tbuckley/cabot-search huggingface dataset:
When 7 times angioplasty on Saphenous Vein graft would not compete the Native vessel Percutaneous Coronary intervention
Authors: Ehsan Khalilipur
Journal: Clinical Cardiology and Cardiovascular Interventions (2021)

Coronary artery bypass graft (CABG) has been the first option for revascularization in multiple vessel coronary artery disease. One of the most major obstacles after CABGs is atherosclerotic changes of SVGand more than 50 percent ofSVGare occluded at 10 years and 25 percent show severe stenosis at angiographic follow-up. Whether native vessel percutaneous coronary intervention (PCI) on native vessel or saphenous vein graft intervention is of benefit in these patients is still a debate. In this case report we want to clarify a common clinical scenario in a patient with prior CABG seven years ago which a proper decision in the right time could save many futile efforts. The patient underwent 7 PCI on the diseased SVG on OM with frequent occlusion due to stent thrombosis and in-stent restenosis which finally native vessel antegrade CTO PCI alleviated the problem and patient followed up 2 months after the procedure without any chest pain in his ordinary activities.
Family Genetic Risk Scores and the Genetic Architecture of Major Affective and Psychotic Disorders in a Swedish National Sample
Authors: Kenneth S. Kendler, Henrik Ohlsson, Jan Sundquist, Kristina Sundquist
Journal: JAMA Psychiatry (2021)

Family and genetic approaches have traditionally been used to evaluate our diagnostic concepts. Using a novel method, the family genetic risk score (FGRS), can we validate the genetic architecture of major affective and psychotic disorders in a national Swedish sample?
Discontinuation of infliximab in patients with ulcerative colitis in remission (HAYABUSA): a multicentre, open-label, randomised controlled trial
Authors: Taku Kobayashi, Satoshi Motoya, Shiro Nakamura, Takayuki Yamamoto, Masakazu Nagahori, Shinji Tanaka, Tadakazu Hisamatsu, Fumihito Hirai, Hiroshi Nakase, Kenji Watanabe, Takayuki Matsumoto, Masanori Tanaka, Takayuki Abe, Yasuo Suzuki, Mamoru Watanabe, Toshifumi Hibi, Shingo Kato, Atsushi Maemoto, Minoru Matsuura, Ryosuke Sakemi, Makoto Sasaki, Tomoyuki Tsujikawa, Motohiro Esaki, Norimasa Fukata, Kazuya Kitamura, Sakiko Hiraoka, Ryota Hokari, Shunji Ishihara, Tsutomu Mizoshita, Yuji Naito, Fumio Omata, Masayuki Saruta, Takuya Yoshino
Journal: The Lancet. Gastroenterology & hepatology (2021)
Coronary Microvascular Dysfunction Assessed by Pressure Wire and CMR After STEMI Predicts Long-Term Outcomes
Authors: Roberto Scarsini, Mayooran Shanmuganathan, Giovanni Luigi De Maria, Alessandra Borlotti, Rafail A. Kotronias, Matthew K. Burrage, Dimitrios Terentes-Printzios, Jeremy Langrish, Andrew Lucking, Gregor Fahrni, Florim Cuculi, Flavio Ribichini, Robin P. Choudhury, Rajesh Kharbanda, Vanessa M. Ferreira, Keith M. Channon, Adrian P. Banning
Journal: JACC. Cardiovascular imaging (2021)
Дисбіоз кишечника та ефективність використання пробіотика-біоентеросептика Ентерожерміна в його корекції (методичні рекомендації)
Authors: Yu.M. Stepanov, T.Y. Boiko
Journal: GASTROENTEROLOGY (2016)

У статті подані методичні рекомендації з лікування дисбіозу кишечника. Приділено увагу використанню пробіотика-біоентеросептика Ентерожерміна в комплексному лікуванні даної категорії пацієнтів.
Fibroblast-Specific Proteotranscriptomes Reveal Distinct Fibrotic Signatures of Human Sinoatrial Node in Nonfailing and Failing Hearts
Authors: Anuradha Kalyanasundaram, Ning Li, Miranda L. Gardner, Esthela J. Artiga, Brian J. Hansen, Amy Webb, Michael A. Freitas, Maciej Pietrzak, Bryan A. Whitson, Nahush A. Mokadam, Paul M.L. Janssen, Peter J. Mohler, Vadim V. Fedorov
Journal: Circulation (2021)

Up to 50% of the adult human sinoatrial node (SAN) is composed of dense connective tissue. Cardiac diseases including heart failure (HF) may increase fibrosis within the SAN pacemaker complex, leading to impaired automaticity and conduction of electric activity to the atria. Unlike the role of cardiac fibroblasts in pathologic fibrotic remodeling and tissue repair, nothing is known about fibroblasts that maintain the inherently fibrotic SAN environment.Intact SAN pacemaker complex was dissected from cardioplegically arrested explanted nonfailing hearts (non-HF; n=22; 48.7±3.1 years of age) and human failing hearts (n=16; 54.9±2.6 years of age). Connective tissue content was quantified from Masson trichrome-stained head-center and center-tail SAN sections. Expression of extracellular matrix proteins, including collagens 1 and 3A1, CILP1 (cartilage intermediate layer protein 1), and POSTN (periostin), and fibroblast and myofibroblast numbers were quantified by in situ and in vitro immunolabeling. Fibroblasts from the central intramural SAN pacemaker compartment (≈10×5×2 mm3) and right atria were isolated, cultured, passaged once, and treated ± transforming growth factor β1 and subjected to comprehensive high-throughput next-generation sequencing of whole transcriptome, microRNA, and proteomic analyses.Intranodal fibrotic content was significantly higher in SAN pacemaker complex from HF versus non-HF hearts (57.7±2.6% versus 44.0±1.2%; P<0.0001). Proliferating phosphorylated histone 3+/vimentin+/CD31- (cluster of differentiation 31) fibroblasts were higher in HF SAN. Vimentin+/α-smooth muscle actin+/CD31- myofibroblasts along with increased interstitial POSTN expression were found only in HF SAN. RNA sequencing and proteomic analyses identified unique differences in mRNA, long noncoding RNA, microRNA, and proteomic profiles between non-HF and HF SAN and right atria fibroblasts and transforming growth factor β1-induced myofibroblasts. Specifically, proteins and signaling pathways associated with extracellular matrix flexibility, stiffness, focal adhesion, and metabolism were altered in HF SAN fibroblasts compared with non-HF SAN.This study revealed increased SAN-specific fibrosis with presence of myofibroblasts, CILP1, and POSTN-positive interstitial fibrosis only in HF versus non-HF human hearts. Comprehensive proteotranscriptomic profiles of SAN fibroblasts identified upregulation of genes and proteins promoting stiffer SAN extracellular matrix in HF hearts. Fibroblast-specific profiles generated by our proteotranscriptomic analyses of the human SAN provide a comprehensive framework for future studies to investigate the role of SAN-specific fibrosis in cardiac rhythm regulation and arrhythmias.
Evaluation of Pathologic Response in Lymph Nodes of Patients With Lung Cancer Receiving Neoadjuvant Chemotherapy
Authors: Apar Pataer, Annikka Weissferdt, Ara A. Vaporciyan, Arlene M. Correa, Boris Sepesi, Ignacio I. Wistuba, John V. Heymach, Tina Cascone, Stephen G. Swisher
Journal: Journal of Thoracic Oncology (2021)

IntroductionMajor pathologic response (MPR), defined as residual viable tumor of less than or equal to 10%, currently serves as a surrogate end point for survival for patients with resectable NSCLC after neoadjuvant chemotherapy. However, the significance of pathologic response in lymph nodes harboring metastatic tumors in such patients remains uncertain. Therefore, we studied the effect of neoadjuvant chemotherapy on resected positive lymph nodes and determined if the degree of pathologic response in the lymph nodes alone (LN-MPR) or in combination with that of the primary tumor (PT-MPR) was able to predict the outcome.MethodsA total of 75 patients with NSCLC who underwent neoadjuvant chemotherapy and completed surgical resection were included in this study. Tissue specimens were retrospectively evaluated by two pathologists blinded to the patients’ treatments and outcomes. Specimens were reviewed for the degree of pathologic response in the primary tumor and in any involved lymph nodes. The prognostic performance of LN-MPR alone or in combination with PT-MPR with respect to overall survival (OS) was evaluated using the Kaplan-Meier method and Cox regression model.ResultsLN-MPR was significantly predictive of long-term OS after neoadjuvant chemotherapy. A combination of PT-MPR with LN-MPR was significantly associated with outcome and allowed stratification of patients into three prognostic groups (p = 0.001).ConclusionsLN-MPR in isolation is a reliable predictor of OS in patients with NSCLC receiving neoadjuvant chemotherapy. A combination of LN-MPR with PT-MPR seems to correlate well with the outcome and can be used to predict prognosis in this patient population.
Large-Scale Phylogenomic Analyses Reveal the Monophyly of Bryophytes and Neoproterozoic Origin of Land Plants
Authors: Danyan Su, Lingxiao Yang, Xuan Shi, Xiaoya Ma, Xiaofan Zhou, S Blair Hedges, Bojian Zhong
Journal: Molecular Biology and Evolution (2021)

The relationships among the four major embryophyte lineages (mosses, liverworts, hornworts, vascular plants) and the timing of the origin of land plants are enigmatic problems in plant evolution. Here, we resolve the monophyly of bryophytes by improving taxon sampling of hornworts and eliminating the effect of synonymous substitutions. We then estimate the divergence time of crown embryophytes based on three fossil calibration strategies, and reveal that maximum calibration constraints have a major effect on estimating the time of origin of land plants. Moreover, comparison of priors and posteriors provides a guide for evaluating the optimal calibration strategy. By considering the reliability of fossil calibrations and the influences of molecular data, we estimate that land plants originated in the Precambrian (980-682 Ma), much older than widely recognized. Our study highlights the important contribution of molecular data when faced with contentious fossil evidence, and that fossil calibrations used in estimating the timescale of plant evolution require critical scrutiny.
Trial of Psilocybin versus Escitalopram for Depression
Authors: Robin Carhart-Harris, Bruna Giribaldi, Rosalind Watts, Michelle Baker-Jones, Ashleigh Murphy-Beiner, Roberta Murphy, Jonny Martell, Allan Blemings, David Erritzoe, David J. Nutt
Journal: New England Journal of Medicine (2021)

Psilocybin may have antidepressant properties, but direct comparisons between psilocybin and established treatments for depression are lacking.In a phase 2, double-blind, randomized, controlled trial involving patients with long-standing, moderate-to-severe major depressive disorder, we compared psilocybin with escitalopram, a selective serotonin-reuptake inhibitor, over a 6-week period. Patients were assigned in a 1:1 ratio to receive two separate doses of 25 mg of psilocybin 3 weeks apart plus 6 weeks of daily placebo (psilocybin group) or two separate doses of 1 mg of psilocybin 3 weeks apart plus 6 weeks of daily oral escitalopram (escitalopram group); all the patients received psychological support. The primary outcome was the change from baseline in the score on the 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR-16; scores range from 0 to 27, with higher scores indicating greater depression) at week 6. There were 16 secondary outcomes, including QIDS-SR-16 response (defined as a reduction in score of >50%) and QIDS-SR-16 remission (defined as a score of ≤5) at week 6.A total of 59 patients were enrolled; 30 were assigned to the psilocybin group and 29 to the escitalopram group. The mean scores on the QIDS-SR-16 at baseline were 14.5 in the psilocybin group and 16.4 in the escitalopram group. The mean (±SE) changes in the scores from baseline to week 6 were -8.0±1.0 points in the psilocybin group and -6.0±1.0 in the escitalopram group, for a between-group difference of 2.0 points (95% confidence interval [CI], -5.0 to 0.9) (P = 0.17). A QIDS-SR-16 response occurred in 70% of the patients in the psilocybin group and in 48% of those in the escitalopram group, for a between-group difference of 22 percentage points (95% CI, -3 to 48); QIDS-SR-16 remission occurred in 57% and 28%, respectively, for a between-group difference of 28 percentage points (95% CI, 2 to 54). Other secondary outcomes generally favored psilocybin over escitalopram, but the analyses were not corrected for multiple comparisons. The incidence of adverse events was similar in the trial groups.On the basis of the change in depression scores on the QIDS-SR-16 at week 6, this trial did not show a significant difference in antidepressant effects between psilocybin and escitalopram in a selected group of patients. Secondary outcomes generally favored psilocybin over escitalopram, but the analyses of these outcomes lacked correction for multiple comparisons. Larger and longer trials are required to compare psilocybin with established antidepressants. (Funded by the Alexander Mosley Charitable Trust and Imperial College London's Centre for Psychedelic Research; ClinicalTrials.gov number, NCT03429075.).
Germline Cancer Susceptibility Gene Testing in Unselected Patients With Colorectal Adenocarcinoma: A Multicenter Prospective Study
Authors: Pedro L.S. Uson, Douglas Riegert-Johnson, Lisa Boardman, John Kisiel, Luke Mountjoy, Neej Patel, Blanca Lizaola-Mayo, Mitesh J. Borad, Daniel Ahn, Mohamad B. Sonbol, Jeremy Jones, Jonathan A. Leighton, Suryakanth Gurudu, Harminder Singh, Margaret Klint, Katie L. Kunze, Michael A. Golafshar, Ed D. Esplin, Robert L. Nussbaum, A. Keith Stewart, Tanio S. Bekaii-Saab, Niloy Jewel Samadder
Journal: Clinical Gastroenterology and Hepatology (2021)
The impact of genomics on precision public health: beyond the pandemic
Authors: Muin J. Khoury, Kathryn E. Holt
Journal: Genome Medicine (2021)

Precision public health has been defined in many ways [1].It can be viewed as an emerging multidisciplinary field that uses genomics, big data, and machine learning/ artificial intelligence to predict health risks and outcomes and to improve health at the population level.Just like precision medicine seeks to provide the right intervention to the right patient at the right time, the aim of precision public health is to provide the right intervention to the right population at the right time, with the goal of improving health for all.Genomic technologies have been at the leading edge of applications in clinical medicine and have the potential to revolutionize public health.We are pleased to introduce this special issue of Genome Medicine on the impact of genomics on precision public health, which highlights the utility of genomic tools in public health research and practice in the fight against communicable and noncommunicable diseases.This is particularly timely, given the battle against the COVID-19 pandemic, which has necessitated the application of genomic approaches to track the origin, transmission and evolution of the SARS-CoV-2 virus globally, as well as to understand differential host susceptibility, response, severity, and outcomes.Beyond genomics, granular data from population surveillance approaches are being used to target public health interventions.In addition, big data, digital technologies, and mobile health applications have been instrumental in defining the natural history of COVID-19 and identifying prognostic factors through machine learning and artificial intelligence [2].
ZEB1 enhances Warburg effect to facilitate tumorigenesis and metastasis of HCC by transcriptionally activating PFKM
Authors: Yanming Zhou, Furong Lin, Tao Wan, Ai Chen, Huihui Wang, Bin Jiang, Wentao Zhao, Shan Liao, Shijie Wang, Guannan Li, Zhenzhen Xu, Jinyang Wang, Jia Zhang, Huanhuan Ma, Donghai Lin, Qinxi Li
Journal: Theranostics (2021)

Metabolic reprogramming, especially Warburg effect, is a key event in tumor initiation and progression. ZEB1 plays a vital role in metastasis of various cancers. We previously found that ZEB1 was excessively expressed in hepatocellular carcinoma (HCC) and its high expression was closely correlated with metastasis and recurrence of HCC. We want to know whether glycolytic enzymes are regulated by ZEB1 and contribute to carcinogenesis and metastasis of HCC. Methods: To explore whether ZEB1 could enhance glycolysis in HCC, we knocked down ZEB1 by short hairpin RNA (shRNA) in MHCC-97H and HCC-LM3 cells and performed glucose uptake, lactate production, ECAR and OCR assays. To investigate how ZEB1 enhances glycolysis, the protein levels of glycolytic enzymes were detected in the same cell lines using Western blot. The regulatory effect of ZEB1 on PFKM mRNA level was confirmed by RT-qPCR, luciferase report assay and ChIP assay. In order to assess the role of ZEB1-PFKM axis in cell proliferation, cell counting and CCK-8 assays were performed in MHCC-97H and HCC-LM3 cell lines knocked down for ZEB1 and further re-expressed for either ZEB1 or PFKM or not. To explored whether the ZEB1-PFKM axis also functions in HCC cell migration, invasion and metastasis, the same MHCC-97H and HCC-LM3 cell lines were performed for wound healing assays, transwell assays and colony formation assays, meanwhile, MHCC-97H cell lines were performed for orthotopic liver transplantation assays. Finally, the expression of ZEB1 and PFKM were examined in human liver cancer specimens and non-tumorous liver tissues using immunohistochemical and Western blot. Results: We found that ZEB1 transcriptionally upregulates the expression of the muscle isoform of phosphofructokinase-1 (PFKM), a rate-limiting enzyme in glycolysis. Intriguingly, a non-classic ZEB1-binding sequence in the promoter region of PFKM was identified through which ZEB1 directly activates the transcription of PFKM. Silencing of ZEB1 in MHCC-97H and HCC-LM3 cell leads to impaired PFKM expression, glycolysis, proliferation and invasion, and such impairments are rescued by exogenous expression of PFKM. Importantly, in-situ HCC xenograft assays and studies from TCGA database demonstrate that ZEB1-PFKM axis is crucial for carcinogenesis and metastasis of HCC. Conclusions: Our study reveals a novel mechanism of ZEB1 in promoting HCC by activating the transcription of PFKM, establishing the direct link of ZEB1 to the promotion of glycolysis and Warburg effect and suggesting that inhibition of ZEB1 transcriptional activity toward PFKM may be a potential therapeutic strategy for HCC.
East Kent trust pleads guilty to criminal offence of unsafe care over baby’s death
Authors: Clare Dyer
Journal: BMJ (2021)

A hospital trust has pleaded guilty to the criminal offence of failing to provide safe care and treatment for a newborn baby and his mother, in the first such prosecution of an acute NHS trust.

East Kent Hospitals University NHS Foundation Trust admitted at Folkestone magistrates court to providing unsafe care to Harry Richford, who died a week after his emergency delivery in 2017 at Queen Elizabeth the Queen Mother Hospital in Margate, and to his mother, Sarah. The trust will be sentenced at a later date.

The prosecution by the Care Quality Commission under …
The anterior cingulate cortex directs exploration of alternative strategies
Authors: D. Gowanlock R. Tervo, Elena Kuleshova, Maxim Manakov, Mikhail Proskurin, Mattias Karlsson, Andy Lustig, Reza Behnam, Alla Y. Karpova
Journal: Neuron (2021)

The ability to adjust one's behavioral strategy in complex environments is at the core of cognition. Doing so efficiently requires monitoring the reliability of the ongoing strategy and, when appropriate, switching away from it to evaluate alternatives. Studies in humans and non-human primates have uncovered signals in the anterior cingulate cortex (ACC) that reflect the pressure to switch away from the ongoing strategy, whereas other ACC signals relate to the pursuit of alternatives. However, whether these signals underlie computations that actually underpin strategy switching or merely reflect tracking of related variables remains unclear. Here we provide causal evidence that the rodent ACC actively arbitrates between persisting with the ongoing behavioral strategy and temporarily switching away to re-evaluate alternatives. Furthermore, by individually perturbing distinct output pathways, we establish that the two associated computations—determining whether to switch strategy and committing to the pursuit of a specific alternative—are segregated in the ACC microcircuitry.
Occurrence of Lead and Other Toxic Metals Derived from Drinking-Water Systems in Three West African Countries
Authors: Michael B. Fisher, Amy Z. Guo, J. Wren Tracy, Sridevi K. Prasad, Ryan D. Cronk, Emily G. Browning, Kaida R. Liang, Emma R. Kelly, Jamie K. Bartram
Journal: Environmental Health Perspectives (2021)

Background: Exposure to toxic metals (TMs) such as lead can cause lifelong neurodevelopmental impairment and other adverse outcomes. TMs enter drinking water from human activity, geogenic contamination, and corrosion of water system components. Several studies report TM contamination in piped systems and private wells in high-income countries (HICs). However, few robust studies report on TM contamination in low- and middle-income countries (LMICs). Objectives: We characterized the occurrence and investigated sources of TM contamination in 261 rural water systems in three West African LMICs to inform prevention and management. Methods: Water samples were collected from 261 community water systems (handpumps and public taps) across rural Ghana, Mali, and Niger. Scrapings were collected from accessible components of a subset of these systems using a drill with acid-washed diamond-tipped bits. Samples were analyzed by inductively coupled plasma (ICP) mass spectrometry or ICP optical emission spectroscopy. Results: Of the TMs studied, lead most frequently occurred at levels of concern in sampled water system components and water samples. Lead mass fractions exceeded International Plumbing Code (IPC) recommended limits (0.25% wt/wt) for components in 82% (107/130) of systems tested; brass components proved most problematic, with 72% (26/36) exceeding IPC limits. Presence of a brass component in a water system increased expected lead concentrations in drinking-water samples by 3.8 times. Overall, lead exceeded World Health Organization (WHO) guideline values in 9% (24/261) of drinking-water samples across countries; these results are broadly comparable to results observed in many HICs. Results did not vary significantly by geography or system type. Discussion: Ensuring use of lead-free (<0.25%) components in new water systems and progressively remediating existing systems could reduce drinking-water lead exposures and improve health outcomes for millions. However, reflexive decommissioning of existing systems may deprive users of sufficient water for health or drive them to riskier sources. Because supply chains for many water system components are global, TM monitoring, prevention, and management may be warranted in other LMICs beyond the study area as well. https://doi.org/10.1289/EHP7804