bluuebunny/crossref_metadata_2025_split huggingface dataset:
Procedural sedation for direct current cardioversion: a feasibility study between two management strategies in the emergency department
Authors: Stronati Giulia , Capucci Alessandro , Dello Russo Antonio , Adrario Erica , Carsetti Andrea , Casella Michela , Donati Abele , Guerra Federico 
Published: August 2020

Abstract
Background
A cardiologist-only approach to procedural sedation with midazolam in the setting of elective cardioversion (DCC) for AF has already been proven as safe as sedation with propofol and anaesthesiologist assistance. No data exist regarding the safety of such a strategy during emergency procedures. The aim of this study is to compare the feasibility of sedation with midazolam, administered by a cardiologist, to an anaesthesiologist-assisted protocol with propofol in emergency DCC.

Methods
Single centre, prospective, open blinded, randomized study including all consecutive patients admitted to the Emergency Department requiring urgent or emergency DCC. Patients were randomized in a 1:1 fashion to either propofol or midazolam treatment arm. Patients in the midazolam group were managed by the cardiologist only, while patients treated with propofol group underwent DCC with anaesthesiologist assistance.

Results
Sixty-nine patients were enrolled and split into two groups. Eighteen patients (26.1%) experienced peri-procedural adverse events (bradycardia, severe hypotension and severe hypoxia), which were similar between the two groups and all successfully managed by the cardiologist. No deaths, stroke or need for invasive ventilation were registered. Patients treated with propofol experienced a greater decrease in systolic and diastolic blood pressure when compared with those treated with midazolam.
As the procedure was shorter when midazolam was used, the median cost of urgent/emergency DCC with midazolam was estimated to be 129.0 € (1st-3rd quartiles 114.6–151.6) and 195.6 € (1st-3rd quartiles 147.3–726.7) with propofol (p < .001).

Conclusions
Procedural sedation with midazolam given by the cardiologist alone was feasible, well-tolerated and cost-effective in emergency DCC.
Measuring clinical uncertainty and equipoise by applying the agreement study methodology to patient management decisions
Authors: Fahed Robert , Darsaut Tim E. , Farzin Behzad , Chagnon Miguel , Raymond Jean 
Published: August 2020

Abstract
Background
Clinical uncertainty and equipoise are vague notions that play important roles in contemporary problems of medical care and research, including the design and conduct of pragmatic trials. Our goal was to show how the reliability study methods normally used to assess diagnostic tests can be applied to particular management decisions to measure the degree of uncertainty and equipoise regarding the use of rival management options.

Methods
We first use thrombectomy in acute stroke as an illustrative example of the method we propose. We then review, item by item, how the various design elements of diagnostic reliability studies can be modified in order to measure clinical uncertainty.

Results
The thrombectomy example shows sufficient disagreement and uncertainty to warrant the conduct of additional randomized trials. The general method we propose is that a sufficient number of diverse individual cases sharing a similar clinical problem and covering a wide spectrum of clinical presentations be assembled into a portfolio that is submitted to a variety of clinicians who routinely manage patients with the clinical problem.

Discussion
Clinicians are asked to independently choose one of the predefined management options, which are selected from those that would be compared within a randomized trial that would address the clinical dilemma. Intra-rater agreement can be assessed at a later time with a second evaluation. Various professional judgments concerning individual patients can then be compared and analyzed using kappa statistics or similar methods. Interpretation of results can be facilitated by providing examples or by translating the results into clinically meaningful summary sentences.

Conclusions
Measuring the uncertainty regarding management options for clinical problems may reveal substantial disagreement, provide an empirical foundation for the notion of equipoise, and inform or facilitate the design/conduct of clinical trials to address the clinical dilemma.
Osteopontin promoter polymorphisms and risk of urolithiasis: a candidate gene association and meta-analysis study
Authors: Amar Ali , Afzal Ayesha , Hameed Athar , Ahmad Mumtaz , Khan Abdul Rafay , Najma Humaira , Abid Aiysha , Khaliq Shagufta 
Published: August 2020

Abstract
Background
Urolithiasis is a worldwide urological problem with significant contribution of genetic factors. Pakistan, which resides within the Afro-Asian stone belt, has a high reported prevalence (12%) of urolithiasis. Osteopontin (SPP1) is a urinary macromolecule with a suggested critical role in modulating renal stone formation, genetic polymorphisms of which may determine individual risk of developing urolithiasis. However, results of previous studies regarding SPP1 polymorphisms and susceptibility to urolithiasis have apparent inconsistencies with no data available for local population.

Methods
A total of 235 urolithiasis patients and 243 healthy controls, all of Pakistani ancestry, underwent genotyping for six SPP1 genetic polymorphisms in an effort to investigate potential association with urolithiasis using indigenous candidate gene association study design. Further, a comprehensive meta-analysis following a systematic literature search was also done to ascertain an evidence based account of any existent association regarding SPP1 promoter polymorphisms and risk of developing urolithiasis.

Results
Three SPP1 promoter polymorphisms, rs2853744:G > T, rs11730582:T > C and rs11439060:delG>G, were found to be significantly associated with risk of urolithiasis in indigenous genetic association study (OR = 3.14; p = 0.006, OR = 1.78; p = 0.006 and OR = 1.60; p = 0.012, respectively). We also observed a 1.68-fold positive association of a tri-allelic haplotype of these SPP1 promoter polymorphisms (G-C-dG) with risk of urolithiasis (OR = 1.68; p = 0.0079). However, no association was evident when data were stratified according to gender, age at first presentation, stone recurrence, stone multiplicity, parental consanguinity and family history of urolithiasis. The overall results from meta-analysis, which included 4 studies, suggested a significant association of SPP1 rs2853744:G > T polymorphism with susceptibility of urolithiasis (OR = 1.37; p = 0.004), but not for other SPP1 polymorphic variants analyzed.

Conclusions
In conclusion, we report significant association of 3 SPP1 polymorphisms with urolithiasis for the first time from South Asia, however, this association persisted only for SPP1 rs2853744:G > T polymorphism after meta-analysis of pooled studies. Further studies with a larger sample size will be required to validate this association and assess any potential usefulness in diagnosis and prognosis of renal stone disease.
Factors affecting the relationship between ionized and corrected calcium levels in peritoneal dialysis patients: a retrospective cross-sectional study
Authors: Morishita Masamitsu , Maruyama Yukio , Nakao Masatsugu , Matsuo Nanae , Tanno Yudo , Ohkido Ichiro , Ikeda Masato , Yokoo Takashi 
Published: August 2020

Abstract
Background
Chronic kidney disease-mineral and bone disorder (CKD-MBD) management in patients with end-stage renal disease is important owing to the risk of cardiovascular diseases. In clinical practice, we manage patients not by monitoring the levels of biologically active ionized calcium (iCa) but by monitoring total serum calcium or corrected calcium (cCa). We previously reported that iCa/cCa ratio was different between patients with hemodialysis and those with peritoneal dialysis (PD). In PD patients, several factors are expected to affect iCa/cCa ratio. Therefore, modifying the strategy to achieve better CKD-MBD management might be necessary; however, no reports have studied this to date. Therefore, we investigated the factors influencing iCa/cCa ratio in PD patients.

Methods
This retrospective cross-sectional study examined background and laboratory data, including iCa, collected at routine outpatient visits. The patients were divided into the first, second, and third tertile of iCa/cCa ratio groups to compare patient background and laboratory data. Multiple regression analysis was used to investigate the factors influencing iCa/cCa ratio. We used multiple imputation to deal with missing covariate data.

Results
In total, 169 PD patients were enrolled. In PD patients with lower iCa/cCa ratio, PD duration was longer and pH was higher. Urine volume and weekly renal Kt/V were lower in the patients with lower iCa/cCa ratio than in those with higher iCa/cCa ratio. iCa/cCa ratio and weekly renal Kt/V were directly correlated (r = 0.41, p < 0.01), and weekly renal Kt/V and pH were independent factors affecting iCa/cCa ratio (t = 2.86, p < 0.01 and t = − 5.42, p < 0.01, respectively).

Conclusions
iCa levels were lower in PD patients with lower residual renal function (RRF) even though their cCa levels were equal to those with maintained RRF, warranting caution in the assessment and management of CKD-MBD in PD patients.
Lens-induced myopization and intraocular pressure in young guinea pigs
Authors: Dong Li , Li Yi Fan , Wu Hao Tian , Di Kou Hai , Lan Yin Jun , Wang Ya Xing , Jonas Jost B. , Wei Wen Bin 
Published: August 2020

AbstractBackgroundIntraocular pressure (IOP) is an important physiological measure of the eye and is associated with some ocular disorders. We aimed to assess the influence of topical beta blocker-induced IOP reduction on lens-induced axial elongation in young guinea pigs.MethodsThe experimental study included 20 pigmented guinea pigs (age: 2–3 weeks). Myopia was induced in the right eyes for 5 weeks with − 10 diopter lenses. The right eyes additionally received either one drop of carteolol 2% (study group,n = 10) or one drop of artificial tears daily (control group,n = 10), while the contralateral eyes of all animals remained untouched. The outcome parameter was axial elongation during the follow-up period. The mean of all IOP measurements taken during the study was referred to as mean IOP.ResultsGreater axial elongation was associated with a shorter axial length at baseline (P < 0.001; standardized regression coefficient beta: − 0.54) and lens-induced myopization (P < 0.001; beta: 0.55). In the multivariable model, axial elongation was not significantly correlated with the IOP at study end (P = 0.59), the mean IOP during the study period (P = 0.12), the mean of all IOP measurements (P = 0.17), the difference between the IOP at study end and baseline IOP (P = 0.38), the difference between the mean IOP during the study period and the baseline IOP (P = 0.11), or the application of carteolol eye drops versus artificial tears eye drops (P = 0.07). The univariate analysis of the relationships between axial elongation and the IOP parameters yielded similar results. The inter-eye difference between the right eye and the left eye in axial elongation was significantly associated with the inter-eye difference in baseline axial length (P = 0.001; beta:-0.67) but not significantly correlated with the inter-eye difference in any of the IOP-related parameters (allP > 0.25).ConclusionsIn young guinea pigs with or without lens-induced axial elongation, neither the physiological IOP nor the IOP reduced by carteolol, a topical beta-blocker, was associated with the magnitude of axial elongation. These results suggest that IOP, regardless of whether it is influenced by carteolol, does not play a major role in axial elongation in young guinea pigs.
A clinical prediction model for complicated appendicitis in children younger than five years of age
Authors: Feng Wei , Zhao Xu-Feng , Li Miao-Miao , Cui Hua-Lei 
Published: August 2020

Abstract
Background
No reliably specific method for complicated appendicitis has been identified in children younger than five years of age. This study aimed to analyze the independent factors for complicated appendicitis in children younger than five years of age, develop and validate a prediction model for the differentiation of simple and complicated appendicitis.

Methods
A retrospective study of 382 children younger than five years of age with acute appendicitis from January 2007 to December 2016 was conducted with assessments of demographic data, clinical symptoms and signs, and pre-operative laboratory results. According to intraoperative findings and postoperative pathological results, acute appendicitis was divided into simple and complicated appendicitis. Univariate and multivariate analyses were used to screen out the independent factors of complicated appendicitis, and develop a prediction model for complicated appendicitis. Then 156 such patients from January 2017 to December 2019 were collected as validation sample to validate the prediction model. Test performance of the prediction model was compared with the ALVARADO score and Pediatric Appendicitis Score (PAS).

Results
Of the 382 patients, 244 (63.9%) had complicated appendicitis. Age, white blood cell count, and duration of symptoms were the independent factors for complicated appendicitis in children younger than five years of age. The final predication model for complicated appendicitis included factors above. In validation sample, the prediction model exhibited a high degree of discrimination (area under the curve [AUC]: 0.830; 95% confidence interval [CI]: 0.762–0.885) corresponding to a optimal cutoff value of 0.62, and outperformed the PAS (AUC: 0.735; 95% CI: 0.658–0.802), ALVARADO score (AUC: 0.733; 95% CI: 0.657–0.801).

Conclusion
Age, white blood cell count, and duration of symptoms could be used to predict complicated appendicitis in children younger than five years of age with acute appendicitis. The prediction model is a novel but promising method that aids in the differentiation of acute simple and complicated appendicitis.
The state of child nutrition in Ethiopia: an umbrella review of systematic review and meta-analysis reports
Authors: Mohammed Shimels Hussien , Habtewold Tesfa Dejenie , Arero Amanuel Godana , Esmaillzadeh Ahmad 
Published: August 2020

Abstract
Background
Malnutrition remains to be a major public health problem in developing countries, particularly among children under-5 years of age children who are more vulnerable to both macro and micro-nutrient deficiencies. Various systematic review and meta-analysis (SRM) studies were done on nutritional statuses of children in Ethiopia, but no summary of the findings was done on the topic. Thus, this umbrella review was done to summarize the evidence from SRM studies on the magnitude and determinants of malnutrition and poor feeding practices among under-5 children in Ethiopia.

Methods
PubMed, Embase, Scopus, Web of Sciences, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, and Google Scholar were searched for SRM studies on magnitude and risk factors of malnutrition and child feeding practice indicators in Ethiopia. The methodological quality of the included studies was assessed using the Assessment of Multiple Systematic Reviews (AMSTAR) tool. The estimates of the included SRM studies on the prevalence and determinants of stunting, wasting, underweight, and poor child feeding practices were pooled and summarized with random-effects meta-analysis models.

Result
We included nine SRM studies, containing a total of 214,458 under-5 children from 255 observation studies. The summary estimates of prevalence of stunting, underweight, and wasting were 42% (95%CI = 37–46%), 33% (95%CI = 27–39%), and 15% (95%CI = 12–19%), respectively. The proportion of children who met the recommendations for timely initiation of breastfeeding, exclusive breastfeeding during the first 6 months, and timely initiation of complementary feeding were 65, 60, and 62%, respectively. The proportion of children who met the recommendations for dietary diversity and meal frequency were 20, and 56%, respectively. Only 10% of children fulfilled the minimum criteria of acceptable diet. There was a strong relationship between poor feeding practices and the state of malnutrition, and both conditions were related to various health, socio-economic, and environmental factors.

Conclusion
Child malnutrition and poor feeding practices are highly prevalent and of significant public health concern in Ethiopia. Only a few children are getting proper complementary feeding. Multi-sectoral efforts are needed to improve children’s feeding practices and reduce the high burden of malnutrition in the country.
Epigenetic silencing of long non-coding RNA BM742401 in multiple myeloma: impact on prognosis and myeloma dissemination
Authors: Li Zhenhai , Kumar Shaji , Jin Dong-Yan , Calin George A. , Chng Wee-Joo , Siu Kam-Leung , Poon Ming-Wai , Chim Chor Sang 
Published: August 2020

Abstract
Background
Long non-coding RNA (lncRNA) BM742401 is a tumor suppressor in gastric cancer and chronic lymphocytic leukemia. As the promoter and coding region of BM742401 are fully embedded in a CpG island, we hypothesized that BM742401 is a tumor suppressor lncRNA epigenetically silenced by promoter DNA methylation in multiple myeloma.

Methods
Methylation-specific PCR and quantitative bisulfite pyrosequencing were performed to detect the methylation of BM742401 in normal plasma cells, myeloma cell lines and primary myeloma samples. The expression of BM742401 was measured by qRT-PCR. The function of BM742401 in multiple myeloma cells was analyzed by lentivirus transduction followed by migration assay.

Results
BM742401 methylation was detected in 10 (66.7%) myeloma cell lines but not normal plasma cells, and inversely correlated with expression of BM742401. In primary samples, BM742401 methylation was detected in 3 (12.5%) monoclonal gammopathy of undetermined significance, 9 (15.8%) myeloma at diagnosis and 8 (17.0%) myeloma at relapse/progression. Moreover, BM742401 methylation at diagnosis was associated with inferior overall survival (median OS: 25 vs. 39 months; P = 0.0496). In myeloma cell line JJN-3, stable overexpression of BM742401 by lentivirus transduction resulted in reduced cell migration (P = 0.0001) but not impacting cell death or proliferation.

Conclusions
This is the first report of tumor-specific methylation-mediated silencing of BM742401 in myeloma, which is likely an early event in myelomagenesis with adverse impact on overall survival. Moreover, BM742401 is a tumor suppressor lncRNA by inhibiting myeloma cell migration, hence implicated in myeloma plasma cell homing, metastasis and disease progression.
CREB5 promotes invasiveness and metastasis in colorectal cancer by directly activating MET
Authors: Wang Shuyang , Qiu Junfeng , Liu Lei , Su Cailin , Qi Lu , Huang Chengmei , Chen Xiaoning , Zhang Yaxin , Ye Yaping , Ding Yanqing , Liang Li , Liao Wenting 
Published: August 2020

AbstractBackgroundcAMP responsive element binding protein 5 (CREB5) is a transcriptional activator in eukaryotic cells that can regulate gene expression. Previously, we found that CREB5 was involved in the occurrence and development of colorectal cancer (CRC) using bioinformatics analysis. However, the biological roles and underlying regulatory mechanism of CREB5 in CRC remain unclear.MethodsReal-time PCR, western blotting, and immunohistochemistry were used to examine CREB5 expression. In vitro experiments including migration assay, wound-healing assay, chicken chorioallantoic membrane assay, and human umbilical vein endothelial cells tube formation assay were used to investigate the effects of CREB5 on CRC cell migration and tumor angiogenesis ability. Additionally, an orthotopic implantation assay was performed in nude mice to confirm the effects of CREB5 in vivo. Furthermore, gene set enrichment analysis was performed to explore the potential mechanism of CREB5 in CRC.ResultsWe found that CREB5 expression was highly upregulated in CRC. CREB5 overexpression was positively correlated with advanced WHO stages and TNM stages and shorter survival in CRC patients. Moreover, CREB5 overexpression promoted while CREB5 silencing reduced the invasiveness and metastatic capacity of CRC cells both in vitro and in vivo. Furthermore, CREB5 directly interacted with the MET promoter and activated the hepatocyte growth factor-MET signalling pathway. Importantly, inhibition of MET reduced the invasion and metastasis of CREB5-overexpressing CRC cells, suggesting that CREB5 promotes metastasis mainly through activation of MET signalling.ConclusionOur study demonstrates a crucial role for CREB5 in CRC metastasis by directly upregulating MET expression. CREB5 may be both a potential prognostic marker and a therapeutic target to effectively overcome metastasis in CRC.
A lactate-targeted resuscitation strategy may be associated with higher mortality in patients with septic shock and normal capillary refill time: a post hoc analysis of the ANDROMEDA-SHOCK study
Authors: Kattan Eduardo , Hernández Glenn , Ospina-Tascón Gustavo , Valenzuela Emilio Daniel , Bakker Jan , Castro Ricardo ,   The ANDROMEDA-SHOCK Study Investigators and the Latin America Intensive Care Network (LIVEN)
Published: August 2020

Abstract
Background
Capillary refill time (CRT) may improve more rapidly than lactate in response to increments in systemic flow. Therefore, it can be assessed more frequently during septic shock (SS) resuscitation. Hyperlactatemia, in contrast, exhibits a slower recovery in SS survivors, probably explained by the delayed resolution of non-hypoperfusion-related sources. Thus, targeting lactate normalization may be associated with impaired outcomes. The ANDROMEDA-SHOCK trial compared CRT- versus lactate-targeted resuscitation in early SS. CRT-targeted resuscitation associated with lower mortality and organ dysfunction; mechanisms were not investigated. CRT was assessed every 30 min and lactate every 2 h during the 8-h intervention period, allowing a first comparison between groups at 2 h (T2). Our primary aim was to determine if SS patients evolving with normal CRT at T2 after randomization (T0) exhibited a higher mortality and organ dysfunction when allocated to the LT arm than when randomized to the CRT arm. Our secondary aim was to determine if those patients with normal CRT at T2 had received more therapeutic interventions when randomized to the LT arm. To address these issues, we performed a post hoc analysis of the ANDROMEDA-SHOCK dataset.

Results
Patients randomized to the lactate arm at T0, evolving with normal CRT at T2 exhibited significantly higher mortality than patients with normal CRT at T2 initially allocated to CRT (40 vs 23%, p = 0.009). These results replicated at T8 and T24. LT arm received significantly more resuscitative interventions (fluid boluses: 1000[500–2000] vs. 500[0–1500], p = 0.004; norepinephrine test in previously hypertensive patients: 43 (35) vs. 19 (19), p = 0.001; and inodilators: 16 (13) vs. 3 (3), p = 0.003). A multivariate logistic regression of patients with normal CRT at T2, including APACHE-II, baseline lactate, cumulative fluids administered since emergency admission, source of infection, and randomization group) confirmed that allocation to LT group was a statistically significant determinant of 28-day mortality (OR 3.3; 95%CI[1.5–7.1]); p = 0.003).

Conclusions
Septic shock patients with normal CRT at baseline received more therapeutic interventions and presented more organ dysfunction when allocated to the lactate group. This could associate with worse outcomes.