tbuckley/cabot-search huggingface dataset:
Do anti‐psoriatic drugs work better in women than men?
Journal: British Journal of Dermatology (2021)

Linked Article: Maul et al. Br J Dermatol 2021; 185:1160-1168. Psoriasis is a chronic, scaly skin condition affecting about 2·5% of the population. It has a negative impact on people's quality of life, more so in women. It is usually treated with creams but is sometimes severe enough to need strong medicines, which are not always effective. This study examines differences between men and women in their responses to treatment. The 5346 adult patients were identified from Swiss and German patient registries; 60% were male. The men were heavier than women (average 91 kg versus 78 kg). At the start of treatment men had worse psoriasis whereas women had worse quality of life scores. All received systemic medicines, including non-biologics (methotrexate, fumaric acid esters, ciclosporin, acitretin or apremilast) or biologics (adalimumab, etanercept, infliximab, ustekinumab or secukinumab). They were followed up for up to a year after starting treatment and women showed better improvements on two scales called the Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) than men. These results might reflect better drug adherence in women, or their lower bodyweight - where the same dose is used for men and women, women will receive a higher dose per kilogram of body tissue. Also, because of hormonal factors, women's bodies contain a higher proportion of fat, which may allow the drug to spread more easily through the body. Finally, women experience their psoriasis more negatively than men and so there was more room for improvement in DLQI. These findings indicate a need for more personalized treatment, taking gender into account.
Food allergy across the globe
Authors: Vanitha Sampath, Elissa M Abrams, Bahman Adlou, Cezmi Akdis, Mübeccel Akdis, Helen A Brough, Susan Chan, Pantipa Chatchatee, R Sharon Chinthrajah, Renata Rodrigues Cocco, Antoine Deschildre, Philippe Eigenmann, Cesar Galvan, Ruchi Gupta, Elham Hossny, Jennifer J Koplin, Gideon Lack, Michael Levin, Lynette P Shek, Mika Makela, David Mendoza-Hernandez, Antonella Muraro, Nikolaos G Papadopoulous, Ruby Pawankar, Kirsten P Perrett, Graham Roberts, Cansin Sackesen, Hugh Sampson, Mimi L K Tang, Alkis Togias, Carina Venter, Christopher Michael Warren, Lisa M Wheatley, Gary W K Wong, Kirsten Beyer, Kari C Nadeau, Harald Renz
Journal: Journal of Allergy and Clinical Immunology (2021)
Microcirculatory Resistance Predicts Allograft Rejection and Cardiac Events After Heart Transplantation
Authors: Jung-Min Ahn, Frederik M. Zimmermann, Lars Gullestad, Oskar Angerås, Kristjan Karason, Kristoffer Russell, Ketil Lunde, Kozo Okada, Helen Luikart, Kiran K. Khush, Yasuhiro Honda, Nico H.J. Pijls, Sang Eun Lee, Jae-Joong Kim, Seung-Jung Park, Ole-Geir Solberg, William F. Fearon
Journal: Journal of the American College of Cardiology (2021)
Spatio-temporal analysis of nanoparticles in live tumor spheroids impacted by cell origin and density
Authors: Aria Ahmed-Cox, Elvis Pandzic, Stuart T. Johnston, Celine Heu, John McGhee, Friederike M. Mansfeld, Edmund J. Crampin, Thomas P. Davis, Renee M. Whan, Maria Kavallaris
Journal: Journal of Controlled Release (2021)

Nanoparticles hold great preclinical promise in cancer therapy but continue to suffer attrition through clinical trials. Advanced, three dimensional (3D) cellular models such as tumor spheroids can recapitulate elements of the tumor environment and are considered the superior model to evaluate nanoparticle designs. However, there is an important need to better understand nanoparticle penetration kinetics and determine how different cell characteristics may influence this nanoparticle uptake. A key challenge with current approaches for measuring nanoparticle accumulation in spheroids is that they are often static, losing spatial and temporal information which may be necessary for effective nanoparticle evaluation in 3D cell models. To overcome this challenge, we developed an analysis platform, termed the Determination of Nanoparticle Uptake in Tumor Spheroids (DONUTS), which retains spatial and temporal information during quantification, enabling evaluation of nanoparticle uptake in 3D tumor spheroids. Outperforming linear profiling methods, DONUTS was able to measure silica nanoparticle uptake to 10 μm accuracy in both isotropic and irregularly shaped cancer cell spheroids. This was then extended to determine penetration kinetics, first by a forward-in-time, center-in-space model, and then by mathematical modelling, which enabled the direct evaluation of nanoparticle penetration kinetics in different spheroid models. Nanoparticle uptake was shown to inversely relate to particle size and varied depending on the cell type, cell stiffness and density of the spheroid model. The automated analysis method we have developed can be applied to live spheroids in situ, for the advanced evaluation of nanoparticles as delivery agents in cancer therapy.
Mandatory vaccination for healthcare workers: consequences of denying bodily autonomy
Authors: Matteo Pizzo
Journal: BMJ (2021)

<h3>Abstract</h3> Impairments of working memory (WM) are commonly observed in a variety of neurodegenerative disorders but they are difficult to quantitatively assess in clinical cases. Recent studies in experimental animals have used low-dose ketamine (an NMDA receptor antagonist) to disrupt WM, partly mimicking the pathophysiology of schizophrenia. Here, we developed a novel behavioral paradigm to assess multiple components of WM and applied it to monkeys with and without ketamine administration. In an oculomotor foraging task, the animals were presented with 15 identical objects on the screen. One of the objects was associated with a liquid reward, and monkeys were trained to search for the target by generating sequential saccades under a time constraint. We assumed that the occurrence of recursive movements to the same object might reflect WM dysfunction. We constructed a “foraging model” that incorporated (1) memory capacity, (2) memory decay, and (3) utility rate; this model was able to explain more than 92% of the variations in behavioral data obtained from three monkeys. Following systemic administration of low dosages of ketamine, the memory capacity and utility rate were dramatically reduced by 15% and 57%, respectively, while memory decay remained largely unchanged. These results suggested that the behavioral deficits during the blockade of NMDA receptors were mostly due to the decreased usage of short-term memory. Our oculomotor paradigm and foraging model appear to be useful for quantifying multiple components of WM and could be applicable to clinical cases in future studies.
Expansion of Phenotypically Senescent CD57+ CD8 T Cells Is Associated with Impaired Immunocompetence after Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Sarah Morin, Amandine Pradier, Federica Giannotti, Anne-Claire Mamez, Diem-Lan Vu-Cantero, Marta Fabra-Urdiola, Caroline Stephan, Chiara Bernardi, Astrid Melotti, Stavroula Masouridi-Levrat, Eddy Roosnek, Laurent Kaiser, Yves Chalandon, Federico Simonetta
Journal: Blood (2021)
COVID-19 Testing and Case Rates and Social Contact Among Residential College Students in Connecticut During the 2020-2021 Academic Year
Authors: Olivia Schultes, Victoria Clarke, A. David Paltiel, Matthew Cartter, Lynn Sosa, Forrest W. Crawford
Journal: JAMA Network Open (2021)

During the 2020-2021 academic year, many institutions of higher education reopened to residential students while pursuing strategies to mitigate the risk of SARS-CoV-2 transmission on campus. Reopening guidance emphasized polymerase chain reaction or antigen testing for residential students and social distancing measures to reduce the frequency of close interpersonal contact, and Connecticut colleges and universities used a variety of approaches to reopen campuses to residential students.To characterize institutional reopening strategies and COVID-19 outcomes in 18 residential college and university campuses across Connecticut.This retrospective cohort study used data on COVID-19 testing and cases and social contact from 18 college and university campuses in Connecticut that had residential students during the 2020-2021 academic year.Tests for COVID-19 performed per week per residential student.Cases per week per residential student and mean (95% CI) social contact per week per residential student.Between 235 and 4603 residential students attended the fall semester across each of 18 institutions of higher education in Connecticut, with fewer residential students at most institutions during the spring semester. In census block groups containing residence halls, the fall student move-in resulted in a 475% (95% CI, 373%-606%) increase in mean contact, and the spring move-in resulted in a 561% (95% CI, 441%-713%) increase in mean contact compared with the 7 weeks prior to move-in. The association between test frequency and case rate per residential student was complex; institutions that tested students infrequently detected few cases but failed to blunt transmission, whereas institutions that tested students more frequently detected more cases and prevented further spread. In fall 2020, each additional test per student per week was associated with a decrease of 0.0014 cases per student per week (95% CI, -0.0028 to -0.00001).The findings of this cohort study suggest that, in the era of available vaccinations and highly transmissible SARS-CoV-2 variants, colleges and universities should continue to test residential students and use mitigation strategies to control on-campus COVID-19 cases.
Development and clinical advancement of small molecules for ex vivo expansion of hematopoietic stem cell
Authors: Jiaxing Li, Xiao Wang, Jiayu Ding, Yasheng Zhu, Wenjian Min, Wenbing Kuang, Kai Yuan, Chengliang Sun, Peng Yang
Journal: Acta Pharmaceutica Sinica B (2021)

Hematopoietic stem cell (HSC) transplantation is the only curative therapy for many diseases. HSCs from umbilical cord blood (UCB) source have many advantages over from bone marrow. However, limited HSC dose in a single CB unit restrict its widespread use. Over the past two decades, ex vivo HSC expansion with small molecules has been an effective approach for obtaining adequate HSCs. Till now, several small-molecule compounds have entered the phase I/II trials, showing safe and favorable pharmacological profiles. As HSC expansion has become a hot topic over recent years, many newly identified small molecules along with novel biological mechanisms for HSC expansion would help solve this challenging issue. Here, we will give an overview of HSC biology, discovery and medicinal chemistry development of small molecules, natural products targeting for HSC expansion, and their recent clinical progresses, as well as potential protein targets for HSC expansion.
Non-symbolic and symbolic number and the approximate number system
Authors: David Maximiliano Gómez
Journal: Behavioral and Brain Sciences (2021)

Abstract The distinction between non-symbolic and symbolic number is poorly addressed by the authors despite being relevant in numerical cognition, and even more important in light of the proposal that the approximate number system (ANS) represents rational numbers. Although evidence on non-symbolic number and ratios fits with ANS representations, the case for symbolic number and rational numbers is still open.
The immunotoxicity, but not anti-tumor efficacy, of anti-CD40 and anti-CD137 immunotherapies is dependent on the gut microbiota
Authors: Stephen J. Blake, Jane James, Feargal J. Ryan, Jose Caparros-Martin, Georgina L. Eden, Yee C. Tee, John R. Salamon, Saoirse C. Benson, Damon J. Tumes, Anastasia Sribnaia, Natalie E. Stevens, John W. Finnie, Hiroki Kobayashi, Deborah L. White, Steve L. Wesselingh, Fergal O’Gara, Miriam A. Lynn, David J. Lynn
Journal: Cell Reports Medicine (2021)

Immune agonist antibodies (IAAs) are promising immunotherapies that target co-stimulatory receptors to induce potent anti-tumor immune responses, particularly when combined with checkpoint inhibitors. Unfortunately, their clinical translation is hampered by serious dose-limiting, immune-mediated toxicities, including high-grade and sometimes fatal liver damage, cytokine release syndrome (CRS), and colitis. We show that the immunotoxicity, induced by the IAAs anti-CD40 and anti-CD137, is dependent on the gut microbiota. Germ-free or antibiotic-treated mice have significantly reduced colitis, CRS, and liver damage following IAA treatment compared with conventional mice or germ-free mice recolonized via fecal microbiota transplant. MyD88 signaling is required for IAA-induced CRS and for anti-CD137-induced, but not anti-CD40-induced, liver damage. Importantly, antibiotic treatment does not impair IAA anti-tumor efficacy, alone or in combination with anti-PD1. Our results suggest that microbiota-targeted therapies could overcome the toxicity induced by IAAs without impairing their anti-tumor activity.
Abstract 11295: Out-of-Hospital Cardiac Arrest Characteristics According to Arrest Location in Urban, Suburban, and Rural Areas of Denmark
Authors: Mads Christian Tofte Gregers, Linn Andelius, Carolina Malta Hansen, Sidsel Gamborg Møller, Christian Torp-Pedersen, Julie Kjoelbye, Fredrik Folke
Journal: Circulation (2021)

Introduction: Cardiopulmonary resuscitation (CPR) and early defibrillation are two of the most important factors for survival after out-of-hospital cardiac arrest (OHCA). However, little is known whether bystander interventions and survival are impaired in rural areas compared to more urbanized areas in Denmark. We hypothesized that bystander interventions and survival are lower in rural areas compared to urbanized areas. Methods: We included all non-EMS witnessed OHCAs with known GPS-location in Denmark (January 1, 2016 to December 31, 2019) and geocoded them according to county. All counties in Denmark were classified either as urban, suburban, or rural according to the degree of urbanization tool defined by the European Statistical Agency. Results: A total of 16,670 OHCAs were included, of which 4,555 (27%), 5,457 (33%), and 6,658 (40%) arrests occurred in urban, suburban, and rural areas respectively. The median age (73 vs. 74 vs. 73 years, p=0.003), ambulance response time (6 vs. 7 vs. 8 minutes, p&lt;0.0001), and proportion of arrests occurring in residential areas (77 vs. 79 vs. 78%, p=0.05) differed significantly between degrees of urbanization (from high to low). Fewer OHCAs received bystander CPR in urban and suburban areas compared to rural (76 vs. 77 vs. 79%, p=0.0002). The proportion of patients defibrillated by bystanders remained equal across urbanization. However, return of spontaneous circulation (ROSC) (27 vs. 27 vs. 24%, p&lt;0.0001) and 30-day survival was lower in rural areas (15 vs. 14 vs. 12, p&lt;0.0001) (Figure 1). Conclusion: Degree of urbanization was associated with increased rates of bystander CPR in rural areas. Despite this, ROSC and 30-day survival were higher in urban and suburban areas compared to rural areas which could not be explained by cardiac arrest characteristics.
The ECHELON-2 Trial: 5-year results of a randomized, phase III study of brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma
Authors: S. Horwitz, O.A. O'Connor, B. Pro, L. Trümper, S. Iyer, R. Advani, N.L. Bartlett, J.H. Christensen, F. Morschhauser, E. Domingo-Domenech, G. Rossi, W.S. Kim, T. Feldman, T. Menne, D. Belada, Á. Illés, K. Tobinai, K. Tsukasaki, S.-P. Yeh, A. Shustov, A. Hüttmann, K.J. Savage, S. Yuen, P.L. Zinzani, H. Miao, V. Bunn, K. Fenton, M. Fanale, M. Puhlmann, T. Illidge
Journal: Annals of Oncology (2021)

For patients with peripheral T-cell lymphoma (PTCL), outcomes using frontline treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like therapy are typically poor. The ECHELON-2 study demonstrated that brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (A+CHP) exhibited statistically superior progression-free survival (PFS) per independent central review and improvements in overall survival versus CHOP for the frontline treatment of patients with systemic anaplastic large cell lymphoma or other CD30-positive PTCL.
Association of Second-generation Antiandrogens With Depression Among Patients With Prostate Cancer
Authors: Malgorzata K. Nowakowska, Xiudong Lei, Mackenzie R. Wehner, Paul G. Corn, Sharon H. Giordano, Kevin T. Nead
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Previous studies have shown a consistent association between hormone therapy (HT), such as androgen deprivation therapy, to treat prostate cancer and depression risk. However, the association between second-generation antiandrogens (AAs) and depression is unknown. <h3>Objective</h3> To test the a priori hypothesis that second-generation AAs are associated with an increased risk of depression, including compared with traditional forms of HT. <h3>Design, Setting, and Participants</h3> This retrospective cohort study analyzed patients aged 66 years and older who were diagnosed with prostate cancer without a second cancer in 12 months from January 2011 to December 2015. Patients with continuous Medicare Parts A, B, and D coverage were included. Individuals who received any form of HT prior to prostate cancer diagnosis and those previously diagnosed with depression were excluded. Data were collected from the Surveillance, Epidemiology, and End Results–Medicare and Texas Cancer Registry–Medicare linked databases. Data were analyzed from February to May 2021. <h3>Exposures</h3> The following treatment groups were compared: (1) no HT group, (2) traditional HT group (HT without second-generation AA exposure), and (3) second-generation AA group. <h3>Main Outcomes and Measures</h3> Risk of depression in the second-generation AA group compared with the no HT and traditional HT groups, determined prior to data collection, stratified by diagnosis stage. <h3>Results</h3> Of 210 804 patients diagnosed with prostate cancer during the study window, 30 069 men (11 484 [38%] aged 66-70 years; 22 594 [75%] White) who met inclusion criteria were identified. Overall, 17 710 (59%) received no HT, 11 311 (38%) received traditional HT only, and 1048 (3%) received a second-generation AA. Those receiving a second-generation AA were more likely to be older (aged ≥81 years: second-generation AA group, 246 [24%]; traditional HT group, 1997 [18%]; no HT group, 1173 [7%]) and present with advanced disease (eg, distant disease: second-generation AA group, 562 [24%]; traditional HT group, 876 [8%]; no HT group, 129 [0.7%]). Multivariable Cox proportional hazards analysis showed that the second-generation AA group had an increased risk of depression compared with the no HT group (hazard ratio [HR], 2.15; 95% CI, 1.79-2.59;<i>P</i> &lt; .001) and the traditional HT group (HR, 2.26; 95% CI, 1.88-2.73;<i>P</i> &lt; .001), including specifically among those with metastatic disease at diagnosis (HR, 2.40; 95% CI, 1.38-4.15;<i>P</i> = .002). <h3>Conclusions and Relevance</h3> In this cohort study, patients with prostate cancer who received a second-generation AA had a large and clinically significant increased risk of depression compared with patients who received traditional HT alone or no HT, including when limiting our analysis to individuals with metastatic disease at diagnosis.
Loss of Integrin-Linked Kinase Sensitizes Breast Cancer to SRC Inhibitors
Authors: Henry Beetham, Billie G.C. Griffith, Olga Murina, Alexander E.P. Loftus, David A. Parry, Carolin Temps, Jayne Culley, Morwenna Muir, Asier Unciti-Broceta, Andrew H. Sims, Adam Byron, Valerie G. Brunton
Journal: Cancer Research (2021)

Abstract SRC is a nonreceptor tyrosine kinase with key roles in breast cancer development and progression. Despite this, SRC tyrosine kinase inhibitors have so far failed to live up to their promise in clinical trials, with poor overall response rates. We aimed to identify possible synergistic gene–drug interactions to discover new rational combination therapies for SRC inhibitors. An unbiased genome-wide CRISPR-Cas9 knockout screen in a model of triple-negative breast cancer revealed that loss of integrin-linked kinase (ILK) and its binding partners α-Parvin and PINCH-1 sensitizes cells to bosutinib, a clinically approved SRC/ABL kinase inhibitor. Sensitivity to bosutinib did not correlate with ABL dependency; instead, bosutinib likely induces these effects by acting as a SRC tyrosine kinase inhibitor. Furthermore, in vitro and in vivo models showed that loss of ILK enhanced sensitivity to eCF506, a novel and highly selective inhibitor of SRC with a unique mode of action. Whole-genome RNA sequencing following bosutinib treatment in ILK knockout cells identified broad changes in the expression of genes regulating cell adhesion and cell–extracellular matrix. Increased sensitivity to SRC inhibition in ILK knockout cells was associated with defective adhesion, resulting in reduced cell number as well as increased G1 arrest and apoptosis. These findings support the potential of ILK loss as an exploitable therapeutic vulnerability in breast cancer, enhancing the effectiveness of clinical SRC inhibitors. Significance: A CRISPR-Cas9 screen reveals that loss of integrin-linked kinase synergizes with SRC inhibition, providing a new opportunity for enhancing the clinical effectiveness of SRC inhibitors in breast cancer.
Error in Table 1
Journal: JAMA Psychiatry (2021)

Richard A. Brown, PhD; Haruka Minami, PhD; Jacki Hecht, RN; Christopher W. Kahler, PhD; Lawrence H. Price, MD; Kimberly L. Kjome, MD; Erika Litvin Bloom, PhD; Douglas E. Levy, PhD; Kelly M. Carpenter, PhD; Ashleigh Smith, LCSW; Jasper A. J. Smits, PhD; Nancy A. Rigotti, MD
Mapping Macrophage Polarization and Origin during the Progression of the Foreign Body Response to a Poly(ethylene glycol) Hydrogel Implant
Authors: Leila S. Saleh, Luke D. Amer, Brittany J. Thompson, Thomas Danhorn, Jennifer R. Knapp, Sophie L. Gibbings, Stacey Thomas, Lea Barthel, Brian P. O'Connor, William J. Janssen, Scott Alper, Stephanie J. Bryant
Journal: Advanced Healthcare Materials (2021)

Poly(ethylene glycol) (PEG) hydrogels hold promise for in vivo applications but induce a foreign body response (FBR). While macrophages are key in the FBR, many questions remain. This study investigates temporal changes in the transcriptome of implant-associated monocytes and macrophages. Proinflammatory pathways are upregulated in monocytes compared to control monocytes but subside by day 28. Macrophages are initially proinflammatory but shift to a profibrotic state by day 14, coinciding with fibrous capsule emergence. Next, this study assesses the origin of macrophages responsible for fibrous encapsulation using wildtype, C-C Motif Chemokine Receptor 2 (CCR2)-/- mice that lack recruited macrophages, and Macrophage Fas-Induced Apoptosis (MaFIA) mice that enable macrophage ablation. Subpopulations of recruited and tissue-resident macrophages are identified. Fibrous encapsulation proceeds in CCR2-/- mice similar to wildtype mice. However, studies in MaFIA mice indicate that macrophages are necessary for fibrous capsule formation. These findings suggest that macrophage origin impacts the FBR progression and provides evidence that tissue-resident macrophages and not the recruited macrophages may drive fibrosis in the FBR to PEG hydrogels. This study demonstrates that implant-associated monocytes and macrophages have temporally distinct transcriptomes in the FBR and that profibrotic pathways associated with macrophages may be enriched in tissue-resident macrophages.
Re: Jeremy Yuen-Chun Teoh, Daniele Castellani, Claudia Mercader, et al. A Quantitative Analysis Investigating the Prevalence of “Manels” in Major Urology Meetings. Euro Urol 2021;80:442–9
Authors: James T Rutka, Neil Fleshner, Avery B Nathens
Journal: European Urology (2021)