bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel renal biomarkers show that creatine supplementation is safe: a double-blind, placebo-controlled randomized clinical trial
Authors: de Oliveira Vilar Neto José , da Silva Carlos Alberto , Meneses Gdayllon Cavalcante , Pinto Daniel Vieira , Brito Luciana Catunda , da Cruz Fonseca Said Goncalves , de Sousa Alves Renata , Martins Alice Maria Costa , de Oliveira Assumpção Cláudio , De Francesco Daher Elizabeth 
Published: April 2020

Abstract
The aim of this study was to evaluate the impact of creatine supplementation (CS) on renal function in young, healthy, and active subjects. We used a randomized, double-blind, placebo-controlled clinical trial as the study design. Thirty-six healthy male university students were recruited and divided into three groups: group placebo, group G3 (3 g/day of CS), and group G5 (5 g/day of CS). To assess renal function, new kidney biomarkers, kidney injury molecule-1 (KIM-1) and monocyte chemoattractant protein-1 (MCP-1), were quantified. Serum albumin, serum creatinine, serum urea, estimated glomerular filtration rate (eGFR), proteinuria, and albuminuria were also measured. All groups were evaluated at two times: prior CS or placebo (pre) and after 35 days on CS or placebo (post). After 35 days of intervention, all characteristics were maintained without significant difference (P &gt; 0.05) between the groups, including serum creatinine, eGFR, and more sensitive kidney biomarker concentrations (KIM-1 and MCP-1). The paired analysis showed that the supplemented groups (G3 and 5G) had increased serum creatinine and decreased eGFR levels (P &lt; 0.05). However, the values were still within the normal reference range. In conclusion, the results of renal function evaluation did not show any difference between the evaluated groups. Increased serum creatinine and decreased eGFR levels in CS groups can be explained by increased creatine stores and metabolism, since creatinine is a by-product of creatine metabolism. These findings indicate that the use of CS at doses of 3 g and 5 g/day for a short period (35 days) is safe and did not impair the kidneys or renal function in young healthy subjects.
Systems Genetics and Systems Biology Analysis of Paraquat Neurotoxicity in BXD Recombinant Inbred Mice
Authors: Torres-Rojas Carolina , Zhuang Daming , Jimenez-Carrion Paola , Silva Isabel , O’Callaghan James P , Lu Lu , Zhao Wenyuan , Mulligan Megan K , Williams Robert W , Jones Byron C 
Published: April 2020

Abstract
Paraquat (PQ) is an herbicide used in many countries, including the United States. It is also implicated as a risk factor for sporadic Parkinson’s disease, especially in those living in agricultural areas and drinking well water. Studies linking PQ to sporadic Parkinson’s disease are not consistent however and there appears to be interindividual differential susceptibility. One likely reason is genetically based differential susceptibility to paraquat neurotoxicity in subpopulations. To address this issue, we tested the effects of paraquat in a genetic reference population of mice (the BXD recombinant inbred strain family). In our earlier work, we showed that in genetically susceptible mice, paraquat increases iron in the ventral midbrain, the area containing the substantia nigra. Our hypothesis is that genetic variability contributes to diverse PQ-related susceptibility and iron concentration. To test this hypothesis, we treated male mice from 28 to 39 BXD strains plus the parental strains with 1 of 3 doses of paraquat, 1, 5, and 10 mg/kg 3 times on a weekly basis. At the end of the treatment period, we analyzed the ventral midbrain for concentrations of iron, copper, and zinc, also we measured the concentration of paraquat in cerebellum, and proinflammatory cytokines in serum and cerebellum. The effect on paraquat-treated mice with 5 mg/kg and principal component analysis of iron showed suggestive quantitative trait loci on chromosome 5. Overall, our results suggest that gene Prkag2 and related networks may serve as potential targets against paraquat toxicity and demonstrate the utility of genetically diverse mouse models for the study of complex human toxicity.
Evaluating Associations Between Nonclinical Cardiovascular Functional Endpoints and Repeat-dose Cardiovascular Toxicity in the Beagle Dog: A Cross-company Initiative
Authors: Milliken Philip , Aylott Mike , Edmunds Nick , Engle Steven , Ewart Lorna , Fleurance Renaud , Guffroy Magali , Hargreaves Adam , Heinz-Taheny Kathleen , Kirk Sarah , Leishman Derek , Leong Louise , McMahon Nick , Valentin Jean-Pierre , Watson David , Wallis Rob , Clements Peter 
Published: April 2020

Abstract
Integrating nonclinical in vitro, in silico, and in vivo datasets holistically can improve hazard characterization and risk assessment. In pharmaceutical development, cardiovascular liabilities are a leading cause of compound attrition. Prior to clinical studies, functional cardiovascular data are generated in single-dose safety pharmacology telemetry studies, with structural pathology data obtained from repeat-dose toxicology studies with limited concurrent functional endpoints, eg, electrocardiogram via jacketed telemetry. Relationships between datasets remain largely undetermined. To address this gap, a cross-pharma collaboration collated functional and structural data from 135 compounds. Retrospective functional data were collected from good laboratory practice conscious dog safety pharmacology studies: effects defined as hemodynamic blood pressure or heart rate changes. Morphologic pathology findings (mainly degeneration, vacuolation, inflammation) from related toxicology studies in the dog (3–91 days repeat-dosing) were reviewed, harmonized, and location categorized: cardiac muscle (myocardium, epicardium, endocardium, unspecified), atrioventricular/aortic valves, blood vessels. The prevalence of cardiovascular histopathology changes was 11.1% of compounds, with 53% recording a functional blood pressure or heart rate change. Correlations were assessed using the Mantel-Haenszel Chi-square trend test, identifying statistically significant associations between cardiac muscle pathology and (1) decreased blood pressure, (2) increased heart rate, and between cardiovascular vessel pathology and increased heart rate. Negative predictive values were high, suggesting few compounds cause repeat-dose cardiovascular structural change in the absence of functional effects in single-dose safety pharmacology studies. Therefore, observed functional changes could prompt moving (sub)chronic toxicology studies forward, to identify cardiovascular liabilities earlier in development, and reduce late-stage attrition.
Efficacy and Safety of Single and Multiple Doses of a Fixed-dose Combination of Ibuprofen and Acetaminophen in the Treatment of Postsurgical Dental Pain
Authors: Searle Shawn , Muse Derek , Paluch Ed , Leyva Rina , DePadova Elizabeth , Cruz-Rivera Mario , Kellstein David 
Published: April 2020

Objectives:
A previous pilot study demonstrated that various fixed-dose combinations (FDCs) of ibuprofen (IBU) and acetaminophen (APAP) provided analgesic efficacy comparable to a higher dose of IBU, with the same safety profile. These studies further evaluated the chosen FDC IBU/APAP 250/500 mg formulation.

Materials and Methods:
Two phase 3 dental pain studies enrolled healthy young patients with ≥moderate pain after ≥3 third molar extractions who received single-dose FDC IBU/APAP 250/500 mg, IBU 250 mg, APAP 650 mg, or placebo evaluated over 12 hours (study 1) or multiple-dose FDC or placebo every 8 hours, evaluated over 48 hours (study 2). Time-weighted sum of pain intensity differences over 8 (SPID[11]0-8) and 24 (SPID[11]0-24) hours were primary outcomes, respectively. Time to meaningful pain relief and duration of pain relief were assessed; tolerability was evaluated by adverse events.

Results:
Five hundred sixty-eight patients were randomized in study 1; 123 in study 2. Study 1: SPID[11]0-8 favored FDC significantly over placebo, IBU, and APAP (P<0.001, P=0.008, and P<0.001, respectively); study 2: SPID[11]0-24 significantly favored FDC over placebo (P<0.001), with sustained efficacy during multiple dosing. Time to meaningful pain relief occurred within 1 hour; pain relief duration was >8 hours in both studies. Adverse event rates were lowest with the FDC.

Discussion:
FDC IBU/APAP 250/500 mg provides superior analgesic efficacy to individual monocomponents (IBU 250 mg and APAP 650 mg), a rapid onset of action, >8-hour duration of pain relief, is generally well tolerated, and may provide an additional nonopioid treatment option for acute pain.
Stereotactic Navigation for Rectal Surgery: Comparison of 3-Dimensional C-Arm−Based Registration to Paired-Point Registration
Authors: Okada Tomoaki , Kawada Kenji , Sumii Atsuhiko , Itatani Yoshiro , Hida Koya , Hasegawa Suguru , Sakai Yoshiharu 
Published: April 2020

BACKGROUND:
Stereotactic navigation enables surgeons to use the preoperative CT or MRI images as a real-time “navigation map.” Although stereotactic navigation has been established in neurosurgery and orthopedic surgery, whether this technology is applicable to GI tract surgery remains challenging because of tissue deformation and organ motion. A critical component of this technology is the registration that links the patient’s actual body to the preoperative imaging data.

OBJECTIVE:
The objective was to assess the applicability of stereotactic navigation in rectal surgery, focusing on the registration method.

DESIGN:
This study was based on a prospective case series.

SETTING:
The study was conducted in a single university hospital.

PATIENTS:
Four patients who underwent laparoscopic rectal surgery were included.

INTERVENTIONS:
Paired-point registration was performed for 2 cases, whereas 3-dimensional C-arm−based registration was performed for the other 2 cases. In addition, 3-dimensional C-arm−based registration was performed twice during the operation.

MAIN OUTCOME MEASURE:
Navigation accuracy was evaluated by measuring target registration error at 8 anatomical landmarks.

RESULTS:
Target registration error of the 3-dimensional C-arm−based registration group was significantly smaller than that of the paired-point registration group (median, 19.5 mm vs 54.1 mm; p < 0.001). In particular, the error of Z-axis (cranial-to-caudal direction) was significantly smaller in 3-dimensional C-arm−based registration (median, 12.4 mm vs 48.8 mm; p < 0.001). In one case in the 3-dimensional C-arm−based registration group, target registration error of the second registration became significantly smaller than that of the first registration (p = 0.008).

LIMITATIONS:
This was an observational study with small sample size.

CONCLUSION:
Three-dimensional C-arm−based registration could be performed with the patient in a lithotomy position with head down and lateral tilt without being affected by positional changes. Three-dimensional C-arm−based registration resulted in significantly higher navigation accuracy than paired-point registration, and its accuracy could be further improved by intraoperative re-registration.
Clinically significant pseudophakic cystoid macular edema after bag-in-the-lens implantation
Authors: Scheers Dorothée , Van Os Luc , Ní Dhubhghaill Sorcha , Wouters Kristien , Tassignon Marie-José 
Published: April 2020

Purpose:
To determine the incidence of clinically significant pseudophakic cystoid macular edema (CSPME) after phacoemulsification using the bag-in-the-lens intraocular lens (BIL IOL) implantation technique and to examine the influence of associated risk factors, both ocular and systemic.

Setting:
Monocentric, Antwerp University Hospital, Belgium.

Design:
Retrospective.

Methods:
This study included 1 077 first-operated eyes of 1 077 adults who underwent phaco-emulsification cataract surgery using the BIL IOL implantation technique between January 2013 and December 2015.

Results:
The 3-month incidence of CSPME in the subgroup without risk factors was 0% (95% CI, 0.0-0.0). The 3-month incidence of CSPME in the subgroup with risk factors was 2.8% (95% CI, 1.3-4.3). The 3-month incidence of CSPME in the total group of 1077 patients was 1.4% (95% CI, 0.6-2.1). The risk factors most significantly associated with CSPME included diabetes (hazard ratio [HR]: 5.37; 95% CI, 1.5-19.3; P = .019), exudative age-related macular degeneration (HR: 121; 95% CI, 36.1-409; P < .001), and macular traction (HR: 6.47; 95% CI, 1.9-22.1; P < .009).

Conclusions:
The incidence of CSPME was zero in eyes without risk factors. The incidence was consistent with previous reports in the literature regarding the lens-in-the-bag IOL implantation technique in eyes with risk factors. This indicates that the BIL IOL implantation technique is a safe procedure and does not confer a higher risk for developing cystoid macular edema after cataract surgery compared with the lens-in-the-bag IOL implantation technique, despite the requirement of a primary posterior continuous curvilinear capsulorhexis.
A risk score based on simple angiographic characteristics to aid in choosing the optimal revascularization strategy for patients with multivessel disease presenting with ST-elevation myocardial infarction
Authors: Schamroth Pravda Nili , Witberg Guy , Zusman Oren , Landes Uri , Bental Tamir , Assali Abid , Vaknin Assa Hana , Greenberg Gabriel , Codner Pablo , Perl Leor , Kornowski Ran 
Published: April 2020

Background:
The optimal revascularization strategy is not clearly defined for patients with ST-elevation myocardial infarction with multivessel disease (MV-STEMI). We aimed to develop a simple angiographic risk score for identifying patients with MV-STEMI that might benefit from a multivessel percutaneous coronary intervention (MV-PCI), compared to a PCI for only the infarct-related artery (IRA-PCI).

Methods and results:
This retrospective study acquired data from a single-center STEMI registry on 841 consecutive patients with MV-STEMI (645 IRA-PCI and 196 MV-PCI). Patients were stratified according to high- and low-risk scores. We devised a score based on three characteristics of non-culprit lesions previously reported to predict overall mortality (proximal left anterior descending artery involvement, maximal % stenosis, and number of involved vessels). The primary endpoint was major adverse cardiac events (MACEs: a composite of death/MI/urgent repeat revascularization). After a median follow-up of 1909 days, MACE occurred in 205/841 (24.4%) patients. MACE risk was higher in the high-risk than in the low-risk group (HR 1.43, P < 0.001). In comparing the IRA-PCI and MV-PCI approaches within each risk group, we found that these revascularization strategies had differential effects on outcome. Compared to the MV-PCI, IRA-PCI was associated with less MACE in the low-risk group (HR 0.597, P = 0.033), and more MACE in the high-risk group (HR 3.14, P < 0.001).

Conclusion:
For patients with MV-STEMI that undergo primary PCI, a simple risk score based on three angiographic characteristics could identify patients at high risk of future adverse events. This score might facilitate choosing the optimal revascularization strategy.
Bilateral internal thoracic artery grafting in patients with left main disease: a single-center experience
Authors: Gordon Amit , Nesher Nachum , Mohr Raphael , Pevni Dmitry , Kramer Amir , Ziv-Baran Tomer , Paz Yosef , Ben-Gal Yanai 
Published: April 2020

Objective
We compared early and long-term outcomes between bilateral internal thoracic artery (BITA) grafting and single internal thoracic artery (SITA) grafting in patients with LM disease.

Methods
We evaluated the outcomes of all patients with LM disease who underwent revascularization in our center during 1996–2011. Variables that were adjusted for in a multivariate analysis and in propensity matching included age, sex, comorbid diseases, repeat operation, the number of diseased vessels, other conduits used, the use of sequential grafting, the number of grafts constructed, and the operative era (1996–2000 vs. 2001–2011).

Results
In total, 949 patients with LM disease underwent BITA grafting and 564 underwent SITA grafting during the study period. SITA patients were more often female and more likely to have comorbidities such as chronic obstructive pulmonary disease, ejection fraction <30%, recent myocardial infarction, diabetes, congestive heart failure, chronic renal failure, and peripheral vascular disease, and to have undergone an emergency operation. We found no statistically significant difference between the SITA and BITA groups in 30-day mortality (4.8% vs. 3.3%, P = 0.136), sternal wound infection (2.0% vs. 2.4%, P = 0.548), and stroke (3.2% vs. 4.4%, P = 0.234). BITA patients had improved long-term survival (70.1% vs. 52.0% p<0.001), median follow-up of 15 years. In multivariate analysis, after propensity score matching (477 matched pairs), this finding was not statistically significant (P = 0.135).

Conclusion
This study did not demonstrate a clear benefit of BITA grafts among patients with LM disease.
Supporting African American Mothers during Nurse Home Visits in Adopting Safe Sleep Practices
Authors: Stiffler Deborah , Matemachani Sherry Mukasa , Crane Lisa 
Published: April 2020

Abstract

Background:
Nurses providing home visits were concerned that some mothers were not routinely using safe sleep practices for their newborns and infants.

Purpose:
The purpose of this study was to listen to how home visit nurses offer education to their African American clients about the safe to sleep guidelines during the prenatal and postpartum periods and discuss ways nurses could support mothers to be more successful in using safe sleep practices.

Study Design and Methods:
A focus group was conducted with home visit nurses who partner with pregnant mothers and follow them through the first 2 years of their child's life. We asked the nurses to discuss how they offer information and education to their African American clients about safe sleep practices and what could be done to support adoption of the guidelines. A qualitative narrative approach was used for data analysis.

Results:
Seventeen home visit nurses participated in the focus group. We identified two overall themes with eight subthemes. The first theme focused on nurses' perceptions about challenges some mothers have in following the recommendations. The second theme included nurses' perspectives on how to better promote the safe sleep message and educating mothers within their cultural context.

Clinical Implications:
Expectant and new mothers need advice and knowledge about the Safe to Sleep® guidelines that provide ways to decrease risk of infant death. Nurses must be aware of their clients' culture and beliefs so they can offer support and information on infant safety within that context.
Hybrid origin ofPopulus tomentosaCarr. identified through genome sequencing and phylogenomic analysis
Authors: An Xinmin , Gao Kai , Chen Zhong , Li Juan , Yang Xiong , Yang Xiaoyu , Zhou Jing , Guo Ting , Zhao Tianyun , Huang Sai , Miao Deyu , Khan Wasif Ullah , Rao Pian , Ye Meixia , Lei Bingqi , Liao Weihua , Wang Jia , Ji Lexiang , Li Ying , Guo Bing , Mustafa Nada Siddig , Li Shanwen , Yun Quanzheng , Keller Stephen R. , Mao Jianfeng , Zhang Rengang , Strauss Steven H. 
Published: April 2020

AbstractPopulus tomentosais widely distributed and cultivated in the Northern and Central China, where it is of great economic and ecological importance. However, the origin ofP. tomentosaremains controversial. Here, we used a PacBio+Hi-C+Illumina strategy to sequence and assemble its 740.2 Mb (2n) genome. The assembly accounts for greater than 92.1% of the 800-megabase genome, comprises 38 chromosomes, and contains 59,124 annotated protein-coding genes. Phylogenomic analyses elucidated dynamic genome evolution events among its closely related white poplars, and revealed thattomentosais comprised of two subgenomes, which we deomonstrate is likely to have resulted from hybridization betweenPopulus adenopodaas the female, andPopulus albavar.pyramidalisas the male, around 3.93 Mya. We also detected structural variations and allele-indels across genome. Our study presents a high quality and well assembled genome, unveils the origin of the widely distributed and plantedP. tomentosa, and provides a powerful resource for comparative plant biology, breeding, and biotechnology.
Cognitive Flexibility Deficits in Rats with Dorsomedial Striatal 6-OHDA Lesions Tested Using a 3-Choice Serial Reaction Time Task with Reversal Learning
Authors: Wang Zhuo , Flores Ilse , Donahue Erin K. , Lundquist Adam J. , Guo Yumei , Jakowec Michael W. , Holschneider Daniel P. 
Published: April 2020

AbstractLesions of the dorsomedial striatum elicit deficits in cognitive flexibility that are an early feature of Parkinson’s disease (PD), and presumably reflect alterations in frontostriatal processing. The current study aimed to examine deficits in cognitive flexibility in rats with bilateral 6-hydroxydopamine (6-OHDA) lesions in the dorsomedial striatum. While deficits in cognitive flexibility have previously been examined in rodent PD models using the cross-maze, T-maze, and a food-digging task, the current study is the first to examine such deficits using a 3-choice serial reaction time task (3-CSRT) with reversal learning (3-CSRT-R). Although the rate of acquisition in 3-CSRT was slower in lesioned compared to control rats, lesioned animals were able to acquire a level of accuracy comparable to that of control animals following 16 days of training. In contrast, substantial and persistent deficits were apparent during the reversal learning phase. Our results demonstrate that deficits in cognitive flexibility can be robustly unmasked by reversal learning in the 3-CSRT-R paradigm, which can be a useful test for evaluating effects of dorsomedial striatal deafferentation.
New Insights Into the Effect of Residue Mutation on the Rotavirus VP1 Function Using Molecular Dynamic Simulations
Authors: Abid Nabil , Salemi Marco , Chillemi Giovanni 
Published: April 2020

AbstractRotavirus group A remains a major cause of diarrhea in infants and young children worldwide. The permanently emergence of new genotypes puts the potential effectiveness of vaccines under serious question. Thirteen VP1 mutants were analyzed using molecular dynamic simulations and the results were combined with the experimental findings, reported previously. The results revealed structural fluctuations and secondary structure change of VP1 protein that may alter its function during viral replication/transcription. Altogether, the structural analysis of VP1 may boost efforts to develop antivirals, as they might complement the available vaccines.