bluuebunny/crossref_metadata_2025_split huggingface dataset:
Earth science as a philosophical background to medicine: an essay based on the autobiography of Dr Otto Sperling (1602–81)
Authors: Hoch Ella 
Published: April 2017

Abstract

Earth science was not taught in schools in the seventeenth century. Geology began in principle with Steno's
Prodromus
of 1669, which reflected tendencies in the European curiosity about nature, but had little contemporary impact. As a child in busy Protestant Hamburg, Otto Sperling was influenced by Renaissance ideas in the early 1600s and investigated plants with his family's encouragement; he continued in pharmacy and later in medicine in Leiden. As a student he visited the relatively strong medicine milieu in Copenhagen and had the opportunity to sail as a participant in King Christian IV's official visit to Bergen. Venturing into southern Norway's mountainous landscapes, he studied plants, animals and rocks. Sperling's nature studies continued on journeys in northern and southern Europe and he graduated as
Doctor medicinae
in Padova in 1627.
En route
towards England, his ship was driven to Norway, where the locals persuaded him to settle as a physician. An encounter with the Danish nobleman Corfitz Ulfeldt (1606–64) took Sperling to some of the highest medical posts and later, during Denmark–Norway's decline, dragged him into the political maelstrom. Sperling's autobiography, written in his late sixties in a Copenhagen prison, is testimony to the importance of Earth science to Sperling's philosophy and performance as a doctor.
Multifunctional Telodendrimer Nanocarriers Restore Synergy of Bortezomib and Doxorubicin in Ovarian Cancer Treatment
Authors: Wang Lili , Shi Changying , Wright Forrest A. , Guo Dandan , Wang Xu , Wang Dongliang , Wojcikiewicz Richard J.H. , Luo Juntao 
Published: April 2017

AbstractWe have developed multifunctional nanoparticles for codelivery of bortezomib and doxorubicin to synchronize their pharmacokinetic profiles and synergize their activities in solid tumor treatment, a need still unmet in the clinic. Micellar nanoparticles were formed by a spatially segregated, linear-dendritic telodendrimer containing three segments: a hydrophilic polyethylene glycol (PEG), a bortezomib-conjugating intermediate, and a dendritic doxorubicin-affinitive interior. Bortezomib-conjugated telodendrimers, together with doxorubicin, self-assembled into monodispersed micelles [NP(BTZ-DOX)] with small particle sizes (20–30 nm) for dual drug delivery. NP(BTZ-DOX) displayed excellent drug-loading capacity and stability, which minimized premature drug leakage and synchronized drug release profiles. Bortezomib release was accelerated significantly by acidic pH, facilitating drug availability in the acidic tumor microenvironment. Synergistic anticancer effects of combined bortezomib and doxorubicin were observed in vitro against both multiple myeloma and ovarian cancer cells. NP(BTZ-DOX) prolonged payload circulation and targeted tumors in vivo efficiently with superior signal ratios of tumor to normal organs. In vitro and in vivo proteasome inhibition analysis and biodistribution studies revealed decreased toxicity and efficient intratumoral bortezomib and doxorubicin delivery by nanoformulation. NP(BTZ-DOX) exhibited significantly improved ovarian cancer treatment in SKOV-3 xenograft mouse models in comparison with free drugs and their combinations, including bortezomib and Doxil. In summary, tumor-targeted and synchronized delivery system elicits enhanced anticancer effects and merits further development in the clinical setting. Cancer Res; 77(12); 3293–305. ©2017 AACR.
Blind SELEX Approach Identifies RNA Aptamers That Regulate EMT and Inhibit Metastasis
Authors: Yoon Sorah , Armstrong Brian , Habib Nagy , Rossi John J. 
Published: April 2017

Abstract
Identifying targets that are exposed on the plasma membrane of tumor cells, but expressed internally in normal cells, is a fundamental issue for improving the specificity and efficacy of anticancer therpeutics. Using blind cell Systemic Evolution of Ligands by EXponetial enrichment (SELEX), which is untargeted SELEX, we have identified an aptamer, P15, which specifically bound to the human pancreatic adenocarcinoma cells. To identify the aptamer binding plasma membrane protein, liquid chromatography tandem mass spectrometry (LC-MS/MS) was used. The results of this unbiased proteomic mass spectrometry approach identified the target of P15 as the intermediate filament vimentin, biomarker of epithelial–mesenchymal transition (EMT), which is an intracellular protein but is specifically expressed on the plasma membrane of cancer cells. As EMT plays a pivotal role to transit cancer cells to invasive cells, tumor cell metastasis assays were performed in vitro. P15-treated pancreatic cancer cells showed the significant inhibition of tumor metastasis. To investigate the downstream effects of P15, EMT-related gene expression analysis was performed to identify differently expressed genes (DEG). Among five DEGs, P15-treated cells showed the downregulated expression of matrix metallopeptidase 3 (MMP3), which is involved in cancer invasion. These results, for the first time, demonstrate that P15 binding to cell surface vimentin inhibits the tumor cell invasion and is associated with reduced MMP3 expression. Thus, suggesting that P15 has potential as an anti-metastatic therapy in pancreatic cancer.
Implications: This study reveals that anti-vimentin RNA aptamers selected via blind-SELEX inhibit the tumor cell metastasis. Mol Cancer Res; 15(7); 811–20. ©2017 AACR.
Bioactivity of Oral Linaclotide in Human Colorectum for Cancer Chemoprevention
Authors: Weinberg David S. , Lin Jieru E. , Foster Nathan R. , Della'Zanna Gary , Umar Asad , Seisler Drew , Kraft Walter K. , Kastenberg David M. , Katz Leo C. , Limburg Paul J. , Waldman Scott A. 
Published: April 2017

Abstract
Guanylate cyclase C (GUCY2C) is a tumor-suppressing receptor silenced by loss of expression of its luminocrine hormones guanylin and uroguanylin early in colorectal carcinogenesis. This observation suggests oral replacement with a GUCY2C agonist may be an effective targeted chemoprevention agent. Linaclotide is an FDA-approved oral GUCY2C agonist formulated for gastric release, inducing fluid secretion into the small bowel to treat chronic idiopathic constipation. The ability of oral linaclotide to induce a pharmacodynamic response in epithelial cells of the colorectum in humans remains undefined. Here, we demonstrate that administration of 0.87 mg of oral linaclotide daily for 7 days to healthy volunteers, after oral colon preparation with polyethylene glycol solution (MoviPrep), activates GUCY2C, resulting in accumulation of its product cyclic (c)GMP in epithelial cells of the cecum, transverse colon, and distal rectum. GUCY2C activation by oral linaclotide was associated with homeostatic signaling, including phosphorylation of vasodilator-stimulated phosphoprotein and inhibition of proliferation quantified by reduced Ki67-positive epithelial cells. In the absence of the complete oral colonoscopy preparation, linaclotide did not alter cGMP production in epithelial cells of the colorectum, demonstrating that there was an effect related to the laxative preparation. These data show that the current FDA-approved formulation of oral linaclotide developed for small-bowel delivery to treat chronic idiopathic constipation is inadequate for reliably regulating GUCY2C in the colorectum to prevent tumorigenesis. The study results highlight the importance of developing a novel GUCY2C agonist formulated for release and activity targeted to the large intestine for colorectal cancer prevention. Cancer Prev Res; 10(6); 345–54. ©2017 AACR.
Tollip Deficiency Alters Atherosclerosis and Steatosis by Disrupting Lipophagy
Authors: Chen Keqiang , Yuan Ruoxi , Zhang Yao , Geng Shuo , Li Liwu 
Published: April 2017

Background
Compromised lipophagy with unknown mechanisms may be critically involved in the intracellular accumulation of lipids, contributing to elevated atherosclerosis and liver steatosis. We hypothesize that toll‐interacting protein (Tollip), a key innate immune molecule involved in the fusion of autolysosome, may play a significant role in lipophagy and modulate lipid accumulation during the pathogenesis of atherosclerosis and liver steatosis.

Methods and Results

By comparing mice fed with either a Western high‐fat diet or a regular chow diet, we observed that both atherosclerosis and liver steatosis were aggravated in apolipoprotein E–deficient (ApoE
−/−
)/Tollip
−/−
mice as compared with ApoE
−/−
mice. Through electron microscopy analyses, we observed compromised fusion of lipid droplets with lysosomes within aortic macrophages as well as liver hepatocytes from ApoE
−/−
/Tollip
−/−
mice as compared with ApoE
−/−
mice. As a molecular indicator for disrupted lysosome fusion, the levels of p62 were significantly elevated in aortic and liver tissues from ApoE
−/−
/Tollip
−/−
mice. Molecules involved in facilitating lipophagy completion such as Ras‐related protein 7 and gamma‐aminobutyric acid receptor‐associated protein were reduced in ApoE
−/−
/Tollip
−/−
mice as compared with ApoE
−/−
mice. Intriguingly, ApoE
−/−
/Tollip
−/−
mice had reduced circulating levels of inflammatory cytokines such as tumor necrosis factor‐α and increased levels of transforming growth factor‐β. The reduced inflammation due to Tollip deficiency is consistent with a stable atherosclerotic plaque phenotype with increased levels of plaque collagen and smooth muscle cells in ApoE
−/−
/Tollip
−/−
mice.

Conclusions
Tollip deficiency selectively leads to enlarged yet stable atherosclerotic plaques, increased circulating lipids, liver steatosis, and reduced inflammation. Compromised lipophagy and reduced expression of inflammatory mediators due to Tollip deficiency may be the underlying causes. Our data suggest that lipid accumulation and inflammation may be intertwined yet independent processes during the progression of atherosclerosis and steatosis.
Phanera larseniana (Leguminosae: Cercidoideae), a new species from Thailand
Authors: CHANTARANOTHAI PRANOM , MATTAPHA SAWAI , WANGWASIT KHANIT 
Published: April 2017

Phanera larseniana, a new species from north–eastern Thailand, is described and illustrated. It most closely resembles P. rubro-villosa but differs in the length of the floral parts, and in the number and position of the staminodes. The species is known only from a single locality in north-eastern Thailand. An illustration and photos of the new species are provided.
The impact of a multi-component physical activity programme in low-income elementary schools
Authors: Massey William V , Stellino Megan B , Holliday Megan , Godbersen Travis , Rodia Rachel , Kucher Greta , Wilkison Megan 
Published: April 2017

Objective: To identify the effects of a structured and multifaceted physical activity and recess intervention on student and adult behaviour in school. Design: Mixed-methods and community-based participatory approach. Setting: Large, urban, low-income school district in the USA. Methods: Data were collected at three time points over a 1-year period. Sources included recess observations at four elementary schools, in-class behavioural observations of fifth-grade students ( n = 21) and focus groups with fourth- and fifth-grade students ( n = 75). Results: Results suggested an increased amount of positive interactions between adults and students and a decreased amount of conflict in the playground post intervention. Results also suggested that a peer-leadership training programme had beneficial effects on students’ classroom behaviour. Conclusion: Results from this study provide evidence that school recess can be used to teach social–emotional competencies that can impact student behaviour during recess and in the classroom.
A Population‐Based Analysis of Survival for Sinonasal Rhabdomyosarcoma
Authors: Unsal Aykut A. , Chung Sei Yeon , Unsal Aylin B. , Baredes Soly , Eloy Jean Anderson 
Published: April 2017

ObjectivesLiterature detailing factors affecting survival in sinonasal rhabdomyosarcoma (SNRMS) is limited due to its rarity. We analyze the demographics, potential prognostic factors, overall survival, and treatment efficacy of SNRMS.Study Design and SettingAdministrative database study.MethodsSNRMS was queried in the SEER database (1973‐2013; Surveillance, Epidemiology, and End Results). Data were analyzed for demographic and clinicopathologic trends. Kaplan‐Meier model was utilized for assessing survival.ResultsA total of 286 cases of SNRMS were identified. The median age at diagnosis was 24.5 years, and the mean tumor size was 5.1 cm. Overall 5‐, 10‐, and 20‐year disease‐specific survival was 35.1%, 25.4%, and 12.0%, respectively. Regional lymph node involvement was present at diagnosis in more than half of cases (54.3%) and distant metastasis in 32.2% of cases. Alveolar rhabdomyosarcoma (54.9%) and embryonal rhabdomyosarcoma (23.8%) were the primary histologies. Alveolar‐type SNRMS was more likely than the embryonal type to metastasize to distant sites (41.7% vs 24.1%), and it possessed poorer 5‐year survival (29.2% vs 45.6%). Distant metastasis decreased 5‐year survival from 35.1% to 3.8%, whereas lymph node involvement did not significantly affect survival. Patients <10 years old had the highest survival rates. Primary tumor origin by subsite did not significantly affect survival. Smaller tumor sizes and earlier Intergroup Rhabdomyosarcoma Study Group stages were associated with improved outcomes. Surgical therapy had the highest survival rates.ConclusionSNRMS has overall poorer prognosis than all other parameningeal rhabdomyosarcomas studied. Age <10 years, smaller tumor sizes, lack of distant metastasis, localized tumors, earlier Intergroup Rhabdomyosarcoma Study Group stages, and embryonal histology were all associated with improved outcomes.
Titanium Ossicular Chain Reconstruction Revision Success and Preoperative Factors Predicting Success
Authors: Le Phong T. , O’Connell Brendan P. , Baker Andrew B. , Keller Robert G. , Lambert Paul R. 
Published: April 2017

ObjectiveDetermine rates of success after revision titanium ossicular chain reconstruction with either partial or total ossicular replacement prosthesis and assess preoperative factors predicting positive outcomes.Study DesignCase series with planned data collection.SettingTertiary hospital.Subjects and MethodsThe charts of 76 surgical patients who underwent revision titanium ossicular chain reconstruction from 2003 to 2014 were abstracted from a prospectively maintained database at the Medical University of South Carolina. Postoperative air‐bone gap (ABG) after revision surgery at short‐term (<6 months) and intermediate to long‐term (>1 year) follow‐up and preoperative factors associated with postoperative ABG ≤20 dB were recorded. A paired t test or Wilcoxon signed‐rank sum test was utilized to compare preoperative, short‐term, or intermediate to long‐term results.ResultsSeventy‐six patients underwent revision ossiculoplasty and met inclusion criteria. Mean postoperative ABG was 22.5 at short‐term follow‐up (P <. 0001) and 24.4 at intermediate to long‐term follow‐up (P =. 003). Postoperative ABG ≤20 dB was achieved in 51.5% of patients. The only preoperative factor associated with postoperative ABG ≤20 dB was location of original primary ossiculoplasty (P =. 01).ConclusionsThis is one of the larger studies involving revision titanium ossiculoplasty. Revision surgery showed a significant improvement in postoperative ABG. The location of the original ossiculoplasty correlated with success of revision surgery (defined as postoperative ABG ≤20 dB). Patients who had the primary ossiculoplasty at an outside hospital may have better audiometric outcomes than patients who had it at a tertiary hospital.
Primary Squamous Cell Carcinoma of the Thyroid: A Population‐Based Analysis
Authors: Au Joshua K. , Alonso Jose , Kuan Edward C. , Arshi Armin , St. John Maie A. 
Published: April 2017

ObjectivesTo analyze the epidemiology and describe the prognostic indicators of patients with primary squamous cell carcinoma of the thyroid.Study Design and SettingRetrospective cohort study based on a national database.MethodsThe US National Cancer Institute’s SEER registry (Surveillance, Epidemiology, and End Results) was reviewed for patients with primary squamous cell carcinoma of the thyroid from 1973 to 2012. Study variables included age, sex, race, tumor size, tumor grade, regional and distant metastases, and treatment modality. Survival measures included overall survival (OS) and disease‐specific survival (DSS).ResultsA total of 199 cases of primary squamous cell carcinoma of the thyroid were identified. Mean age at diagnosis was 68.1 years; 58.3% were female; and 79.4% were white. Following diagnosis, 46.3% of patients underwent surgery; 55.7%, radiation therapy; and 45.8%, surgery with radiation therapy. Kaplan‐Meier analysis demonstrated OS and DSS of 16% and 21% at 5 years, respectively. Median survival after diagnosis was 9.1 months. Multivariate Cox regression analysis showed that predictors of OS and DSS included age (P <. 001, P <. 001, respectively), tumor grade (P <. 001, P =. 001), and tumor size (P <. 001, P =. 001). Surgical management was a predictor of OS but not DSS.ConclusionSquamous cell carcinoma of the thyroid is a rare malignancy with a very poor prognosis. Surgical resection confers an overall survival benefit. Age, tumor grade, and tumor size are predictors of OS and DSS.
Survival and Margin Status in Head and Neck Radiation‐Induced Sarcomas and De Novo Sarcomas
Authors: Rosko Andrew J. , Birkeland Andrew C. , Chinn Steven B. , Shuman Andrew G. , Prince Mark E. , Patel Rajiv M. , McHugh Jonathan B. , Spector Matthew E. 
Published: April 2017

ObjectiveTo describe histologic subtypes and oncologic outcomes among patients with radiation‐induced and de novo sarcomas of the head and neck.Study DesignRetrospective case series with chart review.SettingTertiary academic center.Subject and MethodsIn total, 166 adult patients with sarcoma of the head and neck treated from January 1, 1985, to January 1, 2010, were included. Tumors were characterized as radiation induced (15.1%) vs de novo sarcomas (84.9%). Clinical and tumor characteristics were compared. The primary outcomes were overall survival (OS) and disease‐specific survival (DSS).ResultsRadiation‐induced sarcomas were more likely to be high grade (P =. 006) and advanced stage (P =. 03). Chondrosarcoma was more common in de novo tumors (P =. 02) while leiomyosarcoma (P =. 01), sarcoma not otherwise specified (P =. 02), and undifferentiated pleomorphic sarcoma (P <. 001) were more common in radiation‐induced sarcomas. Radiation‐induced sarcomas were associated with statistically significantly worse DSS (P =. 019) and OS (P =. 005) compared with de novo sarcomas, but when only high‐grade soft tissue sarcomas were analyzed, neither DSS (P =. 48) nor OS (P =. 29) differed. Margin status was a significant predictor of survival as both R0 and R1 resections correlated with statistically better DSS and OS compared with R2 (P <. 001) resections and patients treated with radiation therapy/chemoradiation therapy alone (P =. 005).ConclusionRadiation‐induced sarcomas of the head and neck correlate with worse survival compared with de novo tumors; however, when controlling for tumor grade and resection status, there is no statistically significant difference in observed outcomes.
Volatile anaesthetics added to cardiopulmonary bypass are associated with reduced cardiac troponin
Authors: Bignami Elena , Guarnieri Marcello , Pieri Marina , De Simone Francesco , Rodriguez Alcira , Cassarà Luigi , Lembo Rosalba , Landoni Giovanni , Zangrillo Alberto 
Published: April 2017

Background: Every year, over 1 million cardiac surgical procedures are performed all over the world. Reducing myocardial necrosis could have strong implications in postoperative clinical outcomes. Volatile anaesthetics have cardiac protective properties in the perioperative period of cardiac surgery. However, little data exists on the administration of volatile agents during cardiopulmonary bypass. The aim of this study was to assess if volatile anaesthetics administration during cardiopulmonary bypass reduces cardiac troponin release after cardiac surgery. Materials and methods: We retrospectively analysed data from 942 patients who underwent cardiac surgery in a teaching hospital. The only difference between the groups was the management of anaesthesia during CPB. The volatile group received sevoflurane or desflurane while the control group received a combination of propofol infusion and fentanyl boluses. Patients who received volatile anaesthetics during cardiopulmonary bypass (n=314) were propensity-matched 1:2 with patients who did not receive volatile anaesthetics during CPB (n=628). Results: We found a reduction in peak postoperative troponin I, from 7.8 ng/ml (4.8-13.1) in the non-volatile group to 6.8 ng/ml (3.7-11.8) in the volatile group (p=0.013), with no differences in mortality [2 (0.6%) in the volatile group and 2 (0.3%) in the non-volatile group (p=0.6)]. Conclusions: Adding volatile anaesthetics during cardiopulmonary bypass was associated with reduced peak postoperative troponin levels. Larger studies are required to confirm our data and to assess the effect of volatile agents on survival.
Functional Impairment of Patients Undergoing Surgical Correction for Charcot Foot Arthropathy
Authors: Kroin Ellen , Schiff Adam , Pinzur Michael S. , Davis Elissa S. , Chaharbakhshi Edwin , DiSilvio Frank A. 
Published: April 2017

Background: Investigations using the Medical Outcomes Study Short Form 36 Healthy Survey (SF-36) and the American Orthopaedic Foot & Ankle Society Diabetic Foot Questionnaire (AOFAS-DFQ) have demonstrated a poor quality of life in patients with Charcot foot arthropathy. The Short Musculoskeletal Function Assessment (SMFA) questionnaire has been widely used in patients with a broad range of musculoskeletal disorders. Methods: Twenty-five consecutive patients undergoing operative correction for diabetes-related Charcot foot arthropathy of the midfoot completed the SMFA prior to undergoing surgery. There were 16 males and 9 females. The average body mass index (BMI) was 37.4 (range 25.8-50.2), and the average hemoglobin A1c was 7.5 (range 5.3-10.1) prior to surgery. Results: All 25 patients exhibited significant impairment in all 6 domains of the SMFA ( P < .0001) as compared to the normative data. There was a high correlation between each of the 6 domains of the SMFA, even after correcting for BMI. Conclusion: Charcot foot severely impaired the quality of life in patients beyond the impact of morbid obesity. This impairment equally impacted all of the functional and emotional domains measured with the SMFA as compared with population norms. This investigation provides a benchmark for measuring the impact of operative correction of the deformity. In addition, the SMFA appears to be a valid tool for measuring impairment in this complex patient population. Level of Evidence: Level II, prospective comparative investigation