Miracle-dz/UniFAR-FTUs huggingface dataset:
Local microvascular leakage promotes trafficking of activated neutrophils to remote organs

Increased microvascular permeability to plasma proteins and neutrophil emigration are hallmarks of innate immunity and key features of numerous inflammatory disorders. Although neutrophils can promote microvascular leakage, the impact of vascular permeability on neutrophil trafficking is unknown. Here, through the application of confocal intravital microscopy, we report that vascular permeability–enhancing stimuli caused a significant frequency of neutrophil reverse transendothelial cell migration (rTEM). Furthermore, mice with a selective defect in microvascular permeability enhancement (VEC-Y685F-ki) showed reduced incidence of neutrophil rTEM. Mechanistically, elevated vascular leakage promoted movement of interstitial chemokines into the bloodstream, a response that supported abluminal-to-luminal neutrophil TEM. Through development of an in vivo cell labeling method we provide direct evidence for the systemic dissemination of rTEM neutrophils, and showed them to exhibit an activated phenotype and be capable of trafficking to the lungs where their presence was aligned with regions of vascular injury. Collectively, we demonstrate that increased microvascular leakage reverses the localization of directional cues across venular walls, thus causing neutrophils engaged in diapedesis to reenter the systemic circulation. This cascade of events offers a mechanism to explain how local tissue inflammation and vascular permeability can induce downstream pathological effects in remote organs, most notably in the lungs.
Implications of AI (un-)fairness in higher education admissions: the effects of perceived AI (un-)fairness on exit, voice and organizational reputation

Algorithmic decision-making (ADM) is becoming increasingly important in all areas of social life. In higher education, machine-learning systems have manifold uses because they can efficiently process large amounts of student data and use these data to arrive at effective decisions. Despite the potential upsides of ADM systems, fairness concerns are gaining momentum in academic and public discourses. The criticism largely focuses on the disparate effects of ADM. That is, algorithms may not serve as objective and fair decision-makers but, rather, reproduce biases existing within the respective training data. This study adopted a different approach by focusing on individual perceptions of fairness. Specifically, we looked at two different dimensions of perceived fairness: (i) procedural fairness and (ii) distributive fairness. Using cross-sectional survey data (n = 304) from a large German university, we tested whether students' assessments of fairness differ with respect to algorithmic vs. human decision-making (HDM) within the higher education context. Furthermore, we investigated whether fairness perceptions have subsequent effects on three different outcome variables, which are hugely important for universities: (1) exit, (2) voice, and (3) organizational reputation. The results of our survey suggest that participants evaluated ADM higher than HDM in terms of both procedural and distributive fairness. Concerning the subsequent effects of fairness perceptions, we find that (1) distributive fairness as well as procedural fairness perceptions have a negative impact on the intention to protest against an ADM system, whereas (2) only procedural fairness perceptions negatively affect the likelihood of exiting. Finally, (3) distributive fairness, but not procedural fairness perceptions have a positive effect on organizational reputation. For universities aiming to implement ADM systems, it is crucial, therefore, to take possible fairness issues and their further implications into account.
Prospective Multicenter Validation of Androgen Receptor Splice Variant 7 and Hormone Therapy Resistance in High-Risk Castration-Resistant Prostate Cancer: The PROPHECY Study

PURPOSE Androgen receptor splice variant 7 (AR-V7) results in a truncated receptor, which leads to ligand-independent constitutive activation that is not inhibited by anti-androgen therapies, including abiraterone or enzalutamide. Given that previous reports suggested that circulating tumor cell (CTC) AR-V7 detection is a poor prognostic indicator for the clinical efficacy of secondary hormone therapies, we conducted a prospective multicenter validation study. PATIENTS AND METHODS PROPHECY (ClinicalTrials.gov identifier: NCT02269982) is a multicenter, prospective-blinded study of men with high-risk mCRPC starting abiraterone acetate or enzalutamide treatment. The primary objective was to validate the prognostic significance of baseline CTC AR-V7 on the basis of radiographic or clinical progression free-survival (PFS) by using the Johns Hopkins University modified-AdnaTest CTC AR-V7 mRNA assay and the Epic Sciences CTC nuclear-specific AR-V7 protein assay. Overall survival (OS) and prostate-specific antigen responses were secondary end points. RESULTS We enrolled 118 men with mCRPC who were starting abiraterone or enzalutamide treatment. AR-V7 detection by both the Johns Hopkins and Epic AR-V7 assays was independently associated with shorter PFS (hazard ratio, 1.9 [95% CI, 1.1 to 3.3; P = .032] and 2.4 [95% CI, 1.1 to 5.1; P = .020], respectively) and OS (hazard ratio, 4.2 [95% CI, 2.1 to 8.5] and 3.5 [95% CI, 1.6 to 8.1], respectively) after adjusting for CTC number and clinical prognostic factors. Men with AR-V7–positive mCRPC had fewer confirmed prostate-specific antigen responses (0% to 11%) or soft tissue responses (0% to 6%). The observed percentage agreement between the two AR-V7 assays was 82%. CONCLUSION Detection of AR-V7 in CTCs by two blood-based assays is independently associated with shorter PFS and OS with abiraterone or enzalutamide, and such men with mCRPC should be offered alternative treatments.
The Effect of Optical Flow Motion Direction on Vection Strength

In some phenomena of visual perception, the motion direction of visual stimuli can affect perception. In particular, asymmetries between oblique directions and cardinal (horizontal and vertical) directions have been reported and are known as oblique effects (e.g., contrast sensitivity and motion threshold). In this study, we investigated how vection strength depends on motion direction. Participants observed random-dot optical flow in a circular field and rated the perceived vection strength. Dot movement was systematically controlled using the following angles: 0° (up), 30°, 45°, 60°, 90°, 120°, 135°, 150°, and 180° (down). We found that vection strength depended on motion direction and was weaker in the oblique directions than cardinal directions. Thus, the effect of motion direction on vection strength was variable, as seen in the shape of the oblique effect.
Structural analysis of the intrinsically disordered splicing factor Spp2 and its binding to the DEAH-box ATPase Prp2

Significance The G-patch domain is found in eukaryotic and viral proteins involved in protein–protein and protein–nucleic acid interactions. Some G-patch proteins play a vital role in the spliceosome by stimulating the DEAH-box ATPases Prp2 and Prp43; however, their structural characterization and exact binding mode have remained elusive. By studying the Prp2-specific G-patch domain of Spp2 by means of X-ray crystallography and nuclear magnetic resonance spectroscopy, we could show that the G-patch is mostly disordered in solution but adopts a defined fold on binding to Prp2. The disordered nature of Spp2 might be important for the positioning of Prp2 during its recruitment to the spliceosome. The spliceosome consists of five small RNAs and more than 100 proteins. Almost 50% of the human spliceosomal proteins were predicted to be intrinsically disordered or to contain disordered regions, among them the G-patch protein Spp2. The G-patch region of Spp2 binds to the DEAH-box ATPase Prp2, and both proteins together are essential for promoting the transition from the Bact to the catalytically active B* spliceosome. Here we show by circular dichroism and nuclear magnetic resonance (NMR) spectroscopy that Spp2 is intrinsically disordered in solution. Crystal structures of a complex consisting of Prp2-ADP and the G-patch domain of Spp2 demonstrate that the G-patch gains a defined fold when bound to Prp2. While the N-terminal region of the G-patch always folds into an α-helix in five different crystal structures, the C-terminal part is able to adopt two alternative conformations. NMR studies further revealed that the N-terminal part of the Spp2 G-patch, which is the most conserved region in different G-patch proteins, transiently samples helical conformations, possibly facilitating a conformational selection binding mechanism. The structural analysis unveils the role of conserved residues of the G-patch in the dynamic interaction mode of Spp2 with Prp2, which is vital to maintain the binding during the Prp2 domain movements needed for RNA translocation.
Re-assessing the validity of the Moral Sensitivity Questionnaire (MSQ): Two new scales for moral deliberation and paternalism.

RATIONALE, AIMS, AND OBJECTIVES The current study and previous research have called the six-component model of Lützen's 30-item Moral Sensitivity Questionnaire (MSQ) into question. For this reason, we re-examined the construct validity of this instrument. METHODS In this cross-sectional study, which was based on a convenience sample of Dutch nurse practitioners (NPs) and physician assistants (PAs), we tested the validity of MSQ items using exploratory and confirmatory factor analyses (EFA and CFA, respectively). RESULTS The EFA revealed a two-component model, which was then tested as a target model with CFA and was found to have good model fit. Some items were correlated with two uncorrelated latent constructs, which we labelled as "paternalistic" and "deliberate" attitudes towards patients. CONCLUSIONS As in previous studies, the analyses in the current study, which was conducted among PAs and NPs, did not reveal six dimensions for the 30 items. Two new latent dimensions of moral sensitivity were psychometrically tested and confirmed. These two components relate to studies investigating ethical behaviour, and they can be used to describe the moral climate in healthcare organizations. The scales are indicators of the extent to which health professionals behave in a deliberate (sensitive) or paternalistic (insensitive) manner towards the opinions of patients within the context of medical decision-making.
Ready for the Challenge of Depression Care in the Medical Home

Adolescent depression is common and often debilitating, yet frequently goes undiagnosed and untreated. A national shortage of child and adolescent psychiatrists is long-standing and unlikely to improve, leaving primary care providers (PCPs) to fill this care gap. Historically, PCPs have been reluctant to provide depression care. In a 2011 survey, local PCPs reported they were unaware of national guidelines, felt inadequately trained, and lacked confidence to diagnose and manage these patients. To assess PCPs’ current attitudes and behaviors regarding providing depression care in the medical home, we recently repeated the survey. We compared findings from the 2 surveys to assess any change in PCPs’ attitudes and behaviors. In this article, we report our findings to inform capacity building efforts.
Study of G-Protein Coupled Receptor Signaling in Membrane Environment by Plasmon Waveguide Resonance.

Here we describe an experimental technique, termed plasmon waveguide resonance (PWR) spectroscopy that enables the characterization of molecular interactions occurring at the level of anisotropic thin films as lipid membranes and therein inserted or interacting molecules. PWR allows one to characterize such molecular interactions at different levels: (1) acquire binding curves and calculate dissociation constants; (2) obtain kinetic information; (3) obtain information about associated anisotropy changes and changes in membrane thickness; (4) obtain insight about lateral homogeneity (formation of domains). Points 1, 2, and 4 can be directly obtained from the data. Point 3 requires spectral fitting procedures so that the different optical parameters characterizing thin films as proteolipid membranes, namely refractive index and extinction coefficient for both p- (TM component of light that is parallel to the incident light) and s- (TE component of light that is perpendicular to the incident light) polarizations and thickness, can be determined. When applied to membrane proteins as the G-protein coupled receptor (GPCR) family, both ligand-induced conformational changes of the receptor can be followed as well as interactions with effectors (e.g., G-proteins). Additionally, by either altering the lipid composition in cellular membranes or specifically controlling its composition in the case of lipid model membranes with reconstituted proteins, the role of the lipid environment in receptor activation and signaling can be determined. Additionally, the eventual partition of receptors in different lipid microdomains (e.g., lipid rafts) can be followed. Such information can be obtained ex cellulo with mammalian cell membrane fragments expressing the protein of interest and/or in vitro with lipid model systems where the protein under investigation has been reconstituted. Moreover, PWR can also be applied to directly follow the reconstitution of membrane proteins in lipid model membranes. The measurements are performed directly (no labeling of molecular partners), in real time and with very high sensitivity. Here we will discuss different aspects of GPCR activation and signaling where PWR brought important information in parallel with other approaches. The utility of PWR is not limited to GPCRs but can be applied to any membrane protein. PWR is also an excellent tool to characterize the interaction of membrane active molecules (as cell penetrating, antimicrobial, viral and amyloid peptides) with lipids. A brief section is dedicated to such applications, with particular emphasis on amyloid peptides. To finalize, as PWR is a homemade technology, ongoing instrument developments aiming at breaking current experimental limitations are briefly discussed, namely, the coupling of PWR with electrochemical measurements and the expansion of measurements from the visible to the infrared region.
A More Robust Gut Microbiota in Calorie-Restricted Mice Is Associated with Attenuated Intestinal Injury Caused by the Chemotherapy Drug Cyclophosphamide

Improving the gut microbiota via calorie restriction is beneficial for human health. Our findings showed differential responses between calorie-restricted mice and ad libitum-fed mice. Compared with the ad libitum-fed mice, the calorie-restricted mice were less susceptible to cyclophosphamide side effects otherwise observed on the gut integrity and its microbiota. These results show the potential benefits of manipulating the gut microbiota with CR prior to cancer chemotherapy. ABSTRACT Cyclophosphamide (CTX) is widely used in cancer chemotherapy, but it often induces mucositis, in which the disruption of the gut microbiota might play a pivotal role. Whether the manipulation of the gut microbiota can be used as a strategy to improve CTX-induced mucositis remains to be studied. Here we observed the effects of a 4-week calorie restriction (CR) on CTX-induced mucositis. Compared with ad libitum-fed mice, CR mice showed significantly less mucositis in response to CTX, including lower intestinal permeability, less bacterial translocation, higher number of epithelial stem cells, and less epithelium damage. CTX induced significant shifts of the gut microbiota of the gut microbiota in ad libitum-fed control mice. In contrast, CR mice showed no significant change in their gut microbiota in responding to CTX treatment. CR significantly enriched the gut microbiota in Lactobacillus and Lachnospiraceae which are known to mitigate inflammation and improve gut barrier function. These findings suggest that CR remodeled gut microbiota is more robust and may contribute to attenuate the side effects of cyclophosphamide, which supports the concept that cancer chemotherapy would benefit from strategies targeting the gut microbiota. IMPORTANCE Improving the gut microbiota via calorie restriction is beneficial for human health. Our findings showed differential responses between calorie-restricted mice and ad libitum-fed mice. Compared with the ad libitum-fed mice, the calorie-restricted mice were less susceptible to cyclophosphamide side effects otherwise observed on the gut integrity and its microbiota. These results show the potential benefits of manipulating the gut microbiota with CR prior to cancer chemotherapy.
End-to-end Speech Recognition Using a High Rank LSTM-CTC Based Model

Long Short Term Memory Connectionist Temporal Classification (LSTM-CTC) based end-to-end models are widely used in speech recognition due to its simplicity in training and efficiency in decoding. In conventional LSTM-CTC based models, a bottleneck projection matrix maps the hidden feature vectors obtained from LSTM to softmax output layer. In this paper, we propose to use a high rank projection layer to replace the projection matrix. The output from the high rank projection layer is a weighted combination of vectors that are projected from the hidden feature vectors via different projection matrices and non-linear activation function. The high rank projection layer is able to improve the expressiveness of LSTM-CTC models. The experimental results show that on Wall Street Journal (WSJ) corpus and LibriSpeech data set, the proposed method achieves 4% – 6% relative word error rate (WER) reduction over the baseline CTC system. They outperform other published CTC based end-to-end (E2E) models under the condition that no external data or data augmentation is applied. Code has been made available at https://github.com/mobvoi/lstm_ctc.
Micronutrient Supplementation and Fortification Interventions on Health and Development Outcomes among Children Under-Five in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis

Micronutrient deficiencies continue to be widespread among children under-five in low- and middle-income countries (LMICs), despite the fact that several effective strategies now exist to prevent them. This kind of malnutrition can have several immediate and long-term consequences, including stunted growth, a higher risk of acquiring infections, and poor development outcomes, all of which may lead to a child not achieving his or her full potential. This review systematically synthesizes the available evidence on the strategies used to prevent micronutrient malnutrition among children under-five in LMICs, including single and multiple micronutrient (MMN) supplementation, lipid-based nutrient supplementation (LNS), targeted and large-scale fortification, and point-of-use-fortification with micronutrient powders (MNPs). We searched relevant databases and grey literature, retrieving 35,924 papers. After application of eligibility criteria, we included 197 unique studies. Of note, we examined the efficacy and effectiveness of interventions. We found that certain outcomes, such as anemia, responded to several intervention types. The risk of anemia was reduced with iron alone, iron-folic acid, MMN supplementation, MNPs, targeted fortification, and large-scale fortification. Stunting and underweight, however, were improved only among children who were provided with LNS, though MMN supplementation also slightly increased length-for-age z-scores. Vitamin A supplementation likely reduced all-cause mortality, while zinc supplementation decreased the incidence of diarrhea. Importantly, many effects of LNS and MNPs held when pooling data from effectiveness studies. Taken together, this evidence further supports the importance of these strategies for reducing the burden of micronutrient malnutrition in children. Population and context should be considered when selecting one or more appropriate interventions for programming.
Anaerobic Threshold Biophysical Characterisation of the Four Swimming Techniques

Abstract The anaerobic threshold (AnT) seems to be not only a physiologic boundary but also a transition after which swimmers technique changes, modifying their biomechanical behaviour. We expanded the AnT concept to a biophysical construct in the four conventional swimming techniques. Seventy-two elite swimmers performed a 5×200 m incremental protocol in their preferred swimming technique (with a 0.05 m·s−1 increase and a 30 s interval between steps). A capillary blood samples were collected from the fingertip and stroke rate (SR) and length (SL) determined for the assessment of [La], SR and SL vs. velocity inflexion points (using the interception of a pair of linear and exponential regression curves). The [La] values at the AnT were 3.3±1.0, 3.9±1.1, 2.9±1 . 34 and 4.5±1.4 mmol·l−1 (mean±SD) for front crawl, backstroke, breaststroke and butterfly, and its corresponding velocity correlated highly with those at SR and SL inflection points (r=0.91–0.99, p<0.001). The agreement analyses confirmed that AnT represents a biophysical boundary in the four competitive swimming techniques and can be determined individually using [La] and/or SR/SL. Blood lactate increase speed can help characterise swimmers’ anaerobic behaviour after AnT and between competitive swimming techniques.
Dietary Inflammatory Index and S-Klotho Plasma Levels in Middle-Aged Adults

Background: Soluble Klotho (S-Klotho) is an aging suppressor with a close link with inflammation. However, it is still unknown whether the dietary inflammatory potential is associated with S-Klotho plasma level. We aimed to investigate the association of the Dietary Inflammatory Index (DII) with S-Klotho plasma levels in middle-aged sedentary adults. Methods: 73 middle-aged sedentary adults (40–65 years old) participated in the present study. DII was determined from 28 dietary items obtained by 24 h recalls and food frequency questionnaires. The S-Klotho plasma levels were measured using a solid-phase sandwich enzyme-linked immunosorbent assay. Results: a weak positive association was observed between DII and S-Klotho plasma levels (β = 52.223, R2 = 0.057, p = 0.043), which disappeared after controlling for body mass index (p = 0.057). Conclusions: A pro-inflammatory dietary pattern measured with the DII was slightly and positively associated with S-Klotho plasma levels in middle-aged sedentary adults.
The utility of single operator cholangioscope (Spyglass) to diagnose and treat radiographically negative biliary stones: A case series and review

Gallstone disease is a common health concern around the world. In the Unites States, it is estimated that 12- 15% of the adult population- roughly 20 to 25 million Americans- have, or will have, gallstones over the course of their lives [1]. Similarly, gallstone disease is a leading cause of gastrointestinal ambulatory care visits, with 1.8 million reported every year [1]. Although 1.2 million cholecystectomies are performed yearly in the United States for symptom and complication relief, up to 5% of patients do not experience resolution of symptoms secondary to persistent common bile duct stones discovered days to years after surgery [2,3].