tbuckley/cabot-search huggingface dataset:
Liposomal cytarabine and daunorubicin (CPX-351/Vyxeos)–associated distinct purpuric subtype of toxic erythema of chemotherapy: A retrospective review of 54 patients
Authors: Joseph R. Stoll, Laura Battle, Andrea Moy, Stephen W. Dusza, Jae H. Park, Martin S. Tallman, Justin Taylor, Alina Markova
Journal: Journal of the American Academy of Dermatology (2021)
The thymoproteasome hardwires the TCR repertoire of CD8+ T cells in the cortex independent of negative selection
Authors: Izumi Ohigashi, Melina Frantzeskakis, Alison Jacques, Sayumi Fujimori, Aya Ushio, Fusano Yamashita, Naozumi Ishimaru, Da Yin, Margaret Cam, Michael C. Kelly, Parirokh Awasthi, Kensuke Takada, Yousuke Takahama
Journal: The Journal of Experimental Medicine (2021)

The thymoproteasome expressed specifically in thymic cortical epithelium optimizes the generation of CD8+ T cells; however, how the thymoproteasome contributes to CD8+ T cell development is unclear. Here, we show that the thymoproteasome shapes the TCR repertoire directly in cortical thymocytes before migration to the thymic medulla. We further show that the thymoproteasome optimizes CD8+ T cell production independent of the thymic medulla; independent of additional antigen-presenting cells, including medullary thymic epithelial cells and dendritic cells; and independent of apoptosis-mediated negative selection. These results indicate that the thymoproteasome hardwires the TCR repertoire of CD8+ T cells with cortical positive selection independent of negative selection in the thymus.
Continuing Peanut Oral Immunotherapy via Telemedicine During the COVID-19 Pandemic
Authors: Anna Schoonover, Anny Uyehara, Michael Goldman
Journal: Journal of Allergy and Clinical Immunology (2021)

Peanut oral immunotherapy (OIT) is a treatment to desensitize patients with peanut allergy. OIT up-doses are typically conducted in the office to ensure tolerance of the next dosing level. Due to the COVID-19 pandemic, we adapted our protocol to enable up-dosing via telemedicine. We sought to determine whether telemedicine up-doses are safe, defined as minimal reactions which can be treated at home, under provider supervision. A retrospective chart review was performed for patients electing to continue peanut OIT up-doses via telemedicine during COVID-19 (March-August 2020). Cases were assessed for number of up-doses, number and type of adverse reactions, and type of treatment administered. Prior to instituting telemedicine up-doses, risks and benefits were reviewed. We modified our standard OIT regimen so each up-dose occurred over 2 days. Twenty-one patients, ages 6 months - 17 years, were included. We conducted 130 up-doses via telemedicine, with doses ranging from 0.5mg to 500mg of peanut protein. Three patients initiated OIT via telemedicine. In total, there were 8 adverse reactions (6.2% of up-doses), in 5 patients, all mild. Of these reactions, 6 required no treatment, 2 required oral antihistamine, and none required injectable epinephrine or emergency medical services. All reactions were managed by video call with the provider. Our findings indicate that modified OIT up-doses via telemedicine are safe. During COVID-19, this protocol allowed us to minimize interruptions in therapy and continue OIT with the convenience of home dosing. This may provide an alternative method of OIT for patients who cannot manage frequent in-office up-doses.
Correction: Outcomes in first relapsed-refractory younger patients with mantle cell lymphoma: results from the MANTLE-FIRST study
Authors: Carlo Visco, Alice Di Rocco, Andrea Evangelista, Francesca Maria Quaglia, Maria Chiara Tisi, Lucia Morello, Vittorio Ruggero Zilioli, Chiara Rusconi, Stefan Hohaus, Roberta Sciarra, Alessandro Re, Cristina Tecchio, Annalisa Chiappella, Ana Marin-Niebla, Rory McCulloch, Guido Gini, Tommasina Perrone, Luca Nassi, Elsa Pennese, Piero Maria Stefani, Maria Christina Cox, Valentina Bozzoli, Alberto Fabbri, Valentina Polli, Simone Ferrero, Maria Isabel Alvarez De Celis, Antonello Sica, Luca Petrucci, Luca Arcaini, Simon Rule, Mauro Krampera, Umberto Vitolo, Monica Balzarotti
Journal: Leukemia (2021)
Association of Temporary Financial Assistance With Housing Stability Among US Veterans in the Supportive Services for Veteran Families Program
Authors: Richard E. Nelson, Thomas H. Byrne, Ying Suo, James Cook, Warren Pettey, Adi V. Gundlapalli, Tom Greene, Lillian Gelberg, Stefan G. Kertesz, Jack Tsai, Ann Elizabeth Montgomery
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Temporary financial assistance (TFA) for housing-related expenses is a key component of interventions to prevent homelessness or to quickly house those who have become homeless. Through the US Department of Veterans Affairs (VA) Supportive Services for Veteran Families (SSVF) program, the department provides TFA to veterans in need of housing assistance. <h3>Objective</h3> To assess the association between TFA and housing stability among US veterans enrolled in the SSVF program. <h3>Design, Setting, and Participants</h3> This retrospective cohort study analyzed data on veterans who were enrolled in the SSVF program at 1 of 203 partner organizations in 49 US states and territories. Some veterans had repeat SSVF episodes, but only the first episodes were included in this analysis. An episode was defined as the period between entry into and exit from the program occurring between October 1, 2015, and September 30, 2018. <h3>Exposures</h3> Receipt of TFA. <h3>Main Outcomes and Measures</h3> The main outcome was stable housing, defined as permanent, independent residence with payment by the program client or housing subsidy after exit from the SSVF program. Covariates included demographic characteristics, monthly income and source, public benefits, health insurance, use of other VA programs for homelessness, comorbidities, and geographic location. Multivariable mixed-effects logistic regression, inverse probability of treatment weighting, and instrumental variable approaches were used. <h3>Results</h3> The overall cohort consisted of 41 969 veterans enrolled in the SSVF program, of whom 29 184 (mean [SD] age, 50.4 [12.9] years; 25 396 men [87.0%]) received TFA and 12 785 (mean [SD] age, 50.0 [13.3] years; 11 229 men [87.8%]) did not receive TFA. The mean (SD) duration of SSVF episodes was 90.5 (57.7) days. A total of 69.5% of SSVF episodes involved receipt of TFA, and the mean (SD) amount of TFA was $6070 ($7272). Stable housing was obtained in 81.4% of the episodes. Compared with those who did not receive TFA, veterans who received TFA were significantly more likely to have stable housing outcomes (risk difference, 0.253; 95% CI, 0.240-0.265). An association between the amount of TFA received and stable housing was also found, with risk differences ranging from 0.168 (95% CI, 0.149-0.188) for those who received $0 to $2000 in TFA to 0.226 (95% CI, 0.203-0.249) for those who received more than $2000 to $4000 in TFA. <h3>Conclusions and Relevance</h3> This study found that receipt of TFA through the SSVF program was associated with increased rates of stable housing. These results may inform national policy debates regarding the optimal solutions to prevent and reduce housing instability.
Abstract 15482: Angiotensin-(1-7)-MAS Receptor Gene Knockout Impairs Post-Ischemic Hindlimb Neovascularization
Authors: Jousie M Pereira, Robson A Santos, Brigida A Schirmer, Luciola S Barcelos
Journal: Circulation (2012)

Introduction: Angiotensin-(1-7) is known by its cardiovascular protective effects by activating MAS receptor. It has been shown that Angiotensin-(1-7) stimulates proliferation of endothelial progen...
Restoration of SIRT3 gene expression by airway delivery resolves age-associated persistent lung fibrosis in mice
Authors: Mohammad Rehan, Deepali Kurundkar, Ashish R. Kurundkar, Naomi J. Logsdon, Samuel R. Smith, Diptiman Chanda, Karen Bernard, Yan Y. Sanders, Jessy S. Deshane, Kevin G. Dsouza, Sunad Rangarajan, Jaroslaw W. Zmijewski, Victor J. Thannickal
Journal: Nature Aging (2021)
GeneWalk identifies relevant gene functions for a biological context using network representation learning
Authors: Robert Ietswaart, Benjamin M. Gyori, John A. Bachman, Peter K. Sorger, L. Stirling Churchman
Journal: Genome biology (2021)

Abstract A bottleneck in high-throughput functional genomics experiments is identifying the most important genes and their relevant functions from a list of gene hits. Gene Ontology (GO) enrichment methods provide insight at the gene set level. Here, we introduce GeneWalk ( github.com/churchmanlab/genewalk ) that identifies individual genes and their relevant functions critical for the experimental setting under examination. After the automatic assembly of an experiment-specific gene regulatory network, GeneWalk uses representation learning to quantify the similarity between vector representations of each gene and its GO annotations, yielding annotation significance scores that reflect the experimental context. By performing gene- and condition-specific functional analysis, GeneWalk converts a list of genes into data-driven hypotheses.
Methodological insights from pre-pilot phases of two complex respiratory interventions (IMP2ART; TANDEM)
Authors: Elizabeth Steed, Kirstie McClatchey, Susan Morrow, Ratna Sohanpal, Stephanie Taylor, Hilary Pinnock
Journal: European Respiratory Journal (2020)

Introduction: Complex behavioural interventions, often encounter implementation issues in real-world application. Enhancing the MRC framework for developing and evaluating complex interventions, we included a real-world pre-pilot before formal piloting of two complex interventions: IMPlementing IMProved Asthma self-management as RouTine (IMP2ART) which is developing a whole-systems implementation strategy to improve supported asthma self-management in primary care, and Tailored intervention for ANxiety and DEpression Management in COPD (TANDEM), which uses a cognitive behavioural approach to manage anxiety and depression before attendance at pulmonary rehabilitation in COPD.  Methods: Following extensive development, feasibility testing and refining, each study tested the multi-level components of their interventions with up to 4 ‘real-world sites’ to optimise design for the trial. Qualitative feedback from key stakeholders was reviewed by the development groups and integrated into the final design.  Results: There were many lessons learnt. In IMP2ART we changed delivery of professional education from facilitated use of a team e-learning module to a more open facilitated team session and individual access to the module. In TANDEM, training of respiratory professionals was made less threatening by replacing role-play with actors to an individual video-recorded session.  Conclusion: Real-world pre-pilots resulted in significant changes to the delivery of IMP2ART and TANDEM and should be considered before formal piloting of complex interventions.  Method: IMP2ART NIHR PGfAR (RP-PG-1016-20008); TANDEM: M+NIHR HTA (13/146/02)
The transcriptional coactivator CBP/p300 is an evolutionarily conserved node that promotes longevity in response to mitochondrial stress
Authors: Terytty Yang Li, Maroun Bou Sleiman, Hao Li, Arwen W. Gao, Adrienne Mottis, Alexis Maximilien Bachmann, Gaby El Alam, Xiaoxu Li, Ludger J. E. Goeminne, Kristina Schoonjans, Johan Auwerx
Journal: Nature Aging (2021)
Consequences of the COVID-19 pandemic on grocery shopping habits of food allergic families
Authors: Michael Golding, Cathérine Lemoine-Courcelles, Elissa Abrams, Moshe Ben-Shoshan, Philippe Begin, Edmond Chan, Derek Chu, Jennifer Gerdts, Harold Kim, Elinor Simons, Julia Upton, Jennifer Protudjer
Journal: Journal of Allergy and Clinical Immunology (2021)

Physical distancing requirements during the early months of the COVID-19 pandemic changed peoples' ability and willingness to access grocery stores. We hypothesize that families with food allergy, who rely on label reading to minimize the risk of accidental exposure to a known allergen, were negatively impacted by these changes. Canadian-based families with food allergy completed an anonymous, online survey on the consequences of COVID-19-related changes on shopping habits and behaviours between 1 May and 30 June 2020. We used descriptive and comparative statistics to assess grocery shopping experiences, and motivation for product choice. The unavailability of certain foods had, on average, consequences on these families (N=191). The most common consequence was greater stress while shopping (n=94; 49.2%), but a sizeable minority also reported buying higher priced products (n=74; 38.7%), products they enjoy less (n=51; 26.7%), switching types of foods (n=44; 23.0%), and buying products that required more preparation (n=45; 23.6%). Moreover, during the pandemic, 12.0% (n=23) of food allergic families reported buying foods labeled with "may contain" precautionary allergen labelling although they avoided such purchases pre-COVID-19. Food allergic families report that the COVID-19 pandemic has had negative consequences on their grocery shopping habits, including the purchase of foods with precautionary allergen labelling.
Mitochondria: their role in spermatozoa and in male infertility
Authors: Magalie Boguenet, Pierre-Emmanuel Bouet, Andrew Spiers, Pascal Reynier, Pascale May-Panloup
Journal: Human Reproduction Update (2021)

Abstract BACKGROUND The best-known role of spermatozoa is to fertilize the oocyte and to transmit the paternal genome to offspring. These highly specialized cells have a unique structure consisting of all the elements absolutely necessary to each stage of fertilization and to embryonic development. Mature spermatozoa are made up of a head with the nucleus, a neck, and a flagellum that allows motility and that contains a midpiece with a mitochondrial helix. Mitochondria are central to cellular energy production but they also have various other functions. Although mitochondria are recognized as essential to spermatozoa, their exact pathophysiological role and their functioning are complex. Available literature relative to mitochondria in spermatozoa is dense and contradictory in some cases. Furthermore, mitochondria are only indirectly involved in cytoplasmic heredity as their DNA, the paternal mitochondrial DNA, is not transmitted to descendants. OBJECTIVE AND RATIONAL This review aims to summarize available literature on mitochondria in spermatozoa, and, in particular, that with respect to humans, with the perspective of better understanding the anomalies that could be implicated in male infertility. SEARCH METHODS PubMed was used to search the MEDLINE database for peer-reviewed original articles and reviews pertaining to human spermatozoa and mitochondria. Searches were performed using keywords belonging to three groups: ‘mitochondria’ or ‘mitochondrial DNA’, ‘spermatozoa’ or ‘sperm’ and ‘reactive oxygen species’ or ‘calcium’ or ‘apoptosis’ or signaling pathways’. These keywords were combined with other relevant search phrases. References from these articles were used to obtain additional articles. OUTCOMES Mitochondria are central to the metabolism of spermatozoa and they are implicated in energy production, redox equilibrium and calcium regulation, as well as apoptotic pathways, all of which are necessary for flagellar motility, capacitation, acrosome reaction and gametic fusion. In numerous cases, alterations in one of the aforementioned functions could be linked to a decline in sperm quality and/or infertility. The link between the mitochondrial genome and the quality of spermatozoa appears to be more complex. Although the quantity of mtDNA, and the existence of large-scale deletions therein, are inversely correlated to sperm quality, the effects of mutations seem to be heterogeneous and particularly related to their pathogenicity. WIDER IMPLICATIONS The importance of the role of mitochondria in reproduction, and particularly in gamete quality, has recently emerged following numerous publications. Better understanding of male infertility is of great interest in the current context where a significant decline in sperm quality has been observed.
COVID-19 Impact on Participant Engagement with a School-centered Asthma Navigator Program
Authors: Melanie Gleason, Arthur McFarlane, Mfonobong Udoko, Elizabeth Konon, Stanley Szefler
Journal: Journal of Allergy and Clinical Immunology (2021)

The COVID-19 pandemic has made an impact on how health care/support services are accessed with up to 60% decline in visits to primary care providers. This study evaluated the impact of COVID-19 on participant engagement with asthma navigators and asthma outcomes in a school-centered asthma program. Step Up Asthma program is implemented in 40 Colorado schools. Asthma navigators enrolled 2 cohorts (Cohort 1/2018-2019 and Cohort 2/2019-2020) of students with poorly controlled asthma to participate in a comprehensive asthma navigator program. Study visits were scheduled every 3 months over a 12-month period. Due to COVID-19 school closures, we transitioned to telehealth visits beginning in March 2020. We compared participation rates and indicators of asthma control (ACT score, ED and hospitalizations) before and during the COVID-19 crisis to identify if there was an impact on program engagement. We compared rates for participation at 3-time points: start of school year, mid-year, and end of school year. Cohort 1 (n=113) had participation rates of 100%, 99.1% and 88.5% respectively and Cohort 2 (n=119) had rates of 100%, 87.4% and 70.6%. The results demonstrate an 11.5% decline from start of year to end of year for Cohort 1, compared to a 29.4% decline for Cohort 2 during the COVID-19 crisis. No change in asthma outcomes was noted. Our school-centered asthma program maintained high levels of participant engagement through telehealth mechanisms. This study demonstrates the effectiveness of asthma navigators in maintaining close monitoring. Anecdotally, families expressed how important these outreach visits were to them.
Abstract 15528: Tafamidis Free Acid 61 Mg in Patients With Transthyretin Amyloid Cardiomyopathy
Authors: Jose Nativi-Nicolau, peter van der meer, Balarama Gundapaneni, Marla B Sultan, Pablo Garcia-Pavia
Journal: Circulation (2020)

Introduction: Tafamidis meglumine, available as 20 mg capsules, is approved around the world for the treatment of transthyretin amyloidosis in early stage polyneuropathy (20 mg) and more recently in cardiomyopathy (80 mg). A new formulation, tafamidis free acid 61 mg (a single capsule bioequivalent to tafamidis meglumine 80 mg), was subsequently developed as a more convenient option for patients with transthyretin amyloid cardiomyopathy (ATTR-CM) and further characterization of its safety profile would be of value. Methods: Patients who completed the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) were eligible to enroll in a long-term, extension study (LTE). The LTE was subsequently expanded to include ATTR-CM patients not previously enrolled in ATTR-ACT, with all patients receiving tafamidis free acid 61 mg (tafamidis 61 mg). As of 20 July, 2018, patients in the LTE were transitioned to tafamidis free acid 61 mg (data assessed for patients treated with tafamidis 80 mg in the LTE who transitioned to tafamidis free acid 61 mg [tafamidis 80/61 mg]). Adverse events (AEs) during the LTE are described (as of 1 Aug, 2019) and compared with AEs with tafamidis 80 mg in ATTR-ACT. Results: There were 164 patients treated with tafamidis 80/61 mg and 715 newly enrolled patients treated with tafamidis 61 mg; with 157 (95.7%) AEs with tafamidis 80/61 mg and 458 (64.1%) with tafamidis 61 mg. The most common AEs by system organ class were cardiac disorders ( Table ). AEs with tafamidis 80/61 mg were broadly similar to those with tafamidis 80 mg in ATTR-ACT (previously shown to be similar to placebo). While there were fewer AEs with tafamidis 61 mg, the notably shorter exposure time in this group limits direct comparisons. Nevertheless, no new safety concerns emerged in patients who transitioned to, or started, tafamidis 61 mg. Conclusions: For patients with ATTR-CM, tafamidis free acid 61 mg is a safe treatment which also offers improved patient convenience.
Ipilimumab and nivolumab/pembrolizumab in advanced hepatocellular carcinoma refractory to prior immune checkpoint inhibitors
Authors: Jeffrey Sum Lung Wong, Gerry Gin Wai Kwok, Vikki Tang, Bryan Cho Wing Li, Roland Leung, Joanne Chiu, Ka Wing Ma, Wong Hoi She, Josephine Tsang, Chung Mau Lo, Tan To Cheung, Thomas Yau
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Programmed cell death protein 1 (PD-1) pathway blockade with immune checkpoint inhibitors (ICIs) is a standard therapy in advanced hepatocellular carcinoma (HCC) nowadays. No strategies to overcome ICI resistance have been described. We aimed to evaluate the use of ipilimumab and anti-PD-1 ICIs (nivolumab or pembrolizumab) combinations in patients with advanced HCC with progression on prior ICIs. Methods Patients with advanced HCC with documented tumor progression on prior ICIs and subsequently received ipilimumab with nivolumab/pembrolizumab were analyzed. Objective response rate (ORR), median duration of response (DOR), time-to-progression (TTP), overall survival (OS), and treatment-related adverse events (TRAEs) were assessed. Results Twenty-five patients were included. The median age was 62 (range: 51–83). About 68% were of Child-Pugh (CP) Grade A and 48% had primary resistance to prior ICI. At median follow-up of 37.7 months, the ORR was 16% with a median DOR of 11.5 months (range: 2.76–30.3). Three patients achieved complete response. The median TTP was 2.96 months (95% CI: 1.61 to 4.31). Median OS was 10.9 months (95% CI: 3.99 to 17.8) and the 1 year, 2 year and 3 year survival rates were 42.4%, 32.3% and 21.6%, respectively. The ORR was 16.7% in primary resistance group and 15.4% in acquired resistance group (p=1.00). All responders were of CP A and Albumin-Bilirubin (ALBI) Grade 1 or 2. CP and ALBI Grades were significantly associated with OS (p=0.006 and p&lt;0.001, respectively). Overall, 52% of patients experienced TRAEs and 12% experienced Grade 3 or above TRAEs. Conclusions Ipilimumab and nivolumab/pembrolizumab can achieve durable antitumor activity and encouraging survival outcomes with acceptable toxicity in patients with advanced HCC who had prior treatment with ICIs.