bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cannabidiol treatment in hand osteoarthritis and psoriatic arthritis: a randomized, double-blind, placebo-controlled trial
Authors: Vela Jonathan , Dreyer Lene , Petersen Kristian Kjær , Arendt-Nielsen Lars , Duch Kirsten Skjærbæk , Kristensen Salome 
Published: September 2021

Abstract
Cannabidiol (CBD) is increasingly used as analgesic medication although the recent International Association for the Study of Pain Presidential Task Force on cannabis and cannabinoid analgesia found a lack of trials examining CBD for pain management. This trial examines CBD as add-on analgesic therapy in patients with hand osteoarthritis or psoriatic arthritis experiencing moderate pain intensity despite therapy. Using a randomized, double-blind, placebo-controlled design, patients received synthetic CBD 20 to 30 mg or placebo daily for 12 weeks. The primary outcome was pain intensity during the past 24 hours (0-100 mm); safety outcomes were percentage of patients experiencing adverse events and a characterization of serious adverse events. Explorative outcomes included change in Pittsburgh Sleep Quality Index, Hospital Anxiety and Depression Scale, Pain Catastrophizing Scale (PCS), and Health Assessment Questionnaire Disability Index. One hundred thirty-six patients were randomized, of which 129 were included in the primary analysis. Between-group difference in pain intensity at 12 weeks was 0.23 mm (95% confidence interval −9.41 to 9.90; P = 0.96). Twenty-two percent patients receiving CBD and 21% receiving placebo experienced a reduction in pain intensity of more than 30 mm. We found neither clinically nor statistically significant effects of CBD for pain intensity in patients with hand osteoarthritis and psoriatic arthritis when compared with placebo. In addition, no statistically significant effects were found on sleep quality, depression, anxiety, or pain catastrophizing scores.
Behavioral outcomes of complete Freund adjuvant–induced inflammatory pain in the rodent hind paw: a systematic review and meta-analysis
Authors: Burek Dominika J. , Massaly Nicolas , Yoon Hye Jean , Doering Michelle , Morón Jose A. 
Published: September 2021

Abstract:
Many analgesics inadequately address the psychiatric comorbidities of chronic and persistent pain, but there is no standard preclinical model of pain-altered behavior to support the development of new therapies. To explore this conflicting and inconclusive literature, we conducted a focused systematic review and meta-analysis on the effect of complete Freund adjuvant–induced (CFA) rodent hind paw inflammation on multiple classical indicators of exploratory behavior, stress coping, and naturalistic behavior. Our primary objective was to define CFA's effect on assays including, but not limited to, the elevated plus maze and forced swim test. Our secondary objective was to discover how variables such as species and strain may influence outcomes in such assays. We searched Ovid MEDLINE, Embase, Scopus, and Web of Science in April and October 2020 for studies with adult rodents injected with CFA into the hind paw and subsequently tested for aspects of “anxiety-like” or “depressive-like” behaviors. Forty-four studies evaluated performance in the elevated plus or zero maze, open field test, light–dark box, place escape and avoidance paradigm, forced swim test, tail suspension test, sucrose preference test, wheel running, and burrowing assay. Complete Freund adjuvant modestly but significantly decreased exploratory behavior, significantly increased passive stress coping in the tail suspension test but not the forced swim test, and significantly decreased preference for sucrose and naturally rewarding activity. Subgroup analyses revealed significant differences between species and animal sourcing. Based on the evidence provided here, we conclude future studies should focus on CFA's effect on natural rewards and naturalistic behaviors.
Use of NOACs Versus Vitamin K Antagonist in Atrial Fibrillation Catheter Ablation: An Updated Meta-analysis With Subgroup Analysis
Authors: Bhogal Sukhdeep , Mawa Kajal , Bhandari Tarun , Ramu Vijay 
Published: September 2021

Background:
Current guidelines give class I recommendations for uninterrupted use of dabigatran rivaroxaban as an alternative to vitamin K antagonist (VKA) in patients of atrial fibrillation (AF) who are undergoing catheter ablation. The recent randomized controlled trials have shown similar efficacy of novel oral anticoagulants when compared to VKA in these patients. We sought to perform a meta-analysis with a focus on subgroup analysis of novel oral anticoagulants.

Methods:
We searched PubMed, Clinical trials registry and the Cochrane Center Register of Controlled Trials were searched through August 2020. Six RCTs studies (n = 2260) comparing the use of NOACs versus VKA in patients with AF undergoing catheter ablation were included. The odds ratio (OR) with 95% confidence interval was computed and P < 0.05 was considered as a level of significance. Major adverse cardiac events (MACE) were considered as a primary endpoint.

Results:
Our results showed a significant difference in MACE between NOACs and VKA [OR 0.57 (0.37–0.88); P = 0.01] and in major bleeding events [OR 0.55 (0.35–0.86); P = 0.009], which is mainly derived from the use of dabigatran. No significant difference in MACE or major bleeding events was found on the subgroup analysis of rivaroxaban and apixaban over VKA therapy.

Conclusion:
Uninterrupted use of NOACs is safe and effective alternative for the prevention of cerebral thromboembolism and reducing the risk of major bleeding in patients undergoing catheter ablation of AF. However, the individual subgroup analysis showed that only dabigatran is superior to VKA in terms of reducing MACE through a reduction in major bleeding. The rivaroxaban, apixaban and edoxaban are non-inferior to VKA therapy based on these results. Further studies are needed to generalize these recommendations in morbidly obese patients.
Prediction of Genetic Alterations in Oncogenic Signaling Pathways in Squamous Cell Carcinoma of the Head and Neck: Radiogenomic Analysis Based on Computed Tomography Images
Authors: Wu Linyong , Lin Peng , Zhao Yujia , Li Xin , Yang Hong , He Yun 
Published: September 2021

Objective
This study investigated the role of radiomics in evaluating the alterations of oncogenic signaling pathways in head and neck cancer.

Methods
Radiomics features were extracted from 106 enhanced computed tomography images with head and neck squamous cell carcinoma. Support vector machine–recursive feature elimination was used for feature selection. Support vector machine algorithm was used to develop radiomics scores to predict genetic alterations in oncogenic signaling pathways. The performance was evaluated by the area under the curve (AUC) of the receiver operating characteristic curve.

Results
The alterations of the Cell Cycle, HIPPO, NOTCH, PI3K, RTK RAS, and TP53 signaling pathways were predicted by radiomics scores. The AUC values of the training cohort were 0.94, 0.91, 0.94, 0.93, 0.87, and 0.93, respectively. The AUC values of the validation cohort were all greater than 0.7.

Conclusions
Radiogenomics is a new method for noninvasive acquisition of tumor molecular information at the genetic level.
Comparison of Radiation Dose and Image Quality Between Split-Filter Twin Beam Dual-Energy Images and Single-Energy Images in Single-Source Contrast-Enhanced Chest Computed Tomography
Authors: Zhou Li-Na , Zhao Shi-Jun , Wang Ruo-Bing , Wang Ya-Wen , Yang Shou-Xin , Wu Ning 
Published: September 2021

Objective
To compare image quality and radiation dose of split-filter TwinBeam dual-energy (SF-TBDE) with those of single-energy images (SECT) in the contrast-enhanced chest computed tomography (CT).

Methods
Two hundred patients who underwent SF-TBDE (n = 100) and SECT (n = 100) contrast-enhanced chest scanning were retrospectively analyzed. The contrast-to-noise ratio (CNR) and figure of merit (FOM)-CNR of 5 structures (lung, aorta, pulmonary artery, thyroid, and erector spinae) were calculated and subjectively evaluated by 2 independent radiologists. Radiation dose was compared using volume CT dose index and size-specific dose estimate.

Results
The CNR and FOM-CNR of lung and erector spinae in SF-TBDE were higher than those of SECT (P < 0.001). The differences in the subjective image quality between the 2 groups were not significant (P = 0.244). Volume CT dose index and size-specific dose estimate of SF-TBDE were lower than those of SECT (6.60 ± 1.56 vs 7.81 ± 3.02 mGy, P = 0.001; 9.25 ± 1.60 vs. 10.55 ± 3.54; P = 0.001).

Conclusions
The SF-TBDE CT can provide similar image quality at a lower radiation dose compared with SECT.
Modified Maximal Levator Palpebrae Superioris Shortening in Correcting Congenital Severe Ptosis in Children
Authors: Liu Ninghua , He Aijuan , Wu Dan , Zhang Jing , Song Nan 
Published: September 2021

Objective
This study aims to evaluate the clinical effect of modified maximal levator palpebrae superioris shortening method for severe congenital ptosis.

Methods
A retrospective case series was performed including 66 eyes from 62 patients who underwent modified maximal levator palpebrae superioris shortening surgery to treat severe congenital ptosis between February 2015 and November 2018. Preoperative and postoperative margin reflex distance 1 and levator muscle function were recorded. The surgical results were graded as good, satisfied, and poor for functional and cosmetic improvement of the eyelids, and the incidence of complications was also documented.

Results
The mean patient age at the time of surgery was 4.6 ± 1.8 years (2–9 years), and the mean follow-up time was 36.3 ± 14.1 (12–55 months). A mean significant improvement in margin reflex distance 1 and levator function after operation was noted (P < 0.01). The eyelid height and symmetry were satisfied in 59 patients, with success rate of 95.2%. For the patients in the levator function (≤2 mm) group, the success rate was 87.5%. Moreover, the levator function (≤2 mm) group had a higher rate of poor results than levator function (2–4 mm) group (12.5% vs 2.2%). Overcorrection (6.5%) and eyelid fold deformity (11.3%) were the most frequent postoperative complications.

Conclusion
Modified maximal levator palpebrae superioris shortening was effective and endurable in the treatment of severe congenital ptosis with poor levator function, including in patients whose levator function was less than 2 mm.
Covid-19 Vaccine Effectiveness in Healthcare Personnel in six Israeli Hospitals (CoVEHPI)
Authors: Katz Mark A. , Harlev Efrat Bron , Chazan Bibiana , Chowers Michal , Greenberg David , Peretz Alon , Tshori Sagi , Levy Joseph , Yacobi Mili , Hirsch Avital , Amichay Doron , Weinberger Ronit , Dor Anat Ben , Taraday Elena Keren , Reznik Dana , Chayat Chen Barazani , Sagas Dana , Zvi Haim Ben , Berdinstein Rita , Rashid Gloria , Avni Yonat Shemer , Mandelboim Michal , Zuckerman Neta , Rainy Nir , Akriv Amichay , Dagan Noa , Kepten Eldad , Barda Noam , Balicer Ran D. 
Published: September 2021

AbstractBackgroundMethodologically rigorous studies on Covid-19 vaccine effectiveness (VE) in preventing SARS-CoV-2 infection are critically needed to inform national and global policy on Covid-19 vaccine use. In Israel, healthcare personnel (HCP) were initially prioritized for Covid-19 vaccination, creating an ideal setting to evaluate real-world VE in a closely monitored population.MethodsWe conducted a prospective study among HCP in 6 hospitals to estimate the effectiveness of the BNT162b2 mRNA Covid-19 vaccine in preventing SARS-CoV-2 infection. Participants filled out weekly symptom questionnaires, provided weekly nasal specimens, and three serology samples – at enrollment, 30 days and 90 days. We estimated VE against PCR-confirmed SARS-CoV-2 infection using the Cox Proportional Hazards model and against a combined PCR/serology endpoint using Fisher’s exact test.FindingsOf the 1,567 HCP enrolled between December 27, 2020 and February 15, 2021, 1,250 previously uninfected participants were included in the primary analysis; 998 (79.8%) were vaccinated with their first dose prior to or at enrollment, all with Pfizer BNT162b2 mRNA vaccine. There were four PCR-positive events among vaccinated participants, and nine among unvaccinated participants. Adjusted two-dose VE against any PCR- confirmed infection was 94.5% (95% CI: 82.6%-98.2%); adjusted two-dose VE against a combined endpoint of PCR and seroconversion for a 60-day follow-up period was 94.5% (95% CI: 63.0%-99.0%). Five PCR-positive samples from study participants were sequenced; all were alpha variant.InterpretationOur prospective VE study of HCP in Israel with rigorous weekly surveillance found very high VE for two doses of Pfizer BNT162b2 mRNA vaccine against SARS-CoV-2 during a period of predominant alpha variant circulation.FundingClalit Health Services
Cardiovascular disease and all-cause mortality risk prediction from abdominal CT using deep learning
Authors: Elton Daniel C. , Chen Andy , Pickhardt Perry J. , Summers Ronald M. 
Published: September 2021

ABSTRACTCardiovascular disease is the number one cause of mortality worldwide. Risk prediction can help incentivize lifestyle changes and inform targeted preventative treatment. In this work we explore utilizing a convolutional neural network (CNN) to predict cardiovascular disease risk from abdominal CT scans taken for routine CT colonography in otherwise healthy patients aged 50-65. We find that adding a variational autoencoder (VAE) to the CNN classifier improves its accuracy for five year survival prediction (AUC 0.787 vs. 0.768). In four-fold cross validation we obtain an average AUC of 0.787 for predicting five year survival and an AUC of 0.767 for predicting cardiovascular disease. For five year survival prediction our model is significantly better than the Framingham Risk Score (AUC 0.688) and of nearly equivalent performance to method demonstrated in Pickhardt et al. (AUC 0.789) which utilized a combination of five CT derived biomarkers.
Combined PD-L1 and TIM-3 blockade improves the expansion of fit human CD8+ antigen-specific T cells for adoptive immunotherapy
Authors: Lak Shirin , Janelle Valérie , Djedid Anissa , Boudreau Gabrielle , Brasey Ann , Lisi Véronique , Carli Cédric , Busque Lambert , Lavallée Vincent-Philippe , Delisle Jean-Sébastien 
Published: September 2021

AbstractBackgroundThe stimulation and expansion of antigen-specific T cells ex vivo enables the targeting of a multitude of cancer antigens. However, clinical scale T-cell expansion from rare precursors requires repeated stimulations ex vivo leading to T-cell terminal effector differentiation and exhaustion that adversely impact therapeutic potential. We leveraged immune checkpoint blockade relevant to antigen-specific CD8+ human T cells to improve the expansion and function of T cells targeting clinically relevant antigens.MethodsA clinically-compliant protocol relying on peptide-pulsed monocyte-derived dendritic cells and cytokines was used to expand antigen-specific CD8+ targeting the oncogenic Epstein-Barr virus (EBV) and the tumor associated antigen (TAA) Wilms Tumor 1 (WT1) protein. The effects of antibody-mediated blockade of immune checkpoints applied to the cultures (T-cell expansion, phenotypes and function) were assessed at various time points. Genomic studies including single cell RNA (scRNA) sequencing and T-cell receptor sequencing were performed on EBV-specific T cells to inform about the impact of immune checkpoint blockade on the clonal distribution and gene expression of the expanded T cells.ResultsSeveral immune checkpoints were expressed early by ex vivo expanded antigen-specific CD8+ T cells, including PD-1 and TIM-3 with co-expression matching evidence of T-cell dysfunction as the cultures progressed. The introduction of anti-PD-L1 (expressed by the dendritic cells) and anti-TIM-3 antibodies in combination (but not individually) to the culture led to markedly improved antigen-specific T-cell expansion based on cell counts, fluorescent multimer staining and functional tests. This was not associated with evidence of T-cell dysfunction when compared to T cells expanded without immune checkpoint blockade. Genomics studies largely confirmed these results, showing that double blockade does not impart specific transcriptional programs or patterns on TCR repertoires. However, our data indicate that combined blockade may nonetheless alter gene expression in a minority of clonotypes and have donor-specific impacts.ConclusionsThe manufacturing of antigen-specific CD8+ T cells can be improved in terms of yield and functionality using blockade of TIM-3 and the PD-L1/PD-1 axis in combination. Overcoming the deleterious effects of multiple antigenic stimulations through PD-L1/TIM-3 blockade is a readily applicable approach for several adoptive-immunotherapy strategies.
Early versus late third trimester maternal SARS-CoV-2 BNT162b2 mRNA immunization maximizes transplacental antibody transfer and neonatal neutralizing antibody levels
Authors: Rottenstreich Amihai , Zarbiv Gila , Oiknine-Djian Esther , Vorontsov Olesya , Zigron Roy , Kleinstern Geffen , Wolf Dana G. , Porat Shay 
Published: September 2021

AbstractObjectiveWe aimed to assess the impact of early versus late third trimester maternal SARS-CoV-2 vaccination on transplacental transfer and neonatal levels of SARS-CoV-2 antibodies.MethodsMaternal and cord blood sera were collected following term delivery after antenatal SARS-CoV-2 BNT162b2 mRNA vaccination, with the first vaccine dose administered during 27-36 weeks gestation. SARS-CoV-2 spike protein (S) and receptor binding domain (RBD)- specific, IgG levels and neutralizing potency were evaluated in maternal and cord blood samples.ResultsThe study cohort consisted of 171 parturients (median age, 31 years; median gestational age, 39.7 weeks): 83 (48.5%) immunized at early 3rdtrimester (1stdose at 27-31 weeks), and 88 (51.5%) immunized at late 3rdtrimester (1stdose at 32-36 weeks). All mother-infant paired sera were positive for anti S- and anti-RBD-specific IgG. Anti-RBD-specific IgG concentrations in neonatal sera were higher following early versus late 3rdtrimester vaccination and were positively correlated with increasing time since vaccination (r=□0.26; P=0.001). The median placental transfer ratios of anti-S and anti-RBD specific IgG were increased following early versus late 3rdtrimester immunization (anti-S ratio:1.3 vs. 0.9, anti-RBD-specific ratio:2.3 vs. 0.7, P<0.001). Neutralizing antibodies placental transfer ratio was greater following early versus late 3rdtrimester immunization (1.9 vs. 0.8, P<0.001), and was positively associated with longer duration from vaccination (r=□0.77; P<0.001).ConclusionsEarly- as compared to late third trimester maternal SARS-CoV-2 immunization enhanced transplacental antibody transfer and increased neonatal neutralizing antibody levels. Our findings highlight that vaccination of pregnant women early in the third trimester may optimize neonatal seroprotection.
Elastomeric Harnesses Decrease Aerosol Particles Leak and Improve the Fit of Surgical Masks
Authors: Ingabire Jeannette , McKenney Hannah , Sebesta Charles , Badhiwala Krishna , Avants Ben , Kemere Caleb , Kapur Sahil , Robinson Jacob T. 
Published: September 2021

ABSTRACTImportanceThe outbreak of Coronavirus diseases 2019 (COVID-19) disease has increased demand for N95 respirators, surgical masks, and other facial coverings to stop the spread of SARS-CoV-2. Research shows that N95 respirators perform the best at filtering viral droplets and aerosols, however these masks are much more difficult to manufacture and expensive to distribute on a large scale, which led to shortages during the pandemic. Surgical masks, on the other hand, were more widely available and have been previously used to mitigate the spread of tuberculosis and influenza.ObjectivesTo evaluate the filter filtration efficiency (FFE) of three elastomeric harness designs in hospital and research settings in order to improve facemask seal.Design, setting and participantsA multi-institutional collaboration between engineers and health professionals, conducted between November 2020 and March 2021, was set up to design an elastomeric harness to improve the face seal of a surgical mask. Three elastomeric harness designs were created with harness designs 1 and 2 tested in a research laboratory setting and harness design 2.1 tested in a hospital setting. The initial harness design 1 was laser cut for testing and design 2 was developed to improve the detected particle leakage around the nose bridge area by introducing more material in that region. Design 2.1 is developed for hospital settings with less material around the nose bridge to reduce vision disruption. The designs were tested on mannequins and human volunteers using IR imaging and standard fit testing equipment.Main Outcomes and MeasuresOur elastomeric harness can improve the seal of a surgical mask allowing it to pass the fit test used to evaluate N95 respirators. 24/39 participants achieved a passing score of 100 or more while wearing the second harness design. IR imaging determined that the nasal sidewalls region of the mask is most prone to leakage when using our first elastomeric harness.Conclusions and RelevanceOverall, these results confirm that elastomeric harnesses combined with surgical masks improve their ability to filter aerosolized particles, which is especially important when in close proximity to individuals who are infectious or while performing aerosol-generating medical procedures.
Multi-omic profiling of histone variant H3.3 lysine 27 methylation reveals a distinct role from canonical H3 in stem cell differentiation
Authors: Kori Yekaterina , Lund Peder J. , Trovato Matteo , Sidoli Simone , Yuan Zuo-Fei , Noh Kyung-Min , Garcia Benjamin A. 
Published: September 2021

AbstractHistone variants, such as histone H3.3, replace canonical histones within the nucleosome to alter chromatin accessibility and gene expression. Although the biological roles of selected histone post-translational modifications (PTMs) have been extensively characterized, the potential differences in the function of a given PTM on different histone variants is almost always elusive. By applying proteomics and genomics techniques, we investigate the role of lysine 27 tri-methylation specifically on the histone variant H3.3 (H3.3K27me3) in the context of mouse embryonic stem cell pluripotency and differentiation as a model system for development. We demonstrate that while the steady state overall levels of methylation on both H3K27 and H3.3K27 decrease during differentiation, methylation dynamics studies indicate that methylation on H3.3K27 is maintained more than on H3K27. Using a custom-made antibody, we identify a unique enrichment of H3.3K27me3 at lineage-specific genes, such as olfactory receptor genes, and at binding motifs for the transcription factors FOXJ2/3. REST, a predicted FOXJ2/3 target that acts as a transcriptional repressor of terminal neuronal genes, was identified with H3.3K27me3 at its promoter region. H3.3K27A mutant cells confirmed an upregulation of FOXJ2/3 targets upon the loss of methylation at H3.3K27. Thus, while canonical H3K27me3 has been characterized to regulate the expression of transcription factors that play a general role in differentiation, our work suggests H3.3K27me3 is essential for regulating distinct terminal differentiation genes. This work highlights the importance of understanding the effects of PTMs not only on canonical histones but also on specific histone variants, as they may exhibit distinct roles.