bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-S100A4 Antibody Therapy Is Efficient in Treating Aggressive Prostate Cancer and Reversing Immunosuppression: Serum and BiopsyS100A4as a Clinical Predictor
Authors: Ganaie Arsheed A. , Mansini Adrian P. , Hussain Tabish , Rao Arpit , Siddique Hifzur R. , Shabaneh Ashraf , Ferrari Marina G. , Murugan Paari , Klingelhöfer Jörg , Wang Jinhua , Ambartsumian Noona , Warlick Christopher A. , Konety Badrinath R. , Saleem Mohammad 
Published: September 2020

AbstractS100A4 oncoprotein plays a critical role during prostate cancer progression and induces immunosuppression in host tissues. We hypothesized that S100A4-regulated oncogenic activity in immunosuppressed prostate tumors promotes growth of neoplastic cells, which are likely to become aggressive. In the current study, we investigated whether biopsy-S100A4 gene alteration independently predicts the outcome of disease in patients and circulatory-S100A4 is druggable target for treating immunosuppressive prostate cancer. Aided by DECIPHER-genomic test, we show biopsy-S100A4 overexpression as predictive of (i) poor ADT response and (ii) high risk of mortality in 228 radical prostatectomy-treated patients. Furthermore, analysis of tumor genome data of more than 1,000 patients with prostate cancer (PRAD/SU2C/FHCRC studies) validated the association of S100A4-alteration to poor survival and metastasis. We show that increased serum-S100A4 levels are associated to the prostate cancer progression in patients. The prerequisite for metastasis is the escape of tumor cells via vascular system. We show that extracellular-S100A4 protein as a growth factor induces vascular transmigration of prostate cancer cells and bone demineralization thus forms an ideal target for therapies for treating prostate cancer. By employing surface plasmon resonance and isothermal titration calorimetry, we show that mab6B12 antibody interacts with and neutralizes S100A4 protein. When tested for therapeutic efficacy, the mab6B12 therapy reduced the (i) osteoblastic demineralization of bone-derived MSCs, (ii) S100A4-target (NFκB/MMP9/VEGF) levels in prostate cancer cells, and (iii) tumor growth in a TRAMPC2 syngeneic mouse model. The immuno-profile analysis showed that mAb6B12-therapy (i) shifted Th1/Th2 balance (increased Stat4+/T-bet+ and decreased GATA2+/CD68+/CD45+/CD206+ cells); (ii) modulated cytokine levels in CD4+ T cells; and (iii) decreased levels of IL5/6/12/13, sTNFR1, and serum-RANTES. We suggest that S100A4-antibody therapy has clinical applicability in treating immunosuppressive prostate cancer in patients.
Association of Common Use Pharmaceuticals in Reducing Risk of Esophageal Adenocarcinoma: A SEER–Medicare Analysis
Authors: Loomans-Kropp Holli A. , Chaloux Matthew , Richmond Ellen , Umar Asad 
Published: September 2020

Abstract
Barrett's esophagus (BE), a recognized risk factor for esophageal adenocarcinoma (EAC), is routinely managed with proton pump inhibitors (PPIs) when symptomatic. Several lines of evidence suggest that PPIs may prevent malignant transformation. Chronic use of other common drugs, namely, statins nonsteroidal anti-inflammatory drugs (NSAIDs) and metformin, may also interfere with BE carcinogenesis, but confirmatory evidence is lacking. We identified 1,943 EAC cases and 19,430 controls (matched 10:1) between 2007 and 2013 that met our specified inclusion criteria in the SEER–Medicare database. Conditional logistic regression was used to generate odds ratios (OR) and 95% confidence intervals (95% CI). Wald χ2 tests were used to assess significance of covariates. Compared with controls, EAC cases had a higher prevalence of BE (26.2%). Use of PPIs, NSAIDs, statins, or metformin reduced the odds of EAC (PPIs: 0.10; 95% CI, 0.09–0.12; NSAIDs: 0.62; 95% CI, 0.51–0.74; statins: 0.15; 95% CI, 0.13–0.17; metformin: 0.76; 95% CI, 0.62–0.93). When stratified by BE, these associations persisted, though no association was found between NSAID use and EAC risk for participants with BE. Dual use of PPIs with NSAIDs or statins, and NSAID, statin, or metformin use alone also showed significant EAC risk reduction among all participants and those without BE. Use of PPIs alone and with NSAIDs, statins, or metformin was associated with reduced risk of EAC; however, a history of BE may diminish drug efficacy. These results indicate that common pharmacologic agents alone or in combination may decrease EAC development.
Prevention Relevance: The use of common drugs, such as proton pump inhibitors, statins, non-steroidal anti-inflammatory drugs, or metformin, may reduce one's risk of developing esophageal adenocarcinoma. These results suggest that repurposing agents often used for common chronic conditions may be a new strategy for cancer prevention efforts.
Cardiac Inflammation Impedes Response to Cardiac Resynchronization Therapy in Patients With Idiopathic Dilated Cardiomyopathy
Authors: Verdonschot Job A.J. , Merken Jort J. , van Stipdonk Antonius M.W. , Pliger Philipp , Derks Kasper W.J. , Wang Ping , Henkens Michiel T.H.M. , van Paassen Pieter , Abdul Hamid Myrurgia A. , van Empel Vanessa P.M. , Knackstedt Christian , Luermans Justin G.L.M. , Crijns Harry J.G.M. , Brunner-La Rocca Hans-Peter , Brunner Han G. , Poelzl Gerhard , Vernooy Kevin , Heymans Stephane R.B. , Hazebroek Mark R. 
Published: September 2020

Background:
Cardiac resynchronization therapy (CRT) is an established therapy in patients with dilated cardiomyopathy (DCM) and conduction disorders. Still, one-third of the patients with DCM do not respond to CRT. This study aims to depict the underlying cardiac pathophysiological processes of nonresponse to CRT in patients with DCM using endomyocardial biopsies.

Methods:

Within the Maastricht and Innsbruck registries of patients with DCM, 99 patients underwent endomyocardial biopsies before CRT implantation, with histological quantification of fibrosis and inflammation, where inflammation was defined as >14 infiltrating cells/mm
2
. Echocardiographic left ventricular end-systolic volume reduction ≥15% after 6 months was defined as response to CRT. RNA was isolated from cardiac biopsies of a representative subset of responders and nonresponders.

Results:

Sixty-seven patients responded (68%), whereas 32 (32%) did not respond to CRT. Cardiac inflammation before implantation was negatively associated with response to CRT (25% of responders, 47% of nonresponders; odds ratio 0.3 [0.12–0.76];
P
=0.01). Endomyocardial biopsies fibrosis did not relate to CRT response. Cardiac inflammation improved the robustness of prediction beyond well-known clinical predictors of CRT response (likelihood ratio test
P
<0.001). Cardiac transcriptomic profiling of endomyocardial biopsies reveals a strong proinflammatory and profibrotic signature in the hearts of nonresponders compared with responders. In particular,
COL1A1, COL1A2, COL3A1, COL5A1, POSTN, CTGF, LOX, TGFβ1, PDGFRA, TNC, BGN
, and
TSP2
were significantly higher expressed in the hearts of nonresponders.

Conclusions:
Cardiac inflammation along with a transcriptomic profile of high expression of combined proinflammatory and profibrotic genes are associated with a poor response to CRT in patients with DCM.
Development of Helical Myofiber Tracts in the Human Fetal Heart: Analysis of Myocardial Fiber Formation in the Left Ventricle From the Late Human Embryonic Period Using Diffusion Tensor Magnetic Resonance Imaging
Authors: Nishitani Saori , Torii Narisa , Imai Hirohiko , Haraguchi Ryo , Yamada Shigehito , Takakuwa Tetsuya 
Published: September 2020

Background
Detection of the fiber orientation pattern of the myocardium using diffusion tensor magnetic resonance imaging lags ≈12 weeks of gestational age (WGA) behind fetal myocardial remodeling with invasion by the developing coronary vasculature (8 WGA). We aimed to use diffusion tensor magnetic resonance imaging tractography to characterize the evolution of fiber architecture in the developing human heart from the later embryonic period.

Methods and Results
Twenty human specimens (8–24 WGA) from the Kyoto Collection of Human Embryos and Fetuses, including specimens from the embryonic period (Carnegie stages 20–23), were used. Diffusion tensor magnetic resonance imaging data were acquired with a 7T magnetic resonance system. Fractional anisotropy and helix angle were calculated using standard definitions. In all samples, the fibers ran helically in an organized pattern in both the left and right ventricles. A smooth transmural change in helix angle values (from positive to negative) was detected in all 16 directions of the ventricles. This feature was observed in almost all small (Carnegie stage 23) and large samples. A higher fractional anisotropy value was detected at the outer side of the anterior wall and septum at Carnegie stage 20 to 22, which spread around the ventricular wall at Carnegie stage 23 and in the early fetal samples (11–12 WGA). The fractional anisotropy value of the left ventricular walls decreased in samples with ≥13 WGA, which remained low (≈0.09) in larger samples.

Conclusions
From the human late embryonic period (from 8 WGA), the helix angle arrangement of the myocardium is comparable to that of the adult, indicating that the myocardial structure blueprint, organization, and integrity are already formed.
The Anomalous Sun
Authors: Gessner Samuel , Korey Michael , Gaulke Karsten 
Published: September 2020

Abstract
Four clockwork-driven planetary automata built to show the true motion of the planets according to Ptolemaic theory, not just their mean motion, survive from the sixteenth century: one each in Paris, Vienna, Kassel, and Dresden. Close, on-site examination of their mechanisms by a team of historians of science and clockmakers has gone beyond existing accounts and revealed that, though they share a common aim, the machines differ fundamentally in their realization of even the “simplest” of the planetary motions, namely that of the Sun. Indeed, three different ways have been detected for producing the solar anomaly, the Sun’s non-uniform motion along the ecliptic in the course of a year. The oldest of the surviving machines (Paris) uses the uniform motion of an eccentric gear, another (Vienna) adapts what would be a geometrically equivalent epicycle, and the two other machines (Kassel and Dresden) make use of a centered gear with non-uniformly spaced teeth. This paper discusses these findings in detail. It argues that such differing approaches not only reflect varying degrees of collaboration among the actors involved in the construction of these four technical masterpieces – princely commissioners, learned astronomers, and artful craftsmen (with these categories sometimes overlapping) – but also that they offer a further, mechanical contribution to the centuries-old reception and refinement of Ptolemaic planetary theory.
Lunar Crater Models
Authors: Devoy Louise E. 
Published: September 2020

Abstract
This article traces the story of three amateur astronomers who created relief models to help them depict the changing illumination of certain lunar craters, examples of which can be found in UK museum collections today. English chemist Henry Blunt (1806–1853) adopted the emerging technology of electrotyping to reproduce and distribute his plaster model of the Eratosthenes crater to a wider audience. Scottish industrial engineer James Nasmyth (1808–1890) used a combination of drawing, modelling and photography to support his thesis on the volcanic origin of lunar craters in his popular book The Moon Considered … (1874). Spanish sculptor Dionis Renart (1878–1946) produced a series of plaster models for the Exposición General De Estudios Lunares (1912) that eventually came to Greenwich via the British selenographer Hugh Percy Wilkins (1896–1960). These three case studies provide us with valuable insights into the rationale behind the production, use and distribution of lunar crater models within amateur and popular astronomy.
To Boldly Remember Where We Have Already Been
Authors: Moir Nathaniel L. 
Published: September 2020

Abstract
This article revisits the Cutter Incident in the United States in April 1955 when mass-produced doses of polio vaccine containing insufficiently inactivated (killed) live polio virus were released to the U.S. public. The Cutter Incident also affected subsequent vaccine development and these lessons remain relevant in the international quest to create a rapidly developed vaccine for COVID-19. The Cutter Incident shows how things can go wrong when a vaccine is manufactured in haste and without adequate safety precautions during mass-production. In the article’s later section, liability without fault, among other consequences resulting from the incident, are also assessed in the context of current vaccine development through Operation Warp Speed, the public-private partnership funded by the U.S. government to develop a remedy for COVID-19.
Concomitant Traumatic Brain Injury and Hemorrhagic Shock: Outcomes Using the Spanish Trauma ICU Registry (RETRAUCI)
Authors: Chico-Fernández Mario , Barea-Mendoza Jesús A. , Pérez-Bárcena Jon , García-Sáez Iker , Quintana-Díaz Manuel , Marina Luis , Mayor-García Dolores M. , Serviá-Goixart Luis , Jiménez-Moragas José M. , Llompart-Pou Juan A. 
Published: September 2020

Background To compare the main outcomes of trauma patients with and without traumatic brain injury (TBI), hemorrhagic shock, and the combination of both using data from the Spanish trauma intensive care unit (ICU) registry (RETRAUCI). Methods Patients admitted to the participating ICUs from March 2015 to May 2019 were included in the study. The main outcomes were analyzed according to the presence of TBI, hemorrhagic shock, and/or both. Comparison of groups with quantitative variables was performed using the Kruskal-Wallis test, and differences between groups with categorical variables were compared using the Chi-square test or Fisher’s exact test as appropriate. A P value <.05 was considered significant. Results Overall, 310 patients (3.98%) were presented with TBI and hemorrhagic shock. Patients with TBI and hemorrhagic shock received more red blood cell (RBC) concentrates, fresh frozen plasma (FFP), a higher ratio FFP/RBC, and had a higher incidence of trauma-induced coagulopathy (60%) ( P < .001). These patients had higher mortality ( P < .001). Intracranial hypertension was the leading cause of death (50.4%). Conclusions Concomitant TBI and hemorrhagic shock occur in nearly 4% of trauma ICU patients. These patients required a higher amount of RBC concentrates and FFP and had an increased mortality.
A Contemporary Analysis of Delayed Diagnoses After Traumatic Injury
Authors: Hatchimonji Justin S. , Sharoky Catherine E. , Kaufman Elinore J. , Ma Lucy W. , Garcia Whitlock Anna E. , Smith Brian P. , Holena Daniel N. 
Published: September 2020

Background Factors associated with delayed injury diagnosis (DID) have been examined, but incompletely researched. Methods We evaluated demographics, mechanism, and measures of mental status and injury severity among 10 years’ worth of adult trauma patients at our center for association with DID in a multivariable regression model. Descriptions of DID injuries were reviewed to highlight characteristics of these injuries. Results We included 13 509 patients, 89 (0.7%) of whom had a recognized DID. In regression analysis, ISS (OR 1.04 per point, 95% CI 1.02-1.06) and number of injuries (OR 1.08 per injury, 95% CI 1.04-1.11) were associated with DID. Operative patients had twice the odds of DID (OR 2.02, 95% CI 1.18-3.44). The most common category of DID was orthopedic extremity injury (22/89). Conclusion DID is associated with injury severity and operative intervention. This suggests that the presence of an injury requiring operation may distract the trauma team from additional injuries.
Neuroprotective effect of apigenin against cerebral ischemia/reperfusion injury
Authors: Ling Chengli , Lei Chang , Zou Manshu , Cai Xiong , Xiang Yun , Xie Yu , Li Xuran , Huang Dan , Wang Yuhong 
Published: September 2020

Objective The therapeutic efficacy of apigenin in PC12 cells and rats remains uncertain. The aim of this study was to investigate the neuroprotective effects of apigenin against cerebral ischemia/reperfusion injury, both in vitro and in vivo. Methods We first treated PC12 cells with cobalt chloride (CoCl2) to create a model of oxidative stress injury. Cell viability was then determined using a multifunctional microplate reader. In addition, reactive oxygen species (ROS) levels, apoptosis, and mitochondrial membrane potentials (MMPs) were examined using high-content cytometer analysis. The efficacy of apigenin treatment was also analyzed in a rat middle cerebral artery occlusion (MCAO) model using TTC staining and neurological deficit scores. Results The half-inhibitory concentration of CoCl2 was 1.2 mM. Pretreatment with 10 µg ⋅ mL−1 apigenin significantly enhanced cell viability, reduced ROS levels, alleviated apoptosis, and improved MMP in PC12 cells with CoCl2-induced injury in vitro. In addition, apigenin treatment in vivo significantly improved neurological deficit scores and reduced infarct areas in MCAO rats. These results suggest that the neuroprotective mechanisms of apigenin may be related to mitochondrial activation. Conclusions Apigenin had excellent neuroprotective effects for the treatment of cerebral ischemia/reperfusion injury in vitro and in vivo.
Prevalence of Overweight and Obesity Among Children Enrolled in Head Start, 2012–2018
Authors: Imoisili Omoye , Dooyema Carrie , Kompaniyets Lyudmyla , Lundeen Elizabeth A. , Park Sohyun , Goodman Alyson B. , Blanck Heidi M. 
Published: September 2020

Purpose: Determine prevalence of overweight and obesity as reported in Head Start Program Information Reports. Design: Serial cross-sectional census reports from 2012–2018. Setting: Head Start programs countrywide, aggregated from program level to state and national level. Subjects: Population of children enrolled in Head Start with reported weight status data. Measures: Prevalence of overweight (body mass index [BMI] ≥85th percentile to <95th percentile) and obesity (BMI ≥95th percentile). Analysis: Used descriptive statistics to present the prevalence of overweight and obesity by state. Performed unadjusted regression analysis to examine annual trends or average annual changes in prevalence. Results: In 2018, the prevalence of overweight was 13.7% (range: 8.9% in Alabama to 20.4% in Alaska). The prevalence of obesity was 16.6% (range: 12.5% in South Carolina to 27.1% in Alaska). In the unadjusted regression model, 34 states and the District of Columbia did not have a linear trend significantly different from zero. There was a statistically significant positive trend in obesity prevalence for 13 states and a negative trend for 3 states. Conclusion: The prevalence of obesity and overweight in Head Start children remained stable but continues to be high. Head Start reports may be an additional source of surveillance data to understand obesity prevalence in low-income young children.
Healthcare failure mode and effect analysis in the chemotherapy preparation process
Authors: Pueyo-López Cristina , Sánchez-Cuervo Marina , Vélez-Díaz-Pallarés Manuel , Ortega-Hernández-Agero Teresa , Salazar-López de Silanes Esther Gómez de 
Published: September 2020

Purpose To conduct a Health Care Failure Mode and Effects Analysis (HFMEA) of the chemotherapy preparation process to identify the steps with the potential to cause errors, and to develop further strategies to improve the process and thus minimize the risk of errors. Methods An HFMEA was conducted to identify and reduce preparation errors during the chemotherapy preparation process. A multidisciplinary team mapped the preparation process, formally identified all the steps, and then conducted a brainstorming session to determine potential failure modes and their potential effects. A severity and probability score for each failure mode, a hazard score (HS) and a total HS were calculated. A hazard analysis was conducted for each HS equal to or more than 8. Finally, an action plan was identified for each failure mode. After the action plan was implemented, failure modes were revaluated and a new HS score was calculated as well as the percentage decrease in risk. Results The team identified five main steps in the chemotherapy preparation process and nine potential failure modes. After implementing the control measures, all the HSs decreased. The total HS associated with the chemotherapy preparation process decreased from 54 to 26 (-52%). This reduction in the total HS was mainly achieved by updating the Standard Operating Procedures (SOPs) and implementing bar code and gravimetric control system. Conclusion The application of HFMEA to the chemotherapy preparation process in centralized chemotherapy units can be very useful in identifying actions aimed at reducing errors in the healthcare setting.
Can School Mental Health Providers Deliver Psychosocial Treatment Improving Youth Attention and Behavior in Mexico? A Pilot Randomized Controlled Trial of CLS-FUERTE
Authors: Haack Lauren Marie , Araujo Eva Angelina , Meza Jocelyn , Friedman Lauren M. , Spiess Madeline , Alcaraz Beltrán Dulce Karely , Delucchi Kevin , Mojardín Herladez Ambrocio , Pfiffner Linda 
Published: September 2020

Background: Despite well-established Evidence-Based Treatments (EBTs) for Attention-Deficit/Hyperactivity Disorder (ADHD) and Oppositional Defiant Disorder (ODD), many low-resource settings lack EBT access. Methods: We conducted a school-clustered randomized controlled pilot of CLS-FUERTE (a multicomponent behavioral EBT adapted for children in Mexico) with 58 students. We randomly assigned four schools to receive CLS-FUERTE and four to receive school services as usual. We compared groups post-treatment on parent- and teacher-rated ADHD/ODD symptoms and impairment. Results: CLS-FUERTE fidelity, attendance, engagement, and acceptability was high and students receiving CLS-FUERTE showed greater improvement in teacher-rated ADHD, ODD, and impairment, as well as parent-rated ADHD and impairment, compared to students receiving usual services. Conclusions: Pilot results suggest that psychosocial EBTs can be successfully implemented by School Mental Health Providers in Mexico.
From Interpretation to Protection: Is There a Theoretical Basis?
Authors: Ham Sam H. 
Published: September 2020

Perhaps the most oft-cited phrase in all the interpretation literature is a sentence written by an anonymous U.S. National Park Service ranger in an obscure administrative manual a half century ago: Through interpretation, understanding; through understanding, appreciation; through appreciation, protection. When Freeman Tilden quoted the manual in Interpreting Our Heritage, little did he know that those few words would evolve into a philosophical orientation around which interpreters all across the globe would soon rally. In this article, Tilden's claim is reexamined in light of contemporary cognitive and social psychology. Does the chain of events Tilden describes really stand up, or is it just a nice, warm, and fuzzy phrase? Is there a substantiated theoretical basis for claiming that “interpretation” can create a kind of “understanding” that would indeed lead people to “protect” the places they visit? According to the weight of evidence from cognitive science, the answer is yes.