title stringlengths 1 1.19k | keywords stringlengths 0 668 | concept stringlengths 0 909 | paragraph stringlengths 0 61.8k | PMID stringlengths 10 11 |
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Discussion | teeth movements, orthodontic | PLAQUE | Objective wear time of both groups demonstrated sub-optimal compliance with instructed wear time. The utilization of audiovisual instructions has shown a statistically significant positive effect on improving adherence with the recommended wear time in comparison to delivering verbal instructions only after 6 months. N... | PMC10219970 |
Limitations | Microsensors have shown substantial accuracy in | PMC10219970 | ||
Author contributions | K.W. contributed to conception, design, data acquisition and interpretation, analysis, drafted and critically revised the manuscript; H.M. contributed to conception, design, drafted and critically revised the manuscript; A.E.S. contributed to data analysis and interpretation, drafted and critically revised the manuscri... | PMC10219970 | ||
Funding | This study was funded by the Health commission of Henan province, with number: SBGJ202002074. | PMC10219970 | ||
Data availability | Datasets are available with the corresponding author upon reasonable request. | PMC10219970 | ||
Competing interests | The authors declare no competing interests. | PMC10219970 | ||
References | PMC10219970 | |||
Background | ARDS | ARDS, ACUTE RESPIRATORY DISTRESS SYNDROME | The use of glucocorticoids has given contradictory results for treating acute respiratory distress syndrome (ARDS). The use of intravenous Interferon beta (IFN β) for the treatment of ARDS was recently tested in a phase III ARDS trial (INTEREST), in which more than half of the patients simultaneously received glucocort... | PMC10018638 |
Methods | We first sequenced the genes encoding the IFN α/β receptor of the patients, who participated in the INTEREST study (ClinicalTrials.gov Identifier: | PMC10018638 | ||
Results | ARDS, coronavirus diseases | MINOR, DISEASE, ARDS | We found a novel disease association of a SNP rs9984273, which is situated in the interferon α/β receptor subunit 2 (IFNAR2) gene in an area corresponding to a binding motif of the glucocorticoid receptor (GR). The minor allele of SNP rs9984273 associates with higher IFNAR expression, more rapid decrease of IFN γ and i... | PMC10018638 |
Conclusions | ARDS | ARDS | The distribution of this SNP within clinical study arms may explain the contradictory results of multiple ARDS studies and outcomes in COVID-19 concerning type I IFN signaling and glucocorticoids. | PMC10018638 |
Graphical abstract | PMC10018638 | |||
Supplementary Information | The online version contains supplementary material available at 10.1186/s13054-023-04388-8. | PMC10018638 | ||
Keywords | PMC10018638 | |||
Methods | PMC10018638 | |||
Clinical study populations | sepsis, pneumonia, ARDS | SEPSIS, ARDS, PNEUMONIA | The clinical study population has been extensively characterized and reported [The association of rs9984273 with survival is reported using the entire study population with genetic data available. For the IFN γ analyses, only patients with ARDS due to pneumonia or sepsis or pulmonary origin and using glucocorticoids we... | PMC10018638 |
Lung specimens | cancer | CANCER, LUNG | Lung specimen from 14 different individuals was obtained by postsurgical resection of anonymous lung tissue (typically for cancer resections). The lung sections from lung regions having normal macro- and microscopic appearance were used. Several small pieces were cut from all samples and 5–6 pieces/well/condition were ... | PMC10018638 |
Immunohistochemistry | 9167S | SECONDARY | Five-µm-thick frozen sections were cut from lung pieces and fixed with acetone for 5 min. Thereafter, the endogenic peroxidase was blocked using Bloxall Blocking solution (Vector laboratories) for 15 min at room temperature RT. The first-stage antibodies were against alpha and beta chains (IFNAR1 and IFNAR2) of the IFN... | PMC10018638 |
MX1 response | PBMCs were isolated from 9 mL of EDTA blood by Ficoll gradient centrifugation. The cells were plated 0.5 × 10 | PMC10018638 | ||
Genetic analyses | The AmpliSeq® custom panel was used to sequence | PMC10018638 | ||
Binding site analysis | We investigated putative binding sites of GR within the SNP rs9984273 region utilizing the Transfac database (version 2020.3) [ | PMC10018638 | ||
COVID-19 host genetics initiative database analyses | DISEASE | The COVID-19 Host Genetics Initiative (COVID19-hg) GWAS meta-analyses rounds 4 and 6 summary results were used to identify the association of the SNP rs9984273 with disease severity [ | PMC10018638 | |
Statistics | REGRESSION | Several statistical methods such as repeated measures ANCOVA, multivariate Cox model, logistic regression analysis, Cochran's Q heterogeneity test, Chi-square test, two-way ANOVA with Šídák's multiple comparisons test, and two-tailed Mann–Whitney U-test were used. Their use is indicated in the text and/or figure legend... | PMC10018638 | |
Results | PMC10018638 | |||
Discovery of rs9984273 in clinical trials investigating intravenous IFN β-1a for the treatment of ARDS | death, ARDS | MINOR, DISEASE, ARDS | We have performed two significant clinical trials investigating the use of intravenous IFN β-1a for the treatment of ARDS [Further, pre-defined targeted resequencing and genetic analyses of entire gene regions were performed for genes encoding CD73 (The effect of the rs9984273 genotype on mortality and cytokine levels ... | PMC10018638 |
Rs9984273 associates with IFN γ and IL-6 production in patients receiving glucocorticoid treatment | ARDS | ARDS | The SNP rs9984273 locates in the 3’ untranslated region (3’-UTR) of the IFNAR2 gene (chr21:33,262,760 (GRCh38)). To investigate potential binding sites of GR in the region, we utilized position weight matrices compiled from individual genomic sites from the Transfac database (Transfac matrix table, Release 2020.3) or d... | PMC10018638 |
Rs9984273 contributes to the expression of IFNAR together with rs2236757 | ARDS | DISEASE, ARDS | After the discovery of rs9984273, and recognizing its role in the outcome of the previous clinical ARDS studies, we then investigated, whether this polymorphism contributes to the expression of the IFNAR (composed of IFNAR1 and IFNAR2 subunits) by immunohistochemistry using antibodies against IFNAR subunits of the rece... | PMC10018638 |
CT and TT patients display different features in IFN β-induced STAT1 and STAT2 signaling and responsiveness to glucocorticoids | MINOR | As the immune status and IFNAR expression are at least partially under the control of rs9984273 and the formation of the signal transducer and activator of transcription 1/2 and interferon regulatory factor 9 (STAT1/STAT2/IRF9) complex and its translocation into the nucleus is required to trigger type I IFN responsive ... | PMC10018638 | |
Rs9984273 is associated with COVID-19 hospitalization | ARDS | DISEASE PROGRESSION, DISEASE, ARDS, MINOR | Adhering to our recent clinical and laboratory findings, and the outbreak of the SARS-CoV2, we also explored the role of rs9984273 in COVID-19 through publicly available databases. After all, without a doubt both endogenous and exogenous type I IFNs and steroids play a fundamental role in disease progression and surviv... | PMC10018638 |
Discussion | ARDS, ill | LUNG, MINOR, VIRAL INFECTION, CRITICAL ILLNESS, ARDS | Both type I IFN and cortisol responses are needed in viral induced critical illness, but at different times, IFNs first and steroids later. In most people, both endogenous and exogenous steroids block the organ protective effects of IFN β on the endothelium, if there is no preceding type I IFN response. We have discove... | PMC10018638 |
Acknowledgements | The authors want to thank the INTEREST-trial study group for the data analyzed further in this manuscript. We also thank Sari Mäki and Teija Kanasuo for their expert technical help and Dr. Joe Hettinger and Miro Viitala for help and advice. | PMC10018638 | ||
Author contributions | MH, JJ | JJ and SJ were involved in conceptualization, SK, TH, MH, KE, NW, LE, and SJ helped in methodology, JJ, SK, and SJ contributed to investigation, MH was involved in visualization, SJ and LE helped in funding acquisition, JJ and SK contributed to writing of the original draft and all authors contributed to writing, revie... | PMC10018638 | |
Funding | The EU FP7 program, Traumakine, the Finnish Academy, the Jane and Aatos Erkko Foundation, and the Sigrid Juselius Foundation. | PMC10018638 | ||
Availability of data and materials | All data are available in the main text or the supplementary materials. Patient samples are not available. | PMC10018638 | ||
Declarations | PMC10018638 | |||
Ethics approval and consent to participate | Genetic analyses are part of the multi-center INTEREST trial (ClinicalTrials.gov Identifier: NCT02622724 | PMC10018638 | ||
Consent for publications | Not applicable. | PMC10018638 | ||
Competing interests | MH, JJ | JJ is an employee and TH consultant of Faron Pharmaceuticals, JJ, MH, and SJ own stocks of Faron Pharmaceuticals. | PMC10018638 | |
References | PMC10018638 | |||
Purpose | AML | ACUTE MYELOID LEUKEMIA, AML | Gemtuzumab ozogamicin (GO) is indicated for treatment of relapsed/refractory (R/R) acute myeloid leukemia (AML). The QT interval, pharmacokinetics (PK), and immunogenicity following the fractionated GO dosing regimen have not been previously assessed. This phase IV study was designed to obtain this information in patie... | PMC9996548 |
Methods | AML | Patients aged ≥ 18 years with R/R AML received the fractionated dosing regimen of GO 3 mg/m | PMC9996548 | |
Results | thrombocytopenia, TEAEs, Treatment-emergent adverse, febrile neutropenia | THROMBOCYTOPENIA, FEBRILE NEUTROPENIA | Fifty patients received ≥ 1 dose of GO during Cycle 1. The upper limit of the 2-sided 90% confidence interval for least squares mean differences in QTc using Fridericia’s formula (QTcF) was < 10 ms for all time points during Cycle 1. No patients had a post-baseline QTcF > 480 ms or a change from baseline > 60 ms. Treat... | PMC9996548 |
Conclusion | Fractionated GO dosing regimen (3 mg/m | PMC9996548 | ||
Trial registry | Clinicaltrials.gov ID: NCT03727750 (November 1, 2018). | PMC9996548 | ||
Supplementary Information | The online version contains supplementary material available at 10.1007/s00280-023-04516-9. | PMC9996548 | ||
Keywords | PMC9996548 | |||
Introduction | death, neutropenia, AML, thrombocytopenia, anemia, aggressive malignancy, CD33-positive AML, undifferentiated myeloblasts | NEUTROPENIA, THROMBOCYTOPENIA, ACUTE MYELOID LEUKEMIA, DNA DAMAGE, AML, ANEMIA | Acute myeloid leukemia (AML) is an aggressive malignancy characterized by rapid clonal expansion of undifferentiated myeloblasts, leading to anemia, neutropenia, and thrombocytopenia [Gemtuzumab ozogamicin (GO) is a CD33-directed antibody–drug conjugate consisting of a monoclonal antibody targeting CD33 linked to a cyt... | PMC9996548 |
Materials and methods | PMC9996548 | |||
Study design and patients | CD33-positive AML | This was a single-arm, open-label, phase IV study (ClinicalTrials.gov ID: NCT03727750) of GO monotherapy in adult (≥ 18 years) and pediatric (≥ 12–17 years) patients with R/R CD33-positive AML. This paper focuses on adults only. Key eligibility criteria included: initial peripheral white blood cell counts < 30 × 10 | PMC9996548 | |
Study treatment | Patients received a fractionated dosing regimen of GO 3 mg/m | PMC9996548 | ||
Study assessments | ADVERSE EVENTS, REMISSION | The primary endpoint was the mean change from baseline in QTc. Secondary endpoints included assessment of PK parameters, adverse events (AEs), incidence of antidrug antibodies (ADAs)/neutralizing antibodies (NAbs), overall survival (OS), and response rate (CR/CRi) (see Supplementary methods in the Online Resource). Tri... | PMC9996548 | |
Results | PMC9996548 | |||
Patient characteristics | Fifty-one adult patients (median [range] age of 67 [22–82] years) were enrolled in the study. Among enrolled patients, 27 (52.9%) had received 1 prior induction regimen; 11 (21.6%), 8 (15.7%), and 4 (7.8%) had received 2, 3, or > 3 prior induction regimens, respectively (see Supplementary Table 1 in the Online Resource... | PMC9996548 | ||
QT interval | The upper limit of the 2-sided 90% confidence interval (CI) for least squares (LS) mean differences in QTc using Fridericia’s formula (QTcF) was < 10 ms for all time points during Cycle 1, including those on D4 and D7 assessed in the primary analysis (Fig. QTcF change from baseline during C1. Baseline is defined as the... | PMC9996548 | ||
Pharmacokinetics | Following administration of multiple fractionated infusions of GO at 3 mg/m | PMC9996548 | ||
Immunogenicity | pyrexia, anaphylaxis, urticaria | ANAPHYLAXIS, SEQUELAE, HYPERSENSITIVITY, URTICARIA | Of 50 patients treated with GO, 12 (24.0%) had positive ADAs against GO at baseline. This was likely due to pre-existing host antibodies that were cross-reactive with GO. There was no treatment-boosted ADA response.Treatment-induced ADA was detected in 6 (12.0%) patients. No patients experienced anaphylaxis, hypersensi... | PMC9996548 |
Efficacy | ELN, deaths | DISEASE PROGRESSION | The best overall response was CR in 2 (3.9% [95% CI 0.5–13.5]) patients and CRi in 3 (5.9% [95% CI 1.2–16.2]) patients (see Supplementary Table 3 in the Online Resource), with an overall rate of 9.8% (95% CI 3.3–21.4). CR + CRi was achieved by 3 (6.0%) of the 50 patients in Cycle 1. Nine of the 50 patients receiving Cy... | PMC9996548 |
Discussion | AML, anaphylaxis | ANAPHYLAXIS, SEQUELAE, HYPERSENSITIVITY, AML | This study showed that fractionated dosing of GO (3 mg/mAs part of a review of the PK for the prior marketing application of GO, a population PK model was used to simulate exposure for the fractionated GO regimen, based on 8 previous trials in patients with R/R AML or de novo AML [This current study enables comparison ... | PMC9996548 |
Acknowledgements | This study was sponsored by Pfizer. The authors thank the patients and their families/caregivers, investigators, research nurses, study coordinators, and operations staff who contributed to this study. Medical writing support was provided by Simon Stones, PhD, of Engage Scientific Solutions, and was funded by Pfizer. | PMC9996548 | ||
Data availability | Upon request, and subject to review, Pfizer will provide the data that support the findings of this study. Subject to certain criteria, conditions, and exceptions, Pfizer may also provide access to the related individual de-identified participant data. See | PMC9996548 | ||
Declarations | PMC9996548 | |||
Conflict of interest | Pierre | Pau Montesinos has served as a consultant for Agios, Astellas, Celgene, Daiichi Sankyo, Forma Therapeutics, Glycomimetics, and Tolero Pharmaceutical; has been an advisor for AbbVie, Astellas, Celgene, Daiichi Sankyo, Incyte, Janssen, Karyopharm, Novartis, Pfizer, Sanofi, and Teva; has received research funding from Abb... | PMC9996548 | |
References | PMC9996548 | |||
Subject terms | RCC, NRS | RCC | Many intensive care unit patients who undergo endotracheal extubation experience extubation failure and require reintubation. Because of the high mortality rate associated with reintubation, postextubation respiratory management is crucial, especially for high-risk populations. We conducted the present study to compare... | PMC10033681 |
Introduction | Approximately 10–15% of intensive care unit (ICU) patients who undergo endotracheal extubation experience extubation failure and require reintubationHigh-flow oxygen therapy can be administered using a nasal cannula | PMC10033681 | ||
Results | COPD | CHRONIC OBSTRUCTIVE PULMONARY DISEASE, COPD | A total of 40 patients were enrolled and assigned to the NIPPV and HFNC groups, with 20 patients in each group (see Supplementary Fig. Characteristics of patients at inclusion.Data are presented as frequencies (%), medians [interquartile range] or mean ± standard deviations.NIPPV: noninvasive positive pressure ventilat... | PMC10033681 |
Discussion | atelectasis, pulmonary edema, postextubation respiratory failure, RCC, NRS | ATELECTASIS, PULMONARY EDEMA, RCC | The results of this RCT indicate that patients with PMV who undergo HFNC have a higher intubation rate than do those who receive NIPPV. All the patients in this study had been receiving mechanical ventilation for more than 2 weeks (30 and 26 days on average in the NIPPV and HFNC groups, respectively). A total of 25% of... | PMC10033681 |
Methods | PMC10033681 | |||
Study design | RCC, NCT04564859 | RCC | This single-center, prospective, nonblinded RCT and equivalent RCT that compared NIPPV (intervention group) and HFNC (control group) after extubation was conducted between January 2017 and December 2020 at the respiratory care center (RCC) of Shin Kong Wu Ho-Su Memorial Hospital in Taipei, Taiwan. The study was approve... | PMC10033681 |
Participants | RCC | RCC, NEUROMUSCULAR DISEASES | Patients aged more than 20 years who were ready for extubation, had received mechanical ventilation for more than 6 h per day for at least 14 consecutive days, and who had been transferred from the ICU to the RCC were immediately enrolled into this study. The exclusion criteria for this study were tracheostomy, do-not-... | PMC10033681 |
Intervention | NRS | The clinical weaning protocol involved a daily evaluation of weaning readiness up to the time of extubation, and the readiness was determined on the basis of the following criteria: recovery from the precipitating illness; respiratory measures of PaOAfter undergoing extubation, each patient was randomly assigned to the... | PMC10033681 | |
NRS weaning protocol | All participants were screened for weaning readiness daily according to the following criteria: (1) pH value of ≥ 7.35; (2) oxygen saturation (SpO | PMC10033681 | ||
Failure criteria | Postextubation respiratory failure | Postextubation respiratory failure was defined as follows: (1) lack of improvement in pH or in the partial pressure of carbon dioxide (PaCO | PMC10033681 | |
Outcome measurement | RCC, NRS | SECONDARY, RCC | The primary outcome was reintubation within 72 h after extubation. The secondary outcomes were reintubation within 7 days of extubation, changes in physiological parameters and arterial blood gas analysis results, time to liberation from NRS, duration of respiratory support, length of RCC and hospital stay, ventilator-... | PMC10033681 |
Statistical analysis | The primary outcome of this study was the reintubation rate. We assumed the reintubation rates of the HFNC and NIPPV groups to be 50% and 10%, respectively. A sample size of 20 for each group was required to achieve an alpha level of 5% (two tailed) and power of 80%. Sample size calculation was conducted using G*Power,... | PMC10033681 | ||
Ethics approval and consent to participate | We conducted the trial in accordance with good clinical practice guidelines and the Declaration of Helsinki. The study was approved by local institutional review committees (IRB number: 20160901R). Informed written consent was obtained from all participants. | PMC10033681 | ||
Supplementary Information | The online version contains supplementary material available at 10.1038/s41598-023-31444-8. | PMC10033681 | ||
Author contributions | C.W.T., K.Y.C., H.L.W., C.C.L., and H.S.H. designed the study and prepared the clinical protocol; C.W.T., KYC, HLW, and CCL implemented the clinical trial and were involved in data acquisition; CWT and KYC analyzed and interpreted data; CWT, KYC and HSH drafted and revised the manuscript, KYC, HLW, CCL and HSH contribu... | PMC10033681 | ||
Funding | This work was supported by a research grant from Shin Kong Wu Ho-Su Memorial Hospital (SKH8302106NDR05). This funding source had no role in the design of this study and did not have any role during its execution, analyses, interpretation of the data, or decision to submit results. | PMC10033681 | ||
Data availability | The datasets used and/or analysed during the current study available from the corresponding author on reasonable request. | PMC10033681 | ||
Competing interests | The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants... | PMC10033681 | ||
References | PMC10033681 | |||
Purpose | CIN | CERVICAL CANCER, CIN | Cervical cancer screening by visual inspection with acetic acid (VIA) during colposcopy can be challenging and is highly dependent on the clinical experience of the examiner. Health-care systems lack qualified physicians able to perform the examination in both industrialized and low- and middle-income countries. Previo... | PMC10520109 |
Methods | CIN | CIN | In this study, we evaluate the feasibility of a commercially available HSI system for CIN detection in a prospective monocentric clinical trial. | PMC10520109 |
Results | CIN | CIN | By obtaining spectral fingerprints of 41 patients with CIN 1–3 we show that HSI-based differentiation between CIN and normal tissue is possible with high statistical significance. Major spectral differences were seen in the 555–585 wavelength area. | PMC10520109 |
Conclusion | CIN | CIN | HSI advances tissue differentiation by associating each pixel with high-dimensional spectra and thereby obtains morphological and biochemical information of the observed tissue. Currently available and medically approved HSI systems may represent a contact- and marker-free examiner-independent method for the diagnosis ... | PMC10520109 |
Supplementary Information | The online version contains supplementary material available at 10.1007/s00404-023-07171-w. | PMC10520109 | ||
Keywords | Open Access funding enabled and organized by Projekt DEAL. | PMC10520109 | ||
What does this study add to the clinical work | PMC10520109 | |||
Introduction | cancer, precancerous lesions, inflammation | PRECANCEROUS LESIONS, VASCULARIZATION, CANCER, DYSPLASTIC, DISEASE, INFLAMMATION, CERVICAL CANCER, CERVICAL INTRAEPITHELIAL NEOPLASIA (CIN), SEVERE DYSPLASIA | Cervical intraepithelial neoplasia (CIN) refers to a spectrum of serious precancerous lesions and is classified into three grades based on the extent and severity of cellular and architectural abnormalities. Whereas CIN1 represents mild dysplastic lesions, CIN2 and CIN3 indicate moderate to severe dysplasia. Cervical c... | PMC10520109 |
Materials and methods | PMC10520109 | |||
Study design | The present prospective, monocentric study (DRKS00013486) aimed to investigate the suitability of the TIVITA | PMC10520109 | ||
HSI system | For hyperspectral imaging of the portio, the TIVITA | PMC10520109 | ||
Statistics | For data analysis, HSI images were compared with the high-resolution images of the colposcopic assessment by VIA. Ten respective HSI spectra of 500–995 nm were extracted from the HSI images out of the most representative area of VIA changes and an unsuspicious control area using the TIVITA | PMC10520109 | ||
Results | PMC10520109 | |||
Patient characteristics | CIN1/2 lesions, CIN, anxiety | CIN | From 06/2018 to 01/2020, we assessed 110 participants for study eligibility. HSI was prospectively applied in 41 patients with histologically proven CIN 1–3 in a controlled clinical trial (DRKS00013486) at the Department of Women’s Health, Tübingen, Germany. CIN was histologically diagnosed by colposcopy-directed biops... | PMC10520109 |
Statistical comparison of absorption per wavelength between CIN lesions and healthy tissue | CIN lesions | The comprehensive analysis of the entire wavelength spectrum, ranging from 500 to 990 nm, revealed substantial and statistically significant differences between CIN lesions and healthy tissue of the portio (Obtained HSI spectra of CIN lesions vs. control. Graphs depict the mean accumulative reflectance of CIN lesions (... | PMC10520109 | |
Discussion | CIN | DYSPLASTIC, INVASIVE CERVICAL CANCER, CIN, CERVICAL CANCER, CAVITY | Colposcopy, as the current gold standard, plays a vital role in evaluating cervical abnormalities. It has significantly contributed to cervical cancer screening, diagnosis, and decision-making processes. By providing enhanced visualization of the cervix, colposcopy, combined with VIA and iodine staining, enables the id... | PMC10520109 |
Acknowledgements | This work was supported by Erbe Elektromedizin GmbH, Tübingen (loaner of the TIVITA | PMC10520109 | ||
Author contributions | All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by MW, LS, and MW. The first draft of the manuscript was written by LS and MW and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscrip... | PMC10520109 |
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