tbuckley/cabot-search huggingface dataset:
P3-14-18: Primary Tumor Response to Neoadjuvant Chemotherapy Is Significantly Associated with Nodal Pathological Complete Response in Breast Cancer Patients with Cytologically Proven Axillary Node Metastasis.
Authors: H Hwang, S Park, JS Lee, S-I Kim, B-W Park
Journal: Cancer Research (2011)

Abstract Background: Axillary node status is the most significant factor for the prediction of outcome in breast cancer patients whether they received neoadjuvant chemotherapy or not. However, a reliable method to predict nodal response to neoadjuvant chemotherapy is not established yet. The aim of this study was to identify the predictive factors of axillary pathological complete response (pCR) after neoadjuvant chemotherapy in breast cancer patients with cytologically proven axillary lymph node metastases. Patients and methods: A total of 123 patients with axillary metastases confirmed by ultrasound-guided fine-needle aspiration biopsy were subsequently treated with four cycles of anthracycline (60mg/m2) plus cyclophosphamide (600mg/m2) followed by doxetaxel (75-100mg/m2) between August 2008 and March 2011. After neoadjuvant chemotherapy, all patients underwent a definite breast surgery with complete axillary lymph node dissection. Clinicopathological parameters were evaluated using a chi-square test and logistic regression model in association with node pCR. Results: The mean age at diagnosis was 47.9 years in all patients. Eighty-one (65.9%) patients were preoperative clinical T2 stage, 74 (60.2%) showed estrogen receptor (ER)-positivity, and 36 (29.3%) demonstrated HER2−positivity. A pCR of the axilla and breast was determined in 56 (46%) and 40 (31.7%) patients, respectively. Breast Pcr rate is significantly associated with age≤50 at diagnosis, ER(−),PR(−) and higher Ki-67 proliferation. Axillary pCR rate is significantly associated with age at diagnosis of 50 or less, smaller primary tumor size at diagnosis, tumor responsiveness to neoadjuvant chemotherapy, estrogen hormone receptors-negativity, higher Ki-67 proliferative index at diagnosis, and subtypes of HER2−enriched or triple negative breast cancer. When these factors entered logistic regression model, tumor response( SD+PD vs CR+PR: OR 8.603, P=0.007), Ki67((−) vs (+): OR 7.157, p=0.009), ER status((+) vs (−) : OR 4.943, P=0.036), pre-operation tumor size(&amp;gt;2cm vs ≤2cm: OR 5.116, p=0.044), HER2 status( (−) vs (+): OR 5.029,p=0.046) remained to be significant for the prediction of axillary pCR, favorable nodal response. Conclusion: Our study suggests that primary tumor response to neoadjuvant chemotherapy is significantly associated with favorable nodal response. The factors of tumor and nodal response were similar. There are many issues remained to be determined yet. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-14-18.
Pericarditis Associated With Inflammatory Bowel Disease
Authors: Dipankar Mukhopadhyay
Journal: JAMA (1970)

Pericarditis associated with inflammatory bowel disease occurred in three patients. This is an uncommon extraintestinal complication of inflammatory bowel disease, but it is one that should not be overlooked and one that further emphasizes the systemic nature of these diseases. Two of the patients had ulcerative colitis, and a third had probable granulomatous colitis. All three patients recovered from the pericarditis; however, one patient had repeated exacerbations of the pericarditis requiring corticosteroid therapy. We recommend corticosteroid treatment for this complication.
LATE RIGHT HEART FAILURE AFTER LEFT VENTRICULAR ASSIST DEVICE IMPLANTATION: CLINICAL PREDICTORS AND OUTCOMES
Authors: Shikhar Saxena, John Um, Ioana Dumitru, Samantha Pilmaier, Timothy Ryan, Shannon Yannone, Michael Moulton, Brian Lowes, Eugenia Raichlin
Journal: Journal of the American College of Cardiology (2013)
Marathon Running After Myocardial Infarction
Authors: Terry Kavanagh
Journal: JAMA (1974)

Eight patients, who had an aerobic power (maximum oxygen consumption) initially predicted as 72% of normal, were trained to the point of participation in the Boston Marathon one to four years after a demonstrated myocardial infarction. Seven of the eight completed the race at an average speed of 5.4 mph, corresponding to 81% of their maximum oxygen consumption. Symptoms and signs, both immediately after the race and later, were remarkably few. However, a substantial (4 kg) weight loss was incurred, with attendant dangers of heat stress. There was evidence of increased membrane permeability and protein catabolism (elevated levels of blood urea, creatinine, and creatinine phosphokinase) to a total of some 50 gm. Resting serum uric acid levels were normal. Marathon running should not be undertaken as a routine endeavor in post-myocardial infarction rehabilitation. (<i>JAMA</i>229:1602-1605, 1974)
GOLD; WITH ESPECIAL REFERENCE TO ITS CLINICAL APPLICATION.
Authors: JOHN V. SHOEMAKER
Journal: JAMA (1893)

<i>Pharmacology</i>.—The only form in wrhich gold is officinal is that of the so-called double chloride of gold and sodium, a combination of equal parts of the two salts, the compound corresponding to 32.4 of the metal. Auric chloride, though itself soluble in water, is not well absorbed. The dose of the chloride of gold and sodium may be stated as from 1/50 to 1/10 grain. The bromide has been employed, but has the disadvantage of being a less soluble salt than the double chloride. The bromide may be given in daily doses varying from 1/10 to ⅙ grain. The cyanide of gold has also been used. This salt is a yellowish crystalline powder devoid of taste, insoluble in water, alcohol and ether. The dose of the cyanide is 1/50 to 1/10 grain. <i>Physiological Action</i>.—Concentrated preparations of gold have an escharotic effect when locally applied. When taken internally in small doses
IMPROVED EAR ELECTRODES.
Authors: SETH S. BISHOP
Journal: JAMA (1891)

These electrodes consist of two metallic cones covered with chamois, and held in position for treatment by an elastic ribbon buckled around the head. The tips of the cones are moistened before inserting them in the external auditory canal. In order to keep them clean, it is well to place a small covering of cotton, moistened with warm water, over the tips of the cones while in use. It is a simple matter to adjust the cones to heads of any size by having one or two extra apertures in the ribbon, through which one of the cones can be easily passed. Or a second buckle can be put between the cones, at the back of the head, in order to alter the distance. The ribbon should never be buckled so firmly as to occasion uncomfortable pressure. The advantages of these electrodes over the old ones commonly employed for ear
P5-11-13: Rates of Upgrade to Malignancy for 271 Cases of Atypical Columnar Cell Hyperplasia Diagnosed by Breast Core Biopsy.
Authors: A Peres, E Barranger, V Becette, A Boudinet, J-M Guinebretiere, P Cherel
Journal: Cancer Research (2011)

Abstract Purpose: Atypical columnar cell hyperplasia (ACCH) is a borderline lesion that might represent an early stage in the development of certain low-grade carcinomas in situ (CIS) and invasive cancers. There are no guidelines on its management. Our objectives were to determine the upgrade to malignancy rate and identify a subpopulation of patients that might undergo just mammographic surveillance. Methods: We retrospectively reviewed the data for 271 ACCH cases among 5555 breast core biopsies obtained over a 7-year period (Jan. 2003 — Jan. 2010). We collated clinical data (age, history of cancer, menopausal status), radiological data (lesion type, size, Bi-Rads category), technical data (number of biopsies, needle gauge, excision quality) and histological data and sought correlations between these factors and upgrade rate. Results: The 271 ACCH comprised 128 cases of pure ACCH, 135 cases of ACCH + atypical ductal hyperplasia, and 8 cases of ACCH + atypical lobular hyperplasia. Overall, 184 patients underwent surgery and 46 mammographic surveillance. Surgery detected 34 cases of malignancy (23 CIS, 7 invasive cancers, and 4 mixed cases) giving a 15% upgrade rate. Quality of excision was the only factor associated with under-diagnosis. Conclusion: The presence of ACCH at biopsy warrants surgery. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-11-13.
Positive Gallium 67 Photoscan in Myeloblastoma
Authors: Steven M. Larson
Journal: JAMA (1972)

Whole-body rectilinear photoscans demonstrated active concentration of gallium citrate Ga 67 in myeloblastomas of the breast in two patients with acute myeloblastic leukemia. Clinical response to chemotherapy was associated with normal follow-up photoscans in both patients.
About Hallucinogenic Drugs
Authors: G. Birdwood
Journal: BMJ (1971)

and can only be judged in isolation.Combined together as separate chapters in this book they make a strange potpourri.It is stated in the preface that the book contains something for all specialists.Unfortunately, the corollary is also true that there is not very much for anybody.There is an obvious need for a widely published permanent record of the lectures so that they may take their place in the literature, and to- gether they will form an historical commen- tary on contemporary interests.But who is to buy this book to read it from cover to cover?Twenty chapters include such diverse titles as "The present status of fluoridation," "The biochemical pharmacology of tolerance to opioid analgesics," "The ageing eye," and "Recent advances in the understanding of the muscle spindle."The combined summaries might be required reading for some nightmare postgraduate cocktail party.The need to keep on a general front is accepted in the age of increasing specializa- tion, but who in active practice has time enough or is sufficiently motivated to en- compass more than one or two of these?In any case, a serious effort to keep up must be much more systematic than awaiting the in- evitably random offerings of this high- powered medical "Readers' Digest."
Management of ankle fractures
Authors: S. Mordecai, N. Al-Hadithy
Journal: BMJ (2011)

A 73 year old woman presented to the accident and emergency department after having fallen down a flight of stairs near her local shops. She had not injured her head; lost consciousness; or had a preceding event, such as chest pain, shortness of breath, or dizziness. After her fall she sustained a closed injury to her left ankle, which was swollen and painful to palpation over both malleoluses. She was also unable to bear weight on her left ankle. Her medical history included hypertension, hypercholesterolaemia, and osteoporosis. She had undergone hemiarthroplasty for a fracture to the neck of the right femur 10 years ago. She lived with her husband in a bungalow and was fully independent in activities of daily living, using a stick to mobilise. She was an ex-smoker and did not drink. The anterioposterior and lateral radiographs on admission are shown below (figs 1⇓ and 2⇓).



Fig 1 Anterioposterior radiograph on admission





Fig 2 Lateral radiograph on admission





### 1 When should a radiograph be ordered after an ankle injury?

#### Short answer

If there is bony tenderness over the medial malleolus or lateral malleolus and the patient cannot bear weight.

#### Long answer

The Ottawa ankle rules are a set of guidelines aimed at helping doctors in emergency medicine decide whether a patient with foot or ankle pain should be offered radiographic investigation.1 The guidelines were developed by a team of doctors working in the emergency department of the Ottawa Hospital, Canada, and have been adopted in emergency departments worldwide. Their main purpose is to limit the number of unnecessary radiographs, which are not only costly and time consuming but also expose …
Role of drug metabolism in drug discovery and development
Authors: Gondi N. Kumar, Sekhar Surapaneni
Journal: Medicinal Research Reviews (2001)

Abstract Metabolism by the host organism is one of the most important determinants of the pharmacokinetic profile of a drug. High metabolic lability usually leads to poor bioavailability and high clearance. Formation of active or toxic metabolites will have an impact on the pharmacological and toxicological outcomes. There is also potential for drug–drug interactions with coadministered drugs due to inhibition and/or induction of drug metabolism pathways. Hence, optimization of the metabolic liability and drug–drug interaction potential of the new chemical entities are some of the most important steps during the drug discovery process. The rate and site(s) of metabolism of new chemical entities by drug metabolizing enzymes are amenable to modulation by appropriate structural changes. Similarly, the potential for drug–drug interactions can also be minimized by appropriate structural modifications to the drug candidate. However, the optimization of the metabolic stability and drug–drug interaction potential during drug discovery stage has been largely by empirical methods and by trial and error. Recently, a lot of effort has been applied to develop predictive methods to aid the optimization process during drug discovery and development. This article reviews the role of drug metabolism in drug discovery and development. © 2001 John Wiley &amp; Sons, Inc. Med Res Rev, 21, No. 5, 397–411, 2001
Bicarbonate Therapy in Severe Diabetic Ketoacidosis
Authors: LAWRENCE R. MORRIS
Journal: Annals of Internal Medicine (1986)

Twenty-one adult patients with severe diabetic ketoacidosis entered a randomized prospective protocol in which variable doses of sodium bicarbonate, based on initial arterial pH (6.9 to 7.14), were administered to 10 patients (treatment group) and were withheld from 11 patients (control group). During treatment, there were no significant differences in the rate of decline of glucose or ketone levels or in the rate of increase in pH or bicarbonate levels in the blood or cerebrospinal fluid in either group. Similarly, there were no significant differences in the time required for the plasma glucose level to reach 250 mg/dL, blood pH to reach 7.3, or bicarbonate level to reach 15 meq/L. We conclude that in severe diabetic ketoacidosis (arterial pH 6.9 to 7.14), the administration of bicarbonate does not affect recovery outcome variables as compared with those in a control group.
Epithelial cells as regulators of airway inflammation
Authors: Albert J. Polito, David Proud
Journal: Journal of Allergy and Clinical Immunology (1998)

The past decade has seen major advances in our understanding of the metabolic and biochemical functions of the epithelial cell. As a result, the traditional view of the epithelium as a relatively passive physical barrier to the external environment has been superseded by the concept that the epithelial cell plays a key role in regulating airway inflammation. The epithelial cell exerts this modulatory effect in several ways. Epithelial cells can function to maintain mucosal integrity and to modulate local immune responses. They can also limit inflammatory processes by degrading, or inhibiting, proinflammatory mediators and proteins. However, the epithelium also responds to a range of stimuli by producing biologically active mediators that can influence airway inflammation. These include, but are not limited to, a broad range of cytokines and chemokines that can exert profound effects on inflammatory cells, as well as lipid and peptide mediators. This review will highlight some of these aspects of the role of the epithelium in regulating airway inflammation. (J Allergy Clin Immunol 1998;102:714-8.)
A Preliminary Report of Experimental Researches concerning the Infectious Nature of Traumatic Tetanus
Authors: E. O. Shakespeare
Journal: BMJ (1887)

forty to ninety grains of the powdered collinsonia root will, in many cases, render any operative procedure unnecessary.The first patient was a woman, aged 45, who suffered for years from darting pains in the rectum, especially severe just before defaecation.Sie has visited numerous celebrated springs, and consulted several regular and irregular physicians without obtaining marked relief.
725. Correction of Laminin-5-Deficient Junctional Epidermolysis Bullosa by Transplantation of Genetically Modified Epidermal Stem Cells. A Phase-I Clinical Trial
Authors: Fulvio Mavilio, Stefano Ferrari, Francesca Di Nunzio, Giulietta Maruggi, Chiara Bonini, Sergio Capurro, Andrea Conti, Alberto Giannetti, Graziella Pellegrini, Michele De Luca
Journal: Molecular Therapy (2006)

Mutations in genes encoding the laminin-5 heterotrimer, a key component of the epidermal-dermal junction, cause junctional epidermolysis bullosa (JEB), a severe and often fatal skin adhesion defect. Epidermal stem cells isolated from patients affected by β3 chain-deficient JEB were transduced with a retroviral vector expressing a β3 cDNA, and used to generate uniformly transduced cultured skin implants. The transgene was steadily expressed for >160 cell doublings in culture, leading to restoration of normal laminin 5 levels, assembly of functional hemidesmosomes, and full phenotypic correction. Cloning and sequencing of vector integrations showed that <20 stem cells are responsible for long-term maintenance of a transplantable skin culture. A phase-I clinical trial started in October 2005, aimed at proving the safety of the transduction/transplantation procedure, and analyzing persistence of transgene expression and long-term survival of transduced stem cells. The first patient was a 30-yr-old male affected by non-lethal JEB, carrying a null mutation in one LAMB3 allele and a point mutation (E212K) in the other one. The mutation affects the assembly of the laminin-5 heterotrimer, present at residual levels (<5%) in vitro and in vivo. Six genetically modified, cultured epidermal sheets of 100 sq cm were transplanted on both legs after removal of the outer skin layer using a minimally invasive technique. The procedure was well tolerated, and the patient discharged after five days. Engraftment was completed after 10 days, and transplanted skin remained stable on both legs in the absence of blistering or inflammation for the duration of the follow-up (4 months at the time of writing). 3-mm punch biopsies were taken 1 and 3 months after transplantation, and analyzed for vector presence by quantitative PCR and for protein expression by immunohistochemistry. A vector signal compatible with full transduction of the transplanted epidermis was observed at both time points. Synthesis and assembly of normal levels of heterotrimeric laminin-5 and α6β4 integrin was observed at the level of the basal lamina in all biopsies, together with the development of a firmly adherent, fully differentiated epidermis. Epidermal stem cells (p64+) were detected in the basal layer of the transplanted skin in normal numbers. These data show that gene therapy of JEB by transplantation of genetically corrected stem cells is feasible, and leads to full phenotypic correction of the adhesion defect in vivo. Safety studies are under way, which include detection or humoral or cytotoxic immune responses against laminin-5, and ex vivo cloning and sequencing of the integrated proviruses.
Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration
Authors: Erik S. Musiek, Miranda M. Lim, Guangrui Yang, Adam Q. Bauer, Laura Qi, Yool Lee, Jee Hoon Roh, Xilma Ortiz-Gonzalez, Joshua T. Dearborn, Joseph P. Culver, Erik D. Herzog, John B. Hogenesch, David F. Wozniak, Krikor Dikranian, Benoit I. Giasson, David R. Weaver, David M. Holtzman, Garret A. FitzGerald
Journal: Journal of Clinical Investigation (2013)

Brain aging is associated with diminished circadian clock output and decreased expression of the core clock proteins, which regulate many aspects of cellular biochemistry and metabolism. The genes encoding clock proteins are expressed throughout the brain, though it is unknown whether these proteins modulate brain homeostasis. We observed that deletion of circadian clock transcriptional activators aryl hydrocarbon receptor nuclear translocator-like (Bmal1) alone, or circadian locomotor output cycles kaput (Clock) in combination with neuronal PAS domain protein 2 (Npas2), induced severe age-dependent astrogliosis in the cortex and hippocampus. Mice lacking the clock gene repressors period circadian clock 1 (Per1) and period circadian clock 2 (Per2) had no observed astrogliosis. Bmal1 deletion caused the degeneration of synaptic terminals and impaired cortical functional connectivity, as well as neuronal oxidative damage and impaired expression of several redox defense genes. Targeted deletion of Bmal1 in neurons and glia caused similar neuropathology, despite the retention of intact circadian behavioral and sleep-wake rhythms. Reduction of Bmal1 expression promoted neuronal death in primary cultures and in mice treated with a chemical inducer of oxidative injury and striatal neurodegeneration. Our findings indicate that BMAL1 in a complex with CLOCK or NPAS2 regulates cerebral redox homeostasis and connects impaired clock gene function to neurodegeneration.
KaKs_Calculator: Calculating Ka and Ks Through Model Selection and Model Averaging
Authors: Zhang Zhang, Jun Li, Xiao-Qian Zhao, Jun Wang, Gane Ka-Shu Wong, Jun Yu
Journal: Genomics Proteomics & Bioinformatics (2006)

Abstract KaKs_Calculator is a software package that calculates nonsynonymous (Ka) and synonymous (Ks) substitution rates through model selection and model averaging. Since existing methods for this estimation adopt their specific mutation (substitution) models that consider different evolutionary features, leading to diverse estimates, KaKs_Calculator implements a set of candidate models in a maximum likelihood framework and adopts the Akaike information criterion to measure fitness between models and data, aiming to include as many features as needed for accurately capturing evolutionary information in protein-coding sequences. In addition, several existing methods for calculating Ka and Ks are also incorporated into this software. KaKs_Calculator, including source codes, compiled executables, and documentation, is freely available for academic use at http://evolution.genomics.org.cn/software.htm.
Adult Lactose Tolerance
Authors: Robert D. McCracken
Journal: JAMA (1970)

Few aspects of human behavior are characterized by more ethnocentrism than a group's dietary habits and practices. People around the world usually tend to assume that their foods are the most tasty and the most nutritious. Often such beliefs find expression as dietary prescriptions for others. Here the assumption is "because we find these foods 'tasty' and nutritious, you should also." Such beliefs, of course, could not be farther from the truth, and in an article to appear later this year in the anthropological journal<i>Current Anthropology</i>, I have reviewed evidence from several disciplines which seems to indicate that (1) Westerners, despite the trappings of civilization, are not free from such biases; (2) racial-cultural groups differ greatly in their ability to benefit nutritionally from certain foods, in particular milk and many milk products; and (3) such differences can be accounted for in terms of a model dealing with the interaction