tbuckley/cabot-search huggingface dataset:
Targeting the gut to treat multiple sclerosis
Authors: Laura Ghezzi, Claudia Cantoni, Gabriela V. Pinget, Yanjiao Zhou, Laura Piccio
Journal: Journal of Clinical Investigation (2021)

The gut-brain axis (GBA) refers to the complex interactions between the gut microbiota and the nervous, immune, and endocrine systems, together linking brain and gut functions. Perturbations of the GBA have been reported in people with multiple sclerosis (pwMS), suggesting a possible role in disease pathogenesis and making it a potential therapeutic target. While research in the area is still in its infancy, a number of studies revealed that pwMS are more likely to exhibit altered microbiota, altered levels of short chain fatty acids and secondary bile products, and increased intestinal permeability. However, specific microbes and metabolites identified across studies and cohorts vary greatly. Small clinical and preclinical trials in pwMS and mouse models, in which microbial composition was manipulated through the use of antibiotics, fecal microbiota transplantation, and probiotic supplements, have provided promising outcomes in preventing CNS inflammation. However, results are not always consistent, and large-scale randomized controlled trials are lacking. Herein, we give an overview of how the GBA could contribute to MS pathogenesis, examine the different approaches tested to modulate the GBA, and discuss how they may impact neuroinflammation and demyelination in the CNS.
Editorial: Breast cancer in young women.
Journal: BMJ (1975)

A discussion of the management of breast cancer in young women is presented. The rate of growth of breast cancer is not influenced by the age of the patient, as reflected in the fact that the expected survival rate for women of all ages is 50% at 5 years. Although it has been reported that the time lapse for the recurrence of cancer was less for younger women with affected nodes than older women, the literature is not in agreement on this point. The prognosis for women in whom cancer is diagnosed in late pregnancy, or during lactation, is usually grave. Pregnancy subsequent to treatment of breast cancer poses problems, though it has been reported that the survival rate of pregnant women following mastectomy is improved. It is recommended that a young, nulliparous woman should not be discouraged from having children after the removal of a small localized tumor. Permanent sterilization may be preferable to oral contraception for women who probably should not have another pregnancy. In the United Kingdom, the mortality rate from breast cancer in women aged 35-44 has increased by almost 20% from 1968 to 1972. A marked reduction in the early recurrence of breast cancer in premenopausal women with nodal deposits has been reported as a result of adjuvant systemic chemotherapy.
Epidermolysis bullosa
Authors: Ajoy Bardhan, Leena Bruckner-Tuderman, Iain L. C. Chapple, Jo-David Fine, Natasha Harper, Cristina Has, Thomas M. Magin, M. Peter Marinkovich, John F. Marshall, John A. McGrath, Jemima E. Mellerio, Rex Polson, Adrian H. Heagerty
Journal: Nature Reviews Disease Primers (2020)
Chemical carcinogens: a review of the science and its associated principles. U.S. Interagency Staff Group on Carcinogens.
Journal: Environmental Health Perspectives (1986)

In order to articulate a view of chemical carcinogenesis that scientists generally hold in common today and to draw upon this understanding to compose guiding principles that can be used as a bases for the efforts of the regulatory agencies to establish guidelines for assessing carcinogenic risk to meet the specific requirements of the legislative acts they are charged to implement, the Office of Science and Technology Policy, Executive Office, the White House drew on the expertise of a number of regulatory agencies to elucidate present scientific views in critical areas of the major disciplines important to the process of risk assessment.The document is composed of two major sections, Principles and the State-of-the-Science.The latter consists of subsections on the mechanisms of carcinogenesis, short-term and long-term testing, and epi- demiology, which are important components in the risk assessment step of hazard identification.These subsections are followed by one on exposure assessment, and a final section which includes analyses of dose-response (hazard) assessment and risk characterization.The principles are derived from considerations in each of the subsections.Because of present gaps in understanding, the principles contain judgmental (science policy) decisions on major unresolved issues as well as statements of what is generally accepted as fact.These judgments are basically assumptions which are responsible for much of the uncertainty in the process of risk assessment.There was an attempt to clearly distinguish policy and fact.The subsections of the State-of-the-Science portion provide the underlying support to the principles articulated, and to read the "Principles" section without a full appreciation of the State-of-the-Science section is to invite oversimplification and misinterpretation.Finally, suggestions are made for future research efforts which will improve the process of risk as- sessment.
Endometriosis
Authors: Serdar E Bulun, Bahar D Yilmaz, Christia Sison, Kaoru Miyazaki, Lia Bernardi, Shimeng Liu, Amanda Kohlmeier, Ping Yin, Magdy Milad, JianJun Wei
Journal: Endocrine Reviews (2019)

Abstract Pelvic endometriosis is a complex syndrome characterized by an estrogen-dependent chronic inflammatory process that affects primarily pelvic tissues, including the ovaries. It is caused when shed endometrial tissue travels retrograde into the lower abdominal cavity. Endometriosis is the most common cause of chronic pelvic pain in women and is associated with infertility. The underlying pathologic mechanisms in the intracavitary endometrium and extrauterine endometriotic tissue involve defectively programmed endometrial mesenchymal progenitor/stem cells. Although endometriotic stromal cells, which compose the bulk of endometriotic lesions, do not carry somatic mutations, they demonstrate specific epigenetic abnormalities that alter expression of key transcription factors. For example, GATA-binding factor-6 overexpression transforms an endometrial stromal cell to an endometriotic phenotype, and steroidogenic factor-1 overexpression causes excessive production of estrogen, which drives inflammation via pathologically high levels of estrogen receptor-β. Progesterone receptor deficiency causes progesterone resistance. Populations of endometrial and endometriotic epithelial cells also harbor multiple cancer driver mutations, such as KRAS, which may be associated with the establishment of pelvic endometriosis or ovarian cancer. It is not known how interactions between epigenomically defective stromal cells and the mutated genes in epithelial cells contribute to the pathogenesis of endometriosis. Endometriosis-associated pelvic pain is managed by suppression of ovulatory menses and estrogen production, cyclooxygenase inhibitors, and surgical removal of pelvic lesions, and in vitro fertilization is frequently used to overcome infertility. Although novel targeted treatments are becoming available, as endometriosis pathophysiology is better understood, preventive approaches such as long-term ovulation suppression may play a critical role in the future.
Radiopharmaceutical Sciences
Authors: Johannes Ermert, Martina Benešová, Verena Hugenberg, Viplav Gupta, Ingo Spahn, Hans-Jürgen Pietzsch, Christos Liolios, Klaus Kopka
Journal: Clinical Nuclear Medicine (2020)

Radiopharmaceutical sciences summarizes all scientific aspects comprising chemistry, physics, and biology/pharmacology that deal with incorporating a suitable radionuclide into a pharmaceutical or other biologically active molecule or molecular entity. The resulting radiopharmaceuticals are used in nuclear medicine applications both for diagnosis [meaning noninvasive scintigraphic imaging] and for internal radiotherapy [1]. Internal radiotherapy is nowadays called radioligand therapy (RLT) or endoradiotherapy and altogether, i.e., noninvasive scintigraphic imaging and therapy, is summarized under the term radiothera(g)nostics.
Acute Glomerulonephritis With Normal Results From Urinalyses
Authors: Michael J. Dunn
Journal: JAMA (1967)

Two cases of acute poststreptococcal glomerulonephritis were found with paradoxically normal results from urinalyses. Three additional cases of acute glomerulonephritis with no proteinuria but with hematuria and one case with transient proteinuria and no hematuria were also found. The pitfalls of diagnosis with these unusual presentations of acute glomerulonephritis are apparent.
Trends in Sentinel Lymph Node Biopsies in Patients With Inflammatory Breast Cancer in the US
Authors: Alan Sosa, Xiudong Lei, Wendy A. Woodward, Mariana Chavez Mac Gregor, Anthony Lucci, Sharon H. Giordano, Kevin T. Nead
Journal: JAMA Network Open (2022)

The standard of care for inflammatory breast cancer (IBC) is neoadjuvant chemotherapy, total mastectomy with axillary lymph node dissection (ALND), and postmastectomy radiation therapy. Existing studies suggest that sentinel lymph node biopsy (SLNB) may not be reliable in IBC. The use and frequency of SLNB in women with IBC is not well characterized.To determine the frequency and temporal trend of SLNB in patients with IBC.This retrospective cohort study used the National Cancer Database, a nationwide hospital-based cancer registry, and included women who were diagnosed with nonmetastatic IBC and underwent axillary surgery from 2012 to 2017. Data were analyzed from January 2021 to May 2021.Any SLNB, including SLNB alone and SLNB followed by ALND, and ALND alone.Scatterplot fit with a linear regression model were used to evaluate the yearly increase of any SLNB use. Multivariable logistic regression models to evaluate the association of study variables with the outcome of any SLNB.This study included a total of 1096 women (mean [SD] age, 56.1 [12.9] years) who were 18 years or older with nonmetastatic IBC diagnosed between 2012 and 2017. Of the 186 of 1096 women (17%) who received any SLNB, 137 (73.7%) were White individuals; and of the 910 of 1096 women (83%) who received an ALND only, 676 (74.3%) were White individuals. Among women undergoing any SLNB, 119 of 186 (64%) did not undergo a completion ALND. There was a statistically significant increasing trend in the use of SLNB from 2012 to 2017 (22 of 205 patients [11%] vs 32 of 148 patients [22%]; P = .004). In multivariable analysis, the use of SLNB was associated with diagnosis year (2017 vs 2012; odds ratio [OR], 2.26; 95% CI, 1.26-4.20), clinical nodal status (cN3 vs 0; OR, 0.39; 95% CI, 0.22-0.67), and receipt of reconstructive surgery (OR, 1.80; 95% CI, 1.09-2.96).The findings of this cohort study suggest that there is frequent and increasing use of SLNB in patients with IBC that is not evidence-based or supported by current treatment guidelines.
Posaconazole bioavailability of the solid oral tablet is reduced during severe intestinal mucositis
Authors: Anouk M.E. Jansen, Eline W. Muilwijk, Walter J.F.M. van der Velden, Johan A. Maertens, Robina Aerts, Angela Colbers, David Burger, Paul E. Verweij, Rob ter Heine, Nicole M.A. Blijlevens, Roger J.M. Brüggemann
Journal: Clinical Microbiology and Infection (2022)

ObjectivesThis study aimed to describe the absolute oral bioavailability of the solid oral formulation of posaconazole and the impact of severe intestinal mucositis in haematology patients. This study also aimed to describe posaconazole protein binding in haematology patients.MethodsA pharmacokinetic study was performed of patients receiving induction chemotherapy or a haematopoietic cell transplantation who were randomized to receive 7 days of intravenous posaconazole therapy followed by 9 days of oral therapy, or vice versa. Patients received a posaconazole licensed dose until day 12, after which a reduced once-daily dose of 200 mg was given. At days 7, 12, and 16, blood samples were obtained for pharmacokinetic curves, and trough samples were collected on all other days. Total and unbound posaconazole pharmacokinetics were analyzed by population pharmacokinetic modelling. The presence of severe intestinal mucositis was assessed by plasma citrulline levels and analyzed as a binary covariate using 10 μmol/L as the cut-off. Monte Carlo simulations were performed to simulate posaconazole exposure at a steady state.ResultsTwenty-three patients were included for analysis, with 581 total posaconazole concentrations and 91 paired unbound concentrations. Absolute bioavailability in the final model was estimated at 51.4% (percentage relative standard error (%RSE): 56.5) and 67.6% (%RSE: 75.0) in patients with and without severe intestinal mucositis, respectively. Posaconazole unbound fraction was estimated at 2.7% (%RSE: 3.9).DiscussionPosaconazole bioavailability is reduced in haematological patients with severe intestinal mucositis, requiring an increase in oral posaconazole dose to 400 mg twice daily on day 1, followed by 400 mg once daily or a switch to intravenous therapy.
Otolaryngology: Present Status and Concepts
Journal: JAMA (1963)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Investigation of outbreak cases infected with the SARS-CoV-2 B.1.640 variant in a fully vaccinated elderly population, Normandy, France, November to December 2021
Authors: Brice Mastrovito, Chloé Naimi, Leslie Kouam, Xavier Naudot, Lucie Fournier, Guillaume Spaccaferri, Jean-Christophe Plantier, Anaïs Soares, Fabienne De Oliveira, Marie Gueudin, Véronique Jacomo, Céline Leroy, Alice Moisan, Mélanie Martel
Journal: Eurosurveillance (2022)

Three confirmed infections with the SARS-CoV-2 B.1.640 variant under monitoring were reported in Normandy, north-western France in late November 2021. Investigations led to the identification of two events linked to the same cluster. A total of 75 confirmed and probable B.1.640 cases were reported. All had completed the primary vaccination series. Sixty-two cases were older than 65 years. Fifty-six cases had symptoms and four were hospitalised. This investigation provides preliminary results concerning a variant with limited information currently available.
Cerebral palsy
Authors: H. Kerr Graham, Peter Rosenbaum, Nigel Paneth, Bernard Dan, Jean-Pierre Lin, Diane L. Damiano, Jules G. Becher, Deborah Gaebler-Spira, Allan Colver, Dinah S. Reddihough, Kylie E. Crompton, Richard L. Lieber
Journal: Nature Reviews Disease Primers (2016)
Intelligent lesion blood–brain barrier targeting nano-missiles for Alzheimer's disease treatment by anti-neuroinflammation and neuroprotection
Authors: Xueqin He, Xiaorong Wang, Lianyi Yang, Zhihang Yang, Wenqi Yu, Yazhen Wang, Rui Liu, Meiwan Chen, Huile Gao
Journal: Acta Pharmaceutica Sinica B (2022)

The treatment of Alzheimer's disease (AD) is one of the most difficult challenges in neurodegenerative diseases due to the insufficient blood‒brain barrier (BBB) permeability and unsatisfactory intra-brain distribution of drugs. Therefore, we established an ibuprofen and FK506 encapsulated drug co-delivery system (Ibu&FK@RNPs), which can target the receptor of advanced glycation endproducts (RAGE) and response to the high level of reactive oxygen species (ROS) in AD. RAGE is highly and specifically expressed on the lesion neurovascular unit of AD, this property helps to improve targeting specificity of the system and reduce unselective distribution in normal brain. Meanwhile, these two drugs can be specifically released in astrocytes of AD lesion in response to high levels of ROS. As a result, the cognition of AD mice was significantly improved and the quantity of Aβ plaques was decreased. Neurotoxicity was also alleviated with structural regeneration and functional recovery of neurons. Besides, the neuroinflammation dominated by NF-κB pathway was significantly inhibited with decreased NF-κB and IL-1β in the brain. Overall, Ibu&FK@RNPs can efficiently and successively target diseased BBB and astrocytes in AD lesion. Thus it significantly enhances intracephalic accumulation of drugs and efficiently treats AD by anti-neuroinflammation and neuroprotection.
Early predictive value of platelet function for clinical outcome in sepsis
Authors: Yan Cao, Wenfeng Ma, Zhengyu Liu, Yanfang Pei, Yimin Zhu, Fang Chen, Lianhong Zou, Yu Jiang, Xiehong Liu, Jie Huang, Weiwei Xiao, Xiaotong Han
Journal: Journal of Infection (2022)

ObjectiveSepsis is the leading course of morbidity and mortality in critically ill patients. This study aimed to evaluate the predictive value of the platelet aggregation for mortality in patients with sepsis. In addition, the relationship between impaired mitochondria and the platelet aggregation was explored.MethodThis was a prospective, observational cohort study. The platelet aggregation rate in response to adenosine diphosphate (ADP) was assessed. The primary outcome was 28-day mortality. Platelet mitochondrial parameters, including adenosine triphosphate(ATP), mitochondrial membrane potential (MMP) and mitochondrial permeability transition pore (mPTP) opening, were measured. Platelet mitochondrial ultrastructure was observed using transmission electron microscopy.Results86 patients with 65 survivors and 21 non-survivors were enrolled. Platelets of non-survivors with sepsis were hyporesponsive to ADP, in terms of maximal aggregation rate (P < 0.001). Receiver operating characteristic curves analysis demonstrated that the AUC estimated 28-day mortality for platelet aggregation rate was 0.814. At the optimal cut-off value of 35.8% for platelet aggregation rate, the sensitivity was 86.2% and the specificity was 66.7%. Kaplan-Meier analysis showed that a platelet aggregation rate of less than 35.8% was associated closely with poor survival. After adjusting for lactate by Cox regression analysis, platelet aggregation rate was identified as an independent predictor for the probability of 28-day mortality. Compared with survivors, non-survivors showed a significant reduction in platelet ATP and MMP-index (both P < 0.001), and a remarkable increase in mPTP opening (P < 0.001). ATP and MMP-index were positively correlated with platelet aggregation rate (R square=0.75, R square=0.44, respectively).ConclusionPlatelet aggregation rate could be an early predictive biomarker for mortality in sepsis. Impaired platelet mitochondrial activity affects platelet aggregation and correlates with the severity of sepsis.
Proteogenomic Characterization of Ovarian HGSC Implicates Mitotic Kinases, Replication Stress in Observed Chromosomal Instability
Authors: Jason E. McDermott, Osama A. Arshad, Vladislav A. Petyuk, Yi Fu, Marina A. Gritsenko, Therese R. Clauss, Ronald J. Moore, Athena A. Schepmoes, Rui Zhao, Matthew E. Monroe, Michael Schnaubelt, Chia-Feng Tsai, Samuel H. Payne, Chen Huang, Liang-Bo Wang, Steven Foltz, Matthew Wyczalkowski, Yige Wu, Ehwang Song, Molly A. Brewer, Mathangi Thiagarajan, Christopher R. Kinsinger, Ana I. Robles, Emily S. Boja, Henry Rodriguez, Daniel W. Chan, Bing Zhang, Zhen Zhang, Li Ding, Richard D. Smith, Tao Liu, Karin D. Rodland
Journal: Cell Reports Medicine (2020)

[This corrects the article PMC7289043.].
Ad26.COV2.S breakthrough infections induce high titers of neutralizing antibodies against Omicron and other SARS-CoV-2 variants of concern
Authors: Dale Kitchin, Simone I. Richardson, Mieke A. van der Mescht, Thopisang Motlou, Nonkululeko Mzindle, Thandeka Moyo-Gwete, Zanele Makhado, Frances Ayres, Nelia P. Manamela, Holly Spencer, Bronwen Lambson, Brent Oosthuysen, Haajira Kaldine, Marizane du Pisanie, Mathilda Mennen, Sango Skelem, Noleen Williams, Ntobeko A.B. Ntusi, Wendy A. Burgers, Glenda G. Gray, Linda-Gail Bekker, Michael T. Boswell, Theresa M. Rossouw, Veronica Ueckermann, Penny L. Moore
Journal: Cell Reports Medicine (2022)

The Janssen (Johnson & Johnson) Ad26.COV2.S non-replicating viral vector vaccine has been widely deployed for COVID-19 vaccination programs in resource-limited settings. Here we confirm that neutralizing and binding antibody responses to Ad26.COV2.S vaccination are stable for 6 months post-vaccination, when tested against multiple SARS-CoV-2 variants. Secondly, using longitudinal samples from individuals who experienced clinically mild breakthrough infections 4 to 5 months after vaccination, we show dramatically boosted binding antibodies, Fc effector function, and neutralization. These high titer responses are of similar magnitude to humoral immune responses measured in convalescent donors who had been hospitalized with severe illness, and are cross-reactive against diverse SARS-CoV-2 variants, including the neutralization-resistant Omicron (B.1.1.529) variant that currently dominates global infections, as well as SARS-CoV-1. These data have implications for population immunity in areas where the Ad26.COV2.S vaccine has been widely deployed, but where ongoing infections continue to occur at high levels.
Lateral Curvature of the Spine and Round Shoulders.
Journal: JAMA (1907)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal