62 research outputs found
Post COVID-19 Analysis Of Barrier Method Use And Sex Practices Among Undergraduate Students
Background: Undergraduate students are often between ages 18-24 and have a high predisposition for engaging in risky sexual behaviors. The COVID-19 pandemic increased the normality of socially protective behaviors and communicable disease knowledge for public health defense. Purpose: To measure the frequency of barrier method use among undergraduate students in response to the COVID-19 pandemic including variables of relationship status, forms of sex, and barrier method communication comfort. Methods: A researcher-created questionnaire was used to collect data on the COVID-19 safety habits, sexual behaviors, and communication practices of the previous 12 months among respondents. Results: Precautionary behaviors related to COVID-19 were not predictive of safer sex behaviors like barrier method use among the undergraduate population from August 2020-August 2021. Additional tests that demonstrated statistical significance included: Upperclassmen comfort in barrier method communication with non-monogamous partners; Increased face mask use and handwashing among fully-vaccinated participants before vaccination than afterward; and Self-identified “Lesbians” were the least likely sexual identity to use any form of barrier method. Discussion: Tests did not prove overall significance between socially and sexually protective behaviors, but future research could compare the identities and sexual practices of individuals on their knowledge and application of population and public health preservation
The Role of CD38 on the Function of Regulatory B Cells in a Murine Model of Lupus
Previous work from our group has shown that Cd38-/- mice develop a milder
pristane-induced lupus disease than WT or Art2-/- counterparts, demonstrating a new role for
CD38 in promoting aberrant inflammation and lupus-like autoimmunity via a Transient Receptor
Potential Melastatin 2 (TRPM2)-dependent apoptosis-driven mechanism. In this study we asked
whether CD38 may play a role in the expression and function of regulatory B cells (IL-10-producing
B cells or B10 cells). In pristane-treated mice the frequency of spleen CD19+CD1dhiCD5+ B cells,
which are highly enriched in B10 cells, was significantly increased in Cd38-/- splenocytes compared
to WT, while the frequency of peritoneal plasmacytoid dendritic cells (pDCs), which are major type I
Interferon (IFN) producers, was greatly diminished. The low proportion of pDCs correlated with
lower amounts of IFN-α in the peritoneal lavage fluids of the Cd38-/- mice than of WT and Art2-/-
mice. Functional ex vivo assays showed increased frequencies of IL-10-producing B cells in Cd38-/-
splenocytes than in WT upon stimulation with an agonist anti-CD40 mAb. Overall these results
strongly suggest that Cd38-/- mice are better suited than WT mice to generate and expand regulatory
B10 cells following the appropriate stimulation.Work performed in the Sancho and Zubiaur labs was supported in part by the European Commission
in collaboration with the following Funding Agencies: (i) Junta de Andalucía, Consejería Innovación Ciencia y
Empresa y Consejería Educación y Ciencia, Project: PC08-CTS-04046 to Jaime Sancho and Mercedes Zubiaur,
and (ii) Ministerio de Economía y Competitividad (MINECO), Projects: SAF-2011-27261 and SAF-2017-89801-R to
Jaime Sancho and Mercedes Zubiaur. The stay of B.B. and G.R. in Sancho’s lab was supported by National Science
Foundation: Grant #HRD-0963629 (G-STEM). USA.; and U.S. Department of Education; Student Aid and Fiscal
Responsibility Act; Title III Grant (SAFRA, Part F). Grant SAF-2017-89801-R covers in part the costs to publish in
open access
Evolutionary Events in a Mathematical Sciences Research Collaboration Network
This study examines long-term trends and shifting behavior in the
collaboration network of mathematics literature, using a subset of data from
Mathematical Reviews spanning 1985-2009. Rather than modeling the network
cumulatively, this study traces the evolution of the "here and now" using
fixed-duration sliding windows. The analysis uses a suite of common network
diagnostics, including the distributions of degrees, distances, and clustering,
to track network structure. Several random models that call these diagnostics
as parameters help tease them apart as factors from the values of others. Some
behaviors are consistent over the entire interval, but most diagnostics
indicate that the network's structural evolution is dominated by occasional
dramatic shifts in otherwise steady trends. These behaviors are not distributed
evenly across the network; stark differences in evolution can be observed
between two major subnetworks, loosely thought of as "pure" and "applied",
which approximately partition the aggregate. The paper characterizes two major
events along the mathematics network trajectory and discusses possible
explanatory factors.Comment: 30 pages, 14 figures, 1 table; supporting information: 5 pages, 5
figures; published in Scientometric
AI is a viable alternative to high throughput screening: a 318-target study
: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery
Comparative Treatment Outcomes for Patients With Idiopathic Subglottic Stenosis.
To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadImportance: Surgical treatment comparisons in rare diseases are difficult secondary to the geographic distribution of patients. Fortunately, emerging technologies offer promise to reduce these barriers for research.
Objective: To prospectively compare the outcomes of the 3 most common surgical approaches for idiopathic subglottic stenosis (iSGS), a rare airway disease.
Design, setting, and participants: In this international, prospective, 3-year multicenter cohort study, 810 patients with untreated, newly diagnosed, or previously treated iSGS were enrolled after undergoing a surgical procedure (endoscopic dilation [ED], endoscopic resection with adjuvant medical therapy [ERMT], or cricotracheal resection [CTR]). Patients were recruited from clinician practices in the North American Airway Collaborative and an online iSGS community on Facebook.
Main outcomes and measures: The primary end point was days from initial surgical procedure to recurrent surgical procedure. Secondary end points included quality of life using the Clinical COPD (chronic obstructive pulmonary disease) Questionnaire (CCQ), Voice Handicap Index-10 (VHI-10), Eating Assessment Test-10 (EAT-10), the 12-Item Short-Form Version 2 (SF-12v2), and postoperative complications.
Results: Of 810 patients in this cohort, 798 (98.5%) were female and 787 (97.2%) were white, with a median age of 50 years (interquartile range, 43-58 years). Index surgical procedures were ED (n = 603; 74.4%), ERMT (n = 121; 14.9%), and CTR (n = 86; 10.6%). Overall, 185 patients (22.8%) had a recurrent surgical procedure during the 3-year study, but recurrence differed by modality (CTR, 1 patient [1.2%]; ERMT, 15 [12.4%]; and ED, 169 [28.0%]). Weighted, propensity score-matched, Cox proportional hazards regression models showed ED was inferior to ERMT (hazard ratio [HR], 3.16; 95% CI, 1.8-5.5). Among successfully treated patients without recurrence, those treated with CTR had the best CCQ (0.75 points) and SF-12v2 (54 points) scores and worst VHI-10 score (13 points) 360 days after enrollment as well as the greatest perioperative risk.
Conclusions and relevance: In this cohort study of 810 patients with iSGS, endoscopic dilation, the most popular surgical approach for iSGS, was associated with a higher recurrence rate compared with other procedures. Cricotracheal resection offered the most durable results but showed the greatest perioperative risk and the worst long-term voice outcomes. Endoscopic resection with medical therapy was associated with better disease control compared with ED and had minimal association with vocal function. These results may be used to inform individual patient treatment decision-making.Patient-Centered Outcomes Research Institute - PCOR
Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial
Background
Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear.
Methods
RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047.
Findings
Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths.
Interpretation
Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population
Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial
Background
Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain.
Methods
RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and
ClinicalTrials.gov
,
NCT00541047
.
Findings
Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths.
Interpretation
Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy.
Funding
Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society
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