tbuckley/cabot-search huggingface dataset:
Pulmonology (is) on the air
Authors: C. Robalo Cordeiro
Journal: Pulmonology (2020)

Pulmonology (is) on the air ''We are what we think.All that we are arises with our thoughts.With our thoughts we make our world''.BuddhaThe coronavirus disease 2019 , caused by a betacoronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), represents a new global challenge.As I write this Editorial, there are almost 3 million people infected with SARS-Cov-2 worldwide and more than 200,000 people have died.This pandemic scenario, of a dimension not experienced for over a century, has globally determined extreme measures that can mitigate, as far as possible, the most serious consequences for public health.Just one week after the first cases occurred in Portugal and when there were still no deaths registered, the Portuguese Medical Schools decided, on March 9, to suspend all classroom teaching activities, implementing distance-learning measures, which was the lever for the first universities to take the decision, on March 11, to suspend classes and other face-to-face activities.Before that, on February 25, the Faculty of Medicine of the University of Coimbra (FMUC) had already suspended any teaching which involved direct contact with patients, due to the circulation of students from areas that in Italy were starting a cordon scenario.In fact, in an unprecedented mobilization, involving teachers, students and administrative staff, all Portuguese Medical Schools set up, in record time, distance learning models, using the latest technology at their disposal.This also proved to be an excellent opportunity to explore new pedagogical methodologies in Medical Education in Portugal, highlighting the proactive role of the Academy and the University in a modern country.Teaching pulmonology in this period of lock down has been quite a challenge.How can face-to-face teaching be effectively replaced, specifically with regard to contact with the patient?In recent years, the use of Biomedical Simulation and Virtual Clinical Cases has been progressively implemented in the teaching-learning of FMUC as a very useful tool in the development of the clinical reasoning of our students.
Estimation of Intraglomerular Pressure Using Invasive Renal Arterial Pressure and Flow Velocity Measurements in Humans
Authors: Didier Collard, Peter M. van Brussel, Lennart van de Velde, Gilbert W.M. Wijntjens, Berend E. Westerhof, John M. Karemaker, Jan J. Piek, Jim A. Reekers, Liffert Vogt, Robbert J. de Winter, Bert-Jan H. van den Born
Journal: Journal of the American Society of Nephrology (2020)

Glomerular hyperfiltration resulting from an elevated intraglomerular pressure (Pglom) is an important cause of CKD, but there is no feasible method to directly assess Pglom in humans. We developed a model to estimate Pglom in patients from combined renal arterial pressure and flow measurements.We performed hemodynamic measurements in 34 patients undergoing renal or cardiac angiography under baseline conditions and during hyperemia induced by intrarenal dopamine infusion (30 μg/kg). For each participant during baseline and hyperemia, we fitted an adapted three-element Windkessel model that consisted of characteristic impedance, compliance, afferent resistance, and Pglom.We successfully analyzed data from 28 (82%) patients. Median age was 58 years (IQR, 52-65), median eGFR was 95 ml/min per 1.73 m2 (IQR, 74-100) using the CKD-EPI formula, 30% had microalbuminuria, and 32% had diabetes. The model showed a mean Pglom of 48.0 mm Hg (SD=10.1) at baseline. Under hyperemia, flow increased by 88% (95% CI, 68% to 111%). This resulted in a 165% (95% CI, 79% to 294%) increase in afferent compliance and a 13.1-mm Hg (95% CI, 10.0 to 16.3) decrease in Pglom. In multiple linear regression analysis, diabetes (coefficient, 10.1; 95% CI, 5.1 to 15.1), BMI (0.99 per kg/m2; 95% CI, 0.38 to 1.59), and renal perfusion pressure (0.42 per mm Hg; 95% CI, 0.25 to 0.59) were significantly positively associated with baseline Pglom.We constructed a model on the basis of proximal renal arterial pressure and flow velocity measurements that provides an overall estimate of glomerular pressure and afferent and efferent resistance in humans. The model provides a novel research technique to evaluate the hemodynamics of CKD on the basis of direct pressure and flow measurements.Functional HEmodynamics in patients with and without Renal Artery stenosis (HERA), NL40795.018.12 at the Dutch national trial registry (toetsingonline.nl).
A review of the application of nanoparticles in the diagnosis and treatment of chronic kidney disease
Authors: Yanhong Ma, Fanghao Cai, Yangyang Li, Jianghua Chen, Fei Han, Weiqiang Lin
Journal: Bioactive Materials (2020)

Chronic kidney disease (CKD) poses a great burden to global public health as current therapies are generally ineffective. Early detection and effective therapy are crucial for the future prevention and progression of CKD. Nanoparticles (NPs) vary by particle size, charge, shape and the density of targeting ligands and are associated with enhancement of the pharmacokinetic properties, targetability, or the bioavailability of drugs. Thus, the emergence of NPs in medicine has provided novel solutions to the potential diagnosis and treatment of CKD. This review describes the current experimental research, clinical applications of NPs, the current challenges, and upcoming opportunities in the diagnosis and treatment of CKD.
Utility and Patterns of Vitamin B12 and Folate Testing in Patients with Isolated Thrombocytopenia
Authors: Emma P. DeLoughery, Aishwarya Ravindran, Aneel A. Ashrani, Kebede H. Begna, C. Christopher Hook, Ariela L. Marshall, Rajiv K Pruthi, Alexandra P. Wolanskyj-Spinner, Ronald S. Go
Journal: Blood (2017)
Quantitative Structure–Activity Relationship Models for Predicting Inflammatory Potential of Metal Oxide Nanoparticles
Authors: Yang Huang, Xuehua Li, Shujuan Xu, Huizhen Zheng, Lili Zhang, Jingwen Chen, Huixiao Hong, Rebecca Kusko, Ruibin Li
Journal: Environmental Health Perspectives (2020)

Although substantial concerns about the inflammatory effects of engineered nanomaterial (ENM) have been raised, experimentally assessing toxicity of various ENMs is challenging and time-consuming. Alternatively, quantitative structure-activity relationship (QSAR) models have been employed to assess nanosafety. However, no previous attempt has been made to predict the inflammatory potential of ENMs.By employing metal oxide nanoparticles (MeONPs) as a model ENM, we aimed to develop QSAR models for prediction of the inflammatory potential by their physicochemical properties.We built a comprehensive data set of 30 MeONPs to screen a proinflammatory cytokine interleukin (IL)-1 beta (IL-1β) release in THP-1 cell line. The in vitro hazard ranking was validated in mouse lungs by oropharyngeal instillation of six randomly selected MeONPs. We established QSAR models for prediction of MeONP-induced inflammatory potential via machine learning. The models were further validated against seven new MeONPs. Density functional theory (DFT) computations were exploited to decipher the key mechanisms driving inflammatory responses of MeONPs.Seventeen out of 30 MeONPs induced excess IL-1β production in THP-1 cells. In vivo disease outcomes were highly relevant to the in vitro data. QSAR models were developed for inflammatory potential, with predictive accuracy (ACC) exceeding 90%. The models were further validated experimentally against seven independent MeONPs (ACC=86%). DFT computations and experimental results further revealed the underlying mechanisms: MeONPs with metal electronegativity lower than 1.55 and positive ζ-potential were more likely to cause lysosomal damage and inflammation.IL-1β released in THP-1 cells can be an index to rank the inflammatory potential of MeONPs. QSAR models based on IL-1β were able to predict the inflammatory potential of MeONPs. Our approach overcame the challenge of time- and labor-consuming biological experiments and allowed for computational assessment of MeONP inflammatory potential by characterization of their physicochemical properties. https://doi.org/10.1289/EHP6508.
Abstract A27: Differential protein-interactome of MYB-NF1B fusion in adenoid cystic carcinoma
Authors: Joseph O. Humtsoe, Hyun-Su Kim, Margaret Soucheray, Danielle Swaney, Patrick K. Ha
Journal: Clinical Cancer Research (2020)

Abstract Chromosomal translocations occur frequently in adenoid cystic carcinomas (ACC). In salivary gland ACC, the commonly identified rearrangement occurs at chromosome t(6:9), resulting in the fusion of the transcription factor genes, MYB and NF1B. The gene fusion encoding a chimeric MYB-NF1B is a unique genetic feature, regarded as a hallmark in ACC carcinogenesis. Although MYB-NF1B may be involved in the deregulation of MYB expression and its downstream gene targets, the precise role of MYB-NF1B in the development and maintenance of ACC remains to be clearly defined. Here, we engineered an inducible system to express either MYB or MYB-NF1B in ACC-01 cells, which express low levels of endogenous MYB but not MYB-NF1B, to study the molecular and mechanistic role of MYB-NF1B. Immunoprecipitation and mass spectrometry analysis revealed the presence of previously unreported MYB- and MYB-NF1B-interacting partners, including vimentin and nuclear myosin (MYO1C). These interactions were positively validated in several patient-derived xenograft models of ACC. Interestingly, MYB and MYB-NF1B interaction with vimentin and MYO1C appeared to be differentially regulated, and altering vimentin expression reduces MYB levels, while maintaining relatively steady levels of MYB-NF1B. MYO1C is involved in transcriptional regulation, and altered MYB-NF1B binding activity with nuclear myosin may modulate downstream gene targets. While detailed further study is needed, these findings suggest a potential distinct function of MYB-NF1B that may play an important role in ACC pathogenesis. Citation Format: Joseph O. Humtsoe, Hyun-Su Kim, Margaret Soucheray, Danielle Swaney, Patrick K. Ha. Differential protein-interactome of MYB-NF1B fusion in adenoid cystic carcinoma [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr A27.
Awake prone positioning in COVID-19
Authors: David Koeckerling, Joseph Barker, Nadeesha L Mudalige, Oluwatobiloba Oyefeso, Daniel Pan, Manish Pareek, Jonathan P Thompson, G Andre Ng
Journal: Thorax (2020)

In the absence of effective targeted therapies for COVID-19, optimisation of supportive care is essential. Lung injury with features of acute respiratory distress syndrome (ARDS) appears to be the principal characteristic of severe acute respiratory syndrome coronavirus 2 infection.1 Recent guidance by the UK Intensive Care Society (ICS) advocates awake prone positioning to become standard of care for suspected or confirmed COVID-19, in patients requiring an FiO2 ≥28%0.2 These recommendations are extrapolated from physiological principles and clinical evidence obtained in a distinct study population—patients with severe ARDS undergoing invasive mechanical ventilation (IMV).

The physiological rationale behind prone positioning in typical ARDS is to reduce ventilation/perfusion mismatching, hypoxaemia and shunting.2 Prone positioning decreases the pleural pressure gradient between dependent and non-dependent lung regions as a result of gravitational effects and conformational shape matching of the lung to the chest cavity. This is believed to generate more homogenous lung aeration and strain distribution, thus enhancing recruitment of dorsal lung units.3 Prone positioning does not appear to alter regional distribution of pulmonary blood flow, with perfusion predominating towards dorsal lung aspects due to non-gravitational factors.4 With improvements in ventilatory homogeneity and relatively constant perfusion patterns, a subsequent reduction in shunting is observed.5 The use of positive end-expiratory pressure via non-invasive ventilation (NIV) or CPAP in the management of ARDS is beneficial by preventing alveolar de-recruitment but may also result in …
Phenotyping peach‐allergic patients sensitized to lipid transfer protein and analysing severity biomarkers
Authors: Gador Bogas, Rosa Muñoz‐Cano, Cristobalina Mayorga, Rocio Casas, Joan Bartra, Natalia Pérez, Mariona Pascal, Francisca Palomares, María José Torres, Francisca Gómez
Journal: Allergy (2020)

Patients with peach allergy due to nsLTP sensitization constitute a heterogeneous group in terms of sensitization profile and severity. This could be due to the presence of additional allergies to pollens. The aim of this study was to analyse the clinical characteristics, sensitization profile and severity of reactions in peach-allergic patients sensitized to nsLTP from two Mediterranean areas with different pollen exposure.Patients with diagnosis of LTP allergy from the Allergy Unit of Hospital Regional Universitario de Malaga (HRUM) and Hospital Clinic de Barcelona (HCB) were prospectively included and classified into two groups; (a) LTP-monoallergic: those that presented reaction only with peach and (b) LTP-Allergy: those that presented reaction with peach and at least another plant-food containing LTP.A total of 252 patients were included, 235 (93.2%) had LTP-syndrome and 17 (6.8%) were LTP-monoallergic. We found a higher percentage of anaphylaxis and delayed onset of symptoms in the LTP-monoallergic group (P = .02 and P = .04, respectively). Moreover, anaphylaxis was less frequent in patients with profilin sensitization (P = .03). The comparison of patients' data from HRUM with data from HCB showed differences in sensitization to olive tree pollen and profilin (P = .01 and P = .001, respectively).This study was undertaken to characterize two large group of subjects from to two regions with differing exposures to pollen. We found that more than 90% of peach-allergic patients in both populations evolved to LTP-Allergy and showed an early onset. Profilin sensitization could be more useful as a severity biomarker than the number of nsLTP, aeroallergen sensitizations or sIgE levels. This could provide clues regarding sensitization and severity patterns that might be relevant in other geographical areas.
Abstract A23: Transoral robotic surgery for primary oncologic resection: Outcomes from a rural academic medical center
Authors: Eric Eisen, Christiaan Rees, Isabelle Magro, Karissa LeClair, Joseph Paydarfar
Journal: Clinical Cancer Research (2020)

Abstract Objective: to report the outcomes of oncologic transoral robotic surgery (TORS) performed by a single surgeon. Study Design: Retrospective chart review. Methods: All patients who underwent a TORS primary oncologic resection between the years of 2010-2018 were reviewed. Data regarding demographics, comorbidities, prior treatment, tumor characteristics, surgery, complications, adjuvant therapy, and survival were obtained. Results: Sixty-four patients were included in the chart review with a median age of 60.8 years. Fifty patients were male and 17 were female. Average overall robotic operating time was 137.9 minutes. Forty-one cases were presented using the Da Vinci Si while 23 cases were performed using the Da Vinci Xi. There was no significant difference between these two groups with regards to operative time, complication rate, or survival. Average robotic operative times for tonsil and tongue base primaries were 151.3 and 112.1 minutes, respectively. The difference was approaching statistical significance (p=0.053). Forty-two patients underwent ligation of external carotid artery (ECA) branches whereas 23 patients did not. One major oropharyngeal bleeding complication occurred in a patient who did not receive ECA branch ligation, which resulted in death. No major bleeding complication occurred in the ligation cohort. There was no significant difference in the overall rate of complications between low ACE 27 and high ACE 27 individuals (p = 0.22). However, the number of reported complications is significantly greater in the high ACE 27 group relative to the low ACE 27 group (0.74 vs. 1.82, p = 0.016). There was no significant difference in survival between HPV+ and HPV- tumors. Conclusion: Transoral robotic surgery represents a safe and effective means for resection of malignancies of the oropharynx. Although statistical significance cannot be demonstrated, ECA branch ligation should be considered prior to TORS given the severity of potential complications. Citation Format: Eric Eisen, Christiaan Rees, Isabelle Magro, Karissa LeClair, Joseph Paydarfar. Transoral robotic surgery for primary oncologic resection: Outcomes from a rural academic medical center [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr A23.
Reply to Decroo <i>et al.</i>: High-Dose First-Line Treatment Regimen for Recurrent Rifampicin-Susceptible Tuberculosis
Authors: Kelly E. Dooley, Sachiko Miyahara, Florian von Groote-Bidlingmaier, Xin Sun, Richard Hafner, Susan L. Rosenkranz, Elisa H. Ignatius, Eric L. Nuermberger, Laura Moran, Kathleen Donahue, Susan Swindells, Naadira Vanker, Andreas H. Diacon
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

GenoType MTBDRplus.rpoB mutations outside the 81-bp rifampicin resistance determining region are not covered by these commercial assays.Another, not unusual cause of missed rifampicin resistance is heteroresistance resulting from a mixed population of both susceptible and resistant TB bacilli (3).If patients with resistance to isoniazid and missed rifampicin resistance were treated with the World Health Organization levofloxacin-strengthened first-line regimen, resistance to fluoroquinolone would emerge rapidly.Because the efficacy of second-line TB treatment relies on a fluoroquinolone as a core drug, treatment options would be dramatically reduced.Finally, as shown by Dooley and colleagues, as well as by previous studies (4), high-dose isoniazid may overcome mutations that confer resistance to isoniazid and render normal doses ineffective (4).Excluding isoniazid, which has the highest early bactericidal activity of all first-line drugs, increases the risk of acquiring rifampicin resistance, as mutant bacilli may survive the early phase of TB treatment.Moreover, Boeree and colleagues showed that high-dose rifampicin (35 mg/kg) was safe and reduced time to culture conversion when compared with normal-dose rifampicin (10 mg/kg) (5).Although isoniazid is used for its bactericidal activity against actively replicating bacilli, rifampicin has both a bactericidal effect against rapidly replicating bacilli and a sterilizing effect against dormant bacilli.Both types of action are needed to ensure a relapse-free cure (6).Globally, about 11.6% of patients with recurrent TB have rifampicin-susceptible/isoniazid-resistant TB.Studies should compare high-dose first-line regimens with normal-dose regimens in terms of safety, treatment success, and acquired rifampicin resistance in patients with rifampicin-susceptible/isoniazid-resistant TB.If it is shown to be safe and efficacious, high-dose first-line treatment could be used in all patients with recurrent rifampicin-susceptible TB, regardless of initial isoniazid resistance, thus avoiding delays in retreatment.Such an improved use of first-line anti-TB drugs would have major advantages.No additional susceptibility testing beyond rifampicin testing would be required and there would be no delay between a diagnosis of rifampicin-susceptible recurrent TB and initiation of treatment.If first-line treatment could rely on first-line drugs only, second-line treatment options would be maximally safeguarded.
COVID-19 and the liver
Authors: Dinesh Jothimani, Radhika Venugopal, Mohammed Forhad Abedin, Ilankumaran Kaliamoorthy, Mohamed Rela
Journal: Journal of Hepatology (2020)

The current coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become a major public health crisis over the past few months. Overall case fatality rates range between 2-6%; however, the rates are higher in the elderly and those with underlying comorbidities like diabetes, hypertension and heart disease. Recent reports showed that about 2-11% of patients with COVID-19 had underlying chronic liver disease. During the previous SARS epidemic, around 60% of patients were reported to develop various degrees of liver damage. In the current pandemic, hepatic dysfunction has been seen in 14-53% of patients with COVID-19, particularly in those with severe disease. Cases of acute liver injury have been reported and are associated with higher mortality. Hepatic involvement in COVID-19 could be related to the direct cytopathic effect of the virus, an uncontrolled immune reaction, sepsis or drug-induced liver injury. The postulated mechanism of viral entry is through the host angiotensin-converting enzyme 2 (ACE2) receptors that are abundantly present in type 2 alveolar cells. Interestingly, ACE2 receptors are expressed in the gastrointestinal tract, vascular endothelium and cholangiocytes of the liver. The effects of COVID-19 on underlying chronic liver disease require detailed evaluation and, with data currently lacking, further research is warranted in this area.
Controlled release of odontogenic exosomes from a biodegradable vehicle mediates dentinogenesis as a novel biomimetic pulp capping therapy
Authors: W. Benton Swanson, Ting Gong, Zhen Zhang, Miranda Eberle, David Niemann, Ruonan Dong, Kunal J. Rambhia, Peter X. Ma
Journal: Journal of Controlled Release (2020)
Regulation of EMT markers by the KISS1 metastasis suppressor gene
Authors: Lewis Stafford, Kedar Vaidya, Douglas Hurst, Danny Welch
Journal: Cancer Research (2008)

5375  Epithelial to mesenchymal Transition (EMT) is a normal developmental process in which epithelial cells temporarily acquire mesenchymal characteristics. EMT is also proposed to be a mechanism used by neoplastic cells to escape the primary tumor and migrate into the circulatory system, which are key steps in metastasis. Three genes central to EMT - SNAI1 (SNAIL), SNAI2 (SLUG) and TWIST (TWIST) - repress E-cadherin, which thought to be the critical regulatory change for EMT. We hypothesized that the KISS1 metastasis suppressor might regulate EMT. Re-expression of KISS1 in metastatic human C8161.9 melanoma cells blocks metastasis without inhibiting orthotopic tumor growth. At both the protein and RNA levels, KISS1 re-expression reduced SNAIL, but not TWIST, compared to vector control. E-cadherin RNA expression is restored in the C8161.9KISS1. Genes regulated by SNAIL, such as VEGF and IL-8, are also reduced in C8161.9KISS1. Since KISS1 is secreted, we investigated whether deletion of the secretion signal (KFMΔSS) had an effect on these EMT markers. Neither SNAIL nor TWIST expression was affected by KFMΔSS yet E-cadherin was re-expressed at the RNA level. These studies suggest that KISS1 may suppress metastasis, in part, by modulating processes involved in EMT. The data further suggests alternate roles of KISS1 or KISS-derived peptides inside the cell.  Support: Natl. Fndn. for Cancer Res, CA87728, F32CA113037, and Komen PDF 1122006
A Modest Proposal to Spur Innovation in Chronic Dialysis Care
Authors: Thomas H. Hostetter
Journal: Journal of the American Society of Nephrology (2020)

The kidney care community bemoans the lack of innovation not only in treatment of CKD but also, in the therapy of chronic kidney failure by dialysis. To be sure, chronic kidney failure care is better today than at the inception of its modern era, which I take to be the federal Medicare legislation