Miracle-dz/UniFAR-FTUs huggingface dataset:
Association of etiological factors across the extreme end and continuous variation in disordered eating in female Swedish twins

Abstract Background Accumulating evidence suggests that many psychiatric disorders etiologically represent the extreme end of dimensionally distributed features rather than distinct entities. The extent to which this applies to eating disorders (EDs) is unknown. Methods We investigated if there is similar etiology in (a) the continuous distribution of the Eating Disorder Inventory-2 (EDI-2), (b) the extremes of EDI-2 score, and (c) registered ED diagnoses, in 1481 female twin pairs at age 18 years (born 1992–1999). EDI-2 scores were self-reported at age 18. ED diagnoses were identified through the Swedish National Patient Register, parent-reported treatment and/or self-reported purging behavior of a frequency and duration consistent with DSM-IV criteria. We differentiated between anorexia nervosa (AN) and other EDs. Results The heritability of the EDI-2 score was 0.65 (95% CI 0.61–0.68). The group heritabilities in DeFries–Fulker extremes analyses were consistent over different percentile-based extreme groups [0.59 (95% CI 0.37–0.81) to 0.65 (95% CI 0.55–0.75)]. Similarly, the heritabilities in liability threshold models were consistent over different levels of severity. In joint categorical-continuous models, the twin-based genetic correlation was 0.52 (95% CI 0.39–0.65) between EDI-2 score and diagnoses of other EDs, and 0.26 (95% CI 0.08–0.42) between EDI-2 score and diagnoses of AN. The non-shared environmental correlations were 0.52 (95% CI 0.32–0.70) and 0.60 (95% CI 0.38–0.79), respectively. Conclusions Our findings suggest that some EDs can partly be conceptualized as the extreme manifestation of continuously distributed ED features. AN, however, might be more distinctly genetically demarcated from ED features in the general population than other EDs.
Resilience in reef‐building corals: The ecological and evolutionary importance of the host response to thermal stress

Coral reefs are under extreme threat due to a number of stressors, but temperature increases due to changing climate are the most severe. Rising ocean temperatures coupled with local extremes lead to extensive bleaching, where the coral‐algal symbiosis breaks down and corals may die, compromising the structure and function of reefs. Although the symbiotic nature of the coral colony has historically been a focus of research on coral resilience, the host itself is a foundational component in the response to thermal stress. Fixed effects in the coral host set trait baselines through evolutionary processes, acting on many loci of small effect to create mosaics of thermal tolerance across latitudes and individual coral reefs. These genomic differences can be strongly heritable, producing wide variation among clones of different genotypes or families of a specific larval cross. Phenotypic plasticity is overlaid on these baselines and a growing body of knowledge demonstrates the potential for acclimatization of reef‐building corals through a variety of mechanisms that promote resilience and stress tolerance. The long‐term persistence of coral reefs will require many of these mechanisms to adjust to warmer temperatures within a generation, bridging the gap to reproductive events that allow recombination of standing diversity and adaptive change. Business‐as‐usual climate scenarios will probably lead to the loss of some coral populations or species in the future, so the interaction between intragenerational effects and evolutionary pressure is critical for the survival of reefs.
Horizontal Gene Transfer Phylogenetics: A Random Walk Approach.

The dramatic decrease in time and cost for generating genetic sequence data has opened up vast opportunities in molecular systematics, one of which is the ability to decipher the evolutionary history of strains of a species. Under this fine systematic resolution, the standard markers are too crude to provide a phylogenetic signal. Nevertheless, among prokaryotes, genome dynamics in the form of horizontal gene transfer (HGT) between organisms and gene loss seem to provide far richer information by affecting both gene order and gene content. The synteny index (SI) between a pair of genomes combines these latter two factors, allowing comparison of genomes with unequal gene content, together with order considerations of their common genes. Although this approach is useful for classifying close relatives, no rigorous statistical modelling for it has been suggested. Such modelling is valuable, as it allows observed measures to be transformed into estimates of time periods during evolution, yielding the additivity of the measure. To the best of our knowledge, there is no other additivity proof for other gene order/content measures under HGT. Here we provide a first statistical model and analysis for the synteny index measure. We model the gene neighbourhood as a birth-death-immigration process affected by the HGT activity over the genome, and analytically relate the HGT rate and time to the expected SI. This model is asymptotic and thus provides accurate results, assuming infinite size genomes. Therefore, we also developed a heuristic model following an exponential decay function, accounting for biologically realistic values, which performed well in simulations. Applying this model to 1133 prokaryotes partitioned to 39 clusters by the rank of genus, yields that the average number of genome dynamics events per gene in the phylogenetic depth of genus, is around half with significant variability between genera. This result extends and confirms similar results obtained for individual genera in different manners.
Progression of Investigation in the Treatment of Tinnitus with TCM

Tinnitus is one kind of clinical common symptom,of which cause is complex,less understanding of its mechanism.Although there are many western medicine for the treatment of tinnitus,no one recognized by the medical profession has the exact effect of the treatment.Chinese medicine treatment of tinnitus has certain advantages.Accordingly,advances in the research of tinnitus in recent years are summarized in etiopathogenisis,pathogenesis and the advancement of treatment.
The Anti-CD38 Antibody Therapy in Multiple Myeloma

Multiple myeloma (MM) is the second-most common hematologic malignancy after diffuse large B-cell lymphoma. Despite the improvement in response and survival rates following the introduction of novel therapies, only a few patients are cured, and the majority of MM patients experience several relapses and receive multiple lines of treatment. Currently, bortezomib and lenalidomide are the core component of treatment both at the time of diagnosis and at the relapse as well as the new proteasome inhibitors (PIs), such as carfilzomib and ixazomib, and the next-generation immunomodulatory drug, pomalidomide, are now available for patients in relapse. In addition, drugs with a different mechanism of action, such as the histone deacetylase inhibitor and the monoclonal antibodies (MoAb) targeting SLAMF7 or CD38, are a part of the anti-myeloma armamentarium and are very important for heavily pretreated or double refractory to a PI and IMiD patients. In this paper, we focus on the efficacy as well as toxicities of CD38 antibodies used both as a single agent and in combination as multiple myeloma treatment.
The relative risk of noncervical high‐risk human papillomavirus‐related (pre)malignancies after recurrent cervical intraepithelial neoplasia grade 3: A population‐based study

Women with cervical intraepithelial neoplasia grade 3 (CIN3) have a long‐lasting increased risk for noncervical high‐risk human papillomavirus (hrHPV)‐related (pre)malignancies. The aim of our study was to estimate this risk in women with recurrent CIN3 compared to women without a history of CIN3 and women with a single episode of CIN3. Women with a CIN3 diagnosis between 1990 and 2010 were obtained from the Dutch Pathology Registry (PALGA) and matched with a control group of women without CIN3. Analysis has been conducted in a subset of women with recurrent CIN3, defined as reoccurrence minimally 2 years post‐treatment. Cases of noncervical hrHPV‐related (pre)malignancies of the anus, vulva, vagina and oropharynx were identified until 2015 and incidence rate ratios (IRRs) were estimated. Then, 1,797 women with recurrent CIN3 were included with a median age of 34 years (range 18–76) and 31,594 person‐years of follow‐up. Women with recurrent CIN3 had an increased risk of developing noncervical hrHPV‐related (pre)malignancies compared to women without CIN3 with an IRR of 25.96 (95%CI 6.32–106.58). The IRR was 2.48 (95% CI 1.87–3.30) compared to women with a single episode of CIN3. Studies on posttreatment follow‐up and prophylactic hrHPV vaccination are warranted.
Immuno-metabolic profile of human macrophages after Leishmania and Trypanosoma cruzi infection

Macrophages can reprogram their metabolism in response to the surrounding stimuli, which affects their capacity to kill intracellular pathogens. We have investigated the metabolic and immune status of human macrophages after infection with the intracellular trypanosomatid parasites Leishmania donovani, L. amazonensis and T. cruzi and their capacity to respond to a classical polarizing stimulus (LPS and IFN-γ). We found that macrophages infected with Leishmania preferentially upregulate oxidative phosphorylation, which could be contributed by both host cell and parasite, while T. cruzi infection did not significantly increase glycolysis or oxidative phosphorylation. Leishmania and T. cruzi infect macrophages without triggering a strong inflammatory cytokine response, but infection does not prevent a potent response to LPS and IFN-γ. Infection appears to prime macrophages, since the cytokine response to activation with LPS and IFN-γ is more intense in infected macrophages compared to uninfected ones. Metabolic polarization in macrophages can influence infection and immune evasion of these parasites since preventing macrophage cytokine responses would help parasites to establish a persistent infection. However, macrophages remain responsive to classical inflammatory stimuli and could still trigger inflammatory cytokine secretion by macrophages.
Ion Binding and Selectivity of the Na+/H+ Antiporter MjNhaP1 from Experiment and Simulation

Cells employ membrane-embedded antiporter proteins to control their pH, salt concentration, and volume. The large family of cation/proton antiporters is dominated by Na+/H+ antiporters that exchange sodium ions against protons, but homologous K+/H+ exchangers have recently been characterized. We show experimentally that the electroneutral antiporter NhaP1 of Methanocaldococcus jannaschii (MjNhaP1) is highly selective for Na+ ions. We then characterize the ion selectivity in both the inward-open and outward-open states of MjNhaP1 using classical molecular dynamics simulations, free energy calculations, and hybrid quantum/classical (QM/MM) simulations. We show that MjNhaP1 is highly selective for binding of Na+ over K+ in the inward-open state, yet it is only weakly selective in the outward-open state. These findings are consistent with the function of MjNhaP1 as a sodium-driven deacidifier of the cytosol that maintains a high cytosolic K+ concentration in environments of high salinity. By combining experiment and computation, we gain mechanistic insight into the Na+/H+ transport mechanism and help elucidate the molecular basis for ion selectivity in cation/proton exchangers.
Endogenous Toll-like Receptor 2 Modulates Th1/Treg-Promoting Dendritic Cells in Mice Corneal Transplantation Model

ABSTRACT Purpose Endogenous toll-like receptor (TLR) 2 is linked to allograft rejection in corneal transplantation. TLR2 also could modulate dendritic cell (DC) phenotype, resulting in T cell polarization. Thus, we investigated the role of endogenous TLR2 on DC development and T cell polarization during corneal rejection. Materials and Methods Corneas of BALB/c mice were transplanted into the eyes of C57BL/6 wild-type (WT) recipients and TLR2−/- (KO) recipients. Graft survival and TLR2 mRNA expression were assessed. At day 14 after transplantation, to study endogenous TLR2 effects on DC development and function, surface expression of MHC classⅡ (MHCⅡ), CD86, CD80 and CD40 in ipsilateral cervical draining lymph nodes (DLNs) is measured by flow cytometry, and DC phenotype in corneas is detected by immunofluorescence. The levels of IL-12, IL-10 and IL-4 in corneas were measured by real time-qPCR (RT-qPCR). The ability of DCs to stimulate T cell polarization was assessed by IFN-γ expressions via RT-qPCR and immunohistochemistry. Results TLR2 mRNA expression in corneas was peaked at day 14 post-transplantation in WT group. KO group improved corneal allograft survival compared to the WT group. In addition, the KO group decreased expression of CD86, CD80 and CD40 on DCs compared to the WT group. There was no difference in MHCⅡ expression in two groups. The CD11c+MHCⅡ+CD40high DCs could not be detected in corneas of the KO group. Moreover, the KO group decreased IL-12 (Th1-promoting cytokines) mRNA expression and increasing IL-10 (Treg-promoting cytokines) mRNA expression compared to the WT group. IL-4 (Th2-promoting cytokines) mRNA expression gained no difference between the two groups. The IFN-γ (Th1 cytokines) expression was significantly decreased in the KO group compared to the WT group. Conclusions Endogenous TLR2 may contribute to allogeneic corneal rejection via Th1 immunity by activating Th1-promoting DCs and suppressing Treg-promoting DCs.
Leader-Following Consensus and Formation Control of VTOL-UAVs with Event-Triggered Communications †

This article presents the design and implementation of an event-triggered control approach, applied to the leader-following consensus and formation of a group of autonomous micro-aircraft with capabilities of vertical take-off and landing (VTOL-UAVs). The control strategy is based on an inner–outer loop control approach. The inner control law stabilizes the attitude and position of one agent, whereas the outer control follows a virtual leader to achieve position consensus cooperatively through an event-triggered policy. The communication topology uses undirected and connected graphs. With such an event-triggered control, the closed-loop trajectories converge to a compact sphere, centered in the origin of the error space. Furthermore, the minimal inter-sampling time is proven to be below bounded avoiding the Zeno behavior. The formation problem addresses the group of agents to fly in a given shape configuration. The simulation and experimental results highlight the performance of the proposed control strategy.
Evaluation of an automated point-of-care test system for measuring thrombin-antithrombin complex in dogs.

OBJECTIVE To evaluate the utility of the chemiluminescent enzyme immunoassay (CLEIA) method for point-of-care (POC) measurement of canine plasma thrombin-antithrombin complex (TAT) concentration. ASSESSMENT AND MAIN RESULTS Plasma TAT concentration was measured in 54 healthy dogs and in 72 dogs with various diseases. A significant correlation was found between TAT concentration measured by CLEIA and that measured by an ELISA that was previously used in dogs. The upper limit of the reference value of TAT concentrations measured by CLEIA was determined to be 0.2 ng/mL based on the TAT concentration in 54 healthy dogs. TAT concentrations exceeded the reference interval in a portion of dogs when a hypercoagulable state may be present. CONCLUSIONS Canine plasma TAT concentrations measured using CLEIA were correlated with that measured using ELISA. Hence, a POC testing instrument may be used for early detection of activation of thrombin generation in emergency and critical care settings.
Adaptive PI Control for Consensus of Multiagent Systems With Relative State Saturation Constraints

The relative state between neighbors represents the difference of two connected agents’ states, and it possesses specific physical meanings in practice. Under this background, the saturation constraints in the relative state inevitably occur. This article studies the consensus problems under the relative state saturation constraints. Novel adaptive proportional–integral (PI) protocols are designed to solve the constrained consensus problem. Specifically, the adaptive coupling weights and the saturation functions are embedded into the proposed protocols, and the former can render the protocols independent of any global topology graph information, while the latter can confine the relative state to stay in its constrained set. Sufficient conditions are identified under which the constrained consensus can be achieved. Considering that the solution matrix is required to be diagonally dominant, an iterative learning-based heuristic algorithm is proposed to seek the diagonally dominant positive-definite solution matrix. For the special case that the input matrix is row full rank, more stringent saturation functions are constructed, and it not only achieves the constrained consensus but also realizes the nonovershoot and shorter settling time associated with edge states. Besides, this result can be applied to preserve connectivity of the communication network. The theoretical analyses are validated by a simulation example.
Association between religiosity and depression varies with age and sex among adults in South America: Evidence from the CESCAS I study

Prior studies have suggest that religiosity mitigates symptoms of depression. However, population-based data in South America are limited. This study determines the prevalence of religiosity and explores its association with depression in four cities of the Southern cone of Latin-America. In the CESCAS I study 7524 participants aged between 35 and 74 years old were recruited between 2011 and 2012 from randomly selected samples in 4 cities (Bariloche and Marcos Paz, Argentina; Temuco, Chile; and Pando-Barros Blancos, Uruguay). Religiosity was assessed with a questionnaire from the Hispanic Community Health Study/Study of Latinos. Two dimensions were used: 1) recognition as belonging to a religion; and 2) frequency of participation in religious activities. Depression was measured using the PHQ-9. Prevalence of religiosity was described by sociodemographic characteristics. Association between religiosity and depression was examined through logistic regression models controlling for sex, age and other potential confounders. Weekly religious activities were reported by 32.3% (95% CI: 30.1, 33.6) of participants. Prevalence of major depressive episode (MDE) was 14.6% (95% CI: 13.6, 15.6). After controlling for confounders, older women (≥65 years) who reported religious affiliation had 70% lower likelihood of having MDE (OR: 0.3; 95% CI, 0.1, 0.8). Moreover, in this group, women participating in religious activities more than once per week compared with “never” had 50% lower likelihood of having a MDE (OR: 0.5; 95% CI: 0.3, 0.9). No association between religious activities and depression was found in men. Religiosity is highly prevalent among adults in four cities of South America. Our study found an inverse association between religiosity and depression only in women, stronger in olders. Although longitudinal studies are necessary to determine the true nature of these relationships, religiosity may be a relevant factor that health care providers could take into account when exploring depression in their patients.
From Rank Estimation to Rank Approximation: Rank Residual Constraint for Image Restoration

In this paper, we propose a novel approach to the rank minimization problem, termed rank residual constraint (RRC) model. Different from existing low-rank based approaches, such as the well-known nuclear norm minimization (NNM) and the weighted nuclear norm minimization (WNNM), which estimate the underlying low-rank matrix directly from the corrupted observations, we progressively approximate the underlying low-rank matrix via minimizing the rank residual. Through integrating the image nonlocal self-similarity (NSS) prior with the proposed RRC model, we apply it to image restoration tasks, including image denoising and image compression artifacts reduction. Towards this end, we first obtain a good reference of the original image groups by using the image NSS prior, and then the rank residual of the image groups between this reference and the degraded image is minimized to achieve a better estimate to the desired image. In this manner, both the reference and the estimated image are updated gradually and jointly in each iteration. Based on the group-based sparse representation model, we further provide an analytical investigation on the feasibility of the proposed RRC model. Experimental results demonstrate that the proposed RRC method outperforms many state-of-the-art schemes in both the objective and perceptual quality.
Ivosidenib induces deep durable remissions in patients with newly diagnosed IDH1-mutant acute myeloid leukemia.

Ivosidenib (AG-120) is an oral, targeted agent that suppresses production of the oncometabolite 2-hydroxyglutarate via inhibition of the mutant isocitrate dehydrogenase 1 (mIDH1) enzyme. From a phase 1 study of 258 patients with IDH1-mutant advanced hematologic malignancies, we report results for 34 patients with newly diagnosed acute myeloid leukemia (AML) ineligible for standard therapy who received ivosidenib 500 mg once daily. Median age was 76.5 years, 26 (76%) patients had secondary AML and 16 (47%) had received {greater than or equal to}1 hypomethylating agent for an antecedent hematologic disorder. The most common all-grade adverse events were diarrhea (n=18; 53%), fatigue (n=16; 47%), nausea (n=13; 38%), and decreased appetite (n=12; 35%). Differentiation syndrome was reported in 6 (18%) patients (grade {greater than or equal to}3 in 3 [9%]) and did not require treatment discontinuation. Complete remission (CR) + CR with partial hematologic recovery (CRh) rate was 42.4% (95% confidence interval [CI], 25.5-60.8%); CR rate was 30.3% (95% CI, 15.6-48.7%). Median durations of CR+CRh and CR were not reached, with 95% CI lower bounds of 4.6 and 4.2 months, respectively; 61.5% and 77.8% of patients remained in remission at 1 year. With median follow-up of 23.5 months (range, 0.6-40.9), median overall survival was 12.6 months (95% CI, 4.5-25.7). Of 21 (63.6%) patients who were transfusion dependent at baseline, 9 (42.9%) became transfusion independent. IDH1 mutation clearance was seen in 9/14 patients achieving CR+CRh (5/10 CR, 4/4 CRh). Ivosidenib monotherapy was well tolerated and induced durable remissions and transfusion independence in patients with newly diagnosed AML. (Trial registered at www.clinicaltrials.gov #NCT02074839.).