tbuckley/cabot-search huggingface dataset:
Cytokine release syndrome in a patient with colorectal cancer after vaccination with BNT162b2
Authors: Lewis Au, Annika Fendler, Scott T. C. Shepherd, Karolina Rzeniewicz, Maddalena Cerrone, Fiona Byrne, Eleanor Carlyle, Kim Edmonds, Lyra Del Rosario, John Shon, Winston A. Haynes, Barry Ward, Ben Shum, William Gordon, Camille L. Gerard, Wenyi Xie, Nalinie Joharatnam-Hogan, Kate Young, Lisa Pickering, Andrew J. S. Furness, James Larkin, Ruth Harvey, George Kassiotis, Sonia Gandhi, George Kassiotis, Sonia Gandhi, Charles Swanton, Charles Swanton, Charlotte Fribbens, Katalin A. Wilkinson, Robert J. Wilkinson, David K. Lau, Susana Banerjee, Naureen Starling, Ian Chau, Lewis Au, Annika Fendler, Scott T. C. Shepherd, Fiona Byrne, Ben Shum, Camille Gerard, Kate Young, Lisa Pickering, Andrew J. S. Furness, James Larkin, George Kassiotis, Katalin A. Wilkinson, Robert J. Wilkinson, Susana Banerjee, Naureen Starling, Ian Chau, Samra Turajlic, Samra Turajlic
Journal: Nature Medicine (2021)

Abstract Patients with cancer are currently prioritized in coronavirus disease 2019 (COVID-19) vaccination programs globally, which includes administration of mRNA vaccines. Cytokine release syndrome (CRS) has not been reported with mRNA vaccines and is an extremely rare immune-related adverse event of immune checkpoint inhibitors. We present a case of CRS that occurred 5 d after vaccination with BTN162b2 (tozinameran)—the Pfizer-BioNTech mRNA COVID-19 vaccine—in a patient with colorectal cancer on long-standing anti-PD-1 monotherapy. The CRS was evidenced by raised inflammatory markers, thrombocytopenia, elevated cytokine levels (IFN-γ/IL-2R/IL-18/IL-16/IL-10) and steroid responsiveness. The close temporal association of vaccination and diagnosis of CRS in this case suggests that CRS was a vaccine-related adverse event; with anti-PD1 blockade as a potential contributor. Overall, further prospective pharmacovigillence data are needed in patients with cancer, but the benefit–risk profile remains strongly in favor of COVID-19 vaccination in this population.
AB0902-HPR COVID-19 PANDEMIC: KNOWLEDGE, BELIEVES AND FEARS IN PATIENTS WITH CHRONIC INFLAMMATORY RHEUMATIC DISEASES IN A DEVELOPING COUNTRY
Authors: T. El Joumani, H. Rkain, T. Fatima Zahrae, H. Kenza, A. Radouan, N. Laila, S. Bahloul, E. A. Nada, T. Latifa, N. Hajjaj-Hassouni, F. Allali
Journal: Annals of the Rheumatic Diseases (2021)

Objectives: To investigate the knowledge, believes, and fears of patients with Chronic Inflammatory Rheumatic Diseases (CIRD) in Morocco regarding the Covid-19 pandemic. Methods: COVID-19 related knowledge was evaluated through following items: clinical presentations, age of infection, transmission routes, self-reported preventive behaviors, patient’s approach in case of suspicion of being infected by COVID-19 and vaccination. We also investigated the source of the patients’ information. Believes and fears of patients regarding COVID-19 was assessed using 2 items that explored participant’s perception of the degree of threat to public health and their individual infection susceptibility compared to the general population. Results: A cross-sectional study was conducted among patients with rheumatic diseases using a questionnaire providing information on patients and disease characteristics. 350 patients had participated in this online survey (mean age of 46,1 ± 14,4, 68% were women, 15.7% were illiterate, 45.7% were unemployed, rural residence in 11.7% of cases). The correct answer rates of the 6 questions of the knowledge section of the questionnaire were 53.4-100% with an average mean of 90.7%. The mean COVID-19 knowledge score was 5,43/6 (SD:0,48). Most participants (96.6%) correctly identified the age group concerned about Covid-19 infection. Remarkably 92.3% of the participants recognized 3 clinical features when 97.7% and 72.3% of the sample recognized perfectly modes of transmission and disease prevention measures. 87.4% of patients knew the recommended course of action to do if they have fever or cough and have recently been in contact with an infected patient. 64% of the study population thought that there was no vaccine available yet. The sources of information on COVID-19 were in descending order: rheumatologist (56.6 %), personal research (on the internet or other) (43.4%), video broadcasts on national television channels (28%), other Awareness Video (24.2%). Regarding the patients believes and fears toward COVID-19, 81.7% of patients believed that the pandemic is a serious threat for the public health and 80.6% thought that their CIRD makes them more exposed to the risk of contamination than general population. Conclusion: The results of this survey show a high prevalence of patient concern about COVID-19. However, the majority of patients responded correctly on the mode of transmission and the means of protection for the COVID-19 infection. Those results could be explained by enormous awareness-raising efforts carried out by our differents departments of our government. Disclosure of Interests: None declared
Neoplastic and immune single-cell transcriptomics define subgroup-specific intra-tumoral heterogeneity of childhood medulloblastoma
Authors: Kent A Riemondy, Sujatha Venkataraman, Nicholas Willard, Anandani Nellan, Bridget Sanford, Andrea M Griesinger, Vladimir Amani, Siddhartha Mitra, Todd C Hankinson, Michael H Handler, Martin Sill, Jennifer Ocasio, Seth J Weir, Daniel S Malawsky, Timothy R Gershon, Alexandra Garancher, Robert J Wechsler-Reya, Jay R Hesselberth, Nicholas K Foreman, Andrew M Donson, Rajeev Vibhakar
Journal: Neuro-Oncology (2021)

Abstract Background Medulloblastoma (MB) is a heterogeneous disease in which neoplastic cells and associated immune cells contribute to disease progression. We aimed to determine the influence of neoplastic and immune cell diversity on MB biology in patient samples and animal models. Methods To better characterize cellular heterogeneity in MB we used single-cell RNA sequencing, immunohistochemistry, and deconvolution of transcriptomic data to profile neoplastic and immune populations in patient samples and animal models across childhood MB subgroups. Results Neoplastic cells cluster primarily according to individual sample of origin which is influenced by chromosomal copy number variance. Harmony alignment reveals novel MB subgroup/subtype-associated subpopulations that recapitulate neurodevelopmental processes, including photoreceptor and glutamatergic neuron-like cells in molecular subgroups GP3 and GP4, and a specific nodule-associated neuronally differentiated subpopulation in the sonic hedgehog subgroup. We definitively chart the spectrum of MB immune cell infiltrates, which include subpopulations that recapitulate developmentally related neuron-pruning and antigen-presenting myeloid cells. MB cellular diversity matching human samples is mirrored in subgroup-specific mouse models of MB. Conclusions These findings provide a clearer understanding of the diverse neoplastic and immune cell subpopulations that constitute the MB microenvironment.
Sutureless Transplantation of Amniotic Membrane Using a Visible Light‐Curable Protein Bioadhesive for Ocular Surface Reconstruction
Authors: Seong‐Woo Maeng, Tae Yoon Park, Ji Sang Min, Longyu Jin, Kye Il Joo, Woo Chan Park, Hyung Joon Cha
Journal: Advanced Healthcare Materials (2021)

The conjunctiva is a thin mucous membrane of the eye. Pterygium, a commonly appearing disease on the ocular surface, requires surgery to excise the conjunctiva to prevent visual deterioration. Recently, transplantation of the amniotic membrane (AM), which is the innermost membrane of the placenta, has been highlighted as an efficient method to cure conjunctiva defects because of its advantages of no side effects compared to mitomycin C treatment and not leaving additional scars on donor site compared to conjunctival autografting. However, to minimize additional damage to the ocular surface by suturing, AM transplantation (AMT) needs to be simplified by using a less invasive, time-saving method. In this work, a visible light-curable protein bioadhesive (named FixLight) for efficient sutureless AMT is applied. FixLight, which is based on bioengineered mussel adhesive protein (MAP), is easily applied between damaged ocular surfaces and transplanted AM, and rapidly cured by harmless blue light activation. Through in vivo evaluation using a rabbit model, the authors demonstrated that FixLight enabled facile, fast, and strong attachment of AM on sclera and promoted ocular surface reconstruction with good biocompatibility. Thus, FixLight can be successfully used as a promising clinical bioadhesive in opthalmological surgeries that require sutureless and rapid operation.
Medical algorithm: Diagnosis and management of antibody immunodeficiencies
Authors: Anna Šedivá, Tomáš Milota, Jiří Litzman, Isabella Quinti, Isabelle Meyts, Siobhan Burns, Stephen Jolles
Journal: Allergy (2021)

Dr. Sediva reports grants from Motol University Hospital, personal fees from Takeda, personal fees from Octapharma, personal fees from CSL Behring, during the conduct of the study; Dr. Milota has nothing to disclose. Dr. Litzman reports personal fees from Octapharma and Takeda. Dr. Quinti reports other from null, outside the submitted work; Dr. Meyts reports grants from CSL Behring, outside the submitted work. Dr. Burns reports grants from NIHR, grants from UCLH III BRC, grants from UKRI/ MRC, grants from GOSH/ICH BRC, personal fees from Immunodeficiency Canada/IAACI, non-financial support from CSL Behring, from Baxalta, personal fees from Biotest, grants from Wellcome Trust, grants from Rosetrees Foundation, grants from Jeffrey Modell Foundation, during the conduct of the study; Dr. Jolles reports grants, personal fees and other from CSL Behring, grants, personal fees and other from Octapharma, grants, personal fees and other from Takeda, personal fees and other from LFB, personal fees and other from Grifols, personal fees and other from Biotest, outside the submitted work.
Improving in vitro and in vivo corrosion resistance and biocompatibility of Mg–1Zn–1Sn alloys by microalloying with Sr
Authors: Yafeng Wen, Qingshan Liu, Jingfeng Wang, Qiming Yang, Weikang Zhao, Bo Qiao, Yuling Li, Dianming Jiang
Journal: Bioactive Materials (2021)

Magnesium (Mg) and its alloys have attracted attention as potential biodegradable materials in orthopedics due to their mechanical and physical properties, which are compatible with those of human bone. However, the effect of the mismatch between the rapid material degradation and fracture healing caused by the adverse effect of hydrogen (H2), which is generated during degradation, on surrounding bone tissue has severely restricted the application of Mg and its alloys. Thus, the development of new Mg alloys to achieve ideal degradation rates, H2 evolution and mechanical properties is necessary. Herein, a novel Mg–1Zn–1Sn-xSr (x = 0, 0.2, 0.4, and 0.6 wt%) quaternary alloy was developed, and the microstructure, mechanical properties, corrosion behavior and biocompatibility in vitro/vivo were investigated. The results demonstrated that a minor amount of strontium (Sr) (0.2 wt %) enhanced the corrosion resistance and mechanical properties of Mg–1Zn–1Sn alloy through grain refinement and second phase strengthening. Simultaneously, due to the high hydrogen overpotential of tin (Sn), the H2 release of the alloys was significantly reduced. Furthermore, Sr-containing Mg–1Zn–1Sn-based alloys significantly enhanced the viability, adhesion and spreading of MC3T3-E1 cells in vitro due to their unique biological activity and the ability to spontaneously form a network structure layer with micro/nanotopography. A low corrosion rate and improved biocompatibility were also maintained in a rat subcutaneous implantation model. However, excessive Sr (>0.2 wt %) led to a microgalvanic reaction and accelerated corrosion and H2 evolution. Considering the corrosion resistance, H2 evolution, mechanical properties and biocompatibility in vitro and in vivo, Mg–1Zn–1Sn-0.2Sr alloy has tremendous potential for clinical applications.
Covid-19: Is it safe to lift all restrictions in England from 21 June?
Authors: Elisabeth Mahase
Journal: BMJ (2021)

England is set to remove all legal limits on social contact from 21 June and allow nightclubs to reopen, although masks may still be required in some public spaces and the test and trace system will continue.

However, the emergence of the B.1.617.2 variant, first detected in India, has led to concerns that further easing may need to be delayed. As cases of this variant spread across the country, The BMJ looks at what we know.

Although it has given a date for the easing, the government has said that this is about “data, not dates” and that the final decision to list restrictions will be based on four tests1:

It’s not clear when the final decision will be made on the last stage of easing restrictions. On 27 May England’s health secretary, Matt Hancock, said that it was still too early to say, and the prime minister, Boris Johnson, said that nothing in the data currently suggested a need to “deviate from the roadmap, but we may need to wait.”2

Latest data from Public Health England (PHE) show that cases of the B.1.617.2 variant have risen by 3535 from 12 May to 19 May, totalling 6959. While Bolton, Bedford, and Blackburn with Darwen still have the highest prevalence, most parts of the country now have cases of the variant. The report says that B.1.617.2 is likely more transmissible than the B.1.1.7 variant, first identified in the UK.

“In some affected areas, hospitalisations are rising,” said PHE. “Hospital attendances and admissions are predominantly in unvaccinated individuals, highlighting how crucial it is that …
Correspondence on ‘Immunogenicity and safety of anti-SARS-CoV-2 mRNA vaccines in patients with chronic inflammatory conditions and immunosuppressive therapy in a monocentric cohort’
Authors: Giuseppe A Ramirez, Emanuel Della-Torre, Luca Moroni, Mona-Rita Yacoub, Lorenzo Dagna
Journal: Annals of the Rheumatic Diseases (2021)

We read with interest the recent report by Geisen et al ,1 who describe the immunogenicity and safety profile of two mRNA-based anti-SARS-CoV-2 vaccines in a cohort of 26 patients with chronic arthritides, psoriasis and other inflammatory diseases, compared with 42 healthy controls. The majority of subjects were health professionals, which makes the 14-day post-vaccinal observations provided by the authors particularly informative for high-risk settings, such as hospitals. Extensive data about the impact of anti-SARS-CoV-2 vaccines in patients with immune-mediated disorders are eagerly awaited, since people living with these diseases were excluded from registration trials,2–4 despite constituting a risk group for severe SARS-CoV-2-realated disease (COVID-19)5–7 and, potentially, for adverse immune-mediated post-vaccinal events.8–11

To contribute in filling this knowledge gap, we studied 55 consecutive patients (54 health professionals) with rheumatic diseases and primary immunodeficiencies, for a median (IQR) of 66 (42–75) days from the first and 45 (20–52) days from the second dose of the BNT162b2 vaccine2 (detailed methods: online supplemental material 1). Thirty-eight patients (69%) had one or more comorbidities, including allergy in 22 cases (table 1).### Supplementary data

[annrheumdis-2021-220539supp001.pdf]

View this table:

Table 1 
Clinical features of the study cohort



At time of vaccination, 42/55 patients had been in remission for 20 (5–29) months. The median disease duration was 11 (5–18) years. Fifty-one patients (93%) were taking one or more immunosuppressive/immunomodulating drugs beside other treatments (online supplemental tables 1 and 2).### Supplementary data

[annrheumdis-2021-220539supp002.pdf]

### Supplementary data

[annrheumdis-2021-220539supp003.pdf]

No patient had evidence of …
Availability of fixed-dose, child-friendly formulations of first-line tuberculosis drugs in Europe
Authors: Antoni Noguera-Julian, Danilo Buonsenso, Lindsay McKenna, James A. Seddon, Nicole Ritz
Journal: European Respiratory Journal (2021)

<b>The paediatric fixed-dose combinations of TB drugs are not available in Europe, where the pill burden and palatability of paediatric TB treatment is not acceptable. The introduction of child-friendly TB drugs into Europe is urgently needed.</b>https://bit.ly/3fTgw1I
COVID-19 mRNA vaccine-related adenopathy mimicking metastatic melanoma
Authors: Peter A Prieto, Kathleen Mannava, Deepak M Sahasrabudhe
Journal: The Lancet Oncology (2021)

A 48-year-old white female patient underwent wide excision and sentinel lymph node biopsy for a T2a melanoma of the left deltoid region at Strong Memorial Hospital of the University of Rochester Medical Center (Rochester, NY, USA) on Dec 11, 2020. Final pathology revealed a negative excision margin and one of two sentinel lymph nodes with micrometastatic disease (with no extracapsular extension); T2aN1 pathological stage IIIA. Staging brain MRI was negative; however, a PET–CT scan showed substantial fluorodeoxyglucose (18F-FDG) avidity in the contralateral axilla and neck (figure, A) and postoperative changes in the ipsilateral axilla and shoulder (small seroma and biopsy clips from sentinel lymph node biopsy). Image-guided biopsy of an FDG-avid right axillary lymph node was done on Jan 13, 2021. Histological immunohistochemical stains for melanocytes (Melan-A and SOX10) were negative, which is consistent with a diagnosis of reactive lymphoid tissue. Further questioning of the patient revealed that she had received her first dose of the COVID-19 mRNA vaccine (the vaccine produced by Moderna [Cambridge, MA, USA]) in the right deltoid muscle 5 days prior to the initial staging PET–CT scan. Her second dose of the vaccine was administered in the right thigh on Jan 28, 2021. A repeat PET–CT scan done 5 days after her second dose of the vaccine revealed resolution of the hypermetabolic right axillary and neck nodes with normal radiographic morphology (figure, B) and the development of hypermetabolic right inguinal and pelvic adenopathy. Clinicians should be aware of the transient appearance of hypermetabolic regional lymph nodes after injection of the COVID-19 mRNA vaccine and possibly other vaccines. As COVID-19 vaccination programmes expand worldwide, it will be important for oncologists to include history of vaccination in interpreting the results of staging imaging studies. Contributors PAP made the clinical diagnosis. PAP and DMS proposed the manuscript. KM made the pathological diagnosis and reviewed the immunohistochemical stains. PAP, KM, and DMS all contributed equally to the drafting the manuscript and writing and editing. All authors developed and approved the manuscript. Written informed consent to publication was obtained. We declare no competing interests.
Urinary Dickkopf-3 and Contrast-Associated Kidney Damage
Authors: Giuseppina Roscigno, Cristina Quintavalle, Giuseppe Biondi-Zoccai, Francesca De Micco, Giacomo Frati, Alessandra Affinito, Silvia Nuzzo, Gerolama Condorelli, Carlo Briguori
Journal: Journal of the American College of Cardiology (2021)
Randomized Phase II Study of PET Response–Adapted Combined Modality Therapy for Esophageal Cancer: Mature Results of the CALGB 80803 (Alliance) Trial
Authors: Karyn A. Goodman, Fang-Shu Ou, Nathan C. Hall, Tanios Bekaii-Saab, Briant Fruth, Erin Twohy, Michael O. Meyers, Daniel J. Boffa, Kisha Mitchell, Wendy L. Frankel, Donna Niedzwiecki, Anne Noonan, Yelena Y. Janjigian, Paul J. Thurmes, Alan P. Venook, Jeffrey A. Meyerhardt, Eileen M. O'Reilly, David H. Ilson
Journal: Journal of Clinical Oncology (2021)

To evaluate the use of early assessment of chemotherapy responsiveness by positron emission tomography (PET) imaging to tailor therapy in patients with esophageal and esophagogastric junction adenocarcinoma.
Evaluation of Seropositivity Following BNT162b2 Messenger RNA Vaccination for SARS-CoV-2 in Patients Undergoing Treatment for Cancer
Authors: Amir Massarweh, Noa Eliakim-Raz, Amos Stemmer, Adva Levy-Barda, Shlomit Yust-Katz, Alona Zer, Alexandra Benouaich-Amiel, Haim Ben-Zvi, Neta Moskovits, Baruch Brenner, Jihad Bishara, Dafna Yahav, Boaz Tadmor, Tal Zaks, Salomon M. Stemmer
Journal: JAMA Oncology (2021)

Patients with cancer undergoing treatment are at high risk of COVID-19 following SARS-CoV-2 infection; however, their ability to produce an adequate antibody response to messenger RNA SARS-CoV-2 vaccines is unclear.
Author Correction: Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda
Authors: Aline Uwimana, Eric Legrand, Barbara H. Stokes, Jean-Louis Mangala Ndikumana, Marian Warsame, Noella Umulisa, Daniel Ngamije, Tharcisse Munyaneza, Jean-Baptiste Mazarati, Kaendi Munguti, Pascal Campagne, Alexis Criscuolo, Frédéric Ariey, Monique Murindahabi, Pascal Ringwald, David A. Fidock, Aimable Mbituyumuremyi, Didier Menard
Journal: Nature Medicine (2021)

In the version of this article initially published, the numbers of cells in the third sentence of the second paragraph of the Methods subsection ' Antibody-dependent neutrophil phagocytosis' (500,000) and in the fifth sentence of the first paragraph of the Methods subsection ' Antibody-dependent monocyte phagocytosis' (250,000) were incorrect.The correct numbers are 50,000 and 25,000 (respectively).The errors have been corrected in the HTML and PDF versions of the article.
Pivoting From PTH to FGF23 to Mend Breaking Hearts on Dialysis
Authors: Susan L. Murray, Myles Wolf
Journal: Circulation Research (2021)

atients with end-stage kidney disease (ESKD) suffer from exceptionally high rates of heart disease and poor responsiveness to treatments that are of proven benefit in the general population.Pathological left ventricular hypertrophy (LVH) affects a majority of patients with ESKD and is perhaps the most common cardiac complication of ESKD.Clinically, LVH can have multiple manifestations.During dialysis sessions, diastolic dysfunction due to LVH can precipitate episodes of intradialytic hypotension that prevent sufficient ultrafiltration.Between dialysis sessions, patients' limited capacity to tolerate excess volume can precipitate hospitalizations for pulmonary edema and emergent dialysis.By increasing myocardial oxygen demand in patients who often manifest a combination of coronary atherosclerosis and nonatherosclerotic coronary arterial calcification, LVH can also elicit episodes of cardiac ischemia.High filling pressures, atrial chamber dilation, intramyocardial fibrosis, and ischemia often culminate in atrial fibrillation and sudden death, which is a leading cause of death in ESKD.These daunting consequences of LVH suggest that targeting its modifiable mechanisms in ESKD could lead to breakthroughs for a large population in desperate need of novel therapeutics.
Abstract 13635: Heterozygous Ablation of Ryanodine Receptor Phosphorylation at Ser2808 Exacerbates Disease in a Genetic Model of Ca-Dependent Heart Failure
Authors: Bin Liu, Hsiang-Ting Ho, Hector Valdivia, Sandor Gyorke
Journal: Circulation (2012)

RyR2 dysfunction (i.e. “leaky” RyRs) due to hyperphosphorylation at Ser-2808 by PKA has been implicated in the pathophysiology of heart failure (HF), although this remains uncertain. We recently ge...