tbuckley/cabot-search huggingface dataset:
Associations of Trabecular and Cortical Volumetric Bone Mineral Density With Coronary Artery Calcification Score
Authors: Thomas Funck-Brentano, Louise Grahnemo, Ola Hjelmgren, John Brandberg, Göran Bergström, Claes Ohlsson
Journal: JAMA Cardiology (2020)

The link between osteoporosis and cardiovascular diseases has been extensively reported, and previous studies show an inverse association between trabecular bone volumetric bone mineral density (Tb.vBMD) in the spine and coronary artery calcification score (CACS). 1,2However, the association between cortical vBMD (Ct.vBMD) in the long bones and CACS may differ from the association for Tb.vBMD because the 2 bone compartments are largely differentially regulated. 3 Methods | To compare the associations of Tb.vBMD and Ct.vBMD with CACS, we used the cross-sectional population-based Swedish Cardiopulmonary Bioimage Study (SCAPIS) pilot cohort, consisting of randomly selected participants aged 50 to 64 years. 4 Coronary artery calcification score expressed as Agatston score, 4 Tb.vBMD in the vertebral body of the 12th thoracic vertebra, 5 and Ct.vBMD at the right midshaft femur 5 were all assessed in 1060 participants (519 men and 541 women) using computed tomography (Table ).Institutional ethical review board approval was obtained, and written consent was obtained for all patients.A 2-sided P value less than .05was considered significant.Results | The association between Tb.vBMD and Ct.vBMD was modest (variance explained r 2 = 11%), demonstrating that these parameters may provide substantial nonoverlapping information for prediction of CACS.In combined models also adjusted for cardiovascular risk factors (full model in the Figure), Tb.
Highly sensitive and full-genomeinterrogation of SARS-CoV-2 using multiplexed PCRenrichment followed by next-generation sequencing
Authors: Chenyu Li, David N. Debruyne, Julia Spencer, Vidushi Kapoor, Lily Y. Liu, Bo Zhou, Utsav Pandey, Moiz Bootwalla, Dejerianne Ostrow, Dennis T. Maglinte, David Ruble, Alex Ryutov, Lishuang Shen, Lucie Lee, Rounak Feigelman, Grayson Burdon, Jeffrey Liu, Alejandra Oliva, Adam Borcherding, Hongdong Tan, Alexander E. Urban, Xiaowu Gai, Jennifer Dien Bard, Guoying Liu, Zhitong Liu
Journal: Clinical Cancer Research (2020)

Many detection methods have been used or reported for the diagnosis and/or surveillance of COVID-19  Amongthem, reverse transcription polymerase chain reaction (RT-PCR) is the most commonly used because of its highsensitivity, typically claiming detection of about 5 copies of viruses  However, it has been reported that only 47-59%of the positive cases were identified by some RT-PCR methods, probably due to low viral load, timing of sampling, degradation of virus RNA in the sampling process, or possible mutations spanning the primer binding sites Therefore, alternative and highly sensitive methods are imperative  With the goal of improving sensitivity andaccommodating various application settings, we developed a multiplex-PCR-based method comprising 343 pairs ofspecific primers and demonstrated its efficiency at detecting SARS-CoV-2 at low copy numbers  The assayproduced clean characteristic target peaks of defined sizes, which allowed for direct identification of positives byelectrophoresis  We further amplified the entire SARS-CoV-2 genome from 8 to half a million viral copies purifiedfrom 13 COVID-19 positive specimens and detected mutations through next-generation sequencing  Finally, wedeveloped a multiplex-PCR-based metagenomic method in parallel that required modest sequencing depth foruncovering SARS-CoV-2 mutational diversity and potentially novel or emerging isolates
Health care coach support in reducing acute care use in patients with cancer.
Authors: Manali I. Patel, Kim Smith, Etsegenet Sisay, David J. Park
Journal: Journal of Clinical Oncology (2020)

4 Background: Lay health workers (LHWs) who are trained to proactively discuss goals of care and assess patient symptoms have improved value-based cancer care among Veterans and a Medicare Advantage population. Little data exists regarding the effect of integrating LHWs into community oncology care among commercially insured populations. In this study, we implemented an LHW intervention to assist with goals of care and symptom management in collaboration with a private community oncology practice among patients with advanced cancer. This randomized controlled trial evaluates the effect of the intervention on acute care use and secondarily on goals of care documentation and patient satisfaction. Methods: Newly diagnosed patients with advanced stages of solid and hematologic malignancies were randomized from 8/11/2016 through 6/5/2019 into the intervention and control groups. All patients were followed for 12 months or death, whichever was first. Patients reported satisfaction with care using the Consumer Assessment of Healthcare Providers and Systems survey at time of enrollment and 9 months follow-up. We compared risk of death using Cox Models and compared rates of acute care, palliative care and hospice use using generalized models adjusted for length of follow-up. Results: A total of 104 patients were randomized with 52 in the intervention and 52 in the control. In both groups, the mean age was 67 years; 70% were non-Hispanic white, 25% Asian Pacific Islander, 1% Native Hawaiian, 1% American Indian/Alaskan Native, 3% multiple races/ethnicities. There were no differences in cancer diagnoses or stages. There were no differences in rates of survival between the two groups. Intervention patients as compared to the control had lower mean emergency department visits (0.80 +/- 0.17 versus 1.9 +/- 0.46, p = 0.02) and hospitalizations (0.67 +/- 0.19 versus 1.49 +/- 0.37, p = 0.04), greater rates of goals of care documentation (92% versus 33% p = 0.002) and no differences in palliative care (88% versus 77% p = 0.16) or hospice use (27% versus 21% p = 0.45). At 9 months follow-up as compared to baseline, patients in the intervention experienced greater improvements in satisfaction with their care (difference-in-difference: 0.41, 95% CI 0.22-0.60, p &lt; 0.001). Conclusions: An LHW intervention significantly reduced acute care use and improved patient experiences with cancer care as compared to a control group. This intervention may be a solution to improve care delivery and experiences for patients after a diagnosis of cancer in community oncology settings. Clinical trial information: NCT03154190 .
Priadel: Plan to withdraw bipolar drug is paused while competition watchdog investigates
Authors: Jacqui Wise
Journal: BMJ (2020)

The manufacturer of Priadel, a brand of lithium widely used to treat bipolar disorder, has halted plans to withdraw the drug after the Competition and Markets Authority (CMA) launched an investigation into whether the company had broken the law.1

Essential Pharma had previously announced it would withdraw the drug in April 2021 forcing patients to switch to alternative, more expensive brands.

Priadel costs £4.02 (€4.4; $5) for a pack of 400 mg tablets. The company also owns the other main brand of lithium, Camcolit, and recently increased its price to £48.18 per pack of 400 mg tablets.

The CMA is investigating whether Essential Pharma has “abused a dominant position” by withdrawing Priadel and pushing patients towards its more expensive alternative treatment. It said it has reasonable grounds to suspect Essential …
Development and evaluation of an ultrasound-triggered microbubble combined transarterial chemoembolization (TACE) formulation on rabbit VX2 liver cancer model
Authors: Doyeon Kim, Jae Hwan Lee, Hyungwon Moon, Minkyu Seo, Hyounkoo Han, Hongkeun Yoo, Howon Seo, Jingu Lee, Sujung Hong, Pilhan Kim, Hak Jong Lee, Jin Wook Chung, Hyuncheol Kim
Journal: Theranostics (2020)

Transarterial chemoembolization (TACE) is an image-guided locoregional therapy used for the treatment of patients with primary or secondary liver cancer. However, conventional TACE formulations are rapidly dissociated due to the instability of the emulsion, resulting in insufficient local drug concentrations in the target tumor. Methods: To overcome these limitations, a doxorubicin-loaded albumin nanoparticle-conjugated microbubble complex in an iodized oil emulsion (DOX-NPs-MB complex in Lipiodol) has been developed as a new ultrasound-triggered TACE formulation. Results: (1) Microbubbles enhanced therapeutic efficacy by effectively delivering doxorubicin- loaded nanoparticles into liver tumors via sonoporation under ultrasound irradiation (US+). (2) Microbubbles constituting the complex retained their function as an ultrasound contrast agent in Lipiodol. In a rabbit VX2 liver cancer model, the in vivo study of DOX-NPs-MB complex in Lipiodol (US+) decreased the viability of tumor more than the conventional TACE formulation, and in particular, effectively killed cancer cells in the tumor periphery. Conclusion: Incorporation of doxorubicin-loaded microbubble in the TACE formulation facilitated drug delivery to the tumor with real-time monitoring and enhanced the therapeutic efficacy of TACE. Thus, the enhanced TACE formulation may represent a new treatment strategy against liver cancer.
Evaluating the impact of COVID-19 on medical oncology workforce and cancer care in Canada: A serial survey study
Authors: Sharlene Gill, Bruce Colwell, Hal Hirte, Welch Stephen, Alexi Campbell, Desiree Hao
Journal: Clinical Cancer Research (2020)

Background: The first case of COVID-19 (SARS-CoV-2, C19) was reported to Health Canada on Jan 25th, 2020 By March 18th, states of emergency were declared across multiple provinces  The pandemic has presentedprofessional and personal challenges for the medical oncology workforce and cancer care  Under the auspices ofthe Canadian Association of Medical Oncology (CAMO), we sought to examine the temporal effects of C19 onmedical oncologists and care practices across Canada  Methods: Two serial multiple-choice, web-based national surveys were conducted in 2020from March 30th toApril 4th (S1) and May 6th to May 15 , 2020 (S2)  The surveys were distributed by email to medical oncologistsidentified through CAMO and the Royal College of Physicians and Surgeons Medical Oncology directory (n=618) Participation was voluntary with no compensation  Descriptive analyses with frequency distributions are reported  Results: A total of 157 completed responses were received for S1 and 159 responses for S2 (25% response rate) Demographics were similar between S1/S2: from comprehensive cancer centre (87%/86%), greater than 15 years inpractice (41%/46%), CAMO member (60%/65%)  Moderate to extreme concern of C19 exposure decreased overtime for self (79%/54%), for family (82%/65%), and for patient (pt) (71%/54%)  Routine use of PPE increased(67%/100%) with less concern around PPE access (69%/28%)  Frequent anxiety (54%/32%) and depression(19%/14%) lessened while frequent lack of interest (18%/17%) and lack of focus (33%/31%) were unchanged  Useof telemedicine for >50% of pts remained high (82%/86%), and confidence in adequate health care access for ptsincreased (39%/59%)  Centre accrual activity to clinical trials increased (46%/67%)  Change in chemotherapy for>20% of pts was reported infrequently (33%/23%)  Cancer prognosis and treatment benefit remained the primarydeterminant in treatment decision-making (rank score: 7 50/7 95) while resource access (6 19/5 68) and pt risk ofC19 (6 05/5 72) became less important  Conclusions: As the pandemic curve flattens and Canadian medical oncologists adjust to a new normal, positivetrends can be observed in concerns around C19 exposure, frequency of anxiety and depression, concerns aboutPPE access, confidence in health care access, and accrual to clinical trials  Chemotherapy plans remainedunchanged for the majority of pts  A high rate of early adoption of telemedicine was observed and maintained  Serialfollow-up is valuable to understand changing perceptions and practices
Identification of human long noncoding RNAs associated with nonalcoholic fatty liver disease and metabolic homeostasis
Authors: Xiangbo Ruan, Ping Li, Yonghe Ma, Cheng-fei Jiang, Yi Chen, Yu Shi, Nikhil Gupta, Fayaz Seifuddin, Mehdi Pirooznia, Yasuyuki Ohnishi, Nao Yoneda, Megumi Nishiwaki, Gabrijela Dumbovic, John L. Rinn, Yuichiro Higuchi, Kenji Kawai, Hiroshi Suemizu, Haiming Cao
Journal: Journal of Clinical Investigation (2020)

A growing number of long noncoding RNAs (lncRNAs) have emerged as vital metabolic regulators. However, most human lncRNAs are nonconserved and highly tissue specific, vastly limiting our ability to identify human lncRNA metabolic regulators (hLMRs). In this study, we established a pipeline to identify putative hLMRs that are metabolically sensitive, disease relevant, and population applicable. We first progressively processed multilevel human transcriptome data to select liver lncRNAs that exhibit highly dynamic expression in the general population, show differential expression in a nonalcoholic fatty liver disease (NAFLD) population, and respond to dietary intervention in a small NAFLD cohort. We then experimentally demonstrated the responsiveness of selected hepatic lncRNAs to defined metabolic milieus in a liver-specific humanized mouse model. Furthermore, by extracting a concise list of protein-coding genes that are persistently correlated with lncRNAs in general and NAFLD populations, we predicted the specific function for each hLMR. Using gain- and loss-of-function approaches in humanized mice as well as ectopic expression in conventional mice, we validated the regulatory role of one nonconserved hLMR in cholesterol metabolism by coordinating with an RNA-binding protein, PTBP1, to modulate the transcription of cholesterol synthesis genes. Our work overcame the heterogeneity intrinsic to human data to enable the efficient identification and functional definition of disease-relevant human lncRNAs in metabolic homeostasis.
Disparities in COVID-19 severity and risk of death in cancer patients: Experiences from a U.K. cancer center.
Authors: Beth Russell, Charlotte L Moss, Sophie Papa, Harriet Wylie, Anna Haire, Fidelma Cahill, Mary Lei, Sharmistha Ghosh, Richard Sullivan, Anne Sagar Rigg, Saoirse Dolly, Mieke Van Hemelrijck
Journal: Journal of Clinical Oncology (2020)

285 Background: There has been widespread evidence emerging regarding disparities between COVID-19 outcomes in patients of varying ethnicities and background. It is, however, unclear how various patient characteristics affect COVID-19 severity and risk of death in a cancer population. Methods: Our Cancer Centre was at the epicentre of the COVID-19 outbreak in the UK. A total of 156 cancer patients had a confirmed COVID-19 diagnosis between the 29th of February through the 12th of May 2020. Logistic/Cox proportional hazards models were used to identify which demographic and/or clinical characteristics were associated with COVID-19 severity/death. The regression models were defined through a directed acyclic graph (DAG) to decide upon the minimal adjustments required for each statistical model. Results: Of the 156 COVID-19 positive cancer patients, the most frequently reported tumour types were urological/gynaecological (29%), followed by haematological (18%) and breast (15%). 128 (82%) presented with mild/moderate COVID-19 and 28 (18%) with severe disease. Initial diagnosis of cancer &gt;24m before COVID-19 (OR:1.74 (95%CI: 0.71-4.26)), presenting with fever (6.21 (1.76-21.99)), dyspnoea (2.60 (1.00-6.76)), gastro-intestinal symptoms (7.38 (2.71-20.16)), or higher levels of CRP (9.43 (0.73-121.12)) were linked with greater COVID-19 severity. During median follow-up of 37 days, 34 patients had died of COVID-19 (22%). Asian ethnicity (3.73 (1.28-10.91), palliative treatment (5.74 (1.15-28.79), initial diagnosis of cancer &gt;24m before (2.14 (1.04-4.44), dyspnoea (4.94 (1.99-12.25), and increased CRP levels (10.35 (1.05-52.21)) were positively associated with COVID-19 death. Socioeconomic status (SES) was not found to be associated with either COVID-19 severity or risk of death. We will present updated data with more mature follow-up. Conclusions: In cancer patients, Asian ethnicity was found to be positively associated with COVID-19 death compared to Caucasian patients. However, SES was not associated with COVID-19 severity or risk of death thereby implying this was not due to poor access to healthcare. Future studies hence need to identify the underlying biological and/or societal reasons explaining these ethnic disparities in COVID-19 outcomes for cancer patients.
COVID-19 in relation to hematologicevents and mortality in subset of inpatient cancer patients
Authors: Saikrishna Gadde, Ambuga Badari, John Cole, Nikhil Manjunath
Journal: Clinical Cancer Research (2020)

COVID-19 is a newly diagnosed entity that has been identified for about 6 months  With the US now being theprevalent nation affected, we aimed to identify factors that were relevant to survival and hematologic events inCOVID patients  Our group had primarily been assessing COVID-19-confirmed patients as per PCR at OchsnerMedical Center in Louisiana;we primarily studied patients who were admitted between January 2020 to May 2020 Main events that are currently being studied include factors such as mortality, length of stay, and bleeding orthrombotic events  Secondary endpoints included factors such as influence on blood type and also amount oftransfusions required by these patients  Our overall analysis of 1,773 patients yielded a number of 60 patients whomwe were able to identify as having an active cancer diagnosis  This disproportionate number of patients may berelated to factors such as reluctance to visit the hospital among cancer patients, a phenomenon noted similarly inCardiology, where the number of admissions for cardiac causes had declined suddenly during this pandemictimeline  One half of our population was African American and included an even proportion of males and females The age range of patients was between 35-93 years  The most common malignancies that were noted to co-occur with COVID-19 in our population seemed to be lung, prostate, and hematologic malignancies  Although finalanalyses regarding mortality are to be completed, the proportion of patients who had died with a diagnosis of cancer was around 50% per collection of our current data  Twenty three out of 60 (38%) patients required bloodtransfusions  In comparison to other reports that had reported bleeding events and thrombotic events, our reportrevealed a much lower rate of bleeding events (5/60) and thrombotic events (5/60)  We plan to repeat our analysisto assess for any confounders in identifying these events, as noted, since some earlier literature had reportedbetween one quarter to two thirds of patients having a thrombotic event  Our analysis also looks at other descriptivevariables such as use of anticoagulant and antiplatelet agents, absolute counts of neutrophils and lymphocytes, platelets, and coagulation markers  Also, our assessment includes a study in assessment of any delays noted inchemotherapy dates for these patients
The impact of Covid-19 on publicgenerosity toward cancer-related crowdfunding efforts
Authors: Katrina A. Fischer, Robert E. Miller, Sidharth Anand, John Glaspy
Journal: Clinical Cancer Research (2020)

Background: Many patients with cancer rely on public crowdfunding platforms to generate financial support towardcosts associated with their medical care  It is unclear how financial uncertainties resulting from the Covid-19pandemic may impact patient need and public support toward routine cancer-focused campaigns  Methods: Using custom code for web scraping, we identified all campaigns that were generated on thecrowdfunding platform GoFundMe com in the “Medical, Illness and Healing” category between 8/17/2019 and5/8/2020  This date represents six months of fundraising prior to the first official shelter-in-place order on 3/17/2020 We then abstracted campaigns that included the word “cancer,” originated in the United States, and had raised atleast one dollar  Of these cancer-related campaigns, we collected the dollar amount raised in the first 30 days ofcampaign generation and the total raised to date  Campaigns generated between 2/17/2020 and 3/16/2020 were notincluded in pre/post-Covid calculations because these campaigns would potentially include contributions made after3/17/2020 within their first 30-day values  Results: 19,669 cancer campaigns were identified during the study period (16,823 between 8/17/19 and 2/17/20and 2,846 between 3/17/20 and 5/8/20), raising on average 83% of total funds within the first 30 days of campaigngeneration  In the six months prior to the first shelter-in-place order (8/17/19-2/17/20), there were on average 91new cancer campaigns generated daily  Within the first 30 days, these campaigns averaged $4,472 (median$1,815)  After 3/17/20, an average of 54 campaigns were generated daily, representing a 40% decline in dailycampaign generation  Within the first 30 days, these campaigns averaged $6,130 (median $2,950), representing a36% and 60% increase from baseline respectively  Conclusion: Public generosity has increased toward cancer fundraising campaigns since the Covid-19 pandemic, but fewer patients are creating new campaigns  Patients can be reassured that they will likely continue to benefitfrom public support and should not feel limited in asking for help during this period of economic uncertainty  Asphilanthropy sometimes increases during disaster periods, it is unclear if continued support will persist as longer-term economic changes take effect
Bone Regeneration: Membranes for Guided Bone Regeneration: A Road from Bench to Bedside (Adv. Healthcare Mater. 19/2020)
Authors: Paola Aprile, Didier Letourneur, Teresa Simon‐Yarza
Journal: Advanced Healthcare Materials (2020)

Membranes for guided bone regeneration (GBR) strategies are a class of medical devices (MDs) developed to elicit new bone formation by protecting the defect site. In article number 2000707, Didier Letourneur and co-workers elucidate the complex scientific translation of biomaterials for such a class of MDs. Hence, the focus in their review is set on the latest advancements in GBR membranes, their regulatory framework, and the industrialization process that brings these MDs to market.
Oxidative stress and glutamate excretion in alcoholic steatosis: Metabolic synapse between hepatocyte and stellate cell
Authors: Hee-Hoon Kim, Sung Eun Choi, Won-Il Jeong
Journal: Clinical and Molecular Hepatology (2020)

Chronic alcohol consumption induces the development of alcoholic steatosis in the liver, which is one of the most widespread liver diseases worldwide. During general alcohol metabolism, hepatocytes generate mitochondria- and cytochrome P450 2E1 (CYP2E1)-mediated reactive oxygen species (ROS) whose accumulation elicits activation of the hepatic anti-oxidant system, including glutathione (GSH). However, chronic alcohol consumption decreases GSH generation through cysteine deficiency by suppressing the methionine cycle and trans-sulfuration system, whereas it turns on an alternative defense pathway, such as the xCT transporter, to compensate for GSH shortage. The xCT transporter mediates the uptake of cystine coupled to the efflux of glutamate, leading to an increase in blood glutamate. In response to the elevated glutamate in the liver, the expression of metabotropic glutamate receptor 5 (mGluR5) is up-regulated in hepatic stellate cells (HSCs) along with enhanced production of 2-arachidonoylglycerol, which in turn stimulates cannabinoid receptor 1 (CB1R) on neighboring hepatocytes to increase de novo lipogenesis. On the other hand, blockade of mGluR5 and CB1R attenuates alcoholic steatosis. Interestingly, although the increased expression of CYP2E1-mediated xCT and ROS generation are mainly observed at the perivenous area (zone 3), fat accumulation is mostly detected at hepatic zone 2. To resolve this discrepancy, this review summarizes recent advances on glutamate/mGluR5-derived alcoholic steatosis and zone-dependently different responses to alcohol intake. In addition, the bidirectional loop pathway and its unique metabolic synapse between hepatocytes and HSCs are discussed.