tbuckley/cabot-search huggingface dataset:
Nanomedicines for the topical treatment of vulvovaginal infections: Addressing the challenges of antimicrobial resistance
Authors: Željka Vanić, May Wenche Jøraholmen, Nataša Škalko-Basnet
Journal: Advanced Drug Delivery Reviews (2021)

Recent years have, surprisingly, witnessed an increase in incidence of sexually transmitted infections (STIs). At the same time, antimicrobial therapy came under the threat of ever rising antimicrobial resistance (AMR), resulting in STIs with extremely limited therapy options. In this review, we addressed the challenges of treating vaginal infections in an era of AMR. We focused on published work regarding nanomedicine destined for localized treatment of vaginal infections. Localized therapy offers numerous advantages such as assuring high drug concentration at the infection site, limiting systemic drug exposure that can lead to faster development of AMR reduction in the systemic side effects and potentially safe therapy in pregnancy. We provided a state-of-the-art overview of nanoformulations proposed to topically treat STIs, emphasizing the challenges and advantages of each type of nanocarriers, as well as issues of potential toxicity.
Retrospective Monocentric Study on Acute Myeloid Leukemias with Complex Karyotype: Clinical Outcomes and Cytogenetic Features
Authors: Giovanni Grillo, Ivana Lotesoriere, Elisa Zucchetti, Valentina Mancini, Barbara Forno, Giambattista Bertani, Elena Inzoli, Silvia Soriani, Roberto Cairoli
Journal: Blood (2017)
Aggregation‐Induced Emission‐Based Platforms for the Treatment of Bacteria, Fungi, and Viruses
Authors: Xiaohui Chen, Haijie Han, Zhe Tang, Qiao Jin, Jian Ji
Journal: Advanced Healthcare Materials (2021)

Abstract The prevention and control of pathogenic bacteria, fungi, and viruses is a herculean task for all the countries since they greatly threaten global public health. Rapid detection and effective elimination of these pathogens is crucial for the treatment of related diseases. It is urgently demanded to develop new diagnostic and therapeutic strategies to combat bacteria, fungi, and viruses‐induced infections. The emergence of aggregation‐induced emission (AIE) luminogens (AIEgens) is a revolutionary breakthrough for the treatment of many diseases, including pathogenic infections. In this review, the main focus is on the applications of AIEgens for theranostic treatment of pathogenic bacteria, fungi, and viruses. Due to the AIE characteristic, AIEgens are promising fluorescent probes for the detection of bacteria, fungi, and viruses with excellent sensitivity and photostability. Moreover, AIEgen‐based theranostic platforms can be fabricated by introducing bactericidal moieties or designing AIE photosensitizers and AIE photothermal agents. The current strategies and ongoing developments of AIEgens for the treatment of pathogenic bacteria, fungi, and viruses will be discussed in detail.
Abstract 268: Advanced Glycation End Products Effect on the Polarization of Macrophages Cardiac After Acute Myocardial Infarction in Wistar Rats
Authors: Juliana O Rangel, Bianca Fracasso, Amanda Phaelante, Fernanda Curuja, Daniel Sturza, Nadine Clausell, Andreia Biolo, Luis E Rohde, Michael Andrades
Journal: Circulation Research (2016)

Macrophage phenotypes play an important role in post-MI cardiac remodeling. M1 macrophages have a proinflammatory phenotype and are found in the heart early after MI whereas M2 macrophages arise after and replace M1 macrophages in order to mediate the resolution of inflammation and angiogenesis. Advanced glycation end products (AGE) may modulate macrophage polarization but its functional role in the context of post-MI remains incompletely understood. Our goal is to assess whether AGE can polarize macrophages in post-MI and interfere in cardiac remodeling. We have collected experimental data from 68 male Wistar rats (2-3 month-old) divided in 4 groups: sham, MI + 0.9% NaCl (i.p.), MI + methylglyoxal (AGE inducer, 17 mg/kg/day; i.p.); and MI + aminoguanidine (anti-AGE agent, 0.5 g/L in drinking water). Subgroups were euthanized on days 2, 6, and 10 days post-MI. The echocardiographic analysis did not show differences in ejection fraction or akinetic/hypokinetic area among the MI groups. Cytokine levels were assessed by multiplex analysis in cardiac tissue homogenate. There was an increase of proinflammatory cytokine IL-6 on 10th day after surgery in MI group at the remote area, while IL-1β and IL-12 showed reduction compared with the sham group. Anti-inflammatory cytokine IL-10 did not show any difference among the groups. Until now, it is not possible to conclude whether AGE can induce macrophage polarization in vivo. More analyses are necessary to respond our objective.
Identification of matrix metalloproteinase-10 as a key mediator of podocyte injury and proteinuria
Authors: Yangyang Zuo, Cong Wang, Xiaoli Sun, Chengxiao Hu, Jixing Liu, Xue Hong, Weiwei Shen, Jing Nie, Fan Fan Hou, Lili Zhou, Youhua Liu
Journal: Kidney International (2021)
HepaCAM controls astrocyte self-organization and coupling
Authors: Katherine T. Baldwin, Christabel X. Tan, Samuel T. Strader, Changyu Jiang, Justin T. Savage, Xabier Elorza-Vidal, Ximena Contreras, Thomas Rülicke, Simon Hippenmeyer, Raúl Estévez, Ru-Rong Ji, Cagla Eroglu
Journal: Neuron (2021)
Respiratory disease, and treatment / thematic poster session COVID-19 outcome-based pathology reveals the birth of fibrosing interstitial pneumonitis
Authors: S. S. Batah, M. Benatti, L. Syung, W. Telini, V. Capelozzi, A. Cetlin, M. Santos, A. Fabro
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

RATIONALE: Fibrosing interstitial pneumonitis can be the common end result to many different lung diseases, including chronic viral inflammations, as COVID-19. Some SARS-CoV-2 infected patients develop the acute respiratory distress syndrome. This condition is histopathologically known as diffuse alveolar damage which may be followed by a proliferative phase. Whereas COVID-19 has showed a longer disease outcome until clinical cure or death compared to other chronic infections, our hypothesis is that COVID-19 patients tend to develop a more prominently proliferative phase, even those who progress to death, with an exacerbated fibroblast and myofibroblast proliferation. METHODS: Minimally invasive autopsy(MIA) was performed on 47 confirmed COVID- 19 patients for lung samples. Clinical, demographic, mechanical ventilation parameters and radiological data were collected by electronic medical record. A detailed histomorphological analysis by two pulmonary pathologists was performed by HE2) Better lung outcome - a progressive increase in PaO2/FiO2 ratio and low complacency levels, usual pattern of elastic and collagen fibers and SMA+ cells, but sudden death due to acute pulmonary thromboembolism. Moreover, SARS-CoV-2 viral genome was detected in all lung tissue collected(47), with a mean of 3,403,775 and 90,683,263 copies/mg for N2 and E genes respectively. CONCLUSIONS: The fibrotic septal thickening is related to poor lung outcome by progressive decline in PaO2/FiO2 ratio and late death. This pathophysiological process may be an important sequel in pos- COVID19 patients to trigger a fibrosing interstitial pneumonitis. Further investigations with larger studies are warranted. .
Trends in First-Line Glucose-Lowering Drug Use in Adults With Type 2 Diabetes in Light of Emerging Evidence for SGLT-2i and GLP-1RA
Authors: HoJin Shin, Sebastian Schneeweiss, Robert J. Glynn, Elisabetta Patorno
Journal: Diabetes Care (2021)

OBJECTIVE We evaluated recent use trends and predictors of first-line antidiabetes treatment in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Using two large U.S. health insurance databases (Clinformatics and Medicare), we identified adult patients with type 2 diabetes who initiated antidiabetes treatment from 2013 through 2019. Quarterly trends in use of first-line antidiabetes treatment were plotted overall and stratified by cardiovascular disease (CVD). Multinomial logistic regressions were fit to estimate predictors of first-line antidiabetes treatment, using metformin, the recommended first-line treatment for type 2 diabetes, as the common referent. RESULTS Metformin was the most frequently initiated medication, used by 80.6% of Medicare beneficiaries and 83.1% of commercially insured patients. Sulfonylureas were used by 8.7% (Medicare) and 4.7% (commercial). Both populations had low use of sodium–glucose cotransporter 2 inhibitors (SGLT-2i, 0.8% [Medicare] and 1.7% [commercial]) and glucagon-like peptide 1 receptor agonists (GLP-1Ra; 1.0% [Medicare] and 3.5% [commercial]), with increasing trends over time (P &amp;lt; 0.01). Initiators of antidiabetes drugs with established cardiovascular benefits (SGLT-2i and GLP-1RA) were more likely to be younger and had prevalent CVD or higher socioeconomic status compared with initiators of metformin. CONCLUSIONS Among adult patients with type 2 diabetes, metformin was by far the most frequent first-line treatment. While the use of SGLT-2i and GLP-1RA was low from 2013 through 2019, it increased among patients with CVD.
Abstract 237: Transient Activation of Pkc Results in Long-lasting Detrimental Effects on Systolic [ca <sup>2+</sup> ] <sub>I</sub> in Cardiomyocytes by Altering Actin Cytoskeletal Dynamics and T-tubule Integrity
Authors: Ang Guo, Long-Sheng Song, Biyi Chen, Rong Chen, Chunkai Huang, Yihui Wang
Journal: Circulation Research (2016)

Protein kinase C (PKC) family isozymes contribute to the development of heart failure through dysregulation of Ca 2+ handling properties and disruption of contractile function in cardiomyocytes. However, the majority of studies have examined either the acute or chronic effects of PKC activation or inhibition, yet PKC is likely only transiently activated under pathological conditions. Herein, we report that transient activation of PKC in cultured cardiomyocytes promotes long-term deleterious effects on the integrity of the transverse (T)- tubule system, resulting in a significant decrease in the amplitude and increase in the rising kinetics of Ca 2+ transients. Treatment with a PKCα/β inhibitor restored the synchronization of Ca 2+ transients and maintained T-tubule integrity in cultured cardiomyocytes. Studies using a dominant negative PKCα identified PKCα as the mediator of T-tubule remodeling in cardiomyocytes. Supporting these data, PKCα/β inhibition protected against T-tubule remodeling and cardiac dysfunction in a mouse model of pressure overload-induced heart failure. Mechanistically, transient activation of PKC resulted in biphasic actin cytoskeletal rearrangement. Transient inhibition of actin polymerization or depolymerization resulted in severe T-tubule damage, recapitulating the T-tubule damage induced by PKC activation. Moreover, inhibition of stretch activated channels (SAC) protected against T-tubule remodeling and E-C coupling dysfunction induced by transient PKC activation and actin cytoskeletal rearrangement. These data identify a key mechanistic link between transient PKC activation and long-term Ca 2+ handling defects through PKC-induced actin cytoskeletal rearrangement and resultant T-tubule damage.
Bayesian inference using hierarchical and spatial priors for intravoxel incoherent motion MR imaging in the brain: Analysis of cancer and acute stroke
Authors: Georg Ralph Spinner, Christian Federau, Sebastian Kozerke
Journal: Medical Image Analysis (2021)

The intravoxel incoherent motion (IVIM) model allows to map diffusion (D) and perfusion-related parameters (F and D*). Parameter estimation is, however, error-prone due to the non-linearity of the signal model, the limited signal-to-noise ratio (SNR) and the small volume fraction of perfusion in the in-vivo brain. In the present work, the performance of Bayesian inference was examined in the presence of brain pathologies characterized by hypo- and hyperperfusion. In particular, a hierarchical and a spatial prior were combined. Performance was compared relative to conventional segmented least squares regression, hierarchical prior only (non-segmented and segmented data likelihoods) and a deep learning approach. Realistic numerical brain IVIM simulations were conducted to assess errors relative to ground truth. In-vivo, data of 11 central nervous system cancer patients and 9 patients with acute stroke were acquired. The proposed method yielded reduced error in simulations for both the cancer and acute stroke scenarios compared to other methods across the whole investigated SNR range. The contrast-to-noise ratio of the proposed method was better or on par compared to the other techniques in-vivo. The proposed Bayesian approach hence improves IVIM parameter estimation in brain cancer and acute stroke.
Financial Implications of Early Hospital Discharge After AML-Like Induction Chemotherapy: A 4-Year Retrospective Analysis
Authors: Nathan J. Moore, Megan Othus, Anna B. Halpern, Nicholas P. Howard, Linyi Tang, Kyle E. Bastys, Mary-Elizabeth M. Percival, Paul C. Hendrie, Garrett A. Hartley, Verna L. Welch, Elihu H. Estey, Roland B. Walter
Journal: Journal of the National Comprehensive Cancer Network (2021)

Background: Early hospital discharge (EHD) after intensive acute myeloid leukemia (AML) induction chemotherapy has become routine at the University of Washington/Seattle Cancer Care Alliance over the past several years. We assessed the financial implications of EHD over the first 4 years after its broad adoption for patients with AML and other high-grade myeloid neoplasms undergoing AML-like induction chemotherapy. Patients and Methods: We retrospectively compared charges between 189 patients with EHD who received all postinduction inpatient/outpatient care within our care system between August 2014 and July 2018 and 139 medically matched control patients who remained hospitalized for logistical reasons. Charges from the day of initial discharge (patients with EHD) or end of chemotherapy (control patients) until blood count recovery, additional chemotherapy or care transition, hospital discharge (for control patients only), an elapse of 42 days, or death were extracted from financial databases and separated into categories: facility/provider, emergency department, transfusions, laboratory, imaging, pharmacy, and miscellaneous. Results: Combined charges averaged $4,157/day (range, $905–$13,119/day) for patients with EHD versus $9,248/day (range, $4,363–$48,522/day) for control patients ( P &lt;.001). The EHD cohort had lower mean facility/provider, transfusion, laboratory, and pharmacy charges but not imaging or miscellaneous charges. During readmissions, there was no statistically significant difference in daily inpatient charges between the EHD and control cohorts. After multivariable adjustment, average charges were $3,837/day lower for patients with EHD ( P &lt;.001). Conclusions: Together with previous data from our center showing that EHD is safe and associated with reduced healthcare resource utilization, this study further supports this care approach for AML and other high-grade myeloid neoplasms if infrastructure is available to enable close outpatient follow-up.
TNFR2/14-3-3ε signaling complex instructs macrophage plasticity in inflammation and autoimmunity
Authors: Wenyu Fu, Wenhuo Hu, Young-Su Yi, Aubryanna Hettinghouse, Guodong Sun, Yufei Bi, Wenjun He, Lei Zhang, Guanmin Gao, Jody Liu, Kazuhito Toyo-oka, Guozhi Xiao, David B. Solit, Png Loke, Chuan-ju Liu
Journal: Journal of Clinical Investigation (2021)

TNFR1 and TNFR2 have received prominent attention because of their dominance in the pathogenesis of inflammation and autoimmunity. TNFR1 has been extensively studied and primarily mediates inflammation. TNFR2 remains far less studied, although emerging evidence demonstrates that TNFR2 plays an antiinflammatory and immunoregulatory role in various conditions and diseases. Herein, we report that TNFR2 regulates macrophage polarization, a highly dynamic process controlled by largely unidentified intracellular regulators. Using biochemical copurification and mass spectrometry approaches, we isolated the signaling molecule 14-3-3ε as a component of TNFR2 complexes in response to progranulin stimulation in macrophages. In addition, 14-3-3ε was essential for TNFR2 signaling-mediated regulation of macrophage polarization and switch. Both global and myeloid-specific deletion of 14-3-3ε resulted in exacerbated inflammatory arthritis and counteracted the protective effects of progranulin-mediated TNFR2 activation against inflammation and autoimmunity. TNFR2/14-3-3ε signaled through PI3K/Akt/mTOR to restrict NF-κB activation while simultaneously stimulating C/EBPβ activation, thereby instructing macrophage plasticity. Collectively, this study identifies 14-3-3ε as a previously unrecognized vital component of the TNFR2 receptor complex and provides new insights into the TNFR2 signaling, particularly its role in macrophage polarization with therapeutic implications for various inflammatory and autoimmune diseases with activation of the TNFR2/14-3-3ε antiinflammatory pathway.
Prostate-Specific Membrane Antigen Expression in Metastatic Angiosarcoma Detected on 18F-PMSA PET/CT
Authors: Fahad Marafi, Abdulredha Esmail, Sharjeel Usmani
Journal: Clinical Nuclear Medicine (2021)

18F-PSMA is a promising tracer for both staging and detection of biochemical recurrence in prostate cancer. PSMA is also expressed in the endothelium of tumor-associated neovasculature of various solid malignancies possibly due to tumor-associated angiogenic factors and endothelial cell sprouting. We report a case of a 59-year-old man with known case of prostate cancer underwent 18F-PSMA for restaging. 18F-PSMA PET/CT shows multiple lytic bone lesions with high PSMA expression. Histopathological evaluation showed metastatic angiosarcoma. 18F-PSMA expression in the angiosarcoma can be potentially guided to radionuclide legend therapy.
Abstract 82: Reduction of SHP2’s Phosphatase Activity Improves Cardiac Adaptation to Pressure and Volume Overload
Authors: Rajika Roy, Kathryn Crombie, Diana Douglas, Maike Krenz
Journal: Circulation Research (2016)

Since the inability of the heart to adapt to pathological stress results in heart failure, supporting cardiac stress adaptation may improve clinical outcome. We hypothesized that the protein tyrosine phosphatase SHP2 controls adaptation by modulating several signaling pathways involved. To test whether SHP2 plays an active role in stress adaptation, we generated transgenic (TG) mice with cardiomyocyte-specific overexpression of Q510E-SHP2, which is a dominant-negative mutant (dnSHP2). Under unstressed conditions, TG mice do not exhibit a cardiac phenotype. TG and nonTG (NTG) mice were subjected to pressure overload by transverse aortic constriction (TAC) or to volume overload by inducing large myocardial infarction (MI) via coronary artery ligation. Expression of dnSHP2 significantly improved stress adaptation after TAC (n=17 TG, n=13 NTG). Twelve weeks after banding, TG mice exhibited well preserved contractile function with significantly higher fractional shortening (FS) [TG 33.2±1.7 vs. NTG 22.2±1.5 %, p&lt;0.001] and ejection fraction (EF) [TG 67.7±2.7 vs. NTG 50.3±3.0 %, p&lt;0.001]. dnSHP2 TGs also had smaller left ventricular (LV) chamber dimensions [LV inner diameter at end-diastole (LVIDd) TG 4.4±0.2 vs. NTG 5.1±0.2 mm, p=0.02]. There were no significant differences in ventricular wall thickness or heart weights, indicating that the degree of hypertrophy in response to TAC was not affected by dnSHP2 expression. In response to volume overload induced by large MI (n=22 TG, n=24 NTG), TG hearts displayed only a trend towards improved contractile function [FS TG 21.3±1.5 vs. NTG 18.9±1.1%, EF TG 48.4±2.7 vs. NTG 44.2±2.1%]. However, chamber dimensions were better preserved in TGs [LVIDd TG 5.1±0.1 vs. NTG 5.7±0.2 mm, p=0.03]. In summary, dnSHP2 expression ameliorated LV chamber dilation and increased contractile function under pressure overload. In TGs subjected to volume overload, reduced LV dimensions were observed but with only a trend towards improved contractile function. Taken together, it is evident that reducing SHP2’s phosphatase activity indeed improves cardiac stress adapation, making SHP2 a potential novel therapeutic target.
Identification of the source events for aerosol generation during oesophago-gastro-duodenoscopy
Authors: Florence K A Gregson, Andrew J Shrimpton, Fergus Hamilton, Tim M Cook, Jonathan P Reid, Anthony E Pickering, Dimitri J Pournaras, Bryan R Bzdek, Jules Brown
Journal: Gut (2021)

Objective To determine if oesophago-gastro-duodenoscopy (OGD) generates increased levels of aerosol in conscious patients and identify the source events. Design A prospective, environmental aerosol monitoring study, undertaken in an ultraclean environment, on patients undergoing OGD. Sampling was performed 20 cm away from the patient’s mouth using an optical particle sizer. Aerosol levels during OGD were compared with tidal breathing and voluntary coughs within subject. Results Patients undergoing bariatric surgical assessment were recruited (mean body mass index 44 and mean age 40 years, n=15). A low background particle concentration in theatres (3 L −1 ) enabled detection of aerosol generation by tidal breathing (mean particle concentration 118 L −1 ). Aerosol recording during OGD showed an average particle number concentration of 595 L −1 with a wide range (3–4320 L −1 ). Bioaerosol-generating events, namely, coughing or burping, were common. Coughing was evoked in 60% of the endoscopies, with a greater peak concentration and a greater total number of sampled particles than the patient’s reference voluntary coughs (11 710 vs 2320 L −1 and 780 vs 191 particles, n=9 and p=0.008). Endoscopies with coughs generated a higher level of aerosol than tidal breathing, whereas those without coughs were not different to the background. Burps also generated increased aerosol concentration, similar to those recorded during voluntary coughs. The insertion and removal of the endoscope were not aerosol generating unless a cough was triggered. Conclusion Coughing evoked during OGD is the main source of the increased aerosol levels, and therefore, OGD should be regarded as a procedure with high risk of producing respiratory aerosols. OGD should be conducted with airborne personal protective equipment and appropriate precautions in those patients who are at risk of having COVID-19 or other respiratory pathogens.
Динамика содержания ЦОГ-2 в слизистой желудка и двенадцатиперстной кишки на фоне медикаментозной коррекции НПВП-гастропатий
Authors: Yu.M. Stepanov, Yu.S. Breslavets
Journal: GASTROENTEROLOGY (2013)

Приведены результаты иммуногистохимического исследования уровня содержания циклооксигеназы 2-го типа (ЦОГ-2) у 120 пациентов с воспалительными и эрозивными поражениями желудка и двенадцатиперстной кишки на фоне длительного приема нестероидных противовоспалительных препаратов (НПВП) до и после лечения поражений гастродуоденальной области. Средний уровень ЦОГ-2 у больных с поражением гастродуоденальной зоны, вызванным приемом НПВП, снизился в 1,5 раза и составил (2,02 ± 0,11) усл.ед. до лечения и (1,27 ± 0,09) усл.ед. после его проведения по схеме № 1, а также уменьшился в 2 раза и составил (2,00 ± 0,16) усл.ед. и (0,95 ± 0,09) усл.ед. до и после лечения соответственно при схеме терапии № 2. Данные показатели свидетельствуют о снижении защитных свойств слизистой оболочки желудка и двенадцатиперстной кишки при длительном приеме НПВП.
Abstract 15129: Follow-Up for Cardiovascular Disease Risk in Women With Preeclampsia One Year After Delivery
Authors: Jenny Huang, Duane Eisaman, Kathryn Berlacher, Joe Suyama
Journal: Circulation (2018)

Introduction: Preeclampsia is a disorder of pregnancy characterized by hypertension (BP >140/90mmHg), proteinuria, and end organ dysfunction affecting 3-4% of pregnancies per year. Women with preec...