tbuckley/cabot-search huggingface dataset:
Ovarian tissue cryopreservation in a prepubertal girl after fertility impairing therapy.
Authors: Yasmin C. Gosiengfiao, Marleta Reynolds, Veena Rajaram, Barbara Lockart, Kristin Smith, Min Xu, Teresa K. Woodruff
Journal: Journal of Clinical Oncology (2012)

e20001 Background: Advances in cancer therapy have improved the long-term survival of patients suffering from malignancies. High doses of alkylating agents and radiation are known to cause infertility in cancer survivors. Ovarian stimulation is not an option for prepubertal females, leaving experimental ovarian tissue cryopreservation (OTC) as the only option for preserving the reproductive potential of prepubescent girls. Little data is available regarding the condition of a prepubertal ovary after cancer treatment is received. This case study demonstrates the possibility of OTC post cancer treatment in a prepubertal female. Methods: A 9-year-old girl with multiply recurrent vaginal rhabdomyosarcoma presented for fertility preservation upon local recurrence of her tumor. Prior therapy included 32,200 mg/m 2 of cyclophosphamide, 9,000 mg/m 2 of ifosfamide and vaginal brachytherapy after ovarian transposition. A unilateral oophorectomy was performed with therapeutic partial vaginectomy, total hysterectomy and bilateral salpingectomy. A 1 cm section of the ovary was dissected and sent to pathology. The ovarian tissue planes were separated and the cortical tissue removed from the medulla. The cortical tissue was then cut into approximately 2 cm x 0.5cm x 0.1cm strips. 80% of this tissue was cryopreserved using a slow-freeze method for the patient’s future reproductive use and 20% was provided to the Oncofertility Consortium for research as per the ovarian tissue cryopreservation protocol. Results: Follicle stimulating hormone (FSH) level prior to oophorectomy was 0.5 mIU/mL (Normal 1-6 mlU/mL).The ovary was small and fibrotic. Microscopically, primordial follicular density was 1.41/mm 2 . No follicles of more mature stage were noted. There was no evidence of malignancy in the tissue. Conclusions: The presence of viable follicles in the ovarian tissue suggests that fertility preservation may still be possible even in patients who have received therapy that is considered to be likely to impair fertility. For this patient, who was scheduled to have an invasive surgery, adding on ovarian tissue cryopreservation presented a very minimal risk with a potential for a great benefit.
Reply from Authors re: Mikkel Fode, Jens Sønksen. Towards a Greater Understanding of Underactive Bladder. Eur Urol 2017;72:408–9
Authors: Alan D. Uren, Nikki Cotterill, Christopher Harding, Christopher Hillary, Christopher Chapple, Monique Klaver, Dominique Bongaerts, Zalmai Hakimi, Paul Abrams
Journal: European Urology (2017)
Changes in pulmonary exercise haemodynamics in scleroderma: a 4-year prospective study
Authors: Gabor Kovacs, Alexander Avian, Nora Wutte, Franz Hafner, Florentine Moazedi-Fürst, Sonja Kielhauser, Elisabeth Aberer, Marianne Brodmann, Winfried Graninger, Vasile Foris, Andrea Olschewski, Horst Olschewski
Journal: European Respiratory Journal (2017)

Pulmonary arterial hypertension (PAH) is a feared complication of systemic sclerosis. In this prospective cohort study, we monitored the changes in resting and exercise pulmonary haemodynamics of scleroderma patients without initial PAH over a mean follow-up period of ∼4 years. All patients underwent exercise echocardiography and cardiopulmonary exercise testing at baseline and follow-up. A subgroup underwent exercise right heart catheter (RHC) investigations. The primary end-point was the echocardiographic systolic pulmonary arterial pressure at 50 W exercise (sPAP 50 ). We included 99 patients, of whom 58 had a complete dataset. Three out of 99 patients developed RHC-confirmed PAH (0.75 cases per 100 patient-years). sPAP 50 increased (p&lt;0.001) and peak oxygen uptake (secondary end-point) decreased significantly (p=0.001) during follow-up, but there was no significant change in resting sPAP (p=0.38). In the RHC subgroup (n=28), mean (m)PAP and pulmonary vascular resistance at 50 W increased significantly (p=0.02 and p=0.002, respectively), but resting mPAP was unchanged. Scleroderma patients without PAH develop a mild but significant deterioration of pulmonary exercise haemodynamics and exercise capacity over a 4-year follow-up period, indicating a progression of pulmonary vascular disease. The manifestation rate of RHC-confirmed PAH was 0.75 cases per 100 patient-years.
High Resolution Igh Repertoire Analysis Reveals the Human Fetal Liver As the Origin of Life-Long, Innate B Lymphopoiesis
Authors: Anindita Roy, Vojtech Bystry, Georg Bohn, Katerina Goudevenou, Tomas Reigl, Maria Papaioannou, Adam Krejci, Sorcha O'Byrne, Aristeidis Chaidos, Andrea Grioni, Nikos Darzentas, Irene Roberts, Anastasios Karadimitris
Journal: Blood (2016)
Phase IB study of pembrolizumab (Pembro) and pegylated-interferon alfa-2b (Peg-IFN) in advanced melanoma (MEL).
Authors: Diwakar Davar, Hong Wang, Joe-Marc Chauvin, Zhaojun Sun, Ornella Pagliano, Amy Rose, Carrie Muniz, Cindy Sander, Julien J. Fourcade, Uma N. M. Rao, Nageatte Ibrahim, Scot Ebbinghaus, Hussein Abdul-Hassan Tawbi, Ahmad A. Tarhini, John M. Kirkwood, Hassane M. Zarour, Giuseppe Russo
Journal: Journal of Clinical Oncology (2016)

9539 Background: Overall responses (OR) are reported in 34% of patients (pts) with advanced MEL treated with Pembro. Landmark survival is 66%/49% at 1-/2- years respectively. Pre-existing CD8+ T-cell infiltrates and IFN gene signature at tumor sites correlate with response to PD-1 blockade. To evaluate synergy between PD-1 blockade and Peg-IFN, we implemented a phase Ib study of Pembro/Peg-IFN combination with dose-seeking and dose-expansion phases in stage IV MEL. Methods: Pts with IV MEL were enrolled. Peg-IFN was dose-escalated using modified toxicity probability interval (mTPI) design in 3 cohorts (4 pts each) at 1,2 and 3 mcg/kg SC while Pembrolizumab was dosed at 2mg/kg q3weeks in all pts. Primary endpoints were safety and incidence of dose-limiting toxicities (DLTs). Secondary endpoints were OR rate (ORR), progression free and overall survival. Response was assessed every 12 weeks (RECIST 1.1). Sequential blood draws and tumor biopsies were collected. Here, we report on response observed in 24 pts treated in phase Ib portion. Results: 24 pts with advanced MEL were enrolled (20 cutaneous, 2 mucosal, 2 with no primary) to 3 dose-levels. Disease sub-stage is as follows: 11/24 (45.8%) M1a, 5/24 (20.8%) M1b, 8/24 (33.3%) M1c including 4/24 pts (16.7%) with treated CNS metastases. 34.8% were BRAF mutant while 10.5% were NRAS mutant. 11/24 (45.8%) of pts had prior Ipilimumab; 6/24 (25.0%) ≥ 2 lines of systemic therapy. G1/2 toxicities included anemia, nausea, hyponatremia and transaminitis. G3 toxicities of note included rash (11%), hyponatremia (15%), neutropenia (15%) and fatigue (30%). No DLTs were observed. Pembro 2mg/kg + Peg-IFN 3mcg/kg identified as RP2D – to which 12 further pts enrolled. Responses were seen at all 3 dose levels among 21 evaluable pts including 2 CR (9.5%), 7 PR (33.3%) for ORR 42.9%. Autoimmune toxicities included adrenal insufficiency and Vogt-Koyonagi-Harada uveitis seen in 2 pts with ongoing PR off therapy. Conclusions: Pembro/Peg-IFN combination has an acceptable toxicity profile and shows evidence of clinical efficacy in stage IV MEL. Observed ORR has prompted further expansion at RP2D. Clinical trial information: NCT02112032.
HER2 status in locally advanced rectal cancer and metachronous metastases: Opportunity for a new therapeutic approach?
Authors: Lena-Christin Conradi, Hanna Styczen, Thilo Sprenger, Kia Homayounfar, Hendrik A. Wolff, Annalen Bleckmann, Josef Rüschoff, Peter Middel, Heinz Becker, B. Michael Ghadimi, Tim Beissbarth, Torsten Liersch
Journal: Journal of Clinical Oncology (2012)

3600 Background: Even though the implementation of multimodal treatment strategies including neoadjuvant radiochemotherapy (RCT) has led to improved survival distant metastases are still limiting the prognosis of rectal cancer patients. In this context, we investigated the HER-2 status in rectal cancer patients, UICC stages II and III. Our aim was to assess the HER-2 positivity rate in primary tumors and metachronous metastases. Methods: In this study 264 rectal cancer patients (192 male, 72 female; median age 64 years) from phase-II/-III-trials of the German Rectal Cancer Study Group (CAO/ARO/AIO-94 and 04) were included. HER-2 status was determined pretherapeutically in tumor biopsies as well as resection specimens and metachronous metastases (n=27) using immunohistochemistry (IHC0 to IHC3+) scoring and S-ISH-amplification detection. Tumors with IHC3+ or S-ISH ratio ?2.0 were classified as HER-2 positive; results were correlated with clinicopathological parameters and long-term survival. Results: A positive HER-2 status was found in 12.4% of pre-treatment biopsies, in 29.3% of the resection specimens and 22.2% (n=6) of metastases. With a median follow-up of 46.5 months patients with HER-2-positivity showed better disease free survival (p=0.06) and cancer-specific survival (CSS, p=0.05). The 5-years survival rate was 96.4% (HER-2-positive) versus 79.5% (HER-2-negative). In multivariate analyses HER-2 status was as an independent (p=0.0053) predictor for CSS along with (y)pN-status (p&lt;0.0001) and R-status (p=0.023). Conclusions: HER-2 amplification is detectable in a significant proportion (about 30%) of primary tumors of patients with advanced rectal cancer. Furthermore HER-2 amplification was detectable in 22% of resected metachronous metastases during follow-up. Therefore HER-2 represents a promising target and should be further assessed within prospective clinical trials.
Protein kinase D at the Golgi controls NLRP3 inflammasome activation
Authors: Zhirong Zhang, Gergö Meszaros, Wan-ting He, Yanfang Xu, Helena de Fatima Magliarelli, Laurent Mailly, Michael Mihlan, Yansheng Liu, Marta Puig Gámez, Alexander Goginashvili, Adrien Pasquier, Olga Bielska, Bénédicte Neven, Pierre Quartier, Rudolf Aebersold, Thomas F. Baumert, Philippe Georgel, Jiahuai Han, Romeo Ricci
Journal: The Journal of Experimental Medicine (2017)

The inflammasomes are multiprotein complexes sensing tissue damage and infectious agents to initiate innate immune responses. Different inflammasomes containing distinct sensor molecules exist. The NLRP3 inflammasome is unique as it detects a variety of danger signals. It has been reported that NLRP3 is recruited to mitochondria-associated endoplasmic reticulum membranes (MAMs) and is activated by MAM-derived effectors. Here, we show that in response to inflammasome activators, MAMs localize adjacent to Golgi membranes. Diacylglycerol (DAG) at the Golgi rapidly increases, recruiting protein kinase D (PKD), a key effector of DAG. Upon PKD inactivation, self-oligomerized NLRP3 is retained at MAMs adjacent to Golgi, blocking assembly of the active inflammasome. Importantly, phosphorylation of NLRP3 by PKD at the Golgi is sufficient to release NLRP3 from MAMs, resulting in assembly of the active inflammasome. Moreover, PKD inhibition prevents inflammasome autoactivation in peripheral blood mononuclear cells from patients carrying NLRP3 mutations. Hence, Golgi-mediated PKD signaling is required and sufficient for NLRP3 inflammasome activation.
Follow-up of Prostatectomy versus Observation for Early Prostate Cancer
Authors: Timothy J. Wilt, Karen M. Jones, Michael J. Barry, Gerald L. Andriole, Daniel Culkin, Thomas Wheeler, William J. Aronson, Michael K. Brawer
Journal: New England Journal of Medicine (2017)

We previously found no significant differences in mortality between men who underwent surgery for localized prostate cancer and those who were treated with observation only. Uncertainty persists regarding nonfatal health outcomes and long-term mortality.
CTLA4 Promotes Tyk2-STAT3–Dependent B-cell Oncogenicity
Authors: Andreas Herrmann, Christoph Lahtz, Toshikage Nagao, Joo Y. Song, Wing C. Chan, Heehyoung Lee, Chanyu Yue, Thomas Look, Ronja Mülfarth, Wenzhao Li, Kurt Jenkins, John Williams, Lihua E. Budde, Stephen Forman, Larry Kwak, Thomas Blankenstein, Hua Yu
Journal: Cancer Research (2017)

Abstract CTL–associated antigen 4 (CTLA4) is a well-established immune checkpoint for antitumor immune responses. The protumorigenic function of CTLA4 is believed to be limited to T-cell inhibition by countering the activity of the T-cell costimulating receptor CD28. However, as we demonstrate here, there are two additional roles for CTLA4 in cancer, including via CTLA4 overexpression in diverse B-cell lymphomas and in melanoma-associated B cells. CTLA4-CD86 ligation recruited and activated the JAK family member Tyk2, resulting in STAT3 activation and expression of genes critical for cancer immunosuppression and tumor growth and survival. CTLA4 activation resulted in lymphoma cell proliferation and tumor growth, whereas silencing or antibody-blockade of CTLA4 in B-cell lymphoma tumor cells in the absence of T cells inhibits tumor growth. This inhibition was accompanied by reduction of Tyk2/STAT3 activity, tumor cell proliferation, and induction of tumor cell apoptosis. The CTLA4–Tyk2–STAT3 signal pathway was also active in tumor-associated nonmalignant B cells in mouse models of melanoma and lymphoma. Overall, our results show how CTLA4-induced immune suppression occurs primarily via an intrinsic STAT3 pathway and that CTLA4 is critical for B-cell lymphoma proliferation and survival. Cancer Res; 77(18); 5118–28. ©2017 AACR.
EXERCISE ASSOCIATED HYPONATREMIA (EAH) AND FLUID INTAKE DURING THE 2016 LONDON MARATHON
Authors: Steven Whatmough, Stephen Mears, Courtney Kipps
Journal: British Journal of Sports Medicine (2017)

<h3>Background</h3> Exercise-Associated Hyponatremia (EAH) is a potentially fatal condition during endurance exercise (Petzold <i>et al</i>, 2007). Excessive fluid intake over and above normal fluid losses is the most common risk factor in the development of EAH. A “drink to thirst” fluid regime is considered best practice (Hew-Butler <i>et al</i>, 2015). <h3>Objective</h3> To investigate fluid intake and changes in serum sodium concentrations ([Na]<sup>+</sup>) in runners during a marathon <h3>Design</h3> Prospective observational study. <h3>Setting</h3> 2016 London Marathon. <h3>Participants</h3> 28 amateur athletes were recruited at the marathon registration. <h3>Independent Variables</h3> Online and printed medical advice was available to all participants. A drink to thirst fluid regime was recommended to all athletes by the event organisers. <h3>Main Outcome Measures</h3> Serum sodium samples were collected and body mass measured at the marathon start and finish lines. Questionnaires regarding estimated fluid intake data were collected at the finish. <h3>Results</h3> The average volume of fluid intake during the marathon was 1.4 litres (range 0–5.5 litres). Change in serum sodium concentration was inversely correlated with change in body mass (r=−0.383, p=0.044) and with estimated fluid intake (r=−0.406, p=0.032). A significant correlation between fluid intake and weight change was not found. The average pre-race and post-race [Na]<sup>+</sup> were 141.7 mmol/L and 141.5 mmol/L, respectively (p=0.8673). One runner (1/28, 3.6%) was found to have asymptomatic hyponatraemia ([Na]<sup>++</sup>=130 mmol/L). This runner had consumed an estimated 5l of fluid over the course of the marathon. A trend in correlation was seen between fluid intake and race time (r=0.349, p=0.069). <h3>Conclusions</h3> Runners consumed potentially dangerous volumes of fluid during a marathon despite the written guidance recommending against such practices. The consequence of this behaviour is overhydration and an increased risk of developing potentially fatal EAH. The optimal medium for runner education on safe drinking practices is yet to be determined.
Exploring the potential of natural and synthetic neuroprotective steroids against neurodegenerative disorders: A literature review
Authors: Ranju Bansal, Ranjit Singh
Journal: Medicinal Research Reviews (2017)

Abstract Neurodegeneration is a complex process, which leads to progressive brain damage due to loss of neurons. Despite exhaustive research, the cause of neuronal loss in various degenerative disorders is not entirely understood. Neuroprotective steroids constitute an important line of attack, which could play a major role against the common mechanisms associated with various neurodegenerative disorders like Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Natural endogenous steroids induce the neuroprotection by protecting the nerve cells from neuronal injury through multiple mechanisms, therefore the structural modifications of the endogenous steroids could be helpful in the generation of new therapeutically useful neuroprotective agents. The review article will keep the readers apprised of the detailed description of natural as well as synthetic neuroprotective steroids from the medicinal chemistry point of view, which would be helpful in drug discovery efforts aimed toward neurodegenerative diseases.
A Tumor-pH-Responsive Supramolecular Photosensitizer for Activatable Photodynamic Therapy with Minimal <i>In Vivo</i> Skin Phototoxicity
Authors: Xingshu Li, Bi-Yuan Zheng, Mei-Rong Ke, Yongfan Zhang, Jian-Dong Huang, Juyoung Yoon
Journal: Theranostics (2017)

A major challenge in photodynamic therapy (PDT) is the development of new tumor-targeting photosensitizers.The tumor-specific activation is considered to be an effective strategy for designing these photosensitizers.Herein, we describe a novel tumor-pH-responsive supramolecular photosensitizer, LDH-ZnPcS 8 , which is not photoactive under neutral conditions but is precisely and efficiently activated in a slightly acidic environment (pH 6.5).LDH-ZnPcS 8 is prepared by using a simple coprecipitation method based on the electrostatic interaction between negatively charged octasulfonate-modified zinc(II) phthalocyanine (ZnPcS 8 ) and cationic hydroxide layers of layered double hydroxide (LDH).The in vitro photodynamic activities of LDH-ZnPcS 8 in cancer cells are dramatically enhanced relative to those of ZnPcS 8 alone.The results of in vivo fluorescence imaging demonstrate that the nanohybrid is activated in tumor tissues, where it displays an excellent PDT effect resulting in 95.3% tumor growth inhibition.Furthermore, the minimal skin phototoxicity of LDH-ZnPcS 8 highlights its high potential as a novel photosensitizer for activatable PDT.
Innate Immunity and Neurodegeneration
Authors: Larisa I. Labzin, Michael T. Heneka, Eicke Latz
Journal: Annual Review of Medicine (2017)

The innate immune system plays diverse roles in health and disease. It represents the first line of defense against infection and is involved in tissue repair, wound healing, and clearance of apoptotic cells and cellular debris. Excessive or nonresolving innate immune activation can lead to systemic or local inflammatory complications and cause or contribute to the development of inflammatory diseases. In the brain, microglia represent the key innate immune cells, which are involved in brain development, brain maturation, and homeostasis. Impaired microglial function, either through aberrant activation or decreased functionality, can occur during aging and during neurodegeneration, and the resulting inflammation is thought to contribute to neurodegenerative diseases. This review highlights recent advances in our understanding of the influence of innate immunity on neurodegenerative disorders such as Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, and Huntington's disease.
BCL-2, a Therapeutic Target for High Risk Hypodiploid B-Cell Acute Lymphoblastic Leukemia
Authors: Ernesto Diaz-Flores, Evan Q. Comeaux, Kailyn Kim, Kyle Beckman, Kara L. Davis, Kevin Wu, Jon Akutagawa, Linda Holmfeldt, Benjamin S. Braun, Charles Mullighan, Mignon L. Loh
Journal: Blood (2016)
Ketamine for the Treatment of Depression
Authors: Keith G. Rasmussen
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
Hypertensive disorders of pregnancy
Authors: Helen L Barrett, Leonie K Callaway
Journal: BMJ (2017)

The combined incidences and prevalences of the various hypertensive disorders in pregnancy are said to be about 6–8% with wide variations depending on the populations at risk but chiefly on the closeness of observation and on who makes the diagnoses. The disorders are sometimes fatal, and they predispose to potentially lethal complications such as abruptio placentae, acute renal failure, cerebral hemorrhage, circulatory collapse, and disseminated intravascular coagulation. They are major causes of maternal, fetal, and neonatal morbidity and mortality and in some areas, including the United States,1 England, and Wales,2 they are the leading cause of maternal death.
The Cutaneous Cancer of Ferdinando Orsini, 5th Duke of Gravina
Authors: Raffaele Gaeta, Luca Ventura, Gino Fornaciari
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
Going Beyond Guideline-Concordant Opioid Therapy to Improve Patient Safety
Authors: Scott R. Bauer, Mitchell H. Katz
Journal: JAMA Internal Medicine (2017)

Jane M. Liebschutz, MD, MPH; Ziming Xuan, ScD, SM; Christopher W. Shanahan, MD; Marc LaRochelle, MD, MPH; Julia Keosaian, MPH; Donna Beers, MSN, RN-BC, CARN; George Guara, RN, BSN; Kristen O’Connor, RN, BSN; Daniel P. Alford, MD, MPH; Victoria Parker, DBA, EdM; Roger D. Weiss, MD; Jeffrey H. Samet, MD, MA, MPH; Julie Crosson, MD; Phoebe A. Cushman, MD; Karen E. Lasser, MD, MPH