tbuckley/cabot-search huggingface dataset:
Guidelines for cardiopulmonary resuscitation and emergency cardiac care, I: Introduction
Authors: R. E. Kerber, J. P. Ornato, D. D. Brown, L. Chameides, N. C. Chandra, R. O. Cummins, M. F. Hazinski, R. J. Melker, W. D. Weaver, N. S. Abramson, H. P. Adams, R. V. Aghababian, R. Albarran-Sotelo, J. S. Alpert, J. A. Atkins, T. P. Aufderheide, M. J. Banner, G. Bar-Joseph, L. Becker
Journal: JAMA (1992)
Male breast cancer retrospective institution review of a 17-year period
Authors: C. Rodriguez Franco, D. Aguiar Bujanda, S. Saura Grau, U. Bohn Sarmiento, J. Aguiar Morales
Journal: Journal of Clinical Oncology (2009)

e11638 Background: Male breast cancer (MBC) is a very uncommon illness relative to female breast cancer (FBC) The are some differences between both that could influence the management, like gene expression, hormonal enviroment and anatomy of the gland. Methods: Retrospective review of patients diagnosed in a seventeen year period (1990–2007). Results: There were 22 male patients diagnosed in our institution with a median age of 62.4 years (range 34 to 83 years) during the period. One had bilateral breast cancer. Stage of disease was I-II in 13 patients (59%), III in 8 patients (36%), and IV in 1 patient (5%). Five patients (22.7%) had familiar history of breast cancer and 3 patients (13%) had familiar history of other kind of neoplasias. Hormonal receptor were positive in thirteen patiens (59%) and 5 were unknown (23%). Ductal carcinoma was the predominant histologic subtype with 17 patients (77%). Other types were pleomorfic, mucoid and papilar carcinoma (one each type) and 3 patients with intrapapilar carcinoma with microinfiltration. Eleven of 20 patologic available axilla had node positive (55%). Grade were I in 3 patients (13%), II in 4 patients (18%), III in 8 (37%) and undefined in in 7 (32%). Surgery was the initial treatment in 18 patients (81%), just 2 of them performing tumorectomy and the other 16 radical mastectomy. 3 patients receive neoadyuvant chemotherapy with 1 complete response and one partial response. 13 patients (59%) received adjuvant radiotherapy (RT) and 17 (77%) adjuvant hormonal therapy (HT) mostly of them with tamoxifen (14/17) and the others 3 patients with aromatase inhibitors. Adjuvant chemotherapy was used in 9 (41%) patients with an antracycline regimen. With a median follow-up of 78 months (range 7–125), overall survival was 77 % with 3 patients died with progression disease and two patients died because of intercurrent illness without evidence of cancer progression. Regarding to our population area we had an incidence of 0.96/100.000 inhabitants during this 17 year period. Conclusions: MBC in our area are in the upper limit of occidental countries incidence. Most cases can be treated with radical intention with surgery (mostly radical) and adjuvant treatment with a good survival percentage. We manage MBC like we do FBC because of absence of clinical randomized trial specific for MBC. No significant financial relationships to disclose.
Fatty Acid-Modified Gapmer Antisense Oligonucleotide and Serum Albumin Constructs for Pharmacokinetic Modulation
Authors: Michael Lykke Hvam, Yunpeng Cai, Frederik Dagnæs-Hansen, Jesper Sejrup Nielsen, Jesper Wengel, Jørgen Kjems, Kenneth A. Howard
Journal: Molecular Therapy (2017)

Delivery technologies are required for realizing the clinical potential of molecular medicines. This work presents an alternative technology to preformulated delivery systems by harnessing the natural transport properties of serum albumin using endogenous binding of gapmer antisense oligonucleotides (ASOs)/albumin constructs. We show by an electrophoretic mobility assay that fatty acid-modified gapmer and human serum albumin (HSA) can self-assemble into constructs that offer favorable pharmacokinetics. The interaction was dependent on fatty acid type (either palmitic or myristic acid), number, and position within the gapmer ASO sequence, as well as phosphorothioate (PS) backbone modifications. Binding correlated with increased blood circulation in mice (t1/2 increased from 23 to 49 min for phosphodiester [PO] gapmer ASOs and from 28 to 66 min for PS gapmer ASOs with 2× palmitic acid modification). Furthermore, a shift toward a broader biodistribution was detected for PS compared with PO gapmer ASOs. Inclusion of 2× palmitoyl to the ASOs shifted the biodistribution to resemble that of natural albumin. This work, therefore, presents a novel strategy based on the proposed endogenous assembly of gapmer ASOs/albumin constructs for increased circulatory half-life and modulation of the biodistribution of gapmer ASOs that offers tunable pharmacokinetics based on the gapmer modification design.
Type 1 Diabetes and Autism: Is there a link?
Authors: Denis Daneman
Journal: Diabetes Care (2006)

We thank Harjutsalo and Tuomilehto (1) for their most informative comments. There can be no doubt that they have thoroughly investigated the potential association between type 1 diabetes and autism spectrum disorder (ASD) in a large population-based cohort of Finnish children and failed to find any suggestion of an association. Why might their data differ from ours?

Based on clinical experiences, we reported what had appeared to be a higher-than-expected prevalence of ASD in our …
Episodic memory as an explanation for the insurance hypothesis in obesity
Authors: Kirsty Mary Davies, Lucy Gaia Cheke, Nicola Susan Clayton
Journal: Behavioral and Brain Sciences (2017)

Abstract In evaluating the insurance hypothesis as an explanation for obesity, we propose one missing piece of the puzzle. Our suggested explanation for why individuals report food insecurity is that an individual may have an impaired episodic ability to plan for the future.
Cortactin in invadopodia formation
Authors: Emily S. Clark, Nicole S. Bryce, Alissa M. Weaver
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

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Invadopodia are invasive foot processes used by cancer cells to degrade extracellular matrix and move through tissue barriers, that depend on src kinase signaling and branched actin assembly. Podosomes are analogous structures found in src kinase-transformed cells that are molecularly and functionally similar to invadopodia. We studied the role of cortactin, a prominent invadopodia component, actin assembly molecule and src kinase substrate in cancer cell invasion and invadopodia formation. We found that cortactin promotes cancer cell invasion, through a domain that includes the src kinase phosphorylation sites and SH3 domain. To address the role of cortactin specifically in src-kinase-induced invadopodia/podosome formation, we knocked down cortactin in src-kinase transformed mouse embryonic fibroblasts. We found that cortactin knockdown inhibited podosome ring formation and matrix degradation in a time-dependent manner. We hypothesize that enhanced invadopodia formation may account for the aggressive behavior of cancers with amplifications in the cortactin/EMS1 gene.
A Retrospective Review of Response to Donor Leukocyte Infusions In Adults with Acute Myeloid Leukemia After Reduced Intensity Conditioned Allogeneic Hematopoietic Cell Transplantation.
Authors: Loretta Nastoupil, Mark A. Schroeder, Qin Zhang, Uy Geoffrey, Amanda Cashen, Keith E. Stockerl-Goldstein, Camille N. Abboud, Peter Westervelt, John F. DiPersio, Ravi Vij
Journal: Blood (2010)
Arthritis in the Mediterranean Theater of Operations
Authors: Charles L. Short
Journal: New England Journal of Medicine (1947)

THE types of joint disease often encountered in the Mediterranean Theater, in addition to rheumatoid arthritis, which was discussed in a previous paper,1 included hypertrophic arthritis, arthralgia and similar disorders, and psychogenic rheumatism.Hypertrophic ArthritisThe aspects of hypertrophic arthritis that seemed of importance in the Theater are covered in this section, no attempt being made to discuss the definitive treatment of the disease. Because it was usually employed, the designation "hypertrophic arthritis" is used throughout to avoid confusion, although in some ways its synonyms, such as "degenerative joint disease" and "osteoarthritis," are preferable. When possible, the two types of . . .
Topography‐Guided Control of Local Migratory Behaviors and Protein Expression of Cancer Cells
Authors: Jung‐Youn Shin, Hong Nam Kim, Suk Ho Bhang, Jeong‐Kee Yoon, Kahp‐Yang Suh, Noo Li Jeon, Byung‐Soo Kim
Journal: Advanced Healthcare Materials (2017)

In vivo cancer cell migration and invasion are directed by biophysical guidance mechanisms such as pre‐existing microtracks and basement membrane extracellular matrices. Here, this paper reports the correlation of the local migratory behavior of cancer cells and the biochemical signal expression using the topography that can guide or inhibit cell behaviors. To this end, the local apparent migration and the protein expression level are investigated with respect to the topographical feature size (flat, nanoline, and microline) and orientation (microline, microconcentric, and microradial) with the collectively migrating (A431) and individually migrating (MDA‐MB‐231 and U‐87‐MG) cancer cells. The results show that the migration and the protein expression of focal adhesion kinase, rho‐associated protein kinase, and extracellular signal‐regulated kinase are localized in the periphery of cell colony. Furthermore, the inhibition of migratory behavior at the periphery recues the protein expression, while the guidance of migration enhances the aforementioned protein expression. The results may imply the employ of biophysical inhibitory factors can help to control invasiveness of cancer cells during the progression state.
A phase II trial of mFOLFOX-bevacizumab (bev) followed by single-agent axitinib (ax) as maintenance therapy for patients (pts) with first-line metastatic colorectal cancer (mCRC).
Authors: Mathew John Joseph, Kirk Barnes, Ronald Blachly, Michel E. Kuzur, Johanna C. Bendell
Journal: Journal of Clinical Oncology (2015)

e14673 Background: Maintenance therapy is commonly used in the first-line treatment of mCRC. Maintenance therapy options include fluorouracil plus bev and bev single agent. Ax is an oral, potent, and selective inhibitor of vascular endothelial growth factor receptors 1, 2, and 3. Ax is an attractive option for oral maintenance therapy. This phase II, nonrandomized study evaluated the efficacy of ax as maintenance therapy following first-line mFOLFOX-bev for pts with mCRC. Methods: Pts with mCRC received mFOLFOX plus bev (5mg/kg) d 1 & 15 of each 28 d cycle and were restaged every 2 cycles. After 4 cycles, maintenance ax (5mg PO BID) was given d 1 through 28 of each cycle. The primary endpoint was progression-free survival (PFS). Secondary endpoints included response rate (RR), time to progression (TTP), overall survival (OS), and safety. Results: Seventy pts were treated: median age 60 yrs (range, 36-90), 51% male, 53% ECOG 1, KRAS mutation 41%. Pts received a median of 3 cycles (range, 1-6) of FOLFOX-bev and 3 cycles (range, 1-23) of maintenance ax. Common treatment-related toxicities (% grade 1/2; % grade 3/4) included fatigue (54%; 13%), peripheral neuropathy (56%; 4%), diarrhea (44%; 11%), nausea (50%; 6%), and HTN (19%; 20%). Frequent toxicities from axitinib were fatigue (33%; 17%), HTN (21%; 25%), diarrhea (23%; 10%), and nausea (25%; 4%). One pt did develop RPLS. Of the 61 pts evaluable for response, 21 (34%) achieved objective response (1 CR, 20 PRs); 35 pts (57%) had a best response of stable disease. The overall RR was 30%. Disease progression (48%) and toxicity (26%) were the most common reasons for discontinuation. Median PFS was 8.3 months (95% C: 7.8 – 9.4) with a median TTP of 8.8 months (95% CI: 8.1 – 10.2). Median OS was 24.2 months (95% CI: 16 – 30.9). Conclusions: Treatment with FOLFOX-bev followed by maintenance ax in pts with first-line mCRC showed PFS that approximates that seen with historical controls of first-line mCRC regimens. A randomized study could give more data as to whether ax could be used as a maintenance therapy. Clinical trial information: NCT01490866.
Calcium-binding protein S100A4 confers mesenchymal progenitor cell fibrogenicity in idiopathic pulmonary fibrosis
Authors: Hong Xia, Adam Gilbertsen, Jeremy Herrera, Emilian Racila, Karen Smith, Mark Peterson, Timothy Griffin, Alexey Benyumov, Libang Yang, Peter B. Bitterman, Craig A. Henke
Journal: Journal of Clinical Investigation (2017)

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a prevalence of 1 million persons worldwide. The fibrosis spreads from affected alveoli into contiguous alveoli and leads to death by asphyxiation. We previously discovered that the IPF lung harbors fibrogenic mesenchymal progenitor cells (MPCs) that serve as a cell of origin for disease-mediating myofibroblasts. In a prior genomewide transcriptional analysis, we found that IPF MPCs displayed increased expression of S100 calcium-binding A4 (S100A4), a protein linked to cancer cell proliferation and invasiveness. Here, we have examined whether S100A4 mediates MPC fibrogenicity. Ex vivo analysis revealed that IPF MPCs had increased levels of nuclear S100A4, which interacts with L-isoaspartyl methyltransferase to promote p53 degradation and MPC self-renewal. In vivo, injection of human IPF MPCs converted a self-limited bleomycin-induced mouse model of lung fibrosis to a model of persistent fibrosis in an S100A4-dependent manner. S100A4 gain of function was sufficient to confer fibrotic properties to non-IPF MPCs. In IPF tissue, fibroblastic foci contained cells expressing Ki67 and the MPC markers SSEA4 and S100A4. The expression colocalized in an interface region between myofibroblasts in the focus core and normal alveolar structures, defining this region as an active fibrotic front. Our findings indicate that IPF MPCs are intrinsically fibrogenic and that S100A4 confers MPCs with fibrogenicity.
The Effect of Initial Molecular Profile on Response to Recombinant Interferon Alpha (rIFNα) Treatment in Early Myelofibrosis
Authors: Richard T. Silver, Ariella Barel, Elena Lascu, Ellen K. Ritchie, Gail J. Roboz, Paul Christos, Attilio Orazi, Duane C Hassane, Wayne Tam, Nicholas C.P. Cross
Journal: Blood (2016)
Can Microsatellite Status of Colorectal Cancer Be Reliably Assessed after Neoadjuvant Therapy?
Authors: Jennifer B. Goldstein, William Wu, Ester Borras, Gita Masand, Amanda Cuddy, Maureen E. Mork, Sarah A. Bannon, Patrick M. Lynch, Miguel Rodriguez-Bigas, Melissa W. Taggart, Ji Wu, Paul Scheet, Scott Kopetz, Y. Nancy You, Eduardo Vilar
Journal: Clinical Cancer Research (2017)

Purpose: Determination of microsatellite instability (MSI) by PCR is the gold standard; however, IHC of mismatch repair (MMR) proteins is frequently performed instead. The reliability of these methods on postneoadjuvant therapy specimens is unknown. We examined the effect of neoadjuvant therapy on MSI results by PCR and IHC.Experimental design: A total of 239 colorectal cancers resected after neoadjuvant therapy were assessed for MSI with PCR and IHC. PCR and IHC results for matched paired pre- and posttreatment specimens were compared. In parallel, 2 isogenic cell lines conditioned for MMR functioning and 2 different patient-derived xenografts (PDXs) were exposed to chemotherapy, radiation, or both. We also examined whether establishment of PDXs induced MSI changes in 5 tumors. IHC and MSI were tested after treatment to assess for changes.Results: We identified paired pre- and posttreatment specimens for 37 patients: 2 with PCR only, 34 with IHC only, and 1 with both. All 3 patients with PCR had microsatellite stable pre- and posttreatment specimens. Of the 35 patients with IHC, 30 had intact MMR proteins in pre- and posttreatment specimens, 1 had equivocal MLH1 staining in the pretreatment and loss in the posttreatment specimen, and 4 had intact pretreatment MSH6 but variable posttreatment staining. In the experimental setting, no changes in MSI status were detected after treatment or tumor implantation in animals.Conclusions: Our findings show that the expression of MMR proteins, commonly MSH6, can change after neoadjuvant therapy and confirm PCR as the gold-standard test for MSI after neoadjuvant therapy. Clin Cancer Res; 23(17); 5246-54. ©2017 AACR.
Pregnancy following surgery and chemotherapy for ovarian germ cell tumors.
Authors: Karen Murphy, Scheryll Paula Alken, John McCaffrey, Desmond Carney, Miriam O Connor
Journal: Journal of Clinical Oncology (2013)

e16550 Background: Malignant ovarian germ cell tumours(OGCT) are a rare disease, accounting for 2% of all malignant ovarian tumours diagnosed in Ireland between 1994 - 2010. They affect a younger population than epithelial ovarian cancer, with the highest number of cases in the second and third decade. In this report, we present a review of patients treated in a tertiary referral centre. Methods: We performed a retrospective review over a 26 year period in our institution. We examined clinical records, pathology, pharmacy and surgical databases to identify patients with ovarian germ cell tumours who were treated in our institution. Results: During the period 1986 – 2012, twenty patients were treated and followed at this institution for malignant ovarian germ cell tumor (OGCT). Eighteen patients are alive and well at a median follow up of 14.5 years (range 0.5 – 26). Nineteen patients received platinum based chemotherapy with a median number of four cycles (range 2 – 6) required to achieve complete remission. Twenty percent of patients had yolk sac histology; the next commonest were immature teratomas and mixed germ cell tumour (10 &amp; 15% respectively). The commonest chemotherapy regimen used was BEP (bleomyocin, etoposide and cistplatin). Six patients (30%) underwent resection of residual disease post chemo revealing mature teratoma/necrotic tissue. During follow up, four patients had progressive or recurrent disease. Two patients at resection had mature teratomas found on histological examination. The remaining two patients (10%) had progressive disease and died within a short time period. In our patient population, nine of nine attempting pregnancy have been successful. There have been 12 pregnancies carried to term; mother and child in each case are well. At a median follow up of 14.5 years (range 0.5 – 26), there have been no second malignancies and no toxicities attributable to chemotherapy. Conclusions: We have shown that platinum based chemo in OGCT is associated with preservation of fertility in these young women. In our series there have been no adverse affects in women or their infants. Platinum based chemo highly successful in curing OGCT and this confirms that it is associated with preserved fertility in these young women.
Prevalence of exercise-induced bronchoconstriction and exercise-induced laryngeal obstruction in a general adolescent population
Authors: Henrik Johansson, Katarina Norlander, Christer Jansson, Andrei Malinovschi, Lennart Nordvall, Leif Nordang, Margareta Emtner
Journal: European Respiratory Journal (2014)

Introduction:  Exercise can provoke transient narrowing of the airways as seen in exercise-induced bronchoconstriction (EIB). Exercise-induced laryngeal obstruction (EILO) comprising conditions involving vocal cords and/or supraglottic structures where airflow in larynx is hampered can also occur during physical exertion. Prevalence of EILO in a general population of adolescents, and its relation to exercise-induced bronchoconstriction (EIB), has not been previously investigated.   Aim:  To investigate prevalence of EIB and EILO, with standardized exercise tests, in a general adolescent population.   Method:  A questionnaire on exercise-induced dyspnea was sent to all adolescents born 1997-98 living in Uppsala, Sweden (n=3838). A randomized subsample of 146 adolescents were exercise tested (99 with self-reported exercise-induced dyspnea, 47 without). EIB-test was performed on treadmill while breathing dry air. A positive test was defined as a fall ≥10% in FEV 1 . EILO-test was performed on treadmill with filming of larynx and obstruction was graded according to criteria (Maat  et al  Eur Arch Otorhin 2009). Estimated prevalence for the whole population was calculated according to the theory for stratified samples.   Results:  The prevalence of EIB was 19.2% and the prevalence of EILO was 5.7% with no gender differences. In the group with exercise induced dyspnea 39.8% had EIB, 6% had EILO and 4.8% had both EIB and EILO.   Conclusion:  Though not as common as EIB, EILO is not uncommon in a general population and can be an important differential diagnosis in adolescents with exercise-induced dyspnea. EILO is equally common among girls and boys and can coexist with EIB.
STUDIES OF PPLO INFECTION
Authors: Fernando Aleu, Lewis Thomas
Journal: The Journal of Experimental Medicine (1966)

The ultrastructure of the experimental encephalopathy caused by Mycoplasma neurolyticum toxin has been studied. The primary changes are (a) massive distention of astrocytes by fluid, associated with degenerative changes in these cells, (b) mechanical displacement and compression of myelinated axons by swollen astrocytic processes, (c) the appearance of free, extracellular fluid in the white matter, and (d) early primary myelin degeneration without damage to axons.
Central-acting therapeutics alleviate respiratory weakness caused by heart failure–induced ventilatory overdrive
Authors: Andrew J. Foster, Mathew J. Platt, Jason S. Huber, Ashley L. Eadie, Alicia M. Arkell, Nadya Romanova, David C. Wright, Todd E. Gillis, Coral L. Murrant, Keith R. Brunt, Jeremy A. Simpson
Journal: Science Translational Medicine (2017)

Diaphragmatic weakness is a feature of heart failure (HF) associated with dyspnea and exertional fatigue. Most studies have focused on advanced stages of HF, leaving the cause unresolved. The long-standing theory is that pulmonary edema imposes a mechanical stress, resulting in diaphragmatic remodeling, but stable HF patients rarely exhibit pulmonary edema. We investigated how diaphragmatic weakness develops in two mouse models of pressure overload-induced HF. As in HF patients, both models had increased eupneic respiratory pressures and ventilatory drive. Despite the absence of pulmonary edema, diaphragmatic strength progressively declined during pressure overload; this decline correlated with a reduction in diaphragm cross-sectional area and preceded evidence of muscle weakness. We uncovered a functional codependence between angiotensin II and β-adrenergic (β-ADR) signaling, which increased ventilatory drive. Chronic overdrive was associated with increased PERK (double-stranded RNA-activated protein kinase R-like ER kinase) expression and phosphorylation of EIF2α (eukaryotic translation initiation factor 2α), which inhibits protein synthesis. Inhibition of β-ADR signaling after application of pressure overload normalized diaphragm strength, Perk expression, EIF2α phosphorylation, and diaphragmatic cross-sectional area. Only drugs that were able to penetrate the blood-brain barrier were effective in treating ventilatory overdrive and preventing diaphragmatic atrophy. These data provide insight into why similar drugs have different benefits on mortality and symptomatology, despite comparable cardiovascular effects.