tbuckley/cabot-search huggingface dataset:
Film: The Keys to the House (Le Chiavi di Casa)
Authors: Khalid Ali
Journal: BMJ (2005)

Films about disabled characters have rarely made entertaining cinema. Jim Sheridan's My Left Foot (1989) is an exception: its portrayal of the Irish artist and writer Christy Brown, whose cerebral palsy confined him to a wheelchair, won Daniel Day-Lewis a well deserved Oscar.

About two children out of every thousand born in this country have some form of cerebral palsy. The Keys to the House, based on a book by Giuseppe Pontiggia about his relationship with his son, tells the story of Paolo, a 15 year old boy with cerebral palsy, coming to know his father, Gianni, after years of abandonment. Gianni (played by Kim Rossi Stuart) is forced into accompanying his son (played by Andrea Rossi, who has cerebral palsy) on a journey to a specialist clinic for disabled children in Germany, where they come across the mother of a girl with a learning disability. Initially there is apprehension and resentment between father and son, but their journey becomes one of self discovery and transformation as they share intimate moments, experiences, and dreams.

Through the interaction of the two parents—the mother is played by Charlotte Rampling—and their two children, the film provides a thought provoking dissection of family life when coping with the stresses of looking after a disabled child. Paolo is portrayed as an inquisitive soul with an independent personality, compensating for his physical disability with determination and resilience. However, the film also portrays his limitations, dependence, and tantrums factually without any contrived attempt to make him lovable or cute. It sensitively handles his natural desire for a physical and emotional relationship with girls, as well as his frustrations.​frustrations.




Figure 1



Moments of humour: actors Kim Rossi Stuart and Andrea Rossi




In addition the film does not shy away from dealing with the heavy responsibility that parents, especially mothers, of disabled children have to cope with: “This is the mother's dirty work, fathers can't take it.” It illustrates the difficulty of trying to discipline a disabled child, without giving in to the emotional blackmail of the children using their disability as a weapon. The film also explores the mixed feelings of shame and guilt that parents are in some way responsible for their children's disability, highlighting the need for parents to be supported emotionally and psychologically. One poignant scene shows the importance of everyday routine as a coping mechanism, distracting the parents from worrying about the future when their children grow older. The film also touches on doctors' and physiotherapists' expectations of disabled children, which can sometimes be too demanding.

Despite its sensitive subject, The Keys to the House has its moments of humour. Its message is that disabled people are neither heroes nor disadvantaged, but are different human beings with their own strengths and weaknesses.
Allogeneic stem cell transplantation for patients over age 65 with acute myelogenous leukemia and myelodysplastic syndrome.
Authors: Henry Jacob Conter, Gabriela Rondon, Nhu-Nhu Nguyen, Julianne Chen, Elizabeth J. Shpall, Issa F. Khouri, Sergio Giralt, Richard E. Champlin, Marcos J.G. De Lima
Journal: Journal of Clinical Oncology (2012)

6529 Background: ASCT represents a potentially curative approach for AML and MDS, diseases that primarily affects patients in 7 th and 8 th decade of life. Here, we report outcomes of patients older than 64 treated at the MD Anderson Cancer Center from 1996 until December 2011. Methods: 182 patients older than 64 received an ASCT for AML (n=143) or MDS (n=39). Outcomes of interest were transplant-related mortality (TRM), incidence of acute and chronic graft-versus-host disease (GVHD), incidence of relapse, and overall survival (OS) - which were estimated from the date of transplant. Results: The median age of patients was 67 (range 65-79). Most patients were transplanted with active disease (table). Median follow-up for alive patients was 12.6 months (n=63; range 0-118). The cumulative incidence of 100-day, 1 year, and 3 year TRM was 14%, 18%, and 21%, respectively. 26% of patients developed grade II-IV acute GVHD and 35% suffered from chronic GVHD. The actuarial incidence of relapse was 46% at 1 year and 53% at 3 and 5 years. Actuarial OS was estimated to be 45% at 1 year, 28% at 3 years, and 21% at 5 years. 3 year OS for patients transplanted in CR and with active disease was 40% versus 23% (p=0.02). OS of patients age 65-69 or &gt;69 was 30% vs. 20% (p=0.06) at 3 years for all patients; compared to 38% versus 27% (p=0.23) for patients in those age groups transplanted in CR. Conclusions: Although a significant minority of patients older than 64 years may achieve long-term disease control, new approaches are needed to reduce TRM and relapse in this cohort of patients. [Table: see text]
The Gamma Globulins and Their Clinical Significance
Authors: Paul A. M. Gross, David Gitlin, Charles A. Janeway
Journal: New England Journal of Medicine (1959)

(Concluded)*Clinical Uses of Gamma GlobulinThe separation of gamma globulins from human plasma for use in the prevention and treatment of infectious diseases was made possible during World War II by the procurement of large plasma pools by the American Red Cross and by the successful development of human plasma-fractionation technics. Although the gamma-globulin fraction (fraction II of Cohn) contains almost all the plasma antibodies against many bacteria and viruses, the specific antibody content of any given lot of gamma globulin depends entirely upon the particular immune antibodies present in the plasma of the donors. The concentration and variety . . .
A favorable population among clinical stage IIIA-N2 non-small cell lung cancer: The importance of the location of the primary tumor and involved nodes.
Authors: Takeshi Matsunaga, Kenji Suzuki, Kazuya Takamochi, Shiaki Oh
Journal: Journal of Clinical Oncology (2013)

7575 Background: The number of station of involved N2 nodes has been considered to be one of the most important prognostic factors for lung cancer. However most reports detailed with not clinical nodal status, but pathological nodal status. We investigated the relationship between prognosis and the location of the primary tumor and involved nodes. Methods: A retrospective study was conducted on 1257 patients with primary lung cancer, which was resected between 1996 and 2009. Among them, 79 patients (6.3%) had cN2, c-stage IIIA, pN2 and NSCLC. Mediastinal lymph node with a diameter of 10mm or more in the short axis was diagnosed as metastasis. We defined cN2α as only involvement of upper mediastinal lymph node (UMLN) in main tumor located on upper lobe or as that of lower mediastinal lymph node (LMLN) in main tumor located on lower lobe. And we did cN2β as involvement of LMLN in main tumor located on upper lobe with or without metastatic UMLN or as that of UMLN in main tumor located on lower lobe with or without metastatic LMLN. We analyzed preoperative clinical factors and investigated overall and disease-free survival. Results: The overall 5-year survival rate was 30.2% and median follow-up was 52.8 months. The disease-free 5-year survival rate was 22.2%. The differences in survival between cN2α and cN2β were statistically significant (29.5% vs. 0%, p-value=0.0007), whereas no significant differences was found between cN2 single station and multiple station (23.3% vs. 19.4%, p-value=0.1220). Multivariate analysis with cox’s hazard model disclosed that cN2α was independent good disease-free prognostic factor(HR: 0.426, 95%CI: 0.193-0.941). The sensitivity, specificity and positive predictive value for pN2 single station based on cN2 single station were 71.4%, 49.1% and 34.9% (p=0.1269). Conclusions: Clinical mediastinal lymph node status based on the location of the primary tumor and involved nodes was an important preoperative prognostic factor. Thus this factor should be taken into consideration for planning and evaluating clinical trials. Another fruit of the study was that clinical single nodal N2 was not always pathological single N2 disease.
Diet and the risk of head and neck cancer: A pooled analysis in the INHANCE consortium
Authors: Shu-Chun Chuang, Mazda Jenab, Julia Heck, Andrew Olshan, Vladimir Bencko, Stimson Schantz, Maria Paula Curado, Dana Mates, Michael McClean, Alexander Daudt, Silvia Franceschi, David Zaridze, Sergio Koifman, Philip Lazarus, Rolando Herrero, Eleonora Fabianova, Dal Maso Luigino, Zuo-Feng Zhang, Joshua Muscat, Renato Talamini, Peter Rudnai, Leticia Fernandez, Jola Lissowska, Ana Menezes, Fabio Levi, Richard Hayes, Simone Benhamou, Jose Eluf-Neto, Stefania Boccia, Elena Matos
Journal: Cancer Research (2009)

Author(s): Chuang, Shu-Chun; Jenab, Mazda; Heck, Julia; Olshan, Andrew; Bencko, Vladimir; Schantz, Stimson; Paula Curado, Maria; Mates, Dana; McClean, Michael; Daudt, Alexander; Franceschi, Silvia; Zaridze, David; Koifman, Sergio; Lazarus, Philip; Herrero, Rolando; Fabianova, Eleonora; Maso Luigino, Dal; Zhang, Zuo-Feng; Muscat, Joshua; Talamini, Renato; Rudnai, Peter; Fernandez, Leticia; Lissowska, Jola; Menezes, Ana; Levi, Fabio; Hayes, Richard; Benhamou, Simone; Eluf-Neto, Jose; Boccia, Stefania; Matos, Elena
Risk factors for venous thromboembolism (VTE) in outpatients with pancreatic cancer.
Authors: Joshua Michael Ruch, Michelle A Anderson, Suman Lata Sood
Journal: Journal of Clinical Oncology (2012)

e14578 Background: The incidence of VTE is increased in pancreatic cancer. Predictive models for cancer-associated VTE have been developed, but none specific for the pancreas. Our primary objective was to identify risk factors for VTE in outpatients with pancreatic cancer. Secondary objective was to develop a predictive model. Methods: Patients seen at the University of Michigan Comprehensive Cancer Center (UMCC) and previously consented and enrolled in a prospective cohort study were eligible. Inclusion criteria included a diagnosis of pancreatic adenocarcinoma, evaluation at UMCC, and follow up in the Electronic Medical Record (EMR) at least every 6 months. Demographics, clinical data, and VTE events (defined as deep vein thrombosis [DVT], portal vein thrombosis [PVT], or pulmonary embolism [PE]) were obtained from the EMR. A retrospective cohort study was performed including univariate and multivariate regression analysis. Results: Between 2005 and 2011, 92 patients were eligible for analysis. Median follow-up was 263.5 (18-2433) days. Twenty (21.7%) patients had a VTE; 10 (50%) DVT, 2 (10%) PE, 4 (20%) PVT, and 4 (20%) multiple VTEs. Mean (SD) age was 63.4 (8.9) with and 65.6 (11.8) without VTE. 55% of patients with and 47% without VTE were women. Higher body mass index (BMI) (median 28.8 [21.2-44.7] vs. 25.5 [16.4-43.3], p=0.02) and lower platelet count (median 241 [145-323] vs. 288 [75-645], p=0.04) were associated with VTE in univariate analysis. In multivariate regression analysis, lower platelet count (β -0.01, SE 0.004) and lower hemoglobin (β -0.44, SE 0.20) were predictive of VTE after adjusting for BMI, tumor location, and treatment with surgery, chemotherapy or radiation (area under the ROC curve 0.78). Conclusions: Pancreatic cancer outpatients with higher BMI, lower platelet count, and lower hemoglobin were more likely to develop VTE. Other clinical variables did not add additional predictive information. Given the small magnitude of difference, basic clinical criteria alone may be inadequate to identify patients at highest risk for developing VTE who may benefit from thromboprophylaxis. Additional studies are warranted to further define risk factors for VTE in this population, including novel biomarkers.
Abstract 13199: Women With Hypertrophic Cardiomyopathy: Obstructed and Underdiagnosed? Results From the International SHaRe Registry
Authors: Neal K Lakdawala, Iacoppo Olivotto, Sharlene Day, Daniel Jacoby, Euan Ashley, Michelle Michels, Alexandre Pereira, Steven Colan, Carolyn Y Ho
Journal: Circulation (2018)

Introduction: In hypertrophic cardiomyopathy (HCM) the relationship between female sex, genetic status and presenting clinical characteristics has not been well studied. Hypothesis: Compared to men...
Adherence to a Mediterranean diet is associated with a lower risk of later-onset Crohn’s disease: results from two large prospective cohort studies
Authors: Hamed Khalili, Niclas Håkansson, Simon S Chan, Ye Chen, Paul Lochhead, Jonas F Ludvigsson, Andrew T Chan, Andrew R Hart, Ola Olén, Alicja Wolk
Journal: Gut (2020)

To examine the relationship between Mediterranean diet and risk of later-onset Crohn's disease (CD) or ulcerative colitis (UC).We conducted a prospective cohort study of 83 147 participants (age range: 45-79 years) enrolled in the Cohort of Swedish Men and Swedish Mammography Cohort. A validated food frequency questionnaire was used to calculate an adherence score to a modified Mediterranean diet (mMED) at baseline in 1997. Incident diagnoses of CD and UC were ascertained from the Swedish Patient Register. We used Cox proportional hazards modelling to calculate HRs and 95% CI.Through December of 2017, we confirmed 164 incident cases of CD and 395 incident cases of UC with an average follow-up of 17 years. Higher mMED score was associated with a lower risk of CD (Ptrend=0.03) but not UC (Ptrend=0.61). Compared with participants in the lowest category of mMED score (0-2), there was a statistically significant lower risk of CD (HR=0.42, 95% CI 0.22 to 0.80) but not UC (HR=1.08, 95% CI 0.74 to 1.58). These associations were not modified by age, sex, education level, body mass index or smoking (all Pinteraction >0.30). The prevalence of poor adherence to a Mediterranean diet (mMED score=0-2) was 27% in our cohorts, conferring a population attributable risk of 12% for later-onset CD.In two prospective studies, greater adherence to a Mediterranean diet was associated with a significantly lower risk of later-onset CD.
Small molecule JQ1 promotes prostate cancer invasion via BET-independent inactivation of FOXA1
Authors: Leiming Wang, Mafei Xu, Chung-Yang Kao, Sophia Y. Tsai, Ming-Jer Tsai
Journal: Journal of Clinical Investigation (2019)

Recent findings have shown that inhibitors targeting bromodomain and extraterminal domain (BET) proteins, such as the small molecule JQ1, are potent growth inhibitors of many cancers and hold promise for cancer therapy. However, some reports have also revealed that JQ1 can activate additional oncogenic pathways and may affect epithelial-to-mesenchymal transition (EMT). Therefore, it is important to address the potential unexpected effect of JQ1 treatment, such as cell invasion and metastasis. Here, we showed that in prostate cancer, JQ1 inhibited cancer cell growth but promoted invasion and metastasis in a BET protein–independent manner. Multiple invasion pathways including EMT, bone morphogenetic protein (BMP) signaling, chemokine signaling, and focal adhesion were activated by JQ1 to promote invasion. Notably, JQ1 induced upregulation of invasion genes through inhibition of Forkhead box protein A1 (FOXA1), an invasion suppressor in prostate cancer. JQ1 directly interacted with FOXA1 and inactivated FOXA1 binding to its interacting repressors TLE3, HDAC7, and NFIC, thereby blocking FOXA1-repressive function and activating the invasion genes. Our findings indicate that JQ1 has an unexpected effect of promoting invasion in prostate cancer. Thus, the ill effect of JQ1 or its derived therapeutic agents cannot be ignored during cancer treatment, especially in FOXA1-related cancers.
Targeted destruction of cancer stem cells using multifunctional magnetic nanoparticles that enable combined hyperthermia and chemotherapy
Authors: Dandan Liu, Yingcai Hong, Yaping Li, Chong Hu, Tak-Chun Yip, Wai-Kin Yu, Yu Zhu, Chi-Chun Fong, Weimao Wang, Siu-Kie Au, Shubin Wang, Mengsu Yang
Journal: Theranostics (2020)

Cancer stem cells (CSCs) have been implicated in cancer recurrence and therapy resistance. Therefore, a CSC-targeted therapy that disrupts the maintenance and survival of CSCs may offer an effective approach in killing tumor cells in primary tumors and preventing the metastasis caused by CSCs. Nanoparticles (NPs)-based thermotherapy and/or chemotherapy are promising therapeutic methods for cancer treatment. Methods: A silica-based multifunctional NP system was present, which encapsulated a chemotherapeutic agent and magnetic cores and coated with a specific antibody against the lung CSCs. The efficacy of this novel therapeutic strategy was systematically studied both in vitro and in vivo by simultaneous activating the combined thermotherapy and chemotherapy via CSC-targeted NPs. Results: These NPs were systematically administered and activated for targeted chemotherapy and thermotherapy by using an externally applied alternating magnetic field (AMF). The antibody-modified NPs targeted to lung CSCs with enhanced cellular uptake in vitro and extended accumulation in tumor in vivo. Up to 98% of lung CSCs was killed in vitro with 30-min application of AMF, due to the combined effects of hyperthermia and chemotherapeutic drug treatment. In in vivo models, this combined therapy significantly suppressed tumor growth and metastasis in lung CSC xenograft-bearing mice, with minimal side effects and adverse effects. Conclusion: With good biocompatibility and targeting capability, the nanodrug delivery system may offer a promising clinical platform for the combined thermotherapy and chemotherapy. This work demonstrated the feasibility of developing multifunctional nanomedicine targeting CSCs for effective cancer treatment.
Heparan sulfate chains contribute to the anticoagulant milieu in malignant pleural effusion
Authors: Emilia Hardak, Eli Peled, Yonatan Crispel, Shourouk Ghanem, Judith Attias, Keren Asayag, Inna Kogan, Yona Nadir
Journal: Thorax (2019)

Background While malignant pleural effusion (MPE) is a common and significant cause of morbidity in patients with cancer, current treatment options are limited. Human heparanase, involved in angiogenesis and metastasis, cleaves heparan sulfate (HS) side chains on the cell surface. Aims To explore the coagulation milieu in MPE and infectious pleural effusion (IPE) focusing on the involvement of heparanase. Methods Samples of 30 patients with MPE and 44 patients with IPE were evaluated in comparison to those of 33 patients with transudate pleural effusions, using heparanase ELISA, heparanase procoagulant activity assay, thrombin and factor Xa chromogenic assays and thromboelastography. A cell proliferation assay was performed. EMT-6 breast cancer cells were injected to the pleural cavity of mice. A peptide inhibiting heparanase activity was administered subcutaneously. Results Levels of heparanase, factor Xa and thrombin were significantly higher in exudate than transudate. Thromboelastography detected almost no thrombus formation in the whole blood, mainly on MPE addition. This effect was completely reversed by bacterial heparinase. Direct measurement revealed high levels of HS chains in pleural effusions. Higher proliferation was observed in tumour cell lines incubated with exudate than with transudate and it was reduced when bacterial heparinase was added. The tumour size in the pleural cavity of mice treated with the heparanase inhibitor were significantly smaller compared with control (p=0.005). Conclusions HS chains released by heparanase form an anticoagulant milieu in MPE, preventing local thrombosis and enabling tumour cell proliferation. Inhibition of heparanase might provide a therapeutic option for patients with recurrent MPE.
Investigating the effects of dexamethasone on blood-brain barrier permeability and inflammatory response following focused ultrasound and microbubble exposure
Authors: Dallan McMahon, Wendy Oakden, Kullervo Hynynen
Journal: Theranostics (2020)

Rationale: Clinical trials are currently underway to test the safety and efficacy of delivering therapeutic agents across the blood-brain barrier (BBB) using focused ultrasound and microbubbles (FUS+MBs).While acoustic feedback control strategies have largely minimized the risk of overt tissue damage, transient induction of inflammatory processes have been observed following sonication in preclinical studies.The goal of this work was to explore the potential of post-sonication dexamethasone (DEX) administration as a means to mitigate treatment risk.Vascular permeability, inflammatory protein expression, blood vessel growth, and astrocyte activation were assessed.Methods: A single-element focused transducer (transmit frequency = 580 kHz) and Definity TM microbubbles were used to increase BBB permeability unilaterally in the dorsal hippocampi of adult male rats.Sonicating pressure was calibrated based on ultraharmonic emissions.Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used to quantitatively assess BBB permeability at 15 min (baseline) and 2 hrs following sonication.DEX was administered following baseline imaging and at 24 hrs post-FUS+MB exposure.Expression of key inflammatory proteins were assessed at 2 days, and astrocyte activation and blood vessel growth were assessed at 10 days post-FUS+MB exposure.Results: Compared to saline-treated control animals, DEX administration expedited the restoration of BBB integrity at 2 hrs, and significantly limited the production of key inflammation-related proteins at 2 days, following sonication.Indications of FUS+MB-induced astrocyte activation and vascular growth were diminished at 10 days in DEX-treated animals, compared to controls.Conclusions: These results suggest that DEX provides a means of modulating the duration of BBB permeability enhancement and may reduce the risk of inflammation-induced tissue damage, increasing the safety profile of this drug-delivery strategy.This effect may be especially relevant in scenarios for which the goal of treatment is to restore or preserve neural function and multiple sonications are required.
Self-assembled natural phytochemicals for synergistically antibacterial application from the enlightenment of traditional Chinese medicine combination
Authors: Xuehao Tian, Penglong Wang, Tong Li, Xuemei Huang, Wenbo Guo, Yuqin Yang, Mengmeng Yan, Hao Zhang, Desheng Cai, Xiaohui Jia, Feifei Li, Bing Xu, Tao Ma, Cong Yan, Haimin Lei
Journal: Acta Pharmaceutica Sinica B (2019)

The application of nanotechnology for antimicrobial delivery has capacity to improve antibacterial efficacy. Currently, the usage of various inorganic and organic carriers, such as metal ions, nano-silicon and surfactants, might increase the potential toxicity of nanoparticles and make their clinical transformation more difficult. Herein, a nano-delivery system was constructed by direct self-assembly of antibacterial phytochemicals (berberine and rhein) originated from traditional Chinese medicine Coptis chinensis Franch. and Rheum palmatum L., respectively. Combining X-ray single crystal diffraction, nuclear magnetic resonance and other spectra characterizations, the stacked structure of nanoparticles was profoundly demonstrated. Briefly, rhein acted as the layered backbone and berberine embedded in it. In vitro bacteriostasis experiment showed the minimum bactericidal concentration of nanoparticles was 0.1 μmol/mL, which was lower than that of berberine and rhein. The results of confocal laser scanning microscope, biofilm quantitive assay and scanning electron microscopy indicated that nanoparticles had strong inhibitory effects on Staphylococcus aureus biofilm. More importantly, transmission electron microscopy and mass spectra indicated the further bacteriostatic mechanism of nanoparticles. Meanwhile, the nanoparticles had well biocompatibility and safety. Current study will open up new prospect that the design of self-assemblies between active phytochemicals can be originated from traditional Chinese medicine combination.