bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sildenafil for bronchopulmonary dysplasia and pulmonary hypertension: a meta‐analysis
Authors: van der Graaf Marisa , Rojer Leonne Arindah , Helbing Willem Arnold , Reiss Irwin Karl Marcel , Etnel Jonathan Richard Gregory , Bartelds Beatrijs 
Published: February 2019

Bronchopulmonary dysplasia (BPD) is the most common complication in preterm infants and often complicated by pulmonary hypertension (PH), leading to substantial morbidity and mortality. Sildenafil is often used to treat PH and improve symptoms in this condition, even though evidence of safety and effectiveness is scarce. The aim of this study was to perform a systematic review and meta‐analysis about the effectiveness and safety of chronic use of sildenafil in preterm infants with BPD‐associated PH. Data sources were PubMed, EMBASE, and Medline. Studies reporting the effectiveness of sildenafil therapy in BPD‐associated PH in newborns and infants were included. All‐cause mortality, improvement in PH, improvement in respiratory scores, and adverse events were extracted. Five studies were included, yielding a total of 101 patients with 94.2 patient‐years of total follow‐up. The pooled mortality rate was 29.7%/year (95% confidence interval [CI] = 6.8–52.7). Estimated pulmonary arterial pressure improved > 20% in 69.3% (95% CI = 56.8–81.8) of patients within 1–6 months. Respiratory scores improved in 15.0% (95% CI = 0.0–30.4) of patients within 2–7 days. There were no serious adverse events during sildenafil therapy. This systematic review shows that in the treatment of BPD‐associated PH in preterm infants, sildenafil may be associated with improvement in PAP and respiratory scores. However, there is no clear evidence of its effect on mortality rates. Considering BPD as a complex disease with variable expression patterns, these results support the need for a prospective registry and standardized approach.
What influences chronic pain management? A best–worst scaling experiment with final year medical students and general practitioners
Authors: Rankin Linda , Fowler Christopher John , Stålnacke Britt-Marie , Gallego Gisselle 
Published: February 2019

Background: Chronic pain education is an essential determinant for optimal chronic pain management. Given that attitudes and preferences are involved in making treatment decisions, identifying which factors are most influential to final year medical students’ and general practitioners’ (GPs) chronic pain management choices is of importance. This study investigates Swedish and Australian students’ preferences with respect to a chronic pain condition, using a best–worst scaling (BWS) experiment, which is designed to rank alternatives. Methods: BWS, a stated-preference method grounded in random utility theory, was used to explore the importance of factors influencing chronic pain management. Results: All three cohorts considered the patients’ pain description and previous treatment experience as the most important factors in making treatment decisions, whereas their demographics and voices or facial expressions while describing their pain were considered least important. Factors such as social support, patient preferences and treatment adherence were, however, disregarded by all cohorts in favour of pain assessment factors such as pain ratings, description and history. Swedish medical students and GPs show very high correlation in their choices, although the GPs consider their professional experience as more important compared to the students. Conclusion: This study suggests that the relative importance of treatment factors is cemented early and thus underline the critical importance of improving pain curricula during undergraduate medical education.
Using podcasts to deliver pediatric educational content: Development and reach of PediaCast CME
Authors: Patrick Michael D. , Stukus David R. , Nuss Kathryn E. 
Published: February 2019

Objective Pediatricians have used podcasts to communicate with the public since 2006 and medical students since 2008. Previous work has established quality criteria for medical education podcasts and examined the benefit of offering continuing medical education (CME) credit for online activities. This is the first descriptive study to outline the development and reach of a pediatric podcast that targets post-graduate healthcare providers, enhances communication by incorporating quality criteria, and offers free accredited CME to listeners. Methods We produced 26 podcast episodes from March 2015 to May 2017. Episodes incorporated quality criteria for medical education podcasts and offered free CME credit. They were published on a website, available for listening on multiple digital platforms and promoted through several social media channels. Data were analyzed for frequency of downloads and geographic location of listeners. Results The cumulative total of episode downloads was 91,159 with listeners representing 50 U.S. states and 108 countries. Podcast listenership grew over time. Individual episodes had their largest number of downloads immediately following release, but continued recruiting new listeners longitudinally, suggesting use of the archive as an “on-demand” source of educational content. Conclusions Pediatric podcasts that incorporate quality criteria and offer free CME credit can be used to deliver educational content to a large global audience of post-graduate healthcare providers. Since podcast communication is rapidly growing, future work should focus on identifying the professional roles of listeners; exploring listener perceptions of quality, value and satisfaction; and examining podcast impact on knowledge transfer, clinical practice, public policy and health outcomes.
Do Noncoding RNAs Mediate the Efficacy of Energy Psychology?
Authors: Yount Garret , Church Dawson , Rachlin Kenneth , Blickheuser Katharina , Cardonna Ippolito 
Published: February 2019

Background There are over 100 published studies of a therapy called Emotional Freedom Techniques (EFT). This popular form of energy psychology combines elements of established methods like cognitive therapy with acupressure. Our group reported the first evidence of its mechanisms of action at the molecular level, showing that it can influence levels of the stress hormone cortisol. Objectives Given recent advances in molecular genomics that have identified noncoding ribonucleic acid (RNA) molecules as important regulators of gene expression, the aim of this study is to explore the possibility that microRNAs play a role in mediating the effects of EFT. Methods We measured microRNA levels in stored blood samples from our previous study in which veterans were randomized into an EFT group receiving EFT and treatment as usual throughout a 10-week intervention period, and a control group receiving only treatment as usual during the intervention period and then receiving EFT. A broad panel of 800 microRNAs was probed using a multiplexed, direct hybridization, and detection system. Results All of the microRNA targets were expressed at low levels and most were below thresholds established by negative control probes. Baseline variability was determined using samples collected from the control group at the start and end of the intervention period, and used to filter out targets that were too noisy under control conditions to be able to distinguish a response to treatment. Analysis of the remaining viable targets found a general trend of reduced expression following EFT, compared to expression levels in samples from the control group during the intervention period. The most notable decreases in expression levels were found for 2 microRNAs: let-7b and let-7c, although no significance was found after adjusting for multiple comparisons. Conclusions These preliminary data support the feasibility of measuring microRNA expression level changes that correlate with effective EFT therapy.
Diagnosis of periprosthetic joint bacterial infections by culture of sonication fluid from infected implants
Authors: Kim Hee-June , Kim Shukho , Mun Jong-Uk , Bae Ki-Cheor , Kim Jungmin , Kyung Hee-Soo 
Published: February 2019

Purpose: This study compared the results of a culture method using sonication with those yielded by the conventional culture method, for patients with infected total knee arthroplasty (TKA). We also evaluated the usefulness of sonication for the identification of pathogens in infected TKA cases. Methods: Isolates were cultured from 13 implants that had been removed from 13 patients with infected TKA. Preoperative culture was performed on aspirated joint fluid, and during the operation, infected tissue was collected for culture. The removed prosthetic implants were cultured before and after sonication. Next, we identified the cultured bacteria using API biochemical kits and 16 S rRNA sequencing. Results: The cultures from preoperative joint fluid and intraoperative tissue were positive in 9 of 13 cases (69.2%). For the removed implants, 10 cases were positive before sonication. After sonication, 12 cases (92.3%) had positive cultures. The pathogen most commonly isolated from the cultures was Staphylococcus aureus. Conclusions: This study found that a culturing workflow incorporating sonication diagnosed pathogens in patients with infected TKA with higher sensitivity than did the conventional culturing method.
Ontogeny of platelet function
Authors: Margraf Andreas , Nussbaum Claudia , Sperandio Markus 
Published: February 2019

AbstractAlthough the hemostatic potential of adult platelets has been investigated extensively, regulation of platelet function during fetal life is less clear. Recent studies have provided increasing evidence for a developmental control of platelet function during fetal ontogeny. Fetal platelets feature distinct differences in reactive properties compared with adults. These differences very likely reflect a modified hemostatic and homeostatic environment in which platelet hyporeactivity contributes to prevent pathological clot formation on the one hand but still ensures sufficient hemostasis on the other hand. In this review, recent findings on the ontogeny of platelet function and reactivity are summarized, and implications for clinical practice are critically discussed. This includes current platelet-transfusion practice and its potential risk in premature infants and neonates.
The impact of the graft-versus-leukemia effect on survival in acute lymphoblastic leukemia
Authors: Yeshurun Moshe , Weisdorf Daniel , Rowe Jacob M. , Tallman Martin S. , Zhang Mei-Jie , Wang Hai-Lin , Saber Wael , de Lima Marcos , Sandmaier Brenda M. , Uy Geoffrey , Kamble Rammurti T. , Cairo Mitchell S. , Cooper Brenda W. , Cahn Jean-Yves , Ganguly Siddhartha , Camitta Bruce , Verdonck Leo F. , Dandoy Christopher , Diaz Miguel Angel , Savani Bipin N. , George Biju , Liesveld Jane , McGuirk Joseph , Byrne Michael , Grunwald Michael R. , Drobyski William R. , Pulsipher Michael A. , Abdel-Azim Hisham , Prestidge Tim , Wieduwilt Matthew J. , Martino Rodrigo , Norkin Maxim , Beitinjaneh Amer , Seo Sachiko , Nishihori Taiga , Wirk Baldeep , Frangoul Haydar , Bashey Asad , Mori Shahram , Marks David I. , Bachanova Veronika 
Published: February 2019

AbstractAllogeneic hematopoietic cell transplant is a potential curative therapy for acute lymphoblastic leukemia (ALL). Delineating the graft-versus-leukemia (GVL) effect as a function of graft-versus-host disease (GVHD) offers the potential to improve survival. We examined 5215 transplant recipients with ALL reported to the Center for International Blood and Marrow Transplant Research registry. Overall survival (OS) was compared according to the presence and severity of GVHD and evaluated in 3 cohorts: 2593 adults in first or second complete remission (CR1/CR2), 1619 pediatric patients in CR1/CR2, and 1003 patients with advanced (CR ≥3 or active disease) ALL. For patients in CR1/CR2, development of acute GVHD (aGVHD) or chronic GVHD (cGVHD) was associated with lower risk of relapse than no GVHD (hazard ratio [HR], 0.49-0.69). Patients with advanced ALL developing grades III and IV aGVHD or cGVHD were also at lower risk of relapse (HRs varied from 0.52 to 0.67). Importantly, adult and children in CR1/CR2 with grades I and II aGVHD without cGVHD experienced the best OS compared with no GVHD (reduction of mortality with HR, 0.83-0.76). Increased nonrelapse mortality accompanied grades III and IV aGVHD (HRs varied from 2.69 to 3.91) in all 3 cohorts and abrogated any protection from relapse, resulting in inferior OS. Patients with advanced ALL had better OS (reduction in mortality; HR, 0.69-0.73) when they developed cGVHD with or without grades I and II aGVHD. In conclusion, GVHD was associated with an increased GVL effect in ALL. GVL exerted a net beneficial effect on OS only if associated with low-grade aGVHD in CR1/CR2 or with cGVHD in advanced ALL.
Inhibition of contact-mediated activation of factor XI protects baboons against S aureus–induced organ damage and death
Authors: Silasi Robert , Keshari Ravi Shankar , Lupu Cristina , Van Rensburg Walter Janse , Chaaban Hala , Regmi Girija , Shamanaev Aleksandr , Shatzel Joseph J. , Puy Cristina , Lorentz Christina U. , Tucker Erik I. , Gailani David , Gruber András , McCarty Owen J. T. , Lupu Florea 
Published: February 2019

Abstract
Staphylococcus aureus infections can produce systemic bacteremia and inflammation in humans, which may progress to severe sepsis or septic shock, even with appropriate antibiotic treatment. Sepsis may be associated with disseminated intravascular coagulation and consumptive coagulopathy. In some types of mouse infection models, the plasma coagulation protein factor XI (FXI) contributes to the pathogenesis of sepsis. We hypothesize that FXI also contributes to the pathogenesis of sepsis in primates, and that pharmacological interference with FXI will alter the outcome of Staphylococcus aureus–induced lethality in a baboon model. Pretreatment of baboons with the anti-FXI antibody 3G3, a humanized variant of the murine monoclonal 14E11 that blocks FXI activation by FXIIa, substantially reduced the activation of coagulation, as reflected by clotting times and plasma complexes of coagulation proteases (FXIIa, FXIa, FIXa, FXa, FVIIa, and thrombin) with serpins (antithrombin or C1 inhibitor) following infusion of heat-inactivated S aureus. 3G3 treatment reduced fibrinogen and platelet consumption, fibrin deposition in tissues, neutrophil activation and accumulation in tissues, cytokine production, kininogen cleavage, cell death, and complement activation. Overall, 3G3 infusion protected the structure and function of multiple vital organs, including lung, heart, liver, and kidney. All treated animals reached the end point survival (7 days), whereas all nontreated animals developed terminal organ failure within 28 hours. We conclude that FXI plays a role in the pathogenesis of S aureus–induced disseminated intravascular coagulation and lethality in baboons. The results provide proof of concept for future therapeutic interventions that may prevent sepsis-induced organ failure and save lives in certain forms of sepsis.
Evolution of plastid genomes of Holcoglossum (Orchidaceae) with recent radiation
Authors: Li Zhang-Hai , Ma Xiao , Wang De-Yi , Li Yun-Xia , Wang Cheng-Wang , Jin Xiao-Hua 
Published: February 2019

AbstractBackgroundThe plastid is a semiautonomous organelle with its own genome. Plastid genomes have been widely used as models for studying phylogeny, speciation and adaptive evolution. However, most studies focus on comparisons of plastid genome evolution at high taxonomic levels, and comparative studies of the process of plastome evolution at the infrageneric or intraspecific level remain elusive.Holcoglossumis a small genus of Orchidaceae, consisting of approximately 20 species of recent radiation.This made it an ideal group to explore the plastome mutation mode at the infrageneric or intraspecific level.ResultsIn this paper, we reported 15 complete plastid genomes from 12 species ofHolcoglossumand 1 species ofVanda.The plastid genomes ofHolcoglossumhave a total length range between 145 kb and 148 kb, encoding a set of 102 genes. The whole set ofndh-gene families inHolcoglossumhave been truncated or pseudogenized. Hairpin inversion in the coding region of the plastid geneycf2has been found.ConclusionsUsing a comprehensive comparative plastome analysis, we found that all the indels between different individuals of the same species resulted from the copy number variation of the short repeat sequence, which may be caused by replication slippage. Annotation of tandem repeats shows that the variation introduced by tandem repeats is widespread in plastid genomes. The hairpin inversion found in the plastid geneycf2occurred randomly in the Orchidaceae.
Therapeutic effect of palbociclib in chondrosarcoma: implication of cyclin-dependent kinase 4 as a potential target
Authors: Ouyang Zhengxiao , Wang Sisi , Zeng Ming , Li Zhihong , Zhang Qing , Wang Wanchun , Liu Tang 
Published: February 2019

Abstract
Background
Chondrosarcoma is a malignant cartilaginous neoplasm of the bone which resistant to radiation therapy and chemotherapy. Cyclin-dependent kinase 4 (CKD4) is highly expressed in human cancer, and palbociclib, the inhibitor of CDK4 has been used clinically under FDA approval for application in cancer therapeutic remedies. However, the level of CDK4 and the treatment possibility in chondrosarcoma require further exploration. Thus, we aim to investigate the level of CDK4 and accompanying therapeutic effects of palbociclib in chondrosarcoma.

Methods
We used immunohistochemistric analysis to evaluate human CDK4 productions in chondrosarcoma tissues. The inhibitory expression of CDK4 by siRNA or palbociclib on cell proliferation, invasion, migration, apoptosis and cycle arrest of chondrosarcoma were determined by MTT, wound healing, transwell and flow cytometry. CDK4/Rb signaling pathway were determined by western blot and Immunofluorescence assay. The inhibition effect of palbociclib on tumor growth within the bone were determined by bioluminescence imaging in vivo.

Results
CDK4 was found to express significantly in human chondrosarcoma samples. The enhanced levels of CDK4 were interlinked with malignant metastasis and undesirable prognosis of chondrosarcoma patients. CDK4 was also highly expressed in human chondrosarcoma cell lines and its inhibition by specific siRNA and palbociclib lead to a decrease in cell proliferation, accompanied by the phosphorylation of Rb. Furthermore, palbociclib also induced cell cycle arrest in G1 phase and decreased cell migration and invasion via CDK4/Rb signaling pathway. Administration of palbociclib in vivo could reduce tumor burden in chondrosarcoma.

Conclusions
In summary, these data highlight CDK4 inhibitors, such as palbociclib, as potential promising therapeutics in the treatment of human chondrosarcoma.
Developing a systematic approach to determine the sequence of impressions of Japanese woodblock prints: the case of Hokusai’s ‘Red Fuji’
Authors: Korenberg Capucine F. , Pereira-Pardo Lucia , McElhinney Peter J. , Dyer Joanne 
Published: February 2019

Abstract
Ukiyo-e Japanese woodblock prints were mass-produced in the Edo Period and early impressions of a given print are generally of higher quality and more sought after by connoisseurs than late impressions. The present publication presents an innovative approach that combines the classical method of examining line quality with a systematic study of colourants. This approach was used to compare an impression of Hokusai’s iconic ‘Red Fuji’ with its rare variant, ‘Pink Fuji’. Woodblock wear and printing effects were studied using high resolution photographs and the colourants were characterised using non-destructive methods. Signs of greater woodblock wear were identified in ‘Red Fuji’ compared to ‘Pink Fuji’ and there were indications that much more thought had been given to the selection and application of the colourants in ‘Pink Fuji’. This showed that ‘Pink Fuji’ was printed before ‘Red Fuji’ and is possibly a first edition. The approach developed here represents a novel way of studying Japanese woodblock prints and can be used to determine the sequence of impressions of other prints.
Antibiofilm activity of epoxy sealer incorporated with quaternary ammonium macromolecule
Authors: Becker Tal , Sterer Nir , Greenstein Ronit Bar-Ness , Toledano Tamar , Solomonov Michael 
Published: February 2019

Abstract

Background
A common reason for failure of root canal treatment is residual bacterial biofilm or reinfection due to coronal seal inadequacy. Recently, the idea of using macromolecules with antibacterial features has evolved. The addition of nanoparticle macromolecules to sealers gained antibiofilm properties as shown in several in vitro studies. Nevertheless, no technique has yet been able to completely eliminate the residual biofilm. We evaluated the in vitro antibacterial effect of epoxy sealer, BJM ROOT CANAL SEALER® (BJM Laboratories Ltd., Or-Yehuda, Israel), incorporated with non-nanoparticle quaternary ammonium macromolecule (BIOSAFE HM4100, Pittsburg, PA, USA) against existing biofilm of Enterococcus faecalis and its ability to inhibit it de-novo.

Methods
Six mm diameter discs of epoxy sealer (BJM) incorporated with various concentrations of immobilized ammonium particles (0, 0.4, 0.8, 1.6, and 3.3% w/v) were tested for its antibacterial effect on de-novo biofilm formation (by Biofilm Formation assay), and on existing biofilm (by Biofilm Viability assay). The Live/Dead bacterial ratio was determined using fluorescence microscopy.

Results
Biofilm formation assay showed significant reductions in de-novo biofilm formation of 25 and 72% in the higher ammonium particle concentrations of 1.6 and 3.3% w/v respectively (p < 0.001 for both). Biofilm viability assay showed significant reductions in existing biofilm viability of 20 and 36% in the higher ammonium particle concentrations of 1.6 and 3.3% w/v respectively (p < 0.001 for both).

Conclusions
Biosafe incorporated in epoxy root canal sealer discs showed a pronounced reduction of de-novo biofilm formation in the higher concentrations (1.6 and 3.3% w/v), as well as some antibacterial effect against existing biofilm of E. faecalis. This sealer may be effective for prevention of de-novo formation of bacterial biofilm in treated root canals.
Identification of Obsidian Sources on Milos, Greece
Authors: Sterba Johannes H , Eder Fabienne , Bichler Max 
Published: February 2019

Obsidian, a natural volcanic glass, was used extensively in ancient times because of its quality as a raw material for sharp blades. As such, obsidian is of high interest for provenancing studies, since reliable provenancing can provide information about trade routes, extension of territory, long-distance contacts and the mobility of prehistoric peoples. In general, well-established databases of the characteristic elemental composition, the chemical fingerprint, are needed for reliable provenancing. On Milos Island, two sources of raw obsidian, namely Agia Nychia (Cape Bombarda) and Demenegakion are known. Recent literature claims a third source close to Agios Ioannis. In a sampling expedition with the goal to complete the Atominstitut’s database on the chemical fingerprints of obsidian, samples at Agios Ioannis were collected to include this new source. At the location, 16 scattered samples were taken for analysis, even though no direct outcrop could be identified. On the nearby island Kimolos, several more samples were found. Using instrumental neutron activation analysis (INAA), the chemical fingerprint of the samples was measured and compared to the values in the database. All samples from Agios Ioannis were identified as either from Demenegakion or Agia Nychia, indicating that no further source of obsidian exists at the location.