tbuckley/cabot-search huggingface dataset:
Rociletinib (CO-1686) enhanced the efficacy of chemotherapeutic agents in ABCG2-overexpressing cancer cells in vitro and in vivo
Authors: Fanpu Zeng, Fang Wang, Zongheng Zheng, Zhen Chen, Kenneth Kin Wah To, Hong Zhang, Qian Han, Liwu Fu
Journal: Acta Pharmaceutica Sinica B (2020)

Overexpression of adenosine triphosphate (ATP)-binding cassette subfamily G member 2 (ABCG2) in cancer cells is known to cause multidrug resistance (MDR), which severely limits the clinical efficacy of chemotherapy. Currently, there is no FDA-approved MDR modulator for clinical use. In this study, rociletinib (CO-1686), a mutant-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), was found to significantly improve the efficacy of ABCG2 substrate chemotherapeutic agents in the transporter-overexpressing cancer cells in vitro and in MDR tumor xenografts in nude mice, without incurring additional toxicity. Mechanistic studies revealed that in ABCG2-overexpressing cancer cells, rociletinib inhibited ABCG2-mediated drug efflux and increased intracellular accumulation of ABCG2 probe substrates. Moreover, rociletinib, inhibited the ATPase activity, and competed with [125I] iodoarylazidoprazosin (IAAP) photolabeling of ABCG2. However, ABCG2 expression at mRNA and protein levels was not altered in the ABCG2-overexpressing cells after treatment with rociletinib. In addition, rociletinib did not inhibit EGFR downstream signaling and phosphorylation of protein kinase B (AKT) and extracellular signal-regulated kinase (ERK). Our results collectively showed that rociletinib reversed ABCG2-mediated MDR by inhibiting ABCG2 efflux function, thus increasing the cellular accumulation of the transporter substrate anticancer drugs. The findings advocated the combination use of rociletinib and other chemotherapeutic drugs in cancer patients with ABCG2-overexpressing MDR tumors.
Multicenter Validation of Association Between Decline in MRI‐PDFF and Histologic Response in NASH
Authors: Rohit Loomba, Brent A Neuschwander‐Tetri, Arun Sanyal, Naga Chalasani, Anna Mae Diehl, Norah Terrault, Kris Kowdley, Srinivasan Dasarathy, David Kleiner, Cynthia Behling, Joel Lavine, Mark Van Natta, Michael Middleton, James Tonascia, Claude Sirlin
Journal: Hepatology (2020)

Emerging data from a single-center study suggests that a 30% relative reduction in liver fat content as assessed by magnetic resonance imaging-proton density fat fraction (MRI-PDFF) from baseline may be associated with histologic improvement in nonalcoholic steatohepatitis (NASH). There are limited multicenter data comparing an active drug versus placebo on the association between the quantity of liver fat reduction assessed by MRI-PDFF and histologic response in NASH. This study aims to examine the association between 30% relative reduction in MRI-PDFF and histologic response in obeticholic acid (OCA) versus placebo-treated patients in the FLINT (farnesoid X receptor ligand obeticholic acid in NASH trial).This is a secondary analysis of the FLINT trial including 78 patients with MRI-PDFF measured before and after treatment along with paired liver histology assessment. Histologic response was defined as a 2-point improvement in nonalcoholic fatty liver disease activity score without worsening of fibrosis. OCA (25 mg orally once daily) was better than placebo in improving MRI-PDFF by an absolute difference of -3.4% (95% confidence interval [CI], -6.5 to -0.2%, P value = 0.04) and relative difference of -17% (95% CI, -34 to 0%, P value = 0.05). The optimal cutoff point for relative decline in MRI-PDFF for histologic response was 30% (using Youden's index). The rate of histologic response in those who achieved less than 30% decline in MRI-PDFF versus those who achieved a 30% or greater decline in MRI-PDFF (MRI-PDFF responders) relative to baseline was 19% versus 50%, respectively. Compared with MRI-PDFF nonresponders, MRI-PDFF responders demonstrated both a statistically and clinically significant higher odds 4.86 (95% CI, 1.4-12.8, P value < 0.009) of histologic response, including significant improvements in both steatosis and ballooning.OCA was better than placebo in reducing liver fat. This multicenter trial provides data regarding the association between 30% decline in MRI-PDFF relative to baseline and histologic response in NASH.
A32 Evaluation of the Mutant KRAS-Driven NSCLC Tumor Immune Microenvironment Using Patient-Derived Cell Line Xenografts in a Humanized Mouse Preclinical Model for Development of New Immunotherapy Approaches
Authors: H. Li, C. Han, H. Park, A. Zhang, Z. Liu, L. Girard, N. Sorrelle, R.A. Brekken, Y. Fu, J.D. Minna
Journal: Journal of Thoracic Oncology (2020)
HIFI: estimating DNA-DNA interaction frequency from Hi-C data at restriction-fragment resolution
Authors: Christopher JF Cameron, Josée Dostie, Mathieu Blanchette
Journal: Genome biology (2020)

Abstract Hi-C is a popular technique to map three-dimensional chromosome conformation. In principle, Hi-C’s resolution is only limited by the size of restriction fragments. However, insufficient sequencing depth forces researchers to artificially reduce the resolution of Hi-C matrices at a loss of biological interpretability. We present the Hi-C Interaction Frequency Inference (HIFI) algorithms that accurately estimate restriction-fragment resolution Hi-C matrices by exploiting dependencies between neighboring fragments. Cross-validation experiments and comparisons to 5C data and known regulatory interactions demonstrate HIFI’s superiority to existing approaches. In addition, HIFI’s restriction-fragment resolution reveals a new role for active regulatory regions in structuring topologically associating domains.
Cortical Transplantation of Brain‐Mimetic Glycosaminoglycan Scaffolds and Neural Progenitor Cells Promotes Vascular Regeneration and Functional Recovery after Ischemic Stroke in Mice
Authors: Myles R. McCrary, Kaleena Jesson, Zheng Z. Wei, Meghan Logun, Christopher Lenear, Stephen Tan, Xiaohuan Gu, Michael Q. Jiang, Lohitash Karumbaiah, Shan Ping Yu, Ling Wei
Journal: Advanced Healthcare Materials (2020)

Stroke causes significant mortality and morbidity. Currently, there are no treatments which can regenerate brain tissue lost to infarction. Neural progenitor cells (NPCs) are at the forefront of preclinical studies for regenerative stroke therapies. NPCs can differentiate into and replace neurons and promote endogenous recovery mechanisms such as angiogenesis via trophic factor production and release. The stroke core is hypothetically the ideal location for replacement of neural tissue since it is in situ and develops into a potential space where injections may be targeted with minimal compression of healthy peri-infarct tissue. However, the compromised perfusion and tissue degradation following ischemia create an inhospitable environment resistant to cellular therapy. Overcoming these limitations is critical to advancing cellular therapy. In this work, the therapeutic potential of mouse-induced pluripotent stem cell derived NPCs is tested encapsulated in a basic fibroblast growth factor (bFGF) binding chondroitin sulfate-A (CS-A) hydrogel transplanted into the infarct core in a mouse sensorimotor cortex mini-stroke model. It is shown that CS-A encapsulation significantly improves vascular remodeling, cortical blood flow, and sensorimotor behavioral outcomes after stroke. It is found these improvements are negated by blocking bFGF, suggesting that the sustained trophic signaling endowed by the CS-A hydrogel combined with NPC transplantation can promote tissue repair.
단기간의 라미부딘 투여중 라미부딘 내성을 가진 HBV 변이형의 출현에 관한 연구
Authors: 백용한, 한광협, 전재윤, 문영명, 정효영
Journal: Clinical and Molecular Hepatology (1999)

Background/Aims: The emergence of lamivudine-resistant mutant hepatitis B virus (HBV), with aminoacid substitution in the YMDD motif of DNA polymerase, has been reported in the long-term lamivudine use group. However there is no report about the emergence of mutant viruses during the short-term lamivudine therapy. The objective of this study was to investigate the emergence of YMDD mutant HBV during short-term lamivudine therapy. Methods: We evaluated twenty-eight chronic hepatitis B patients who were HBeAg and HBV DNA positive and treated with lamivudine 100mg p.o. daily for 12 weeks. First, we investigated the emergence of YMDD mutants by nested polymerase chain reaction (PCR) method developed by Chayama et al in 19 patients who lost HBV DNA during lamivudine therapy but showed HBV DNA re-emergence 2 weeks after the end of therapy. Second, DNA subcloning and sequencing of HBV DNA polymerase including YMDD motif was undertaken in one patient's serial blood samples at 0, 8, 12 weeks to confirm the results of nested PCR. Results: YMDD motif mutation was detected in 17(90%) out of 19 patients at the end of therapy and the type of mutations were YIDD only. At the end of therapy, mutant was predominant in 5 patients, both mutant and wild type were similar in proportion in 3 patients, and wild type was predominant in 9 patients. When we carried out nested PCR serially with samples of 0, 2, 4, 8, 12, 14 weeks after initiation of therapy in 5 patients who were mutant predominant at 12 weeks, YIDD mutant began to be detected from 2 weeks in 4 patients and from 4 weeks in one patient. However, rapid turnover from mutant to wild type happened after the end of therapy, so only wild type was detected in 3 patients and wild type became predominant in 2 patients at 2 weeks after the end of therapy. All the sequencing results of serial blood samples in one patient were consistent with nested PCR data. Conclusions: The presence of YMDD motif HBV polymerase mutant may be possible before administration of lamivudine in Korean chronic hepatitis B patients. Nested PCR assay would be an useful method to detect YMDD mutant. (Korean J Hepatol 1999;5:173－183)
Assessment of the anti-CD40 antibody iscalimab in patients with primary Sjögren's syndrome: a multicentre, randomised, double-blind, placebo-controlled, proof-of-concept study
Authors: Benjamin A Fisher, Antonia Szanto, Wan-Fai Ng, Michele Bombardieri, Maximilian G Posch, Athena S Papas, Arwa M Farag, Thomas Daikeler, Bettina Bannert, Diego Kyburz, Alan J Kivitz, Steven E Carsons, David A Isenberg, Francesca Barone, Simon J Bowman, Pascal Espié, David Floch, Cyrielle Dupuy, Xiaohui Ren, Petra M Faerber, Andrew M Wright, Hans-Ulrich Hockey, Michael Rotte, Julie Milojevic, Alexandre Avrameas, Marie-Anne Valentin, James S Rush, Peter Gergely
Journal: The Lancet Rheumatology (2020)
Vaccination of Infants with Meningococcal Group B Vaccine (4CMenB) in England
Authors: Shamez N. Ladhani, Nick Andrews, Sydel R. Parikh, Helen Campbell, Joanne White, Michael Edelstein, Xilian Bai, Jay Lucidarme, Ray Borrow, Mary E. Ramsay
Journal: New England Journal of Medicine (2020)

In September 2015, the United Kingdom introduced the multicomponent meningococcal group B vaccine (4CMenB, Bexsero) into its publicly funded national immunization program at a reduced two-dose priming schedule for infants, with a 12-month booster.
Racial Ethnic Disparities in Youth With Type 1 Diabetes Participating in Diabetes Summer Camps
Authors: Jessica M. Valenzuela, Sam E. Records, Kelly A. Mueller, Megan T. Martin, Risa M. Wolf
Journal: Diabetes Care (2020)

OBJECTIVE Diabetes camps are beneficial for campers and include benefits such as increases in diabetes knowledge, glycemic control, and psychological functioning. Racial/ethnic minority youth are likely to have poorer disease management and glycemic control. We hypothesized that minority youth with type 1 diabetes have reduced participation in diabetes summer camps. RESEARCH DESIGN AND METHODS We analyzed deidentified data from 5,256 campers with type 1 diabetes who participated in a network of 48 American Diabetes Association–affiliated summer camps in 2018, and we compared participation rates by racial/ethnic category to the most recent SEARCH for Diabetes in Youth study prevalence rates. RESULTS Camper demographics were significantly different than in the general population of children with type 1 diabetes (P &amp;lt; 0.001). Minority youth were more likely to attend day camp, be first-time campers, and request financial aid, and they were less likely to be on insulin pump therapy or use continuous glucose monitors. CONCLUSIONS Racial/ethnic minority youth with diabetes are underrepresented in diabetes camps nationwide.
Gastric microbes associated with gastric inflammation, atrophy and intestinal metaplasia 1 year after<i>Helicobacter pylori</i>eradication
Authors: Joseph J Y Sung, Olabisi Oluwabukola Coker, Eagle Chu, Chun Ho Szeto, Simson Tsz Yat Luk, Harry Cheuk Hay Lau, Jun Yu
Journal: Gut (2020)

Helicobacter pylori is associated with gastric inflammation, precancerous gastric atrophy (GA) and intestinal metaplasia (IM). We aimed to identify microbes that are associated with progressive inflammation, GA and IM 1 year after H. pylori eradication.A total of 587 H. pylori-positive patients were randomised to receive H. pylori eradication therapy (295 patients) or placebo (292 patients). Bacterial taxonomy was analysed on 404 gastric biopsy samples comprising 102 pairs before and after 1 year H. pylori eradication and 100 pairs before and after 1 year placebo by 16S rRNA sequencing.Analysis of microbial sequences confirmed the eradication of H. pylori in treated group after 1 year. Principal component analysis revealed distinct microbial clusters reflected by increase in bacterial diversity (p<0.00001) after H. pylori eradication. While microbial interactions remained largely unchanged after placebo treatment, microbial co-occurrence was less in treated group. Acinetobacter lwoffii, Streptococcus anginosus and Ralstonia were enriched while Roseburia and Sphingomonas were depleted in patients with persistent inflammation 1 year after H. pylori eradication. A distinct cluster of oral bacteria comprising Peptostreptococcus, Streptococcus, Parvimonas, Prevotella, Rothia and Granulicatella were associated with emergence and persistence of GA and IM. Probiotic Faecalibacterium praustznii was depleted in subjects who developed GA following H. pylori eradication. Functional pathways including amino acid metabolism and inositol phosphate metabolism were enriched while folate biosynthesis and NOD-like receptor signalling decreased in atrophy/IM-associated gastric microbiota.This study identified that gastric microbes contribute to the progression of gastric carcinogenesis after H. pylori eradication.
Efficacy of Therapy for Eosinophilic Esophagitis in Real-World Practice
Authors: Emilio J. Laserna-Mendieta, Sergio Casabona, Edoardo Savarino, Antonia Perelló, Isabel Pérez-Martínez, Danila Guagnozzi, Jesús Barrio, Antonio Guardiola, Teresa Asensio, Susana de la Riva, Miriam Ruiz-Ponce, Juan Armando Rodríguez-Oballe, Cecilio Santander, Ángel Arias, Alfredo J. Lucendo
Journal: Clinical Gastroenterology and Hepatology (2020)
A Biocompatible and Near‐Infrared Liposome for In Vivo Ultrasound‐Switchable Fluorescence Imaging
Authors: Yang Liu, Tingfeng Yao, Wenbin Cai, Shuai Yu, Yi Hong, Kytai T. Nguyen, Baohong Yuan
Journal: Advanced Healthcare Materials (2020)

Abstract Fluorescence imaging is a remarkable tool for molecular targeting and multicolor imaging, but it suffers from low resolution in centimeter‐deep tissues. The recently developed ultrasound‐switchable fluorescence (USF) imaging has overcome this challenge and achieved in vivo imaging in a mouse with help from the indocyanine green (ICG) dye encapsulated poly(N‐isopropylacrylamide) (ICG‐PNIPAM) contrast agent. However, the ICG‐PNIPAM has shortcomings, such as concerns about cytotoxicity and blueshifted excitation and emission spectra. This study introduces a newly developed ICG‐encapsulated liposome to broaden the contrast agent selection for USF imaging and resolve the issues mentioned above. The emission peak of the ICG‐liposome is 836 nm with excellent biostability and USF imaging capability. Furthermore, the cell viability test verifies the low cytotoxicity feature. Eventually, both ex vivo and in vivo USF imaging are successfully achieved and 3D USF images are acquired. The ex vivo result confirms that the ICG‐liposome maintains the thermoresponsive characteristic at the right lobe of the liver and is able to conduct the USF imaging. The further in vivo USF imaging demonstrates that although the whole liver emitted fluorescence, only the right lobe of the liver contains the working ICG‐liposome.
A Chimeric Signal Peptide–Galectin-3 Conjugate Induces Glycosylation-Dependent Cancer Cell–Specific Apoptosis
Authors: Sok-Hyong Lee, Fatima Khwaja Rehman, Kari C. Tyler, Bing Yu, Zhaobin Zhang, Satoru Osuka, Abdessamad Zerrouqi, Milota Kaluzova, Costas G. Hadjipanayis, Richard D. Cummings, Jeffrey J. Olson, Narra S. Devi, Erwin G. Van Meir
Journal: Clinical Cancer Research (2020)

Exploitation of altered glycosylation in cancer is a major goal for the design of new cancer therapy. Here, we designed a novel secreted chimeric signal peptide-Galectin-3 conjugate (sGal-3) and investigated its ability to induce cancer-specific cell death by targeting aberrantly N-glycosylated cell surface receptors on cancer cells.sGal-3 was genetically engineered from Gal-3 by extending its N-terminus with a noncleavable signal peptide from tissue plasminogen activator. sGal-3 killing ability was tested on normal and tumor cells in vitro and its antitumor activity was evaluated in subcutaneous lung cancer and orthotopic malignant glioma models. The mechanism of killing was investigated through assays detecting sGal-3 interaction with specific glycans on the surface of tumor cells and the elicited downstream proapoptotic signaling.We found sGal-3 preferentially binds to β1 integrin on the surface of tumor cells due to aberrant N-glycosylation resulting from cancer-associated upregulation of several glycosyltransferases. This interaction induces potent cancer-specific death by triggering an oncoglycan-β1/calpain/caspase-9 proapoptotic signaling cascade. sGal-3 could reduce the growth of subcutaneous lung cancers and malignant gliomas in brain, leading to increased animal survival.We demonstrate that sGal-3 kills aberrantly glycosylated tumor cells and antagonizes tumor growth through a novel integrin β1-dependent cell-extrinsic apoptotic pathway. These findings provide proof-of-principle that aberrant N-oncoglycans represent valid cancer targets and support further translation of the chimeric sGal-3 peptide conjugate for cancer therapy.
Bariatric Surgery as a Long-Term Treatment for Type 2 Diabetes/Metabolic Syndrome
Authors: Zubaidah Nor Hanipah, Philip R. Schauer
Journal: Annual Review of Medicine (2020)

Metabolic surgery is increasingly becoming recognized as a more effective treatment for patients with type 2 diabetes (T2D) and obesity as compared to lifestyle modification and medical management alone. Both observational studies and clinical trials have shown metabolic surgery to result in sustained weight loss (20-30%), T2D remission rates ranging from 23% to 60%, and improvement in cardiovascular risk factors such as hypertension and dyslipidemia. Metabolic surgery is cost-effective and relatively safe, with perioperative risks and mortality comparable to low-risk procedures such as cholecystectomy, hysterectomy, and appendectomy. International diabetes and medical organizations have endorsed metabolic surgery as a standard treatment for T2D with obesity.
Improved Survival in Patients with Metastatic Castration Resistant Prostate Cancer (MCRPC) Treated on Clinical Trials
Authors: C. Pezaro, A.G. Omlin, D. Mukherji, S. Sandhu, D. Bianchini, A. Mulick Cassidy, G. Maier, D. Olmos, G. Attard, J.S. de Bono
Journal: Annals of Oncology (2012)
Cancer Theranostics: A Tumor Microenvironment‐Responsive Biodegradable Mesoporous Nanosystem for Anti‐Inflammation and Cancer Theranostics (Adv. Healthcare Mater. 2/2020)
Authors: Jianrong Wu, Shiwei Niu, David H. Bremner, Wei Nie, Zi Fu, Dejian Li, Li‐Min Zhu
Journal: Advanced Healthcare Materials (2020)

In article number 1901307, Dejian Li, Li-Min Zhu, and co-workers, successfully develop an intelligent theranostics platform based on bovine serum albumin-iridium oxide gated heat shock protein 90 inhibitor-encapsulated hollow mesoporous organosilica. The resulting AHBIP-mediated synergistic PTT/PDT offers an outstanding therapeutic outcome.
Association between adiposity measures and COPD risk in Chinese adults
Authors: Jiachen Li, Lu Zhu, Yuxia Wei, Jun Lv, Yu Guo, Zheng Bian, Huaidong Du, Ling Yang, Yiping Chen, Yonglin Zhou, Ruqin Gao, Junshi Chen, Zhengming Chen, Weihua Cao, Canqing Yu, Liming Li
Journal: European Respiratory Journal (2020)

Bodyweight and fat distribution may be related to COPD risk. Limited prospective evidence linked COPD to abdominal adiposity. We investigated the association of body mass index (BMI) and measures of abdominal adiposity with COPD risk in a prospective cohort study. The China Kadoorie Biobank recruited participants aged 30–79 years from 10 areas across China. Anthropometric indexes were objectively measured at the baseline survey during 2004–2008. After exclusion of participants with prevalent COPD and major chronic diseases, 452 259 participants were included and followed-up until the end of 2016. We used Cox models to estimate adjusted hazard ratios relating adiposity to risk of COPD hospitalisation or death. Over an average of 10.1 years of follow-up, 10 739 COPD hospitalisation events and deaths were reported. Compared with subjects with normal BMI (18.5–&lt;24.0 kg·m −2 ), underweight (BMI &lt;18.5 kg·m −2 ) individuals had increased risk of COPD, with adjusted hazard ratio 1.78 (95% CI 1.66–1.89). Overweight (BMI 24.0–&lt;28.0 kg·m −2 ) and obesity (BMI ≥28.0 kg·m −2 ) were not associated with an increased risk after adjustment for waist circumference. A higher waist circumference (≥85 cm for males and ≥80 cm for females) was positively associated with COPD risk after adjustment for BMI. Additionally, waist-to-hip ratio and waist-to-height ratio were positively related to COPD risk. Abdominal adiposity and underweight were risk factors for COPD in Chinese adults. Both BMI and measures of abdominal adiposity should be considered in the prevention of COPD.
Babylon Health holds talks with “significant” number of NHS trusts
Authors: Gareth Iacobucci
Journal: BMJ (2020)

The digital provider Babylon Health is in talks with a “significant number” of hospital trusts in England as it seeks to expand its service in the NHS, the company has told The BMJ. 

Babylon’s managing director for NHS services, Paul Bate, said that the company wanted to spearhead a “fundamental transformation” in the way people accessed healthcare. His comments came as Babylon announced a major 10 year partnership with Royal Wolverhampton NHS Trust, a large acute and community provider that also runs 10 general practices, to deliver joined-up digital care to the city’s population.

The service, which is expected to go live later this year, will allow patients …