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Nevin Manimala Statistics

Extended live-cell barcoding approach for multiplexed mass cytometry

Sci Rep. 2021 Jun 11;11(1):12388. doi: 10.1038/s41598-021-91816-w.

ABSTRACT

Sample barcoding is essential in mass cytometry analysis, since it can eliminate potential procedural variations, enhance throughput, and allow simultaneous sample processing and acquisition. Sample pooling after prior surface staining termed live-cell barcoding is more desirable than intracellular barcoding, where samples are pooled after fixation and permeabilization, since it does not depend on fixation-sensitive antigenic epitopes. In live-cell barcoding, the general approach uses two tags per sample out of a pool of antibodies paired with five palladium (Pd) isotopes in order to preserve appreciable signal-to-noise ratios and achieve higher yields after sample deconvolution. The number of samples that can be pooled in an experiment using live-cell barcoding is limited, due to weak signal intensities associated with Pd isotopes and the relatively low number of available tags. Here, we describe a novel barcoding technique utilizing 10 different tags, seven cadmium (Cd) tags and three Pd tags, with superior signal intensities that do not impinge on lanthanide detection, which enables enhanced pooling of samples with multiple experimental conditions and markedly enhances sample throughput.

PMID:34117319 | DOI:10.1038/s41598-021-91816-w

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Nevin Manimala Statistics

An open tool for creating battery-electric vehicle time series from empirical data, emobpy

Sci Data. 2021 Jun 11;8(1):152. doi: 10.1038/s41597-021-00932-9.

ABSTRACT

There is substantial research interest in how future fleets of battery-electric vehicles will interact with the power sector. Various types of energy models are used for respective analyses. They depend on meaningful input parameters, in particular time series of vehicle mobility, driving electricity consumption, grid availability, or grid electricity demand. As the availability of such data is highly limited, we introduce the open-source tool emobpy. Based on mobility statistics, physical properties of battery-electric vehicles, and other customizable assumptions, it derives time series data that can readily be used in a wide range of model applications. For an illustration, we create and characterize 200 vehicle profiles for Germany. Depending on the hour of the day, a fleet of one million vehicles has a median grid availability between 5 and 7 gigawatts, as vehicles are parking most of the time. Four exemplary grid electricity demand time series illustrate the smoothing effect of balanced charging strategies.

PMID:34117257 | DOI:10.1038/s41597-021-00932-9

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Nevin Manimala Statistics

Family history of early onset acute lymphoblastic leukemia is suggesting genetic associations

Sci Rep. 2021 Jun 11;11(1):12370. doi: 10.1038/s41598-021-90542-7.

ABSTRACT

Childhood acute lymphoblastic leukemia (ALL) has an origin in the fetal period which may distinguish it from ALL diagnosed later in life. We wanted to test whether familial risks differ in ALL diagnosed in the very early childhood from ALL diagnosed later. The Swedish nation-wide family-cancer data were used until year 2016 to calculate standardized incidence ratios (SIRs) for familial risks in ALL in three diagnostic age-groups: 0-4, 5-34 and 35 + years. Among 1335 ALL patients diagnosed before age 5, familial risks were increased for esophageal (4.78), breast (1.42), prostate (1.40) and connective tissue (2.97) cancers and leukemia (2.51, ALL 7.81). In age-group 5-34 years, rectal (1.73) and endometrial (2.40) cancer, myeloma (2.25) and leukemia (2.00, ALL 4.60) reached statistical significance. In the oldest age-group, the only association was with Hodgkin lymphoma (3.42). Diagnostic ages of family members of ALL patients were significantly lower compared to these cancers in the population for breast, prostate and rectal cancers. The patterns of increased familial cancers suggest that BRCA2 mutations could contribute to associations of ALL with breast and prostate cancers, and mismatch gene PMS2 mutations with rectal and endometrial cancers. Future DNA sequencing data will be a test for these familial predictions.

PMID:34117277 | DOI:10.1038/s41598-021-90542-7

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Nevin Manimala Statistics

Dynamic self-assembly of compartmentalized DNA nanotubes

Nat Commun. 2021 Jun 11;12(1):3557. doi: 10.1038/s41467-021-23850-1.

ABSTRACT

Bottom-up synthetic biology aims to engineer artificial cells capable of responsive behaviors by using a minimal set of molecular components. An important challenge toward this goal is the development of programmable biomaterials that can provide active spatial organization in cell-sized compartments. Here, we demonstrate the dynamic self-assembly of nucleic acid (NA) nanotubes inside water-in-oil droplets. We develop methods to encapsulate and assemble different types of DNA nanotubes from programmable DNA monomers, and demonstrate temporal control of assembly via designed pathways of RNA production and degradation. We examine the dynamic response of encapsulated nanotube assembly and disassembly with the support of statistical analysis of droplet images. Our study provides a toolkit of methods and components to build increasingly complex and functional NA materials to mimic life-like functions in synthetic cells.

PMID:34117248 | DOI:10.1038/s41467-021-23850-1

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Nevin Manimala Statistics

Immunogenicity and Safety of a Tetravalent Dengue Vaccine Administered Concomitantly or Sequentially With Tdap Vaccine: Randomized Phase IIIb Trial in Healthy Participants 9-60 Years of Age in the Philippines

Pediatr Infect Dis J. 2021 Jun 10. doi: 10.1097/INF.0000000000003220. Online ahead of print.

ABSTRACT

BACKGROUND: Incorporating dengue vaccination into existing childhood vaccination programs could increase vaccine coverage. This study assessed the safety and immunogenicity of concomitant versus sequential administration of the combined tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine and the tetravalent dengue vaccine (CYD-TDV).

METHODS: This phase IIIb, randomized, open-label, multicenter study was conducted in the Philippines in individuals 9-≤60 years of age (NCT02992418). Participants were to receive 3 CYD-TDV doses 6 months apart, the first dose administered either concomitantly or sequentially (28 days post-Tdap). Antibody levels were measured at baseline and 28 days post-first doses of Tdap vaccine and CYD-TDV, using enzyme-linked immunosorbent assay (pertussis, tetanus), micrometabolic inhibition test-toxin neutralization assay (diphtheria) and plaque reduction neutralization test (dengue). Immunogenicity was assessed for all participants, and statistical analysis reported for baseline dengue seropositive participants. Safety was assessed throughout.

RESULTS: Among 688 randomized participants, 629 (91.4%) were baseline dengue seropositive (concomitant group, n = 314 and sequential group, n = 315). After the first dose, non-inferiority of immune responses between concomitant and sequential vaccination was achieved; between-group geometric mean antibody concentration ratios were close to 1 for anti-PT, anti-FHA, anti-PRN and anti-FIM, between-group differences in percent achieving seroprotection (titers ≥0.1 IU/mL) were 0.26% (diphtheria) and 0.66% (tetanus), and between-group geometric mean antibody titer ratios were close to 1 for dengue serotypes 1-4. Safety profiles in both study groups were comparable.

CONCLUSIONS: CYD-TDV and Tdap vaccine administered concomitantly or sequentially in baseline dengue seropositive participants elicited comparable immunogenicity and safety profiles.

PMID:34117198 | DOI:10.1097/INF.0000000000003220

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Nevin Manimala Statistics

Highly sensitive active pixel image sensor array driven by large-area bilayer MoS2 transistor circuitry

Nat Commun. 2021 Jun 11;12(1):3559. doi: 10.1038/s41467-021-23711-x.

ABSTRACT

Various large-area growth methods for two-dimensional transition metal dichalcogenides have been developed recently for future electronic and photonic applications. However, they have not yet been employed for synthesizing active pixel image sensors. Here, we report on an active pixel image sensor array with a bilayer MoS2 film prepared via a two-step large-area growth method. The active pixel of image sensor is composed of 2D MoS2 switching transistors and 2D MoS2 phototransistors. The maximum photoresponsivity (Rph) of the bilayer MoS2 phototransistors in an 8 × 8 active pixel image sensor array is statistically measured as high as 119.16 A W-1. With the aid of computational modeling, we find that the main mechanism for the high Rph of the bilayer MoS2 phototransistor is a photo-gating effect by the holes trapped at subgap states. The image-sensing characteristics of the bilayer MoS2 active pixel image sensor array are successfully investigated using light stencil projection.

PMID:34117235 | DOI:10.1038/s41467-021-23711-x

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Nevin Manimala Statistics

Agreement Between Clinical Examination and Magnetic Resonance Imaging in Acute Knee Trauma With Hemarthrosis

Clin J Sport Med. 2021 Jun 9. doi: 10.1097/JSM.0000000000000950. Online ahead of print.

ABSTRACT

OBJECTIVE: Hemarthrosis after knee trauma often indicates serious joint injury. Few studies have evaluated agreement between clinical examination and findings from magnetic resonance imaging (MRI). We aimed to describe the agreement between acute clinical examination and subacute MRI findings after acute knee trauma with hemarthrosis and the importance of the subspecialty of the examiner.

DESIGN: Longitudinal cohort study. Agreement with MRI findings was evaluated by logistic regression.

SETTING: Helsingborg hospital.

PATIENTS: Thousand one hundred forty-five consecutive patients with hemarthrosis after knee trauma.

INTERVENTIONS: Clinical examination and MRI.

MAIN OUTCOME MEASURES: agreement between clinical examination and findings from MRI. We considered the radiologist’s report as the gold standard.

RESULTS: Median time (25th, 75th percentile) from injury to clinical examination was 2 (1, 7) days, and from injury to imaging was 8 (5, 15) days. The overall sensitivity and specificity of clinical examination versus MRI for major ligament injury or lateral patella dislocation (LPD) were 70% [95% confidence interval 67-73) and 66% (61-72), respectively. Orthopedic subspecialist knee had the highest agreement with anterior cruciate ligament rupture (adjusted odds ratios were 1.7 (95% confidence interval 1.2-2.3), 1.9 (1.2-3.0) and 5.9 (3.7-9.5) for orthopedic trainees, orthopedic subspecialists other, and orthopedic subspecialist knee, respectively]. For other ligament injuries and LPD, we did not find statistically significant differences.

CONCLUSIONS: Clinical diagnosis after acute knee injury is relatively unreliable versus MRI findings even when performed by orthopedic specialists. However, the agreement is improved when the examination is performed by an orthopedic knee subspecialist.

PMID:34117155 | DOI:10.1097/JSM.0000000000000950

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Nevin Manimala Statistics

Unintended Consequences and Workarounds of Electronic Medical Record Implementation in Clinical Nursing Practice

Comput Inform Nurs. 2021 Jun 11. doi: 10.1097/CIN.0000000000000785. Online ahead of print.

ABSTRACT

Nurses have experienced unintended consequences and workarounds associated with health information technology implementation. However, examination of this occurrence is rare. This study aimed to examine the unintended consequences and workarounds produced by the implementation of electronic medical record systems in clinical nursing practice. A total of 143 nurses participated in a survey using statistically tested instruments. The data were analyzed using descriptive statistics and a nonparametric test. The descriptive data were analyzed by meaning. The participants experienced unintended consequences and workarounds related to electronic medical record implementation at moderate or high levels based on the responses to questions scored on 5-point Likert scales. The unintended consequences were closely associated with workarounds. The degree of experience with unintended consequences and the use of workarounds differed significantly according to the level of education, job position, and years in nursing practice. The nursing examples of unintended consequences and workarounds were organized into four categories of unintended consequences. By presenting unintended consequences and workarounds together, this study enhances the understanding of the problems encountered in EMR implementation and the action of nurses. Nurses’ needs should be considered as an important resource in developing, redesigning, or purchasing and implementing health information technology in healthcare settings.

PMID:34117159 | DOI:10.1097/CIN.0000000000000785

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Nevin Manimala Statistics

Electronic Family History Screening Tool for Detection of Inherited Cancer Risk: A Prospective Pilot Study

Am J Med Qual. 2021 Jun 10. doi: 10.1097/01.JMQ.0000735504.65700.25. Online ahead of print.

ABSTRACT

Family history screening to identify individuals at increased risk for hereditary cancers could be a powerful strategy to prevent cancer but is used inconsistently in primary care. The objective was to improve identification of women with at-risk family histories using a point-of-care family history screening tool administered on an electronic tablet device during well-woman appointments. A total of 288 women were invited to participate and 136 women (47.2%) completed the electronic family history screening tool. Significantly more women were identified and referred to the genetics department with the electronic family history screening tool than the standard-of-care paper questionnaire (11.8% versus 0.8%, P < 0.001). There were no statistically significant differences in the proportion of referred women who were evaluated by the genetic counselors, and no pathogenic variants were found with either family history screening method. Implementing innovative self-reporting tools may improve inherited cancer risk detection.

PMID:34117164 | DOI:10.1097/01.JMQ.0000735504.65700.25

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Nevin Manimala Statistics

Phase II clinical trial using anti-CD3 × anti-HER2 bispecific antibody armed activated T cells (HER2 BATs) consolidation therapy for HER2 negative (0-2+) metastatic breast cancer

J Immunother Cancer. 2021 Jun;9(6):e002194. doi: 10.1136/jitc-2020-002194.

ABSTRACT

BACKGROUND: Metastatic human epidermal growth receptor II (HER2) negative breast cancer remains incurable. Our phase I study showed that anti-CD3 × anti-HER2 bispecific antibody armed activated T cells (HER2 BATs) may be effective against HER2-tumors. This phase II trial evaluates the efficacy and immune responses of HER2 BATs given to patients with metastatic HER2-estrogen and/or progesterone receptor positive (HR+) and triple negative breast cancer (TNBC) as immune consolidation after chemotherapy. The primary objective of this study was to increase the traditional median time to progression after failure of first-line therapy of 2-4 months with the secondary endpoints of increasing overall survival (OS) and immune responses.

METHODS: HER2- metastatic breast cancer (MBC) patients received 3 weekly infusions of HER2 BATs and a boost after 12 weeks.

RESULTS: This phase II study included 24 HER2-HR+ and 8 TNBC patients who received a mean of 3.75 and 2.4 lines of prior chemotherapy, respectively. Eight of 32 evaluable patients were stable at 4 months after the first infusion. There were no dose limiting toxicities. Tumor markers decreased in 13 of 23 (56.5%) patients who had tumor markers. The median OS was 13.1 (95% CI 8.6 to 17.4), 15.2 (95% CI 8.6 to 19.8), and 12.3 (95% CI 2.1 to 17.8) months for the entire group, HER2-HR+, and TNBC patients, respectively. Median OS for patients with chemotherapy-sensitive and chemotherapy-resistant disease after chemotherapy was 14.6 (9.6-21.8) and 8.6 (3.3-17.3) months, respectively. There were statistically significant increases in interferon-γ immunospots, Th1 cytokines, Th2 cytokines, and chemokines after HER2 BATs infusions.

CONCLUSIONS: In heavily pretreated HER2-patients, immune consolidation with HER2 BATs after chemotherapy appears to increase the proportion of patients who were stable at 4 months and the median OS for both groups as well as increased adaptive and innate antitumor responses. Future studies combining HER2 BATs with checkpoint inhibitors or other immunomodulators may improve clinical outcomes.

PMID:34117114 | DOI:10.1136/jitc-2020-002194