers highly preferred (odds ratio (OR): 7.34, 95% confidence interval (CI): 5.00–10.79) a tool that tracked medication ingestion using a pill embedded with an ingestible event market (IEM) sensor and tracked patients’ physical activity, mood, and rest than a non-digital pill organizer. Additionally, caregivers were willing to pay $255 per month (95% CI: $123–$387) more for this tool compared to a pill organizer. Conclusion Caregivers of SMI patients highly preferred and were willing to pay more for digital tools that not only measures medication ingestion but also tracks general health.
The Role of Athlete Competitiveness in High School Sport Specialization in the United States
Authors: Warmath Dee , Bell David R. , Winterstein Andrew P. 
Published: March 2022

Background: Sport specialization has been associated with increased injury and negative psychosocial effects on young athletes. With the continuing trend toward specialization, studies have begun to examine what motivates this decision (eg, building a skill, getting a scholarship). No study has directly assessed the personal characteristics underlying these stated reasons. Purpose/Hypothesis: This study examined the role of athlete competitiveness (enjoyment of competition and competitive contentiousness) as a characteristic associated with propensity to specialize in the United States. We hypothesized that, at the high school level, athletes would be more likely to engage in sport specialization owing to enjoyment of competition versus competitive contentiousness. Study Design: Cross-sectional study; Level of evidence, 3. Methods: We conducted an online survey of 975 high school athletes in the United States who were recruited via the Dynata research panel. Measures included a previously published sport specialization categorization (low, medium, high) and the 2 dimensions of the Revised Competitiveness Index (enjoyment of competition and competitive contentiousness). Also collected were athlete characteristics, sports played by the athletes, level of competition, and whether they planned to play sports in college. Analytical methods employed included cross-tabulations, multinomial logit, and ordinary least squares regression. Results: Overall, 22.4% of the athletes reported a high, 34.8% reported a medium, and 42.9% reported a small level of specialization. No differences in the distribution of sport specialization by sex or age were observed; however, athletes who definitely planned to play in college were significantly more likely to have a high level of specialization ( P < .001). Enjoyment of competition was associated with greater specialization (beta = .196; P < .001), whereas competitive contentiousness was associated with lower levels of specialization (beta = −.299; P < .001). These findings were robust to all 3 different analytical methods we employed. Conclusion: Study findings indicated that, while athlete competitiveness is associated with sport specialization, the nature of that competitiveness determined the association. Being an argumentative contrarian may predispose athletes to lower levels of sport specialization, whereas enjoying competition may encourage higher levels of specialization.
Exosomes in multiple myeloma: from bench to bedside
Authors: Menu Eline , Vanderkerken Karin 
Published: March 2022

Abstract
Multiple myeloma (MM) remains an incurable plasma cell malignancy that develops in the bone marrow (BM). This BM is partially responsible for protecting the MM cells against current standard-of-care therapies and for accommodating MM-related symptoms such as bone resorption and immune suppression. Increasing evidence has implicated extracellular vesicles (EV), including exosomes in the different processes within the BM. Exosomes are &lt;150-nm-sized vesicles secreted by different cell types including MM cells. These vesicles contain protein and RNA cargo that they deliver to the recipient cell. In this way, they have been implicated in MM-related processes including osteolysis, angiogenesis, immune suppression, and drug resistance. Targeting exosome secretion could therefore potentially block these different processes. In this review, we will summarize the current findings of exosome-related processes in the BM and describe not only the current treatment strategies to counter them but also how exosomes can be harnessed to deliver toxic payloads. Finally, an overview of the different clinical studies that investigate EV cargo as potential MM biomarkers in liquid biopsies will be discussed.
HLA-DQ heterodimers in hematopoietic cell transplantation
Authors: Petersdorf Effie W. , Bengtsson Mats , Horowitz Mary , McKallor Caroline , Spellman Stephen R. , Spierings Eric , Gooley Ted A. , Stevenson Phil ,   on behalf of the International Histocompatibility Working Group in Hematopoietic Cell Transplantation
Published: March 2022

Abstract
HLA-DQ heterodimers increase the susceptibility to autoimmune diseases, but their role in hematopoietic cell transplantation is unknown. We tested the hypothesis that outcome after HLA-matched and HLA-DQ–mismatched hematopoietic cell transplantation is influenced by HLA-DQ heterodimers. Heterodimers were defined in 5164 HLA-matched and 520 HLA-DQ–mismatched patients and their transplant donors according to well-established crystallographic criteria. Group 1 (G1) heterodimers are any DQA1*02/03/04/05/06α paired with any DQB1*02/03/04β. Group 2 (G2) heterodimers are DQA1*01α paired with any DQB1*05/06β. Multivariable models identified significantly higher relapse risk in G1G2 and G2G2 compared with G1G1 HLA-matched patients with malignant disease; risk increased with an increasing number of G2 molecules. In HLA-DQ–mismatched transplantation for malignant diseases, matching or mismatching for G2 increased relapse risk. G2 lowered disease-free survival after both HLA-matched and HLA-DQ–mismatched transplantation. A paradigm based on HLA-DQ heterodimers provides a functional definition of the hematopoietic cell transplantation barrier and a means to lower risks for future patients.
GRK2 regulates group 2 innate lymphoid cell mobilization in sepsis
Authors: Lai Dengming , Chen Weiwei , Zhang Kai , Scott Melanie J. , Li Yuehua , Billiar Timothy R. , Wilson Mark A. , Fan Jie 
Published: March 2022

Abstract
Background
Sepsis induces group 2 innate lymphoid cell (ILC2) expansion in the lung. However, the origin of these lung-recruited ILC2 and the mechanism of ILC2 expansion are unclear. This study aims to determine the origin of lung-recruited ILC2 and its underlying mechanism in sepsis.

Methods
Sepsis was induced by cecal ligation and puncture (CLP) model in wild-type, IL-33-deficient and ST2-deficient mice. The frequency, cell number and C-X-C chemokine receptor 4 (CXCR4) expression of ILC2 in bone marrow (BM), blood and lung were measured by flow cytometry. In the in vitro studies, purified ILC2 progenitor (ILC2p) were challenged with IL-33 or G protein-coupled receptor kinase 2 (GRK2) inhibitor, the CXCR4 expression and GRK2 activity were detected by confocal microscopy or flow cytometry.

Results
We show that IL-33 acts through its receptor, ST2, on BM ILC2p to induce GRK2 expression and subsequent downregulation of cell surface expression of CXCR4, which results in decreasing retention of ILC2p in the BM and promoting expansion of ILC2 in the lung. Importantly, we demonstrate that reduced IL-33 level in aging mice contributes to impaired ILC2 mobilization from BM and accumulation in the lung following sepsis.

Conclusion
This study identifies a novel pathway in regulating ILC2p mobilization and expansion during sepsis and indicates BM as the main source of ILC2 in the lung following sepsis.
Sero-survey on long-term care facility residents reveals increased risk of sub-optimal antibody response to BNT162b2: implications for breakthrough prevention
Authors: Caimi Barbara , Franzetti Marco , Velleca Rossella , Lai Alessia , Gatti Antonella , Rossi Pier Luigi , D’Orso Marco , Pregliasco Fabrizio , Balotta Claudia , Calicchio Giuseppe 
Published: March 2022

Abstract
Background
The impact of coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) on residents of long-term care facilities (LTCFs) has been dramatic on global scale as older age and comorbidities pose an increased risk of severe disease and death.

Methods
Aim of this study was to evaluate SARS-CoV-2 Spike-specific IgG (S-IgG) antibody titers in 478 residents and 649 health care workers of a large Italian long-term care facility two months after complete vaccination with BNT162b2. Associations among resident-related factors and predictors of humoral response were investigated.

Results
By stratifying levels of humoral responses, we found that 62.1%, 21.6%, 12.1% and 4.2% of residents had high (>1,000 BAU/ml), medium (101-1,000), low (1-100) and null (<1 BAU/mL) S-IgG titers, respectively. Residents with documented previous COVID-19 and those with SARS-CoV-2 nucleocapsid-specific IgG (N-IgG) positive serology showed higher level of serological response, while significant associations were observed for cancer with suboptimal response (p = 0.005) and the administration of corticosteroid for suboptimal response (p = 0.028) and a null one (p = 0.039). According to multivariate logistic regression, predictors of an increased risk of null response were advanced age (Odd ratio, OR: 2.630; Confidence interval, CI: 1.13-6.14; p = 0.025), corticosteroid therapy (OR: 4.964; CI: 1.06-23.52; p = 0.042) and diabetes mellitus (OR:3.415; CI:1.08-10.8; p = 0.037). In contrast, previous diagnosis of COVID-19 was strongly associated with a reduced risk of null response to vaccination (OR:0.126; CI:0.02-0.23; p < 0.001).

Conclusions
SARS-CoV-2 specific antibodies in elderly individuals should be consider when deciding the need of a third dose of vaccine for prevention of reinfections in LTCFs despite the maintenance of barrier measures.
An integrative gene expression signature analysis identifies CMS4 KRAS-mutated colorectal cancers sensitive to combined MEK and SRC targeted therapy
Authors: Yang Mingli , Davis Thomas B. , Pflieger Lance , Nebozhyn Michael V. , Loboda Andrey , Wang Heiman , Schell Michael J. , Thota Ramya , Pledger W. Jack , Yeatman Timothy J. 
Published: March 2022

Abstract
Background
Over half of colorectal cancers (CRCs) are hard-wired to RAS/RAF/MEK/ERK pathway oncogenic signaling. However, the promise of targeted therapeutic inhibitors, has been tempered by disappointing clinical activity, likely due to complex resistance mechanisms that are not well understood. This study aims to investigate MEK inhibitor-associated resistance signaling and identify subpopulation(s) of CRC patients who may be sensitive to biomarker-driven drug combination(s).

Methods
We classified 2250 primary and metastatic human CRC tumors by consensus molecular subtypes (CMS). For each tumor, we generated multiple gene expression signature scores measuring MEK pathway activation, MEKi “bypass” resistance, SRC activation, dasatinib sensitivity, EMT, PC1, Hu-Lgr5-ISC, Hu-EphB2-ISC, Hu-Late TA, Hu-Proliferation, and WNT activity. We carried out correlation, survival and other bioinformatic analyses. Validation analyses were performed in two independent publicly available CRC tumor datasets (n = 585 and n = 677) and a CRC cell line dataset (n = 154).

Results
Here we report a central role of SRC in mediating “bypass”-resistance to MEK inhibition (MEKi), primarily in cancer stem cells (CSCs). Our integrated and comprehensive gene expression signature analyses in 2250 CRC tumors reveal that MEKi-resistance is strikingly-correlated with SRC activation (Spearman P < 10–320), which is similarly associated with EMT (epithelial to mesenchymal transition), regional metastasis and disease recurrence with poor prognosis. Deeper analysis shows that both MEKi-resistance and SRC activation are preferentially associated with a mesenchymal CSC phenotype. This association is validated in additional independent CRC tumor and cell lines datasets. The CMS classification analysis demonstrates the strikingly-distinct associations of CMS1-4 subtypes with the MEKi-resistance and SRC activation. Importantly, MEKi + SRCi sensitivities are predicted to occur predominantly in the KRAS mutant, mesenchymal CSC-like CMS4 CRCs.

Conclusions
Large human tumor gene expression datasets representing CRC heterogeneity can provide deep biological insights heretofore not possible with cell line models, suggesting novel repurposed drug combinations. We identified SRC as a common targetable node–-an Achilles’ heel–-in MEKi-targeted therapy-associated resistance in mesenchymal stem-like CRCs, which may help development of a biomarker-driven drug combination (MEKi + SRCi) to treat problematic subpopulations of CRC.
The impact of nursing staff education on diabetes inpatient glucose management: a pilot cluster randomised controlled trial
Authors: Piya Milan K. , Fletcher Therese , Myint Kyaw P. , Zarora Reetu , Yu Dahai , Simmons David 
Published: March 2022

AbstractBackgroundAn increasing number of patients in hospital have diabetes, with most of them cared for by non-specialist staff. The effect of diabetes education for staff on patient outcomes, as well as the most effective method of staff education is unclear. Therefore, the aim of this study was to compare diabetes outcomes in medical wards where nursing staff were offered one face-to-face (F2F) session followed by access to online education (online), F2F education only, or standard care (control).MethodsWe conducted a pilot cluster randomised controlled trial involving 16-weeks baseline/rollout followed by a 28-week post-intervention period across three medical wards (clusters) in a Sydney Teaching Hospital. The online ward provided an online competency-based diabetes education program and 1-h F2F teaching from a diabetes nurse educator (DNE), the F2F ward provided four separate 1-h teaching sessions by a DNE, with no additional sessions in the control ward. The primary outcome was length of stay (LOS); secondary outcomes included good diabetes days (GDD), hypoglycaemia and medication errors. Poisson and binary logistic regression were used to compare clusters.ResultsStaff attendance/completion of ≥ 2 topics was greater with online than F2F education [39/48 (81%) vs 10/33 (30%);p < 0.001]. Among the 827/881 patients, there was no difference in LOS change between online [Median(IQR) 5(2–8) to 4(2–7) days], F2F [7(4–14) to 5(3–13) days] or control wards [5(3–9) to 5(3–7) days]. GDD improved only in the online ward 4.7(2.7–7.0) to 6.0(2.3–7.0) days;p = 0.038. Total patients with hypoglycaemia and appropriately treated hypoglycaemia increased in the online ward.ConclusionsThe inclusion of online education increased diabetes training uptake among nursing staff. GDD and appropriate hypoglycaemia management increased in the online education wards.Trial registrationProspectively registered on the Australia New Zealand Clinical Trials Registry (ANZCTR) on 24/05/2017:ACTRN12617000762358.
The level of knowledge about palliative care in Iranian patients with cancer
Authors: Atena Dadgari , Imane Bagheri , Maryam Rassouli , Naiire Salmani , Fatemeh Tahani 
Published: March 2022

Abstract
Background
Patient awareness plays an important role in integrating palliative care into the patient care process. Lack of awareness can create a negative attitude towards palliative care and affect patients' decisions during the treatment process. The present study was conducted to determine the level of knowledge about palliative care in Iranian patients with cancer.

Methods
The descriptive study was conducted with a convenience sample of 103 cancer patients admitted to an oncology center in Yazd, Iran, A three-part questionnaire including demographic information, sources of palliative care information and the Palliative Care Knowledge Scale (PaCKS) was used to collect data. All statistical analyses were performed using software SPSS 21.

Results
The mean age of patients was 36.2 ± 13.5 years. Of the total, 38.8% of patients received information about palliative care through the media and 36.9% from the treatment team. On a scale of 0 to 13, the mean PaCKS score was 6.7 ± 3.7. A ‘good’ level of knowledge was reported by 29.1% of participants; however 84.5% stated that they should leave other doctors at the time of receiving palliative care, 71.8% considered palliative care for patients in the last six months of life, 84.5% considered palliative care for patients with cancer, and 70.9% stated that palliative care encourages people to discontinue treatments aimed at treating their disease.

Conclusion
Our study found most cancer patients have a moderate to weak level of knowledge and considerable misinformation about palliative care, which highlights the importance of providing palliative care education. The development of training programs in this area could play an effective role in improving patients' knowledge of palliative care.
Icariin regulates stem cell migration for endogenous repair of intervertebral disc degeneration by increasing the expression of chemotactic cytokines
Authors: Zhang Zhaofei , Qin Fengwei , Feng Yonghui , Zhang Sineng , Xie Chunliang , Huang He , Sang Chaohui , Hu Shaoyu , Jiao Feng , Jiang Jie , Qin Yi 
Published: March 2022

AbstractBackgroundIcariin (ICA) can promote the migration and bone formation of bone marrow mesenchymal stem cells. This study explored a potential role of ICA in recruiting stem cell niches (SCNs) within the intervertebral disc region (ISN)-derived stem cells (ISN-SCs) to treat intervertebral disc degeneration (IVDD).Materials and methodsEdU staining, transwell, and wound healing tests were used to analyze the function of ICA on ISN-SCs proliferation and migration ability. Simultaneously, the IVDD rat model was constructed by the acupuncture and divided into Sham, Sham + ICA, IVDD, and IVDD + ICA groups. H&E and PAS staining were performed to detect the pathological changes of IVDD tissues. Immunofluorescence was performed to discover relevant marker expression on the surface of stem cells in the IVDD tissues. Western blot and qPCR were executed to find the protein and mRNA expression of related cytokines in the IVDD tissues.ResultsISN-SCs treated with 1 μM ICA obtained the better ability of proliferation and migration. H&E staining showed that the annulus fibrosus in the IVDD group was obviously hyperplasia with cavities and fissures; the nucleus pulposus was reduced. PAS staining showed that the content of polysaccharides was significantly reduced in the nucleus pulposus of IVDD group. However, the ICA treatment alleviated the pathological trends of the IVDD tissues. Simultaneously, ICA treatment increased significantly the expression of stem cells and IGF-1, TGF-β, SDF-1, CCL-5, Collagen I, Collagen II, Aggrecan, and SOX9 in IVDD tissues.ConclusionsICA treatment promoted the migration of stem cell in IVDD by increasing the expression of chemotactic cytokines, including IGF-1, TGF-β, SDF-1, and CCL-5.