tbuckley/cabot-search huggingface dataset:
Physicochemical properties of β-cyclodextrin solutions and precipitates prepared from injectable vehicles
Authors: Sai Myo Thurein, Nutdanai Lertsuphotvanit, Thawatchai Phaechamud
Journal: Asian Journal of Pharmaceutical Sciences (2018)

β-Cyclodextrin (β-CyD) is cyclic oligosaccharide of a glucopyranose, containing a relatively hydrophobic central cavity and hydrophilic outer surface. However, the usefulness of β-CyD is limited owing to its low aqueous solubility whereas we found that its apparent high solubility was evident in some injectable solvents including 2-pyrrolidone (PYR), N-methyl pyrrolidone (NMP) and dimethyl sulfoxide (DMSO). Therefore, in the present study, the physicochemical properties of the 30-60% w/w β-CyD in PYR, NMP and DMSO were investigated such as viscosity, water resistant, matrix formation rate and syringeability. The higher the concentration of β-CyD resulted in the increased viscosity and the higher force and energy of syringeability. β-CyD in PYR gave the highest viscosity which contributed to the lowest syringeability while β-CyD in DMSO exhibited the highest syringeability. The β-CyD in DMSO and NMP exhibited the higher rate of matrix formation. β-CyD in PYR showed the highest water resistant for phase separation while β-CyD in NMP gave the faster de-mixing rate compared to that from PYR. The difference in physicochemical properties of β-CyD dried ppts studied by scanning electron microscope (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR) and thermogravimetric analysis (TGA) revealed that there was partial complexation of β-CyD with respective solvents. Both solution and precipitate characteristic properties will be useful for using β-CyD in further investigation as matrix material dissolved in the injectable vehicles as the in situ forming gel for periodontitis treatment.
Our Other Prescription Drug Problem
Authors: Anna Lembke, Jennifer Papac, Keith Humphreys
Journal: New England Journal of Medicine (2018)

The adverse effects of benzodiazepine overuse, misuse, and addiction continue to go largely unnoticed. Efforts to reduce overprescribing of opioids and educate the medical and lay communities about their risks could be expanded to target benzodiazepines as well.
Positive End-Expiratory Pressure Ventilation Induces Longitudinal Atrophy in Diaphragm Fibers
Authors: Johan Lindqvist, Marloes van den Berg, Robbert van der Pijl, Pleuni E. Hooijman, Albertus Beishuizen, Judith Elshof, Monique de Waard, Armand Girbes, Angelique Spoelstra-de Man, Zhong-Hua Shi, Charissa van den Brom, Sylvia Bogaards, Shengyi Shen, Joshua Strom, Henk Granzier, Jeroen Kole, René J. P. Musters, Marinus A. Paul, Leo M. A. Heunks, Coen A. C. Ottenheijm
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Rationale: Diaphragm weakness in critically ill patients prolongs ventilator dependency and duration of hospital stay and increases mortality and healthcare costs. The mechanisms underlying diaphragm weakness include cross-sectional fiber atrophy and contractile protein dysfunction, but whether additional mechanisms are at play is unknown.Objectives: To test the hypothesis that mechanical ventilation with positive end-expiratory pressure (PEEP) induces longitudinal atrophy by displacing the diaphragm in the caudal direction and reducing the length of fibers.Methods: We studied structure and function of diaphragm fibers of mechanically ventilated critically ill patients and mechanically ventilated rats with normal and increased titin compliance.Measurements and Main Results: PEEP causes a caudal movement of the diaphragm, both in critically ill patients and in rats, and this caudal movement reduces fiber length. Diaphragm fibers of 18-hour mechanically ventilated rats (PEEP of 2.5 cm H2O) adapt to the reduced length by absorbing serially linked sarcomeres, the smallest contractile units in muscle (i.e., longitudinal atrophy). Increasing the compliance of titin molecules reduces longitudinal atrophy.Conclusions: Mechanical ventilation with PEEP results in longitudinal atrophy of diaphragm fibers, a response that is modulated by the elasticity of the giant sarcomeric protein titin. We postulate that longitudinal atrophy, in concert with the aforementioned cross-sectional atrophy, hampers spontaneous breathing trials in critically ill patients: during these efforts, end-expiratory lung volume is reduced, and the shortened diaphragm fibers are stretched to excessive sarcomere lengths. At these lengths, muscle fibers generate less force, and diaphragm weakness ensues.
Large and middle hepatitis B surface antigen: the lower the better?
Authors: Hsuan-Ho Lin, Tai-Chung Tseng, Jia-Horng Kao
Journal: Gut (2018)

We read with great interest the article entitled ‘Quantification of large and middle proteins of hepatitis B virus surface antigen (HBsAg) as a novel tool for the identification of inactive HBV carriers’ by Pfefferkorn et al .1 Serum hepatitis B surface antigen (HBsAg) level has been shown to complement HBV DNA level in predicting clinical outcomes of patients with chronic HBV infection.2 3 In Asian patients, mostly genotype B and C infection, with a low viral load (HBV DNA ≤2000 IU/mL), HBsAg level >1000 IU/mL indicates …
LEFT ATRIAL ENLARGEMENT AND SYSTOLIC FAILURE IS RELATED TO CHYMASE ACTIVATION IN PATIENTS WITH MITRAL REGURGITATION AND PRESERVED LEFT VENTRICULAR EJECTION FRACTION
Authors: Brittany Butts, Ryan Wong, Pamela C. Powell, Silvio Litovsky, Himanshu Gupta, Steven Lloyd, Thomas Denney, Xiaoxia Zhang, Inmaculada Aban, Xun Ai, James Collawn, James Davies, Louis Dell'Italia
Journal: Journal of the American College of Cardiology (2018)
I have an MD in pathology from India and I want to pursue a career in forensic medicine. Who should I contact?
Authors: Roy Palmer
Journal: BMJ (2004)

Got a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone (www.bmjcareers.com/advicezone) for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site.
How can I go about getting publications in medical journals as a senior house officer?
Authors: Tim Albert
Journal: BMJ (2004)

Have a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone (www.bmjcareers.com/advicezone) for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site.
Workshop on evidence based practice
Authors: Mohammad Heetun
Journal: BMJ (2012)

The workshop on evidence based practice is a one day course run by the Centre for Evidence Based Medicine, which is affiliated to the University of Oxford. 

The course is aimed at clinicians in all specialties and other healthcare professionals who want to learn the basics of critical appraisal and evidence based practice. Participants on the course when I did it included doctors at various levels of training and members of the nursing profession.

The information and evidence that we use to make key clinical decisions about patient care come from a variety of sources. It is vital that clinicians can competently appraise the scientific literature to establish whether new research findings can be applied …
I have completed my foundation year 2 post (A&amp;E, general practice, and public health) and I'm currently doing a stand alone A&amp;E non-training job. How can I increase my chances of getting a training post as an SHO in anaesthesia next year?
Authors: Michael Dobson
Journal: BMJ (2005)

Have a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site. <b>www.bmjcareers.com/advicezone</b>
Abstract OT1-03-08: A multicenter, phase I/II trial of anastrozole, palbociclib, trastuzumab and pertuzumab in HR-positive, Her2-positive metastatic breast cancer
Authors: KP Cascetta, P Poulikakos, C Shapiro, J Fasano, A Bhardwaj, H Irie, A Goel, P Klein, S Adams, K Kalinsky, L Vahdat, M Ru, A Tiersten
Journal: Cancer Research (2018)

Abstract Background: Overexpression or amplification of HER2 occurs in approximately 15 – 20% of patients and about half of these tumors are hormone receptor (HR) positive. Studies suggest that this 10% of all breast cancer cases may derive less benefit from endocrine therapy than those with HR positive disease without HER2 overexpression. The use of aromatase inhibitors in the metastatic setting is well established while significant improvement in overall survival has been established with the use of trastuzumab or pertuzumab in HER2-overexpressing tumors. To date, no studies have examined the combination of endocrine therapy, palbociclib, and dual HER2 therapy with pertuzumab and trastuzumab in this patient population. Trial Design: Multicenter, Phase I/II Trial of Anastrozole, Palbociclib, Trastuzumab and Pertuzumab in HR-positive, Her2-positive Metastatic Breast Cancer. Eligibility Criteria: Stage IV hormone receptor positive, HER2 positive breast cancer patients. Specific Aims: Phase I: To determine the maximum dose tolerated of palbociclib. Phase II: To determine the clinical benefit rate (CBR) of treatment with anastrozole, palbociclib, trastuzumab, and pertuzumab in HR+, HER2+ metastatic breast cancer patients. Exploratory: Examine potential biomarkers of response to palbociclib including cyclin D1 expression levels, phosphorylated retinoblastoma expression and p16 levels. RNA sequencing will be used to assess for other predictors of response in an unbiased manner to see if there is correlation with inhibition of Ki-67 and phosphorylated retinoblastoma expression as well as evaluate for potential mechanisms of resistance. Statistical Methods: This study will evaluate the maximum tolerated dose (MTD) of the Anastrozole, Palbociclib, Trastuzumab and Pertuzumab. If ≥ 33 % of patients experience a dose limiting toxicity (DLT) at any dose level, the dose level below that level will be considered the MTD. Or, if the highest level has been reached and &amp;lt; 33% of patients have experienced DLT, that will be considered the MTD. Once the MTD is reached, we will assess the clinical benefit rate using a Simon's II stage design among a maximum 30 patients. Accrual: Maximum of 36 subjects. Citation Format: Cascetta KP, Poulikakos P, Shapiro C, Fasano J, Bhardwaj A, Irie H, Goel A, Klein P, Adams S, Kalinsky K, Vahdat L, Ru M, Tiersten A. A multicenter, phase I/II trial of anastrozole, palbociclib, trastuzumab and pertuzumab in HR-positive, Her2-positive metastatic breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT1-03-08.
INHIBITORY MECHANISMS OF VERY LOW DOSE RIVAROXABAN IN NON-ST-ELEVATION MYOCARDIAL INFARCTION
Authors: Tobias Geisler, Patrick Muenzer, Nada Alnaggar, Sascha Geue, Roland Tegtmeyer, Dominik Rath, Michal Droppa, Peter Seizer, Stefan Heitmeier, Johan W.M. Heemskerk, Lisa Jennings, Robert Storey, Dominick Angiolillo, Bianca Rocca, Henri Spronk, Hugo Ten Cate, Meinrad Gawaz, Oliver Borst
Journal: Journal of the American College of Cardiology (2018)
Papworth research skills course
Authors: Muhammad E A Khan
Journal: BMJ (2011)

Papworth Hospital is a teaching hospital of the University of Cambridge that takes pride in its clinical and research excellence. The hospital is a partner of the newly designated Cambridge University Health Partners Academic Health Science Centre and is the UK’s top centre for cardiothoracic surgery. The faculty at Papworth Hospital includes many eminent clinicians and academics and is at the forefront of training its own staff and others in a variety of clinical and research skills.

The course has been developed by the hospital’s Research and Development Unit in association with the Medical Research Council (MRC) Biostatistics Unit and the Health Economics Research Unit at Brunel University. This course is now run twice a year in March and November in …
Air Pollutants Undermine Infant Brain Development
Authors: M. J. Friedrich
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Almost 95% of CCGs are ready to take on commissioning budgets in April
Authors: Helen Jaques
Journal: BMJ (2012)

Nearly all (94%) of the emerging clinical commissioning groups (CCGs) in England have passed the strategic health authority risk assessments of their configuration and will be able to take on primary care trust commissioning budgets this April.

Of the 243 emerging groups in England, 62% were rated “green” by their strategic health authority cluster on their engagement with member practices, geography and patient population, relationship with local authority boundaries, and size. A third (33%) were rated as amber overall, and only 6% were rated as red.

The groups were required to undergo a risk assessment of their configuration by December 2011 as the first step towards authorisation by the NHS Commissioning Board. 

They were rated as “green,” “amber,” or “red” on four areas, three of which relate to requirements in the …
Reversible opening of the blood-brain barrier by claudin-5-binding variants of Clostridium perfringens enterotoxin's claudin-binding domain
Authors: Winfried Neuhaus, Anna Piontek, Jonas Protze, Miriam Eichner, Anne Mahringer, Eva-Anne Subileau, In-Fah M. Lee, Jörg D. Schulzke, Gerd Krause, Jörg Piontek
Journal: Biomaterials (2018)
Combination of selective polo-like kinase 1 (PLK1) inhibitor PCM-075 with abiraterone in prostate cancer and non-androgen-driven cancer models.
Authors: Jesse Christopher Patterson, Shohreh Varmeh, Mark G. Erlander, Michael B. Yaffe
Journal: Journal of Clinical Oncology (2018)

369 Background: The majority of metastatic castration-resistant prostate cancer (mCRPC) patients will become resistant to abiraterone. Drug combinations with abiraterone offer the possibility to extend patient benefit to anti-androgen therapy. PLK1, an essential mitotic kinase for onset of G2/M transition and cytokinesis, is over-expressed in prostate cancer, correlated positively with Gleason grade and PLK1 RNAi induces G2/M arrest and apoptosis in prostate cancer cells. PCM-075 (formerly NMS-1286937) is a potent, highly selective PLK1 inhibitor currently in clinical trials for the treatment of acute myeloid leukemia. Combination of PCM-075 with abiraterone was examined in mCRPC models and other cancer types for synergistic interaction. Methods: We used a variety of tumor cell lines (C4-2, LNCaP, BT-20, AU565, SK-OV-3), animal and computational modeling techniques to elucidate the mechanism and assess the potential clinical utility of synergistic tumor cell killing by PLK1 inhibitors (PLK1i), including PCM-075, with abiraterone. Results: Synergy was observed between abiraterone and PLK1i, including PCM-075, in models of CRPC (C4-2). In addition, PLK1i and abiraterone were synergistic in murine C4-2 xenografts. Unexpectedly, PLK1i sensitized a subset of non-prostate cancer cells to abiraterone, including AR-negative breast and ovarian cancer cells. In contrast to PLK1i, other mitotic arrest agents do not synergize with abiraterone. To elucidate the molecular basis this synergy, we screened a panel of cell lines and implemented a new computational method that links RNA expression patterns to drug combination synergy. This analysis implicated signaling through the retinoic acid (RA) nuclear receptors as a component of this synergy, which was validated experimentally. Increased basal expression of genes involved in RA metabolism in cancer cells is associated with increased synergy. Conclusions: Abiraterone has AR-independent effects that provide a mechanism and biomarkers predictive for synergistic killing when combined with the PLK1i PCM-075. This combination has potential to extend mCRPC patient benefit to abiraterone regardless of AR status.
When is<i>Helicobacter pylori</i>acquired in populations in developing countries? A birth-cohort study in Bangladeshi children
Authors: Sabine Kienesberger, Guillermo I. Perez-Perez, Asalia Z. Olivares, Pradip Bardhan, Shafiqul A. Sarker, Kh. Zahid Hasan, R. Bradley Sack, Martin J. Blaser
Journal: Gut Microbes (2018)

Helicobacter pylori colonization is prevalent throughout the world, and is predominantly acquired during childhood. In developing countries, >70% of adult populations are colonized with H. pylori and >50% of children become colonized before the age of 10 years. However, the exact timing of acquisition is unknown. We assessed detection of H. pylori acquisition among a birth cohort of 105 children in Mirzapur, Bangladesh. Blood samples collected at time 0 (cord blood), and at 6, 12, 18, and 24 months of life were examined for the presence of IgG and IgA antibodies to whole cell H. pylori antigen and for IgG antibodies to the CagA antigen using specific ELISAs and immunoblotting. Breast milk samples were analyzed for H. pylori-specific IgA antibodies. Cord blood was used to establish maternal colonization status. H. pylori seroprevalence in the mothers was 92.8%. At the end of the two-year follow-up period, 50 (47.6%) of the 105 children were positive for H. pylori in more than one assay. Among the colonized children, CagA prevalence was 78.0%. A total of 58 children seroconverted: 50 children showed persistent colonization and 8 (7.6%) children showed transient seroconversion, but immunoblot analysis suggested that the transient seroconversion observed by ELISA may represent falsely positive results. Acquisition of H. pylori was not influenced by the mother H. pylori status in serum or breastmilk. In this population with high H. pylori prevalence, we confirmed that H. pylori in developing countries is detectable mainly after the first year of life.
PROGNOSTIC FACTORS OF EXTRACORPOREAL MEMBRANE OXYGENATOR THERAPY FOR REFRACTORY CARDIOGENIC SHOCK OR CARDIAC ARREST IN ACUTE MYOCARDIAL INFARCTION
Authors: Ki-Hyun Jeon, Pil Sang Song, Min-Jung Kim, Kyung-Hee Kim, Ji-Bak Kim, Ho-Jun Jang, Je Sang Kim, Tae Hoon Kim, Hyunjong Lee, Jin-Sik Park, Young Jin Choi, Myoung-Mook Lee, Rak Kyeong Choi
Journal: Journal of the American College of Cardiology (2018)
COMPLEX GENOTYPE ASSOCIATED WITH A COMPLEX PHENOTYPE: NOVEL VARIANT MUTATION IN A 37 YEAR-OLD FEMALE WITH LEFT VENTRICULAR NON-COMPACTION AND SUSTAINED VENTRICULAR TACHYCARDIA
Authors: Rola Khedraki, Rajeev Mohan, J. Heywood, Ajay Srivastava
Journal: Journal of the American College of Cardiology (2018)
Journal retracts article for plagiarism after editorial board members resign in protest
Authors: Owen Dyer
Journal: BMJ (2018)

Scientific Reports , a Nature Publishing Group journal, has retracted a 2016 article after 19 Johns Hopkins researchers on its editorial board resigned in protest, claiming that an algorithm created by one of their colleagues had been copied and presented as original work in the journal.1

Michael Beer of Johns Hopkins University in Baltimore notified the editors in April 2016 that he believed the paper to have reworded his text and used his equations without proper attribution.

Three authors from the Shenzhen campus of the Harbin Institute of Technology in China reused equations developed by Beer to improve the identification of regulatory sequences in DNA. Using the technique to identify recombination spots in DNA, they called the algorithm SVM-gkm. …
Response to comment on Lent et al. All-Cause and Specific-Cause Mortality Risk After Roux-en-Y Gastric Bypass in Patients With and Without Diabetes. Diabetes Care 2017;40:1379–1385
Authors: Michelle R. Lent, Peter N. Benotti, G. Craig Wood
Journal: Diabetes Care (2018)

We thank Drs. Pontiroli and Zakaria (1) for their thoughtful comments in response to our recent study (2). Our results indicate that the large, significant overall reduction in mortality risk (when combining patients with and without diabetes) is driven by patients with diabetes. We found that Roux-en-Y gastric bypass (RYGB) patients with diabetes at the time of surgery experienced a survival benefit compared with nonsurgical control subjects with diabetes. The mortality risk in RYGB patients without diabetes was weaker and did …
Can recurrence patterns after curative resection for gastric adenocarcinoma (GCa) inform the selection of adjuvant treatment?
Authors: Shelly Luu, Jossie Swett-Cosentino, Shubham Shan, Stephanie Tung, Mina Siddiqui, Jolie Ringash, Savtaj Singh Brar, Natalie Coburn, Carol Jane Swallow
Journal: Journal of Clinical Oncology (2018)

136 Background: Despite improvements in multidisciplinary care and surgical technique, ≈40% of patients recur after curative resection for GCa. Adjuvant treatment decisions should be informed by the expected timing and site of failure, but accurate data are limited. The aim of our study was to describe and analyze the patterns of recurrence at our center. Methods: Patients who underwent curative intent margin-negative resection from 2006-16 were identified from a prospective GCa database. Date of first detection and site of recurrence were determined. Survival curves were calculated by the KM method. Univariate and multivariable analyses (MVA) were performed to identify predictive variables. Significance was set at p &lt; 0.05. Results: Of 123 patients who met inclusion criteria, median age was 70 yrs, 37% were female, and median follow-up after resection was 24 mos (IQR 11-40). Five-year OS was 72% and RFS 69%. In 34 of 36 patients who recurred, recurrence was detected within 2 yrs. Receipt of adjuvant therapy (Macdonald or MAGIC) was associated with better 5-year OS and RFS than surgery alone (79% vs. 60%, 77% vs. 60%) and delayed time to recurrence (median 10.4 vs. 7.1 mos). Receipt of CRT by the Macdonald protocol appeared to lower the risk of locoregional recurrence vs. surgery alone (see Table) despite routine D2 lymphadenectomy. On MVA, recurrence at any site was predicted by age £ 60y (OR 3.8), male gender (4.0), and AJCC stage &gt; II (4.6). Peritoneal recurrence was predicted only by age £ 60y (3.2). Conclusions: Recurrence after curative resection occurred within 2 yrs of resection. Locoregional recurrence was uncommon in patients who received postoperative CRT. Peritoneal recurrence, which might be abrogated by prophylactic HIPEC at the time of resection, is not well explained by clinicopathologic variables, and novel molecular predictors are required. [Table: see text]