tbuckley/cabot-search huggingface dataset:
Cavity Shave Margins in Breast Cancer
Authors: Long Jiang, Shanshan Jiang, Hao Long
Journal: New England Journal of Medicine (2015)

To the Editor: The results of the clinical trial reported by Chagpar et al. (Aug. 6 issue)1 may be broadly applied to help both surgeons and patients avoid positive margins and reoperation after partial mastectomy for breast cancer. However, in this study, both the original resection of margins and the additional resection of circumferential margins (in the shave group) were simply defined as the standards according to the usual practice of four surgeons. The exact original and additional margins for resection were not standardized for clinical practice. There is no question that surgeons at the Yale Cancer Center were experienced in performing breast-conserving operations. Nevertheless, in their clinical practices in other centers, how can surgeons determine the proper resection of both original and additional margins? Since frozensection examination was not used in the intraoperative pathological evaluation, can the authors clearly address the exact criterion used to determine the original margins for resection? Long Jiang, M.D.
Clozapine and fertility [letter]
Authors: Dickson Ra, Edwards A
Journal: American Journal of Psychiatry (1997)

Outcome measures beyond standard psychopathology scales are now being used to determine the impact of clozapine on the quality of life of patients families and society; one area that has been neglected is fertility.  Clozapine unlike traditional neuroleptics does not cause sustained increases in serum prolactin levels.  This hyperprolactinemia associated with neuroleptic treatment has caused impotence in men and anovulatory cycles or amenorrhea in women.  Normalization of prolactin secretion may restore reproductive function in cases where the hyperprolactinemia is not associated with neuroleptics.  Pregnancies wanted and unwanted have been reported in women taking clozapine.  Although retrograde ejaculation has been reported in men taking clozapine nothing appears in the literature concerning the fertility of men taking clozapine.  The Calgary General Day Hospital treats 235 patients with psychotic disorders (mainly schizophrenia); 12% are taking clozapine.  Of these one man fathered a child; one woman who continued her medication throughout her pregnancy had a healthy baby; and one mans partner had twins.  During the same period five children (two were fathered by one man) were born to the 88% of clinic patients who were not taking clozapine.  Although these numbers are not controlled for age sex and marital status it appears that the birth rate among patients who take clozapine may be higher than among those who take conventional neuroleptics.  This could be due to improvement in both reproductive and social functioning.  Most studies on clozapine and fertility have focused on women and pregnancy; however more male than female patients are treated with clozapine and a mans fertile years greatly outnumber those of a woman.  Further research in this area is needed.
Engagement of the B-cell receptor of chronic lymphocytic leukemia cells drives global and MYC-specific mRNA translation
Authors: Alison Yeomans, Stephen M. Thirdborough, Beatriz Valle-Argos, Adam Linley, Sergey Krysov, Marina Sanchez Hidalgo, Elodie Leonard, Muhammad Ishfaq, Simon D. Wagner, Anne E. Willis, Andrew J. Steele, Freda K. Stevenson, Francesco Forconi, Mark J. Coldwell, Graham Packham
Journal: Blood (2015)
Hypoxia-Activated Prodrug TH-302 Targets Hypoxic Bone Marrow Niches in Preclinical Leukemia Models
Authors: Juliana Benito, Marc S. Ramirez, Niki Zacharias Millward, Juliana Velez, Karine G. Harutyunyan, Hongbo Lu, Yue-xi Shi, Polina Matre, Rodrigo Jacamo, Helen Ma, Sergej Konoplev, Teresa McQueen, Andrei Volgin, Marina Protopopova, Hong Mu, Jaehyuk Lee, Pratip K. Bhattacharya, Joseph R. Marszalek, R. Eric Davis, James A. Bankson, Jorge E. Cortes, Charles P. Hart, Michael Andreeff, Marina Konopleva
Journal: Clinical Cancer Research (2015)

To characterize the prevalence of hypoxia in the leukemic bone marrow, its association with metabolic and transcriptional changes in the leukemic blasts and the utility of hypoxia-activated prodrug TH-302 in leukemia models.Hyperpolarized magnetic resonance spectroscopy was utilized to interrogate the pyruvate metabolism of the bone marrow in the murine acute myeloid leukemia (AML) model. Nanostring technology was used to evaluate a gene set defining a hypoxia signature in leukemic blasts and normal donors. The efficacy of the hypoxia-activated prodrug TH-302 was examined in the in vitro and in vivo leukemia models.Metabolic imaging has demonstrated increased glycolysis in the femur of leukemic mice compared with healthy control mice, suggesting metabolic reprogramming of hypoxic bone marrow niches. Primary leukemic blasts in samples from AML patients overexpressed genes defining a "hypoxia index" compared with samples from normal donors. TH-302 depleted hypoxic cells, prolonged survival of xenograft leukemia models, and reduced the leukemia stem cell pool in vivo In the aggressive FLT3/ITD MOLM-13 model, combination of TH-302 with tyrosine kinase inhibitor sorafenib had greater antileukemia effects than either drug alone. Importantly, residual leukemic bone marrow cells in a syngeneic AML model remain hypoxic after chemotherapy. In turn, administration of TH-302 following chemotherapy treatment to mice with residual disease prolonged survival, suggesting that this approach may be suitable for eliminating chemotherapy-resistant leukemia cells.These findings implicate a pathogenic role of hypoxia in leukemia maintenance and chemoresistance and demonstrate the feasibility of targeting hypoxic cells by hypoxia cytotoxins.
Dehydrated hereditary stomatocytosis
Authors: David Mark Layton, Barbara J. Bain
Journal: American Journal of Hematology (2015)

A 27-year-old woman of Northern European origin initially presented at the age of 11 years with symptoms of cholelithiasis. Prior to laparoscopic cholecystectomy mild normocytic anemia (Hb 100 g/l) with reticulocytosis and unconjugated hyperbilirubinemia had been noted. Her mother reported that she had required phototherapy for neonatal jaundice and had suffered from fatigue and jaundice intermittently since early childhood. There was no antecedent family history of anemia or hemolysis. Extensive investigations for congenital hemolytic anemia failed to identify a clear cause but revealed increased resistance to osmotic lysis (mean cell fragility 3.15 g/l NaCl; reference range 4.0–4.45) with an elevated MCHC (356–378 g/l) and reduced 2,3-DPG content (10.4 μmol/g Hb; reference range 12.7–17.9) and DPG/ATP ratio (1.8; reference range 2.4–3.6). Based on this and the red cell morphology, a diagnosis of dehydrated hereditary stomatocytosis (also known as hereditary xerocytosis) was suspected. The blood film showed stomatocytosis, polychromatic macrocytes, and occasional target cells and irregularly contracted cells (images). In both dehydrated and overhydrated forms of hereditary stomatocytosis, red cells typically exhibit reduced intracellular potassium [K]i and increased [Na]i content due to passive cation flux. Measurement of [Na]i and [K]i of the patient's red cells was unremarkable but isotopic flux studies using 86Rb as a surrogate demonstrated increased permeability of red cells to potassium with a 4–5 fold increase in K influx resistant to ouabain and bumetanide (to inhibit the NaK pump and NaKCl cotransport). Taken together, these findings are consistent with dehydrated hereditary stomatocytosis. In addition to cholelithiasis, dehydrated hereditary stomatocytosis is associated with several extra-hematological features including perinatal edema, neonatal hepatitis, pseudohyperkalemia, and a propensity to nontransfusional iron overload. Splenectomy is contraindicated due to an increased risk of thromboembolism. Inheritance is autosomal dominant. Gain-of-function mutations in PIEZO, encoding a mechanosensitive cation channel, and deleterious mutations of KCNN4, encoding the Gardos channel have been implicated 1, 2. Despite well-compensated hemolysis with an Hb in the range 95–115 g/l the patient suffers significant fatigue and physical limitation. This may be explained by the effect of a low red cell 2,3 DPG concentration on tissue oxygen delivery consistent with which the oxygen dissociation curve was left shifted with a p50 of 20.76 mmHg (reference range 27–33). The authors wish to thank Professor Gordon Stewart for the intracellular cation flux studies.
Anatomical Organization of Macaque Monkey Striate Visual Cortex
Authors: J S Lund
Journal: Annual Review of Neuroscience (1988)

I hope that this review of the internal anatomy of the monkey primary visual cortex makes clear the high degree of specialization that exists in each of the cortical laminae and their constituent neurons. Each lamina is driven by different patterns of relays from the LGN and by different patterns of intrinsic interlaminar projections. The elaborate laminar and intralaminar segregation of efferent neuron arrays suggests that the extraordinary precision of inter- and intralaminar connectivity provides a unique functional role for each set of efferent neurons. The organization of aspinous (presumed inhibitory) local circuit neurons suggests that they are highly specialized, and within each lamina and via interlaminar relays each variety may only accomplish a single, particular task. The cortex neuropil does not give the immediate impression of "random" networks, and if such exist, they must surely be between very tightly determined subgroups of neurons. Clearly a very detailed physiological exploration of V1 is still needed, with new consideration of thalamic axon function, of efferent neuron characteristics, of laminar differences, and of spatial organization of properties within laminae, in order to match known anatomical detail with function. The concept of columnar organization in cortical organization of V1 may eventually be redefined in more complex terms that accurately describe the anatomical and functional parcellation evident in cortical depth and perhaps may link it to a means by which a correlation of different aspects of the visual image is achieved.
The Application of Bacteriology to Public Health
Authors: W. C. C. Pakes
Journal: BMJ (1900)

<h3>Background</h3> Quality improvement (QI) is a priority for national regulatory bodies in health and care in the UK. However, many health and care staff do not know where to go for support in gaining the required skills and knowledge in QI. This paper reviews Improvement Fundamentals, a massive open online course (MOOC), designed to address this gap, run by an improvement team in the national regulatory body. <h3>Methods</h3> In 2015, National Health Service (NHS) Improving Quality (subsequently the sustainable improvement team in NHS England) established Improvement Fundamentals: a programme of online, self-directed courses in QI for those involved in heath or social care. The programme ran in two cycles: twice in 2015, followed by a re-launch in 2018 (this programme also ran into 2019). A mixed-methods evaluation was carried out of the 2015 programme involving surveys, interviews and social listening. The 2018–2019 programme was evaluated using post-course surveys of participants and activity data from the platform. <h3>Outcomes</h3> Since the start of the 2015 programme, 604 improvement projects have been developed, run and submitted for formal assessment, with some demonstrating clear improvements in services. Themes from participant feedback on both programmes have included improved understanding of QI tools and methods; greater energy for QI; a greater sense of community and connectedness in participants’ work and increased confidence in using QI tools and techniques. <h3>Discussion</h3> Both programmes delivered benefits for participants, and the team’s investment in improvement skills on these programmes has helped to increase capability for future change endeavours. The collaborative nature of the programmes has been key to their successes. <h3>Conclusion</h3> Improvement Fundamentals demonstrates that MOOCs can be instrumental in driving forward improvements in health and care. The programmes may have utility as a model for future MOOCs, both in QI and other topics, to help drive further improvements in health and care.
Association of Height with Elevated Mortality Risk in ESRD
Authors: Mohamed E. Elsayed, John P. Ferguson, Austin G. Stack
Journal: Journal of the American Society of Nephrology (2015)

The association of adult height with mortality has been extensively investigated in the general population, but little is known about this relationship among dialysis patients. We explored the relationship between height and mortality in a retrospective cohort study of 1,171,842 adults who began dialysis in the United States from 1995 to 2008 and were followed until December 31, 2010. We evaluated height-mortality associations in sex-specific quintiles of increasing height (Q1-Q5) using multivariable Cox regression models adjusted for demographics, comorbid conditions, lifestyle and disability indicators, socioeconomic status, and body weight. For men, compared with the referent quintile (Q1 <167 cm), successive height quintiles had significantly increased hazard ratios (HRs [95% confidence interval]) for mortality: 1.04 (1.02-1.06), 1.08 (1.06-1.10), 1.12 (1.11-1.14), and 1.18 (1.16-1.20) for Q2-Q5, respectively. For women (referent Q1 <155 cm), HRs for mortality were 1.00 (0.99-1.02), 1.05 (1.03-1.06), 1.05 (1.03-1.07), and 1.08 (1.06-1.10) for Q2-Q5, respectively. However, stratification by race showed the pattern of association differed significantly by race (P<0.001 for interaction). For black men, unlike other race groups, height only associated with mortality in Q5, with an HR of 1.06 (1.02-1.09). For black women, HRs for mortality were 0.94 (0.91-0.97), 0.98 (0.95-1.02), 0.96 (0.93-0.99), and 0.99 (0.96-1.02) for Q2-Q5, respectively. These results indicate tallness is associated with higher mortality risks for adults starting dialysis, but this association did not extend to black patients.
Axonal Transport: Components, Mechanisms, and Specificity
Authors: J H Schwartz
Journal: Annual Review of Neuroscience (1979)

The neuron is a regionally differentiated cell. Axonal transport is the pro­ cess by which materials, chiefly membranous and metabolically active, are moved rapidly from one region to another. The study of transport has recently attracted neurobiologists with widely different interests. Some are drawn to it because of their primary interest in neuronal physiology and biochemistry; these are eager to understand transport in order to compre­ hend the cellular dynamics of neuronal functioning. Others, interested in the organization of the brain, have used transport as a neuroanatomical tool. Axonal transport occurs in two directions, from the cell body to terminals (anterograde) and from terminals to the cell body (retrograde). Once it is recognized that almost all macromolecular synthesis occurs in the peri­ caryon, the functional significance of anterograde transport becomes obvi­ ous. Essentially all subcellular organelles and membrane components in axons, dendrites, and nerve terminals must originate in the cell body, if not fully assembled, then at least in some precursor form. Transport also occurs in the retrograde direction, returning worn out materials from nerve termi­ nals to the cell body for either degradation or restoration. Although its role in the pathogenesis of neurotropic viral diseases was suggested in the 1920s (see Baringer 1975), retrograde transport only recently has been shown to play an important part in the life cycle of the synaptic vesicle (see Heuser & Reese 1974, Holtzman 1977). Both anterograde and retrograde axonal transport have also been widely used during the past decade as the basis for
The Duty to Disclose Adverse Clinical Trial Results
Authors: S. Matthew Liao, Mark Sheehan, Steve Clarke
Journal: The American Journal of Bioethics (2009)

Participants in some clinical trials are at risk of being harmed and sometimes are seriously harmed as a result of not being provided with available, relevant risk information. We argue that this situation is unacceptable and that there is a moral duty to disclose all adverse clinical trial results to participants in clinical trials. This duty is grounded in the human right not to be placed at risk of harm without informed consent. We consider objections to disclosure grounded in considerations of commercial interest, and we argue that these concerns are insufficient to override the moral duty to disclose adverse clinical trial results. However, we also develop a proposal that enables commercial interests to be protected, while promoting the duty to disclose adverse clinical trial results.
WITHDRAWN: Optimization of trans-resveratrol extraction from peanut kernels using supercritical fluid extraction
Authors: Kritamorn Jitrangsri, Amornrut Chaidedgumjorn, Malai Satiraphan
Journal: Asian Journal of Pharmaceutical Sciences (2015)

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.
LumeNEXT: A Practical Method to Pattern Luminal Structures in ECM Gels
Authors: José A. Jiménez‐Torres, Stephen L. Peery, Kyung E. Sung, David J. Beebe
Journal: Advanced Healthcare Materials (2015)

In vitro biomimetic modeling of physio­logical structures bridges the gap between 2D in vitro culture and animal models. Lumens (tubular structures) are ubiquitous in vivo, being present in blood vessels, mammary ducts, and the lymphatic system. A method ‘LumeNEXT' is presented here that allows the fabrication of 3D embedded lumens where size, structure, distance, and configuration can be controlled using standard poly­dimethylsiloxane micromolding methods. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
<i>SFTPA2</i> Mutations in Familial and Sporadic Idiopathic Interstitial Pneumonia
Authors: Coline H. M. van Moorsel, Liesbeth ten Klooster, Matthijs F. M. van Oosterhout, Pim A. de Jong, Human Adams, H. Wouter van Es, Henk J. T. Ruven, Joanne J. van der Vis, Jan C. Grutters
Journal: American Journal of Respiratory and Critical Care Medicine (2015)
A clinical and pharmacokinetic study of mitoxantrone in acute nonlymphocytic leukemia.
Authors: R A Larson, K M Daly, K E Choi, D S Han, J A Sinkule
Journal: Journal of Clinical Oncology (1987)

Twenty-two patients with relapsed or refractory acute leukemia received 31 treatment courses of mitoxantrone (10 to 12 mg/m2/d) as a one-hour infusion for five days. Seven of the 13 patients who had greater than or equal to 95% reduction in the leukemia cell mass, calculated using the bone marrow examination on day 6, achieved a complete remission (CR). These remissions lasted up to 14 months without additional therapy. There were no CRs among the 18 patients who had less than 95% cytoreduction by day 6. The sequential addition of 5-azacytidine (200 mg/m2/d) for three days in those patients with residual disease on day 6 provided little additional benefit. Nonhematological toxicity from mitoxantrone was mild, although fever and infection were common. A new high-performance liquid chromatography (HPLC) assay was used to describe the clinical pharmacokinetics of mitoxantrone. Neither clinical response nor toxicity was strongly correlated with the peak plasma mitoxantrone concentration on the first day (mean +/- SD, 510 +/- 206 ng/mL), nor the area under the concentration-time curve (484 +/- 229 ng X h/mL), nor the systemic clearance (405 +/- 124 mL/min/m2). Mitoxantrone causes rapid cytoreduction in acute nonlymphocytic leukemia (ANLL), but the optimal dose and schedule remain to be determined.
Extended pre-exposure prophylaxis with lopinavir–ritonavir versus lamivudine to prevent HIV-1 transmission through breastfeeding up to 50 weeks in infants in Africa (ANRS 12174): a randomised controlled trial
Authors: Nicolas Nagot, Chipepo Kankasa, James K Tumwine, Nicolas Meda, G Justus Hofmeyr, Roselyne Vallo, Mwiya Mwiya, Mary Kwagala, Hugues Traore, Amwe Sunday, Mandisa Singata, Chafye Siuluta, Eric Some, David Rutagwera, Desire Neboua, Grace Ndeezi, Debra Jackson, Valérie Maréchal, Dorine Neveu, Ingunn M S Engebretsen, Carl Lombard, Stéphane Blanche, Halvor Sommerfelt, Claire Rekacewicz, Thorkild Tylleskär, Philippe Van de Perre, Philippe Van de Perre, Nicolas Nagot, Roselyne Vallo, Valerie Marechal, Marianne Peries, Dorine Neveu, Vincent Foulongne, Michel Segondy, Stephane Blanche, Jean-Marc Treluyer, Deborah Hirt, James K Tumwine, Grace Ndeezi, Charles Karamagi, Philippa Musoke, Proscovia M Mugaba, Mary Kwagala, Joan Murungi, Hawa Nabuuma Muweesi, Evelyn Ninsiima, Simon Baryeija, Frederic Juma, Caleb Bwengye Kata, Stuart Katushabe, Nicolas Meda, Rasmata Ouédraogo, Diarra Yé, Eric Somé, Hugues A Traoré, Christelle Nadembega, Justin Konaté, Arsène Zongo, Abass Ouédraogo, Désiré Néboua, Aissatou Bélemviré, Armel Bambara, Justine Boncoungou, Danielle Zoungrana, Cheryl Nikodem, Justus Hofmeyr, Kim Harper, Debra Jackson, David Sanders, Mandisa Singata, Amwe Aku, Collins Okegbe-Eze, Xoliswa Williams, Nolundi Mshweshwe, Vatiswa Henge, Fikiswa Gomba, Tapiwa Gundu, Oswell Khondowe, Chipepo Kankasa, Mwiya Mwiya, Mildred Lusaka, Mary Chizyuka, Mary Phiri, Billies Imakando, Mwenechanya Musaku, Monica Kapasa, David Rutagwera, Gondwe Clement, Hilton Mwila Mwaba, Japhet Matoba, Chafye Siuluta, Katai Chola, Patricia Mwamutanda, Thorkild Tylleskär, Halvor Sommerfelt, Ingunn Engebretsen, Jørn Klungsøyr, Jan van den Broeck, Jörn Blume, Claire Rekacewicz
Journal: The Lancet (2015)
ACTIVITY OF NIAMID<sup>®</sup>AGAINST MYCOBACTERIUM TUBERCULOSIS AND CROSS RESISTANCE TO ISONIAZID
Authors: George A. Klugh, Philip C. Pratt, Robert J. Atwell
Journal: American Journal of Psychiatry (1960)

This study shows that there is cross resistance of tubercle bacilli to Niamid® and Isoniazid. When Niamid is administered to a patient, thorough studies should be carried out to determine if the patient also has active tuberculosis. If so, a second anti-tuberculous drug should also be used, in accordance with currently established principles of combined drug therapy for tuberculosis.
The role of inflammatory cells in tendinopathy: is the picture getting any clearer?
Authors: Jonathan D Rees
Journal: British Journal of Sports Medicine (2015)

The role of inflammation in chronic tendinopathy is controversial and highly debated. For these reasons the systematic review by Dean et al 1 is a welcome contribution. It is a dispassionate examination of the role of inflammatory cells in chronic tendinopathy. It highlights that macrophages and mast cells in particular are present in elevated levels in chronic symptomatic tendinopathy in humans. Clearly this does not imply that chronic tendinopathy is primarily an inflammatory condition. Nevertheless this review adds weight to the argument that to think of chronic tendinopathy as purely a degenerative condition is an oversimplification.2 The fact that the Dean et al review is restricted to human tissue adds to the importance of the conclusions.



1.  Chronic tendinopathy is extremely common. It is often career threatening to the athlete and causes enormous …