tbuckley/cabot-search huggingface dataset:
Effects of Weight Loss on Obstructive Sleep Apnea Severity. Ten-Year Results of the Sleep AHEAD Study
Authors: Samuel T. Kuna, David M. Reboussin, Elsa S. Strotmeyer, Richard P. Millman, Gary Zammit, Michael P. Walkup, Thomas A. Wadden, Rena R. Wing, F. Xavier Pi-Sunyer, Adam P. Spira, Gary D. Foster, Jon Freeman, Jennifer Patricio, Andrea Sifferman, Brian McGuckin, Stephanie Krauthamer-Ewing, Mary Jones-Parker, Matthew Anastasi, Beth Staley, Liz Roben, Marie Kearns, Caitlin Egan, Alexis Wojtanowski, Nida Cassim, Valerie Darcey, Sakhena Hin, Stephanie Vander Veur
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: Weight loss is recommended to treat obstructive sleep apnea (OSA).Objectives: To determine whether the initial benefit of intensive lifestyle intervention (ILI) for weight loss on OSA severity is maintained at 10 years.Methods: Ten-year follow-up polysomnograms of 134 of 264 adults in Sleep AHEAD (Action for Health in Diabetes) with overweight/obesity, type 2 diabetes mellitus, and OSA were randomized to ILI for weight loss or diabetes support and education (DSE).Measurements and Main Results: Change in apnea-hypopnea index (AHI) was measured. Mean ± SE weight losses of ILI participants of 10.7 ± 0.7, 7.4 ± 0.7, 5.1 ± 0.7, and 7.1 ± 0.8 kg at 1, 2, 4, and 10 years, respectively, were significantly greater than the 1-kg weight loss at 1, 2, and 4 years and 3.5 ± 0.8 kg weight loss at 10 years for the DSE group (P values ≤ 0.0001). AHI was lower with ILI than DSE by 9.7, 8.0, and 7.9 events/h at 1, 2, and 4 years, respectively (P values ≤ 0.0004), and 4.0 events/h at 10 years (P = 0.109). Change in AHI over time was related to amount of weight loss, baseline AHI, visit year (P values < 0.0001), and intervention independent of weight change (P = 0.01). OSA remission at 10 years was more common with ILI (34.4%) than DSE (22.2%).Conclusions: Participants with OSA and type 2 diabetes mellitus receiving ILI for weight loss had reduced OSA severity at 10 years. No difference in OSA severity was present between ILI and DSE groups at 10 years. Improvement in OSA severity over the 10-year period with ILI was related to change in body weight, baseline AHI, and intervention independent of weight change.
Reward-Processing Behavior in Depressed Participants Relative to Healthy Volunteers
Authors: D. Chamith Halahakoon, Karel Kieslich, Ciarán O’Driscoll, Akshay Nair, Glyn Lewis, Jonathan P. Roiser
Journal: JAMA Psychiatry (2020)

Dysfunctional reward processing is a leading candidate mechanism for the development of certain depressive symptoms, such as anhedonia. However, to our knowledge, there has not yet been a systematic assessment of whether and to what extent depression is associated with impairments on behavioral reward-processing tasks.To determine whether depression is associated with impairments in reward-processing behavior.The MEDLINE/PubMed, Embase, and PsycInfo databases were searched for studies that investigated reward processing using performance on behavioral tasks by individuals with depression and nondepressed control groups, published between January 1, 1946, and August 16, 2019.Studies that contained data regarding performance by depressed and healthy control groups on reward-processing tasks were included in the systematic review and meta-analysis.Summary statistics comparing performance between depressed and healthy groups on reward-processing tasks were converted to standardized mean difference (SMD) scores, from which summary effect sizes for overall impairment in reward processing and 4 subcomponent categories were calculated. Study quality, heterogeneity, replicability-index, and publication bias were also assessed.Performance on reward-processing tasks.The final data set comprised 48 case-control studies (1387 healthy control individuals and 1767 individuals with major depressive disorder). The mean age was 37.85 years and 58% of the participants were women. These studies used tasks assessing option valuation (n = 9), reward bias (n = 6), reward response vigor (n = 12), reinforcement learning (n = 20), and grip force (n = 1). Across all tasks, depression was associated with small to medium impairments in reward-processing behavior (SMD = 0.345; 95% CI, 0.209-0.480). When examining reward-processing subcomponent categories, impairment was associated with tasks assessing option valuation (SMD = 0.309; 95% CI, 0.147-0.471), reward bias (SMD = 0.644; 95% CI, 0.270-1.017), and reinforcement learning (SMD = 0.352; 95% CI, 0.115-0.588) but not reward response vigor (SMD = 0.083; 95% CI, -0.144 to 0.309). The medication status of the major depressive disorder sample did not explain any of the variance in the overall effect size. There was significant between-study heterogeneity overall and in all subcomponent categories other than option valuation. Significant publication bias was identified overall and in the reinforcement learning category.Relative to healthy control individuals, individuals with depression exhibit reward-processing impairments, particularly for tests of reward bias, option valuation, and reinforcement learning. Understanding the neural mechanisms driving these associations may assist in designing novel interventions.
Reactive oxygen species generation and glutathione depletion in the apoptotic response to salvicine, a novel topoisomerase II inhibitor, in human leukemia K562 cells
Authors: Yu-Jun Cai, Xiong-Wen Zhang, Li-Ping Lin, Jian Ding
Journal: Cancer Research (2005)

1740   Salvicine (SAL) is a novel topoisomerase II inhibitor, synthesized by the structural modification of natural product lead isolated from a Chinese medicinal plant  Salvia prionitis . It exerts potent  in vitro  and  in vivo  anti-tumor effects, and is in phase I clinical trial in China. In the present study, we explored the roles of reactive oxygen species (ROS) and glutathione (GSH) in SAL-mediated apoptosis in K562 cells. Our data revealed that SAL stimulated intracellular H 2 O 2  generation and GSH depletion, and subsequently elicited notable DNA double-strand breaks (DSBs) and the apoptotic cell death in K562 cells. SAL resulted in activation of ROS-related proteins JNK and p38 MAPK, and mitochondrial-dependent apoptosis. SAL also down-regulated DSBs repair proteins Ku70, Ku86 and Rad51 levels through its apoptotic pathway. Furthermore, SAL mediated DSBs in a concentration-dependent manner. The DSBs of SAL was much prior to apoptosis induction. SAL significantly stimulated intracellular H 2 O 2  generation and GSH depletion in the early stage. Thiol antioxidants, such as  N -Acetylcysteine (NAC) and GSH, and a special H 2 O 2  inhibitor, catalase (CAT), but not other antioxidants, such as SOD, Trolox, BHA, ascorbic acid, EGCG and diphenylene iodonium (DPI), significantly inhibited SAL-mediated H 2 O 2  level increase, DSBs and apoptosis. These thiol antioxidants also attenuated SAL-mediated JNK and p38 MAPK activation, and the change of apoptosis-related proteins and DSBs repair proteins. These results identify a novel mechanism that H 2 O 2  generation and GSH depletion play critical roles in SAL-mediated DSBs and apoptosis in K562 cells. Additionally, we propose that GSH relox systems are associated with SAL mediated-H 2 O 2  generation and GSH depletion. Recently, we have reported that SAL is cytotoxic for multidrug resistance (MDR) tumor cells and down-regulates  mdr-1 expression in MDR K562/A02 cells (Miao Z. H. and Ding J. (2003)  Cancer Res . 63, 4527-4532). In this study, we also investigated the roles of ROS and GSH in SAL-mediated DSBs and apoptosis in MDR K562/A02 cells. SAL provided similar effects and mechanisms in both MDR and parental K562 cells, further demonstrating the effects of SAL against MDR tumor cells.
Arginase impedes the resolution of colitis by altering the microbiome and metabolome
Authors: Julia Baier, Maximilian Gänsbauer, Claudia Giessler, Harald Arnold, Mercedes Muske, Ulrike Schleicher, Sören Lukassen, Arif Ekici, Manfred Rauh, Christoph Daniel, Arndt Ha rtmann, Benjamin Schmid, Philipp Tripal, Katja Dettmer, Peter J. Oefner, Raja Atreya, Stefan Wirtz, Christian Bogdan, Jochen Mattner
Journal: Journal of Clinical Investigation (2020)

Arginase 1 (Arg1), which converts l-arginine into ornithine and urea, exerts pleiotropic immunoregulatory effects. However, the function of Arg1 in inflammatory bowel disease (IBD) remains poorly characterized. Here, we found that Arg1 expression correlated with the degree of inflammation in intestinal tissues from IBD patients. In mice, Arg1 was upregulated in an IL-4/IL-13- and intestinal microbiota-dependent manner. Tie2-Cre Arg1fl/fl mice lacking Arg1 in hematopoietic and endothelial cells recovered faster from colitis than Arg1-expressing (Arg1fl/fl) littermates. This correlated with decreased vessel density, compositional changes in intestinal microbiota, diminished infiltration by myeloid cells, and an accumulation of intraluminal polyamines that promote epithelial healing. The proresolving effect of Arg1 deletion was reduced by an l-arginine-free diet, but rescued by simultaneous deletion of other l-arginine-metabolizing enzymes, such as Arg2 or Nos2, demonstrating that protection from colitis requires l-arginine. Fecal microbiota transfers from Tie2-Cre Arg1fl/fl mice into WT recipients ameliorated intestinal inflammation, while transfers from WT littermates into Arg1-deficient mice prevented an advanced recovery from colitis. Thus, an increased availability of l-arginine as well as altered intestinal microbiota and metabolic products accounts for the accelerated resolution from colitis in the absence of Arg1. Consequently, l-arginine metabolism may serve as a target for clinical intervention in IBD patients.
Vania Hungria—treating myeloma with restricted resources
Authors: Tony Kirby
Journal: The Lancet Haematology (2020)

A love of sport almost saw Vania Hungria become a physical education teacher. "But at university I soon realised doing sport and teaching sport were not the same thing!" Hungria tells The Lancet Haematology. She then transferred to a medical degree at the Santa Casa de São Paulo Medical School (Sao Paulo, Brazil), where she realised her interest lay more in clinical medicine than surgical disciplines. "During my residency at Santa Casa Hospital, I got to work with and bond with many young patients with leukaemia.
Prognostic value of the genomic grade index (GGi) as compared to centrally measured Ki-67 IHC and mitotic index in early breast cancer patients
Authors: F. Bertucci, J. M. Le Doussal, D. Birnbaum, R. Tagett, A. Martinec, F. Hermitte, L. Marisa, A. L. Martin, J. Geneve, H. Roché, F. Penault-Llorca
Journal: Journal of Clinical Oncology (2009)

11094 Background: Genomic grading has been proposed to improve tumor grading. The genomic grade index (GGi) is a 97-gene continuous measure which resolves 80% of histological grade 2 (HG 2) tumors into HG 1 and HG 3 risk categories. GGi has higher prognostic value than HG in patients treated with and without systemic adjuvant endocrine and chemotherapy. A key issue is whether the GGi adds prognostic information to centrally-determined mitotic index and Ki-67 IHC. Methods: The control arm of the PACS 01 trial included 996 women with node-positive (N+) early breast cancer treated with six cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC) and tamoxifen as required. 128 genomic profiles could be obtained from available frozen tumor samples using Affymetrix U133 Plus 2.0 gene chips through the “Carte d'Identite des Tumeurs” program of the French Ligue Nationale contre le Cancer. The Genomic Grade index (GGi) was computed using Ipsogen MapQuant Dx(R). Central Elston-Ellis grade, mitotic index (mitosis / mm2), and Ki-67 IHC (% positive cells) were available for 125 patients. The GGi and histological parameters were correlated to the 5-year metastasis status (MFS-5) by ROC analysis and to the metastasis hazard (follow-up of 6.2 ± years) by Cox regression. Results: In ER+ patients (n=93), the GGi was the only significant correlate to metastasis hazard in multivariate Cox regression with histological parameters (HR = 3.5 [1.7–7.5], p&lt;0.001). It was the best predictor of MFS-5 (ROC AUC = 0.83, p=1E-6) when compared to histological parameters (ROC AUC = 0.71, 0.72 and 0.66 resp. p=0.003 to 0.03). In HG 2 subgroup (n=43), the GGi was the only significant predictor of MFS-5 (ROC AUC = 0.81, p=0.016). Conclusions: In our sample of N+ ER+ breast cancer patients, the GGi improved prognostication compared to centrally-measured mitotic index and Ki-67 IHC used alone and in combination. Moreover, the GGi was the only prognostic factor in histological grade 2 patients. [Table: see text]
Assessment of Community-Level Disparities in Coronavirus Disease 2019 (COVID-19) Infections and Deaths in Large US Metropolitan Areas
Authors: Samrachana Adhikari, Nicholas P. Pantaleo, Justin M. Feldman, Olugbenga Ogedegbe, Lorna Thorpe, Andrea B. Troxel
Journal: JAMA Network Open (2020)

Farhaan S. Vahidy, PhD, MBBS, MPH; Ashley L. Drews, MD; Faisal N. Masud, MD; Roberta L. Schwartz, PhD; Belimat "Billy" Askary, MA; Marc L. Boom, MD; Robert A. Phillips, MD, PhD
Sterol-O-acyltransferase-1 has a role in kidney disease associated with diabetes and Alport syndrome
Authors: Xiaochen Liu, Gloria Michelle Ducasa, Shamroop Kumar Mallela, Jin-Ju Kim, Judith Molina, Alla Mitrofanova, Sydney Symone Wilbon, Mengyuan Ge, Antonio Fontanella, Christopher Pedigo, Javier Varona Santos, Robert G. Nelson, Yelena Drexler, Gabriel Contreras, Hassan Al-Ali, Sandra Merscher, Alessia Fornoni
Journal: Kidney International (2020)
Fusion of the CRM1 nuclear export receptor to AF10 causes leukemia and transcriptional activation of HOXA genes
Authors: Waitman K. Aumann, Jessica L. Heath, Amanda E. Conway, Sei-Gyung Kim Sze, Veerain K. Gupta, Rafi R. Kazi, Donald R. Tope, Daniel S. Wechsler, Catherine P. Lavau
Journal: Leukemia (2020)
From blockbuster to “nichebuster”: how a flawed legislation helped create a new profit model for the drug industry
Authors: Daan Marselis, Lucien Hordijk
Journal: BMJ (2020)

Twenty years ago, the EU passed a law to motivate the drug industry to develop medicines for rare diseases. But a system intended to help patients with neglected maladies primarily turned into a corporate cash machine. <b>Daan Marselis</b> and <b>Lucien Hordijk</b> report
Emerging evidence of a COVID-19 thrombotic syndrome has treatment implications
Authors: Joan T. Merrill, Doruk Erkan, Jerald Winakur, Judith A. James
Journal: Nature Reviews Rheumatology (2020)

Reports of widespread thromboses and disseminated intravascular coagulation (DIC) in patients with coronavirus disease 19 (COVID-19) have been rapidly increasing in number. Key features of this disorder include a lack of bleeding risk, only mildly low platelet counts, elevated plasma fibrinogen levels, and detection of both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and complement components in regions of thrombotic microangiopathy (TMA). This disorder is not typical DIC. Rather, it might be more similar to complement-mediated TMA syndromes, which are well known to rheumatologists who care for patients with severe systemic lupus erythematosus or catastrophic antiphospholipid syndrome. This perspective has critical implications for treatment. Anticoagulation and antiviral agents are standard treatments for DIC but are gravely insufficient for any of the TMA disorders that involve disorders of complement. Mediators of TMA syndromes overlap with those released in cytokine storm, suggesting close connections between ineffective immune responses to SARS-CoV-2, severe pneumonia and life-threatening microangiopathy.
Distinct Early Serological Signatures Track with SARS-CoV-2 Survival
Authors: Caroline Atyeo, Stephanie Fischinger, Tomer Zohar, Matthew D. Slein, John Burke, Carolin Loos, Denise J. McCulloch, Kira L. Newman, Caitlin Wolf, Jingyou Yu, Kiel Shuey, Jared Feldman, Blake Marie Hauser, Tim Caradonna, Aaron G. Schmidt, Todd J. Suscovich, Caitlyn Linde, Yongfei Cai, Dan Barouch, Edward T. Ryan, Richelle C. Charles, Douglas Lauffenburger, Helen Chu, Galit Alter
Journal: Immunity (2020)

As SARS-CoV-2 infections and death counts continue to rise, it remains unclear why some individuals recover from infection, whereas others rapidly progress and die. Although the immunological mechanisms that underlie different clinical trajectories remain poorly defined, pathogen-specific antibodies often point to immunological mechanisms of protection. Here, we profiled SARS-CoV-2-specific humoral responses in a cohort of 22 hospitalized individuals. Despite inter-individual heterogeneity, distinct antibody signatures resolved individuals with different outcomes. Although no differences in SARS-CoV-2-specific IgG levels were observed, spike-specific humoral responses were enriched among convalescent individuals, whereas functional antibody responses to the nucleocapsid were elevated in deceased individuals. Furthermore, this enriched immunodominant spike-specific antibody profile in convalescents was confirmed in a larger validation cohort. These results demonstrate that early antigen-specific and qualitative features of SARS-CoV-2-specific antibodies point to differences in disease trajectory, highlighting the potential importance of functional antigen-specific humoral immunity to guide patient care and vaccine development.
SUMOylation of Enzymes and Ion Channels in Sensory Neurons Protects against Metabolic Dysfunction, Neuropathy, and Sensory Loss in Diabetes
Authors: Nitin Agarwal, Francisco J. Taberner, Daniel Rangel Rojas, Mirko Moroni, Damir Omberbasic, Christian Njoo, Alexandra Andrieux, Pooja Gupta, Kiran K. Bali, Esther Herpel, Faramarz Faghihi, Thomas Fleming, Anne Dejean, Stefan G. Lechner, Peter P. Nawroth, Gary R. Lewin, Rohini Kuner
Journal: Neuron (2020)
Abstract 164: Comparison of Tracheal Intubation vs. Supraglottic Airway Following Pediatric Out of Hospital Cardiac Arrest
Authors: Maryam Y Naim, Heather Griffis, Robert A Berg, Richard N Bradley, Matthew L Hansen, David Markenson, Bryan F McNally, Vinay M Nadkarni, Kimberly Vellano, Joseph W Rossano
Journal: Circulation (2018)

Introduction: There are few data comparing Tracheal Intubation (TI) and SupraGlottic Airway (SGA) following pediatric out of hospital cardiac arrest (OHCA). Hypothesis: TI is associated with improved outcomes compared to SGA following pediatric OHCA. Methods: Analysis of the Cardiac Arrest Registry to Enhance Survival database. Inclusion criteria were age ≤ 18 years, non-traumatic OHCA from 2013 through 2017, resuscitated by Emergency Medical Services (EMS). To adjust for covariate imbalance, propensity score matching and entropy balancing were utilized; variables included age category, sex, bystander CPR, and initial rhythm. Primary outcome was neurologically favorable survival defined as a cerebral performance category scale of 1 or 2. Secondary outcome was survival to hospital discharge. Results: Of 2653 cardiac arrests evaluated, 2178 (82.1%) had TI and 475 (17.9%) had SGA placed during OHCA. 835 (31.2%) arrests were resuscitated by agencies used bag valve mask (BVM) and TI and 1818 (68.0%) arrests had agencies that used all 3 airway types (BVM/TI/SGA). Overall, unadjusted favorable neurological survival was 5.7% for TI and 5.3% for SGA, p=0.67 and survival to hospital discharge was 7.9% for TI and 7.5% for SGA, p=0.73. In multivariable analysis (adjusting for age, sex, race/ethnicity, bystander witness, bystander CPR, initial rhythm, AED use, year of arrest, and agency category), SGA was associated with lower neurologically favorable survival compared to TI (adjusted proportion 3.7% vs. 6.3%, OR 0.49, p=0.01), and lower survival to hospital discharge (5.5% vs. 8.5%, OR 0.57, 95% CI 0.36, 0.89). These results were robust on tests for unmeasured confounding and covariate balance; propensity analysis neurologically favorable survival 4.4% vs.7.6% (OR 0.54, 95% CI 0.30, 0.96), survival to hospital discharge 6.6% vs.10.5% (OR 0.58, 95% CI 0.35, 0.95); and entropy balance neurologically favorable survival 5.0 % vs. 9.7% for ETI (OR 0.44, 95% CI 0.27, 0.72), survival to hospital discharge 7.3% vs.12.5% (OR 0.51, 95% CI 0.34, 0.78). Conclusion: In pediatric OHCA, TI, compared with SGA advanced airway management is associated with improved neurologically favorable survival and survival to hospital discharge.
AB0900 FREQUENCY OF LOCAL COMPLICATIONS AFTER TOTAL HIP ARTHROPLASTY IN PATIENTS WITH RHEUMATIC DISEASES.
Authors: A. Khramov, M. Makarov, S. Makarov, E. Naryshkin, S. Maglevaniy
Journal: Annals of the Rheumatic Diseases (2020)

Background: Surgical treatment of patients with rheumatic diseases (RD) is associated with an increased risk of complications. It is caused by presence of an inflammatory process, osteoporosis, reduced physical activity, severity of functional impairment, long-term glucocorticoid therapy, biological and disease-modifying antirheumatic drugs. All this provides elongated wound healing period, the development of infectious complications and increased risk of periprosthetic fractures. Objectives: To study a frequency of local complications of total hip arthroplasty (THA) in patients with inflammatory RD and osteoarthritis (OA). Methods: We analyzed 1591 THA, which were performed to RD patients between 2000 and 2019 years. Results: We performed 882 arthroplasties in patients with inflammatory RD, which consisted of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), juvenile rheumatoid arthritis (JRA), ankylosing spondylitis (AS), systemic scleroderma (SSD), and also 709 operations in OA patients. Local complications after THA were 120 (7.54%), of these 83 (9.41%) in patients with inflammatory RD and 37 (5.22%) in OA patients. We revealed a significantly greater number of complications in patients with inflammatory RD (p&lt;0.005). Conclusion: Inflammatory RD (RA, SLE, JRA, AS, SSD) patients have local complications after THA (9.41%) 1.8 times more often than OA patients (5.22%). It shows that the operative treatment of patients with RD requires a special approach, management and careful treatment of the bone and surrounding tissues during surgery. Disclosure of Interests: None declared
Reduced Nogo expression inhibits diet-induced metabolic disorders by regulating ChREBP and insulin activity
Authors: Shuang Zhang, Fangling Guo, Miao Yu, Xiaoxiao Yang, Zhi Yao, Qi Li, Zhuo Wei, Ke Feng, Peng Zeng, Dan Zhao, Xiaoju Li, Yan Zhu, Qing Robert Miao, Yasuko Iwakiri, Yuanli Chen, Jihong Han, Yajun Duan
Journal: Journal of Hepatology (2020)