tbuckley/cabot-search huggingface dataset:
Relationships among Maternal Stress and Depression, Type 2 Responses, and Recurrent Wheezing at Age 3 Years in Low-Income Urban Families
Authors: Sima K. Ramratnam, Cynthia M. Visness, Katy F. Jaffee, Gordon R. Bloomberg, Meyer Kattan, Megan T. Sandel, Robert A. Wood, James E. Gern, Rosalind J. Wright
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: Maternal depression and prenatal and early life stress may influence childhood wheezing illnesses, potentially through effects on immune development.Objectives: To test the hypothesis that maternal stress and/or depression during pregnancy and early life are associated with recurrent wheezing and aeroallergen sensitivity and altered cytokine responses (enhanced type 2 or reduced virus-induced cytokine responses) from stimulated peripheral blood mononuclear cells at age 3 years.Methods: URECA (Urban Environment and Childhood Asthma) is a birth cohort at high risk for asthma (n = 560) in four inner cities. Maternal stress, depression, and childhood wheezing episodes were assessed by quarterly questionnaires beginning at birth. Logistic and linear regression techniques were used to examine the relation of maternal stress/depression to recurrent wheezing and peripheral blood mononuclear cell cytokine responses at age 3 years.Measurements and Main Results: Overall, 166 (36%) children had recurrent wheeze at age 3 years. Measures of maternal perceived stress at Years 2 and 3 were positively associated with recurrent wheeze (P < 0.05). Maternal depression (any year) was significantly associated with recurrent wheezing (P ≤ 0.01). These associations were also significant when considered in a longitudinal analysis of cumulative stress and depression (P ≤ 0.02). Neither stress nor depression was significantly related to aeroallergen sensitization or antiviral responses. Contrary to our original hypothesis, prenatal and Year 1 stress and depression had significant inverse associations with several type 2 cytokine responses.Conclusions: In urban children at high risk for asthma, maternal perceived stress and depression were significantly associated with recurrent wheezing but not increased atopy or reduced antiviral responses.
Ledipasvir/Sofosbuvir in NS3/4A Protease Inhibitor-Experienced Subjects with HCV Genotype 1 and HIV-Co-Infection Final Results of the ANRS HC31 Softrih Study
Authors: E. Rosenthal, C. Fougerou-Leurent, A. Renault, E. Teicher, S. Dominguez, A. Naqvi, S. Metivier, L. Cotte, J. Reynes, M. -A. Valantin, V. Leroy, G. -P. Pageaux, S. Pol, L. Piroth, P. Perré, P. Morlat, D. Salmon-Ceron, J. Chas, V. Jeantils, P. De Truchis, T. Allegre, M. Dupon, F. Raffi, Y. Yazdanpanah, I. Poizot-Martin, D. Neau, P. -M. Girard, D. Zucman, R. Garraffo, S. Chevaliez, P. Carrieri, H. Aumaitre, K. Lacombe, F. Bailly, E. Billaud, A. Pailhe, I. Amri, M. Bourlière, E. Bellissant, J. -M. Molina
Journal: Journal of Hepatology (2016)
Review of John D. Lantos and Diane S. Lauderdale,<i>Preterm Babies, Fetal Patients, and Childbearing Choices</i><sup>1</sup>
Authors: Michelle L. McGowan
Journal: The American Journal of Bioethics (2016)

Preterm birth is defined as any birth that occurs prior to 37 weeks gestation, and is a leading cause of infant mortality, neurological disabilities, breathing, feeding and vision problems, and hea...
The influence of age plus standard clinical approach with or without comprehensive geriatric assessment (CGA) on treatment decisions in older cancer patients: Final results.
Authors: Lore Decoster, Cindy Kenis, Katrien Van Puyvelde, Jacques De Greve, Godelieve Conings, Marie Claire Knapen, Jean Pierre Lobelle, Koen Milisen, Katrien Vanorle, Johan Flamaing, Hans Wildiers
Journal: Journal of Clinical Oncology (2012)

9035 Background: The aim of this prospective study was to examine how age and standard clinical approach with and without CGA results determine treatment decisions in older cancer patients (pts). Methods: This study,conducted in 2 Belgian university hospitals, included pts ≥ 70 years with a malignant tumor (breast, colorectal, ovarian, lung, prostate and hematological) if a new cancer therapy was considered. All pts underwent a uniform CGA. Results were communicated to the treating physician. After the treatment decision, an interview with the treating physician was performed, using a predefined questionnaire: 1/ What would be your oncological treatment proposal in case the pt was 55y without other comorbidity? 2/ Is this different from your treatment proposal for this pt according to age and standard clinical approach without CGA results? 3/ Is this different from your treatment proposal for this pt with CGA results? Results: From October 2009 till July 2011, 937 pts were included in the study. Median age was 76y (range 70-95) and 63.5% was female. A total of 902 (96.3%) questionnaires were completed and 56.2% of the physicians were aware of the CGA results at treatment decision. In 381 pts (42.2%; 95%CI 39.0-45.5) age and standard clinical approach led to a different treatment decision compared to younger pts without comorbidity. This influence was most prominent for chemotherapy decisions: 309 patients did not receive standard chemotherapy (reduced dose (13), less toxic regimen (163), less toxic regimen at reduced dose (5) or no chemotherapy (128)). When the physician was aware of the CGA, these results influenced their treatment in 6.7% (95%CI: 4.5-8.9), mostly concerning chemotherapy. In 8 pts CGA results encouraged the treating physician to choose a more aggressive chemotherapy regimen and in 11 pts CGA results led to a decision of palliative care. Conclusions: Based on this prospective trial, we conclude that physicians use adapted treatment regimens in older versus younger pts, only based on age and standard clinical approach. CGA results change the treatment decision in 6.7% and sometimes trigger the use of a more aggressive treatment.
A phase Ib dose escalation, safety, and tolerability study of sonidegib in combination with gemcitabine in patients with locally advanced or metastatic pancreatic adenocarcinoma.
Authors: Teresa Macarulla, Josep Tabernero, Daniel H. Palmer, Sunil Sharma, Kenneth H. Yu, Dalila B. Sellami, Jocelyn Zhou, Wu Yi, Hildegard Boss, Eunice L Kwak
Journal: Journal of Clinical Oncology (2016)

371 Background: Sonidegib (LDE225) is a potent, selective, and orally bioavailable inhibitor of smoothened receptor that demonstrated preclinical activity in combination with gemcitabine (GEM). Here, we present data from a phase 1b trial of sonidegib in combination with GEM in patients (pts) with pancreatic adenocarcinoma (PA). Methods: Pts with histologically or cytologically confirmed, locally advanced, or metastatic PA who had not been treated previously or had progressed despite prior chemotherapy (other than GEM) were included in the study. Dose escalation started with sonidegib 400 mg, once a day, in combination with GEM 1000 mg/m 2 IV infusion on days 1, 8, and 15 of a 28-day cycle. Results: A total of 18 pts were enrolled (9 pts each the in dose escalation and dose expansion phases). Pts discontinued the study because of disease progression (n = 11, 61.1%), consent withdrawal (n = 3, 16.7%), administrative problems (n = 3, 16.7%), and grade 3 or 4 blood creatine kinase (CK) elevation (n = 1, 5.6%). Three of 9 pts in dose escalation phase experienced dose-limiting toxicities during the first 8 weeks including grade 3 mucositis (n = 1), grade 3 CK elevation (n = 1), and grade 3 aspartate aminotransferase elevation (n = 1). Drug-related adverse events (AEs) of all grades were reported in 14 pts (77.8%) and grade 3 or 4 AEs were reported in 10 pts (55.6%). The most commonly reported AEs were anemia and nausea. No pharmacokinetic (PK) interaction was observed. Based on considerations of the statistical model, clinical assessment of safety, tolerability, PK, and pharmacodynamic results, maximum-tolerated dose and recommended dose were established as 400 mg of sonidegib in combination with the fixed standard dose of GEM (1000 mg/m 2 ).The objective response rate was 11.1% and the median progression-free survival (PFS) was 4.9 months. Conclusions: The combination of sonidegib and GEM was generally well tolerated with moderate activity. Although no formal comparison can be made due to small sample size of this study, this combination provided a median PFS comparable to the current standard of care without conferring any additional clinical benefit. Clinical trial information: NCT01487785.
Taliban militants kill doctor working to eradicate polio
Authors: Ashfaq Yusufzai
Journal: BMJ (2016)

Taliban militants have shot dead a senior doctor working on north west Pakistan’s polio eradication campaign as part of their protest against vaccination.

Zakaullah Khan had led the Union Council Polio Eradication Committee in Peshawar for the last 10 years.

Pakistan’s health minister, Shahram Khan, told The BMJ that Khan had continued with his work despite threats from militants opposed to the vaccine.

“Militants have killed 78 polio workers, including three senior doctors, and have wounded 85 others to thwart vaccination,” he said. However, he added, “We are determined to reach 35 million children in every campaign and do away with this …
Potential of the Antibody Against <i>cis</i>–Phosphorylated Tau in the Early Diagnosis, Treatment, and Prevention of Alzheimer Disease and Brain Injury
Authors: Kun Ping Lu, Asami Kondo, Onder Albayram, Megan K. Herbert, Hekun Liu, Xiao Zhen Zhou
Journal: JAMA Neurology (2016)

Alzheimer disease (AD) and chronic traumatic encephalopathy (CTE) share a common neuropathologic signature-neurofibrillary tangles made of phosphorylated tau-but do not have the same pathogenesis or symptoms. Although whether traumatic brain injury (TBI) could cause AD has not been established, CTE is shown to be associated with TBI. Until recently, whether and how TBI leads to tau-mediated neurodegeneration was unknown. The unique prolyl isomerase Pin1 protects against the development of tau-mediated neurodegeneration in AD by converting the phosphorylated Thr231-Pro motif in tau (ptau) from the pathogenic cis conformation to the physiologic trans conformation, thereby restoring ptau function. The recent development of antibodies able to distinguish and eliminate both conformations specifically has led to the discovery of cis-ptau as a precursor of tau-induced pathologic change and an early driver of neurodegeneration that directly links TBI to CTE and possibly to AD. Within hours of TBI in mice or neuronal stress in vitro, neurons prominently produce cis-ptau, which causes and spreads cis-ptau pathologic changes, termed cistauosis. Cistauosis eventually leads to widespread tau-mediated neurodegeneration and brain atrophy. Cistauosis is effectively blocked by the cis-ptau antibody, which targets intracellular cis-ptau for proteasome-mediated degradation and prevents extracellular cis-ptau from spreading to other neurons. Treating TBI mice with cis-ptau antibody not only blocks early cistauosis but also prevents development and spreading of tau-mediated neurodegeneration and brain atrophy and restores brain histopathologic features and functional outcomes. Thus, cistauosis is a common early disease mechanism for AD, TBI, and CTE, and cis-ptau and its antibody may be useful for early diagnosis, treatment, and prevention of these devastating diseases.
Initial Cytoreductive Treatment with Thalidomide Plus Bolus Vincristine/Doxorubicin and Reduced Dexamethasone (T-bVAd) Followed by Autologous Stem Cell Transplantation (ASCT) for Multiple Myeloma.
Authors: Jae-Cheol Jo, Byung Wook Kang, Sun Jin Sym, Sung Sook Lee, Geundoo Jang, Dae Ho Lee, Sang-We Kim, Cheolwon Suh
Journal: Blood (2007)
BRD4 Proteolysis Targeting Chimera (PROTAC) Leads to Sustained Degradation of BRD4 with Broad Activity Against Acute Leukemias and Overcomes Stroma Mediated Resistance By Modulating Surface Expression of CXCR4
Authors: Sujan Piya, Teresa McQueen, Duncan Mak, Marina Konopleva, Patrick Zweidler-McKay, Jing Lu, Yimin Qian, Michael Andreeff, Gautam Borthakur
Journal: Blood (2015)
Early Detection and Curative Treatment of Hepatocellular Carcinoma: A Cost Effectiveness Analysis Based on Prospective French Cohort (ANRS CO12 CirVir and CHANGH)
Authors: B. Cadier, J. Bulsei, P. Nahon, O. Seror, A. Laurent, I. Rosa, R. Layese, None Isabelle, None Durand-Zaleski, K. Chevreu
Journal: Journal of Hepatology (2016)
Sumo-Specific Protease 3 is an Important Regulator of Lipid Metabolism in Nonalcoholic Fatty Liver Disease
Authors: Y. Liu, F. Yu, Z. Cao, X. Xiang, Q. Li, H. Wang, Y. Han, W. Cai, J. Lu, X. Wang, S. Bao, Q. Xie
Journal: Journal of Hepatology (2016)
Long-Term Survival Analyses of an Ongoing Phase 2 Study of Brentuximab Vedotin in Patients with Relapsed or Refractory Hodgkin Lymphoma
Authors: Robert W. Chen, Ajay K. Gopal, Scott E. Smith, Stephen M. Ansell, Joseph D. Rosenblatt, Kerry J. Savage, Joseph M. Connors, Andreas Engert, Emily K. Larsen, Eric L. Sievers, Anas Younes
Journal: Blood (2012)
Incidence of pseudoprogression in low-grade gliomas treated with radiotherapy
Authors: Sophie E. van West, Hein G. de Bruin, Bart van de Langerijt, Annemarie T. Swaak-Kragten, Martin J. van den Bent, Walter Taal
Journal: Neuro-Oncology (2016)

As the incidence of pseudo-progressive disease (psPD), or pseudoprogression, in low-grade glioma (LGG) is unknown, we retrospectively investigated this phenomenon in a cohort of LGG patients given radiotherapy (RT).All MRI scans and clinical data from patients with histologically proven LGG treated with radiation between 2000 and 2011 were reviewed. PsPD was scored when a new enhancing lesion occurred after RT and subsequently disappeared or remained stable for at least a year without therapy, including dexamethasone.Sixty-three out of 71 patients who received RT for LGG were deemed eligible for evaluation of psPD. The median follow-up was 5 years (range 1‒10 y). PsPD was seen in 13 patients (20.6%). PsPD occurred after a median of 12 months with a range of 3-78 months. The median duration of psPD was 6 months, with a range of 2-26 months and always occurred within the RT high dose fields of at least 45 Gy. The area of the enhancement at the time of psPD was significantly smaller compared with the area of enhancement during "true" progression (median size 54mm2 [range 12-340mm2] vs 270mm2 [range 30-3420mm2], respectively; P = .009).PsPD occurs frequently in LGG patients receiving RT. This supports the policy to postpone a new line of treatment until progression is evident, especially when patients have small contrast enhancing lesions within the RT field.
Genetic variants in <i>MDR1</i> and <i>CYP3A5</i> and vincristine toxicity in children with acute lymphoblastic leukemia.
Authors: D. M. Te Loo, M. M. Hagleitner, R. van Schie, I. M. van der Sluis, M. J. Coenen, P. Hoogerbrugge
Journal: Journal of Clinical Oncology (2010)

9526 Background: Vincristine plays a key role in the treatment of acute lymphoblastic leukemia (ALL) in children. Constipation and peripheral or central neurotoxicity's are the most common side effects. Pharmacokinetic parameters are unreliable to determine which patients are at risk for developing these side effects. Pharmacogenetic studies might help to identify those patients at risk. Therefore we investigated the role of functional single nucleotide polymorphisms (SNPs) in two genes encoding enzymes that play an important role in the metabolism of vincristine, namely the multi-drug resistance (MDR1) gene and the cytochrome P450 enzyme (CYP3A5). Methods: We genotyped 105 children with ALL. In each patient, vincristine toxicity was graded retrospectively according to the National Cancer Institute toxicity scale. SNPs were genotyped by TaqMan SNP genotyping assays. The association between vincristine toxicity and each SNP was estimated using logistic regression models. Two-way interactions between the MDR1 and CYP3A5 were investigated using multivariate logistic models. Results: Elevated liver enzymes were associated with a variant in CYP3A5, namely rs776746 (CYP3A5*3; p=0.040). Peripheral polyneuropathy was associated with the 3435C>T polymorphism in MDR1 (rs1128503; p=0.025). Interaction between 3435C>T and 2677C>T (rs2032582) in MDR1 showed a significant relationship with CNS toxicity (p=0.044). Conclusions: This study shows that genetic variations in genes involved in vincristine metabolism are probably related with toxicity. Future studies are necessary to determine whether these SNPs in MDR1 and CYP3A5 can be used for adjustment of vincristine treatment. No significant financial relationships to disclose.
Phase III randomized, double-blind, active-controlled study of momelotinib versus ruxolitinib in patients with myelofibrosis.
Authors: Elliott F. Winton, Timothy Devos, Stephen T. Oh, Uwe Platzbecker, Martha Wadleigh, Susie Jun, Peter Lee, Wei Deng, Vikas Gupta
Journal: Journal of Clinical Oncology (2015)

TPS7101 Background: Momelotinib (MMB) is a JAK1/2 inhibitor that displays potent in vitro inhibitory activity against cells dependent on JAK2, including cells with the JAK2V617F mutation. In a completed phase I/II study of MMB which enrolled 166 subjects with myelofibrosis (MF) (CCL09101), the rate of spleen response was 39%, and the rate of anemia response was 53% (Pardanani et al, Blood 2013). Assessment at 3 months showed improvement of constitutional symptoms. Most common treatment-related adverse events were thrombocytopenia (46%), peripheral neuropathy (44%), diarrhea (25%), dizziness (24%), and nausea (22%). Dizziness is believed to be part of the first-dose effect of MMB. Methods: 420 subjects with primary (PMF), post-polycythemia vera (PPV-MF), or post-essential thrombocythemia MF (PET-MF) will be randomized in a 1:1 manner to receive either MMB plus ruxolitinib (RUX) placebo, or RUX plus MMB placebo in this double-blind, active-controlled study for 24 weeks, with the option for eligible subjects to subsequently continue open-label MMB treatment for up to an additional 168 weeks. Key inclusion criteria include palpable splenomegaly ≥ 5 cm, high risk or intermediate-2 risk MF, or intermediate-1 risk MF with symptoms, and platelet count ≥ 50 x 109/L. Prior use of a JAK inhibitor is not allowed. The primary endpoint is Splenic Response Rate at Week 24, defined as the proportion of subjects achieving ≥ 35% reduction in spleen volume at Week 24 as measured by MRI or CT scan. Secondary endpoints include Response Rate in Total Symptom Score at Week 24 defined as the proportion of subjects who achieves ≥ 50% reduction from baseline in total symptom score to Week 24 as measured by the modified MPNSAF TSS diary. The Data Monitoring Committee last reviewed the trial in November 2014 and recommended that the trial continue as planned. Clinical trial registry number: NCT01969838. Clinical trial information: NCT01969838.
Human Liver Fibrogenesis: The Proof of Concept of HCV-, Ethanol- or Palmitate-Induced Liver Fibrosis in the Ex Vivo Model of Human Liver Slices Culture
Authors: S. Lagaye, J. Gaston, J. Guéchot, P.-P. Massault, J.-C. Vaillant, S. Pol
Journal: Journal of Hepatology (2016)
Oral Treatment with PBI-4425 Decreases Fibrosis in Carbon Tetrachloride (CCL4)-Induced Hepatic Fibrosis Model
Authors: B. Grouix, F. Sarra-Bournet, K. Hince, A. Felton, M. Tremblay, S. Abbott, J.-S. Duceppe, B. Zacharie, P. Laurin, L. Gagnon
Journal: Journal of Hepatology (2016)
Upper and lower limbs muscle in patients with COPD: Similar muscle efficiency but differences in resistance to fatigue
Authors: Eduardo Foschini Miranda, Carla Malaguti, Paulo Marchetti, Simone Dal Corso
Journal: European Respiratory Journal (2011)

Background: It is still controversy whether the impairment of muscle function is homogeneous between the upper and lower limbs in patients with COPD.

Objective: To compare muscle function between quadriceps femoris (QF) and middle deltoid (MD) after a fatigue protocol and also the recovery time fatigue.

Methods: Twenty-one patients (VEF1: 46±10% predicted) performed for both muscles: maximum voluntary isometric contraction (MVIC) pre and post 10, 30, 60min and 24h after completing an isometric endurance test (IET, 60%MVIC). All measurements were made with surface electromyograpy (sEMG) recording. For the temporal analysis the amplitude of the sEMG signals was expressed as root mean square (RMS, 1-s moving window), normalized by MVIC and then, the RMS EMG was integrated (iEMG). For the time-frequency analysis, EMG data were analyzed with a FFT applied to 1-s epochs and the median frequency (MF) of the spectrum for each epoch was obtained. Mid-arm and mid-thigh muscle mass were estimated from anthropometric measurements.

Results: No significant difference was observed between muscles when MVIC was corrected for muscle mass. The endurance time differed significantly between MD and QF (50±40s vs 127±77s). During IET, iEMG increased significantly just for QF but a significant reduction in MF was observed for QF [92.7 (90.4–94.2) vs 88.5 (85.4–89.4)] and MD [89.5 Hz (81.7–91.0) vs 73.5 Hz (67.4–83.6)]. A significant reduction in MVIC after IET was observed just for MD at moments 10, 30, 60 minutes and it was recovered in 24h.

Conclusion: Despite similar muscle efficiency (strength/muscle mass), muscle fatigue was early and more pronounced for MD.
Vaccine-Escape HBsAg Mutations Circulating in a Relevant Proportion of HBV Genotype D Infected Patients Correlate with Atypical Serological Profiles, High Viremia and Transaminases: Potential Implication for Vaccine Success
Authors: R. Salpini, A. Battisti, L. Colagrossi, C. Alteri, A. Bertoli, L. Fabeni, C. Sarrecchia, D. Di Carlo, M. Pollicita, M. Lichtner, C. Mastroianni, G. De Sanctis, M. Paoloni, M. Marignani, C. Pasquazzi, D. Di Paolo, N. Iapadre, T. Mari, G. Parruti, S. Romano, M. Visca, I. Vecchiet, M. Andreoni, G. Cappiello, A. Spanò, M. Angelico, C.F. Perno, V. Svicher
Journal: Journal of Hepatology (2016)
Efficacy and Safety Of Eltrombopag In Korean Adult Patients With Refractory Chronic Immune Thrombocytopenia
Authors: Yeo-Kyeoung Kim, Sung-Hoon Chung, Jae-Sook Ahn, Deok-Hwan Yang, Il-Kwon Lee, Nan-Young Kim, Li Yu, Je-Jung Lee, Hyeoung-Joon Kim
Journal: Blood (2013)
Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukemia
Authors: Rizwan Romee, Maximillian Rosario, Melissa M. Berrien-Elliott, Julia A. Wagner, Brea A. Jewell, Timothy Schappe, Jeffrey W. Leong, Sara Abdel-Latif, Stephanie E. Schneider, Sarah Willey, Carly C. Neal, Liyang Yu, Stephen T. Oh, Yi-Shan Lee, Arend Mulder, Frans Claas, Megan A. Cooper, Todd A. Fehniger
Journal: Science Translational Medicine (2016)

Natural killer (NK) cells are an emerging cellular immunotherapy for patients with acute myeloid leukemia (AML); however, the best approach to maximize NK cell antileukemia potential is unclear. Cytokine-induced memory-like NK cells differentiate after a brief preactivation with interleukin-12 (IL-12), IL-15, and IL-18 and exhibit enhanced responses to cytokine or activating receptor restimulation for weeks to months after preactivation. We hypothesized that memory-like NK cells exhibit enhanced antileukemia functionality. We demonstrated that human memory-like NK cells have enhanced interferon-γ production and cytotoxicity against leukemia cell lines or primary human AML blasts in vitro. Using mass cytometry, we found that memory-like NK cell functional responses were triggered against primary AML blasts, regardless of killer cell immunoglobulin-like receptor (KIR) to KIR-ligand interactions. In addition, multidimensional analyses identified distinct phenotypes of control and memory-like NK cells from the same individuals. Human memory-like NK cells xenografted into mice substantially reduced AML burden in vivo and improved overall survival. In the context of a first-in-human phase 1 clinical trial, adoptively transferred memory-like NK cells proliferated and expanded in AML patients and demonstrated robust responses against leukemia targets. Clinical responses were observed in five of nine evaluable patients, including four complete remissions. Thus, harnessing cytokine-induced memory-like NK cell responses represents a promising translational immunotherapy approach for patients with AML.