bluuebunny/crossref_metadata_2025_split huggingface dataset:
Knockdown of CENPW Inhibits Hepatocellular Carcinoma Progression by Inactivating E2F Signaling
Authors: Zhou Yajing , Chai Hua , Guo Lei , Dai Zhongqiu , Lai Jianming , Duan Jianping , Liu Yanting , Ding Qian 
Published: May 2021

Aim: This study aimed to evaluate the effects of centromere protein W (CENPW, also known as CUG2) in hepatocellular carcinoma (HCC). Methods: CENPW expression in HCC tissues and cells was detected by RT-qPCR assay. CCK-8 and colony formation assay were used to assess cell proliferation. Wound healing and Transwell assay was used to detect cell migration and invasion, respectively. The flow cytometry was used to analyze the cell cycle distribution and apoptosis. Results: CENPW expression was upregulated in HCC tissues and cells. Knockdown of CENPW inhibited cell proliferation, migration, and invasion and induced the G0/G1 phase arrest and cell apoptosis in HCC cells, which might involve the E2F signaling regulation. Conclusion: CENPW acted as an oncogenic role in HCC progression via activation E2F signaling. Our findings may provide new insights into the studying mechanisms of HCC.
Baricitinib in the treatment of rheumatoid arthritis: clinical and ultrasound evaluation of a real-life single-centre experience
Authors: Tesei Giulia , Cometi Laura , Nacci Francesca , Terenzi Riccardo , Tofani Lorenzo , Capassoni Marco , Bartoli Francesca , Fiori Ginevra , Matucci-Cerinic Marco , Bruni Cosimo 
Published: May 2021

Background: Ultrasound (US) is useful in monitoring RA patients, with the US7 score allowing grey-scale and power-Doppler (PD) semi-quantitative evaluation of synovitis and teno-synovitis. We evaluated real-life efficacy and safety of Baricitinib, an oral selective JAK1-2 inhibitor, in RA patients using clinical, clinimetric, and US assessments. Methods: Disease activity score in 28 joints calculated with C-reactive protein (DAS28-CRP), disease activity score in 28 joints calculated with erythrocyte sedimentation rate (DAS28-ESR), clinical disease activity index (CDAI), simplified disease activity index (SDAI), visual analogue scale (VAS)-pain, health assessment questionnaire (HAQ), COCHIN scale, adverse events (AE), concomitant medications, laboratory parameters, and US7 were performed/recorded at baseline, 1, 3, and 6 months in RA patients starting Baricitinib. Responder/non-responder status was determined according to the EULAR Response Criteria at 3 months. SDAI clinical remission or low disease activity (LDA) were calculated at 3 and 6 months. Results: In 43 enrolled patients, a significant improvement in disease activity and US7 components (except tendon PD) and a reduction of steroid dosage were observed. Responders at 3 months showed a significantly higher reduction of CDAI, SDAI, COCHIN scale, VAS-pain, and US7 synovialPD, compared with non-responders. At 3 and 6 months, remission/LDA was achieved by 12.8/53.8% and 21.6/51.3% patients, respectively. The csDMARD co-treatment was independently associated with remission/LDA at 3 months. Safety-related drop-outs were in line with literature data. The steroid dosage was associated with AE development at 6 months. Conclusion: The real-life data, also obtained with US evaluation, confirmed the Baricitinib efficacy in RA disease control, as well as the utility of assessment during the follow up of disease activity.
Psychoeducational Program for the Family Member Caregivers of People with Dementia to Reduce Perceived Burden and Increase Patient’s Quality of Life: A Randomized Controlled Trial
Authors: Tawfik Nadia M. , Sabry Noha A. , Darwish Hatem , Mowafy Maha , Soliman Saeed S.A. 
Published: May 2021

Background: Dementia is one of the world’s greatest public health issues. Most people with dementia receive home care, and family members are vulnerable to feeling burdened and depressed that reinforces the need for caregiver-driven services to mitigate these negative effects. Objective: The purpose of this research was to evaluate the effect of the psychoeducational program on burden and quality of life of family caregivers for people with dementia. Methods: This randomized controlled trial (RCT) was conducted on 60 family caregivers. Participants were randomly assigned to receive either the 8-session psychoeducational program (study group) or routine care only (control group). The demographic data of the caregivers and their patients, the burden of caregivers using Zarit Burden Interview (ZBI), and the quality of life of the patients using Quality of Life in Alzheimer Disease (QoL-AD) questionnaire were measured before and after the psychoeducational program and compared between the study group and the control group. Results: The results revealed that 80% of the family caregivers were female and 42% were daughters. The mean ± SD of the baseline burden was 61 ± 13.7 and 60.9 ± 10 in the study and the control group, respectively. ZBI burden score in the study group demonstrated a significant drop after the psychoeducational program compared to the control group. Logistic regression analysis showed that caregivers who received the psychoeducational program have OR (95% CI) of 14 (3.1-67.8) compared to those who did not receive the psychoeducational program. Conclusions: Psychoeducational program is effective in reducing the family caregivers’ perceived burden. These findings need to be considered in developing comprehensive dementia care programs to well increase the strategies that help caregivers to deal with their patients.
Translating Data Analytics Into Improved Spine Surgery Outcomes: A Roadmap for Biomedical Informatics Research in 2021
Authors: Greenberg Jacob K. , Otun Ayodamola , Ghogawala Zoher , Yen Po-Yin , Molina Camilo A. , Limbrick David D. , Foraker Randi E , Kelly Michael P. , Ray Wilson Z. 
Published: May 2021

Study Design: Narrative review. Objectives: There is growing interest in the use of biomedical informatics and data analytics tools in spine surgery. Yet despite the rapid growth in research on these topics, few analytic tools have been implemented in routine spine practice. The purpose of this review is to provide a health information technology (HIT) roadmap to help translate data assets and analytics tools into measurable advances in spine surgical care. Methods: We conducted a narrative review of PubMed and Google Scholar to identify publications discussing data assets, analytical approaches, and implementation strategies relevant to spine surgery practice. Results: A variety of data assets are available for spine research, ranging from commonly used datasets, such as administrative billing data, to emerging resources, such as mobile health and biobanks. Both regression and machine learning techniques are valuable for analyzing these assets, and researchers should recognize the particular strengths and weaknesses of each approach. Few studies have focused on the implementation of HIT, and a variety of methods exist to help translate analytic tools into clinically useful interventions. Finally, a number of HIT-related challenges must be recognized and addressed, including stakeholder acceptance, regulatory oversight, and ethical considerations. Conclusions: Biomedical informatics has the potential to support the development of new HIT that can improve spine surgery quality and outcomes. By understanding the development life-cycle that includes identifying an appropriate data asset, selecting an analytic approach, and leveraging an effective implementation strategy, spine researchers can translate this potential into measurable advances in patient care.
Odontoid Fracture as Proximal Junctional Failure in Patients With Multilevel Spine Fusions
Authors: Ladd Bryan M. , Martin Christopher T. , Sembrano Jonathan N. , Jones Kristen E. , Polly David W. , Hunt Matthew A. 
Published: May 2021

Study Design: Retrospective study. Objective: Proximal junctional failure (PJF) commonly occurs as a recognized potential outcome of fusion surgery. Here we describe a unique series of patients with multilevel spine fusion including the cervical spine, who developed PJF as an odontoid fracture. Methods: We performed a single site retrospective review of patients with prior fusion that included a cervical component, who presented with an odontoid fracture between 2012 and 2019. Radiographic measurements included C2-C7 SVA, C2-C7 lordosis, T1 slope, Occiput-C2 angle, proximal junctional kyphosis, and cervical mismatch. Associated fractures, medical comorbidities, and treatments were determined via chart review after IRB approval. Results: Nine patients met inclusion criteria. 5 reported trauma with subsequent onset of pain. All patients sustained a Type II odontoid fracture. 5 with associated C1/Jefferson fractures. In all patients, pre-injury Occiput-C2 angle was outside normative range; C2-C7 SVA was greater than 4 cm in 6 patients; T1-slope minus cervical lordosis was greater than 18.5 degrees in 6 patients. 7 patients were treated operatively with extension of fusion to C1 and 2 patients declined operative treatment. Conclusion: In this series of 9 patients with multilevel fusion with type II odontoid fractures, all patients demonstrated abnormal pre-fracture sagittal alignment parameters and a greater than normal association of C1 fractures was noted. Further study is needed to establish the role of poor sagittal alignment with compensatory occiput-C2 angulation as a predisposing factor for odontoid fracture as a proximal junctional failure mechanism.
Using the Lower Limb Adduction Angle to Predict Postoperative Knee Joint-Line Obliquity After Open-Wedge High Tibial Osteotomy
Authors: Park Jun-Gu , Bin Seong-Il , Kim Jong-Min , Lee Bum-Sik 
Published: May 2021

Background: Knee joint-line orientation is altered after open-wedge high tibial osteotomy (OWHTO), and excessive joint-line obliquity (JLO) can adversely affect outcomes. Little is known regarding preoperative prediction of postoperative knee JLO. Purpose/Hypothesis: The purpose of this study was to assess the correlation between the amount of lower limb adduction and changes in knee JLO after OWHTO. The hypothesis was that postoperative knee JLO could be predicted using the amount of lower limb adduction after OWHTO. Study Design: Case series; Level of evidence, 4. Methods: The records of 67 patients (77 knees) who underwent OWHTO for medial compartment osteoarthritis were retrospectively reviewed. The mechanical hip-knee-ankle (HKA) axis, lateral distal femoral angle, medial proximal tibial angle (MPTA), knee JLO, ankle JLO, and joint-line convergence angle were measured on standing whole-leg plain radiographs preoperatively and at 1 year postoperatively. The limb adduction angle was defined as the angle between the native weightbearing line (WBL) and the planned WBL on preoperative standing whole-leg plain radiographs. The predicted knee JLO was calculated as the sum of the preoperative knee JLO and the limb adduction angle. Multivariable linear regression analysis was used to identify the preoperative radiologic factors associated with the postoperative knee JLO. The agreement between postoperative and predicted values was determined using intraclass correlation coefficients (ICCs). Results: The estimated limb adduction angle was 4.2° ± 1.3°, and the predicted knee JLO was 4.9° ± 3.0°. The actual postoperative knee JLO was 4.5° ± 2.4°, which was a significant increase from 0.7° ± 2.4° preoperatively ( P < .001). Excellent agreement was found between the predicted knee JLO and postoperative knee JLO (ICC = 0.928; P < .001). Limb adduction angle and changes in preoperative MPTA were significantly associated with changes in knee JLO ( P < .001). On multivariable linear regression analysis, preoperative knee JLO and limb adduction angle were significantly associated with postoperative knee JLO ( P < .001; R 2 = 0.83). Conclusion: Changes in knee JLO after OWHTO were associated with adduction of the lower limb after OWHTO. During preoperative planning, postoperative knee JLO can be predicted as the sum of the preoperative knee JLO and the limb adduction angle between the preoperative WBL and planned WBL.
European Stroke Organisation (ESO) guidelines on blood pressure management in acute ischaemic stroke and intracerebral haemorrhage
Authors: Sandset Else Charlotte , Anderson Craig S , Bath Philip M , Christensen Hanne , Fischer Urs , Gąsecki Dariusz , Lal Avtar , Manning Lisa S , Sacco Simona , Steiner Thorsten , Tsivgoulis Georgios 
Published: May 2021

The optimal blood pressure (BP) management in acute ischaemic stroke (AIS) and acute intracerebral haemorrhage (ICH) remains controversial. These European Stroke Organisation (ESO) guidelines provide evidence-based recommendations to assist physicians in their clinical decisions regarding BP management in acute stroke. The guidelines were developed according to the ESO standard operating procedure and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. The working group identified relevant clinical questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and made specific recommendations. Expert consensus statements were provided where insufficient evidence was available to provide recommendations based on the GRADE approach. Despite several large randomised-controlled clinical trials, quality of evidence is generally low due to inconsistent results of the effect of blood pressure lowering in AIS. We recommend early and modest blood pressure control (avoiding blood pressure levels >180/105 mm Hg) in AIS patients undergoing reperfusion therapies. There is more high-quality randomised evidence for BP lowering in acute ICH, where intensive blood pressure lowering is recommended rapidly after hospital presentation with the intent to improve recovery by reducing haematoma expansion. These guidelines provide further recommendations on blood pressure thresholds and for specific patient subgroups. There is ongoing uncertainty regarding the most appropriate blood pressure management in AIS and ICH. Future randomised-controlled clinical trials are needed to inform decision making on thresholds, timing and strategy of blood pressure lowering in different acute stroke patient subgroups.
Therapeutic administration of etoposide coincides with reduced systemic HMGB1 levels in macrophage activation syndrome
Authors: Palmblad Karin , Schierbeck Hanna , Sundberg Erik , Horne Anna-Carin , Erlandsson Harris Helena , Henter Jan-Inge , Andersson Ulf 
Published: May 2021

Abstract
Background
Macrophage activation syndrome (MAS) is a potentially fatal complication of systemic inflammation. HMGB1 is a nuclear protein released extracellularly during proinflammatory lytic cell death or secreted by activated macrophages, NK cells, and additional cell types during infection or sterile injury. Extracellular HMGB1 orchestrates central events in inflammation as a prototype alarmin. TLR4 and the receptor for advanced glycation end products operate as key HMGB1 receptors to mediate inflammation.

Methods
Standard ELISA and cytometric bead array-based methods were used to examine the kinetic pattern for systemic release of HMGB1, ferritin, IL-18, IFN-γ, and MCP-1 before and during treatment of four children with critical MAS. Three of the patients with severe underlying systemic rheumatic diseases were treated with biologics including tocilizumab or anakinra when MAS developed. All patients required intensive care therapy due to life-threatening illness. Add-on etoposide therapy was administered due to insufficient clinical response with standard treatment. Etoposide promotes apoptotic rather than proinflammatory lytic cell death, conceivably ameliorating subsequent systemic inflammation.

Results
This therapeutic intervention brought disease control coinciding with a decline of the increased systemic HMGB1, IFN-γ, IL-18, and ferritin levels whereas MCP-1 levels evolved independently.

Conclusion
Systemic HMGB1 levels in MAS have not been reported before. Our results suggest that the molecule is not merely a biomarker of inflammation, but most likely also contributes to the pathogenesis of MAS. These observations encourage further studies of HMGB1 antagonists. They also advocate therapeutic etoposide administration in severe MAS and provide a possible biological explanation for its mode of action.
Predictive value of standard serum markers for bone metastases in prostate cancer
Authors: Ozdemir Semra , Ersay Ahmet Reşit , Koc Ozturk Fulya , Ozdemir Beril Su 
Published: May 2021

Abstract
Background
The early detection of bone metastases is very important in prostate cancer follow-up. This study aimed to compare conventional tumor markers, namely free prostate-specific antigen (free PSA), total prostate-specific antigen (total PSA), free PSA/total PSA ratio, alkaline phosphatase (ALP) values, Gleason scores and 99 m Tc-MDP bone scintigraphy findings in the prediction of bone metastases in prostate cancer.

Methods
In total, 175 patients with prostate cancer who underwent whole-body bone scintigraphy were included in the study. All selected scintigraphic studies were reprocessed. Free PSA, total PSA, free PSA/total PSA ratio, alkaline phosphatase (ALP) values and Gleason scores of patients were recorded.

Results
The results of our study show that the presence of bone metastasis correlates very weakly with free PSA/total PSA ratio (rho = 0.179), weakly with total PSA (rho = 0.318) and Gleason score (rho = 0.382), moderately with ALP (rho = 0.539), free PSA (0.416). Only ALP variable had a diagnostic value and ALP cutoff value was 76.50 IU/L, with 80% sensitivity and 82.1% specificity.

Conclusion
According to the results of our study; the free PSA, total PSA, free PSA/total PSA ratio and Gleason score values were not considered as a reliable parameter in the prostate cancer cases follow-up for bone metastasis development. Only ALP had a diagnostic value and ALP cutoff value was 76.50 IU / L with 80% sensitivity and 82.1% specificity in predicting bone metastases in prostate cancer.
Methylene blue associated with maghemite nanoparticles has antitumor activity in breast and ovarian carcinoma cell lines
Authors: Silva Ana Luísa G. , Carvalho Natália V. , Paterno Leonardo G. , Moura Ludmilla D. , Filomeno Cleber L. , de Paula Eneida , Báo Sônia N. 
Published: May 2021

Abstract
Background
Cancer constitutes group of diseases responsible for the second largest cause of global death, and it is currently considered one of the main public health concerns nowadays. Early diagnosis associated with the best choice of therapeutic strategy, is essential to achieve success in cancer treatment. In women, breast cancer is the second most common type, whereas ovarian cancer has the highest lethality when compared to other neoplasms of the female genital system. The present work, therefore, proposes the association of methylene blue with citrate-coated maghemite nanoparticles (MAGCIT–MB) as a nanocomplex for the treatment of breast and ovarian cancer.

Results
In vitro studies showed that T-47D and A2780 cancer cell lines underwent a significant reduction in cell viability after treatment with MAGCIT–MB, an event not observed in non-tumor (HNTMC and HUVEC) cells and MDA-MB-231, a triple-negative breast cancer cell line. Flow cytometry experiments suggest that the main mechanism of endocytosis involved in the interiorization of MAGCIT–MB is the clathrin pathway, whereas both late apoptosis and necrosis are the main types of cell death caused by the nanocomplex. Scanning electron microscopy and light microscopy reveal significant changes in the cell morphology. Quantification of reactive oxygen species confirmed the MAGCIT–MB cytotoxic mechanism and its importance for the treatment of tumor cells. The lower cytotoxicity of individual solution of maghemite nanoparticles with citrate (MAGCIT) and free methylene blue (MB) shows that their association in the nanocomplex is responsible for its enhanced therapeutic potential in the treatment of breast and ovarian cancer in vitro.

Conclusions
Treatment with MAGCIT–MB induces the death of cancer cells but not normal cells. These results highlight the importance of the maghemite core for drug delivery and for increasing methylene blue activity, aiming at the treatment of breast and ovarian cancer.

Graphic Abstract
tRNA-derived fragments as novel potential biomarkers for relapsed/refractory multiple myeloma
Authors: Xu Cong , Liang Ting , Zhang Fangrong , Liu Jing , Fu Yunfeng 
Published: May 2021

Abstract
Background
tRNA-derived fragments have been reported to be key regulatory factors in human tumors. However, their roles in the progression of multiple myeloma remain unknown.

Results
This study employed RNA-sequencing to explore the expression profiles of tRFs/tiRNAs in new diagnosed MM and relapsed/refractory MM samples. The expression of selected tRFs/tiRNAs were further validated in clinical specimens and myeloma cell lines by qPCR. Bioinformatic analysis was performed to predict their roles in multiple myeloma progression.We identified 10 upregulated tRFs/tiRNAs and 16 downregulated tRFs/tiRNAs. GO enrichment and KEGG pathway analysis were performed to analyse the functions of 1 significantly up-regulated and 1 significantly down-regulated tRNA-derived fragments. tRFs/tiRNAs may be involved in MM progression and drug-resistance.

Conclusion
tRFs/tiRNAs were dysregulated and could be potential biomarkers for relapsed/refractory MM.
Perioperative adherence to continuous positive airway pressure and its effect on postoperative nocturnal hypoxemia in obstructive sleep apnea patients: a prospective cohort study
Authors: Suen Colin , Wong Jean , Warsame Kahiye , Subramani Yamini , Panzarella Tony , Waseem Rida , Auckley Dennis , Chaudhry Rabail , Islam Sazzadul , Chung Frances 
Published: May 2021

Abstract
Background
Although continuous positive airway pressure (CPAP) is the first line treatment for obstructive sleep apnea (OSA) patients, the perioperative adherence rate is unclear. The objective of this study was to determine the perioperative adherence rate of patients with OSA with a CPAP prescription and the effect of adherence on nocturnal oxygen saturation.

Methods
This prospective cohort study included adult surgical patients with a diagnosis of OSA with CPAP prescription undergoing elective non-cardiac surgery. Patients were divided into CPAP adherent and non-adherent groups based on duration of usage (≥ 4 h/night). Overnight oximetry was performed preoperatively and on postoperative night 1 and 2 (N1, N2). The primary outcome was adherence rate and the secondary outcome was nocturnal oxygen saturation.

Results
One hundred and thirty-two patients completed the study. CPAP adherence was 61% preoperatively, 58% on postoperative N1, and 59% on N2. Forty-nine percent were consistently CPAP adherent pre- and postoperatively. Using a linear fixed effects regression, oxygen desaturation index (ODI) was significantly improved by CPAP adherence (p = 0.0011). The interaction term CPAP x N1 was significant (p = 0.0015), suggesting that the effect of CPAP adherence varied on N1 vs preoperatively. There was no benefit of CPAP adherence on postoperative mean SpO2, minimum SpO2, and percentage of sleep duration with SpO2 < 90%. Use of supplemental oxygen therapy was much lower in the CPAP adherent group vs non-adherent group (9.8% vs 46.5%, p <  0.001).

Conclusions
Among patients with a preoperative CPAP prescription, approximately 50% were consistently adherent. CPAP adherence was associated with improved preoperative ODI and the benefit was maintained on N1. These modest effects may be underestimated by a higher severity of OSA in the CPAP adherent group and a higher rate of oxygen supplementation in the non-adherent group.

Trial registration
ClinicalTrials.Gov registry (NCT02796846).