tbuckley/cabot-search huggingface dataset:
Co-delivery of siPTPN13 and siNOX4 <i>via</i> (myo)fibroblast-targeting polymeric micelles for idiopathic pulmonary fibrosis therapy
Authors: Jiwei Hou, Qijian Ji, Jie Ji, Shenghong Ju, Chun Xu, Xueqing Yong, Xiaoxuan Xu, Mohd. Muddassir, Xiang Chen, Jinbing Xie, Xiaodong Han
Journal: Theranostics (2021)

Rationale: (Myo)fibroblasts are the ultimate effector cells responsible for the production of collagen within alveolar structures, a core phenomenon in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Although (myo)fibroblast-targeted therapy holds great promise for suppressing the progression of IPF, its development is hindered by the limited drug delivery efficacy to (myo)fibroblasts and the vicious circle of (myo)fibroblast activation and evasion of apoptosis. Methods: Here, a dual small interfering RNA (siRNA)-loaded delivery system of polymeric micelles is developed to suppress the development of pulmonary fibrosis via a two-arm mechanism. The micelles are endowed with (myo)fibroblast-targeting ability by modifying the Fab' fragment of the anti-platelet-derived growth factor receptor-α (PDGFRα) antibody onto their surface. Two different sequences of siRNA targeting protein tyrosine phosphatase-N13 (PTPN13, a promoter of the resistance of (myo)fibroblasts to Fas-induced apoptosis) and NADPH oxidase-4 (NOX4, a key regulator for (myo)fibroblast differentiation and activation) are loaded into micelles to inhibit the formation of fibroblastic foci. Results: We demonstrate that Fab'-conjugated dual siRNA-micelles exhibit higher affinity to (myo)fibroblasts in fibrotic lung tissue. This Fab'-conjugated dual siRNA-micelle can achieve remarkable antifibrotic effects on the formation of fibroblastic foci by, on the one hand, suppressing (myo)fibroblast activation via siRNA-induced knockdown of NOX4 and, on the other hand, sensitizing (myo)fibroblasts to Fas-induced apoptosis by siRNA-mediated PTPN13 silencing. In addition, this (myo)fibroblast-targeting siRNA-loaded micelle did not induce significant damage to major organs, and no histopathological abnormities were observed in murine models. Conclusion: The (myo)fibroblast-targeting dual siRNA-loaded micelles offer a potential strategy with promising prospects in molecular-targeted fibrosis therapy.
Treatment of multiple myeloma-related bone disease: recommendations from the Bone Working Group of the International Myeloma Working Group
Authors: Evangelos Terpos, Elena Zamagni, Suzanne Lentzsch, Matthew T Drake, Ramón García-Sanz, Niels Abildgaard, Ioannis Ntanasis-Stathopoulos, Fredrik Schjesvold, Javier de la Rubia, Charalampia Kyriakou, Jens Hillengass, Sonja Zweegman, Michele Cavo, Philippe Moreau, Jesus San-Miguel, Meletios A Dimopoulos, Nikhil Munshi, Brian G M Durie, Noopur Raje
Journal: The Lancet Oncology (2021)
Percutaneous cholangioscopy to remove endovascular coils that had migrated into the bile duct after right hepatic artery pseudoaneurysm embolization
Authors: Jérôme Rivory, Badis Menassel, Thomas Lambin, Florian Rostain, Laurent Milot, Thierry Ponchon, Mathieu Pioche
Journal: Endoscopy (2021)

Right hepatic arterial injury is a common vascular injury during laparoscopic cholecystectomy, occurring in approximately 25 % of patients with biliary injuries [1]. We report the case of a 78-year-old man who, 1 month after undergoing a laparoscopic cholecystectomy, was referred for hemobilia and collapse caused by the rupture of a cystic artery pseudoaneurysm into the common bile duct (CBD). Angiography showed active bleeding that was treated by conventional coil embolization [2] ([Fig. 1]).
Genome-wide association study in patients with pulmonary <i>Mycobacterium avium</i> complex disease
Authors: Ho Namkoong, Yosuke Omae, Takanori Asakura, Makoto Ishii, Shoji Suzuki, Kozo Morimoto, Yosuke Kawai, Katsura Emoto, Andrew J. Oler, Eva P. Szymanski, Mitsunori Yoshida, Shuichi Matsuda, Kazuma Yagi, Isano Hase, Tomoyasu Nishimura, Yuka Sasaki, Takahiro Asami, Tetsuya Shiomi, Hiroaki Matsubara, Hisato Shimada, Junko Hamamoto, Byung Woo Jhun, Su-Young Kim, Hee Jae Huh, Hong-Hee Won, Manabu Ato, Kenjiro Kosaki, Tomoko Betsuyaku, Koichi Fukunaga, Atsuyuki Kurashima, Hervé Tettelin, Hideki Yanai, Surakameth Mahasirimongkol, Kenneth N. Olivier, Yoshihiko Hoshino, Won-Jung Koh, Steven M. Holland, Katsushi Tokunaga, Naoki Hasegawa
Journal: European Respiratory Journal (2021)

Nontuberculous mycobacteria (NTM) are environmental mycobacteria that can cause a chronic progressive lung disease. Although epidemiological data indicate potential genetic predisposition, its nature remains unclear.We aimed to identify host susceptibility loci for Mycobacterium avium complex (MAC), the most common NTM pathogen.This genome-wide association study (GWAS) was conducted in Japanese patients with pulmonary MAC and healthy controls, followed by genotyping of candidate single-nucleotide polymorphisms (SNPs) in another Japanese cohort. For verification by Korean and European ancestry, we performed SNP genotyping.The GWAS discovery set included 475 pulmonary MAC cases and 417 controls. Both GWAS and replication analysis of 591 pulmonary MAC cases and 718 controls revealed the strongest association with chromosome 16p21, particularly with rs109592 (p=1.64×10-13, OR 0.54), which is in an intronic region of the calcineurin-like EF-hand protein 2 (CHP2). Expression quantitative trait loci analysis demonstrated an association with lung CHP2 expression. CHP2 was expressed in the lung tissue in pulmonary MAC disease. This SNP was associated with the nodular bronchiectasis subtype. Additionally, this SNP was significantly associated with the disease in patients of Korean (p=2.18×10-12, OR 0.54) and European (p=5.12×10-03, OR 0.63) ancestry.We identified rs109592 in the CHP2 locus as a susceptibility marker for pulmonary MAC disease.
Abstract 16270: Protein Kinase C Beta II Peptide Inhibitor Elicits Potent Cardioprotective Effects on Attenuating Ischemia/Reperfusion Injury
Authors: Jennifer Dang, Daphne Metellus, Christina Lipscomb, Chinyere Ebo, Arjun Nair, Harsh Patel, Annam Humayun, Megan Michaels, Matthew Finnegan, Tameka Dean, Lucy Checchio, Faosat Muftau-Lediju, Rose M Martorana, Anahi Mcintyre, Qian Chen, Robert Barsotti, Lindon Young
Journal: Circulation (2019)

Ischemia-reperfusion (I/R) injury mediated by excessive reactive oxygen species (ROS) is a well-known mechanism of myocardial tissue damage following cardio-angioplasty in the treatment of heart at...
Simplified bedside assessment of pulmonary gas exchange in very preterm infants at 36 weeks’ postmenstrual age
Authors: Benjamin Stoecklin, Y Jane Choi, Abhijeet Rakshasbhuvankar, Jenny Svedenkrans, Gareth Jones, Jane Pillow
Journal: Thorax (2021)

Introduction We aimed to develop and validate a prediction table for a simplified measure of rightward shift of the fetal oxyhaemoglobin saturation (SpO 2 ) versus inspired oxygen pressure ( P I O 2 ) curve as an objective marker of lung disease severity in very preterm infants, independent of unit altitude or oxygen prescribing policies. Methods Very preterm infants (n=219) had an oxygen reduction test at median (IQR) test age of 35 4 (34 5 –36 0 ) weeks’ postmenstrual age (PMA). Shift was derived from at least three paired SpO 2 versus P I O 2 measurements using a computer algorithm, using the fetal oxyhaemoglobin dissociation curve as the reference. Linear regression of resultant shift values enabled construction of a table to predict shift using a single paired SpO 2 versus P I O 2 measurement, validated subsequently in a separate infant cohort using Bland-Altman analysis. Receiver operating curve analysis provided threshold values equating to a clinical diagnosis of mild bronchopulmonary dysplasia (BPD) or moderate to severe BPD. Results The median (IQR) age of 63 infants in the validation cohort was 36 0 (35 6 –36 2 ) weeks’ PMA. Mean difference (95% CI) between predicted and measured shift was 2.1 (−0.8% to 4.9%) with wide limits of agreement (−20.7% to 24.8%). Predicted shift &gt;10.1 kPa identified mild BPD with 71% sensitivity and 88% specificity while values&gt;13.0 kPa identified moderate to severe BPD with 81% sensitivity and 100% specificity. Discussion Shift predicted from a single paired SpO 2 versus P I O 2 measurement using our validated table enables objective bedside screening of lung disease severity in very preterm infant cohorts at 36 weeks’ PMA.
Medium-term impact of COVID-19 on pulmonary function, functional capacity and quality of life
Authors: Fabio Anastasio, Sarah Barbuto, Elisa Scarnecchia, Paolo Cosma, Alessandro Fugagnoli, Giulio Rossi, Mirco Parravicini, Pierpaolo Parravicini
Journal: European Respiratory Journal (2021)

Coronavirus disease 2019 (COVID-19) has spread worldwide, having a dramatic impact on healthcare systems. The aim of this study is to evaluate mid-term clinical impact of COVID-19 on respiratory function.379 patients were evaluated 4 months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnosis. Patients were divided in two groups based on the presence of pneumonia during COVID-19. Clinical conditions, quality of life, symptomatology, 6-min walk test, pulmonary function test with spirometry and diffusing capacity of the lung for carbon monoxide were analysed. Data were compared to clinical evolution during COVID-19 (development of acute respiratory distress syndrome, need of invasive mechanical ventilation, partial oxygen saturation (SpO2 )/inspiratory oxygen fraction (FIO2 ) ratio and pneumonia severity index (PSI)).After a median 135 days, 260 (68.6%) out of 379 patients referred at least one symptom. Patients who developed pneumonia during COVID-19 showed lower SpO2 at rest (p<0.001), SpO2 during 6-min walk test (p<0.001), total lung capacity (p<0.001), airway occlusion pressure after 0.1 s (P0.1) (p=0.02), P0.1/maximal inspiratory pressure ratio (p=0.005) and higher Borg category-ratio scale (p=0.006) and modified Medical Research Council breathlessness scale (p=0.003), compared to patients without pneumonia. SpO2 /FIO2 ratio and PSI during SARS-CoV-2 pneumonia were directly associated with mid-term alteration of SpO2 at rest (p<0.001) and during 6-min walk test (p<0.001), residual volume (p<0.001), total lung capacity (p<0.001 and p=0.003, respectively) and forced vital capacity (p=0.004 and p=0.03, respectively).Lung damage during COVID-19 correlates to the reduction of pulmonary function 4 months after acute infection.
Audio Interview: Covid-19 and the States — A Conversation with Ralph Northam
Authors: Eric J. Rubin, Lindsey R. Baden, Ralph S. Northam, Stephen Morrissey
Journal: New England Journal of Medicine (2021)

Covid-19 and the States — A Conversation with Ralph Northam In this audio interview conducted on February 3, 2021, the editors are joined by Dr. Ralph Northam, the governor of Virginia, to discuss ...
Second-line therapy to improve overall survival in primary refractory non small-cell lung cancer (NSCLC) patients.
Authors: Sacha Rothschild, Rebecca Nachbur, Natascha Herzog, Jakob Passweg, Miklos Pless
Journal: Journal of Clinical Oncology (2018)

e21069 Background: The effect of palliative chemotherapy (chemo) for non-small cell lung cancer (NSCLC) is well established. Recently, immune checkpoint inhibitors have shown promising efficacy in NSCLC patients (pts) progressing after platinum-based chemo. However, little is known on the efficacy of systemic therapies in pts whose tumors are refractory to first-line chemo. Methods: From an institutional database, consecutive pts with metastatic NSCLC diagnosed between 1990 and 2016 were assessed. Outcome parameters were collected and pts were characterized as either having primary progressive disease or clinical benefit (CB; defined as complete/partial response (CR, PR) or stable disease (SD)). Chi-square test was used for discrete and Mann Whitney U tests for continuous variables, respectively. Probabilities of survival were calculated using the Kaplan-Meier estimator. The log-rank test was used for comparing groups. Results: 576 pts with median age of was 62.9 years were analyzed. 68% were male, 81% were smokers and 55% had adenocarcinoma histology. 61% received more than one treatment line. 62.7% were treated with a platinum-based first-line chemo. Median PFS for first-line therapy was 3.2 months (95% CI 2.9-3.5). Median OS was 9.0 months (8.1-10.0). 222 pts (38.5%) were primary refractory to first-line therapy. Median OS was significantly shorter for those pts (7.0 vs. 11.0 months, p < 0.0001). Poorer initial performance status was significantly associated with primary refractory disease (p = 0.015). 81 (36.5%) primary refractory pts received a second-line therapy. Median OS was significantly longer for refractory pts receiving second-line therapy vs. best supportive care (9.4 vs. 5.0 months, p < 0.0001). Conclusions: Nearly 40% of pts are primary refractory to palliative first-line therapy and have a poor prognosis. Active second-line therapy can significantly improve the outcome. Therefore, pts with primary refractory NSCLC should be offered further active therapy. These real life data for primary refractory pts form the basis against which immunotherapies, the current standard second line treatment, can be compared.
Zooming for FPIES? Impact of COVID on FPIES Re-evaluation: Parental Attitudes on Remote At-Home Oral Challenges in the FPIES Toddler Population
Authors: Jason Ohayon, Tyler Seto, Tenzin Gyaltsen, Ijaz Ogeer, Vince Wu, Wardha. Wardha
Journal: Journal of Allergy and Clinical Immunology (2021)
Injury rates decreased in men’s professional football: an 18-year prospective cohort study of almost 12 000 injuries sustained during 1.8 million hours of play
Authors: Jan Ekstrand, Armin Spreco, Håkan Bengtsson, Roald Bahr
Journal: British Journal of Sports Medicine (2021)

The UEFA Elite Club Injury Study is the largest and longest running injury surveillance programme in football.To analyse the 18-season time trends in injury rates among male professional football players.3302 players comprising 49 teams (19 countries) were followed from 2000-2001 through 2018-2019. Team medical staff recorded individual player exposure and time-loss injuries.A total of 11 820 time-loss injuries were recorded during 1 784 281 hours of exposure. Injury incidence fell gradually during the 18-year study period, 3% per season for both training injuries (95% CI 1% to 4% decrease, p=0.002) and match injuries (95% CI 2% to 3% decrease, p<0.001). Ligament injury incidence decreased 5% per season during training (95% CI 3% to 7% decrease, p<0.001) and 4% per season during match play (95% CI 3% to 6% decrease, p<0.001), while the rate of muscle injuries remained constant. The incidence of reinjuries decreased by 5% per season during both training (95% CI 2% to 8% decrease, p=0.001) and matches (95% CI 3% to 7% decrease, p<0.001). Squad availability increased by 0.7% per season for training sessions (95% CI 0.5% to 0.8% increase, p<0.001) and 0.2% per season for matches (95% CI 0.1% to 0.3% increase, p=0.001).Over 18 years: (1) injury incidence decreased in training and matches, (2) reinjury rates decreased, and (3) player availability for training and match play increased.
Meta-analyses of Results From Randomized Outcome Trials Comparing Cardiovascular Effects of SGLT2is and GLP-1RAs in Asian Versus White Patients With and Without Type 2 Diabetes
Authors: Matthew M.Y. Lee, Nazim Ghouri, Darren K. McGuire, Martin K. Rutter, Naveed Sattar
Journal: Diabetes Care (2021)

BACKGROUND Results of cardiovascular outcome trials (CVOTs) suggest Asians may derive greater benefit than Whites from newer classes of antihyperglycemic medications. PURPOSE To provide summary hazard ratio (HR) estimates for cardiovascular efficacy of sodium–glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) stratified by race (Asian vs. White). DATA SOURCES A systematic review performed in PubMed from 1 January 2015 to 8 December 2020. STUDY SELECTION Randomized placebo-controlled CVOTs of SGLT2is and GLP-1RAs that reported HRs (95% CIs) for 1) major adverse cardiovascular event (MACE) in patients with diabetes and 2) cardiovascular (CV) death/hospitalization for heart failure (HHF) in patients with HF and reduced ejection fraction (HFrEF). DATA EXTRACTION AND SYNTHESIS HRs (95% CIs) for selected outcomes in Asians and Whites were extracted from each trial, adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Random-effects meta-analyses were performed to examine differences between the selected outcomes in Asians versus Whites. RESULTS In four SGLT2i trials in type 2 diabetes, the MACE outcome HR (95% CI) in 3,298 Asians versus 20,258 Whites was 0.81 (0.57, 1.04) vs. 0.90 (0.80, 1.00), respectively (Pinteraction = 0.46). In two SGLT2i trials in patients with HFrEF, the CV death/HHF outcome HR in 1,788 Asians versus 5,962 Whites was 0.60 (0.47, 0.74) vs. 0.82 (0.73, 0.92), respectively (Pinteraction = 0.01). In six GLP-1RA trials, the MACE outcome HR in 4,195 Asians versus 37,530 Whites was 0.68 (0.53, 0.84) vs. 0.87 (0.81, 0.94), respectively (Pinteraction = 0.03). LIMITATIONS Lack of individual patient–level data, relatively short duration of trial observation, and lack of granular categorization of race within broadly defined Asian subgroups. CONCLUSIONS Compared with Whites, Asians may derive greater CV death/HHF benefit from SGLT2is in patients with HFrEF, and MACE benefit from GLP-1RAs in patients with type 2 diabetes.
A Novel Soluble ACE2 Variant with Prolonged Duration of Action Neutralizes SARS-CoV-2 Infection in Human Kidney Organoids
Authors: Jan Wysocki, Minghao Ye, Luise Hassler, Ashwani Kumar Gupta, Yuguo Wang, Vlad Nicoleascu, Glenn Randall, Jason A. Wertheim, Daniel Batlle
Journal: Journal of the American Society of Nephrology (2021)

There is an urgent need for approaches to prevent and treat SARS-CoV-2 infection. Administration of soluble ACE2 protein acting as a decoy to bind to SARS-CoV-2 should limit viral uptake mediated by binding to membrane-bound full-length ACE2, and further therapeutic benefit should result from ensuring enzymatic ACE2 activity to affected organs in patients with COVID-19.
John Cash: former director of the Scottish National Blood Transfusion Service, who warned against imported blood products
Authors: Joanna Lyall
Journal: BMJ (2021)

Credit: Keith Breeden, Royal College of Physicians of Edinburgh

John Cash, whose persistent warnings about the dangers of imported blood products largely fell on deaf ears, has died aged 84. He had a fatal heart attack at home in Edinburgh while watching the proceedings of the Infected Blood Inquiry, chaired by Brian Langstaff, to which he was to give evidence. Self-sufficiency in blood products is one of the main matters being investigated by the inquiry, which was set up in 2017.

As early as 1976 Cash called for greater investment in blood services to avoid reliance on costly, commercial blood products.1

In a wide ranging critique of the National Blood Transfusion Service of England and Wales in September 19872 Cash accused civil servants of “a lack of interest, vision, and commitment” in failing to improve provision. “The National Blood Transfusion Service is a fragmented and disorganised shambles,” he said. He criticised …
Size Variation of the Nonrecombining Region on the Mating-Type Chromosomes in the Fungal <i>Podospora anserina</i> Species Complex
Authors: Fanny E Hartmann, Sandra Lorena Ament-Velásquez, Aaron A Vogan, Valérie Gautier, Stephanie Le Prieur, Myriam Berramdane, Alodie Snirc, Hanna Johannesson, Pierre Grognet, Fabienne Malagnac, Philippe Silar, Tatiana Giraud
Journal: Molecular Biology and Evolution (2021)

Abstract Sex chromosomes often carry large nonrecombining regions that can extend progressively over time, generating evolutionary strata of sequence divergence. However, some sex chromosomes display an incomplete suppression of recombination. Large genomic regions without recombination and evolutionary strata have also been documented around fungal mating-type loci, but have been studied in only a few fungal systems. In the model fungus Podospora anserina (Ascomycota, Sordariomycetes), the reference S strain lacks recombination across a 0.8-Mb region around the mating-type locus. The lack of recombination in this region ensures that nuclei of opposite mating types are packaged into a single ascospore (pseudohomothallic lifecycle). We found evidence for a lack of recombination around the mating-type locus in the genomes of ten P. anserina strains and six closely related pseudohomothallic Podospora species. Importantly, the size of the nonrecombining region differed between strains and species, as indicated by the heterozygosity levels around the mating-type locus and experimental selfing. The nonrecombining region is probably labile and polymorphic, differing in size and precise location within and between species, resulting in occasional, but infrequent, recombination at a given base pair. This view is also supported by the low divergence between mating types, and the lack of strong linkage disequilibrium, chromosomal rearrangements, transspecific polymorphism and genomic degeneration. We found a pattern suggestive of evolutionary strata in P. pseudocomata. The observed heterozygosity levels indicate low but nonnull outcrossing rates in nature in these pseudohomothallic fungi. This study adds to our understanding of mating-type chromosome evolution and its relationship to mating systems.
Health-Related Quality of Life Impairment Among Patients With Severe Chronic Rhinosinusitis With Nasal Polyps in the SINUS-24 Trial
Authors: Jorge Maspero, Carl Philpott, Peter Hellings, Claire Hopkins, Martin Wagenmann, Shahid Siddiqui, Juby Jacob-Nara, Jerome Msihid, Chien-Chia Chuang, Siddhesh Kamat, Asif Khan
Journal: Journal of Allergy and Clinical Immunology (2021)
Early innate and adaptive immune perturbations determine long-term severity of chronic virus and Mycobacterium tuberculosis coinfection
Authors: Wenxi Xu, Laura M. Snell, Mengdi Guo, Giselle Boukhaled, Bethany L. Macleod, Ming Li, Michael V. Tullius, Cynthia J. Guidos, Ming-Sound Tsao, Maziar Divangahi, Marcus A. Horwitz, Jun Liu, David G. Brooks
Journal: Immunity (2021)