tbuckley/cabot-search huggingface dataset:
Dental remineralization via poly(amido amine) and restorative materials containing calcium phosphate nanoparticles
Authors: Kunneng Liang, Suping Wang, Siying Tao, Shimeng Xiao, Han Zhou, Ping Wang, Lei Cheng, Xuedong Zhou, Michael D. Weir, Thomas W. Oates, Jiyao Li, Hockin H. K. Xu
Journal: International Journal of Oral Science (2019)

Tooth decay is prevalent, and secondary caries causes restoration failures, both of which are related to demineralization. There is an urgent need to develop new therapeutic materials with remineralization functions. This article represents the first review on the cutting edge research of poly(amido amine) (PAMAM) in combination with nanoparticles of amorphous calcium phosphate (NACP). PAMAM was excellent nucleation template, and could absorb calcium (Ca) and phosphate (P) ions via its functional groups to activate remineralization. NACP composite and adhesive showed acid-neutralization and Ca and P ion release capabilities. PAMAM+NACP together showed synergistic effects and produced triple benefits: excellent nucleation templates, superior acid-neutralization, and ions release. Therefore, the PAMAM+NACP strategy possessed much greater remineralization capacity than using PAMAM or NACP alone. PAMAM+NACP achieved dentin remineralization even in an acidic solution without any initial Ca and P ions. Besides, the long-term remineralization capability of PAMAM+NACP was established. After prolonged fluid challenge, the immersed PAMAM with the recharged NACP still induced effective dentin mineral regeneration. Furthermore, the hardness of pre-demineralized dentin was increased back to that of healthy dentin, indicating a complete remineralization. Therefore, the novel PAMAM+NACP approach is promising to provide long-term therapeutic effects including tooth remineralization, hardness increase, and caries-inhibition capabilities.
Cost-Utility of Early Breast Cancer Surveillance in Survivors of Thoracic Radiation-Treated Adolescent Hodgkin Lymphoma
Authors: Jill Furzer, Lauren Tessier, David Hodgson, Cecilia Cotton, Paul C Nathan, Sumit Gupta, Petros Pechlivanoglou
Journal: JNCI Journal of the National Cancer Institute (2019)

Adolescent women treated for Hodgkin lymphoma (HL) are at increased risk of breast cancer (BC). We evaluate the cost-utility of eight high-risk BC surveillance strategies for this population, including the Children's Oncology Group guideline of same-day annual mammography and magnetic resonance imaging (MRI) beginning at age 25 years.A discrete event simulation model was used to simulate the life histories of a cohort of 500 000 25-year-old women treated for HL at age 15 years. We estimated BC incidence and mortality, life expectancy, quality-adjusted life-years (QALYs), health-care costs, and the relative cost-utility (incremental cost-utility ratio [ICUR]) under the eight assessed surveillance strategies. One-way sensitivity analysis enabled modeling of uncertainty evaluation. A publicly funded health-care payer perspective was adopted.Costs across the eight screening strategies ranged from $32 643 to $43 739, whereas QALYs ranged from 24.419 to 24.480. In an incremental cost-effectiveness analysis, annual mammography beginning at age 25 years was associated with an ICUR of $43 000/QALY gained, annual MRI beginning at age 25 years with a switch to annual mammography at age 50 years had an ICUR of $148 000/QALY, and annual MRI beginning at age 25 years had an ICUR of $227 222/QALY. Among all assessed surveillance strategies, the differences in life expectancy were small.Current high-risk BC surveillance guidelines do not reflect the most cost-effective strategy in survivors of adolescent HL. The results suggest that groups at high risk of BC may require high-risk surveillance guidelines that reflect their specific risk profile.
Not a disorder, but a different order
Authors: Fiona Elisabeth Price-Kuehne
Journal: BMJ (2011)

It is not often that a work of fiction challenges the way that I would think about a patient. However this remarkable book does just that. Shortlisted for the Orange Prize for Fiction 2011, Kathleen Winter’s debut novel Annabel is a moving portrayal of a child who was born with both male and female sexual organs, growing up in rural Canada. The story may begin in 1968 but the issues that are sensitively and astutely raised by the author are wholly relevant to the medical student of 2011.

From birth, our gender forms an integral part of our identity. “Is the baby a boy or a girl?” is often the first question asked of new parents. What happens, however, when the baby has ambiguous genitalia? How do the parents feel …
Abstract P6-03-03: Withdrawn
Authors: Z Penzvalto, JQ Chen, RD Cardiff, B Willis, NE Hubbard, A Piersigilli, AD Borowsky
Journal: Cancer Research (2019)

Abstract This abstract was withdrawn by the authors. Citation Format: Penzvalto Z, Chen JQ, Cardiff RD, Willis B, Hubbard NE, Piersigilli A, Borowsky AD. Withdrawn [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-03-03.
Discovery of short-course antiwolbachial quinazolines for elimination of filarial worm infections
Authors: Malina A. Bakowski, Roohollah Kazem Shiroodi, Renhe Liu, Jason Olejniczak, Baiyuan Yang, Kerstin Gagaring, Hui Guo, Pamela M. White, Laura Chappell, Alain Debec, Frédéric Landmann, Bettina Dubben, Franziska Lenz, Dominique Struever, Alexandra Ehrens, Stefan J. Frohberger, Hanna Sjoberg, Nicolas Pionnier, Emma Murphy, John Archer, Andrew Steven, Valerine C. Chunda, Fanny F. Fombad, Patrick W. Chounna, Abdel J. Njouendou, Haelly M. Metuge, Bertrand L. Ndzeshang, Narcisse V. Gandjui, Desmond N. Akumtoh, Tayong D. B. Kwenti, Ashley K. Woods, Sean B. Joseph, Mitchell V. Hull, Wen Xiong, Kelli L. Kuhen, Mark J. Taylor, Samuel Wanji, Joseph D. Turner, Marc P. Hübner, Achim Hoerauf, Arnab K. Chatterjee, Jason Roland, Matt S. Tremblay, Peter G. Schultz, William Sullivan, Xin-Jie Chu, H. Michael Petrassi, Case W. McNamara
Journal: Science Translational Medicine (2019)

This study identifies oral, highly efficacious antiwolbachial compounds to cure filarial infections in mice.
Cell-penetrating mechanism of intracellular targeting albumin: Contribution of macropinocytosis induction and endosomal escape
Authors: Shota Ichimizu, Hiroshi Watanabe, Hitoshi Maeda, Keisuke Hamasaki, Komei Ikegami, Victor Tuan Giam Chuang, Ryo Kinoshita, Kento Nishida, Taro Shimizu, Yu Ishima, Tatsuhiro Ishida, Takahiro Seki, Hiroshi Katsuki, Shiroh Futaki, Masaki Otagiri, Toru Maruyama
Journal: Journal of Controlled Release (2019)
Abstract P6-17-37: Therapy landscape of patients with metastatic, HER2 positive breast cancer - Data from the real world breast cancer registry PRAEGNANT (NCT02338167)
Authors: MP Lux, AD Hartkopf, J Huober, B Volz, F-A Taran, F Overkamp, P Hadji, H Tesch, L Haeberle, J Ettl, DI Lueftner, M Wallwiener, V Müller, MW Beckmann, E Belleville, P Wimberger, C Hielscher, M Geberth, J Lermann, W Abenhardt, C Kurbacher, R Wuerstlein, C Thomssen, M Untch, PA Fasching, W Janni, TN Fehm, D Wallwiener, SY Brucker, A Schneeweiss, H-C Kolberg
Journal: Cancer Research (2019)

Abstract Purpose: This analysis describes comprehensive real-world data concerning the use of anti-HER2 therapies in HER2 positive metastatic breast cancer (MBC). Specifically, it describes the therapy patterns of treatments with trastuzumab (TZM), pertuzumab+trastuzumab (PTZ/TZM), lapatinib (LAP) and trastuzumab emtansine (T-DM1). Methods: The PRAEGNANT study is a real-time, real-world registry for patients with MBC. Patients can be registered for PRAEGNANT at any time during the course of their metastatic disease and are followed up until death. All therapy lines are documented. This analysis presents the utilization of anti-HER2 therapies as well as therapy sequences. Results: Of 1936 patients within PRAEGNANT at the time of database closure 451 were HER2 positive (23.3%). Within the analysis set (417 patients after an unilateral breast cancer diagnosis), of which 53% were included in PRAEGNANT in the 1stline setting, 241 were treated with TZM (58%), 237 with PTZ (57%), 85 with LAP (20%) and 125 with T-DM1 (30%) during the course of their therapies. The sequence PTZ/TZMàT-DM1 was given to 51 patients (12%). Worse ECOG, negative hormone receptor status, and visceral or brain metastases were associated with a more frequent use of this therapy sequence. Most patients received T-DM1 after a therapy with pertuzumab. Conclusions: Both novel therapies (PTZ/TZM and T-DM1) are utilized in a high proportion of HER2 positive breast cancer patients. As most patients receive T-DM1 after pertuzumab real world data might help to understand whether this sequence has similar efficacy like in the approval study. Citation Format: Lux MP, Hartkopf AD, Huober J, Volz B, Taran F-A, Overkamp F, Hadji P, Tesch H, Haeberle L, Ettl J, Lueftner DI, Wallwiener M, Müller V, Beckmann MW, Belleville E, Wimberger P, Hielscher C, Geberth M, Lermann J, Abenhardt W, Kurbacher C, Wuerstlein R, Thomssen C, Untch M, Fasching PA, Janni W, Fehm TN, Wallwiener D, Brucker SY, Schneeweiss A, Kolberg H-C. Therapy landscape of patients with metastatic, HER2 positive breast cancer - Data from the real world breast cancer registry PRAEGNANT (NCT02338167) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-17-37.
Military healthcare strategy and leadership
Authors: Adebowale Oyegoke, Ben Williamson
Journal: BMJ (2013)

Robin Cordell is involved in medical strategy and policy at the UK’s Ministry of Defence, and supports medical students and trainees in leadership and management

Robin Cordell is head of medical strategy and policy at Headquarters Surgeon General, Defence Medical Services UK. He develops strategy for the Defence Medical Services, which provides healthcare to 196 000 servicemen and women to ensure they are medically fit for duty. He trained as a GP, then an occupational physician, and now works in a full time management capacity. He supports medical students and trainees through his work with the faculty of medical leadership and management.



I suppose I have always been interested in leadership, even at school. We were encouraged to feel part of a wider family with shared values, as well as to take part in community service and other activities that promoted initiative and teamwork. I think this laid a good foundation for developing leadership skills during my career.

I had spent a gap year in the infantry just before …
<i>HNF4α</i> pathway mapping identifies wild-type <i>IDH1</i> as a targetable metabolic node in gastric cancer
Authors: Chang Xu, Wen Fong Ooi, Aditi Qamra, Jing Tan, Benjamin Yan-Jiang Chua, Shamaine Wei Ting Ho, Kakoli Das, Zul Fazreen Adam Isa, Zhimei Li, Xiaosai Yao, Tingdong Yan, Manjie Xing, Kie Kyon Huang, Joyce Suling Lin, Tannistha Nandi, Su Ting Tay, Ming Hui Lee, Angie Lay Keng Tan, Xuewen Ong, Hassan Ashktorab, Duane Smoot, Shang Li, Shyh-Chang Ng, Bin Tean Teh, Patrick Tan
Journal: Gut (2019)

Objective Gastric cancer (GC) is a leading cause of cancer mortality. Previous studies have shown that hepatocyte nuclear factor-4α (HNF4α) is specifically overexpressed in GC and functionally required for GC development. In this study, we investigated, on a genome-wide scale, target genes of HNF4α and oncogenic pathways driven by HNF4α and HNF4α target genes. Design We performed HNF4α chromatin immunoprecipitation followed by sequencing across multiple GC cell lines, integrating HNF4α occupancy data with (epi)genomic and transcriptome data of primary GCs to define HNF4α target genes of in vitro and in vivo relevance. To investigate mechanistic roles of HNF4α and HNF4α targets, we performed cancer metabolic measurements, drug treatments and functional assays including murine xenograft experiments. Results Gene expression analysis across 19 tumour types revealed HNF4α to be specifically upregulated in GCs. Unbiased pathway analysis revealed organic acid metabolism as the top HNF4α -regulated pathway, orthogonally supported by metabolomic analysis. Isocitrate dehydrogenase 1 ( IDH1 ) emerged as a convergent HNF4α direct target gene regulating GC metabolism. We show that wild-type IDH1 is essential for GC cell survival, and that certain GC cells can be targeted by IDH1 inhibitors. Conclusions Our results highlight a role for HNF4α in sustaining GC oncogenic metabolism, through the regulation of IDH1 . Drugs targeting wild-type IDH1 may thus have clinical utility in GCs exhibiting HNF4α overexpression, expanding the role of IDH1 in cancer beyond IDH1/2 mutated malignancies.
A serious finger problem
Authors: Declan McDonnell, James T H Paget, Oliver Harley
Journal: BMJ (2013)

A 30 year old woman presents to the emergency department complaining of a painful left middle finger that she first noticed the previous night. She tells you that she had been bitten earlier in the week by her pet hamster. You establish that she is left hand dominant, a non-smoker, and she works as an artist. She is systemically well and has no evidence of pyrexia. You inspect the picture and record your findings (see figure).⇓ Palpating the digit along the volar (palm) side aspect elicits tenderness, which is made worse with passive extension (whereby the examiner moves the finger).



1. What are your findings on inspection?

2. What are your differential diagnoses?

3. What are Kanavel’s four cardinal signs1?

4. How should this condition be managed?

(1) On inspection, you notice her left middle finger is erythematous, swollen, and held in flexion in relation to the other fingers. There are bite marks on the volar and dorsal sides.

(2) Osteomyelitis, or inflammation of the bones of …
P12.06 Significantly Mutated Genes for Radiation-Associated Meningioma
Authors: E. B. Claus, S. Greenhalgh, S. G. Gaffney, K. Bilguvar, L. Calvocoressi, L. Lu, O. Al-Mefty, Z. Zi-Ming Zhao, J. P. Townsend
Journal: Neuro-Oncology (2017)

Meningioma is the most commonly diagnosed primary brain tumor and is associated with significant morbidity. Children treated with therapeutic radiation to the head are at almost ten-fold risk of radiation-associated meningioma (RAM). RAM tumors are associated with aggressive histological features and reduced survival but treatment options remain limited. To discover genes associated with RAM we performed whole-exome sequencing on matched constitutional and tumor materials from 20 patients treated in childhood with ionizing radiation to the head and subsequently diagnosed with cranial meningioma. The mean number of protein-altering somatic mutations was 139.2 (median=94, range=49-541) and did not vary significantly by sex, grade, age at initial or meningioma diagnosis, time since radiation, dose, meningioma location or initial diagnosis (Acute Lymphoblastic Leukemia (ALL) versus other). The average proportion of the genome with copy number variation (CNV) was 6.4 (range 1.2-15.4). Males had twice the CNV rate of females (8.4 vs 4.8, respectively, p=0.05). Although no other variable was significantly associated with difference in CNV rate, of the 5 patients with a CNV value of 10% or more, 4 (80%) had a prior diagnosis of ALL. Eleven genes with significantly more somatic mutations than expected by chance were identified (NF2, VKORC1, GAB1, METTL25, AK3, IL15RA, MIPOL1, MetAP2, AWAT1, ERO1L, ATP6V0D2). The most common were NF2 (n=4 samples) and AK3 (n=4 samples). Two samples had mutations in MetAP2, a gene that encodes the protein methionine aminopeptidase (MetAP2). MetAP2 inhibitors are currently in use for the treatment of a number of cancers suggesting a possible new treatment for some patients with RAM. Our findings suggest a high rate of mutations in RAM; with the exception of NF2 these changes are dissimilar from those reported in non-radiation associated meningioma.
Performance of Baveno VI and Expanded Baveno VI Criteria for Excluding High-Risk Varices in Patients With Chronic Liver Diseases: A Systematic Review and Meta-analysis
Authors: Maria Stafylidou, Paschalis Paschos, Anastasia Katsoula, Konstantinos Malandris, Konstantinos Ioakim, Eleni Bekiari, Anna-Bettina Haidich, Evangelos Akriviadis, Apostolos Tsapas
Journal: Clinical Gastroenterology and Hepatology (2019)
Abstract P4-06-20: Delivering tumour antigens survivin and mucin-1 on virus-like particles for breast cancer immunotherapy
Authors: K Kramer, D Braeden, VL Young, GF Walker, VK Ward, SL Young
Journal: Cancer Research (2019)

Abstract Breast cancer is the most frequently diagnosed cancer in women worldwide. Although there are a variety of treatment options available, breast cancer is a difficult disease to treat and many patients experience recurrence following treatment. We have previously shown that tumour antigens delivered on virus-like particles (VLP) induce a targeted anti-cancer immune response. In this study we investigated whether combining the two tumour antigens survivin and mucin 1 as vaccine targets can induce a superior anti-cancer immune response for breast cancer immunotherapy. VLP were designed to recombinantly express the murine survivin epitope. Following expression of Survivin-VLP, aberrantly glycosylated mucin 1 (MUC1) peptide was conjugated onto the Survivin-VLP using intracellular cleavable bis-arylhydrazone linking strategy. Western Blot analysis and electron microscopy confirmed Survivin-VLP expression and UV absorption confirmed conjugation of the MUC1 peptide to the Survivin-VLP. C57mg.MUC1 breast cancer cells were injected into the mammary fat pad of C57Bl/6 and MUC1 transgenic mice. Once tumours were palpable, mice were vaccinated with the Survivin-MUC1-VLP and controls of DPBS, VLP without antigen or VLP delivering either survivin or MUC1 antigen. Tumour growth and mouse survival were monitored for 80 days. Mice vaccinated with Survivin-MU1-VLP delivering both antigens showed enhanced survival (D78) compared to mice vaccinated with VLP delivering only one of the antigens (D66) and controls (D53). Delivery of two tumour antigens induced an enhanced anti-tumour immune response compared to delivery of single tumour antigens. The induction of multiple immune responses against different tumour antigens may apply additional evolutionary pressure upon tumours, prolonging the ability for tumours to develop resistance, or escape through the proliferation of a resistant subpopulation. The use of VLP for the delivery of multiple antigens and adjuvants represents a promising approach to improve cancer immunotherapy for breast cancer. Citation Format: Kramer K, Braeden D, Young VL, Walker GF, Ward VK, Young SL. Delivering tumour antigens survivin and mucin-1 on virus-like particles for breast cancer immunotherapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-06-20.
Compulsory rural service for medical graduates in India
Authors: Sutanay Bhattacharyya
Journal: BMJ (2014)

The Medical Council of India and government of India have decided to force newly qualified doctors to spend a year in a post in rural India after completing their internships, although the decision has been put on hold by the Medical Council of India.1 Medical students wanting to sit the postgraduate examination will have to serve this one year stint to be eligible for it, although the Minister of Health has said that this would not apply to students sitting the examination in 2015-16.This decision to enforce a year of working in the villages has created a stir across the country, with medical students and doctors protesting and striking against it.2

Behind the decision is the need to improve the deteriorating rural health service …
Medical Reference Guides
Authors: Neil Chanchlani
Journal: BMJ (2010)

From “pocketcards,” sets of plastic cards that can fit in your trouser pocket or purse, to “pockettools,” sets of credit card sized information, Medical Reference Guides gives you the essential facts and quick overviews of topics that medical students and junior doctors are expected to know. Organised well, with clear headings, bold titles, and coloured tables and graphs, these compact guides are informative and visually stimulating.

From broad topics, such as …
Reciprocal Activation within a Kinase-Effector Complex Underlying Persistence of Structural LTP
Authors: Takeo Saneyoshi, Hitomi Matsuno, Akio Suzuki, Hideji Murakoshi, Nathan G. Hedrick, Emily Agnello, Rory O’Connell, Margaret M. Stratton, Ryohei Yasuda, Yasunori Hayashi
Journal: Neuron (2019)
Abstract 1759: A 27 year-old Man from ’the Valley’ with Shortness of Breath
Authors: Jennifer E Ho, Yerem Yeghiazarians
Journal: Circulation (2007)

A 27 year-old man with no significant past medical history was admitted with shortness of breath and subjective fevers. He was diagnosed with Valley fever based on pulmonary infiltrates on chest x-ray and elevated Coccidiomycosis immitis IgG and IgM titers and was treated with antifungal therapy. He subsequently developed worsening dyspnea, orthopnea, and lower extremity swelling. On exam his jugular venous pressure was elevated and he had bilateral pleural effusions, lower extremity edema, and a positive Kussmaul sign. The electrocardiogram showed sinus tachycardia with diffuse T-wave inversions. Echocardiography demonstrated thickened adhesive pericardium, exaggerated respirophasic variation of the tricuspid and mitral inflow Doppler patterns and a prominent septal bounce. Cardiac MRI showed markedly thickened enhancing pericardium with an associated small pericardial effusion and prominent septal bounce. There was no delayed enhancement to suggest myocarditis. Cardiac catheterization showed equalization of diastolic pressures in all four chambers, low cardiac output, and simultaneous right and left ventricular pressures showed respirophasic discordance suggestive of increased ventricular interdependence. All of the above findings were consistent with constrictive pericarditis in the setting of disseminated coccidioidomycosis, and the patient underwent urgent surgical pericardiectomy with improvement in his symptoms. Pathology specimens demonstrated fungal spherules and active inflammation consistent with Coccidiomycosis immitis infection of the pericardium. This case illustrates the multi-disciplinary diagnostic approach that is often needed to distinguish constrictive pericarditis from restrictive cardiomyopathy. It highlights classic features of constrictive physiology seen on imaging and cardiac catheterization in a unique case of fungal pericarditis. Pericardial involvement in disseminated coccidioidomycosis is rare, and constrictive pericarditis treated with pericardiectomy has been described in only two prior cases in the literature.
African evolutionary history inferred from whole genome sequence data of 44 indigenous African populations
Authors: Shaohua Fan, Derek E. Kelly, Marcia H. Beltrame, Matthew E. B. Hansen, Swapan Mallick, Alessia Ranciaro, Jibril Hirbo, Simon Thompson, William Beggs, Thomas Nyambo, Sabah A. Omar, Dawit Wolde Meskel, Gurja Belay, Alain Froment, Nick Patterson, David Reich, Sarah A. Tishkoff
Journal: Genome biology (2019)

Africa is the origin of modern humans within the past 300 thousand years. To infer the complex demographic history of African populations and adaptation to diverse environments, we sequenced the genomes of 92 individuals from 44 indigenous African populations.