Miracle-dz/UniFAR-FTUs huggingface dataset:
Implementing the Lexicographic Maxmin Bargaining Solution

There has been much work on exhibiting mechanisms that implement various bargaining solutions, in particular, the Kalai-Smorodinsky solution \cite{moulin1984implementing} and the Nash Bargaining solution. Another well-known and axiomatically well-studied solution is the lexicographic maxmin solution. However, there is no mechanism known for its implementation. To fill this gap, we construct a mechanism that implements the lexicographic maxmin solution as the unique subgame perfect equilibrium outcome in the n-player setting. As is standard in the literature on implementation of bargaining solutions, we use the assumption that any player can grab the entire surplus. Our mechanism consists of a binary game tree, with each node corresponding to a subgame where the players are allowed to choose between two outcomes. We characterize novel combinatorial properties of the lexicographic maxmin solution which are crucial to the design of our mechanism.
ChainQueen: A Real-Time Differentiable Physical Simulator for Soft Robotics

Physical simulators have been widely used in robot planning and control. Among them, differentiable simulators are particularly favored, as they can be incorporated into gradient-based optimization algorithms that are efficient in solving inverse problems such as optimal control and motion planning. Therefore, rigid body simulators and recently their differentiable variants are studied extensively. Simulating deformable objects is, however, more challenging compared to rigid body dynamics. The underlying physical laws of deformable objects are more complex, and the resulting systems have orders of magnitude more degrees of freedom and there-fore they are significantly more computationally expensive to simulate. Computing gradients with respect to physical design or controller parameters is typically even more computationally challenging. In this paper, we propose a real-time, differentiable hybrid Lagrangian-Eulerian physical simulator for deformable objects, ChainQueen, based on the Moving Least Squares Material Point Method (MLS-MPM). MLS-MPM can simulate deformable objects with collisions and can be seamlessly incorporated into soft robotic systems. We demonstrate that our simulator achieves high precision in both forward simulation and backward gradient computation. We have successfully employed it in a diverse set of inference, control and co-design tasks for soft robotics.
Gene Expression Profiling Reveals Aberrant T-cell Marker Expression on Tumor Cells of Waldenström's Macroglobulinemia

Purpose: That the malignant clone of Waldenström's macroglobulinemia (WM) demonstrates significant intraclonal heterogeneity with respect to plasmacytoid differentiation indicates the mechanistic complexity of tumorigenesis and progression. Identification of WM genes by comparing different stages of B cells may provide novel druggable targets. Experimental Design: The gene expression signatures of CD19+ B cells (BC) and CD138+ plasma cells (PC) from 19 patients with WM were compared with those of BCs from peripheral blood and tonsil and to those of PCs from the marrow of healthy (N-PC) and multiple myeloma donors (MM-PC), as well as tonsil (T-PC). Flow cytometry and immunofluorescence were used to examine T-cell marker expression on WM tumor cells. Results: Consistent with defective differentiation, both BCs and PCs from WM cases expressed abnormal differentiation markers. Sets of 55 and 46 genes were differentially expressed in WM-BC and WM-PC, respectively; and 40 genes uniquely dysregulated in WM samples were identified. Dysregulated genes included cytokines, growth factor receptors, and oncogenes not previously implicated in WM or other plasma cell dyscrasias. Interestingly, strong upregulation of both IL6 and IL6R was confirmed. Supervised cluster analysis of PC revealed that marrow-derived WM-PC was either MM-PC–like or T-PC–like, but not N-PC–like. The aberrant expression of T-cell markers was confirmed at the protein level in WM-BC. Conclusions: We showed that comparative microarray profiles allowed gaining more comprehensive insights into the biology of WM. The data presented here have implications for the development of novel therapies, such as targeting aberrant T-cell markers in WM.
Current approaches to middle molecule removal: room for innovation

Abstract Aggressive removal of middle molecules or larger low-molecular-weight proteins (LMWPs) has been a growing concern following studies on their harmful effects on the mortality and morbidity of chronic dialysis patients. To remove larger LMWPs and some protein-bound uremic toxins (PBUTs), high- and medium-cutoff (HCOs and MCOs, respectively) membranes, convective therapy and protein adsorptive membranes are available. When we use HCO or MCO membranes for convective therapy, we have to take care to avoid massive albumin leakage during a dialysis session. Convection volume is an important element to increase middle molecule removal; however, a larger convection volume has a risk of larger leakage of albumin. Predilution hemodiafiltration is a useful measurement to increase larger LMWPs without massive albumin leakage. β2-microglobulin (B2M), α1-microglobulin (A1M) and albumin leakage during a dialysis session are useful parameters for assessing middle-molecule removal. Reduction ratios of B2M >80% and of A1M >35% are favorable to improve severe dialysis-related symptoms. The efficacy of middle molecule removal should be evaluated in comparison with clinical outcomes, mortality, morbidity and the improvement of dialysis-related symptoms. Recently some dialysis-related symptoms such as sleep disturbance, skin itchiness and dialysis hypotension have been recognized as good surrogate makers for mortality. Further studies to evaluate the relationship between middle molecule or PBUTs removal and the improvement of patient symptoms should be performed in well-designed randomized controlled trials.
Glycogen synthase kinase (GSK) 3 in pregnancy and parturition: a systematic review of literature

Abstract Introduction: Multiple factors and pathways have been reported as critical machineries for cell differentiation and survival during pregnancy; a number of them involve glycogen synthase kinase (GSK) 3a/β. Several reports on GSK3's functional role exist; however, the specific role of GSK3 in reproductive tissues and its contribution to normal or abnormal parturition are still unclear. To fill this knowledge gap, a systematic review of literature was conducted to better understand the functional role of GSK3 in various intrauterine tissues during implantation, pregnancy, and parturition. Methods: We conducted a systematic review of literature on GSK3's expression and function reported between 1980 and 2017 in reproductive tissues during pregnancy using three electronic databases (Web of Science, Medline, and ClinicalTrials.gov). Study selection, data extraction, quality assessment and analyses were performed in duplicate by two independent reviewers. Results: A total of 738 citations were identified; 80 were selected for full text evaluation and 25 were included for final review. GSK3's regulation and function were mostly studied in tissues and cells from placentas (12), fetuses (8), uteruses (6), and ovaries (2). GSK3 is primarily reported as a downstream responder of protein kinase B (AKT)-, Wnt-, and reactive oxygen species (ROS)-related pathways where it plays a critical role in cell survival and growth in reproductive tissues. Conclusions: Though GSK3 has been functionally linked to a number of biological processes in reproductive tissues, it has primarily been studied as a secondary signaler of various conserved cell signaling pathways. Lack of scientific rigor in studying GSK3's role in reproductive tissues makes this molecule's function still obscure. No studies have reported GSK3 in the cervix, and very few reports exist in myometrium and decidua. This systematic review suggests more functional and mechanistic studies focusing on GSK3 need to be conducted in reproductive biology.
Construction of a risk prediction model of vancomycin‐associated nephrotoxicity to be used at the time of initial therapeutic drug monitoring: A data mining analysis using a decision tree model

OBJECTIVES In our previous study, we built a risk prediction model of vancomycin (VCM)-associated nephrotoxicity using decision tree (DT) analysis. However, this has several limitations in clinical applications. Our objective here was to construct a clinically applicable risk prediction model to be used at the time of initial therapeutic drug monitoring (TDM), in patients with uncomplicated infections. METHOD A retrospective study was conducted at Hokkaido University Hospital. Subjects that had received VCM were extracted between November 2011 and April 2017. Nephrotoxicity was defined as an increase in serum creatinine of 0.5 mg/dL or 50% or higher from baseline. The additional inclusion criteria in this study were as follows: (1) the target trough level of VCM was set to 10 to 15 mg/L, and (2) the duration of therapy was 7 to 14 days. Patients were assumed to have uncomplicated infections. Risk factors for nephrotoxicity were evaluated, which could be extracted at the initial TDM. In the DT analysis, a chi-squared automatic interaction detection algorithm was constructed. RESULTS A total of 402 patients were enrolled, and 56 (13.9%) patients developed nephrotoxicity. In the DT analysis, concomitant medications (furosemide, piperacillin-tazobactam, and vasopressor drugs) and an initial VCM trough concentration ≥ 15.0 mg/L were extracted as predictive variables by which patients were divided into six subgroups. The incidence of nephrotoxicity was 5.2% to 70.0%, with subgroups classified as low to high risk of nephrotoxicity. The accuracy of DT model was favourable (87.1%). CONCLUSION We propose that the DT model built in this study is applicable to clinical practice.
Large batch size training of neural networks with adversarial training and second-order information

The most straightforward method to accelerate Stochastic Gradient Descent (SGD) computation is to distribute the randomly selected batch of inputs over multiple processors. To keep the distributed processors fully utilized requires commensurately growing the batch size. However, large batch training often leads to poorer generalization. A recently proposed solution for this problem is to use adaptive batch sizes in SGD. In this case, one starts with a small number of processes and scales the processes as training progresses. Two major challenges with this approach are (i) that dynamically resizing the cluster can add non-trivial overhead, in part since it is currently not supported, and (ii) that the overall speed up is limited by the initial phase with smaller batches. In this work, we address both challenges by developing a new adaptive batch size framework, with autoscaling based on the Ray framework. This allows very efficient elastic scaling with negligible resizing overhead (0.32\% of time for ResNet18 ImageNet training). Furthermore, we propose a new adaptive batch size training scheme using second order methods and adversarial training. These enable increasing batch sizes earlier during training, which leads to better training time. We extensively evaluate our method on Cifar-10/100, SVHN, TinyImageNet, and ImageNet datasets, using multiple neural networks, including ResNets and smaller networks such as SqueezeNext. Our method exceeds the performance of existing solutions in terms of both accuracy and the number of SGD iterations (up to 1\% and $5\times$, respectively). Importantly, this is achieved without any additional hyper-parameter tuning to tailor our method in any of these experiments.
Stability and Transport of Spent Hen-Derived ACE-Inhibitory Peptides IWHHT, IWH, and IW in Human Intestinal Caco-2 Cell Monolayers.

Ile-Trp-His-His-Thr (IWHHT), initially identified as an ACE inhibitory peptide, was shown to have antioxidant and anti-inflammatory activities in cells and blood pressure lowering activity in animals. IWHHT was degraded into IWH and IW during simulated gastrointestinal digestion. The purpose of this study was to investigate the stability, permeability, and transport pathways of IWHHT, IWH, and IW across intestinal epithelium using human intestinal Caco-2 cell monolayers. IWHHT, IWH, and IW were partly degraded by aminopeptidase N or dipeptidyl peptidase IV, but they were transported intact, with apparent permeability coefficients of (22.0 ± 1.42) × 10-8, (37.5 ± 1.11) × 10-8, and (19.6 ± 0.62) × 10-8 cm s-1, respectively. The results firstly evidenced an important role of aminopeptidase N in cleaving small ACE inhibitory peptides during transport. IWH was transported via both peptide transporter 1 (PepT1) and paracellular route, while IW was via PepT1 and IWHHT was via paracellular route only. Transport of IW implied that hydrophobic peptides (even with a small size), consisting of only highly hydrophobic amino acid residues, might not be transported via paracellular diffusion. This study suggested that all three peptides could pass through the intestinal epithelium and that the degraded IWH and IW might also contribute to the antihypertensive activity of IWHHT.
Social-emotional functioning in planned lesbian families: does biological versus non-biological mother status matter? An Italian pilot study

ABSTRACT To date, few studies have investigated the social-emotional functioning of planned lesbian families, wherein only one parent is the biological mother of the child. We examined if being a biological versus non-biological mother plays a role in planned lesbian couple functioning and mother-infant play interactions. The present study analyzes the attachment state of mind, couple alliance, parenting stress, and emotional availability in a sample of 40 mothers (20 biological and 20 non-biological). The results showed that mothers’ life-long attachment experiences and related mental states of mind, rather than biological relatedness between the parent and child, matter in a mother and child’s emotional involvement in parent-child interaction. Furthermore, the results confirmed the different impact of the perceived quality of the couple alliance on biological and non-biological mothers. The findings obtained elucidated what counts in this new family typology, and constitute a heuristic solicitation for future studies to better understand the key factors and mechanisms implied in social-emotional functioning.
Growing body of evidence supports intrauterine insemination as first line treatment and rejects unfounded concerns about its efficacy, risks and cost effectiveness

IUI has been practiced for five decades but only three unconvincing trials attempted to demonstrate the superiority of IUI over sexual intercourse (SI). In the absence of evidence of its effectiveness, the National Institute for Clinical Excellence (NICE) recommended IVF over IUI after 2 years of unprotected SI. High-quality recent data in well-constructed studies suggest that biases against IUI procedures and in favour of IVF are invalid. It is unethical to continue to misinform patients and stakeholders. The well-constructed randomised controlled trials (RCT) show IUI procedure to be efficient, with minimal risk, and above all improved cost-effectiveness when compared to IVF for live birth. IUI as first-line treatment should be offered to most patients, while funding agencies and stakeholders need to be urgently informed of the cost-benefit in offering IUI. Fertility clinics, IVF interest groups, and regulatory bodies should amend their patient information and guidance to state that IUI should be the first line treatment and that IVF should be offered only when essential. Reappraising and promoting IUI based on evidence enhances patient autonomy, choices, and trust, while allowing the fertility industry to operate within an ethical and acceptable framework not seen as exploitative toward vulnerable patients.
Genome-wide meta-analysis identifies BARX1 and EML4-MTA3 as new loci associated with infantile hypertrophic pyloric stenosis

Abstract Infantile hypertrophic pyloric stenosis (IHPS) is a disorder of young infants with a population incidence of ∼2/1000 live births, caused by hypertrophy of the pyloric sphincter smooth muscle. Reported genetic loci associated with IHPS explain only a minor proportion of IHPS risk. To identify new risk loci, we carried out a genome-wide meta-analysis on 1395 surgery-confirmed cases and 4438 controls, with replication in a set of 2427 cases and 2524 controls. We identified and replicated six independent genomic loci associated with IHPS risk at genome wide significance (P < 5 × 10−8), including novel associations with two single nucleotide polymorphisms (SNPs). One of these SNPs, rs6736913 [odds ratio (OR) = 2.32; P = 3.0 × 10−15], is a low frequency missense variant in EML4 at 2p21. The second SNP, rs1933683 (OR = 1.34; P = 3.1 × 10−9) is 1 kb downstream of BARX1 at 9q22.32, an essential gene for stomach formation in embryogenesis. Using the genome-wide complex trait analysis method, we estimated the IHPS SNP heritability to be 30%, and using the linkage disequilibrium score regression method, we found support for a previously reported genetic correlation of IHPS with lipid metabolism. By combining the largest collection of IHPS cases to date (3822 cases), with results generalized across populations of different ancestry, we elucidate novel mechanistic avenues of IHPS disease architecture.
Post-Exercise Appetite and Ad Libitum Energy Intake in Response to High-Intensity Interval Training versus Moderate- or Vigorous-Intensity Continuous Training among Physically Inactive Middle-Aged Adults

High-intensity interval training (HIIT) is considered a time-efficient exercise strategy for weight management. However, data regarding the acute appetite and energy intake responses to HIIT versus continuous training remain inconclusive. This study investigated the ad libitum energy intake and appetite responses to a single session of HIIT versus moderate-intensity continuous training (MICT) and vigorous-intensity continuous training (VICT). Using a randomized crossover design, 11 middle-aged physically inactive men (45.7 ± 7.4 years, 23.5 ± 2.1 kg m−2) participated in three treadmill trials at 7-day intervals. HIIT comprised 10 1-min periods at 100% VO2max interspersed with 1-min periods of active recovery. MICT comprised a 40-min session at 65% VO2max, while VICT comprised a 20-min session at 80% VO2max. After each trial, the participants consumed an ad libitum buffet meal for which the energy intake was recorded. The participants’ perceived appetite was assessed before and after exercise sessions using the Visual Analogue Scale (VAS). No significant differences in post-exercise ad libitum energy intake were observed between trials (HIIT: 645 ± 262.9 kcal; MICT: 614.7 ± 271.2 kcal; VICT: 623.1 ± 249.0 kcal, p > 0.05). Although the perceived appetite responses exhibited a significant main effect of time (p < 0.01), no group differences were observed (p > 0.05). In summary, these findings suggest that the interval or continuous nature of exercise has no significant effect on appetite responses in physically inactive middle-aged adults, at least during the short-term post-exercise period.
Dietary intake of anthocyanins and risk of cardiovascular disease: A systematic review and meta-analysis of prospective cohort studies

Abstract Accumulating evidence suggests flavonoid intake is associated with reduced risk of non-communicable diseases. We aimed to systematically determine and quantify the potential association between dietary anthocyanin intake and risk of cardiovascular diseases (CVD). A systematic literature search of studies reporting anthocyanin intake and risk of fatal or nonfatal CVD was performed using SCOPUS, MEDLINE, CINAHL and Cochrane Library. The relative risk (RR) or hazard ratio (HR) of highest category of anthocyanin foods were pooled in a random-effects meta-analysis. Subgroup analysis were conducted to determine possible sources of heterogeneity. The meta-analysis suggested intake of dietary anthocyanins and reduced risk of CHD (RR = 0.91, 95% CI: 0.83, 0.99; I2 = 12.0, Ph = 0.337) and CVD mortality (RR = 0.92, 95% CI: 0.87, 0.97; I2 = 0.0, Ph = 0.584). However, there was no relationship between the intake of these compounds and reduced risk of MI, stroke or total CVD. Subgroup analysis determined reduced risk of CHD and CVD mortality was more prominent for anthocyanidin intake, as opposed to anthocyanin or berries. Our systematic review and meta-analysis provides evidence that anthocyanins, specifically anthocyanidins, reduce the risk of CHD and CVD mortality. Further randomized controlled trials on anthocyanin intake and CVD risk factors are needed to support these findings.
Energy-Based Hindsight Experience Prioritization

In Hindsight Experience Replay (HER), a reinforcement learning agent is trained by treating whatever it has achieved as virtual goals. However, in previous work, the experience was replayed at random, without considering which episode might be the most valuable for learning. In this paper, we develop an energy-based framework for prioritizing hindsight experience in robotic manipulation tasks. Our approach is inspired by the work-energy principle in physics. We define a trajectory energy function as the sum of the transition energy of the target object over the trajectory. We hypothesize that replaying episodes that have high trajectory energy is more effective for reinforcement learning in robotics. To verify our hypothesis, we designed a framework for hindsight experience prioritization based on the trajectory energy of goal states. The trajectory energy function takes the potential, kinetic, and rotational energy into consideration. We evaluate our Energy-Based Prioritization (EBP) approach on four challenging robotic manipulation tasks in simulation. Our empirical results show that our proposed method surpasses state-of-the-art approaches in terms of both performance and sample-efficiency on all four tasks, without increasing computational time. A video showing experimental results is available at this https URL
Nano-sized carriers in gene therapy for renal fibrosis in vivo

ABSTRACT Renal fibrosis is the final common pathway leading to end-stage renal failure regardless of underlying initial nephropathies. No specific therapy has been established for renal fibrosis. Gene therapy is a promising strategy for the treatment of renal fibrosis. Nano-sized carriers including viral vectors and non-viral vectors have been shown to enhance the delivery and treatment effects of gene therapy for renal fibrosis in vivo. This review focuses on the mechanisms of renal fibrosis and the in vivo technologies and methodologies of nano-sized carriers in gene therapy for renal fibrosis. RESPONSIBLE EDITOR Alexander Seifalian Director of Nanotechnology & Regenerative Medicine Ltd., The London BioScience Innovation Centre, London, UNITED KINGDOM
Truncated Laplacian Mechanism for Approximate Differential Privacy

We derive a class of noise probability distributions to preserve $(\epsilon, \delta)$-differential privacy for single real-valued query function. The proposed noise distribution has a truncated exponential probability density function, which can be viewed as a truncated Laplacian distribution. We show the near-optimality of the proposed \emph{truncated Laplacian} mechanism in various privacy regimes in the context of minimizing the noise amplitude and noise power. Numeric experiments show the improvement of the truncated Laplacian mechanism over the optimal Gaussian mechanism by significantly reducing the noise amplitude and noise power in various privacy regions.