tbuckley/cabot-search huggingface dataset:
P01.11 Clinical Outcomes After Discontinuation of Immunotherapy in Patients With Non-Progressing Metastatic Lung Cancer
Authors: M. Cerini, V. Bluthgen, V. Peuchot, M. Rizzo, F. Rizzi, A. Kuzminin, G. Recondo, V. Faura, M. Naveira, A. Perfetti, L. Lupinacci, J. Minatta
Journal: Journal of Thoracic Oncology (2021)
MA11.07 Phase 1/2 TRIDENT-1 Study of Repotrectinib in Patients with ROS1+ or NTRK+ Advanced Solid Tumors
Authors: B.C. Cho, R.C. Doebele, J. Lin, M. Nagasaka, C. Baik, A. Van Der Wekken, V. Velcheti, K.H. Lee, S. Liu, B. Solomon, S. Kao, M.G. Krebs, V. Zhu, S. Stopatschinskaja, R. Camidge, A. Drilon
Journal: Journal of Thoracic Oncology (2021)
Overcoming Mfsd2a‐Mediated Low Transcytosis to Boost Nanoparticle Delivery to Brain for Chemotherapy of Brain Metastases
Authors: Xiufeng Ju, Tongtong Miao, Haiyan Chen, Jiang Ni, Liang Han
Journal: Advanced Healthcare Materials (2021)

Microvessels of the blood-brain barrier (BBB) exclusively express the major facilitator superfamily domain-containing protein 2a (Mfsd2a), which is the key transporter for docosahexaenoic acid uptake into the brain. Mfsd2a suppresses caveolae-mediated transcytosis to regulate BBB transcellular permeability via controlling lipid composition of BBB endothelial cells. It is speculated that Mfsd2a can restrain BBB crossing efficiency and brain accumulation efficiency of brain-targeting drug delivery systems, which penetrate the BBB often through the receptor-mediated transcytosis pathway. Transcytosis across the BBB is a crucial bottleneck for targeted chemotherapy of brain metastases. To overcome this issue, a pair of priming nanoparticles (NPs) and following drug-loaded NPs are designed. Tunicamycin-(TM)-loaded transcytosis-targeting-peptide-(TTP)-decorated NPs (TM@TTP) are used to boost BBB transcytosis via inhibiting Mfsd2a. Doxorubicin (DOX)-loaded TTP and CD44-specific hyaluronic acid (HA)-comodified NPs (DOX@TTP-HA) are designed as following drug-loaded NPs. The brain accumulation efficacy of following DOX@TTP-HA with priming is 4.30-fold higher than that without priming through the enhanced transcytosis pathway rather than the tight junction opening. Effective BBB crossing and brain accumulation, selective tumor uptake, excellent antitumor efficacy, and low hepatotoxicity are achieved by TM@TTP and DOX@TTP-HA, suggesting this tactic as a significant therapeutic strategy against breast cancer brain metastases.
Reply to Anirban P. Mitra, Tanner Miest, and Colin P.N. Dinney’s Words of Wisdom re: Genomic Predictors of Good Outcome, Recurrence, or Progression in High-Grade T1 Non-Muscle-Invasive Bladder Cancer. Eur Urol 2021;79:428–9
Authors: Júlia Perera-Bel, Joaquim Bellmunt
Journal: European Urology (2021)
Analysis of Fungal Genomes Reveals Commonalities of Intron Gain or Loss and Functions in Intron-Poor Species
Authors: Chun Shen Lim, Brooke N Weinstein, Scott W Roy, Chris M Brown
Journal: Molecular Biology and Evolution (2021)

Abstract Previous evolutionary reconstructions have concluded that early eukaryotic ancestors including both the last common ancestor of eukaryotes and of all fungi had intron-rich genomes. By contrast, some extant eukaryotes have few introns, underscoring the complex histories of intron–exon structures, and raising the question as to why these few introns are retained. Here, we have used recently available fungal genomes to address a variety of questions related to intron evolution. Evolutionary reconstruction of intron presence and absence using 263 diverse fungal species supports the idea that massive intron reduction through intron loss has occurred in multiple clades. The intron densities estimated in various fungal ancestors differ from zero to 7.6 introns per 1 kb of protein-coding sequence. Massive intron loss has occurred not only in microsporidian parasites and saccharomycetous yeasts, but also in diverse smuts and allies. To investigate the roles of the remaining introns in highly-reduced species, we have searched for their special characteristics in eight intron-poor fungi. Notably, the introns of ribosome-associated genes RPL7 and NOG2 have conserved positions; both intron-containing genes encoding snoRNAs. Furthermore, both the proteins and snoRNAs are involved in ribosome biogenesis, suggesting that the expression of the protein-coding genes and noncoding snoRNAs may be functionally coordinated. Indeed, these introns are also conserved in three-quarters of fungi species. Our study shows that fungal introns have a complex evolutionary history and underappreciated roles in gene expression.
Sleep Abnormalities in Schizophrenia: State of the Art and Next Steps
Authors: Fabio Ferrarelli
Journal: American Journal of Psychiatry (2021)

Sleep disturbances are commonly observed in schizophrenia, including in chronic, early-course, and first-episode patients. This has generated considerable interest, both in clinical and research endeavors, in characterizing the relationship between disturbed sleep and schizophrenia. Sleep features can be objectively assessed with EEG recordings. Traditionally, EEG studies have focused on sleep architecture, which includes non-REM and REM sleep stages. More recently, numerous studies have investigated alterations in sleep-specific rhythms, including EEG oscillations, such as sleep spindles and slow waves, in individuals with schizophrenia compared with control subjects. In this article, the author reviews state-of-the-art evidence of disturbed sleep in schizophrenia, starting from the relationship between sleep disturbances and clinical symptoms. First, the author presents studies demonstrating abnormalities in sleep architecture and sleep-oscillatory rhythms in schizophrenia and related psychotic disorders, with an emphasis on recent work demonstrating sleep spindles and slow-wave deficits in early-course and first-episode schizophrenia. Next, the author shows how these sleep abnormalities relate to the cognitive impairments in patients diagnosed with schizophrenia and point to dysfunctions in underlying thalamocortical circuits, Ca+ channel activity, and GABA-glutamate neurotransmission. Finally, the author discusses some of the next steps needed to further establish the role of altered sleep in schizophrenia, including the need to investigate sleep abnormalities across the psychotic spectrum and to establish their relationship with circadian disturbances, which in turn will contribute to the development of novel sleep-informed treatment interventions.
A simple method to determine the proper length of the gastric myotomy during peroral endoscopic myotomy for achalasia
Authors: Hugo Uchima, Juan Colán-Hernández, Ariadna Aguilar, Jenny Haya, Eugeni Domènech, Vicente Moreno, Ingrid Marín
Journal: Endoscopy (2021)

Peroral endoscopic myotomy (POEM) was first performed in 2008 by Inoue and since then has been used widely, with noninferiority to Heller's myotomy [1]. A critical step during POEM is ensuring an appropriate length of the gastric myotomy (2–2.5 cm), as a short myotomy can lead to a lack of response, and if too long, a higher incidence of moderate reflux esophagitis may occur without improving clinical efficacy [2] [3].
Spatial mapping of SARS-CoV-2 and H1N1 lung injury identifies differential transcriptional signatures
Authors: Camilla Margaroli, Paul Benson, Nirmal S. Sharma, Matthew C. Madison, Sarah W. Robison, Nitin Arora, Kathy Ton, Yan Liang, Liang Zhang, Rakesh P. Patel, Amit Gaggar
Journal: Cell Reports Medicine (2021)

Severe SARS-CoV-2 infection often leads to the development of acute respiratory distress syndrome (ARDS), with profound pulmonary patho-histological changes post-mortem. It is not clear whether ARDS from SARS-CoV-2 is similar to that observed in influenza H1N1, another common viral cause of lung injury. Here, we analyze specific ARDS regions of interest utilizing a spatial transcriptomic platform on autopsy-derived lung tissue from patients with SARS-CoV-2 (n = 3), H1N1 (n = 3), and a dual infected individual (n = 1). Enhanced gene signatures in alveolar epithelium, vascular tissue, and lung macrophages identify not only increased regional coagulopathy but also increased extracellular remodeling, alternative macrophage activation, and squamous metaplasia of type II pneumocytes in SARS-CoV-2. Both the H1N1 and dual-infected transcriptome demonstrated an enhanced antiviral response compared to SARS-CoV-2. Our results uncover regional transcriptional changes related to tissue damage/remodeling, altered cellular phenotype, and vascular injury active in SARS-CoV-2 and present therapeutic targets for COVID-19-related ARDS.
HSR21-052: Prediction of Readmission and Complications After Pituitary Adenoma Resection via the National Surgical Quality Improvement Program (NSQIP) Database
Authors: Joshua C. Hunsaker, Majid Khan, Serge Makarenko, James Evans, William T. Couldwell, Michael Karsy
Journal: Journal of the National Comprehensive Cancer Network (2021)

"HSR21-052: Prediction of Readmission and Complications After Pituitary Adenoma Resection via the National Surgical Quality Improvement Program (NSQIP) Database" published on 17 Mar 2021 by National Comprehensive Cancer Network.
P60.08 Impact of CD24 and CD47 Tumor Expression on Efficacy and Serum Cytokine Alteration with PD-1/L1 Inhibitors in Non-Small Cell Lung cancer.
Authors: Y. Ozawa, Y. Harutani, J. Oyanagi, E. Murakami, K. Sato, H. Akamatsu, A. Hayata, S. Teraoka, H. Ueda, Y. Kitamura, J. Fukuoka, N. Tokudome, M. Nakanishi, Y. Koh, N. Yamamoto
Journal: Journal of Thoracic Oncology (2021)
Oxidation‐Responsive, Tunable Growth Factor Delivery from Polyelectrolyte‐Coated Implants
Authors: John R. Martin, MayLin T. Howard, Sheryl Wang, Adam G. Berger, Paula T. Hammond
Journal: Advanced Healthcare Materials (2021)

Abstract Polyelectrolyte multilayer (PEM) coatings, constructed on the surfaces of tissue engineering scaffolds using layer‐by‐layer assembly (LbL), promote sustained release of therapeutic molecules and have enabled regeneration of large‐scale, pre‐clinical bone defects. However, these systems primarily rely on non‐specific hydrolysis of PEM components to foster drug release, and their pre‐determined drug delivery schedules potentially limit future translation into innately heterogeneous patient populations. To trigger therapeutic delivery directly in response to local environmental stimuli, an LbL‐compatible polycation solely degraded by cell‐generated reactive oxygen species (ROS) was synthesized. These thioketal‐based polymers were selectively cleaved by physiologic doses of ROS, stably incorporated into PEM films alongside growth factors, and facilitated tunable release of therapeutic bone morphogenetic protein‐2 (BMP‐2) upon oxidation. These coatings' sensitivity to oxidation was also dependent on the polyanions used in film construction, providing a simple method for enhancing ROS‐mediated protein delivery in vitro. Correspondingly, when implanted in critically‐sized rat calvarial defects, the most sensitive ROS‐responsive coatings generated a 50% increase in bone regeneration compared with less sensitive formulations and demonstrated a nearly threefold extension in BMP‐2 delivery half‐life over conventional hydrolytically‐sensitive coatings. These combined results highlight the potential of environmentally‐responsive PEM coatings as tunable drug delivery systems for regenerative medicine.
P84.02 A Phase II Trial of Alectinib-Refractory Non-Small-Cell Lung Cancer with EML4-ALK Fusion Genes; Okayama Lung Cancer Study Group 1405
Authors: T. Yokoyama, H. Yoshioka, D. Harada, T. Kozuki, H. Isozaki, A. Bessho, S. Hosokawa, I. Takata, N. Takigawa, K. Hotta, K. Kiura
Journal: Journal of Thoracic Oncology (2021)
Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PIMS-TS): Prospective, national surveillance, United Kingdom and Ireland, 2020
Authors: Jessica Flood, Joseph Shingleton, Emma Bennett, Brodie Walker, Zahin Amin-Chowdhury, Godwin Oligbu, Jacob Avis, Richard M. Lynn, Peter Davis, Tara Bharucha, Clare E Pain, Deepthi Jyothish, Elizabeth Whittaker, Buvana Dwarakanathan, Rachael Wood, Christopher Williams, Olivia Swann, Malcolm G Semple, Mary E Ramsay, Christine E Jones, Athimalaipet V Ramanan, Nick Gent, Shamez N Ladhani
Journal: The Lancet Regional Health - Europe (2021)

Paediatric Multisystem Inflammatory Syndrome temporally associated with SARS-CoV-2 (PIMS-TS), first identified in April 2020, shares features of both Kawasaki disease (KD) and toxic shock syndrome (TSS). The surveillance describes the epidemiology and clinical characteristics of PIMS-TS in the United Kingdom and Ireland. Public Health England initiated prospective national surveillance of PIMS-TS through the British Paediatric Surveillance Unit. Paediatricians were contacted monthly to report PIMS-TS, KD and TSS cases electronically and complete a detailed clinical questionnaire. Cases with symptom onset between 01 March and 15 June 2020 were included. There were 216 cases with features of PIMS-TS alone, 13 with features of both PIMS-TS and KD, 28 with features of PIMS-TS and TSS and 11 with features of PIMS-TS, KD and TSS, with differences in age, ethnicity, clinical presentation and disease severity between the phenotypic groups. There was a strong geographical and temporal association between SARS-CoV-2 infection rates and PIMS-TS cases. Of those tested, 14.8% (39/264) children had a positive SARS-CoV-2 RT-PCR, and 63.6% (75/118) were positive for SARS-CoV-2 antibodies. In total 44·0% (118/268) required intensive care, which was more common in cases with a TSS phenotype. Three of five children with cardiac arrest had TSS phenotype. Three children (1·1%) died. The strong association between SARS-CoV-2 infection and PIMS-TS emphasises the importance of maintaining low community infection rates to reduce the risk of this rare but severe complication in children and adolescents. Close follow-up will be important to monitor long-term complications in children with PIMS-TS. PHE.
Abstract 14463: A Novel Mouse Model of the Effect of Acute Kidney Injury on Neointima After Injury of an Artery
Authors: Yanpeng Diao, Yuanqing Lu, Mark S Segal
Journal: Circulation (2020)

Introduction and Hypothesis: Acute kidney injury (AKI), even if renal function returns to normal, is associated with an increased risk of cardiovascular disease. We have developed a novel, mouse model that allows investigation into the mechanism of this clinical scenario. We hypothesized that AKI, particular at a severe level, may result in a permanent change to the vasculature that would promote atherosclerotic lesions. Methods and Results: AKI was induced by clamping the bilateral renal vessels of male, C57/BL mice for 28-30 minutes. The creatinine (Cr) was measured two days later to determine the severity of the AKI. An increase in the Cr of at least three-fold, was defined as severe damage, corresponding to Kidney Disease Improving Global Outcomes (KDIGO) AKI Stage 3. If the Cr increased less than three times, this was defined as mild/moderate AKI. Ten weeks after AKI, the Cr was measured to determine if renal function returned to baseline and the femoral artery was injured by repeated introduction of a guidewire. After four weeks, the animals were sacrificed and the neointima lesions were analyzed. Immunohistochemistry for smooth muscle myosin heavy chain revealed that the neointima was mostly composed of smooth muscle cells. The re-endothelialization was almost complete, as determined by anti-CD31 staining. More interestingly, the narrowing rate of the injured artery in animals who suffered severe AKI was higher than in the mild/moderate AKI animals (53.2% vs 27.2%; P= 0.04). There is no difference between the sham-AKI animals and the mild/moderate AKI animals (34.9 % vs 27.2%, see picture). Conclusions: Severe AKI induces a permanent change to the vasculature and/or the immune cells that hastens the development of neointima even after renal function recovers. This work has implications for the development of human atherosclerosis in the clinical setting after AKI. Potential mechanisms for this increased propensity will be discussed.
Colon capsule endoscopy: the evidence is piling up
Authors: George Koulaouzidis, Alexander Robertson, Hagen Wenzek, Anastasios Koulaouzidis
Journal: Gut (2021)

We read with interest the multicentre comparison study by Cash et al on the diagnostic yield (DY) of colon capsule endoscopy (CCE) versus CT colonography (CTC) in a screening population.1 Out of 320 enrolled, data from 286 (89.4%) subjects were evaluated. CCE was superior to CTC in the detection of polyps ≥6 mm and non-inferior for polyps ≥10 mm. A recent meta-analysis2 of the use of CCE and CTC in patients with incomplete optical colonoscopy (OC) showed the DY of CTC at 10% (95% CI 7%–15%) and of CCE at 37% (95% CI 30%–43%) for any size polyp, suggesting the increased DY of CCE could outweigh its lower completion rate compared with the superiority of CTC there. Furthermore, a recent systematic review,3 including 2485 patients across 13 studies, confirmed that CCE is highly sensitive for clinically …
MA03.05 Hierarchy of Adverse-Prognosis Quality Markers after Curative-Intent Resection of Non-Small Cell Lung Cancer (NSCLC)
Authors: R. Osarogiagbon, Y. Lee, N. Faris, C. Fehnel, O. Akinbobola, M. Ray, C. Jones, M. Meadows-Taylor, A. Saulsberry, H. Patel, R. Eubanks, A. Halal, V. Sachdev, D. Talton, G. Valaulikar, B. Wolf, H. Wiggins, P. Levy, E. Robbins, M. Smeltzer
Journal: Journal of Thoracic Oncology (2021)
Abstract 16831: Effect of a Virtual Cardiac Rehabilitation Program on Functional Capacity and Risk Factor Modification in Veterans With Ischemic Heart Disease
Authors: Arash Harzand, Alexander A Vakili, Michelle Davis-Watts, Rene Nazar, Phyllis Wright, Cate G Parrish, Pratik Rout, Alaaeddin Alrohaibani, Amit J Shah
Journal: Circulation (2020)

Background: Cardiac rehabilitation (CR) is a comprehensive lifestyle change program proven to reduce cardiovascular disease (CVD) risk and improve quality of life in patients with ischemic heart disease but remains highly underutilized (&lt;20% of eligible patients) due to the inconvenience and cost of attending a facility-based program. We evaluated the efficacy of a home-based, virtual CR program using mobile health (mHealth) in veterans with coronary artery disease (CAD) on improving functional capacity, CVD risk factors, and depressive symptoms. Methods: We enrolled 196 Veterans with a qualifying CR diagnosis between May 2016 and April 2020. All participants underwent baseline functional evaluation with a 6-minute walk test (6MWT), followed by a 12-week home-based, virtual CR program delivered via the Movn smartphone app (Movn by Moving Analytics). The Movn app featured daily alerts to exercise, a digital diary to record activity and vital signs, and connectivity with a health coach who remotely monitored participants through an integrated dashboard and scheduled weekly phone visits. We compared the risk factor profile pre-intervention versus post-intervention with paired t-tests. Results: Among enrolled Veterans, the mean (SD) age was 61 (9) years, 95% were male, and 50% were black. A majority (63%) completed the full 12-week virtual CR program including an exit visit. Participants completed an average of 10.4 ± 1.9 (range 3–13) phone visits with the coach. There were concurrent improvements in 6MWT distance (443.9 vs. 481.9 meters; mean difference [MD], 38 meters; 95% CI, 26.6 – 50.8, P&lt;0.001), low-density lipoprotein cholesterol (80 vs. 69 mg/dL, MD, -10.9; 95% CI, -17.9 to -3.9, P=0.003), body mass index (31.1 vs 30.8; MD, -0.33; 95% CI, -0.60 to -0.06; P=0.001), and PHQ-9 depression scores (7.4 vs. 6; MD, -1.4, 95% CI, -2.4 to -0.44; P=0.005) among program completers. Conclusions: Among veterans with ischemic heart disease, a virtual CR program results in moderate improvements in functional capacity, CVD risk factors, and mood. The durability of these effects and whether virtual CR improves longer-term outcomes such as readmissions, survival, and cost remain to be determined.
DNA Damage Response Protein CHK2 Regulates Metabolism in Liver Cancer
Authors: Matteo Lulli, Laura Del Coco, Tommaso Mello, Caecilia Sukowati, Stefania Madiai, Laura Gragnani, Paolo Forte, Francesco Paolo Fanizzi, Antonio Mazzocca, Krista Rombouts, Andrea Galli, Vinicio Carloni
Journal: Cancer Research (2021)

Defective mitosis with chromosome missegregation can have a dramatic effect on genome integrity by causing DNA damage, activation of the DNA damage response (DDR), and chromosomal instability. Although this is an energy-dependent process, mechanisms linking DDR to cellular metabolism are unknown. Here we show that checkpoint kinase 2 (CHK2), a central effector of DDR, regulates cellular energy production by affecting glycolysis and mitochondrial functions. Patients with hepatocellular carcinoma (HCC) had increased CHK2 mRNA in blood, which was associated with elevated tricarboxylic acid cycle (TCA) metabolites. CHK2 controlled expression of succinate dehydrogenase (SDH) and intervened with mitochondrial functions. DNA damage and CHK2 promoted SDH activity marked by increased succinate oxidation through the TCA cycle; this was confirmed in a transgenic model of HCC with elevated DNA damage. Mitochondrial analysis identified CHK2-controlled expression of SDH as key in sustaining reactive oxygen species production. Cells with DNA damage and elevated CHK2 relied significantly on glycolysis for ATP production due to dysfunctional mitochondria, which was abolished by CHK2 knockdown. This represents a vulnerability created by the DNA damage response that could be exploited for development of new therapies. SIGNIFICANCE: This study uncovers a link between a central effector of DNA damage response, CHK2, and cellular metabolism, revealing potential therapeutic strategies for targeting hepatocellular carcinoma.
Government must produce long term plan for adult social care in England this year, says watchdog
Authors: Gareth Iacobucci
Journal: BMJ (2021)

Short term funding fixes and the failure to produce a long term vision for adult social care in England is hindering planning, innovation, and investment in the sector, the spending watchdog has concluded.

The National Audit Office (NAO) also warned that current accountability and supervision of the care system were ineffective for overseeing the market, in a report published on 25 March.1

The Department of Health and Social Care has increased its focus on adult social care in response to covid-19, the NAO found, but it has not fulfilled previous commitments to tackle recruitment and retention challenges for the 1.5 million people who work …
Nrf2 Is a Critical Mediator of CD4 T Cell-Induced Acute Graft-Versus-Host Disease
Authors: Jennifer Tsai, Enrico Velardi, Yusuke Shono, Kimon Argyropoulos, Odette M. Smith, Amina Lazrak, Chen Liu, George F Murphy, Ya-Yuan Fu, Alan M. Hanash, Robert R. Jenq, Jarrod A Dudakov, Marcel R.M. van den Brink
Journal: Blood (2017)