tbuckley/cabot-search huggingface dataset:
The influence of romantic relationships on mental wellbeing for people who experience psychosis: A systematic review
Authors: Rebecca White, Gillian Haddock, Carolina Campodonico, Maria Haarmans, Filippo Varese
Journal: Clinical Psychology Review (2021)

Whilst it is generally accepted that supportive relationships facilitate recovery from psychosis, much less is known about the role of romantic relationships in people with psychosis. This review aimed to synthesise quantitative literature regarding the impact of romantic relationships on the mental health and general wellbeing of people who experience psychosis. A systematic review of electronic databases (PsychINFO, PubMed, Web of Science) was carried out using search terms relating to psychosis and romantic relationships. Papers were selected for inclusion by independent reviewers. Quality assessment was completed and a narrative synthesis produced. Fifty-eight studies reporting the association between romantic relationships and psychotic symptoms, depression, posttraumatic stress disorder, suicidality, quality of life, satisfaction with life and self-esteem were included. Results were mixed but indicated having a romantic partner may be associated with reduced positive and negative symptoms of psychosis, but increased depressive symptoms. Tentative explanations for these findings, such as functioning prior to onset of psychosis, social support and relationship quality are explored. Findings highlight the importance of this often-overlooked area in clinical practice. Studies with robust design, which specifically aim to understand the relationship between romantic relationships and wellbeing for people who experience psychosis are needed.
P18.05 Immunotherapy Beyond First-Line in NSCLC, Still An Option
Authors: A. Modrego, H. Bote, E. Jimenez-Aguilar, S. Ponce-Aix, J. Zugazagoitia, J. Baena, J.M. Mazarico, J.A. Nuñez, L.C. Iglesias, L. Paz-Ares
Journal: Journal of Thoracic Oncology (2021)
Meta-analysis of genome-wide DNA methylation identifies shared associations across neurodegenerative disorders
Authors: Marta F. Nabais, Simon M. Laws, Tian Lin, Costanza L. Vallerga, Nicola J. Armstrong, Ian P. Blair, John B. Kwok, Karen A. Mather, George D. Mellick, Perminder S. Sachdev, Leanne Wallace, Anjali K. Henders, Ramona A. J. Zwamborn, Paul J. Hop, Katie Lunnon, Ehsan Pishva, Janou A. Y. Roubroeks, Hilkka Soininen, Magda Tsolaki, Patrizia Mecocci, Simon Lovestone, Iwona Kłoszewska, Bruno Vellas, Sarah Furlong, Fleur C. Garton, Robert D. Henderson, Susan Mathers, Pamela A. McCombe, Merrilee Needham, Shyuan T. Ngo, Garth Nicholson, Roger Pamphlett, Dominic B. Rowe, Frederik J. Steyn, Kelly L. Williams, Tim J. Anderson, Steven R. Bentley, John Dalrymple-Alford, Javed Fowder, Jacob Gratten, Glenda Halliday, Ian B. Hickie, Martin Kennedy, Simon J. G. Lewis, Grant W. Montgomery, John Pearson, Toni L. Pitcher, Peter Silburn, Futao Zhang, Peter M. Visscher, Jian Yang, Anna J. Stevenson, Robert F. Hillary, Riccardo E. Marioni, Sarah E. Harris, Ian J. Deary, Ashley R. Jones, Aleksey Shatunov, Alfredo Iacoangeli, Wouter van Rheenen, Leonard H. van den Berg, Pamela J. Shaw, Cristopher E. Shaw, Karen E. Morrison, Ammar Al-Chalabi, Jan H. Veldink, Eilis Hannon, Jonathan Mill, Naomi R. Wray, Allan F. McRae
Journal: Genome biology (2021)

Abstract Background People with neurodegenerative disorders show diverse clinical syndromes, genetic heterogeneity, and distinct brain pathological changes, but studies report overlap between these features. DNA methylation (DNAm) provides a way to explore this overlap and heterogeneity as it is determined by the combined effects of genetic variation and the environment. In this study, we aim to identify shared blood DNAm differences between controls and people with Alzheimer’s disease, amyotrophic lateral sclerosis, and Parkinson’s disease. Results We use a mixed-linear model method (MOMENT) that accounts for the effect of (un)known confounders, to test for the association of each DNAm site with each disorder. While only three probes are found to be genome-wide significant in each MOMENT association analysis of amyotrophic lateral sclerosis and Parkinson’s disease (and none with Alzheimer’s disease), a fixed-effects meta-analysis of the three disorders results in 12 genome-wide significant differentially methylated positions. Predicted immune cell-type proportions are disrupted across all neurodegenerative disorders. Protein inflammatory markers are correlated with profile sum-scores derived from disease-associated immune cell-type proportions in a healthy aging cohort. In contrast, they are not correlated with MOMENT DNAm-derived profile sum-scores, calculated using effect sizes of the 12 differentially methylated positions as weights. Conclusions We identify shared differentially methylated positions in whole blood between neurodegenerative disorders that point to shared pathogenic mechanisms. These shared differentially methylated positions may reflect causes or consequences of disease, but they are unlikely to reflect cell-type proportion differences.
Cellular senescence in hepatocellular carcinoma induced by a long non-coding RNA-encoded peptide PINT87aa by blocking FOXM1-mediated <i>PHB2</i>
Authors: Xiaohong Xiang, Yunong Fu, Kun Zhao, Runchen Miao, Xing Zhang, Xiaohua Ma, Chang Liu, Nu Zhang, Kai Qu
Journal: Theranostics (2021)

Rationale: Recently, long non-coding RNAs (lncRNAs), known to be involved in human cancer progression, have been shown to encode peptides with biological functions, but the role of lncRNA-encoded peptides in cellular senescence is largely unexplored. We previously reported the tumor-suppressive role of PINT87aa, a peptide encoded by the long intergenic non-protein coding RNA, p53 induced transcript (LINC-PINT). Here, we investigated PINT87aa's role in hepatocellular carcinoma (HCC) cellular senescence. Methods: We examined PINT87aa and truncated PINT87aa functions in vitro by monitoring cell proliferation and performed flow cytometry, senescence-associated β-galactosidase staining, JC-1 staining indicative of mitochondrial membrane potential, the ratio of the overlapping area of light chain 3 beta (LC3B) and mitochondrial probes and the ratio of lysosomal associated membrane protein 1 (LAMP1) overlapping with cytochrome c oxidase subunit 4I1 (COXIV) denoting mitophagy. PINT87aa and truncated PINT87aa functions in vivo were verified by subcutaneously transplanted tumors in nude mice. The possible binding between PINT87aa and forkhead box M1 (FOXM1) was predicted through structural analysis and verified by co-immunoprecipitation and immunofluorescence co-localization. Rescue experiments were performed in vivo and in vitro following FOXM1 overexpression. Further, chromatin immunoprecipitation, polymerase chain reaction, and dual-luciferase reporter gene assay were conducted to validate FOXM1 binding to the prohibitin 2 (PHB2) promoter. Results: PINT87aa was significantly increased in the hydrogen peroxide-induced HCC cell senescence model. Overexpression of PINT87aa induced growth inhibition, cellular senescence, and decreased mitophagy in vitro and in vivo. In contrast, FOXM1 gain-of-function could partially reduce the proportion of senescent HCC cells and enhance mitophagy. PINT87aa overexpression did not affect the expression of FOXM1 itself but reduced that of its target genes involved in cell cycle and proliferation, especially PHB2, which was involved in mitophagy and transcribed by FOXM1. Structural analysis indicated that PINT87aa could bind to the DNA-binding domain of FOXM1, which was confirmed by co-immunoprecipitation and immunofluorescence co-localization. Furthermore, we demonstrated that the 2 to 39 amino acid truncated form of the peptide exerted effects similarly to the full form. Conclusion: Our study established the role of PINT87aa as a novel biomarker and a key regulator of cellular senescence in HCC and identified PINT87aa as a potential therapeutic target for HCC.
Running after ghosts: are dead bacteria the dark matter of the human gut microbiota?
Authors: Sara Bellali, Jean-Christophe Lagier, Matthieu Million, Hussein Anani, Gabriel Haddad, Rania Francis, Edmond Kuete Yimagou, Saber Khelaifia, Anthony Levasseur, Didier Raoult, Jacques Bou Khalil
Journal: Gut Microbes (2021)

The human gut microbiota has been explored by a wide range of culture-dependent and culture-independent methods, revealing that many microbes remain uncharacterized and uncultured. In this work, we aimed to confirm the hypothesis that some of the species present in the human gut microbiota remain uncultured not because of culture limitations, but because all members of such species are dead before reaching the end of the gastro-intestinal tract.We evaluate this phenomenon by studying the microbial viability and culturability of the human gut microbiota from the fresh fecal materials of eight healthy adults. For the first time, we applied fluorescence-activated cell sorting (FACS) combined with 16S metagenomics analysis and microbial culturomics.We identified a total of 1,020 bacterial OTUs and 495 bacterial isolates through metagenomics and culturomics, respectively. Among the FACS metagenomics results, only 735 bacterial OTUs were alive, comprising on average 42% of known species and 87% of relative abundance per individual. The remaining uncultured bacteria were rare, dead, or injured.Our strategy allowed us to shed light on the dark matter of the human gut microbiota and revealed that both metagenomics and culturomics approaches are needed for greater insight into the diversity and richness of bacteria in the human gut microbiota. Further work on culture is needed to enhance the repertoire of cultured gut bacteria by targeting low abundance bacteria and optimizing anaerobic sample conditioning and processing to preserve the viability of bacteria.
Third-line therapy for chronic myeloid leukemia: current status and future directions
Authors: Jorge Cortes, Fabian Lang
Journal: Journal of Hematology & Oncology (2021)

Abstract Chronic myeloid leukemia (CML) is driven by the BCR-ABL1 fusion protein, formed by a translocation between chromosomes 9 and 22 that creates the Philadelphia chromosome. The BCR-ABL1 fusion protein is an optimal target for tyrosine kinase inhibitors (TKIs) that aim for the adenosine triphosphate (ATP) binding site of ABL1. While these drugs have greatly improved the prognosis for CML, many patients ultimately fail treatment, some requiring multiple lines of TKI therapy. Mutations can occur in the ATP binding site of ABL1, causing resistance by preventing the binding of many of these drugs and leaving patients with limited treatment options. The approved TKIs are also associated with adverse effects that may lead to treatment discontinuation in some patients. Efficacy decreases with each progressive line of therapy; data suggest little clinical benefit of treatment with a third-line (3L), second-generation tyrosine kinase inhibitor (2GTKI) after failure of a first-generation TKI and a 2GTKI. Novel treatment options are needed for the patient population that requires treatment in the 3L setting and beyond. This review highlights the need for clear guidelines and new therapies for patients requiring 3L treatment and beyond.
Safety of Neoadjuvant Chemoradiotherapy Followed by Surgery for Patients With Locally Advanced Esophageal Squamous Cell Carcinoma
Authors: Fernando A. M. Herbella, Marco G. Patti
Journal: JAMA Surgery (2021)

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YBX1 is required for maintaining myeloid leukemia cell survival by regulating <i>BCL2</i> stability in an m6A-dependent manner
Authors: Mengdie Feng, Xueqin Xie, Guoqiang Han, Tiantian Zhang, Yashu Li, Yicun Li, Rong Yin, Qifan Wang, Tong Zhang, Peipei Wang, Jin Hu, Ying Cheng, Zhuying Gao, Jing Wang, Jiwei Chang, Manman Cui, Kexin Gao, Jihua Chai, Weidong Liu, Chengli Guo, Shaoguang Li, Lingbo Liu, Fuling Zhou, Jianjun Chen, Haojian Zhang
Journal: Blood (2021)
Author Correction: A novel digital approach to describe real world outcomes among patients with constipation
Authors: Allison Shapiro, Benjamin Bradshaw, Sabine Landes, Petra Kammann, Beatrice Bois De Fer, Wei-Nchih Lee, Robert Lange
Journal: npj Digital Medicine (2021)

A Correction to this paper has been published: https://doi.org/10.1038/s41746-021-00434-3
P76.36 A Phase 2 Study of Anlotinib Combined with Pemetrexed-Platinum (PP) as Second-Line Treatment in EGFR-Positive Non-Small Cell Lung Cancer (NSCLC)
Authors: J. Li, J. Ge, Y. Tian, Y. Yang, M. Zheng, P. Yu, W. Yao
Journal: Journal of Thoracic Oncology (2021)
Abstract S05-02: Plant viral nanoparticle-based adjuvants for cancer immunotherapy and COVID-19 vaccines
Authors: Nicole F. Steinmetz, Jonathan K. Pokorski, Steven N. Fiering, P. Jack Hoopes, Sourabh Shukla, Oscar A. Ortega-Rivera, Steven King, Cyril J. Empig
Journal: Clinical Cancer Research (2021)

Abstract Plant virus nanoparticles are recognized as a platform technology for potential applications in nanomedicine. While non-infectious toward mammals, many plant virus nanoparticles are recognized by the immune system and act as potent adjuvants, both in the classical setting of vaccination and cancer immunotherapy. In the context of cancer immunotherapy, we have demonstrated potent efficacy of plant virus, particularly cowpea mosaic virus (CPMV) when applied intratumorally; CPMV signals through and activates multiple toll-like receptors, which primes a potent innate immune activation leading to reprogramming of the tumor microenvironment from an immunosuppressed to immune-activated state. Data in mouse models of melanoma, colon cancer, ovarian cancer, glioma, and breast cancer demonstrate potent efficacy through priming of the innate immune system leading to adaptive and systemic anti-tumor immunity and most importantly immune memory. Efficacy was also replicated in canine patients with melanoma. Given the promise of the plant virus nanotechnology as an adjuvant for cancer immunotherapy, we also have begun to utilize the technology as a vaccination platform for the generation of COVID-19 vaccine candidates. We formulated multivalent COVID-19 vaccine candidates using plant virus nanoparticles displaying SARS-CoV-2 S protein peptide B cell epitopes. The plant virus nanoparticle confers efficient lymphatic trafficking and targeting of antigen-presenting cells; the adjuvant properties of the nanotechnology lead to robust antibody levels against the target, S protein. While other vaccine candidates have advanced through clinical testing, our approach has unique advantages: The high thermal and pH stability of the plant virus nanotechnology alleviates cold chain requirements; further, the stability of the platform technology enables its integration into vaccine delivery devices such as microneedle patches that can be shipped globally and be self-administered. In this presentation, we will discuss our data on the cancer immunotherapy and highlight the potential to pivot the technology for infectious disease vaccines with unique attributes. This work was funded in part through grants from the National Cancer Institute (U01CA218292) and National Science Foundation (RAPID CMMI-2027668). Citation Format: Nicole F. Steinmetz, Jonathan K. Pokorski, Steven N. Fiering, P. Jack Hoopes, Sourabh Shukla, Oscar A. Ortega-Rivera, Steven King, Cyril J. Empig. Plant viral nanoparticle-based adjuvants for cancer immunotherapy and COVID-19 vaccines [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2021 Feb 3-5. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(6_Suppl):Abstract nr S05-02.
Durable or Biodegradable Polymer Stent Coatings
Authors: Robert A. Byrne, Colm G. Hanratty
Journal: Circulation (2021)

It is an increasingly widely held belief that a substantial proportion of clinical trials in cardiovascular medicine are not fit for purpose. 1 Frequently, patients enrolled do not well represent those encountered in routine practice.Trials that investigate medications or medical devices that have already received regulatory approval often take too long to set up, are too cumbersome to conduct, and are too costly. 2This can lead to unwanted effects on clinical practice, steering clinical management by the results of strictly controlled trials in highly selected patients.It also means that large-scale trials may rely on industry funding, which may affect the choice of clinical question that is asked. 3hange is in the air and is gathering pace.Ongoing initiatives such as the sensible clinical trials initiative aim to draw the attention of academic and regulatory authorities to the matter and propose slimmed down requirements for trial design and conduct. 4The key advantages of randomized trials are not only that measured and unmeasured confounding factors tend to be well balanced between treatment groups but also measurement errors and deviations from standard procedures or processes.In addition, increasing availability of large-scale, granular data collection within collaborative networks or national outcome registries facilitates the conduct of pragmatic randomized clinical trials in an efficient manner. 5n the current issue of Circulation, Kim and colleagues 6 report results from a large-scale, investigator-initiated randomized trial of patients undergoing percutaneous coronary intervention comparing both antithrombotic and stent treatment strategies in 3413 patients with acute coronary syndrome.HOST-REDUCE-POLY-TECH-ACS (Harmonizing Optimal Strategy for Treatment of Coronary Artery Diseases Trial: Comparison of Reduction of Prasugrel Dose & Polymer Technology in ACS Patients) makes use of a large network of collaborating investigators enrolling patients at 35 sites in Korea and was funded partly through the contribution of a variety of industry sponsors.The trial had a 2×2 factorial design comparing outcomes of patients randomly allocated to less potent antithrombotic therapy versus standard antithrombotic therapy and implantation of durable polymer (experimental device) versus biodegradable polymer drug-eluting stents (DES; control device). 7he results of the antithrombotic treatment comparison have already been published. 8The data showed that a prasugrel-based dose deescalation strategy 1 month after stenting reduced the overall risk of adverse clinical outcomesas measured by the composite of all-cause death, nonfatal myocardial infarction, stent thrombosis, repeat revascularization, stroke, and bleeding events of grade 2 or higher according to Bleeding Academic Research Consortium criteria-at 1 year, mainly because of a reduction in bleeding events.The article in the current issue of Circulation reports results from the stent comparison. 6 Durable or Biodegradable Polymer Stent Coatings
How covid-19 has exacerbated LGBTQ+ health inequalities
Authors: Callum Phillips
Journal: BMJ (2021)

How covid-19 has exacerbated LGBTQ+ health inequalitiesDespite inadequate monitoring of health in the LGBTQ+ community, the data we have suggest a disproportionate effect of the covid pandemic and its control measures, writes Callum Phillips Callum Phillips BMJ Clegg scholar "Wherever you meaningfully look for LGBTQ+ health inequalities, you find them," says Michael Brady, national adviser for LGBT health at NHS England."And yet we're still not properly looking.
Left Ventricular Longitudinal Strain in Characterization and Outcome Assessment of Mixed Aortic Valve Disease Phenotypes
Authors: Yoshihito Saijo, Nicolas Isaza, Julijana Z. Conic, Milind Y. Desai, Douglas Johnston, Eric E. Roselli, Richard A. Grimm, Lars G. Svensson, Samir Kapadia, Nancy A. Obuchowski, Brian P. Griffin, Zoran B. Popović
Journal: JACC. Cardiovascular imaging (2021)
P86.12 Cardiac Safety Assessment of Lazertinib in Patients with EGFR Mutation-Positive Advanced Non-Small Cell Lung Cancer
Authors: N. Haddish-Berhane, B.C. Cho, M. Ahn, J. Han, S. Kim, K.H. Lee, E.K. Cho, J. Mehta, J. Xie, S.M. Shreeve, R.E. Knoblauch, J. Freeman, A. Roshak, S.B. Jang, H. Lee, S. Kang, K.B. Kim, S. Oh
Journal: Journal of Thoracic Oncology (2021)
Bacterial pulmonary superinfections are associated with longer duration of ventilation in critically ill COVID-19 patients
Authors: Philipp K. Buehler, Annelies S. Zinkernagel, Daniel A. Hofmaenner, Pedro David Wendel Garcia, Claudio T. Acevedo, Alejandro Gómez-Mejia, Srikanth Mairpady Shambat, Federica Andreoni, Martina A. Maibach, Jan Bartussek, Matthias P. Hilty, Pascal M. Frey, Reto A. Schuepbach, Silvio D. Brugger
Journal: Cell Reports Medicine (2021)
P70.02 Clinicopathologic Characteristics and Outcomes of East Asian Patients With Non-Small-Cell Lung Cancer and FLT3 Mutations
Authors: X. Liang, C. Xu, W. Wang, D. Wang, Y. Zhu, W. Zhuang, M. Fang, T. Lv, Y. Song
Journal: Journal of Thoracic Oncology (2021)
Rubisco Adaptation Is More Limited by Phylogenetic Constraint Than by Catalytic Trade-off
Authors: Jacques W Bouvier, David M Emms, Timothy Rhodes, Jai S Bolton, Amelia Brasnett, Alice Eddershaw, Jochem R Nielsen, Anastasia Unitt, Spencer M Whitney, Steven Kelly
Journal: Molecular Biology and Evolution (2021)

Rubisco assimilates CO2 to form the sugars that fuel life on earth. Correlations between rubisco kinetic traits across species have led to the proposition that rubisco adaptation is highly constrained by catalytic trade-offs. However, these analyses did not consider the phylogenetic context of the enzymes that were analyzed. Thus, it is possible that the correlations observed were an artefact of the presence of phylogenetic signal in rubisco kinetics and the phylogenetic relationship between the species that were sampled. Here, we conducted a phylogenetically resolved analysis of rubisco kinetics and show that there is a significant phylogenetic signal in rubisco kinetic traits. We re-evaluated the extent of catalytic trade-offs accounting for this phylogenetic signal and found that all were attenuated. Following phylogenetic correction, the largest catalytic trade-offs were observed between the Michaelis constant for CO2 and carboxylase turnover (∼21-37%), and between the Michaelis constants for CO2 and O2 (∼9-19%), respectively. All other catalytic trade-offs were substantially attenuated such that they were marginal (<9%) or non-significant. This phylogenetically resolved analysis of rubisco kinetic evolution also identified kinetic changes that occur concomitant with the evolution of C4 photosynthesis. Finally, we show that phylogenetic constraints have played a larger role than catalytic trade-offs in limiting the evolution of rubisco kinetics. Thus, although there is strong evidence for some catalytic trade-offs, rubisco adaptation has been more limited by phylogenetic constraint than by the combined action of all catalytic trade-offs.