tbuckley/cabot-search huggingface dataset:
Abstract 16158: Comparative Effects of Bone Marrow Derived versus Umbilical Cord Tissue Mesenchymal Stem Cells in an Experimental Model of Bronchopulmonary Dysplasia
Authors: Merline Benny, Benjamin Courchia, Sebastian Shrager, Mayank Sharma, Joanne Duara, Krystalenia Valasaki, Huang Jian, Pingping Chen, Ronald Zambrano, Shu Wu, Omaida C Velazquez, Joshua M Hare, Aisha Khan, Karen C Young
Journal: Circulation (2020)

Introduction: Bronchopulmonary dysplasia (BPD) or chronic lung injury of newborn is a life-threatening condition in preterm infants with few effective therapies. Mesenchymal stem cells (MSC) are a promising therapeutic strategy for BPD. The ideal MSC source for BPD prevention is however unknown. Umbilical cord tissue (UCT) MSC may potentially have more anti-inflammatory and pro-angiogenic properties. Hypothesis: We hypothesized that the UCT-MSC will have superior lung regenerative effect in BPD owing to superior anti-inflammatory and pro-angiogenic properties as compared to BM-MSC. Methods: Newborn rats (n=10-12/group) were randomly assigned to normoxia or hyperoxia (85% O 2 ) from postnatal day (P) 1 to 21 were given intra-tracheal (IT) BM or UCT-MSC (1 x 10 6 cells/50 μl), or placebo (PL) on P3. Results: Hyperoxia PL-treated pups had marked alveolar simplification, vascular rarefaction, remodeling and lung inflammation. Administration of both BM-MSC and UCT-MSC significantly improved alveolar structure, vascular density, pulmonary hypertension, vascular remodeling and lung inflammation. However, the improvement in alveolar structure and lung inflammation was more marked in hyperoxic pups who received UCT-MSC. In vitro studies demonstrated greater TSG-6 and IL-10 expression in UCT-MSC as compared to BM-MSC. Moreover, lung epithelial cells incubated with UCT-MSC conditioned media had greater wound healing following scratch injury. Conclusion: These findings demonstrate that while both BM and UCT-MSC have lung regenerative effects, UCT-MSC have greater anti-inflammatory and alveolar protective effects in experimental BPD. These findings have significant implications for cellular therapy in BPD, as it suggests that UCT-MSC are a superior cellular source for preterm lung protection.
Prevalence of Bacterial Meningitis Among Febrile Infants Aged 29-60 Days With Positive Urinalysis Results
Authors: Brett Burstein, Vikram Sabhaney, Jeffrey N. Bone, Quynh Doan, Fahad F. Mansouri, Garth D. Meckler
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Fever in the first months of life remains one of the most common pediatric problems. Urinary tract infections are the most frequent serious bacterial infections in this population. All published guidelines and quality initiatives for febrile young infants recommend lumbar puncture (LP) and cerebrospinal fluid (CSF) testing on the basis of a positive urinalysis result to exclude bacterial meningitis as a cause. For well infants older than 28 days with an abnormal urinalysis result, LP remains controversial. <h3>Objective</h3> To assess the prevalence of bacterial meningitis among febrile infants 29 to 60 days of age with a positive urinalysis result to evaluate whether LP is routinely required. <h3>Data Sources</h3> MEDLINE and Embase were searched for articles published from January 1, 2000, to July 25, 2018, with deliberate limitation to recent studies. Before analysis, the search was repeated (October 6, 2019) to ensure that new studies were included. <h3>Study Selection</h3> Studies that reported on healthy, full-term, well-appearing febrile infants 29 to 60 days of age for whom patient-level data could be ascertained for urinalysis results and meningitis status were included. <h3>Data Extraction and Synthesis</h3> Data were extracted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and used the Newcastle-Ottawa Scale to assess bias. Pooled prevalences and odds ratios (ORs) were estimated using random-effect models. <h3>Main Outcomes and Measures</h3> The primary outcome was the prevalence of culture-proven bacterial meningitis among infants with positive urinalysis results. The secondary outcome was the prevalence of bacterial meningitis, defined by CSF testing or suggestive history at clinical follow-up. <h3>Results</h3> The parent search yielded 3227 records; 48 studies were included (17 distinct data sets of 25 374 infants). The prevalence of culture-proven meningitis was 0.44% (95% CI, 0.25%-0.78%) among 2703 infants with positive urinalysis results compared with 0.50% (95% CI, 0.33%-0.76%) among 10 032 infants with negative urinalysis results (OR, 0.74; 95% CI, 0.39-1.38). The prevalence of bacterial meningitis was 0.25% (95% CI, 0.14%-0.45%) among 4737 infants with meningitis status ascertained by CSF testing or clinical follow-up and 0.28% (95% CI, 0.21%-0.36%) among 20 637 infants with positive and negative urinalysis results (OR, 0.89; 95% CI, 0.48-1.68). <h3>Conclusions and Relevance</h3> In this systematic review and meta-analysis, the prevalence of bacterial meningitis in well-appearing febrile infants 29 to 60 days of age with positive urinalysis results ranged from 0.25% to 0.44% and was not higher than that in infants with negative urinalysis results. These results suggest that for these infants, the decision to use LP should not be guided by urinalysis results alone.
Simultaneous Pneumopericardium and Pneumomediastinum following pericardiocentesis: an unusual condition
Authors: Ehsan Khalilipur
Journal: Clinical Cardiology and Cardiovascular Interventions (2021)

An 80-year-old lady was referred to our cardiology emergency department with complaints of increasing shortness of breath since 45 days earlier, which had gradually worsened over the last week. She had a history of chronic obstructive pulmonary disease, diabetes mellitus, hypertension and chronic kidney disease
Abstract 16503: Comparison of Management Strategies for the Neonate With Symptomatic Tetralogy of Fallot and Hypoplastic Branch Pulmonary Arteries: Results From the Congenital Catheterization Research Collaborative
Authors: Christopher J Petit, Mark Law, Andrew C Glatz, Paul Chai, Jennifer Romano, Jeffrey Zampi, Jeffery J Meadows, George Nicholson, Shabana Shahanavaz, Michael Kelleman, Courtney McCracken, Christopher Mascio, Sarosh P Batlivala, Ivor Asztalos, Alicia Kamsheh, Steven Healan, Justin Smith, Joelle A Pettus, Andrew Dailey Schwartz, James Raulston, Krissie Hock, Amy Pajk, Bryan H Goldstein
Journal: Circulation (2020)

Introduction: Symptomatic neonates with tetralogy of Fallot (sTOF) and hypoplastic branch pulmonary arteries (hPA) are at high risk. Management strategies include staged repair (SR) - initial palliation (IP) followed by later complete repair (CR) - or primary repair (PR). A balanced comparison of these approaches is needed in the sTOF neonate with hPA. Methods: Consecutive neonates with sTOF and hPA - defined as one hPA z-score &lt;-2.0 with contralateral z-score &lt;0 - who underwent SR or PR from 2005-17 were retrospectively reviewed by the Congenital Catheterization Research Collaborative. Primary outcome was mortality and secondary outcomes included component (IP, CR, PR) and cumulative (SR): hospital, ICU and surgical morbidities, and reintervention. Outcomes were compared between treatment strategies using propensity score adjustment (PSA) to account for baseline differences between groups (PR=reference group). Results: The cohort comprised 188 neonates including 121 SR (IP: 29 transcatheter; 54 surgery) and 67 PR patients. Presence of pulmonary atresia, lower gestational age and birthweight were more common in the SR cohort. Median right and left hPA z-scores were -2.19 (IQR -2.65, -1.92) and -2.33 (-2.84, -1.99), respectively. There were significant differences in treatment strategy across centers (p&lt;0.01). Overall survival was similar between groups, before (p=0.33) and after PSA (HR 1.91, 0.48-7.7, p=0.36). Reintervention was more common in the SR group overall (HR 1.7, 1.03-2.7, p=0.04), but there was no difference after definitive repair (HR 1.21, 0.71-2.0, p=0.49). Secondary outcomes are shown in Table 1. Conclusions: In this multicenter comparison of SR or PR for management of neonates with sTOF and hPA, after PSA, no difference in mortality was found. Neonatal morbidities largely favored the SR group, but cumulative morbidities and reintervention favored the PR group. Further study is needed to determine late impact of these early advantages to SR.
Abstract 16529: Frailty in Fontan Patients - A Sign of Premature Aging?
Authors: Erika Ouimet Grennan, Carlos Guerrero, Judith Therrien, Aihua Liu, Liming Guo, Jonathan Afilalo, Ariane J Marelli
Journal: Circulation (2020)

Introduction: Patients submitted to a Fontan operation sustain a lifelong state of reduced cardiac output and increased venous pressure potentially inducing premature aging. We hypothesize that Fontan patients, despite their young age, resemble more elderly patients compared to age-matched controls. Methods: At a tertiary care center, we evaluated 17 Fontan patients who had a recent abdominal CT scan for Fontan associated liver disease follow-up. Psoas muscle area (PMA), a recognized marker of frailty, was measured on the axial plane at the level of L4. The distributions of PMA scores were compared between Fontan and 1) patients undergoing a transcatheter aortic valve replacement (TAVR); and 2) an age-matched healthy cohort, separately with Kruskal-Wallis test. Results: The Fontan group comprised six males and 11 females aged 19-40. The proportions of systemic left ventricle and heterotaxy syndrome were 82% and 18% respectively in females and 33% and 33% respectively in males. The TAVR cohort included 241 males and 184 females aged 70-99. The healthy cohort enrolled 59 males and 66 females age-matched to the Fontan group. Among the Fontan patients, median and interquartile range of PMA were 18.1, 14.85-21.12 cm2 in females and 23.41, 22.25-30.21 cm2 in males. The comparison between the groups for males (Panel A) and females (Panel B) are illustrated in the Figure. Conclusions: Males Fontan appear to have reduced muscle mass that resembles more patients who are candidates for TAVR than aged-matched controls, an observation that, interestingly, was not seen in females in this small well-characterized cohort. To our knowledge, this is the first study to document a direct comparison of Fontan patients to other subgroups illustrating a mismatch between chronological and biological age in Fontan. Further studies are needed to elucidate the possible protective effect of female sex.
Comorbidity-Driven Risk across Preparative Regimens for Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Joshua Fein, Noga Shem-Tov, Ronit Yerushalmi, Ivetta Danylesko, Nadav Furie, Arie Apel, Avichai Shimoni, Arnon Nagler, Roni Shouval
Journal: Blood (2017)
BCR-ABL,Kit,PDGFRα,およびSrcキナーゼの野性型およびゲートキーパー変異に対する小分子II型阻害剤の発見:新規のゲートキーパー変異II型阻害剤 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Weisberg Ellen, Choi Hwan Geun, Ray Arghya, Barrett Rosemary, Zhang Jianming, Sim Taebo, Zhou Wenjun, Seeliger Markus, Cameron Michael, Azam Mohammed, A Fletcher Jonathan, Debiec-Rychter Maria, Mayeda Mark, Moreno Daisy, L Kung Andrew, Janne Pasi Antero, Khosravi-Far Roya, V Melo Junia, W Manley Paul, Adamia Sophia, WU Gatherine, Gray Nathanael, D Griffin James
Journal: Blood (2010)
Abstract P190: Social Isolation Associates With The Expression Of NKp46 On Natural Killer Cells Through A Relationship Partially Mediated By RANTES In African-American Women
Authors: Veronica C Gray, Briana S Turner, Cristhian A Gutierrez-Huerta, Sam Neally, Kaveri Curlin, Nithya Vijayakumar, Erika Ortiz-Chaparro, Brian A Tirado, Valerie Mitchell, Billy S Collins, Yvonne Baumer, Tiffany M Powell-Wiley
Journal: Circulation (2021)

Chronic exposure to psychosocial and environmental stressors (PSES) has been shown to increase risk for diabetes, obesity, and cardiovascular disease and alter immune cell distribution and function. In Natural Killer (NK) cells, the impact of PSES has been demonstrated by a loss of NK cell numbers or function and a shift in NK cell subpopulations. NKp46 is an activating receptor on NK cells crucial for NK cell function. In this study, we aimed to determine if PSES is associated with NKp46 expression. We recruited 27 African-American women (age 59.85±1.91; BMI 34.06±1.67), characterized NKp46 expression from blood samples using flow cytometry, and determined serum cytokine levels using Luminex. Furthermore, study participants answered questionnaires to determine various psychosocial measures, socioeconomic status (SES), and home address for neighborhood deprivation (NDI). First, we determined that social isolation significantly associated with NKp46 expression (β=-0.51, p=0.02), while NDI and SES did not. Second, we identified biomarkers associated with social isolation. Social isolation significantly associated with the cytokine RANTES (β=0.64, p=0.01) after adjustment for cardiovascular risk and BMI. Third, we determined that RANTES also associated with NKp46 expression after adjustment (β=-0.54, p=0.01). We performed a mediation analysis using structural equation modeling to determine if RANTES could be a potential biological mediator between social isolation and NKp46 expression levels; this revealed that RANTES mediates 51.07% of the association (Figure). Thus, our study highlights the importance of further understanding the impact of PSES on immune cells and inflammation. Work to unravel the biology of adversity is crucial to address health disparities. In the future, larger studies should be conducted to identify underlying signaling molecules and pathways altering NK cells during chronic PSES that accelerate disease development and progression and ultimately, serve as targets for intervention.
Abstract 17034: The AKT/AMPK/FOXO3 Axis in Pulmonary Arterial Hypertension
Authors: Yann Grobs, Charlotte romanet, Valerie Nadeau, Junichi Omura, Mark Orcholski, Tsukasa Shimauchi, Victoria Toro, Eve Tremblay, Alice Bourgeois, Roxane Paulin, Olivier BOUCHERAT, Sebastien Bonnet, Steeve Provencher
Journal: Circulation (2020)

Like cancer, pulmonary arterial hypertension (PAH) is characterized by exaggerated proliferation and resistance to apoptosis related to metabolic alterations (Warburg effect) of pulmonary smooth muscle cells (PASMCs). These anomalies result in a progressive narrowing of the pulmonary arteries, increasing pulmonary resistance and leading to right heart failure and premature death. In cancer cells, unphosphorylated and nuclear FOXO3 has been extensively studied as a crucial protein that functions as a tumor suppressor by regulating expression of genes involved in apoptosis and cell cycle arrest. These functions combined with other FOXO3 attributes, including its key role in communicating mitochondrial-nuclear signals, make the FOXO3 a suitable candidate for controlling the cancer-like phenotype of PAH-PASMCs. Interestingly, AKT and AMPK known to be implicated in PAH exert antagonistic effects on FOXO3; AKT promoting its nuclear exclusion while AMPK favors its nuclear and mitochondrial accumulation. The thus made the hypothesis that FOXO3’s nuclear exclusion (secondary to AKT/AMPK imbalance) promotes metabolic reprogramming towards glycolysis leading to enhanced proliferation/resistance to apoptosis of PAH-PASMCs and vascular remodeling. Using Western blot and immunofluorescence in isolated PASMCs from both PAH and control patients (n=10), we found that nuclear and mitochondrial exclusion of FOXO3 due to its phosphorylation is a feature of PAH-PASMCs. In vitro, we demonstrated that nuclear localization of FOXO3 using an adenovirus expressing a constitutively active, non-phosphorylable form of FOXO3 or trifluoperazine (TFP) resulted in reduced PAH-PASMC proliferation (Ki67 labeling, p&lt;0,0005) and resistance to apoptosis (Annexin V assay, p&lt;0,05). These effects were accompanied by increased expression of P27 and SOD2 and diminished expression of Survivin (p&lt;0,05). In vivo, we showed that FOXO3 activation using TPF improved established PAH in the monocrotaline rats (reduced RVSP and increased Sv and CO, by right catheterization, p&lt;0,01, n=29) without any sign of toxicity. We showed that FOXO3 is implicated in pulmonary vascular remodeling. Pharmacological activation of FOXO3 may represent a novel avenue to improve PAH.
Abstract 16174: Combined Mechanotransduction and Pharmacological Conditioning for Improved Therapeutic Angiogenesis of Mesenchymal Stem Cells
Authors: Andrew Sligar, Jason Lee, Kayla Henderson, Pablo Maceda, Miguel Armenta Ochoa, Eun Yoon, Lara Samarneh, Austin Veith, Mitchell Wong, Andrew Dunn, Aaron Baker
Journal: Circulation (2019)

Introduction: Stem cell therapies have immense potential for the treatment of cardiovascular disease. However, their full potential has not yet been realized in clinical trials due to limited effic...
Association of Rotavirus Vaccines With Reduction in Rotavirus Gastroenteritis in Children Younger Than 5 Years
Authors: Zi-Wei Sun, Yu Fu, Hai-Ling Lu, Rui-Xia Yang, Hemant Goyal, Ye Jiang, Hua-Guo Xu
Journal: JAMA Pediatrics (2021)

<h3>Importance</h3> Rotavirus vaccines have been introduced worldwide, and the clinical association of different rotavirus vaccines with reduction in rotavirus gastroenteritis (RVGE) after introduction are noteworthy. <h3>Objective</h3> To evaluate the comparative benefit, risk, and immunogenicity of different rotavirus vaccines by synthesizing randomized clinical trials (RCTs) and observational studies. <h3>Data Sources</h3> Relevant studies published in 4 databases: Embase, PubMed, the Cochrane Library, and Web of Science were searched until July 1, 2020, using search terms including "rotavirus" and "vaccin*." <h3>Study Selection</h3> Randomized clinical trials and cohort and case-control studies involving more than 100 children younger than 5 years that reported the effectiveness, safety, or immunogenicity of rotavirus vaccines were included. <h3>Data Extraction and Synthesis</h3> A random-effects model was used to calculate relative risks (RRs), odds ratios (ORs), risk differences, and 95% CIs. Adjusted indirect treatment comparison was performed to assess the differences in the protection of Rotarix and RotaTeq. <h3>Main Outcomes and Measures</h3> The primary outcomes were RVGE, severe RVGE, and RVGE hospitalization. Safety-associated outcomes involved serious adverse events, intussusception, and mortality. <h3>Results</h3> A meta-analysis of 20 RCTs and 38 case-control studies revealed that Rotarix (RV1) significantly reduced RVGE (RR, 0.316 [95% CI, 0.224-0.345]) and RVGE hospitalization risk (OR, 0.347 [95% CI, 0.279-0.432]) among children fully vaccinated; RotaTeq (RV5) had similar outcomes (RVGE: RR, 0.350 [95% CI, 0.275-0.445]; RVGE hospitalization risk: OR, 0.272 [95% CI, 0.197-0.376]). Rotavirus vaccines also demonstrated higher protection against severe RVGE. Additionally, no significant differences in the protection of RV1 and RV5 against rotavirus disease were noted in adjusted indirect comparisons. Moderate associations were found between reduced RVGE risk and Rotavac (RR, 0.664 [95% CI, 0.548-0.804]), Rotasiil (RR, 0.705 [95% CI, 0.605-0.821]), and Lanzhou lamb rotavirus vaccine (RR, 0.407 [95% CI, 0.332-0.499]). All rotavirus vaccines demonstrated no risk of serious adverse events. A positive correlation was also found between immunogenicity and vaccine protection (eg, association of RVGE with RV1: coefficient, −1.599; adjusted<i>R</i><sup>2</sup>, 99.7%). <h3>Conclusions and Relevance</h3> The high protection and low risk of serious adverse events for rotavirus vaccines in children who were fully vaccinated emphasized the importance of worldwide introduction of rotavirus vaccination. Similar protection provided by Rotarix and RotaTeq relieves the pressure of vaccines selection for health care authorities.
Reactor-based boron neutron capture therapy for 44 cases of recurrent and refractory high-grade meningiomas with long-term follow-up
Authors: Satoshi Takai, Masahiko Wanibuchi, Shinji Kawabata, Koji Takeuchi, Yoshinori Sakurai, Minoru Suzuki, Koji Ono, Shin-Ichi Miyatake
Journal: Neuro-Oncology (2021)

Abstract Background High-grade meningioma (HGM) is difficult to treat, and recurrent HGM after radiotherapy has an especially poor prognosis. We retrospectively analyzed the cases of 44 consecutive patients with recurrent and refractory HGM who were treated by reactor-based boron neutron capture therapy (BNCT). Methods In 2005–2019, we treated 44 recurrent and refractory HGMs by reactor-based BNCT. We analyzed the patients’ tumor shrinkage, overall survival (OS) after initial diagnosis, OS after BNCT, progression-free survival (PFS) post-BNCT, and treatment failure patterns. Results The median OS (mOS) after BNCT and mOS after initial diagnosis were 29.6 (95% CI: 16.1–40.4) and 98.4 (95% CI: 68.7–169.4) months, respectively. The median follow-up after BNCT was 26 (6.4–103) months. The grade 2 (20 cases) and 3 (24 cases) post-BNCT mOS values were 44.4 (95% CI: 27.4–not determined) and 21.55 (10.6–30.6) months, respectively (P = .0009). Follow-up images were obtained from 36 cases at &amp;gt;3 months post-BNCT; 35 showed tumor shrinkage during the observation period. The post-BNCT median PFS (mPFS) of 36 cases was 13.7 (95% CI: 8.3–28.6) months. The post-BNCT mPFS values in patients with grade 2 and 3 disease were 24.3 (95% CI: 9.8–not determined) and 9.4 (6.3–14.4) months, respectively (P = .0024). Local recurrence was observed in only 22.2% of cases. These results showed good local tumor control and prolonged survival for recurrent HGM cases. Conclusions Most of these cases had relatively large tumor volumes. The proportion of grade 3 patients was extremely high. Our patients thus seemed to have poor prognoses. Nevertheless, reactor-based BNCT exerted relatively good local control and favorable survival for recurrent and refractory HGMs.
The clinical role of host and bacterial-derived extracellular vesicles in pneumonia
Authors: Anna Lena Jung, Bernd Schmeck, Marie Wiegand, Katrin Bedenbender, Birke J. Benedikter
Journal: Advanced Drug Delivery Reviews (2021)

Pneumonia is among the leading causes of morbidity and mortality worldwide. Due to constant evolution of respiratory bacteria and viruses, development of drug resistance and emerging pathogens, it constitutes a considerable health care threat. To enable development of novel strategies to control pneumonia, a better understanding of the complex mechanisms of interaction between host cells and infecting pathogens is vital. Here, we review the roles of host cell and bacterial-derived extracellular vesicles (EVs) in these interactions. We discuss clinical and experimental as well as pathogen-overarching and pathogen-specific evidence for common viral and bacterial elicitors of community- and hospital-acquired pneumonia. Finally, we highlight the potential of EVs for improved management of pneumonia patients and discuss the translational steps to be taken before they can be safely exploited as novel vaccines, biomarkers, or therapeutics in clinical practice.