Miracle-dz/UniFAR-FTUs huggingface dataset:
Director’s Perceived Competition and Its Relationship with Hospital’s Competitive Behaviors: Evidence from County Hospitals in China

Background This study was conducted for assessing the degrees of perceived competition reported by county hospital directors in rural China as well as hospitals’ competitive behaviors in response to competition. Methods The data were collected from Analysis of Provider Payment Reforms on Advancing China’s Health (APPROACH) project which had been implemented among county hospitals in China’s Guizhou province. Competition was measured by asking hospital directors to rate the levels of competitive pressure as they perceived. Hospitals’ competitive behaviors were obtained by asking hospitals’ directors about specific strategies they had adopted. A multivariable linear regression model was developed to examine the relationship between perceived competition and the positivity of competitive behavior, and multivariable logistic regressions were used to evaluate the influence of perceived competition on the adoption of specific competitive strategies. Results Among 218 directors engaged in this study, 210 (96.3%) directors reported the perception of certain degrees of competition, for which the competitive pressure was mainly posed by public hospitals (42.4%). Director-perceived competition level was found to be positively associated with the positivity of competitive behavior, and directors under higher competitive pressure were found to be more likely to adopt multiple competitive strategies including improving the efficiency of hospitals’ internal management, optimizing hospitals’ environment as well as promoting health-care services. Conclusion This study suggested that almost all of the county hospital directors in rural China perceived certain degrees of competitive pressure, and higher levels of perceived competition were found to be significantly associated with increased positivity in adopting competitive strategies. Our findings are expected to provide evidence-based implications for the implementation of a series of pro-competition policies throughout health-care reforms.
Murine Type III interferons are functionally redundant and correlate with bacterial burden during influenza/bacterial super-infection

Background Type III interferon, or interferon lambda (IFNλ) is a crucial antiviral cytokine induced by influenza infection. While IFNλ is important for anti-viral host defense, published data demonstrate that IFNλ is pathogenic during influenza/bacterial super-infection. It is known that polymorphisms in specific IFNλ genes affect influenza responses, but the effect of IFNλ subtypes on bacterial super-infection is unknown. Methods Using an established model of influenza, Staphylococcus aureus super-infection, we studied IFNλ3-/- and control mice to model a physiologically relevant reduction in IFNλ and to address its role in super-infection. Results Surprisingly, IFNλ3-/- mice did not have significantly lower total IFNλ than co-housed controls, and displayed no change in viral or bacterial clearance. Importantly, both control and IFNλ3-/- mice displayed a positive correlation between viral burden and total IFNλ in the bronchoalveolar lavage during influenza/bacterial super-infection, suggesting that higher influenza viral burden drives a similar total IFNλ response regardless of IFNλ3 gene integrity. Interestingly, total IFNλ levels positively correlated with bacterial burden, while viral burden and bronchoalveolar lavage cellularity did not. Conclusions These data suggest IFNλ2 can compensate for IFNλ3 to mount an effective antiviral and defense, revealing a functional redundancy in these highly similar IFNλ subtypes. Further, the IFNλ response to influenza, as opposed to changes in cellular inflammation or viral load, significantly correlates with susceptibility to bacterial super-infection. Moreover, the IFNλ response is regulated and involves redundant subtypes, suggesting it is of high importance to pulmonary pathogen defense.
Reduced physical activity and weight gain are associated with an increase of depressive symptoms during the COVID-19 pandemic. A general practitioners’ prospective observational study

Objectives We aimed to assess associations between depressive symptoms, lifestyle, and somatic symptoms during the COVID-19 pandemic. Design A prospective, observational study using a self-designed questionnaire. Setting Three general practitioners’ (GP) offices in rural Germany. Participants 271 adult patients without manifest cardiovascular or pulmonary disease with (n = 82) and without (n = 189) hypertension reporting to our GP offices. Main outcome measures The reported increase of depressive symptoms (loneliness, sleeplessness, joylessness, listlessness) prior to the first documented case in Germany on 27.01. 2020 (t0) as opposed to patients’ health perception during the Corona pandemic (t1) was the primary outcome measure. The secondary outcome measures were changes in physical activity (PA), dyspnea and angina in the two groups. Results Out of 271 patients (50.8 ± 16.8 years, 55.1% females), 1.5% were tested positive for COVID-19. Overall, listlessness (8.5%, p = 0.001), sleeplessness (5.2%, p = 0.001) and joylessness (4.2%, p = 0.003) were increased. Dyspnea significantly increased (9.2%, p < 0.001) and employment status worsened (6.5%, p < 0.001). There were significant associations between the increase of depressive symptoms, weight increase (p = 0.017), and reduction in physical activity (p = 0.046). However, after adjusting for age, hypertensive patients did not show more depressive symptoms (p = 0.704), dyspnea (p = 0.063) or angina (p = 0.432), nor was there any difference in PA (p = 0.906) compared to healthy individuals. Conclusions We demonstrate an association between the deterioration of depressive symptoms, weight gain, and reduced physical activity during COVID-19, both in hypertensives and healthy controls. Hypertension is no driver of symptom deterioration during the pandemic. The trial was registered in the German Clinical Trials Registry (DRKS00022157).
Microbial ecology of sulfur cycling near the sulfate-methane transition of deep-sea cold seep sediments.

Microbial sulfate reduction is largely associated with anaerobic methane oxidation and alkane degradation in sulfate-methane transition zone (SMTZ) of deep-sea cold seeps. How the sulfur cycling is mediated by microbes near SMTZ has not been fully understood. In this study, we detected a shallow SMTZ in three of eight sediment cores sampled from two cold seep areas in the South China Sea. 110 genomes representing sulfur-oxidizing bacteria (SOB) and sulfur-reducing bacteria (SRB) strains were identified from three SMTZ-bearing cores. In the layers above SMTZ, SOB were mostly constituted by Campylobacterota, Gammaproteobacteria and Alphaproteobacteria that probably depended on nitrogen oxides and/or oxygen for oxidation of sulfide and thiosulfate in near-surface sediment layers. In the layers below the SMTZ, the deltaproteobacterial SRB genomes and metatranscriptomes revealed CO2 fixation by Wood-Ljungdahl pathway, sulfate reduction and nitrogen fixation for syntrophic or fermentative lifestyles. 68% of the MAGs were not adjacent to known species in a phylogenomic tree, indicating a high diversity of bacteria involved in sulfur cycling. With the large number of genomes for SOB and SRB, our study uncovers the microbial populations that potentially mediate sulfur metabolism and associated carbon and nitrogen cycles, which sheds light on complex biogeochemical processes in deep-sea environments. This article is protected by copyright. All rights reserved.
DPODv2: Dense Correspondence-Based 6 DoF Pose Estimation

We propose a three-stage 6 DoF object detection method called DPODv2 (Dense Pose Object Detector) that relies on dense correspondences. We combine a 2D object detector with a dense correspondence estimation network and a multi-view pose refinement method to estimate a full 6 DoF pose. Unlike other deep learning methods that are typically restricted to monocular RGB images, we propose a unified deep learning network allowing different imaging modalities to be used (RGB or Depth). Moreover, we propose a novel pose refinement method, that is based on differentiable rendering. The main concept is to compare predicted and rendered correspondences in multiple views to obtain a pose which is consistent with predicted correspondences in all views. Our proposed method is evaluated rigorously on different data modalities and types of training data in a controlled setup. The main conclusions is that RGB excels in correspondence estimation, while depth contributes to the pose accuracy if good 3D-3D correspondences are available. Naturally, their combination achieves the overall best performance. We perform an extensive evaluation and an ablation study to analyze and validate the results on several challenging datasets. DPODv2 achieves excellent results on all of them while still remaining fast and scalable independent of the used data modality and the type of training data.
Deep learning‐based classification and structure name standardization for organ at risk and target delineations in prostate cancer radiotherapy

Abstract Radiotherapy (RT) datasets can suffer from variations in annotation of organ at risk (OAR) and target structures. Annotation standards exist, but their description for prostate targets is limited. This restricts the use of such data for supervised machine learning purposes as it requires properly annotated data. The aim of this work was to develop a modality independent deep learning (DL) model for automatic classification and annotation of prostate RT DICOM structures. Delineated prostate organs at risk (OAR), support‐ and target structures (gross tumor volume [GTV]/clinical target volume [CTV]/planning target volume [PTV]), along with or without separate vesicles and/or lymph nodes, were extracted as binary masks from 1854 patients. An image modality independent 2D InceptionResNetV2 classification network was trained with varying amounts of training data using four image input channels. Channel 1–3 consisted of orthogonal 2D projections from each individual binary structure. The fourth channel contained a summation of the other available binary structure masks. Structure classification performance was assessed in independent CT (n = 200 pat) and magnetic resonance imaging (MRI) (n = 40 pat) test datasets and an external CT (n = 99 pat) dataset from another clinic. A weighted classification accuracy of 99.4% was achieved during training. The unweighted classification accuracy and the weighted average F1 score among different structures in the CT test dataset were 98.8% and 98.4% and 98.6% and 98.5% for the MRI test dataset, respectively. The external CT dataset yielded the corresponding results 98.4% and 98.7% when analyzed for trained structures only, and results from the full dataset yielded 79.6% and 75.2%. Most misclassifications in the external CT dataset occurred due to multiple CTVs and PTVs being fused together, which was not included in the training data. Our proposed DL‐based method for automated renaming and standardization of prostate radiotherapy annotations shows great potential. Clinic specific contouring standards however need to be represented in the training data for successful use. Source code is available at https://github.com/jamtheim/DicomRTStructRenamerPublic
Alterations of spontaneous brain activity in systematic lupus erythematosus patients without neuropsychiatric symptoms: A resting-functional MRI study

Purpose To explore the alterations of spontaneous neuronal activity using amplitude of low-frequency fluctuation (ALFF), fractional amplitude of low-frequency fluctuation (fALFF), and regional homogeneity (ReHo) in non-NPSLE patients and their relationship with the anxiety and depression statuses. Methods Twenty-three non-NPSLE patients and 28 healthy controls were enrolled in this study. Resting-state functional magnetic resonance imaging was firstly analyzed by ALFF, fALFF, and ReHo. The relationships between ALFF/fALFF/ReHo values of abnormal regions and anxiety/depression rating scales, including Self-Rating Anxiety (SAS) and Self-Rating Depression (SDS), were also analyzed. Results Compared with HC, non-NPSLE had decreased ALFF values in the bilateral postcentral gyrus, while increased ALFF values in the bilateral inferior temporal gyrus, left putamen, and bilateral precuneus. Non-NPSLE showed reduced fALFF values in the left lingual gyrus, left middle occipital gyrus, right postcentral gyrus, and left superior parietal gyrus, while increased fALFF values were in the left inferior temporal gyrus, right hippocampus, bilateral precuneus, and bilateral superior frontal gyrus. Reduced ReHo values were in the bilateral postcentral gyrus and higher ReHo values were in the left inferior temporal gyrus, left putamen, and bilateral superior frontal gyrus. In the non-NPSLE group, the mean ALFF values of bilateral precuneus were positively correlated with the SAS rating scales (R = 0.5519, p = 0.0176); either were the mean ALFF values of right inferior temporal gyrus and SAS rating scales (R = 0.5380, p = 0.0213). The mean fALFF values of left inferior temporal gyrus were positively correlated with SAS rating scales (R = 0.5700, p = 0.0135). And the mean ReHo values of left putamen were positively correlated with SDS (R = 0.5477, p = 0.0186). Conclusion Non-NPSLE exhibited abnormal spontaneous neural activity and coherence in several brain regions mainly associated with cognitive and emotional functions. The ALFF values of bilateral PCUN, the right ITG, the fALFF values of left ITG, and the ReHo values of left PUT may be complementary biomarkers for assessing the psychiatric symptoms.
Efficacy of biologics and oral small molecules for atopic dermatitis: a systematic review and meta-analysis

Abstract Background As new targeted therapies continue to emerge for atopic dermatitis (AD), comparisons between agents are necessary to inform clinical decision-making. Objectives Assess the efficacy of biologics and oral small molecules on the clinical signs, symptoms, and quality of life in AD. Methods A systematic literature review identified phase II and III randomized clinical trials of biologics and oral small molecules in AD. Clinical benefit was assessed for three outcome measures: Eczema Area and Severity Index (EASI), Dermatology Life Quality Index (DLQI), and Peak Pruritus Numerical Rating Scale (PP-NRS) by performing a meta-analysis using the inverse variance heterogeneity model ((IVhet)). Results The highest achievement of 75% reduction in EASI was seen with the higher dose of upadacitinib (30 mg) followed by abrocitinib and lebrikizumab, which outperformed dupilumab. Similarly, the highest proportion achieving at least a 4-point reduction of PP-NRS was seen with lebrikizumab followed by upadacitinib and abrocitinib which had greater reduction of itch than dupilumab. Abrocitinib had the greatest improvement in DLQI. Conclusions Upadacitinib, abrocitinib, and lebrikizumab had greater improvement of clinical signs, symptoms, and quality of life in AD compared to dupilumab and other targeted therapies.
Predicted Vitamin D Status and Colorectal Cancer Incidence in the Black Women's Health Study

Background: Observational studies, mostly among White populations, suggest that low vitamin D levels increase colorectal cancer risk. African Americans, who are disproportionately burdened by colorectal cancer, often have lower vitamin D levels compared with other populations. Methods: We assessed predicted vitamin D score in relation to colorectal cancer among 49,534 participants in the Black Women's Health Study, a cohort of African American women followed from 1995 to 2017 through biennial questionnaires. We derived predicted vitamin D scores at each questionnaire cycle for all participants using a previously validated prediction model based on actual 25-hydroxyvitamin D values from a subset of participants. We calculated cumulative average predicted vitamin D score at every cycle by averaging scores from cycles up to and including that cycle. Using Cox proportional hazards regression, we estimated hazard ratios (HR) and 95% confidence intervals (CI) for colorectal cancer incidence according to predicted score quartiles. Results: Over follow-up, 488 incident colorectal cancers occurred. Compared with women in the highest quartile of predicted vitamin D score, those in the lowest had an estimated 41% (HR = 1.41; 95% CI, 1.05–1.90) higher colorectal cancer risk. Comparable HRs were 1.44 (95% CI, 1.02–2.01) for colon and 1.34 (95% CI, 0.70–2.56) for rectal cancer. Conclusions: Low vitamin D status may lead to elevated colorectal cancer risk in African American women. Impact: Our findings, taken together with established evidence that vitamin D levels are generally lower in African Americans than other U.S. groups, suggest that low vitamin D status may contribute to the disproportionately high colorectal cancer incidence among African Americans.
Low-dose ticagrelor with or without acetylsalicylic acid in patients with acute coronary syndrome: Rationale and design of the ELECTRA-SIRIO 2 trial

This article is available in open access under Creative Common Attribution-Non-Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0) license, allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially. Low-dose ticagrelor with or without acetylsalicylic acid in patients with acute coronary syndrome: Rationale and design of the ELECTRA-SIRIO 2 trial
Normalization strategy for the LC-MS bioanalysis of protein kinetics assays via internal proteolytic analyte utilized as control standard: application in studies of HIV-1 protease cleavage of HIV-1 Gag polyprotein in HIV maturation inhibition research

The human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) pandemic continues to adversely affect human health and life. Although several classes of HIV treatment drugs (antiretrovirals, ARVs) are available, there is a continuing need for new drug modalities, due to inferior drug safety profiles and development of virus resistance. A potential novel class of ARVs are the maturation inhibitors (MIs), which inhibit the ultimate step of HIV-1 protease cleavage during final virus assembly, resulting in immature virus particles incapable of productively infecting other cells. To support ongoing studies on MIs that focus on the biochemical process at the mechanistic level, a liquid chromatography-mass spectrometric (LC-MS) based in vitro assay was developed to quantitatively characterize the HIV-1 protease driven rate of cleavage of HIV-1 virus-like particles (VLPs, fully assembled immature HIV-1 Gag polyprotein), thereby affording kinetic cleavage profiles. Utilizing surrogate analyte methodology on proteinaceous analytes and high resolution accurate mass analysis allowed for the multidimensional design of experiments affording quality data on variables such as Gag (VLP) polymorphic variants, structure–activity-relationship (SAR) of MIs, reagent concentrations, and sampling times. The unique approach of data normalization to an assay internal proteolytic analyte as a control standard eliminated the need for external stable isotope labeled analytes but nevertheless resulted in precise bioanalytical assay data utilized in comparative MIs inhibitory studies.
Dynamics of ligand-protein interactions : impact on drug discovery

Introducing a new drug to market is a lengthy and expensive process (typically 10-15 years and $1.7 billion). Better understanding of how and why a drug molecule binds to a target and what changes in the atomistic structure and chemistry could improve the binding affinity and shorten the process. In addition to structure-based approaches, the role of thermodynamics and molecular motions in binding selectivity and efficiency have attracted increasing attention. Whilst calorimetric methods can quantify total free energy and entropy change, it is difficult to estimate contributions from the different components of entropy, one of the largest unknowns being the magnitude of the configurational entropy. Molecular dynamics (MD) simulations of the drug and target protein can provide more details of the different atomistic movements contributing to the total entropy change, thus potentially providing valuable clues for lead optimisation. In this study we use the well characterised N-terminal domain of the Hsp90 chaperone protein as a model system to study the changes in conformational flexibility (configurational entropy) upon binding of small molecule inhibitors using MD simulations, NMR and ITC. We show that the two inhibitors studied cause different changes in the protein dynamics. These effects were seen with NMR relaxation dispersion methods and with MD but the dynamic changes however are not reflected in the global ITC parameters. Here the water is assumed to have a dominating effect in the overall entropy change. However, as some Hsp90 clients have been shown to preferentially interact with only one conformation of the protein, we propose that the changes seen with NMR and MD could be of interest for drug design. Manipulating the dynamics by small molecules could favour interaction with a subset of client proteins, without affecting the interaction of others, all together providing specificity and potentially allowing to design an ‘ideal’ drug that only prevents the folding of ‘bad’ cancer related proteins without affecting Hsp90 functions in the normal cells. As the MD simulations also reflect these dynamic changes, we propose that simulations could be also used as a screening tool for selecting which inhibitors could be taken for further development in the lab.