tbuckley/cabot-search huggingface dataset:
Curing pancreatic cancer
Authors: Benno Traub, Karl-Heinz Link, Marko Kornmann
Journal: Seminars in Cancer Biology (2021)

The distinct biology of pancreatic cancer with aggressive and early invasive tumor cells, a tumor promoting microenvironment, late diagnosis, and high therapy resistance poses major challenges on clinicians, researchers, and patients. In current clinical practice, a curative approach for pancreatic cancer can only be offered to a minority of patients and even for those patients, the long-term outcome is grim. This bitter combination will eventually let pancreatic cancer rise to the second leading cause of cancer-related mortalities. With surgery being the only curative option, complete tumor resection still remains the center of pancreatic cancer treatment. In recent years, new developments in neoadjuvant and adjuvant treatment have emerged. Together with improved perioperative care including complication management, an increasing number of patients have become eligible for tumor resection. Basic research aims to further increase these numbers by new methods of early detection, better tumor modelling and personalized treatment options. This review aims to summarize the current knowledge on clinical and biologic features, surgical and non-surgical treatment options, and the improved collaboration of clinicians and basic researchers in pancreatic cancer that will hopefully result in more successful ways of curing pancreatic cancer.
Mapping Contemporary Biopsy Zones to Traditional Prostatic Anatomy: The Key to Understanding Relationships Between Prostate Cancer Topography, Magnetic Resonance Imaging Conspicuity, and Clinical Risk
Authors: Pranav Satish, Benjamin Simpson, Alex Freeman, Francesco Giganti, Alex Kirkham, Clement Orczyk, Hayley Whitaker, Mark Emberton, Joseph M. Norris
Journal: European Urology (2021)
Adeno-associated virus gene therapy to the rescue for Charcot-Marie-Tooth disease type 4J
Authors: John Svaren
Journal: Journal of Clinical Investigation (2021)

The genetic peripheral neuropathy known as Charcot-Marie-Tooth disease type 4J (CMT4J) is caused by recessive mutations in the FIG4 gene. The transformational success of adeno-associated virus (AAV) gene therapy for spinal muscular atrophy has generated substantial interest in using this approach to create similar treatments for CMT. In this issue of the JCI, Presa et al. provide a preclinical demonstration of efficacy using AAV-directed gene therapy for CMT4J. The study showed a dramatic improvement in both survival and neuropathy symptoms in a severe mouse model of CMT4J after administration of AAV gene therapy at several time points. The authors’ approach advances the technique for delivering treatments to individuals with CMT, for which FDA-approved therapies have not yet come to the clinic.
European Association of Urology Guidelines on Urethral Stricture Disease (Part 1): Management of Male Urethral Stricture Disease
Authors: Nicolaas Lumen, Felix Campos-Juanatey, Tamsin Greenwell, Francisco E. Martins, Nadir I. Osman, Silke Riechardt, Marjan Waterloos, Rachel Barratt, Garson Chan, Francesco Esperto, Achilles Ploumidis, Wesley Verla, Konstantinos Dimitropoulos
Journal: European Urology (2021)
AB0017 IMMUNE CHARACTERISTICS OF PERIPHERAL BLOOD IN SECONDARY SJOGREN’S SYNDROME PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: R. Su, Y. Y. Wang, C. Wang
Journal: Annals of the Rheumatic Diseases (2021)

Background: Secondary Sjogren’s Syndrome (sSS) is diagnosed when symptoms of SS coexist with other systemic connective tissue disease, often secondary to rheumatoid arthritis(RA).The occurrence of SS secondary with RA will worsen the course of disease and increase the high incidence and mortality of RA. At present, the immune characteristics of peripheral blood of sSS with RA are not clear. Objectives: To observe the difference of immune Immune characteristics in peripheral blood between sSS secondary to RA, primary Sjogren’s syndrome(pSS) and RA patients. Methods: 20 sSS with RA patients, 20 pSS paients and 20 RA pateints hospitalized in ShanXi medical university the second Hospital were enrolled. The percentage and absolute numbers of lymphocyte phenotypes and CD4+ T subsets in peripheral blood were examined by flow cytometry. Results: As for the percentage and absolute number of total T, B, NK, CD4+T,CD8+ T and the ratio of CD4 + T to CD8+ T cells, there was no significant difference between the sSS with RA, RA, and SS group. There was also no statistical difference in the percentage of CD4+T subsets(Th1,Th2,Th17 and Treg) between the three groups. But the ratio of Th17 and Treg in sSS with RA group was increased than pSS group.About comparison of absolute number of CD4+T subsets, there was no statistical difference among the three groups except that the Th1 cells in RA group was significantly higher than SS group. Conclusion: Elevated Th17/Treg may be an immunological feature that differentiates sSS with RA patients from pSS patients. In addition, in general, peripheral blood of patients with RA and SS have similar immune characteristics. References: [1]Wei W,Ahmad S S, Chi S. From Molecular Mechanism to the Etiology of Sjogren Syndrome.Curr Pharm Des. 2018;24(35):4177-4185. [2]Hajiabbasi A, Masooleh I S,Alizadeh Y, Secondary Sjogren’s Syndrome in 83 Patients With Rheumatoid Arthritis.Acta Med Iran.2016;54(7):448-53. Figure 1. The comparsion about the lymphocyte phenotypes and CD4+ T subsets in peripheral blood of sSS with RA(n=20), pSS(n=20) and RA patients(n=20).(*p&lt;0.05,**p&lt;0.001,*p&lt;0.0001) Disclosure of Interests: None declared
Protective T cell receptor identification for orthotopic reprogramming of immunity in refractory virus infections
Authors: Tanja A. Stief, Theresa Kaeuferle, Thomas R. Müller, Michaela Döring, Lena M. Jablonowski, Kilian Schober, Judith Feucht, Kevin M. Dennehy, Semjon Willier, Franziska Blaeschke, Rupert Handgretinger, Peter Lang, Dirk H. Busch, Tobias Feuchtinger
Journal: Molecular Therapy (2021)

Viral infections cause life-threatening disease in immunocompromised patients and especially following transplantation. T cell receptor (TCR) engineering redirects specificity and can bring significant progress to emerging adoptive T cell transfer (ACT) approaches. T cell epitopes are well described, although knowledge is limited on which TCRs mediate protective immunity. In this study, refractory adenovirus (AdV) infection after hematopoietic stem cell transplantation (HSCT) was treated with ACT of highly purified Hexon5-specific T cells using peptide major histocompatibility complex (pMHC)-Streptamers against the immunodominant human leukocyte antigen (HLA)-A∗0101-restricted peptide LTDLGQNLLY. AdV was successfully controlled through this oligoclonal ACT. Novel protective TCRs were isolated ex vivo and preclinically engineered into the TCR locus of allogeneic third-party primary T cells by CRISPR-Cas9-mediated orthotopic TCR replacement. Both TCR knockout and targeted integration of the new TCR in one single engineering step led to physiological expression of the transgenic TCR. Reprogrammed TCR-edited T cells showed strong virus-specific functionality such as cytokine release, effector marker upregulation, and proliferation capacity, as well as cytotoxicity against LTDLGQNLLY-presenting and AdV-infected targets. In conclusion, ex vivo isolated TCRs with clinical proven protection through ACT could be redirected into T cells from naive third-party donors. This approach ensures that transgenic TCRs are protective with potential off-the-shelf use and widened applicability of ACT to various refractory emerging viral infections.
A new KSRP-binding compound suppresses distant metastasis of colorectal cancer by targeting the oncogenic KITENIN complex
Authors: Jeong A Bae, Woo Kyun Bae, Sung Jin Kim, Yoo-Seung Ko, Keon Young Kim, So-Yeon Park, Young Hyun Yu, Eun Ae Kim, Ik Joo Chung, Hangun Kim, Hyung-Ho Ha, Kyung Keun Kim
Journal: Molecular Cancer (2021)

Abstract Background Distant metastasis is the major cause of death in patients with colorectal cancer (CRC). Previously, we identified KITENIN as a metastasis-enhancing gene and suggested that the oncogenic KITENIN complex is involved in metastatic dissemination of KITENIN-overexpressing CRC cells. Here, we attempted to find substances targeting the KITENIN complex and test their ability to suppress distant metastasis of CRC. Methods We screened a small-molecule compound library to find candidate substances suppressing the KITENIN complex in CRC cells. We selected a candidate compound and examined its effects on the KITENIN complex and distant metastasis through in vitro assays, a molecular docking model, and in vivo tumor models. Results Among several compounds, we identified DKC1125 (Disintegrator of KITENIN Complex #1125) as the best candidate. DKC1125 specifically suppressed KITENIN gain of function. After binding KH-type splicing regulatory protein (KSRP), DKC1125 degraded KITENIN and Dvl2 by recruiting RACK1 and miRNA-124, leading to the disintegration of the functional KITENIN–KSRP–RACK1–Dvl2 complex. A computer docking model suggested that DKC1125 specifically interacted with the binding pocket of the fourth KH-domain of KSRP. KITENIN-overexpressing CRC cells deregulated certain microRNAs and were resistant to 5-fluorouracil, oxaliplatin, and cetuximab. DKC1125 restored sensitivity to these drugs by normalizing expression of the deregulated microRNAs, including miRNA-124. DKC1125 effectively suppressed colorectal liver metastasis in a mouse model. Interestingly, the combination of DKC1125 with 5-fluorouracil suppressed metastasis more effectively than either drug alone. Conclusion DKC1125 targets the KITENIN complex and could therefore be used as a novel therapeutic to suppress liver metastasis in CRC expressing high levels of KITENIN.
POS1137 IDENTIFYING ADULT HYPOPHOSPHATASIA IN THE RHEUMATOLOGY UNIT
Authors: J. Feurstein, M. Behanova, J. Haschka, K. Roetzer, G. Uyanik, M. Witsch-Baumgartner, G. Schett, J. Zwerina, R. Kocijan
Journal: Annals of the Rheumatic Diseases (2021)

Background: The most frequent manifestation in adult Hypophosphatasia (HPP) is musculoskeletal pain. 1,2 The unspecific nature of its clinical presentation may prevent correct diagnosis. 3 Objectives: Identifying adult hypophosphatasia in the rheumatology unit. Methods: Over a period of 10 years 9,522 patients were screened in a rheumatological outpatient unit. Serum ALP levels ≤ 40 U/l were found in 524 patients. After screening for secondary causes, 73 patients were invited for clinical evaluation. Genetic testing was performed in 23 patients with suspected HPP. Logistic regression models were used to estimate the association of each clinical factor with HPP. Results: Mutations in the ALPL gene were observed in 57% of genetically screened patients. Arthralgia, fractures and pain were the leading symptoms in HPP patients. Chondrocalcinosis (OR 29.12; 95% CI 2.02-1593.52) and dental disease (OR 8.33; 95% CI 0.93-143.40) were associated with HPP independent of BMI. Onset of symptoms in HPP was at 35.1 (14.3) years, with a mean duration from symptoms to diagnosis of 14.4 (8.1) years. Bone mineral density (BMD) and trabecular bone score (TBS) as well as bone turnover markers were not indicative for HPP. Conclusion: HPP can mimic joint diseases. 4 Thus, in patients with uncertain rheumatologic complaints and low ALP, HPP should be considered as potential diagnosis. References: [1]Durrough C, Colazo JM, Simmons J, et al. Characterization of physical, functional, and cognitive performance in 15 adults with hypophosphatasia. Bone 2021;142:115695. [2]Seefried L, Kishnani PS, Moseley S, et al. Pharmacodynamics of asfotase alfa in adults with pediatric-onset hypophosphatasia. Bone 2021;142:115664. [3]Högler W, Langman C, Gomes da Silva H, et al. Diagnostic delay is common among patients with hypophosphatasia: initial findings from a longitudinal, prospective, global registry. BMC musculoskeletal disorders 2019;20(1):80. [4]Seefried L, Dahir K, Petryk A, et al. Burden of Illness in Adults With Hypophosphatasia: Data From the Global Hypophosphatasia Patient Registry. Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 2020;35(11):2171-78. Disclosure of Interests: None declared.
AB0221 CURRENT IMPLEMENTATION OF TREAT-TO-TARGET APPROACH IN RHEUMATOID ARTHRITIS TREATMENT: THE PERSPECTIVE OF CHINESE RHEUMATOLOGISTS
Authors: J. L. Zhao, X. Liu, L. Zhan, H. Tang, J. Li, M. Liu, E. Holdsworth, Y. Zhao
Journal: Annals of the Rheumatic Diseases (2021)

Background: Treat-to-target (T2T) approach is recommended as a standard management strategy in rheumatoid arthritis (RA) treatment by Chinese guideline for diagnosis and treatment of RA [1] . However, there is little known about its current implementation in China. Objectives: This study aimed to evaluate the implementation and achievement of T2T approach and explore their associated factors in Chinese RA cohort. Methods: A comprehensive cross-sectional survey of rheumatologists and their RA patients was conducted in China. Data were collected during May-Aug 2019 via physician-completed patient record forms. 60 rheumatologists provided data on demographic, clinical characteristics, treatments, and T2T approach implementation for 600 RA patients. Two logistic regressions were used to evaluate factors associated with T2T approach implementation and T2T goal achievement, respectively. Patients with missing data were not included in the models. Results: 600 patients were included in this study (48.8±11.7 years, 70.3% female). 39.0% (N=234) of 600 patients were being treated with T2T approach, and 64.9% (N=366) of 564 patients had achieved T2T goal. Patients with longer disease duration (&gt;2 years diagnosis) (odds ratio (OR) [95%CI]=1.61 [1.05, 2.49], vs. diagnosis ≤2 years), higher pain score (OR [95%CI]=1.26 [1.04, 1.51]), or receiving advanced therapy (OR [95%CI]=6.91 [3.64, 13.13]) were more likely to use T2T. Patients with BMI &gt;23.9kg/m 2 (OR [95%CI]=2.83 [1.59, 5.04], vs. BMI≤23.9kg/m 2 ), or who worked full-time (OR [95%CI]=2.12 [1.26, 3.57]) were more likely to achieve T2T goal, while patients with more pain (OR [95%CI]=0.77 [0.64, 0.92]) were less likely to achieve T2T goal. Conclusion: Low implementation of T2T approach is observed in Chinese RA treatment. Longer disease duration, more pain, and receiving advanced therapy are associated with higher probability of T2T use, while higher BMI, full-time work and less pain are associated with higher probability of T2T goal achievement. Standard diagnosis and treatment according to guidelines may improve T2T approach implementation. References: [1]Association, C.R., 2018 Chinese guideline for the diagnosis and treatment of rheumatoid arthritis. Zhonghua nei ke za zhi, 2018. 57(4): p. 242. Disclosure of Interests: Jiu-liang Zhao: None declared, Xin Liu Employee of: Eli Lilly and Company, Lujing Zhan Employee of: Eli Lilly and Company, Hongyu Tang Employee of: Eli Lilly and Company (Intern), Jinnan Li Employee of: Eli Lilly and Company, Mengru Liu Employee of: Eli Lilly and Company, Elizabeth Holdsworth Consultant of: Eli Lilly and Company, Employee of: Adelphi Real World, Yan Zhao: None declared
Text-Book of Mental Diseases, with special reference to the Pathological Aspects of Insanity.
Journal: JAMA (1899)

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
Author Correction: Dysregulated ribonucleoprotein granules promote cardiomyopathy in RBM20 gene-edited pigs
Authors: Jay W. Schneider, Saji Oommen, Muhammad Y. Qureshi, Sean C. Goetsch, David R. Pease, Rhianna S. Sundsbak, Wei Guo, Mingming Sun, Han Sun, Hidehito Kuroyanagi, Dennis A. Webster, Alexander W. Coutts, Kimberly A. Holst, Brooks S. Edwards, Nikolas Newville, Matthew A. Hathcock, Tamene Melkamu, Francesca Briganti, Wu Wei, Maria G. Romanelli, Scott C. Fahrenkrug, Doug E. Frantz, Timothy M. Olson, Lars M. Steinmetz, Daniel F. Carlson, Timothy J. Nelson, Susana Cantero Peral, Sarah Edgerton, Joan Wobig, Boyd Rasmussen, Jodi A. Scholz, Frank Cetta, Scott H. Suddendorf, Joanne M. Pedersen, Steve Krage, Craig S. Frisk, Chelsea L. Reece, Angela R. Miller, Sara E. Martineau, Rebecca K. Johnson, Amanda L. Breuer, Janell K. Fox
Journal: Nature Medicine (2021)
Dysregulated immunity in PID patients with low GARP expression on Tregs due to mutations in LRRC32
Authors: Peter Lehmkuhl, Magdalena Gentz, Andres Caballero Garcia de Otezya, Bodo Grimbacher, Hendrik Schulze-Koops, Alla Skapenko
Journal: Cellular and Molecular Immunology (2021)

Immune dysregulation diseases are characterized by heterogeneous clinical manifestations and may have severe disease courses. The identification of the genetic causes of these diseases therefore has critical clinical implications. We performed whole-exome sequencing of patients with immune dysregulation disorders and identified two patients with previously undescribed mutations in LRRC32, which encodes glycoprotein A repetitions predominant (GARP). These patients were characterized by markedly reduced numbers and frequencies of regulatory T cells (Tregs). Tregs with mutated LRRC32 exhibited strongly diminished cell-surface GARP expression and reduced suppressor function. In a model of conditional Garp deficiency in mice, we confirmed increased susceptibility to inflammatory diseases once GARP expression on Tregs was decreased. Garp deficiency led to an unstable Treg phenotype due to diminished Foxp3 protein acetylation and stability. Our study reinforces the understanding of the immunological mechanisms of immune dysregulation and expands the knowledge on the immunological function of GARP as an important regulator of Treg stability.
Wireless Power Transfer and Telemetry for Implantable Bioelectronics
Authors: Seungwon Yoo, Jonghun Lee, Hyunwoo Joo, Sung‐Hyuk Sunwoo, Sanghoek Kim, Dae‐Hyeong Kim
Journal: Advanced Healthcare Materials (2021)

Implantable bioelectronic devices are becoming useful and prospective solutions for various diseases owing to their ability to monitor or manipulate body functions. However, conventional implantable devices (e.g., pacemaker and neurostimulator) are still bulky and rigid, which is mostly due to the energy storage component. In addition to mechanical mismatch between the bulky and rigid implantable device and the soft human tissue, another significant drawback is that the entire device should be surgically replaced once the initially stored energy is exhausted. Besides, retrieving physiological information across a closed epidermis is a tricky procedure. However, wireless interfaces for power and data transfer utilizing radio frequency (RF) microwave offer a promising solution for resolving such issues. While the RF interfacing devices for power and data transfer are extensively investigated and developed using conventional electronics, their application to implantable bioelectronics is still a challenge owing to the constraints and requirements of in vivo environments, such as mechanical softness, small module size, tissue attenuation, and biocompatibility. This work elucidates the recent advances in RF-based power transfer and telemetry for implantable bioelectronics to tackle such challenges.
Dermoscopic features of 61 skin lesions in xeroderma pigmentosum patients: A cross-sectional study
Authors: Lílian Kelly Faria Licarião Rocha, Paula Ferreira, João Avancini, Ligia P. Castro, Zilda Najjar, Maria C. Rivitti-Machado, Luciana Paula Samorano, Caroline F. Barbosa, Caroline Colacique, Cyro Festa-Neto
Journal: Journal of the American Academy of Dermatology (2021)
Integrated treatment of hepatitis C virus infection among people who inject drugs: A multicenter randomized controlled trial (INTRO-HCV)
Authors: Lars T. Fadnes, Christer Frode Aas, Jørn Henrik Vold, Rafael Alexander Leiva, Christian Ohldieck, Fatemeh Chalabianloo, Svetlana Skurtveit, Ole Jørgen Lygren, Olav Dalgård, Peter Vickerman, Håvard Midgard, Else-Marie Løberg, Kjell Arne Johansson
Journal: PLoS Medicine (2021)

Background The standard pathways of testing and treatment for hepatitis C virus (HCV) infection in tertiary healthcare are not easily accessed by people who inject drugs (PWID). The aim of this study was to evaluate the efficacy of integrated treatment of chronic HCV infection among PWID. Methods and findings INTRO-HCV is a multicenter, randomized controlled clinical trial. Participants recruited from opioid agonist therapy (OAT) and community care clinics in Norway over 2017 to 2019 were randomly 1:1 assigned to the 2 treatment approaches. Integrated treatment was delivered by multidisciplinary teams at opioid agonist treatment clinics or community care centers (CCCs) for people with substance use disorders. This included on-site testing for HCV, liver fibrosis assessment, counseling, treatment, and posttreatment follow-up. Standard treatment was delivered in hospital outpatient clinics. Oral direct-acting antiviral (DAA) medications were administered in both arms. The study was not completely blinded. The primary outcomes were time-to-treatment initiation and sustained virologic response (SVR), defined as undetectable HCV RNA 12 weeks after treatment completion, analyzed with intention to treat, and presented as hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals. Among 298 included participants, 150 were randomized to standard treatment, of which 116/150 (77%) initiated treatment, with 108/150 (72%) initiating within 1 year of referral. Among those 148 randomized to integrated care, 145/148 (98%) initiated treatment, with 141/148 (95%) initiating within 1 year of referral. The HR for the time to initiating treatment in the integrated arm was 2.2 (1.7 to 2.9) compared to standard treatment. SVR was confirmed in 123 (85% of initiated/83% of all) for integrated treatment compared to 96 (83% of initiated/64% of all) for the standard treatment (OR among treated: 1.5 [0.8 to 2.9], among all: 2.8 [1.6 to 4.8]). No severe adverse events were linked to the treatment. Conclusions Integrated treatment for HCV in PWID was superior to standard treatment in terms of time-to-treatment initiation, and subsequently, more people achieved SVR. Among those who initiated treatment, the SVR rates were comparable. Scaling up of integrated treatment models could be an important tool for elimination of HCV. Trial registration ClinicalTrials.gov.no NCT03155906