bluuebunny/crossref_metadata_2025_split huggingface dataset:
“The Secret Life of Human Donor Hearts”
Authors: Lei Ienglam , Wang Zhong , Chen Y. Eugene , Ma Peter X. , Huang Wei , Kim Elaine , Lam Hugo Y.K. , Goldstein Daniel R. , Aaronson Keith D. , Pagani Francis D. , Tang Paul C. 
Published: April 2020

Background:
Ischemic tolerance of donor hearts has a major impact on the efficiency in utilization and clinical outcomes. Molecular events during storage may influence the severity of ischemic injury.

Methods:
RNA sequencing was used to study the transcriptional profile of the human left ventricle (LV, n=4) and right ventricle (RV, n=4) after 0, 4, and 8 hours of cold storage in histidine-tryptophan-ketoglutarate preservation solution. Gene set enrichment analysis and gene ontology analysis was used to examine transcriptomic changes with cold storage. Terminal deoxynucleotidyl transferase 2´-Deoxyuridine, 5´-Triphosphate nick end labeling and p65 staining was used to examine for cell death and NFκB activation, respectively.

Results:
The LV showed activation of genes related to inflammation and allograft rejection but downregulation of oxidative phosphorylation and fatty acid metabolism pathway genes. In contrast, inflammation-related genes were down-regulated in the RV and while oxidative phosphorylation genes were activated. These transcriptomic changes were most significant at the 8 hours with much lower differences observed between 0 and 4 hours. RNA velocity estimates corroborated the finding that immune-related genes were activated in the LV but not in the RV during storage. With increasing preservation duration, the LV showed an increase in nuclear translocation of NFκB (p65), whereas the RV showed increased cell death close to the endocardium especially at 8 hours.

Conclusions:
Our results demonstrated that the LV and RV of human donor hearts have distinct responses to cold ischemic storage. Transcriptomic changes related to inflammation, oxidative phosphorylation, and fatty acid metabolism pathways as well as cell death and NFκB activation were most pronounced after 8 hours of storage.
Safety, Performance, and Efficacy of Cardiac Contractility Modulation Delivered by the 2-Lead Optimizer Smart System
Authors: Wiegn Phi , Chan Rodrigo , Jost Charles , Saville Benjamin R. , Parise Helen , Prutchi David , Carson Peter E. , Stagg Angela , Goldsmith Rochelle L. , Burkhoff Daniel 
Published: April 2020

Background:
Prior studies of cardiac contractility modulation (CCM) employed a 3-lead Optimizer system. A new 2-lead system eliminated the need for an atrial lead. This study tested the safety and effectiveness of this 2-lead system compared with the 3-lead system.

Methods:

Patients with New York Heart Association III/IVa symptoms despite medical therapy, left ventricular ejection fraction 25% to 45%, and not eligible for cardiac resynchronization therapy could participate. All subjects received an Optimizer 2-lead implant. The primary end point was the estimated difference in the change of peak VO
2
from baseline to 24 weeks between FIX-HF-5C2 (2-lead system) subjects relative to control subjects from the prior FIX-HF-5C (3-lead system) study. Changes in New York Heart Association were a secondary end point. The primary safety end point was a comparison of device-related adverse events between FIX-HF-5C2 and FIX-HF-5C subjects.

Results:

Sixty subjects, 88% male, 66±9 years old with left ventricular ejection fraction 34±6% were included. Baseline characteristics were similar between FIX-HF-5C and FIX-HF-5C2 subjects except that 15% of FIX-HF-5C2 subjects had permanent atrial fibrillation versus 0% in FIX-HF-5C. CCM delivery did not differ significantly between 2- and 3-lead systems (19 892±3472 versus 19 583±4998 CCM signals/day, CI of difference [−1228 to 1847]). The change of peak VO
2
from baseline to 24 weeks was 1.72 (95% Bayesian credible interval, 1.02–2.42) mL/kg per minute greater in the 2-lead device group versus controls. 83.1% of 2-lead subjects compared with 42.7% of controls experienced ≥1 class New York Heart Association improvement (
P
<0.001). There were decreased Optimizer-related adverse events with the 2-lead system compared with the 3-lead system (0% versus 8%;
P
=0.03).

Conclusions:

The 2-lead system effectively delivers comparable amount of CCM signals (including in subjects with atrial fibrillation) as the 3-lead system, is equally safe and improves peak VO
2
and New York Heart Association. Device-related adverse effects are less with the 2-lead system.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03339310
The Role of the Judiciary in Promoting the Right to a Clean Environment in Kuwait, Egypt and the United States
Authors: Al-Otaibi Ahmad S. , Minan John H. 
Published: April 2020

Abstract
The judiciary has a very significant role to play in safeguarding the environment and promoting the right to a clean environment. This study focuses on the role of the judiciary in promoting the right to a clean environment, and, in this regard, will examine the Kuwaiti and Egyptian experience, as both legal systems are among the civil law practice. In addition, it is of importance to expand the study to a different legal practice, such as the common law system. Therefore, this research will also shed light on the role of the judiciary in the United States of America to establish a comparison between three different legal systems. In the course of this study, constitutional, administrative, and other legal provisions will be examined. In addition, significant cases of concern will be provided and discussed in a descriptive, analytical, and critical manner.
Node frequency alters stem biomechanics and hydraulics in four deciduous woody species
Authors: Jacobsen Anna L. , Fickle Jaycie C. , Castro Viridiana , Madsen Angela , Ennajeh Mustapha , Pratt R. Brandon 
Published: April 2020

AbstractAlong the distal stems of woody plants, nodes occur along the stem length separated by internode regions. Nodes typically include a leaf or leaf scar and an axillary bud that are connected to the xylem tissue within the stem through vascular leaf and bud traces. The diversion of xylem tissue into these lateral appendages creates a node gap that is typically occupied by parenchyma. We hypothesized that node-associated changes in structure within the stem tissues would result in alterations to stem biomechanics and hydraulic transport. We examined four deciduous species, Juglans californica, Populus trichocarpa, Quercus robur, and Rhus aromatica and measured node frequency, stem density, biomechanics, and hydraulic conductivity in 36 stems from each species. Vessel diameters within nodes and internodes were measured on a subset of these stems, as well as measures of xylem, pith, and node gap areas. Increased node frequency was correlated with decreased stem strength (modulus of rupture; MOR), decreased stem stiffness (modulus of elasticity; MOE), increased stem density, and decreased hydraulic conductivity. There were no differences in vessel diameter or xylem area between node and internode regions. Reduced hydraulic conductivity with increasing node frequency could have been due to increased vessel termini associated with nodes as has been found in prior research. Increased length of hydraulic pathways due to divergence of vessels around node gaps could also decrease hydraulic conductivity. Variation within the tree crown in node frequency may be an important morphological feature that has implications for crown tolerance of periodic mechanical stresses, such as wind events and fruit load.
Hepcidin gene polymorphisms and iron overload in β-thalassemia major patients refractory to iron chelating therapy
Authors: Zarghamian Parinaz , Azarkeivan Azita , Arabkhazaeli Ali , Mardani Ahmad , Shahabi Majid 
Published: April 2020

Abstract
Background
β Thalassemia is one of the most common groups of hereditary haemoglobinopathies. Affected people with thalassemia major are dependent on regular blood transfusion which on the long term leads to iron overload. Hepcidin is a peptide hormone and an important regulator of iron homeostasis, especially in thalassemia. Expression of this hormone is influenced by polymorphisms within the hepcidin gene, HAMP. Several studies emphasized the role of single nucleotide polymorphisms (SNPs) located in the promoter region of the gene. This study aimed to analyze the association between three SNPs in promoter of HAMP, c.-582A > G, c.-443C > T, and c.-153C > T, with iron overload in β-thalassemia major patients.

Methods
A total of 102 samples from β thalassemia major patients were collected. Genomic DNA was extracted and segments of DNA encompassing rs10421768 and rs142126068 were sequenced. Statistical analysis was performed by SPSS Statistics 23 using independent t test and Fisher’s exact test.

Results
A total of 102 adult β-thalassemia major patients were genotyped for three SNPs in the promoter region of HAMP gene by PCR and direct sequencing. Most of the patients (71.3%) were iron overloaded (based on plasma ferritin > 1000 ng/ml) in spite of receiving regular iron-chelating therapy. Our analysis revealed a statistically significant difference between the level of cardiac iron accumulation and c.-582A > G variant (p = 0.02). For c.-443C > T statistical analysis was on the edge of the significant relationship between the minor allele and serum ferritin (p = 0.058). All samples were homozygous for allele C of c.-153C > T.

Conclusions
Despite chelating therapy, iron overload is still one of the main complications of thalassemia. Our findings and others emphasize the role of hepcidin -582A > G polymorphism as a key component of iron homeostasis in these patients.
Comparative neutralizing potencies of antibodies suggest conservation as well as mechanistic differences in human cytomegalovirus entry into epithelial and endothelial cells
Authors: Qi Ying , He Li , Cui Xiaohong , Hertel Laura , Freed Daniel C. , Fu Tong-Ming , Kauvar Lawrence M. , McVoy Michael A. , Ruan Qiang 
Published: April 2020

AbstractAntibody neutralization of cytomegalovirus (CMV) entry into diverse cell types is a key consideration for development of vaccines and immunotherapeutics. CMV entry into fibroblasts differs significantly from entry into epithelial or endothelial cells: fibroblast entry is mediated by gB and gH/gL/gO, whereas both epithelial and endothelial cell entry require an additional pentameric complex (PC) comprised of gH/gL/UL128/UL130/UL131A. Because PC-specific antibodies in CMV-seropositive human sera do not affect fibroblast entry but potently block entry into epithelial or endothelial cells, substantially higher neutralizing potencies for CMV-positive sera are observed when assayed using epithelial cells as targets than when using fibroblasts. That certain sera exhibit similar discordances between neutralizing potencies measured using epithelial vs. endothelial cells (Gerna G. et al.J Gen Virol, 89:853–865, 2008) suggested that additional mechanistic differences may also exist between epithelial and endothelial cell entry. To further explore this issue, neutralizing potencies using epithelial and endothelial cells were simultaneously determined for eight CMV-positive human sera, CMV-hyperimmune globulin, and a panel of monoclonal or anti-peptide antibodies targeting specific epitopes in gB, gH, gH/gL, or the PC. No significant differences were observed between epithelial and endothelial neutralizing potencies of epitope-specific antibodies, CMV-hyperimmune globulin, or seven of the eight human sera. However, one human serum exhibited a six-fold higher potency for neutralizing entry into epithelial cells vs. endothelial cells. These results suggest that epitopes exist that are important for epithelial entry but are less critical, or perhaps dispensable, for endothelial cell entry. Their existence should be considered when developing monoclonal antibody therapies or subunit vaccines representing limited epitopes.
Angiostrongylus cantonensis Galectin-1 interacts with Annexin A2 to impair the viability of macrophages via activating JNK pathway
Authors: Shi Xiaomeng , Xiao Mengran , Xie Zhiyue , Shi Qing , Zhang Yuanjiao , Leavenworth Jianmei W. , Yan Baolong , Huang Huicong 
Published: April 2020

Abstract
Background
Angiostrongylus cantonensis can cause severe symptoms of central nervous system infections. In the host, this parasite localizes in the blood and cerebrospinal fluid, and its secreted components can impact immune responses. Our previous study demonstrated that immune responses were inhibited in A. cantonensis-infected mice immunized with Ac-Galectin-1 (AcGal-1). However, the mechanisms by which AcGal-1 regulates the immune responses remain unclear. Macrophages are innate immune cells that rapidly respond to infection. The direct impact of AcGal-1 on macrophages may affect the immune responses.

Methods
AcGal-1 protein was purified by nickel ion affinity chromatography. The effect of AcGal-1 on the apoptosis of macrophages was detected using CCK-8 assay, flow cytometry and western blot. Macrophage membrane proteins bound to AcGal-1 were obtained using the His-tag-based pull-down assay and identified via mass spectrometry. Co-localization of AcGal-1 and the macrophage membrane protein Annexin A2 was observed by immunofluorescence microscopy, and their interaction was validated by co-immunoprecipitation experiments. SiRNA-mediated knockdown of Annexin A2 was used to determine if AcGal-1-induced macrophage apoptosis required interaction with Annexin A2. The phosphorylation level of apoptotic signal pathway protein was detected by phospho-antibody microarray and western blot.

Results
Our study showed that AcGal-1 caused apoptosis of the macrophages. AcGal-1 increased the expression of apoptosis proteins caspase-3, caspase-9, Bax, but reduced the expression of anti-apoptosis protein Bcl-2. AcGal-1 interacted with the membrane protein Annexin A2, and knockdown of Annexin A2 expression increased Bcl-2 but decreased Bax levels in AcGal-1-treated cells. Moreover, AcGal-1 increased JNK phosphorylation and the inhibition of JNK phosphorylation in AcGal-1-treated cells decreased the expression of caspase-3, -9, Bax and almost restored Bcl-2 to the level observed in control cells.

Conclusions
AcGal-1 can induce the apoptosis of macrophages by binding to Annexin A2 and activating JNK downstream the apoptotic signaling pathway.
Melatonin: new insights on its therapeutic properties in diabetic complications
Authors: Pourhanifeh Mohammad Hossein , Hosseinzadeh Azam , Dehdashtian Ehsan , Hemati Karim , Mehrzadi Saeed 
Published: April 2020

AbstractDiabetes and diabetic complications are considered as leading causes of both morbidity and mortality in the world. Unfortunately, routine medical treatments used for affected patients possess undesirable side effects, including kidney and liver damages as well as gastrointestinal adverse reactions. Therefore, exploring the novel therapeutic strategies for diabetic patients is a crucial issue. It has been recently shown that melatonin, as main product of the pineal gland, despite its various pharmacological features including anticancer, anti-aging, antioxidant and anti-inflammatory effects, exerts anti-diabetic properties through regulating various cellular mechanisms. The aim of the present review is to describe potential roles of melatonin in the treatment of diabetes and its complications.
Added value of 68Ga-PSMA PET/CT for the detection of bone metastases in patients with newly diagnosed prostate cancer and a previous 99mTc bone scintigraphy
Authors: Zacho Helle D. , Ravn Søren , Afshar-Oromieh Ali , Fledelius Joan , Ejlersen June A. , Petersen Lars J. 
Published: April 2020

Abstract
Purpose
To investigate the added value and diagnostic accuracy of 68Ga-PSMA PET/CT versus bone scintigraphy (BS) for bone metastasis detection at the primary staging of prostate cancer (PCa).

Methods
Inclusion criteria involved consecutive patients with newly diagnosed intermediate- to high-risk PCa, who had undergone BS, mostly with supplementary SPECT/low-dose CT, and 68Ga-PSMA-11 PET/CT within less than 3 months without therapy initiation between the two investigations. BS was evaluated according to clinical routine and reported as no bone metastases (M0), bone metastases (M1), or equivocal (Me). The 68Ga-PSMA-11 PET/CT was blindly evaluated by three specialists as M0, M1, or Me at the patient level. Sensitivity analyses were conducted using a “best valuable comparator” using all available imaging and clinical follow-up as a reference.

Results
In total, 112 patients were included; 68Ga-PSMA-11 PET/CT showed a sensitivity of 1.00, specificity of 0.93–0.96, positive predictive value of 0.74–0.81, and negative predictive value of 1.00. 68Ga-PSMA-11 PET/CT revealed bone metastases in 8 of 81 patients with M0 disease according to BS. 68Ga-PSMA-11 PET/CT confirmed the presence of bone metastases in all patients (n = 9) with M1 disease according to BS. In patients with Me by BS, 68Ga-PSMA PET/CT provided a definite result in 20 of 22 patients. 68Ga-PSMA-11 PET/CT resulted in a false-positive answer in four patients with solitary rib lesions.

Conclusion
68Ga-PSMA-11 PET/CT revealed bone metastases in 10% of patients without bone metastases on BS and in 36% patients with indeterminate BS. However, solitary PSMA-avid lesions in the ribs should be interpreted cautiously as they may represent false-positive findings.
Traditional Chinese herbal medicine for treating novel coronavirus (COVID-19) pneumonia: protocol for a systematic review and meta-analysis
Authors: Li Yuxi , Liu Xiaobo , Guo Liuxue , Li Juan , Zhong Dongling , Zhang Yonggang , Clarke Mike , Jin Rongjiang 
Published: April 2020

Abstract
Background
A new type of coronavirus, novel coronavirus (COVID-19), is causing an increasing number of cases of pneumonia and was declared a Public Health Emergency of International Concern by the World Health Organization on 30 January 2020. The virus first appeared in Wuhan, China, in late December 2019, and traditional Chinese herbal medicine is being used for its treatment. This systematic review and meta-analysis will assess studies of the effects of traditional Chinese herbal medicine in COVID-19 pneumonia.

Methods
We will search electronic databases including PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), and Wanfang database using keywords related to COVID-19 and traditional Chinese herbal medicine. Reference lists of relevant trials and reviews will be searched. We will manually search gray literature, such as conference proceedings and academic degree dissertations, and trial registries. Two independent reviewers will screen studies (XL and DZ), extract data (YL and LG), and evaluate risk of bias (YL and DZ). Data analysis will be conducted using the Review Manager software (version 5.3.5) and R software (version 3.6.1). Statistical heterogeneity will be assessed using a standard chi-square test with a significance level of P < 0.10. Biases associated with study size (e.g., publication bias) will be investigated using funnel plots, Egger’s test and Begg’s test, and Trim and Fill analysis.

Discussion
This study will provide a high-quality synthesis of the effects of traditional Chinese herbal medicine for COVID-19. The use of traditional Chinese herbal medicine for treatment or prevention of these novel viral infections affecting the pneumonia will be investigated.

Systematic review registration
PROSPERO registration number: CRD42020168004
Vaccine coverage within the first year of life and associated factors with incomplete immunization in a Brazilian birth cohort
Authors: Buffarini Romina , Barros Fernando C. , Silveira Mariângela F. 
Published: April 2020

Abstract
Background
Immunization has been held as a major achievement for global health, however, still exist many children who are not completely vaccinated. Knowledge about factors contributing to the incomplete immunization is important to develop effective strategies and interventions to achieve universal coverage to control or eradicate vaccine-preventable diseases. This study aimed to describe immunization coverage within the first year of life and associated factors with incompleteness among participants of the 2015 Pelotas Birth Cohort, Brazil.

Methods
Cross-sectional analyses were performed using data from a population-based cohort. Information on vaccination status was collected from immunization cards and verbal mother’s reports from 4014 children aged 24 months. Coverage was described for each vaccine, for the basic and the complete national schedule. Incomplete vaccination was defined as failure to receive the recommended number of doses by the National Immunization Program in 2015. Bivariate and multivariate Poisson regressions with robust variance were conducted to identify factors associated with incompleteness.

Results
Vaccine coverage of individual vaccines varied from 81% (Hepatitis A) to 97% (BCG). Full immunization coverage were 77% (95% CI: 75.8; 78.4) and 66.1% (95% CI: 64.6; 67.5), for basic and expanded indicators, relatively. Multivariate analyses showed that factors associated with incompleteness (for both basic and expanded coverage) were high family income, high parity, low number of prenatal consultations, not have done the tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine during pregnancy, not have breastfeed the child until at age 12 months and not have used public health care services for child’s vaccination.

Conclusion
Findings of our study show the need to develop and implement policies and programs to achieve complete immunization during the first year of life. Some strategies would include an increase in the primary health care services networks, improving their quality and access, the dissemination of scientific-based evidence about the benefits of vaccination, through communication campaigns and guidance provided by health professionals, especially those responsible for prenatal care.
Miniature force sensor for absolute laser power measurements via radiation pressure at hundreds of watts
Authors: Artusio-Glimpse Alexandra B. , Ryger Ivan , Azarova Natalia A. , Williams Paul A. , Hadler Joshua A. , Lehman John H. 
Published: April 2020

We present a small power meter that detects the radiation pressure of an incident high-power laser. Given its small package and non-destructive interaction with the laser, this power meter is well suited to realizing a robust real-time, high-accuracy power measurement in laser-based manufacturing environments. The incident laser power is determined through interferometric measurement of displacement of a 20 mm diameter high reflectivity mirror, mounted at the center of a dual element spiral flexure. This device can measure laser power from 25 W to 400 W with a

260

m
W

/

H
z

noise floor and ≤ 3.2% expanded uncertainty. We validate our device against a calibrated thermopile with simultaneous measurements of an unpolarized 1070 nm laser and report good agreement between the two systems. Finally, by referencing to an identical mechanical spring that does not see the incident laser, we suppress vibration noise in the power measurement by 14.8 dB over a 600 Hz measured bandwidth. This is an improvement over other radiation pressure based power meters that have previously been demonstrated.