Miracle-dz/UniFAR-FTUs huggingface dataset:
Community factors associated with local epidemic timing of respiratory syncytial virus: A spatiotemporal modeling study

RSV epidemic dynamics are influenced by local community characteristics and spatial spread. Respiratory syncytial virus (RSV) causes a large burden of morbidity in young children and the elderly. Spatial variability in the timing of RSV epidemics provides an opportunity to probe the factors driving its transmission, including factors that influence epidemic seeding and growth rates. Using hospitalization data from Connecticut, New Jersey, and New York, we estimated epidemic timing at the ZIP code level using harmonic regression and then used a Bayesian meta-regression model to evaluate correlates of epidemic timing. Earlier epidemics were associated with larger household size and greater population density. Nearby localities had similar epidemic timing. Our results suggest that RSV epidemics grow faster in areas with more local contact opportunities, and that epidemic spread follows a spatial diffusion process based on geographic proximity. Our findings can inform the timing of delivery of RSV extended half-life prophylaxis and maternal vaccines and guide future studies on the transmission dynamics of RSV.
Hemorrhage in patients with polycythemia vera receiving aspirin with an anticoagulant: a prospective, observational study

Polycythemia vera (PV) is associated with increased risk of thrombosis and hemorrhage. Aspirin, recommended for primary thromboprophylaxis, is often combined with anticoagulants during management of acute thrombotic events. The safety of dual antiplatelet and anticoagulant therapy is not established in PV. In a prospective, observational study, 2,510 patients with PV were enrolled at 227 sites in the United States. Patients were monitored for the development of hemorrhage and thrombosis after enrollment. A total of 1,602 patients with PV received aspirin with median follow-up of 2.4 years (range, 0-3.6 years). The exposure-adjusted rate of all hemorrhages in patients receiving aspirin alone was 1.40 per 100 patient-years (95% confidence interval [CI]: 0.99-1.82). The combination of aspirin plus anticoagulant was associated with an incidence of hemorrhage of 6.75 per 100 patient-years (95% CI: 3.04-10.46). The risk of hemorrhage was significantly greater in patients receiving the combination of aspirin and anticoagulant compared with aspirin alone (total hemorrhages, hazard ratio [HR]: 5.83; 95% CI: 3.36-10.11; P<0.001; severe hemorrhage, HR: 7.49; 95% CI: 3.02-18.62; P<0.001). Periods of thrombocytosis (>600×109/L) were associated with an increased risk of hemorrhage (HR: 2.25; 95% CI: 1.16-4.38; P=0.02). Rates of hemorrhage were similar for aspirin in combination with warfarin or direct-acting oral anticoagulants. We conclude that the combination of aspirin and anticoagulants is associated with significantly increased risk of hemorrhage in patients with PV (clinicaltrials gov. Identifier: NCT02252159).
MRI-detected synovitis of the small joints predicts rheumatoid arthritis development in large joint undifferentiated inflammatory arthritis

Abstract Objectives New onset undifferentiated large joint inflammatory arthritis can be diagnostically challenging. It is unknown how often these patients progress to RA, and how they can be identified at first presentation. We assessed clinical and serological features associated with RA development in patients with an undifferentiated mono- or oligo-articular large joint arthritis, and with keen interest in whether an MRI of the small joints of the hand and foot would aid diagnosis. Methods Leiden Early Arthritis Clinic includes 4018 patients; this prospective study follows 221 consecutively included patients with new onset undifferentiated large joint arthritis. Baseline clinical data and serology were obtained. Forty-five patients had MRIs (hand and foot). MRIs were scored according to the OMERACT RAMRIS. Univariable and multivariable logistic regression were assessed. Test characteristics, predictive values and net reclassification index (NRI) for RA were determined. Results Patients mostly presented with knee or ankle mono-arthritis. During the 12 months’ follow-up 17% developed RA. Autoantibody positivity (ACPA and/or RF) and MRI-detected synovitis in hands and feet were independently associated with RA development in multivariable analyses [odds ratio 10.29 (P = 0.014) and 7.88 (P = 0.017), respectively]. Positive predictive value of autoantibodies, MRI-detected synovitis and combination of both features was 63%, 55% and 100%, respectively. The addition of MRI-detected synovitis to autoantibody status improved diagnostic accuracy (NRI 18.1%). Conclusion In patients presenting with undifferentiated large joint arthritis, 17% will develop RA. Autoantibody positivity and subclinical synovitis are independent predictors. The data suggest MRI of small joints is beneficial for early identification of RA in large joint arthritis.
Real Life Data of Treat And Extend Intravitreal Ranibizumab and Aflibercept Therapy in Wet Age Related Macular Degeneration Patients: 3 Year Results.

Purpose To compare functional and anatomic outcome of intravitreal ranibizumab (IVR) and intravitreal aflibercept (IVA) treatments in neovascular age related macular degeneration (nAMD) by using the treat an extend (TE) protocol. Methods In this retrospective chart study, treatment naïve 74 eyes of 74 nAMD patients treated with IVR and IVA (38 eyes in IVR and 36 eyes in IVA group) with TE protocol were included. Following three consecutive monthly intravitreal injections, TE protocol was applied to each group. Patients were followed up for at least 36 months. Mean change in best corrected visual acuity (BCVA), central macula thickness (CMT) and injection numbers over 3 years were compared. Results Among 36 months period, the mean number of injection was 17±4 for both groups (p>0.05). In terms of CMT, there was no statistically significant difference between groups at 36 months compared to baseline. A decrease of 72.55±39.37 μm in CMT was detected in IVR group, whereas the decrease was 70.58±33.96 μm in IVA group (p>0.05). There was a significant increase in BCVA at 36 months of measurements. In addition, BCVA demonstrated an increase of 4.1±0.44 letters in IVR group and 4.36±0.67 letters in IVA group after 36 months compared to the baseline (p>0.05). Conclusions Both IVR and IVA injections provided significant improvements and stability in BCVA and CMT, however there was no significant difference between IVR and IVA injections with TE protocol of 36 months.
Predictability of early changes in derived neutrophil-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio in patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitors

Background As association between systemic inflammation and disease progression has been suggested, early changes in neutrophil-to-lymphocyte ratio (NLR) and derived NLR (dNLR) may have accurate predictability for prognosis in non-small cell lung cancer (NSCLC) treated with ICI therapy. Methods Complete blood count (CBC) was measured immediately before the first and second cycles of ICI therapy in patients with advanced NSCLC. Differences in NLR and dNLR were measured. When the increase in NLR was ≥1, the patient was classified into the increased NLR group. Similarly, when the increase in dNLR was ≥1, the patient was classified into the increased dNLR group; otherwise, they were classified into the non-increased NLR or dNLR group. Results A total of 89 patients was selected for evaluation. Median progression-free survival (PFS) was significantly shorter in the increased NLR group than in the non-increased NLR group (2.6 vs. 9.5 months, P<0.001). The increased dNLR group showed significantly shorter median PFS than the non-increased dNLR group (4.2 vs. 9.2 months, P=0.001). Association with PFS was analyzed using the Cox regression model. In model 1, increase ≥1 in NLR showed significant association (HR =3.085, 95% CI, 1.657–5.742, P<0.001). In model 2, increase ≥1 in dNLR showed significant association (HR =2.826, 95% CI, 1.436–5.561, P=0.003). Conclusions Early changes in dNLR were shown to have prognostic value in patients undergoing immunotherapy. It can be an accurate and a comprehensive biomarker for predicting ICI response.
Risk factors for carriage of meningococcus in third-level students in Ireland: an unsupervised machine learning approach

ABSTRACT The aim of this study was to examine the risk factors for pharyngeal carriage of meningococci in third-level students using an unsupervised machine learning approach. Data were gathered as part of meningococcal prevalence studies conducted by the Irish Meningitis and Sepsis Reference Laboratory (IMSRL). Pharyngeal swab cultures for meningococcal carriage were taken from each student once they had completed a single-page anonymous questionnaire addressing basic demographics, social behaviors, living arrangements, vaccination, and antibiotic history. Data were analyzed using multiple correspondence analysis through a machine learning approach. In total, 16,285 students who had a pharyngeal throat swab taken returned a fully completed questionnaire. Overall, meningococcal carriage rate was 20.6%, and the carriage of MenW was 1.9% (n = 323). Young Irish adults aged under 20 years and immunized with the meningococcal C vaccine had a higher MenW colonization rate (n = 171/1260, 13.5%) compared with non-Irish adults aged 20 years or older without the MenC vaccine (n = 5/81, 6%, chi-square = 3.6, p = .05). Unsupervised machine learning provides a useful technique to explore meningococcal carriage risk factors. The issue is very complex, and asked risk factors only explain a small proportion of the carriage. This technique could be used on other conditions to explore reasons for carriage.
Pharmacoepidemiology, Machine Learning and COVID-19: An intent-to-treat analysis of hydroxychloroquine, with or without azithromycin, and COVID-19 outcomes amongst hospitalized US Veterans

Abstract Hydroxychloroquine (HCQ) was proposed as an early therapy for coronavirus disease 2019 (COVID-19) after in vitro studies indicated possible benefit. Previous in vivo observational studies have presented conflicting results, though recent randomized clinical trials have reported no benefit from HCQ amongst hospitalized COVID-19 patients. We examined the effects of HCQ alone, and in combination with azithromycin, in a hospitalized COVID-19 positive, United States (US) Veteran population using a propensity score adjusted survival analysis with imputation of missing data. From March 1, 2020 through April 30, 2020, 64,055 US Veterans were tested for COVID-19 based on Veteran Affairs Healthcare Administration electronic health record data. Of the 7,193 positive cases, 2,809 were hospitalized, and 657 individuals were prescribed HCQ within the first 48-hours of hospitalization for the treatment of COVID-19. There was no apparent benefit associated with HCQ receipt, alone or in combination with azithromycin, and an increased risk of intubation when used in combination with azithromycin [Hazard Ratio (95% Confidence Interval): 1.55 (1.07, 2.24)]. In conclusion, we assessed the effectiveness of HCQ with or without azithromycin in treating patients hospitalized with COVID-19 using a national sample of the US Veteran population. Using rigorous study design and analytic methods to reduce confounding and bias, we found no evidence of a survival benefit from the administration of HCQ.
Graph theoretical analysis of evoked potentials shows network influence of epileptogenic mesial temporal region

It is now widely accepted that seizures arise from the coordinated activity of epileptic networks, and as a result, traditional methods of analyzing seizures have been augmented by techniques like single‐pulse electrical stimulation (SPES) that estimate effective connectivity in brain networks. We used SPES and graph analytics in 18 patients undergoing intracranial EEG monitoring to investigate effective connectivity between recording sites within and outside mesial temporal structures. We compared evoked potential amplitude, network density, and centrality measures inside and outside the mesial temporal region (MTR) across three patient groups: focal epileptogenic MTR, multifocal epileptogenic MTR, and non‐epileptogenic MTR. Effective connectivity within the MTR had significantly greater magnitude (evoked potential amplitude) and network density, regardless of epileptogenicity. However, effective connectivity between MTR and surrounding non‐epileptogenic regions was of greater magnitude and density in patients with focal epileptogenic MTR compared to patients with multifocal epileptogenic MTR and those with non‐epileptogenic MTR. Moreover, electrodes within focal epileptogenic MTR had significantly greater outward network centrality compared to electrodes outside non‐epileptogenic regions and to multifocal and non‐epileptogenic MTR. Our results indicate that the MTR is a robustly connected subnetwork that can exert an overall elevated propagative influence over other brain regions when it is epileptogenic. Understanding the underlying effective connectivity and roles of epileptogenic regions within the larger network may provide insights that eventually lead to improved surgical outcomes.
Association between Plasma Osmolality and Case Fatality within 1 Year after Severe Acute Ischemic Stroke

Purpose Plasma osmolality, a marker of dehydration, is associated with cardiovascular mortality. We aimed to investigate whether elevated plasma osmolality is associated with case fatality within 1 year after severe acute ischemic stroke. Materials and Methods We included severe ischemic stroke patients (defined as National Institutes of Health Stroke Scale ≥15 score) within 24 hours from symptom onset admitted to the Department of Neurology, West China Hospital between January 2017 and June 2019. Admission plasma osmolality was calculated using the equation 1.86*(sodium+potassium)+1.15*glucose+urea+14. Elevated plasma osmolality was defined as plasma osmolality >296 mOsm/kg, indicating a state of dehydration. Study outcomes included 3-month and 1-year case fatalities. Multivariable logistic regression was performed to determine independent associations between plasma osmolality and case fatalities at different time points. Results A total of 265 patients with severe acute ischemic stroke were included. The mean age was 71.2±13.1 years, with 51.3% being males. Among the included patients, case fatalities were recorded for 31.7% (84/265) at 3 months and 39.6% (105/265) at 1 year. Elevated plasma osmolality (dehydration) was associated with 3-month case fatality [odds ratio (OR) 1.98, 95% confidence interval (CI) 1.07–3.66, p=0.029], but not 1-year case fatality (OR 1.51, 95% CI 0.84–2.72, p=0.165), after full adjustment for confounding factors. Conclusion Elevated plasma osmolality was independently associated with 3-month case fatality, but not 1-year case fatality, for severe acute ischemic stroke.
Introgression shapes fruit color convergence in invasive Galápagos tomato

Invasive species represent one of the foremost risks to global biodiversity. Here, we use population genomics to evaluate the history and consequences of an invasion of wild tomato—Solanum pimpinellifolium—onto the Galápagos Islands from continental South America. Using >300 archipelago and mainland collections, we infer this invasion was recent and largely the result of a single event from central Ecuador. Patterns of ancestry within the genomes of invasive plants also reveal post-colonization hybridization and introgression between S. pimpinellifolium and the closely related Galápagos endemic Solanum cheesmaniae. Of admixed invasive individuals, those that carry endemic alleles at one of two different carotenoid biosynthesis loci also have orange fruits—characteristic of the endemic species—instead of typical red S. pimpinellifolium fruits. We infer that introgression of two independent fruit color loci explains this observed trait convergence, suggesting that selection has favored repeated transitions of red to orange fruits on the Galápagos.
Prevalence of adult atopic dermatitis in the general population, with a focus on moderate‐to‐severe disease: results from the Lifelines Cohort Study

Previous epidemiologic studies on atopic dermatitis (AD) indicate a large variation (0.3-17.6%) in the prevalence of adult AD, depending on differences in the methodology, AD definitions and study population1,2 . Here, we conducted a large cross-sectional study to firstly estimate the prevalence of adult AD in the Dutch general population, with a focus on moderate to severe AD.
Are body roundness index and a body shape index in the first trimester related to foetal macrosomia?

Abstract This study investigated the effectiveness of maternal Body Roundness Index (BRI), Body Shape Index (ASBI), and Visceral Adiposity Index (VAI) in predicting foetal macrosomia and small for gestational age (SFGA) babies in obese and non-obese pregnant women. This prospective trial included 168 pregnant women (99 obese and 69 non-obese). A logistic regression model was used to identify the independent risk factors of foetal macrosomia and SFGA. BRI, waist/hip ratio, HbA1c and HOMA-IR were found to be significantly associated with increased macrosomia risk in obese women (OR = 1.469, % CI: 1.126–1.917, p = .005; OR = 4.289, % CI: 0.178–1.030, p = .012, OR = 6.277, %Cl: 1.233–31.948, p = .027, and OR = 1.393, %Cl: 1.060–1.832, p = .017). The present study indicates that first-trimester BRI and waist/hip ratio may be powerful determinants in predicting foetal macrosomia in obese pregnant women. Impact statement What is already known on this subject? Obesity is a major risk factor for maternal and foetal morbidity and mortality. The rate of obesity continues to increase rapidly around the world. The accuracy of ultrasound in estimated foetal weight is reduced in obese pregnant women. The Body Roundness Index (BRI) is a new anthropometric index that shows body fat distribution. What do the results of this study add? Our results show that the BRI was an independent risk factor associated with foetal macrosomia in obese pregnant women. What are the implications of these findings for future clinical practice and/or further research? BRI measurements should be taken before pregnancy to help predict shoulder dystocia, GDM, FGR and foetal macrosomia in obese women.
PD‐1‐induced proliferating T cells exhibit a distinct transcriptional signature

Ligation of the inhibitory receptor PD‐1 on T cells results in the inhibition of numerous cellular functions. Despite the overtly inhibitory outcome of PD‐1 signalling, there are additionally a collection of functions that are activated. We have observed that CD4+ T cells stimulated through the T‐cell receptor and PD‐1 primarily do not proliferate; however, there is a population of cells that proliferates more than T‐cell receptor stimulation alone. These highly proliferating cells could potentially be associated with PD‐1‐blockade unresponsiveness in patients. In this study, we have performed RNA sequencing and found that following PD‐1 ligation proliferating and non‐proliferating T cells have distinct transcriptional signatures. Remarkably, the proliferating cells showed an enrichment of genes associated with an activated state despite PD‐1 signalling. Additionally, circulating follicular helper T cells were significantly more prevalent in the non‐proliferating population, demonstrated by enrichment of the associated genes CXCR5, CCR7, TCF7, BCL6 and PRDM1 and validated at the protein level. Translationally, we also show that there are more follicular helper T cells in patients that respond favourably to PD‐1 blockade. Overall, the presence of transcriptionally and functionally distinct T cell populations responsive to PD‐1 ligation may provide insights into the clinical differences observed following therapeutic PD‐1 blockade.
Identifying the determinants of emotion regulation choice: a systematic review with meta-analysis

ABSTRACT Day-to-day life is inundated with attempts to control emotions and a wealth of research has examined what strategies people use and how effective these strategies are. However, until more recently, research has often neglected more basic questions such as whether and how people choose to regulate their emotions (i.e. emotion regulation choice). In an effort to identify what we know and what we need to know, we systematically reviewed studies that examined potential determinants of whether and how people choose to regulate their emotions. Eighteen determinants were identified across 219 studies and were categorised as being affective, cognitive, motivational, individual or social-cultural in nature. Where there were sufficient primary studies, meta-analysis was used to quantify the size of the associations between potential determinants and measures of whether and how people choose to regulate their emotions. Based on the findings, we propose that people’s decisions about whether and how to regulate their emotions are determined by factors relating to the individual doing the regulating, the emotion that is being regulated, and both the immediate situation and the broader social context in which the regulation is taking place.
Excessive mechanical stretch-mediated osteoblasts promote the catabolism and apoptosis of chondrocytes via the Wnt/β-catenin signaling pathway

Excessive biomechanical loading is considered an important cause of osteoarthritis. Although the mechanical responses of chondrocytes and osteoblasts have been investigated, their communication during mechanical loading and the underlying molecular mechanisms are not yet fully known. The present study investigated the effects of excessive mechanically stretched osteoblasts on the metabolism and apoptosis of chondrocytes, and also assessed the involvement of the Wnt/β-catenin signaling pathway. In the present study, rat chondrocytes and osteoblasts were subjected to mechanical tensile strain, and an indirect chondrocyte-osteoblast co-culture model was established. Reverse transcription-quantitative PCR and western blotting were performed to determine the expression levels of genes and proteins of interest. An ELISA was performed to investigate the levels of cytokines, including matrix metalloproteinase (MMP) 13, MMP 3, interleukin-6 (IL-6) and prostaglandin E2 (PG E2), released from osteoblasts. Flow cytometry was performed to detect the apoptosis of chondrocytes exposed to stretched osteoblast conditioned culture medium. The levels of MMP 13, IL-6 and PG E2 increased significantly in the supernatants of stretched osteoblasts compared with the un-stretched group. By contrast, the mRNA expression levels of Collagen 1a and alkaline phosphatase were significantly decreased in osteoblasts subjected to mechanical stretch compared with the un-stretched group. The mRNA expression level of Collagen 2a was significantly decreased, whereas the expression levels of MMP 13 and a disintegrin and metalloproteinase with thrombospondin-like motifs 5 were significantly increased in chondrocytes subjected to mechanical stretch compared with the un-stretched group. In the co-culture model, the results indicated that excessive mechanically stretched osteoblasts induced the catabolism and apoptosis of chondrocytes, which was partly inhibited by Wnt inhibitor XAV-939. The results of the present study demonstrated that excessive mechanical stretch led to chondrocyte degradation and inhibited osteoblast osteogenic differentiation; furthermore, excessive mechanically stretched osteoblasts induced the catabolism and apoptosis of chondrocytes via the Wnt/β-catenin signaling pathway.