tbuckley/cabot-search huggingface dataset:
Failure to prescribe: UK workers with occupational long covid-19 have been ignored
Authors: Andrew Watterson
Journal: BMJ (2021)

Workers with long covid will raise major questions and challenges for UK governments.12 In 3872 covid-19 “workplace” outbreaks and 4253 education outbreaks, occupational morbidity has been seriously underestimated.3 If all employee covid-19 cases in these outbreaks were listed as occupational, then Industrial Injuries Disablement Board benefits would be triggered, assuming the UK Industrial Injuries Advisory Council (IIAC) so advised. Yet covid-19 is still not recognised as a prescribed industrial disease in the UK.

By contrast, …
先天性拘縮性くも指趾症(Beals症候群)に僧帽弁逸脱症・感染性心内膜炎を合併した一例
Authors: 千田啓介, 麻生真一, 馬渡栄一郎, 鈴木智裕, 櫻井俊平, 高井文恵, 鈴木博之, 橋本昌紀, 大澤肇, 藤松利浩, 池田宇一
Journal: Circulation (2009)
Prevalence and Correlates of Cannabis Use and Cannabis Use Disorder Among U.S. Veterans: Results From the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III)
Authors: Kendall C. Browne, Malki Stohl, Kipling M. Bohnert, Andrew J. Saxon, David S. Fink, Mark Olfson, Magdalena Cerda, Scott Sherman, Jaimie L. Gradus, Silvia S. Martins, Deborah S. Hasin
Journal: American Journal of Psychiatry (2021)

The authors sought to estimate the prevalence of past-12-month and lifetime cannabis use and cannabis use disorder among U.S. veterans; to describe demographic, substance use disorder, and psychiatric disorder correlates of nonmedical cannabis use and cannabis use disorder; and to explore differences in cannabis use and cannabis use disorder prevalence among veterans in states with and without medical marijuana laws.Participants were 3,119 respondents in the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III) who identified as U.S. veterans. Weighted prevalences were calculated. Logistic regression analyses tested associations of nonmedical cannabis use and cannabis use disorder with demographic and clinical correlates and examined whether prevalence differed by state legalization status.The prevalences of any past-12-month cannabis use and cannabis use disorder were 7.3% and 1.8%, respectively. Lifetime prevalences were 32.5% and 5.7%, respectively. Past-12-month and lifetime cannabis use disorder prevalence estimates among nonmedical cannabis users were 24.4% and 17.4%, respectively. Sociodemographic correlates of nonmedical cannabis use and use disorder included younger age, male gender, being unmarried, lower income, and residing in a state with medical marijuana laws. Nonmedical cannabis use and use disorder were associated with most psychiatric and substance use disorders examined.Among veterans, the odds of nonmedical cannabis use and use disorder were elevated among vulnerable subgroups, including those with lower income or psychiatric disorders and among survey participants residing in states with medical marijuana laws. The study findings highlight the need for clinical attention (e.g., screening, assessment) and ongoing monitoring among veterans in the context of increasing legalization of cannabis.
The rising preterm birth rate in China: a cause for concern
Authors: Jun Zhang, Kun Sun, Yongjun Zhang
Journal: The Lancet Global Health (2021)

Globally, one in ten babies are born preterm, and the preterm birth rate has been increasing.1 The second highest number of preterm births are reported in China, with more than 1 million babies born preterm every year. Our meta-analysis showed an increase in preterm rate by 1·1% per year from 1990 to 2016.2 In the Lancet Global Health, Kui Deng and colleagues3 estimated an increase of 1·3% per year from 2012 to 2018. Their data also suggested that the increasing preterm birth rate might have accelerated after the introduction of the universal two child policy in China.
Quantification of Translocation-Specific ctDNA Provides an Integrating Parameter for Early Assessment of Treatment Response and Risk Stratification in Ewing Sarcoma
Authors: Manuela Krumbholz, Johanna Eiblwieser, Andreas Ranft, Jakob Zierk, Christian Schmidkonz, Adrian M Stütz, Peter Peneder, Eleni M. Tomazou, Abbas Agaimy, Tobias Bäuerle, Wolfgang Hartmann, Uta Dirksen, Markus Metzler
Journal: Clinical Cancer Research (2021)

Abstract Purpose: We evaluated the predictive and prognostic value of circulating tumor DNA (ctDNA) in patients with Ewing sarcoma (EWS) treated in the EWING2008 trial. Experimental Design: Plasma samples from 102 patients with EWS enrolled in the EWING2008 trial were obtained before and during induction chemotherapy. Genomic EWSR1 fusion sequence spanning primers and probes were used for highly specific and sensitive quantification of the levels of ctDNA by digital droplet PCR. ctDNA levels were correlated to established clinical risk factors and outcome parameters. Results: Pretreatment ctDNA copy numbers were correlated with event-free and overall survival. The reduction in ctDNA levels below the detection limit was observed in most cases after only two blocks of vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) induction chemotherapy. The persistence of ctDNA after two VIDE blocks was a strong predictor of poor outcomes. ctDNA levels correlated well with most established clinical risk factors; an inverse correlation was found only for the histologic response to induction therapy. ctDNA levels did not provide simple representations of tumor volume, but integrated information from various tumor characteristics represented an independent EWS tumor marker with predictive and prognostic value. Conclusions: ctDNA copy number in the plasma of patients with EWS is a quantifiable parameter for early risk stratification and can be used as a dynamic noninvasive biomarker for early prediction of treatment response and outcome of patients.
circ-EIF6 encodes EIF6-224aa to promote TNBC progression via stabilizing MYH9 and activating the Wnt/beta-catenin pathway
Authors: Yaming Li, Zekun Wang, Peng Su, Yiran Liang, Zheng Li, Hanwen Zhang, Xiaojin Song, Dianwen Han, Xiaolong Wang, Ying Liu, Jingwen Yang, Bing Chen, Lijuan Wang, Wenjing Zhao, Qifeng Yang
Journal: Molecular Therapy (2021)

The protein-coding ability of circular RNAs (circRNAs) has recently been a hot topic, but the expression and roles of protein-coding circRNAs in triple-negative breast cancer (TNBC) remain uncertain. By intersecting circRNA sequencing data from clinical samples and cell lines, we identified a circRNA, termed circ-EIF6, which predicted a poorer prognosis and correlated with clinicopathological characteristics in a cohort of TNBC patients. Functionally, we showed that circ-EIF6 promoted the proliferation and metastasis of TNBC cells in vitro and in vivo. Mechanistically, we found that circ-EIF6 contains a 675-nucleotide (nt) open reading frame (ORF) and that the -150-bp sequence from ATG functioned as an internal ribosome entry site (IRES), which is required for translation initiation in 5' cap-independent coding RNAs. circ-EIF6 encodes a novel peptide, termed EIF6-224 amino acid (aa), which is responsible for the oncogenic effects of circ-EIF6. The endogenous expression of EIF6-224aa was further examined in TNBC cells and tissues by specific antibody. Moreover, EIF6-224aa directly interacted with MYH9, an oncogene in breast cancer, and decreased MYH9 degradation by inhibiting the ubiquitin-proteasome pathway and subsequently activating the Wnt/beta-catenin pathway. Our study provided novel insights into the roles of protein-coding circRNAs and supported circ-EIF6/EIF6-224aa as a novel promising prognostic and therapeutic target for tailored therapy in TNBC patients.
Hepatitis E virus infection activates NOD‐like receptor family pyrin domain‐containing 3 inflammasome antagonizing interferon response but therapeutically targetable
Authors: Yang Li, Peifa Yu, Amy L. Kessler, Jingyi Shu, Xiaoyan Liu, Zhaochao Liang, Jiaye Liu, Yunlong Li, Pengfei Li, Ling Wang, Yining Wang, Zhongren Ma, Aixia Liu, Ling Wang, Marco J. Bruno, Robert A. de Man, Maikel P. Peppelenbosch, Sonja I. Buschow, Lin Wang, Yijin Wang, Qiuwei Pan
Journal: Hepatology (2021)

Abstract Background and Aims HEV infection is the most common cause of liver inflammation, but the pathogenic mechanisms remain largely unclear. We aim to explore whether HEV infection activates inflammasomes, crosstalk with antiviral interferon response, and the potential of therapeutic targeting. Approach and Results We measured IL‐1β secretion, the hallmark of inflammasome activation, in serum of HEV‐infected patients and rabbits, and in cultured macrophage cell lines and primary monocyte‐derived macrophages. We found that genotypes 3 and 4 HEV infection in rabbits elevated IL‐1β production. A profound increase of IL‐1β secretion was further observed in HEV‐infected patients (1,733 ± 1,234 pg/mL; n = 70) compared to healthy persons (731 ± 701 pg/mL; n = 70). Given that macrophages are the drivers of inflammatory response, we found that inoculation with infectious HEV particles robustly triggered NOD‐like receptor family pyrin domain‐containing 3 (NLRP3) inflammasome activation in primary macrophages and macrophage cell lines. We further revealed that the ORF2 capsid protein and the formed integral viral particles are responsible for activating inflammasome response. We also identified NF‐κB signaling activation as a key upstream event of HEV‐induced NLRP3 inflammasome response. Interestingly, inflammasome activation antagonizes interferon response to facilitate viral replication in macrophages. Pharmacological inhibitors and clinically used steroids can effectively target inflammasome activation. Combining steroids with ribavirin simultaneously inhibits HEV and inflammasome response without cross‐interference. Conclusions HEV infection strongly activates NLRP3 inflammasome activation in macrophages, which regulates host innate defense and pathogenesis. Therapeutic targeting of NLRP3, in particular when combined with antiviral agents, represents a viable option for treating severe HEV infection.
Immunotherapy combinations overcome resistance to bispecific T cell engager treatment in T cell–cold solid tumors
Authors: Brian Belmontes, Deepali V. Sawant, Wendy Zhong, Hong Tan, Anupurna Kaul, Famke Aeffner, Sarah A. O’Brien, Matthew Chun, Rajkumar Noubade, Jason Eng, Hayley Ma, Markus Muenz, Peng Li, Benjamin M. Alba, Melissa Thomas, Kevin Cook, Xiaoting Wang, Jason DeVoss, Jackson G. Egen, Olivier Nolan-Stevaux
Journal: Science Translational Medicine (2021)

Therapeutic approaches are needed to promote T cell-mediated destruction of poorly immunogenic, "cold" tumors typically associated with minimal response to immune checkpoint blockade (ICB) therapy. Bispecific T cell engager (BiTE) molecules induce redirected lysis of cancer cells by polyclonal T cells and have demonstrated promising clinical activity against solid tumors in some patients. However, little is understood about the key factors that govern clinical responses to these therapies. Using an immunocompetent mouse model expressing a humanized CD3ε chain (huCD3e mice) and BiTE molecules directed against mouse CD19, mouse CLDN18.2, or human EPCAM antigens, we investigated the pharmacokinetic and pharmacodynamic parameters and immune correlates associated with BiTE efficacy across multiple syngeneic solid-tumor models. These studies demonstrated that pretreatment tumor-associated T cell density is a critical determinant of response to BiTE therapy, identified CD8+ T cells as important targets and mediators of BiTE activity, and revealed an antagonistic role for CD4+ T cells in BiTE efficacy. We also identified therapeutic combinations, including ICB and 4-1BB agonism, that synergized with BiTE treatment in poorly T cell-infiltrated, immunotherapy-refractory tumors. In these models, BiTE efficacy was dependent on local expansion of tumor-associated CD8+ T cells, rather than their recruitment from circulation. Our findings highlight the relative contributions of baseline T cell infiltration, local T cell proliferation, and peripheral T cell trafficking for BiTE molecule-mediated efficacy, identify combination strategies capable of overcoming resistance to BiTE therapy, and have clinical relevance for the development of BiTE and other T cell engager therapies.
Establishing the exposure–outcome relation between airborne particulate matter and children’s health
Authors: Renyi Zhang, Natalie M Johnson, Yixin Li
Journal: Thorax (2021)

With increasing urbanisation, industrialisation and economic growth worldwide, air pollution has emerged as one of the greatest global public health epidemics in the 21st century. The impacts of air pollution on human health are enormous. Globally, nine in ten people breathe air containing high levels of pollutants, and one in nine of the deaths are caused by exposure to air pollution, reaching an annual premature mortality of over seven million.1 Air pollutants comprise a complex mixture of gases and particulate matter (PM), which are directly emitted from natural and anthropogenic sources or are formed in air via a multitude of chemical processes.2 In particular, fine PM (diameter smaller than 2.5 µm or PM2.5) has been unequivocally linked to various adverse human health effects, ranging from aggravated allergies to the development of chronic diseases, to premature death.3 Exposure of vulnerable individuals to air pollution is especially worrisome, such as pregnant women and children.4 5 The morbidity and mortality associated with air pollution for children are relevant to both prenatal and postnatal exposures. For example, epidemiological and animal model studies have revealed that maternal exposure to fine PM results in adverse birth outcomes and postnatal health conditions.5 Specifically, animal model experiments employing ultrafine particles (diameter smaller than 0.1 µm or UFP) have shown that prenatal exposure predisposes offspring to long-term metabolic syndrome and pulmonary immunosuppression, with profound implications for respiratory infection risks.6 7

In this issue, Fang …
The location-based resect and discard strategy for diminutive colorectal polyps: a prospective clinical study
Authors: Mahsa Taghiakbari, Heiko Pohl, Roupen Djinbachian, Alan Barkun, Paola Marques, Mickael Bouin, Eric Deslandres, Benoit Panzini, Simon Bouchard, Audrey Weber, Daniel von Renteln
Journal: Endoscopy (2021)

Clinical implementation of the resect-and-discard strategy has been difficult because optical diagnosis is highly operator dependent. This prospective study aimed to evaluate a resect-and-discard strategy that is not operator dependent.The study evaluated a resect-and-discard strategy that uses the anatomical polyp location to classify colonic polyps into non-neoplastic or low risk neoplastic. All rectosigmoid diminutive polyps were considered hyperplastic and all polyps located proximally to the sigmoid colon were considered neoplastic. Surveillance interval assignments based on these a priori assumptions were compared with those based on actual pathology results and on optical diagnosis. The primary outcome was ≥ 90 % agreement with pathology in surveillance interval assignment.1117 patients undergoing complete colonoscopy were included and 482 (43.1 %) had at least one diminutive polyp. Surveillance interval agreement between the location-based strategy and pathological findings using the 2020 US Multi-Society Task Force guideline was 97.0 % (95 % confidence interval [CI] 0.96-0.98), surpassing the ≥ 90 % benchmark. Optical diagnoses using the NICE and Sano classifications reached 89.1 % and 90.01 % agreement, respectively (P < 0.001), and were inferior to the location-based strategy. The location-based resect-and-discard strategy allowed a 69.7 % (95 %CI 0.67-0.72) reduction in pathology examinations compared with 55.3 % (95 %CI 0.52-0.58; NICE and Sano) and 41.9 % (95 %CI 0.39-0.45; WASP) with optical diagnosis.The location-based resect-and-discard strategy achieved very high surveillance interval agreement with pathology-based surveillance interval assignment, surpassing the ≥ 90 % benchmark and outperforming optical diagnosis in surveillance interval agreement and the number of pathology examinations avoided.
27886 Optimized delivery of a novel acetyl dipeptide provides clinical and consumer perceivable benefits to antiaging attributes of the lower face, including firming and jawline contour
Authors: Brenda L. Edison, Neena K. Tierney, Heather A. Smith, Allison Rush, Derrick Chua, Marisa Dufort, Barbara A. Green, Clara Milikowski, Patricia Farris
Journal: Journal of the American Academy of Dermatology (2021)
Conventional upper gastrointestinal endoscope retroflexion method for emergent biliary drainage in a patient with esophageal stricture
Authors: Sho Kitagawa, Shori Ishikawa, Keiya Okamura
Journal: Endoscopy (2021)

Endoscopic ultrasound-guided biliary drainage (EUS-BD) is being increasingly used as an alternative treatment to percutaneous transhepatic biliary drainage (PTBD) for biliary obstruction in patients in whom transpapillary drainage fails or for whom this intervention is unsuitable [1] [2] [3]. Although endoscopic ultrasound-guided intrahepatic bile duct fistulation from a reconstructed gastric tube has recently been reported [4], EUS-BD cannot be performed in patients who have problems with ultrasound endoscope passage in the esophagus. Here we report successful performance of emergent endoscopic transpapillary biliary drainage using a conventional upper gastrointestinal endoscope.
Covid-19: Protection from two doses of vaccine wanes within six months, data suggest
Authors: Gareth Iacobucci
Journal: BMJ (2021)

Protection provided by two doses of the Pfizer and the AstraZeneca covid-19 vaccines wanes within six months, an analysis of UK data suggests.

The latest analysis from the Zoe Covid Study, which investigates real world vaccine effectiveness, examined data from positive PCR test results between May and July 2021 among 1.2 million people who had received two doses of Pfizer or AstraZeneca vaccine.

The results, released in a press release, show that protection after two doses of the Pfizer vaccine decreased from 88% at one month to 74% at five to six months; protection for AstraZeneca decreased was from …
Artificial tumor microenvironment regulated by first hemorrhage for enhanced tumor targeting and then occlusion for synergistic bioactivation of hypoxia-sensitive platesomes
Authors: Wenhui Tao, Dongyang Zhao, Guanting Li, Lingxiao Li, Songhao Li, Hao Ye, Chutong Tian, Yutong Lu, Shuying Li, Yinghua Sun, Zhonggui He, Jin Sun
Journal: Acta Pharmaceutica Sinica B (2021)

The unique characteristics of the tumor microenvironment (TME) could be exploited to develop antitumor nanomedicine strategies. However, in many cases, the actual therapeutic effect is far from reaching our expectations due to the notable tumor heterogeneity. Given the amplified characteristics of TME regulated by vascular disrupting agents (VDAs), nanomedicines may achieve unexpected improved efficacy. Herein, we fabricate platelet membrane-fusogenic liposomes (PML/DP&PPa), namely "platesomes", which actively load the hypoxia-activated pro-prodrug DMG-PR104A (DP) and physically encapsulate the photosensitizer pyropheophorbide a (PPa). Considering the different stages of tumor vascular collapse and shutdown induced by a VDA combretastatin-A4 phosphate (CA4P), PML/DP&PPa is injected 3 h after intraperitoneal administration of CA4P. First, CA4P-mediated tumor hemorrhage amplifies the enhanced permeation and retention (EPR) effect, and the platesome-biological targeting further promotes the tumor accumulation of PML/DP&PPa. Besides, CA4P-induced vascular occlusion inhibits oxygen supply, followed by photodynamic therapy-caused acute tumor hypoxia. This prolonged extreme hypoxia contributes to the complete activation of DP and then high inhibitory effect on tumor growth and metastasis. Thus, such a combining strategy of artificially-regulated TME and bio-inspired platesomes pronouncedly improves tumor drug delivery and boosts tumor hypoxia-selective activation, and provides a preferable solution to high-efficiency cancer therapy.
Functional Th1-oriented T follicular helper cells that infiltrate human breast cancer promote effective adaptive immunity
Authors: Grégory Noël, Mireille Langouo Fontsa, Soizic Garaud, Pushpamali De Silva, Alexandre de Wind, Gert G. Van den Eynden, Roberto Salgado, Anaïs Boisson, Hanne Locy, Noémie Thomas, Cinzia Solinas, Edoardo Migliori, Céline Naveaux, Hugues Duvillier, Sophie Lucas, Ligia Craciun, Kris Thielemans, Denis Larsimont, Karen Willard-Gallo
Journal: Journal of Clinical Investigation (2021)

We previously demonstrated that tumor-infiltrating lymphocytes (TIL) in human breast cancer sometimes form organized tertiary lymphoid structures (TLS) characterized by CXCL13-producing T follicular helper (Tfh) cells. The present study found that CD4+ Tfh TIL, CD8+ TIL, and TIL-B, colocalizing in TLS, all express the CXCL13 receptor CXCR5. An ex vivo functional assay determined that only activated, functional Th1-oriented Tfh TIL (PD-1hiICOSint phenotype) provide help for immunoglobulin and IFN-γ production. A functional Tfh TIL presence signals an active TLS, characterized by humoral (immunoglobulins, Ki-67+ TIL-B in active germinal centers) and cytotoxic (GZMB+CD8+ and GZMB+CD68+ TIL plus Th1 gene expression) immune responses. Analysis of active versus inactive TLS in untreated patients revealed that the former are associated with positive clinical outcomes. TLS also contain functional T follicular regulatory (Tfr) TIL, which are characterized by a CD25+CXCR5+GARP+FOXP3+ phenotype and a demethylated FOXP3 gene. Functional Tfr inhibited functional Tfh activities via a glycoprotein A repetitions predominant (GARP)-associated TGF-β–dependent mechanism. The activity of tumor-associated TLS was dictated by the relative balance between functional Tfh TIL and functional Tfr TIL. These data provide mechanistic insight into TLS processes orchestrated by functional Th1-oriented Tfh TIL, including TIL-B and CD8+ TIL activation and immunological memory generation. Tfh TIL, regulated by functional Tfr TIL, are an expected key target of PD-1/PD-L1 blockade.
PARPs in lipid metabolism and related diseases
Authors: Magdolna Szántó, Rebecca Gupte, W. Lee Kraus, Pal Pacher, Peter Bai
Journal: Progress in Lipid Research (2021)

PARPs and tankyrases (TNKS) represent a family of 17 proteins. PARPs and tankyrases were originally identified as DNA repair factors, nevertheless, recent advances have shed light on their role in lipid metabolism. To date, PARP1, PARP2, PARP3, tankyrases, PARP9, PARP10, PARP14 were reported to have multi-pronged connections to lipid metabolism. The activity of PARP enzymes is fine-tuned by a set of cholesterol-based compounds as oxidized cholesterol derivatives, steroid hormones or bile acids. In turn, PARPs modulate several key processes of lipid homeostasis (lipotoxicity, fatty acid and steroid biosynthesis, lipoprotein homeostasis, fatty acid oxidation, etc.). PARPs are also cofactors of lipid-responsive nuclear receptors and transcription factors through which PARPs regulate lipid metabolism and lipid homeostasis. PARP activation often represents a disruptive signal to (lipid) metabolism, and PARP-dependent changes to lipid metabolism have pathophysiological role in the development of hyperlipidemia, obesity, alcoholic and non-alcoholic fatty liver disease, type II diabetes and its complications, atherosclerosis, cardiovascular aging and skin pathologies, just to name a few. In this synopsis we will review the evidence supporting the beneficial effects of pharmacological PARP inhibitors in these diseases/pathologies and propose repurposing PARP inhibitors already available for the treatment of various malignancies.
25696 Impact of guselkumab on quality of life and work productivity outcomes among patients with moderate-to severe plaque psoriasis in the Corrona Psoriasis Registry
Authors: April W. Armstrong, Kristina Callis-Duffin, Timothy Fitzgerald, Amanda Teeple, Jonathan Uy, Mobolaji Olurinde, Katelyn Rowland, Robert R. McLean, Lin Guo, Ying Shan, Abby S. Van Voorhees
Journal: Journal of the American Academy of Dermatology (2021)