tbuckley/cabot-search huggingface dataset:
Metal–Organic Framework Modified MoS<sub>2</sub> Nanozyme for Synergetic Combating Drug‐Resistant Bacterial Infections via Photothermal Effect and Photodynamic Modulated Peroxidase‐Mimic Activity
Authors: Zi‐Yang Liao, Ya‐Mu Xia, Jia‐Min Zuo, Tao Wang, Da‐Tong Hu, Ming‐Zhe Li, Ning‐Ning Shao, Dong Chen, Kai‐Xin Song, Xuan Yu, Xin‐Yue Zhang, Wei‐Wei Gao
Journal: Advanced Healthcare Materials (2021)

Abstract Bacterial infections have become major threats to public health all over the world. With the emergence of antibiotic resistance, it is urgent to develop novel antimicrobial materials to efficiently overcome drug resistance with high bactericidal activity. In this work, UiO‐66‐NH‐CO‐MoS 2 nanocomposites (UNMS NCs) are constructed through the amidation reaction. The UNMS NCs are positively charged which is beneficial for capturing and restricting bacteria. Significantly, UNMS NCs possess a synergistic bactericidal efficiency based on near‐infrared irradiation (808 nm) regulated combination of photothermal, photodynamic, and peroxidase‐like enzymatic activities. Both the photodynamic property and nanozymatic activity of UNMS NCs can lead to the generation of reactive oxygen species. The UNMS NCs show high catalytic activity in a wide pH range and exhibit excellent antibacterial ability against ampicillin‐resistant Escherichia coli and methicillin‐resistant Staphylococcus aureus with negligible cytotoxicity. Interestingly, due to the 808 nm irradiation‐induced hyperthermia in the presence of UNMS NCs, the glutathione oxidation process can be accelerated, resulting in bacterial death more easily. Mice wound models are established to further manifest that UNMS NCs can promote wound healing with good biosafety in living systems.
Female participation in U.S. oncology clinical trials registered on ClinicalTrials.gov from 2008 to 2020.
Authors: Nirosha D. Perera, Tiffany R. Bellomo, Henry K. Litt, Sayeh Fattahi, Alexander Bell, MaKenna A. Stavins, Massoud Saleki, Ruxandra Ionescu, Margaret Shyu, Max M. Wang, Jacqueline Tao, Nadeen Sarsour, Sunjong Ji, Ryan M O'Keefe, Matthew Pun, Jordan M. Takasugi, Jecca R. Steinberg, Roderick King, Amit Mahipal, Brandon E. Turner
Journal: Journal of Clinical Oncology (2021)

85 Background: Females are thought to be underrepresented in clinical trials, which may lead to care disparities. We characterized female enrollment trends in U.S. oncology trials registered on ClinicalTrials.gov and identified features associated with accurate representation. Methods: We employed a cross-sectional study design with descriptive, logistic regression, and cox regression analyses. We downloaded 270,172 studies registered on the Aggregate Analysis of the ClinicalTrials.gov database from October 1, 2008 to March 9, 2020, excluding non-interventional and reproductive organ specific trials. We then applied cancer/oncology specific Medical Subject Heading terms and manually reviewed the remaining 27,521 trials for true oncology content. Prevalence-corrected estimates for female participation were calculated as the percentage of females among trial participants divided by the percentage of females in the disease population per U.S. Surveillance, Epidemiology, and End Results Program (SEER) data (participation to prevalence ratio [PPR]), with a range between 0.8 and 1.2 reflecting accurate female representation in the trial. Results: Of 26,894 trials meeting eligibility criteria, 9,059 trials were completed in the U.S., 2,499 trials reported completed study status, and only 1,256 trials reported sex. Among 1,256 oncology trials and 229,056 participants, overall female representation was 46.9% (95% CI, 45.4-48.4%). 43% of trials were industry funded, 29% academic, and 28% U.S. government. Females were underrepresented compared to their disease burden in anal canal (PPR 0.21), thyroid (PPR 0.57), stomach (PPR 0.68), kidney (PPR 0.77), and bone (PPR 0.79) cancer trials. They were accurately represented in head and neck (PPR 0.80), lung (PPR 0.84), bladder (PPR 0.85), skin (PPR 0.88), pancreas (PPR 0.88), colon (PPR 0.90), hematologic (PPR 0.91), liver (PPR 1.01), CNS (PPR 1.03), soft tissue (PPR 1.05), and esophagus (PPR 1.05) cancer trials. Accurate representation was significantly associated with industry funding and pancreas cancer trial focus, but not associated with trial type (medical, surgical, radiation, other invasive, other) (Table). Conclusions: Females are underrepresented compared to their disease burden in many solid tumor clinical trials. Stakeholders can look to industry funded and pancreas cancer trials as models of improvement, but must increase female representation in clinical trials to improve cancer care. [Table: see text]
Mitochondrial reactive oxygen species trigger metformin-dependent antitumor immunity via activation of Nrf2/mTORC1/p62 axis in tumor-infiltrating CD8T lymphocytes
Authors: Mikako Nishida, Nahoko Yamashita, Taisaku Ogawa, Keita Koseki, Eiji Warabi, Tomoyuki Ohue, Masaaki Komatsu, Hirokazu Matsushita, Kazuhiro Kakimi, Eiryo Kawakami, Katsuyuki Shiroguchi, Heiichiro Udono
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Metformin (Met) is the first-line treatment for type 2 diabetes mellitus and plays an effective role in treating various diseases, such as cardiovascular disease, neurodegenerative disease, cancer, and aging. However, the underlying mechanism of Met-dependent antitumor immunity remains to be elucidated. Methods MitoTEMPO, a scavenger of mitochondrial superoxide, abolished the antitumor effect of Met, but not antiprogrammed cell death (PD-1) antibody (Ab) treatment. Consequently, we studied the mechanism of the Met-induced antitumor effect. Expressions of glucose transporter (Glut)-1, mitochondrial reactive oxygen species (mtROS), interferon (IFN)-γ, Ki67, autophagy markers, activation markers for NF-E2-related factor 2 (Nrf2), and mammalian target of rapamaycin complex 1 (mTORC1) in CD8 + tumor-infiltrating T lymphocytes (CD8TILs) were examined by flow cytometry analysis. In addition, conditional knockout mice for Nrf2 and p62 were used to detect these markers, together with the monitoring of in vivo tumor growth. RNA sequencing was performed for CD8TILs and tumor cells. Melanoma cells containing an IFN-γ receptor (IFNγR) cytoplasmic domain deletion mutant was overexpressed and used for characterization of the metabolic profile of those tumor cells using a Seahorse Flux Analyzer. Results Met administration elevates mtROS and cell surface Glut-1, resulting in the production of IFN-γ in CD8TILs. mtROS activates Nrf2 in a glycolysis-dependent manner, inducing activation of autophagy, glutaminolysis, mTORC1, and p62/SQSTM1. mTORC1-dependent phosphorylation of p62 at serine 351 (p-p62(S351)) is also involved in activation of Nrf2. Conditional deletion of Nrf2 in CD8TILs abrogates mTORC1 activation and antitumor immunity by Met. In synergy with the effect of anti-PD-1 Ab, Met boosts CD8TIL proliferation and IFN-γ secretion, resulting in decreased glycolysis and oxidative phosphorylation in tumor cells. Consequently, Glut-1 is elevated in CD8TILs, together with the expansion of activated dendritic cells. Moreover, tumor cells lacking in IFNγR signaling abolish IFN-γ production and proliferation of CD8TILs. Conclusions We found that Met stimulates production of mtROS, which triggers Glut-1 elevation and Nrf2 activation in CD8TILs. Nrf2 activates mTORC1, whereas mTORC1 activates Nrf2 in a p-p62(S351)-dependent manner, thus creating a feedback loop that ensures CD8TILs’ proliferation. In combination with anti-PD-1 Ab, Met stimulates robust proliferation of CD8TILs and IFN-γ secretion, resulting in an IFN-γ-dependent reprogramming of the tumor microenvironment.
P04.17 Antigen heterogeneity in glioblastoma cell lines, patient-derived cells, and patients’ glioblastoma tissue is an obstacle for CAR-T cell therapy development
Authors: V Dufner, E Schulz, C Monoranu, M Hudecek, R Ernestus, C Hagemann, M Löhr, T Nerreter
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Immunotherapy targeting surface antigens, e.g. CAR-T-cell therapy has become a promising therapeutic approach for glioblastoma (GBM) treatment. Antigen heterogeneity constitutes a major obstacle not only for preclinical in vitro studies but also for clinical translation. Here, we provide information about the surface expression of the eight in GBM CAR-T-cell therapy most targeted antigens (GD2, CSPG4, CD133, CD70, HER2, Il13Rα2, EGFRvIII and EphA2) by analyzing GBM cell lines (GCL), patient-derived cells (PDCL) and patients’ tumor tissue (PT) and comparing the expression profiles. MATERIAL AND METHODS We measured expression of the above-mentioned antigens in 7 GCL (GaMG, U87, U373, U343, U251, U138, DKMG), 7 PDCL and PT of 9 patients by flow cytometry (FACSCanto II). After evaluation with FlowJo software (TreeStar), we scored antigen expression (0–1.0: low expression, 1.1–2.0: medium expression, 2.1–3.0: high expression) and calculated the mean expression and range. RESULTS GD2 showed a medium expression in GCL (x̅=1.3) but was highly expressed in PDCL (x̅=2.6) and PT (x̅=2.4). In contrast, CSPG4 displayed low expression in GCL (x̅=0.3) and PT (x̅=0.4), but medium expression in PDCL (x̅=1.9). CD133, a stem cell marker, showed low expression in GCL (x̅=0.8) and PDCL (x̅=0.4), whereas the expression in PT was medium (x̅=1.4). Both CD70 and Il13Rα2 were weakly expressed in GCL, PDCL and PT (x̅=0.2, 0.4, 0.0 and 0.5, 0.6, 0.4, respectively). HER2 displayed medium expression in GCL (x̅=1.4) and PDCL (x̅=1.4) and low expression in PT (x̅=0.6). For EGFRvIII medium expression was detectable in all three entities (x̅=1.4, 1.1 and 1.1). EphA2 was mildly expressed in GCL (x̅=0.1), medium expressed in PT (x̅=2.0) and highly expressed in PDCL (x̅=2.6). Overall, there was high variability of antigen surface expression even within each of the groups. CONCLUSION GCL, PDCL and PT display heterogenic antigen surface expression with high variability within each group, thereby complicating clinical translation of in vitro results obtained using cell lines. This aspect should be taken into account in GBM target antigen research.
外国的“免费搭车”和美国高昂的药价
Authors: Donald, Joel, Lexchin, 张拓红（译）
Journal: BMJ (2006)

在美国制药行业的支持下，美国政府打算让人们接受这种说法，即美国人之所以支付较高的药价，是因为他们承担了过高的研发成本，而这部分研发成本超出了他们应该承担的份额。本文的两位研究者从证据出发，认为事实并非如此。
MXene-infused bioelectronic interfaces for multiscale electrophysiology and stimulation
Authors: Nicolette Driscoll, Brian Erickson, Brendan B. Murphy, Andrew G. Richardson, Gregory Robbins, Nicholas V. Apollo, Georgios Mentzelopoulos, Tyler Mathis, Kanit Hantanasirisakul, Puneet Bagga, Sarah E. Gullbrand, Matthew Sergison, Ravinder Reddy, John A. Wolf, H. Isaac Chen, Timothy H. Lucas, Timothy R. Dillingham, Kathryn A. Davis, Yury Gogotsi, John D. Medaglia, Flavia Vitale
Journal: Science Translational Medicine (2021)

Soft bioelectronic interfaces for mapping and modulating excitable networks at high resolution and at large scale can enable paradigm-shifting diagnostics, monitoring, and treatment strategies. Yet, current technologies largely rely on materials and fabrication schemes that are expensive, do not scale, and critically limit the maximum attainable resolution and coverage. Solution processing is a cost-effective manufacturing alternative, but biocompatible conductive inks matching the performance of conventional metals are lacking. Here, we introduce MXtrodes, a class of soft, high-resolution, large-scale bioelectronic interfaces enabled by Ti3C2 MXene (a two-dimensional transition metal carbide nanomaterial) and scalable solution processing. We show that the electrochemical properties of MXtrodes exceed those of conventional materials and do not require conductive gels when used in epidermal electronics. Furthermore, we validate MXtrodes in applications ranging from mapping large-scale neuromuscular networks in humans to cortical neural recording and microstimulation in swine and rodent models. Last, we demonstrate that MXtrodes are compatible with standard clinical neuroimaging modalities.
Phimosis in childhood
Journal: BMJ (2013)

The last sentence recommends that in refractory cases of balanoposthitis or balanitis, "a combined steroid and antibiotic cream (such as Fucidin) . . .for a bacterial infection may be useful."In fact, Fucidin is just an antibiotic, and it is Fucidin H that is a combined steroid and antibiotic cream.
Designing Clinical Trials for Combination Immunotherapy: A Framework for Glioblastoma
Authors: Kirit Singh, Kristen A. Batich, Patrick Y. Wen, Aaron C. Tan, Stephen J. Bagley, Michael Lim, Michael Platten, Howard Colman, David M. Ashley, Susan M. Chang, Rifaquat Rahman, Evanthia Galanis, Alireza Mansouri, Vinay K. Puduvalli, David A. Reardon, Solmaz Sahebjam, John H. Sampson, John Simes, Donald A. Berry, Gelareh Zadeh, Tim F. Cloughesy, Minesh P. Mehta, Steven Piantadosi, Michael Weller, Amy B. Heimberger, Mustafa Khasraw
Journal: Clinical Cancer Research (2021)

Abstract Immunotherapy has revolutionized treatment for many hard-to-treat cancers but has yet to produce significant improvement in outcomes for patients with glioblastoma. This reflects the multiple and unique mechanisms of immune evasion and escape in this highly heterogeneous tumor. Glioblastoma engenders profound local and systemic immunosuppression and is remarkably effective at inducing T-cell dysfunction, posing a challenge to any immunotherapy-based approach. To overcome these mechanisms, multiple disparate modes of immune-oriented therapy will be required. However, designing trials that can evaluate these combinatorial approaches requires careful consideration. In this review, we explore the immunotherapy resistance mechanisms that have been encountered to date and how combinatorial approaches may address these. We also describe the unique aspects of trial design in both preclinical and clinical settings and consider endpoints and markers of response best suited for an intervention involving multiple agents.
Longitudinal Trends in Body Mass Index Before and During the COVID-19 Pandemic Among Persons Aged 2–19 Years — United States, 2018–2020
Authors: Samantha J. Lange, Lyudmyla Kompaniyets, David S. Freedman, Emily M. Kraus, Renee Porter, Heidi M. Blanck, Alyson B. Goodman
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Obesity is a serious health concern in the United States, affecting more than one in six children (1) and putting their long-term health and quality of life at risk.* During the COVID-19 pandemic, children and adolescents spent more time than usual away from structured school settings, and families who were already disproportionally affected by obesity risk factors might have had additional disruptions in income, food, and other social determinants of health.† As a result, children and adolescents might have experienced circumstances that accelerated weight gain, including increased stress, irregular mealtimes, less access to nutritious foods, increased screen time, and fewer opportunities for physical activity (e.g., no recreational sports) (2,3). CDC used data from IQVIA's Ambulatory Electronic Medical Records database to compare longitudinal trends in body mass index (BMI, kg/m2) among a cohort of 432,302 persons aged 2-19 years before and during the COVID-19 pandemic (January 1, 2018-February 29, 2020 and March 1, 2020-November 30, 2020, respectively). Between the prepandemic and pandemic periods, the rate of BMI increase approximately doubled, from 0.052 (95% confidence interval [CI] = 0.051-0.052 to 0.100 (95% CI = 0.098-0.101) kg/m2/month (ratio = 1.93 [95% CI = 1.90-1.96]). Persons aged 2-19 years with overweight or obesity during the prepandemic period experienced significantly higher rates of BMI increase during the pandemic period than did those with healthy weight. These findings underscore the importance of efforts to prevent excess weight gain during and following the COVID-19 pandemic, as well as during future public health emergencies, including increased access to efforts that promote healthy behaviors. These efforts could include screening by health care providers for BMI, food security, and social determinants of health, increased access to evidence-based pediatric weight management programs and food assistance resources, and state, community, and school resources to facilitate healthy eating, physical activity, and chronic disease prevention.
Activated osteoarthritis following immune checkpoint inhibitor treatment: an observational study
Authors: Pankti Reid, David FL Liew, Rajshi Akruwala, Anne R Bass, Karmela K Chan
Journal: Journal for ImmunoTherapy of Cancer (2021)

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy but can result in toxicities, known as immune-related adverse events (irAEs), due to a hyperactivated immune system. ICI-related inflammatory arthritis has been described in literature, but herewith we introduce and characterize post-ICI-activated osteoarthritis (ICI-aOA). We conducted a multicenter, retrospective, observational study of patients with cancer treated with ICIs and diagnosed with ICI-aOA by a rheumatologist. ICI-aOA was defined by (1) an increase in non-inflammatory joint pain after ICI initiation, (2) in joints characteristically affected by osteoarthritis, and (3) lack of inflammation on exam. Cases were graded using the Common Terminology Criteria for Adverse Events (CTCAE) V.6.0 rubric for arthralgia. Response Evaluation Criteria in Solid Tumors V.1.1 (v.4.03) guidelines determined tumor response. Results were analyzed using χ2 tests of association and multivariate logistic regression. Thirty-six patients had ICI-aOA with a mean age at time of rheumatology presentation of 66 years (51-81 years). Most patients had metastatic melanoma (10/36, 28%) and had received a PD-1/PD-L1 inhibitor monotherapy (31/36, 86%) with 5/36 (14%) combination therapy. Large joint involvement (hip/knee) was noted in 53% (19/36), small joints of hand 25% (9/36), and spine 14% (5/36). Two-thirds (24/36) suffered multiple joint involvement. Three of 36 (8%) had CTCAE grade 3, 14 (39%) grade 2 and 19 (53%) grade 1 manifestations. Symptom onset ranged from 6 days to 33.8 months with a median of 5.2 months after ICI initiation; five patients suffered from ICI-aOA after ICI cessation (0.6, 3.5, 4.4, 7.3, and 15.4 months after ICI cessation). The most common form of therapy was intra-articular corticosteroid injections only (15/36, 42%) followed by non-steroidal anti-inflammatory drugs only (7/36, 20%). Twenty patients (56%) experienced other irAEs, with rheumatic and dermatological being the most common. All three patients with high-grade ICI-aOA also had another irAE diagnosis at some point after ICI initiation. ICI-aOA should be recognized as an adverse event of ICI immunotherapy. Early referral to a rheumatologist can facilitate the distinction between ICI induced inflammatory arthritis from post-ICI mechanical arthropathy, the latter of which can be managed with local therapy that will not compromise ICI efficacy.
Sustained Increases in IGFBP-7 May Be Related to Doxorubicin in Breast Cancer Patients
Authors: Nicholas S. Wilcox, Biniyam G. Demessei, Amanda M. Smith, Joseph R. Carver, Liyong Zhang, Peter Liu, James L. Januzzi, Bonnie Ky
Journal: JACC CardioOncology (2021)

Insulin-like growth factor-binding protein-7 (IGFBP-7) is involved in cell senescence, and higher IGFBP-7 levels are associated with impaired myocardial compliance and diastolic dysfunction in patients with heart failure (HF) (1).However, the role of IGFBP-7 in cardio-oncology remains uncertain.We examined associations between changes in IGFBP-7 levels and echocardiographic measures of diastolic function in breast cancer patients receiving doxorubicin with or without trastuzumab.The Penn Cardiotoxicity of Cancer Therapy Study (NCT01173341) is a prospective longitudinal cohort of breast cancer patients from the Rena Rowan Breast Center of the Abramson Cancer Center at the University of Pennsylvania (Philadelphia, Pennsylvania).Details of the study design, population, and procedures have been described elsewhere (2).The study was approved by the local institutional review board.All patients provided written informed consent.Plasma IGFBP-7 was measured with the use of a precommercial COBAS Elecsys assay (Roche Diagnostics).The IGFBP-7 assay has a coefficient of variation (CV) of intra-assay precision <3% and interassay precision <6%.Quantitative echocardiography was performed by a sonographer blinded to patient clinical characteristics at the Penn Center for Quantitative Echocardiography (Philadelphia, Pennsylvania) with the use of TomTec Imaging Systems.Associations between baseline clinical variables and IGFBP-7 levels were evaluated by means of linear regression.Estimates of the mean (95% confidence interval [CI]) change from baseline, determined by means of repeated-measures linear regression via generalized estimating equations (GEE), were plotted over time to characterize changes in IGFBP-7 levels following doxorubicin initiation.Associations between changes in IGFBP-7 levels and echocardiographic diastolic function measures were determined with the use of repeated-measures linear regression via GEE.IGFBP-7
Minimizing the risk of Clostridium difficile infection as an early complication of autologous stem cell transplantation.
Authors: Joseph Van Galen, Samuel Maldonado, Leonid Volodin, Michael Kenneth Keng
Journal: Journal of Clinical Oncology (2021)

219 Background: Clostridium difficile infection (CDI) is one of the most important affecting patients immunocompromised by autologous stem cell transplantation (ASCT), and can be associated with increased morbidity and length of stay. One precipitating factor for index CDI cases in the ASCT population is heavy antibiotic exposure, which often includes prophylaxis. A retrospective review identified 11 cases of CDI (17%) in the 30-day period following ASCT performed at the University of Virginia Medical Center (UVAMC) between about June 2016 and July 2017. Various institutional and multicenter studies have reported incidence rates in this population ranging from less than 5% to more than 10%. Methods: To decrease CDI rate, a multidisciplinary team comprised of oncology and infectious diseases physicians, pharmacists, and nurses was formed. The group used quality improvement principles to identify and target areas of greatest significance. A first PDSA cycle was conducted between approximately July 2017 and June 2018, during which time administration of standard-of-care ciprofloxacin prophylaxis between T+0 and count recovery was suspended. A second PDSA cycle was executed between approximately May 2018 and July 2019, incorporating UV light equipment into existing post-discharge cleaning practices. Data were analyzed using process control charts with 3-sigma limits for ASCT length-of-stay (LOS) and 30-day post-transplant CDI incidence. Results: Suspension of prophylactic antibiotics did not have a significant effect on CDI incidence in our first PDSA cycle. In our second improvement cycle, most of which elapsed after prophylactic ciprofloxacin had been re-implemented, CDI incidence was almost halved, from 17 to 9%. A numerical decreased in LOS was observed in each subsequent PDSA cycle. Conclusions: Our multidisciplinary team applied quality improvement methods to drive a clinically significant reduction in the 30-day CDI incidence after ASCT at UVAMC. This outcome should be associated with an improved patient experience. Future PDSA cycles are scheduled and may include other cancer patients, beyond those receiving stem cell transplantation.[Table: see text]