Miracle-dz/UniFAR-FTUs huggingface dataset:
Mixed chimerism and acceptance of kidney transplants after immunosuppressive drug withdrawal

Persistent mixed chimerism protects against rejection of HLA-matched and mismatched kidney transplants without graft-versus-host disease. Staving off immunosuppression Kidney transplant recipients are continually at risk of rejection despite intense immunosuppressive regimens that can have detrimental side effects. Busque et al. conducted kidney transplants with a selected composition of donor hematopoietic cells to attempt to evade graft-versus-host disease. They monitored mixed chimerism, defined as at least 1% of circulating cells being of donor origin, and kidney graft health. Most patients in the fully human leukocyte antigen (HLA)–matched cohort experienced persistent chimerism and no rejection episodes after removal of immunosuppressive drugs. Persistent chimerism was less prevalent in a partially HLA-matched cohort, and long-term withdrawal of immunosuppressants was not feasible in these patients. These findings indicate that methods to promote mixed chimerism may improve kidney transplant outcomes. Preclinical studies have shown that persistent mixed chimerism is linked to acceptance of organ allografts without immunosuppressive (IS) drugs. Mixed chimerism refers to continued mixing of donor and recipient hematopoietic cells in recipient tissues after transplantation of donor cells. To determine whether persistent mixed chimerism and tolerance can be established in patients undergoing living donor kidney transplantation, we infused allograft recipients with donor T cells and hematopoietic progenitors after posttransplant lymphoid irradiation. In 24 of 29 fully human leukocyte antigen (HLA)–matched patients who had persistent mixed chimerism for at least 6 months, complete IS drug withdrawal was achieved without subsequent evidence of rejection for at least 2 years. In 10 of 22 HLA haplotype–matched patients with persistent mixed chimerism for at least 12 months, reduction of IS drugs to tacrolimus monotherapy was achieved. Withdrawal of tacrolimus during the second year resulted in loss of detectable chimerism and subsequent rejection episodes, unless tacrolimus therapy was reinstituted. Posttransplant immune reconstitution of naïve B cells and B cell precursors was more rapid than the reconstitution of naïve T cells and thymic T cell precursors. Robust chimerism was observed only among naïve T and B cells but not among memory T cells. No evidence of rejection was observed in all surveillance graft biopsies obtained from mixed chimeric patients withdrawn from IS drugs, and none developed graft-versus-host disease. In conclusion, persistent mixed chimerism established in fully HLA- or haplotype-matched patients allowed for complete or partial IS drug withdrawal without rejection.
Genome wide association study of incomplete hippocampal inversion in adolescents

Incomplete hippocampal inversion (IHI), also called hippocampal malrotation, is an atypical presentation of the hippocampus present in about 20% of healthy individuals. Here we conducted the first genome-wide association study (GWAS) in IHI to elucidate the genetic underpinnings that may contribute to the incomplete inversion during brain development. A total of 1381 subjects contributed to the discovery cohort obtained from the IMAGEN database. The incidence rate of IHI was 26.1%. Loci with P<1e-5 were followed up in a validation cohort comprising 161 subjects from the PING study. Summary statistics from the discovery cohort were used to compute IHI heritability as well as genetic correlations with other traits. A locus on 18q11.2 (rs9952569; OR = 1.999; Z = 5.502; P = 3.755e-8) showed a significant association with the presence of IHI. A functional annotation of the locus implicated genes AQP4 and KCTD1. However, neither this locus nor the other 16 suggestive loci reached a significant p-value in the validation cohort. The h2 estimate was 0.54 (sd: 0.30) and was significant (Z = 1.8; P = 0.036). The top three genetic correlations of IHI were with traits representing either intelligence or education attainment and reached nominal P< = 0.013.
Computer-Aided Diagnosis of Skin Cancer: A Review.

Cancer is currently one of the main health issues in the world. Among different varieties of cancers, skin cancer is the most common cancer in the world and accounts for 75% of the world's cancer. Indeed, skin cancer involves abnormal changes in the outer layer of the skin. Although most people with skin cancer are healed, it is one of the major concerns of people due to its high prevalence. Most types of skin cancers grow only locally and invade adjacent tissues, but some of them, especially melanoma (cancer of the pigment cells), which is the rarest type of skin cancer, may spread through the circulatory system or lymphatic system and reach the farthest points of the body. Many papers have been reviewed about the application of image processing in cancer detection. In this paper, a literature review on the automatic skin cancer detection and also different steps of such a are discussed process based on the implantation capabilities.
Mechanisms of physical activity behavior change in an incentive-based intervention: Mediation analysis.

OBJECTIVE The physical activity loyalty (PAL) scheme was a cluster randomized controlled trial of a 6-month complex intervention targeting workplace physical activity. Financial incentives were incorporated in an evidence-based behavior change program, including self-regulation techniques. This article examines short-term (< 6 months) and long-term (≥ 6 months) mediation effects on physical activity. METHOD Participants included 853 adults (457 intervention, 396 control). Physical activity was objectively assessed using pedometers at baseline and at 6 and 12 months. Hypothesized short-term mediators (e.g., self-efficacy, intentions) were assessed at baseline and 4 weeks. Hypothesized long-term mediators (e.g., habit, intrinsic motivation) were assessed at baseline and 6 months. Mediation models employed the structural equation modeling product-of-coefficients approach. RESULTS Intervention participants experienced significant decreases in 6-month pedometer steps/day versus controls (b = -336, p = .02), which were partially mitigated by positive indirect effects through 6-month integrated regulation (ab = 94.7, 95% CI [18.7, 204.4]), intrinsic motivation (ab = 59.0, 95% CI [3.09, 154.5]), and habit (ab = 198.7, 95% CI [84.3, 369.9]). There were no between-groups differences in 12-month pedometer steps/day but positive indirect effects through 6-month integrated regulation (ab = 128.0, 95% CI [27.3, 313.2]), planning (ab = 115.0, 95% CI [3.71, 285.5]), and habit (ab = 153.3, 95% CI [39.3, 333.1]). CONCLUSIONS Most examined mediators were nonsignificant, and mediation analyses did not explain decreases in physical activity for interventions versus controls. Results show that, contrary to self-determination theory hypotheses, intrinsic motivation is not necessarily adversely impacted if financial incentives are embedded in a complex intervention. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
MODER2: first-order Markov modeling and discovery of monomeric and dimeric binding motifs

Abstract Motivation Position-specific probability matrices (PPMs, also called position-specific weight matrices) have been the dominating model for transcription factor (TF)-binding motifs in DNA. There is, however, increasing recent evidence of better performance of higher order models such as Markov models of order one, also called adjacent dinucleotide matrices (ADMs). ADMs can model dependencies between adjacent nucleotides, unlike PPMs. A modeling technique and software tool that would estimate such models simultaneously both for monomers and their dimers have been missing. Results We present an ADM-based mixture model for monomeric and dimeric TF-binding motifs and an expectation maximization algorithm MODER2 for learning such models from training data and seeds. The model is a mixture that includes monomers and dimers, built from the monomers, with a description of the dimeric structure (spacing, orientation). The technique is modular, meaning that the co-operative effect of dimerization is made explicit by evaluating the difference between expected and observed models. The model is validated using HT-SELEX and generated datasets, and by comparing to some earlier PPM and ADM techniques. The ADM models explain data slightly better than PPM models for 314 tested TFs (or their DNA-binding domains) from four families (bHLH, bZIP, ETS and Homeodomain), the ADM mixture models by MODER2 being the best on average. Availability and implementation Software implementation is available from https://github.com/jttoivon/moder2. Supplementary information Supplementary data are available at Bioinformatics online.
Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia

Abstract Background The initial cases of novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the first 425 confirmed cases in Wuhan to determine the epidemiologic characteristics of NCIP. Methods We collected information on demographic characteristics, exposure history, and illness timelines of laboratory-confirmed cases of NCIP that had been reported by January 22, 2020. We described characteristics of the cases and estimated the key epidemiologic time-delay distributions. In the early period of exponential growth, we estimated the epidemic doubling time and the basic reproductive number. Results Among the first 425 patients with confirmed NCIP, the median age was 59 years and 56% were male. The majority of cases (55%) with onset before January 1, 2020, were linked to the Huanan Seafood Wholesale Market, as compared with 8.6% of the subsequent cases. The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days. In its early stages, the epidemic doubled in size every 7.4 days. With a mean serial interval of 7.5 days (95% CI, 5.3 to 19), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9). Conclusions On the basis of this information, there is evidence that human-to-human transmission has occurred among close contacts since the middle of December 2019. Considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere. Measures to prevent or reduce transmission should be implemented in populations at risk. (Funded by the Ministry of Science and Technology of China and others.)
Epigenetic Heterogeneity and Mitotic Heritability Prime Endothelial Cell Gene Induction

Key Points VCAM1 is heterogeneously expressed in endothelial cells after TNF-α induction. Heterogeneous VCAM1 promoter DNA methylation is mitotically heritable. Heterogeneity in cytokine responsiveness occurs in many endothelial genes. Homogeneous populations of mature differentiated primary cell types can display variable responsiveness to extracellular stimuli, although little is known about the underlying mechanisms that govern such heterogeneity at the level of gene expression. In this article, we show that morphologically homogenous human endothelial cells exhibit heterogeneous expression of VCAM1 after TNF-α stimulation. Variability in VCAM1 expression was not due to stochasticity of intracellular signal transduction but rather to preexisting established heterogeneous states of promoter DNA methylation that were generationally conserved through mitosis. Variability in DNA methylation of the VCAM1 promoter resulted in graded RelA/p65 and RNA polymerase II binding that gave rise to a distribution of VCAM1 transcription in the population after TNF-α stimulation. Microarray analysis and single-cell RNA sequencing revealed that a number of cytokine-inducible genes shared this heterogeneous response pattern. These results show that heritable epigenetic heterogeneity is fundamental in inflammatory signaling and highlight VCAM1 as a metastable epiallele.
Multiple Mittag-Leffler Stability of Delayed Fractional-Order Cohen–Grossberg Neural Networks via Mixed Monotone Operator Pair

This article mainly investigates the multiple Mittag-Leffler stability of delayed fractional-order Cohen–Grossberg neural networks with time-varying delays. By using mixed monotone operator pair, the conditions of the coexistence of multiple equilibrium points are obtained for fractional-order Cohen–Grossberg neural networks, and these conditions are eventually transformed into algebraic inequalities based on the vertex of the divided region. In particular, when the symbols of these inequalities are determined by the dominant term, several verifiable corollaries are given. And then, the sufficient conditions of the Mittag-Leffler stability are derived for fractional-order Cohen–Grossberg neural networks with time-varying delays. In addition, two numerical examples are provided to illustrate the effectiveness of the theoretical results.
Deep vein thrombosis in the lower extremities after femoral neck fracture: A retrospective observational study

Purpose: The actual incidence of deep vein thrombosis (DVT) in femoral neck fractures is underestimated. This study aimed to investigate the incidence of DVT in the lower extremities after femoral neck fracture before and after operation. Methods: The clinical data of patients with femoral neck fractures treated at Xi’an Honghui Hospital between July 1, 2016, and December 31, 2018, were collected. The patients were examined with ultrasonography before and after operation and divided into thrombosis and non-thrombosis groups according to their ultrasonographic results. The incidence of DVT was reported as a percentage. Results: The incidence rates of preoperative and postoperative DVT were 32% and 56%, respectively. DVT on the uninjured side constituted 45% of all preoperative DVT and 43% of all postoperative DVT. Peripheral DVT constituted 90% and 84% of all preoperative and postoperative DVT, respectively. Diabetes was an independent risk factor of preoperative DVT. Blood loss was an independent risk factor of postoperative DVT, and open reduction and internal fixation surgical procedure was independent protective factor of postoperative DVT as compared with hemiarthroplasty and total hip replacement. Conclusions: The incidence rates of preoperative and postoperative DVT in the patients with femoral neck fracture were high, and orthopedists should pay more attention to DVT as a complication.
Is telehealthcare for heart failure patients cost-effective? An economic evaluation alongside the Danish TeleCare North heart failure trial

Objective This study aimed to assess the cost-effectiveness of telehealthcare in heart failure patients as add-on to usual care. Design A cost-utility analysis was conducted from a public payer perspective alongside the randomised controlled TeleCare North trial. Setting The North Denmark Region, Denmark. Participants The study included 274 heart failure patients with self-reported New York Heart Association class II-IV. Interventions Patients in the intervention group were provided with a Telekit consisting of a tablet, a digital blood pressure monitor, and a scale and were instructed to perform measurements one to two times a week. The responsibility of the education, instructions and monitoring of the heart failure (HF) patients was placed on municipality nurses trained in HF and telemonitoring. Both groups received usual care. Outcome measures Cost-effectiveness was reported as incremental net monetary benefit (NMB). A micro-costing approach was applied to evaluate the derived savings in the first year in the public health sector. Quality-adjusted life-years (QALY) gained were estimated using the EuroQol 5-Dimensions 5-Levels questionnaire at baseline and at a 1-year follow-up. Results Data for 274 patients were included in the main analysis. The telehealthcare solution provided a positive incremental NMB of £5164. The 1-year adjusted QALY difference between the telehealthcare solution and the usual care group was 0.0034 (95% CI: −0.0711 to 0.0780). The adjusted difference in costs was -£5096 (95% CI: −8736 to −1456) corresponding to a reduction in total healthcare costs by 35%. All sensitivity analyses showed the main results were robust. Conclusions The TeleCare North solution for monitoring HF was highly cost-effective. There were significant cost savings on hospitalisations, primary care contacts and total costs. Trial registration number ClinicalTrials.gov: NCT02860013.
The Role of Nanoparticle Shapes and Structures in Material Characterisation of Polyvinyl Alcohol (PVA) Bionanocomposite Films

Three different types of nanoparticles, 1D Cloisite 30B clay nanoplatelets, 2D halloysite nanotubes (HNTs), and 3D nanobamboo charcoals (NBCs) were employed to investigate the impact of nanoparticle shapes and structures on the material performance of polyvinyl alcohol (PVA) bionanocomposite films in terms of their mechanical and thermal properties, morphological structures, and nanomechanical behaviour. The overall results revealed the superior reinforcement efficiency of NBCs to Cloisite 30B clays and HNTs, owing to their typical porous structures to actively interact with PVA matrices in the combined formation of strong mechanical and hydrogen bondings. Three-dimensional NBCs also achieved better nanoparticle dispersibility when compared with 1D Cloisite 30B clays and 2D HNTs along with higher thermal stability, which was attributed to their larger interfacial regions when characterised for the nanomechanical behaviour of corresponding bionanocomposite films. Our study offers an insightful guidance to the appropriate selection of nanoparticles as effective reinforcements and the further sophisticated design of bionanocomposite materials.
Antibacterial activity of chlorogenic acid-loaded SiO2 nanoparticles caused by accumulation of reactive oxygen species

Diseases caused by pathogenic bacilli pose an increasing threat to human health. A common feature of these bacteria is a complete cell wall; therefore, drugs that can penetrate this protective barrier could be used as a novel approach for treating these infections. Here we present a simple method for synthesizing a silica mesoporous material loaded with cadmium selenide (CdSe) and chlorogenic acid. Using UV–visible, fluorescence, and infrared imaging in combination with transmission electron microscopy, it was shown that CdSe and chlorogenic acid could be successfully embedded in the mesopores of silica nanoparticles (CSC NPs), and these NPs presented with a strong fluorescence, uniform size, and good dispersion. Additionally, the results of these analyses indicated that the fluorescence of the CSC NPs was localized within the cells of Escherichia coli and Bacillus subtilis, signifying that these NPs could breach the cell wall and enter the cells of these two bacilli. Additional assessments found that these CSC NPs inhibited the proliferation of the bacteria by disrupting the cell wall, and this was most likely due to the overproduction of reactive oxygen species induced by chlorogenic acid. Importantly, histopathology analysis indicated that the CSC NPs had limited side effects and high biocompatibility.
Polygenic score for neuroticism is related to sleep difficulties

Neuroticism, a broad trait measure of the tendency to experience negative emotions and vulnerability to stress, is consistently related to poor sleep quality. Less is known about potential pleiotropy in the genetic risk for high neuroticism and poor sleep. Therefore, the present study examined whether polygenic score (PGS) for neuroticism is related to sleep quality in two large samples of adults. In addition, depressive symptoms, anxiety and phenotypical neuroticism were tested as mediators in both samples. Participants were 8316 individuals aged from 50 to 101 years (mean age = 68.29, SD = 9.83) from the Health and Retirement Study, and 4973 individuals aged from 63 to 67 years (mean age = 64.30, SD = 0.68) from the Wisconsin Longitudinal Study. Participants from both samples were genotyped and answered questions on sleep quality. A higher PGS for neuroticism was related to lower sleep quality concurrently and over time in both samples. Anxiety, depressive symptoms and neuroticism mediated these relationships in the two samples. Although effect sizes were small, the present study provides replicable evidence that individuals with a higher genetic predisposition to experience negative emotions and distress are at risk of sleep difficulties.
Prediction of Freezing of Gait in Patients With Parkinson’s Disease by Identifying Impaired Gait Patterns

Freezing of gait (FoG) prediction, combined with rhythmic laser cues, may help Parkinson’s disease (PD) patients overcome FoG episodes. This study aimed to utilize the impaired gait patterns preceding FoG to build a machine-learning-based model for FoG prediction. Acceleration signals were collected using an accelerometer attached to the lower back of 12 PD patients with FoG while they were performing designed FoG-provoking walking tasks. Step-based impaired gait features and conventional FoG detection features were extracted from the signals, based on which two FoG prediction models were built using AdaBoost to validate if the use of the impaired gait features can better predict FoG. For the correct labeling of the gait prior to FoG (pre-FoG), the personalized pre-FoG phase was defined according to the slope of the impaired gait pattern. The impaired gait features were relabeled based on the pre-FoG phase upon which the personalized labeled FoG prediction model was built. This was compared with the model built using unified labeling. Results showed that impaired gait features could better predict FoG than conventional FoG detection features with low time latency, and personalized labeling could further improve the FoG prediction accuracy. Using impaired gait features and personalized labeling, we built a FoG prediction model with 0.93 sec of latency. Compared to using conventional features and unified labeling, our model achieved 5.7% higher accuracy (82.7%) in patient-dependent test and 9.8% higher accuracy (77.9%) in patient-independent test. Therefore, using the impaired gait patterns is a promising approach to accurately predict FoG with low latency.
Ultrafast Spectroscopy of [Mn(CO)3] Complexes: Tuning the Kinetics of Light-Driven CO Release and Solvent Binding.

Manganese tricarbonyl complexes are promising catalysts for CO2 reduction, but complexes in this family are often photosensitive and decompose rapidly upon exposure to visible light. In this report, synthetic and photochemical studies probe the initial steps of light-driven speciation for Mn(CO)3(Rbpy)Br complexes bearing a range of 4,4'-disubstituted 2,2'-bipyridyl ligands (Rbpy, where R = tBu, H, CF3, NO2). Transient absorption spectroscopy measurements for Mn(CO)3(Rbpy)Br coordination compounds with R = tBu, H, and CF3 in acetonitrile reveal ultrafast loss of a CO ligand on the femtosecond time scale, followed by solvent coordination on the picosecond time scale. The Mn(CO)3(NO2bpy)Br complex is unique among the four compounds in having a longer-lived excited state that does not undergo CO release or subsequent solvent coordination. The kinetics of photolysis and solvent coordination for light-sensitive complexes depend on the electronic properties of the disubstituted bipyridyl ligand. The results indicate that both metal-to-ligand charge-transfer (MLCT) and dissociative ligand-field (d-d) excited states play a role in the ultrafast photochemistry. Taken together, the findings suggest that more robust catalysts could be prepared with appropriately designed complexes that avoid crossing between the excited states that drive photochemical CO loss.