bluuebunny/crossref_metadata_2025_split huggingface dataset:
Achieving Consensus in the Measurement of Psychological Adjustment to Cleft Lip and/or Palate at Age 8+ Years
Authors: Stock Nicola Marie , Hammond Vanessa , Hearst Daniela , Owen Tina , Edwards Zoe , Ridley Matthew , Rumsey Nichola 
Published: January 2020

Background: Consensus regarding optimal outcome measurement has been identified as one of the most important, yet most challenging developments for the future of cleft lip and/or palate (CL/P) services. In 2011, a process began to adopt a shared conceptual framework and to identify a set of core outcome measures for the comprehensive assessment of psychological adjustment. Objectives: The aim of the current article is to outline the collaborative process used to achieve consensus in the academic and clinical measurement of psychological adjustment to CL/P from the age of 8 years onward. Results: A conceptual framework and corresponding parent- and self-reported outcome measures for use at ages 8, 10, 12, 15, 18, 20, and 25 years have been agreed upon by clinicians, researchers, and patient and parent representatives. All measures have been evaluated according to their psychometric properties, clinical utility, ability to produce meaningful longitudinal data, and a range of pragmatic considerations. Conclusions: Although the collaborative process has been challenging and has required ongoing dedication from multiple stakeholders, consistency in data collection over time will allow for key research questions in CL/P to be addressed, both in the United Kingdom (UK) and internationally. The process has also demonstrated the clinical utility of the measures and the potential for the gradual integration of the measures into clinical practice. UK progress has sparked global interest, and the adaptation of the framework and its corresponding measures for worldwide use is now a prominent focus.
A new intraocular lens with artificial iris for treating a case of iris extrusion secondary to traumatic opening of a radial keratotomy
Authors: Frisina Rino , De Biasi Chiara Sofia , Londei Davide , Gambato Catia , Midena Edoardo 
Published: January 2020

Purpose: Traumatic globe rupture can lead to aniridia with subsequent glare, light sensitivity and psychological discomfort. The authors report the results of a sulcus implantation of a new intraocular lens with artificial iris (Reper) in an eye affected by traumatic opening of a radial keratotomy incision with total iris extrusion and subluxated cataract. Methods: A case of 56-year-old female affected by aniridia and subluxated cataract in left eye secondary to a traumatic opening of one of 12 radial keratotomy underwent a Reper implantation with three-point transcleral fixation. The following parameters were collected at 1, 3 and 6 postoperative months: best-corrected visual acuity (BCVA), intraocular pressure (IOP), central corneal thickness (CCT), simulated keratometry (Sim K), endothelial cell count (ECC) and anterior chamber depth (ACD). Pupil spread function study was performed to evaluate the high-order aberrations and the quality of vision. Results: BCVA improved from light perception to 20/20 (Snellen fraction) at 6 postoperative months. No IOP postoperative peaks were detected. CCT was 520 μm at 6 postoperative months. Corneal topography showed regularization with symmetrical flattening of the central part and a residual peripheral curvature. No significant reduction of ECC was detected. ACD was stable, superior to 3 mm at each time point of follow-up. Pupil spread function study highlighted that the quality of vision was the same in both eyes at the end of follow-up. Conclusion: Reper is a promising functional and cosmetic solution for the treatment of aphakia and aniridia.
Acidic Exopolysaccharide Produced from Marine Bacillus amyloliquefaciens 3MS 2017 for the Protection and Treatment of Breast Cancer
Authors: Ibrahim Abeer Y , Youness Eman R , Mahmoud Manal G , Asker Mohsen S , El-Newary Samah A 
Published: January 2020

Purpose: This study was planned to investigate the anti-breast-cancer property of acidic exopolysaccharide produced from marine Bacillus amyloliquefaciens 3MS 2017 (BAEPS) in an animal model, which previously showed in-vitro anti-breast-cancer activity, by studying its potential participation in various targeted mechanisms. Methods: Mammary carcinoma in female Sprague-Dawley rats, both in prophylactic and in curative designs, was chemically induced using 7,12-dimethylebenz-(a)-anthracene (DMBA). B. amyloliquefaciens 3MS 2017 anti-breast-cancer property was evaluated by studying its effects on cancer-growth-rate-limiting enzymes (aromatase and Na+/K+ ATPase), sexual hormones (estrogen and progesterone), antioxidant and inflammatory biomarkers (cyclooxygenase-1; COX-1 and cyclooxygenase-2; COX-2). The incidence of breast cancer by DMBA was dependent on the level of carcinoembryonic antigen (CEA) and aromatase. Results: 7,12-Dimethylebenz-(a)-anthracene female rats were characterized by a significant increase in cancer-related biomarkers with an increase of oxidative stress biomarkers, in comparison with the negative control. Potent BAEPS anticancer activity on DMBA rats was exhibited either as a prophylactic or as a curative agent, which appeared via restoring the aromatase and Na+/K+ ATPase subunits levels and CEA close to the normal level. Besides, BAEPS modulated a sexual hormone, in comparison with the cancer control group ( P ⩽ .05). B. amyloliquefaciens 3MS 2017 selectively inhibited COX-2 in parallel with promising antioxidant properties. The curative characters of BAEPS were more promising than the prophylactic. Conclusion: The anti-breast-cancer characters accompanied with a good safety margin may be attributed to its inhibitory effect on cancer-growth-rate-limiting enzymes, estrogen production, COX-2 level and lipid peroxidation, concurrent with enhancing COX-1 level, progesterone production, and antioxidant status.
Use of Pulse Pressure Variation as Predictor of Fluid Responsiveness in Patients Ventilated With Low Tidal Volume: A Systematic Review and Meta-Analysis
Authors: Alvarado Sánchez Jorge Iván , Caicedo Ruiz Juan Daniel , Diaztagle Fernández Juan José , Ospina-Tascón Gustavo Adolfo , Cruz Martínez Luis Eduardo 
Published: January 2020

Introduction: Pulse pressure variation (PPV) has been shown to be useful to predict fluid responsiveness in patients ventilated at tidal volume (Vt) >8 mL kg−1. Nevertheless, most conditions in critical care force to use lower Vt. Thus, we sought to evaluate the operative performance of PPV when a Vt ⩽8 mL kg−1 is used during mechanical ventilation support. Methods: We searched PubMed and Embase databases for articles evaluating the operative performance of PPV as a predictor of fluid responsiveness in critical care and perioperative adult patients ventilated with tidal volume ⩽8 mL kg−1 without respiratory effort and arrhythmias, between January 1990 and January 2019. We included cohort and cross-sectional studies. Two authors performed an Independently selection using predefined terms of search. The fitted data of sensitivity, specificity, and area under the curve (AUC) were assessed by bivariate and hierarchical analyses. Results: We retrieved 19 trials with a total of 777 patients and a total of 935 fluid challenges. The fitted sensitivity of PPV to predict fluid responsiveness during mechanical ventilation at Vt ⩽8 mL kg−1 was 0.65 (95% confidence interval [CI]: 0.57-0.73), the specificity was 0.79 (95% CI: 0.73-0.84), and the AUC was 0.75. The diagnostic odds ratio was 5.5 (95% CI: 3.08-10.01, P < .001) by the random-effects model. Conclusions: Pulse pressure variation shows a fair operative performance as a predictor of fluid responsiveness in critical care and perioperative patients ventilated with a tidal volume ⩽8 mL kg−1 without respiratory effort and arrhythmias.
Gray matter atrophy cannot be fully explained by white matter damage in patients with MS
Authors: Zhang Jian , Giorgio Antonio , Vinciguerra Claudia , Stromillo Maria Laura , Battaglini Marco , Mortilla Marzia , Tappa Brocci Riccardo , Portaccio Emilio , Amato Maria Pia , De Stefano Nicola 
Published: January 2020

Background: Source-based morphometry (SBM) was recently used for non-random “patterns” of gray matter (GM) atrophy or white matter (WM) microstructural damage. Objective: To assess whether and to what extent such patterns may be inter-related in MS. Methods: SBM was applied to images of GM concentration and fractional anisotropy (FA) in MS patients ( n = 41, median EDSS = 1) and normal controls (NC, n = 28). The same procedure was repeated on an independent and similar data set (39 MS patients and 13 NC). Results: We found in MS patterns of GM atrophy and reduced FA ( p < 0.05, corrected). Deep GM atrophy was mostly (70%) explained by lesion load in projection tracts and lower FA in posterior corona radiata and thalamic radiation. By contrast, sensorimotor and posterior cortex atrophy was less (50%) dependent from WM damage. All patterns correlated with EDSS ( r from −0.33 to −0.56, p < 0.03) while the only cognition-related correlation was between posterior GM atrophy pattern and processing speed ( r = 0.45, p = 0.014). Reliability analysis showed similar results. Conclusion: In relatively early MS, we found a close link between deep GM atrophy pattern and WM damage while sensorimotor and posterior cortex patterns were partially independent from WM damage and perhaps related to primary mechanisms. Patterns were clinically relevant.
Lower circulating adiponectin is associated with higher risk of renal cell carcinoma: A meta-analysis
Authors: Fang Jiajie , Xu Xuanli , Mao Qiqi , Ying Yufan , Zhang Xu , Xie Liping 
Published: January 2020

Background: Changes in circulating adiponectin have been related to the risks of various cancers. However, the association between circulating adiponectin and the risk of renal cell carcinoma has not been fully determined. A meta-analysis was performed to evaluate the relationship between circulating adiponectin and renal cell carcinoma risk. Methods: Observational studies that evaluated the association between circulating adiponectin and renal cell carcinoma risk were identified via a systematic search of PubMed and Embase databases. The difference between circulating adiponectin in renal cell carcinoma cases and healthy controls, and the multivariable adjusted association between circulating adiponectin and renal cell carcinoma risk were evaluated. A random effects model was used if significant heterogeneity existed; otherwise a fixed effects model was applied. Results: Eight case-control studies with 2624 renal cell carcinoma cases and 2904 healthy controls were included. Pooled results showed that circulating adiponectin was significantly lower in renal cell carcinoma cases than in healthy controls (mean difference = −1.08 ug/mL; 95% confidence interval (CI) −1.62, −0.54; P < 0.001). Higher circulating adiponectin was independently associated with a significantly lowered risk of renal cell carcinoma (adjusted odds ratio for 1 SD increment of adiponectin = 0.78; 95% CI: 0.63, 0.96; P = 0.02). Subgroup analyses according to characteristics including study design, ethnics of participants, blood samples, numbers of participants, mean ages of participants, and study quality showed consistent results. Conclusions: Lower circulating adiponectin is associated with increased risk of renal cell carcinoma. The potential pathophysiological mechanisms underlying the role of circulating adiponectin in the pathogenesis of renal cell carcinoma deserve further investigation.
The protein C activator AB002 rapidly interrupts thrombus development in baboons
Authors: Tucker Erik I. , Verbout Norah G. , Markway Brandon D. , Wallisch Michael , Lorentz Christina U. , Hinds Monica T. , Shatzel Joseph J. , Pelc Leslie A. , Wood David C. , McCarty Owen J. T. , Di Cera Enrico , Gruber András 
Published: January 2020

Abstract
Although thrombin is a key enzyme in the coagulation cascade and is required for both normal hemostasis and pathologic thrombogenesis, it also participates in its own negative feedback via activation of protein C, which downregulates thrombin generation by enzymatically inactivating factors Va and VIIIa. Our group and others have previously shown that thrombin’s procoagulant and anticoagulant activities can be effectively disassociated to varying extents through site-directed mutagenesis. The thrombin mutant W215A/E217A (WE thrombin) has been one of the best characterized constructs with selective activity toward protein C. Although animal studies have demonstrated that WE thrombin acts as an anticoagulant through activated protein C (APC) generation, the observed limited systemic anticoagulation does not fully explain the antithrombotic potency of this or other thrombin mutants. AB002 (E-WE thrombin) is an investigational protein C activator thrombin analog in phase 2 clinical development (clinicaltrials.gov NCT03963895). Here, we demonstrate that this molecule is a potent enzyme that is able to rapidly interrupt arterial-type thrombus propagation at exceedingly low doses (&lt;2 µg/kg, IV), yet without substantial systemic anticoagulation in baboons. We demonstrate that AB002 produces APC on platelet aggregates and competitively inhibits thrombin-activatable fibrinolysis inhibitor (carboxypeptidase B2) activation in vitro, which may contribute to the observed in vivo efficacy. We also describe its safety and activity in a phase 1 first-in-human clinical trial. Together, these results support further clinical evaluation of AB002 as a potentially safe and effective new approach for treating or preventing acute thrombotic and thromboembolic conditions. This trial was registered at www.clinicaltrials.gov as #NCT03453060.
The complement C5 inhibitor crovalimab in paroxysmal nocturnal hemoglobinuria
Authors: Röth Alexander , Nishimura Jun-ichi , Nagy Zsolt , Gaàl-Weisinger Julia , Panse Jens , Yoon Sung-Soo , Egyed Miklos , Ichikawa Satoshi , Ito Yoshikazu , Kim Jin Seok , Ninomiya Haruhiko , Schrezenmeier Hubert , Sica Simona , Usuki Kensuke , Sicre de Fontbrune Flore , Soret Juliette , Sostelly Alexandre , Higginson James , Dieckmann Andreas , Gentile Brittany , Anzures-Cabrera Judith , Shinomiya Kenji , Jordan Gregor , Biedzka-Sarek Marta , Klughammer Barbara , Jahreis Angelika , Bucher Christoph , Peffault de Latour Régis 
Published: January 2020

Abstract
Complement C5 inhibition is the standard of care (SoC) for patients with paroxysmal nocturnal hemoglobinuria (PNH) with significant clinical symptoms. Constant and complete suppression of the terminal complement pathway and the high serum concentration of C5 pose challenges to drug development that result in IV-only treatment options. Crovalimab, a sequential monoclonal antibody recycling technology antibody was engineered for extended self-administered subcutaneous dosing of small volumes in diseases amenable for C5 inhibition. A 3-part open-label adaptive phase 1/2 trial was conducted to assess safety, pharmacokinetics, pharmacodynamics, and exploratory efficacy in healthy volunteers (part 1), as well as in complement blockade–naive (part 2) and C5 inhibitor–treated (part 3) PNH patients. Twenty-nine patients were included in part 2 (n = 10) and part 3 (n = 19). Crovalimab concentrations exceeded the prespecified 100-µg/mL level and resulted in complete and sustained terminal complement pathway inhibition in treatment-naive and C5 inhibitor–pretreated PNH patients. Hemolytic activity and free C5 levels were suppressed below clinically relevant thresholds (liposome assay &lt;10 U/mL and &lt;50 ng/mL, respectively). Safety was consistent with the known profile of C5 inhibition. As expected, formation of drug-target-drug complexes was observed in all 19 patients switching to crovalimab, manifesting as transient mild or moderate vasculitic skin reactions in 2 of 19 participants. Both events resolved under continued treatment with crovalimab. Subcutaneous crovalimab (680 mg; 4 mL), administered once every 4 weeks, provides complete and sustained terminal complement pathway inhibition in patients with PNH, warranting further clinical development (ClinicalTrials.gov identifier, NCT03157635).
Early peripheral clearance of leukemia-associated immunophenotypes in AML: centralized analysis of a randomized trial
Authors: Gianfaldoni Giacomo , Mannelli Francesco , Intermesoli Tamara , Bencini Sara , Giupponi Damiano , Farina Giorgio , Cutini Ilaria , Bonetti Maria Ida , Masciulli Arianna , Audisio Ernesta , Ferrero Dario , Pavoni Chiara , Scattolin Anna Maria , Bosi Alberto , Rambaldi Alessandro , Bassan Renato 
Published: January 2020

Abstract
Although genetics is a relevant risk factor in acute myeloid leukemia (AML), it can be minimally informative and/or not readily available for the early identification of patients at risk for treatment failure. In a randomized trial comparing standard vs high-dose induction (ClinicalTrials.gov #NCT00495287), we studied early peripheral blast cell clearance (PBC) as a rapid predictive assay of chemotherapy response to determine whether it correlates with the achievement of complete remission (CR), as well as postremission outcome, according to induction intensity. Individual leukemia-associated immunophenotypes (LAIPs) identified pretherapy by flow cytometry were validated and quantified centrally after 3 days of treatment, expressing PBC on a logarithmic scale as the ratio of absolute LAIP+ cells on day 1 and day 4. Of 178 patients, 151 (84.8%) were evaluable. Patients in CR exhibited significantly higher median PBC (2.3 log) compared with chemoresistant patients (1.0 log; P &lt; .0001). PBC &lt; 1.0 predicted the worst outcome (CR, 28%). With 1.5 log established as the most accurate cutoff predicting CR, 87.5% of patients with PBC &gt;1.5 (PBChigh, n = 96) and 43.6% of patients with PBC ≤1.5 (PBClow, n = 55) achieved CR after single-course induction (P &lt; .0001). CR and PBChigh rates were increased in patients randomized to the high-dose induction arm (P = .04) and correlated strongly with genetic/cytogenetic risk. In multivariate analysis, PBC retained significant predictive power for CR, relapse risk, and survival. Thus, PBC analysis can provide a very early prediction of outcome, correlates with treatment intensity and disease subset, and may support studies of customized AML therapy.
Bacterial burden in the lower airways predicts disease progression in idiopathic pulmonary fibrosis and is independent of radiological disease extent
Authors: Invernizzi Rachele , Barnett Joseph , Rawal Bhavin , Nair Arjun , Ghai Poonam , Kingston Shaun , Chua Felix , Wu Zhe , Wells Athol U. , Renzoni Elizabeth R. , Nicholson Andrew G. , Rice Alexandra , Lloyd Clare M. , Byrne Adam J. , Maher Toby M. , Devaraj Anand , Molyneaux Philip L. 
Published: January 2020

Increasing bacterial burden in the lower airways of patients with idiopathic pulmonary fibrosis confers an increased risk of disease progression and mortality. However, it remains unclear whether this increased bacterial burden directly influences progression of fibrosis or simply reflects the magnitude of the underlying disease extent or severity.We prospectively recruited 193 patients who underwent bronchoscopy and received a multidisciplinary diagnosis of idiopathic pulmonary fibrosis. Quantification of the total bacterial burden in bronchoalveolar lavage fluid was performed by 16S rRNA gene qPCR. Imaging was independently evaluated by two readers assigning quantitative scores for extent, severity and topography of radiographic changes and relationship of these features with bacterial burden was assessed.Increased bacterial burden significantly associated with disease progression (HR 2.1; 95% CI 1.287–3.474; p=0.0028). Multivariate stepwise regression demonstrated no relationship between bacterial burden and radiological features or extent of disease. When specifically considering patients with definite or probable usual interstitial pneumonia there was no difference in bacterial burden between these two groups. Despite a postulated association between pleuroparenchymal fibroelastosis and clinical infection, there was no relationship between either the presence or extent of pleuroparenchymal fibroelastosis and bacterial burden.We demonstrate that bacterial burden in the lower airways is not simply secondary to the extent of the underlying architectural destruction of the lung parenchyma seen in idiopathic pulmonary fibrosis. The independent nature of this association supports a relationship with the underlying pathogenic mechanisms and highlights the urgent need for functional studies.
Association between adiposity measures and COPD risk in Chinese adults
Authors: Li Jiachen , Zhu Lu , Wei Yuxia , Lv Jun , Guo Yu , Bian Zheng , Du Huaidong , Yang Ling , Chen Yiping , Zhou Yonglin , Gao Ruqin , Chen Junshi , Chen Zhengming , Cao Weihua , Yu Canqing , Li Liming 
Published: January 2020

Bodyweight and fat distribution may be related to COPD risk. Limited prospective evidence linked COPD to abdominal adiposity. We investigated the association of body mass index (BMI) and measures of abdominal adiposity with COPD risk in a prospective cohort study.The China Kadoorie Biobank recruited participants aged 30–79 years from 10 areas across China. Anthropometric indexes were objectively measured at the baseline survey during 2004–2008. After exclusion of participants with prevalent COPD and major chronic diseases, 452 259 participants were included and followed-up until the end of 2016. We used Cox models to estimate adjusted hazard ratios relating adiposity to risk of COPD hospitalisation or death.Over an average of 10.1 years of follow-up, 10 739 COPD hospitalisation events and deaths were reported. Compared with subjects with normal BMI (18.5–<24.0 kg·m−2), underweight (BMI <18.5 kg·m−2) individuals had increased risk of COPD, with adjusted hazard ratio 1.78 (95% CI 1.66–1.89). Overweight (BMI 24.0–<28.0 kg·m−2) and obesity (BMI ≥28.0 kg·m−2) were not associated with an increased risk after adjustment for waist circumference. A higher waist circumference (≥85 cm for males and ≥80 cm for females) was positively associated with COPD risk after adjustment for BMI. Additionally, waist-to-hip ratio and waist-to-height ratio were positively related to COPD risk.Abdominal adiposity and underweight were risk factors for COPD in Chinese adults. Both BMI and measures of abdominal adiposity should be considered in the prevention of COPD.