tbuckley/cabot-search huggingface dataset:
Dynamic transcriptome analysis unveils key proresolving factors of chronic inflammatory arthritis
Authors: Jin-Sun Kong, Ji-Hwan Park, Seung-Ah Yoo, Ki-Myo Kim, Yeung-Jin Bae, Yune-Jung Park, Chul-Soo Cho, Daehee Hwang, Wan-Uk Kim
Journal: Journal of Clinical Investigation (2020)

Despite recent advances in understanding chronic inflammation remission, global analyses have not been explored to systematically discover genes or pathways underlying the resolution dynamics of chronic inflammatory diseases. Here, we performed time-course gene expression profiling of mouse synovial tissues along progression and resolution of collagen-induced arthritis (CIA) and identified genes associated with inflammation resolution. Through network analysis of these genes, we predicted 3 key secretory factors responsible for the resolution of CIA: Itgb1, Rps3, and Ywhaz. These factors were predominantly expressed by Tregs and antiinflammatory M2 macrophages, suppressing production of proinflammatory cytokines. In particular, Ywhaz was elevated in the sera of mice with arthritis resolution and in the urine of rheumatoid arthritis (RA) patients with good therapeutic responses. Moreover, adenovirus-mediated transfer of the Ywhaz gene to the affected joints substantially inhibited arthritis progression in mice with CIA and suppressed expression of proinflammatory cytokines in joint tissues, lymph nodes, and spleens, suggesting Ywhaz is an excellent target for RA therapy. Therefore, our comprehensive analysis of dynamic synovial transcriptomes provides previously unidentified antiarthritic genes, Itgb1, Rps3, and Ywhaz, which can serve as molecular markers to predict disease remission, as well as therapeutic targets for chronic inflammatory arthritis.
A phase II study of gefitinib in patients with advanced thyroid cancer
Authors: N. A. Pennell, G. H. Daniels, R. I. Haddad, D. S. Ross, L. J. Wirth, P. H. Fidias, J. S. Temel, S. Gurubhagavatula, J. R. Clark, T. J. Lynch
Journal: Journal of Clinical Oncology (2007)

6020 Background: There are few effective treatments for locally advanced or metastatic thyroid cancers that are refractory to radioactive iodine (RaI). The epidermal growth factor receptor (EGFR) is highly expressed on normal and malignant thyroid tissue, and has been associated with a worse prognosis in well-differentiated thyroid cancer. The EGFR tyrosine kinase inhibitor gefitinib is effective in inhibiting the growth of thyroid cancer cells in vitro. This study sought to determine the efficacy and tolerability of gefitinib in patients with advanced thyroid cancer. Methods: In this open-label phase II trial, patients with RaI-refractory, locally advanced or metastatic thyroid cancer received 250mg of daily gefitinib. Anaplastic and medullary thyroid carcinoma were considered RaI refractory based on histology. The primary endpoint was overall response rate. Secondary endpoints were toxicity, progression-free survival (PFS), overall survival (OS), and tumor marker responses. Tumor markers consisted of serum thyroglobulin (Tg) in the differentiated cancers and serum calcitonin and carcinoembryonic antigen in medullary thyroid cancer. Results: A total of 27 patients were enrolled. 59% were male and the median age was 65. Histologic subtypes included papillary (41%), follicular (22%), anaplastic (19%), medullary (15%), and Hürthle cell carcinoma (4%). There were no objective tumor responses among the 25 patients evaluated, at which point the trial was halted. However, 32% of patients had objective reductions in tumor volume that did not meet criteria for PR. 48%, 24%, and 12% of patients had stable disease (SD) after 3, 6, and 12 months of treatment. Median PFS and OS were 3.7 [95% CI; 1.8, 5.7] and 17.5 months [9.2, not yet reached]. Five patients with SD had a decrease in Tg to &lt;90% of baseline level that was maintained for at least 3 months. Gefitinib was well tolerated, with 11% of patients experiencing grade 3 toxicity. Conclusions: Gefitinib therapy did not result in any objective tumor responses. However, reductions in tumor volume, falling Tg levels, and prolonged SD in a subset of patients may indicate biologic activity. The OS of 17.5 months was superior to historical rates in this population. However, the significance of this is difficult to interpret in the absence of a randomized comparison group. No significant financial relationships to disclose.
Response to Comment on Timmers et al. Resveratrol as Add-on Therapy in Subjects With Well-Controlled Type 2 Diabetes: A Randomized Controlled Trial. Diabetes Care 2016;39:2211–2217
Authors: Marlies de Ligt, Silvie Timmers, Patrick Schrauwen
Journal: Diabetes Care (2017)

We appreciate the interest of Mendez-del Villar et al. (1) in our experimental work with resveratrol (2). It is true that we used a relatively low dose of resveratrol (150 mg/day) in our study, and we could not agree more that indeed more human clinical trials are needed before it can be concluded whether resveratrol can be beneficial for the treatment or prevention of type 2 diabetes. In such future studies, the working mechanism of resveratrol should be further investigated as well. On the basis of a long series of preclinical and clinical studies, we examined whether resveratrol could improve glucose homeostasis via the improvement of …
Covid-19: Mental health services must be boosted to deal with “tsunami” of cases after lockdown
Authors: Ingrid Torjesen
Journal: BMJ (2020)

Mental health should be a “core element” of the response to the covid-19 pandemic, with greater investment to cope with a predicted surge in cases after lockdown, say psychiatrists and the World Health Organization.

A survey by the Royal College of Psychiatrists of 1369 of its members at the beginning of May found that 43% were seeing an increase in urgent and emergency cases, including patients who had suicidal thoughts or were self-harming.

At the same time 45% reported a fall in routine appointments, suggesting that self-isolation, shielding, school closures, and fear of engaging with health services because of the risk of infection may be keeping patients away.

Wendy Burn, president of the Royal College of Psychiatrists, said, “We are already seeing the devastating impact of covid-19 on mental health with more people in crisis. But we …
State-Transition Analysis of Time-Sequential Gene Expression Identifies Critical Points That Predict Development of Acute Myeloid Leukemia
Authors: Russell C. Rockne, Sergio Branciamore, Jing Qi, David E. Frankhouser, Denis O'Meally, Wei-Kai Hua, Guerry Cook, Emily Carnahan, Lianjun Zhang, Ayelet Marom, Herman Wu, Davide Maestrini, Xiwei Wu, Yate-Ching Yuan, Zheng Liu, Leo D. Wang, Stephen Forman, Nadia Carlesso, Ya-Huei Kuo, Guido Marcucci
Journal: Cancer Research (2020)

Temporal dynamics of gene expression inform cellular and molecular perturbations associated with disease development and evolution. Given the complexity of high-dimensional temporal genomic data, an analytic framework guided by a robust theory is needed to interpret time-sequential changes and to predict system dynamics. Here we model temporal dynamics of the transcriptome of peripheral blood mononuclear cells in a two-dimensional state-space representing states of health and leukemia using time-sequential bulk RNA-seq data from a murine model of acute myeloid leukemia (AML). The state-transition model identified critical points that accurately predict AML development and identifies stepwise transcriptomic perturbations that drive leukemia progression. The geometry of the transcriptome state-space provided a biological interpretation of gene dynamics, aligned gene signals that are not synchronized in time across mice, and allowed quantification of gene and pathway contributions to leukemia development. Our state-transition model synthesizes information from multiple cell types in the peripheral blood and identifies critical points in the transition from health to leukemia to guide interpretation of changes in the transcriptome as a whole to predict disease progression. SIGNIFICANCE: These findings apply the theory of state transitions to model the initiation and development of acute myeloid leukemia, identifying transcriptomic perturbations that accurately predict time to disease development.See related commentary by Kuijjer, p. 3072 GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/15/3157/F1.large.jpg.
Cisplatin Plus Gemcitabine as Standard of Care for Germline <i>BRCA/PALB2</i>‐Mutated Pancreatic Adenocarcinoma: Are We Moving Too Fast?
Authors: Nicola Fazio
Journal: Journal of Clinical Oncology (2020)

O'Reilly et al 1 reporting the results of a study assessing the overall response rate (ORR) of cisplatin and gemcitabine with or without veliparib as first-line treatment of advanced germline breast cancer 1-2/partner and localizer of BRCA2-mutated (gBRCA-mutated/PALB2) pancreatic ductal adenocarcinoma (PDAC).Although veliparib did not significantly change the activity of chemotherapy, an impressively high ORR in both arms led the authors to conclude that cisplatin and gemcitabine should be considered a standard of care in gBRCA-mutated/PALB21 PDAC.We congratulate the authors for providing these important data in such a poor-prognosis disease like PDCA; however, we think that such a strong statement deserves further consideration.Thus, we invite them to help us clarify the following points.
SUCCESSFUL CLOSURE OF A LARGE TYPE I ERCP-RELATED PERFORATION WITH AN OVER-THE-SCOPE CLIP (OTSC) DEVICE: A VIDEO REPORT
Authors: M Velegraki, E Vardas, G Delibaltadakis, G Paspatis
Journal: Endoscopy (2020)

Duodenal perforations during ERCP are associated with high morbidity and mortality rates. Traditionally, duodenal perforations caused by the duodenoscope itself (Stapfer type I) have been treated surgically. The OTSC is already recommended for the treatment of iatrogenic perforations, but there is scarce data about its use related to ERCP-related duodenal perforations.
THE BENEFITS OF ADDING DIGITAL CHOLANGIOSCOPY IN THE EVALUATION AND TREATMENT OF POST-TRANSPLANT BILIARY COMPLICATIONS
Authors: P Karagyozov, I Boeva, I Tishkov
Journal: Endoscopy (2020)

Aims We aim to explore diagnostic, therapeutic benefits and safety profile of Digital Single-Operator Cholangioscopy (DSOC)in patients with biliary complications after liver transplantation (LT) in cases,failed to be managed with ERCP.
Big Data Begin in Psychiatry
Authors: Myrna M. Weissman
Journal: JAMA Psychiatry (2020)

The last 40 years of JAMA Psychiatry are reviewed as a celebration of its achievements. The focus of this article is on the evolution of big data as reflected in key journal articles. The review begins in 1984 with the introduction of the Epidemiology Catchment Area (ECA) study and Freedman's editorial "Psychiatric Epidemiology Counts." The ECA study (N = 17 000), for the first time in a survey, used clinical diagnosis in 5 urban communities, thus linking research and care to population rates of psychiatric diagnosis. The review then traces the subsequent evolution of big data to 5 overlapping phases, other population surveys in the US and globally, cohort studies, administrative claims, large genetic data sets, and electronic health records. Each of these topics are illustrated in articles in JAMA Psychiatry. The many caveats to these choices, the historical roots before 1984, as well as the controversy around the choice of topics and the term big data are acknowledged. The foundation for big data in psychiatry was built on the development of defined and reliable diagnosis, assessment tools that could be used in large samples, the computational evolution for handling large data sets, hypothesis generated by smaller studies of humans and animals with carefully crafted phenotypes, the welcoming of investigators from all over the world with calls for broader diversity, open access and the sharing of data, and introduction of electronic health records more recently. Future directions as well as the opportunities for the complementary roles of big and little data are described. JAMA Psychiatry will continue to be a rich resource of these publications.
Covid-19: Doctors sound alarm over hospital transmissions
Authors: Gareth Iacobucci
Journal: BMJ (2020)

The BMJ Doctors have told The BMJ they are deeply concerned at the number of patients becoming infected with covid-19 in NHS hospitals in England and have called for more stringent infection control measures to combat its spread.They cite limited capacity for testing and retesting as a barrier to keeping covid and non-covid patients separated in so called "green" and "red" zones.There also have concerns about the availability of side rooms and cubicles to keep patients separate and believe that poor ventilation in areas other than intensive care units may be contributing to nosocomial infections.Jan Coebergh, a consultant neurologist in Surrey who has worked on covid wards at several sites since the outbreak began, told The BMJ that he had seen distressing cases of patients becoming infected with the virus from other patients while in hospital and who were likely to die as a result.
CLINICAL OUTCOME OF PATIENTS EXAMINED BY SMALL BOWEL CAPSULE ENDOSCOPY WITH NON-SPECIFIC ENTERITIS
Authors: S Sihag, B Tan, MS Ismail, S Semenov, B Ryan, A O’Connor, N Breslin, D McNamara
Journal: Endoscopy (2020)

Aims As with isolated ileitis on colonoscopy the finding of nonspecific enteritis (NSE) on capsule endoscopy (CE) not meeting established diagnostic criteria poses a clinical challenge. There is lack of available evidence to help clinicians to predict significant disease and long-term prognosis. We aimed to define the natural history of NSE in an Irish cohort.
Risk stratification by hormonal receptor (ER, PgR) and HER2 status in small (≤1cm) invasive breast cancer: Who might be a possible candidate for adjuvant treatment?
Authors: Y. Park, S. Kim, O. Ok, H. Baek, J. Lee, S. Nam, J. Yang, E. Cho, J. Ahn, Y. Im
Journal: Journal of Clinical Oncology (2009)

564 Background: With the increasing use of screening mammography, the proportion of ≤ 1 cm invasive breast cancer is increasing. Identification of breast cancer molecular subtypes has resulted in a better appreciation of the biologic heterogeneity, which is not fully explained by clinicopathologic features including staging system. The aims of this study were: 1) to identify the risk factors of systemic metastases in patients with ≤ 1 cm invasive breast cancer and 2) to investigate the patients group at greatest risk of such failure even in these small tumors. Method: Data were collected retrospectively in the breast cancer registry of our institution for patients with invasive breast cancer from October 1994 to December 2004. Results: Of 4,036 patients who received curative breast cancer surgery, 466 patients who had T1a or T1b breast cancer were identified. 39 patients who received neoadjuvant chemotherapy were excluded in this study. Ipsilateral axillary lymph node involvement was found in 13% (57/427) at the time of surgery. Axillary lymph node involvement was much more common in HER-2 positive group (33% vs 11%, p &lt; 0.0001) and triple negative (TN) group (24% vs 11%, p = 0.002) than in hormone receptor positive group. During median 61 months of follow-up, overall 10 year estimated distant relapse-free survival (DRFS) and overall survival (OS) were 95% and 92%, respectively. Multivariate analysis was conducted in 370 (T1aN0, T1bN0) patients, who had no lymph node involvement. In Cox-regression model, HER-2 positivity and triple negativity were identified as independent prognostic factors to predict DRFS [Hazard ratio (HR) 8.8, p = 0.003 for HER-2 positive group; HR 5.1, p = 0.026 for TN group] and OS (HR 5.0, p = 0.067 for HER-2 positive group; HR 11.1, p = 0.017 for TN group) in T1bN0 tumors. Limiting to T1aN0 tumors, statistical significance was not maintained. Conclusions: Even though T1aN0 and T1bN0 tumors have been known to have a relative low risk of systemic failure, anti-HER-2 directed therapy for HER-2 positive group and new innovative adjuvant systemic treatment for TN group in patients with T1bN0 tumor should be considered. Prospective adjuvant trials should be warranted in these subgroups of patients. No significant financial relationships to disclose.
ENDOSCOPIC ULTRASOUND GUIDED GASTROENTERIC ANASTOMOSES IN FIVE PATIENTS WITH UPPER GASTROINTESTINAL MALIGNANCIES – A RETROSPECTIVE CASE SERIES
Authors: A Bartholdy, PN Schmidt, E Feldager, S Novovic, JG Karstensen
Journal: Endoscopy (2020)

Aims Gastric outlet obstruction (GOO) is a common complication to advanced malignancies in the upper gastrointestinal (GI) tract. Traditionally, first line palliative treatment consists of duodenal stenting or surgical gastroenteric anastomosis (GEA). The effect of duodenal stenting may be limited by tissue ingrowth (uncovered stents) or stent migration (fully or partially covered stents) and the patient may be unfit for surgery. Endoscopic ultrasound-guided GEA (EUS-GEA) may then be an alternative.
Human CD34+ hematopoietic stem cells capable of multilineage engrafting NOD/SCID mice express flt3: distinct flt3 and c-kit expression and response patterns on mouse and human hematopoietic stem cells
Authors: S Jacobsen, E Sitnicka, C Brakebusch, I L Martensson, M Svensson, W W Agace, M Sigvardsson, N Buza-Vidas, D Bryder, C M Cilio, H Ahlenius, E Maraskovsky, J J Peschon
Journal: The Journal of Experimental Medicine (2015)
Support From Hospital to Home for Elders
Authors: L. Elizabeth Goldman, Urmimala Sarkar, Eric Kessell, David Guzman, Michelle Schneidermann, Edgar Pierluissi, Barbara Walter, Eric Vittinghoff, Jeff Critchfield, Margot Kushel
Journal: Annals of Internal Medicine (2014)

Hospitals are implementing discharge support programs to reduce readmissions, which have had mixed success. This trial in an ethnically and linguistically diverse community found that a nurse-led p...
COLD PIECEMEAL ENDOSCOPIC MUCOSAL RESECTION (EMR) FOR LARGE ADENOMAS AND SERRATED POLYPS: A TERTIARY REFERRAL CENTRE EXPERIENCE
Authors: R Rameshshanker, A Wawszczak, B Saunders
Journal: Endoscopy (2020)

Aims: Background Conventional EMR carries a risk of delayed bleeding, perforation and post polypectomy syndrome. Incomplete polyp resection could lead to recurrence and post colonoscopy cancer.
DNACPR notices: campaigner for patients’ right to be consulted says government has misunderstood her demands
Authors: Clare Dyer
Journal: BMJ (2020)

A campaigner for the rights of patients to be consulted before a “do not attempt cardiopulmonary resuscitation” (DNACPR) notice is placed in their medical notes has reiterated her threat to take legal action if necessary, after accusing the UK government of “misunderstanding” her demands.

Kate Masters is the daughter of David Tracey, who brought a successful legal action to establish …
CLOSURE OF AN OESOPHAGO-BRONCHIAL FISTULA BY AMPLATZER PROTHESIS
Authors: A Belle, S Leblanc, C Lorut, EA Ali, B Bordacahar, R Coriat, S Chaussade, M Barret
Journal: Endoscopy (2020)

The procedure of closing a confirmed oesophago-bronchial fistula (OBF) was performed using a gastroscope and a bronchoscope in an intubated patient, under air insufflation. The OBF was cannulated using the gastroscope with a cap. The Amplatzer Vascular Plug II 14 mm has been placed under double endoscopic control. Both extremities were released, under endoscopic control, successively in the trachea and in the esophagus, No adverse effects were identified. Since the procedure, the patient has had no new episodes of inhalation pneumopathy or cough. The opacification scanner confirmed the absence of reopening of the OBF and allowed a normal oral diet.
TCT-605 Impact Of Stent Overlap On Long-Term Clinical Outcomes In Patients Treated With Newer-Generation Drug-Eluting Stents
Authors: Crochan O'Sullivan, Crochan O'Sullivan, Giulio Stefanini, Lorenz Räber, Dik Heg, Masanori Taniwaki, Bindu Kalesan, Thomas Pilgrim, Thomas Zanchin, Aris Moschovitis, Lutz Büllesfeld, Ahmed Khattab, Peter Wenaweser, Bernhard Meier, Peter Juni, Stephan Windecker
Journal: Journal of the American College of Cardiology (2012)
Complement activation in patients with COVID-19: A novel therapeutic target
Authors: Massimo Cugno, Pier Luigi Meroni, Roberta Gualtierotti, Samantha Griffini, Elena Grovetti, Adriana Torri, Mauro Panigada, Stefano Aliberti, Francesco Blasi, Francesco Tedesco, Flora Peyvandi
Journal: Journal of Allergy and Clinical Immunology (2020)
An evolutionarily ancient mechanism for regulation of hemoglobin expression in vertebrate red cells
Authors: Masato Miyata, Nynke Gillemans, Dorit Hockman, Jeroen A. A. Demmers, Jan-Fang Cheng, Jun Hou, Matti Salminen, Christopher A. Fisher, Stephen Taylor, Richard J. Gibbons, Jared J. Ganis, Leonard I. Zon, Frank Grosveld, Eskeatnaf Mulugeta, Tatjana Sauka-Spengler, Douglas R. Higgs, Sjaak Philipsen
Journal: Blood (2020)
WHICH EUS FEATURE BEST PREDICT THE DIAGNOSIS OF PANCREATIC NEUROENDOCRINE TUMORS
Authors: A Saizu, G Becheanu, M Dumbrava, R Costache, R Iacob, C Gheorghe
Journal: Endoscopy (2020)

Aims Endoscopic ultrasound (EUS) associated with fine needle aspiration (FNA) has become the standard when it comes to evaluate pancreatic mass lesions. Our aim is to determine if beside specific ultrasound characteristics, a particular hypoechoic rim feature can predict a pancreatic neuroendocrine tumor (pNET) diagnosis.
ENDOSCOPIC ASSESSMENT OF ADVANCED SERRATED LESIONS OF THE COLORECTUM
Authors: A Dhillon, N Suzuki
Journal: Endoscopy (2020)

Sessile serrated lesions (SSLs) with dysplasia (irregardless of grade) are considered advanced lesions requiring en-bloc resection where appropriate. Careful endoscopic assessment is essential and facilitates optimal decision making and management. We suggest the following stepwise approach:
THE NEED FOR LAPAROSCOPIC CHOLECYSTECTOMY IN THE PATIENT WITHOUT GB STONE AFTER CBD STONE CLEARANCE
Authors: DW Shin, JW Lee, WY Jang, HJ Kim, KI Shin, SY Lee, KB Cho
Journal: Endoscopy (2020)

Aims Cholecystectomy after endoscopic removal of the common bile duct stones is generally recommended to prevent recurrence of biliary complications. The rate of following these recommendation is low. The aim of this study was to evaluate the need for laparoscopic cholecystectomy in the patient without GB stone after CBD stone clearance.
MEASURING THE VALUE OF ENDOSCOPIC ULTRASOUND (EUS)- GUIDED DRAINAGE OF PANCREATIC FLUID COLLECTIONS: A SINGLE CENTER COMPARATIVE STUDY OF PLASTIC AND LUMEN APPOSING METAL STENTS
Authors: V Parihar, Y Bashir, D Nally, G Mellotte, T Manoharan, C Walker, P Ridgway, K Conlon, N Breslin, G Harewood, BM Ryan
Journal: Endoscopy (2020)

Aims This study aimed to characterize the value of Endoscopic Ultrasound (EUS)-guided drainage of Pancreatic Fluid collections (PFCs) with either plastic or Lumen Apposing Metal Stents (LAMS).
Reassessing advance care planning in the light of covid-19
Authors: Sarah A Hopkins, Roberta Lovick, Louisa Polak, Ben Bowers, Tessa Morgan, Michael P Kelly, Stephen Barclay
Journal: BMJ (2020)

Compared with younger people, older people and those with frailty are more likely to die from acute infections, such as covid-19, and less likely to survive intensive care. 1 2 This has prompted calls internationally for advance care planning in these vulnerable populations, focusing on documenting individuals' preferences for resuscitation and hospital admission. 3 4 We suggest that the benefits of advance care planning derive more from its process than from the plans it produces, and that recognising this is essential for provision of optimum care for patients and their families.Moreover, an overemphasis on achieving individual choice, the stated purpose of advance care plans, may paradoxically undermine good care.
SPUTUM IL-5 CONCENTRATION IS ASSOCIATED WITH A SPUTUM EOSINOPHILIA AND ATTENUATED BY CORTICOSTEROID THERAPY IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE
Authors: M Bafadhel, S Saha, R Siva, M McCormick, W Monterio, P Rugman, P Dodson, I D Pavord, P Newbold, C E Brightling
Journal: Thorax (2008)