tbuckley/cabot-search huggingface dataset:
Adiponectin-mimetic novel nonapeptide rescues aberrant neuronal metabolic-associated memory deficits in Alzheimer’s disease
Authors: Tahir Ali, Shafiq Ur Rehman, Amjad Khan, Haroon Badshah, Noman Bin Abid, Min Woo Kim, Myeung Hoon Jo, Seung Soo Chung, Hyoung-gon Lee, Bart P. F. Rutten, Myeong Ok Kim
Journal: Molecular Neurodegeneration (2021)

Abstract Background Recently, we and other researchers reported that brain metabolic disorders are implicated in Alzheimer’s disease (AD), a progressive, devastating and incurable neurodegenerative disease. Hence, novel therapeutic approaches are urgently needed to explore potential and novel therapeutic targets/agents for the treatment of AD. The neuronal adiponectin receptor 1 (AdipoR1) is an emerging potential target for intervention in metabolic-associated AD. We aimed to validate this hypothesis and explore in-depth the therapeutic effects of an osmotin-derived adiponectin-mimetic novel nonapeptide (Os-pep) on metabolic-associated AD. Methods We used an Os-pep dosage regimen (5 μg/g, i.p., on alternating days for 45 days) for APP/PS1 in amyloid β oligomer-injected, transgenic adiponectin knockout (Adipo−/−) and AdipoR1 knockdown mice. After behavioral studies, brain tissues were subjected to biochemical and immunohistochemical analyses. In separate cohorts of mice, electrophysiolocal and Golgi staining experiments were performed. To validate the in vivo studies, we used human APP Swedish (swe)/Indiana (ind)-overexpressing neuroblastoma SH-SY5Y cells, which were subjected to knockdown of AdipoR1 and APMK with siRNAs, treated with Os-pep and other conditions as per the mechanistic approach, and we proceeded to perform further biochemical analyses. Results Our in vitro and in vivo results show that Os-pep has good safety and neuroprotection profiles and crosses the blood-brain barrier. We found reduced levels of neuronal AdipoR1 in human AD brain tissue. Os-pep stimulates AdipoR1 and its downstream target, AMP-activated protein kinase (AMPK) signaling, in AD and Adipo−/− mice. Mechanistically, in all of the in vivo and in vitro studies, Os-pep rescued aberrant neuronal metabolism by reducing neuronal insulin resistance and activated downstream insulin signaling through regulation of AdipoR1/AMPK signaling to consequently improve the memory functions of the AD and Adipo−/− mice, which was associated with improved synaptic function and long-term potentiation via an AdipoR1-dependent mechanism. Conclusion Our findings show that Os-pep activates AdipoR1/AMPK signaling and regulates neuronal insulin resistance and insulin signaling, which subsequently rescues memory deficits in AD and adiponectin-deficient models. Taken together, the results indicate that Os-pep, as an adiponectin-mimetic novel nonapeptide, is a valuable and promising potential therapeutic candidate to treat aberrant brain metabolism associated with AD and other neurodegenerative diseases.
Abstract 16418: Physical Frailty Phenotype and Development of Geriatric Syndromes in Older Adults With Coronary Heart Disease
Authors: Abdulla A Damluji, Shang-En Chung, Qian-Li Xue, Rani K Hasan, Daniel E Forman, Wayne Batchelor, Jon R Resar, Gary Gerstenblith
Journal: Circulation (2020)

Introduction: Frailty, a clinical state of vulnerability, is associated with subsequent adverse geriatric syndromes in the general population. Hypothesis: We hypothesized that frailty influence health outcomes among older patients with coronary heart disease (CHD). Methods: We used the National Health and Aging Trends Study, a prospective cohort study linked to a Medicare sample. CHD was identified by self-report and/or ICD codes one-year prior to the baseline visit. Frailty was measured using the Fried physical frailty phenotype (PFP). Geriatric outcomes were assessed during five-year follow-up. Results: Of the 4,656 study participants, 1,395 (28%) had a history of CHD one-year prior to their baseline visit. Compared to those without frailty, subjects with frailty were older (Age ≥75: 69.9% vs. 57.1%, p &lt;0.001), more likely to be female, belong to an ethnic minority, and had lower BMI. The prevalence of hypertension, stroke, falls, disability, anxiety/depression, and multimorbidity were much higher in the frail, than non-frail, participants. In a multivariable Cox regression model, the incidences of geriatric syndromes including (1) dementia, (2) loss of independence, (3) impairment in activities of daily living, (4) impairment in instrumental activities of daily living (ADLs), (5) and mobility disability were significantly higher in the frail, than in the non-frail CHD Conclusion: Among patients with CHD, frailty is a risk factor for accelerated development of geriatric outcomes. Efforts to identify frailty in the context of CHD are needed, as well as interventions to limit or reverse frailty status in CHD patients.
Impact of chronic use of heat-not-burn cigarettes on oxidative stress, endothelial dysfunction and platelet activation: the SUR-VAPES Chronic Study
Authors: Lorenzo Loffredo, Roberto Carnevale, Simona Battaglia, Roberta Marti, Stefano Pizzolo, Simona Bartimoccia, Cristina Nocella, Vittoria Cammisotto, Sebastiano Sciarretta, Isotta Chimenti, Elena De Falco, Elena Cavarretta, Mariangela Peruzzi, Antonino Marullo, Fabio Miraldi, Francesco Violi, Andrea Morelli, Giuseppe Biondi-Zoccai, Giacomo Frati
Journal: Thorax (2021)

Tobacco habit still represents the leading preventable cause of morbidity and mortality worldwide. Heat-not-burn cigarettes (HNBCs) are considered as an alternative to traditional combustion cigarettes (TCCs) due to the lack of combustion and the absence of combustion-related specific toxicants. The aim of this observational study was to assess the effect of HNBC on endothelial function, oxidative stress and platelet activation in chronic adult TCC smokers and HNBC users. The results showed that both HNBC and TCC display an adverse phenotype in terms of endothelial function, oxidative stress and platelet activation. Future randomised studies are strongly warranted to confirm these data.
Physical inactivity is associated with a higher risk for severe COVID-19 outcomes: a study in 48 440 adult patients
Authors: Robert Sallis, Deborah Rohm Young, Sara Y Tartof, James F Sallis, Jeevan Sall, Qiaowu Li, Gary N Smith, Deborah A Cohen
Journal: British Journal of Sports Medicine (2021)

To compare hospitalisation rates, intensive care unit (ICU) admissions and mortality for patients with COVID-19 who were consistently inactive, doing some activity or consistently meeting physical activity guidelines.We identified 48 440 adult patients with a COVID-19 diagnosis from 1 January 2020 to 21 October 2020, with at least three exercise vital sign measurements from 19 March 2018 to 18 March 2020. We linked each patient's self-reported physical activity category (consistently inactive=0-10 min/week, some activity=11-149 min/week, consistently meeting guidelines=150+ min/week) to the risk of hospitalisation, ICU admission and death after COVID-19 diagnosis. We conducted multivariable logistic regression controlling for demographics and known risk factors to assess whether inactivity was associated with COVID-19 outcomes.Patients with COVID-19 who were consistently inactive had a greater risk of hospitalisation (OR 2.26; 95% CI 1.81 to 2.83), admission to the ICU (OR 1.73; 95% CI 1.18 to 2.55) and death (OR 2.49; 95% CI 1.33 to 4.67) due to COVID-19 than patients who were consistently meeting physical activity guidelines. Patients who were consistently inactive also had a greater risk of hospitalisation (OR 1.20; 95% CI 1.10 to 1.32), admission to the ICU (OR 1.10; 95% CI 0.93 to 1.29) and death (OR 1.32; 95% CI 1.09 to 1.60) due to COVID-19 than patients who were doing some physical activity.Consistently meeting physical activity guidelines was strongly associated with a reduced risk for severe COVID-19 outcomes among infected adults. We recommend efforts to promote physical activity be prioritised by public health agencies and incorporated into routine medical care.
U-Sleep: resilient high-frequency sleep staging
Authors: Mathias Perslev, Sune Darkner, Lykke Kempfner, Miki Nikolic, Poul Jørgen Jennum, Christian Igel
Journal: npj Digital Medicine (2021)

Sleep disorders affect a large portion of the global population and are strong predictors of morbidity and all-cause mortality. Sleep staging segments a period of sleep into a sequence of phases providing the basis for most clinical decisions in sleep medicine. Manual sleep staging is difficult and time-consuming as experts must evaluate hours of polysomnography (PSG) recordings with electroencephalography (EEG) and electrooculography (EOG) data for each patient. Here, we present U-Sleep, a publicly available, ready-to-use deep-learning-based system for automated sleep staging ( sleep.ai.ku.dk ). U-Sleep is a fully convolutional neural network, which was trained and evaluated on PSG recordings from 15,660 participants of 16 clinical studies. It provides accurate segmentations across a wide range of patient cohorts and PSG protocols not considered when building the system. U-Sleep works for arbitrary combinations of typical EEG and EOG channels, and its special deep learning architecture can label sleep stages at shorter intervals than the typical 30 s periods used during training. We show that these labels can provide additional diagnostic information and lead to new ways of analyzing sleep. U-Sleep performs on par with state-of-the-art automatic sleep staging systems on multiple clinical datasets, even if the other systems were built specifically for the particular data. A comparison with consensus-scores from a previously unseen clinic shows that U-Sleep performs as accurately as the best of the human experts. U-Sleep can support the sleep staging workflow of medical experts, which decreases healthcare costs, and can provide highly accurate segmentations when human expertize is lacking.
Sample pooling: burden or solution?
Authors: Nadja Grobe, Alhaji Cherif, Xiaoling Wang, Zijun Dong, Peter Kotanko
Journal: Clinical Microbiology and Infection (2021)

Pool-testing strategies combine samples from multiple people and test them as a group. A pool-testing approach may shorten the screening time and increase the test rate during times of limited test availability and inadequate reporting speed. Pool testing has been effectively used for a wide variety of infectious disease screening settings. Historically, it originated from serological testing in syphilis. During the current coronavirus disease 2019 (COVID-19) pandemic, pool testing is considered across the globe to inform opening strategies and to monitor infection rates after the implementation of interventions.
Age as a prognostic factor in small cell lung cancer: a pooled analysis of randomized clinical trials from the Manchester lung cancer group (MLCG) and theUK medical research council clinical trials unit (MRC CTU)
Authors: Paul Wheatley-Price, Elham Sabri, Linda Ashcroft, Shane White, Paul Lorigan, Nicholas Thatcher, Fiona Blackhall
Journal: Journal of Thoracic Oncology (2013)
'uncovered COVID': The addition of a clinicoradiological pre-follow up multidisciplinary team review improves the provision of followup pathways in COVID-19
Authors: J. Rossdale, A. Dereham, E. Peter, R. Tan, G. Robinson, T. Hartley, J. Suntharalingam, J. Rodrigues
Journal: Gut (2021)

Introductions and Objectives BTS guidelines advise that patients with a clinico-radiological diagnosis of COVID-19 undergo follow-up based on severity of disease: either Group 1 (required ICU/HDU admission or significant respiratory support), or Group 2 (any other admitted patients)  The BTS guidelines themselves address concerns that delivering this follow-up might prove difficult due to disrupted working patterns and large caseloads  To address these concerns, we established a post-COVID-19 Pre-Follow Up Multi- Disciplinary Team (pre-FU-MDT)  We have reviewed its impact on COVID-19 follow-up streams  Methods To capture all relevant patients we cross-referenced a list of all RT-PCR swabs sent for symptomatic purposes against those who had a recent CXR  The CXR reports, coded in real time, were used to establish a list of patients who had CXRs consistent with or indeterminate for COVID- 19 pneumonia  The database was screened by a specialist respiratory nurse who assigned follow-up streams based on level of respiratory support required and CXR report  All Group 1, Group 2 and Indeterminate cases were discussed at MDT, which consisted of a consultant respiratory physician and a thoracic radiologist  Cases were discussed with discharge summaries, results and imaging  Follow-up streams were reallocated as necessary  Time for MDT was re-allocated from services reduced during the pandemic  Results Of 1532 'symptomatic' swabs, there were 495 patients with a potential clinico-radiological diagnosis of COVID-19 pneumonia discussed at the Pre-FU-MDT  We performed a subgroup analysis on 392 consecutive cases (Table 1)  The pre-FU-MDT changed the follow-up pathway in 21% of non-indeterminate cases (23/108)  Follow up was ceased in 5% (17/108)  Patients with indeterminate CXRs represented the largest cohort  The pre-FU-MDT ceased follow-up in 57% (150/261) and the remaining 43% (111/261) were stratified to Group 1, Group 2 or other appropriate non- COVID follow up  Conclusions A Pre-FU-MDT has significant clinical impact  By redistributing clinicians' time, an efficient mechanism has been created to reduce unnecessary CXRs and clinic appointments, and focus on those most likely to require follow-up  Review of our follow-up outcomes is ongoing and the results will be available at the time of the BTS meeting
An update on the regulatory mechanisms of NLRP3 inflammasome activation
Authors: Seungwha Paik, Jin Kyung Kim, Prashanta Silwal, Chihiro Sasakawa, Eun-Kyeong Jo
Journal: Cellular and Molecular Immunology (2021)

Abstract The NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome is a multiprotein complex involved in the release of mature interleukin-1β and triggering of pyroptosis, which is of paramount importance in a variety of physiological and pathological conditions. Over the past decade, considerable advances have been made in elucidating the molecular mechanisms underlying the priming/licensing (Signal 1) and assembly (Signal 2) involved in NLRP3 inflammasome activation. Recently, a number of studies have indicated that the priming/licensing step is regulated by complicated mechanisms at both the transcriptional and posttranslational levels. In this review, we discuss the current understanding of the mechanistic details of NLRP3 inflammasome activation with a particular emphasis on protein-protein interactions, posttranslational modifications, and spatiotemporal regulation of the NLRP3 inflammasome machinery. We also present a detailed summary of multiple positive and/or negative regulatory pathways providing upstream signals that culminate in NLRP3 inflammasome complex assembly. A better understanding of the molecular mechanisms underlying NLRP3 inflammasome activation will provide opportunities for the development of methods for the prevention and treatment of NLRP3 inflammasome-related diseases.
Plasma‐Functionalized Isotactic Polypropylene Assembled with Conducting Polymers for Bacterial Quantification by NADH Sensing
Authors: Brenda G. Molina, Luis J. del Valle, Jordi Casanovas, Sonia Lanzalaco, Maria M. Pérez‐Madrigal, Pau Turon, Elaine Armelin, Carlos Alemán
Journal: Advanced Healthcare Materials (2021)

Abstract Rapid detection of bacterial presence on implantable medical devices is essential to prevent biofilm formation, which consists of densely packed bacteria colonies able to withstand antibiotic‐mediated killing. In this work, a smart approach is presented to integrate electrochemical sensors for detecting bacterial infections in biomedical implants made of isotactic polypropylene (i‐PP) using chemical assembly. The electrochemical detection is based on the capacity of conducting polymers (CPs) to detect extracellular nicotinamide adenine dinucleotide (NADH) released from cellular respiration of bacteria, which allows distinguishing prokaryotic from eukaryotic cells. Oxygen plasma‐functionalized free‐standing i‐PP, coated with a layer (≈1.1 µm in thickness) of CP nanoparticles obtained by oxidative polymerization, is used as working electrode for the anodic polymerization of a second CP layer (≈8.2 µm in thickness), which provides very high electrochemical activity and stability. The resulting layered material, i‐PP f /CP 2 , detects the electro‐oxidation of NADH in physiological media with a sensitivity 417 µA cm −2 and a detection limit up to 0.14 × 10 −3 m , which is below the concentration of extracellular NADH found for bacterial cultures of biofilm‐positive and biofilm‐negative strains.
Covid-19: Rare immune response may cause clots after AstraZeneca vaccine, say researchers
Authors: Jacqui Wise
Journal: BMJ (2021)

Covid-19: Rare immune response may cause clots after AstraZeneca vaccine, say researchers Jacqui WiseTwo teams of researchers have published detailed observations of patients who developed thrombotic thrombocytopenia after receiving the AstraZeneca vaccine and have speculated about a possible mechanism.
Corrigendum to ‘Acute myeloid leukaemia in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up’
Authors: M. Heuser, Y. Ofran, N. Boissel, S. Brunet Mauri, C. Craddock, J. Janssen, A. Wierzbowska, C. Buske
Journal: Annals of Oncology (2021)
Association of Postoperative Infections After Fractures With Long-term Income Among Adults
Authors: Nathan N. O’Hara, C. Daniel Mullins, Gerard P. Slobogean, Anthony D. Harris, Dionne S. Kringos, Niek S. Klazinga
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Postoperative infections after a fracture exert tremendous costs on the health care system. However, the patient economic burden associated with a postoperative infection is unclear. <h3>Objective</h3> To evaluate the association between a postoperative infection and long-term income among patients with surgically treated fractures. <h3>Design, Setting, and Participants</h3> A retrospective cohort study linked academic trauma center data with Maryland tax records using inverse probability of treatment weighting to estimate between-group differences among 11 673 adults who underwent surgery to treat fractures of the extremities or pelvis between January 1, 2003, and December 31, 2016. Statistical analysis was performed from November 5, 2019, to August 30, 2020. <h3>Exposure</h3> A postoperative infection within 1 year of injury. <h3>Main Outcomes and Measures</h3> The primary outcome was the annual household income up to 6 years after injury. Household income incorporates multiple types of income, including wage earnings, taxable Social Security benefits, workers' compensation, and disability benefits. Secondary outcomes included individual earnings, Social Security benefits, unemployment benefits, and catastrophic income loss. <h3>Results</h3> The study included 11 673 patients (7756 male patients [66.4%]; mean [SD] age, 45.2 [19.2] years) with a mean (SD) preinjury household income of $30 505 ($89 030). A total of 403 patients (3.5%) had a postoperative infection. Postoperative infections were associated with a $6080 annual decrease (95% CI, −$12 114 to −$47;<i>P</i> = .048) in household income in the 6 years after injury. Postoperative infections were associated with a 6.6% increase (95% CI, 4.9%-8.3%;<i>P</i> &lt; .001) in the risk of catastrophic wage loss within 2 years of the fracture and were associated with a 45% increase in the odds of receiving Social Security benefits (odds ratio, 1.45; 95% CI, 1.25-1.68;<i>P</i> &lt; .001). However, incurring a postoperative infection was not associated with an increase in the value of the Social Security benefits received. <h3>Conclusions and Relevance</h3> This study suggests that postoperative infections have significant and sustained income-associated implications for patients who experience a fracture. Current Social Security mechanisms may not offset the decreased income.
Imaging <i>Enterobacterales</i> infections in patients using pathogen-specific positron emission tomography
Authors: Alvaro A. Ordonez, Luz M. Wintaco, Filipa Mota, Andres F. Restrepo, Camilo A. Ruiz-Bedoya, Carlos F. Reyes, Luis G. Uribe, Sudhanshu Abhishek, Franco R. D’Alessio, Daniel P. Holt, Robert F. Dannals, Steven P. Rowe, Victor R. Castillo, Martin G. Pomper, Ulises Granados, Sanjay K. Jain
Journal: Science Translational Medicine (2021)

18 F-FDS PET/CT can detect and localize infections due to Enterobacterales in patients and noninvasively monitor response to antibiotic treatment.
Endoscopic ultrasound-guided liver biopsy: down but not out
Authors: Nadeem Akhter Tehami, Keith Siau, Ryan Buchanan, Eleanor Jaynes, Ben Maher
Journal: Gut (2021)

The paper by Bang et al 1 is a much-needed randomised study, which concluded that conventional ultrasound-guided percutaneous liver biopsy was superior to the relatively new endoscopic ultrasound (EUS)-guided approach. We wish to share two recent cases where EUS-guided liver biopsy safely and effectively provided a definitive diagnosis, and debate the conclusions raised by the authors.

In the first case, a 55-year-old woman with lupus was referred with transaminitis, mild IgG elevation and ultrasound evidence of splenomegaly and unexplained dilatation of the common bile duct (16 mm) confirmed on MRI. Elastography revealed elevated liver stiffness of 21 kPa. In a single visit, she underwent gastroscopy for variceal screening, EUS-guided assessment for ductal dilatation and EUS-guided liver biopsy. An adequate sample was obtained and a diagnosis of moderate …