tbuckley/cabot-search huggingface dataset:
PiggyBac transposon-mediated gene delivery efficiently generates stable transfectants derived from cultured primary human deciduous tooth dental pulp cells (HDDPCs) and HDDPC-derived iPS cells
Authors: Emi Inada, Issei Saitoh, Satoshi Watanabe, Reiji Aoki, Hiromi Miura, Masato Ohtsuka, Tomoya Murakami, Tadashi Sawami, Youichi Yamasaki, Masahiro Sato
Journal: International Journal of Oral Science (2015)

The ability of human deciduous tooth dental pulp cells (HDDPCs) to differentiate into odontoblasts that generate mineralized tissue holds immense potential for therapeutic use in the field of tooth regenerative medicine. Realization of this potential depends on efficient and optimized protocols for the genetic manipulation of HDDPCs. In this study, we demonstrate the use of a PiggyBac (PB)-based gene transfer system as a method for introducing nonviral transposon DNA into HDDPCs and HDDPC-derived inducible pluripotent stem cells. The transfection efficiency of the PB-based system was significantly greater than previously reported for electroporation-based transfection of plasmid DNA. Using the neomycin resistance gene as a selection marker, HDDPCs were stably transfected at a rate nearly 40-fold higher than that achieved using conventional methods. Using this system, it was also possible to introduce two constructs simultaneously into a single cell. The resulting stable transfectants, expressing tdTomato and enhanced green fluorescent protein, exhibited both red and green fluorescence. The established cell line did not lose the acquired phenotype over three months of culture. Based on our results, we concluded that PB is superior to currently available methods for introducing plasmid DNA into HDDPCs. There may be significant challenges in the direct clinical application of this method for human dental tissue engineering due to safety risks and ethical concerns. However, the high level of transfection achieved with PB may have significant advantages in basic scientific research for dental tissue engineering applications, such as functional studies of genes and proteins. Furthermore, it is a useful tool for the isolation of genetically engineered HDDPC-derived stem cells for studies in tooth regenerative medicine. A method that enables the efficient, effective delivery of genes into human baby teeth cells could aid research into tooth regeneration. Dental pulp cells found inside baby teeth give rise to other cells that make dentin, one of the major components of teeth. Masahiro Sato from Kagoshima University, Japan, and colleagues now show that a gene delivery system called 'PiggyBac' can be used to introduce DNA into these pulp cells or stem cells derived from them, yielding modified cells that stably express one or two genes for months at a time. The PiggyBac system greatly outperforms other more conventional gene delivery systems, but because of safety risks is not suited for clinical application. Rather, the system is expected to boost functional studies of genes and proteins related to tooth development.
Abstract 3046: Survival of Patients with Aortic Stenosis Referred for Percutaneous Aortic Valve Replacement
Authors: Alan Zajarias, Helene Eltchaninoff, Godin Matthieu, Alain Cribier
Journal: Circulation (2008)

Transcatheter aortic valve replacement (TAVR) has emerged as a treatment alternative for patients with severe symptomatic aortic stenosis (AS) who are poor candidates for surgical aortic valve repl...
Pancreatic circulating tumor cells as a diagnostic adjunct in pancreatic cancer.
Authors: Jacob S Ankeny, Shuang Hou, Millicent Lin, Hank OuYang, Min Song, Matthew M Rochefort, Mark D Girgis, William H. Isacoff, Zev A. Wainberg, Hsian-Rong Tseng, James S Tomlinson
Journal: Journal of Clinical Oncology (2014)

175 Background: Current diagnosis of pancreatic ductal adenocarcinoma (PDAC) relies upon image guided tissue sampling, which is expensive, inconvenient, and not without patient risk. Circulating tumor cells (CTCs) may improve our ability to diagnose PDAC, obtain pure molecular information uncontaminated by stromal cells, and potentially improve our ability to accurately stage patients at the time of diagnosis. Therefore, we evaluated CTCs as an adjunctive diagnostic biomarker of PDAC at the time of presentation. Methods: We performed a prospective analysis on 50 consecutive pre-treatment patients with either suspicion for, or recent diagnosis of PDAC who were referred to our UCLA Center for Pancreatic Diseases. 2 mL venous blood was evaluated for the presence and number of CTCs. Capture and enumeration was carried out with a novel microfluidic NanoVelcro technology enhanced by anti-EpCAM enrichment. CTCs were defined by size &gt; 10 um and IHC staining pattern (DAPI+, CK+, and CD45-). Of note, KRAS mutational status was assessed in CTCs from 3 patients to confirm PDAC origin of CTCs. Diagnostic performance was then assessed via analysis of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and receiver operating characteristic (ROC) curves. Results: Of the 50 patients, 32 patients had PDAC and 18 had non-malignant pathology on tissue biopsy. CTCs were detected in 62.5% of PDAC patients, and in 5.5% of patients with non-malignant pathology. Specificity of CTCs for the diagnosis of PDAC was 94.4%, PPV 95.2%, and NPV 58.6%. ROC curve analysis determined optimal ability for CTCs to distinguish between benign and malignant disease with detection of ≥ 1 CTC. Additionally, in patients with a diagnosis of PDAC, CTC number correlated with stage and the presence of ≥ 2 CTCs distinguished local from systemic disease. Conclusions: In this study, CTCs were a useful adjunct for diagnosis of PDAC. Additionally, CTCs were capable of identifying patients with metastases. Addition of outcomes data may allow CTCs to be established as a biomarker for improved staging at the time of diagnosis, with subsequent improvement in delivery of stage-specific treatments.
Capsaicin-induced cough reflex is inhibited by deep inspiration in children with mild asthma
Authors: Renata Pecova, Tatiana Michnova, Jaroslav Fabry, Tomas Zatko, Martina Neuschlova, Zoltan Tomori
Journal: European Respiratory Journal (2011)

Background:  Asthma is characterized by bronchospasms accompanied with frequent coughing, the pathogenesis of which is not clear. In healthy adults deep inspirations  (DIs) provide a protective effect against bronchoconstriction  triggered by metacholin, which correlates with the number of accompanying cough efforts. In adult asthmatics DIs have some spasmolytic effect, which decreases with age and severity of the disease. Our aim was to test the elicitability of cough reflex by capsaicin in children with mild asthma and their presupposed inhibition by DIs.   Methods:  In 21 children (8 girls and 13 boys of median age 13.3 yr) with mild asthma (FEV 1 >80%) the cough reaction to inhalation of increasing concentrations of capsaicin from a compressed air-driven nebulizer manifesting with  2 and 5 or more cough efforts  (C2 and C5) was tested. The effect of previous DIs was also examined.   Results:  In control conditions 20.86 (14.58-29.8) umol/l of capsaicin provoked two cough reflexes (C2), but after 3-5 DIs similar reaction required significantly higher concentrations 29.02 (18.88-44.6) umol/l;  P=0.016.  Five or more cough efforts required increasing doses inhaled repeatedly in 1 minute intervals, which were not significantly higher after DIs 161.49 (77.31-337.33) umol/l, than without DIs 141.52 (68.77-291);  P=0.54.    Conclusion:  A series of 5  DIs decreased the sensitivity of cough reflex  provoked by capsaicin in children with mild asthma, but such inhibitory effect of DIs disappeared after repeated applications of increasing doses of capsaicin, suggesting  reflex character of protective effect of DIs.   Supported by a Grant of Ministry of Health of Slovak Republic 2007/50-UK-14.
Nova et Vetera
Authors: W PAGEL
Journal: BMJ (1950)

machinery from the international centres at Geneva or elsewhere to the national components.He quoted his chief, Dr. Brock Chisholm, as stating that perhaps the success of W.H.O.should be judged not by the amount of money which it could persuade its member Governments to spend in the international field, but by the amount which it could persuade them to spend on health in their own countries.In his presidential address to the World Federation, Professor LiNE made the point that the man in the street had confidence in the leadership of medicine so far as his physical needs were concerned, and was content that medicine should advise public-health departments in the interests of his own physical and environmental well-being.He had in fact handed over his responsibility in this respect to professional medicine, and medicine was worthy of the trust.But the man in the street must be made to realize that in the field of mental health, involving the effectiveness with which he could live with other people and with himself, he could not afford to delegate his responsibility.This was something that could not be turned over to the expert because it concerned personality development, character formation, and social adaptation, which last was expressed in that loosely used word " democracy."
Is primary tumor metabolic activity a risk factor for occult lymph node metastasis in T1-2N0M0 non-small cell lung cancer patients?
Authors: Fatma Yildirim, Murat Türk, Ümit Özgür Akdemir, Irfan Tastepe, Ahmet Selim Yurdakul
Journal: European Respiratory Journal (2014)

Objective:In our study we aimed to evaluate the potential risk factors for occult lymph node metastasis with PET-CT in patients with clinically stage I NSCLC.  Methods:Hospital records of 26 patients who were clinically diagnosed with stage 1 NSNLC in our unit with PET-CT, operated and underwent systemic lymph node dissection were retrospectively analysed. Demographic features, time to surgery and histologic type, differentiation grade, localisation, diameter at PET-CT and SUVmax values of the tumor were recorded. The patients were divided into three groups according to the diameter and the median SUVmax value of the primary mass at PET-CT: Group 1 (low risk group) T≤ 3 cm and SUVmax  Conclusion:In patients with T1-2N0M0 disease, the size and the SUVmax of the primary tumor cann9t be used for the prediction of occult node metastasis.
Safety and efficacy of 7% hypertonic saline in patients with bronchiectasis
Authors: Claire Hodgekiss, Jane Slough, Toby Capstick, Daniel Peckham, Ian Clifton
Journal: European Respiratory Journal (2013)

Introduction:  Hypertonic saline (HS) is becoming more established as an aid to physiotherapy in patients with both non-CF and CF related bronchiectasis(1). This study aimed to review our current use of nebulised hypertonic saline.  Methods:  Patients received a test of nebulised 7% HS (Nebusal). Spirometry measurements were taken pre-nebulisation and 30 minutes post-nebulisation of 7% HS. If the patient’s spirometry remained stable they then proceeded onto regular therapy with 7% HS. Longer term outcome data were obtained from reviewing clinic letters.  Results:  Forty patients received a test dose of 7% HS of whom 32 (80%) had a diagnosis of bronchiectasis. The remaining patients had a diagnosis of asthma (4 (10%)), COPD (1 (2.5%)), recurrent pneumonia (1 (2.5%)) and chronic cough (2 (5%)).  Immediately post-HS administration the spirometry values for 32 (80%) of patients were within 10% of baseline. Seven (17.5%) of patients had a greater than 10% improvement in FEV1 immediately post-nebulisation of 7%HS. One (2.5%) patient had a 36% drop in FEV1 post-HS so long term therapy was discontinued.  Long-term follow up data were available for 32 patients. Twenty-one (66%) derived long-term symptomatic benefit and continued with therapy. Eleven (34%) patients stopped therapy, 4 (13%) of these due to lack of benefit and 7 (22%) due to worsening symptoms.  Conclusions:  Nebulised HS would seem to be a safe therapy, but we would advocate that test doses should be administered in controlled environment due to the risk of bronchospasm. The majority of our patients derived symptomatic benefit, but the commonest side-effect resulting in cessation of therapy was wheeze.  1. Kellet and Niven. Respiratory Medicine (2011) 105, 1831-5.
Abstract 18731: Direct Assessment of St. Jude Mechanical Mitral Valve Orifice Area by 3 Dimensional Transesophageal Echocardiography
Authors: Selim R Krim, Rey P Vivo, Ankit Patel, Jiaqiong Xu, William A Zoghbi, Stephen H Little
Journal: Circulation (2010)

Background: We aimed to test the feasibility of 3D transesophageal echo (3DTEE) to directly measure mechanical mitral valve (MV) orifice area. 3D anatomic diastolic area (ADA) and 3D color Doppler ...
Making every contact count for physical activity—for tomorrow's patients: the launch of the interdisciplinary, undergraduate, resources on exercise medicine and health in the UK
Authors: Ann B Gates
Journal: British Journal of Sports Medicine (2015)

In 2014, we reported a game-changing initiative to provide all UK, undergraduate medical schools, with a curricula and free resources on exercise medicine in the prevention and treatment of non-communicable diseases.1 The second phase of this philanthropic project, sees the September 2015 launch of: an interdisciplinary, undergraduate, curricula and resources. This now raises the game for all healthcare professionals.

These latest, completely revised resources, now include: pregnancy, osteoarthritis/rheumatoid arthritis, osteoporosis/sarcopenia, falls prevention and motivational interviewing, in addition to 14 presentations and a textual module, covering chronic diseases, surgery and exercise. These new teaching materials supersede all previous versions. They are valid for 3 years, and will be updated annually, by the international team of contributors and, when the national and international physical activity guidelines are revised.

This global, interdisciplinary resource has been evaluated by 29 national and international, multidisciplinary, expert reviewers whose median rating was 8/10: excellent. The University of Nottingham, School of Health Sciences, led the evaluation (P Callaghan. The University of Nottingham, School of Medicine and Health Sciences, UK; personal communication). 

The resources are available, free, only to undergraduate schools of medicine and health sciences, in the UK and worldwide. All student: doctors, nurses, midwives and all allied health professionals should be able to access the content via their University (contact ann@exercise-works.org for access details).

A series of questions on the role of exercise medicine in the prevention and treatment of ill health is undergoing a quality assurance process by the Medical Schools Council Assessment Alliance for inclusion into the national multiple choice question (MCQ) question bank, for finals examination, for the undergraduate medical degree. This means that all UK medical schools, will be able to access finals’ examination questions on exercise medicine and health. To the best of our knowledge, this is a world first!

The success …
Pringle Maneuver accelerates liver metastasis by over-expression of tumor vasculature in murine model of colon cancer.
Authors: Shutaro Ozawa, Naoe Akimoto, Masami Yamada, Hideyuki Tawara, Takashi Matsumoto, Nozomi Shinoduka, Tatsuo Yamazaki, Isamu Koyama
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

3592 

The major cause of death from colorectal cancer is hepatic metastasis that is resistant to conventional therapy. In the case of resectable liver metastasis, we propose hepatic resection. The prognosis of patients received hepatic resection is disappointing. Main reason for this poor prognosis is that many patients received hepatic resection for liver metastasis reproduce new hepatic metastasis. The production of metastasis depends on induction of adequate and new blood supply, i.e., angiogenesis. VEGF is one of the stimulator for angiogenesis and the expression of VEGF is correlated with tumor vasculature and colon cancer liver metastasis. The expression of VEGF is up regulated by hypoxia. Hepatectomy can be performed with a low mortality rate, but massive hemorrhage during surgery remains a potentially lethal problem. The Pringle maneuver is traditionally used during hepatectomy to reduce blood loss. The mechanism of metastasis in ischemic condition is unknown. We investigated whether Pringle Maneuver will accelerates liver metastasis by over-expression of tumor vasculature induced by VEGF in murine model of colon cancer liver metastasis. The orthotopic model of murine colon cancer in syngeneic BALB/c mice was used. CT-26 cells were implanted into the spleen of mice. One week after tumor implantation, mice were received laparotomy and hepato-duodenal ligament was clamped for 0 or 10 minutes (Pringle Maneuver). 2 weeks after tumor implantation, the number of hepatic metastasis was counted. The group of mice received pringle maneuver produced larger number of hepatic metastasis. Immunohistochemical analysis revealed that the expression of microvessel density and VEGF were higher in this group. Also mice received pringle maneuver produced higher level of protein production for VEGF in serum. We suggested that pringle maneuver induced tumor vasculature and produced the large number of liver metastasis.
Tuberculosis and gender: Epidemiological trends since 1957 in Poland
Authors: Maria Korzeniewska Kosela
Journal: European Respiratory Journal (2011)

Aim of the study:  To describe changes in TB epidemiology since 1957 in Poland in relation to gender.   Methods:  Retrospective analysis of data from National TB Register.   Results:  The incidence rates (IRs) of tuberculosis in general Polish population decreased very much between 1957 and 2009 from 290,4 to 21,6 per 100000. The constant regularity in this study period was that IRs among men were higher than among women in every adult age group. It happened that the IR in men group was more than four times higher in comparison to female group. In males the linear relation of IRs and age was observed with the peak usually in 50-59 age group. In women group the more complex pattern occurred. Till the end of nineties the bi-modal relation of IR with age was observed. Originally the highest IRs were among younger and oldest women. Since the end of nineties the distribution of IRs has been similar in both gender groups, namely the older age group the higher was IR of tuberculosis.   Conclusions:  The big differences in IRs of tuberculosis among men and women were constantly observed in Poland between 1957 and 2009. The relation of IRs and age in both gender groups came to be similar in the end of nineties. The task is to explain the higher proportion of men among TB cases.
Hepatitis B virus-human chimeric transcript HBx-LINE1 promotes hepatic injury via sequestering cellular microRNA-122
Authors: Hong-Wei Liang, Nan Wang, Yanbo Wang, Feng Wang, Zheng Fu, Xin Yan, Hao Zhu, Wenli Diao, Yitao Ding, Xi Chen, Chen-Yu Zhang, Ke Zen
Journal: Journal of Hepatology (2015)
Prognostic Impact of Novel Molecular Subtypes of Small Intestinal Neuroendocrine Tumor
Authors: Anna Karpathakis, Harpreet Dibra, Chistodoulos Pipinikas, Andrew Feber, Tiffany Morris, Joshua Francis, Dahmane Oukrif, Dalvinder Mandair, Marinos Pericleous, Mullan Mohmaduvesh, Stefano Serra, Olagunju Ogunbiyi, Marco Novelli, TuVinh Luong, Sylvia L. Asa, Matthew Kulke, Christos Toumpanakis, Tim Meyer, Martyn Caplin, Matthew Meyerson, Stephan Beck, Christina Thirlwell
Journal: Clinical Cancer Research (2015)

Small intestinal neuroendocrine tumors (SINET) are the commonest malignancy of the small intestine; however, underlying pathogenic mechanisms remain poorly characterized. Whole-genome and -exome sequencing has demonstrated that SINETs are mutationally quiet, with the most frequent known mutation in the cyclin-dependent kinase inhibitor 1B gene (CDKN1B) occurring in only ∼8% of tumors, suggesting that alternative mechanisms may drive tumorigenesis. The aim of this study is to perform genome-wide molecular profiling of SINETs in order to identify pathogenic drivers based on molecular profiling. This study represents the largest unbiased integrated genomic, epigenomic, and transcriptomic analysis undertaken in this tumor type.Here, we present data from integrated molecular analysis of SINETs (n = 97), including whole-exome or targeted CDKN1B sequencing (n = 29), HumanMethylation450 BeadChip (Illumina) array profiling (n = 69), methylated DNA immunoprecipitation sequencing (n = 16), copy-number variance analysis (n = 47), and Whole-Genome DASL (Illumina) expression array profiling (n = 43).Based on molecular profiling, SINETs can be classified into three groups, which demonstrate significantly different progression-free survival after resection of primary tumor (not reached at 10 years vs. 56 months vs. 21 months, P = 0.04). Epimutations were found at a recurrence rate of up to 85%, and 21 epigenetically dysregulated genes were identified, including CDX1 (86%), CELSR3 (84%), FBP1 (84%), and GIPR (74%).This is the first comprehensive integrated molecular analysis of SINETs. We have demonstrated that these tumors are highly epigenetically dysregulated. Furthermore, we have identified novel molecular subtypes with significant impact on progression-free survival.
Positions of multiple insertions in SSU rDNA of lichen-forming fungi.
Authors: A Gargas, P T DePriest, J W Taylor
Journal: Molecular Biology and Evolution (1995)

Lichen-forming fungi, in symbiotic associations with algae, frequently have nuclear small subunit ribosomal DNA (SSU rDNA) longer than the 1,800 nucleotides typical for eukaryotes. The lichen-forming ascomycetous fungus Lecanora dispersa contains insertions at eight distinct positions of its SSU rDNA; the lichen-forming fungi Calicium tricolor and Porpidia crustulata each contain one insertion. Insertions are not limited to fungi that form lichens; the lichen ally Mycocalicium albonigrum also contains two insertions. Of the 11 insertion positions now reported for lichen-forming fungi and this ally, 6 positions are known only from lichen-forming fungi. Including the 4 newly reported in this study, insertions are now known from at least 17 positions among all reported SSU rDNA sequences. Insertions, most of which are Group I introns, are reported in fungal and protistan lineages and occur at corresponding positions in genomes as phylogenetically distant as the nuclei of fungi, green algae, and red algae. Many of these positions are exposed in the mature rRNA tertiary structure and may be subject to independent insertion of introns. Insertion of introns, accompanied by their sporadic loss, accounts for the scattered distribution of insertions observed within the SSU rDNA of these diverse organisms.