tbuckley/cabot-search huggingface dataset:
Mutations affecting the actin regulator WD repeat–containing protein 1 lead to aberrant lymphoid immunity
Authors: Laurène Pfajfer, Nina K. Mair, Raúl Jiménez-Heredia, Ferah Genel, Nesrin Gulez, Ömür Ardeniz, Birgit Hoeger, Sevgi Köstel Bal, Christoph Madritsch, Artem Kalinichenko, Rico Chandra Ardy, Bengü Gerçeker, Javier Rey-Barroso, Hanna Ijspeert, Stuart G. Tangye, Ingrid Simonitsch-Klupp, Johannes B. Huppa, Mirjam van der Burg, Loïc Dupré, Kaan Boztug
Journal: Journal of Allergy and Clinical Immunology (2018)

The actin-interacting protein WD repeat-containing protein 1 (WDR1) promotes cofilin-dependent actin filament turnover. Biallelic WDR1 mutations have been identified recently in an immunodeficiency/autoinflammatory syndrome with aberrant morphology and function of myeloid cells.Given the pleiotropic expression of WDR1, here we investigated to what extent it might control the lymphoid arm of the immune system in human subjects.Histologic and detailed immunologic analyses were performed to elucidate the role of WDR1 in the development and function of B and T lymphocytes.Here we identified novel homozygous and compound heterozygous WDR1 missense mutations in 6 patients belonging to 3 kindreds who presented with respiratory tract infections, skin ulceration, and stomatitis. In addition to defective adhesion and motility of neutrophils and monocytes, WDR1 deficiency was associated with aberrant T-cell activation and B-cell development. T lymphocytes appeared to develop normally in the patients, except for the follicular helper T-cell subset. However, peripheral T cells from the patients accumulated atypical actin structures at the immunologic synapse and displayed reduced calcium flux and mildly impaired proliferation on T-cell receptor stimulation. WDR1 deficiency was associated with even more severe abnormalities of the B-cell compartment, including peripheral B-cell lymphopenia, paucity of B-cell progenitors in the bone marrow, lack of switched memory B cells, reduced clonal diversity, abnormal B-cell spreading, and increased apoptosis on B-cell receptor/Toll-like receptor stimulation.Our study identifies a novel role for WDR1 in adaptive immunity, highlighting WDR1 as a central regulator of actin turnover during formation of the B-cell and T-cell immunologic synapses.
The Importance of Oral Health in Comprehensive Health Care
Authors: Janice S. Lee, Martha J. Somerman
Journal: JAMA (2018)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Controlled attenuation parameter is useful in the diagnosis of fatty liver disease and allows to identify patients with high vascular risk as well as those with advanced liver disease
Authors: M. González, J.A. Guerra, D. Escudero-García, María T.A. Loste, M. Hernández Conde, P. Iruzubieta, Ángel Estébanez, L. Puchades, E. Llop, J.C. Gonzalez, M. Serra, José L.C. Panero, J. Crespo
Journal: Journal of Hepatology (2018)
Efficient, reproducible, and long-term hepatitis B virus infection in cryopreserved primary human hepatocytes
Authors: M. Yu, L. Gamelin, S. Xu, X. Xie, J.J. Chia, T. Cheung, J. Song, D. Burdette, C. Niu, S. Daffis, R. Choy, H. Yang, B. Delaney, G. Cheng
Journal: Journal of Hepatology (2018)
Pseudoprogression manifesting as recurrent ascites with anti-PD-1 immunotherapy in urothelial bladder cancer
Authors: Randy F. Sweis, Yuanyuan Zha, Lomax Pass, Brian Heiss, Tara Chongsuwat, Jason J. Luke, Thomas F. Gajewski, Russell Szmulewitz
Journal: Journal for ImmunoTherapy of Cancer (2018)

<h3>Background</h3> Immunotherapies targeting the PD-1 checkpoint pathway have recently gained regulatory approval in numerous cancer types. With the widespread use of immune checkpoint therapies, varying patterns of responses and immune-related adverse events are being observed. <h3>Case Presentation</h3> In this case, we highlight a patient who developed recurrent, large-volume ascites, while simultaneously having a 49% reduction in peritoneal tumor lesion size by RECIST criteria. Sampling of the fluid revealed high levels of IL-6 and IL-15. Cytology revealed no malignant cells on 4 separate paracenteses over a period of 6&nbsp;weeks. Cell counts revealed that 45% of cells were lymphocytes, and further analysis was performed by fluorescence-activated cell sorting (FACS). The majority of lymphocytes were CD8<sup>+</sup>, of which 78% were PD-1<sup>+</sup> and 43% were HLA-DR<sup>+</sup> indicating an activated phenotype. <h3>Conclusions</h3> In summary, treatment with anti-PD-1 therapy may result in pseudoprogression manifested by ascitic fluid accumulation due to the influx of activated T cells. Since worsening of ascites is typically associated with disease progression, it is important to consider the possibility of pesudoprogression in such patients undergoing therapy with immune checkpoint inhibitors.
Liposomal delivery of a Pin1 inhibitor complexed with cyclodextrins as new therapy for high-grade serous ovarian cancer
Authors: Concetta Russo Spena, Lucia De Stefano, Stefano Palazzolo, Barbara Salis, Carlotta Granchi, Filippo Minutolo, Tiziano Tuccinardi, Roberto Fratamico, Sara Crotti, Sara D'Aronco, Marco Agostini, Giuseppe Corona, Isabella Caligiuri, Vincenzo Canzonieri, Flavio Rizzolio
Journal: Journal of Controlled Release (2018)
Antidepressive effects of targeting ELK-1 signal transduction
Authors: Kallia Apazoglou, Séverine Farley, Victor Gorgievski, Raoul Belzeaux, Juan Pablo Lopez, Julien Grenier, El Chérif Ibrahim, Marie-Anne El Khoury, Yiu C. Tse, Raphaele Mongredien, Alexandre Barbé, Carlos E. A. de Macedo, Wojciech Jaworski, Ariane Bochereau, Alejandro Orrico, Elsa Isingrini, Chloé Guinaudie, Lenka Mikasova, Franck Louis, Sophie Gautron, Laurent Groc, Charbel Massaad, Ferah Yildirim, Vincent Vialou, Sylvie Dumas, Fabio Marti, Naguib Mechawar, Elise Morice, Tak P. Wong, Jocelyne Caboche, Gustavo Turecki, Bruno Giros, Eleni T. Tzavara
Journal: Nature Medicine (2018)
Fratricide of NK Cells in Daratumumab Therapy for Multiple Myeloma Overcome by <i>Ex Vivo</i>–Expanded Autologous NK Cells
Authors: Yufeng Wang, Yibo Zhang, Tiffany Hughes, Jianying Zhang, Michael A. Caligiuri, Don M. Benson, Jianhua Yu
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Daratumumab and its use in combination with other agents is becoming a new standard of care for the treatment of multiple myeloma. We mechanistically studied how daratumumab acts on natural killer (NK) cells. Experimental Design: Quantities of NK cells in peripheral blood and/or bone marrow of patients with multiple myeloma or healthy donors were examined by flow cytometry. NK-cell apoptosis and the associated mechanism were assessed by flow cytometry and immunoblotting. Patients' NK cells were expanded in vitro using feeder cells. Combination treatment of daratumumab and expanded NK cells was performed using an MM.1S xenograft animal model. Results: CD38−/low NK cells survived, whereas CD38+ NK cells were almost completely eliminated, in peripheral blood and bone marrow of daratumumab-treated multiple myeloma patients. NK-cell depletion occurred due to daratumumab-induced NK-cell fratricide via antibody-dependent cellular cytotoxicity. Consequently, CD38−/low NK cells were more effective for eradicating multiple myeloma cells than were CD38+ NK cells in the presence of daratumumab. Blockade of CD38 with the F(ab)2 fragments of daratumumab inhibited the antibody-mediated NK-cell fratricide. CD38−/low NK cells displayed a significantly better potential for expansion than CD38+ NK cells, and the expanded NK cells derived from the former population were more cytotoxic than those derived from the latter against multiple myeloma cells. Therefore, infusion of ex vivo–expanded autologous NK cells from daratumumab-treated patients may improve the antibody therapy. Conclusions: We unravel a fratricide mechanism for daratumumab-mediated NK-cell depletion and provide a potential therapeutic strategy to overcome this side effect in daratumumab-treated patients with multiple myeloma. Clin Cancer Res; 24(16); 4006–17. ©2018 AACR.
Lifetime Prevalence and Prognosis of Prediabetes Without Progression to Diabetes
Authors: Justin B. Echouffo-Tcheugui, Teemu J. Niiranen, Elizabeth L. McCabe, Mohit Jain, Ramachandran S. Vasan, Martin G. Larson, Susan Cheng
Journal: Diabetes Care (2018)

Impaired fasting glucose, also termed prediabetes, is increasingly prevalent and is associated with adverse cardiovascular risk (1). The cardiovascular risks attributed to prediabetes may be driven primarily by the conversion from prediabetes to overt diabetes (2). Given limited data on outcomes among nonconverters in the community, the extent to which some individuals with prediabetes never go on to develop diabetes and yet still experience adverse cardiovascular risk remains unclear. We therefore investigated the frequency of cardiovascular versus noncardiovascular deaths in people who developed early- and late-onset prediabetes without ever progressing to diabetes.

We used data from the Framingham Heart Study collected on the Offspring Cohort participants aged 18–77 years at the time of initial fasting plasma glucose (FPG) assessment (1983–1987) who had serial FPG testing over subsequent examinations with continuous surveillance for outcomes including cause-specific mortality (3). As applied in prior epidemiological investigations (4), we used a case-control design focusing on the cause-specific outcome of cardiovascular death to minimize the competing risk issues that would be encountered in time-to-event analyses. To focus on outcomes associated with a given chronic glycemic state maintained over the entire lifetime, we restricted our analyses to only those participants for whom data were available over the life course and until death. We included participants who attended …
Misclassification of Upper Tract Urothelial Carcinoma in Patients With Lynch Syndrome—Reply
Authors: N. Jewel Samadder, Jathine Wong, Karen Curtin
Journal: JAMA Oncology (2018)

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 Oncology 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 Oncology journal
Impact of Adjuvant Radiotherapy in Node-positive Prostate Cancer Patients: The Importance of Patient Selection
Authors: Firas Abdollah, Deepansh Dalela, Akshay Sood, Jacob Keeley, Shaheen Alanee, Alberto Briganti, Francesco Montorsi, James O. Peabody, Mani Menon
Journal: European Urology (2018)
간세포암종 환자의 새로운 예후 지표 - Modified CLIP Score -
Authors: 한승호, 한상영, 고병성, 김민지, 이정현, 구영훈, 유승훈, 조정환, 장진석, 이종훈, 노명환, 최석렬, 최종철, Lee， Sung Wook
Journal: Clinical and Molecular Hepatology (2006)

목적: 간세포암종 환자의 예후는 잔존 간기능과 종양의 특성에 따라 좌우되는 것으로 알려져 있다. CLIP score는 종양 인자와 간기능 인자를 모두 포함하고 있는 병기체계로서 최근에 가장 흔히 사용되고 있다. 본 연구의 목적은 간세포암종 환자에 대한 새로운 예후의 지표로서 CLIP score의 일부를 변형시킨 modified CLI...
39 Is it time to revisit the red flag referral system
Authors: Raj Spence, Adr Spence, E Mackle
Journal: Gut (2017)

Background  The ‘red flag referral’ system is currently under stress due to the number of suspected cancer referrals. There are guidelines from the Northern Ireland Cancer Network regarding specific criteria for what constituents a red flag referral.  Aim  To a ss e ss  the efficacy of the 31- and 62 day referral pathways over a 1 year period for both upper and lower gastrointestinal cancers in a district general hospital.  Method  All upper and lower GI suspected cancer referrals were assessed over a 1 year period (October 2015 – September 2016). Both 31 day and 62 day referral pathways were analysed following investigation. Data were obtained from cancer trackers.  Results  For suspected Upper GI cancers, there were 2629 (1109 31 day in-hospital referrals; 1520 62 day general practice referrals) referrals over the 1 year period. There were 164 confirmed cancers (overall 6.24%, 31 day: 9.64%, 62 day: 3.75%). For lower GI cancers, there were 3951 (1299 31 day in-hospital referrals; 2652 62 day general practice referrals) referrals over the 1 year period. There were 188 confirmed cancers (overall 4.76%, 31 day: 9.62%, 62 day: 2.38%).  Conclusions  There was a very low diagnosis of cancer from red flag referrals for both upper and lower GI symptoms. In the current environment of increasing demands on the NHS—is it time for current red flag referral criteria to be revisited?
Government must investigate rising excess deaths in England and Wales, experts warn
Authors: Gareth Iacobucci
Journal: BMJ (2018)

Research experts have urged the government and MPs to investigate rising numbers of deaths in England and Wales, after new figures showed over 20 000 “excess deaths” so far in 2018.

Earlier this year an analysis of the Office for National Statistics’ data on weekly provisional deaths in England and Wales, published in The BMJ ,1 found that by week seven of 2018 (ending 16 February) 10 000 more people had died than the average from the past five years.

Lucinda Hiam, honorary research fellow at the London School of Hygiene and Tropical Medicine, …
A 10-year longitudinal follow-up study of a U.K. paediatric transplant population to assess for skin cancer
Authors: S.H. Foo, P.G. Nightingale, P. Gazzani, E. Bader, M. Ogboli, A. Martin-Clavijo, D.V. Milford, D.A. Kelly, C. Moss, M.A. Thomson
Journal: British Journal of Dermatology (2018)

Our earlier study, published in 2004,1found no skin cancer in a cohort of paediatric organ transplant recipients (POTRs) 5–16 years post‐transplantation. We re‐evaluated the same cohort 10 years later. To determine the prevalence of premalignant and malignant skin lesions and identify known risk factors associated with melanocytic naevi in a U.K. paediatric transplant population. Ninety‐eight POTRs from the original 2004 study were invited to participate in this longitudinal follow‐up study. History of sun exposure, demographics and transplantation details were collected using face‐to‐face interviews, questionnaires and case note reviews. Skin examination was performed for regional count of malignant lesions, benign and atypical naevi. Of the 98 patients involved in the initial study, 45 POTRs (eight kidney, 37 liver), with a median follow‐up of 19 years (range 15–26 years), agreed to participate. Neither skin cancer nor premalignant lesions were detected in these patients. When compared with the 2004 cohort, 41 patients in our current cohort had increased numbers of benign naevi (P <0·001) with 11 patients having ≥ 50 benign naevi. Seventy‐one per cent of benign naevi in our 2014 cohort occurred on sun‐exposed sites (13% head/neck, 35% arms and 23% legs). Patients who regularly used sunscreen had more benign naevi on their arms (P =0·008). Although skin cancer was not observed in our cohort, we identified a significant increase in the number of benign naevi, particularly in those reporting frequent sunburn and sunscreen use.
Effect of Needle Aspiration of Pneumothorax on Subsequent Chest Drain Insertion in Newborns
Authors: Madeleine C. Murphy, Christian Heiring, Nicoletta Doglioni, Daniele Trevisanuto, Mats Blennow, Kajsa Bohlin, Gianluca Lista, Ilaria Stucchi, Colm P. F. O’Donnell
Journal: JAMA Pediatrics (2018)

Treatment options for a symptomatic pneumothorax in newborns include needle aspiration (NA) and chest drain (CD) insertion. There is little consensus as to the preferred treatment, reflecting a lack of evidence from clinical trials.To investigate whether treating pneumothoraces diagnosed on chest radiography (CR) in newborns receiving respiratory support with NA results in fewer infants having CDs inserted within 6 hours of diagnosis.This randomized clinical trial was conducted from October 7, 2013, to December 21, 2016. The setting was 5 tertiary European neonatal intensive care units. Infants receiving respiratory support (endotracheal ventilation, continuous positive airway pressure, or supplemental oxygen >40%) who had a pneumothorax on CR that clinicians deemed needed treatment were eligible for inclusion.Infants were randomly assigned (1:1) to drainage using NA or CD insertion, stratified by center and gestation at birth (<32 vs ≥32 weeks). Caregivers were not masked to group assignment. For NA, a needle was inserted between the ribs to aspirate air and was removed once air was no longer aspirated. A CD was inserted if clinicians deemed that the response was inadequate. For CD insertion, a drain was inserted between the ribs and was left in situ.The primary outcome was whether a CD was inserted on the side of the pneumothorax within 6 hours of diagnosis.A total of 76 infants were randomly assigned, and 6 (4 assigned to NA and 2 to CD) were excluded because they met exclusion criteria at enrollment. Of the 70 remaining infants, 33 (16 male [48%]) were assigned to NA and 37 (22 male [59%]) to CD insertion. Their median (interquartile range [IQR]) gestational age was 31 (27-38) vs 31 (27-35) weeks, and their median (IQR) birth weight was 1385 (1110-3365) vs 1690 (1060-2025) g, respectively. Fewer infants assigned to NA had a CD inserted within 6 hours (55% [18 of 33] vs 100% [37 of 37]; relative risk, 0.55; 95% CI, 0.40-0.75) and during hospitalization (70% [23 of 33] vs 100% [37 of 37]; relative risk, 0.70, 95% CI, 0.56-0.87).Needle aspiration reduced the rate of CD insertion in symptomatic newborns with pneumothorax on CR. It should be used as the initial method of draining radiologically confirmed pneumothorax in symptomatic infants.isrctn.org Identifier: ISRCTN65161530.
Targeted Drug and Cell Delivery: A Capsule‐Type Microrobot with Pick‐and‐Drop Motion for Targeted Drug and Cell Delivery (Adv. Healthcare Mater. 9/2018)
Authors: Seungmin Lee, Soyeun Kim, Sangwon Kim, Jin‐Young Kim, Cheil Moon, Bradley J. Nelson, Hongsoo Choi
Journal: Advanced Healthcare Materials (2018)

A capsule-type microrobot exhibits “Pick-and-Drop” (P&D) motion for possible drug and cell transport via a corkscrew motion. Drugs or cells can be encapsulated in the microrobot's container by the P&D motion or attached to the surface of the cap, which can be used as a cell supporting structure. This work is discussed in article number 1700985 by Hongsoo Choi and co-workers.
P310HDL-function in atrial fibrillation
Authors: P Buettner, M Trieb, G Marsche, G Hindricks, A Arya, P Sommer, B Dinov, A Bollmann, D Husser, J Kornej
Journal: Cardiovascular Research (2018)

epicardial adipocytes and left atrial myocytes has revealed important changes in ionic currents in a rabbit model.Based on these experimental data, we adapted 6 ion currents for adipose induced remodelling, namely I_CaL, I_to, I_Kur, the sodium current (I_Na), slow delayed rectifying potassium current (I_Ks) and inward rectifying potassium current (I_K1).In a 2D tissue model containing a circular region of remodelled myocytes, burst pacing protocols are used to induce arrhythmias (Figure).Results: The predicted changes due to tissue remodelling were a higher resting membrane potential (at 1 Hz pacing: -78.05 mV vs. -80.84mV for normal tissue, -79.07 mV vs. -81.04mV for AF remodelled tissue) and longer action potential duration (at 1 Hz pacing: APD_90 equals 470 ms vs. 310 ms for normal tissue, 450 ms vs. 230 ms for AF remodelled tissue).Simulations at tissue level show that in absence of remodelling due to adipose infiltrates no arrhythmias are induced, while in the presence of remodelling we observe the onset of cardiac arrhythmias (first appearance at: 1.7 Hz for normal tissue, 2.5 Hz for AF remodelled tissue).Conclusion(s): Ionic remodelling due to the presence of adipose tissue results in higher arrhythmogenicity, due to heterogeneity of the tissue.
Gene Therapy as a Curative Option for β-Thalassemia
Authors: Alessandra Biffi
Journal: New England Journal of Medicine (2018)

With an estimated global prevalence of 288,000 cases, β-thalassemia is one of the most common genetic diseases in the world, and every year another 60,000 infants are born with the disease. Of these patients, 60 to 80% have a severe form of the disease and require regular red-cell transfusions and iron chelation for proper treatment of disease manifestations. In the United States and the European Union, the prevalence is estimated to be 15,000, with approximately 1500 infants born each year with the disease. However, in North Africa, the Middle East, and Asia, β-thalassemia is more prevalent. In many of these . . .