tbuckley/cabot-search huggingface dataset:
Cyanobacteria-based self-oxygenated photodynamic therapy for anaerobic infection treatment and tissue repair
Authors: Bailiang Wang, Liyang Zhou, Yishun Guo, Hanwen Guo, Yiming Zhong, Xiaomin Huang, Yifan Ge, Qingying Wang, Xiaoying Chu, Yingying Jin, Kaiyue Lan, Mei Yang, Jia Qu
Journal: Bioactive Materials (2021)

Photodynamic therapy (PDT) is an important technique to deal with drug-resistant bacterial infections in the post-antibiotic era. However, the hypoxic environment in intractable infections such as refractory keratitis and periodontitis, makes PDT more difficult. In this work, spontaneous oxygen-producing cyanobacteria were used as the carrier of photosensitizer (Ce6), and ultrasmall Cu5.4O nanoparticles (Cu5.4O USNPs) with catalase activity for infection and inflammation elimination and rapid tissue repair (CeCycn-Cu5.4O). The loading of Ce6 and Cu5.4O USNPs onto cyanobacteria surface were confirmed by transmission electron microscopy, nano particle size analyzer, scanning electron microscopy. In vitro sterilization and biofilm removal experiments demonstrated that the restriction of hypoxic environment to PDT was significantly alleviated due to the oxygen production of cyanobacteria. Under laser irradiation, the close transfer of energy photons to oxygen produced by cyanobacteria reduced more than 90% of Ce6 dosages (660 nm, 200 mW/cm2, 2 min). It is worth mentioning that both rapid sterilization through PDT and long-term oxidized free radicals elimination were achieved by adjusting the ratio of Ce6 and Cu5.4O USNPs. Both periodontitis and refractory keratitis animal models proved the excellent self-oxygenation enhanced antibacterial property and promotion of tissue repair.
Stanford Neuromodulation Therapy (SNT): A Double-Blind Randomized Controlled Trial
Authors: Eleanor J. Cole, Angela L. Phillips, Brandon S. Bentzley, Katy H. Stimpson, Romina Nejad, Fahim Barmak, Clive Veerapal, Naushaba Khan, Kirsten Cherian, Emily Felber, Randi Brown, Elizabeth Choi, Sinead King, Heather Pankow, James H. Bishop, Azeezat Azeez, John Coetzee, Rachel Rapier, Nicole Odenwald, David Carreon, Jessica Hawkins, Maureen Chang, Jennifer Keller, Kristin Raj, Charles DeBattista, Booil Jo, Flint M. Espil, Alan F. Schatzberg, Keith D. Sudheimer, Nolan R. Williams
Journal: American Journal of Psychiatry (2021)

Depression is the leading cause of disability worldwide, and half of patients with depression have treatment-resistant depression. Intermittent theta-burst stimulation (iTBS) is approved by the U.S. Food and Drug Administration for the treatment of treatment-resistant depression but is limited by suboptimal efficacy and a 6-week duration. The authors addressed these limitations by developing a neuroscience-informed accelerated iTBS protocol, Stanford neuromodulation therapy (SNT; previously referred to as Stanford accelerated intelligent neuromodulation therapy, or SAINT). This protocol was associated with a remission rate of ∼90% after 5 days of open-label treatment. Here, the authors report the results of a sham-controlled double-blind trial of SNT for treatment-resistant depression.Participants with treatment-resistant depression currently experiencing moderate to severe depressive episodes were randomly assigned to receive active or sham SNT. Resting-state functional MRI was used to individually target the region of the left dorsolateral prefrontal cortex most functionally anticorrelated with the subgenual anterior cingulate cortex. The primary outcome was score on the Montgomery-Åsberg Depression Rating Scale (MADRS) 4 weeks after treatment.At the planned interim analysis, 32 participants with treatment-resistant depression had been enrolled, and 29 participants who continued to meet inclusion criteria received either active (N=14) or sham (N=15) SNT. The mean percent reduction from baseline in MADRS score 4 weeks after treatment was 52.5% in the active treatment group and 11.1% in the sham treatment group.SNT, a high-dose iTBS protocol with functional-connectivity-guided targeting, was more effective than sham stimulation for treatment-resistant depression. Further trials are needed to determine SNT's durability and to compare it with other treatments.
Chronic viral infections persistently alter marrow stroma and impair hematopoietic stem cell fitness
Authors: Stephan Isringhausen, YeVin Mun, Larisa Kovtonyuk, Nike J. Kräutler, Ute Suessbier, Alvaro Gomariz, Gianluca Spaltro, Patrick M. Helbling, Hui Chyn Wong, Takashi Nagasawa, Markus G. Manz, Annette Oxenius, César Nombela-Arrieta
Journal: The Journal of Experimental Medicine (2021)

Chronic viral infections are associated with hematopoietic suppression, bone marrow (BM) failure, and hematopoietic stem cell (HSC) exhaustion. However, how persistent viral challenge and inflammatory responses target BM tissues and perturb hematopoietic competence remains poorly understood. Here, we combine functional analyses with advanced 3D microscopy to demonstrate that chronic infection with lymphocytic choriomeningitis virus leads to (1) long-lasting decimation of the BM stromal network of mesenchymal CXCL12-abundant reticular cells, (2) proinflammatory transcriptional remodeling of remaining components of this key niche subset, and (3) durable functional defects and decreased competitive fitness in HSCs. Mechanistically, BM immunopathology is elicited by virus-specific, activated CD8 T cells, which accumulate in the BM via interferon-dependent mechanisms. Combined antibody-mediated inhibition of type I and II IFN pathways completely preempts degeneration of CARc and protects HSCs from chronic dysfunction. Hence, viral infections and ensuing immune reactions durably impact BM homeostasis by persistently decreasing the competitive fitness of HSCs and disrupting essential stromal-derived, hematopoietic-supporting cues.
Evaluation of COVID-19 Mortality and Adverse Outcomes in US Patients With or Without Cancer
Authors: Mariana Chavez-MacGregor, Xiudong Lei, Hui Zhao, Paul Scheet, Sharon H. Giordano
Journal: JAMA Oncology (2021)

As the COVID-19 pandemic continues, understanding the clinical outcomes of patients with cancer and COVID-19 has become critically important.To compare the outcomes of patients with or without cancer who were diagnosed with COVID-19 and to identify the factors associated with mortality, mechanical ventilation, intensive care unit (ICU) stay, and hospitalization.This cohort study obtained data from the Optum de-identified COVID-19 electronic health record data set. More than 500 000 US adults who were diagnosed with COVID-19 from January 1 to December 31, 2020, were analyzed.The patient groups were (1) patients without cancer, (2) patients with no recent cancer treatment, and (3) patients with recent cancer treatment (within 3 months before COVID-19 diagnosis) consisting of radiation therapy or systemic therapy.Mortality, mechanical ventilation, ICU stay, and hospitalization within 30 days of COVID-19 diagnosis were the main outcomes. Unadjusted rates and adjusted odds ratios (ORs) of adverse outcomes were presented according to exposure group.A total of 507 307 patients with COVID-19 were identified (mean [SD] age, 48.4 [18.4] years; 281 165 women [55.4%]), of whom 493 020 (97.2%) did not have cancer. Among the 14 287 (2.8%) patients with cancer, 9991 (69.9%) did not receive recent treatment and 4296 (30.1%) received recent treatment. In unadjusted analyses, patients with cancer, regardless of recent treatment received, were more likely to have adverse outcomes compared with patients without cancer (eg, mortality rate: 1.6% for patients without cancer, 5.0% for patients with no recent cancer treatment, and 7.8% for patients with recent cancer treatment). After adjustment, patients with no recent cancer treatment had similar or better outcomes than patients without cancer (eg, mortality OR, 0.93 [95% CI, 0.84-1.02]; mechanical ventilation OR, 0.61 [95% CI, 0.54-0.68]). In contrast, a higher risk of death (OR, 1.74; 95% CI, 1.54-1.96), ICU stay (OR, 1.69; 95% CI, 1.54-1.87), and hospitalization (OR, 1.19; 95% CI, 1.11-1.27) was observed in patients with recent cancer treatment. Compared with patients with nonmetastatic solid tumors, those with metastatic solid tumors and hematologic malignant neoplasms had worse outcomes (eg, mortality OR, 2.36 [95% CI, 1.96-2.84]; mechanical ventilation OR, 0.87 [95% CI, 0.70-1.08]). Recent chemotherapy and chemoimmunotherapy were also associated with worse outcomes (eg, chemotherapy mortality OR, 1.84 [95% CI, 1.51-2.26]).This cohort study found that patients with recent cancer treatment and COVID-19 had a significantly higher risk of adverse outcomes, and patients with no recent cancer treatment had similar outcomes to those without cancer. The findings have risk stratification and resource use implications for patients, clinicians, and health systems.
Sulfated Alginate Hydrogels Prolong the Therapeutic Potential of MSC Spheroids by Sequestering the Secretome (Adv. Healthcare Mater. 21/2021)
Authors: Marissa Gionet‐Gonzales, Alena Casella, Daphne Diloretto, Clara Ginnell, Katherine H. Griffin, Anne Bigot, J. Kent Leach
Journal: Advanced Healthcare Materials (2021)

Mesenchymal Stromal Cells In article number 2101048 by J. Kent Leach and co-workers, spheroids of mesenchymal stromal cells (MSCs) secrete high levels of relevant growth factors (GFs) for tissue regeneration. Sulfated alginate can sequester these GFs through ionic interactions, allowing increased therapeutic potency to invading cells. This paper investigates how MSC spheroidsecreted GFs are retained in sulfated alginate and their ability to influence cell function in vitro.
Acid hydrolases in blister fluid.
Authors: GUNNAR VOLDEN
Journal: British Journal of Dermatology (1978)

Seven glycoside hydrolases have been investigated in suction blister fluid, interstitial fluid and in serum. Six of these have been characterized; no diflerences could be demonstrated between the corresponding enzymes from the various sources. The remaining enzyme (β‐glucosidase) was not found. Quantitative data suggest that 2 enzymes (β‐acetylglucosaminidase and β ‐glucuronidase) diffuse freely from the epidermis into blister fluid, whereas 4 (β ‐glucosidase, α‐ and β ‐galactosidase and α‐mannosidase) are almost entirely retained in the roof of the bulla.
SPARC overexpression enhances sensitivity to nab-paclitaxel in vivo
Authors: Vuong Trieu, Jaiweon Hwang, Seema Zaidi, Christine Lowe, Neha Mathiel, Dan Knauer, Neil Desai
Journal: Cancer Research (2007)

3480  Background: SPARC (Secreted Protein Acidic and Rich in Cysteine) is overexpressed in many cancers including breast, prostate, lung, brain, head-and-neck, and kidney. We have previously shown that SPARC expression appeared to correlate with response to nanoparticle albumin-bound (nab) paclitaxel (Abraxane, ABX) in head-and-neck cancer patients, and increase in SPARC suggested improved response to ABX in tumor models. To further define the role of SPARC, a cell line engineered to overexpress SPARC was used to test whether SPARC overexpression would result in increased albumin binding and increased response to ABX in vivo.  Methods: Recombinant human SPARC was expressed and purified using HEK 293 cells. Biologic activities of rhSPARC were characterized by testing cytotoxicity against human cancer cell lines and normal rat hepatocytes, angiogenesis in a HUVEC tube formation assay, and affinity for albumin in a solid phase binding assay with Alexa 488 labeled BSA binding to rhSPARC immobilized onto PVDF. To examine the effect of SPARC overexpression on tumor response to ABX, SPARC cDNA was subcloned into an expression vector and stable SPARC overexpressing lines of PC3 prostate cancer cells were generated by calcium phosphate transfection and G418 selection. The PC3 SPARC overexpressor (HN104) and WT PC3 were grown as xenografts in vivo and examined for response to ABX (30 mg/kg, qdx5, N=5).  Results: Purified rhSPARC had a N-terminal sequence identical to native human SPARC, expected amino acid composition, and mature, low mannose glycosylation. In the HUVEC tube formation assay, rhSPARC was pro-angiogenic at 10 µg/mL and anti-angiogenic at 100 µg/mL. rhSPARC was noncytotoxic against HT29, MX-1, HepG2, and normal rat hepatocytes at all dose levels. The SPARC albumin binding assay revealed a pattern of saturable and specific binding with an estimated Kd of 700 µM. The HN104 SPARC overexpressing xenograft exhibited enhanced response to ABX with T-C of 36 days compared with the parent WT PC3 xenograft with T-C of 25 days (p  Conclusions: rhSPARC exhibited an affinity for albumin at physiologic concentrations, potentially leading to targeting of nanoparticle albumin-bound drugs in vivo. Exogenous rhSPARC stimulated angiogenesis (tube formation) in vitro, supporting the role of SPARC in tumor angiogenesis and invasiveness. The SPARC overexpressing prostate cancer PC3 xenograft exhibited enhanced response to ABX relative to WT PC3, supporting the hypothesis that SPARC overexpression could lead to enhanced anti-tumor effect of nanoparticle albumin-bound drugs.
Mortality trends in multiple myeloma after the introduction of novel therapies in the United States
Authors: Moritz Binder, Bharat Nandakumar, S. Vincent Rajkumar, Prashant Kapoor, Francis K. Buadi, David Dingli, Martha Q. Lacy, Morie A. Gertz, Suzanne R. Hayman, Nelson Leung, Amie Fonder, Miriam Hobbs, Yi Lisa Hwa, Eli Muchtar, Rahma Warsame, Taxiarchis V. Kourelis, Wilson I. Gonsalves, Stephen Russell, Yi Lin, Mustaqeem Siddiqui, Robert A. Kyle, Angela Dispenzieri, Shaji K. Kumar
Journal: Leukemia (2021)
Cardiac and Visceral Signs of Connective Tissue Dysplasia in Children with Juvenile Rheumatoid Arthritis According to Ultrasound Examination Data
Authors: A. A. Yusufov, I. A. Cherkasova, E. A. Lavrova, A. A. Plyukhin
Journal: Radiology - Practice (2021)

To study the cardiac and visceral signs of connective tissue dysplasia in children with juvenile rheumatoid arthritis, a comprehensive ultrasound examination of the abdominal cavity organs and echocardiography examination were conducted according to the standard protocol in 52 children aged from 5 to 16 years with the diagnosis of juvenile rheumatoid arthritis. The reference group consisted of 26 patients with autonomic dysfunction (vegetative-vascular dystonia). The incidence of such visceral dysplasia types as duodenogastric reflux, gastroesophageal reflux, and gallbladder malformations among children with juvenile rheumatoid arthritis was shown higher than in the reference group. The main cardiac sign of connective tissue dysplasia in patients with juvenile rheumatoid arthritis are an excessive chord of the left ventricle.
TCT-332 Machine Learning Methods in Prediction of Acute Kidney Injury: Application of the US National Cardiovascular Data Registry Model on Japanese Percutaneous Coronary Intervention Patients
Authors: Toshiki Kuno, Takahisa Mikami, Yuki Sahashi, Yohei Numasawa, Masahiro Suzuki, Shigetaka Noma, Keiichi Fukuda, Shun Kohsaka
Journal: Journal of the American College of Cardiology (2021)
The estimated health impact of sodium reduction through food reformulation in Australia: A modeling study
Authors: Kathy Trieu, Daisy H. Coyle, Ashkan Afshin, Bruce Neal, Matti Marklund, Jason H. Y. Wu
Journal: PLoS Medicine (2021)

Background The Australian Government recently established sodium targets for packaged foods to encourage voluntary reformulation to reduce population sodium consumption and related diseases. We modeled the health impact of Australia’s sodium reformulation targets and additional likely health gains if more ambitious, yet feasible sodium targets had been adopted instead. Methods and findings Using comparative risk assessment models, we estimated the averted deaths, incidence, and disability-adjusted life years (DALYs) from cardiovascular disease (CVD), chronic kidney disease (CKD) and stomach cancer after implementation of (a) Australia’s sodium targets (overall and by individual companies); (b) United Kingdom’s targets (that covers more product categories); and (c) an optimistic scenario (sales-weighted 25th percentile sodium content for each food category included in the UK program). We used nationally representative data to estimate pre- and post-intervention sodium intake, and other key data sources from the Global Burden of Disease study. Full compliance with the Australian government’s sodium targets could prevent approximately 510 deaths/year (95% UI, 335 to 757), corresponding to about 1% of CVD, CKD, and stomach cancer deaths, and prevent some 1,920 (1,274 to 2,600) new cases and 7,240 (5,138 to 10,008) DALYs/year attributable to these diseases. Over half (59%) of deaths prevented is attributed to reformulation by 5 market-dominant companies. Compliance with the UK and optimistic scenario could avert approximately an additional 660 (207 to 1,227) and 1,070 (511 to 1,856) deaths/year, respectively, compared to Australia’s targets. The main limitation of this study (like other modeling studies) is that it does not prove that sodium reformulation programs will prevent deaths and disease events; rather, it provides the best quantitative estimates and the corresponding uncertainty of the potential effect of the different programs to guide the design of policies. Conclusions There is significant potential to strengthen Australia’s sodium reformulation targets to improve its health impact. Promoting compliance by market-dominant food companies will be critical to achieving the potential health gains.
Light-triggered nitric oxide release and structure transformation of peptide for enhanced intratumoral retention and sensitized photodynamic therapy
Authors: Lingdong Jiang, Danyang Chen, Zhaokui Jin, Chao Xia, Qingqing Xu, Mingjian Fan, Yunlu Dai, Jia Liu, Yuanpei Li, Qianjun He
Journal: Bioactive Materials (2021)

Tumor-targeted delivery of nanomedicine is of great importance to improve therapeutic efficacy of cancer and minimize systemic side effects. Unfortunately, nowadays the targeting efficiency of nanomedicine toward tumor is still quite limited and far from clinical requirements. In this work, we develop an innovative peptide-based nanoparticle to realize light-triggered nitric oxide (NO) release and structural transformation for enhanced intratumoral retention and simultaneously sensitizing photodynamic therapy (PDT). The designed nanoparticle is self-assembled from a chimeric peptide monomer, TPP-RRRKLVFFK-Ce6, which contains a photosensitive moiety (chlorin e6, Ce6), a β-sheet-forming peptide domain (Lys-Leu-Val-Phe-Phe, KLVFF), an oligoarginine domain (RRR) as NO donor and a triphenylphosphonium (TPP) moiety for targeting mitochondria. When irradiated by light, the constructed nanoparticles undergo rapid structural transformation from nanosphere to nanorod, enabling to achieve a significantly higher intratumoral accumulation by 3.26 times compared to that without light irradiation. More importantly, the conversion of generated NO and reactive oxygen species (ROS) in a light-responsive way to peroxynitrite anions (ONOO-) with higher cytotoxicity enables NO to sensitize PDT in cancer treatment. Both in vitro and in vivo studies demonstrate that NO sensitized PDT based on the well-designed transformable nanoparticles enables to eradicate tumors efficiently. The light-triggered transformable nanoplatform developed in this work provides a new strategy for enhanced intratumoral retention and improved therapeutic outcome.
Altering phosphoinositides in high‐fat diet‐associated prostate tumor xenograft growth
Authors: Mingguo Huang, Atsushi Koizumi, Shintaro Narita, Hiroki Nakanishi, Hiromi Sato, Soki Kashima, Taketoshi Nara, Sohei Kanda, Kazuyuki Numakura, Mitsuru Saito, Shigeru Satoh, Hiroshi Nanjo, Takehiko Sasaki, Tomonori Habuchi
Journal: MedComm (2021)

Abstract The metabolic reprogramming of phospholipids may affect intracellular signal transduction pathways. A high‐fat diet (HFD) is attributed to prostate cancer (PCa) progression, but the expression pattern and role of phospholipids in HFD‐mediated PCa progression remains unclear. In this study, HFD enhanced LNCaP xenograft tumor growth by upregulating the phosphatidylinositol (PI) 3‐kinase (PI3K)/AKT signaling pathway. A lipidomic analysis using xenograft tumors showed that phosphoinositides, especially PI (3,4,5)‐trisphosphate (PIP 3 ), including several species containing C38:4, C38:3, and C40:4 fatty acids, increased in the HFD group compared to control. Fatty acid synthase (FASN) was significantly upregulated in xenograft tumors under HFD in both gene and protein levels. PCa cell growth was significantly inhibited through the decreased AKT signaling pathway by treatment with cerulenin, a chemical FASN inhibitor, which also downregulated PIP, PIP 2 , and PIP 3 but not PI. Thus, dietary fat influences PCa progression and alters phosphoinositides, especially PIP 3 , a critical player in the PI3K/AKT pathway. These results may offer appropriate targets, such as FASN, for dietary intervention and/or chemoprevention to reduce PCa incidence and progression.
Abstract 15289: Identification of Emetine as a Therapeutic Agent for Pulmonary Arterial Hypertension-Novel Effects of an Old Drug
Authors: Mohammad Abdul Hai Siddique, Kimio Satoh, Ryo Kurosawa, Nobuhiro Kikuchi, Md. Elias Al-Mamun, Junichi Omura, Taijyu Satoh, Masamichi Nogi, Shinichiro Sunamura, Satoshi Miyata, Hirofumi Udea, Hidetoshi Tokuyama, Hiroaki Shimokawa
Journal: Circulation (2019)

Introduction: The imbalance between proliferation and apoptosis in pulmonary artery smooth muscle cells (PASMCs) promotes the development of pulmonary arterial hypertension (PAH). Hypothesis: To di...
A mixture model for signature discovery from sparse mutation data
Authors: Itay Sason, Yuexi Chen, Mark D.M. Leiserson, Roded Sharan
Journal: Genome Medicine (2021)

Mutational signatures are key to understanding the processes that shape cancer genomes, yet their analysis requires relatively rich whole-genome or whole-exome mutation data. Recently, orders-of-magnitude sparser gene-panel-sequencing data have become increasingly available in the clinic. To deal with such sparse data, we suggest a novel mixture model, Mix. In application to simulated and real gene-panel sequences, Mix is shown to outperform current approaches and yield mutational signatures and patient stratifications that are in higher agreement with the literature. We further demonstrate its utility in several clinical settings, successfully predicting therapy benefit and patient groupings from MSK-IMPACT pan-cancer data. Availability: https://github.com/itaysason/Mix-MMM .