bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liposomal bupivacaine during subcutaneous implantable cardioverter defibrillator implantation for pain management
Authors: Lee Justin Z. , Glasgow Amy E. , Habermann Elizabeth B. , Scott Luis , Shen Win‐Kuang , Kusumoto Fred M. , McLeod Christopher J. , Goel Vasudha , Kaginele Pranita , Cha Yong‐Mei , Friedman Paul A. , Asirvatham Samuel J. , Mulpuru Siva K. 
Published: January 2021

AbstractBackgroundThe subcutaneous implantable cardioverter‐defibrillator (S‐ICD) has a larger generator and its implantation involves more dissection and tunneling compared to traditional transvenous defibrillator system. Liposomal bupivacaine, an extended‐release bupivacaine with 72 h of duration has been used for postoperative pain management in patients undergoing S‐ICD implantation. Our aim was to compare postoperative pain and opioid prescription patterns among patients undergoing S‐ICD implantation who received intraprocedural liposomal bupivacaine and those who did not.MethodsWe performed a retrospective analysis of all patients who underwent subcutaneous ICD implantation from January 1, 2013 to March 30, 2018 at the Mayo Clinic in Rochester, Minnesota. Patients were categorized into those who received liposomal bupivacaine and those who did not. Data on inpatient pain score, outpatient opioid prescription rates at discharge, and doses based on oral morphine equivalents (OME) were collected.ResultsA total of 104 patients underwent S‐ICD implantation. Intraprocedural liposomal bupivacaine was used in 69% of patients. Patients who received intraprocedural liposomal bupivacaine had similar mean inpatient pain scores (2.9 vs. 2.9, p = .786). There was also no difference in the rate of inpatient opioid administration (79.2% vs. 87.5%, p = .4139), outpatient opioid prescription (23.6% vs. 12.5%, p = .29), or mean OME (41.7‐mg vs. 16.6‐mg, p = .188) when comparing patients those who received intraprocedural liposomal bupivacaine and those who did not.ConclusionIntraprocedural liposomal bupivacaine administration was not associated with any significant impact on postoperative pain scores, inpatient opioid administration, and outpatient opioid prescription rates or OME amounts at discharge.
Impact of cold and flu medication on obstructive sleep apnoea and its underlying traits: A pilot randomized controlled trial
Authors: Taranto‐Montemurro Luigi , Sands Scott , Azarbarzin Ali , Calianese Nicole , Vena Daniel , Hess Lauren , Kim Sang‐Wook , White David P. , Wellman Andrew 
Published: January 2021

ABSTRACTBackground and objectiveAnimal studies indicate that alpha‐1 adrenergic receptor agonists and antimuscarinic agents improve genioglossus muscle activity during sleep and may be candidates for the pharmacological treatment of OSA. On the other hand, noradrenergic stimulants may be wake‐promoting or cause insomnia symptoms if taken before bedtime, and the addition of a medication with sedative properties, such as an antihistaminic, may reduce these side effects. In this study, we aimed to determine the effects of the combination of an alpha‐1 adrenergic agonist (pseudoephedrine) and an antihistaminic‐antimuscarinic (diphenhydramine) on OSA severity (AHI), genioglossus responsiveness and other endotypic traits (Vpassive, muscle compensation, LG and arousal threshold).MethodsTen OSA patients performed a randomized, placebo‐controlled, double‐blind, crossover trial comparing one night of pseudoephedrine 120 mg plus diphenhydramine 50 mg (DAW1033D) to placebo administered prior to sleep. The AHI, genioglossus muscle responsiveness to negative oesophageal pressure and the endotypic traits were measured via PSG.ResultsThe participants' median (interquartile range) age was 50 (46–53) years and body mass index (BMI) was 34.3 (30.6–39.2) kg/m2. The drug combination had no effect on AHI (21.6 (9.1–49.8) on placebo vs 37.9 (5.1–55.4) events/h on DAW1033D, P > 0.5) or genioglossus responsiveness (6.0 (2.6–9.2) on placebo vs 4.0 (3.5–7.3) %/cm H2O). Amongst the phenotypic traits, only Vpassive was improved by 29 (3–55) % eupnoea, P = 0.03 (mean (95% CI)).ConclusionThe combination of pseudoephedrine and diphenhydramine did not improve OSA severity or genioglossus responsiveness but induced a small improvement in upper airway collapsibility, possibly due to the decongestant effect of the medications. The results of this study do not support the use of these medications for OSA treatment.
A Donatello for Rome, a Memling for Florence. The maritime transports of the Sermattei of Florence†
Authors: Daniels Tobias , Esch Arnold 
Published: January 2021

AbstractThis article deals with the maritime transports of a little known but not unimportant Florentine merchant family. On the basis of previously unknown archival source material, we address questions of family history, mercantile networks, maritime trade connections, and merchandise (including some famous artworks), shedding new light not only on the Florentine merchant navy, but also on the history of maritime trade between the Mediterranean and the North in the Renaissance. In particular, we show what impact factors like bankruptcy and exile had on Florentine merchant families conducting in longdistance trade, and of how setbacks in Medicean Florence could be mastered. After establishing a business enterprise between Venice, Apulia and Poland, the Sermattei were disfavoured by the regime Cosimo de’ Medici established in Florence, struck by bankruptcy, exiled and murdered. In order to overcome this existential crisis and to re‐establish the bonds with the Medici, the Sermattei moved to Pisa and started trading. The story of the Sermattei illustrates what the exile and return of the Medici meant for Italian merchant families and their businesses, and how it was possible for them to overcome a business failure via mare transporting a specialised assortment of goods and artworks for the Medici.
Davidson on Self‐Knowledge: A Transcendental Explanation
Authors: Hossein Khani Ali 
Published: January 2021

AbstractDavidson has attempted to offer his own solution to the problem of self‐knowledge, but there has been no consensus between his commentators on what this solution is. Many have claimed that Davidson's account stems from his remarks on disquotational specifications of self‐ascriptions of meaning and mental content, the account which I will call the “Disquotational Explanation.” It has also been claimed that Davidson's account rather rests on his version of content externalism, which I will call the “Externalist Explanation.” I will argue that not only are these explanations of self‐knowledge implausible, but Davidson himself has already rejected them. Thus, neither can be attributed to Davidson as his suggested account of self‐knowledge. I will then introduce and support what I take to be Davidson's official and independent account of self‐knowledge, that is, his “Transcendental Explanation.” I will defend this view against certain potential objections and finally against the objections made by William Child.
ABO blood group and SARS‐CoV‐2 antibody response in a convalescent donor population
Authors: Bloch Evan M. , Patel Eshan U. , Marshall Christi , Littlefield Kirsten , Goel Ruchika , Grossman Brenda J. , Winters Jeffrey L. , Shrestha Ruchee , Burgess Imani , Laeyendecker Oliver , Shoham Shmuel , Sullivan David , Gehrie Eric A. , Redd Andrew D. , Quinn Thomas C. , Casadevall Arturo , Pekosz Andrew , Tobian Aaron A. R. 
Published: January 2021

Background and ObjectivesABO blood group may affect risk of SARS‐CoV‐2 infection and/or severity of COVID‐19. We sought to determine whether IgG, IgA and neutralizing antibody (nAb) to SARS‐CoV‐2 vary by ABO blood group.Materials and MethodsAmong eligible convalescent plasma donors, ABO blood group was determined via agglutination of reagent A1 and B cells, IgA and IgG were quantified using the Euroimmun anti‐SARS‐CoV‐2 ELISA, and nAb titres were quantified using a microneutralization assay. Differences in titre distribution were examined by ABO blood group using non‐parametric Kruskal–Wallis tests. Adjusted prevalence ratios (aPR) of high nAb titre (≥1:160) were estimated by blood group using multivariable modified Poisson regression models that adjusted for age, sex, hospitalization status and time since SARS‐CoV‐2 diagnosis.ResultsOf the 202 potential donors, 65 (32%) were blood group A, 39 (19%) were group B, 13 (6%) were group AB, and 85 (42%) were group O. Distribution of nAb titres significantly differed by ABO blood group, whereas there were no significant differences in anti‐spike IgA or anti‐spike IgG titres by ABO blood group. There were significantly more individuals with high nAb titre (≥1:160) among those with blood group B, compared with group O (aPR = 1·9 [95%CI = 1·1–3·3], P = 0·029). Fewer individuals had a high nAb titre among those with blood group A, compared with group B (aPR = 0·6 [95%CI = 0·4‐1·0], P = 0·053).ConclusionEligible CCP donors with blood group B may have relatively higher neutralizing antibody titres. Additional studies evaluating ABO blood groups and antibody titres that incorporate COVID‐19 severity are needed.
Simulation-based surgical education for glaucoma versus conventional training alone: the GLAucoma Simulated Surgery (GLASS) trial. A multicentre, multicountry, randomised controlled, investigator-masked educational intervention efficacy trial in Kenya, South Africa, Tanzania, Uganda and Zimbabwe
Authors: Dean William H , Buchan John , Gichuhi Stephen , Philippin Heiko , Arunga Simon , Mukome Agrippa , Admassu Fisseha , Lewis Karinya , Makupa William , Otiti Juliet , Kim Min J , Macleod David , Cook Colin , Burton Matthew J 
Published: January 2021

Background/AimGlaucoma accounts for 8% of global blindness and surgery remains an important treatment. We aimed to determine the impact of adding simulation-based surgical education for glaucoma.MethodsWe designed a randomised controlled, parallel-group trial. Those assessing outcomes were masked to group assignment. Fifty-one trainee ophthalmologists from six university training institutions in sub-Saharan Africa were enrolled by inclusion criteria of having performed no surgical trabeculectomies and were randomised. Those randomised to the control group received no placebo intervention, but received the training intervention after the initial 12-month follow-up period. The intervention was an intense simulation-based surgical training course over 1 week. The primary outcome measure was overall simulation surgical competency at 3 months.ResultsTwenty-five were assigned to the intervention group and 26 to the control group, with 2 dropouts from the intervention group. Forty-nine were included in the final intention-to-treat analysis. Surgical competence at baseline was comparable between the arms. This increased to 30.4 (76.1%) and 9.8 (24.4%) for the intervention and the control group, respectively, 3 months after the training intervention for the intervention group, a difference of 20.6 points (95% CI 18.3 to 22.9, p<0.001). At 1 year, the mean surgical competency score of the intervention arm participants was 28.6 (71.5%), compared with 11.6 (29.0%) for the control (difference 17.0, 95% CI 14.8 to 19.4, p<0.001).ConclusionThese results support the pursuit of financial, advocacy and research investments to establish simulation surgery training units and courses including instruction, feedback, deliberate practice and reflection with outcome measurement to enable trainee glaucoma surgeons to engage in intense simulation training for glaucoma surgery.Trial registration numberPACTR201803002159198.
Differential associations between body mass index with diabetes and vision-threatening diabetic retinopathy in an adult Chinese population
Authors: Han Xiaotong , Jiang Yu , Niu Yong , Zhu Yongjuan , Huang Wenyong , He Mingguang 
Published: January 2021

PurposeTo investigate the associations between body mass index (BMI) with diabetes mellitus (DM) and vision-threatening diabetic retinopathy (VTDR).MethodsThis was a longitudinal study which included DM-free participants aged ≥40 years from the Lingtou Eye Cohort Study at baseline (2008–2010). Physical and ocular examinations were performed at baseline and annual follow-ups under standardised protocol. Two 45° non-mydriatic colour digital retinal photographs were obtained for each eye at all study visits, and presence of VTDR at the 2016 follow-up was graded by a deep-learning algorithm (LableMe) with proved high accuracy for detection of VTDR.ResultsA total of 2934 participants were included with a mean (SD) age of 59.5 (7.3) years (58.3% men). Participants with incident DM (441/2934, 15%) were significantly older (p<0.001), had higher obesity levels (p<0.001), higher systolic blood pressure (SBP) (p<0.001), diastolic blood pressure (p<0.001), fasting plasma glucose (FPG) (p<0.001), triglycerides (p=0.002) and high-density lipoprotein cholesterol (p<0.001), as compared with those without. Participants with incident VTDR (48/2934, 1.63%) were also older (p<0.001), had higher SBP (p=0.013) and FPG (p<0.001), but did not differ in baseline BMI, comparing with those without. Regression analysis showed that higher baseline BMI was significantly related to incident DM (p<0.005), but not incident VTDR, during the follow-up. Subgroup analysis among participants with incident DM also revealed no association between BMI and VTDR.ConclusionsHigher baseline BMI increased the risk of incident DM, but was not related to the risk of VTDR in this adult Chinese population.
Elevated levels of prostaglandin E2in the tears of patients with severe allergic conjunctivitis and primary cultured conjunctival cells are suppressed by ketotifen and dexamethasone
Authors: Yamanishi Ryutaro , Okada Naoko , Shimizu Eisuke , Fujishima Hiroshi 
Published: January 2021

ObjectiveWe examined the production of prostaglandin E2(PGE2), which is the key prostaglandin involved in inflammatory disorders of the ocular surface. Tears and conjunctival fibroblasts were evaluated in order to assess allergic inflammation and the effect of specific drugs.Methods and analysisPGE2was measured in tears from both patients and normal volunteers. Primary cultures of human conjunctival fibroblasts were incubated with interleukin (IL)-4 and tumour necrosis factor (TNF)-α with or without ketotifen fumarate or dexamethasone. The culture supernatants were removed 24 hours after exposure and the concentrations of PGE2were quantified by ELISA.ResultsSignificantly higher levels of PGE2were observed in the tears of patients with severe allergic conjunctivitis than in those with post-surgical inflammation (p=0.02), and this production was reduced by eye drops. Stimulation with IL-4 and TNF-α induced the generation of PGE2in supernatants of conjunctival fibroblasts, and this production was significantly downregulated by ketotifen fumarate or steroids.ConclusionPGE2may participate in the pathogenesis of severe ocular allergic disease, and both ketotifen fumarate and steroid reduce the production of PGE2.
Long-term effectiveness of faecal immunochemical test screening for proximal and distal colorectal cancers
Authors: Chiu Han-Mo , Jen Grace Hsiao-Hsuan , Wang Ying-Wei , Fann Jean Ching-Yuan , Hsu Chen-Yang , Jeng Ya-Chung , Yen Amy Ming-Fang , Chiu Sherry Yueh-Hsia , Chen Sam Li-Sheng , Hsu Wen-Feng , Lee Yi-Chia , Wu Ming-Shiang , Wu Chien-Yuan , Jou Yann-Yuh , Chen Tony Hsiu-Hsi 
Published: January 2021

ObjectiveTo measure the effects of faecal immunochemical test (FIT) for colorectal cancer (CRC) screening on overall and site-specific long-term effectiveness of population-based organised service screening.DesignA prospective cohort study of Taiwanese nationwide biennial FIT screening was performed. A total of 5 417 699 eligible subjects were invited to attend screening from 2004 through 2009 and were followed up until 2014. We estimated the adjusted relative rates (aRRs) on the effectiveness of reducing advanced-stage CRC (stage II+) and CRC death by Bayesian Poisson regression models with the full adjustment for a cascade of self-selection factors (including the screening rate and the colonoscopy rate) and the completeness of colonoscopy together with demographic features.ResultsFIT screening (exposed vs unexposed) reduced the incidence of advanced-stage CRC (48.4 vs 75.7 per 100 000) and mortality (20.3 vs 41.3 per 100 000). Statistically significant reductions of both incidence of advanced-stage CRCs (aRR=0.66, 95% CI 0.63 to 0.70) and deaths from CRC (aRR=0.60, 95% CI 0.57 to 0.64) were noted. FIT screening was more effective in reducing distal advanced-stage CRCs (aRR=0.61, 95% CI 0.58 to 0.64) and CRC mortality (aRR=0.56, 95% CI 0.53 to 0.69) than proximal advanced CRCs (aRR=0.84, 95% CI 0.77 to 0.92) and CRC mortality (aRR=0.72, 95% CI 0.66 to 0.80).ConclusionA large-scale population-based biennial FIT screening demonstrates 34% significant reduction of advanced-stage CRCs and 40% reduction of death from CRC with larger long-term effectiveness in the distal colon than the proximal colon. Our findings provide a strong and consistent evidence-based policy for supporting a sustainable population-based FIT organised service screening worldwide. The disparity of site-specific long-term effectiveness also provides an insight into the remedy for lower effectiveness of FIT screening in the proximal colon.
MUC1-C integrates activation of the IFN-γ pathway with suppression of the tumor immune microenvironment in triple-negative breast cancer
Authors: Yamashita Nami , Long Mark , Fushimi Atsushi , Yamamoto Masaaki , Hata Tsuyoshi , Hagiwara Masayuki , Bhattacharya Atrayee , Hu Qiang , Wong Kwok-Kin , Liu Song , Kufe Donald 
Published: January 2021

BackgroundImmune checkpoint inhibitors (ICIs) have had a profound impact on the treatment of many tumors; however, their effectiveness against triple-negative breast cancers (TNBCs) has been limited. One factor limiting responsiveness of TNBCs to ICIs is a lack of functional tumor-infiltrating lymphocytes (TILs) in ‘non-inflamed’ or ‘cold’ tumor immune microenvironments (TIMEs), although by unknown mechanisms. Targeting MUC1-C in a mouse transgenic TNBC tumor model increases cytotoxic tumor-infiltrating CD8+ T cells (CTLs), supporting a role for MUC1-C in immune evasion. The basis for these findings and whether they extend to human TNBCs are not known.MethodsHuman TNBC cells silenced for MUC1-C using short hairpin RNAs (shRNAs) were analyzed for the effects of MUC1-C on global transcriptional profiles. Differential expression and rank order analysis was used for gene set enrichment analysis (GSEA). Gene expression was confirmed by quantitative reverse-transcription PCR and immunoblotting. The The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) datasets were analyzed for effects of MUC1 on GSEA, cell-type enrichment, and tumor immune dysfunction and exclusion. Single-cell scRNA-seq datasets of TNBC samples were analyzed for normalized expression associations between MUC1 and selected genes within tumor cells.ResultsOur results demonstrate that MUC1-C is a master regulator of the TNBC transcriptome and that MUC1-C-induced gene expression is driven by STAT1 and IRF1. We found that MUC1-C activates the inflammatory interferon (IFN)-γ-driven JAK1→STAT1→IRF1 pathway and induces the IDO1 and COX2/PTGS2 effectors, which play key roles in immunosuppression. Involvement of MUC1-C in activating the immunosuppressive IFN-γ pathway was extended by analysis of human bulk and scRNA-seq datasets. We further demonstrate that MUC1 associates with the depletion and dysfunction of CD8+ T cells in the TNBC TIME.ConclusionsThese findings demonstrate that MUC1-C integrates activation of the immunosuppressive IFN-γ pathway with depletion of TILs in the TNBC TIME and provide support for MUC1-C as a potential target for improving TNBC treatment alone and in combination with ICIs. Of translational significance, MUC1-C is a druggable target with chimeric antigen receptor (CAR) T cells, antibody-drug conjugates (ADCs) and a functional inhibitor that are under clinical development.
Prognostic value of left ventricular mitral annular longitudinal displacement obtained by tissue Doppler imaging in patients with heart failure with reduced ejection fraction
Authors: Sengeløv Morten , Jørgensen Peter Godsk , Bruun Niels Eske , Olsen Flemming Javier , Fritz-Hansen Thomas , Biering-Sørensen Tor 
Published: January 2021

BackgroundTissue Doppler imaging (TDI) can be used to measure the mitral annular longitudinal displacement (LD) during systole. However, the prognostic utility of global and regional LD in patients with heart failure with reduced ejection fraction (HFrEF) is unknown.MethodsEchocardiographic examinations from 907 patients with HFrEF were analysed obtaining conventional echocardiographic measurements. Regional LD was obtained from colour TDI projections in six mitral annular regions and global LD was calculated as an average.ResultsMean age was 67 years, 26.9% were women and mean left ventricular ejection fraction was 27%. During a median follow-up period of 40 months, 150 (16.5 %) patients died. The risk of dying increased with decreasing tertile of global LD and was approximately five times higher for patients in the lowest tertile compared with the highest (1. tertile vs 3. tertile, HR 4.9, 95% CI: 3.0 to 7.9, p<0.001).Global LD was a significant independent predictor of mortality after adjusting for age, gender, body mass index, pacemaker, heart rate, atrial fibrillation, diabetes and conventional echocardiographic measures and global longitudinal strain: HR 1.16 (95% CI: 1.00 to 1.34, p=0.044) per 1 mm decrease.For regional measures, inferior LD was also a significant independent predictor in the multivariable model: HR 1.16 (95% CI: 1.04 to 1.29, p=0.006) and adding inferior LD to the conventional measures yielded a significant increase in Harrell’s C-statistic (95% CI: 0.75 to 0.78, p=0.009).ConclusionIn patients with HFrEF, global and inferior LD are independent predictors of all-cause mortality. Furthermore, inferior LD proved to be a significant prognosticator when compared with all the conventional echocardiographic parameters.