tbuckley/cabot-search huggingface dataset:
Community and health system intervention to reduce disrespect and abuse during childbirth in Tanga Region, Tanzania: A comparative before-and-after study
Authors: Stephanie A. Kujawski, Lynn P. Freedman, Kate Ramsey, Godfrey Mbaruku, Selemani Mbuyita, Wema Moyo, Margaret E. Kruk
Journal: PLoS Medicine (2017)

Abusive treatment of women during childbirth has been documented in low-resource countries and is a deterrent to facility utilization for delivery. Evidence for interventions to address women's poor experience is scant. We assessed a participatory community and health system intervention to reduce the prevalence of disrespect and abuse during childbirth in Tanzania.We used a comparative before-and-after evaluation design to test the combined intervention to reduce disrespect and abuse. Two hospitals in Tanga Region, Tanzania were included in the study, 1 randomly assigned to receive the intervention. Women who delivered at the study facilities were eligible to participate and were recruited upon discharge. Surveys were conducted at baseline (December 2011 through May 2012) and after the intervention (March through September 2015). The intervention consisted of a client service charter and a facility-based, quality-improvement process aimed to redefine norms and practices for respectful maternity care. The primary outcome was any self-reported experiences of disrespect and abuse during childbirth. We used multivariable logistic regression to estimate a difference-in-difference model. At baseline, 2,085 women at the 2 study hospitals who had been discharged from the maternity ward after delivery were invited to participate in the survey. Of these, 1,388 (66.57%) agreed to participate. At endline, 1,680 women participated in the survey (72.29% of those approached). The intervention was associated with a 66% reduced odds of a woman experiencing disrespect and abuse during childbirth (odds ratio [OR]: 0.34, 95% CI: 0.21-0.58, p < 0.0001). The biggest reductions were for physical abuse (OR: 0.22, 95% CI: 0.05-0.97, p = 0.045) and neglect (OR: 0.36, 95% CI: 0.19-0.71, p = 0.003). The study involved only 2 hospitals in Tanzania and is thus a proof-of-concept study. Future, larger-scale research should be undertaken to evaluate the applicability of this approach to other settings.After implementation of the combined intervention, the likelihood of women's reports of disrespectful treatment during childbirth was substantially reduced. These results were observed nearly 1 year after the end of the project's facilitation of implementation, indicating the potential for sustainability. The results indicate that a participatory community and health system intervention designed to tackle disrespect and abuse by changing the norms and standards of care is a potential strategy to improve the treatment of women during childbirth at health facilities. The trial is registered on the ISRCTN Registry, ISRCTN 48258486.ISRCTN Registry, ISRCTN 48258486.
Updated efficacy and safety of avelumab in metastatic urothelial carcinoma (mUC): Pooled analysis from 2 cohorts of the phase 1b Javelin solid tumor study.
Authors: Andrea B. Apolo, John Allan Ellerton, Jeffrey R. Infante, Manish Agrawal, Michael S. Gordon, Raid Aljumaily, Carolyn D. Britten, Luc Yves Dirix, Keun-Wook Lee, Matthew H. Taylor, Patrick Schöffski, Ding Wang, Alain Ravaud, Arnold Gelb, Junyuan Xiong, Galit Rosen, Manish R. Patel
Journal: Journal of Clinical Oncology (2017)

4528 Background: Avelumab, a fully human anti‒PD-L1 IgG1 antibody, has shown promising efficacy and safety in 2 cohorts of patients (pts) with mUC. We now report updated data from a pooled analysis of these pts with mUC from JAVELIN Solid Tumor (NCT01772004) and further characterize the clinical activity of avelumab in this disease. Methods: Pts with mUC progressed after platinum-based therapy or cisplatin ineligible received avelumab 10 mg/kg 1-hour IV Q2W. Tumors were assessed every 6 weeks by independent review (RECIST v1.1). Endpoints included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety (NCI CTCAE v4.0), and tumor PD-L1 expression. Results: As of Jun 9, 2016, 249 pts had received avelumab for a median of 12 weeks (range 2-92) and were followed up for a minimum of 6 weeks. Primary tumor site was upper tract (renal pelvis/ureter) in 23.3% and lower tract (bladder/urethra) in 76.7%. 242 pts (97.2%) had progressed on prior platinum therapy and 7 pts (2.8%) were platinum naive. In 161 post-platinum pts with ≥6 months of follow-up, confirmed ORR was 17.4% (95% CI 11.9-24.1; complete response in 6.2%) with a disease control rate of 39.8%. Response was ongoing in 23/28 responders at data cut (82.1%; median DOR not reached), and the 24-week durable response rate was 92.3% (95% CI 72.6-98.0). Responses occurred across PD-L1 expression levels tested (≥5% and &lt; 5% tumor cell‒staining [25.4% and 13.2%]). In all post-platinum pts (n = 242), median PFS was 6.6 weeks (95% CI 6.1-11.6), median OS was 7.4 months (95% CI 5.7-10.3) and 6-month OS rate was 54.9 (95% CI 47.7-61.7). Treatment-related adverse events (TRAE) of any grade occurred in 166/249 pts (66.7%); most common (≥10%) were infusion-related reaction (22.9%, all grade ≤2) and fatigue (16.1%). 21 pts (8.4%) had a grade ≥3 TRAE (fatigue [1.6%] and asthenia [0.8%] in &gt; 1 pt). 34 pts (13.7%) had an immune-related AE (grade ≥3 in 2.4%). There was 1 treatment-related death (pneumonitis). Conclusions: Avelumab was well tolerated and showed durable responses in heavily pretreated pts with mUC, irrespective of tumor PD-L1 expression status. Clinical trial information: NCT01772004.
Is Prior Rituximab Exposure Associated with a Difference in Outcomes in Relapsed Low-Grade Lymphomas Retreated with Rituximab in Comparison to Rituximab NaïVe Patients?
Authors: Abi Vijenthira, Manjula Mangati, Michael Crump, Vishal Kukreti, John Kuruvilla, Rodger Tiedemann, Christine Chen, Anca Prica
Journal: Blood (2016)
Ethical Considerations for Nutrition Counseling About Processed Food
Authors: Stephanie R. Morain, Anne Barnhill
Journal: JAMA Pediatrics (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Abstract 132: Alternative Splicing of Bridging Integrator 1 Is a Novel Regulatory Cue for Cardiomyocyte Proliferation
Authors: Shan-Shan Zhang, Ting-Ting Hong, James W Smyth, Matthew L Wheeler, Tina S Fong, Robin M Shaw
Journal: Circulation Research (2012)

Expanding our knowledge of the genetic pathways of cardiomyocyte proliferation is important to understanding heart formation, disease, and regeneration. Few data exist on the role of multi-domain adaptor proteins in regulating the cardiomyocyte cell cycle. We have identified by RT-PCR a cardiac splice variant of the nucleocytoplasmic adaptor protein, bridging integrator 1 (cBIN1), which is expressed in cardiomyocytes but not in skeletal myocytes (Fig. 1A). We found cBIN1 to be the dominant BIN1 variant of developing mouse cardiomyocytes, and that it is also preferentially located in the nuclei of these immature cells. As the cells mature, the relative abundance of cBIN1 to constitutively expressed variants, by qRT-PCR, decreases from 2.0 in embryonic day 18.5 cardiomyocytes to 0.6 by postnatal day 2 (Fig. 1B). Coincident with altered expression, a majority of cBIN1 redistributes from the nucleus to the cytoplasm and plasma membrane after birth. Moreover, we found that overexpression of exogenous cBIN1 increases the number of actively cycling embryonic cardiomyocytes from 25% to 32%, as assayed by BrdU incorporation and FACS (Fig. 1C). Confirming this result, we found exon-specific siRNA knockdown of cBIN1 suppresses cell proliferation. These studies identify a BIN1 splice variant that exists in cardiac but not skeletal muscle, and that it facilitates cardiomyocyte cell cycle progression during heart maturation.
An Fc-engineered CD19 antibody eradicates MRD in patient-derived MLL-rearranged acute lymphoblastic leukemia xenografts
Authors: Denis M. Schewe, Ameera Alsadeq, Cornelia Sattler, Lennart Lenk, Fotini Vogiatzi, Gunnar Cario, Simon Vieth, Thomas Valerius, Sophia Rosskopf, Fabian Meyersieck, Julia Alten, Martin Schrappe, Martin Gramatzki, Matthias Peipp, Christian Kellner
Journal: Blood (2017)

Antibody therapy constitutes a major advance in the treatment of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). To evaluate the efficacy and the mechanisms of action of CD19 monoclonal antibody therapy in pediatric BCP-ALL, we tested an Fc-engineered CD19 antibody carrying the S239D/I332E mutation for improved effector cell recruitment (CD19-DE). Patient-derived xenografts (PDX) of pediatric mixed-lineage leukemia gene (MLL)-rearranged ALL were established in NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice. Antibody CD19-DE was efficient in prolonging the survival of NSG mice in a minimal residual disease (MRD) model. The majority of surviving mice remained polymerase chain reaction (PCR)-MRD negative after treatment. When antibody therapy was initiated in overt leukemia, antibody CD19-DE was still efficient in prolonging survival of xenografted mice in comparison with nontreated control animals, but the effects were less pronounced than in the MRD setting. Importantly, the combination of antibody CD19-DE and cytoreduction by chemotherapy (dexamethasone, vincristine, PEG-asparaginase) resulted in significantly improved survival rates in xenografted mice. Antibody CD19-DE treatment was also efficient in a randomized phase 2-like PDX trial using 13 MLL-rearranged BCP-ALL samples. Macrophage depletion by liposomal clodronate resulted in a reversal of the beneficial effects of CD19-DE, suggesting an important role for macrophages as effector cells. In support of this finding, CD19-DE was found to enhance phagocytosis of patient-derived ALL blasts by human macrophages in vitro. Thus, Fc-engineered CD19 antibodies may represent a promising treatment option for infants and children with MLL-rearranged BCP-ALL who have a poor outcome when treated with chemotherapy only.
Association of Ozone Exposure With Cardiorespiratory Pathophysiologic Mechanisms in Healthy Adults
Authors: Drew B. Day, Jianbang Xiang, Jinhan Mo, Feng Li, Mingkei Chung, Jicheng Gong, Charles J. Weschler, Pamela A. Ohman-Strickland, Jan Sundell, Wenguo Weng, Yinping Zhang, Junfeng (Jim) Zhang
Journal: JAMA Internal Medicine (2017)

Exposure to ozone has been associated with cardiovascular mortality, but the underlying biological mechanisms are not yet understood.
Regulation of Stat3 gene transcription by triplex-forming oliogonucleotides in mice
Authors: Qi Wu, Steve Carbajal, Jeanine Traag, Penny K. Riggs, Earl F. Walborg, John Digiovanni, Karen M. Vasquez
Journal: Cancer Research (2006)

3013   Triplex-forming oligonucleotides (TFOs) are single-stranded oligonucleotides that can inhibit gene transcription by binding to specific gene sequences. Our goal is to investigate the potential of gene-specific TFOs to inhibit oncogene expression and cell proliferation. To date, gene specific TFOs have been shown to be able to regulate the expression of ∼10 human oncogenes in cells, including BCR/ABL, MYC, EGFR, ERBB2, IGFI, SIS, FOS, Ha-RAS, c-Ki-RAS and SRC. In order to expand our study to other human genes and to mouse models, we identified 27 new triplex-forming sites with high TFO binding affinity and specificity in 17 mouse genes (Egfr, Erbb2, Igf1r, Tgfa, Tnf, Tnfr1, Src, Akt1, Stat1, Stat3, Stat5, Ccnd1, Odc1, Cox2, Icam1, Vegfa, and Nfkbia) and 2 human genes (ODC and COX2). Here we present one example targeting the Stat3 gene with a Stat3-specific TFO in mice. Signal transducers and activators of transcription (STATs) are a family of latent cytoplasmic proteins involved in transmitting extracellular signals to the nucleus. Constitutive activation of Stats, in particular STAT3, is found in a number of primary human epithelial tumors and cancer cell lines, including squamous cell carcinomas of the head and neck, breast, ovary, prostate, and lung. STAT3 participates in cell proliferation through regulation of several genes such as CCND1 and MYC. K14.TGFa mice, which exhibit dramatic and persistent epidermal hyperproliferation, provide a useful mouse model to evaluate the efficacy of TFOs as a gene targeting approach to control epidermal hyperproliferation. A 27-mer TFO, which binds to its target sequence in the Stat3 gene with high affinity and specificity, was injected intradermally into the epidermis of K14.TGFa mice. The transcription level of the Stat3 gene was decreased to ∼45% of that in vehicle-treated control mouse skin, as assessed by real-time PCR. Treatment with the Stat3-specific TFO also resulted in reduction of the transcription levels of the Ccnd1 and Myc genes, which are downstream targets of Stat3. Thus, our findings demonstrate that triplex-induced transcription inhibition of Stat3 can be accomplished in intact animals following intradermal injection.
Drug targeting to myofibroblasts: Implications for fibrosis and cancer
Authors: Saleh Yazdani, Ruchi Bansal, Jai Prakash
Journal: Advanced Drug Delivery Reviews (2017)

Myofibroblasts are the key players in extracellular matrix remodeling, a core phenomenon in numerous devastating fibrotic diseases. Not only in organ fibrosis, but also the pivotal role of myofibroblasts in tumor progression, invasion and metastasis has recently been highlighted. Myofibroblast targeting has gained tremendous attention in order to inhibit the progression of incurable fibrotic diseases, or to limit the myofibroblast-induced tumor progression and metastasis. In this review, we outline the origin of myofibroblasts, their general characteristics and functions during fibrosis progression in three major organs: liver, kidneys and lungs as well as in cancer. We will then discuss the state-of-the art drug targeting technologies to myofibroblasts in context of the above-mentioned organs and tumor microenvironment. The overall objective of this review is therefore to advance our understanding in drug targeting to myofibroblasts, and concurrently identify opportunities and challenges for designing new strategies to develop novel diagnostics and therapeutics against fibrosis and cancer.
Detection of Zika virus RNA in semen of asymptomatic blood donors
Authors: D. Musso, V. Richard, A. Teissier, M. Stone, M.C. Lanteri, G. Latoni, J. Alsina, R. Reik, M.P. Busch
Journal: Clinical Microbiology and Infection (2017)

ObjectivesZika virus (ZIKV) transmission through semen donation has never been reported but the risk is supported by the detection of ZIKV in semen and the demonstration of ZIKV sexual transmission. The potential impact of ZIKV on assisted reproductive procedures should be evaluated.MethodsWe tested longitudinally collected semen samples provided by asymptomatic blood donors who tested positive for ZIKV RNA in plasma during ZIKV outbreaks in Puerto Rico and Florida in 2016.ResultsFive of the 14 (35.7%) asymptomatic blood donors provided semen samples that tested positive for ZIKV RNA, with ZIKV RNA loads ranging from 8.03 × 103 to 2.55 × 106 copies/mL. Plasma collected at the same time as the semen tested negative for ZIKV RNA for most ZIKV RNA-positive semen collections; all corresponding plasma samples tested positive or equivocal for anti-ZIKV IgG antibodies and all except one tested positive for ZIKV IgM antibodies. The rate of detection of ZIKV RNA in semen in asymptomatic donors is not significantly different from the rate previously reported for symptomatic patients.ConclusionsOur results that show a high percentage of detection of ZIKV RNA in the semen of asymptomatic men confirm that ZIKV is a new threat for reproductive medicine and should have important implications for assisted reproductive technology. We recommend that semen donations from men at risk for ZIKV infection should be tested for ZIKV RNA, regardless of symptoms of ZIKV infection.
FGFR pathway genetic aberrations in cholangiocarcinoma: Demographics and experience with targeted therapy.
Authors: Apurva Jain, Rachna T. Shroff, Robin Kate Kelley, Ahmed Omar Kaseb, Ying Wang, Reham Abdel-Wahab, Daniel H. Ahn, Andrea Grace Bocobo, Funda Meric-Bernstam, Randi Isaacs, Tanios S. Bekaii-Saab, Milind M. Javle
Journal: Journal of Clinical Oncology (2016)

109 Background: FGFR pathway genetic aberrations (GAs) occur in an estimated 10% of intrahepatic cholangiocarcinomas (IHCCA). The most common are FGFR2 mutations (mut). The advent of FGFR targeted inhibitors may alter the outcome of this disease subtype. The natural history of FGFR mutant CCA and prognostic role of co-existing mut is unknown. Methods: We reviewed the records of CCA patients (pts) with FGFR pathway GAs identified on next generation sequencing (NGS). Data reviewed included demographics, treatments, progression-free survival (PFS) with first-line chemotherapy, overall survival (OS) and mut data (Foundation Medicine or Institutional NGS). KM plots and log rank tests were used for statistical analysis. Results: A total of 54 pts with FGFR pathway GAs were identified from our database of 321 biliary cancer pts who had NGS. These included: 32 FGFR2 mut, which occurred almost exclusively in IHCCA (except 1 GB cancer pt). Of these, FGFR fusions occurred in 27. Most common FGFR fusion was FGFR2-BICC (n = 7). The median age of pts with FGFR pathway GAs was 55 years (range: 22 to 82), 33 (61%) were females, of which 9 were < 40 years of age. The median PFS with first-line gemcitabine- based therapy for pts with/ without FGFR pathway GAs was 34 weeks vs. 31 weeks, respectively (p = 0.98). Twenty pts received FGFR-directed small molecule inhibitors after failure of first-line chemotherapy. Majority received BGJ398 (n = 16). Pts with FGFR pathway GAs had a superior OS with FGFR targeted therapy as compared with those who received standard of care regimens (p = 0.010). Co-existing p53 (p = .025) and BAP1(p = .04) mut correlated with low OS despite FGFR targeted therapy. Conclusions: FGFR mutant CCA represents a unique subtype occurring more commonly in younger females. The response to first line chemotherapy is comparable to non-FGFR mut cohort. FGFR targeted therapy may offer OS benefit for this subgroup. Coexisting mut may have important prognostic implications for targeted therapy.
Abstract 247: Scaffold-stiffness Dependent Notch1 Activation Regulates Cardiogenic Gene Expression In Cardiac Progenitor Cells
Authors: Archana V Boopathy, Pao L Che, Yoshie Narui, Khalid Salaita, Michael E Davis
Journal: Circulation Research (2013)

Rationale: Cardiac progenitor cells (CPCs) are multipotent, self-renewing cells that can regenerate the myocardium and improve cardiac function in animal models of myocardial infarction (MI). However, limited survival of stem/progenitor cells inhibits cardiac regeneration. Force dependent Notch activation promotes cardiac development and cardiac gene expression in many adult stem cells. As dysregulation of Notch signaling leads to embryonic lethal cardiovascular defects, activating this critical pathway during cell transplantation could improve efficacy of stem cell therapy. Objective: Investigate i) whether self-assembling peptide scaffolds can be used to activate Notch1 signaling in CPCs to promote cardiogenic differentiation and ii) the effect of scaffold stiffness on Notch1 activation and differentiation. Methods: Rat CPCs (c-kit + ) were cultured for 48h in 3D self-assembling scaffolds of varying stiffness (1% low, 2% high): empty scaffolds (RADA), scaffolds modified with peptide mimicking Notch1 ligand, Jagged1 (RJAG), or scaffolds modified with a scrambled peptide (RSCR) and cardiogenic gene expression measured by qRT-PCR. CHO cells expressing Notch1 responsive YFP were also cultured in the above scaffolds for 48h and YFP expression was determined. Results are mean ± SEM with p&lt;0.05 considered significant by one or two-way ANOVA with appropriate post test. Results: In the Notch1 reporter cells, Notch1 activation increased significantly in presence of RJAG (p&lt;0.01) and on increasing scaffold stiffness (p&lt;0.01,n=6) indicating scaffold stiffness-dependent Notch1 activation. Culture of CPCs in RJAG containing 1% scaffolds (low stiffness) significantly increased early endothelial and smooth muscle but not cardiac gene expression while in 2% scaffolds (high stiffness) significantly increased only cardiac and not endothelial or smooth muscle gene expression (p&lt;0.05, n≥4). Conclusions: Taken together, these data show that i) Notch1 activation in 3D is dependent on ligand density and scaffold stiffness and ii) stiffness dependent Notch1 activation differentially regulates cardiogenic gene expression in CPCs. Therefore, delivery of CPCs in JAG containing scaffolds could be used to improve cardiac function following MI.
Pitfalls in surveillance for hepatocellular carcinoma: How successful is it in the real world?
Authors: Linda L. Wong, Ruel J. Reyes, Sandi A. Kwee, Brenda Y. Hernandez, Sumodh C. Kalathil, Naoky C. Tsai
Journal: Clinical and Molecular Hepatology (2017)

Surveillance for hepatocellular carcinoma (HCC) with ultrasound in high-risk populations is generally believed to improve opportunities for treatment. However, tumors are still missed due to various factors. This study explores success versus failure of HCC surveillance.This is a retrospective study of 1,125 HCC cases. Categories considered for successful detection were largest tumor ≤3.0 cm, single tumors ≤3.0 cm and ≤2.0 cm, and adherence to Milan criteria. Examined factors were age <60 years, gender, rural residence, body-mass index (BMI), hepatitis infection, smoking, diabetes, hyperlipidemia, cirrhosis, ascites, and Model for End-Stage Liver Disease <10.HCC was found on surveillance in 257 patients with a mean tumor size of 3.17 cm; multiple tumors were seen in 28% of cases, bilateral tumors in 7.4%, and vascular invasion in 3.7%. Surveillance was successful in 61.5% of cases involving a largest tumor ≤3.0 cm, with BMI ≥35 negatively affecting detection (odds ratio [OR] 0.28, P=0.014) and cirrhosis positively affecting detection (OR 2.31, P=0.036). Ultrasound detected 19.1% of single tumors ≤2.0 cm with ascites improving the detection rate (OR 3.89, P=0.001). Finally, adherence to Milan criteria occurred in 75.1% of cases, revealing negative associations with diabetes (OR 0.48, P=0.044 and male gender (OR 0.49, P=0.08).Although surveillance is recommended for HCC, not all surveillance ultrasound are ideal. Tumor detection can depend on gender, BMI, diabetes, cirrhosis, and ascites and is achieved in 19.1-75% of cases depending on the definition of success. Closer follow-up or additional imaging might be necessary for some patient subgroups.