tbuckley/cabot-search huggingface dataset:
Safety and immunogenicity of two recombinant DNA COVID-19 vaccines containing the coding regions of the spike or spike and nucleocapsid proteins: an interim analysis of two open-label, non-randomised, phase 1 trials in healthy adults
Authors: Jin Young Ahn, Jeongsoo Lee, You Suk Suh, Young Goo Song, Yoon-Jeong Choi, Kyoung Hwa Lee, Sang Hwan Seo, Manki Song, Jong-Won Oh, Minwoo Kim, Han Young Seo, Jeong-Eun Kwak, Jin Won Youn, Jung Won Woo, Eui-Cheol Shin, Young Chul Sung, Su-Hyung Park, Jun Yong Choi
Journal: The Lancet Microbe (2022)

We assessed the safety and immunogenicity of two recombinant DNA vaccines for COVID-19: GX-19 containing plasmid DNA encoding the SARS-CoV-2 spike protein, and GX-19N containing plasmid DNA encoding the SARS-CoV-2 receptor-binding domain (RBD) foldon, nucleocapsid protein, and plasmid DNA encoding the spike protein.Two open-label non-randomised phase 1 trials, one of GX-19 and the other of GX-19N were done at two hospitals in South Korea. We enrolled healthy adults aged 19-49 years for the GX-19 trial and healthy adults aged 19-54 years for the GX-19N trial. Participants who tested positive by serological testing for SARS-CoV-2 were excluded. At 4-week intervals, the GX-19 trial participants received two vaccine doses (either 1·5 mg or 3·0 mg), and the GX-19N trial participants received two 3·0 mg doses. The vaccines were delivered intramuscularly using an electroporator. The participants were followed up for 52 weeks after first vaccination. Data collected up to day 57 after first vaccination were analysed in this interim analysis. The primary outcome was safety within 28 days after each vaccination measured in the intention-to-treat population. The secondary outcome was vaccine immunogenicity using blood samples collected on day 43 or 57 after first vaccination measured in the intention-to-treat population. The GX-19 (NCT044445389) and GX-19N (NCT04715997) trials are registered with ClinicalTrials.gov.Between June 17 and July 30, 2020, we screened 97 individuals, of whom 40 (41%) participants were enrolled in the GX-19 trial (20 [50%] in the 1·5 mg group and 20 [50%] in the 3·0 mg group). Between Dec 28 and 31, 2020, we screened 23 participants, of whom 21 (91%) participants were enrolled on the GX-19N trial. 32 (52%) of 61 participants reported 80 treatment-emergent adverse events after vaccination. All solicited adverse events were mild except one (2%) case of moderate fatigue in the 1·5 mg GX-19 group; no serious vaccine-related adverse events were detected. Binding antibody responses increased after second dose of vaccination in all groups (p=0·0002 in the 1·5 mg GX-19 group; p<0·0001 in the 3·0 mg GX-19; and p=0·0004 for the spike protein and p=0·0001 for the RBD in the 3·0 mg GX-19N group).GX-19 and GX-19N are safe and well tolerated. GX-19N induces humoral and broad SARS-CoV-2-specific T-cell responses. GX-19N shows lower neutralising antibody responses and needs improvement to enhance immunogenicity.The Korea Drug Development Fund, funded by the Ministry of Science and ICT, Ministry of Trade, Industry, and Energy, and Ministry of Health and Welfare.
Deletion of <i>Grin1</i> in mouse megakaryocytes reveals NMDA receptor role in platelet function and proplatelet formation
Authors: James I. Hearn, Taryn N. Green, Colin L. Hisey, Markus Bender, Emma C. Josefsson, Nicholas Knowlton, Juliane Baumann, Raewyn C. Poulsen, Stefan K. Bohlander, Maggie L. Kalev-Zylinska
Journal: Blood (2022)
Association Between High-Deductible Health Plans and Engagement in Routine Medical Care for Type 2 Diabetes in a Privately Insured Population: A Propensity Score–Matched Study
Authors: You M. Wu, Jie Huang, Mary E. Reed
Journal: Diabetes Care (2022)

High-deductible health plans (HDHPs) are increasingly more common but can be challenging for patients to navigate and may negatively affect care engagement for chronic conditions such as type 2 diabetes. We sought to understand how higher out-of-pocket costs affect participation in provider visits, medication adherence, and routine monitoring by patients with type 2 diabetes with an HDHP.In a retrospective cohort of 19,379 Kaiser Permanente Northern California patients with type 2 diabetes (age 18-64 years), 6,801 patients with an HDHP were compared with those with a no-deductible plan using propensity score matching. We evaluated the number of telephone and office visits with primary care, oral diabetic medication adherence, and rates of HbA1c testing, blood pressure monitoring, and retinopathy screening.Patients with an HDHP had fewer primary care office visits compared with patients with no deductible (4.25 vs. 4.85 visits per person; P < 0.001), less retinopathy screening (49.9% vs. 53.3%; P < 0.001), and fewer A1c and blood pressure measurements (46.7% vs. 51.4%; P < 0.001 and 93.2% vs. 94.4%; P = 0.004, respectively) compared with the control group. Medication adherence was not significantly different between patients with an HDHP and those with no deductible (57.4% vs. 58.6%; P = 0.234).HDHPs seem to be a barrier for patients with type 2 diabetes and reduce care participation in both visits with out-of-pocket costs and preventive care without out-of-pocket costs, possibly because of the increased complexity of cost sharing under an HDHP, potentially leading to decreased monitoring of important clinical measurements.
46P AB521, a clinical-stage, potent, and selective Hypoxia-Inducible Factor (HIF)-2α inhibitor, for the treatment of renal cell carcinoma
Authors: K.V. Lawson, K.E. Sivick Gauthier, D. Piovesan, A. Mailyan, G. Mata, J.T.A. Fournier, K. Yu, S. Liu, F. Soriano, L. Jin, E. Ginn, P.G. Schweickert, C.A. Meleza, A. Pham, L. Seitz, K. Liao, E. Paterson, P. Foster, M.J. Walters, M. Leleti
Journal: Annals of Oncology (2022)
VENTRICULAR SEPTAL DEFECT AFTER MYOCARDIAL INFARCTION: WHEN TO NOT STAY AT HOME DURING THE COVID-19 PANDEMIC
Authors: Banveet Kaur Khetarpal, Christoph Sossou, Awad Javaid, Jibran Rana, Omar Al-Talweel, Chowdhury Ahsan
Journal: Journal of the American College of Cardiology (2022)
Which antihypertensive treatment is better for mild to moderate hypertension in pregnancy?
Journal: BMJ (2022)

Which antihypertensive treatment is better for mild to moderate hypertension in pregnancy?In this article by Danielle Ashworth and colleagues (BMJ 2022;376:e066333; doi:), the definition of mild to moderate pregnancy hypertension (given in the last paragraph of the introduction) was incorrect; it should have been defined as systolic blood pressure 140-159 mm Hg and/or diastolic blood pressure 90-109 mm Hg.The online article and PDF have been corrected.
A RARE CASE OF LEFT VENTRICULAR OUTFLOW TRACT-TO-LEFT ATRIAL FISTULA DEVELOPMENT POST-SURGICAL INTERVENTION FOR STREP VIRIDANS MITRAL/AORTIC VALVE ENDOCARDITIS COMPLICATED BY A LARGE AORTIC ROOT ABSCESS
Authors: Cody Schwartz, Neeraj Jain
Journal: Journal of the American College of Cardiology (2022)
CLINICAL PROFILE OF LOW FLOW VS. NORMAL FLOW HIGH GRADIENT HYPERTROPHIC CARDIOMYOPATHY PATIENTS UNDERGOING SEPTAL MYECTOMY
Authors: Kirtivardhan Vashistha, Pietro Bajona, Mark Doyle, Robert W.W. Biederman, Srinivas Murali, Adee Elhamdani, Craig Michael Alpert, Abhas Khurana, Victor Farah, Jennifer Keeley, Gursharan Samra, Sunita Mahabir, Ali J. Noory, Vinh Q. Nguyen
Journal: Journal of the American College of Cardiology (2022)
Fresh water‐induced hemolysis in near‐drowning
Authors: Eitan Mirvis, Barbara J. Bain
Journal: American Journal of Hematology (2022)

A 52-year-old Caucasian man fell into a London canal. After he failed to resurface, he was rescued by bystanders. It took them an estimated 3 min to find him as the water was dirty. After his return to the surface, they started cardiopulmonary resuscitation. When the paramedics arrived, he was breathing with pulses present, but his Glasgow Coma Score was 3/15. He was therefore intubated, was transferred urgently to hospital, and was admitted to the intensive care unit where he was treated for severe aspiration pneumonitis. His alanine transaminase rose to 2376 units/L and aspartate transaminase to 4293 units/L, indicating hypoxic ischemic liver injury. He shortly developed pneumonia, a pleural effusion, and sepsis. Meanwhile, his hemoglobin concentration (Hb), which on admission had been 180 g/L (with leucocytosis, neutrophilia, lymphocytosis, and a normal platelet count) dropped rapidly, over the next 6 days, to 72 g/L. Coagulation tests now suggested disseminated intravascular coagulation (DIC), with platelets 43 × 109/L, prothrombin time 34.5 s, activated partial thromboplastin time 52.1 s, fibrinogen 1.16 g/L, and D-dimer >20 000 μg/L. His blood film (images, ×100 objective) showed schistocytes, irregularly contracted cells, nucleated red blood cells, and polychromasia. There were occasional erythrocytes with retraction of hemoglobin to one side or both ends of the cell (bottom right image). His reticulocyte count was 101 × 109/L on day 5. Bilirubin was 51 μmol/L and conjugated bilirubin 37 μmol/L. Lactate dehydrogenase was 1664 iu/L and haptoglobin 1.97 g/L. A direct antiglobulin test was weakly positive for IgG and negative for C3d. ADAMTS13 was 37 iu/L, excluding thrombotic thrombocytopenic purpura. With intensive support, including blood transfusion, the patient recovered and was discharged after 35 days. The rapid fall in Hb in the absence of any signs of hemorrhage suggests hemolysis. The blood film features are indicative of microangiopathic hemolytic anemia, with the irregularly contracted cells suggesting, in addition, oxidant damage. Drowning and near-drowning in fresh water are known to cause intravascular hemolysis, first reported in 1880; there is hemoglobinuria as a result of osmotic lysis of erythrocytes following absorption of water through the lungs.1, 2 Hypoxia is a contributing factor to the hemolysis.3 Our observations support the interactions of further mechanisms including microangiopathic hemolytic anemia in the context of DIC. DIC has been reported previously.4 Finally, our observation of irregularly contracted cells and hemoglobin retraction within erythrocytes suggests possible oxidant damage. The authors declare no conflicts of interest.
High-speed light-sheet microscopy for the in-situ acquisition of volumetric histological images of living tissue
Authors: Kripa B. Patel, Wenxuan Liang, Malte J. Casper, Venkatakaushik Voleti, Wenze Li, Alexis J. Yagielski, Hanzhi T. Zhao, Citlali Perez Campos, Grace Sooyeon Lee, Joyce M. Liu, Elizabeth Philipone, Angela J. Yoon, Kenneth P. Olive, Shana M. Coley, Elizabeth M. C. Hillman
Journal: Nature Biomedical Engineering (2022)
SUPRANORMAL CARDIAC INDEX DEVELOPS IN PEDIATRIC PULMONARY HYPERTENSION PATIENTS TREATED WITH PARENTERAL PROSTANOID THERAPY.
Authors: Kimberley Miles, Paul Critser, Nicholas Ollberding, Zhiqian Gao, Michelle Cash, Meredith Oneil, Stephanie Melissa Magness, Russel Hirsch
Journal: Journal of the American College of Cardiology (2022)
Airflow obstruction and small airway dysfunction following pulmonary tuberculosis: a cross-sectional survey
Authors: Zhenzhen Xing, Tieying Sun, Jean-Paul Janssens, Di Chai, Weiming Liu, Yaqi Tong, Yuxia Wang, Yali Ma, Mingming Pan, Jia Cui, Chen Wang, YanFei Guo
Journal: Thorax (2022)

Objectives Pulmonary function impairment and chronic respiratory symptoms after tuberculosis are relatively common in low-income and middle-income countries. We aimed to estimate the impact of post-tuberculosis (post-TB) on pulmonary function. Methods This large cross-sectional, population-based study included subjects aged 15 years or older with technically acceptable postbronchodilator spirometry measurements. Post-TB was diagnosed on the basis of radiological evidence and/or medical history. Airflow obstruction was defined as a postbronchodilator forced expiratory volume in 1 s/forced vital capacity ratio below the lower limit of normal of Global Lung Function Initiative (GLI) lung function equations. Small airway dysfunction was diagnosed if at least two of the following indicators were less than 65% of predicted: maximal mid-expiratory flow, forced expiratory flow (FEF) 50% or FEF 75%. Results In this population sample (N=8680, mean age: 40.1 years), 610 (7.0% (95% CI 6.5 to 7.6) participants were post-TB. Post-TB subjects had more frequent respiratory symptoms (46.8% vs 28.3%). Among post-TB subjects, 130 (21.3% (95% CI 18.1 to 24.8)) had airflow obstruction; OR of airflow obstruction was significantly associated with post-TB after adjustment for other confounding factors (OR 1.31, 95% CI 1.05 to 1.62). Post-TB was also associated with small airway dysfunction (OR 1.28, 95% CI1.07 to 1.53), which was present in 297 (48.9% (95% CI 33.9 to 53.0)) post-TB subjects. Conclusions Our findings support existing knowledge that post-TB is positively associated with pulmonary function impairment and make for frequent respiratory symptoms. Post-TB should be considered as a potentially important cause of airflow obstruction and respiratory symptoms in patients originating from countries with a high burden of tuberculosis.
Artificial Intelligence–Powered Spatial Analysis of Tumor-Infiltrating Lymphocytes as Complementary Biomarker for Immune Checkpoint Inhibition in Non–Small-Cell Lung Cancer
Authors: Sehhoon Park, Chan-Young Ock, Hyojin Kim, Sergio Pereira, Seonwook Park, Minuk Ma, Sangjoon Choi, Seokhwi Kim, Seunghwan Shin, Brian Jaehong Aum, Kyunghyun Paeng, Donggeun Yoo, Hongui Cha, Sunyoung Park, Koung Jin Suh, Hyun Ae Jung, Se Hyun Kim, Yu Jung Kim, Jong-Mu Sun, Jin-Haeng Chung, Jin Seok Ahn, Myung-Ju Ahn, Jong Seok Lee, Keunchil Park, Sang Yong Song, Yung-Jue Bang, Yoon-La Choi, Tony S. Mok, Se-Hoon Lee
Journal: Journal of Clinical Oncology (2022)

Biomarkers on the basis of tumor-infiltrating lymphocytes (TIL) are potentially valuable in predicting the effectiveness of immune checkpoint inhibitors (ICI). However, clinical application remains challenging because of methodologic limitations and laborious process involved in spatial analysis of TIL distribution in whole-slide images (WSI).We have developed an artificial intelligence (AI)-powered WSI analyzer of TIL in the tumor microenvironment that can define three immune phenotypes (IPs): inflamed, immune-excluded, and immune-desert. These IPs were correlated with tumor response to ICI and survival in two independent cohorts of patients with advanced non-small-cell lung cancer (NSCLC).Inflamed IP correlated with enrichment in local immune cytolytic activity, higher response rate, and prolonged progression-free survival compared with patients with immune-excluded or immune-desert phenotypes. At the WSI level, there was significant positive correlation between tumor proportion score (TPS) as determined by the AI model and control TPS analyzed by pathologists (P < .001). Overall, 44.0% of tumors were inflamed, 37.1% were immune-excluded, and 18.9% were immune-desert. Incidence of inflamed IP in patients with programmed death ligand-1 TPS at < 1%, 1%-49%, and ≥ 50% was 31.7%, 42.5%, and 56.8%, respectively. Median progression-free survival and overall survival were, respectively, 4.1 months and 24.8 months with inflamed IP, 2.2 months and 14.0 months with immune-excluded IP, and 2.4 months and 10.6 months with immune-desert IP.The AI-powered spatial analysis of TIL correlated with tumor response and progression-free survival of ICI in advanced NSCLC. This is potentially a supplementary biomarker to TPS as determined by a pathologist.
Adjuvant Pembrolizumab versus IFNα2b or Ipilimumab in Resected High-Risk Melanoma
Authors: Kenneth F. Grossmann, Megan Othus, Sapna P. Patel, Ahmad A. Tarhini, Vernon K. Sondak, Michael V. Knopp, Teresa M. Petrella, Thach-Giao Truong, Nikhil I. Khushalani, Justine V. Cohen, Elizabeth I. Buchbinder, Kari Kendra, Pauline Funchain, Karl D. Lewis, Robert M. Conry, Bartosz Chmielowski, Ragini R. Kudchadkar, Douglas B. Johnson, Hongli Li, James Moon, Zeynep Eroglu, Brian Gastman, Magdalena Kovacsovics-Bankowski, Krishna S. Gunturu, Scot W. Ebbinghaus, Sama Ahsan, Nageatte Ibrahim, Elad Sharon, Larissa A. Korde, John M. Kirkwood, Antoni Ribas
Journal: Cancer Discovery (2021)

We conducted a randomized phase III trial to evaluate whether adjuvant pembrolizumab for one year (647 patients) improved recurrence-free survival (RFS) or overall survival (OS) in comparison with high-dose IFNα-2b for one year or ipilimumab for up to three years (654 patients), the approved standard-of-care adjuvant immunotherapies at the time of enrollment for patients with high-risk resected melanoma. At a median follow-up of 47.5 months, pembrolizumab was associated with significantly longer RFS than prior standard-of-care adjuvant immunotherapies [HR, 0.77; 99.62% confidence interval (CI), 0.59-0.99; P = 0.002]. There was no statistically significant association with OS among all patients (HR, 0.82; 96.3% CI, 0.61-1.09; P = 0.15). Proportions of treatment-related adverse events of grades 3 to 5 were 19.5% with pembrolizumab, 71.2% with IFNα-2b, and 49.2% with ipilimumab. Therefore, adjuvant pembrolizumab significantly improved RFS but not OS compared with the prior standard-of-care immunotherapies for patients with high-risk resected melanoma. Adjuvant PD-1 blockade therapy decreases the rates of recurrence, but not survival, in patients with surgically resectable melanoma, substituting the prior standard-of-care immunotherapies for this cancer. See related commentary by Smithy and Shoushtari, p. 599. This article is highlighted in the In This Issue feature, p. 587.
The role of viral genomics in understanding COVID-19 outbreaks in long-term care facilities
Authors: Dinesh Aggarwal, Richard Myers, William L Hamilton, Tehmina Bharucha, Niamh M Tumelty, Colin S Brown, Emma J Meader, Tom Connor, Darren L Smith, Declan T Bradley, Samuel Robson, Matthew Bashton, Laura Shallcross, Maria Zambon, Ian Goodfellow, Meera Chand, Justin O'Grady, M Estée Török, Sharon J Peacock, Andrew J Page
Journal: The Lancet Microbe (2021)

We reviewed all genomic epidemiology studies on COVID-19 in long-term care facilities (LTCFs) that had been published to date. We found that staff and residents were usually infected with identical, or near identical, SARS-CoV-2 genomes. Outbreaks usually involved one predominant cluster, and the same lineages persisted in LTCFs despite infection control measures. Outbreaks were most commonly due to single or few introductions followed by a spread rather than a series of seeding events from the community into LTCFs. The sequencing of samples taken consecutively from the same individuals at the same facilities showed the persistence of the same genome sequence, indicating that the sequencing technique was robust over time. When combined with local epidemiology, genomics allowed probable transmission sources to be better characterised. The transmission between LTCFs was detected in multiple studies. The mortality rate among residents was high in all facilities, regardless of the lineage. Bioinformatics methods were inadequate in a third of the studies reviewed, and reproducing the analyses was difficult because sequencing data were not available in many facilities.
The kākāpō (Strigops habroptilus)
Authors: Nicolas Dussex, Bruce C. Robertson, Love Dalén, Erich D. Jarvis
Journal: Trends in Genetics (2022)

The kākāpō, Strigops habroptilus, is a flightless and critically endangered parrot from New Zealand. The species belongs to a unique lineage of parrots, endemic to the archipelago that diverged from other parrots ~82 million years ago (mya), as New Zealand split from Gondwana. The kākāpō genome represents one of the first high-quality chromosome-level reference genomes sequenced by the Vertebrate Genomes Project (VGP) and is an important resource for future studies on evolution and conservation. Analyses of this new genome provide key insights into kākāpō breeding and recovery. Comparison of modern and historical genomes show that kākāpō experienced a reduction in mutational load through genetic drift and purging. These findings indicate that even extremely inbred and bottlenecked species can survive in the wild, but also caution about the future management strategy for the species. Because kākāpō is a taonga, or treasure for Māori, the project was established in collaboration with Te Rūnanga o Ngāi Tahu. The kākāpō genome comprises 23 chromosomes (2n), making for a total genome size of ~1.19 Gbp. It has a repeat content of 15% and a GC content of 42%. A total of 16 053 annotated protein-coding genes were identified. Kākāpō is one of the most inbred species on earth with 0.4–0.5 heterozygote sites per 1000 bp and an inbreeding coefficient (FROH) of ~53%. The kākāpō diverged from flying New Zealand parrots (kea and kākā) ~28 mya. Population genomics analyses revealed that the divergence time between the extinct mainland and the extant Stewart Island populations dates back to the end of the last glaciation ~15 thousand years ago (kya). The kākāpō used to be one of most common and widespread birds in New Zealand. There are now only 202 kākāpō surviving on island sanctuaries that are part of an intense breeding program. Only one mainland bird, called Richard Henry, and 39 Stewart Island birds survived an extreme bottleneck in 1995 and reproduced. Kākāpō are flightless, nocturnal with a probable well-developed sense of smell and with a pronounced sexual dimorphism in body size. Contrary to other parrots, kākāpō have a polygynous lek breeding system. They only reproduce every 2–5 years, during years of heavy rimu (Dacrydium cupressinum) fruiting. Females reach sexual maturity between 5 and 18 years and males between 11 and 23 years. Kākāpō are believed to be exceedingly long-lived, with one male, Richard Henry, having lived up to ~80 years old. The Z sex chromosome fused with the chromosome 11 equivalent of other bird species, and this since has been found for other parrot species, indicating that the fusion may have occurred at the origin of parrots. KINGDOM: Animalia PHYLUM: Chordata CLASS: Aves ORDER: Psittaciformes FAMILY: Psittacidae GENUS: Strigops