tbuckley/cabot-search huggingface dataset:
Trump’s call for essential drugs to be made in US threatens innovation, says trade group
Authors: Janice Hopkins Tanne
Journal: BMJ (2020)

The trade group for the US pharmaceutical industry has warned that President Donald Trump’s latest executive order calling for essential drugs to be manufactured in the US will stifle innovation.

The executive order, issued on 6 August,1 followed four other executive orders designed to reduce drug prices, which all seem to be part of Trump’s appeal to voters in the November election. All require further action by government agencies and may be challenged in the courts so are unlikely to take effect any time soon.

Stephen Ubl, president of PhRMA, the drug industry organisation, said that Trump’s “buy American” executive order “creates even more barriers to ongoing biopharmaceutical manufacturing and innovation.” He said, “Companies are working around the clock to …
Medicaid Expansion and Rates of Opioid-Related Hospital Use—Reply
Authors: Aparna Soni
Journal: JAMA Internal Medicine (2020)

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Abstract 12789: Comparisons of Clinical Features and Prognosis of Heart Failure Patients With Reduced Ejection Fraction Between Japanese Women and Men
Authors: Yuki Kanno, Yoshihisa Akiomi, Yasuhiro Ichijyo, Takatoyo Kiko, Yusuke Kimishima, Yu Sato, Tetsuro Yokokawa, Satoshi Abe, Tomofumi Misaka, Takamasa Sato, Masayoshi Oikawa, Atsushi Kobayashi, Takayoshi Yamaki, Hiroyuki Kunii, Kazuhiko Nakazato, Takafumi Ishida, Yasuchika Takeishi
Journal: Circulation (2019)

Background: It has been recently reported that women with heart failure with reduced ejection fraction (HFrEF) live longer than men, but women continue to receive suboptimal treatment, compared wit...
Impact of lockdown on rheumatology outpatient care in the age of COVID-19
Authors: Benjamin Sachdev Manjit Singh, Seow Lin Chuah, Yaw Kiet Cheong, Sharifah Aishah Wan, Cheng Lay Teh
Journal: Annals of the Rheumatic Diseases (2020)

We read with great interest the editorial written by McInnes1 who discussed regarding the role of the rheumatologist and the rapidly changing landscape in the practice of rheumatology brought about by the COVID-19 pandemic. European League Against Rheumatism (EULAR)2 had also recently published several recommendations for the management of rheumatic and musculoskeletal diseases when local measures of social distancing are in effect. We were interested in the impact caused by local public health measures to control the pandemic on rheumatology outpatient care at our centre.

Extraordinary measures have been advocated globally to control the spread of the COVID-19 pandemic. Malaysia’s first COVID-19 case was reported on the 25 January 20203 and cases spiked in March 2020 reaching the highest number in South-East Asia in early April. Malaysia instituted a lockdown from 18 March 2020 which was extended 9 June 2020 (a 12-week period) as a public health measure to curb the pandemic.4 5

During the pandemic, our hospital was designated as a COVID-19 hybrid hospital tasked with taking in both COVID-19 and regular patients. Several hospital-wide strategies were implemented to contain the pandemic and decongest the hospital including rescheduling of non-urgent patient appointments, reducing non-essential …
What to do with appraisal: an idea whose time has come
Authors: Sebastian Kraemer
Journal: BMJ (2020)

Gerada writes: “Reflection . . . is a process of discovery with outcomes that might be unexpected, creative, and different for each participant.”1

The current crisis has highlighted the “front line” where, even without a pandemic, there is no doubting the stress of clinical work.2 During the second world war social scientists appointed by the British army to select potential officers …
WHO2016 Vs. WHO2008 Criteria for the Diagnosis of Chronic Myelomonocytic Leukemia
Authors: Sung-Ran Cho, Joon Seong Park, Yeonsook Moon, Mi Hyang Kim, Jeong-Yeal Ahn, Jungwon Huh, Hye Ryoun Kim, Jae Ho Han
Journal: Blood (2017)
Effect of the COVID-19 pandemic response on intrapartum care, stillbirth, and neonatal mortality outcomes in Nepal: a prospective observational study
Authors: Ashish KC, Rejina Gurung, Mary V Kinney, Avinash K Sunny, Md Moinuddin, Omkar Basnet, Prajwal Paudel, Pratiksha Bhattarai, Kalpana Subedi, Mahendra Prasad Shrestha, Joy E Lawn, Mats Målqvist
Journal: The Lancet Global Health (2020)

BackgroundThe COVID-19 pandemic response is affecting maternal and neonatal health services all over the world. We aimed to assess the number of institutional births, their outcomes (institutional stillbirth and neonatal mortality rate), and quality of intrapartum care before and during the national COVID-19 lockdown in Nepal.MethodsIn this prospective observational study, we collected participant-level data for pregnant women enrolled in the SUSTAIN and REFINE studies between Jan 1 and May 30, 2020, from nine hospitals in Nepal. This period included 12·5 weeks before the national lockdown and 9·5 weeks during the lockdown. Women were eligible for inclusion if they had a gestational age of 22 weeks or more, a fetal heart sound at time of admission, and consented to inclusion. Women who had multiple births and their babies were excluded. We collected information on demographic and obstetric characteristics via extraction from case notes and health worker performance via direct observation by independent clinical researchers. We used regression analyses to assess changes in the number of institutional births, quality of care, and mortality before lockdown versus during lockdown.FindingsOf 22 907 eligible women, 21 763 women were enrolled and 20 354 gave birth, and health worker performance was recorded for 10 543 births. From the beginning to the end of the study period, the mean weekly number of births decreased from 1261·1 births (SE 66·1) before lockdown to 651·4 births (49·9) during lockdown—a reduction of 52·4%. The institutional stillbirth rate increased from 14 per 1000 total births before lockdown to 21 per 1000 total births during lockdown (p=0·0002), and institutional neonatal mortality increased from 13 per 1000 livebirths to 40 per 1000 livebirths (p=0·0022). In terms of quality of care, intrapartum fetal heart rate monitoring decreased by 13·4% (−15·4 to −11·3; p<0·0001), and breastfeeding within 1 h of birth decreased by 3·5% (−4·6 to −2·6; p=0·0032). The immediate newborn care practice of placing the baby skin-to-skin with their mother increased by 13·2% (12·1 to 14·5; p<0·0001), and health workers' hand hygiene practices during childbirth increased by 12·9% (11·8 to 13·9) during lockdown (p<0·0001).InterpretationInstitutional childbirth reduced by more than half during lockdown, with increases in institutional stillbirth rate and neonatal mortality, and decreases in quality of care. Some behaviours improved, notably hand hygiene and keeping the baby skin-to-skin with their mother. An urgent need exists to protect access to high quality intrapartum care and prevent excess deaths for the most vulnerable health system users during this pandemic period.FundingGrand Challenges Canada.
Incidence of and trends in hip fracture among adults in urban China: A nationwide retrospective cohort study
Authors: Chenggui Zhang, Jingnan Feng, Shengfeng Wang, Pei Gao, Lu Xu, Junxiong Zhu, Jialin Jia, Lili Liu, Guozhen Liu, Jinxi Wang, Siyan Zhan, Chunli Song
Journal: PLoS Medicine (2020)

Background Hip fracture is a public health concern because of its considerable morbidity, excess mortality, great risk of disability, and high societal healthcare costs. China has the largest population of older people in the world and is experiencing rapid population aging and facing great challenges from an increasing number of hip fractures. However, few studies reported the epidemiology, especially at a national level. We aimed to evaluate trends in hip fracture incidence and associated costs for hospitalization in China. Methods and findings We conducted a population-based study using data between 2012 and 2016 from the national databases of Urban Employee Basic Medical Insurance and Urban Resident Basic Medical Insurance in China, covering about 480 million residents. Data from around 102.56 million participants aged 55 years and older during the study period were analyzed. A total of 190,560 incident hip fracture patients (mean age 77.05 years, standard deviation 8.94; 63.99% female) were identified. Primary outcomes included the age- and sex-specific incidences of hip fracture. Associated annual costs for hospitalization were also calculated. Incidence was described as per 100,000 person-years at risk, and 95% confidence intervals were computed assuming a Poisson distribution. Hip fracture incidence overall in China did not increase during the study period despite rapid population aging. Incidence per 100,000 was 180.72 (95% CI 137.16, 224.28; P < 0.001) in 2012 and 177.13 (95% CI 139.93, 214.33; P < 0.001) in 2016 for females, and 121.86 (95% CI 97.30, 146.42; P < 0.001) in 2012 and 99.15 (95% CI 81.31, 116.99; P < 0.001) in 2016 for males. For both sexes, declines in hip fracture incidence were observed in patients aged 65 years and older, although incidence was relatively stable in younger patients. However, the total absolute number of hip fractures in those 55 years and older increased about 4-fold. The total costs for hospitalization showed a steep rise from US$60 million to US$380 million over the study period. Costs for hospitalization per patient increased about 1.59-fold, from US$4,300 in 2012 to US$6,840 in 2016. The main limitation of the study was the unavailability of data on imaging information to adjudicate cases of hip fracture. Conclusions Our results show that hip fracture incidence among patients aged 55 and over in China reached a plateau between 2012 and 2016. However, the absolute number of hip fractures and associated medical costs for hospitalization increased rapidly because of population aging.
A sequential 3D bioprinting and orthogonal bioconjugation approach for precision tissue engineering
Authors: Claire Yu, Kathleen L. Miller, Jacob Schimelman, Pengrui Wang, Wei Zhu, Xuanyi Ma, Min Tang, Shangting You, Deepak Lakshmipathy, Frank He, Shaochen Chen
Journal: Biomaterials (2020)

Recent advances in 3D bioprinting have transformed the tissue engineering landscape by enabling the controlled placement of cells, biomaterials, and bioactive agents for the biofabrication of living tissues and organs. However, the application of 3D bioprinting is limited by the availability of cytocompatible and printable biomaterials that recapitulate properties of native tissues. Here, we developed an integrated 3D projection bioprinting and orthogonal photoconjugation platform for precision tissue engineering of tailored microenvironments. By using a photoreactive thiol-ene gelatin bioink, soft hydrogels can be bioprinted into complex geometries and photopatterned with bioactive moieties in a rapid and scalable manner via digital light projection (DLP) technology. This enables localized modulation of biophysical properties such as stiffness and microarchitecture as well as precise control over spatial distribution and concentration of immobilized functional groups. As such, well-defined properties can be directly incorporated using a single platform to produce desired tissue-specific functions within bioprinted constructs. We demonstrated high viability of encapsulated endothelial cells and human cardiomyocytes using our dual process and fabricated tissue constructs functionalized with VEGF peptide mimics to induce guided endothelial cell growth for programmable vascularization. This work represents a pivotal step in engineering multifunctional constructs with unprecedented control, precision, and versatility for the rational design of biomimetic tissues.
Letter regarding “Extensive brainstem infiltration, not mass effect, is a common feature of end-stage cerebral glioblastomas”
Authors: Jubayer A Hossain, Hrvoje Miletic
Journal: Neuro-Oncology (2020)

Additional criteria apply.Please refer to protocol 14379-201 for full inclusion and exclusion criteria.† Patients can participate if they had some skin cancers, superficial bladder cancer (cancer that was only on the surface of the lining of the bladder), or carcinoma in situ (cancer that had not spread) of the cervix or breast that had been cured.
Serum Perfluoroalkyl Substances, Vaccine Responses, and Morbidity in a Cohort of Guinea-Bissau Children
Authors: Clara Amalie Gade Timmermann, Kristoffer Jarlov Jensen, Flemming Nielsen, Esben Budtz-Jørgensen, Fiona van der Klis, Christine Stabell Benn, Philippe Grandjean, Ane Bærent Fisker
Journal: Environmental Health Perspectives (2020)

Perfluoroalkyl substances (PFAS) are a group of widely used persistent chemicals with suspected immunotoxic effects.The present study aimed to examine the association between infant PFAS exposure and antibody responses to measles vaccination as well as morbidity in a low-income country.In a randomized controlled trial, children from Guinea-Bissau, West Africa, were followed from inclusion (4-7 months of age) through 2 years of age. Half the children received two measles vaccinations (at inclusion and at 9 months of age), and the other half received only one (at 9 months of age). In a subset of 237 children, six PFAS were quantified in serum at inclusion, and measles antibody concentrations were assessed at inclusion and at approximately 9 months and 2 years of age. At inclusion and at the 9-month visit, mothers were interviewed about infant morbidity.All but one child had detectable serum concentrations of all six PFAS, although levels were lower than seen elsewhere. A doubling in perfluorooctane sulfonic acid (PFOS) and perfluorodecanoic acid (PFDA) were associated with 21% (95% CI: 2, 37%) and 25% (95% CI: 1, 43%), respectively, lower measles antibody concentrations at the 9-month visit among the children who had received a measles vaccine at inclusion. Elevated serum PFAS concentrations were also associated with reduced prevaccination measles antibody concentrations and increased morbidity.The present study documents that PFAS exposure has reached West Africa and that infants show PFAS-associated increases in morbidity and decreases in measles-specific antibody concentrations before and after vaccination. These findings support the evidence on PFAS immunotoxicity at comparatively low serum concentrations. https://doi.org/10.1289/EHP6517.
Association of Sex, Age, and Eastern Cooperative Oncology Group Performance Status With Survival Benefit of Cancer Immunotherapy in Randomized Clinical Trials
Authors: Fang Yang, Svetomir N. Markovic, Julian R. Molina, Thorvardur R. Halfdanarson, Lance C. Pagliaro, Ashish V. Chintakuntlawar, Rutian Li, Jia Wei, Lifeng Wang, Baorui Liu, Grzegorz S. Nowakowski, Michael L. Wang, Yucai Wang
Journal: JAMA Network Open (2020)

Sex, age, and Eastern Cooperative Oncology Group (ECOG) performance status (PS) may affect immune response. However, the association of these factors with the survival benefit of cancer immunotherapy with immune checkpoint inhibitors (ICIs) remains unclear.To assess the potential sex, age, and ECOG PS differences of immunotherapy survival benefit in patients with advanced cancer.PubMed, Web of Science, Embase, and Scopus were searched from inception to August 31, 2019.Published randomized clinical trials comparing overall survival (OS) in patients with advanced cancer treated with ICI immunotherapy vs non-ICI control therapy were included.Pooled OS hazard ratio (HR) and 95% CI for patients of different sex, age (<65 and ≥65 years) or ECOG PS (0 and ≥1) were calculated separately using a random-effects model, and the heterogeneity between paired estimates was assessed using an interaction test by pooling study-specific interaction HRs. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline.The difference in survival benefit of ICIs between sex, age (<65 vs ≥65 years), and ECOG PS (0 vs ≥1), as well as the difference stratified by cancer type, line of therapy, agent of immunotherapy, and immunotherapy strategy in the intervention arm.Thirty-seven phase 2 or 3 randomized clinical trials involving 23 760 patients were included. An OS benefit of immunotherapy was found for both men (HR, 0.75; 95% CI, 0.71-0.81) and women (HR, 0.79; 95% CI, 0.72-0.88); for both younger (<65 years: HR, 0.77; 95% CI, 0.71-0.83) and older (≥65 years: HR, 0.78; 95% CI, 0.72-0.84) patients; and for both patients with ECOG PS 0 (HR, 0.81; 95% CI, 0.73-0.90) and PS greater than or equal to 1 (HR, 0.79; 95% CI, 0.74-0.84). No significant difference of relative benefit from immunotherapy over control therapy was found in patients of different sex (P = .25, I2 = 19.02%), age (P = .94, I2 = 15.57%), or ECOG PS (P = .74, I2 = 0%). No significant difference was found in subgroup analyses by cancer type, line of therapy, agent of immunotherapy, and immunotherapy strategy in the intervention arm.This meta-analysis found no evidence of an association of sex, age (<65 vs ≥65 years), or ECOG PS (0 vs ≥1) with cancer immunotherapy survival benefit. This finding suggests that the use of ICIs in advanced cancer should not be restricted to certain patients in sex, age, or ECOG PS categories.
Empagliflozin improves diabetic renal tubular injury by alleviating mitochondrial fission via AMPK/SP1/PGAM5 pathway
Authors: Xiangyang Liu, Chaofei Xu, Linxin Xu, Xiaoyu Li, Hongxi Sun, Mei Xue, Ting Li, Xiaochen Yu, Bei Sun, Liming Chen
Journal: Metabolism (2020)

Excessive mitochondrial fission was observed in diabetic kidney disease (DKD). Phosphoglycerate mutase family member 5 (PGAM5) plays an important role in mitochondrial fission by dephosphorylating the dynamin-related protein 1 at Ser637 (DRP1S637). Whether PGAM5 participates in the mitochondrial fission in diabetic renal tubular injury is unknown. Clinical trials have observed encouraging effect of Sodium-glucose cotransporter 2 (SGLT2) inhibitors on DKD though the underling mechanisms remain unclear.We used KK-Ay mice as diabetic model and Empagliflozin (Empa) were administrated by oral gavage. The mitochondrial fission and the expressions of phosphorylated AMP-activated protein kinase (p-AMPK), specificityprotein1 (SP1), PGAM5 and DRP1S637 were tested. We also examined these changes in HK2 cells that cultured in normal glucose (NG), high glucose (HG) and high glucose+Empa (HG + Empa) environment. Then we verified our deduction using AMPK activator (5-aminoimidazole-4-carboximide Riboside, AICAR), inhibitor (Compound C), si-SP1 and si-PGAM5. Lastly, we testified the interaction between SP1 and the PGAM5promotor by CHIP assay.The mitochondrial fission and the expression of SP1, PGAM5 increased and the expression of p-AMPK, DRP1S637 decreased in diabetic or HG environment. These changes were all reversed in Empa or AICAR treated groups. These reversal effects of Empa could be diminished by Compound C. Either si-SP1 or si-PGAM5 could alleviate the mitochondrial fission without affection on AMPK phosphorylation. Finally, the CHIP assay confirmed the interaction between SP1 and the PGAM5 promotor.The PGAM5 aggravated the development of diabetic renal tubular injury and the Empa could improve the DKD by alleviating mitochondrial fission via AMPK/SP1/PGAM5 pathway.
Easy-to-Read Informed Consent (ETRIC) Form for Hematopoietic Cell Transplantation (HCT) Clinical Trials: Results from Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 1205 Study
Authors: Navneet S. Majhail, Sergey Tarima, Ellen Denzen, Heather Moore, Sunil Abhyankar, Peter Dawson, Amy Foley, Iris D. Gersten, Mitchell E. Horwitz, Lensa Idossa, Steven Joffe, Naynesh Kamani, Roberta King, Aleksandr Lazaryan, Lawrence E Morris, Mary M. Horowitz, Ryan Spellecy
Journal: Blood (2017)
Integrative analyses of single-cell transcriptome and regulome using MAESTRO
Authors: Chenfei Wang, Dongqing Sun, Xin Huang, Changxin Wan, Ziyi Li, Ya Han, Qian Qin, Jingyu Fan, Xintao Qiu, Yingtian Xie, Clifford A. Meyer, Myles Brown, Ming Tang, Henry Long, Tao Liu, X. Shirley Liu
Journal: Genome biology (2020)

Abstract We present Model-based AnalysEs of Transcriptome and RegulOme (MAESTRO), a comprehensive open-source computational workflow ( http://github.com/liulab-dfci/MAESTRO ) for the integrative analyses of single-cell RNA-seq (scRNA-seq) and ATAC-seq (scATAC-seq) data from multiple platforms. MAESTRO provides functions for pre-processing, alignment, quality control, expression and chromatin accessibility quantification, clustering, differential analysis, and annotation. By modeling gene regulatory potential from chromatin accessibilities at the single-cell level, MAESTRO outperforms the existing methods for integrating the cell clusters between scRNA-seq and scATAC-seq. Furthermore, MAESTRO supports automatic cell-type annotation using predefined cell type marker genes and identifies driver regulators from differential scRNA-seq genes and scATAC-seq peaks.
Wogonin As a Targeted Therapeutic Agent for EBV (+) Lymphoma Cells Involved in LMP1/NF-κB/Mir-155/PU.1 Pathway
Authors: Xue Wu, Ping Liu, Haijun ZHang, Yuan Li, Jumah Masoud Mohammad Salmani, Fei Wang, Ke Yang, Rong Fu, Baoan Chen, Zhewei Chen
Journal: Blood (2017)
Correspondence on ‘<i>Festina lente</i>: hydroxychloroquine, COVID-19 and the role of the rheumatologist’ by Graef<i>et al</i>
Authors: Chien Hsien Lo, Yu-Hsun Wang, Chin Feng Tsai, Kuei Chuan Chan, Li Ching Li, Tse Hsien Lo, Chun Hung Su, James Cheng-Chung Wei
Journal: Annals of the Rheumatic Diseases (2020)

We read with interest the study by Graef et al ,1 who mentioned about the treatment and safety of hydroxychloroquine (HCQ) for the current COVID-19 pandemic. They described that decades of research strongly support the well control of disease activity and survival benefit of HCQ use in rheumatic diseases, such as systemic lupus erythematosus and rheumatoid arthritis (RA). They also highlight that HCQ should be used with caution in patients with COVID-19, including the safety concern, especially when combined with administration of azithromycin because both of them are known corrected QT interval (QTc) prolongation agents.

During early outbreak, HCQ, combined with azithromycin, has been used as a treatment option for COVID-19.2 3 Recently, an observational study with 1446 patients with COVID-19 reported that HCQ administration was not associated with a lower risk of intubation or death.4 However, the reasons for mortality were not illustrated. Multiple confounding factors like histories of ischaemic heart disease, heart failure and cardiac arrhythmia were not well adjusted. The main functional site of HCQ in COVID-19 is the entry via ACE2 preceptor.5 6 We believe that patient selection in early phases of COVID-19 infection would be more appropriate than well-established pneumonia or cytokines storm cases.

The risk of cardiac arrhythmias is an important safety issue. HCQ …