tbuckley/cabot-search huggingface dataset:
ACTsmart – development and feasibility of digital Acceptance and Commitment Therapy for adults with chronic pain
Authors: Charlotte Gentili, Vendela Zetterqvist, Jenny Rickardsson, Linda Holmström, Laura E. Simons, Rikard K. Wicksell
Journal: npj Digital Medicine (2020)

Accessibility of evidence-based behavioral health interventions is one of the main challenges in health care and effective treatment approaches are not always available for patients that would benefit from them. Digitization has dramatically changed the health care landscape. Although mHealth has shown promise in addressing issues of accessibility and reach, there is vast room for improvements. The integration of technical innovations and theory driven development is a key concern. Digital solutions developed by industry alone often lack a clear theoretical framework and the solutions are not properly evaluated to meet the standards of scientifically proven efficacy. On the other hand, mHealth interventions developed in academia may be theory driven but lack user friendliness and are commonly technically outdated by the time they are implemented in regular care, if they ever are. In an ongoing project aimed at scientific innovation, the mHealth Agile Development and Evaluation Lifecycle was used to combine strengths from both industry and academia in the development of ACTsmart - a smartphone-based Acceptance and Commitment Therapy treatment for adult chronic pain patients. The present study describes the early development of ACTsmart, in the process of moving the product from alpha testing to a clinical trial ready solution.
Doctors and paramedics must be better prepared to deal with propranolol overdoses
Authors: Clare Dyer
Journal: BMJ (2020)

Doctors and ambulance services are being alerted to the dangers of a drug commonly prescribed for anxiety and migraine, if the patient overdoses on it.

“Current awareness of the potential impact of propranolol in overdose is limited and hinders the ability of prescribers to exercise clinical judgment when choosing to prescribe it,” warned the Healthcare Safety Investigation Branch (HSIB).

Propranolol is a β blocker that is now mainly used to treat migraine or anxiety. It can rapidly cause significant chemical damage to the heart when taken in overdose and is recognised as one of the most challenging overdoses to treat.

The HSIB opened a national investigation after the death of “Emma,” a clinical scientist in her 20s who died after overdosing on propranolol, prescribed for migraine, and citalopram, which she was taking for …
Abstract P6-06-15: Remodelling of calcium influx pathways in breast cancer associated fibroblasts
Authors: Francisco Sadras, Teneale A Stewart, Melanie Robitaille, Amelia A Peters, Priyakshi Kalita-de Croft, Patsy Soon, Jodi M Saunus, Sunil R Lakhani, Sarah J Roberts-Thomson, Gregory R Monteith
Journal: Cancer Research (2020)

Abstract Disruption of Ca2+ signaling during breast cancer tumorigenesis is now well-established. Despite the increasing recognition of the role of the tumour microenvironment, and cancer associated fibroblasts (CAFs), in tumorigenesis, very few studies have assessed alterations in Ca2+ influx pathways in this context. The aims of this study were to identify changes in the nature of Ca2+ influx in breast CAFs and to define the role of Ca2+ signaling in the induction of CAFs. We first developed a model for CAF induction using an immortalized human mammary fibroblast cell line, HMF3S. These cells were treated with transforming growth factor beta (TGFβ) to induce a CAF phenotype (HMF3S-CAF) as confirmed by the induction established CAF markers, including alpha smooth muscle actin. Fluorescence Imaging Plate Reader Ca2+ assays demonstrated that store operated Ca2+ entry (SOCE) was reduced as a consequence of TGFβ stimulated CAF induction in HMF3S-CAFs. As a potential mechanism, mRNA levels of the SOCE components, ORAI1, STIM1 and STIM2 were assessed. STIM2 was downregulated and ORAI1 was slightly upregulated suggesting that the decrease in SOCE in HMF3S-CAF cells were independent of mRNA expression changes of these genes. Voltage gated calcium channel (VGCC) mRNA expression was measured to determine whether other Ca2+ influx pathways were altered during CAF differentiation. Here, we found that Cav 1.2 and Cav 3.2 were significantly upregulated in HMF3S-CAF cells. Assessment of mRNA levels of SOCE components and VGCC in paired normal and CAF patient samples showed no change in SOCE components while, of the VGCCs, only Cav 1.2 and Cav 3.2 were upregulated, suggesting that increased expression of these channels may be a feature of breast cancer CAFs. The importance of Cav 1.2 and Cav 3.2 in CAF induction was assessed by pharmacological inhibition using nimodipine (Cav 1.2) or ML218 (Cav 3.2), both of which decreased TGFβ-mediated CAF activation. Our preliminary data suggest that siRNA against specific VGCCs may also reduce CAF activation. Our data indicate that Ca2+ signaling is remodelled in CAFs and that VGCC Ca2+ signal is important for breast CAF induction. Citation Format: Francisco Sadras, Teneale A Stewart, Melanie Robitaille, Amelia A Peters, Priyakshi Kalita-de Croft, Patsy Soon, Jodi M Saunus, Sunil R Lakhani, Sarah J Roberts-Thomson, Gregory R Monteith. Remodelling of calcium influx pathways in breast cancer associated fibroblasts [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-06-15.
Dynamic changes of interferon gamma release assay results with latent tuberculosis infection treatment
Authors: H. Xin, X. Cao, H. Zhang, J. Liu, S. Pan, X. Li, L. Guan, F. Shen, Z. Liu, D. Wang, X. Guan, J. Yan, H. Li, B. Feng, M. Zhang, Q. Yang, Q. Jin, L. Gao
Journal: Clinical Microbiology and Infection (2020)
HbA[subscript 1c] and Peripheral Arterial Disease in Diabetes: The Atherosclerosis Risk in Communities study
Authors: Elizabeth Selvin, Keattiyoat Wattanakit, Michael W. Steffes, Josef Coresh, A. Richey Sharrett
Journal: Diabetes Care (2006)

OBJECTIVE:--To assess the relation between HbA[subscript 1c] (A1C) and incident peripheral arterial disease (PAD) in a community-based cohort of diabetic adults from the Atherosclerosis Risk in Communities (ARIC) study. A second aim was to investigate whether the association was stronger for severe, symptomatic disease compared with PAD assessed by low ankle-brachial index (ABI). RESEARCH DESIGN AND METHODS--This was a prospective cohort study of 1,894 individuals with diabetes using ARIC visit 2 as baseline (1990-1992) with follow-up for incident PAD through 2002. We assessed the relation between A1C and incident PAD, defined by intermittent claudication, PAD-related hospitalization, or a low ABI (<0.9). RESULTS:--During a mean follow-up of 9.8 years, the crude incidence rates were 2.1 per 1,000 person-years for intermittent claudication (n = 41), 2.9 per 1,000 person-years for PAD-related hospitalization (n = 57), and 18.9 per 1,000 person-years for low ABI at visit 3 or 4 (n = 123). The relative risk (RR) (95% CI) of an incident PAD event comparing the second and third tertiles of A1C to the first, respectively, after adjustment for cardiovascular risk factors was strongest for severe, symptomatic forms of disease, e.g., PAD-related hospitalization (RR = 4.56 [1.86-11.18] for the third A1C tertile compared with the first, P trend <0.001) than for low ABI (RR = 1.64 [0.94-2.87], P trend = 0.08). CONCLUSIONS:--We found a positive, graded, and independent association between A1C and PAD risk in diabetic adults. This association was stronger for clinical (symptomatic) PAD, whose manifestations may be related to microvascular insufficiency, than for low ABI. Our results suggest that efforts to improve glycemic control in persons with diabetes may substantially reduce the risk of PAD.
Effect of primary tumor size in patients with metastatic non-small cell lung cancer (NSCLC).
Authors: Bing Xia, Feng Gao, Ramaswamy Govindan, Daniel Morgensztern
Journal: Journal of Clinical Oncology (2013)

8041 Background: Primary tumor size is a known prognostic factor for patients with early stage NSCLC treated with either surgery or radiation therapy. Although tumor volume has been associated with outcomes in patients with metastatic disease, it is labor intensive and rarely reported outside of a clinical trial. Since the primary tumor size is more commonly described, we evaluated its prognostic impact in patients with metastatic disease. Methods: The SEER was searched for patients with stage M1b NSCLC, with known tumor (T), lymph node (N) status, and diagnosed between 2004 and 2008. Patients with T0 and malignant pleural effusion were excluded. Tumor size is reported as the largest diameter and was subdivided into S1 (0.1-3 cm), S2 (3.1-5 cm), S3 (5.1-7 cm) and S4 (7.1-20 cm), roughly corresponding to T1, T2a, T2b and T3. Overall survival (OS) was estimated by the Kaplan-Meier method, while the hazard ratios (HR) were estimated and compared by Cox proportional hazard models. Results: Tumor size was available in 21879 (84.4%) out of 25919 patients with complete TNM staging. The frequencies of S1, S2, S3 and S4 were 33.4%, 33.8%, 17.1% and 13.7% respectively. 1-year OS rates for S1 to S4 were 34%, 27.9%, 24.0% and 19.0% respectively. Primary tumor size was an independent predictor for OS after adjustment for age, gender, race, histology, T and N status (p &lt; 0.0001). The decreased OS from each subsequent category of tumor size was statistically significant in both univariate and multivariable analyses (Table). Conclusions: Primary tumor size is readily available and represents a significant prognostic factor for survival in patients with stage M1b NSCLC, independently of T and N status. [Table: see text]
Content Analysis of Negative Online Reviews of Hospice Agencies in the United States
Authors: Elinor J. Brereton, Daniel D. Matlock, Monica Fitzgerald, Grace Venechuk, Chris Knoepke, Larry A. Allen, Channing E. Tate
Journal: JAMA Network Open (2020)

<h3>Importance</h3> As online reviews of health care become increasingly integral to patient decision-making, understanding their content can help health care practices identify and address patient concerns. <h3>Objective</h3> To identify the most frequently cited complaints in negative (ie, 1-star) online reviews of hospice agencies across the United States. <h3>Design, Setting, and Participants</h3> This qualitative study conducted a thematic analysis of online reviews of US hospice agencies posted between August 2011 and July 2019. The sample was selected from a Hospice Analytics database. For each state, 1 for-profit (n = 50) and 1 nonprofit (n = 50) hospice agency were randomly selected from the category of extra-large hospice agencies (ie, serving &gt;200 patients/d) in the database. Data analysis was conducted from January 2019 to April 2019. <h3>Main Outcomes and Measures</h3> Reviews were analyzed to identify the most prevalent concerns expressed by reviewers. <h3>Results</h3> Of 100 hospice agencies in the study sample, 67 (67.0%) had 1-star reviews; 33 (49.3%) were for-profit facilities and 34 (50.7%) were nonprofit facilities. Of 137 unique reviews, 68 (49.6%) were for for-profit facilities and 69 (50.4%) were for nonprofit facilities. A total of 5 themes emerged during the coding and analytic process, as follows: discordant expectations, suboptimal communication, quality of care, misperceptions about the role of hospice, and the meaning of a good death. The first 3 themes were categorized as actionable criticisms, which are variables hospice organizations could change. The remaining 2 themes were categorized as unactionable criticisms, which are factors that would require larger systematic changes to address. For both for-profit and nonprofit hospice agencies, quality of care was the most frequently commented-on theme (117 of 212 comments [55.2%]). For-profit hospice agencies received more communication-related comments overall (34 of 130 [26.2%] vs 9 of 82 [11.0%]), while nonprofit hospice agencies received more comments about the role of hospice (23 of 33 [69.7%] vs 19 of 31 [61.3%]) and the quality of death (16 [48.5%] vs 12 [38.7%]). <h3>Conclusions and Relevance</h3> Regarding actionable criticisms, hospice agencies could examine their current practices, given that reviewers described these issues as negatively affecting the already difficult experience of losing a loved one. The findings indicated that patients and their families, friends, and caregivers require in-depth instruction and guidance on what they can expect from hospice staff, hospice services, and the dying process. Several criticisms identified in this study may be mitigated through operationalized, explicit conversations about these topics during hospice enrollment.
Annals Story Slam - Innovations: Practices That Build Trust - Graphic Medicine to Empower Patients
Authors: Lolita (Maria) Alkureishi
Journal: Annals of Internal Medicine (2020)

Web Exclusives18 February 2020Annals Story Slam - Innovations: Practices That Build Trust - Graphic Medicine to Empower PatientsFREELolita (Maria) AlkureishiLolita (Maria) AlkureishiUniversity of Chicago, Chicago, Illinois (L.A.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W20-0001 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Innovations: Practices That Build Trust - Graphic Medicine to Empower Patients "Innovations: Practices That Build Trust - Graphic Medicine to Empower Patients," by Lolita (Maria) Alkureishi (Duration 3:14)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: University of Chicago, Chicago, Illinois (L.A.)Current Author Address: Lolita (Maria) Alkureishi, University of Chicago, 5841 South Maryland Avenue, MC 6082, Chicago, IL 60637; e-mail, [email protected]bsd.uchicago.edu. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 18 February 2020Volume 172, Issue 4Page: SS1KeywordsInterleukins ePublished: 18 February 2020 Issue Published: 18 February 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.Loading ...
A multilayered valve leaflet promotes cell-laden collagen type I production and aortic valve hemodynamics
Authors: Aline L.Y. Nachlas, Siyi Li, Benjamin W. Streeter, Kenneth J. De Jesus Morales, Fatiesa Sulejmani, David Immanuel Madukauwa-David, Donald Bejleri, Wei Sun, Ajit P. Yoganathan, Michael E. Davis
Journal: Biomaterials (2020)
Effectiveness and safety of ruxolitinib for the treatment of refractory systemic idiopathic juvenile arthritis like associated with interstitial lung disease : a case report
Authors: Brigitte Bader-Meunier, Alice Hadchouel, Laureline Berteloot, Laura Polivka, Vivien Béziat, Jean-Laurent Casanova, Romain Lévy
Journal: Annals of the Rheumatic Diseases (2020)

We read with interest the report of a series of 61 patients with systemic juvenile idiopathic arthritis (s-JIA) or s-JIA-like associated with high-fatality lung diseases.1 Lung disease was associated with digital clubbing, a high frequency of anaphylactic reactions to tocilizumab, and macrophage activation syndrome (MAS). Because of the low 5-year survival probability of 42%, there is an urgent need to identify efficient drugs to treat such patients. Herein we report the effectiveness and safety of ruxolitinib in one patient demonstrating clinical and radiological characteristics consistent to those reported by Saper et al 

A 2-year-old girl born to non-consanguineous parents presented with s-JIA-like since the age of 12 months, including recurring episodes of unexplained fever, urticaria, arthralgia, poor general health status, leukocytosis and elevated serum C-reactive protein (CRP). The use of corticosteroids resulted in a complete remission but the patient relapsed when prednisone was tapered below 0.5 mg/kg/day. Owing to this corticosteroid dependence, the patient received several lines of biological agents from the …
Evolutionary Analysis of the Bacillus subtilis Genome Reveals New Genes Involved in Sporulation
Authors: Lei Shi, Abderahmane Derouiche, Santosh Pandit, Shadi Rahimi, Aida Kalantari, Momir Futo, Vaishnavi Ravikumar, Carsten Jers, Venkata R S S Mokkapati, Kristian Vlahoviček, Ivan Mijakovic
Journal: Molecular Biology and Evolution (2020)

Bacilli can form dormant, highly resistant, and metabolically inactive spores to cope with extreme environmental challenges. In this study, we examined the evolutionary age of Bacillus subtilis sporulation genes using the approach known as genomic phylostratigraphy. We found that B. subtilis sporulation genes cluster in several groups that emerged at distant evolutionary time-points, suggesting that the sporulation process underwent several stages of expansion. Next, we asked whether such evolutionary stratification of the genome could be used to predict involvement in sporulation of presently uncharacterized genes (y-genes). We individually inactivated a representative sample of uncharacterized genes that arose during the same evolutionary periods as the known sporulation genes and tested the resulting strains for sporulation phenotypes. Sporulation was significantly affected in 16 out of 37 (43%) tested strains. In addition to expanding the knowledge base on B. subtilis sporulation, our findings suggest that evolutionary age could be used to help with genome mining.
Mitochondrial PAK6 inhibits prostate cancer cell apoptosis <i>via</i> the PAK6-SIRT4-ANT2 complex
Authors: Tingting Li, Yang Li, Tong Liu, Bingtao Hu, Jiabin Li, Chen Liu, Tao Liu, Feng Li
Journal: Theranostics (2020)

Rationale: P21-activated kinase 6 (PAK6) is a member of the class II PAKs family, which is a conserved family of serine/threonine kinases.Although the effects of PAK6 on many malignancies, especially in prostate cancer, have been studied for a long time, the role of PAK6 in mitochondria remains unknown.Methods: The expression of PAK6, SIRT4 and ANT2 in prostate cancer and adjacent non-tumor tissues was detected by immunohistochemistry. Immunofuorescence and immunoelectron microscopy were used to determine the subcellular localization of PAK6.Immunoprecipitation, immunofuorescence and ubiquitination assays were performed to determine how PAK6 regulates SIRT4, how SIRT4 regulates ANT2, and how PAK6 regulates ANT2.Flow cytometry detection and xenograft models were used to evaluate the impact of ANT2 mutant expression on the prostate cancer cell cycle and apoptosis regulation.Results: The present study revealed that the PAK6-SIRT4-ANT2 complex is involved in mitochondrial apoptosis in prostate cancer cells.It was found that PAK6 is mainly located in the mitochondrial inner membrane, in which PAK6 promotes SIRT4 ubiquitin-mediated proteolysis.Furthermore, SIRT4 deprives the ANT2 acetylation at K105 to promote its ubiquitination degradation.Hence, PAK6 adjusts the acetylation level of ANT2 through the PAK6-SIRT4-ANT2 pathway, in order to regulate the stability of ANT2.Meanwhile, PAK6 directly phosphorylates ANT2 atT107 to inhibit the apoptosis of prostate cancer cells.Therefore, the phosphorylation and deacetylation modifications of ANT2 are mutually regulated, leading to tumor growth in vivo.Consistently, these clinical prostate cancer tissue evaluations reveal that PAK6 is positively correlated with ANT2 expression, but negatively correlated with SIRT4.Conclusion: These present findings suggest the pivotal role of the PAK6-SIRT4-ANT2 complex in the apoptosis of prostate cancer.This complex could be a potential biomarker for the treatment and prognosis of prostate cancer.
Localized anesthesia of a specific brain region using ultrasound-responsive barbiturate nanodroplets
Authors: Harriet Lea-Banks, Meaghan A. O'Reilly, Clement Hamani, Kullervo Hynynen
Journal: Theranostics (2020)

Background: Targeted neuromodulation is a valuable technique for the study and treatment of the brain.Using focused ultrasound to target the local delivery of anesthetics in the brain offers a safe and reproducible option for suppressing neuronal activity.Objective: To develop a potential new tool for localized neuromodulation through the triggered release of pentobarbital from ultrasound-responsive nanodroplets.Method: The commercial microbubble contrast agent, Definity, was filled with decafluorobutane gas and loaded with a lipophilic anesthetic drug, before being condensed into liquid-filled nanodroplets of 210 ± 80 nm.Focused ultrasound at 0.58 MHz was found to convert nanodroplets into microbubbles, simultaneously releasing the drug and inducing local anesthesia in the motor cortex of rats (n=8).Results: Behavioral analysis indicated a 19.1 ± 13% motor deficit on the contralateral side of treated animals, assessed through the cylinder test and gait analysis, illustrating successful local anesthesia, without compromising the blood-brain barrier.Conclusion: Pentobarbital-loaded decafluorobutane-core Definity-based nanodroplets are a potential agent for ultrasound-triggered and targeted neuromodulation.
Abstract 16855: Machine Learning Generated Risk Model to Predict Unplanned Hospital Admission in Heart Failure
Authors: Francis O'Donovan, Tom Brecht, Charles Kekeh, Zhaohui Su, Costas Boussios, Vandana Menon, Rich Gliklich, Gregg Fonarow
Journal: Circulation (2017)

Introduction: Heart failure (HF) is a leading cause of hospitalization. There are few tools to accurately identify patients at high risk for unplanned admission in the outpatient setting. We used m...
WHO’s path to elimination of mother-to-child transmission of HIV and syphilis
Authors: Nathan Shaffer, Melanie Taylor, Morkor Newman, Innocent Nuwagira, Francoise Bigirimana, Merceline Dahl Regis, Angela Mushavi, Meg Doherty, Marc Bulterys, Ian Askew, Gottfried Hirnschall
Journal: BMJ (2020)

In their recent article in The BMJ (“Is elimination of vertical transmission of HIV in high prevalence settings achievable?”)1 Goga and colleagues make several important points, including that more realistic targets are needed to maintain momentum to reduce vertical transmission of HIV in countries with high prevalence. They also make a constructive proposal to encourage countries to use “dashboards” to track key coverage and process indicators, particularly during the “pre-elimination period,” and to encourage continuous programme assessment and use of data for improvement.

We are concerned, however, that they misrepresent the World Health Organization (WHO) and global partners’ elimination of mother-to-child transmission of HIV and syphilis (EMTCT) initiative.2 The authors include a box showing the criteria for elimination of vertical transmission of HIV from the …
Cadherin‐related family member 3 upregulates the effector functions of eosinophils
Authors: Kazuyuki Nakagome, Toshiaki Shimizu, Yury A. Bochkov, Toru Noguchi, Takehito Kobayashi, Tomoyuki Soma, Shigeharu Ueki, James E. Gern, Makoto Nagata
Journal: Allergy (2020)

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