tbuckley/cabot-search huggingface dataset:
Trial of Pimavanserin in Dementia-Related Psychosis
Authors: Pierre N. Tariot, Jeffrey L. Cummings, Maria E. Soto-Martin, Clive Ballard, Deniz Erten-Lyons, David L. Sultzer, Davangere P. Devanand, Daniel Weintraub, Bradley McEvoy, James M. Youakim, Srdjan Stankovic, Erin P. Foff
Journal: New England Journal of Medicine (2021)

Patients with dementia due to neurodegenerative disease can have dementia-related psychosis. The effects of the oral 5-HT2A inverse agonist and antagonist pimavanserin on psychosis related to various causes of dementia are not clear.We conducted a phase 3, double-blind, randomized, placebo-controlled discontinuation trial involving patients with psychosis related to Alzheimer's disease, Parkinson's disease dementia, dementia with Lewy bodies, frontotemporal dementia, or vascular dementia. Patients received open-label pimavanserin for 12 weeks. Those who had a reduction from baseline of at least 30% in the score on the Scale for the Assessment of Positive Symptoms-Hallucinations and Delusions (SAPS-H+D, with higher scores indicating greater psychosis) and a Clinical Global Impression-Improvement (CGI-I) score of 1 (very much improved) or 2 (much improved) at weeks 8 and 12 were randomly assigned in a 1:1 ratio to continue receiving pimavanserin or to receive placebo for up to 26 weeks. The primary end point, assessed in a time-to-event analysis, was a relapse of psychosis as defined by any of the following: an increase of at least 30% in the SAPS-H+D score and a CGI-I score of 6 (much worse) or 7 (very much worse), hospitalization for dementia-related psychosis, stopping of the trial regimen or withdrawal from the trial for lack of efficacy, or use of antipsychotic agents for dementia-related psychosis.Of the 392 patients in the open-label phase, 41 were withdrawn for administrative reasons because the trial was stopped for efficacy; of the remaining 351 patients, 217 (61.8%) had a sustained response, of whom 105 were assigned to receive pimavanserin and 112 to receive placebo. A relapse occurred in 12 of 95 patients (13%) in the pimavanserin group and in 28 of 99 (28%) in the placebo group (hazard ratio, 0.35; 95% confidence interval, 0.17 to 0.73; P = 0.005). During the double-blind phase, adverse events occurred in 43 of 105 patients (41.0%) in the pimavanserin group and in 41 of 112 (36.6%) in the placebo group. Headache, constipation, urinary tract infection, and asymptomatic QT prolongation occurred with pimavanserin.In a trial that was stopped early for efficacy, patients with dementia-related psychosis who had a response to pimavanserin had a lower risk of relapse with continuation of the drug than with discontinuation. Longer and larger trials are required to determine the effects of pimavanserin in dementia-related psychosis. (Funded by Acadia Pharmaceuticals; HARMONY ClinicalTrials.gov number, NCT03325556.).
Impact of baseline patient characteristics on dupilumab efficacy in type 2 asthma
Authors: William W. Busse, Pierluigi Paggiaro, Xavier Muñoz, Thomas B. Casale, Mario Castro, G. Walter Canonica, Jo A. Douglass, Yuji Tohda, Nadia Daizadeh, Benjamin Ortiz, Nami Pandit-Abid
Journal: European Respiratory Journal (2021)

<b>Dupilumab treatment <i>versus</i> placebo improved exacerbation rate and lung function outcomes in patients with uncontrolled moderate-to-severe asthma and high type 2 biomarkers at baseline, regardless of baseline characteristics in the phase 3 QUEST study</b>https://bit.ly/3yR7MlD
Prospects and Challenges of MXenes as Emerging Sensing Materials for Flexible and Wearable Breath‐Based Biomarker Diagnosis
Authors: Angga Hermawan, Tahta Amrillah, Anung Riapanitra, Wee‐Jun Ong, Shu Yin
Journal: Advanced Healthcare Materials (2021)

A fully integrated, flexible, and functional sensing device for exhaled breath analysis drastically transforms conventional medical diagnosis to non-invasive, low-cost, real-time, and personalized health care. 2D materials based on MXenes offer multiple advantages for accurately detecting various breath biomarkers compared to conventional semiconducting oxides. High surface sensitivity, large surface-to-weight ratio, room temperature detection, and easy-to-assemble structures are vital parameters for such sensing devices in which MXenes have demonstrated all these properties both experimentally and theoretically. So far, MXenes-based flexible sensor is successfully fabricated at a lab-scale and is predicted to be translated into clinical practice within the next few years. This review presents a potential application of MXenes as emerging materials for flexible and wearable sensor devices. The biomarkers from exhaled breath are described first, with emphasis on metabolic processes and diseases indicated by abnormal biomarkers. Then, biomarkers sensing performances provided by MXenes families and the enhancement strategies are discussed. The method of fabrications toward MXenes integration into various flexible substrates is summarized. Finally, the fundamental challenges and prospects, including portable integration with Internet-of-Thing (IoT) and Artificial Intelligence (AI), are addressed to realize marketization.
Call for papers: A special issue on tackling emerging infectious diseases
Authors: Robert M. Frederickson, Roland W. Herzog
Journal: Molecular Therapy (2021)

In 2020, the world faced a devasting global pandemic caused by the spread of a novel respiratory virus. While the coronavirus disease 2019 (COVID-19) pandemic exposed the vulnerability of the modern world to emerging infectious disease, mRNA- and viral vector-based vaccines have quickly proven to be remarkably efficacious against the causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This monumental accomplishment was made possible by years of prior experimentation with recombinant genetic vaccine and nucleic acid delivery technologies by members of the gene and cell therapy community worldwide. Similar vaccines are being developed or have already been approved to protect against other infectious diseases such as Ebola or Zika virus. Other cutting-edge technologies that fall under the molecular therapy umbrella, such as monoclonal antibody therapy and even chimeric antigen receptor (CAR)-T cell therapy complement modern treatment of infectious diseases. Further development of these technologies will be crucial for preparing for the next pandemic, which is bound to come sooner rather than later. In addition, early-stage monitoring and tracking of new and emerging infectious agents will be key to limiting their impact worldwide. We must also examine the possible role of climate change in the emergence of new pathogenic agents as permafrost melts and ecosystems and habitats are stressed by human activity and changing weather patterns across the globe. In light of this, the editors of the journal are thrilled to announce the development of a special issue of Molecular Therapy that will feature original research and review articles from leaders in the fields of vaccine development, infectious disease, and global health. The issue will cover, among other aspects: advances and innovation in development of mRNA vaccine technologies against infectious diseases; the current status of mRNA vaccine development against COVID-19; innate immunity to coronavirus and viral evasion; adenoviral vaccines against infectious diseases; advances in DNA vaccines against infectious diseases; antibody-based treatments of malaria; emerging global threats; and global challenges in the co-ordinated response to epidemic diseases. Guest editors of this special issue include Andrew Baker, David Weiner, Niek Sanders, Ami Patel, and Weidong Xiao. Authors are encouraged to contact one of the above or the editorial team at [email protected] to submit presubmission inquiries. Submissions to this special issue should adhere to our standard manuscript guidelines available on the journal website. The deadline for submissions is October 1, 2021 and publication of the issue is targeted for quarter one of 2022.
The Chicken Pan-Genome Reveals Gene Content Variation and a Promoter Region Deletion in <i>IGF2BP1</i> Affecting Body Size
Authors: Kejun Wang, Haifei Hu, Yadong Tian, Jingyi Li, Armin Scheben, Chenxi Zhang, Yiyi Li, Junfeng Wu, Lan Yang, Xuewei Fan, Guirong Sun, Donghua Li, Yanhua Zhang, Ruili Han, Ruirui Jiang, Hetian Huang, Fengbin Yan, Yanbin Wang, Zhuanjian Li, Guoxi Li, Xiaojun Liu, Wenting Li, David Edwards, Xiangtao Kang
Journal: Molecular Biology and Evolution (2021)

Domestication and breeding have reshaped the genomic architecture of chicken, but the retention and loss of genomic elements during these evolutionary processes remain unclear. We present the first chicken pan-genome constructed using 664 individuals, which identified an additional approximately 66.5-Mb sequences that are absent from the reference genome (GRCg6a). The constructed pan-genome encoded 20,491 predicated protein-coding genes, of which higher expression levels are observed in conserved genes relative to dispensable genes. Presence/absence variation (PAV) analyses demonstrated that gene PAV in chicken was shaped by selection, genetic drift, and hybridization. PAV-based genome-wide association studies identified numerous candidate mutations related to growth, carcass composition, meat quality, or physiological traits. Among them, a deletion in the promoter region of IGF2BP1 affecting chicken body size is reported, which is supported by functional studies and extra samples. This is the first time to report the causal variant of chicken body size quantitative trait locus located at chromosome 27 which was repeatedly reported. Therefore, the chicken pan-genome is a useful resource for biological discovery and breeding. It improves our understanding of chicken genome diversity and provides materials to unveil the evolution history of chicken domestication.
Use of High-risk Medications Among Lonely Older Adults
Authors: Ashwin A. Kotwal, Michael A. Steinman, Irena Cenzer, Alexander K. Smith
Journal: JAMA Internal Medicine (2021)

Loneliness, the emotional distress resulting from a discrepancy between one's actual and desired level of social connection, is associated with physical and psychological symptoms in older adults, including pain, insomnia, depression, and anxiety. 1 The relationship of loneliness to these symptoms is likely bidirectional; in some situations it acts as a risk factor for the symptoms and in others it is the consequence of symptoms.In either case, lonely older adults may be at risk for using high-risk medications commonly prescribed for physical or psychological symptoms. 2 Our objective was therefore to investigate the relationship between loneliness and high-risk medication use. 2 A better understanding of this relationship might inform strategies for addressing symptoms and deprescribing potentially risky medications through the use of nonpharmacologic, social interventions.Methods | We used cross-sectional data from the National Social Life, Health, and Aging Project (NSHAP), waves 1 through 3 (2005, 2010, 2015), an in-home nationally representative survey of community-dwelling adults older than 65 years. 3 We included 6336 participants who responded to the NSHAP leave-behind questionnaire (85% response rate among 7045 total participants), and excluded an additional 254 participants (4%) with incomplete responses to the loneliness scale and 65 participants (1%) with missing medications data, resulting in a final sample of 6017 participants.Loneliness was categorized as none, low/moderate, or high based on the 3-item UCLA Loneliness Scale.
P39-4 Activities report of a support program for cancer patients and their families at Jichi Medical University Hospital
Authors: Rie Yamamoto, Kaori Komatsuzaki, Yoshiko Kojima, Miwako Inada, Yumi Ooeda, Akiko Nakayama, Saori Chiba, Kiyoe Sato, Hironori Yamaguchi, Hirofumi Fujii
Journal: Annals of Oncology (2021)
Covid-19 in Liver Transplant Recipients: A National Cohort
Authors: Gokhan Kabacam, Ilker Turan, Murat Kiyici, Zeynep Ellik, Suleyman Dolu, Murat Dayangac, Derya Ari, Dilara Gokce, Abdullah Yildirim, Genco Gencdal, Murat Harputluoglu, Aysun Kartal, Emine Demiray, Feyza Gündüz, Ilkay Ergenc, Cumali Efe, Hale Sumer, Meral Kayhan, Murat Gülşen, Murat Akyildiz, Cigdem Arikan, Sedat Karademir, Deniz Balci, Halit Dündar, Mesut Akarsu, Fulya Günşar, Abdullah Karasu, Ramazan Idilman
Journal: Journal of Hepatology (2021)
Anti-EpCAM functionalized graphene oxide vector for tumor targeted siRNA delivery and cancer therapy
Authors: Si Chen, Shuang Zhang, Yifan Wang, Xin Yang, Hong Yang, Chunying Cui
Journal: Asian Journal of Pharmaceutical Sciences (2021)

Graphene oxide (GO) has emerged as a potential drug delivery vector. For siRNA delivery, GO should be modified to endow it with gene delivery ability and targeting effect. However, the cationic materials used previously usually had greater toxicity. In this study, GO was modified with a non-toxicity cationic material (chitosan) and a tumor specific monoclonal antibody (anti-EpCAM) for the delivery of survivin-siRNA (GCE/siRNA). And the vector (GCE) prepared was proved with excellent biosafety and tumor targeting effect. The GCE exhibited superior performance in loading siRNA, maintained stability in different solutions and showed excellent protection effect for survivin-siRNA in vitro. The gene silencing results in vitro showed that the mRNA level and protein level were down-regulated by 48.24% ± 2.50% and 44.12% ± 3.03%, respectively, which was equal with positive control (P > 0.05). It was also demonstrated that GCE/siRNA had a strong antitumor effect in vitro, which was attributed to the efficient antiproliferation, and migration and invasion inhibition effect of GCE/siRNA. The results in vivo indicated that GCE could accumulate siRNA in tumor tissues. The tumor inhibition rate of GCE/siRNA 54.74% ± 5.51% was significantly higher than control 4.87% ± 8.49%. Moreover, GCE/siRNA showed no toxicity for blood and main organs, suggesting that it is a biosafety carrier for gene delivery. Taken together, this study provides a novel design strategy for gene delivery system and siRNA formulation.
Antibody and T cell immune responses following mRNA COVID-19 vaccination in patients with cancer
Authors: Sidse Ehmsen, Anders Asmussen, Stefan S. Jeppesen, Anna Christine Nilsson, Sabina Østerlev, Hanne Vestergaard, Ulrik S. Justesen, Isik S. Johansen, Henrik Frederiksen, Henrik J. Ditzel
Journal: Cancer Cell (2021)
Marginating transitional B cells modulate neutrophils in the lung during inflammation and pneumonia
Authors: John Podstawka, Sarthak Sinha, Carlos H. Hiroki, Nicole Sarden, Elise Granton, Elodie Labit, Jung Hwan Kim, Graciela Andonegui, Yuefei Lou, Brendan D. Snarr, Donald C. Sheppard, Nicole L. Rosin, Jeff Biernaskie, Bryan G. Yipp
Journal: The Journal of Experimental Medicine (2021)

Pulmonary innate immunity is required for host defense; however, excessive neutrophil inflammation can cause life-threatening acute lung injury. B lymphocytes can be regulatory, yet little is known about peripheral transitional IgM+ B cells in terms of regulatory properties. Using single-cell RNA sequencing, we discovered eight IgM+ B cell subsets with unique gene regulatory networks in the lung circulation dominated by transitional type 1 B and type 2 B (T2B) cells. Lung intravital confocal microscopy revealed that T2B cells marginate in the pulmonary capillaries via CD49e and require CXCL13 and CXCR5. During lung inflammation, marginated T2B cells dampened excessive neutrophil vascular inflammation via the specialized proresolving molecule lipoxin A4 (LXA4). Exogenous CXCL13 dampened excessive neutrophilic inflammation by increasing marginated B cells, and LXA4 recapitulated neutrophil regulation in B cell–deficient mice during inflammation and fungal pneumonia. Thus, the lung microvasculature is enriched in multiple IgM+ B cell subsets with marginating capillary T2B cells that dampen neutrophil responses.
Nanotechnologies for the delivery of biologicals: Historical perspective and current landscape
Authors: Matilde Durán-Lobato, Ana María López-Estévez, Ana Sara Cordeiro, Tamara G. Dacoba, José Crecente-Campo, Dolores Torres, María José Alonso
Journal: Advanced Drug Delivery Reviews (2021)

Biological macromolecule-based therapeutics irrupted in the pharmaceutical scene generating a great hope due to their outstanding specificity and potency. However, given their susceptibility to degradation and limited capacity to overcome biological barriers new delivery technologies had to be developed for them to reach their targets. This review aims at analyzing the historical seminal advances that shaped the development of the protein/peptide delivery field, along with the emerging technologies on the lead of the current landscape. Particularly, focus is made on technologies with a potential for transmucosal systemic delivery of protein/peptide drugs, followed by approaches for the delivery of antigens as new vaccination strategies, and formulations of biological drugs in oncology, with special emphasis on mAbs. Finally, a discussion of the key challenges the field is facing, along with an overview of prospective advances are provided.
Effect of Ventral vs Dorsal Spinal Surgery in Patients With Cervical Spondylotic Myelopathy—Reply
Authors: Zoher Ghogawala, Fred G. Barker, Edward C. Benzel
Journal: JAMA (2021)

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Single-nucleus transcriptome analysis of human brain immune response in patients with severe COVID-19
Authors: John F. Fullard, Hao-Chih Lee, Georgios Voloudakis, Shengbao Suo, Behnam Javidfar, Zhiping Shao, Cyril Peter, Wen Zhang, Shan Jiang, André Corvelo, Heather Wargnier, Emma Woodoff-Leith, Dushyant P. Purohit, Sadhna Ahuja, Nadejda M. Tsankova, Nathalie Jette, Gabriel E. Hoffman, Schahram Akbarian, Mary Fowkes, John F. Crary, Guo-Cheng Yuan, Panos Roussos
Journal: Genome Medicine (2021)

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has been associated with neurological and neuropsychiatric illness in many individuals. We sought to further our understanding of the relationship between brain tropism, neuro-inflammation, and host immune response in acute COVID-19 cases. Three brain regions (dorsolateral prefrontal cortex, medulla oblongata, and choroid plexus) from 5 patients with severe COVID-19 and 4 controls were examined. The presence of the virus was assessed by western blot against viral spike protein, as well as viral transcriptome analysis covering > 99% of SARS-CoV-2 genome and all potential serotypes. Droplet-based single-nucleus RNA sequencing (snRNA-seq) was performed in the same samples to examine the impact of COVID-19 on transcription in individual cells of the brain. Quantification of viral spike S1 protein and viral transcripts did not detect SARS-CoV-2 in the postmortem brain tissue. However, analysis of 68,557 single-nucleus transcriptomes from three distinct regions of the brain identified an increased proportion of stromal cells, monocytes, and macrophages in the choroid plexus of COVID-19 patients. Furthermore, differential gene expression, pseudo-temporal trajectory, and gene regulatory network analyses revealed transcriptional changes in the cortical microglia associated with a range of biological processes, including cellular activation, mobility, and phagocytosis. Despite the absence of detectable SARS-CoV-2 in the brain at the time of death, the findings suggest significant and persistent neuroinflammation in patients with acute COVID-19.
Impact of COVID‐19 Pandemic on Liver Transplantation and Alcohol‐Associated Liver Disease in the USA
Authors: George Cholankeril, Karthik Goli, Abbas Rana, Ruben Hernaez, Alexander Podboy, Prasun Jalal, Ben L. Da, Sanjaya K. Satapathy, Donghee Kim, Aijaz Ahmed, John Goss, Fasiha Kanwal
Journal: Hepatology (2021)

Background and Aims The surge in unhealthy alcohol use during the COVID‐19 pandemic may have detrimental effects on the rising burden of alcohol‐associated liver disease (ALD) on liver transplantation (LT) in the USA. We evaluated the effect of the pandemic on temporal trends for LT including ALD. Approach and Results Using data from United Network for Organ Sharing, we analyzed wait‐list outcomes in the USA through March 1, 2021. In a short‐period analysis, patients listed or transplanted between June 1, 2019, and February 29, 2020, were defined as the "pre‐COVID" era, and after April 1, 2020, were defined as the "COVID" era. Interrupted time‐series analyses using monthly count data from 2016‐2020 were constructed to evaluate the rate change for listing and LT before and during the COVID‐19 pandemic. Rates for listings (P = 0.19) and LT (P = 0.14) were unchanged during the pandemic despite a significant reduction in the monthly listing rates for HCV (−21.69%, P < 0.001) and NASH (−13.18%; P < 0.001). There was a significant increase in ALD listing (+7.26%; P < 0.001) and LT (10.67%; P < 0.001) during the pandemic. In the COVID era, ALD (40.1%) accounted for more listings than those due to HCV (12.4%) and NASH (23.4%) combined. The greatest increase in ALD occurred in young adults (+33%) and patients with severe alcohol‐associated hepatitis (+50%). Patients with ALD presented with a higher acuity of illness, with 30.8% of listings and 44.8% of LT having a Model for End‐Stage Liver Disease–Sodium score ≥30. Conclusions Since the start of COVID‐19 pandemic, ALD has become the most common indication for listing and the fastest increasing cause for LT. Collective efforts are urgently needed to stem the rising tide of ALD on health care resources.