Evaluating Options and Ethics in Pediatric Dentistry due to Declining Access to Hospital Operating Rooms.

AbstractPediatric dentists rely on access to hospital operating rooms for safe, effective, and humane delivery of dental care. The children who benefit most from dental treatment in a hospital operating room are those who are very young, have dental anxieties or phobias, are precommunicative or noncommunicative, need extensive or invasive dental treatments, or have special healthcare needs. Diminishing access to hospital operating rooms for pediatric dental treatment has become an escalating problem in contemporary times.

Donor Genetic Predisposition to High Interleukin-10 Production Appears Protective against Acute Graft-Versus-Host Disease.

The persistence of graft-versus-host disease (GVHD) as the principal complication of allogeneic hematopoietic cell transplantation (HCT) demonstrates that HLA matching alone is insufficient to prevent alloreactivity. We performed molecular and functional characterization of 22 candidate cytokine genes for their potential to improve matching in 315 myeloablative, 10/10 HLA-matched donor−recipient pairs. Recipients of a graft carrying the -1082GG IL10 gene promoter region variant had a three-fold lower incidence of grade II−IV acute GVHD compared to IL10-1082AA graft recipients (SHR = 0.

Incomplete chimerism following myeloablative and anti-thymocyte globulin-conditioned hematopoietic cell transplantation is a risk factor for relapse and chronic graft-versus-host disease.

Background Aims: The value of routine chimerism determination after myeloablative hematopoietic cell transplantation (HCT) is unclear, particularly in the setting of anti-thymocyte globulin (ATG)-based graft-versus-host disease (GVHD) prophylaxis.

Methods: Blood samples were collected at 3 months post-HCT from 558 patients who received myeloablative conditioning and ATG-based GVHD prophylaxis. Chimerism was assessed using multiplex polymerase chain reaction of short tandem repeats in sorted T cells (CD3+) and leukemia lineage cells (CD13+CD33+ for myeloid malignancies and CD19+ for B-lymphoid malignancies).

StarGazer: A Hybrid Intelligence Platform for Drug Target Prioritization and Digital Drug Repositioning Using Streamlit.

Target prioritization is essential for drug discovery and repositioning. Applying computational methods to analyze and process multi-omics data to find new drug targets is a practical approach for achieving this. Despite an increasing number of methods for generating datasets such as genomics, phenomics, and proteomics, attempts to integrate and mine such datasets remain limited in scope.

Accurate Step Count with Generalized and Personalized Deep Learning on Accelerometer Data.

Physical activity (PA) is globally recognized as a pillar of general health. Step count, as one measure of PA, is a well known predictor of long-term morbidity and mortality. Despite its popularity in consumer devices, a lack of methodological standards and clinical validation remains a major impediment to step count being accepted as a valid clinical endpoint.

OSPred Tool: A Digital Health Aid for Rapid Predictive Analysis of Correlations Between Early End Points and Overall Survival in Non-Small-Cell Lung Cancer Clinical Trials.

Purpose: Overall survival (OS) is the gold standard end point for establishing clinical benefits in phase III oncology trials. However, these trials are associated with low success rates, largely driven by failure to meet the primary end point. Surrogate end points such as progression-free survival (PFS) are increasingly being used as indicators of biologic drug activity and to inform early go/no-go decisions in oncology drug development.

Analysis of Use and Outcomes of the Balance Digital Disease Management Tool for Patients with Type 2 Diabetes.

Management of type 2 diabetes mellitus (T2DM) is a serious medical need for millions of patients and clinicians worldwide. Numerous smartphone apps for T2DM management are available. Due to their global accessibility, computing power and cellular connectivity, the pervasiveness of mobile phones now provide an opportunity for non-invasive Digital Therapeutics that have the potential to manage disease by modifying patient behavior as new modality for disease management and intervention.

Impact of FLT3 internal tandem duplication and NPM1 mutations in acute myeloid leukemia treated with allogeneic hematopoietic cell transplantation.

Background Aims: The internal tandem duplication of FLT3 (FLT3) and NPM1 mutations (NPM1) are well-established prognostic factors in cytogenetically intermediate-risk acute myeloid leukemia (AML) when treated with chemotherapy alone. However, their prognostic value in the setting of allogeneic hematopoietic cell transplantation (HCT) is controversial.

Methods: FLT3 and NPM1 mutational status was determined at diagnosis using single-gene polymerase chain reaction or next-generation sequencing in 247 adult patients with cytogenetically intermediate-risk AML who underwent myeloablative HCT.

Correlation Between Early Endpoints and Overall Survival in Non-Small-Cell Lung Cancer: A Trial-Level Meta-Analysis.

Early endpoints, such as progression-free survival (PFS), are increasingly used as surrogates for overall survival (OS) to accelerate approval of novel oncology agents. Compiling trial-level data from randomized controlled trials (RCTs) could help to develop a predictive framework to ascertain correlation trends between treatment effects for early and late endpoints. Through trial-level correlation and random-effects meta-regression analysis, we assessed the relationship between hazard ratio (HR) OS and (1) HR PFS and (2) odds ratio (OR) PFS at 4 and 6 months, stratified according to the mechanism of action of the investigational product.

A biomarker-guided, prospective, phase 2 trial of pre-emptive graft-versus-host disease therapy using anti-thymocyte globulin.

Background Aims: Intensified immunosuppressive prophylaxis for graft-versus-host disease (GVHD) may be toxic and therefore warranted only in patients at high risk of developing GVHD. In patients who underwent allogeneic hematopoietic cell transplant at the authors' center, high serum soluble IL-2 receptor alpha (sIL-2Rα) and low IL-15 levels on day 7 post-transplant were found to predict a high risk of developing clinically significant GVHD (sGVHD), defined as grade 2-4 acute GVHD or moderate to severe chronic GVHD.

Methods: This was a prospective, phase 2 trial in which high-risk patients (serum sIL-2Rα >4500 ng/L or IL-15 <31 ng/L) received rabbit anti-thymocyte globulin (ATG) 3 mg/kg on day 8 post-transplant.

COVID-19 infection among international travellers: a prospective analysis.

Objectives: This report estimates the risk of COVID-19 importation and secondary transmission associated with a modified quarantine programme in Canada.

Design And Participants: Prospective analysis of international asymptomatic travellers entering Alberta, Canada.

Interventions: All participants were required to receive a PCR COVID-19 test on arrival.

Efficacy of Allogeneic Hematopoietic Cell Transplantation for Autoimmune Diseases.

Allogeneic hematopoietic cell transplantation (HCT) may be efficacious for autoimmune diseases (AIDs), but its efficacy for individual AIDs is unknown. Factors influencing the likelihood of relapse for each AID are also unknown. This study aimed to determine the likelihood of relapse for each common AID and to generate hypotheses about factors influencing the likelihood of relapse.

Impaired natural killer cell counts and cytolytic activity in patients with severe COVID-19.

The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-driven coronavirus disease 2019 (COVID-19) has caused unprecedented human death and has seriously threatened the global economy. Early data suggest a surge in proinflammatory cytokines in patients with severe COVID-19, which has been associated with poor outcomes. We recently postulated that the inflammatory response in patients with severe COVID-19 disease is not inhibited by natural killer (NK) cells, resulting in a "cytokine storm.

Assessment of Objectively Measured Physical Activity as an Independent Estimator of Functional Status in Clinical Trials.

Functional status of patients is an important concept in clinical trials. It subsumes functional capacity, which is traditionally estimated by exercise tests, and functional performance, which is often estimated by questionnaires. Objectively measured physical activity by means of wearables devices containing accelerometers (PA) have recently been proposed as a novel and advantageous way to estimate physical status including capacity and performance.

Hematopoietic cell transplant outcomes after myeloablative conditioning with fludarabine, busulfan, low-dose total body irradiation, and rabbit antithymocyte globulin.

Optimal conditioning and graft-vs-host disease (GVHD) prophylaxis for hematopoietic cell transplantation (HCT) are unknown. Here, we report on outcomes after low toxicity, myeloablative conditioning consisting of fludarabine, busulfan, and 4 Gy total body irradiation, in combination with thymoglobulin and post-transplant methotrexate and cyclosporine. We retrospectively studied 700 patients with hematologic malignancies who received blood stem cells from 7 to 8/8 HLA-matched unrelated or related donors.

Curability and transferability of atopy with allogeneic hematopoietic cell transplantation.

Atopy is excessive production of IgE in response to allergens. We evaluated in patients undergoing allogeneic hematopoietic cell transplantation (HCT) the following hypotheses: (1) Atopy is "curable" in atopic patients receiving HCT from a nonatopic donor (D-R+), and (2) Atopy is transferable from atopic donors to nonatopic recipients (D+R-). Atopic patients with atopic donors (D+R+) and non-atopic patients with non-atopic donors (D-R-) served as controls.

Comparison of abacavir-specific effector and proliferating functions of CD8 T cells in abacavir-treated HIV-1 patients.

Susceptibility to abacavir hypersensitivity (ABH) in HIV-1-positive patients is strongly linked to the carriage of HLA-B*57:01 and the potential mechanism includes drug-specific activation of cytokine producing CD8 T cells exclusively in individuals carrying HLA-B*57:01. Here, we report a detailed characterization of abacavir-induced functional response of CD8 T cells in HLA-B*57:01 individuals. Peripheral blood mononuclear cells (PBMNCs) from HLA-B*57:01 ABH and HLA-B*57:01 ABH individuals were stimulated with abacavir.

More acute lymphoid leukemia than acute myeloid leukemia blasts are killed by rabbit antithymocyte globulin.

Rabbit antithymocyte globulin (ATG, thymoglobulin), a polyclonal antibody, is used to prevent graft-versus-host disease (GVHD) and graft failure in the setting of allogeneic hematopoietic cell transplantation (HCT). Recent in vitro studies suggest that ATG also has anti-leukemic activity. Whether acute lymphoid leukemia (ALL) or acute myeloid leukemia (AML) is more sensitive to ATG is not known.

High incidence of hematologic malignancy relapse after allogeneic transplantation in patients with low Epstein-Barr virus-specific T-cell counts.

Background: Association between low counts of herpesvirus-specific T cells and subsequent relapse of hematologic malignancy has been shown in two retrospective studies.

Methods: Here we present results of a prospective validation study. Multiple subsets of Epstein-Barr virus (EBV)-specific T cells were measured in 69 patients on day 56 and 84, using intracellular flow cytometry after incubation of blood mononuclear cells (MNCs) with EBV peptides or lysate.

Comparison of sequence-specific oligonucleotide probe vs next generation sequencing for HLA-A, B, C, DRB1, DRB3/B4/B5, DQA1, DQB1, DPA1, and DPB1 typing: Toward single-pass high-resolution HLA typing in support of solid organ and hematopoietic cell transplant programs.

Many clinical laboratories supporting solid organ transplant programs use multiple HLA genotyping technologies, depending on individual laboratory needs. Sequence-specific primers and quantitative polymerase chain reaction (qPCR) serve the rapid turnaround necessary for deceased donor workup, while sequence-specific oligonucleotide probe (SSOP) technology is widely employed for higher volumes. When clinical need mandates high-resolution data, Sanger sequencing-based typing (SBT) has been the "gold standard.

Antirelapse effect of pretransplant exposure to rabbit antithymocyte globulin.

It remains unknown why rabbit antithymocyte globulin (ATG; Thymoglobulin) has not affected relapse after hematopoietic cell transplantation (HCT) in randomized studies. We hypothesized that high pre-HCT ATG area under the curve (AUC) would be associated with a low incidence of relapse, whereas high post-HCT AUC would be associated with a high incidence of relapse. We measured serum levels of ATG capable of binding to mononuclear cells (MNCs), lymphocytes, T cells, CD4 T cells, or CD33 cells.

Rabbit Antithymocyte Globulin Serum Levels: Factors Impacting the Levels and Clinical Outcomes Impacted by the Levels.

Antithymocyte globulin (ATG) levels and clearance vary significantly among patients receiving the same weight-based dose of ATG. To date, ATG area under the curve (AUC), its determinants, and its impact on clinical outcomes have been examined in pediatric hematopoietic cell transplant (HCT) and adult nonmyeloablative HCT. Here we set out to examine ATG AUC in 219 uniformly treated adults undergoing myeloablative allogeneic HCT at our institution.

Interval Kernels for Combining Biometric Measurements from Multiple Prostate Samples per Patient in Prognostic Models with Transductive Semi-Supervised Support Vector Regression.

Prostate cancer is the most prevalent form of cancer and second most common form of cancer deaths among men in the United States. Physicians work with patients to make difficult treatment decisions. They are often aided by a multitude of prognostic models to assess risk and predict outcomes.

Comparing Immunofluorescent versus H&E Glandular Architecture Features in Prognostic Models from Prostate Biopsies.

Determining the best treatment for prostate cancer patients with a newly diagnosed positive biopsy can be challenging. Multivariate prognostic models are often employed to stratify patients into risk populations. Many models leverage quantitative features derived from morphological analysis of the tumor architecture in the biopsy specimen.