tbuckley/cabot-search huggingface dataset:
Colorectal cancer incidence in Texas border versus non-border counties.
Authors: Michael Brian LaPelusa, Michael Machiorlatti
Journal: Journal of Clinical Oncology (2022)

21 Background: There are 32 counties and 2.8 million people in the Texas border region. The population is 88.4% Hispanic with estimates that 47% lack health insurance - not including non-US citizens, who are more likely to lack health insurance than US citizens. In 2014, 7 of the 20 US counties with the lowest CRC screening rates were in Texas, 6 of which were Texas border counties. It is unknown how the incidence of CRC in Texas border counties has changed over time compared to non-border counties. In this study, we investigate changes in the incidence of CRC in Texas border counties between 2000 and 2017. Methods: Data were obtained from the Texas Department of State Health Service’s Texas Cancer Registry. Cases of patients aged 18 or older between 2000 and 2017 were included in our analysis. Cases were excluded if they contained incomplete information regarding age, sex, year of diagnosis, site of diagnosis or poverty level. Simple descriptive statistics were calculated for all covariates. Chi-square tests of independence were created to examine the association between each categorical variable and border county status. Age-adjusted incidence rates (AAIR) were created for the state overall and by border status. SAS v9.4 was used for all data analysis. Results: In border counties from 2000 to 2017, the overall AAIR decreased from 65.9 (per 100,000) to 56.7. In those 50-64 years old and 65 years and older residing in border counties, the AAIR increased from 63.3 to 78.1 and decreased from 244 to 176.1, respectively. In non-border counties from 2000 to 2017, the overall AAIR decreased from 85.2 (per 100,000) to 57.3. In those 50-64 years old and 65 years and older residing in non-border counties, the AAIR decreased from 94.9 to 78.0 and from 303 to 168.5, respectively. Conclusions: The overall AAIR of CRC was lower in Texas border counties compared to non-border counties, which is likely a consequence of lower screening rates in border counties. The overall AAIR decreased at a slower rate in Texas border counties compared to non-border counties, which may represent lower rates of utilization of CRC screening over time in border counties. The increase in the AAIR among those 50-64 years old in Texas border counties warrants further investigation.
Randomized Phase III Trial of Paclitaxel and Carboplatin Versus Paclitaxel and Ifosfamide in Patients With Carcinosarcoma of the Uterus or Ovary: An NRG Oncology Trial
Authors: Matthew A. Powell, Virginia L. Filiaci, Martee L. Hensley, Helen Q. Huang, Kathleen N. Moore, Krishnansu S. Tewari, Larry J. Copeland, Angeles A. Secord, David G. Mutch, Alessandro Santin, David P. Warshal, Nick M. Spirtos, Paul A. DiSilvestro, Olga B. Ioffe, David S. Miller
Journal: Journal of Clinical Oncology (2022)

This phase III randomized trial (NCT00954174) tested the null hypothesis that paclitaxel and carboplatin (PC) is inferior to paclitaxel and ifosfamide (PI) for treating uterine carcinosarcoma (UCS).Adults with chemotherapy-naïve UCS or ovarian carcinosarcoma (OCS) were randomly assigned to PC or PI with 3-week cycles for 6-10 cycles. With 264 events in patients with UCS, the power for an overall survival (OS) hybrid noninferiority design was 80% for a null hazard ratio (HR) of 1.2 against a 13% greater death rate on PI with a type I error of 5% for a one-tailed test.The study enrolled 536 patients with UCS and 101 patients with OCS, with 449 and 90 eligible, respectively. Primary analysis was on patients with UCS, distributed as follows: 40% stage I, 6% stage II, 31% stage III, 15% stage IV, and 8% recurrent. Among eligible patients with UCS, PC was assigned to 228 and PI to 221. PC was not inferior to PI. The median OS was 37 versus 29 months (HR = 0.87; 90% CI, 0.70 to 1.075; P < .01 for noninferiority, P > .1 for superiority). The median progression-free survival was 16 versus 12 months (HR = 0.73; P = < 0.01 for noninferiority, P < .01 for superiority). Toxicities were similar, except that more patients in the PC arm had hematologic toxicity and more patients in the PI arm had confusion and genitourinary hemorrhage. Among 90 eligible patients with OCS, those in the PC arm had longer OS (30 v 25 months) and progression-free survival (15 v 10 months) than those in the PI arm, but with limited precision, these differences were not statistically significant.PC was not inferior to the active regimen PI and should be standard treatment for UCS.
De Novo Design of A Membrane‐Anchored Probe for Multidimensional Quantification of Endocytic Dynamics
Authors: Kangqiang Qiu, Ryo Seino, Guanqun Han, Munetaka Ishiyama, Yuichiro Ueno, Zhiqi Tian, Yujie Sun, Jiajie Diao
Journal: Advanced Healthcare Materials (2022)

As a process of cellular uptake, endocytosis, with gradient acidity in different endocytic vesicles, is vital for the homeostasis of intracellular nutrients and other functions. To study the dynamics of endocytic pathway, a membrane-anchored pH probe, ECGreen, is synthesized to visualize endocytic vesicles under structured illumination microscopy (SIM), a super-resolution technology. Being sensitive to acidity with increasing fluorescence at low pH, ECGreen can differentiate early and late endosomes as well as endolysosomes. Meanwhile, membrane anchoring not only improves the durability of ECGreen, but also provides an excellent anti-photobleaching property for long-time imaging with SIM. Moreover, by taking these advantages of ECGreen, a multidimensional analysis model containing spatial, temporal, and pH information is successfully developed for elucidating the dynamics of endocytic vesicles and their interactions with mitochondria during autophagy, and reveals a fast conversion of endosomes near the plasma membrane.
Persistent Prescription Drug Affordability Challenges for Medicare Beneficiaries With Multiple Chronic Conditions—What Goes Up Must Come Down?
Authors: Robert J. Besaw, Stacie B. Dusetzina
Journal: JAMA Internal Medicine (2022)

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 Internal Medicine 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 Internal Medicine journal
Selective publication of antidepressant trials and its influence on apparent efficacy: Updated comparisons and meta-analyses of newer versus older trials
Authors: Erick H. Turner, Andrea Cipriani, Toshi A. Furukawa, Georgia Salanti, Ymkje Anna de Vries
Journal: PLoS Medicine (2022)

Background Valid assessment of drug efficacy and safety requires an evidence base free of reporting bias. Using trial reports in Food and Drug Administration (FDA) drug approval packages as a gold standard, we previously found that the published literature inflated the apparent efficacy of antidepressant drugs. The objective of the current study was to determine whether this has improved with recently approved drugs. Methods and findings Using medical and statistical reviews in FDA drug approval packages, we identified 30 Phase II/III double-blind placebo-controlled acute monotherapy trials, involving 13,747 patients, of desvenlafaxine, vilazodone, levomilnacipran, and vortioxetine; we then identified corresponding published reports. We compared the data from this newer cohort of antidepressants (approved February 2008 to September 2013) with the previously published dataset on 74 trials of 12 older antidepressants (approved December 1987 to August 2002). Using logistic regression, we examined the effects of trial outcome and trial cohort (newer versus older) on transparent reporting (whether published and FDA conclusions agreed). Among newer antidepressants, transparent publication occurred more with positive (15/15 = 100%) than negative (7/15 = 47%) trials (OR 35.1, CI 95% 1.8 to 693). Controlling for trial outcome, transparent publication occurred more with newer than older trials (OR 6.6, CI 95% 1.6 to 26.4). Within negative trials, transparent reporting increased from 11% to 47%. We also conducted and contrasted FDA- and journal-based meta-analyses. For newer antidepressants, FDA-based effect size (ES FDA ) was 0.24 (CI 95% 0.18 to 0.30), while journal-based effect size (ES Journals ) was 0.29 (CI 95% 0.23 to 0.36). Thus, effect size inflation, presumably due to reporting bias, was 0.05, less than for older antidepressants (0.10). Limitations of this study include a small number of trials and drugs—belonging to a single class—and a focus on efficacy (versus safety). Conclusions Reporting bias persists but appears to have diminished for newer, compared to older, antidepressants. Continued efforts are needed to further improve transparency in the scientific literature.
Table of Contents
Authors: F Hilbers, P Aftimos, S Lomnicki, N Setia, D Catenacci, V Grünwald, E Calvo, K Nakamura, D Maruyama, L De Mattos-Arruda, M Vazquez, F Finotello, R Lepore, E Porta, J Hundal, P Amengual-Rigo, C Ng, A Valencia, J Carrillo, T Chan, V Guallar, N Mcgranahan, J Blanco, M Griffith, D Ross, B Liu, A Schram, P Razavi, S Lagana, Y Zhang, M Scaltriti, J Bromberg, M Ladanyi, D Hyman, A Drilon, A Zehir, R Benayed, S Chandarlapaty, J Hechtman, H Rugo, F André, T Yamashita, H Cerda, I Toledano, S Stemmer, J Jurado, D Juric, I Mayer, E Ciruelos, H Iwata, P Conte, M Campone, C Wilke, D Mills, A Lteif, M Miller, F Gaudenzi, S Loibl, S Derks, L De Klerk, X Xu, T Fleitas, K Liu, Y Liu, F Dietlein, C Margolis, A Chiaravalli, Da Silva, S Ogino, F Akarca, G Freeman, S Rodig, J Hornick, E Van Allen, B Li, S Liu, V Thorsson, A Bass
Journal: Annals of Oncology (2020)
Early nivolumab addition to regorafenib in patients with hepatocellular carcinoma progressing under first-line therapy (GOING trial), interim analysis and safety profile.
Authors: Marco Sanduzzi Zamparelli, Ana Matilla, Jose Luis Lledó, Sergio Muñoz Martínez, Maria Varela, Mercedes Iñarrairaegui, Christie Perelló, Beatriz Minguez, Neus Llarch, Laura Márquez, Antonio Guerrero, Gemma Iserte, Andrés Castaño-García, Laura Carrión, Jordi Rimola, Ángeles Garcia-Criado, Gema Domenech, Loreto Boix, Jordi Bruix, Maria Reig
Journal: Journal of Clinical Oncology (2022)

428 Background: Regorafenib (Rego) improves survival in patients with hepatocellular carcinoma (HCC) (RESORCE trial) while nivolumab (Nivo) is also safe and active in terms of radiologic response (15-20% objective response) in second-line. The GOING trial (NCT04170556) is an investigator-initiated phase I/IIa study assessing the safety of Rego plus Nivo in HCC patients who progress and tolerate sorafenib (Cohort A) or who discontinue atezolizumab plus bevacizumab (Cohort B). Methods: Patients from cohort A receive Rego as monotherapy for the first 2 cycles (starting dose 160 mg/day, 3 weeks on/1 week off and adjusted for adverse events [AEs]) and Nivo is added at day 1 of cycle 3 (the first 10 patients at 3 mg/kg; since they did not present serious-AE (SAE), the final dose is 240 mg every two weeks). Treatment continues until unacceptable AEs, symptomatic tumor progression, patient decision or death. Safety is measured by the rate of AEs, rate of treatment related-AEs (Tr-AE), rate of AEs leading to treatment discontinuation and rate of death. Severity of AEs are evaluated according to CTCAE v.5.0. A futility analysis using the non-binding Lan &amp; DeMets beta-spending functions with a boundary of p=0.814 is mandated when 32.8% of cohort A has data of tumor assessment at least at week 16 by RECIST 1.1. Results: Fifty-one patients have been enrolled in cohort A as of May 15, 2021. The first 30 (BCLC-C 73%) were considered in this safety analysis. All patients developed at least one AE, 29 (96.7%) had Tr-AEs of any grade and 10 (33.3%) had grade 3 (no grades 4 or 5 have been reported). Ten (33.3%) patients had a Rego-related AE, 4 (13.3%) Nivo-related, and 4 (13.3%) Tr-AE grade 3 of special interest. The table describes the profile Tr-AE occurring in &gt; 10% of patients. Only 4 (13.3%) patients developed Tr-SAE, 3 (10 %) Rego-related and 3 (10 %) Nivo-related. Four patients discontinued the study due to physician decision, 2 for progression, and 2 for AEs (one related to study treatment). One patient had surgical resection after treatment discontinuation and a complete necrosis was observed at pathology. Conclusions: The sequential combination of Rego-Nivo has a manageable safety profile. Less than one third of the patients developed grade 3/4 Tr-AE and there was no treatment-related death. Futility analysis allowed to continuing recruitment. Clinical trial information: NCT04170556. [Table: see text]
Officials of the Association 1980-1981
Journal: JAMA (1981)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
LGR4: Not Just for Wnt Anymore?
Authors: Payton D. Stevens, Bart O. Williams
Journal: Cancer Research (2021)

Abstract Leucine-rich repeat-containing G protein–coupled receptor 4 (LGR4) is best known for its role in regulating the ability of cells to respond to Wnt ligands. In this well-known role, LGR4 serves as a receptor for R-spondins and forms a complex with the ubiquitin E3 ligases ring finger protein 43 (RNF43) and zinc and ring finger 3 (ZNRF3). RNF43 and ZNRF3 ubiquitinate Frizzleds (FZD), which are a family of ten WNT receptors. This ubiquitination decreases FZD receptor levels on the cell surface, reducing Wnt ligands' ability to activate signaling. While there were some previous indications of Wnt-independent functions of LGR4, this WNT-centric view has remained predominant. In this issue of Cancer Research, Yue and colleagues report that LGR4 also functions to regulate signaling through the EGF receptor. This work was stimulated by observing that while high levels of LGR4 expression in breast tumors correlated with poor patient outcomes, LGR4 levels did not correlate with a well-established Wnt-associated gene signature in these same patients. In contrast, high levels of Lgr4 expression strongly correlated with EGFR signaling. Reducing Lgr4 expression also inhibited signaling through the EGFR, potentially via regulation of the Casitas B-lineage lymphoma ubiquitin E3 ligase. Consistent with this model, LGR4 could be coimmunoprecipitated with a complex that contained EGFR and was capable of inhibiting EGFR ubiquitination. The implications of this work and how it challenges our understanding of the contributions of Wnt signaling and EGFR signaling in cancer are discussed as our several interesting future directions. See related article by Yue et al., p. 4441
Thumbsucker
Authors: Iain McClure
Journal: BMJ (2005)

Written and directed by Mike Mills On general release www.sonyclassics.com/thumbsucker/ Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> The facts about attention deficit hyper-activity disorder are well known. Some children (mainly boys) seem unable to concentrate as well as their peers and, to a greater or lesser extent, exhibit disabling over-activity. In consequence, they miss out on valuable social and academic opportunities and can pressurise family dynamics. ADHD (or ADD, if hyperkinesis is not present) can be addressed by behavioural interventions, but some patients do not respond, leading to the option of medication that stimulates dopamine release. The concern about use of … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Detailed resume of RNA m6A demethylases
Authors: Dandan Shen, Bo Wang, Ya Gao, Lijuan Zhao, Yaping Bi, Jinge Zhang, Ning Wang, Huiqin Kang, Jingru Pang, Ying Liu, Luping Pang, Zhe-Sheng Chen, Yi-Chao Zheng, Hong-Min Liu
Journal: Acta Pharmaceutica Sinica B (2022)

N6-Methyladenosine (m6A) is the most abundant internal modification in eukaryotic mRNA, playing critical role in various bioprocesses. Like other epigenetic modifications, m6A modification can be catalyzed by the methyltransferase complex and erased dynamically to maintain cells homeostasis. Up to now, only two m6A demethylases have been reported, fat mass and obesity-associated protein (FTO) and alkylation protein AlkB homolog 5 (ALKBH5), involving in a wide range of mRNA biological progress, including mRNA shearing, export, metabolism and stability. Furthermore, they participate in many significantly biological signaling pathway, and contribute to the progress and development of cancer along with other diseases. In this review, we focus on the studies about structure, inhibitors development and biological function of FTO and ALKBH5.
Preoperative plasma concentration ratio of atrial natriuretic peptide to brain natriuretic peptide (ANP/BNP) is a biochemical marker for predicting the outcome of the maze procedure Fumiki Yoshihara, Toshio Mishikimi, Yoshikado Sasako, Junjiro Kobayashi, Kenji Minatoya, Ko Bando, Yoshio Kosakai, Takeshi Horio, Shin-ichi Suga, Yoshihiko Ikeda, Chikao Yutani, Soichiro Kitamura, Hisayuki Matsuo, Kenji Kangawa. National Cardiovascular Center, Suita, Japan, Dokkyo University School of Medicine, Mibu…
Journal: Journal of the American College of Cardiology (2001)
Termination of professional relationships with patients
Authors: M. L. DiCorleto
Journal: JAMA (1979)

<h3>To the Editor.—</h3> I was pleased to find the SPECIAL COMMUNICATION "Terminating the Physician-Patient Relationship in Primary Care" (241:819, 1979). Too often the importance of the relationship between physician and patient is ignored, yet the interaction between physical and psychological functioning cannot be denied. Physicians may find that even absences because of vacation may result in some of the patient behaviors described by the authors. I would like to mention that psychiatrists and social workers are not the only professionals familiar with the concept of termination. Psychologists have contributed voluminously to the literature on this subject.
Usefulness of an S-1 dosage formula: An exploratory analysis of randomized clinical trial (JCOG1001).
Authors: Takeshi Kawakami, Hirofumi Yasui, Junki Mizusawa, Hiroko Hasegawa, Hiroshi Imazeki, Kazuki Kano, Yuya Sato, Satoru Iwasa, Shuji Takiguchi, Yukinori Kurokawa, Yuichiro Doki, Narikazu Boku, Takaki Yoshikawa, Masanori Terashima
Journal: Journal of Clinical Oncology (2022)

288 Background: Although the S-1 dose is determined by body surface area (BSA), its blood concentration and adverse events are affected by renal function. One study had reported the clinical utility of an S-1 dosage formula for calculating the dose for target blood concentration based on renal function (Booka E. Gastric Cancer 2016;19:876-86.). The present study aimed to explore the usefulness of this formula in adjuvant chemotherapy for gastric cancer. Methods: Ad hoc analyses was performed using data from patients enrolled in a phase III trial, JCOG1001, to evaluate the role of bursectomy for resectable advanced gastric cancer. In the abovementioned trial, patients with stage II/III received adjuvant S-1 chemotherapy based on BSA. The present study calculated the S-1 dose using the following formula: 1447.8 * (14.5+0.301*CLcr+8.23*SEX [male=1, female=0])*BSA (mg/day). Patients were divided into three groups, overdosed (OD), equal dosed (ED), and underdosed (UD), by comparing the initial dosage administered with that recommended by the formula. Results: Among the 686 eligible pts, 324, 304, and 58 were respectively classified as OD/ED/UD, with the following characteristics: median age, 67.5/64/53.5 years; men 188/229/57 (58%/75%/98%); undifferentiated type, 168/172/38 (52%/57%/66%); and pStage III, 212/200/41 (65%/66%/71%). Median relative dose intensity in OD/ED/UD pts was 93.8%/108.8%/75.0% based on the formula-recommended dose. The planned adjuvant S-1 therapy was completed in 69%/74%/74%, dose reduction and treatment schedule alteration were required in 31%/21%/9% and 20%/17%/9%, and treatment was terminated due to adverse events in 25%/18%/12%. The 5-year relapse-free (RFS) and overall survival (OS) OD/ED/UD patients were 66.6%/69.2%/74.0% and 77.0%/74.3%/77.3%, in pStage II 80.2%/85.6%/93.8% and 88.3%/90.1%/100%, and pStage III 59.6%/60.4%/65.8% and 67.0%/70.0%/67.7%, respectively. OD pts had significantly higher incidences of grade 3 or higher anemia, thrombocytopenia, diarrhea, stomatitis than ED and UD pts. Conclusions: Despite no difference in survival, this formula improved treatment compliance in OD patients receiving adjuvant S-1 chemotherapy for gastric cancer.[Table: see text]