tbuckley/cabot-search huggingface dataset:
One-year water-ageing of calcium phosphate composite containing nano-silver and quaternary ammonium to inhibit biofilms
Authors: Lei Cheng, Ke Zhang, Chen-Chen Zhou, Michael D Weir, Xue-Dong Zhou, Hockin H K Xu
Journal: International Journal of Oral Science (2016)

Dental composites are commonly used restorative materials; however, secondary caries due to biofilm acids remains a major problem. The objectives of this study were (1) to develop a composite containing quaternary ammonium dimethacrylate (QADM), nanoparticles of silver (NAg), and nanoparticles of amorphous calcium phosphate (NACP), and (2) to conduct the first investigation of the mechanical properties, biofilm response and acid production vs water-ageing time from 1 day to 12 months. A 4 × 5 design was utilized, with four composites (NACP-QADM composite, NACP-NAg composite, NACP-QADM-NAg composite, and a commercial control composite), and five water-ageing time periods (1 day, and 3, 6, 9, and 12 months). After each water-ageing period, the mechanical properties of the resins were measured in a three-point flexure, and antibacterial properties were tested via a dental plaque biofilm model using human saliva as an inoculum. After 12 months of water-ageing, NACP-QADM-NAg had a flexural strength and elastic modulus matching those of the commercial control (P>0.1). Incorporation of QADM or NAg into the NACP composite greatly reduced biofilm viability, metabolic activity and acid production. A composite containing both QADM and NAg possessed a stronger antibacterial capability than one with QADM or NAg alone (P<0.05). The anti-biofilm activity was maintained after 12 months of water-ageing and showed no significant decrease with increasing time (P>0.1). In conclusion, the NACP-QADM-NAg composite decreased biofilm viability and lactic acid production, while matching the load-bearing capability of a commercial composite. There was no decrease in its antibacterial properties after 1 year of water-ageing. The durable antibacterial and mechanical properties indicate that NACP-QADM-NAg composites may be useful in dental restorations to combat caries. Antibacterial properties of dental restorations improve on addition of nano-silver and an ammonium compound. Amorphous calcium phosphate is widely used for restoration because of its biocompatibility and similar composition to minerals in hard tissues. However, the detrimental formation of biofilms on dental resins and hence, the promotion of secondary caries, are problems. Hockin Xu at the University of Maryland, US, and Xuedong Zhou at Sichuan University, China, monitored the mechanical and antibacterial properties of a range of calcium phosphate composites to assess the effects of adding nano-silver and quaternary ammonium dimethylacrylate. Both additives decreased the formation of biofilms as well as lactic acid production over one year. Moreover, composites that incorporated both additives showed significantly enhanced antibacterial properties compared to those with a single additive. The composites' mechanical properties were not compromised by additive incorporation.
Abstract 4622: Identification of p62/SQSTM1 as a component of non-canonical WNT VANGL2-JNK signaling in breast cancer
Authors: Jean-Paul Borg, Puvirajesinghe Tania, François Bertucci, Daniel Birnbaum, Ashish Jain, Terje Johansen, Pierluigi Scerbo, Laurent Kodjabachian
Journal: Cancer Research (2016)

Abstract Planar cell polarity (PCP), an evolutionarily conserved developmental process originally described in Drosophila melanogaster, is essential to the control of tissue morphogenesis and development of polarized structures in metazoans. Its importance in human diseases is best demonstrated in polycystic kidney disease, hearing loss, Bardet Biedl syndrome, neural tube closure defects and cancer. PCP involves a set of evolutionarily conserved PCP genes encoding WNT ligands, transmembrane (vangl2, frizzled, fat, dachsous) and cytoplasmic (scribble, prickle, dishevelled, diego) molecules triggering a genetically well-defined non-canonical WNT-JNK pathway. Recent work has linked defects of this pathway to breast cancer aggressiveness and proposed non-canonical WNT/PCP signaling as a therapeutic target. Here we show that the archetypal non-canonical WNT/PCP protein VANGL2 is overexpressed in basal breast cancers, associated with poor prognosis and implicated in tumor growth. We identify the scaffold p62/SQSTM1 protein as a novel VANGL2-binding partner and show its key role in an evolutionarily conserved VANGL2-p62/SQSTM1-JNK pathway in breast cancer cells and in Xenopus. This proliferative signaling cascade is upregulated in breast cancer patients with shorter survival, and can be inactivated in patient-derived xenograft cells by inhibition of the JNK pathway or by disruption of the VANGL2-p62/SQSTM1 interaction. VANGL2-JNK signaling is thus a potential target for breast cancer therapy. Puvirajesinghe T.M., et al. Identification of p62/SQSTM1 as a component of non-canonical Wnt VANGL2-JNK signaling in breast cancer. Nature Communications, in press. Sebbagh M. and Borg J.-P. Insight into Planar Cell Polarity. (2014) Invited review in Experimental Cell Research, 328:284-295. Belotti E., et al. The human PDZome: a gateway to PDZ mediated functions. (2013) Mol Cell Proteomics, 12: 2587-603. Citation Format: Jean-Paul Borg, Puvirajesinghe Tania, François Bertucci, Daniel Birnbaum, Ashish Jain, Terje Johansen, Pierluigi Scerbo, Laurent Kodjabachian. Identification of p62/SQSTM1 as a component of non-canonical WNT VANGL2-JNK signaling in breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4622.
Abstract 3794: Novel therapeutic targets in head and neck cancer
Authors: Maria Kondratyev, Aleksandra Pesic, Stephano Marastoni, Troy Ketela, Jason Moffat, Carl Virtanen, Azin Sayad, Mikhail Bashkurov, Alessandro Dati, Laurie Ailles, Reidar Grenman, Marianne Koritzinsky, Brad Wouters
Journal: Cancer Research (2016)

Abstract HNSCC is 6th most common malignancy in the world. Despite advances in diagnosis and treatment, the survival rates remain low due to frequent recurrences the biology of which remains unclear. Using functional genomic technologies we identified new therapeutic targets for metastatic disease in HNSCC. Whole genome shRNA screens were conducted in matched sets of cell lines derived from primary tumors and respective metastatic sites, identifying genes essential for cell survival only following metastasis. To test if knockdown of selected targets inhibits metastasis in a therapeutic setting, we established orthotropic model of HNSCC that metastasize to lymph nodes in the mouse. Components of Notch pathway were identified as essential for survival of cells derived from metastatic sites. Whole exome sequencing identified a novel mutation in one of the EGF domains of Notch3 that was acquired only in the metastatic line. Mutations in EGF domains have been reported to influence interaction with specific ligands, dictating which ligand can activate Notch signaling. Our data indicate that metastatic, but not primary tumor cells, undergo apoptosis upon knockdown of Notch3 and that a distinct set of target genes is induced upon interaction between Notch3 and Jag2 ligand. Furthermore, our results indicate that suppression of Notch3 improves survival in mice bearing orthotropic tumors derived from the metastatic HNSCC lines. Our data demonstrate that metastatic cells from head and neck tumors acquire dependency on Notch3 signaling. Novel treatments targeting components of this pathway may prove effective in targeting metastatic cells alone or in combination with conventional therapies. Citation Format: Maria Kondratyev, Aleksandra Pesic, Stephano Marastoni, Troy Ketela, Jason Moffat, Carl Virtanen, Azin Sayad, Mikhail Bashkurov, Alessandro Dati, Laurie Ailles, Reidar Grenman, Marianne Koritzinsky, Brad Wouters. Novel therapeutic targets in head and neck cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3794.
Expecting the unexpected.
Authors: Blessie Elizabeth Nelson, Adrian Gerard Murphy, Jacquelyn W. Zimmerman
Journal: Journal of Clinical Oncology (2019)

e14066 Background: Myasthenia gravis is an autoimmune neuro-muscular disorder traditionally seen in bi-modal distribution in young women or older men. Discovery of immunotherapy has brought hope in survival outcomes for patients with malignant melanoma, lung, renal and head/neck cancers but it also opens Pandora’s box of immune-related toxicities for which early recognition and appropriate clinical management are paramount. Here we describe a case of immunotherapy induced myasthenia gravis de novo. Methods: A 77-year-old man with HPV+ stage IVA squamous cell carcinoma of the tongue presented with sudden onset orthopnea and dyspnea on exertion for the past day. One week ago, he received his second cycle of nivolumab as part of his neoadjuvant therapy. He was seen at an outside hospital and was found to be acute hypercapnic respiratory failure and placed on BiPAP. He was started on antibiotics for community-acquired pneumonia with levofloxacin and doxycycline and transferred to a tertiary care center for further management. On further evaluation, he endorsed diplopia, blurry vision, fluctuating muscle weakness that is worse at the end of the day, change in voice and proximal muscle weakness. His exam was consistent with bilateral ptosis, weak hip flexion and shoulder abduction, positive sniff test and poor vital capacity and negative inspiratory force values suggestive of impending respiratory and diaphragmatic failure secondary to myasthenic crisis. He was admitted to the ICU and placed on BiPAP and frequent NIF and VC monitoring. He was started on pyridostigmine but showed no clinical improvement on day 1 and hence was initiated on plasmapheresis from day 2 for a total of 10 days. Results: Investigations showed positivity of Ach-R modulating and binding and blocking antibodies with negative voltage gated calcium channel antibodies. EMG revealed decrement of the compound muscle action potential in the repetitive stimulation test indicative of myasthenia gravis. He responded well to the above treatment and underwent successful left partial glossectomy and weaned off mechanical ventilation and has been cancer free so far. He is doing well on maintenance prednisone and pyridostigmine. Conclusions: There is a significant 30.4% MG-specific-related mortality due to immunotherapy alone which this case demonstrates the importance of vigilance and early detection for effective treatment and management. It highlights need for the oncological world and our colleagues in various other disciplines of healthcare to identify and mitigate the effects of immunotherapy which has become our hope in beating cancer.
Principles for RNA metabolism and alternative transcription initiation within closely spaced promoters
Authors: Yun Chen, Athma A Pai, Jan Herudek, Michal Lubas, Nicola Meola, Aino I Järvelin, Robin Andersson, Vicent Pelechano, Lars M Steinmetz, Torben Heick Jensen, Albin Sandelin
Journal: Nature Genetics (2016)
Gut Microbiome Associates With Lifetime Cardiovascular Disease Risk Profile Among Bogalusa Heart Study Participants
Authors: Tanika N. Kelly, Lydia A. Bazzano, Nadim J. Ajami, Hua He, Jinying Zhao, Joseph F. Petrosino, Adolfo Correa, Jiang He
Journal: Circulation Research (2016)

Few studies have systematically assessed the influence of gut microbiota on cardiovascular disease (CVD) risk.To examine the association between gut microbiota and lifetime CVD risk profile among 55 Bogalusa Heart Study participants with the highest and 57 with the lowest lifetime burdens of CVD risk factors.16S ribosomal RNA sequencing was conducted on microbial DNA extracted from stool samples of the Bogalusa Heart Study participants. α Diversity, including measures of richness and evenness, and individual genera were tested for associations with lifetime CVD risk profile. Multivariable regression techniques were used to adjust for age, sex, and race (model 1), along with body mass index (model 2) and both body mass index and diet (model 3). In model 1, odds ratios (95% confidence intervals) for each SD increase in richness, measured by the number of observed operational taxonomic units, Chao 1 index, and abundance-based coverage estimator, were 0.62 (0.39-0.99), 0.61 (0.38-0.98), and 0.63 (0.39-0.99), respectively. Associations were consistent in models 2 and 3. Four genera were enriched among those with high versus low CVD risk profile in all models. Model 1 P values were 2.12×10(-3), 7.95×10(-5), 4.39×10(-4), and 1.51×10(-4) for Prevotella 2, Prevotella 7, Tyzzerella, and Tyzzerella 4, respectively. Two genera were depleted among those with high versus low CVD risk profile in all models. Model 1 P values were 2.96×10(-6) and 1.82×10(-4) for Alloprevotella and Catenibacterium, respectively.The current study identified associations of overall microbial richness and 6 microbial genera with lifetime CVD risk.
Abstract 1808: Nuclear receptor, ESRRG functions as tumor suppressor by preventing Helicobacter pylori infection in gastric cancer
Authors: Myoung-Hee Kang, Yong-Soo Lee, Jin-Hak Jung, Young Soo Park, Jin-Yong Jeong, Mi-Na Kweon, Chan-Ki Paik, Seung-Jae Myung, Yun-Yong Park
Journal: Cancer Research (2016)

Abstract Gastric cancer (GC) is the most common cancer type in Asia. Surgical resection and chemotherapy is standard treatment of GC. Molecular therapeutic targets and mechanism contributing to develop the gastric cancer is poorly understood. To discover the molecular target in gastric cancer, we analyzed gene expression data from gastric cancer patients. Data analysis reveals that nuclear receptor ESRRG is top candidate gene conferring the tumor suppressive property in gastric cancer. ESRRG expression is down-modulated by Helicobacter pylori (H. pylori) infection, which is one of causing factor triggering gastric cancer. In addition, ectopically over-expressed ESRRG protects the cell from H. pylori infection and suppressed cancer cell growth in vitro and in vivo mouse model. Gene expression profile reveals that TFF1, which is well known as tumor suppressor in gastric cancer is down-stream target of ESRRG and ESRRG well reflects clinical outcome in gastric cancer. Our study provides new molecular insights how ESRRG regulates gastric cancer cell growth induced by H. pylori and suggests possibility that ESSRRG can be therapeutic target for the treatment of gastric cancer patients. Citation Format: Myoung-Hee Kang, Yong-Soo Lee, Jin-Hak Jung, Young Soo Park, Jin-Yong Jeong, Mi-Na Kweon, Chan-Ki Paik, Seung-Jae Myung, Yun-Yong Park. Nuclear receptor, ESRRG functions as tumor suppressor by preventing Helicobacter pylori infection in gastric cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1808.
Association of insulin-like growth factor (IGF)-1 gene polymorphisms with plasma levels of IGF-1 and acne severity
Authors: Shekh Mohammad Amanur Rahaman, Dipankar De, Sanjeev Handa, Arnab Pal, Naresh Sachdeva, Tulikalipi Ghosh, Parul Kamboj
Journal: Journal of the American Academy of Dermatology (2016)
Remembering Statins: Do Statins Have Adverse Cognitive Effects?
Authors: Rafael Bitzur
Journal: Diabetes Care (2016)

The issue of statin-associated cognitive impairment has been a hot topic among both patients and health care providers, especially since the U.S. Food and Drug Administration (FDA) issued a statement regarding rare postmarketing reports of ill-defined cognitive impairment associated with statin use. This statement was based on case reports, and no objective measures of cognitive function were used. Nevertheless, many patients at high risk of cardiovascular disease have expressed concerns about possible cognitive decline and may have opted to forgo statin therapy. In this overview, the evidence leading to the statement by the FDA is reviewed. Potential mechanisms of the effect of LDL cholesterol reduction and statin therapy on cognition are discussed. Evidence from observational and prospective randomized trials is summarized, leading to the conclusion that as for now, there is no good evidence that statins cause cognitive impairment to a significant degree. Reported cases seem to be rare, and a causal relationship has not been established.
Review of Paul Knoepfler,<i>GMO Sapiens: The Life-Changing Science of Designer Babies</i>
Authors: I. Glenn Cohen
Journal: The American Journal of Bioethics (2016)

GMO Sapiens: The Life-Changing Science of Designer Babies, by Paul Knoepfler, is a very readable introduction for the general lay public to genetically modified crops, CRISPR-Cas9, gene therapy, an...
Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability
Authors: Stefan H Lelieveld, Margot R F Reijnders, Rolph Pfundt, Helger G Yntema, Erik-Jan Kamsteeg, Petra de Vries, Bert B A de Vries, Marjolein H Willemsen, Tjitske Kleefstra, Katharina Löhner, Maaike Vreeburg, Servi J C Stevens, Ineke van der Burgt, Ernie M H F Bongers, Alexander P A Stegmann, Patrick Rump, Tuula Rinne, Marcel R Nelen, Joris A Veltman, Lisenka E L M Vissers, Han G Brunner, Christian Gilissen
Journal: Nature Neuroscience (2016)
Bleomycin-induced pulmonary changes on restaging CT scans: Frequency and correlation with fibrosis markers.
Authors: Nico-Derk L. Westerink, Sjoukje Lubberts, Martha W. den Hollander, Alphons H.H. Bongaerts, Rienhart F.E. Wolf, Renske Altena, Janine Nuver, Sjoukje Oosting, Elisabeth De Vries, Annemiek M.E. Walenkamp, Coby Meijer, Jourik A. Gietema
Journal: Journal of Clinical Oncology (2015)

4540 Background: Bleomycin-induced pneumonitis (BIP) is a well-known, potentially fatal, side-effect in metastatic testicular cancer (mTC). We prospectively investigated I: prevalence of lesions suspect for bleomycin-induced pulmonary changes on restaging CT scans; II: whether early changes of fibrosis markers Transforming Growth Factor β1 (TGF-β1) and Growth Differentiation Factor 15 (GDF-15) were predictive for these radiological changes. Methods: mTCpatients (pts), 18-50 years of age, treated with BEP (bleomycin, etoposide, cisplatin) chemotherapy were included from 2006 till 2012. Restaging CT scans were analyzed for bleomycin-induced pulmonary changes by 2 blinded radiologists and graded as minor, moderate or severe. Plasma samples were collected before, during and after chemotherapy and quantified for TGF-β1 and GDF-15. Results: 66 Pts were included. 45 Pts (68%) showed signs of bleomycin-induced pulmonary changes. 37 pts were classified as minor and 8 as moderate. Treatment and disease characteristics did not differ between the groups. 3 Pts had clinical signs of BIP (for which bleomycin was halted). Although there was a vast induction of both TGF-β1 and GDF-15 plasma levels (table), this was not different between pts with no and minor vs. pts with moderate radiological signs of bleomycin-induced pulmonary changes. Conclusions: Bleomycin-induced pulmonary changes are very common after BEP chemotherapy for mTC. TGF-β1 and GDF-15 plasma levels before and during treatment were not different between pts with and without radiological signs of bleomycin-induced pulmonary changes and therefore not helpful as predictive markers. Biomarker levels in relation to bleomycin-induced pulmonary changes on restaging CT scan. No and minor changes (n=58) Moderate changes (n=8) P-value* Median Range Median Range Cumulative dose bleomycin (USP) 270 150-360 270 240-360 .231 Biomarker Course Day TGF-β1 1 1 4788 550-24369 5268 2052-13361 .582 (pg/mL) 3 1 7889 1484-49897 8512 3878-20372 .765 C C 5275 595-18839 5116 3223-14207 .527 GDF-15 1 1 383 198-1935 413 187-1876 .397 (pg/mL) 3 8 5222 1439-14400 7246 4130-18959 .087 C C 840 299-2023 1089 442-2601 .073 * Mann-Whitney U test. C= 4 weeks after last course.
Ask patients “What matters to you?” rather than “What’s the matter?”
Authors: Sosena Kebede
Journal: BMJ (2016)

This can help reframe interactions in a more patient centered way

Maureen Bisognano, one of the keynote speakers at this year’s International Forum on Quality and Safety in Healthcare in Gothenburg, Sweden, told delegates that we should ask our patients, “What matters to you?” rather than, “What is the matter?”

The question “What matters to you?” tries to get to the essence of patient centered care, which the Institute of Medicine has listed as one of the priorities for quality improvement.

As physicians, our success in treating illness depends mostly on our ability to diagnose what the matter is with the patient. Pattern recognition, attention to verbal and visual cues from the patient, deductive reasoning, and good clinical judgment are time revered skills that good physicians spend years perfecting.

The emphasis on diagnostic skill sets alone, however, has led …
Clinical features, causes, treatments, and outcomes of peristomal pyoderma gangrenosum (PPG) in 44 patients: The Mayo Clinic experience, 1996 through 2013
Authors: Naiara S. Barbosa, Stanislav N. Tolkachjov, Rokea A. el-Azhary, Mark D.P. Davis, Michael J. Camilleri, Marian T. McEvoy, Alina G. Bridges, David A. Wetter
Journal: Journal of the American Academy of Dermatology (2016)
Case 23-2016
Authors: Victor Chiappa, R. Gilberto Gonzalez, Farrin A. Manian, Vikram Deshpande
Journal: New England Journal of Medicine (2016)

A 46-year-old man had worsening somnolence 1 day after replacement surgery with a femoral endoprosthetic implant. Fever, tachycardia, hypertension, and tachypnea developed, and examination revealed somnolence, gaze deviation, rigidity, and hyperreflexia. A diagnosis was made.