tbuckley/cabot-search huggingface dataset:
Reducing <i>Pseudomonas</i> sputum density in bronchiectasis
Authors: Oriol Sibila
Journal: European Respiratory Journal (2021)

<b>Decreased airway bacterial load may have impact on clinical outcomes in bronchiectasis. The iBEST study demonstrates that tobramycin inhalation powder reduces <i>P. aeruginosa</i> sputum density in a dose-dependent manner in patients with bronchiectasis.</b>https://bit.ly/3miO9fY
Abstract 15570: Pathology of In-stent Neointima in Atherosclerotic Porcine Peripheral Artery Treated by Drug-coated Balloon
Authors: Suguru Migita, Daisuke Kitano, Yutaka Koyama, Yuxin Li, Atsushi Hirayama, Yasuo Okumura, Hiroyuki Hao
Journal: Circulation (2020)

Introduction: The use of drug-coated balloons (DCB) is a promising technique to treat in-stent restenosis without adding another metal scaffold. Clinical non-inferiority of DCB for treatment of in-stent restenosis (ISR) has been demonstrated compared to drug eluting stents (DES) implantation. However, pathology of neointima treated by DCB remains unclear. Aim: Pathological study of neointima after DCB treatment for ISR has not been reported. This study aimed to examine the tissue response after DCB treatment and plain old balloon angioplasty (POBA) for ISR pathologically, by using atherosclerotic femoral artery of porcine model. Methods: Using micromini pigs fed high-cholesterol, high-fat diet for 3 months, we stented bare metal stents in femoral arteries. After one month of stenting, dilatation of in-stent region by using DCB, and non-compliance balloon (NCB) as POBA were performed. Optimal coherence tomography and angioscopy showed drug adhesion on luminal surface. One month after the balloon expansion, treated arteries were dissected and stent segments were fixed with 10% buffered formalin and embedded in plastic. Stents were segmented at 3mm intervals and histologic sections were prepared. The neointimal area and blood vessel area were morphometrically evaluated, and the ratio of neointimal area per blood vessel area was calculated. Additionally, number of cells per 1mm 2 neointimal area was counted with digital morphometry. Results: We compared the histology between DCB (n=3, 18 histological sections) and POBA (n=3, 18 histological sections) lesions. The ratio of neointimal area per blood vessel area treated by DCB was 0.17 ± 0.01, while that of POBA was 0.21 ± 0.01 (P value = 0.02) respectively. Additionally, the number of cells per 1mm 2 neointimal area was significantly less in the neointima dilated by DCB (1940.9 ± 150.9), compared to that dilated by NCB (2599.8 ± 190.3) (P value = 0.01). These results suggest that DCB treatment after ISR prevents neointimal thickening by inhibiting proliferation of smooth muscle cells. Conclusions: We examined the pathology of in-stent neointima dilated by DCB in peripheral artery of atherosclerotic porcine model. Pathological analysis showed suppressed neointimal proliferation after DCB compared to POBA.
Government will appoint patient safety commissioner but rejects call for independent redress agency
Authors: Gareth Iacobucci
Journal: BMJ (2021)

The government plans to appoint a new patient safety commissioner to oversee healthcare in England, in response to the Cumberlege review into treatments that caused avoidable harm.12

But it has rejected recommendations to set up an independent redress agency for people harmed by medicines and medical devices or to appoint an independent taskforce to implement the recommendations of the review, which examined the use of pelvic mesh, Primodos, and sodium valproate.

Nadine Dorries, health minister, said that the government was still considering the review’s recommendation that doctors’ financial and non-pecuniary interests should be declared and publicly available, but she indicated that this would be implemented in the …
Improved analysis of CRISPR fitness screens and reduced off-target effects with the BAGEL2 gene essentiality classifier
Authors: Eiru Kim, Traver Hart
Journal: Genome Medicine (2021)

Abstract Background Identifying essential genes in genome-wide loss-of-function screens is a critical step in functional genomics and cancer target finding. We previously described the Bayesian Analysis of Gene Essentiality (BAGEL) algorithm for accurate classification of gene essentiality from short hairpin RNA and CRISPR/Cas9 genome-wide genetic screens. Results We introduce an updated version, BAGEL2, which employs an improved model that offers a greater dynamic range of Bayes Factors, enabling detection of tumor suppressor genes; a multi-target correction that reduces false positives from off-target CRISPR guide RNA; and the implementation of a cross-validation strategy that improves performance ~ 10× over the prior bootstrap resampling approach. We also describe a metric for screen quality at the replicate level and demonstrate how different algorithms handle lower quality data in substantially different ways. Conclusions BAGEL2 substantially improves the sensitivity, specificity, and performance over BAGEL and establishes the new state of the art in the analysis of CRISPR knockout fitness screens. BAGEL2 is written in Python 3 and source code, along with all supporting files, are available on github ( https://github.com/hart-lab/bagel ).
Detecting HCV infection by means of mass population SARS-CoV-2 screening: A pilot experience in Northern Italy
Authors: Andrea Giacomelli, Gabriele Pagani, Federico Conti, Cinzia Bassoli, Massimo Galli
Journal: Journal of Hepatology (2021)

transplanted patients, and initial evidence of reduced efficacy of vaccination in this population. 7 Currently, vaccination of household members and caregivers of these patients is underway, and among this group immediate prioritisation is being given to those who take care of transplanted patients who could not receive COVID-19 vaccination because they had recently received a graft.We feel that these positive results strongly emphasise how adequate counselling may enhance vaccination uptake and adherence to the recommendations provided by EASL and by national scientific societies. 1,[9][0][11] A structured program may support rapid and complete COVID-19 vaccination for liver transplant recipients, protecting this frail population.
DLBCL-Derived NF-κb Mutations Exploit Senescence and Immune Evasion Mechanisms to Promote Myc-Driven Lymphomagenesis
Authors: Jens F. Schrezenmeier, Maurice Reimann, Sven Masswig, Liam Childs, Dorothee Childs, Philipp Lohneis, Clemens A. Schmitt
Journal: Blood (2017)
Dysglycemia and Acute Myocardial Infarction: The Role of Echocardiography⁎⁎Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.
Authors: David Verhaert, James D. Thomas
Journal: JACC. Cardiovascular imaging (2009)
Delivery of Anti‐microRNA‐712 to Inflamed Endothelial Cells Using Poly(<i>β</i>‐amino ester) Nanoparticles Conjugated with VCAM‐1 Targeting Peptide
Authors: Pere Dosta, Ian Tamargo, Victor Ramos, Sandeep Kumar, Dong Won Kang, Salvador Borrós, Hanjoong Jo
Journal: Advanced Healthcare Materials (2021)

Abstract Endothelial cells (ECs) are an important target for therapy in a wide range of diseases, most notably atherosclerosis. Developing efficient nanoparticle (NP) systems that deliver RNA interference (RNAi) drugs specifically to dysfunctional ECs in vivo to modulate their gene expression remains a challenge. To date, several lipid‐based NPs are developed and shown to deliver RNAi to ECs, but few of them are optimized to specifically target dysfunctional endothelium. Here, a novel, targeted poly( β ‐amino ester) (pBAE) NP is demonstrated. This pBAE NP is conjugated with VHPK peptides that target vascular cell adhesion molecule 1 protein, overexpressed on inflamed EC membranes. To test this approach, the novel NPs are used to deliver anti‐microRNA‐712 (anti‐miR‐712) specifically to inflamed ECs both in vitro and in vivo, reducing the high expression of pro‐atherogenic miR‐712. A single administration of anti‐miR‐712 using the VHPK‐conjugated‐pBAE NPs in mice significantly reduce miR‐712 expression, while preventing the loss of its target gene, tissue inhibitor of metalloproteinase 3 (TIMP3) in inflamed endothelium. miR‐712 and TIMP3 expression are unchanged in non‐inflamed endothelium. This novel, targeted‐delivery platform may be used to deliver RNA therapeutics specifically to dysfunctional endothelium for the treatment of vascular disease.
Abstract 12535: MicroRNA-663 Ameliorates Monocrotaline-induced Pulmonary Arterial Hypertension by Targeting TGFβ1/smad2/3 Signaling
Authors: Ni Zhu, Pan Li, He Du, Yongwen Qin, Xianxian Zhao
Journal: Circulation (2020)

Objective: Pulmonary vascular remodeling due to excessive growth factor production and pulmonary artery smooth muscle cells (PASMCs) proliferation is the hallmark feature of pulmonary arterial hypertension (PAH). Recent studies suggest that miR-663 is a potent modulator for tumorigenesis and atherosclerosis. However, whether miR-663 involves in pulmonary vascular remodeling is still unclear. Methods and Results: By using quantitative RT-PCR, we found that miR-663 was highly expressed in normal human PASMCs. In contrast, circulating level of miR-663 dramatically reduced in PAH patients. In addition, in situ hybridization showed that expression of miR-663 was decreased in PAMSCs of PAH patients. Furthermore, MTT and cell scratch-wound assay showed that transfection of miR-663 mimics significantly inhibited platelet derived growth factor (PDGF)-induced PASMC proliferation and migration, while knockdown of miR-663 expression enhanced these effects. Mechanistically, dual-luciferase reporter assay revealed that miR-663 directly targets the 3’UTR of TGF-β1. Moreover, western blots and ELISA results showed that miR-663 decreased PDGF-induced TGF-β1 expression and secretion, which in turn suppressed the downstream smad2/3 phosphorylation and collagen I expression. Finally, intratracheal instillation of adeno-miR-663 dramatically attenuated pulmonary vascular remodeling and right ventricular hypertrophy, as well as right ventricular systolic pressure and mean pulmonary arterial pressure in MCT-induced PAH rat models. Conclusion: These results indicate that miR-663 is a potential biomarker for PAH. MiR-663 decreases PDGF-BB-induced PAMSCs proliferation and ameliorates pulmonary vascular remodeling and right ventricular hypertrophy in MCT-PAH by targeting TGF-β1/smad2/3 signaling. These findings suggest that miR-663 may represent as an attractive approach for the diagnosis and treatment of PAH.
Clinical outcomes of digital sensor alerting systems in remote monitoring: a systematic review and meta-analysis
Authors: Fahad M. Iqbal, Kyle Lam, Meera Joshi, Sadia Khan, Hutan Ashrafian, Ara Darzi
Journal: npj Digital Medicine (2021)

Abstract Advances in digital technologies have allowed remote monitoring and digital alerting systems to gain popularity. Despite this, limited evidence exists to substantiate claims that digital alerting can improve clinical outcomes. The aim of this study was to appraise the evidence on the clinical outcomes of digital alerting systems in remote monitoring through a systematic review and meta-analysis. A systematic literature search, with no language restrictions, was performed to identify studies evaluating healthcare outcomes of digital sensor alerting systems used in remote monitoring across all (medical and surgical) cohorts. The primary outcome was hospitalisation; secondary outcomes included hospital length of stay (LOS), mortality, emergency department and outpatient visits. Standard, pooled hazard ratio and proportion of means meta-analyses were performed. A total of 33 studies met the eligibility criteria; of which, 23 allowed for a meta-analysis. A 9.6% mean decrease in hospitalisation favouring digital alerting systems from a pooled random effects analysis was noted. However, pooled weighted mean differences and hazard ratios did not reproduce this finding. Digital alerting reduced hospital LOS by a mean difference of 1.043 days. A 3% mean decrease in all-cause mortality from digital alerting systems was noted. There was no benefit of digital alerting with respect to emergency department or outpatient visits. Digital alerts can considerably reduce hospitalisation and length of stay for certain cohorts in remote monitoring. Further research is required to confirm these findings and trial different alerting protocols to understand optimal alerting to guide future widespread implementation.
Poly(2‐oxazoline)‐ and Poly(2‐oxazine)‐Based Self‐Assemblies, Polyplexes, and Drug Nanoformulations—An Update
Authors: Anna Zahoranová, Robert Luxenhofer
Journal: Advanced Healthcare Materials (2021)

For many decades, poly(2-oxazoline)s and poly(2-oxazine)s, two closely related families of polymers, have led the life of a rather obscure research topic with only a few research groups world-wide working with them. This has changed in the last five to ten years, presumably triggered significantly by very promising clinical trials of the first poly(2-oxazoline)-based drug conjugate. The huge chemical and structural toolbox poly(2-oxazoline)s and poly(2-oxazine)s has been extended very significantly in the last few years, but their potential still remains largely untapped. Here, specifically, the developments in macromolecular self-assemblies and non-covalent drug delivery systems such as polyplexes and drug nanoformulations based on poly(2-oxazoline)s and poly(2-oxazine)s are reviewed. This highly dynamic field benefits particularly from the extensive synthetic toolbox poly(2-oxazoline)s and poly(2-oxazine)s offer and also may have the largest potential for a further development. It is expected that the research dynamics will remain high in the next few years, particularly as more about the safety and therapeutic potential of poly(2-oxazoline)s and poly(2-oxazine)s is learned.
The Future Is P-Tau—Anticipating Direct-to-Consumer Alzheimer Disease Blood Tests
Authors: Emily A. Largent, Anna Wexler, Jason Karlawish
Journal: JAMA Neurology (2021)

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Endoscopic full-thickness resection of polyps involving the appendiceal orifice: a multicenter international experience
Authors: Yervant Ichkhanian, Mohammed Barawi, Talal Seoud, Shyam Thakkar, Truptesh H. Kothari, Maan El Halabi, Asad Ullah, Wedi Edris, Patrick Aepli, Thomas Kowalski, Brianna Shinn, Reem Z. Shariaha, Srihari Mahadev, Jeffrey D. Mosko, Gianluca Andrisani, Francesco Maria Di Matteo, Heinz Albrecht, Andrew Q. Giap, Shou-jiang Tang, Yehia M. Naga, Erwin van Geenen, Shai Friedland, Benjamin Tharian, Shayan Irani, Andrew S. Ross, Laith H. Jamil, Daniel Lew, Andrew S. Nett, Jad Farha, Thomas M. Runge, Manol Jovani, Mouen A. Khashab
Journal: Endoscopy (2021)

Abstract Background Endoscopic resection of lesions involving the appendiceal orifice remains a challenge. We aimed to report outcomes with the full-thickness resection device (FTRD) for the resection of appendiceal lesions and identify factors associated with the occurrence of appendicitis. Methods This was a retrospective study at 18 tertiary-care centers (USA 12, Canada 1, Europe 5) between November 2016 and August 2020. Consecutive patients who underwent resection of an appendiceal orifice lesion using the FTRD were included. The primary outcome was the rate of R0 resection in neoplastic lesions, defined as negative lateral and deep margins on post-resection histologic evaluation. Secondary outcomes included the rates of: technical success (en bloc resection), clinical success (technical success without need for further surgical intervention), post-resection appendicitis, and polyp recurrence. Results 66 patients (32 women; mean age 64) underwent resection of colonic lesions involving the appendiceal orifice (mean [standard deviation] size, 14.5 (6.2) mm), with 40 (61 %) being deep, extending into the appendiceal lumen. Technical success was achieved in 59/66 patients (89 %), of which, 56 were found to be neoplastic lesions on post-resection pathology. Clinical success was achieved in 53/66 (80 %). R0 resection was achieved in 52/56 (93 %). Of the 58 patients in whom EFTR was completed who had no prior history of appendectomy, appendicitis was reported in 10 (17 %), with six (60 %) requiring surgical appendectomy. Follow-up colonoscopy was completed in 41 patients, with evidence of recurrence in five (12 %). Conclusions The FTRD is a promising non-surgical alternative for resecting appendiceal lesions, but appendicitis occurs in 1/6 cases.
Activity and components of the granulocyte colony‐stimulating factor pathway in hidradenitis suppurativa*
Authors: K. Wolk, T.‐C. Brembach, D. Šimaitė, E. Bartnik, S. Cucinotta, A. Pokrywka, M.L. Irmer, J. Triebus, E. Witte‐Händel, G. Salinas, T. Leeuw, H.‐D. Volk, K. Ghoreschi, R. Sabat
Journal: British Journal of Dermatology (2021)

Hidradenitis suppurativa (HS) is a chronic inflammatory disease, characterized by painful, purulent and destructive skin alterations in intertriginous areas.We investigated the expression and role in HS of granulocyte colony-stimulating factor (G-CSF), the regulator of neutrophil biology, as clinical signs of a neutrophilic granulocyte-driven inflammation are distinctive in the disease.Skin and blood samples obtained from different cohorts of patients with HS and control individuals were assessed by RNA sequencing, quantitative polymerase chain reaction on reverse transcribed mRNA, and/or enzyme-linked immunosorbent assay. Mechanistic studies using keratinocytes, dermal fibroblasts, immune cell populations and skin biopsies were performed.G-CSF was abundant in HS skin, particularly in inflamed nodules and abscesses. Its levels even exceeded those found in other inflammatory skin diseases. Interleukin (IL)-1 and IL-17, respectively, induced G-CSF production by fibroblasts and keratinocytes. These effects were enhanced by tumour necrosis factor (TNF)-α and IL-36. Accordingly, fibroblasts separated from HS lesions expressed G-CSF, and IL-1 receptor antagonist reduced G-CSF levels in explanted HS skin. G-CSF blood levels positively correlated with severity of HS. Elevated lesional G-CSF receptor levels were linked to upregulation of molecules that contribute to prolonged activation of neutrophils by components of bacteria and damaged host cells [formyl peptide receptor 1 (FPR1), FPR2 and free fatty acid receptor 2 (FFAR2)], neutrophil survival [TNF receptor superfamily member 10C (TNFRSF10C/TRAIL-R3) and TNF receptor superfamily member 6B], kinases (tyrosine-protein kinase HCK and hexokinase 3), and skin destruction [MMP25 (matrix metalloproteinase 25) and ADAM8 (disintegrin and metalloproteinase domain-containing protein 8)]. G-CSF elevated the expression of FPR1, FFAR2, and TNFRSF10C/TRAIL-R3 in neutrophils and synergized with bacterial components to induce skin-destructive enzymes.The G-CSF pathway engages both tissue and immune cells, is strongly activated in HS lesions, and offers the opportunity to target the neutrophil-driven inflammation.
Noninvasive ventilatory support in morbid obesity
Authors: J.R. Bach, A.W. Kazi, T. Pinto, M.R. Gonçalves
Journal: Pulmonology (2021)

In the conventional management of the morbidly obese that normalizes the apnea-hypopnea index (AHI), CO2 levels often remain elevated. A retrospective review of morbidly obese patients using volume preset settings up to 1800 ml to positive inspiratory pressures (PIPs) of 25–55 cm H2O, or pressure control at 25–50 cm H2O pressure via noninvasive interfaces up to continuously (CNVS). Twenty-six patients, mean 55.6 ± 14.8 years of age, weight 108–229 kg, mean BMI 56.1 (35.5–77) kg/m2, mean AHI 69.0 ± 24.9, depended on up to CNVS for 3 weeks to up to 66 years. There were eleven extubations and seven decannulations to CNVS despite failure to pass spontaneous breathing trials. Thirteen were CNVS dependent for 92.2 patient-years with little to no ventilator free breathing ability (VFBA). Six used NVS from 10 to 23 h a day, and others only for sleep. Fifteen patients with cough peak flows (CPF) less than 270 L/m had access to mechanical insufflation-exsufflation (MIE) in the peri-extubation/decannulation period and long-term. The daytime end-tidal (Et)CO2 of 14 who were placed on sleep NVS without extubation or decannulation to it decreased from mean EtCO2 61.0 ± 9.3–38.5 ± 3.6 mm Hg and AHI normalized to 2.2. Blood gas levels were normal while using NVS/CNVS. Pre-intubation PaCO2 levels, when measured, were as high as 183 mm Hg before extubation to CNVS. Ventilator unweanable morbidly obese patients can be safely extubated/decannulated and maintained indefinitely using up to CNVS rather than resort to tracheotomies.
Colonoscopy competence assessment tools: a systematic review of validity evidence
Authors: Rishad Khan, Eric Zheng, Sachin B. Wani, Michael A. Scaffidi, Thurarshen Jeyalingam, Nikko Gimpaya, John T. Anderson, Samir C. Grover, Graham McCreath, Catharine M. Walsh
Journal: Endoscopy (2021)

Abstract Background Assessment tools are essential for endoscopy training, being required to support feedback provision, optimize learner capabilities, and document competence. We aimed to evaluate the strength of validity evidence that supports the available colonoscopy direct observation assessment tools using the unified framework of validity. Methods We systematically searched five databases for studies investigating colonoscopy direct observation assessment tools from inception until 8 April 2020. We extracted data outlining validity evidence (content, response process, internal structure, relations to other variables, and consequences) from the five sources and graded the degree of evidence, with a maximum score of 15. We assessed educational utility using an Accreditation Council for Graduate Medical Education framework and methodological quality using the Medical Education Research Quality Instrument (MERSQI). Results From 10 841 records, we identified 27 studies representing 13 assessment tools (10 adult, 2 pediatric, 1 both). All tools assessed technical skills, while 10 each assessed cognitive and integrative skills. Validity evidence scores ranged from 1–15. The Assessment of Competency in Endoscopy (ACE) tool, the Direct Observation of Procedural Skills (DOPS) tool, and the Gastrointestinal Endoscopy Competency Assessment Tool (GiECAT) had the strongest validity evidence, with scores of 13, 15, and 14, respectively. Most tools were easy to use and interpret, and required minimal resources. MERSQI scores ranged from 9.5–11.5 (maximum score 14.5). Conclusions The ACE, DOPS, and GiECAT have strong validity evidence compared with other assessments. Future studies should identify barriers to widespread implementation and report on the use of these tools in credentialing examinations.