Miracle-dz/UniFAR-FTUs huggingface dataset:
A morphological and functional study of Congenital Hereditary Endothelial Dystrophy.

PURPOSE To contribute to the basic understanding of Congenital Hereditary Endothelial Dystrophy (CHED) by clinical, functional, and histopathological examinations of three cases. METHODS Prior to grafting, corneas were evaluated by slit lamp examination and by assessment of endothelial permeability to fluorescein. Following penetrating keratoplasty, corneal buttons were evaluated by light- and electron microscopy and by assessment of stromal swelling pressure. RESULTS Patients with CHED had a markedly increased corneal thickness (0.93-0.98 mm) with epithelial oedema and a stromal swelling pressure close to zero; suggesting that the stroma was maximally swollen in vivo. Corneal endothelium showed an increased permeability to fluorescein; suggesting a functional barrier defect. Histopathological evaluation revealed: 1) a normal endothelial cell density; 2) an abnormal endothelial morphology with irregular and multi-nucleated cells containing abnormal cell organelles; and 3) a profound thickening of Descemet's membrane, 16-18 microm, with multiple focal areas of abnormal fibrillar deposits in the posterior half. CONCLUSIONS This study suggests that the primary defect in patients with CHED is a degenerated and dysfunctional corneal endothelium, characterized by an increased permeability and an abnormal and accelerated Descemet's membrane secretion. The underlying pathophysiological mechanism(s) may be related to an abnormal endothelial barrier function, leading to secondary swelling of the stroma and epithelium. Further studies are needed to identify the specific functional defect(s) and the embryological origin of the abnormal corneal endothelium in CHED.
Interaction of C225SR1 mutant subunit of ribonucleotide reductase with R2 and nucleoside diphosphates: tales of a suicidal enzyme.

Ribonucleotide reductase (RDPR) from Escherichia coli is composed of two subunits, R1 and R2, both of which are required to catalyze the conversion of nucleotides to deoxynucleotides. This reduction process is accompanied by oxidation of two cysteines within the active site to a disulfide. One of these putative active site cysteines, C225, has been mutated to a serine, and the properties of this mutant (C225SR1) have been investigated in detail. Incubation of C225SR1 and R2 with [3'-3H,U-14C]UDP results in time-dependent inactivation of the enzyme! This inactivation is accompanied by production of 2.4 uracils, 3H2O, and 3H,14C-labeled protein with an absorbance change at 320 nm. There is an isotope effect (kH/k3H) on uracil production of 3.2. In addition, the tyrosyl radical on R2 is reduced. The observation of 3H2O, indicative of 3' carbon-hydrogen bond cleavage and loss of the tyrosyl radical, provides a direct test of our mechanistic hypothesis that cleavage of this bond occurs concomitantly with tyrosyl radical reduction. Incubation of [3'-2H]UDP with C225SR1 and R2 resulted in a V and V/K isotope effect on loss of the radical of 2.0 and 2.0, respectively. These studies provide the first direct evidence for protein radical involvement in catalysis. Reduction of the tyrosyl radical on R2 is accompanied by a stoichiometric cleavage of the R1 polypeptide into two new polypeptides of 26 and 61 kDa. The 26-kDa polypeptide is the N-terminus of R1, and hence cleavage of the polypeptide is occurring in the region of the mutation. The N-terminus of the 61-kDa polypeptide is blocked. (ABSTRACT TRUNCATED AT 250 WORDS)
To be reassured or to understand? A dilemma in communicating normal cervical screening results.

BACKGROUND Receiving negative test results may be associated with two problems: (a). not being reassured and wanting further, unnecessary screening; and (b). not understanding residual risk and not attending future recommended screening. AIM To test two hypotheses: (1). Emphasizing test accuracy and low residual risk when giving negative test results reduces a desire for further unnecessary screening, while also reducing a correct understanding of the meaning of the result. (2). The effect of emphasizing low risk on desire for future screening is mediated by lack of reassurance. DESIGN Experimental, vignette-based study, with a 2 x 2 factorial design. METHOD A sample of 184 women was asked to imagine that they had recently undergone a cervical screening test and received a normal result. They were given one of four hypothetical letters from their GP,differing in whether or not it emphasized test accuracy and low residual risk of developing cervical cancer. Participants completed a questionnaire assessing perceived risk, reassurance about test results, desire for further screening within six months and understanding of the test results. RESULTS Emphasizing test accuracy and low residual risk increases desire for inappropriate screening while reducing the understanding of residual risk. These effects are interactive, in that presenting both together has a larger effect than the sum of the two individual effects. The effect of emphasizing low risk on desire for future screening was mediated by reassurance. CONCLUSION Emphasizing low residual risk and test accuracy is a double-edged sword: it reduces a desire for unnecessary screening, but also reduces correct understanding of the result.
Tesetaxel, an advanced-generation oral taxane, as first-line treatment in women with metastatic breast cancer.

TPS123 Background: Taxanes such as docetaxel and paclitaxel are among the most active agents in metastatic breast cancer (MBC). Tesetaxel is an active novel taxoid that overcomes disadvantages of these standard agents. Among other features, the drug is taken by mouth as an oral capsule. Tesetaxel is not a substrate for P-glycoprotein, a major cause of taxane resistance. The drug is not associated with hypersensitivity reactions, thus obviating the need for both premedications and extended medical/nursing observation. Preclinical studies in human tumor xenografts show activity in taxane-resistant BC as well as reduced peripheral neuropathy. In dose-ranging studies, 8 of 13 evaluable patients (pts) (62%) with MBC achieved prolonged stable disease (SD) (i.e., up to 24 cycles) when the drug was administered once every 3 weeks (wks). A phase II trial of tesetaxel (27-35 mg/m2 p.o. Q3 wks) showed a 38% partial response (PR) rate among 34 pts who had progressed after an anthracycline-containing regimen. Based on these favorable data, we have initiated a multicenter study to assess the efficacy and safety of tesetaxel as 1st-line therapy in MBC. METHODS Eligible patients have: Stage IV, HER2-negative MBC; ECOG PS 0-1; adequate organ function; no prior chemotherapy for MBC, although 1 adjuvant regimen is allowed. Tesetaxel is administered Q3 wks at a starting dose of 27 mg/m2 p.o. , which can be increased to 35 mg/m2 depending on tolerability. A Simon mini-max two-stage design is being used. Target accrual is 25 pts. Response rate, per RECIST 1.1 criteria, is the primary endpoint. Other objectives include progression-free survival and safety. Assuming initial results are favorable, we will examine a weekly dosing schedule in a second pt cohort.
Clinicopathological features of nonspecific invasive breast cancer according to its molecular subtypes.

UNLABELLED The aim of the present study was to investigate the clinical and morphological features of nonspecific invasive breast cancer according to its molecular subtypes. MATERIALS AND METHODS 163 women with nonspecific invasive breast cancer (T1-4N0-3M0) were included in the present study. Luminal A type of breast cancer was detected in 101 women, luminal B type - in 23 women, overexpression of HER2/neu was identified in 14 women and triple-negative cancer - in 25 women. RESULTS The study revealed that various molecular subtypes of breast cancer differ in the morphological structure, the expression characteristics of the primary tumor and the rate of lymphogenous and hematogenous metastasis. Lymphogenous metastases were more frequently (in 71%) detected in HER2/neu overexpressing breast cancer than in luminal A (41%), luminal B (39%) and triple-negative tumors (40%). Hematogenous metastasis did not depend on the morphological structure of carcinoma infiltrative component, the state of tumor stroma as well as the proliferative activity in all the investigated groups. CONCLUSION The revealed clinicopathological characteristics of different molecular subtypes of invasive breast cancer allow to predict the possible outcome of the disease and select personalized treatment strategy for patients more reasonably.
Glucocorticoid-dependent induction of interleukin-6 receptor expression in human hepatocytes facilitates interleukin-6 stimulation of amino acid transport.

OBJECTIVE The authors studied the effects of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) on glutamine and alanine transport in isolated human hepatocytes. They also evaluated the role of dexamethasone in modulating this response and its effects on the expression of the plasma membrane high-affinity IL-6 receptor. SUMMARY BACKGROUND DATA Animal studies indicate that cytokines are important mediators of the increased hepatic amino acid uptake that occurs during cancer and sepsis, but studies in human tissues are lacking. The control of transport by cytokines and cytokine receptor expression in the liver may provide a mechanism by which hepatocytes can modulate amino acid availability during catabolic disease states. METHODS Human hepatocytes were isolated from wedge biopsy specimens and plated in 24-well trays. Interleukin-6 and TNF-alpha, in combination with the synthetic glucocorticoid dexamethasone, were added to hepatocytes in culture, and the transport of radiolabeled glutamine and alanine was measured. Fluorescent-activated cell sorter (FACS) analysis was used to study the effects of dexamethasone on IL-6 receptor number in the well-differentiated human hepatoma HepG2. RESULTS Both IL-6 and TNF-alpha exerted a small stimulatory effect on alanine and glutamine transport. Dexamethasone alone did not alter transport rates, but pretreatment of cells augmented the effects of both cytokines on carrier-mediated amino acid uptake. Dexamethasone pretreatment and a combination of IL-6 and TNF-alpha resulted in a greater than twofold increase in transport activity. Fluorescent-activated cell sorter analysis demonstrated that dexamethasone induced a threefold increase in the expression of high-affinity IL-6 receptors. CONCLUSIONS Interleukin-6 and TNF-alpha work coordinately with glucocorticoids to stimulate amino acid uptake in human hepatocytes. Dexamethasone exerts a permissive effect on cytokine-mediated increases in transport by increasing IL-6 receptor expression on the cell surface. It is likely that this upregulation of IL-6 receptors "primes" human liver cells for subsequent stimulation by cytokines. The resulting increase in hepatic amino acid transport provides the liver with substrate to support key metabolic pathways during catabolic states.
Mechanisms of anabolic therapies for osteoporosis.

Antiresorptive agents help to restore skeletal balance by reducing bone turnover, primarily at the tissue level. Another therapeutic approach is to enhance bone formation with the use of anabolic agents, which differ fundamentally from antiresorptive drugs in their primary mechanism of action. This article reviews the mechanisms of polypeptide anabolic agents and strontium as potential therapeutic options for osteoporosis.
Seasonal persistence of midlatitude total ozone anomalies

Temporal autocorrelations of monthly mean total ozone anomalies over the 35–60°S and 35–60°N latitude bands reveal that anomalies established in the wintertime midlatitude ozone buildup persist (with photochemical decay) until the end of the following autumn, and then are rapidly erased once the next winter's buildup begins. The photochemical decay rate is found to be identical between the two hemispheres. High predictability of ozone through late summer exists based on the late‐spring values. In the northern hemisphere, extending the 1979–2001 springtime ozone trend to other months through regression based on the seasonal persistence of anomalies captures the seasonality of the ozone trends remarkably well. In the southern hemisphere, the springtime trend only accounts for part of the summertime trends. There is a strong correlation between the ozone anomalies in northern hemisphere spring and those in the subsequent southern hemisphere spring, but not the converse.
Low-Temperature, Ion Beam-Assisted SiC Thin Films With Antireflective ZnO Nanorod Arrays for High-Temperature Photodetection

This work demonstrates high-temperature operation of metal-semiconductor-metal photodetectors (MSM PDs) using low-temperature, ion beam-assisted deposition of nanocrystalline SiC thin films and hydrothermal synthesis of ZnO nanorod arrays (NRAs). Due to the incorporation of ZnO NRAs, the photo-to-dark current ratio of SiC MSM PDs is increased from 4.9 to 13.3 at 25 °C and from 4.9 to 7.6 at 200 °C. The enhancement in the sensitivity suggests that the ZnO NRAs could serve as an effective antireflective layer to guide more light into the SiC MSM PDs. This was confirmed through the characterization of reflectance measurements and finite-difference time-domain analysis. These results support the integration of nanocrystalline SiC thin films and ZnO NRAs for use in high-temperature photodetection applications.
Detection of Alzheimer's Disease by Three-Dimensional Displacement Field Estimation in Structural Magnetic Resonance Imaging.

BACKGROUND Within the past decade, computer scientists have developed many methods using computer vision and machine learning techniques to detect Alzheimer's disease (AD) in its early stages. OBJECTIVE However, some of these methods are unable to achieve excellent detection accuracy, and several other methods are unable to locate AD-related regions. Hence, our goal was to develop a novel AD brain detection method. METHODS In this study, our method was based on the three-dimensional (3D) displacement-field (DF) estimation between subjects in the healthy elder control group and AD group. The 3D-DF was treated with AD-related features. The three feature selection measures were used in the Bhattacharyya distance, Student's t-test, and Welch's t-test (WTT). Two non-parallel support vector machines, i.e., generalized eigenvalue proximal support vector machine and twin support vector machine (TSVM), were then used for classification. A 50 × 10-fold cross validation was implemented for statistical analysis. RESULTS The results showed that "3D-DF+WTT+TSVM" achieved the best performance, with an accuracy of 93.05 ± 2.18, a sensitivity of 92.57 ± 3.80, a specificity of 93.18 ± 3.35, and a precision of 79.51 ± 2.86. This method also exceled in 13 state-of-the-art approaches. Additionally, we were able to detect 17 regions related to AD by using the pure computer-vision technique. These regions include sub-gyral, inferior parietal lobule, precuneus, angular gyrus, lingual gyrus, supramarginal gyrus, postcentral gyrus, third ventricle, superior parietal lobule, thalamus, middle temporal gyrus, precentral gyrus, superior temporal gyrus, superior occipital gyrus, cingulate gyrus, culmen, and insula. These regions were reported in recent publications. CONCLUSIONS The 3D-DF is effective in AD subject and related region detection.
Interobserver reproducibility of Gleason grading of prostatic carcinoma: general pathologist.

Only a few large studies of interobserver reproducibility of Gleason grading of prostatic carcinoma exist. Thirty-eight biopsies containing prostate cancer were distributed for Gleason grading to 41 general pathologists in Georgia. These cases had "consensus" Gleason grade groups (2-4, 5-6, 7, and 8-10) that were agreed on by at least 7 of 10 urologic pathologists. The overall kappa (kappa) coefficient for interobserver agreement for these 38 cases was 0.435, barely moderate agreement, with a kappa range from 0.00 to 0.88. There was consistent undergrading of Gleason scores 5-6 (47%), 7 (47%) and, to a lesser extent, 8-10 (25%). In cases with consensus primary patterns, there was consistent undergrading of patterns 2 (32%), 3 (39%), and 5 (30%). Pattern 2 was often (17%) mistaken for pattern 3. Pattern 4 was often undergraded (21%) and also mistaken for pattern 5 (17%). The most significant (P < .005) demographic factor associated with better interobserver agreement was having learned Gleason grading at a meeting or course. We believe that Gleason grading can be learned to a satisfactory level of interobserver reproducibility and have undertaken additional studies that support this belief.
Iron‐chelating agent, deferasirox, inhibits neutrophil activation and extracellular trap formation

Iron‐chelating agents, which are frequently prescribed to transfusion‐dependent patients, have various useful biological effects in addition to chelation. Reactive oxygen species (ROS) produced by neutrophils can cause pulmonary endothelial cell damage, which can lead to acute lung injury (ALI). We previously reported that deferasirox (DFS), an iron‐chelating agent, inhibits phorbol myristate acetate (PMA) or formyl‐methionyl‐leucyl‐phenylalanine (fMLP)‐induced ROS production in neutrophils, in vitro. Here, we investigate whether DFS inhibits vacuolization in neutrophils and neutrophil extracellular trap (NET) formation. Human neutrophils were incubated with DFS and stimulated with PMA or fMLP. Human neutrophils were separated from heparinized peripheral blood using density gradient centrifugation, and subsequently incubated with DFS. After 10 minutes, neutrophils were stimulated by PMA or fMLP. Vacuole formation was observed by electron microscopy. For observing NET formations using microscopes, immunohistological analyses using citrullinated histone H3 and myeloperoxidase antibodies, and SYTOX Green (an impermeable DNA detection dye) staining, were conducted. NET formation was measured as the quantity of double‐stranded DNA (dsDNA), using the AccuBlue Broad Range dsDNA Quantitation Kit. DFS (50 μmol/L) inhibited vacuole formation in the cytoplasm and NET formation. Additionally, 5–100 μmol/L concentration of DFS inhibited the release of dsDNA in a dose‐independent manner. We demonstrate that DFS inhibits not only ROS production but also vacuolization and NET formation in neutrophils. These results suggest the possibility of protective effects of DFS against NET‐related adverse effects, including ALI and thrombosis.
Selection of Mutant Cell Lines Resistant to Infection by Chlamydia spp

The lytic outcome of natural infection by Chlamydia trachomatis was exploited to select CHO (Chinese hamster ovary) cells, following chemical mutagenesis, that were deficient in their ability to sustain productive chlamydial infection. Four distinct mutant cell phenotypes with defects in either attachment or postattachment mechanisms that are required for infection by C. trachomatis and Chlamydia pneumoniae were characterized.
Prevalence of viral markers among refugees from southern Albania: increased incidence of infection with hepatitis A, B and D viruses.

BACKGROUND Since 1991, thousands of refugees from southern Albania have entered north-western Greece, an area with low-to-moderate endemicity for infection with hepatitis viruses. We examined the prevalence of several markers of viral infection in this population in order to ascertain the likely impact of its presence on the epidemiology of hepatitis infections in north-western Greece. DESIGN Consecutive unselected serum samples were obtained from refugees resident in three different reception camps. SETTING A university hospital. STUDY POPULATION One thousand and twenty-five refugees (662 males and 363 females, age range 0-81 years) and 1984 healthy controls (1293 males and 691 females, age range 0-80 years). INTERVENTIONS None. RESULTS We found a significantly greater prevalence of markers of infection with hepatitis A virus (prevalence of antibodies to hepatitis A virus 98.2%), hepatitis B virus (HBV; prevalence of HBV s antigen 22.2%, prevalence of HBV c antibody 70.6%, prevalence of HBV s antibody 40.5%, prevalence of HBV e antigen 21.1%, prevalence of HBV e antibody 46.2%), hepatitis C virus (prevalence of antibodies to hepatis C virus 1.75%) and hepatitis D virus (prevalence of antibodies to hepatis D virus 12.7%) among refugees from southern Albania than in healthy Greek controls. These markers were found with significantly greater frequency among younger refugees (< 30 years of age) than in older members of the same population. CONCLUSIONS We conclude that refugees from southern Albania are a new immigrant population characterized by a high incidence of infection with hepatitis A, B and D viruses. This finding may reflect the low socioeconomic status of the immigrant population and the poor hygienic conditions experienced by its members. The high incidence of HBV and HDV infections in the population from Albania will probably increase the prevalence of infection with these viruses in Ioannina and subsequently in the whole of the Epirus region. We therefore believe that rigorous adherence to general precautions and the initiation of hepatitis B vaccination programmes will be necessary in future, both in our area and in Albania.
Characterization of Mesenchymal Stem Cells Isolated from Mouse Fetal Bone Marrow

Mesenchymal stem cells (MSCs) are defined as cells that can differentiate into multiple mesenchymal lineage cells. MSCs have some features (surface molecules and cytokine production, etc.) common to so‐called traditional bone marrow (BM) stromal cells, which have the capacity to support hemopoiesis. In the present study, we isolated murine MSCs (mMSCs) from the fetal BM using an anti‐PA6 monoclonal antibody (mAb) that is specific for bone marrow stromal cells. The mMSCs, called FMS/PA6‐P cells, are adherent, fibroblastic, and extensively expanded and have the ability to differentiate not only into osteoblasts and adipocytes but also into vascular endothelial cells. The FMS/PA6‐P cells produce a broad spectrum of cytokines and growth factors closely related to hemopoiesis and show good hemopoiesis‐supporting capacity both in vivo and in vitro, suggesting that they are a component of the hemopoietic stem cell niche in vivo. Interestingly, although the FMS/PA6‐P cells express a high level of the PA6 molecule, which is reactive with anti‐PA6 mAb, they gradually lose their ability to express this molecule during the course of differentiation into osteoblasts and adipocytes, indicating that the PA6 molecule might serve as a novel marker of mMSCs.
Spontaneous Eye Blink Rates Vary According to Individual Differences in Generalized Control Perception

This study tested the hypothesis that individual differences in generalized control perception for 43 undergraduate adults may be reflected in Spontaneous Eye Blink Rates during conversation in an interview. Control perception was assessed by means of Rotter's internal-external Locus of Control questionnaires, while Spontaneous Eye Blink Rates were computed from filmed videos of interviews consisting of a series of questions which could presumably have triggered different mental states. Pearson correlations and linear regression analyses indicated that the individual differences in Spontaneous Eye Blink Rates did not differ significantly across different questions, but that Spontaneous Eye Blink Rates measured over the entire interview correlated positively and significantly with an internal Locus of Control (r = .26). This could be interpreted as modest but corroborative evidence that a personality trait reflecting control perception may have a biological component. The possible roles of dopamine neurotransmission and frontal cortex involvement in higher cognition and Locus of Control are discussed.