Miracle-dz/UniFAR-FTUs huggingface dataset:
Stabilization of Foxp3 by Targeting JAK2 Enhances Efficacy of CD8 Induced Regulatory T Cells in the Prevention of Graft-versus-Host Disease

CD8+ induced regulatory T cells (iTregs) have been identified to suppress alloreactive immune responses and expressed regulatory T cell (Treg) ontological markers as similar as CD4+ iTregs. However, adoptive transfer of CD8+ iTreg–based therapy is hampered by the instability of Treg specific-transcription factor, Foxp3. As CD8+ iTregs were previously demonstrated to possess superior tumor-killing ability to CD4+ iTregs, adoptive transfer of stabilized CD8+ iTregs would be a potential therapy to prevent tumor relapse during graft-versus-leukemia disease (GVHD) treatment. In the current study, we generated alloantigen reactive CD8+ iTregs from JAK2−/− T cells and adoptively transferred them to MHC-mismatched and haploidentical murine models of allogeneic bone marrow transplantation. JAK2−/− CD8+ iTregs not only attenuated GVHD but also preserved graft-versus-leukemia effect. Mechanistic analysis revealed that JAK2−/− CD8+ iTregs upregulated natural Treg marker (neuropilin-1), and augmented DNA demethylation of CNS2 region within Foxp3 gene. These properties licensed JAK2−/− CD8+ iTregs to retain high Foxp3 expression resulting in less conversion to type 1 CTLs; as a result, JAK2−/− CD8+ iTregs were able to maintain their suppressive and cytolytic function. Thus, our findings provide a strong rationale and means to stabilize CD8+ iTregs by targeting JAK2, and the stabilized CD8+ iTregs exhibit therapeutic potential for alleviating GVHD and preserving the graft-versus-leukemia effect.
Retinoblastoma in Sub-Saharan Africa: Case Studies of the Republic of Côte d’Ivoire and the Democratic Republic of the Congo

Purpose In most low-income countries, the diagnosis of retinoblastoma is delayed, resulting in a severe prognosis. The objectives of this study were to describe the access to diagnosis and care of children diagnosed with retinoblastoma and the challenges in two sub-Saharan African countries: the Republic of Côte d’Ivoire and the Democratic Republic of the Congo. Patients and Methods A descriptive cross-sectional study was conducted. Data were collected from the medical records of patients admitted during the period of January 1, 2013 to December 31, 2014. Data were entered and analyzed using Epi Info7.1 software and SAS 9.3. Results One hundred sixteen cases of retinoblastoma were collected, including 60 boys and 56 girls. The median diagnosis age was 3 years for both countries. Ninety-eight patients (84%) had unilateral retinoblastoma. Most of the patients presented with advanced disease (76% had extraocular retinoblastoma). Median time between initial symptoms and diagnosis was 8.5 months (range, 0.4 to 116.7 months). Median time between diagnosis and treatment initiation was 31 days (range, 0 to 751 days). The median cost for the treatment of the disease was estimated at $1,954 per patient. Conclusion Late diagnosis of retinoblastoma, with extraocular disease, occurs frequently in both African countries. It is associated with delay in initiating treatment, and the cost of the treatment remains unaffordable for most of the families. Support groups for parents of affected children and the support of the Franco-African Pediatric Oncology Group remain important in improving early diagnosis and providing treatment in sub-Saharan African countries.
Human posterior parietal cortex responds to visual stimuli as early as peristriate occipital cortex

Much of what is known about the timing of visual processing in the brain is inferred from intracranial studies in monkeys, with human data limited to mainly non-invasive methods with lower spatial resolution. Here, we estimated visual onset latencies from electrocorticographic (ECoG) recordings in a patient who was implanted with 112 sub-dural electrodes, distributed across the posterior cortex of the right hemisphere, for pre-surgical evaluation of intractable epilepsy. Functional MRI prior to surgery was used to determine boundaries of visual areas. The patient was presented with images of objects from several categories. Event Related Potentials (ERPs) were calculated across all categories excluding targets, and statistically reliable onset latencies were determined using a bootstrapping procedure over the single trial baseline activity in individual electrodes. The distribution of onset latencies broadly reflected the known hierarchy of visual areas, with the earliest cortical responses in primary visual cortex, and higher areas showing later responses. A clear exception to this pattern was robust, statistically reliable and spatially localized, very early responses on the bank of the posterior intra-parietal sulcus (IPS). The response in the IPS started nearly simultaneously with responses detected in peristriate visual areas, around 60 milliseconds post-stimulus onset. Our results support the notion of early visual processing in the posterior parietal lobe, not respecting traditional hierarchies, and give direct evidence for the upper limit of onset times of visual responses across the human cortex.
Genome‐wide identification of a novel miRNA‐based signature to predict recurrence in patients with gastric cancer

The current tumor node metastasis (TNM) staging system is inadequate for identifying high‐risk gastric cancer (GC) patients. Using a systematic and comprehensive‐biomarker discovery and validation approach, we attempted to build a microRNA (miRNA)‐recurrence classifier (MRC) to improve the prognostic prediction of GC. We identified 312 differentially expressed miRNAs in 446 GC tissues compared to 45 normal controls by analyzing high‐throughput data from The Cancer Genome Atlas (TCGA). Using a Cox regression model, we developed an 11‐miRNA signature that could successfully discriminate high‐risk patients in the training set (n = 372; P < 0.0001). Quantitative real‐time polymerase chain reaction‐based validation in an independent clinical cohort (n = 88) of formalin‐fixed paraffin‐embedded clinical GC samples showed that MRC‐derived high‐risk patients succumb to significantly poor recurrence‐free survival in GC patients (P < 0.0001). Cox and stratification analysis indicated that the prognostic value of this signature was independent of clinicopathological risk factors. Time‐dependent receiver operating characteristic (ROC) analysis revealed that the area under the curve of this signature was significantly larger than that of TNM stage in the TCGA (0.733 vs. 0.589 at 3 years, P = 0.004; 0.802 vs. 0.635 at 5 years, P = 0.005) and validation cohort (0.835 vs. 0.689 at 3 years, P = 0.003). A nomogram was constructed for clinical use, which integrated both MRC and clinical‐related variables (depth of invasion, lymph node status and distance metastasis) and did well in the calibration plots. In conclusion, this novel miRNA‐based signature is superior to currently used clinicopathological features for identifying high‐risk GC patients. It can be readily translated into clinical practice with formalin‐fixed paraffin‐embedded specimens for specific decision‐making applications.
Different prognostic associations of beta-blockers and diuretics in heart failure with preserved ejection fraction with versus without high blood pressure

Objective: No agents have been proven to improve survival in heart failure with preserved ejection fraction (HFpEF), but the phenotypic diversity of HFpEF suggests it may be possible to identify specific HFpEF phenotypes that will benefit from certain treatments. This study compared the risk factors for and prognostic impacts of treatments on in-hospital mortality between HFpEF patients with (+) and without (–) high blood pressure (HBP). Methods: Data on 2238 consecutive HFpEF patients were extracted from Tokyo CCU Network data registry and analysed. HFpEF was defined as an ejection fraction greater than or equal to 50%; HBP was defined as elevated systolic blood pressure (>140 mmHg) at admission. Potential risk factors for in-hospital mortality were selected by univariate analyses and those with P < 0.10 were used in multivariate Cox regression analysis with forward selection (likelihood ratio) to identify significant factors. Results: In-hospital mortality was significantly lower for HFpEF + HBP than HFpEF – HBP patients (log-rank, P < 0.001). Independent risk factors for in-hospital mortality in HFpEF + HBP patients were older age (hazard ratio 1.069) and in-hospital treatment without beta-blockers (hazard ratio 7.946), whereas older age (hazard ratio 1.035), higher C-reactive protein (hazard ratio 1.047), higher B-type natriuretic peptide (hazard ratio 1.000) and in-hospital treatment without diuretics (hazard ratio 4.201) were identified as independent risk factors in HFpEF – HBP patients. Conclusion: There were significant differences in prognostic factors, including beta-blocker and diuretic treatments, for in-hospital mortality between HFpEF patients with and without HBP. These findings suggest possible individualized therapies for patients with HFpEF.
Wetting Transitions of Liquid Gallium Film on Nanopillar-Decorated Graphene Surfaces

Molecular dynamics (MD) simulation has been employed to study the wetting transitions of liquid gallium droplet on the graphene surfaces, which are decorated with three types of carbon nanopillars, and to explore the effect of the surface roughness and morphology on the wettability of liquid Ga. The simulation results showed that, at the beginning, the Ga film looks like an upside-down dish on the rough surface, different from that on the smooth graphene surface, and its size is crucial to the final state of liquid. Ga droplets exhibit a Cassie–Baxter (CB) state, a Wenzel state, a Mixed Wetting state, and a dewetting state on the patterned surfaces by changing distribution and the morphology of nanopillars. Top morphology of nanopillars has a direct impact on the wetting transition of liquid Ga. There are three transition states for the two types of carbon nanotube (CNT) substrates and two for the carbon nanocone (CNC) one. Furthermore, we have found that the substrates show high or low adhesion to the Ga droplet with the variation of their roughness and top morphology. With the roughness decreasing, the adhesion energy of the substrate decreases. With the same roughness, the CNC/graphene surface has the lowest adhesion energy, followed by CNT/graphene and capped CNT/graphene surfaces. Our findings provide not only valid support to previous works but also reveal new theories on the wetting model of the metal droplet on the rough substrates.
Epidemiological, Clinical, and Histopathological Features of Breast Cancer in Haiti

Purpose Little is known about the epidemiology of breast cancer in developing countries, and Haiti has perhaps the least data of any country in the Western Hemisphere. Methods We conducted a retrospective review of all patients enrolled in an ongoing breast cancer treatment program in Port-au-Prince, Haiti, from July 1, 2013, through June 30, 2017. Data were drawn from each patient's electronic medical record, paper chart, and biopsy results. Results The records of 525 women with breast cancer were reviewed for this study. The median age at presentation was 49 years (n = 507). The risk factors observed were as follows: postmenopausal, 50.8% (n = 354); nulliparity, 15.7% (n = 338); hormonal contraception use, 35.0% (n = 309); never breastfed, 20.6% (n = 316); family history of any cancer, 22.0% (n = 295); overweight, 51.5% (n = 332); and smoking, 5.0% (n = 338). Of all those staged, 83.9% (n = 447) of the patients presented with stage III/IV disease and more than half delayed care for > 12 months after first noticing a breast mass. For the subset of tumors for which estrogen receptor (ER; n = 245) and human epidermal growth factor receptor 2 (HER2; n = 179) status was available, the prevalence of ER-positive tumors was 51.8%, of HER2-positive tumors was 19.6%, and of triple-negative tumors was 38.5%. The 12-month mortality rate (n = 425) was 18.4% overall and 27.5% for those who presented with stage IV disease. Median survival was not reached. Conclusion Breast cancer in Haiti presents at an early age and advanced stage. Triple-negative, ER-negative, and high-grade tumors are common. Delays in seeking care and incomplete treatment likely contribute to the high mortality rate; however, as in black women in the United States, the distribution of tumor types may contribute to disparate outcomes.
NADH Dehydrogenase Subunit-2 237 Leu/Met Polymorphism Influences the Association of Coffee Consumption with Serum Chloride Levels in Male Japanese Health Checkup Examinees: An Exploratory Cross-Sectional Analysis

Background: Nicotinamide adenine dinucleotide (NADH) dehydrogenase subunit-2 237 leucine/methionine (ND2-237 Leu/Met) polymorphism has been shown to modify the association of coffee consumption with the risk of hypertension, dyslipidemia, and abnormal glucose tolerance, and low serum chloride levels have been shown to be associated with all-cause and cardiovascular disease mortality. Therefore, the purpose of the present study was to investigate whether ND2-237 Leu/Met polymorphism influences the association of coffee consumption with serum chloride levels in male Japanese health checkup examinees. Methods: From among individuals visiting the hospital for a regular medical checkup, 402 men (mean age ± standard deviation, 53.9 ± 7.8 years) were selected for inclusion in the study. After ND2-237 Leu/Met genotyping, we conducted an exploratory cross-sectional study to examine the combined association of ND2-237 Leu/Met polymorphism and coffee consumption with serum electrolyte levels. Results: After adjusting for age, body mass index, habitual smoking, alcohol consumption, green tea consumption, and antihypertensive medication, coffee consumption significantly increased serum chloride levels (p for trend = 0.001) in men with the ND2-237Leu genotype. After these adjustments, the odds ratios (ORs) for low levels of serum chloride, defined as <100 mEq/L, were found to be dependent on coffee consumption (p for trend = 0.001). In addition, the OR for low levels of serum chloride was significantly lower in men with the ND2-237Leu genotype who consumed ≥4 compared with <1 cup of coffee per day (OR = 0.096, 95% confidence interval = 0.010–0.934; p = 0.044). However, neither serum chloride levels nor risk of low levels of serum chloride appeared to be dependent on coffee consumption. Conclusions: The results suggest that ND2-237 Leu/Met polymorphism modifies the association of coffee consumption with serum chloride levels in middle-aged Japanese men.
Effect of Arbuscular Mycorrhizal Fungi on Pratylenchus penetrans Infestation in Apple Seedlings under Greenhouse Conditions

A major problem in fruit cultivation in Flanders is replant disease due to a lack of uncultivated soils available for new plantings. Replant disease can cause poor growth and affect time to full production, however Arbuscular Mycorrhizal Fungi (AMF) can prove their usefulness with regard to these problems. To further investigate the effect of AMF on nematodes, different AMF species were amended to potted apple seedlings in the presence of the nematode Pratylenchus penetrans. Generally, apple seedlings grew better in the presence of nematodes when mycorrhiza were inoculated into the soil. Moreover, a positive correlation (R2 ≥ 0.88) was found between the percentage root length colonization of the roots of apple seedlings, by AMF species, and nematode reduction in the soil of the seedlings. Indigenous AMF could colonize the roots of apple seedlings the most efficiently, resulting in a higher biocontrol effect. Besides, a synergistic effect was observed when two AMF strains were applied together leading to a significant growth response of the seedlings.
HIV Status and Associated Clinical Characteristics Among Adult Patients With Cancer at the Uganda Cancer Institute

Purpose HIV increases cancer incidence and mortality. In Uganda, the HIV epidemic has led to an elevated incidence of AIDS-defining cancers (ADCs) and non–AIDS-defining cancers (NADCs). Limited information exists about how frequently HIV infection complicates the presentation and manifestations of cancer in sub-Saharan Africa. Methods We abstracted medical records from patients with cancer who were age 18 years or older who registered at the Uganda Cancer Institute from June through September 2015 to determine the burden of HIV. We used χ2 tests and generalized linear models to evaluate factors associated with HIV positivity. A sensitivity analysis estimated HIV prevalence in those untested. Results Among 1,137 patients with cancer, 23% were HIV infected, 48% were HIV negative, and 29% had no recorded HIV status. Of those with recorded HIV status, 32% were HIV positive. Forty-two percent (149 of 361 patients) with ADCs were documented as HIV infected (51% of those with documented status) compared with 14% (108 of 776 patients) of those with NADCs (21% of those with documented status). In multivariable analysis, HIV infection was associated with ADC diagnosis (adjusted prevalence ratio [aPR] compared with NADC, 2.2; 95% CI, 1.5 to 3.0), younger age (aPR, 0.9 per decade increase; 95% CI, 0.8 to 1.0), and worse performance status scores (aPR, 1.2 per point ECOG increase; 95% CI, 1.0 to 1.5). When sensitivity analysis accounted for undocumented HIV status, the expected prevalence of HIV infection was 29% (range, 23% to 32%), and almost one fourth of expected HIV cases were undiagnosed or unrecorded. Conclusion The prevalence of HIV infection among Ugandan patients with cancer is substantially higher than in the general population. Patients with cancer and HIV tend to be younger and have poorer performance status. Greater awareness of the dual burden of cancer and HIV in Uganda and universal testing of patients with cancer may improve outcomes of HIV-associated malignancies.
Path Smoothing Techniques in Robot Navigation: State-of-the-Art, Current and Future Challenges

Robot navigation is an indispensable component of any mobile service robot. Many path planning algorithms generate a path which has many sharp or angular turns. Such paths are not fit for mobile robot as it has to slow down at these sharp turns. These robots could be carrying delicate, dangerous, or precious items and executing these sharp turns may not be feasible kinematically. On the contrary, smooth trajectories are often desired for robot motion and must be generated while considering the static and dynamic obstacles and other constraints like feasible curvature, robot and lane dimensions, and speed. The aim of this paper is to succinctly summarize and review the path smoothing techniques in robot navigation and discuss the challenges and future trends. Both autonomous mobile robots and autonomous vehicles (outdoor robots or self-driving cars) are discussed. The state-of-the-art algorithms are broadly classified into different categories and each approach is introduced briefly with necessary background, merits, and drawbacks. Finally, the paper discusses the current and future challenges in optimal trajectory generation and smoothing research.
Development of an automated detection algorithm for patient motion blur in digital mammograms

The purpose is to develop and validate an automated method for detecting image unsharpness caused by patient motion blur in digital mammograms. The goal is that such a tool would facilitate immediate re-taking of blurred images, which has the potential to reduce the number of recalled examinations, and to ensure that sharp, high-quality mammograms are presented for reading. To meet this goal, an automated method was developed based on interpretation of the normalized image Wiener Spectrum. A preliminary algorithm was developed using 25 cases acquired using a single vendor system, read by two expert readers identifying the presence of blur, location, and severity. A predictive blur severity score was established using multivariate modeling, which had an adjusted coefficient of determination, R2 =0.63±0.02, for linear regression against the average reader-scored blur severity. A heatmap of the relative blur magnitude showed good correspondence with reader sketches of blur location, with a Spearman rank correlation of 0.70 between the algorithmestimated area fraction with blur and the maximum of the blur area fraction categories of the two readers. Given these promising results, the algorithm-estimated blur severity score and heatmap are proposed to be used to aid observer interpretation. The use of this automated blur analysis approach, ideally with feedback during an exam, could lead to a reduction in repeat appointments for technical reasons, saving time, cost, potential anxiety, and improving image quality for accurate diagnosis.
Glial mechanisms underlying substance use disorders

Addiction is a devastating disorder that produces persistent maladaptive changes to the central nervous system, including glial cells. Although there is an extensive body of literature examining the neuronal mechanisms of substance use disorders, effective therapies remain elusive. Glia, particularly microglia and astrocytes, have an emerging and meaningful role in a variety of processes beyond inflammation and immune surveillance, and may represent a promising therapeutic target. Indeed, glia actively modulate neurotransmission, synaptic connectivity and neural circuit function, and are critically poised to contribute to addictive‐like brain states and behaviors. In this review, we argue that glia influence the cellular, molecular, and synaptic changes that occur in neurons following drug exposure, and that this cellular relationship is critically modified following drug exposure. We discuss direct actions of abused drugs on glial function through immune receptors, such as Toll‐like receptor 4, as well as other mechanisms. We highlight how drugs of abuse affect glia‐neural communication, and the profound effects that glial‐derived factors have on neuronal excitability, structure, and function. Recent research demonstrates that glia have brain region‐specific functions, and glia in different brain regions have distinct contributions to drug‐associated behaviors. We will also evaluate the evidence demonstrating that glial activation is essential for drug reward and drug‐induced dopamine release, and highlight clinical evidence showing that glial mechanisms contribute to drug abuse liability. In this review, we synthesize the extensive evidence that glia have a unique, pivotal, and underappreciated role in the development and maintenance of addiction.