tbuckley/cabot-search huggingface dataset:
Implications of host pancreatic hormones in the restart of grafted liver*1
Authors: T KIUCHI
Journal: Hepatology (1995)

Regulatory roles of insulin and glucagon in hepatic metabolism and function are well described. However, little is known about implications of host pancreatic hormones in primary function of grafted liver. This study aimed to investigate it in relation to hepatic mitochondrial function. Insulin, c-peptide, and glucagon in peripheral blood were monitored for 2 days in clinical liver transplantation by a continuous sampling technique to avoid influences of hormonal oscillation. In grafts with immediate function (n = 10), smooth increase of arterial ketone body ratio reflecting hepatic intramitochondrial redox state was accompanied by increased c-peptide and decreased glucagon, resulting in the increase of c-peptide/glucagon ratio. In other functioning grafts (n = 20), where ketone body ratio was rather lower, increased glucagon level, observed also during anhepatic phase, resulted in the slower increase of c-peptide/glucagon ratio. These were accompanied by increased free fatty acid and ketone body levels. In primary nonfunction (n = 4), rapid increase of c-peptide accompanied by hyperglycemia resulted in the accelerated increase of c-peptide/ glucagon ratio, but ketone body ratio did not show any increase. Insulin/c-peptide ratio also showed a rapid increase. These findings suggest that the increase of insulin/glucagon ratio in portal blood, potentially influenced by recipient condition, is associated with the recovery of mitochondrial energy metabolism in survived hepatic grafts. However, this relationship does not work in failed grafts, where irreversible impairment of energy metabolism is attributed to graft itself.
Polymorphisms in the interleukin 4, interleukin 13 and corresponding receptor genes are not associated with systemic sclerosis and do not influence gene expression
Authors: J. C. A. Broen, P. Dieude, M. C. Vonk, L. Beretta, B. Rueda, A. Herrick, J. Worthington, N. Hunzelmann, G. Riemekasten, H. Kiener, R. Scorza, C. P. Simeon, V. Fonollosa, P. Carreira, N. Ortego-Centeno, M. A. Gonzalez-Gay, P. Airo', M. J. H. Coenen, A. Aliprantis, J. Martin, Y. Allanore, T. R. D. J. Radstake
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Aim</h3> Polymorphisms in the interleukin 4 (IL-4), IL-13 and their corresponding receptors have previously been found associated with systemic sclerosis (SSc). In this study the authors aim to validate these previous observations and scrutinise their effects on gene expression. <h3>Patients and methods</h3> The authors genotyped a cohort consisting of 2488 SSc patients and 2246 healthy controls, derived from The Netherlands, Spain, UK, Italy, Germany and France. Taqman assays were used for genotyping two single-nucleotide polymorphisms (SNPs) within <i>IL-4</i> (<i>Q576R</i>/rs1801275) and the <i>IL-4 α receptor</i> (<i>−590C/T</i>/rs2243250). In the <i>IL-13</i> gene two SNPs were genotyped <i>R130Q</i> (rs20541) and <i>−1112C/T</i> (rs1800925.) In the <i>IL-13 α receptor</i> gene, the <i>43163:G/A</i> (rs6646259) variant was genotyped. In addition, the authors investigated the effect of these polymorphisms on corresponding gene expression with RT-PCR in B cells, T cells, plasmacytoid dendritic cells, monocytes and myeloid dendritic cells. <h3>Results</h3> None of these polymorphisms was found to be enriched in the SSc population or in any SSc clinical subtype and there was no influence of these polymorphisms on development of either pulmonary arterial hypertension and declineer of forced vital capacity in 15 years of follow-up. In addition, the authors did not observe an effect on expression levels in the cell subtypes. <h3>Conclusions</h3> This data show that these polymorphisms do not play a role in SSc and do not influence gene expression levels.
“Direct to Drug” screening as a precision medicine tool in multiple myeloma
Authors: Cecilia Bonolo de Campos, Nathalie Meurice, Joachim L. Petit, Alysia N. Polito, Yuan Xiao Zhu, Panwen Wang, Laura A. Bruins, Xuewei Wang, Ilsel D. Lopez Armenta, Susie A. Darvish, Greg J. Ahmann, Kimberly J. Henderson, Shulan Tian, Jonas J. Kruse, William M. Stewart, Jeremy T. Larsen, Craig B. Reeder, David Dingli, Prashant Kapoor, Shaji K. Kumar, Rafael Fonseca, P. Leif Bergsagel, Esteban Braggio, A. Keith Stewart
Journal: Blood Cancer Journal (2020)

Abstract Seventy-six FDA-approved oncology drugs and emerging therapeutics were evaluated in 25 multiple myeloma (MM) and 15 non-Hodgkin’s lymphoma cell lines and in 113 primary MM samples. Ex vivo drug sensitivities were mined for associations with clinical phenotype, cytogenetic, genetic mutation, and transcriptional profiles. In primary MM samples, proteasome inhibitors, dinaciclib, selinexor, venetoclax, auranofin, and histone deacetylating agents had the broadest cytotoxicity. Of interest, newly diagnosed patient samples were globally less sensitive especially to bromodomain inhibitors, inhibitors of receptor tyrosine kinases or non-receptor kinases, and DNA synthesis inhibitors. Clustering demonstrated six broad groupings of drug sensitivity linked with genomic biomarkers and clinical outcomes. For example, our findings mimic clinical observations of increased venetoclax responsiveness in t(11;14) patients but also identify an increased sensitivity profile in untreated patients, standard genetic risk, low plasma cell S-Phase, and in the absence of Gain(1q) and t(4;14). In contrast, increased ex vivo responsiveness to selinexor was associated with biomarkers of poor prognosis and later relapse patients. This “direct to drug” screening resource, paired with functional genomics, has the potential to successfully direct appropriate individualized therapeutic approaches in MM and to enrich clinical trials for likely responders.
PET in Gastrointestinal, Pancreatic, and Liver Cancers
Authors: Majid Assadi
Journal: Clinical Nuclear Medicine (2020)

Positron emission tomography (PET) has been established as a powerful modality in staging, restaging/recurrence, prognostication, and treatment planning for many malignancies, and its use in precision oncology is currently increasing. This chapter reviews the current state-of-the-art use of PET and PET/CT in the management of patients with gastrointestinal cancers, including esophagus, gastric, stroma cell, and colorectal, pancreatic, and liver malignancies, with reference to the currently available literature. Additionally, the current literature is reviewed, and the potential clinical applications of emerging themes and technological advances are addressed, including hybrid PET/MR imaging and alternative radiotracers in the GI, pancreas, and liver oncology.
The immunologic status of newborns born to SARS-CoV-2–infected mothers in Wuhan, China
Authors: Pin Liu, Junwen Zheng, Pu Yang, Xia Wang, Cong Wei, Shiyu Zhang, Shuwen Feng, Jing Lan, Bingyan He, Dongchi Zhao, Jiafu Li, Yuanzhen Zhang
Journal: Journal of Allergy and Clinical Immunology (2020)

Immunologic dysfunction due to coronavirus disease 2019 (COVID-19) is closely related to clinical prognosis, and the inflammatory response of pregnant women may affect the directional differentiation and function of fetal immune cells.We sought to analyze the immune status of newborns from mothers with COVID-19 in the third trimester.Along with collecting the clinical data from 51 newborns and their respective mothers, we recorded the immunophenotypes and cytokine and immunoglobulin levels of the newborns.None of the 51 newborns showed fever or respiratory distress during hospitalization. Detection of severe acute respiratory syndrome coronavirus 2 nucleic acid in pharyngeal swabs was negative. Except for the low level of CD16-CD56 cells, the count and proportion of lymphocytes, CD3, CD4, CD8, and CD19 were all in the normal range. Moreover, the serum IgG and IgM levels were within the normal range, whereas IL-6 showed increased levels. There was no correlation between maternal COVID-19 duration and the lymphocyte subsets or cytokine levels (IFN-γ, IL-2, IL-4, IL-6, IL-10, and TNF-α). There was a positive correlation between IL-6 and IL-10 levels and CD16-CD56 cells. One (1.96%) infant with an extremely elevated IL-6 concentration developed necrotizing enterocolitis in the third week after birth, and the remaining 50 infants did not show abnormal symptoms through the end of the follow-up period.COVID-19 in the third trimester did not significantly affect the cellular and humoral immunity of the fetus, and there was no evidence that the differentiation of lymphocyte subsets was seriously unbalanced.
Association Between Patient-Centered Medical Homes and Adherence to Chronic Disease Medications
Authors: Julie C. Lauffenburger, William H. Shrank, Asaf Bitton, Jessica M. Franklin, Robert J. Glynn, Alexis A. Krumme, Olga S. Matlin, Edmund J. Pezalla, Claire M. Spettell, Gregory Brill, Niteesh K. Choudhry
Journal: Annals of Internal Medicine (2016)

Poor medication adherence is viewed as a key measure of quality of care by major organizations. However, it has not been evaluated in primary care practices that meet recognition criteria for patie...
Prospective study of the effect of safety belts on morbidity and health care costs in motor-vehicle accidents
Authors: E. M. Orsay
Journal: JAMA (1988)

Comparaison de 791 sujets victimes d'accidents alors que leur ceinture etait bouclee et 573 qui n'avaient pas boucle leur ceinture. La gravite des lesions est moindre dans le 1er groupe (indice 1,8 contre 4,51); 6,8% des sujets du 1er groupe sont hospitalises, contre 19,2% du second. Le port de la ceinture permet une reduction importante du prix des traitements
PTH-045 A missed opportunity ? colonoscopy withdrawal times in a large DGH
Authors: Farah Rashid Chawdhary, Frank Muller
Journal: Endoscopy (2018)

<h3>Introduction</h3> Colonoscopy is the gold standard investigation for identification of colorectal pathology. Published evidence has confirmed that a higher adenoma detection rate (ADR) is associated with lower rates of post colonoscopy cancer detection. The ADR increases when withdrawal times from the caecum to the rectum are ≥6 min. Even the most experienced endoscopists (defined as performing &gt;1000 colonoscopies) will miss adenomas if their withdrawal times are &lt;6 min. <h3>Aim</h3> This audit was designed to evaluate compliance with current guidelines on colonoscopy withdrawal times across three East Kent Hospitals. <h3>Guidelines</h3> National guidelines recommend a mean colonoscopy withdrawal time of ≥6 min from caecum to rectum as per the Bowel Cancer Screening colonoscopy quality indicators. <h3>Methods</h3> Over a period of two weeks in 2017, endoscopy nurses across the three Hospitals recorded withdrawal times from the caecum to the rectum for all colonoscopy procedures. The endoscopists were unaware that withdrawal times were being recorded. <h3>Results</h3> 138 colonoscopies were performed. 29 were less than 6 min (21%) (table 1). <h3>Conclusion</h3> In 138 colonoscopy procedures performed in a large Trust, 21% did not adhere to the minimal withdrawal time of 6 min as recommended in the best practice guidelines. If this finding were replicated across the UK, a significant amount of pathology may be missed, increasing risks to our patients.
The Calcineurin-TFEB-p62 Pathway Mediates the Activation of Cardiac Macroautophagy by Proteasomal Malfunction
Authors: Bo Pan, Jie Li, Nirmal Parajuli, Zongwen Tian, Penglong Wu, Megan T. Lewno, Jianqiu Zou, Wenjuan Wang, Lynn Bedford, R. John Mayer, Jing Fang, Jinbao Liu, Taixing Cui, Huabo Su, Xuejun Wang
Journal: Circulation Research (2020)

Rationale: The ubiquitin-proteasome system (UPS) and the autophagic-lysosomal pathway are pivotal to proteostasis. Targeting these pathways is emerging as an attractive strategy for treating cancer. However, a significant proportion of patients who receive a proteasome inhibitor-containing regime show cardiotoxicity. Moreover, UPS and autophagic-lysosomal pathway defects are implicated in cardiac pathogenesis. Hence, a better understanding of the cross-talk between the 2 catabolic pathways will help advance cardiac pathophysiology and medicine. Objective: Systemic proteasome inhibition (PSMI) was shown to increase p62/SQSTM1 expression and induce myocardial macroautophagy. Here we investigate how proteasome malfunction activates cardiac autophagic-lysosomal pathway. Methods and Results: Myocardial macroautophagy, TFEB (transcription factor EB) expression and activity, and p62 expression were markedly increased in mice with either cardiomyocyte-restricted ablation of Psmc1 (an essential proteasome subunit gene) or pharmacological PSMI. In cultured cardiomyocytes, PSMI-induced increases in TFEB activation and p62 expression were blunted by pharmacological and genetic calcineurin inhibition and by siRNA-mediated Molcn1 silencing. PSMI induced remarkable increases in myocardial autophagic flux in wild type mice but not p62 null (p62-KO) mice. Bortezomib-induced left ventricular wall thickening and diastolic malfunction was exacerbated by p62 deficiency. In cultured cardiomyocytes from wild type mice but not p62-KO mice, PSMI induced increases in LC3-II flux and the lysosomal removal of ubiquitinated proteins. Myocardial TFEB activation by PSMI as reflected by TFEB nuclear localization and target gene expression was strikingly less in p62-KO mice compared with wild type mice. Conclusions: (1) The activation of cardiac macroautophagy by proteasomal malfunction is mediated by the Mocln1-calcineurin-TFEB-p62 pathway; (2) p62 unexpectedly exerts a feed-forward effect on TFEB activation by proteasome malfunction; and (3) targeting the Mcoln1 (mucolipin1)-calcineurin-TFEB-p62 pathway may provide new means to intervene cardiac autophagic-lysosomal pathway activation during proteasome malfunction.
Cold agglutinin disease revisited: a multinational, observational study of 232 patients
Authors: Sigbjørn Berentsen, Wilma Barcellini, Shirley D’Sa, Ulla Randen, Tor Henrik Anderson Tvedt, Bruno Fattizzo, Einar Haukås, Megan Kell, Robert Brudevold, Anders E. A. Dahm, Jakob Dalgaard, Hege Frøen, Randi Fykse Hallstensen, Pernille H. Jæger, Henrik Hjorth-Hansen, Agnieszka Małecka, Markku Oksman, Jürgen Rolke, Mallika Sekhar, Jon Hjalmar Sørbø, Eirik Tjønnfjord, Galina Tsykunova, Geir E. Tjønnfjord
Journal: Blood (2020)
CXCR4 mediates matrix stiffness-induced downregulation of UBTD1 driving hepatocellular carcinoma progression via YAP signaling pathway
Authors: Nan Yang, Tianxiang Chen, Liang Wang, Runkun Liu, Yongshen Niu, Liankang Sun, Bowen Yao, Yufeng Wang, Wei Yang, Qingguang Liu, Kangsheng Tu, Zhikui Liu
Journal: Theranostics (2020)

Rational: Increasing evidence indicates that the physical environment is a critical mediator of tumor behavior. Hepatocellular carcinoma (HCC) develops in an altered biomechanical environment, and increased matrix stiffness is a strong predictor of HCC development. C-X-C chemokine receptor type 4 (CXCR4) is known to trigger HCC progression. However, CXCR4 as a mediator of mechanical cues in HCC is not well characterized. Methods: qRT-PCR, Western blot and IHC were used to detect the CXCR4 expression in different matrix stiffness gels. MTT was used to measure the cell proliferation of HCC cells. Immunoblotting was used for detection of epithelial-to-mesenchymal transition (EMT) and stemness on the matrix stiffness. Immunofluorescence (IF) was used to detect the nuclear location in HCC cells. IP was used to show the interaction between YAP, UbcH5c and β-TrCP. Results: We identified CXCR4 as a critical intracellular signal transducer that relays matrix stiffness signals to control mechano-sensitive cellular activities through ubiquitin domain-containing protein 1 (UBTD1)-mediated YAP signaling pathway. We found that CXCR4 expression was remarkably up-regulated in HCC cells with increasing matrix stiffness and mediated proliferation, epithelial to mesenchymal transition, and stemness. Mechanistically, matrix stiffness acts through CXCR4 to decrease the levels of UBTD1, which is involved in the proteasome-dependent degradation of YAP, a major cell mechano-transducer. UBTD1 interacted with components of the YAP degradation complex and promoted the interaction between YAP and its E3 ubiquitin ligase β-TrCP. UBTD1 knockdown decreased YAP ubiquitylation and resulted in the activation of YAP-targeted genes and YAP downstream signaling. Downregulation of UBTD1 in HCC tissues correlated with malignant prognostic features and overall survival. Finally, luteolin, a natural product, suppressed matrix stiffness-induced biological effects and CXCR4-mediated YAP signaling pathway in HCC cells. Conclusion: Our findings reveal CXCR4 as a molecular switch in mechano-transduction, thereby defining a mechano-signaling pathway from matrix stiffness to the nucleus.
LncRNA Nron regulates osteoclastogenesis during orthodontic bone resorption
Authors: Ruilin Zhang, Junhui Li, Gongchen Li, Fujun Jin, Zuolin Wang, Rui Yue, Yibin Wang, Xiaogang Wang, Yao Sun
Journal: International Journal of Oral Science (2020)

Abstract Activation of osteoclasts during orthodontic tooth treatment is a prerequisite for alveolar bone resorption and tooth movement. However, the key regulatory molecules involved in osteoclastogenesis during this process remain unclear. Long noncoding RNAs (lncRNAs) are a newly identified class of functional RNAs that regulate cellular processes, such as gene expression and translation regulation. Recently, lncRNAs have been reported to be involved in osteogenesis and bone formation. However, as the most abundant noncoding RNAs in vivo, the potential regulatory role of lncRNAs in osteoclast formation and bone resorption urgently needs to be clarified. We recently found that the lncRNA Nron (long noncoding RNA repressor of the nuclear factor of activated T cells) is highly expressed in osteoclast precursors. Nron is downregulated during osteoclastogenesis and bone ageing. To further determine whether Nron regulates osteoclast activity during orthodontic treatment, osteoclastic Nron transgenic (Nron cTG) and osteoclastic knockout (Nron CKO) mouse models were generated. When Nron was overexpressed, the orthodontic tooth movement rate was reduced. In addition, the number of osteoclasts decreased, and the activity of osteoclasts was inhibited. Mechanistically, Nron controlled the maturation of osteoclasts by regulating NFATc1 nuclear translocation. In contrast, by deleting Nron specifically in osteoclasts, tooth movement speed increased in Nron CKO mic e . These results indicate that lncRNAs could be potential targets to regulate osteoclastogenesis and orthodontic tooth movement speed in the clinic in the future.
Early experience of an infectious and tropical diseases unit during the coronavirus disease (COVID-19) pandemic, Florence, Italy, February to March 2020
Authors: Filippo Lagi, Matteo Piccica, Lucia Graziani, Iacopo Vellere, Annarita Botta, Marta Tilli, Letizia Ottino, Beatrice Borchi, Marco Pozzi, Filippo Bartalesi, Jessica Mencarini, Michele Spinicci, Lorenzo Zammarchi, Filippo Pieralli, Giovanni Zagli, Carlo Nozzoli, Stefano Romagnoli, Alessandro Bartoloni
Journal: Eurosurveillance (2020)

We analysed the first 84 coronavirus disease (COVID-19) patients hospitalised in an infectious and tropical disease unit in Florence, Italy, over 30 days after the start of the COVID-19 outbreak in Italy. A 12% reduction in the rate of intensive care unit transfer was observed after the implementation of intensity care measures in the regular ward such as increasing the nurse/patient ratio, presence of critical care physicians and using high flow nasal cannulae oxygenation.
The Quandary over Graduates of Foreign Medical Schools in the United States
Authors: John K. Iglehart
Journal: New England Journal of Medicine (1996)

Professional and political concern about the increasing numbers of graduates of foreign medical schools entering U.S. residency programs has re-emerged during the past year. Previous attempts to limit the number of such graduates who fill residency positions have been thwarted by a practical but serious problem: who will care for the millions of people, many of whom are poor, in inner cities and rural communities, if the institutions serving these areas are unable to recruit foreign-trained physicians for the residencies and staff practices that are generally shunned by graduates of American medical schools? In this report, I will discuss the . . .
Future of General Practice
Authors: J. R. Lawless, R. R. W. Nichols, B. Pollak, R. Aspinall, V. G. Radclyffe, M. E. Pennefather, P. J. Hammett, B. H. O'Neill, H. G. Gage, B. I. Brest, W. D. Lobban, R. J. Regan, D. Dowd, A. P. Davidson, R. J. Smith, C. Joseph, A. L. Corbett
Journal: BMJ (1964)

mendation-that the Pool should cover only general medical services-could be made effective without any approach to the Review Body at all.All that is necessary is an organ- ized plan for practitioners to stop all extra services on a due date and a notification to the Ministry that this will happen.Faced with a major breakdowns in maternity ser- vices and a partial breakdown in hospital and other services, our masters would see our point.Let us not be satisfied with the inade- quate half-measures proposed, and instead send this Memorandum back to the G.M.S.
Monitoring respiratory infections in covid-19 epidemics
Authors: Ka Hung Chan, Pak-wing Lee, Crystal Ying Chan, Kin Bong Hubert Lam, Pak-leung Ho
Journal: BMJ (2020)

<b>Ka Hung Chan and colleagues</b> argue that monitoring influenza-like illness could be a complementary approach to assessing the effectiveness of general infection control measures against covid-19
Phylogenetic Reconstruction Based on Synteny Block and Gene Adjacencies
Authors: Guénola Drillon, Raphaël Champeimont, Francesco Oteri, Gilles Fischer, Alessandra Carbone
Journal: Molecular Biology and Evolution (2020)

Gene order can be used as an informative character to reconstruct phylogenetic relationships between species independently from the local information present in gene/protein sequences. PhyChro is a reconstruction method based on chromosomal rearrangements, applicable to a wide range of eukaryotic genomes with different gene contents and levels of synteny conservation. For each synteny breakpoint issued from pairwise genome comparisons, the algorithm defines two disjoint sets of genomes, named partial splits, respectively, supporting the two block adjacencies defining the breakpoint. Considering all partial splits issued from all pairwise comparisons, a distance between two genomes is computed from the number of partial splits separating them. Tree reconstruction is achieved through a bottom-up approach by iteratively grouping sister genomes minimizing genome distances. PhyChro estimates branch lengths based on the number of synteny breakpoints and provides confidence scores for the branches. PhyChro performance is evaluated on two data sets of 13 vertebrates and 21 yeast genomes by using up to 130,000 and 179,000 breakpoints, respectively, a scale of genomic markers that has been out of reach until now. PhyChro reconstructs very accurate tree topologies even at known problematic branching positions. Its robustness has been benchmarked for different synteny block reconstruction methods. On simulated data PhyChro reconstructs phylogenies perfectly in almost all cases, and shows the highest accuracy compared with other existing tools. PhyChro is very fast, reconstructing the vertebrate and yeast phylogenies in <15 min.