Miracle-dz/UniFAR-FTUs huggingface dataset:
Estimating marginal proportions and intraclass correlations with clustered binary data

A logistic regression with random effects model is commonly applied to analyze clustered binary data, and every cluster is assumed to have a different proportion of success. However, it could be of interest to obtain the proportion of success over clusters (i.e. the marginal proportion of success). Furthermore, the degree of correlation among data of the same cluster (intraclass correlation) is also a relevant concept to assess, but when using logistic regression with random effects it is not possible to get an analytical expression of the estimators for marginal proportion and intraclass correlation. In our paper, we assess and compare approaches using different kinds of approximations: based on the logistic‐normal mixed effects model (LN), linear mixed model (LMM), and generalized estimating equations (GEE). The comparisons are completed by using two real data examples and a simulation study. The results show the performance of the approaches strongly depends on the magnitude of the marginal proportion, the intraclass correlation, and the sample size. In general, the reliability of the approaches get worsen with low marginal proportion and large intraclass correlation. LMM and GEE approaches arises as reliable approaches when the sample size is large.
Contrasting stomatal sensitivity to temperature and soil drought in mature alpine conifers.

Conifers growing at high elevations need to optimize their stomatal conductance (gs ) for maximizing photosynthetic yield while minimizing water loss under less favourable thermal conditions. Yet the ability of high-elevation conifers to adjust their gs sensitivity to environmental drivers remains largely unexplored. We used 4 years of sap flow measurements to elucidate intraspecific and interspecific variability of gs in Larix decidua Mill. and Picea abies (L.) Karst along an elevational gradient and contrasting soil moisture conditions. Site- and species-specific gs response to main environmental drivers were examined, including vapour pressure deficit, air temperature, solar irradiance, and soil water potential. Our results indicate that maximum gs of L. decidua is >2 times higher, shows a more plastic response to temperature, and down-regulates gs stronger during atmospheric drought compared to P. abies. These differences allow L. decidua to exert more efficient water use, adjust to site-specific thermal conditions, and reduce water loss during drought episodes. The stronger plasticity of gs sensitivity to temperature and higher conductance of L. decidua compared to P. abies provide new insights into species-specific water use strategies, which affect species' performance and should be considered when predicting terrestrial water dynamics under future climatic change.
Determinants of sporadic Campylobacter infections in Denmark: a nationwide case-control study among children and young adults

Background Each year more than 4,000 cases of campylobacteriosis are reported in Denmark, making it the most common bacterial gastrointestinal infection. Here we describe a case-control study to identify sources of infection with a focus on environmental factors. Methods From January to December 2016, we conducted a prospective case-control study among Danish persons aged 1–30 years. Participants were invited by letter to complete an online questionnaire. Crude and adjusted ORs were calculated and final parsimonious multivariate models developed using logistic regression. Results The study recruited 1366 cases and 4,418 controls, of whom 65% and 66%, respectively, completed the questionnaire. A multivariate model for domestically acquired cases showed, among others, increased risk of infection with bathing in fresh water (OR=5.1), contact to beach sand (OR=1.8), owning a pet dog with diarrhea (OR=4.6), and eating minced beef (OR=2.6) or chicken (OR=2.5). The model for children highlighted similar risk factors but also included bathing in a paddling pool (OR=13.6) and eating fresh strawberries (OR=5.3). A separate analysis for persons reporting foreign travel showed increased infection risk when traveling to Asia, Africa, or Turkey and that eating from street kitchens and having contact to water during traveling were also risk factors. Conclusion Environmental factors and animal contact account for a sizeable proportion of domestic Campylobacter infections in the age group studied. The study also re-confirmed handling/consumption of chicken as an important risk factor while highlighting minced beef as a potential new risk factor. Overall, these results contribute to a better understanding of the transmission dynamics of Campylobacter and will be used to improve national guidelines for prevention of infection.
Radiotherapy as salvage treatment of salivary duct carcinoma in major salivary glands without radical operations

Background Salivary duct carcinoma (SDC) is an extremely rare and highly malignant carcinoma, and surgical radical resection is the most effective therapy. However, there were quite a proportion of patients receiving non-radical resections, and how to treat them remained controversial. Thus, the aim of this study is to evaluate whether postoperative radiotherapy could be a salvage treatment of SDC in major salivary glands without radical operations. Patients and methods We identified 40 pathologically diagnosed SDC patients who came to our hospital and did not receive radical operations. Thirty-three patients received at least one treatment (remedial operation, postoperative radiotherapy and chemotherapy), and seven patients only chose observation and received no further treatment. The prognostic indicators of the local–regional control (LRC) and distant disease-free survival were analyzed using the Kaplan–Meier methods and the Cox proportional hazards regression models. Results Thirteen patients experienced local–regional recurrence or local progression, and distant metastases were observed in 15 patients. Through multivariate analysis, we found that postoperative radiotherapy was associated with better LRC, but this kind of treatment did not show significant efficacy in the prevention of distant metastasis. Conclusion SDC is a rare, aggressive malignancy, and a substantial proportion of these patients experienced inadequate initial treatments. Although postoperative radiotherapy could not decrease distant metastases, it might help to improve LRC in patients with SDC.
Life goes on… Patient perspectives on having a cancer diagnosis and other comorbid diseases: A qualitative study

Objectives Due to a growing population with both cancer and chronic diseases, we explored patients’ experiences of living with a cancer diagnosis and comorbidities, the possible effects on everyday living and management of comorbidities. Methods Semi-structured interviews were conducted during 2016 with 15 patients in Denmark, with finished cancer treatment and preexisting comorbidities. Analysis was performed by Systematic Text Condensation. Results Symptoms which disrupted everyday function were given attention, regardless of the disease from which the symptoms originated. The awareness of cancer and comorbidities constituted an inverse process over time. Most patients perceived cancer as being transient, whereas experiences of comorbidities varied from ignorance to worry. Most patients reported maintaining their chronic illness consultations with their general practitioner as before cancer. Conclusion Patients prioritized an everyday life with normal chores highly in contrast to paying attention to diseases. Disruptive symptoms, rather than specific diseases, took up patients’ attention. Cancer did not change the patients’ attendance at chronic care consultations. General practitioners should focus on maintaining the patient’s functional level in everyday life. Further, they should continue to prioritize the chronic care management, as this might increase the patients’ own view of the importance of self-management.
Microglial cell activation and senescence are characteristic of the pathology FXTAS

Fragile X‐associated tremor/ataxia syndrome (FXTAS) is a late‐onset neurodegenerative disorder associated with premutation alleles of the FMR1 gene. Expansions of more than 200 CGG repeats give rise to fragile X syndrome, the most common inherited form of cognitive impairment. Fragile X‐associated tremor/ataxia syndrome is characterized by cerebellar tremor and ataxia, and the presence of ubiquitin‐positive inclusions in neurons and astrocytes. It has been previously suggested that fragile X‐associated tremor/ataxia syndrome is associated with an inflammatory state based on signs of oxidative stress–mediated damage and iron deposition.
Older Adult Preferences of Mobile Application Functionality Supporting Medication Self-Management

Health systems and insurers alike are increasingly interested in leveraging mHealth (mobile health) tools to support patient health-related behaviors including medication adherence. However, these tools are not widely used by older patients. This study explores patient preferences for functionality in a smartphone application (app) that supports medication self-management among older adults with multiple chronic conditions. We conducted six discussion groups in Chicago, Miami, and Denver (N = 46). English-speaking older adults (55 and older) who owned smartphones and took five or more prescription medicines were invited to participate. Discussions covered familiarity with and use of current apps and challenges with taking multidrug regimens. Participants reviewed a range of possible mobile app functions and were asked to give feedback regarding the acceptability and desirability of each to support medication management. Very few participants (n = 3) reported current use of a mobile app for medication support, although all were receptive. Challenges to medication use were forgetfulness, fear of adverse events, and managing medication information from multiple sources. Desired features included (1) a list and consolidated schedule of medications, (2) identification and warning of unsafe medication interactions, (3) reminder alerts to take medicine, and (4) the ability record when medications were taken. Features relating to refill ordering, pharmacy information, and comparing costs for medication were not considered to be as important for an app.
The potential of BRAF-associated non-coding RNA as a therapeutic target in melanoma

ABSTRACT Introduction: The advent of targeted therapies and immune checkpoints inhibitors has enhanced the treatment of metastatic melanomas. Despite striking improvements of patients’ survival, drug resistance continues to limit the efficacy of such treatments. Genetic and nongenetic/adaptive mechanisms of resistance could be involved; in the latter mechanism, noncoding RNAs (ncRNAs) are emerging as key players. Areas covered: This article outlines the current knowledge of ncRNA involvement in BRAF-mutant melanomas and the development of resistance to targeted/immunotherapies. We also discuss how ncRNAs can be exploited for the development of therapeutic and diagnostic approaches. Expert opinion: ncRNAs can be envisaged as powerful diagnostics and therapeutics. Despite progress in our knowledge about their deregulation in cancer, it is still difficult to derive universal and robust ncRNAs unique signatures of malignancy for diagnostic purposes, which need validation in large cohort of patients. Also, ncRNA specific targeting to melanoma cells in vivo requires the development of improved systemic delivery tools. In this regard, the development of stable nanodelivery particles seems to offer renewed hope for success in the clinic.
Evaluating the Medial Longitudinal Arch of the Foot: Correlations, Reliability, and Accuracy in People With a Low Arch

Background The medial longitudinal arch of the foot is a variable structure, and a decrease in its height could affect several functions and increase the risk of injuries in the lower limbs. There are many different techniques for evaluating it. Objective The objective of this study was to evaluate the correlations of the Navicular Drop Test, several footprint parameters, and the Foot Posture Index‐6 in people with a low medial longitudinal arch. Intrarater reliability and interrater reliability were also estimated. Design This was a repeated‐measures, observational descriptive study. Methods Seventy‐one participants (53.5% women; mean age = 24.13 years; SD = 3.41) were included. All of the parameters were collected from the dominant foot. The correlation coefficients were calculated. The reliability was also calculated using the intraclass correlation coefficient, 95% CI, and kappa coefficient. Results Statistically significant correlations were obtained between the Navicular Drop Test and the footprint parameters, with r absolute values ranging from 0.722 to 0.788. The Navicular Drop Test and the Foot Posture Index‐6 showed an excellent correlation (Spearman correlation coefficient = 0.8), and good correlations (Spearman correlation coefficient = |0.663‐0.703|) were obtained between the footprint parameters and the Foot Posture Index‐6. Excellent intrarater reliability and interrater reliability were obtained for all of the parameters. Limitations Radiographic parameters, the gold standard for evaluating the medial longitudinal arch height, were not used. In addition, the results of this research cannot be generalized to people with normal and high medial longitudinal arches. Conclusions In participants with a low medial longitudinal arch, the Navicular Drop Test showed significant correlations with footprint parameters; correlations were good for the arch angle and Chippaux‐Smirnak Index, and excellent for the Staheli Index. The Foot Posture Index‐6 showed an excellent correlation with the Navicular Drop Test and a good correlation with the footprint parameters evaluated. All of the parameters showed high reliability.
Long noncoding RNA B3GALT5-AS1 suppresses colon cancer liver metastasis via repressing microRNA-203

Long noncoding RNAs (lncRNAs) are implicated in various cancers, including colon cancer. Liver metastasis is the main cause of colon cancer-related death. However, the roles of lncRNAs in colon cancer liver metastasis are still largely unclear. In this study, we identified a novel lncRNA B3GALT5-AS1, which is reduced in colon cancer tissues and further reduced in colon cancer liver metastasis tissues. Reduced expression of B3GALT5-AS1 is associated with liver metastasis and poor outcome of colon cancer patients. Gain-of-function and loss-of-function assays revealed that B3GALT5-AS1 inhibited proliferation but promoted migration and invasion of colon cancer cells. Further investigation revealed that B3GALT5-AS1 directly bound to the promoter of miRNA-203, repressed miR-203 expression, upregulated miR-203 targets ZEB2 and SNAI2, and induced epithelial-to-mesenchymal transition (EMT). In vivo study revealed that B3GALT5-AS1 suppressed colon cancer liver metastasis via its binding on miR-203 promoter and the repression of miR-203. miR-203 is increased and epithelial phenotype is preferred in colon cancer liver metastasis tissues. Collectively, our data revealed the suppressive roles of B3GALT5-AS1/miR-203/EMT regulation axis in colon cancer liver metastasis. Our data suggested that the activating B3GALT5-AS1/miR-203/EMT axis may be potential therapeutic strategy for colon cancer liver metastasis.
Minimal Important and Detectable Differences of Respiratory Measures in Outpatients with AECOPD†

Abstract Interpreting clinical changes during acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is challenging due to the absence of established minimal detectable (MDD) and important (MID) differences for most respiratory measures. This study established MDD and MID for respiratory measures in outpatients with AECOPD following pharmacological treatment. COPD assessment test (CAT), modified Borg scale (MBS), modified British Medical Research Council (mMRC) questionnaire, peripheral oxygen saturation (SpO2), computerised respiratory sounds and forced expiratory volume in one second (FEV1) were collected within 24–48 hour of an AECOPD and after 45 days of pharmacological treatment. MID and MDD were calculated using anchor- (receiver operating characteristic and linear regression analysis) and distribution-based methods (effect size, SEM, 0.5*SD and MDC95) and pooled using Meta XL. Forty-four outpatients with AECOPD (31♂; 68.2 ± 9.1 years; FEV1 51.1 ± 20.3%predicted) participated. Significant correlations with CAT were found for the MBS (r = 0.34), mMRC (r = 0.39) and FEV1 (r = 0.33), resulting in MIDs of 0.8, 0.5–0.6 and 0.03L, respectively. MDD of 0.5–1.4 (MBS), 0.4–1.2 (mMRC), 0.10–0.28L (FEV1), 3.6–10.1% (FEV1%predicted), 0.9–2.4% (SpO2), 0.7–1.9 (number of inspiratory crackles), 1.1–4.5 (number of expiratory crackles), 7.1–25.8% (inspiratory wheeze rate) and 11.8–63.0% (expiratory wheeze rate) were found. Pooled data of MID/MDD showed that improvements of 0.9 for the MBS, 0.6 for the mMRC, 0.15L for the FEV1, 7.6% for the FEV1%predicted, 1.5% for the SpO2, 1.1 for the inspiratory and 2.4 for the number of expiratory number of crackles, 14.1% for the inspiratory and 32.5% for the expiratory wheeze rate are meaningful following an AECOPD managed with pharmacological treatment on an outpatient basis.
Extremists on the Left and Right Use Angry, Negative Language

We propose that political extremists use more negative language than moderates. Previous research found that conservatives report feeling happier than liberals and yet liberals “display greater happiness” in their language than do conservatives. However, some of the previous studies relied on questionable measures of political orientation and affective language, and no studies have examined whether political orientation and affective language are nonlinearly related. Revisiting the same contexts (Twitter, U.S. Congress), and adding three new ones (political organizations, news media, crowdsourced Americans), we found that the language of liberal and conservative extremists was more negative and angry in its emotional tone than that of moderates. Contrary to previous research, we found that liberal extremists’ language was more negative than that of conservative extremists. Additional analyses supported the explanation that extremists feel threatened by the activities of political rivals, and their angry, negative language represents efforts to communicate as much to others.
CCR5 deficiency enhances hepatic innate immune cell recruitment and inflammation in a murine model of acute hepatitis B infection

Human genetic studies demonstrate a link between the 32‐bp deletion that produces a nonfunctional CCR5 receptor and enhanced recovery from acute hepatitis B virus (HBV) infection. To investigate the role of CCR5 in immune responses to acute HBV, we intravenously infected Ccr5+/+ (WT) and Ccr5−/− (KO) mice with a replication‐incompetent adenovirus containing the overlapping HBV1.3 construct (AdHBV), or vector control. At day 3 following AdHBV infection, analysis of intrahepatic leukocytes (IHL) showed KO mice had increased CD11b+ NK cells compared to WT (18.2% versus 7.6% of live IHL, P < 0.01). These CD11b+ NK cells were nonresident (CD49a−) and had capacity to degranulate and produce IFN‐γ following stimulation. At day 3, plasma CXCL10 was significantly increased in KO, but not WT, mice receiving AdHBV as compared to vector control, while CXCR3 expression on hepatic CD11b+ NK cells in AdHBV‐treated KO mice was significantly lower than that in uninfected mice, suggesting these NK cells are recruited along the CXCL10–CXCR3 axis. At days 7 and 14, no differences between genotypes were observed in number, or HBV‐specific function, of intrahepatic CD8+ T cells. Instead, at day 14, KO mice had increased intrahepatic proinflammatory monocytes compared to WT mice (17.56% versus 6.57% of live IHL, P = 0.014), corresponding with an increase in plasma alanine aminotransferase and intrahepatic IL‐1β observed in KO mice. Taken together, these findings demonstrate that loss of CCR5 signaling drives a more robust inflammatory liver microenvironment early in acute HBV infection via enrichment of hepatic innate immune cells.
A new class of antibacterials, the imidazopyrazinones, reveal structural transitions involved in DNA gyrase poisoning and mechanisms of resistance

Abstract Imidazopyrazinones (IPYs) are a new class of compounds that target bacterial topoisomerases as a basis for their antibacterial activity. We have characterized the mechanism of these compounds through structural/mechanistic studies showing they bind and stabilize a cleavage complex between DNA gyrase and DNA (‘poisoning’) in an analogous fashion to fluoroquinolones, but without the requirement for the water–metal–ion bridge. Biochemical experiments and structural studies of cleavage complexes of IPYs compared with an uncleaved gyrase–DNA complex, reveal conformational transitions coupled to DNA cleavage at the DNA gate. These involve movement at the GyrA interface and tilting of the TOPRIM domains toward the scissile phosphate coupled to capture of the catalytic metal ion. Our experiments show that these structural transitions are involved generally in poisoning of gyrase by therapeutic compounds and resemble those undergone by the enzyme during its adenosine triphosphate-coupled strand-passage cycle. In addition to resistance mutations affecting residues that directly interact with the compounds, we characterized a mutant (D82N) that inhibits formation of the cleavage complex by the unpoisoned enzyme. The D82N mutant appears to act by stabilizing the binary conformation of DNA gyrase with uncleaved DNA without direct interaction with the compounds. This provides general insight into the resistance mechanisms to antibiotics targeting bacterial type II topoisomerases.
The effects of blueberry anthocyanins on histone acetylation in rat liver fibrosis

To determine the effects ofanthocyanins from blueberries on hepatic stellate cell (HSCs-T6) and on histone acetylation during liver fibrosis induced by CCl4 in rats. Fifty male SD rats weighing 180 ± 20g were randomly placed into a control group, a hepatic fibrosis group, a blueberry treatment group, a blueberry intervention group, and a natural recovery group. After the rats were sacrificed, the livers and the liver indexes were measured, and the pathological changes were observed by HE staining and Masson staining. The blood was analyzed for the four indexes of liver fibrosis and liver function; nucleoprotein from liver tissues and karyoplasm were isolated to determine the expression of acH3K9, acH3K14, and acH3K18 by Western blotting. Compared with the lethal rate of the control group, the median lethal rate of HSCs-T6 cells treated with a the 50μmol/L concentration was 66.94% (P < 0.05). The protein expression on α-SMA, type I collagen, TIMP1 significantly decreased (P < 0.05) following treatment with 50 ug/ml of anthocyanin for 36 h; moreover, the expression of acH3K9, acH3K14 and acH3K18 modification were up-regulated (P < 0.05). Furthermore, compared with the liver in the model group, the liver in the intervention group showed the most obvious improvement (P < 0.01), and its karyoplasm had increased expression of acH3K9, acH3K14 and acH3K18 (P<0.01). Regulating histone acetylation could improve liver function and liver fibrosis indexes in rats with hepatic fibrosis. The mechanism might be related to certain genes that promote apoptosis, so as to inhibit the effect of anti hepatic fibrosis.
DeepV2D: Video to Depth with Differentiable Structure from Motion

We propose DeepV2D, an end-to-end deep learning architecture for predicting depth from video. DeepV2D combines the representation ability of neural networks with the geometric principles governing image formation. We compose a collection of classical geometric algorithms, which are converted into trainable modules and combined into an end-to-end differentiable architecture. DeepV2D interleaves two stages: motion estimation and depth estimation. During inference, motion and depth estimation are alternated and converge to accurate depth. Code is available this https URL.