Miracle-dz/UniFAR-FTUs huggingface dataset:
No effect of remdesivir or betamethasone on upper respiratory tract SARS-CoV-2 RNA kinetics in hospitalised COVID-19 patients: a retrospective observational study

Abstract Background The viral kinetics of SARS-CoV-2 has been considered clinically important. While remdesivir and corticosteroids are recommended for COVID-19 patients requiring oxygen support, there is a limited number of published reports on viral kinetics in hospitalised patients with COVID-19 treated with remdesivir or corticosteroids. Methods We conducted a retrospective study by collecting longitudinal samples from the nasopharynx/throat of 123 hospitalised patients (median age 55 years, 74% male) with COVID-19, to evaluate the effects of remdesivir and corticosteroid treatment on viral RNA levels. The subjects were divided into four groups: those receiving remdesivir (n = 25), betamethasone (n = 41), both (n = 15), or neither (n = 42). Time to viral RNA clearance was analysed using Kaplan-Meier plots, categorical data were analysed using Fisher’s exact test, and Kruskal-Wallis for continuous data. Viral RNA decline rate was analysed using a mixed effect model. Results We found no significant difference in SARS-CoV-2 RNA decline rate or time to SARS-CoV-2 RNA clearance between the groups. Moreover, clinical status at baseline was not correlated with time to viral clearance. Conclusions Since SARS-CoV-2 RNA kinetics was not affected by treatment, repeated sampling from the upper respiratory tract cannot be used to evaluate treatment response.
Recipient and Center Factors Associated With Immunosuppression Practice Beyond the First Year After Liver Transplantation and Impact on Outcomes

Background. Immunosuppression is a critical aspect of post-transplant management, yet practices at intermediate and late time points after liver transplantation (LT) are poorly characterized. Methods. A retrospective cohort of 11 326 adult first LT alone recipients between 2007 and 2016 was identified by linking United Network for Organ Sharing transplant data to Medicare administrative claims. The immunosuppression regimen was obtained from Medicare billing claims. Factors associated with calcineurin inhibitor (CNI) monotherapy at 1-, 3-, and 5-y post-LT were investigated using mixed-effects logistic regression. Center practice heterogeneity was evaluated. The association of immunosuppression regimen (time-updating) with patient and graft survival was studied. Results. CNI monotherapy was used in 51.9% at 1-y post-LT and 68.6% at 5-y post-LT. Center-specific rates ranged from 20.0%–79.9% to 15.4%–95.2%, respectively. CNI monotherapy at 1- and 3-y post-LT was less likely among Black recipients (P = 0.027 and P = 0.015 versus White, respectively). CNI plus antimetabolite was associated with improved adjusted patient (hazard ratio, 0.59; P < 0.001) and graft (hazard ratio, 0.62; P < 0.001) survival versus CNI monotherapy. The benefit of CNI plus antimetabolite on patient and graft survival increased with older age. Conclusions. In this first longitudinal analysis of LT immunosuppression practices among Medicare beneficiaries, a CNI plus antimetabolite approach led to improved outcomes. Significant center heterogeneity in practice was observed.
Coexistence of Anti-Ro52 Antibodies in Anti-MDA5 Antibody–Positive Dermatomyositis Is Highly Associated With Rapidly Progressive Interstitial Lung Disease and Mortality Risk

Objective Interstitial lung disease (ILD) is a common extramuscular complication contributing to significant morbidity and mortality in patients with dermatomyositis (DM) who are positive for antimelanoma differentiation–associated gene 5 antibody (anti-MDA5+). We conducted this study to investigate the association of anti-Ro52 antibodies with clinical characteristics and prognosis in patients with anti-MDA5+ DM. Methods We assessed a cohort of 246 patients with anti-MDA5+ DM. To calculate hazard ratios and 95% CIs for rapidly progressive ILD (RP-ILD) and death while controlling for potential confounders, variables selected by univariate Cox regression analysis were included in a multivariate Cox regression model with the stepwise forward-selection method. A 2-tailed analysis with P < 0.05 was considered to be statistically significant. Results A total of 246 patients with anti-MDA5+ DM were enrolled; 70 patients were male, and the patient group had an average age of 53.1 (12.4) years. Anti-Ro52 was present in 64.2% (158/246) patients. Patients with anti-MDA5+ DM who were positive for anti-Ro52 had a higher rate of RP-ILD (log-rank P < 0.001) and a higher mortality rate (log-rank P = 0.01). For patients with anti-MDA5+ DM who were positive for anti-Ro52, those with a short disease course and high inflammation were at increased risk of RP-ILD and death. The appearance of active rash was an independent protective factor of death. Conclusion Anti-Ro52 antibodies were highly prevalent in patients with anti-MDA5+ DM, and their coexistence correlated with a higher rate of RP-ILD and mortality. Patients with a short disease course, with increased inflammation, and without rash were more likely to have a poor prognosis.
Rocking of Multiblock stone classical columns

This paper investigates the dynamic behaviour of the simplest structural element, the classical column, considered as a monolithic multiblock. In particular, we studied the behaviour of these structures under harmonic pulses of variable amplitude and frequency, tracing the rocking curves that represent the “dynamic identity card” of such structures. These curves were plotted by varying the quantities that influence the dynamics of the system: slenderness of the column (total height ratio of the column, H, and width of the base, B), the number of drums constituting the column, the contact properties (coefficient of friction, normal and tangential stiffness of the joint) and damping. The slenderness ratio range considered varies between H/B = 4 to H/B = 13, so as to cover all the columns belonging to the Doric and Ionic orders present in the Mediterranean basin. For the numerical analyses, it was used the Distinct Element Method (DEM) that, in the physics of multibody systems, allows us to study the dynamic response with high reliability of systems in which the size of the individual blocks can be compared with the overall size of the structure.
Knowledge, attitudes, and practices towards COVID-19 among college students in China: A systematic review and meta-analysis

Background Since the outbreak of the respiratory infectious disease caused by the novel coronavirus in 2019, the COVID-19 epidemic has posed a serious threat to the life and safety of the public, and has also seriously affected the normal study and life of college students in China. Although a series of studies have been conducted on college students’ knowledge, attitudes and practices of COVID-19, the results vary widely. This study aimed to evaluate the pooled estimated level of knowledge, attitudes, and practices (KAP) about COVID-19 among college students in China. Methods We conducted a comprehensive search on Scopus, ProQuest, PubMed, EMbase, Web of Science, the Cochrane Library, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), VIP Database and Wanfang Database up to 13 February 2022. We then assessed the quality of included studies using a checklist developed by the Joanna Briggs Institute (JBI) for cross-sectional studies and analyzed using STATA.15 after two researchers independently extracted relevant data and entered them into Microsoft Excel. Funnel plots and Egger’s regression tests were used to check for publication bias, and sensitivity analysis was performed to assess the robustness of the results. A random-effects model was used for the meta-analysis, on the basis of which subgroup analyses were performed by time of investigation (study period) and by gender and major of the subjects. Result A total of 42 studies including 174,440 subjects were included in this review, and the quality of the included studies was mainly intermediate and advanced. The findings of the meta-analysis showed that the overall levels of Chinese college students’ knowledge, positive and negative attitudes, and practice of preventive measures towards COVID-19 were 74% (95%CI: 69%-79%), 84% (95%CI: 80%-88%), 31% (95%CI: 23%-38%) and 82% (95%CI: 77%-86%), respectively. The results of subgroup analysis showed that female and medical college students had higher levels of knowledge and practice on COVID-19. Conclusion The study findings showed that the overall KAP level of college students in China included in the study was relatively optimistic. Influenced by gender, major and time, there were differences in the KAP level of college students. In order to promote the effective prophylaxis and control of pandemic, we recommend implementing targeted measures to improve the awareness rate of COVID-19-related knowledge among this group and the implementation rate of COVID-19 preventive measures among male and non-medical college students.
First Dedicated Balloon Catheter for Magnetic Particle Imaging

Vascular interventions are a promising application of Magnetic Particle Imaging enabling a high spatial and temporal resolution without using ionizing radiation. The possibility to visualize the vessels as well as the devices, especially at the same time using multi-contrast approaches, enables a higher accuracy for diagnosis and treatment of vascular diseases. Different techniques to make devices MPI visible have been introduced so far, such as varnish markings or filling of balloons. However, all approaches include challenges for in vivo applications, such as the stability of the varnishing or the visibility of tracer filled balloons in deflated state. In this contribution, we present for the first time a balloon catheter that is molded from a granulate incorporating nanoparticles and can be visualized sufficiently in MPI. Computed tomography is used to show the homogeneous distribution of particles within the material. Safety measurements confirm that the incorporation of nanoparticles has no negative effect on the balloon. A dynamic experiment is performed to show that the inflation as well as deflation of the balloon can be imaged with MPI.
How the Senior Community Service Employment Program Influences Participant Well-Being: A Participatory Research Approach With Program Recommendations

The federal Senior Community Service Employment Program (SCSEP) provides on-the-job training to people 55 years and older with incomes at or below 125% of the federal poverty level with multiple barriers to employment. This study examined the processes by which SCSEP may influence participant financial, physical, and mental well-being. We engaged 15 SCSEP participants and case managers over four virtual and one telephone session using a participatory research method called community-based system dynamics. Activities included identifying key problem trends, variable elicitation, developing a causal map, and identifying changes to the system to increase participant well-being. Respondents identified how individual, organizational, and program and policy factors relate to participant well-being (e.g., SCSEP participation reduces social isolation, which increases desire to participate) and suggested program and policy recommendations to strengthen SCSEP (e.g., benchmarks of success should include health and well-being outcomes). These findings highlight the benefits and potential of this long-running program.
Granzyme K+ CD8 T cells form a core population in inflamed human tissue

T cell–derived pro-inflammatory cytokines are a major driver of rheumatoid arthritis (RA) pathogenesis. Although these cytokines have traditionally been attributed to CD4 T cells, we have found that CD8 T cells are notably abundant in synovium and make more interferon (IFN)–γ and nearly as much tumor necrosis factor (TNF) as their CD4 T cell counterparts. Furthermore, using unbiased high-dimensional single-cell RNA-seq and flow cytometric data, we found that the vast majority of synovial tissue and synovial fluid CD8 T cells belong to an effector CD8 T cell population characterized by high expression of granzyme K (GzmK) and low expression of granzyme B (GzmB) and perforin. Functional experiments demonstrate that these GzmK+ GzmB+ CD8 T cells are major cytokine producers with low cytotoxic potential. Using T cell receptor repertoire data, we found that CD8 GzmK+ GzmB+ T cells are clonally expanded in synovial tissues and maintain their granzyme expression and overall cell state in blood, suggesting that they are enriched in tissue but also circulate. Using GzmK and GzmB signatures, we found that GzmK-expressing CD8 T cells were also the major CD8 T cell population in the gut, kidney, and coronavirus disease 2019 (COVID-19) bronchoalveolar lavage fluid, suggesting that they form a core population of tissue-associated T cells across diseases and human tissues. We term this population tissue-enriched expressing GzmK or TteK CD8 cells. Armed to produce cytokines in response to both antigen-dependent and antigen-independent stimuli, CD8 TteK cells have the potential to drive inflammation. Description GzmK+ GzmB+ CD8 T cells are enriched in inflamed joints in patients with rheumatoid arthritis and represent a distinct effector T cell type. Influencing inflammation Characterizing the cell types that drive rheumatoid arthritis (RA) may lead to new treatment options for patients with RA and other autoimmune diseases. In this study, Jonsson et al. characterized T cell subsets in synovium samples from patients with RA. Although CD4 T cells were present in synovial samples, CD8 T cells were similarly abundant. These CD8 T cells, which have not historically been considered drivers of RA, were highly activated and expressed granzyme K. Furthermore, granzyme K–expressing CD8 T cells were also enriched in inflamed tissue associated with other autoimmune diseases and COVID-19, suggesting that these cells may be associated with different types of human inflammation.
Blockade of interleukin 10 potentiates antitumour immune function in human colorectal cancer liver metastases

Objective Programmed cell death protein 1 (PD-1) checkpoint inhibition and adoptive cellular therapy have had limited success in patients with microsatellite stable colorectal cancer liver metastases (CRLM). We sought to evaluate the effect of interleukin 10 (IL-10) blockade on endogenous T cell and chimeric antigen receptor T (CAR-T) cell antitumour function in CRLM slice cultures. Design We created organotypic slice cultures from human CRLM (n=38 patients’ tumours) and tested the antitumour effects of a neutralising antibody against IL-10 (αIL-10) both alone as treatment and in combination with exogenously administered carcinoembryonic antigen (CEA)-specific CAR-T cells. We evaluated slice cultures with single and multiplex immunohistochemistry, in situ hybridisation, single-cell RNA sequencing, reverse-phase protein arrays and time-lapse fluorescent microscopy. Results αIL-10 generated a 1.8-fold increase in T cell-mediated carcinoma cell death in human CRLM slice cultures. αIL-10 significantly increased proportions of CD8+ T cells without exhaustion transcription changes, and increased human leukocyte antigen - DR isotype (HLA-DR) expression of macrophages. The antitumour effects of αIL-10 were reversed by major histocompatibility complex class I or II (MHC-I or MHC-II) blockade, confirming the essential role of antigen presenting cells. Interrupting IL-10 signalling also rescued murine CAR-T cell proliferation and cytotoxicity from myeloid cell-mediated immunosuppression. In human CRLM slices, αIL-10 increased CEA-specific CAR-T cell activation and CAR-T cell-mediated cytotoxicity, with nearly 70% carcinoma cell apoptosis across multiple human tumours. Pretreatment with an IL-10 receptor blocking antibody also potentiated CAR-T function. Conclusion Neutralising the effects of IL-10 in human CRLM has therapeutic potential as a stand-alone treatment and to augment the function of adoptively transferred CAR-T cells.
Association of Cognition and Dementia With Neuropathologic Changes of Alzheimer Disease and Other Conditions in the Oldest Old

Background and Objectives Age is the largest risk factor for dementia. However, dementia is not universal, even among the oldest-old age groups. Following contemporary neuropathologic guidelines, our objectives were to describe the key neuropathologic lesions and their associations with antemortem cognition in oldest-old individuals. Methods Participants were those enrolled in The 90+ Study, a longitudinal, population-based study of aging/dementia in the oldest old, who agreed to postmortem brain examination. All autopsied brains as of December 2020 were evaluated for the prevalence of Alzheimer disease neuropathologic change (ADNC) and non-ADNC neuropathologic comorbidities. Associations between neuropathologic lesions or the total neuropathologic burden score (sum of the individual scores) and cognition were assessed using multinomial logistic regression and multiple linear regression. Separate regression analyses evaluated relationships between limbic-predominant age-related TDP-43 encephalopathy (LATE-NC) and hippocampal sclerosis (HS) or ADNC/primary age-related tauopathy (PART). Resistance, or failure to develop ADNC/PART, and resilience, inferred from higher-than-expected cognitive functioning, were evaluated in the presence or absence of non-ADNC neuropathologic features. Results The most common neuropathologic features in the sample (n = 367) were ADNC/PART related. Increased dementia odds were associated with elevated total neuropathologic burden (odds ratio [OR] 1.5, 95% CI 1.3–1.7, p < 0.0001), β-amyloid (OR 1.6, 95% CI 1.2–2.0, p < 0.0001), neurofibrillary tangles (OR 2.6, 95% CI 1.7–4.1, p < 0.0001), and LATE-NC (OR 2.3, 95% CI 1.7–3.1, p < 0.0001), correcting for multiple comparisons. LATE-NC was associated with dementia with (OR 6.1, 95% CI 2.0–18.7, p = 0.002) and without (OR 5.0, 95% CI 2.6–9.7, p < 0.0001) co-occurring HS and increased the odds of dementia among participants with ADNC (OR 5.0, 95% CI 2.7–9.2, p < 0.0001). Resistance to moderate/severe ADNC/PART was rare (3%), but resilience to ADNC/PART was not (55%). Resilience was rarer in the presence of non-ADNC comorbid lesions, particularly LATE-NC. Among those with moderate/severe ADNC/PART, dementia odds increased with each non-ADNC comorbid lesion (e.g., 1 lesion: OR 2.4, 95% CI 1.3–4.5, p < 0.005; 2 lesions: OR 5.9, 95% CI 2.8–12.3, p < 0.0001). Discussion These results highlight the importance of non-ADNC neuropathologic comorbidity, predominantly LATE-NC, to cognition in the oldest old. Given the cumulative effects of non-ADNC comorbid neuropathologic abnormalities, reducing their prevalence, especially LATE-NC, will be vital to the ultimate goal of reducing dementia burden in the oldest-old individuals.
A comparison of mortality rates following revision hip arthroplasty for periprosthetic fracture, infection or aseptic loosening

Background: Mortality following revision hip surgery for periprosthetic fracture (PPF) is comparable to neck of femur fractures. Our institution provides a regional “PPF Service”. The aim of this study was to determine the time to surgery and mortality rate for PPF, compared to revision for infection or aseptic loosening. Methods: Revision arthroplasty procedures performed for PPF, infection or aseptic loosening between January 2014 and December 2015 were identified. Comparisons were made between the 3 groups for baseline demographics, admission to higher-level care, length of stay, complications and mortality. Results: There were 37 PPF, 71 infected and 221 aseptic revisions. PPF had a higher proportion of females (65% vs. 39% in infection and 53% in aseptic; p = 0.031) and grade 3 and 4 ASA patients (p = 0.006). Median time to surgery for PPF was 8 days (95% CI, 6–16). Single-stage procedures were performed in 84% of PPF, 42% of infections and 99% of aseptic revisions (p < 0.001). 19% of PPF revisions required HDU admission, 1% in the aseptic group and none in the infection group. Median length of stay was significantly different (PPF 10; infection 14; aseptic 8 days (p < 0.001). The 1-year mortality rate for PPF was 0%, 2.8% for infection and 0.9% in the aseptic group (p = 0.342). Conclusions: Despite the PPF group having higher ASA grades and more HDU admissions, our 1-year mortality rate was 0% and not significantly different to infection or aseptic loosening. Our low complication and 1-year mortality rate is encouraging and supports the safety of a regional “Periprosthetic Fracture Service”.
Building Information Modelling Awareness and Readiness -Among Quantity Surveyors and Quantity Surveying Firms

AIM is to determine the level of awareness among the quantity surveyors and the level of readiness among the quantity surveying firms towards Building Information Modelling (BIM) • QUESTIONNAIRES were used as method of data collection and descriptive statistics were adopted to analyse the data • AWARENESS is exponentially growing though BIM is still at infancy rate • READINESS level is high though some concerns were raised in workforce training supports, legal and integration issues • LIMITATION of the research lies on the number of respondents which restricts the generalisation of the findings • FURTHER data collection will be conducted to substantiate the interim findings of the survey
Comparison of specimen quality among the standard suction, slow-pull, and wet suction techniques for EUS-FNA: A multicenter, prospective, randomized controlled trial

Background and Objectives: Standard suction technique (SST), slow-pull technique (SPT), and wet suction technique (WEST) of EUS-FNA are designed to improve the diagnostic yields of solid and solid-cystic lesions. We conducted a multicenter, prospective, randomized crossover trial to compare SST, SPT, and WEST on specimen quality and diagnostic accuracy using a 22G needle. Methods: Patients with solid or solid-cystic lesions referred for EUS-FNA at four tertiary hospitals from December 2017 to August 2019 were considered eligible. All lesions were sampled using a 22G needle by the three techniques performed consecutively in a randomized order. The primary outcome was quality of the specimen acquired by each technique regarding blood contamination, tissue integrity and cellularity for diagnosis, graded on a predefined scale. The secondary outcomes were the diagnostic yield of EUS-FNA and the incidence of adverse events. ClinicalTrial. gov registration number: NCT03567863. Results: A total of 300 patients (mean age, 60.6 years, 188 men) were enrolled. WEST was superior (mean score 4.02 ± 1.51) over SST (3.67 ± 1.57, P = 0.018), but comparable to SPT (3.83 ± 1.55, P = 0.370) in overall specimen quality evaluation. WEST produced better tissue integrity (1.42 ± 0.74) and higher cellularity (1.32 ± 0.80) than SST and SPT. SPT (1.43 ± 0.69) was superior to SST (1.27 ± 0.72, P = 0.004) and WEST (1.28 ± 0.71, P = 0.006) in avoiding blood contamination. WEST achieved a diagnostic accuracy of 74.7%, higher than SST (64.4%, P = 0.007) and SPT (65.0%, P = 0.012). One bleeding event occurred with a pancreatic lesion. Conclusions: WEST was comparable to SPT and superior to SST in the overall quality of the specimen and achieved highest diagnostic yield.