Miracle-dz/UniFAR-FTUs huggingface dataset:
Critical Defect Healing Assessment in Rat Calvaria Filled with Injectable Calcium Phosphate Cement

(1) Background: The tissue engineering field has been working to find biomaterials that mimic the biological properties of autogenous bone grafts. (2) Aim: To evaluate the osteoconduction potential of injectable calcium phosphate cement implanted in critical defects in rat calvaria. (3) Methods: In the calvarial bone of 36 rats, 7-mm diameter critical size defects were performed. Afterwards, the animals were randomly divided into three groups according to filler material: a blood clot group (BC), blood clot membrane group (BCM), and an injectable β-tricalcium phosphate group (HBS) cement group. After periods of 30 and 60 days, the animals were euthanized, the calvaria was isolated, and submitted to a decalcification process for later blades confection. Qualitative and quantitative analysis of the neoformed bone tissue were conducted, and histometric data were statistically analyzed. (4) Results: Sixty days post-surgery, the percentages of neoformed bone were 10.67 ± 5.57 in group BC, 16.71 ± 5.0 in group BCM, and 55.11 ± 13.20 in group HBS. The bone formation values in group HBS were significantly higher (p < 0.05) than in groups BC and BCM. (5) Conclusions: Based on these results, it can be concluded that injectable calcium phosphate cement is an osteoconductive material that can be used to fill bone cavities.
Childhood Maltreatment Disrupts Brain-Mediated Pathways Between Adolescent Maternal Relationship Quality and Positive Adult Outcomes

The quality of early caregiving may partially shape brain structure and circuits involved in regulating emotions, including the frontal cortex, affecting vulnerability to the development of psychopathology and maladaptation. Given the profound impact of child maltreatment (CM) on psychological and neural development, we tested whether CM alters the pathways linking mother–adolescent relationship, frontal cortex, and adult outcomes. We used structural equation modeling to investigate whether CM history affected the association between mother–child relationship quality during early adolescence, frontal lobe volume in adulthood, and adult internalizing and externalizing symptomatology and competence. Participants from a longitudinal high-risk, low-income sample included 48 adults with a history of CM and 40 adults without such history (M = 30.0 years). Results showed that greater frontal lobe volume predicted higher levels of adult adaptive functioning and fewer adult internalizing symptoms but showed no relation to adult externalizing symptoms. Frontal lobe volume significantly mediated the effect of adolescent maternal relationship quality on both adult internalizing symptoms and adult adaptive functioning, but only for individuals with no maltreatment history. Given the observed relationship between frontal lobe volume and healthy adult functioning across the full sample, it will be important to identify protective factors in maltreated individuals that foster frontal lobe development.
Electrotonic transmission in the retinal vasculature: inhibitory role of the diabetes/VEGF/aPKC pathway

The deleterious impact of diabetes on the retina is a leading cause of vision loss. Ultimately, the hypoxic retinopathy caused by diabetes results in irreversible damage to vascular, neuronal, and glial cells. Less understood is how retinal physiology is altered early in the course of diabetes. We recently found that the electrotonic architecture of the retinovasculature becomes fundamentally altered soon after the onset of this disorder. Namely, the spread of voltage through the vascular endothelium is markedly inhibited. The goal of this study was to elucidate how diabetes inhibits electrotonic transmission. We hypothesized that vascular endothelial growth factor (VEGF) may play a role since its upregulation in hypoxic retinopathy is associated with sight‐impairing complications. In this study, we quantified voltage transmission between pairs of perforated‐patch pipettes sealed onto abluminal cells located on retinal microvascular complexes freshly isolated from diabetic and nondiabetic rats. We report that exposure of diabetic retinal microvessels to an anti‐VEGF antibody or to a small‐molecule inhibitor of atypical PKCs (aPKC) near‐fully restored the efficacy of electrotonic transmission. Furthermore, exposure of nondiabetic microvessels to VEGF mimicked, via a mechanism sensitive to the aPKC inhibitor, the diabetes‐induced inhibition of transmission. Thus, activation of the diabetes/VEGF/aPKC pathway switches the retinovasculature from a highly interactive operational unit to a functionally balkanized complex. By delimiting the dissemination of voltage‐changing vasomotor inputs, this organizational fragmentation is likely to compromise effective regulation of retinal perfusion. Future pharmacological targeting of the diabetes/VEGF/aPKC pathway may serve to impede progression of vascular dysfunction to irreversible diabetic retinopathy.
Therapeutic cooperation between auranofin, a thioredoxin reductase inhibitor and anti‐PD‐L1 antibody for treatment of triple‐negative breast cancer

Triple‐negative breast cancer (TNBCs) is a very aggressive and lethal form of breast cancer with no effective targeted therapy. Neoadjuvant chemotherapies and radiotherapy remains a mainstay of treatment with only 25–30% of TNBC patients responding. Thus, there is an unmet clinical need to develop novel therapeutic strategies for TNBCs. TNBC cells have increased intracellular oxidative stress and suppressed glutathione, a major antioxidant system, but still, are protected against higher oxidative stress. We screened a panel of antioxidant genes using the TCGA and METABRIC databases and found that expression of the thioredoxin pathway genes is significantly upregulated in TNBC patients compared to non‐TNBC patients and is correlated with adverse survival outcomes. Treatment with auranofin (AF), an FDA‐approved thioredoxin reductase inhibitor caused specific cell death and impaired the growth of TNBC cells grown as spheroids. Furthermore, AF treatment exerted a significant in vivo antitumor activity in multiple TNBC models including the syngeneic 4T1.2 model, MDA‐MB‐231 xenograft and patient‐derived tumor xenograft by inhibiting thioredoxin redox activity. We, for the first time, showed that AF increased CD8+Ve T‐cell tumor infiltration in vivo and upregulated immune checkpoint PD‐L1 expression in an ERK1/2‐MYC‐dependent manner. Moreover, combination of AF with anti‐PD‐L1 antibody synergistically impaired the growth of 4T1.2 primary tumors. Our data provide a novel therapeutic strategy using AF in combination with anti‐PD‐L1 antibody that warrants further clinical investigation for TNBC patients.
Delineating Surface Epitopes of Lyme Disease Pathogen Targeted by Highly Protective Antibodies of New Zealand White Rabbits

Lyme disease (LD), the most prevalent vector-borne illness in the United States and Europe, is caused by Borreliella burgdorferi. No vaccine is available for humans. Dogmatically, B. burgdorferi can establish a persistent infection in the mammalian host (e.g., mice) due to a surface antigen, VlsE. This antigenically variable protein allows the spirochete to continually evade borreliacidal antibodies. ABSTRACT Lyme disease (LD), the most prevalent vector-borne illness in the United States and Europe, is caused by Borreliella burgdorferi. No vaccine is available for humans. Dogmatically, B. burgdorferi can establish a persistent infection in the mammalian host (e.g., mice) due to a surface antigen, VlsE. This antigenically variable protein allows the spirochete to continually evade borreliacidal antibodies. However, our recent study has shown that the B. burgdorferi spirochete is effectively cleared by anti-B. burgdorferi antibodies of New Zealand White rabbits, despite the surface expression of VlsE. Besides homologous protection, the rabbit antibodies also cross-protect against heterologous B. burgdorferi spirochetes and significantly reduce the pathology of LD arthritis in persistently infected mice. Thus, this finding that NZW rabbits develop a unique repertoire of very potent antibodies targeting the protective surface epitopes, despite abundant VlsE, prompted us to identify the specificities of the protective rabbit antibodies and their respective targets. By applying subtractive reverse vaccinology, which involved the use of random peptide phage display libraries coupled with next-generation sequencing and our computational algorithms, repertoires of nonprotective (early) and protective (late) rabbit antibodies were identified and directly compared. Consequently, putative surface epitopes that are unique to the protective rabbit sera were mapped. Importantly, the relevance of newly identified protection-associated epitopes for their surface exposure has been strongly supported by prior empirical studies. This study is significant because it now allows us to systematically test the putative epitopes for their protective efficacy with an ultimate goal of selecting the most efficacious targets for development of a long-awaited LD vaccine.
Ultra-Thin ReS2 Nanosheets Grown on Carbon Black for Advanced Lithium-Ion Battery Anodes

ReS2 nanosheets are grown on the surface of carbon black (CB) via an efficient hydrothermal method. We confirmed the ultra-thin ReS2 nanosheets with ≈1–4 layers on the surface of the CB (ReS2@CB) by using analytical techniques of field emission scanning electron microscopy (FESEM) and high-resolution transmission electron microscopy (HRTEM). The ReS2@CB nanocomposite showed high specific capacities of 760, 667, 600, 525, and 473 mAh/g at the current densities of 0.1 (0.23 C), 0.2 (0.46 C), 0.3 (0.7 C), 0.5 (1.15 C) and 1.0 A/g (2.3 C), respectively, in conjunction with its excellent cycling performance (432 mAh/g at 2.3 C; 91.4% capacity retention) after 100 cycles. Such LIB performance is greatly higher than pure CB and ReS2 powder samples. These results could be due to the following reasons: (1) the low-cost CB serves as a supporter enabling the formation of ≈1–4 layered nanosheets of ReS2, thus avoiding its agglomeration; (2) the CB enhances the electrical conductivity of the ReS2@CB nanocomposite; (3) the ultra-thin (1–4 layers) ReS2 nanosheets with imperfect structure can function as increasing the number of active sites for reaction of Li+ ions with electrolytes. The outstanding performance and unique structural characteristics of the ReS2@CB anodes make them promising candidates for the ever-increasing development of advanced LIBs.
Macrophage Tropism of HIV-1 Depends on Efficient Cellular dNTP Utilization by Reverse Transcriptase*

Retroviruses utilize cellular dNTPs to perform proviral DNA synthesis in infected host cells. Unlike oncoretroviruses, which replicate in dividing cells, lentiviruses, such as human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus, are capable of efficiently replicating in non-dividing cells (terminally differentiated macrophages) as well as dividing cells (i.e. activated CD4+ T cells). In general, non-dividing cells are likely to have low cellular dNTP content compared with dividing cells. Here, by employing a novel assay for cellular dNTP content, we determined the dNTP concentrations in two HIV-1 target cells, macrophages and activated CD4+ T cells. We found that human macrophages contained 130-250-fold lower dNTP concentrations than activated human CD4+ T cells. Biochemical analysis revealed that, unlike oncoretroviral reverse transcriptases (RTs), lentiviral RTs efficiently synthesize DNA even in the presence of the low dNTP concentrations equivalent to those found in macrophages. In keeping with this observation, HIV-1 vectors containing mutant HIV-1 RTs, which kinetically mimic oncoretroviral RTs, failed to transduce human macrophages despite retaining normal infectivity for activated CD4+ T cells and other dividing cells. These results suggest that the ability of HIV-1 to infect macrophages, which is essential to establishing the early pathogenesis of HIV-1 infection, depends, at least in part, on enzymatic adaptation of HIV-1 RT to efficiently catalyze DNA synthesis in limited cellular dNTP substrate environments.
3D Point Cloud Generative Adversarial Network Based on Tree Structured Graph Convolutions

In this paper, we propose a novel generative adversarial network (GAN) for 3D point clouds generation, which is called tree-GAN. To achieve state-of-the-art performance for multi-class 3D point cloud generation, a tree-structured graph convolution network (TreeGCN) is introduced as a generator for tree-GAN. Because TreeGCN performs graph convolutions within a tree, it can use ancestor information to boost the representation power for features. To evaluate GANs for 3D point clouds accurately, we develop a novel evaluation metric called Fr\'echet point cloud distance (FPD). Experimental results demonstrate that the proposed tree-GAN outperforms state-of-the-art GANs in terms of both conventional metrics and FPD, and can generate point clouds for different semantic parts without prior knowledge.
Ergodicity of affine processes on the cone of symmetric positive semidefinite matrices

Abstract This article investigates the long-time behavior of conservative affine processes on the cone of symmetric positive semidefinite $d\times d$ matrices. In particular, for conservative and subcritical affine processes we show that a finite $\log$ -moment of the state-independent jump measure is sufficient for the existence of a unique limit distribution. Moreover, we study the convergence rate of the underlying transition kernel to the limit distribution: first, in a specific metric induced by the Laplace transform, and second, in the Wasserstein distance under a first moment assumption imposed on the state-independent jump measure and an additional condition on the diffusion parameter.
Long non-coding RNA MEG3 serves as a ceRNA for microRNA-145 to induce apoptosis of AC16 cardiomyocytes under high glucose condition

Diabetic cardiomyopathy (DCM) is one of the most serious complications of diabetes, but its pathogenesis remains largely unclear. In the present study, we aimed to explore the potential role of long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) and to investigate the underlying mechanisms in human AC16 cardiomyocytes under high glucose (HG) condition. The results demonstrated that MEG3 was overexpressed in HG-treated AC16 cells, and MEG3 knockdown suppressed the HG-induced apoptosis in AC16 cells. Mechanistically, MEG3 directly binds to miR-145 in AC16 cells, thereby up-regulating the expression of PDCD4. Rescue experiments showed that the role of MEG3 in HG-treated AC16 cells was partly dependent on its suppression on miR-145. In summary, our findings suggested that the role of MEG3 in HG-treated human cardiomyocytes is to serve as a competing endogenous RNA (ceRNA), which negatively regulates miR-145. These findings may provide a valuable and promising therapeutic target for the treatment of DCM in the future.
Aflatoxin M1 in raw, pasteurized and UHT milk marketed in Iran

ABSTRACT Aflatoxin M1 (AFM1) is a 2B Group human carcinogens agent and introduces into the human diet by milk consumption. In the present study 257 raw, 143 pasteurized and 61 UHT milk samples were collected from markets in 117 cities throughout Iran, during winter 2017 and AFM1 contents were determined using a HPLC-FLD method after immunoaffinity clean-up. Mean recovery rates and relative standard deviations of the method were 90.6 ± 5.7%. AFM1 was detected in 252 of 461 (54.7%) samples (mean 31.3 ± 8.8 ng/L), ranging from <10 to 150 ng/L. Three samples (0.6%) exceeded the Iranian maximum limit of 100 ng/L. The mean AFM1 content was significantly higher in raw milk samples obtained from humid climate areas. The extrapolated concentration of AFB1 in dairy cattle feed based on the AFM1 value of milk was 1.96 µg/kg. The AFM1 contamination of milk seems not to be a serious public health concern in Iran.
Multivariate Modeling for Sustainable and Resilient Infrastructure Systems and Communities

Sustainability and resilience of urban systems are multifaceted concepts, requiring information about multiple system attributes to adequately evaluate and characterize. However, despite the scientific consensus on the multivariate nature of these concepts, many of the existing techniques to model urban sustainability and resilience are unidimensional in nature, focusing on a characterizing a single element of highly interconnected urban systems. We champion a paradigm shift in modeling urban sustainability and resilience, using an integrated approach to simultaneously estimate multiple interconnected (correlated) system attributes of sustainability and resilience as a function of key environmental factors. We present a novel case study and review a few recent studies to illustrate the applicability and benefits of the multivariate approach to modeling urban sustainability and resilience. Our proposed framework can be utilized by infrastructure managers, urban planners, and researchers to conceptualize and assess urban sustainability and resilience more holistically, and to better understand the key factors in advancing the sustainability and resilience of infrastructure systems.
The Effects of Radiation and Sex Differences on Adaptive Functioning in Adult Survivors of Pediatric Posterior Fossa Brain Tumors

Abstract Objective: Radiation therapy (RT) improves rates of survival of patients with childhood brain tumors but increases deficits in cognition and independent living skills. Previous literature has studied difficulties in basic cognitive processes, but few explore impairment in higher-order skills such as adaptive functioning. Some studies identify females as at risk for cognitive deficits due to RT, but few investigate sex differences in adaptive functioning. It was hypothesized that females would exhibit poorer long-term independent living skills and core cognitive skills relative to males following RT. Methods: Forty-five adult survivors of posterior fossa childhood brain tumors (24 females) completed the Wechsler Abbreviated Scale of Intelligence (WASI-II), Wechsler Memory Scale, Third Edition (WMS-III) Digit Span Forward (DSF) and Backward (DSB), and Oral Symbol Digit Modalities Test (OSDMT). Informants completed the Scales of Independent Behavior-Revised (SIB-R). Results: DSF and OSDMT were positively correlated with all five SIB-R domains, full-scale IQ (FSIQ) was positively correlated with four SIB-R domains, and DSB was positively correlated with three SIB-R domains. There was an interaction between sex and RT for OSDMT and community living skills with trend level interactions for personal living skills and broad independent living skills, where females without RT had higher scores than females with RT. Conclusions: Female survivors were more affected by RT than males across the community living skills domain of adaptive functioning as well as processing speed. Processing speed deficits may have a cascading impact on daily living skills. Future studies should investigate how clinical and biological factors may contribute to personalized treatment plans between sexes. (JINS, 2019, 25, 729–739)
Synergistic interaction of trimethoprim and sulfamethoxazole on Paracoccidioides brasiliensis

The in vitro interaction of trimethoprim and sulfamethoxazole on clinical isolates of Paracoccidioides brasiliensis was studied. With complete inhibition and a visual endpoint used as the criteria, three of four strains had minimal inhibitory concentrations that indicated resistance to sulfamethoxazole, and all four strains were resistant to trimethoprim. A marked synergism in inhibition was noted with the combination of these drugs against sulfa-resistant strains. A sulfamethoxazole/trimethoprim ratio of 5:1 was the most synergistic. Fifty percent inhibition, determined spectrophotometrically, of the strains could be achieved with sulfamethoxazole alone. In summary, the striking synergy observed suggests that combination chemotherapy with these drugs deserves further study.
Bone-Marrow Suppression in Elderly Patients Following Empiric Radioiodine Therapy: Real-Life Data.

Background: Elderly patients with differentiated thyroid cancer (DTC) tend to have more advanced disease at presentation, for which high activities of radioiodine (RAI) are often recommended. However, the 2015 American Thyroid Association guidelines recommend that empirically administered activities of RAI >150 mCi should be avoided in patients >70 years of age, based on calculated bone-marrow exposure according to two dosimetry-based studies. This study aimed to evaluate the effect of RAI treatment on bone-marrow function in elderly DTC patients. Methods: DTC patients ≥70 years of age who received RAI treatment and on whom a complete blood count was performed before and after treatment were included. Blood counts within one year before RAI and one year following treatment were compared in order to assess for marrow suppression. The impact of demographic, clinical, and laboratory variables on complete blood count were assessed. Results: One hundred fifty-three treatments in 122 patients met inclusion criteria, with a mean patient age of 76 ± 4.3 years, and 75% were women. High-risk features at presentation included T4 disease in 17%, lymph node metastases in 34%, and distant metastases in 14%. Mean RAI activity was 136.8 ± 48 mCi (82% ≥ 100 mCi, 66% ≥ 150 mCi). Of 153 RAI treatments analyzed, 114 (74%) were first treatments, 28 (18%) second treatments, seven (5%) third treatments, and four (3%) fourth treatments. At 0-3 months after RAI treatment, there was a statistically significant decrease in platelets (238 ± 66 vs. 216 ± 69 × 109/L, 10% decrease; p < 0.001), white blood cells (WBC; 6.9 ± 2 vs. 6.1 ± 1.9 × 109/L, 13% decrease; p < 0.001), and hemoglobin (Hb) in women (12.8 ± 1.1 vs. 12.4 ± 1.1 g/dL, 3% decrease; p = 0.01). Mean platelets, WBC, Hb in women, and lymphocytes remained decreased (but within the reference range) one year after treatment. Subgroup analysis demonstrated platelet suppression only with activities ≥100 mCi, and WBC and Hb suppression only with activities ≥150 mCi, with mean values within the reference ranges. There were no clinically significant cytopenia events during follow-up. Conclusions: Empiric RAI treatment in elderly patients causes mild bone-marrow suppression, with little clinical significance. Activities of 150-200 mCi can be safely used when indicated.
The effects of adipose tissue and adipocytokines in human pregnancy

During pregnancy, important changes take place in maternal metabolism because of the growing fetus and placental formation. The increase in insulin resistance during pregnancy is paralleled by the progressive increase of maternal adipose tissue deposition. This review examines the topography of fat mass deposition during pregnancy in relation to factors such as parity and maternal age that might affect this deposition. We also examine adipose tissue markers, such as pregravid weight and weight gain during pregnancy, and their effect on fetal growth and pregnancy outcomes. In addition, this review studies the possible effects of cytokines that are produced by adipose tissue and the placenta on maternal metabolism and its complications. Finally, we also consider the possible role of maternal adipocytokines and fetal adipocytokines on fetal growth.