tbuckley/cabot-search huggingface dataset:
How to drain the gallbladder: that is the question
Authors: Auke Bogte, Frank P. Vleggaar
Journal: Endoscopy (2020)

Acute cholecystitis constitutes the most common complication of gallstone disease. Of the patients presenting to the emergency room with acute abdominal complaints, 3 % – 9 % have acute cholecystitis, and over 90 % of those have gallstones [1]. The standard of care is cholecystectomy, either as an emergency procedure or delayed after a cooling down period. However, if the patient has high surgical risk, prompt cholecystectomy is not an option. Techniques to decompress the gallbladder can be utilized instead, for example endoscopic or radiological drainage, which can be used as either a temporary or definitive solution. Each treatment option has its own benefits and adverse events. The most appropriate technique will depend on patient characteristics, presence of gallstones, future treatment plans, risk of recurrence, anatomical considerations, and availability of equipment and experience at each hospital.
Long Term Survival and Immunological Correlates in Metastatic Melanoma Treated with Ipilimumab at 10 Mgs within an Expanded Access Program
Authors: A.M. Di Giacomo, L. Calabrò, R. Danielli, I. Pesce, E. Fonsatti, E. Bertocci, D. Giannarelli, M. Biagioli, M. Altomonte, M. Maio
Journal: Annals of Oncology (2012)
The National Institutes of Health funding for clinical research applying machine learning techniques in 2017
Authors: Amarnath R. Annapureddy, Suveen Angraal, Cesar Caraballo, Alyssa Grimshaw, Chenxi Huang, Bobak J. Mortazavi, Harlan M. Krumholz
Journal: npj Digital Medicine (2020)

Machine learning (ML) techniques have become ubiquitous and indispensable for solving intricate problems in most disciplines. To determine the extent of funding for clinical research projects applying ML techniques by the National Institutes of Health (NIH) in 2017, we searched the NIH Research Portfolio Online Reporting Tools Expenditures and Results (RePORTER) system using relevant keywords. We identified 535 projects, which together received a total of $264 million, accounting for 2% of the NIH extramural budget for clinical research.
成人T細胞白血病(ATL)における共通ガンマ鎖受容体ファミリー(ガンマc:CD132)の病理学的役割:インターロイキン-4Rアルファ(CD124)およびインターロイキン-7Rアルファ(CD127)の発現 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Yamada Y, Tsuruda K, Sugahara K, Harasawa H, Baba K, Mori N, Maeda T, Tomonaga M, Kamihira S
Journal: Blood (2000)
Daratumumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study
Authors: Nizar J. Bahlis, Meletios A. Dimopoulos, Darrell J. White, Lotfi Benboubker, Gordon Cook, Merav Leiba, P. Joy Ho, Kihyun Kim, Naoki Takezako, Philippe Moreau, Jonathan L. Kaufman, Maria Krevvata, Christopher Chiu, Xiang Qin, Linda Okonkwo, Sonali Trivedi, Jon Ukropec, Ming Qi, Jesus San-Miguel
Journal: Leukemia (2020)

In POLLUX, daratumumab (D) plus lenalidomide/dexamethasone (Rd) reduced the risk of disease progression or death by 63% and increased the overall response rate (ORR) versus Rd in relapsed/refractory multiple myeloma (RRMM). Updated efficacy and safety after >3 years of follow-up are presented. Patients (N = 569) with ≥1 prior line received Rd (lenalidomide, 25 mg, on Days 1-21 of each 28-day cycle; dexamethasone, 40 mg, weekly) ± daratumumab at the approved dosing schedule. Minimal residual disease (MRD) was assessed by next-generation sequencing. After 44.3 months median follow-up, D-Rd prolonged progression-free survival (PFS) in the intent-to-treat population (median 44.5 vs 17.5 months; HR, 0.44; 95% CI, 0.35-0.55; P < 0.0001) and in patient subgroups. D-Rd demonstrated higher ORR (92.9 vs 76.4%; P < 0.0001) and deeper responses, including complete response or better (56.6 vs 23.2%; P < 0.0001) and MRD negativity (10-5; 30.4 vs 5.3%; P < 0.0001). Median time to next therapy was prolonged with D-Rd (50.6 vs 23.1 months; HR, 0.39; 95% CI, 0.31-0.50; P < 0.0001). Median PFS on subsequent line of therapy (PFS2) was not reached with D-Rd versus 31.7 months with Rd (HR, 0.53; 95% CI, 0.42-0.68; P < 0.0001). No new safety concerns were reported. These data support using D-Rd in patients with RRMM after first relapse.
Variant Interpretation in Patients With Metastatic Breast Cancer
Authors: Florentia Fostira, Irene Konstantopoulou
Journal: JAMA Oncology (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
TRPV4 channel opening mediates pressure-induced pancreatitis initiated by Piezo1 activation
Authors: Sandip M Swain, Joelle M-J Romac, Rafiq A Shahid, Stephen J Pandol, Wolfgang Liedtke, Steven R Vigna, Rodger A Liddle
Journal: Journal of Clinical Investigation (2020)

Elevated pressure in the pancreatic gland is the central cause of pancreatitis following abdominal trauma, surgery, endoscopic retrograde cholangiopancreatography, and gallstones. In the pancreas, excessive intracellular calcium causes mitochondrial dysfunction, premature zymogen activation, and necrosis, ultimately leading to pancreatitis. Although stimulation of the mechanically activated, calcium-permeable ion channel Piezo1 in the pancreatic acinar cell is the initial step in pressure-induced pancreatitis, activation of Piezo1 produces only transient elevation in intracellular calcium that is insufficient to cause pancreatitis. Therefore, how pressure produces a prolonged calcium elevation necessary to induce pancreatitis is unknown. We demonstrate that Piezo1 activation in pancreatic acinar cells caused a prolonged elevation in intracellular calcium levels, mitochondrial depolarization, intracellular trypsin activation, and cell death. Notably, these effects were dependent on the degree and duration of force applied to the cell. Low or transient force was insufficient to activate these pathological changes, whereas higher and prolonged application of force triggered sustained elevation in intracellular calcium, leading to enzyme activation and cell death. All of these pathological events were rescued in acinar cells treated with a Piezo1 antagonist and in acinar cells from mice with genetic deletion of Piezo1. We discovered that Piezo1 stimulation triggered transient receptor potential vanilloid subfamily 4 (TRPV4) channel opening, which was responsible for the sustained elevation in intracellular calcium that caused intracellular organelle dysfunction. Moreover, TRPV4 gene–KO mice were protected from Piezo1 agonist– and pressure-induced pancreatitis. These studies unveil a calcium signaling pathway in which a Piezo1-induced TRPV4 channel opening causes pancreatitis.
Clinical presentation and outcomes of 2,924 early breast cancer patients (br.ca. pts) treated in a single institution in a 10-year period with a long follow up
Authors: E. Galligioni, R. Triolo, A. Lucenti, A. Ferro, M. Frisinghelli, G. Ambrosini, V. Murgia, R. Micciolo
Journal: Journal of Clinical Oncology (2006)

10669 Background: A consecutive series of br.ca. pts, treated between Jan 1 st 1990 to Dec 31 st 1999 in our Department, is the basis of our retrospective study, aimed to create a data base on routinary clinical management of early br.ca. pts, to which compare similar series and literature data. Methods: All Clinical Records were reviewed and computerized. Disease free and overall survival were estimated using the product-limit method of Kaplan and Meier. The log-rank test was used to compare prognosis between different subgroups. Results: Among 2924 consecutive br.ca. pts, 836 were younger than 50 years (med. age 44) and 2088 older (med. age 63). Regional nodes were negative (N−) in 1754, positive (N+) in 1027 and unknown in the remaining pts. So, 2593 pts were stage I-II and 301 stage IIIA-B. Hormonal Receptor status (available on 2560 pts) was positive for Estrogen (ER+) in 2021 pts and for Progesterone (PgR+) in 1649 pts. Moreover, 1571 pts were ER+Pgr+, 539 ER-PgR−, 78 ER-PgR+ and 461 ER+PgR−. HER2 was overexpressed in 262/1426 (18%) pts. Tumor grading (available on 2176 cases) was G1–2 in 1411 and G3–4 in 765 cases. After surgery, 731 pts received adjuvant Tamoxifen, 507 pts CMF ± Antracyclines chemotherapy, 434 pts both chemotherapy and Tamoxifen and 958 pts none. (no therapy data are available for the remaining 334 pts). At a median f.up of 9.8 years, 993/2924 pts (33.9%) have recurred, (med. DFS 137 mos) with a 5, 10 and 15 y probability of recurrence of 26, 44 and 63% respectively. Corresponding figures of recurrence for N− pts were 14, 30 and 50% (med. DFS 168 mos), while for N+ pts were 41, 61 and 77% (med DFS 81 mos). For younger N+ pts treated with chemotherapy, the 5 years probability of recurrence was 34% while it was 24% for older ER+ pts treated with hormonal therapy. So far, 794/2924 (27.5%) pts have died, with a 5, 10 and 15 y probability of death of 13, 27 and 41%. This was 5, 16 and 28% for N- pts and 22, 41 and 56% for N+ pts. For younger N+ pts treated with chemotherapy, the 5 y probability of death was 14%, as it was for older ER+ pts treated with Tamoxifen. Conclusions: Although this data are not yet conclusive, it appears that large part of the clinical improvements reported in clinical trials may be achieved in the routine management of breast cancer pts. No significant financial relationships to disclose.
Psychiatry on the Streets—Caring for Homeless Patients
Authors: Katherine A. Koh
Journal: JAMA Psychiatry (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Association Between a State Law Allowing Pharmacists to Dispense Naloxone Without a Prescription and Naloxone Dispensing Rates
Authors: Neha S. Gangal, Ana L. Hincapie, Roman Jandarov, Stacey M. Frede, Jill M. Boone, Neil J. MacKinnon, Kathleen Koechlin, Jolene DeFiore-Hyrmer, Amy Holthusen, Pamela C. Heaton
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Between 2015 and 2017, Ohio had the second highest number of opioid-related deaths. In July 2015, the Ohio General Assembly approved a law allowing pharmacists to dispense naloxone without a prescription in accordance with a physician-approved protocol. This change in the law allowed pharmacists to have more opportunity to participate in the management of patients who were addicted to opioids. <h3>Objective</h3> To determine the association between the implementation of an Ohio law allowing pharmacists to dispense naloxone without a prescription in accordance with a physician-approved protocol and naloxone dispensing rates. <h3>Design, Setting, and Participants</h3> A segmented regression analysis of an interrupted time series was performed for 30 consecutive months to evaluate the change in the naloxone dispensing rate before and after the implementation of the state law. Ohio Medicaid naloxone claims and Kroger Pharmacy naloxone claims for all 88 counties in Ohio were examined. Any patient 18 years or older with at least 1 naloxone order dispensed through Ohio Medicaid or by a Kroger Pharmacy in Ohio during the study period of July 16, 2014, to January 15, 2017, was included in the study. Data were analyzed from April 23, 2018, to July 7, 2019. <h3>Exposures</h3> The primary independent variable was implementation of an Ohio law allowing pharmacists to dispense naloxone without a prescription in accordance with a physician-approved protocol, which took effect in July 2015. <h3>Main Outcomes and Measures</h3> The primary outcome measure was the naloxone dispensing rate per month per county. <h3>Results</h3> In the Ohio Medicaid population, the number of naloxone orders dispensed after the policy was implemented increased by 2328%, from 191 in the prepolicy period to 4637 in the postpolicy period. The rate of naloxone orders dispensed per month per county after the policy was implemented increased by 4% in the Ohio Medicaid population and 3% in the Kroger Pharmacy population compared with the prepolicy period. The rate of naloxone orders dispensed after the policy was implemented increased by 18% per month in low-employment counties compared with high-employment counties in the Ohio Medicaid population. <h3>Conclusions and Relevance</h3> The implementation of a state law allowing pharmacists to dispense naloxone without a prescription in accordance with a physician-approved protocol was associated with an increase in the number of naloxone orders dispensed in the Ohio Medicaid and Kroger Pharmacy populations. Moreover, a significant increase was observed in the naloxone dispensing rate among the Ohio Medicaid population in counties with low employment and high poverty.
NOTCH4 maintains quiescent mesenchymal-like breast cancer stem cells via transcriptionally activating SLUG and GAS1 in triple-negative breast cancer
Authors: Lei Zhou, Dong Wang, Dandan Sheng, Jiahui Xu, Weilong Chen, Yuanyuan Qin, Ruikai Du, Xiaoli Yang, Xueyan He, Ni Xie, Suling Liu, Lixing Zhang
Journal: Theranostics (2020)

Rationale: NOTCH4 receptor has been implicated in triple-negative breast cancer (TNBC) development and breast cancer stem cell (BCSC) regulation. However, the potential of NOTCH4 as a BCSC marker and the underlying mechanisms remain unclear. Methods: In this study, we determined the expression and activation of NOTCH4 in breast cancer cell lines and tumor samples by qRT-PCR, western blotting and immunohistochemistry. Subsequently, in vitro and in vivo serial dilution experiments were performed to demonstrate the application of NOTCH4 as an efficient mesenchymal-like (ML)-BCSC marker in TNBC. Stable overexpression of activated NOTCH4 and knockdown cell lines were established using lentivirus. RNA-seq and qRT-PCR were employed to reveal the downstream effectors of NOTCH4, followed by dual-luciferase reporter and chromatin immunoprecipitation assays to identify the genuine binding sites of NOTCH4 on SLUG and GAS1 promoters. Transwell assay, mammosphere formation and chemoresistance experiments were performed to determine the effects of SLUG, GAS1 and NOTCH4 on the mesenchymal-like characteristics of TNBC cells. Survival analysis was used to study the relation of NOTCH4, SLUG and GAS1 with prognosis of breast cancer. Results: NOTCH4 is aberrantly highly expressed and activated in TNBC, which contributes to the maintenance of ML-BCSCs. Furthermore, NOTCH4 shows significantly higher efficiency in labeling ML-BCSCs than the currently commonly used CD24-CD44+ marker. Mechanistically, NOTCH4 transcriptionally upregulates SLUG and GAS1 to promote EMT and quiescence in TNBC, respectively. The effects of NOTCH4 can be mimicked by simultaneous overexpression of SLUG and GAS1. Moreover, SLUG is also involved in harnessing GAS1, a known tumor suppressor gene, via its anti-apoptotic function. Conclusions: Our findings reveal that the NOTCH4-SLUG-GAS1 circuit serves as a potential target for tumor intervention by overcoming stemness of ML-BCSCs and by conquering the lethal chemoresistance and metastasis of TNBC.
Sputum microbiome profiling in COPD: beyond singular pathogen detection
Authors: Benedikt Ditz, Stephanie Christenson, John Rossen, Chris Brightling, Huib A M Kerstjens, Maarten van den Berge, Alen Faiz
Journal: Thorax (2020)

Culture-independent microbial sequencing techniques have revealed that the respiratory tract harbours a complex microbiome not detectable by conventional culturing methods. The contribution of the microbiome to chronic obstructive pulmonary disease (COPD) pathobiology and the potential for microbiome-based clinical biomarkers in COPD are still in the early phases of investigation. Sputum is an easily obtainable sample and has provided a wealth of information on COPD pathobiology, and thus has been a preferred sample type for microbiome studies. Although the sputum microbiome likely reflects the respiratory microbiome only in part, there is increasing evidence that microbial community structure and diversity are associated with disease severity and clinical outcomes, both in stable COPD and during the exacerbations. Current evidence has been limited to mainly cross-sectional studies using 16S rRNA gene sequencing, attempting to answer the question 'who is there?' Longitudinal studies using standardised protocols are needed to answer outstanding questions including differences between sputum sampling techniques. Further, with advancing technologies, microbiome studies are shifting beyond the examination of the 16S rRNA gene, to include whole metagenome and metatranscriptome sequencing, as well as metabolome characterisation. Despite being technically more challenging, whole-genome profiling and metabolomics can address the questions 'what can they do?' and 'what are they doing?' This review provides an overview of the basic principles of high-throughput microbiome sequencing techniques, current literature on sputum microbiome profiling in COPD, and a discussion of the associated limitations and future perspectives.
Deep tissue photoacoustic imaging of nickel(II) dithiolene-containing polymeric nanoparticles in the second near-infrared window
Authors: Byullee Park, Kyung Min Lee, Suhyeon Park, Misun Yun, Hak-Jong Choi, Jeesu Kim, Changho Lee, Hyungwoo Kim, Chulhong Kim
Journal: Theranostics (2020)

Photoacoustic imaging is gaining great attention in the medical world due to its significant potential for clinical translation.Light excitation in the second near-infrared (NIR-II) window (1000-1350 nm) has resolution and penetration depth suitable for several clinical applications.However, the significant challenge exists for clinical translation because of the absence of notable intrinsic chromophores in this clinically significant optical range to generate diagnostic images.Methods: We present newly developed a biocompatible nickel dithiolene-based polymeric nanoparticle (NiPNP), which have a strong and sharp absorption peak at 1064 nm, as a photoacoustic contrast agent to boost specific absorbance in the NIR-II window for in vivo deep tissue imaging.Results: We confirm the enhanced PA signal by NiPNP's strong light absorption in the NIR-II window (287% higher than that of NIR-I) and deep tissue imaging capability (~5.1 cm) through in vitro experiment.We have successfully acquired diagnostic-quality in vivo photoacoustic images in deep tissue (~3.4 cm) of sentinel lymph nodes, gastrointestinal tracts, and bladders of live rats by using clinically viable imaging system.Conclusions: Our results prove that with strong absorption in the NIR-II window and with deeper imaging depth, the clinical translation of photoacoustic imaging with NiPNP is feasible for preclinical studies and thus would facilitate further clinical investigations.
BRMS1: Metastasis suppressor gene methylation as a target for anticancer therapy in breast and ovarian cancer
Authors: Shu Zhang, Curtis Balch, Meiyun Fan, Kenneth P. Nephew
Journal: Cancer Research (2006)

4314  The BRMS1 (breast cancer metastasis suppressor 1) gene has previously been found to suppress metastasis in animal models without inhibiting primary tumor growth. Our prior work indicated that reduced BRMS1 expression is associated with aggressive ovarian carcinomas, nodal metastases, and poor patient survival. Because low BRMS1 RNA expression correlates with poor clinical outcome, we have focused on the regulation of BRMS1 at the transcriptional level. One notable mechanism of transcriptional regulation and gene silencing is hypermethylation of CpG islands within the first exon and promoter regions of tumor and metastasis suppressor. We observed that a high-density CpG island is present in BRMS1 promoter by CpG Island Searcher software, and then hypothesized that DNA methylation regulates BRMS1expression in breast and ovarian cancer. We further hypothesized that treatment with 5-aza-2’-deoxycytidine (5-aza-CdR), a DNA methylation inhibitor, would increase BRMS1 expression in breast and ovarian carcinoma cell lines. Metastasis suppressor gene reactivation may inhibit metastatic colonization and further invasion, resulting in clinical benefit. BRMS1mRNA levels were examined in a panel of breast and epithelial ovarian cancer cell lines and normal ovarian surface epithelial cells (NOSE) by real time quantitative PCR (qPCR) or microarray analyses. Hypermethylation of the BRMS1CpG island in these cell lines was determined by methylation specific PCR (MSP). BRMS1 expression and motility of metastatic cell lines (ovarian cancer HO-8910PM and breast cancer MDA-MB-231) were observed following treatment with 5-aza-CdR. Our qPCR and microarray analyses confirmed that BRMS1 mRNA expression was significantly decreased (P