tbuckley/cabot-search huggingface dataset:
New Drugs, Old Targets: Tweaking the Dopamine System to Treat Psychostimulant Use Disorders
Authors: Amy Hauck Newman, Therese Ku, Chloe J. Jordan, Alessandro Bonifazi, Zheng-Xiong Xi
Journal: The Annual Review of Pharmacology and Toxicology (2021)

The abuse of illicit psychostimulants such as cocaine and methamphetamine continues to pose significant health and societal challenges. Despite considerable efforts to develop medications to treat psychostimulant use disorders, none have proven effective, leaving an underserved patient population and unanswered questions about what mechanism(s) of action should be targeted for developing pharmacotherapies. As both cocaine and methamphetamine rapidly increase dopamine (DA) levels in mesolimbic brain regions, leading to euphoria that in some can lead to addiction, targets in which this increased dopaminergic tone may be mitigated have been explored. Further, understanding and targeting mechanisms underlying relapse are fundamental to the success of discovering medications that reduce the reinforcing effects of the drug of abuse, decrease the negative reinforcement or withdrawal/negative affect that occurs during abstinence, or both. Atypical inhibitors of the DA transporter and partial agonists/antagonists at DA D
Regulatory Action to Protect Access to Hydroxychloroquine for Approved Rheumatic Indications During COVID‐19 in New Zealand
Authors: Eamon Duffy, Nicola Arroll, Richard Beasley, Thomas Hills
Journal: Arthritis & Rheumatology (2021)

To the Editor: The rapid spread of coronavirus disease 2019 (COVID-19) brought into sharp focus the conundrum of how to balance evidence-based prescribing versus empirical treatment with repurposed drugs for a pandemic with a high mortality risk. Initial attention focused on hydroxychloroquine (HCQ)/chloroquine (CQ) due to evidence of in vitro activity against the novel severe acute respiratory syndrome coronavirus 2 (1), yet the external validity of these data was limited by knowledge that in vitro antiviral activity did not equate to efficacy in randomized controlled trials (RCTs) of HCQ/CQ treatment for influenza, dengue fever, chikungunya virus, and HIV infection (1). Nonetheless, there was unprecedented interest in HCQ/CQ for use in clinical practice before the results of RCTs were available, potentially affecting medication supply for rheumatology patients. On March 28, 2020, the US Food and Drug Administration (FDA) issued an emergency use authorization for HCQ/CQ in hospitalized COVID-19 patients in the US (2). Following reports of HCQ toxicity in COVID-19, the FDA issued a statement of caution on April 24, 2020, and the emergency use authorization was revoked on June 15, 2020 after findings from RCTs demonstrated that HCQ was not effective for treating COVID-19 and exposed patients to risk of serious adverse events (2). These actions were associated with a 7-fold increase in new community HCQ/CQ prescriptions during the month of March 2020, compared with March 2019, attributable to clinicians who did not routinely prescribe HCQ/CQ (3) and a marked increase in off-label prescriptions for COVID-19 (4). New prescriptions for HCQ in the US in June 2020 remained slightly higher (1.3-fold) than in June 2019 (3). New Zealand charted a different regulatory path, limiting funded use of HCQ to approved indications, such as rheumatic conditions, on March 24, 2020 (5). CQ is not approved for use in New Zealand. The weeks beginning March 15 and March 22, 2020 saw 4.8-fold and 3.7-fold increases in new HCQ users, respectively. However, prescribing then immediately returned to levels comparable to previous years. Mean rates of new HCQ use in New Zealand (2017–2020) and new HCQ/CQ use in the US (2019–2020) are shown in Figure 1. While the contrasting patterns of use between New Zealand and the US likely reflect numerous differences between the 2 countries, including cultural factors, nonpharmaceutical public health interventions, and contrasting health care and political situations (6), these data suggest that regulatory policy in each country influenced the use of HCQ/CQ for COVID-19. What can we learn from the differing experiences in New Zealand and the US? When potential medications for COVID-19 are proposed for clinical use without RCT evidence of efficacy and safety, strong regulatory action to restrict access circumvents excessive medication dispensing that may cause shortages.
International Impact of COVID-19 on the Diagnosis of Heart Disease
Authors: Andrew J. Einstein, Leslee J. Shaw, Cole Hirschfeld, Michelle C. Williams, Todd C. Villines, Nathan Better, Joao V. Vitola, Rodrigo Cerci, Sharmila Dorbala, Paolo Raggi, Andrew D. Choi, Bin Lu, Valentin Sinitsyn, Vladimir Sergienko, Takashi Kudo, Bjarne Linde Nørgaard, Pál Maurovich-Horvat, Roxana Campisi, Elisa Milan, Lizette Louw, Adel H. Allam, Mona Bhatia, Eli Malkovskiy, Benjamin Goebel, Yosef Cohen, Michael Randazzo, Jagat Narula, Thomas N.B. Pascual, Yaroslav Pynda, Maurizio Dondi, Diana Paez
Journal: Journal of the American College of Cardiology (2021)

The coronavirus disease 2019 (COVID-19) pandemic has adversely affected diagnosis and treatment of noncommunicable diseases. Its effects on delivery of diagnostic care for cardiovascular disease, which remains the leading cause of death worldwide, have not been quantified.The study sought to assess COVID-19's impact on global cardiovascular diagnostic procedural volumes and safety practices.The International Atomic Energy Agency conducted a worldwide survey assessing alterations in cardiovascular procedure volumes and safety practices resulting from COVID-19. Noninvasive and invasive cardiac testing volumes were obtained from participating sites for March and April 2020 and compared with those from March 2019. Availability of personal protective equipment and pandemic-related testing practice changes were ascertained.Surveys were submitted from 909 inpatient and outpatient centers performing cardiac diagnostic procedures, in 108 countries. Procedure volumes decreased 42% from March 2019 to March 2020, and 64% from March 2019 to April 2020. Transthoracic echocardiography decreased by 59%, transesophageal echocardiography 76%, and stress tests 78%, which varied between stress modalities. Coronary angiography (invasive or computed tomography) decreased 55% (p < 0.001 for each procedure). In multivariable regression, significantly greater reduction in procedures occurred for centers in countries with lower gross domestic product. Location in a low-income and lower-middle-income country was associated with an additional 22% reduction in cardiac procedures and less availability of personal protective equipment and telehealth.COVID-19 was associated with a significant and abrupt reduction in cardiovascular diagnostic testing across the globe, especially affecting the world's economically challenged. Further study of cardiovascular outcomes and COVID-19-related changes in care delivery is warranted.
The Effects of Home Care Provider Mix on the Care Recipient: An International, Systematic Review of Articles from 2000 to 2020
Authors: Norma B. Coe, R. Tamara Konetzka, Melissa Berkowitz, Emily Blecker, Courtney H. Van Houtven
Journal: Annual Review of Public Health (2021)

In this systematic review, we examine the literature from 2000 to 2020 to ascertain whether we can make strong conclusions about the relative benefit of adding informal care or formal care providers to the care mix among individuals receiving care in the home, specifically focusing on care recipient outcomes. We evaluate how informal care and formal care affect (or are associated with) health care use of care recipients, health care costs of care recipients, and health outcomes of care recipients. The literature to date suggests that informal care, either alone or in concert with formal care, delivers improvements in the health and well-being of older adults receiving care. The conclusions one can draw about the effects of formal care are less clear.
日本人一般集団におけるJポイント上昇の予後的意義:NIPPON DATA90
Authors: Hisamatsu Takashi, Ohkubo Takayoshi, Miura Katsuyuki, Okamura Tomonori, Kadota Aya, Takashima Naoyuki, Murakami Yoshitaka, Horie Minoru, Okayama Akira, Ueshima Hirotsugu
Journal: Circulation (2011)
Comparison of Diagnostic Accuracy for Lower-Extremity Amputation Codes During the ICD-9 and ICD-10 Eras in a High-Risk Population of Patients With Diabetes
Authors: Alyson J. Littman, Andrew K. Timmons, Kathryn P. Moore, Chin-Lin Tseng, Gregory Landry, Jeffrey M. Robbins, Anna Korpak, Edward J. Boyko
Journal: Diabetes Care (2021)

In fiscal year (FY) 2016, the U.S. transitioned to the ICD-10, which includes eight times more amputation procedure codes than the ICD-9. To evaluate trends over time, researchers need assurance that differences over time are not influenced by a change in the coding system. Thus, we aimed to compare the diagnostic accuracy for ascertaining amputations performed during the ICD-9 era compared with during the ICD-10 era, using medical record review as a gold standard. This information will be valuable for others who use electronic health records to study lower-extremity amputation and whose data span this transition.

The source population was veterans who had a procedure code (ICD or Current Procedural Terminology [CPT]) for an initial toe or ray amputation (hereafter referred to as toe amputations) between FY 2005 and FY 2016 and a diagnosis of diabetes or prescription for a diabetes medication in the year prior to their toe amputation (1). We randomly sampled 150 veterans from the parent study (1) who had initial toe amputations in FY 2014 and follow-up through the end of FY 2015 (during the ICD-9 era) and 150 veterans who had initial toe amputations in FY 2016 (during the ICD-10 era). The outcome of interest was an ipsilateral amputation (at any level) in the year after the toe amputation.

Procedure codes were extracted from the Veterans Affairs (VA) Corporate Data Warehouse, which includes data from the VA electronic medical record. To maximize sensitivity for the parent study, we relied on both ICD and CPT codes for identification …
Abstract 16933: Targeted Inhibition of Histone Deacetylase 1 Promotes the Activation of a Cardiomyogenic/Vasculogenic Genetic Program in Human Cardiac-derived Mesenchymal Stromal Cells
Authors: Joseph B Moore, John Zhao, Marcin Wysoczynski, Roberto Bolli
Journal: Circulation (2015)

Alterations in chromatin structure, as mediated by the inhibition of specific HDAC family members, enhance the cardiogenic differentiation capacity of various progenitor cell types; a key property of donor cell populations shown to contribute to the benefits they provide in cardiac cell therapy applications. The influence of HDAC inhibition on cardiac-derived mesenchymal stromal cell (CStC) transdifferentiation or the role of specific HDAC family members in dictating cardiovascular cell lineage specification has not been investigated. In the current study, the consequences of HDAC inhibition on patient-derived CStC proliferation, early induction of cardiac cell lineage commitment markers, and cardiovascular differentiation/cell lineage specification were investigated using the pan-HDAC inhibitor sodium butyrate (NaBu) or shRNA constructs targeting various HDAC family members. CStCs treated with NaBu for 72 hours resulted in a dose-dependent reduction in cell proliferation and a simultaneous induction of cardiogenic transcripts relative to untreated. Further, NaBu treatment stimulated enhanced expression of myocyte- and endothelial-specific markers following dexamethasone-induced differentiation in vitro. shRNA knockdown screens were employed in effort to identify specific HDAC family members responsible for these effects. Accordingly, we revealed the inhibition of HDAC1, but not HDAC4 or HDAC7 (both previously implicated in cardiac differentiation) to promote the activation of a cardiomyogenic/vasculogenic transcriptional program, as well as enhance the expression of early cardiac lineage commitment proteins. Such results identify HDAC1 as a modulator of CStC cardiovascular transdifferentiation and an exploitable target to facilitate CStC-mediated myocardial repair.
Neoadjuvant Chemotherapy in Pancreatic Cancer—Reply
Authors: Giampaolo Perri, Matthew H. G. Katz
Journal: JAMA Surgery (2021)

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Self-reported symptoms in healthy young adults to predict potential coronavirus disease 2019
Authors: Maya Nitecki, Boris Taran, Itay Ketko, Gil Geva, Roey Yosef, Itay Toledo, Gilad Twig, Eva Avramovitch, Barak Gordon, Estela Derazne, Noam Fink, Ariel Furer
Journal: Clinical Microbiology and Infection (2021)

ObjectiveTo assess the utility of self-reported symptoms in identifying positive coronavirus disease 2019 (COVID-19) cases among predominantly healthy young adults in a military setting.MethodsA questionnaire regarding COVID-19 symptoms and exposure history was administered to all individuals contacting the Israeli Defence Forces Corona call-centre, before PCR testing. Surveyed symptoms included cough, fever, sore throat, rhinorrhoea, loss of taste or smell, chest pain and gastrointestinal symptoms. Factors were compared between positive and negative cases based on confirmatory test results, and positive likelihood ratios (LR) were calculated. Results were stratified by sex, body mass index, previous medical history and dates of questioning, and a multivariable analysis for association with positive test was conducted.ResultsOf 24 362 respondents, 59.1% were men with a median age of 20.5 years (interquartile range 19.6–22.4 years). Significant positive LRs were associated with loss of taste or smell (LR 3.38, 95% CI 3.01–3.79), suspected exposure (LR 1.33, 95% CI 1.28–1.39) and fever (LR 1.26, 95% CI 1.17–1.36). Those factors were also associated with positive PCR result in a multivariable analysis (OR 3.51, 95% CI 3.04–4.06; OR 1.86, 95% CI 1.65–2.09; and OR 1.34, 95% CI 1.19–1.51, respectively). Reports of loss of taste or smell increased gradually over time and were significantly more frequent during the late period of the study (63/5231, 1.21%; 156/7941, 1.96%; and 1505/11 190, 13.45%: p < 0.001).ConclusionLoss of taste or smell, report of a suspicious exposure and fever (>37.5°C) were consistently associated with positive LRs for a positive SARS-CoV-2 PCR test result, in a population of predominantly young and healthy adults.
Effect of autologous hematopoietic stem cell transplant on the development of second primary malignancies in multiple myeloma patients
Authors: A. S. Rosenberg, A. Brunson, J. Tuscano, B. A. Jonas, R. Hoeg, T. Wun, T. H. M. Keegan
Journal: Blood Cancer Journal (2021)

Abstract Autologous stem cell transplant (aHSCT) is associated with improved survival for multiple myeloma (MM) patients but may be associated with second primary malignancy (SPM) development. Using the California Cancer Registry linked to statewide hospitalization data, we determined the cumulative incidence (CMI) of SPMs more than 1 year after MM diagnosis, accounting for the competing risk of death. AHSCT recipients were matched 1:2 to non-aHSCT patients. Adjusted hazard ratios (aHR) were estimated using the Fine and Gray method. Among 16,331 patients, 933 (5.7%) developed a SPM more than 1 year after diagnosis. The 10-year CMI of developing any SPM was 6.6%, 5.7% for solid tumor SPM and 0.9% for hematologic malignancies. The 10-year CMI of developing any SPM was similar among aHSCT [9.1% (7.7–10.7%)] and non-aHSCT [7.5% (6.5–8.6%)] ( P = 0.26) recipients and there was no difference in solid-tumor SPMs ( P = 0.98). The 10-year CMI of hematologic SPMs was higher among aHSCT recipients [2.1% (1.4–2.9%) vs. 0.8% (0.5–1.2%); P = 0.005], corresponding to a 1.3% absolute increase and an aHR of 1.51 (1.01–2.27). Ten-year myeloma-specific and non-cancer mortality rates were 59% (58.2–60.0%) and 18.1% (17.4–18.8%), respectively. Although aHSCT was associated with a small increase in hematologic SPMs, mortality was driven by MM and non-cancer causes.
Association of Mitral Annular Disjunction With Premature Cardiac Mortality in a Large Series of Autopsies
Authors: Nan Zhou, Qianhao Zhao, Xiaofeng Zeng, Da Zheng, Jiacheng Yue, Kai Zhang, Danmi Mao, Jonathan C. Makielski, Jianding Cheng
Journal: Journal of the American College of Cardiology (2021)
Significance of serglycin and its binding partners in autocrine promotion of metastasis in esophageal cancer
Authors: Yun Zhu, Alfred K.Y. Lam, Daisy K.Y. Shum, Di Cui, Jun Zhang, Dong Dong Yan, Bin Li, Wen Wen Xu, Nikki P.Y. Lee, Kin Tak Chan, Simon Law, Sai Wah Tsao, Annie L.M. Cheung
Journal: Theranostics (2021)

Rationale:Little is known about the roles of proteoglycans in esophageal cancer.This study aims to investigate the roles and mechanisms of serglycin (SRGN) proteoglycan in promoting metastasis of esophageal squamous cell carcinoma (ESCC).Methods: Reverse phase protein array analysis was used to identify activated signaling pathways in SRGN-overexpressing cells.Chemokine array was used to identify differentially secreted factors from SRGN-overexpressing cells.Binding between SRGN and potential interacting partners was evaluated using proximity ligation assay and co-immunoprecipitation.The glycosaminoglycan (GAG) chains of SRGN were characterized using fluorophore-assisted carbohydrate electrophoresis.Tissue microarray and serum samples were used to determine the correlation of SRGN expression with clinicopathological parameters and patient survival.Results: In vitro and in vivo experiments showed that SRGN promoted invasion and metastasis in ESCC via activating ERK pathway, stabilizing c-Myc and upregulating the secretion of matrix metalloproteinases.SRGN-knockdown suppressed tumorigenic hallmarks.These SRGN-elicited functions were carried out in an autocrine manner by inducing the secretion of midkine (MDK), which was further identified as a novel binding partner of SRGN for the formation of a SRGN/MDK/CD44 complex.In addition, SRGN interacted with MDK and matrix metalloproteinase 2 in ESCC via its GAG chains, which were mainly decorated with chondroitin sulfate comprising of ∆di-4S and ∆di-6S CS.Clinically, high expression of serum SRGN in serum of patients with ESCC was an independent prognostic marker for poor survival.Conclusions: This study provides the first evidence that elevated serum SRGN has prognostic significance in patients with ESCC, and sheds light on the molecular mechanism by which elevated circulating SRGN in cancer patients might promote cancer progression.
Abstract 9544: Hemodynamic Impact of Glucose-6-phosphate Dehydrogenase Inhibitor in Pulmonary Arterial Hypertension Model Mice
Authors: Atsushi Kitagawa, Sachin Gupte
Journal: Circulation (2019)

Background: Pulmonary arterial hypertension (PAH) is a result of abnormal hyperplasia of pulmonary vascular cells. The pentose phosphate pathway (PPP) is a first committed step of glucose metabolis...
Tissue physiology revolving around the clock: circadian rhythms as exemplified by the intervertebral disc
Authors: Honor Morris, Cátia F Gonçalves, Michal Dudek, Judith Hoyland, Qing-Jun Meng
Journal: Annals of the Rheumatic Diseases (2021)

Circadian clocks in the brain and peripheral tissues temporally coordinate local physiology to align with the 24 hours rhythmic environment through light/darkness, rest/activity and feeding/fasting cycles. Circadian disruptions (during ageing, shift work and jet-lag) have been proposed as a risk factor for degeneration and disease of tissues, including the musculoskeletal system. The intervertebral disc (IVD) in the spine separates the bony vertebrae and permits movement of the spinal column. IVD degeneration is highly prevalent among the ageing population and is a leading cause of lower back pain. The IVD is known to experience diurnal changes in loading patterns driven by the circadian rhythm in rest/activity cycles. In recent years, emerging evidence indicates the existence of molecular circadian clocks within the IVD, disruption to which accelerates tissue ageing and predispose animals to IVD degeneration. The cell-intrinsic circadian clocks in the IVD control key aspects of physiology and pathophysiology by rhythmically regulating the expression of ~3.5% of the IVD transcriptome, allowing cells to cope with the drastic biomechanical and chemical changes that occur throughout the day. Indeed, epidemiological studies on long-term shift workers have shown an increased incidence of lower back pain. In this review, we summarise recent findings of circadian rhythms in health and disease, with the IVD as an exemplar tissue system. We focus on rhythmic IVD functions and discuss implications of utilising biological timing mechanisms to improve tissue health and mitigate degeneration. These findings may have broader implications in chronic rheumatic conditions, given the recent findings of musculoskeletal circadian clocks.
Ways to Support Low-Income, At-Risk Young Children During and After Coronavirus Disease 2019
Authors: Venus Wong
Journal: JAMA Pediatrics (2021)

equipment, and/or therapy services to learn best are not well served by exclusively remote education.Second, individual education plans are important tools for equity.To assure that children with disabilities receive quality education and are appropriately accommodated, individual education plans should proactively account for limitations on class sizes, minimization of group activities, and truncation of the school day.Education in the least restrictive environment, the legal standard, is the goal while assuring safety and mitigating risk.Third, retention of therapy and paraprofessional support in schools has to be prioritized as budget cuts tighten operating margins for school districts.A largescale exodus of these professionals from the education sector would be catastrophic for children with disabilities.In addition to those operational realities, 2 truisms should drive planning to reopen schools.First, keeping children with disabilities safe in schools will necessitate effort.Schools should plan for those who require specialized transportation, those who cannot wear a mask, and those who need cleaning of specialized equipment.Next, there should be creative approaches to replace the socialization and integration that children with disabilities receive in mainstream group academic activities such as art, physical education, and field trips, which are slated to be minimized as schools reopen.Children with disabilities are more isolated than their peers, 4 and reopening plans must not exacerbate that reality.Even before the pandemic, budget cuts made it difficult for schools to implement adaptations critical to optimize learning for children with disabilities.However, these children are not disposable and future legislative and operational efforts should focus on child health and well-being 5 for all children.