tbuckley/cabot-search huggingface dataset:
Salvianolic acid B dry powder inhaler for the treatment of idiopathic pulmonary fibrosis
Authors: Peng Lu, Jiawei Li, Chuanxin Liu, Jian Yang, Hui Peng, Zhifeng Xue, Zhidong Liu
Journal: Asian Journal of Pharmaceutical Sciences (2022)

Idiopathic pulmonary fibrosis (IPF) is a serious and fatal pulmonary inflammatory disease with an increasing incidence worldwide. The drugs nintedanib and pirfenidone, are listed as conditionally recommended drugs in the "Evidence-Based Guidelines for the Diagnosis and Treatment of Idiopathic Pulmonary Fibrosis". However, these two drugs have many adverse reactions in clinical application. Salvianolic acid B (Sal B), a water-soluble component of Salvia miltiorrhiza, could alleviate bleomycin-induced peroxidative stress damage, and prevent or delay the onset of IPF by regulating inflammatory factors and fibrotic cytokines during the disease's progression. However, Sal B is poorly absorbed orally, and patient compliance is poor when administered intravenously. Therefore, there is an urgent need to find a new non-injection route of drug delivery. In this study, Sal B was used as model drug and l-leucine (LL) as excipient to prepare Sal B dry powder inhaler (Sal B-DPI) by spray drying method. Modern preparation evaluation methods were used to assess the quality of Sal B-DPI. Sal B-DPI is promising for the treatment of IPF, according to studies on pulmonary irritation evaluation, in vivo and in vitro pharmacodynamics, metabolomics, pharmacokinetics, and lung tissue distribution.
A call for loiasis to be added to the WHO list of neglected tropical diseases
Authors: Kathryn H Jacobsen, Bailey C Andress, Elina A Bhagwat, Ciera A Bryant, Vipusha R Chandrapu, Caroline G Desmonts, Tania M Matthews, Akeem Ogunkoya, Tristan J Wheeler, A'kayla S Williams
Journal: The Lancet Infectious Diseases (2022)
Meningococcal Vaccination Rates Among People With a New Diagnosis of HIV Infection in the US
Authors: Parinaz K. Ghaswalla, Gary S. Marshall, Lindsay G. S. Bengtson, Ami R. Buikema, Tim Bancroft, Eleena Koep, Patricia Novy, Cosmina S. Hogea
Journal: JAMA Network Open (2022)

In the United States, individuals with HIV infection have been recommended to receive a 2-dose series of the meningococcal A, C, W, Y (MenACWY) vaccine since 2016 owing to their increased risk of meningococcal disease.To examine uptake and time to receipt of the MenACWY vaccine among people with a new diagnosis of HIV.This cohort study used health insurance data from the US Optum Research Database from January 1, 2016, through March 31, 2018, to retrospectively identify 1208 individuals aged 2 years or older with 1 or more inpatient claim or 2 or more outpatient claims evidencing a new diagnosis of HIV infection and with continuous insurance enrollment for 12 or more months before and 6 or more months after diagnosis. Follow-up was 6 to 33 months. Statistical analysis was conducted from March 7, 2019, to January 5, 2022.Receipt of the MenACWY vaccine.The coprimary outcomes were uptake and time to receipt of 1 or more doses of the MenACWY vaccine after a new HIV diagnosis. Secondary outcomes included uptake and time to receipt of 2 or more doses of the MenACWY vaccine. Vaccination uptake and receipt were estimated by Kaplan-Meier analysis; factors associated with receipt of 1 or more doses of the MenACWY vaccine were identified with multivariable Cox proportional hazards regression analysis.Of 1208 individuals eligible for vaccination (1024 male patients [84.8%]; mean [SD] age, 38.8 [12.5] years; 35 [2.9%] Asian; 273 [22.6%] Black; 204 [16.9%] Hispanic; 442 [36.6%] White), 16.3% were estimated to have received a first dose of the MenACWY vaccine in the 2 years after a new HIV diagnosis. Among individuals who received a first dose, at 1 year or more of enrollment after the first dose, 66.2% were estimated to have received a second dose within 1 year of the first dose. Factors statistically significantly associated with uptake of the MenACWY vaccine included receipt of a pneumococcal vaccine (hazard ratio [HR], 23.03; 95% CI, 13.93-38.09), attendance at a well-care visit (HR, 3.67; 95% CI, 1.11-12.12), West or Midwest geographic region (West: HR, 2.24; 95% CI, 1.44-3.47; Midwest: HR, 1.78; 95% CI, 1.16-2.71), and male sex (HR, 2.72; 95% CI, 1.18-6.26), whereas age of 56 years or older was significantly associated with reduced uptake of the MenACWY vaccine (HR, 0.42; 95% CI, 0.18-0.97).This cohort study suggests that MenACWY vaccine uptake among people with a new diagnosis of HIV was low, highlighting the need to educate patients and clinicians about the recommendations for conditions such as HIV infection that increase the risk of meningococcal disease among high-risk populations.
A Large-Scale Genome-Wide Gene-Gene Interaction Study of Lung Cancer Susceptibility in Europeans With a Trans-Ethnic Validation in Asians
Authors: Ruyang Zhang, Sipeng Shen, Yongyue Wei, Ying Zhu, Yi Li, Jiajin Chen, Jinxing Guan, Zoucheng Pan, Yuzhuo Wang, Meng Zhu, Junxing Xie, Xiangjun Xiao, Dakai Zhu, Yafang Li, Demetrios Albanes, Maria Teresa Landi, Neil E. Caporaso, Stephen Lam, Adonina Tardon, Chu Chen, Stig E. Bojesen, Mattias Johansson, Angela Risch, Heike Bickeböller, H-Erich Wichmann, Gadi Rennert, Susanne Arnold, Paul Brennan, James D. McKay, John K. Field, Sanjay S. Shete, Loic Le Marchand, Geoffrey Liu, Angeline S. Andrew, Lambertus A. Kiemeney, Shan Zienolddiny-Narui, Annelie Behndig, Mikael Johansson, Angela Cox, Philip Lazarus, Matthew B. Schabath, Melinda C. Aldrich, Juncheng Dai, Hongxia Ma, Yang Zhao, Zhibin Hu, Rayjean J. Hung, Christopher I. Amos, Hongbing Shen, Feng Chen, David C. Christiani
Journal: Journal of Thoracic Oncology (2022)

Although genome-wide association studies have been conducted to investigate genetic variation of lung tumorigenesis, little is known about gene-gene (G × G) interactions that may influence the risk of non-small cell lung cancer (NSCLC).
Diagnostic and therapeutic approach of central sleep apnea in heart failure – the role of adaptive servo-ventilation. A statement of the Portuguese society of pulmonology and the Portuguese sleep association
Authors: S. Correia, S. Sousa, M. Drummond, P. Pinto, R. Staats, D. Brito, N. Lousada, J.S. Cardoso, J. Moita
Journal: Pulmonology (2022)

It is known that patients with heart failure (HF) have an increased risk of developing central sleep apnoea (CSA), with Cheyne-Stokes respiration. The development of servo-ventilation aimed to treat CSA and improve the quality of life (QoL) of these patients. A large randomized clinical study, SERVE-HF, was conducted in order to test this theory in patients with HF and reduced ejection fraction (HFrEF). The results from this trial seemed to indicate that, in these patients, there was no beneficial effect of the assisted ventilation in CSA treatment. More surprisingly, an increased rate of all-cause or cardiovascular mortality was observed. This has led to dramatic changes in clinical practice, with decreased frequency of servo-ventilation prescription across Europe, including Portugal, due to changes in the guidelines. However, SERVE-HF was conducted only in severe systolic HF patients with CSA, and caution must be taken when extrapolating these results to HF patients with preserved ejection fraction or CSA patients without HF. The study also showed poor adherence, methodological and statistical gaps, including study design, patient selection, data collection and analysis, treatment adherence, and group crossovers, which have not been discussed in the trial as potential confounding factors and raise several concerns. Moreover, the adaptive servo-ventilation (ASV) device used in SERVE-HF was unable to lower the minimum support pressure below 3 mm H20, and this has been suggested as one of the probable contributing reasons to the excess mortality observed in this study. This limitation has since been solved, and this ASV device is no longer used. This paper describes the results of a Portuguese Task Force on the treatment of central sleep apnoea in patients with chronic HF.
Dynamics and Impacts of Transposable Element Proliferation in the <i>Drosophila nasuta</i> Species Group Radiation
Authors: Kevin H.-C. Wei, Dat Mai, Kamalakar Chatla, Doris Bachtrog
Journal: Molecular Biology and Evolution (2022)

Transposable element (TE) mobilization is a constant threat to genome integrity. Eukaryotic organisms have evolved robust defensive mechanisms to suppress their activity, yet TEs can escape suppression and proliferate, creating strong selective pressure for host defense to adapt. This genomic conflict fuels a never-ending arms race that drives the rapid evolution of TEs and recurrent positive selection of genes involved in host defense; the latter has been shown to contribute to postzygotic hybrid incompatibility. However, how TE proliferation impacts genome and regulatory divergence remains poorly understood. Here, we report the highly complete and contiguous (N50 = 33.8-38.0 Mb) genome assemblies of seven closely related Drosophila species that belong to the nasuta species group-a poorly studied group of flies that radiated in the last 2 My. We constructed a high-quality de novo TE library and gathered germline RNA-seq data, which allowed us to comprehensively annotate and compare TE insertion patterns between the species, and infer the evolutionary forces controlling their spread. We find a strong negative association between TE insertion frequency and expression of genes nearby; this likely reflects survivor bias from reduced fitness impact of TEs inserting near lowly expressed, nonessential genes, with limited TE-induced epigenetic silencing. Phylogenetic analyses of insertions of 147 TE families reveal that 53% of them show recent amplification in at least one species. The most highly amplified TE is a nonautonomous DNA element (Drosophila INterspersed Element; DINE) which has gone through multiple bouts of expansions with thousands of full-length copies littered throughout each genome. Across all TEs, we find that TEs expansions are significantly associated with high expression in the expanded species consistent with suppression escape. Thus, whereas horizontal transfer followed by the invasion of a naïve genome has been highlighted to explain the long-term survival of TEs, our analysis suggests that evasion of host suppression of resident TEs is a major strategy to persist over evolutionary times. Altogether, our results shed light on the heterogenous and context-dependent nature in which TEs affect gene regulation and the dynamics of rampant TE proliferation amidst a recently radiated species group.
LD-RAPID technique: Technical refinements – A potential breakthrough in transplant oncology
Authors: Eugenia Rosso, Riccardo Boetto, Bertacco Alessandra, Eugenia Rosso, Alessandro Vitale, Francesco D'Amico, Domenico Bassi, Francesco Enrico D'Amico, Marina Polacco, Enrico Gringeri
Journal: International Journal of Surgery (2022)
Validation of a technical modification of the pancreaticojejunostomy (PJ) after pancreatoduodenectomy (PD). Incidence of postoperative pancreatic fistula (POPF) in 82 consecutive cases adjusted for fistula risk scores (FRS)
Authors: Alfonso Recordare, Rubina Palumbo, Giovanni Pirozzolo, Fiorentia Sulo, Lucrezia D'Alimonte, Alice Albanese, Livio Baiano, Fabrizio Cimino, Alessandro Mardegan, Maurizio Rizzo
Journal: International Journal of Surgery (2022)
Small extracellular vesicles induce resistance to anti-GD2 immunotherapy unveiling tipifarnib as an adjunct to neuroblastoma immunotherapy
Authors: Xiaoming Liu, Carson A Wills, Longgui Chen, Jiawen Zhang, Yuanjun Zhao, Mi Zhou, Jeffrey M Sundstrom, Todd Schell, Vladimir S Spiegelman, Megan M Young, Hong-Gang Wang
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Anti-GD2 monoclonal antibody immunotherapy has significantly improved the overall survival rate for high-risk neuroblastoma patients. However, 40% of patients fail to respond or develop resistance to treatment, and the molecular mechanisms by which this occurs remain poorly understood. Tumor-derived small extracellular vesicles (sEVs) have emerged as critical regulators in modulating the response to immunotherapy. In this study, we investigated the role of neuroblastoma-derived sEVs in promoting resistance to the anti-GD2 monoclonal antibody dinutuximab. Moreover, to determine whether pharmacologic inhibition of sEV secretion sensitizes tumors to dinutuximab treatment, we combined dinutuximab with tipifarnib, a farnesyltransferase inhibitor that inhibits sEV secretion. Methods We investigated the role of neuroblastoma-derived sEVs in modulating the response to dinutuximab by utilizing the syngeneic 9464D-GD2 mouse model. The effect of neuroblastoma-derived sEVs in modulating the tumor microenvironment (TME) and host immune system were evaluated by RNA-sequencing and flow cytometry. Importantly, we used this mouse model to investigate the efficacy of tipifarnib in sensitizing neuroblastoma tumors to dinutuximab. The effect of tipifarnib on both the TME and host immune system were assessed by flow cytometry. Results We demonstrated that neuroblastoma-derived sEVs significantly attenuated the efficacy of dinutuximab in vivo and modulated tumor immune cell infiltration upon dinutuximab treatment to create an immunosuppressive TME that contains more tumor-associated macrophages and fewer tumor-infiltrating NK cells. In addition, we demonstrated that neuroblastoma-derived sEVs suppress splenic NK cell maturation in vivo and dinutuximab-induced NK cell-mediated antibody-dependent cellular cytotoxicity in vitro . Importantly, tipifarnib drastically enhanced the efficacy of dinutuximab-mediated inhibition of tumor growth and prevented the immunosuppressive effects of neuroblastoma-derived sEVs in vivo . Conclusions These preclinical findings uncover a novel mechanism by which neuroblastoma-derived sEVs modulate the immune system to promote resistance to dinutuximab and suggest that tipifarnib-mediated inhibition of sEV secretion may serve as a viable treatment strategy to enhance the antitumor efficacy of anti-GD2 immunotherapy in high-risk neuroblastoma patients.
An intranasal lentiviral booster reinforces the waning mRNA vaccine-induced SARS-CoV-2 immunity that it targets to lung mucosa
Authors: Benjamin Vesin, Jodie Lopez, Amandine Noirat, Pierre Authié, Ingrid Fert, Fabien Le Chevalier, Fanny Moncoq, Kirill Nemirov, Catherine Blanc, Cyril Planchais, Hugo Mouquet, Françoise Guinet, David Hardy, Francina Langa Vives, Christiane Gerke, François Anna, Maryline Bourgine, Laleh Majlessi, Pierre Charneau
Journal: Molecular Therapy (2022)

As the coronavirus disease 2019 (COVID-19) pandemic continues and new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern emerge, the adaptive immunity initially induced by the first-generation COVID-19 vaccines starts waning and needs to be strengthened and broadened in specificity. Vaccination by the nasal route induces mucosal, humoral, and cellular immunity at the entry point of SARS-CoV-2 into the host organism and has been shown to be the most effective for reducing viral transmission. The lentiviral vaccination vector (LV) is particularly suitable for this route of immunization owing to its non-cytopathic, non-replicative, and scarcely inflammatory properties. Here, to set up an optimized cross-protective intranasal booster against COVID-19, we generated an LV encoding stabilized spike of SARS-CoV-2 Beta variant (LV::SBeta-2P). mRNA vaccine-primed and -boosted mice, with waning primary humoral immunity at 4 months after vaccination, were boosted intranasally with LV::SBeta-2P. A strong boost effect was detected on cross-sero-neutralizing activity and systemic T cell immunity. In addition, mucosal anti-spike IgG and IgA, lung-resident B cells, and effector memory and resident T cells were efficiently induced, correlating with complete pulmonary protection against the SARS-CoV-2 Delta variant, demonstrating the suitability of the LV::SBeta-2P vaccine candidate as an intranasal booster against COVID-19. LV::SBeta-2P vaccination was also fully protective against Omicron infection of the lungs and central nervous system, in the highly susceptible B6.K18-hACE2IP-THV transgenic mice.
Ionic co-aggregates (ICAs) based oral drug delivery: Solubilization and permeability improvement
Authors: Xianzi Zheng, Zhezheng Fang, Weizi Huang, Jianping Qi, Xiaochun Dong, Weili Zhao, Wei Wu, Yi Lu
Journal: Acta Pharmaceutica Sinica B (2022)

Due to the overwhelming percentage of poorly water-soluble drugs, pharmaceutical industry is in urgent need of efficient approaches for solubilization and permeability improvement. Salts consisting of lipophilic fatty acid anions and hydrophilic choline cations are found to be surface active and able to form ionic co-aggregates (ICAs) in water. Choline oleate-based ICAs significantly enhance oral absorption of paclitaxel (PTX) as compared with cremophor EL-based micelles (MCs). Aggregation-caused quenching probes enable tracking of intact ICAs in in vivo transport and cellular interaction. Prolonged intestinal retention of ICAs than MCs implies stronger solubilizing capability in vivo. Ex vivo imaging of major organs and intestinal tracts suggests transepithelial transport of intact ICAs. Cellular studies support the enhanced absorption of PTX and transmembrane transport of intact ICAs. In conclusion, ICAs, consisting of lipophilic ions and hydrophilic counter-ions, are of great potential in delivery of poorly water-soluble drugs by enhancing solubility and permeability.
Characterization of metabolic alterations of chronic lymphocytic leukemia in the lymph node microenvironment
Authors: Zhenghao Chen, Helga Simon-Molas, Gaspard Cretenet, Beatriz Valle-Argos, Lindsay D. Smith, Francesco Forconi, Bauke V. Schomakers, Michel van Weeghel, Dean J. Bryant, Jaco A. C. van Bruggen, Fleur S. Peters, Jeffrey C. Rathmell, Gerritje J. W. van der Windt, Arnon P. Kater, Graham Packham, Eric Eldering
Journal: Blood (2022)
First-in-Man Noninvasive Initial Diagnostic Approach of Primary CNS Lymphoma Versus Glioblastoma Using PET With 18F-Fludarabine and l-[methyl-11C]Methionine
Authors: Andrey Postnov, Jérôme Toutain, Igor Pronin, Samuel Valable, Fabienne Gourand, Diana Kalaeva, Nina Vikhrova, Elena Pyzhik, Stéphane Guillouet, Grigoriy Kobyakov, Ekaterina Khokholova, David Pitskhelauri, Dmitry Usachev, Sergey Maryashev, Marina Rizhova, Alexander Potapov, Jean-Michel Derlon
Journal: Clinical Nuclear Medicine (2022)

Objectives This study sought to assess 18 F-fludarabine ( 18 F-FLUDA) PET/CT’s ability in differentiating primary central nervous system lymphomas (PCNSLs) from glioblastoma multiformes (GBMs). Patients and Methods Patients harboring either PCNSL (n = 8) before any treatment, PCNSL treated using corticosteroids (PCNSLh; n = 10), or GBM (n = 13) were investigated with conventional MRI and PET/CT, using 11 C-MET and 18 F-FLUDA. The main parameters measured with each tracer were SUV T and T/N ratios for the first 30 minutes of 11 C-MET acquisition, as well as at 3 different times after 18 F-FLUDA injection. The early 18 F-FLUDA uptake within the first minute of injection was equally considered, whereas this parameter was combined with the later uptakes to obtain R FLUDA 2 and R FLUDA 3 ratios. Results No significant differences in 11 C-MET uptakes were observed among PCNSL, PCNSLh, and GBM. With 18 F-FLUDA, a clear difference in dynamic GBM uptake was observed, which decreased over time after an early maximum, as compared with that of PCNSL, which steadily increased over time, PCNSLh exhibiting intermediate values. The most discriminative parameters consisting of R FLUDA 2 and R FLUDA 3 integrated the early tracer uptake (first 60 seconds), thereby provided 100% specificity and sensitivity. Conclusions 18 F-FLUDA was shown to likely be a promising radiopharmaceutical for differentiating PCNSL from other malignancies, although a pretreatment with corticosteroids might compromise this differential diagnostic ability. The diagnostic role of 18 F-FLUDA should be further investigating, along with its potential of defining therapeutic strategies in patients with PCNSL, while assessing the treatments’ effectiveness.
Pancreatic head cancer overall survival after pancreaticoduodenectomy with total mesopancreas excision
Authors: Alejandro Serrablo-Requejo, Sandra Paterna-López, Marta Gutiérrez-Díez, María Teresa Abadía-Forcen, Mario Serradilla-Martín, Pablo Sancho-Pardo, Consuelo Artigas-Marco
Journal: International Journal of Surgery (2022)
New modular platform based on multi-adjuvanted amphiphilic chitosan nanoparticles for efficient lipopeptide vaccine delivery against group A streptococcus
Authors: Abdin Shakirin Mohamad Norpi, Muhammad Luqman Nordin, Nuraziemah Ahmad, Haliza Katas, Abdullah Al-Hadi Ahmad Fuaad, Asif Sukri, Nirmal Marasini, Fazren Azmi
Journal: Asian Journal of Pharmaceutical Sciences (2022)

An effective vaccine against group A streptococcus (GAS) is highly desirable for definitive control of GAS infections. In the present study, two variants of amphiphilic chitosan nanoparticles-based GAS vaccines were developed. The vaccines were primarily composed of encapsulated KLH protein (a source of T helper cell epitopes) and lipidated M-protein derived B cell peptide epitope (lipoJ14) within the amphiphilic structure of nanoparticles. The only difference between them was one of the nanoparticles vaccines received additional surface coating with poly (I:C). The formulated vaccines exhibited nanosized particles within the range of 220-240 nm. Cellular uptake study showed that nanoparticles vaccine without additional poly (I:C) coating has greater uptake by dendritic cells and macrophages compared to nanoparticles vaccine that was functionalized with poly (I:C). Both vaccines were found to be safe in mice and showed negligible cytotoxicity against HEK293 cells. Upon immunization in mice, both nanoparticle vaccines produced high antigen-specific antibodies titres that were regulated by a balanced Th1 and Th2 response compared to physical mixture. These antibodies elicited high opsonic activity against the tested GAS strains. Overall, our data demonstrated that amphiphilic chitosan nanoparticles platform induced a potent immune response even without additional inclusion of poly (I:C).
Utilization of glycosaminoglycans by the human gut microbiota: participating bacteria and their enzymatic machineries
Authors: Parkash Singh Rawat, Ahkam Saddam Seyed Hameed, Xiangfeng Meng, Weifeng Liu
Journal: Gut Microbes (2022)

Glycosaminoglycans (GAGs) are consistently present in the human colon in free forms and as part of proteoglycans. Their utilization is critical for the colonization and proliferation of gut bacteria and also the health of hosts. Hence, it is essential to determine the GAG-degrading members of the gut bacteria and their enzymatic machinery for GAG depolymerization. In this review, we have summarized the reported GAG utilizers from Bacteroides and presented their polysaccharide utilization loci (PUL) and related enzymatic machineries for the degradation of chondroitin and heparin/heparan sulfate. Although similar comprehensive knowledge of GAG degradation is not available for other gut phyla, we have specified recently isolated GAG degraders from gut Firmicutes and Proteobacteria, and analyzed their genomes for the presence of putative GAG PULs. Deciphering the precise GAG utilization mechanism for various phyla will augment our understanding of their effects on human health.