tbuckley/cabot-search huggingface dataset:
Mechanisms of immune checkpoint inhibitor-mediated liver injury
Authors: Layla Shojaie, Myra Ali, Andrea Iorga, Lily Dara
Journal: Acta Pharmaceutica Sinica B (2021)

The immune checkpoints, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death protein-1/ligand-1 (PD-1/PD-L1) are vital contributors to immune regulation and tolerance. Recently immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy; however, they come with the cost of immune related adverse events involving multiple organs such as the liver. Due to its constant exposure to foreign antigens, the liver has evolved a high capacity for immune tolerance, therefore, blockade of the immune checkpoints can result in aberrant immune activation affecting the liver in up to 20% of patients depending on the agent(s) used and underlying factors. This type of hepatotoxicity is termed immune mediated liver injury from checkpoint inhibitors (ILICI) and is more common when CTLA4 and PD-1/PD-L1 are used in combination. The underlying mechanisms of this unique type of hepatotoxicity are not fully understood; however, the contribution of CD8
Prenatal interleukin 6 elevation increases glutamatergic synapse density and disrupts hippocampal connectivity in offspring
Authors: Filippo Mirabella, Genni Desiato, Sara Mancinelli, Giuliana Fossati, Marco Rasile, Raffaella Morini, Marija Markicevic, Christina Grimm, Clara Amegandjin, Alberto Termanini, Clelia Peano, Paolo Kunderfranco, Graziella di Cristo, Valerio Zerbi, Elisabetta Menna, Simona Lodato, Michela Matteoli, Davide Pozzi
Journal: Immunity (2021)

Early prenatal inflammatory conditions are thought to be a risk factor for different neurodevelopmental disorders. Maternal interleukin-6 (IL-6) elevation during pregnancy causes abnormal behavior in offspring, but whether these defects result from altered synaptic developmental trajectories remains unclear. Here we showed that transient IL-6 elevation via injection into pregnant mice or developing embryos enhanced glutamatergic synapses and led to overall brain hyperconnectivity in offspring into adulthood. IL-6 activated synaptogenesis gene programs in glutamatergic neurons and required the transcription factor STAT3 and expression of the RGS4 gene. The STAT3-RGS4 pathway was also activated in neonatal brains during poly(I:C)-induced maternal immune activation, which mimics viral infection during pregnancy. These findings indicate that IL-6 elevation at early developmental stages is sufficient to exert a long-lasting effect on glutamatergic synaptogenesis and brain connectivity, providing a mechanistic framework for the association between prenatal inflammatory events and brain neurodevelopmental disorders.
Melanoma classification using light-Fields with morlet scattering transform and CNN: Surface depth as a valuable tool to increase detection rate
Authors: Pedro M. M. Pereira, Lucas A. Thomaz, Luis M. N. Tavora, Pedro A. A. Assuncao, Rui M. Fonseca-Pinto, Rui Pedro Paiva, Sergio M. M. de Faria
Journal: Medical Image Analysis (2021)
23P Transient multiple transfection of miR-181a into MCF-7 breast cancer cells induces irreversible resistance to tamoxifen
Authors: O.E. Andreeva, Y.Y. Shchegolev, V.A. Shatskaya, D.V. Sorokin, A.M. Scherbakov, E.I. Mikhaevich, M.V. Gudkova, I.V. Bure, E.B. Kuznetsova, M.V. Nemtsova, M.A. Krasil`nikov
Journal: Annals of Oncology (2021)
Aggregation‐Induced Emission‐Active Poly(phenyleneethynylene)s for Fluorescence and Raman Dual‐Modal Imaging and Drug‐Resistant Bacteria Killing
Authors: Xiang Su, Ruihua Liu, Ying Li, Ting Han, Zhijun Zhang, Niu Niu, Miaomiao Kang, Shuang Fu, Deliang Wang, Dong Wang, Ben Zhong Tang
Journal: Advanced Healthcare Materials (2021)

Abstract Poly(phenyleneethynylene) (PPE) is a widely used functional conjugated polymer with applications ranging from organic optoelectronics and fluorescence sensors to optical imaging and theranostics. However, the fluorescence efficiency of PPE in aggregate states is generally not as good as their solution states, which greatly compromises their performance in fluorescence‐related applications. Herein, a series of PPE derivatives with typical aggregation‐induced emission (AIE) properties is designed and synthesized. In these PPEs, the diethylamino‐substituted tetraphenylethene units function as the long‐wavelength AIE source and the alkyl side chains serve as the functionalization site. The obtained AIE‐active PPEs with large π ‐conjugation show strong aggregate‐state fluorescence, interesting self‐assembly behaviors, inherently enhanced alkyne vibrations in the Raman‐silent region of cells, and efficient antibacterial activities. The PPE nanoparticles with good cellular uptake capability can clearly and sensitively visualize the tumor region and residual tumors via their fluorescence and Raman signals, respectively, to benefit the precise tumor resection surgery. After post‐functionalization, the obtained PPE‐based polyelectrolyte can preferentially image bacteria over mammalian cells and possesses efficient photodynamic killing capability against Gram‐positive and drug‐resistant bacteria. This work provides a feasible design strategy for developing functional conjugated polymers with multimodal imaging capability as well as photodynamic antimicrobial ability.
Non-Invasive Prenatal Testing for “Non-Medical” Traits: Ensuring Consistency in Ethical Decision-Making
Authors: Hilary Bowman-Smart, Christopher Gyngell, Cara Mand, David J. Amor, Martin B. Delatycki, Julian Savulescu
Journal: The American Journal of Bioethics (2021)

The scope of noninvasive prenatal testing (NIPT) could expand in the future to include detailed analysis of the fetal genome. This will allow for the testing for virtually any trait with a genetic contribution, including "non-medical" traits. Here we discuss the potential use of NIPT for these traits. We outline a scenario which highlights possible inconsistencies with ethical decision-making. We then discuss the case against permitting these uses. The objections include practical problems; increasing inequities; increasing the burden of choice; negative impacts on the child, family, and society; and issues with implementation. We then outline the case for permitting the use of NIPT for these traits. These include arguments for reproductive liberty and autonomy; questioning the labeling of traits as "non-medical"; and the principle of procreative beneficence. This summary of the case for and against can serve as a basis for the development of a consistent and coherent ethical framework.
Sixty seconds on . . . Matt Hancock
Authors: Zosia Kmietowicz
Journal: BMJ (2021)

Indeed. The former health secretary for England kept his head down for 108 days after resigning from the cabinet for breaking his own covid rules, but his star was briefly in the ascendancy again last week after the United Nations gave him an (unpaid) role to advise African countries on economic recovery and climate change after the pandemic.1

Yes. No sooner had the man known as “Tigger”2 bounced back and been hailed for …
P70.11 Prevalence and Clinicopathological Characteristics of ARID1A Mutations in East Asian Patients With Non-Small Cell Lung Cancer
Authors: C. Xu, W. Wang, D. Wang, Y. Zhu, W. Zhuang, M. Fang, G. Wang, Q. Wang, Y. Song, S. Lu
Journal: Journal of Thoracic Oncology (2021)
Serial Native T1 Assessment for LV Functional Recovery in Recent-Onset DCM
Authors: Junko Ishiura, Shiro Nakamori, Masaki Ishida, Kyoko Imanaka-Yoshida, Michiaki Hiroe, Keishi Moriwaki, Emiyo Sugiura, Naoki Fujimoto, Masafumi Takafuji, Yasutaka Ichikawa, Kakuya Kitagawa, Hajime Sakuma, Kaoru Dohi
Journal: JACC. Cardiovascular imaging (2021)
Analysis of Electronic Health Record Use and Clinical Productivity and Their Association With Physician Turnover
Authors: Edward R. Melnick, Allan Fong, Bidisha Nath, Brian Williams, Raj M. Ratwani, Richard Goldstein, Ryan T. O’Connell, Christine A. Sinsky, Daniel Marchalik, Mihriye Mete
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Physician turnover takes a heavy toll on patients, physicians, and health care organizations. Survey research has established associations of electronic health record (EHR) use with professional burnout and reduction in professional effort, but these findings are subject to response fatigue and bias. <h3>Objective</h3> To evaluate the association of physician productivity and EHR use patterns, as determined by vendor-derived EHR use data platforms, with physician turnover. <h3>Design, Setting, and Participants</h3> This retrospective cohort study was conducted among nonteaching ambulatory physicians at a large ambulatory practice network based in New England. Data were collected from March 2018 to February 2020. <h3>Main Outcomes and Measures</h3> Physician departure from the practice network; 4 time-based core measures of EHR use, normalized to 8 hours of scheduled clinical time; teamwork, percentage of a physician’s orders that are placed by other members of the care team; and productivity measures of patient volume, intensity, and demand. <h3>Results</h3> Among 335 physicians assessed for eligibility, 314 unique physicians (89.2%) were included in the analysis (123 [39%] women; 100 [32%] aged 45-54 years), with 5663 physician-months of data. The turnover rate was 5.1%/year (32 of 314 physicians). Physicians completed a mean 2.6 appointments/hour (95% CI, 2.5-2.6 appointments/hour) and 206 appointments/month (95% CI, 197-215 appointments/month) with 5.5 hours (95% CI, 5.3-5.8 hours) of EHR time for every 8 hours of scheduled patient time. After controlling for gender, medical specialty, and time, the following variables were associated with turnover: inbox time (odds ratio [OR], 0.70; 95% CI, 0.61-0.82;<i>P</i> &lt; .001), teamwork (OR, 0.68; 95% CI, 0.52-0.87;<i>P</i> = .003), demand (ie, proportion of available appointments filled: OR, 0.49; 95% CI, 0.35-0.70;<i>P</i> &lt; .001), and age 45 to 54 years vs 25 to 34 years (OR, 0.19; 95% CI, 0.04-0.93;<i>P</i> = .04). <h3>Conclusions and Relevance</h3> In this study, physician productivity and EHR use metrics were associated with physician departure. Prospectively tracking these metrics could identify physicians at high risk of departure who would benefit from early, team-based, targeted interventions. The counterintuitive finding that less time spent on the EHR (in particular inbox management) was associated with physician departure warrants further investigation.
Downstream balloon dilation technique for endoscopic removal of an impacted pancreatic duct stone after pancreatoduodenectomy
Authors: Sho Kitagawa, Shori Ishikawa, Keiya Okamura
Journal: Endoscopy (2021)

Endoscopic retrograde pancreatography is an established modality for the treatment of pancreatic duct stones [1] [2]. Although it is technically challenging in patients with prior pancreatoduodenectomy [3] [4], balloon-assisted endoscopic retrograde pancreatography and/or endoscopic ultrasound-guided pancreatic drainage has been increasingly utilized to manage pancreatic diseases in patients with surgically altered anatomy [5]. Here we report a simple and feasible technique for the endoscopic removal of an impacted pancreatic duct stone after pancreatoduodenectomy using a short-type single-balloon enteroscope.
First Description of <scp>Late‐Onset</scp> Autoinflammatory Disease Due to Somatic <scp><i>NLRC4</i></scp> Mosaicism
Authors: Daniela Ionescu, Alejandro Peñín‐Franch, Anna Mensa‐Vilaró, Paola Castillo, Laura Hurtado‐Navarro, Cristina Molina‐López, Silvia Romero‐Chala, Susana Plaza, Virginia Fabregat, Segundo Buján, Joana Marques, Ferran Casals, Jordi Yagüe, Baldomero Oliva, Luis Miguel Fernández‐Pereira, Pablo Pelegrín, Juan I. Aróstegui
Journal: Arthritis & Rheumatology (2021)

Autoinflammatory diseases are inherited disorders of innate immunity that usually start during childhood. However, several recent reports have described an increasing number of patients with autoinflammatory disease starting in adulthood. This study was undertaken to investigate the underlying cause of a case of late-onset uncharacterized autoinflammatory disease.Genetics studies were performed using Sanger sequencing and next-generation sequencing (NGS) methods. In silico, in vitro, and ex vivo analyses were performed to determine the functional consequences of the detected variant.We studied a 57-year-old woman who at the age of 47 years began to have recurrent episodes of fever, myalgias, arthralgias, diffuse abdominal pain, diarrhea, adenopathies, and systemic inflammation, which were relatively well controlled with anti-interleukin-1 (anti-IL-1) drugs. NGS analyses did not detect germline variants in any of the known autoinflammatory disease-associated genes, but they identified the p.Ser171Phe NLRC4 variant in unfractionated blood, with an allele fraction (2-4%) compatible with gene mosaicism. Structural modeling analyses suggested that this missense variant might favor the open, active conformation of the NLRC4 protein, and in vitro and ex vivo analyses confirmed its propensity to oligomerize and activate the NLRC4 inflammasome, with subsequent overproduction of IL-18.Our findings indicate that the postzygotic p.Ser171Phe NLRC4 variant is a plausible cause of the disease in the enrolled patient. Functional and structural studies clearly support, for the first time, its gain-of-function behavior, consistent with previously reported NLRC4 pathogenic variants. These novel findings should be considered in the diagnostic evaluation of patients with adult-onset uncharacterized autoinflammatory disease.
MA02.02 Efficacy and Safety of Pralsetinib in Chinese Patients with Advanced RET Fusion+ Non-Small Cell Lung Cancer
Authors: Q. Zhou, Y. Wu, J. Chang, H. Wang, Y. Fan, J. Zhao, G. Wu, Y. Sun, M. Sun, X. Wang, H. Shi, W. Nian, K. Wang, X. Zheng, L. Qu, S. Yao, Z. Shen, P. Li, J. Yang
Journal: Journal of Thoracic Oncology (2021)
Endoscopic submucosal dissection with early multitraction placed before circumferential incision allows excellent exposure but with a risk of catching the muscularis propria
Authors: Jean Grimaldi, Jérôme Rivory, Thomas Lambin, Pierre Lafeuille, Jérémie Jacques, Thierry Ponchon, Mathieu Pioche
Journal: Endoscopy (2021)

Traction-assisted endoscopic submucosal dissection (ESD) is very effective and is becoming standard for colorectal ESD [1]. Recently, we developed the multitraction strategy to increase traction power in difficult lesions [2]. In order to benefit from the maximum potential of this technique, both to make the resection technically easier and to save time on the procedure, it seemed interesting to try to place the traction as early as possible to take advantage of the exposure power earlier.
Longitudinal atopic dermatitis endotypes: An atopic march paradigm that includes Black children
Authors: Jocelyn M. Biagini, John W. Kroner, Asel Baatyrbek kyzy, Alexandra Gonzales, Hua He, Mariana Stevens, Brittany Grashel, Daniel Spagna, Samuel Paul, Rahul Patel, Angelo Bucci, Michael G. Sherenian, Liza Bronner Murrison, Lisa J. Martin, Gurjit K. Khurana Hershey
Journal: Journal of Allergy and Clinical Immunology (2021)
Continuous noninvasive ventilatory support outcomes for patients with neuromuscular disease: a multicenter data collaboration
Authors: M.R. Gonçalves, J.R. Bach, Y. Ishikawa, L. Saporito, J.C. Winck
Journal: Pulmonology (2021)

Typically, patients with progressive neuromuscular disorders (NMDs) develop acute respiratory failure (ARF), are intubated, and when failing spontaneous breathing trials (SBTs) undergo a tracheotomy and receive tracheostomy mechanical ventilation (TMV). However, increasing numbers of patients use nasal noninvasive ventilation (NIV), initially for sleep and this is extended to continuous dependence (CNVS). This can be used as a strategy to assist in successful extubation . We retrospectively reviewed 19 centers offering CNVS and mechanical insufflation-exsufflation (MI-E) as an alternative to TMV. Centers with publications or presentations concerning CNVS outcomes data were pooled for amyotrophic lateral sclerosis (ALS), Duchenne muscular dystrophy (DMD), and spinal muscular atrophy type 1 (SMA1). Progression to CNVS dependence without hospitalization, duration of dependence, and extubations and decannulations to CNVS were recorded. Prolongation of life was defined by duration of CNVS dependence without ventilator free breathing ability (VFBA). There were 1623 part time (<23 h/day) NVS users with ALS, DMD, and SMA1 from 19 centers in 16 countries of whom 761 (47%) were CNVS dependent for 2218 patient-years. This included: 335 ALS patients for a mean 1.2 ± 1.0 (range to 8) years each; 385 DMD patients for 5.4 ± 1.6 (range to 29) years; and 41 SMA1 patients for 5.9 ± 1.8 (range to 20) years. Thirty-five DMD and ALS TMV users were decannulated to CNVS and MI-E. At data collection 494 (65%) patients were CNVS dependent but 110 (74 of whom with bulbar ALS), had undergone tracheotomies. ALS, DMD, and SMA1 patients can become CNVS dependent without requiring hospitalization but CNVS cannot be used indefinitely for many patients with advanced upper motor neuron diseases.
DNA palindromes: The role of repair functions
Authors: Julia H. Appleby, Susanna M. Lewis
Journal: Cancer Research (2004)

2624  DNA palindromes consist of pairs of inversely repeated sequences having central symmetry that, along with forming typical B-form double helices, are able to form intra-strand hairpin and cruciform structures. However, the ability of palindromes to form hairpins and cruciforms poses a special threat to the genome as these secondary structures can block replication and lead to genetic rearrangements. In human and rodent systems, a unique mechanism for dealing with palindromes has been demonstrated, termed the Center-Break Model. In this mechanism, each of the hairpin tips are nicked, creating a double strand break at the center of symmetry. This break is then repaired by the NHEJ pathway, a process which often results in deletion of sequence creating a central asymmetry. While sequence analysis of breakpoints demonstrates the Center-Break mechanism, it is unknown which pathway(s) of detection and repair functions are involved. Investigations are being undertaken using both chromosomally and extra-chromosomally located palindromes combined with genetic knock-out and knock-down techniques in order to implicate both proteins and a potential pathway. For the chromosomal palindrome investigation, a mouse model carrying a 15.6kb perfect palindrome on chromosome 17, termed the Line 78 mouse is being used. The role of several proteins in palindrome processing are being tested, the first being the Werner’s syndrome protein because it is required for genome stability and affects the stability of the Tg.AC palindrome. Also, the potential roles for DNA-Pk, Ku70 because of their roles in NHEJ, and Artemis, as the hairpin-nicking nuclease in V(D)J recombination are being explored. Abelson cell lines generated from crosses of these mice are then monitored for palindrome rearrangement using subcloning, inverse-PCR and Southern blot techniques. Previous work in the lab had shown that the rate of rearrangement of the Line 78 palindrome in different wild-type backgrounds is 0.5% per generation. By determining the rate of rearrangement, as well as the quality (i.e. larger versus small deletions), in a variety of genetic backgrounds, I will be able to implicate various proteins and pathways in the process of palindrome rearrangement. The second approach to investigate the role of DNA repair functions in palindrome instability is an extra-chromosomal transfection assay. This approach examines rearrangement of a palindromic circular dimer, which can be transfected into cell cultures of interest. This palindrome is reproducibly and site-specifically resolved into monomer circles. This assay is being carried out in cell lines of the genetic backgrounds mentioned above, and is also being combined with RNAi techniques in oreder to expand the number of genetic influences that can be examined. This extra-chromosomal transfections assay will allow for rapid and varied investigation of the role of certain proteins in palindrome processing.
CD103 integrin identifies a high IL‐10‐producing FoxP3<sup>+</sup>regulatory T‐cell population suppressing allergic airway inflammation
Authors: Sofia Tagkareli, Maria Salagianni, Ioanna‐Evdokia Galani, Maria Manioudaki, Eleftherios Pavlos, Kalliopi Thanopoulou, Evangelos Andreakos
Journal: Allergy (2021)

Although FoxP3+ regulatory T (Treg) cells constitute a highly heterogeneous population, with different regulatory potential depending on the disease context, distinct subsets or phenotypes remain poorly defined. This hampers the development of immunotherapy for allergic and autoimmune disorders. The present study aimed at characterizing distinct FoxP3+ Treg subpopulations involved in the suppression of Th2-mediated allergic inflammation in the lung.We used an established mouse model of allergic airway disease based on ovalbumin sensitization and challenge to analyze FoxP3+ Tregs during the induction and resolution of inflammation, and identify markers that distinguish their most suppressive phenotypes. We also developed a new knock-in mouse model (Foxp3cre Cd103dtr ) enabling the specific ablation of CD103+ FoxP3+ Tregs for functional studies.We found that during resolution of allergic airway inflammation in mice >50% of FoxP3+ Treg cells expressed the integrin CD103 which marks FoxP3+ Treg cells of high IL-10 production, increased expression of immunoregulatory molecules such as KLRG1, ICOS and CD127, and enhanced suppressive capacity for Th2-mediated inflammatory responses. CD103+ FoxP3+ Tregs were essential for keeping allergic inflammation under control as their specific depletion in Foxp3cre Cd103dtr mice lead to severe alveocapillary damage, eosinophilic pneumonia, and markedly reduced lifespan of the animals. Conversely, adoptive transfer of CD103+ FoxP3+ Tregs effectively treated disease, attenuating Th2 responses and allergic inflammation in an IL-10-dependent manner.Our study identifies a novel regulatory T-cell population, defined by CD103 expression, programmed to prevent exuberant type 2 inflammation and keep homeostasis in the respiratory tract under control. This has important therapeutic implications.
P59.15 Is CD73 Expression a Druggable Mechanism of Resistance in EGFR-TKI-Treated EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC)?
Authors: I.J. Eide, A.P. Dyrbekk, Å. Helland, S. Ekman, J. Koivunen, S. Cicenas, B. Grønberg, I. Bisha, T. Haberichter, S. Lakis, J. Chan, A. Lewis, P. Martin, Z. Cooper, O.T. Brustugun
Journal: Journal of Thoracic Oncology (2021)