tbuckley/cabot-search huggingface dataset:
MiR-22 modulates brown adipocyte thermogenesis by synergistically activating the glycolytic and mTORC1 signaling pathways
Authors: Pengbo Lou, Xueyun Bi, Yuhua Tian, Guilin Li, Qianqian Kang, Cong Lv, Yongli Song, Jiuzhi Xu, Xiaole Sheng, Xu Yang, Ruiqi Liu, Qingyong Meng, Fazheng Ren, Maksim V. Plikus, Bin Liang, Bing Zhang, Huiyuan Guo, Zhengquan Yu
Journal: Theranostics (2021)

Background: Brown adipose tissue (BAT) dissipates chemical energy as heat and has the potential to be a protective strategy to prevent obesity. microRNAs (miRNAs) are emerging as important posttranscriptional factors affecting the thermogenic function of BAT. However, the regulatory mechanism underlying miRNA-mediated energy metabolism in BAT is not fully understood. Here, we explored the roles of miR-22 in BAT thermogenesis and energy metabolism. Methods: Using global and conditional knockout mice as in vivo models and primary brown adipocytes as an in vitro system, we investigated the function of miR-22 in BAT thermogenesis in vivo and in vitro. Results: miR-22 expression was upregulated in BAT in response to cold exposure and during brown preadipocyte differentiation. Both global and conditional knockout mice displayed BAT whitening, impaired cold tolerance, and decreased BAT thermogenesis. Moreover, we found that miR-22 deficiency impaired BAT glycolytic capacity, which is critical for thermogenesis. The mechanistic results revealed that miR-22 activated the mTORC1 signaling pathway by directly suppressing Tsc1 and concomitantly directly suppressing Hif1an, an inhibitor of Hif1α, which promotes glycolysis and maintains thermogenesis. Conclusions: Our findings identify miR-22 as a critical regulator in the control of thermogenesis in BAT and as a potential therapeutic target for human metabolic disorders.
Prevalence and impact factors of recurrent positive SARS-CoV-2 detection in 599 hospitalized COVID-19 patients
Authors: Chun Gao, Li Zhu, Cheng Cheng Jin, Yi Xin Tong, Ai Tang Xiao, Sheng Zhang
Journal: Clinical Microbiology and Infection (2021)

ObjectivesRepeat-positive tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals with coronavirus disease 2019 (COVID-19) were common. We aimed to investigate the rate and risk factors of recurrent positive detection of SARS-CoV-2 in hospitalized individuals with COVID-19.MethodsOropharyngeal and nasopharyngeal swabs (n = 3513) were collected to detect SARS-CoV-2 during the hospitalization. We analysed the recurrent positive rate after consecutive negative results and its relationship to demographic characteristics.ResultsAmong 599 enrolled individuals with COVID-19, the median time for viral RNA shedding was 24 days (interquartile range 19–33 days). The positive rates of RT-PCR were 35.9% (215/599), 17.0% (65/383) and 12.4% (23/185) after one, two and three consecutive negative RT-PCR test results, respectively. Medians of Ct values of initial positive test, rebound positive test after two consecutive negative results, and rebound positive after three consecutive negative results were 28.8, 32.8 and 36.1, respectively. Compared with male patients, females had a significantly higher rate of recurrent positive RT-PCR after three consecutive negative results (18.2%, 18/99, versus 5.8%, 5/86; p 0.013). Older individuals (≥55 years) had a significantly higher rate of recurrent positive RT-PCR after one negative result (42.3%, 165/390, versus 23.9%, 50/209; p < 0.001). Nasopharyngeal swab tests produced a higher positive rate than oropharyngeal swab tests (37.3%, 152/408, versus 35.8%, 1111/3105).ConclusionOur study revealed the prevalence and dynamic characteristics of recurrent positive RT-PCR to SARS-CoV-2. We showed that around 17.0% (65/383) of patients tested positive for SARS-CoV-2 after two consecutive negative results. Patients with a rebound positive RT-PCR test had a low viral load. Older age and being female were risk factors for recurrent positive results.
Intensive care units, the Achilles heel of France in the COVID-19 battle
Authors: Djillali Annane, Laura Federici, Jean-Luc Chagnon, Jean Luc Diehl, Didier Dreyfuss, Philippe Guiot, Etienne Javouhey, Nicolas Joram, Olivier Lesieur, Jean Philippe Rigaud, Hervé Outin, Arnaud Sement, Chantal Sevens, Didier Thévenin, Samia Touati, Nicolas Terzi
Journal: The Lancet Regional Health - Europe (2021)
Expansion of Alternative Autoantibodies Does Not Follow the Evolution of Anti–Citrullinated Protein Antibodies in Preclinical Rheumatoid Arthritis: An Analysis in At‐Risk First Degree Relatives
Authors: Vidyanand Anaparti, Irene Smolik, Xiaobo Meng, Liam O’Neil, Mackenzie A. Jantz, Marvin J. Fritzler, Hani El‐Gabalawy
Journal: Arthritis & Rheumatology (2021)

Objective Co‐occurrence of autoantibodies specific for ≥1 autoimmune disease is widely prevalent in rheumatoid arthritis (RA) patients. To understand the prevalence of polyautoimmunity in preclinical RA, we performed a comprehensive autoantibody assessment in a First Nations cohort of at‐risk first‐degree relatives (FDR) of RA patients, a subset of whom subsequently developed RA (progressors). Methods Venous blood was collected from all study participants (n = 50 RA patients and 64 FDR) at scheduled visits, and serum was stored at −20°C. High‐sensitivity C‐reactive protein level, anti–citrullinated protein antibody (ACPA) status, and autoantibody status were determined using commercially available enzyme‐linked immunosorbent assay kits. Rheumatoid factor (RF) was detected by nephelometry. Antinuclear autoantibodies (ANA) were identified using Hep‐2 indirect immunofluorescence assay (IFA) and classified according to international consensus nomenclature as various anti‐cell (AC) patterns. Results Of our study cohort, 78.9% had positive ANA reactivity (≥1:80), which was either a homogenous, fine‐speckled (AC‐1 and AC‐4) or mixed IFA pattern. Importantly, the AC‐4 and mixed ANA patterns were also observed in progressors at the time of disease onset. While all of the RA patients showed a high prevalence of arthritis‐associated autoantibodies, they also had a high prevalence of extractable nuclear antigen–positive autoantibodies to other autoantigens. In FDR, we did not observe any increase in serum autoreactivity to nonarthritis autoantigens, either cross‐sectionally or in samples collected longitudinally from progressors prior to RA onset. Conclusion While alternative autoimmunity and ANA positivity are widely prevalent in First Nations populations, including asymptomatic, seronegative FDR, expansion of alternative autoimmunity does not occur in parallel with ACPA expansion in FDR and is restricted to patients with established RA.
A case of double common bile duct visually detected only by cholangioscope
Authors: Shin Miura, Shin Hamada, Kiyoshi Kume, Kazuhiro Kikuta, Tetsuya Takikawa, Naoki Yoshida, Atsushi Masamune
Journal: Endoscopy (2021)

Double common bile duct is a rare congenital anomaly [1] [2] [3]. We report a case of a 53-year-old Japanese man who was incidentally diagnosed with a double common bile duct by cholangioscope examination. He developed mild acute cholecystitis and received antibiotics. Drip-infusion cholangiography-computed tomography demonstrated a filling defect in the common bile duct (CBD) ([Fig. 1 a]). Endoscopic retrograde cholangiography (ERC) showed a normal bile duct image ([Fig. 1 b]), and the patient was diagnosed with spontaneous passage of choledocholithiasis. However, bile cytology detected atypical cells and this patient was referred to our facility.
Robert Booth Tattersall
Authors: Edwin Gale, Rachel Tattersall
Journal: BMJ (2021)

The young Robert Tattersall was working on a study of long term diabetes at King’s College London, when he came across a woman with a 40 year history of diabetes who had stopped taking insulin. So too had some of her relatives. David Pyke—Robert’s mentor—recalled the same phenomenon in another family. This simple clinical observation and some intensive sleuth work led to the discovery of maturity onset diabetes of the young (MODY), the first single gene variant of diabetes to be described. It opened up a whole new field of research, which continues to yield a dividend both for science and for those who carry the genes involved.

Robert was born to two psychiatrists and went on to marry one. This, he said, “may go some way to explaining my interest in the psychological aspects of diabetes and the hinterland between medicine and psychiatry.” He studied at Cambridge and St Thomas’ Hospital and did a senior house officer job at Nottingham General Hospital before joining David Pyke in London. It was an exciting time to be in diabetes. The genetic heterogeneity of the condition was coming to …
Refinement of prognosis and the effect of azacitidine in intermediate-risk myelodysplastic syndromes
Authors: Konstantinos Liapis, Vasileios Papadopoulos, George Vrachiolias, Athanasios G. Galanopoulos, Menelaos Papoutselis, Sotirios G. Papageorgiou, Panagiotis T. Diamantopoulos, Vassiliki Pappa, Nora-Athina Viniou, Alexandra Kourakli, Dimitris Τsokanas, Theodoros P. Vassilakopoulos, Eleftheria Hatzimichael, Eleni Bouronikou, Maria Ximeri, Charalambos Pontikoglou, Aekaterini Megalakaki, Panagiotis Zikos, Panayiotis Panayiotidis, Maria Dimou, Stamatis Karakatsanis, Maria Papaioannou, Anna Vardi, Flora Kontopidou, Nikolaos Harchalakis, Ioannis Adamopoulos, Argiris Symeonidis, Ioannis Kotsianidis
Journal: Blood Cancer Journal (2021)
Algorithmic Stewardship in Health Care
Authors: Yue Li, Junfeng Wang
Journal: JAMA (2021)

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
Seizure Cycles in Focal Epilepsy
Authors: Marc G. Leguia, Ralph G. Andrzejak, Christian Rummel, Joline M. Fan, Emily A. Mirro, Thomas K. Tcheng, Vikram R. Rao, Maxime O. Baud
Journal: JAMA Neurology (2021)

<h3>Importance</h3> Focal epilepsy is characterized by the cyclical recurrence of seizures, but, to our knowledge, the prevalence and patterns of seizure cycles are unknown. <h3>Objective</h3> To establish the prevalence, strength, and temporal patterns of seizure cycles over timescales of hours to years. <h3>Design, Setting, and Participants</h3> This retrospective cohort study analyzed data from continuous intracranial electroencephalography (cEEG) and seizure diaries collected between January 19, 2004, and May 18, 2018, with durations up to 10 years. A total of 222 adults with medically refractory focal epilepsy were selected from 256 total participants in a clinical trial of an implanted responsive neurostimulation device. Selection was based on availability of cEEG and/or self-reports of disabling seizures. <h3>Exposures</h3> Antiseizure medications and responsive neurostimulation, based on clinical indications. <h3>Main Outcomes and Measures</h3> Measures involved (1) self-reported daily seizure counts, (2) cEEG-based hourly counts of electrographic seizures, and (3) detections of interictal epileptiform activity (IEA), which fluctuates in daily (circadian) and multiday (multidien) cycles. Outcomes involved descriptive characteristics of cycles of IEA and seizures: (1) prevalence, defined as the percentage of patients with a given type of seizure cycle; (2) strength, defined as the degree of consistency with which seizures occur at certain phases of an underlying cycle, measured as the phase-locking value (PLV); and (3) seizure chronotypes, defined as patterns in seizure timing evident at the group level. <h3>Results</h3> Of the 222 participants, 112 (50%) were male, and the median age was 35 years (range, 18-66 years). The prevalence of circannual (approximately 1 year) seizure cycles was 12% (24 of 194), the prevalence of multidien (approximately weekly to approximately monthly) seizure cycles was 60% (112 of 186), and the prevalence of circadian (approximately 24 hours) seizure cycles was 89% (76 of 85). Strengths of circadian (mean [SD] PLV, 0.34 [0.18]) and multidien (mean [SD] PLV, 0.34 [0.17]) seizure cycles were comparable, whereas circannual seizure cycles were weaker (mean [SD] PLV, 0.17 [0.10]). Across individuals, circadian seizure cycles showed 5 peaks: morning, mid-afternoon, evening, early night, and late night. Multidien cycles of IEA showed peak periodicities centered around 7, 15, 20, and 30 days. Independent of multidien period length, self-reported and electrographic seizures consistently occurred during the days-long rising phase of multidien cycles of IEA. <h3>Conclusions and Relevance</h3> Findings in this large cohort establish the high prevalence of plural seizure cycles and help explain the natural variability in seizure timing. The results have the potential to inform the scheduling of diagnostic studies, the delivery of time-varying therapies, and the design of clinical trials in epilepsy.
The impact of the COVID-19 lockdown on HIV care in 65 South African primary care clinics: an interrupted time series analysis
Authors: Jienchi Dorward, Thokozani Khubone, Kelly Gate, Hope Ngobese, Yukteshwar Sookrajh, Siyabonga Mkhize, Aslam Jeewa, Christian Bottomley, Lara Lewis, Kathy Baisley, Christopher C Butler, Nomakhosi Gxagxisa, Nigel Garrett
Journal: The Lancet HIV (2021)

The effect of the COVID-19 pandemic on HIV outcomes in low-income and middle-income countries is poorly described. We aimed to measure the impact of the 2020 national COVID-19 lockdown on HIV testing and treatment in KwaZulu-Natal, South Africa, where 1·7 million people are living with HIV.In this interrupted time series analysis, we analysed anonymised programmatic data from 65 primary care clinics in KwaZulu-Natal province, South Africa. We included data from people testing for HIV, initiating antiretroviral therapy (ART), and collecting ART at participating clinics during the study period, with no age restrictions. We used descriptive statistics to summarise demographic and clinical data, and present crude summaries of the main outcomes of numbers of HIV tests per month, ART initiations per week, and ART collection visits per week, before and after the national lockdown that began on March 27, 2020. We used Poisson segmented regression models to estimate the immediate impact of the lockdown on these outcomes, as well as post-lockdown trends.Between Jan 1, 2018, and July 31, 2020, we recorded 1 315 439 HIV tests. Between Jan 1, 2018, and June 15, 2020, we recorded 71 142 ART initiations and 2 319 992 ART collection visits. We recorded a median of 41 926 HIV tests per month before lockdown (January, 2018, to March, 2020; IQR 37 838-51 069) and a median of 38 911 HIV tests per month after lockdown (April, 2020, to July, 2020; IQR 32 699-42 756). In the Poisson regression model, taking into account long-term trends, lockdown was associated with an estimated 47·6% decrease in HIV testing in April, 2020 (incidence rate ratio [IRR] 0·524, 95% CI 0·446-0·615). ART initiations decreased from a median of 571 per week before lockdown (IQR 498-678), to 375 per week after lockdown (331-399), with an estimated 46·2% decrease in the Poisson regression model in the first week of lockdown (March 30, 2020, to April 5, 2020; IRR 0·538, 0·459-0·630). There was no marked change in the number of ART collection visits (median 18 519 visits per week before lockdown [IQR 17 074-19 922] vs 17 863 visits per week after lockdown [17 509-18 995]; estimated effect in the first week of lockdown IRR 0·932, 95% CI 0·794-1·093). As restrictions eased, HIV testing and ART initiations gradually improved towards pre-lockdown levels (slope change 1·183/month, 95% CI 1·113-1·256 for HIV testing; 1·156/month, 1·085-1·230 for ART initiations).ART provision was generally maintained during the 2020 COVID-19 lockdown, but HIV testing and ART initiations were heavily impacted. Strategies to increase testing and treatment initiation should be implemented.Wellcome Trust, Africa Oxford Initiative.
Clinical And Epidemiological Profile Of Atopic Dermatitis (AD) In A Reference Center In An Emerging Country
Authors: Fernanda Vaz, Raissa Roque, Marilia Moraes, Lara Teixeira, Nathalia Vital, Caroline Ferreira, Rafael Saldanha, Pedro Bubach, Danielle Harari, Carolina Aranda, Marcia Mallozi, Dirceu Sole
Journal: Journal of Allergy and Clinical Immunology (2021)
Identification and Therapeutic Targeting of GPR20, Selectively Expressed in Gastrointestinal Stromal Tumors, with DS-6157a, a First-in-Class Antibody–Drug Conjugate
Authors: Kenji Iida, Amr H. Abdelhamid Ahmed, Akiko Kawano Nagatsuma, Tomoko Shibutani, Satoru Yasuda, Michiko Kitamura, Chiharu Hattori, Manabu Abe, Jun Hasegawa, Takuma Iguchi, Tsuyoshi Karibe, Takashi Nakada, Koichiro Inaki, Reiko Kamei, Yuki Abe, Taisei Nomura, Jessica L. Andersen, Sandro Santagata, Matthew L. Hemming, Suzanne George, Toshihiko Doi, Atsushi Ochiai, George D. Demetri, Toshinori Agatsuma
Journal: Cancer Discovery (2021)

Currently, the only approved treatments for gastrointestinal stromal tumor (GIST) are tyrosine kinase inhibitors (TKI), which eventually lead to the development of secondary resistance mutations in KIT or PDGFRA and disease progression. Herein, we identified G protein-coupled receptor 20 (GPR20) as a novel non-tyrosine kinase target in GIST, developed new GPR20 IHC, and assessed GPR20 expression in cell lines, patient-derived xenografts, and clinical samples from two institutes (United States and Japan). We studied GPR20 expression stratified by treatment line, KIT expression, GIST molecular subtype, and primary tumor location. We produced DS-6157a, an anti-GPR20 antibody-drug conjugate with a novel tetrapeptide-based linker and DNA topoisomerase I inhibitor exatecan derivative (DXd). DS-6157a exhibited GPR20 expression-dependent antitumor activity in GIST xenograft models including a GIST model resistant to imatinib, sunitinib, and regorafenib. Preclinical pharmacokinetics and safety profile of DS-6157a support its clinical development as a potential novel GIST therapy in patients who are refractory or have resistance or intolerance to approved TKIs. SIGNIFICANCE: GPR20 is selectively expressed in GIST across all treatment lines, regardless of KIT/PDGFRA genotypes. We generated DS-6157a, a DXd-based antibody-drug conjugate that exhibited antitumor activity in GIST models by a different mode of action than currently approved TKIs, showing favorable pharmacokinetics and safety profiles.This article is highlighted in the In This Issue feature, p. 1307.
Do not routinely offer imaging for uncomplicated low back pain
Authors: Amanda M Hall, Kris Aubrey-Bassler, Bradley Thorne, Chris G Maher
Journal: BMJ (2021)

### What you need to know The past two decades have seen a paradigm shift in the way we use imaging when managing low back pain (LBP). Imaging was once a routine part of the diagnostic workup for most cases of LBP. Evidence now indicates that imaging is useful only in the small subgroup of patients for whom there is suspicion of red flag conditions. These conditions include cancer, infection, inflammatory disease, fracture, and severe neurological deficits—which together account for only 5-10% of LBP presentations in primary care.1 For the remaining 90-95% of LBP cases (called non-specific or uncomplicated LBP), imaging will not guide management and can cause more harm than benefit. International guidelines2 and "Choosing Wisely" campaigns now encourage a diagnostic triage approach to identify those patients who require imaging (box 1). Given these advances in knowledge, imaging rates for LBP should be decreasing, but recent systematic reviews show the opposite, reporting that imaging has increased over the past 20 years3 and that at least a third of all images are unnessary.4 Box 1 ### "Choosing Wisely" statements from different countries related to avoiding the use of routine imaging for low back painRETURN TO TEXT
Abstract 1921: Armed oncolytic myxoma virus demonstrates efficacy in syngeneic tumor models alone and in combination with immune checkpoint inhibitors
Authors: Lina S. Franco, Joseph Mamola, Wazir Abdullahi, Ana de Matos, Mario Abrantes, Benjamin S. Walker, Zachary Tacner, Nicole Grigaitis, Cassandra Kien, Grant McFadden, Leslie L. Sharp
Journal: Cancer Research (2021)

Abstract Oncolytic viruses (OV) selectively replicate in and lyse tumor cells and provide stimulation to the immune system, representing a promising therapeutic option in development to treat cancers that do not respond well to treatment with immune checkpoint inhibitors. Myxoma virus (MYXV) is a member of the Pox family of double stranded DNA viruses. The natural host of MYXV is a subset of rabbits and hares, but MYXV can infect cancer cell lines of humans and other species. The genome of MYXV is relatively large and is amenable to engineering for expression of transgenes making it an excellent oncolytic virus for introduction of immunomodulatory proteins. Oncolytic activity and transgene production capability were examined in multiple mouse cancer cell lines. In vivo efficacy following intratumoral and intravenous administration of armed myxoma virus, both alone and with immune checkpoint inhibitors is demonstrated. Immunomodulatory mechanisms of actions are investigated. Multi-armed myxoma represents a novel, engineerable, oncolytic virus with preclinical characteristics that warrant further investigation as an immunomodulatory cancer therapeutic. Citation Format: Lina S. Franco, Joseph Mamola, Wazir Abdullahi, Ana de Matos, Mario Abrantes, Benjamin S. Walker, Zachary Tacner, Nicole Grigaitis, Cassandra Kien, Grant McFadden, Leslie L. Sharp. Armed oncolytic myxoma virus demonstrates efficacy in syngeneic tumor models alone and in combination with immune checkpoint inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1921.
Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia
Authors: Denis Y Logunov, Inna V Dolzhikova, Dmitry V Shcheblyakov, Amir I Tukhvatulin, Olga V Zubkova, Alina S Dzharullaeva, Anna V Kovyrshina, Nadezhda L Lubenets, Daria M Grousova, Alina S Erokhova, Andrei G Botikov, Fatima M Izhaeva, Olga Popova, Tatiana A Ozharovskaya, Ilias B Esmagambetov, Irina A Favorskaya, Denis I Zrelkin, Daria V Voronina, Dmitry N Shcherbinin, Alexander S Semikhin, Yana V Simakova, Elizaveta A Tokarskaya, Daria A Egorova, Maksim M Shmarov, Natalia A Nikitenko, Vladimir A Gushchin, Elena A Smolyarchuk, Sergey K Zyryanov, Sergei V Borisevich, Boris S Naroditsky, Alexander L Gintsburg
Journal: The Lancet (2021)