tbuckley/cabot-search huggingface dataset:
Potent neutralizing RBD‐specific antibody cocktail against SARS‐CoV‐2 and its mutant
Authors: Lina Jia, Yan‐Ping Liu, Li‐Fei Tian, Chao Xiong, Xin Xu, Honge Qu, Weixi Xiong, Dong Zhou, Feng Wang, Zheng Liu, Xiao‐Xue Yan, Wenqing Xu, Lin Tang
Journal: MedComm (2021)

The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants has posed a serious global public health emergency. Therapeutic interventions or vaccines are urgently needed to treat and prevent the further dissemination of this contagious virus. This study described the identification of neutralizing receptor-binding domain (RBD)-specific antibodies from mice through vaccination with a recombinant SARS-CoV-2 RBD. RBD-targeted monoclonal antibodies (mAbs) with distinct function and epitope recognition were selected to understand SARS-CoV-2 neutralization. High-affinity RBD-specific antibodies exhibited high potency in neutralizing both live and pseudotype SARS-CoV-2 viruses and the SARS-CoV-2 pseudovirus particle containing the spike protein S-RBDV367F mutant (SARS-CoV-2(V367F)). These results demonstrated that these antibodies recognize four distinct groups (I-IV) of epitopes on the RBD and that mAbs targeting group I epitope can be used in combination with mAbs recognizing groups II and/or IV epitope to make mAb cocktails against SARS-CoV-2 and its mutants. Moreover, structural characterization reveals that groups I, III, and IV epitopes are closely located to an RBD hotspot. The identification of RBD-specific antibodies and cocktails may provide an effective therapeutic and prophylactic intervention against SARS-CoV-2 and its isolates.
Regenerative Potential of Hydrogels for Intracerebral Hemorrhage: Lessons from Ischemic Stroke and Traumatic Brain Injury Research
Authors: Josephine M. Thomas, Irene Louca, Faye Bolan, Oana‐Roxana Sava, Stuart M. Allan, Catherine B. Lawrence, Emmanuel Pinteaux
Journal: Advanced Healthcare Materials (2021)

Abstract Intracerebral hemorrhage (ICH) is a deadly and debilitating type of stroke, caused by the rupture of cerebral blood vessels. To date, there are no restorative interventions approved for use in ICH patients, highlighting a critical unmet need. ICH shares some pathological features with other acute brain injuries such as ischemic stroke (IS) and traumatic brain injury (TBI), including the loss of brain tissue, disruption of the blood–brain barrier, and activation of a potent inflammatory response. New biomaterials such as hydrogels have been recently investigated for their therapeutic benefit in both experimental IS and TBI, owing to their provision of architectural support for damaged brain tissue and ability to deliver cellular and molecular therapies. Conversely, research on the use of hydrogels for ICH therapy is still in its infancy, with very few published reports investigating their therapeutic potential. Here, the published use of hydrogels in experimental ICH is commented upon and how approaches reported in the IS and TBI fields may be applied to ICH research to inform the design of future therapies is described. Unique aspects of ICH that are distinct from IS and TBI that should be considered when translating biomaterial‐based therapies between disease models are also highlighted.
Abstract 296: Quality Analysis of Cardiopulmonary Resuscitation From Two Emergency Medical Service Systems Using a Feedback Device
Authors: Mengqi Gao, Chenguang Liu, Stacy Gehman, Thomas Rea, Jennifer E Blackwood, Jonathan R Studnek, Steven Vandeventer, Allison E Infinger, Patricia L Dowbiggin, Dawn Jorgenson
Journal: Circulation (2019)

Background: High quality cardiopulmonary resuscitation (CPR) plays a critical role in the success of out-of-hospital resuscitation from sudden cardiac arrest (SCA). AHA guidelines provide protocol to achieve recommended targets for CPR quality metrics including chest compression fraction (CCF), percentage of chest compressions (CCs) with full chest recoil, CC rate and CC depth. Our objective was to report the CPR quality of two emergency medical services (EMS) agencies with different basic life support (BLS) CPR protocols. Methods: Data from 673 patients, 2015 to 2017, suffering out-of-hospital SCA were obtained from Philips FR3 AEDs. The Philips Q-CPR tool was used for real-time CPR feedback, and CC waveforms were recorded for retrospective CPR analysis using Philips Event Review Pro 5.0 and custom software. The two EMS systems had BLS protocol differences: Site 1(King County, WA, n = 93) applied a compression - ventilation ratio of 30:2, while Site 2 (Mecklenburg County, NC, n = 580) applied 200 compressions in each CPR interval and ventilations were performed during CCs. Analyses were performed comparing CPR metrics between sites and to AHA targets. Results: There were 3,460 minutes of resuscitation data analyzed, representing the initial phase of resuscitation prior to ALS. The proportion of cases with shocks was 21.5% (20 of 93) for site 1 and 16.9% (98 of 580) for site 2 (p = 0.3). Both sites achieved guideline metrics though there were statistical differences (Table 1). Compared to site 1, site 2 was associated with a higher CCF, faster CC rate, but less CC depth on average (p &lt; 0.001). Conclusions: High quality CPR defined by AHA guidelines was achieved with both sites during the early phase of AED resuscitation though some differences were observed. Additional investigation should identify equipment, or rescuer characteristics that are important to consistently achieve high quality CPR and how the combination might be tailored to optimize individual patient outcome.
Atezolizumab in Metastatic Triple-Negative Breast Cancer—No Contradiction in the Eyes of a Dispassionate Observer
Authors: Simon Van Wambeke, Bishal Gyawali
Journal: JAMA Oncology (2021)

This Viewpoint examines the observed differences between the IMpassion 131 and IMpassion130 clinical trials, which tested the benefit of adding atezolizumab to taxane in first-line treatment of metastatic triple-negative breast cancer.
Bile volatile organic compounds, smelling trouble
Authors: Enrique de-Madaria
Journal: Endoscopy (2021)

The sense of smell, or the ability to detect volatile chemicals, is conferred by olfactory receptors in the nasal cavity. It helps us detect both dangers (e. g. spoiled food, poisons, hostile creatures) and opportunities (e. g. delicious food, a good Ribera del Duero wine). Physicians have used the sense of smell to assist in the differential diagnosis of disease since Hippocratic times, and gastroenterologists are accustomed to detecting the specific smells of liver disease (i. e. fetor hepaticus), melena, and other conditions. Dogs can be trained to detect scents on the breath and in stool samples indicative of colorectal cancer (CRC) [1] and even COVID-19 [2].
The Treatment of Tuberculous Disease of the Hip in its Early Stages
Authors: H. Marsh
Journal: BMJ (1897)

ACCORDING to the Bor8enblatt fur den deut8chen Buchhandel the number of new works on medical science published in Germany during last year was 1,545.The total literary out- put of the Fatherland in,j1896 amounted to 23,339 works of various kinds.
Thiotepa-Busulfan-Fludarabine in Comparison to Busulfan-Cyclophosphamide As Myeloablative Conditioning Regimen Pre Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia: A Study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)
Authors: Francesco Saraceni, Eric Beohou, Myriam Labopin, William Arcese, Francesca Bonifazi, Polina Stepensky, Mahmoud Aljurf, Benedetto Bruno, Pietro Pioltelli, Jakob R. Passweg, Gerard Socie, Stella Santarone, Ibrahim Yakoub-Agha, Bipin N. Savani, Mohamad Mohty, Arnon Nagler
Journal: Blood (2017)
Image‐Guided TME‐Improving Nano‐Platform for Ca<sup>2+</sup> Signal Disturbance and Enhanced Tumor PDT
Authors: Yuping Jiang, Wei Meng, Lijuan Wu, Kai Shao, Lili Wang, Mengchao Ding, Jinsheng Shi, Xiaoying Kong
Journal: Advanced Healthcare Materials (2021)

Abstract Dysfunction of the calcium balancing system and disruption of calcium distribution can induce abnormal intracellular calcium overload, further causing serious damage and even cell death, which provides a potential therapeutic approach for tumor treatment. Herein, a nano‐platform, which includes UCNPs‐Ce6@RuR@mSiO 2 @PL‐HA NPs (UCRSPH) and SA‐CaO 2 nanoparticles, is prepared for improving the tumor micro‐environment (TME), Ca 2+ signal disturbance as well as enhanced photodynamic tumor therapy (PDT). UCRSPH combined with SA‐CaO 2 can alter TME and relieve hypoxia of the tumor to realize self‐reinforcing PDT under near‐IR irradiation (980 nm). The ruthenium red (RuR) in the UCRSPH NPs can be released to the cytoplasm after endocytosis of the nanoparticles, target Ca 2+ channel proteins on the endoplasmic reticulum and mitochondria, sarcoplasmic reticulum Ca 2+ ‐ATPase (SERCA), and mitochondrial calcium uniporter (MCU). The combined participation of nanoparticles and RuR promotes Ca 2+ imbalance and cytoplasmic calcium overload with the assistance of CaO 2 , and provides tumor cells higher sensitivity to PDT. Furthermore, the nano‐platform also provides fluorescence imaging and calcification computed tomography imaging for in vivo treatment guidance. In conclusion, this image‐guided nano‐platform show potential for highly specific, efficient combined therapy against tumor cells with minimal side‐effects to normal cells by integrating TME improvement, self‐reinforcing PDT, and Ca 2+ signal disturbance.
Lutetium-177–PSMA-617 for Metastatic Castration-Resistant Prostate Cancer
Authors: Oliver Sartor, Johann de Bono, Kim N. Chi, Karim Fizazi, Ken Herrmann, Kambiz Rahbar, Scott T. Tagawa, Luke T. Nordquist, Nitin Vaishampayan, Ghassan El-Haddad, Chandler H. Park, Tomasz M. Beer, Alison Armour, Wendy J. Pérez-Contreras, Michelle DeSilvio, Euloge Kpamegan, Germo Gericke, Richard A. Messmann, Michael J. Morris, Bernd J. Krause
Journal: New England Journal of Medicine (2021)

Metastatic castration-resistant prostate cancer remains fatal despite recent advances. Prostate-specific membrane antigen (PSMA) is highly expressed in metastatic castration-resistant prostate cancer. Lutetium-177 (177Lu)–PSMA-617 is a radioligand therapy that delivers beta-particle radiation to PSMA-expressing cells and the surrounding microenvironment.
A narrative overview of utilizing biomaterials to recapitulate the salient regenerative features of dental-derived mesenchymal stem cells
Authors: Sevda Pouraghaei Sevari, Sahar Ansari, Alireza Moshaverinia
Journal: International Journal of Oral Science (2021)

Abstract Tissue engineering approaches have emerged recently to circumvent many limitations associated with current clinical practices. This elegant approach utilizes a natural/synthetic biomaterial with optimized physiomechanical properties to serve as a vehicle for delivery of exogenous stem cells and bioactive factors or induce local recruitment of endogenous cells for in situ tissue regeneration. Inspired by the natural microenvironment, biomaterials could act as a biomimetic three-dimensional (3D) structure to help the cells establish their natural interactions. Such a strategy should not only employ a biocompatible biomaterial to induce new tissue formation but also benefit from an easily accessible and abundant source of stem cells with potent tissue regenerative potential. The human teeth and oral cavity harbor various populations of mesenchymal stem cells (MSCs) with self-renewing and multilineage differentiation capabilities. In the current review article, we seek to highlight recent progress and future opportunities in dental MSC-mediated therapeutic strategies for tissue regeneration using two possible approaches, cell transplantation and cell homing. Altogether, this paper develops a general picture of current innovative strategies to employ dental-derived MSCs combined with biomaterials and bioactive factors for regenerating the lost or defective tissues and offers information regarding the available scientific data and possible applications.
Mononuclear phagocyte system blockade using extracellular vesicles modified with CD47 on membrane surface for myocardial infarction reperfusion injury treatment
Authors: Zilun Wei, Zhaoyang Chen, Yongchao Zhao, Fan Fan, Weidong Xiong, Shuai Song, Yong Yin, Jingjing Hu, Kun Yang, Lebing Yang, Biao Xu, Junbo Ge
Journal: Biomaterials (2021)
Dysregulated Phenylalanine Catabolism Plays a Key Role in the Trajectory of Cardiac Aging
Authors: Gabor Czibik, Zaineb Mezdari, Dogus Murat Altintas, Juliette Bréhat, Maria Pini, Thomas d’Humières, Thaïs Delmont, Costin Radu, Marielle Breau, Hao Liang, Cecile Martel, Azania Abatan, Rizwan Sarwar, Ophélie Marion, Suzain Naushad, Yanyan Zhang, Maissa Halfaoui, Nadine Suffee, Didier Morin, Serge Adnot, Stéphane Hatem, Arash Yavari, Daigo Sawaki, Geneviève Derumeaux
Journal: Circulation (2021)

Aging myocardium undergoes progressive cardiac hypertrophy and interstitial fibrosis with diastolic and systolic dysfunction. Recent metabolomics studies shed light on amino acids in aging. The present study aimed to dissect how aging leads to elevated plasma levels of the essential amino acid phenylalanine and how it may promote age-related cardiac dysfunction.We studied cardiac structure and function, together with phenylalanine catabolism in wild-type (WT) and p21-/- mice (male; 2-24 months), with the latter known to be protected from cellular senescence. To explore phenylalanine's effects on cellular senescence and ectopic phenylalanine catabolism, we treated cardiomyocytes (primary adult rat or human AC-16) with phenylalanine. To establish a role for phenylalanine in driving cardiac aging, WT male mice were treated twice a day with phenylalanine (200 mg/kg) for a month. We also treated aged WT mice with tetrahydrobiopterin (10 mg/kg), the essential cofactor for the phenylalanine-degrading enzyme PAH (phenylalanine hydroxylase), or restricted dietary phenylalanine intake. The impact of senescence on hepatic phenylalanine catabolism was explored in vitro in AML12 hepatocytes treated with Nutlin3a (a p53 activator), with or without p21-targeting small interfering RNA or tetrahydrobiopterin, with quantification of PAH and tyrosine levels.Natural aging is associated with a progressive increase in plasma phenylalanine levels concomitant with cardiac dysfunction, whereas p21 deletion delayed these changes. Phenylalanine treatment induced premature cardiac deterioration in young WT mice, strikingly akin to that occurring with aging, while triggering cellular senescence, redox, and epigenetic changes. Pharmacological restoration of phenylalanine catabolism with tetrahydrobiopterin administration or dietary phenylalanine restriction abrogated the rise in plasma phenylalanine and reversed cardiac senescent alterations in aged WT mice. Observations from aged mice and human samples implicated age-related decline in hepatic phenylalanine catabolism as a key driver of elevated plasma phenylalanine levels and showed increased myocardial PAH-mediated phenylalanine catabolism, a novel signature of cardiac aging.Our findings establish a pathogenic role for increased phenylalanine levels in cardiac aging, linking plasma phenylalanine levels to cardiac senescence via dysregulated phenylalanine catabolism along a hepatic-cardiac axis. They highlight phenylalanine/PAH modulation as a potential therapeutic strategy for age-associated cardiac impairment.
Respiratory disease, and treatment / thematic poster session mortality rate in lung transplant recipients infected with COVID-19
Authors: L. L. Seijo, A. Perez, R. J. Shah, N. A. Kolaitis, A. Venado, L. E. Leard, M. Kleinhenz, J. P. Singer, J. A. Golden, J. Kukreja, B. Trinh, S. Hays
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: The emergence of the novel SARS-CoV-2 has caused a global pandemic costing the lives of thousands of people. In the US, COVID-19 is now the third leading cause of death among those aged 45 through 84. Lung transplant (LTx) recipients may be at increased risk for fulminant novel SARS-CoV-2 COVID-19 infection due to their immunosuppressed state. Within solid organ transplant (SOT) recipients, the reported mortality rate has ranged from 5% to 40%. Observational studies of LTx recipients have noted a mortality rate of 10% to 34%. To further understand the mortality rate in LTx recipients, we retrospectively evaluated LTx patients at our center with COVID-19. Method: We identified LTx recipients infected with COVID-19 by nasopharyngeal swab at our institution in the Bay Area. Baseline demographics and clinical data were obtained through review of the electronic medical record (EMR) from 3/20/2020 to 12/18/20. Results: Eighteen LTx recipients were diagnosed with COVID-19 infection. The mean age was 55.1 years (SD ± 3.0) and the majority were male (Table 1). Eightynine percent of patients had 2 or more comorbidities, which included hypertension, diabetes, coronary artery disease, and chronic kidney disease. Clinical presentation ranged from mild to severe, 11% of patients were monitored at home and 89% required hospitalization. Of those hospitalized, 50% were treated in the intensive care unit (ICU). The survival rate of COVID-19 in this population was 94%. One patient who recovered from COVID-19 later died in hospice care related to other comorbidities. Conclusion: Lung transplant recipients infected with COVID-19 were mostly male and most had two or more comorbidities. Most patients had severe infection requiring hospitalization and of these, half necessitated ICU level care. The overall survival rate, however, was higher than has been reported in LTx recipients at other centers. Favorable survival outcomes may be due to disease education and prompt access to healthcare in this LTx population. Additionally, during this study period, the Bay Area did not experience the same overwhelming surge of COVID-19 cases that has been seen in other regions of the United States. Further studies are needed to evaluate factors affecting COVID-19 mortality rate in LTx patients. .
Abstract 15041: Aortic Stiffness is Associated With a Reduced Coronary Flow Reserve
Authors: Jonathan J Lee, Rushik Bhuva, Bilal Ansari, Mary Jo Obeid, Sowjanya Yenigalla, Armghan H Ans, Garrett Oldland, Zeba Hashmath, Anila Hussain, Gurpreet Singh, Qasim Jehangir, Vaibhav Satija, Walter R Witschey, Sujith Kuruvilla, Scott Akers, Julio A Chirinos
Journal: Circulation (2019)

Introduction: Large artery stiffness promotes a steep diastolic pressure decay and an early arrival of wave reflections to the proximal aorta, reducing diastolic pressure augmentation by the reflec...
Single-Nucleus RNA Sequencing Identifies New Classes of Proximal Tubular Epithelial Cells in Kidney Fibrosis
Authors: Yueh-An Lu, Chia-Te Liao, Rachel Raybould, Bnar Talabani, Irina Grigorieva, Barbara Szomolay, Timothy Bowen, Robert Andrews, Philip R. Taylor, Donald Fraser
Journal: Journal of the American Society of Nephrology (2021)

Significance Statement Proximal tubular cells (PTCs) are numerically the predominant constituent of the kidney and are central to regeneration versus organ fibrosis following injury. However, variations in their phenotype are not well characterized. Single-nuclear RNA sequencing revealed phenotypes of PTCs in normal mouse kidney and changes in kidneys undergoing regeneration and fibrosis following aristolochic acid exposure. Five abundant and four rare PTC phenotypes were found, with abundant clusters mapped to different tubular segments and rare phenotypes mapped to proliferative, dedifferentiated, and fibrosis-associated phenotypes. These data identify unrecognized heterogeneity in PTC phenotypes and reveal novel PTCs associated with kidney fibrosis. Background Proximal tubular cells (PTCs) are the most abundant cell type in the kidney. PTCs are central to normal kidney function and to regeneration versus organ fibrosis following injury. This study used single-nucleus RNA sequencing (snRNAseq) to describe the phenotype of PTCs in renal fibrosis. Methods Kidneys were harvested from naïve mice and from mice with renal fibrosis induced by chronic aristolochic acid administration. Nuclei were isolated using Nuclei EZ Lysis buffer. Libraries were prepared on the 10× platform, and snRNAseq was completed using the Illumina NextSeq 550 System. Genome mapping was carried out with high-performance computing. Results A total of 23,885 nuclei were analyzed. PTCs were found in five abundant clusters, mapping to S1, S1–S2, S2, S2-cortical S3, and medullary S3 segments. Additional cell clusters (“new PTC clusters”) were at low abundance in normal kidney and in increased number in kidneys undergoing regeneration/fibrosis following injury. These clusters exhibited clear molecular phenotypes, permitting labeling as proliferating, New-PT1, New-PT2, and (present only following injury) New-PT3. Each cluster exhibited a unique gene expression signature, including multiple genes previously associated with renal injury response and fibrosis progression. Comprehensive pathway analyses revealed metabolic reprogramming, enrichment of cellular communication and cell motility, and various immune activations in new PTC clusters. In ligand-receptor analysis, new PTC clusters promoted fibrotic signaling to fibroblasts and inflammatory activation to macrophages. Conclusions These data identify unrecognized PTC phenotype heterogeneity and reveal novel PTCs associated with kidney fibrosis.
GP is liable only for costs of harm related to her advice in case of “wrongful birth,” say Supreme Court judges
Authors: Clare Dyer
Journal: BMJ (2021)

The UK Supreme Court has delivered a landmark judgment spelling out the extent to which a doctor can be held liable for the consequences of giving negligent advice or information to a patient.1

The case was brought by a mother who was wrongly led to believe by a GP that she was not a carrier of the haemophilia gene. She went on to have a child who was born with haemophilia and autism.

The High Court ruled in 2017 that the GP was liable for the costs of caring for a child with both conditions, even though the mother had sought advice only on the likelihood of having a child with haemophilia, and it awarded her £9m (€10.5m; $12.5m) in damages. …