tbuckley/cabot-search huggingface dataset:
Visualizing the dynamics of tuberculosis pathology using molecular imaging
Authors: Alvaro A. Ordonez, Elizabeth W. Tucker, Carolyn J. Anderson, Claire L. Carter, Shashank Ganatra, Deepak Kaushal, Igor Kramnik, Philana L. Lin, Cressida A. Madigan, Susana Mendez, Jianghong Rao, Rada M. Savic, David M. Tobin, Gerhard Walzl, Robert J. Wilkinson, Karen A. Lacourciere, Laura E. Via, Sanjay K. Jain
Journal: Journal of Clinical Investigation (2021)

Nearly 140 years after Robert Koch discovered Mycobacterium tuberculosis, tuberculosis (TB) remains a global threat and a deadly human pathogen. M. tuberculosis is notable for complex host-pathogen interactions that lead to poorly understood disease states ranging from latent infection to active disease. Additionally, multiple pathologies with a distinct local milieu (bacterial burden, antibiotic exposure, and host response) can coexist simultaneously within the same subject and change independently over time. Current tools cannot optimally measure these distinct pathologies or the spatiotemporal changes. Next-generation molecular imaging affords unparalleled opportunities to visualize infection by providing holistic, 3D spatial characterization and noninvasive, temporal monitoring within the same subject. This rapidly evolving technology could powerfully augment TB research by advancing fundamental knowledge and accelerating the development of novel diagnostics, biomarkers, and therapeutics.
Reconsidering the Ross Procedure
Authors: Robert O. Bonow, Patrick T. O’Gara
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
Effectiveness of Allopurinol in Reducing Mortality: Time‐Related Biases in Observational Studies
Authors: Samy Suissa, Karine Suissa, Marie Hudson
Journal: Arthritis & Rheumatology (2021)

Objective The treatment of gout with allopurinol is effective at reducing urate levels and the frequency of flares. Several observational studies have shown important reductions in mortality with allopurinol use, with wide variations in results. We undertook this review to assess the extent of bias in these studies, particularly time‐related biases such as immortal time bias. Methods We searched the literature to identify all observational studies describing the effect of allopurinol use versus nonuse on all‐cause mortality. Results We identified 12 observational studies, of which 3 were affected by immortal time bias and 3 by immeasurable time bias, while the remaining 6 studies avoided these time‐related biases. Reductions in all‐cause mortality with allopurinol use were observed among the studies with immortal time bias, with a pooled hazard ratio (HR) of death associated with allopurinol of 0.71 (95% confidence interval [95% CI] 0.50–1.01), as well as in those with immeasurable time bias (pooled HR 0.62 [95% CI 0.56–0.67]). The 6 studies that avoided these biases demonstrated a null effect of allopurinol on mortality (pooled HR 0.99 [95% CI 0.87–1.11]), though the lack of an analysis based on treatment adherence may have attenuated the effect. Conclusion Observational studies are important to provide real‐world data on medication effects. The observational studies showing significantly decreased mortality with allopurinol treatment cannot be used as evidence, however, mainly due to time‐related biases that tend to greatly exaggerate the potential benefit of treatments. The ALL‐HEART randomized trial, which is currently underway and evaluates the effect of adding allopurinol to usual care (compared to no added treatment), will provide reliable evidence on mortality.
Identification of vulnerable plaques and patients by intracoronary near-infrared spectroscopy and ultrasound (PROSPECT II): a prospective natural history study
Authors: David Erlinge, Akiko Maehara, Ori Ben-Yehuda, Hans Erik Bøtker, Michael Maeng, Lars Kjøller-Hansen, Thomas Engstrøm, Mitsuaki Matsumura, Aaron Crowley, Ovidiu Dressler, Gary S Mintz, Ole Fröbert, Jonas Persson, Rune Wiseth, Alf Inge Larsen, Lisette Okkels Jensen, Jan Erik Nordrehaug, Øyvind Bleie, Elmir Omerovic, Claes Held, Stefan K James, Ziad A Ali, James E Muller, Gregg W Stone, Ole Ahlehoff, Azad Amin, Oskar Angerås, Praveen Appikonda, Saranya Balachandran, Ståle Barvik, Kristoffer Bendix, Maria Bertilsson, Ulrika Boden, Nigussie Bogale, Vernon Bonarjee, Fredrik Calais, Jörg Carlsson, Steen Carstensen, Christina Christersson, Evald Høj Christiansen, Maria Corral, Ole De Backer, Usama Dhaha, Christian Dworeck, Kai Eggers, Charlotta Elfström, Julia Ellert, Erlend Eriksen, Christian Fallesen, Margareta Forsman, Helena Fransson, Mohsen Gaballa, Marek Gacki, Matthias Götberg, Lars Hagström, Theresa Hallberg, Kristina Hambraeus, Inger Haraldsson, Jan Harnek, Ole Havndrup, Knut Hegbom, Matthias Heigert, Steffen Helqvist, Jon Herstad, Ziad Hijazi, Lene Holmvang, Dan Ioanes, Amjid Iqbal, Allan Iversen, Jaclyn Jacobson, Lars Jakobsen, Ivana Jankovic, Ulf Jensen, Karin Jensevik, Nina Johnston, Torfi Fjalar Jonasson, Erik Jørgensen, Francis Joshi, Ulf Kajermo, Frida Kåver, Henning Kelbæk, Thomas Kellerth, Mitra Kish, Wolfgang Koenig, Sasha Koul, Bo Lagerqvist, Bertil Larsson, Jens Flensted Lassen, Olav Leiren, Zhe Li, Christer Lidell, Rikard Linder, Michael Lindstaedt, Gunilla Lindström, Shen Liu, Kjetil Halvorsen Løland, Jacob Lønborg, László Márton, Habib Mir-Akbari, Shameema Mohamed, Jacob Odenstedt, Christer Ogne, Jonas Oldgren, Göran Olivecrona, Nikolas Östlund-Papadogeorgos, Michael Ottesen, Erik Packer, Åsa Michelgård Palmquist, Quratulain Paracha, Frans Pedersen, Petur Petursson, Truls Råmunddal, Svein Rotevatn, Raquel Sanchez, Giovanna Sarno, Kari I Saunamäki, Fredrik Scherstén, Patrick W Serruys, Iwar Sjögren, Rikke Sørensen, Iva Srdanovic, Zuka Subhani, Eva Svensson, Anne Thuesen, Jan Tijssen, Hans-Henrik Tilsted, Tim Tödt, Thor Trovik, Bjørn Inge Våga, Christoph Varenhorst, Karsten Veien, Emma Vestman, Sebastian Völz, Lars Wallentin, Joanna Wykrzykowska, Leszek Zagozdzon, Manuela Zamfir, Crister Zedigh, Hang Zhong, Zhipeng Zhou
Journal: The Lancet (2021)
Abstract 15424: Clinical Implications of Dual Antiplatelet Therapy Cessation Within 12 Months of Coronary Stenting in Men and Women: A Pooled Analysis From the Platinum Diversity and Promus Element Plus Post-Approval Studies
Authors: Rishi Chandiramani, Davide Cao, Roxana Mehran, Moritz Blum, Anastasios Roumeliotis, Ridhima Goel, Samantha Sartori, Scott Davis, Luis Tami, John Wang, Islam Othman, Osvaldo Gigliotti, Kevin Boran, Henry Liberman, Paul Underwood, Dominic Allocco, Wayne Batchelor
Journal: Circulation (2019)

Introduction: Cessation of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) may increase the risk of recurrent ischemic events. While the incidence and patterns of st...
Maintaining a protective state for human periodontal tissue
Authors: Matsuo Yamamoto, Ryo Aizawa
Journal: Periodontology 2000 (2021)

Abstract Periodontitis, caused by infection with periodontal pathogens, is primarily characterized by inflammatory bone resorption and destruction of connective tissue. Simply describing periodontitis as a specific bacterial infection cannot completely explain the various periodontal tissue destruction patterns observed. Periodontal tissue damage is thought to be caused by various factors. In recent years, research goals for periodontal pathogens have shifted from searching for specific pathogens to investigating mechanisms that damage periodontal tissues. Bacteria interact directly with the host in several ways, influencing expression and activity of molecules that evade host defenses, and destroying local tissues and inhibiting their repair. The host's innate and acquired immune systems are important defense mechanisms that protect periodontal tissues from attack and invasion of periodontal pathogens, thus preventing infection. Innate and acquired immunity have evolved to confront the microbial challenge, forming a seamless defense network in periodontal tissues. In the innate immune response, host cells quickly detect, via specialized receptors, macromolecules and nucleic acids present on bacterial cell walls, and this triggers a protective, inflammatory response. The work of this subsystem of host immunity is performed mainly by phagocytes, beta‐defensin, and the complement system. In addition, the first line of defense in oral innate immunity is the junctional epithelium, which acts as a physical barrier to the entry of oral bacteria and other nonself substances. In the presence of a normal flora, junctional epithelial cells differentiate actively and proliferate apically, with concomitant increase in chemotactic factor expression recruiting neutrophils. These immune cells play an important role in maintaining homeostasis and the protective state in periodontal tissue because they eliminate unwanted bacteria over time. Previous studies indicate a mechanism for attracting immune cells to periodontal tissue with the purpose of maintaining a protective state; although this mechanism can function without bacteria, it is enhanced by the normal flora. A better understanding of the relationship between the protective state and its disruption in periodontal disease could lead to the development of new treatment strategies for periodontal disease.
Abstract 14417: Cardiovascular Health Decline in Adolescent Girls
Authors: Holly C Gooding, Hongyan Ning, Amanda M Perak, Norrina B Allen, Martha Singer, Donald M Lloyd-Jones, Sarah D De Ferranti
Journal: Circulation (2019)

Introduction: Adolescence is a critical time for the preservation or loss of cardiovascular health (CVH). We aimed to describe trajectories of CVH in adolescent girls ages 9-19 years old and to ide...
CircWAC induces chemotherapeutic resistance in triple-negative breast cancer by targeting miR-142, upregulating WWP1 and activating the PI3K/AKT pathway
Authors: Lei Wang, Yehui Zhou, Liang Jiang, Linlin Lu, Tiantian Dai, Aoshuang Li, Yan Chen, Lifeng Zhang
Journal: Molecular Cancer (2021)

Abstract Background Chemotherapeutic resistance is the main cause of clinical treatment failure and poor prognosis in triple-negative breast cancer (TNBC). There is no research on chemotherapeutic resistance in TNBC from the perspective of circular RNAs (circRNAs). Methods TNBC-related circRNAs were identified based on the GSE101124 dataset. Quantitative reverse transcription PCR was used to detect the expression level of circWAC in TNBC cells and tissues. Then, in vitro and in vivo functional experiments were performed to evaluate the effects of circWAC in TNBC. Results CircWAC was highly expressed in TNBC and was associated with worse TNBC patient prognosis. Subsequently, it was verified that downregulation of circWAC can increase the sensitivity of TNBC cells to paclitaxel (PTX) in vitro and in vivo. The expression of miR-142 was negatively correlated with circWAC in TNBC. The interaction between circWAC and miR-142 in TNBC cells was confirmed by RNA immunoprecipitation assays, luciferase reporter assays, pulldown assays, and fluorescence in situ hybridization. Mechanistically, circWAC acted as a miR-142 sponge to relieve the repressive effect of miR-142 on its target WWP1. In addition, the overall survival of TNBC patients with high expression of miR-142 was significantly better than that of patients with low expression of miR-142, and these results were verified in public databases. MiR-142 regulated the expression of WWP1 and the activity of the PI3K/AKT pathway. It was confirmed that WWP1 is highly expressed in TNBC and that the prognosis of patients with high WWP1 expression is poor. Conclusions CircWAC/miR-142/WWP1 form a competing endogenous RNA (ceRNA) network to regulate PI3K/AKT signaling activity in TNBC cells and affect the chemosensitivity of cells.
Clinical Trials Without Clinical Sites
Authors: Steven R. Cummings
Journal: JAMA Internal Medicine (2021)

Clinical trials conducted at clinical sites are limited to enrolling people who live nearby and are able to attend visits at clinics. Some types of clinical trials can be performed without clinical sites, which enables people to participate regardless of proximity to a clinical site or limitations that make visits difficult. Trials at clinical sites involve face-to-face relationships with in-person collection of informed consent, examinations, data, and specimens. In contrast, without clinical sites, informed consent and data are obtained online, limited examinations can be performed by telemedicine or visiting research nurses, biospecimens can be collected by visiting nurses or local laboratories, and treatments can be sent to homes or administered by nurses in participants' homes. Trials without clinical sites require internet access and must adapt to the lack of face-to-face interactions with study staff, with communication conducted by email, telephone, or video. Many trials cannot be performed entirely without clinical sites because they require examinations, tests, or treatments that must be given at a clinical site. However, some of the methods required for trials without sites, such as online data collection, follow-up visits by telemedicine or research nurses, and delivery of treatments to home, could reduce the need for visits to clinical sites and reduce the burden of participating in a clinical trial. When feasible, conducting clinical trials without clinical sites has the potential to expand participation and the generalizability of their results.
High dose expression of heme oxigenase-1 induces retinal degeneration through ER stress-related DDIT3
Authors: Huirong Li, Bo Liu, Lili Lian, Jiajia Zhou, Shengjin Xiang, Yifan Zhai, Yu Chen, Xiaoyin Ma, Wencan Wu, Ling Hou
Journal: Molecular Neurodegeneration (2021)

Abstract Background Oxidative stress is a common cause of neurodegeneration and plays a central role in retinal degenerative diseases. Heme oxygenase-1 (HMOX1) is a redox-regulated enzyme that is induced in neurodegenerative diseases and acts against oxidative stress but can also promote cell death, a phenomenon that is still unexplained in molecular terms. Here, we test whether HMOX1 has opposing effects during retinal degeneration and investigate the molecular mechanisms behind its pro-apoptotic role. Methods Basal and induced levels of HMOX1 in retinas are examined during light-induced retinal degeneration in mice. Light damage-independent HMOX1 induction at two different expression levels is achieved by intraocular injection of different doses of an adeno-associated virus vector expressing HMOX1. Activation of Müller glial cells, retinal morphology and photoreceptor cell death are examined using hematoxylin-eosin staining, TUNEL assays, immunostaining and retinal function are evaluated with electroretinograms. Downstream gene expression of HMOX1 is analyzed by RNA-seq, qPCR examination and western blotting. The role of one of these genes, the pro-apoptotic DNA damage inducible transcript 3 ( Ddit3 ), is analyzed in a line of knockout mice. Results Light-induced retinal degeneration leads to photoreceptor degeneration and concomitant HMOX1 induction. HMOX1 expression at low levels before light exposure prevents photoreceptor degeneration but expression at high levels directly induces photoreceptor degeneration even without light stress. Photoreceptor degeneration following high level expression of HMOX1 is associated with a mislocalization of rhodopsin in photoreceptors and an increase in the expression of DDIT3. Genetic deletion of Ddit3 in knockout mice prevents photoreceptor cell degeneration normally resulting from high level HMOX1 expression. Conclusion The results reveal that the expression levels determine whether HMOX1 is protective or deleterious in the retina. Furthermore, in contrast to the protective low dose of HMOX1, the deleterious high dose is associated with induction of DDIT3 and endoplasmic reticulum stress as manifested, for instance, in rhodopsin mislocalization. Hence, future applications of HMOX1 or its regulated targets in gene therapy approaches should carefully consider expression levels in order to avoid potentially devastating effects.
TGFβ restricts expansion, survival, and function of T cells within the tuberculous granuloma
Authors: Benjamin H. Gern, Kristin N. Adams, Courtney R. Plumlee, Caleb R. Stoltzfus, Laila Shehata, Albanus O. Moguche, Kathleen Busman-Sahay, Scott G. Hansen, Michael K. Axthelm, Louis J. Picker, Jacob D. Estes, Kevin B. Urdahl, Michael Y. Gerner
Journal: Cell Host & Microbe (2021)
Intraosseous Administration of Multipotent Mesenchymal Stromal Cells to Patients with Graft Failure after Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Nataliya Petinati, Natalia Sats, Nina Drize, Natalia Risinskaya, Andrey Sudarikov, Maya Firsova, Natalia Popova, Daria Dubnyak, Olga Koroleva, Larisa A. Kuzmina, Elena N. Parovichnikova, Valeriy G. Savchenko
Journal: Blood (2017)
Prognostic role of docetaxel-induced reduction of free testosterone serum levels in metastatic prostate cancer patients.
Authors: Paula Kappler, Stefan Brunotte, Philipp Ivanyi, Michael A. Morgan, Christoph W. Reuter
Journal: Journal of Clinical Oncology (2021)

144 Background: We have recently demonstrated that a salvage therapy with carboplatin plus weekly docetaxel is effective in docetaxel-refractory prostate cancer (PC) and interferes with testosterone biosynthesis (Reuter et al.; Oncol Res &amp; Treat. 2018, 41 (suppl.1): p.10). In this study, the impact of docetaxel monotherapy on free and total testosterone serum levels (fT, TT) and the prognostic role of fT and TT were analyzed in mPC patients. Methods: 62 consecutive mPC patients were treated with at least two cycles of docetaxel (75 mg/m2 q3w; 50 mg/m2 q2w, or 35 mg/m2 q1w) until disease progression, occurrence of intolerable adverse effects or completion of the planned cycle number. Efficacy measures were done following PCWG2 recommendations. FT and TT were measured before and during chemotherapy. Results: At the current analysis (August 31, 2020), the median follow-up time was 21.2 months. Response of prostate-specific antigen (PSAR; ≥50% PSA reduction) was observed in 42/62 (67.7%) and 12/36 (33.3%) patients with measurable disease exhibited a partial remission (PR). Median progression-free survival (PFS) for all patients was 8.1 months (CI 95% 3.6, 12.5) and median overall survival (OS) was 25.7 months (CI 95% 19.4, 32.1). The most common reversible grade 3/4 toxicity was leukopenia/neutropenia (29/33.9%). Median fT and TT serum levels were reduced below the detection limit during docetaxel treatment (fT: from 0.34 pg/mL to &lt; 0.01 pg/mL and TT: from 0.12 to &lt; 0.05 ng/mL, respectively). Multivariate Cox regression analyses identified PSAR &gt; 50%, fT reduction of 100% and number of organs involved as independent prognostic risk factors for PFS. Furthermore, fT reduction of 100% and FT nadir values &lt; 0.01 pg/mL were independent prognostic risk factors for OS (p &lt; 0.05). Conclusions: These data demonstrate that fT is an important prognostic factor for PFS and OS in mPC patients.
Identifying Primate ACE2 Variants That Confer Resistance to SARS-CoV-2
Authors: Maloyjo Joyraj Bhattacharjee, Jinn-Jy Lin, Chih-Yao Chang, Yu-Ting Chiou, Tian-Neng Li, Chia-Wei Tai, Tz-Fan Shiu, Chi-An Chen, Chia-Yi Chou, Paromita Chakraborty, Yan Yuan Tseng, Lily Hui-Ching Wang, Wen-Hsiung Li
Journal: Molecular Biology and Evolution (2021)

SARS-CoV-2 infects humans through the binding of viral S-protein (spike protein) to human angiotensin I converting enzyme 2 (ACE2). The structure of the ACE2-S-protein complex has been deciphered and we focused on the 27 ACE2 residues that bind to S-protein. From human sequence databases, we identified nine ACE2 variants at ACE2-S-protein binding sites. We used both experimental assays and protein structure analysis to evaluate the effect of each variant on the binding affinity of ACE2 to S-protein. We found one variant causing complete binding disruption, two and three variants, respectively, strongly and mildly reducing the binding affinity, and two variants strongly enhancing the binding affinity. We then collected the ACE2 gene sequences from 57 nonhuman primates. Among the 6 apes and 20 Old World monkeys (OWMs) studied, we found no new variants. In contrast, all 11 New World monkeys (NWMs) studied share four variants each causing a strong reduction in binding affinity, the Philippine tarsier also possesses three such variants, and 18 of the 19 prosimian species studied share one variant causing a strong reduction in binding affinity. Moreover, one OWM and three prosimian variants increased binding affinity by >50%. Based on these findings, we proposed that the common ancestor of primates was strongly resistant to and that of NWMs was completely resistant to SARS-CoV-2 and so is the Philippine tarsier, whereas apes and OWMs, like most humans, are susceptible. This study increases our understanding of the differences in susceptibility to SARS-CoV-2 infection among primates.
Between-trial heterogeneity in ARDS research
Authors: J. Juschten, P. R. Tuinman, T. Guo, N. P. Juffermans, M. J. Schultz, S. A. Loer, A. R. J. Girbes, H. J. de Grooth
Journal: Intensive Care Medicine (2021)

Most randomized controlled trials (RCTs) in patients with acute respiratory distress syndrome (ARDS) revealed indeterminate or conflicting study results. We aimed to systematically evaluate between-trial heterogeneity in reporting standards and trial outcome. A systematic review of RCTs published between 2000 and 2019 was performed including adult ARDS patients receiving lung-protective ventilation. A random-effects meta-regression model was applied to quantify heterogeneity (non-random variability) and to evaluate trial and patient characteristics as sources of heterogeneity. In total, 67 RCTs were included. The 28-day control-group mortality rate ranged from 10 to 67% with large non-random heterogeneity (I2 = 88%, p < 0.0001). Reported baseline patient characteristics explained some of the outcome heterogeneity, but only six trials (9%) reported all four independently predictive variables (mean age, mean lung injury score, mean plateau pressure and mean arterial pH). The 28-day control group mortality adjusted for patient characteristics (i.e. the residual heterogeneity) ranged from 18 to 45%. Trials with significant benefit in the primary outcome reported a higher control group mortality than trials with an indeterminate outcome or harm (mean 28-day control group mortality: 44% vs. 28%; p = 0.001). Among ARDS RCTs in the lung-protective ventilation era, there was large variability in the description of baseline characteristics and significant unexplainable heterogeneity in 28-day control group mortality. These findings signify problems with the generalizability of ARDS research and underline the urgent need for standardized reporting of trial and baseline characteristics.