Miracle-dz/UniFAR-FTUs huggingface dataset:
A two-hybrid antibody micropattern assay reveals specific in cis interactions of MHC I heavy chains at the cell surface

We demonstrate a two-hybrid assay based on antibody micropatterns to study protein-protein interactions at the cell surface of major histocompatibility complex class I (MHC I) proteins. Anti-tag and conformation-specific antibodies are used for individual capture of specific forms of MHC I proteins that allow for location- and conformation-specific analysis by fluorescence microscopy. The assay is used to study the in cis interactions of MHC I proteins at the cell surface under controlled conditions and to define the involved protein conformations. Our results show that homotypic in cis interactions occur exclusively between MHC I free heavy chains, and we identify the dissociation of the light chain from the MHC I protein complex as a condition for MHC I in cis interactions. The functional role of these MHC I protein-protein interactions at the cell surface needs further investigation. We propose future technical developments of our two-hybrid assay for further analysis of MHC I protein-protein interactions.
Comparison of the Physiological Effect of Billroth-I and Roux-en-Y Reconstruction Following Laparoscopic Distal Gastrectomy

Background: Laparoscopic distal gastrectomy (LDG) is a widely used minimally invasive surgery. Following LDG, Billroth-I (B-I) provides physiological reconstruction by preserving the duodenal passage but results in a high incidence of reflux esophagitis that decreases postoperative quality of life. Because of this, Roux-en-Y (R-Y) reconstruction is often considered the first choice after LDG. However, very few studies have investigated differences in physiological function between B-I and R-Y after LDG. We hypothesized that B-I would outperform R-Y in clinical and physiological outcomes, including nutrition parameters. Methods: We compared hemoglobin, ferritin, serum iron, Vitamin B12, 25(OH)-Vitamin D (V-D), body weight, and gastric emptying after LDG in patients with either B-I or R-Y reconstruction. Results: The levels of hemoglobin in the B-I group were significantly higher than that in the R-Y group at all time points later than 6 months postsurgery. The ferritin levels were significantly higher in the B-I group at all time points later than 9 months postsurgery. The concentration of serum V-D in the B-I group was significantly higher than that in the R-Y group at 1 year 6 months, 1 year 9 months, and 2 years after surgery. Gastric emptying in the R-Y group was significantly slower than in the B-I group. Conclusions: Our data indicate that B-I leads to less postsurgical iron deficiency anemia and V-D deficiency compared with R-Y reconstruction. Furthermore, gastric emptying was preserved in B-I reconstruction compared with R-Y reconstruction. In conclusion, after LDG, B-I reconstruction seems to cause fewer nutritional complications than R-Y reconstruction.
Pathogenic Factors Associated With Osgood-Schlatter Disease in Adolescent Male Soccer Players: A Prospective Cohort Study

Background: A previous cross-sectional study reported that pathogenic factors associated with Osgood-Schlatter disease (OSD) in adolescent athletes include increased quadriceps muscle tightness, lower leg malalignment, and development of apophysitis in the tibial tuberosity. Purpose: To confirm these pathogenic factors associated with OSD in a longitudinal study with regard to physical function and performance. Study Design: Cohort study; Level of evidence, 2. Methods: In this study, 37 boys (mean age, 10.2 ± 0.4 years) were recruited from 2 soccer teams at an elementary school. This cohort study was conducted over an observation period of 1 year, with measurements recorded at baseline, followed by screening for OSD every 6 months. Variables evaluated at baseline included physical function (morphometry, joint flexibility, and lower extremity alignment), presence of Sever disease, and kicking motion. Results: Pathogenic factors associated with OSD in the support leg of adolescent male soccer players included height, weight, body mass index, quadriceps femoris muscle tightness in the kicking and support legs, and gastrocnemius muscle tightness, soleus muscle tightness, and medial longitudinal arch in the support leg. Additional factors included a diagnosis of Sever disease and distance from the lateral malleolus of the support leg’s fibula to the center of gravity during kicking. Conclusion: The onset of OSD was found to be affected by many factors, including developmental stage, physical attributes, and pre-existing apophysitis. In particular, a diagnosis of Sever disease and backward shifting of the center of gravity during kicking increased the risk of the subsequent onset of OSD, suggesting that these factors are very important as a possible focus for interventions.
The Effect of Preoperative Administration of Intravenous Tranexamic Acid During Revision Hip Arthroplasty: A Retrospective Study

Background: Revision hip arthroplasty poses several challenges, including the management of perioperative blood loss. Recent studies have validated the use of tranexamic acid in primary total hip arthroplasty, showing reduced blood loss and decreased number of allogenic blood transfusions. The effectiveness of tranexamic acid has not been well studied in the revision hip arthroplasty setting. Methods: We performed a retrospective review of 1,072 patients who underwent revision hip arthroplasty at our institution from 2008 to 2016. A total of 634 patients met the inclusion criteria, and comparisons were made between 232 consecutive patients without the use of tranexamic acid and 402 consecutive patients with the use of tranexamic acid. Patients were subdivided into 4 groups based on the complexity of revision surgical procedures: (1) major revision, (2) isolated femoral component revision, (3) isolated acetabular component revision, and (4) isolated femoral head and acetabular liner exchange. Within these groups, we compared the demographic data, estimated intraoperative blood loss, perioperative blood units transfused, postoperative hemoglobin drop, and thromboembolic complications between patients receiving either tranexamic acid or no antifibrinolytic therapy. Results: The primary outcomes of our study (estimated intraoperative blood loss, postoperative hemoglobin drop, and perioperative blood transfusion) were all reduced in patients who received tranexamic acid compared with patients who received no antifibrinolytic therapy. When analyzed on the basis of the complexity of surgical revision, there was a decrease in estimated intraoperative blood loss following tranexamic acid administration in the major revision group (845 compared with 1,095 mL; p < 0.001). The postoperative drop in hemoglobin was lower in the major revision group with tranexamic acid administration (by 8.9 g/L; p < 0.01) and the isolated acetabular component revision group with tranexamic acid administration (by 11.9 g/L; p < 0.001). The need for perioperative blood transfusion was reduced across all revisions treated with tranexamic acid (major revision group, 1.79 compared with 3.33 units, p < 0.001; femoral revision only, 0.97 compared with 2.25 units, p < 0.01; acetabular revision only, 0.73 compared with 1.72 units, p < 0.001; and head and liner exchange, 0.15 compared with 0.89 unit, p < 0.05). Conclusions: Based on this study, preoperative administration of intravenous tranexamic acid in revision hip arthroplasty reduces allogenic blood transfusions and perioperative blood loss. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Evolution of populations expanding on curved surfaces

The expansion of a population into new habitat is a transient process that leaves its footprints in the genetic composition of the expanding population. How the structure of the environment shapes the population front and the evolutionary dynamics during such a range expansion is little understood. Here, we investigate the evolutionary dynamics of populations consisting of many selectively neutral genotypes expanding on curved surfaces. Using a combination of individual-based off-lattice simulations, geometrical arguments, and lattice-based stepping-stone simulations, we characterise the effect of individual bumps on an otherwise flat surface. Compared to the case of a range expansion on a flat surface, we observe a transient relative increase, followed by a decrease, in neutral genetic diversity at the population front. In addition, we find that individuals at the sides of the bump have a dramatically increased expected number of descendants, while their neighbours closer to the bump's centre are far less lucky. Both observations can be explained using an analytical description of straight paths (geodesics) on the curved surface. Complementing previous studies of heterogeneous flat environments, the findings here build our understanding of how complex environments shape the evolutionary dynamics of expanding populations.
Positive and Negative Regulation of Glycerol Utilization by the c-di-GMP Binding Protein PlzA in Borrelia burgdorferi

The Lyme disease pathogen, Borrelia burgdorferi, has a simple cyclic dimeric GMP (c-di-GMP) signaling system essential for adaptation of the pathogen to the complicated tick environment. The c-di-GMP effector of B. burgdorferi, PlzA, has been shown to regulate multiple cellular processes, including motility, osmolality sensing, and nutrient utilization. The findings of this study demonstrate that PlzA not only controls multiple targets but also has different functional modalities, allowing it to act as both positive and negative regulator of the glp operon expression. This work highlights how bacteria with a small genome can compensate for the limited regulatory repertoire by increasing the complexity of targets and modes of action in their regulatory proteins. ABSTRACT Borrelia burgdorferi, the causative agent of Lyme disease, encounters two disparate host environments during its enzootic life cycle, Ixodes ticks and mammalian hosts. B. burgdorferi has a small genome that encodes a streamlined cyclic dimeric GMP (c-di-GMP) signaling system comprising a single diguanylate cyclase, Rrp1, and two phosphodiesterases. This system is essential for spirochete survival in ticks, in part because it controls the expression of the glp operon involved in glycerol utilization. In this study, we showed that a B. burgdorferi c-di-GMP receptor, PlzA, functions as both a positive and a negative regulator for glp expression. Deletion of plzA or mutation in plzA that impaired c-di-GMP binding abolished glp expression. On the other hand, overexpression of plzA resulted in glp repression, which could be rescued by simultaneous overexpression of rrp1. plzA overexpression in the rrp1 mutant, which is devoid of c-di-GMP, or overexpression of a plzA mutant incapable of c-di-GMP binding further enhanced glp repression. Combined results suggest that c-di-GMP-bound PlzA functions as a positive regulator, whereas ligand-free PlzA acts as a negative regulator for glp expression. Thus, PlzA of B. burgdorferi with a streamlined c-di-GMP signaling system not only controls multiple targets, as previously envisioned, but has also evolved different modes of action. IMPORTANCE The Lyme disease pathogen, Borrelia burgdorferi, has a simple cyclic dimeric GMP (c-di-GMP) signaling system essential for adaptation of the pathogen to the complicated tick environment. The c-di-GMP effector of B. burgdorferi, PlzA, has been shown to regulate multiple cellular processes, including motility, osmolality sensing, and nutrient utilization. The findings of this study demonstrate that PlzA not only controls multiple targets but also has different functional modalities, allowing it to act as both positive and negative regulator of the glp operon expression. This work highlights how bacteria with a small genome can compensate for the limited regulatory repertoire by increasing the complexity of targets and modes of action in their regulatory proteins.
Effect of sodium fluoride pretreatment on the efficacy of an in‐office bleaching agent: An in vitro study

This in vitro study evaluated the effect of sodium fluoride (NaF) on the bleaching efficacy using an artificial discolored bovine tooth model. Twenty specimens were prepared from bovine teeth by staining with black tea extract and were divided into two groups (n = 10). In control group, specimens were immersed in distilled water for 30 min. In NaF group, specimens were applied with 0.2% NaF for 30 min. Then, the specimens in each group were bleached by an in‐office bleaching material (Shofu Hi‐Lite, Shofu, Kyoto, Japan). The CIE L*a*b* values were measured by a dental colorimeter before and after 10 consecutive bleaching treatments, and the color difference (ΔE) was calculated. Brightness and color difference (ΔE) increased in both groups per bleaching cycle. There were no statistical differences in ΔE values between both groups (p > 0.05). It was concluded that the application of NaF before bleaching did not interfere with the bleaching effect.
Why is unsupervised alignment of English embeddings from different algorithms so hard?

This paper presents a challenge to the community: Generative adversarial networks (GANs) can perfectly align independent English word embeddings induced using the same algorithm, based on distributional information alone; but fails to do so, for two different embeddings algorithms. Why is that? We believe understanding why, is key to understand both modern word embedding algorithms and the limitations and instability dynamics of GANs. This paper shows that (a) in all these cases, where alignment fails, there exists a linear transform between the two embeddings (so algorithm biases do not lead to non-linear differences), and (b) similar effects can not easily be obtained by varying hyper-parameters. One plausible suggestion based on our initial experiments is that the differences in the inductive biases of the embedding algorithms lead to an optimization landscape that is riddled with local optima, leading to a very small basin of convergence, but we present this more as a challenge paper than a technical contribution.
SmoothOut: Smoothing Out Sharp Minima to Improve Generalization in Deep Learning

In Deep Learning, Stochastic Gradient Descent (SGD) is usually selected as a training method because of its efficiency; however, recently, a problem in SGD gains research interest: sharp minima in Deep Neural Networks (DNNs) have poor generalization; especially, large-batch SGD tends to converge to sharp minima. It becomes an open question whether escaping sharp minima can improve the generalization. To answer this question, we propose SmoothOut framework to smooth out sharp minima in DNNs and thereby improve generalization. In a nutshell, SmoothOut perturbs multiple copies of the DNN by noise injection and averages these copies. Injecting noises to SGD is widely used in the literature, but SmoothOut differs in lots of ways: (1) a de-noising process is applied before parameter updating; (2) noise strength is adapted to filter norm; (3) an alternative interpretation on the advantage of noise injection, from the perspective of sharpness and generalization; (4) usage of uniform noise instead of Gaussian noise. We prove that SmoothOut can eliminate sharp minima. Training multiple DNN copies is inefficient, we further propose an unbiased stochastic SmoothOut which only introduces the overhead of noise injecting and de-noising per batch. An adaptive variant of SmoothOut, AdaSmoothOut, is also proposed to improve generalization. In a variety of experiments, SmoothOut and AdaSmoothOut consistently improve generalization in both small-batch and large-batch training on the top of state-of-the-art solutions.
InteriorNet: Mega-scale Multi-sensor Photo-realistic Indoor Scenes Dataset

Datasets have gained an enormous amount of popularity in the computer vision community, from training and evaluation of Deep Learning-based methods to benchmarking Simultaneous Localization and Mapping (SLAM). Without a doubt, synthetic imagery bears a vast potential due to scalability in terms of amounts of data obtainable without tedious manual ground truth annotations or measurements. Here, we present a dataset with the aim of providing a higher degree of photo-realism, larger scale, more variability as well as serving a wider range of purposes compared to existing datasets. Our dataset leverages the availability of millions of professional interior designs and millions of production-level furniture and object assets -- all coming with fine geometric details and high-resolution texture. We render high-resolution and high frame-rate video sequences following realistic trajectories while supporting various camera types as well as providing inertial measurements. Together with the release of the dataset, we will make executable program of our interactive simulator software as well as our renderer available at this https URL. To showcase the usability and uniqueness of our dataset, we show benchmarking results of both sparse and dense SLAM algorithms.
Cost-effectiveness of colorectal cancer screening programmes using sigmoidoscopy and immunochemical faecal occult blood test

Objective Several European countries are implementing organized colorectal cancer (CRC) screening programmes using faecal immunochemical test (FIT) and/or flexible sigmoidoscopy (FS), but the cost-effectiveness of these programmes is not yet available. We aimed to assess cost-effectiveness, based on data from the established Piedmont screening programme. Methods Using the Piedmont programme data, a Markov model was constructed comparing three strategies in a simulated cohort of 100,000 subjects: single FS, biennial FIT, or sequential strategy (FS + FIT offered to FS non-responders). Estimates for CRC incidence and mortality prevention were derived from studies of organized screening. Cost analysis for FS and FIT was based on data from organized programmes. Incremental cost-effectiveness ratios (ICER) between the different strategies were calculated. Sensitivity and probabilistic analyses were performed. Results Direct costs for FS, and for FIT at first and subsequent rounds, were estimated as €160, €33, and €21, respectively. All the simulated strategies were effective (10–17% CRC incidence reduction) and cost-effective vs. no screening (ICER <€1000 per life-year saved). FS and FS + FIT were the only cost-saving strategies, with FS least expensive (€15 saving per person invited). FS + FIT and FS were the only non-dominated strategies. FS + FIT were more effective and cost-effective than FS (ICER €1217 per life-year saved). The residual marginal uncertainty was mainly related to parameters inherent to FIT effectiveness and adherence. Conclusions Organized CRC screening programmes are highly cost-effective, irrespective of the test selected. A sequential approach with FS and FIT appears the most cost-effective option. A single FS is the least expensive, but convenient, approach.
Dynamic amplification of extreme precipitation sensitivity

Significance Changes in precipitation extremes under climate change are subject to substantial uncertainty. Atmospheric moisture increases alone would make extreme rain events heavier at a well-understood rate of ∼7% K−1, but a component associated with storm dynamics is much less well-understood and can either amplify or reduce that moisture-driven intensification. This paper uses an idealized modeling framework to understand the coupling of these two components, simulating one actual heavy rain event in both the present climate and hypothetical perturbed climates. The increased heating due to increased moisture drives a dynamical increase in large-scale ascent, amplifying the moisture-driven response by as much as a factor of two for warmer climates. A useful starting hypothesis for predictions of changes in precipitation extremes with climate is that those extremes increase at the same rate as atmospheric moisture does, which is ∼7% K−1 following the Clausius–Clapeyron (CC) relation. This hypothesis, however, neglects potential changes in the strengths of atmospheric circulations associated with precipitation extremes. As increased moisture leads to increased precipitation, the increased latent heating may lead to stronger large-scale ascent and thus, additional increase in precipitation, leading to a super-CC scaling. This study investigates this possibility in the context of the 2015 Texas extreme precipitation event using the Column Quasi-Geostrophic (CQG) method. Analogs to this event are simulated in different climatic conditions with varying surface temperature (Ts) given the same adiabatic quasigeostrophic forcing. Precipitation in these events exhibits super-CC scaling due to the dynamic contribution associated with increasing ascent due to increased latent heating, an increase with importance that increases with Ts. The thermodynamic contribution (attributable to increasing water vapor; assuming no change in vertical motion) approximately follows CC as expected, while vertical structure changes of moisture and diabatic heating lead to negative but secondary contributions to the sensitivity, reducing the rate of increase.
Assessing the Role of DNA Methylation-Derived Neutrophil-to-Lymphocyte Ratio in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a disease of chronic systemic inflammation (SI). In the present study, we used four datasets to explore whether methylation-derived neutrophil-to-lymphocyte ratio (mdNLR) might be a marker of SI in new onset, untreated, and treated prevalent RA cases and/or a marker of treatment response to the tumour necrosis factor inhibitor (TNFi) etanercept. mdNLR was associated with increased odds of being a new onset RA case (OR = 2.32, 95% CI = 1.95–2.80, P < 2 × 10−16) and performed better in distinguishing new onset RA cases from controls compared to covariates: age, gender, and smoking status. In untreated preclinical RA cases and controls, mdNLR at baseline was associated with diagnosis of RA in later life after adjusting for batch (OR = 4.30, 95% CI = 1.52–21.71, P = 0.029) although no association was observed before batch correction. When prevalent RA cases were treated, there was no association with mdNLR in samples before and after batch correction (OR = 0.34, 95% CI = 0.05–1.82, P = 0.23), and mdNLR was not associated with treatment response to etanercept (OR = 1.10, 95% CI = 0.75–1.68, P = 0.64). Our results indicate that SI measured by DNA methylation data is indicative of the recent onset of RA. Although preclinical RA was associated with mdNLR, there was no difference in the mean mdNLR between preclinical RA cases and controls. mdNLR was not associated with RA case status if treatment for RA has commenced, and it is not associated with treatment response. In the future, mdNLR estimates may be used as a valuable research tool to reliably estimate SI in the absence of freshly collected blood samples.