tbuckley/cabot-search huggingface dataset:
THE RECRUIT'S HEART: A MEMORANDUM FOR MEDICAL EXAMINERS
Authors: J. Mackenzie
Journal: BMJ (1915)

THE RECRUIT'S HEARRT.Tha filt Tos 56 OCT.i6q 119151 1~~~~~~~~~~~~~~~~~~~~~~~MEDICAL JOUBL-AL reinoved, anld, as far as the drainage of this part is con- cerned, tlle above considerations lhold good.Drainage of the track, hlowever, is also probably necessary, and the observations made below on tlle thlird type of wound will tlhen apply.3. A Potentia.l 1w.tbutlatrt Space.Tlle track formedl by the passage of a muissile will contain blood clots and debris ; the collapse of its walls will in most cases obliterate the cavity.Tlle injury will lhave opened up a series of connective tissue planes, and the aim of drainage is to prevent the spread of infection along them.As the exact position of the openings of these planes cannot be determined, the ideal drain should' evacuate discharges from tlle entire inner surfaeg of the wound track.Thus a simple tube lying in the track will permit diselarge in the capillary space between its outer surface and ihat of the wound track; but whlen, as rapidly, occurs, this space becomes clogged by clots or the viscidity of the dischlarge, tlle movement vill ceaw.In this instance the action of gravity is acting at a dis- advantage in the small-capillary surface.
The effectiveness of extracorporeal shockwave therapy in common lower limb conditions: a systematic review including quantification of patient-rated pain reduction
Authors: Vasileios Korakakis, Rodney Whiteley, Alexander Tzavara, Nikolaos Malliaropoulos
Journal: British Journal of Sports Medicine (2017)

Objective To evaluate extracorporeal shockwave therapy (ESWT) in treating Achilles tendinopathy (AT), greater trochanteric pain syndrome (GTPS), medial tibial stress syndrome (MTSS), patellar tendinopathy (PT) and proximal hamstring tendinopathy (PHT). Design Systematic review. Eligibility criteria Randomised and non-randomised studies assessing ESWT in patients with AT, GTPS, MTSS, PT and PHT were included. Risk of bias and quality of studies were evaluated. Results Moderate-level evidence suggests (1) no difference between focused ESWT and placebo ESWT at short and mid-term in PT and (2) radial ESWT is superior to conservative treatment at short, mid and long term in PHT. Low-level evidence suggests that ESWT (1) is comparable to eccentric training, but superior to wait-and-see policy at 4 months in mid-portion AT; (2) is superior to eccentric training at 4 months in insertional AT; (3) less effective than corticosteroid injection at short term, but ESWT produced superior results at mid and long term in GTPS; (4) produced comparable results to control treatment at long term in GTPS; and (5) is superior to control conservative treatment at long term in PT. Regarding the rest of the results, there was only very low or no level of evidence. 13 studies showed high risk of bias largely due to methodology, blinding and reporting. Conclusion Low level of evidence suggests that ESWT may be effective for some lower limb conditions in all phases of the rehabilitation.
Weekly paclitaxel and bevacizumab as fourth-line treatment or beyond for metastatic nonsquamous non-small cell lung cancer.
Authors: Stefanie Habib, Julie Delourme, Xavier Dhalluin, Arnaud Scherpereel, Jean-Jacques Lafitte, Alexis B. Cortot
Journal: Journal of Clinical Oncology (2012)

e18066 Background: Paclitaxel (P) and bevacizumab (B) showed synergistic antitumor efficacy in preclinical models. In combination with carboplatin, PB prolonged progression-free survival (PFS) and overall survival (OS) in selected metastatic non-squamous Non Small Cell Lung Cancer (NSCLC) patients compared to carboplatin and paclitaxel. Currently, there are no standard treatments beyond third-line therapy in NSCLC. We sought to determine the efficacy of weekly paclitaxel and bevacizumab (wPB) in non-squamous NSCLC as fourth-line therapy or beyond. Methods: we retrospectively reviewed patients with metastatic non-squamous NSCLC who have been treated with wPB in our institution. Patients were identified from a prospective database. Treatment consisted in P 80mg/m² on days 1, 8, 15 and B 15mg/kg on day 1, every 3 weeks until progression or unacceptable toxicity. Patients were evaluated every 3 cycles. PFS and OS were calculated from the date of initiation of wPB and analyzed using the Kaplan-Meier method. Results: Twenty patients received at least one cycle of wPB between 2008 and 2011. All patients received wPB as fourth-line treatment or beyond. Eight patients (40%) had a partial response, 7 patients (35%) had stable disease and 5 patients (25%) had progressive disease. Grade 3-4 adverse events included neutropenia (20%), onycholysis (10%), infection (10%), pulmonary haemorrhage (5%), neuropathy (5%) and hypertension (5%). One patient died from a bowel perforation following second cycle of wPB. The median PFS was 6.4 months (CI95% 4.1-9) and the median OS was 9.6 months (CI95% 7-19.7). One patient who previously received bevacizumab as part of first-line chemotherapy and another patient harbouring an ALK rearrangement benefited from wPB during more than 8 months and 18 months, respectively. Conclusions: In our experience, wPB exhibited acceptable toxicity and had encouraging anti-tumor efficacy as fourth-line treatment or beyond in non-squamous NSCLC patients, supporting further evaluation in larger prospective studies.
New connections between medical knowledge and patient care
Authors: A. T Carty, D P Kernick, J. Edwards, D. J R Hutchon
Journal: BMJ (1997)

# Human condition is full of decisions that aren't simple yes/no decisions {#article-title-2} Editor—Weed's arguments in favour of introducing information tools into medical practice are fundamentally flawed.1 He has failed to give any example of how knowledge coupling software works in facilitating medical decision making, let alone in supplanting the unaided medical mind, as he advocates. The problem is that computer software is essentially binary. Its natural default is to a yes/no decision. The human condition is full of indecisiveness, and, whatever the character of the doctor, the patient remains human. There can be no contest against the craftsmanship of history taking by an experienced doctor. Heaven forbid that this should be replaced by a questionnaire and a computerised home doctor. The profession is less in the backwoods than Weed allows. The success of tools for updating one's knowledge, such as the Oxford Textbook of Medicine , is an example of our openness to the support of information technology. The shift to problem based learning in the curriculums of many medical schools is an acknowledgement of the futility of overloading minds with facts, which do not endure. By all means let us harness good software to aid our decision making when we are convinced that it is good. But we must remember that the supreme human qualities of happiness, love, and beauty are impervious to the discipline of digitisation. 1. 1.↵1. Weed LL . New connections between medical knowledge and patient care. BMJ 1997;315: 231–5. (26 July.) [OpenUrl][1][FREE Full Text][2] # Intervention of health professionals acts as an inductance, not as a resistor {#article-title-4} Editor—Weed states that voltage drops occur along the pathway from the … [1]: {openurl}?query=rft.jtitle%253DBMJ%26rft.stitle%253DBMJ%26rft.issn%253D0007-1447%26rft.aulast%253DWeed%26rft.auinit1%253DL.%2BL%26rft.volume%253D315%26rft.issue%253D7102%26rft.spage%253D231%26rft.epage%253D235%26rft.atitle%253DNew%2Bconnections%2Bbetween%2Bmedical%2Bknowledge%2Band%2Bpatient%2Bcare%26rft_id%253Dinfo%253Apmid%252F9253272%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=FULL&journalCode=bmj&resid=315/7102/231&atom=%2Fbmj%2F315%2F7118%2F1309.3.atom
Biodegradable Shape Memory Polymers in Medicine
Authors: Gregory I. Peterson, Andrey V. Dobrynin, Matthew L. Becker
Journal: Advanced Healthcare Materials (2017)

Abstract Shape memory materials have emerged as an important class of materials in medicine due to their ability to change shape in response to a specific stimulus, enabling the simplification of medical procedures, use of minimally invasive techniques, and access to new treatment modalities. Shape memory polymers, in particular, are well suited for such applications given their excellent shape memory performance, tunable materials properties, minimal toxicity, and potential for biodegradation and resorption. This review provides an overview of biodegradable shape memory polymers that have been used in medical applications. The majority of biodegradable shape memory polymers are based on thermally responsive polyesters or polymers that contain hydrolyzable ester linkages. These materials have been targeted for use in applications pertaining to embolization, drug delivery, stents, tissue engineering, and wound closure. The development of biodegradable shape memory polymers with unique properties or responsiveness to novel stimuli has the potential to facilitate the optimization and development of new medical applications.
Children’s Lead Exposure: A Multimedia Modeling Analysis to Guide Public Health Decision-Making
Authors: Valerie Zartarian, Jianping Xue, Rogelio Tornero-Velez, James Brown
Journal: Environmental Health Perspectives (2017)

Drinking water and other sources for lead are the subject of public health concerns around the Flint, Michigan, drinking water and East Chicago, Indiana, lead in soil crises. In 2015, the U.S. Environmental Protection Agency (EPA)'s National Drinking Water Advisory Council (NDWAC) recommended establishment of a "health-based, household action level" for lead in drinking water based on children's exposure.The primary objective was to develop a coupled exposure-dose modeling approach that can be used to determine what drinking water lead concentrations keep children's blood lead levels (BLLs) below specified values, considering exposures from water, soil, dust, food, and air. Related objectives were to evaluate the coupled model estimates using real-world blood lead data, to quantify relative contributions by the various media, and to identify key model inputs.A modeling approach using the EPA's Stochastic Human Exposure and Dose Simulation (SHEDS)-Multimedia and Integrated Exposure Uptake and Biokinetic (IEUBK) models was developed using available data. This analysis for the U.S. population of young children probabilistically simulated multimedia exposures and estimated relative contributions of media to BLLs across all population percentiles for several age groups.Modeled BLLs compared well with nationally representative BLLs (0-23% relative error). Analyses revealed relative importance of soil and dust ingestion exposure pathways and associated Pb intake rates; water ingestion was also a main pathway, especially for infants.This methodology advances scientific understanding of the relationship between lead concentrations in drinking water and BLLs in children. It can guide national health-based benchmarks for lead and related community public health decisions. https://doi.org/10.1289/EHP1605.
Abstract #LB-200: A novel two mode-acting inhibitor of ABCG2-mediated multidrug transport and resistance in cancer chemotherapy
Authors: Hui Peng, Zizheng Dong, Jing Qi, Youyun Yang, Yang Liu, Zhaomin Li, Junkang Xu, Jian-Ting Zhang
Journal: Cancer Research (2009)

Human ABCG2, a member of the ATP-binding cassette transporter superfamily, plays a key role in multidrug resistance in cancer chemotherapy and represents a promising target for chemosensitization. In this report, we show finding of a novel specific ABCG2 inhibitor, PZ-39, and its mechanism of action. Unlike any previously known ABC transporter inhibitors, PZ-39 has two modes of actions by inhibiting ABCG2 activity, an acute effect, and by causing ABCG2 conformational change which accelerates its lysosome-dependent degradation, a chronic effect. PZ-39 has no effect on ABCB1 and ABCC1-mediated drug efflux, resistance, and their expression, indicating that it is specific to ABCG2. The structural properties of PZ-39 derivatives have been identified using a structure-activity relationship analysis. PZ-39 is potentially a valuable probe and lead compound for developing therapeutics targeting ABCG2-mediated multidrug resistance in cancer chemotherapy.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-200.
Early clinical activity and pharmacodynamic effects of duvelisib, a PI3K-δ,γ inhibitor, in patients with treatment-naïve CLL.
Authors: Manish R. Patel, Susan Mary O'Brien, Kerrie Faia, Kerry White, Mark Douglas, Kerstin Allen, Jeffrey Lorne Kutok, Jennifer Sweeney, Virginia Kelly, Ian Flinn, John C. Byrd, Howard Stern
Journal: Journal of Clinical Oncology (2015)

7074 Background: Signaling via PI3K-δ and PI3K-γ has distinct and complementary effects on malignant B-cells and nonmalignant immune cells in chronic lymphocytic leukemia (CLL). Duvelisib, an oral PI3K-δ,γ inhibitor, has shown clinical activity in a phase 1 study, IPI-145-02. The activity of duvelisib monotherapy in pts with treatment-naïve (TN) CLL from this study are reported here. Methods: Following dose escalation, an expansion cohort of TN CLL pts was enrolled (n = 18). Response was based on iwCLL (2008) criteria. Safety included AEs and laboratory assessments. Pharmacodynamic assessments included peripheral blood (PB) flow cytometry for phospho-S473 AKT (pAKT) and Ki67, and measurement of serum chemokines and cytokines. Numbers of PB T-cell subsets were also monitored. Results: As of Oct 2014, 18 TN CLL pts received duvelisib 25 mg BID. The best ORR per iwCLL was 82% (PRs in 14/17 evaluable pts) with a median time on treatment of 53 weeks (range 8-69). Ten pts remain on treatment, while 8 discontinued, including 6 pts due to AEs. AEs overall were mostly Gr. 1 or 2. The most common ≥ Gr. 3 AEs were neutropenia (7/18) and ALT/AST increase (3/18). Inhibition of pAKT in CLL cells was rapid following a single dose and sustained through Cycle 2 Day 1 (C2D1). A reduction in the Ki67 proliferative fraction in both CLL and T-cells was also observed. The overall number of T-cells and T-cell subsets (CD4, CD8, memory cells) did not decrease through C3D1. Duvelisib also resulted in reductions in the median serum levels of CCL3, CCL4, CCL17, CCL22, CXCL10, CXCL13, IL-10, IL-12p40, MMP-9, IL-16, and TNFα to ≤ 50% of baseline at C1D8 and/or C2D1 (p < 0.01). Conclusions: Duvelisib 25 mg BID shows clinical activity in TN CLL pts.The inhibition of pAKT and Ki67 in CLL cells suggests duvelisib inhibits the PI3K pathway and suppresses malignant cell proliferation in TN CLL pts. In addition, the effect of duvelisib on serum chemokines, cytokines, and T-cell proliferation suggests that modulation of the tumor microenvironment may contribute to the observed early clinical activity of duvelisib in pts with TN CLL. These data support the further development of duvelisib in TN CLL, including combinations with other targeted therapies. Clinical trial information: NCT01476657.
The effect of asparagine depletion on the cytotoxicity of nelarabine (compound 506U78) in human T-cell leukemia cell lines.
Authors: Nalini Jayaprakash, Peter C. Adamson, Thomas A. Lampkin, Stacey Berg, Frank M. Balis, Elizabeth Fox
Journal: Cancer Research (2004)

3096  Nelarabine (compound 506U78, GlaxoSmithKline), a prodrug of 9-β-D-arabinofuranosyl guanine (ara-G), is preferentially cytotoxic to T-cell lymphoblasts due to enhanced phosphorylation of ara-G and intracellular accumulation of dGTP. Nelarabine was active in T-cell leukemias in the initial clinical trials, and its role in combination regimens is now being studied. L-asparaginase (ASNase) antagonizes the cytotoxic effects of antimetabolites, such as methotrexate and cytarabine in a schedule dependent fashion. Prior to incorporation of nelarabine into multiagent chemotherapy regimens that include ASNase for pediatric T-cell leukemia, we examined the effect of asparagine depletion on the in vitro cytotoxicity of nelarabine in two human T-cell leukemia lines. Molt4 (10,000 cell/well) or CEM (20,000 cell/well) grown in DMEM/10%FBS containing 20mM L-glutamine and 15mM L-asparagine had doubling times of 45 hr and 38 hr, respectively. Asparagine depleted FBS was prepared by incubation of FBS with E coli ASNase (SIGMA Chemical, 0.1U/mL) at 37±2° C for 4 hrs followed by heat inactivation (56±2° C for 1 hr) and added to DMEM/20mM L-glutamine for asparagine depleted media. Cells were dispensed into 96 well plates and nelarabine (0-100μM in dH2O) was added to each well. MTT assay was performed to determine cell survival after 72 hrs of incubation at 37°C/5% CO2. Dose response curves were constructed by plotting the percent cell survival relative to the untreated control as a function of the nelarabine concentration (d). The IC50, maximum effect (ME) and slope of the sigmoidal dose response curve (h) were estimated using MLAB mathematical modeling software by fitting the equation, S(d) = (ND –ME)/(1 + (d/IC50)h) + ME, (where S(d) is the survival at d, ND is survival at d = 0, ME is survival at d = ∞, and IC50 is the mid-effect concentration) to the concentration-survival data. In Molt4 cells, the IC50 of nelarabine in asparagine containing media was 1.61 ± 0.3 μM and in aparagine depleted media was 0.13 ± 0.25 μM. In CEM cells, the IC50 of nelarabine in asparagine containing media was 0.87 ± 0.12 μM and in aparagine depleted media was
Personalised peptide vaccination combined with radiotherapy for patients with advanced hepatocellular carcinoma: a phase 1 study
Authors: Jie Shen, Zheng-Yun Zou, Li-Feng Wang, Jing Yan, Wei-Wei Kong, Fan-Yan Meng, Fang-Jun Chen, Juan Du, Jie Shao, Qiu-Ping Xu, Ru-Tian Li, Jia Wei, Xiao-Ping Qian, Bao-Rui Liu
Journal: The Lancet Oncology (2017)
The Histochemical Society<subtitle>Proceedings, Business Meeting</subtitle>
Authors: George B. Wislocki, Dr.
Journal: JNCI Journal of the National Cancer Institute (1950)

The Histochemical Society: Proceedings, Business Meeting George B. Wislocki, Dr. George B. Wislocki, Dr. Chairman Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 10, Issue 6, June 1950, Pages 1337–1338, https://doi.org/10.1093/jnci/10.6.1337 Published: 01 June 1950
Real Life, Retrospective Analysis of Bortezomib Re-Use As Second Treatment for Relapsed Multiple Myeloma Patients Previously Exposed to Bortezomib-Based Therapies As First Line: The Rebound Study
Authors: Pellegrino Musto, Vittorio Simeon, Nicola Cascavilla, Antonietta Falcone, Maria Teresa Petrucci, Laura Cesini, Francesco Di Raimondo, Concetta Conticello, Roberto Ria, Lucio Catalano, Dalila Salvatore, Lucia Mastrullo, Alfredo Gagliardi, Oreste Villani, Giuseppe Pietrantuono, Giovanni D'Arena, Giovanna Mansueto, Andrea Patriarca, Sara Bringhen, Mariella Genuardi, Nicola Di Renzo, Giovanni Reddiconto, Alberto Fragasso, Tommaso Caravita, Silvia Mangiacavalli, Antonio Palumbo, Alessandro Corso
Journal: Blood (2016)
Whole exome paraffin sequencing (WEPS) of same-patient (pt) primary, extracranial, and melanoma brain metastases (PEB) to identify new driver and clonal evolution genetic events.
Authors: Stergios J. Moschos, Xiaobei Zhao, Wenjin Liu, Dimitri G. Trembath, Michal Tadeusz Krauze, Georgina V. Long, Brindha Sivalingham, Richard A Scolyer, John M. Kirkwood, Ronald L. Hamilton, David N. Hayes, Norman E. Sharpless
Journal: Journal of Clinical Oncology (2015)

e20033 Background: To date, little is known about how primary melanomas clonally evolve to distant metastases, including brain, and how driver mutations are selected during melanoma progression. To identify new driver and clonal evolution genetic events beyond the known mutations in BRAF/NRAS, we performed WEPS of same-pt PEB. Methods: DNA from tumor (T) and adjacent normal (AN) was extracted from macrodissected tissue slides. DNA libraries were captured using Agilent SureSelect Human All Exon v4 and sequenced at 2x48 bp. Variant calling was performed on T vs. matched AN using VARSCAN (default settings). Single nucleotide variations (SNV) were filtered using prior knowledge (COSMIC). We report only genes having probably or possibly damaging non-synonymous SNV (PolyPhen2 score > 0.45) by ANNOVAR analysis and nonsense mutations. Focused analysis for gene copy number alterations previously described in melanoma was performed using our previously published NGScopy package (Bioconductor). We considered analysis for gene copy number alterations if median coverage depth > 20X. We computed T/AN copy number ratio at the gene against the chromosome level. Results: To date, 4 pts with all four tissues (PEB-AN) have been analyzed. Mean coverage depth was 68X and read quality was 37. 85% of reads were uniquely mapped. The 10 most frequently mutated genes across all 12 T samples were APC, ARID1A, CDKN2A, EGFR, FBXW7, KIT, KMT2C, NF1, PTEN, and TET2 (FDR < 0.0001). NF1 mutations were present in all T from 4 pts. All T from 3 out of 4 pts had mutations in BRAF (2 with confirmed V600E), PTEN, IDH2, TET2, CCDC6, PCSK7, and members of the ARID and KMT2 gene family. Both metastatic T from 2 pts had mutations in TRIM27, NCOA1, BCL6, and BCL10 that were not present in primary. All T from 2 pts and all T from one pt had > 30% amplification of the KIT and KDR genes, respectively. Conclusions: Aggressive melanoma bears known mutations in signaling pathways that coexist with mutations in genes associated with chromatin modification, histone/nucleotide methylation, and metabolism. Identifying such mutations in primaries may predict future prognosis.
Intergroup phase III trial of neo-adjuvant chemotherapy, followed by chemoradiation and surgery with and without cetuximab in locally advanced esophageal carcinoma: First results from the SAKK 75/08 trial.
Authors: Thomas Ruhstaller, Peter C. Thuss-Patience, Stefanie Hayoz, Sabina Schacher-Kaufmann, Jorge Riera-Knorrenschild, Annelies Schnider, Ludwig Plasswilm, Wilfried Budach, Wolfgang Eisterer, Hanne Hawle, Christophe Mariette, Viviane Hess, Walter B. Mingrone, Anna Dorothea Wagner, Michael Girschikofsky, Sven-Christian Schmidt, Michael Bitzer, Laurent Bedenne, Peter Brauchli, Michael Stahl
Journal: Journal of Clinical Oncology (2017)

4019 Background: We compared chemoradiotherapy followed by surgery with the addition of neoadjuvant and adjuvant cetuximab (cetux) in patients with esophageal carcinoma. Methods: Pts with resectable esophageal cancer (T2N1-3;T3-4aNx) received two cycles of induction chemotherapy (docetaxel 75mg/m2, cisplatin 75mg/m2) followed by chemoradiation (45 Gy, docetaxel 20mg/m2 and cisplatin 25mg/m2 weekly) and surgery or the same treatment with addition of neoadjuvant cetux 250mg/m 2 weekly and adjuvant cetux 500mg/m2 bi-weekly for three months. Primary endpoint was progression-free survival (PFS). After a median follow-up of 4y 166 of the planned 180 events occurred (plateau reached). Results: 300 pts were treated between 2010-13: 88% male, median age 61y, 63% adenocarcinoma, 85% cT3/4a, 90% cN+. 84% completed neoadjuvant therapy, 87% were operated (cetux: 89%, control: 86%), 67% started and 50% completed adjuvant cetux-therapy. The R0 resection rate was 95% in the cetux-arm and 97% in the control-arm, there were 10 and 14 treatment-related deaths and 9 and 4 postoperative in-hospital deaths, respectively. Major differences in adverse events (grade &gt;2) with addition of cetux were higher rate of allergic reactions and hypomagnesemia, but lower rate of dysphagia (-15%) and esophagitis (-4%) during chemoradiation. Conclusions: The addition of cetuximab to a multimodal therapy showed a statistically significant reduction of loco-regional recurrences which led to a statistically non-significant, but clinically relevant improvement of PFS and OS. Clinical trial information: NCT01107639. [Table: see text]