Miracle-dz/UniFAR-FTUs huggingface dataset:
Socially indiscriminate attachment behavior in the Strange Situation: Convergent and discriminant validity in relation to caregiving risk, later behavior problems, and attachment insecurity

Abstract Socially indiscriminate attachment behavior has been repeatedly observed among institutionally reared children. Socially indiscriminate behavior has also been associated with aggression and hyperactivity. However, available data rely heavily on caregiver report of indiscriminate behavior. In addition, few studies have been conducted with samples of home-reared infants exposed to inadequate care. The current study aimed to develop a reliable laboratory measure of socially indiscriminate forms of attachment behavior based on direct observation and to validate the measure against assessments of early care and later behavior problems among home-reared infants. Strange Situation episodes of 75 socially at-risk mother–infant dyads were coded for infant indiscriminate attachment behavior on the newly developed Rating for Infant–Stranger Engagement. After controlling for infant insecure–organized and disorganized behavior in all analyses, extent of infant–stranger engagement at 18 months was significantly related to serious caregiving risk (maltreatment or maternal psychiatric hospitalization), observed quality of disrupted maternal affective communication, and aggressive and hyperactive behavior problems at age 5. Results are discussed in relation to the convergent and discriminant validity of the new measure and to the potential utility of a standardized observational measure of indiscriminate attachment behavior. Further validation is needed in relation to caregiver report measures of indiscriminate behavior.
The fibrinolytic potential in patients with Cushing's disease: a clue to their hypercoagulable state

The aim of our study was to determine the fibrinolytic potential in a large group of patients with Cushing's disease. These patients had a significant shortening of the activated partial thromboplastin time and increase in factor VIII/von Willebrand factor complex compared to normal controls. The mean levels of plasminogen, tissue plasminogen activator (t-PA) antigen and plasminogen activator inhibitor (PAI) activity were significantly higher than in normal subjects, whereas the basal fibrinolytic activity was similar to that seen in the control group. In 17 out of 30 Cushing patients and in 17 normal subjects the fibrinolytic potential was determined with the venous occlusion test. In the Cushing group, the release of t-PA antigen after 20 min of venous occlusion was comparable to that observed in the control group. However, Cushing patients showed a lower fibrinolytic activity than normal subjects, since a lesser shortening of the euglobulin lysis time and a non-significant rise of plasminogen activator activity levels were found. Moreover, in these patients the PAI activity values remained unchanged and significantly increased after venous occlusion test also. In conclusion, the impaired fibrinolytic activation seen in Cushing patients after venous occlusion can be explained by the inhibitory effect of the high PAI levels on plasminogen activators. The defective fibrinolytic potential could further contribute to the hypercoagulable state in Cushing's disease. High PAI Levels before surgery may represent an additional risk factor for post-surgical thromboembolic complications in Cushing patients.
Computer aided lung cancer diagnosis with deep learning algorithms

Deep learning is considered as a popular and powerful method in pattern recognition and classification. However, there are not many deep structured applications used in medical imaging diagnosis area, because large dataset is not always available for medical images. In this study we tested the feasibility of using deep learning algorithms for lung cancer diagnosis with the cases from Lung Image Database Consortium (LIDC) database. The nodules on each computed tomography (CT) slice were segmented according to marks provided by the radiologists. After down sampling and rotating we acquired 174412 samples with 52 by 52 pixel each and the corresponding truth files. Three deep learning algorithms were designed and implemented, including Convolutional Neural Network (CNN), Deep Belief Networks (DBNs), Stacked Denoising Autoencoder (SDAE). To compare the performance of deep learning algorithms with traditional computer aided diagnosis (CADx) system, we designed a scheme with 28 image features and support vector machine. The accuracies of CNN, DBNs, and SDAE are 0.7976, 0.8119, and 0.7929, respectively; the accuracy of our designed traditional CADx is 0.7940, which is slightly lower than CNN and DBNs. We also noticed that the mislabeled nodules using DBNs are 4% larger than using traditional CADx, this might be resulting from down sampling process lost some size information of the nodules.
A Quantitative Regional Analysis of Amino Acids Involved in Rat Brain Protein Synthesis by High Performance Liquid Chromatography

Abstract: A biochemical method is described for the simultaneous quantitative estimation of unidirectional blood‐brain amino acid influx and protein biosynthesis in individual structures of the rat brain. The method involved a double labeling experiment started by the administration of [14C]carboxyl‐labeled amino acids and terminated 2 min after infusion of 3H‐labeled amino acids, each at tracer quantities, the total labeling period being 45 min. Specific radioactivities of 14C‐ or 3H‐labeled phenyl‐alanine, tyrosine, leucine, isoleucine and valine were determined in plasma and in small brain tissue samples for free amino acids, aminoacyl‐tRNAs and proteins. Amino acids were converted to their corresponding 5‐dimethylamino‐naphthalenesulfonyl (Dns, dansyl) derivatives and separated on HPLC C18 reversed‐phase columns isocratically according to a newly developed optimizing procedure. The order of influx values between the neutral amino acids in relation to each other was Leu > Tyr > Ile > Phe > Val in every structure examined. Although aminoacylation of tRNAs was found to proceed to a comparable degree for neutral amino acids in all regions investigated, the specific radioactivity of amino acids attached to tRNAs differed substantially from that in the free amino acid pool, especially for leucine and valine. The results indicate the necessity of aminoacyl‐tRNA determinations for tracer incorporation studies in protein synthesis analysis. Relative protein synthesis rates in the halothane‐anesthetized rat were determined to be 30 and 67–91 pmol total amino acid incorporation/min/mg tissue for white and gray matter, respectively.
A base pair transition in a DNA sequence with dyad symmetry upstream of the puf promoter affects transcription of the puc operon in Rhodobacter capsulatus

A DNA sequence with dyad symmetry upstream of the transcriptional start of the Rhodobacter capsulatus puf operon, which encodes pigment-binding proteins of the light-harvesting I complex and of the reaction center, has previously been shown to be a protein-binding site (G. Klug, Mol. Gen. Genet. 226:167-176, 1991). When a low-copy-number plasmid with a base pair transition at position -43 within this dyad symmetry in front of the puf structural genes was transferred into a Rhodobacter strain with the puf operon deleted, different phenotypes occurred during cultivation of the transconjugants and the kinetics of the loss of the wild-type phenotype was dependent on the oxygen tension in the culture. After growth for 150 generations, the different phenotypes were stably inherited. The strains having the wild-type phenotype carried the wild-type puf DNA sequence. The original mutation was still present in the strains that showed lighter color. These strains had less light-harvesting II complex in the membrane and showed lower rates of transcription of the puc operon, which encodes the proteins of this complex. This deregulation of puc expression was due to one or more chromosomally located, secondary mutations, not directly to the mutation present on the plasmid. Thus, a single-base-pair transition in the puf upstream region can result in a deregulation of puc expression, suggesting a direct or indirect transcriptional coregulation of both these operons by a common factor.
Development of a novel vesicular system using a binary mixture of sorbitan monostearate and polyethylene glycol fatty acid esters for rectal delivery of rutin

Anorectal diseases, such as hemorrhoids, are bothersome benign conditions that warrant special attention. The design of an optimized vesicular system for localized rectal delivery can be a suitable conservative treatment. The feasibility of preparing proniosomes using different types of Gelucires®, in combination with Span® 60 as binary mixtures of nonionic surfactants, was checked, then the prepared proniosomes using Span 60 or Span 60/Gelucire were compared to conventional niosomes through investigations comprising the following: encapsulation efficiency (EE%); particle-size analysis; transmission electron microscopy; zeta potential (Z), and in vitro release study and ex vivo permeation study using excised rat rectum. All preparations showed satisfactory stability (Z >30 mV), particle size <300 nm with niosomes showing the lowest EE%, and the largest particle size, together with the least amount of drug released or accumulated in the rectal walls. Span 60/Gelucire proniosomes exhibited lower particle size as well as better release and permeation results, compared to Span 60 proniosomes. Span 60/Gelucire 44/14 (2:1) proniosomes attained the highest percentage of drug released (98.39%) and drug deposition in the rectal walls (86.26%) after 8 hours, which therefore seems to be the most suitable formula able to achieve targeted therapeutic efficacy, aiming to improve the patient’s quality of life.
Modulation of the pathology of late xenograft rejection by PAF‐antagonist UR‐12670 in the hamster‐to‐rat liver xenotransplant model

PAF antagonists have been used in xenotransplantation to alleviate the pathogenesis of hyperacute rejection. This study evaluated the ability of the PAF antagonist UR‐12670 to improve graft function in late xenograft rejection (LXR) in an orthotopic liver xenotransplantation model, and the involvement of PAF (platelet activating factor) in this type of rejection. The recipients of a hamster xenograft received standard immunosuppression (tacrolimus 0.2 mg/kg/30 days, MMF 25 mg/kg/8 days). Study groups: group A, without UR‐12670, group B, UR‐12670 (20 mg/kg/8 d) and group C, continuous administration of UR‐12670 (20 mg/kg/d). Serum levels of xenoantibodies were evaluated by flow cytometry and tissue deposits by immunofluorescence. Immunoblot and indirect immunofluorescence assessed specificity of xenoantibodies. Conventional histology was performed. Continuous administration of UR‐12670 improved the histological pattern of liver xenografts, especially necrosis, loss of hepatocytes, hemorrhage, sinusoidal congestion and lymphocyte infiltration. There was not a shift in specificity of xenoantibodies at different times posttransplantation, as demonstrated by immunoblotting and indirect immunofluorescence. UR‐12670 administration had a beneficial effect on graft function and considerably improved the histopathological pattern, but it failed to induce tolerance after withdrawal of immunosuppression. UR‐12670 had an immunomodulatory effect on cellular response but not on antibody production. There was not a change in the specificity of xenoantibodies produced at LXR compared with pretransplant antibodies.
ELF score ≥9.8 indicates advanced hepatic fibrosis and is influenced by age, steatosis and histological activity

There is increasing need to identify individuals with advanced liver fibrosis, who are at risk of complications such as hepatocellular carcinoma. The commercially available enhanced liver fibrosis (ELF) test provides a non‐invasive assessment of fibrosis severity. This study was designed to determine the diagnostic accuracy of the manufacturer's cut‐off value (≥9.8) in identifying advanced fibrosis.
Bortezomib blocks the catabolic process of autophagy via a cathepsin-dependent mechanism, affects endoplasmic reticulum stress, and induces caspase-dependent cell death in antiestrogen–sensitive and resistant ER+ breast cancer cells

In recent studies, we and others showed that autophagy is critical to estrogen receptor positive (ER+) breast cancer cell survival and the development of antiestrogen resistance. Consequently, new approaches are warranted for targeting autophagy in breast cancer cells undergoing antiestrogen therapy. Because crosstalk has been demonstrated between the autophagy- and proteasome-mediated pathways of protein degradation, this study investigated how the proteasome inhibitor bortezomib affects autophagy and cell survival in antiestrogen-treated ER+ breast cancer cells. Bortezomib, at clinically achievable doses, induced a robust death response in ER+, antiestrogen-sensitive and antiestrogen-resistant breast cancer cells undergoing hormonal therapy. Cleavage of PARP and lamin A was detectable as a read-out of cell death, following bortezomib-induced mitochondrial dysfunction. Prior to induction of cell death, bortezomib-treated cells showed high levels of light chain 3 (LC3) and p62, two protein markers for autophagy. The accumulation of these proteins was due to bortezomib-mediated blockade of long-lived protein turnover during macroautophagy. This novel action of bortezomib was linked to its blockade of cathepsin-L activity, which is required for autolysosomal-mediated protein turnover in ER+ breast cancer cells. Further, bortezomib-treated breast cancer cells showed induction of the unfolded protein response, with upregulation of CHOP and GRP78. Bortezomib also induced high levels of the pro-apoptotic protein BNIP3. Knockdown of CHOP and/or BNIP3 expression via RNAi targeting significantly attenuated the death-promoting effects of bortezomib. Thus, bortezomib inhibits prosurvival autophagy, in addition to its known function in blocking the proteasome, and is cytotoxic to hormonally treated ER+ breast cancer cells. These findings indicate that combining a proteasome inhibitor like bortezomib with SERM therapy may have therapeutic advantage in the management of early-stage breast cancer.
Aryl Hydrocarbon Receptor Is Critical for Homeostasis of Invariant γδ T Cells in the Murine Epidermis

An immunoregulatory role of aryl hydrocarbon receptor (AhR) has been shown in conventional αβ and γδ T cells, but its function in skin γδ T cells (dendritic epidermal T cells [DETC]) is unknown. In this study, we demonstrate that DETC express AhR in wild-type mice, and are specifically absent in the epidermis of AhR-deficient mice (AhR-KO). We show that DETC precursors are generated in the thymus and home to the skin. Proliferation of DETC in the skin was impaired in AhR-KO mice, resulting in a >90% loss compared with wild type. Surprisingly, DETC were not replaced by αβ T cells or conventional γδ T cells, suggesting a limited time frame for seeding this niche. We found that DETC from AhR-KO mice failed to express the receptor tyrosine kinase c-Kit, a known growth factor for γδ T cells in the gut. Moreover, we found that c-kit is a direct target of AhR, and propose that AhR-dependent c-Kit expression is potentially involved in DETC homeostasis. DETC are a major source of GM-CSF in the skin. Recently, we had shown that impaired Langerhans cell maturation in AhR-KO is related to low GM-CSF levels. Our findings suggest that the DETCs are necessary for LC maturation, and provide insights into a novel role for AhR in the maintenance of skin-specific γδ T cells, and its consequences for the skin immune network.
Splitting the Two Pore Domains from TOK1 Results in Two Cationic Channels with Novel Functional Properties*

Potassium channels are membrane-spanning proteins with several transmembrane segments and a single pore region where ion conduction takes place (Biggin, P. C., Roosild, T., and Choe, S. (2000) Curr. Opin. Struct. Biol. 4, 456–461; Doyle, D. A. , Morais Cabral, J., Pfuetzner, R. A. , Kuo, A. , Gulbis, J. M. , Cohen, S. L. , Chait, B. T. , and MacKinnon, R. (1998) Science 280, 69–77). TOK1, a potassium channel identified in the yeast Saccharomyces cerevisiae, was the first described member from a growing new family of potassium channels with two pore domains in tandem (2P) (Ketchum, K. A., Joiner, W. J., Sellers, A. J., Kaczmarek, L. K., and Goldstein, S. A. (1995)Nature 376, 690–695). In an attempt to understand the relative contribution of each one of the 2P from TOK1 to the functional properties of this channel, we split and expressed the pore domains separately or in combination. Expression of the two domains separately rescued a potassium transport-deficient yeast mutant, suggesting that each domain forms functional potassium-permeable channels in yeast. InXenopus laevis oocytes expression of each pore domain resulted in the appearance of unique inwardly rectifying cationic channels with novel gating and pharmacological properties. Both pore domains were poorly selective to potassium; however, upon co-expression they partially restored TOK1 channel selectivity. The single channel conductance was different in both pore domains with 7 ± 1 (n = 12) and 15 ± 2 (n = 12) picosiemens for the first and second domain, respectively. In light of the known structure of the Streptomyces lividans KcsA potassium channel pore (see Doyle et al. above), these results suggest a novel non-four-fold-symmetric architecture for 2P potassium-selective channels.
Whole mammogram image classification with convolutional neural networks

Due to the high variability in tumor morphology and the low signal-to-noise ratio inherent to mammography, manual classification of mammogram yields a significant number of patients being called back, and subsequent large number of biopsies performed to reduce the risk of missing cancer. The convolutional neural network (CNN) is a popular deep-learning construct used in image classification. This technique has achieved significant advancements in large-set image-classification challenges in recent years. In this study, we had obtained over 3000 high-quality original mammograms with approval from an institutional review board at the University of Kentucky. Different classifiers based on CNNs were built, and each classifier was evaluated based on its performance relative to truth values generated by histology results from biopsy and two-year negative mammogram follow-up confirmed by expert radiologists. Our results showed that CNN model we had built and optimized via data augmentation and transfer learning have a great potential for automatic breast cancer detection using mammograms.
Three-dimensional asymmetrical modeling of the mitral valve: a finite element study with dynamic boundaries.

BACKGROUND AND AIM OF THE STUDY Previous computational studies of the normal mitral valve have been limited because they assumed symmetrical modeling and artificial boundary conditions. The study aim was to model the mitral valve complex asymmetrically with three-dimensional (3-D) dynamic boundaries obtained from in-vivo experimental data. METHODS Distance tracings between ultrasound crystals placed in the sheep mitral valve were converted into 3-D coordinates to reconstruct an initial asymmetric mitral model and subsequent dynamic boundary conditions. The non-linear, real-time left ventricular and aortic pressure loads were acquired synchronously. A quasi-static solution was applied over one cardiac cycle. RESULTS The mitral valve leaflet stress was heterogeneous. The trigones experienced highest stresses, while the mid-anterior annulus between trigones experienced low stress. High leaflet stress was observed during peak pressure loading. During isovolumic relaxation, the leaflets were highly stretched between the anterolateral trigone and the posteromedial commissure, resulting in a prominent secondary leaflet stress re-increment. This has not been observed previously, as symmetric models with artificial boundary conditions were studied only in the ejection phase. CONCLUSION Here, the first asymmetrical mitral valve model synchronized with 3-D dynamic boundaries and non-linear pressure loadings over the whole cardiac cycle based on in vivo experimental data is described. Despite its limitations, this model provides new insights into the distribution of leaflet stress in the mitral valve.
Switching to darunavir/ritonavir monotherapy vs. triple-therapy on body fat redistribution and bone mass in HIV-infected adults: the Monarch randomized controlled trial

Changes in body fat distribution and bone mass in HIV-infected patients may be associated with long-term use of nucleoside reverse transcriptase inhibitors (NRTIs). The Monarch trial recruited 30 patients receiving non-nucleoside reverse transcriptase inhibitor or protease inhibitor−based highly active antiretroviral therapy, with HIV RNA <40 copies/mL. Patients were randomized to either darunavir/ritonavir 800/100 mg once daily monotherapy or darunavir/ritonavir 800/100 mg once daily + two NRTIs. Bone mass, peripheral lipoatrophy and central fat accumulation were assessed using dual-energy X-ray absorptiometry scanning, supplemented by computed tomography scans. Median age was 43 years, 77% were men. Visceral adipose tissue remained stable from baseline to Week 48 in the whole group (p = 0.261) with no significant difference between arms (p = 0.56). There was a significant reduction in insulin resistance (HOMA-IR, p = 0.013) over 48 weeks in the whole group, but not of body mass index (p = 0.24). In the darunavir/ritonavir monotherapy arm, there was a small but significant increase in both lumbar and femur bone mineral density at 48 weeks and was observed after correction for baseline values. The absolute change in lumbar bone mineral density at 48 weeks was more pronounced in the darunavir/ritonavir arm compared with the darunavir/ritonavir + 2NRTIs arm. In this study, discontinuing nucleoside analogues and switching to darunavir/ritonavir monotherapy was associated with a small but statistically significant increase in bone mineral density, but stable levels of limb fat and visceral adipose tissue.