Miracle-dz/UniFAR-FTUs huggingface dataset:
Painful physical symptoms and treatment outcome in major depressive disorder: a STAR*D (Sequenced Treatment Alternatives to Relieve Depression) report

Background Painful physical symptoms (PPS) are both common and reduce the likelihood of remission in major depressive disorder (MDD), based upon results of clinical trials in selected populations. Whether PPS significantly contribute to poorer treatment outcome overall in primary or specialty psychiatric care settings remains unclear. Method Out-patients (n=2876) with MDD were treated in the first step of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial with citalopram up to 60 mg/day for up to 14 weeks. Presence of painful symptoms, as well as severity of depression, physical illness, and demographic and treatment factors were examined. Time to and overall rates of remission were analysed in relation to the presence of PPS. Results Of the participants, 80% complained of PPS. These patients, both in primary and specialty psychiatric settings, had significantly lower remission rates and took longer to remit. Increasing severity of PPS was associated with greater physical illness burden, lower socio-economic status, absence of private insurance and being female, African-American or Hispanic. After adjustment for these factors, patients with PPS no longer had significantly poorer treatment outcomes. Conclusions Presence and severity of PPS is an indicator of MDD that may have poorer treatment outcome with an initial selective serotonin reuptake inhibitor. These poorer treatment outcomes are multifactorial, however, and are not explained by the presence and severity of pain per se.
Dose proportionality of stavudine in hiv seropositive asymptomatic subjects: Application to bioequivalence assessment of various capsule formulations

The dose proportionality and bioequivalence of the capsule formulations used in clinical trials and the proposed commercial formulations of stavudine were assessed in an openlabel, single‐dose, randomized four‐way crossover study in 16 asymptomatic HIV‐infected males. One capsule of stavudine (5, 10, 20, or 40 mg) was administered orally to each subject in each of the four treatment periods. Serial blood samples were collected for 10 h after each dose and the plasma was assayed for intact stavudine by a validated radioimmunoassay method. The plasma concentration‐time data were subjected to noncompartmental pharmacokinetic analysis. For doses ranging from 5 to 40 mg, mean Cmax and AUC0‐∞ values were in the range of 110.36–889.34 ng mL−1 and 246.46–1945.97 h ng mL−1 respectively. The mean Cmax and AUC0‐∞ of stavudine increased in a dose‐proportional manner. Irrespective of the dose, mean Cmax values were observed at a median tmax of 0.75 h or less. Mean t1/2 values were 1.97, 1.77, 1.67 and 1.66 h for the 5, 10, 20, and 40 mg capsules, respectively. For bioequivalence assessment, Cmax and AUC0‐∞ values were normalized to the 10 mg dose since these parameters were dose proportional. The 10 mg capsule formulation used in phase‐3 clinical trials was chosen as the reference. The relative bioavailability estimates and 90% confidence limits for the dose‐normalized Cmax values with the 10 mg capsule as the reference were 86% (76%, 96%), 99% (88%, 110%), and 90% (80%, 100%) for the 5, 20, and 40 mg capsules, respectively. The differences in the point estimates of the dose‐normalized AUC0‐∞ values for the 5, 20, and 40 mg capsules relative to the 10 mg phase‐3 capsule were 1% or less, and the 90% confidence limits were all within 95–106%. These results indicate that stavudine exhibits linear pharmacokinetics and that the 5, 10, 20, and 40 mg capsules of stavudine are bioequivalent.
Cone outer segment extracellular matrix as binding domain for interphotoreceptor retinoid‐binding protein

Cones are critically dependent on interphotoreceptor retinoid‐binding protein (IRBP) for retinoid delivery in the visual cycle. Cone‐dominant vertebrates offer an opportunity to uncover the molecular basis of IRBP's role in this process. Here, we explore the association of IRBP with the interphotoreceptor matrix (IPM) of cones vs. rods in cone dominant retinas from chicken (Gallus domesticus), turkey (Meleagris gallopavo), and pig (Sus scrofa). Retinas were detached and fixed directly or washed in saline prior to fixation. Disassociated photoreceptors with adherent matrix were also prepared. Under 2 mM CaCl2, insoluble matrix was delaminated from saline washed retinas. The distribution of IRBP, as well as glycans binding peanut agglutinin (cone matrix) and wheat germ agglutinin (rod/cone matrix), was defined by confocal microscopy. Retina flat mounts showed IRBP diffusely distributed in an interconnecting, lattice‐like pattern throughout the entire matrix. Saline wash replaced this pattern with fluorescent annuli surrounding individual cone outer segments. In isolated cones and matrix sheets, IRBP colocalized with the peanut agglutinin binding matrix glycans. Our results reveal a wash‐resistant association of IRBP with a matrix domain immediately surrounding cone outer segments. The cone matrix sheath may be responsible for IRBP‐mediated cone targeting of 11‐cis retinoids. J. Comp. Neurol. , 2012. © 2011 Wiley Periodicals, Inc.
The Saccharomyces cerevisiae mevalonate diphosphate decarboxylase is essential for viability, and a single Leu-to-Pro mutation in a conserved sequence leads to thermosensitivity

The mevalonate diphosphate decarboxylase is an enzyme which converts mevalonate diphosphate to isopentenyl diphosphate, the building block of isoprenoids. We used the Saccharomyces cerevisiae temperature-sensitive mutant defective for mevalonate diphosphate decarboxylase previously described (C. Chambon, V. Ladeveve, M. Servouse, L. Blanchard, C. Javelot, B. Vladescu, and F. Karst, Lipids 26:633-636, 1991) to characterize the mutated allele. We showed that a single change in a conserved amino acid accounts for the temperature-sensitive phenotype of the mutant. Complementation experiments were done both in the erg19-mutated background and in a strain in which the ERG19 gene, which was shown to be an essential gene for yeast, was disrupted. Epitope tagging of the wild-type mevalonate diphosphate decarboxylase allowed us to isolate the enzyme in an active form by a versatile one-step immunoprecipitation procedure. Furthermore, during the course of this study, we observed that a high level of expression of the wild-type ERG19 gene led to a lower sterol steady-state accumulation compared to that of a wild-type strain, suggesting that this enzyme may be a key enzyme in mevalonate pathway regulation.
Beta-Globin Gene Cluster Haplotypes in Iranian Sickle Cell Patients: Relation to Some Hematologic

Sickle cell anemia is relatively common in Khuzestan province located in Southwest Iran. The characteristics of sickle cell disease in Iran are apparently different from other regions; some of these characteristics might be related to β-chain haplotypes. The purpose of this study was to determine the frequency of β-chain haplotypes in 50 patients with homozygous sickle cell anemia in Khuzestan Province. Materials and Methods: The haplotypes were explored around and within the e-Gγ-Aγ-ѱβ-δ-β globin gene complex by analysing seven polymorphic restriction sites ((1) HincII 5ʹ to e (2) XmnI-5ʹγG, (3) Hind III-γG, (4) Hind III- γA, (5) HincII- ѱβ, (6) HincII- 3ʹto Ψβ, and (7) HinfI and RsaI - 5ʹto β), followed by restriction digestion and agarose gel electrophoresis. The effect of beta globin haplotypes upon hematologic parameters such as hemoglobin, hemoglobin F, mean corpuscular hemoglobin concentration, reticulocyte count, serum bilirubin and Lactate Dehydrogenase was also studied. Results: The Arab/Indian was the most frequent haplotype, present in 38 percent of chromosomes, followed by Benin haplotype (18%), Senegal haplotype (16%), Bantu haplotype (16%) and Cameroon haplotype (12%). The mean percentage of hemoglobin F in sickle cell anemia patients was 17.18±8.81%, and in the homozygous Arab/Indian haplotype it was higher (20.90%), but the difference was not significant. The hemoglobin F was significantly higher in females compared to males (19.10 versus 14.50, P<0.005). Conclusion: There was no significant correlation between haplotypes and hematological characteristics like fetal hemoglobin level among our patients.
The Performance of the Contact Lens Dry Eye Questionnaire as a Screening Survey for Contact Lens-related Dry Eye

Purpose. The contact lens dry eye questionnaire (CLDEQ) is a self-administered survey developed to examine the distribution of dry eye symptoms among contact lens wearers. In this report, we examine the CLDEQ as a screening survey for contact lens-related dry eye and compare it with McMonnies' questionnaire. Methods. The CLDEQ and McMonnies' questionnaire were administered to 367 unselected contact lens wearers at six clinics across the United States and Canada. After completion of the surveys, doctors unaware of the survey results completed a separate form indicating contact lens-related dry eye diagnosis at the end of a nondirected clinical examination. The CLDEQ is composed of nine habitual symptom subscales and a self-diagnosis question, which were tested for their predictive value for a diagnosis of contact lens-related dry eye. McMonnies' instrument was scored with use of the algorithm suggested in the literature. Sensitivity, specificity, and receiver operator characteristic (ROC) curve analyses were performed for each instrument on the basis of logistic regression results. Results. The area under the ROC curve for the CLDEQ was 0.74, indicating moderate contact lens-related dry eye discrimination, and the Hosmer–Lemeshow goodness-of-fit test indicated that the CLDEQ was well calibrated (p = 0.84). The area under the ROC curve for McMonnies' questionnaire was 0.56, indicating poorer discrimination, and the Hosmer–Lemeshow goodness-of-fit test indicated it was also poorly calibrated (p = 0.08) for contact lens wearers. Conclusions. These analyses suggest that the CLDEQ is capable of discriminating contact lens-related dry eye and is accurate in doing so, especially in comparison with McMonnies' questionnaire. The CLDEQ is an efficient screening survey and may be used in future clinical research and epidemiologic studies of contact lens-related dry eye.
Pretest prediction of BRCA1 or BRCA2 mutation by risk counselors and the computer model BRCAPRO.

BACKGROUND Because BRCA gene mutation testing is costly, occasionally uninformative, and frequently associated with ethical and legal issues, careful patient selection is required prior to testing. Estimation of BRCA gene mutation probability is an important component of pretest counseling, but the accuracy of these estimates is currently unknown. We measured the performance of eight cancer risk counselors and of a computer model, BRCAPRO, at identifying families likely to carry a BRCA gene mutation. METHODS Eight cancer risk counselors and the computer model BRCAPRO estimated BRCA gene mutation probabilities for 148 pedigrees selected from an initial sample of 272 pedigrees. The final sample was limited to pedigrees with a proband affected by breast or ovarian cancer and BRCA1 and BRCA2 gene sequencing results unequivocally reported as negative or positive for a deleterious mutation. Sensitivity, specificity, negative predictive value, positive predictive value, and areas under receiver operator characteristics (ROC) curves were calculated for each risk counselor and for BRCAPRO. All statistical tests were two sided. RESULTS Using a greater-than-10% BRCA gene mutation probability threshold, the median sensitivity for identifying mutation carriers was 94% (range = 81% to 98%) for the eight risk counselors and 92% (range = 91% to 92%) for BRCAPRO. Median specificity at this threshold was 16% (range = 6% to 34%) for the risk counselors and 32% (range = 30% to 34%) for BRCAPRO (P =.04). Median area under the ROC curves was 0.671 for the risk counselors (range = 0.620 to 0.717) and 0.712 (range = 0.706 to 0.720) for BRCAPRO (P =.04). There was a slight, but not statistically significant, improvement in all counselor performance measures when BRCAPRO-assigned gene mutation probability information was included with the pedigrees. CONCLUSIONS Sensitivity for identifying BRCA gene mutation carriers is similar for experienced risk counselors and the computer model BRCAPRO. Because the computer model consistently demonstrated superior specificity, overall discrimination between BRCA gene mutation carriers and BRCA gene mutation noncarriers was slightly better for BRCAPRO.
THE role of indoleamine 2,3‐dioxygenase in the anti‐tumour activity of human interferon‐γ in vivo

We have studied the relationship between L‐tryptophan metabolism and the response to human IFN‐γ in 3 human ovarian cancer xenografts growing in nude mice. During IFN‐γ therapy all 3 tumours showed a profound depletion in L‐tryptophan and a corresponding rise in L‐kynurenine. The microenvironment surrounding the tumours was also depleted of L‐tryptophan. The IFN‐γ‐inducible enzyme indoleamine dioxygenase, IDO, was induced in treated tumours. While there was a variability in IDO mRNA expression in the different xenografts tested, in situ hybridization showed that the gene was induced at all levels of the tumour, and not just the periphery. These results show that induction of IDO by IFN‐γ in vivo can metabolize L‐tryptophan rapidly enough for it to become depleted, despite a continued supply of L‐tryptophan from the host. The IDO mRNA and protein remained induced after the L‐tryptophan levels had returned to normal, suggesting that the gene may be post‐transcriptionally regulated and/or the IDO co‐factor supply may be limited. Another IFN‐γ‐inducible gene, tryptophanyl tRNA synthetase, was also induced in the tumour. It is possible that this enzyme, which is responsible for synthesizing tryptophanyl tRNA, acts in a compensatory manner by allowing protein synthesis to continue despite low free Ltryptophan concentrations. There was no correlation of the above parameters with the anti‐tumour response to IFN‐γ, suggesting that other mechanisms must play a role. Ltryptophan depletion may be a contributor to a multifactorial growth inhibition of tumour cells following IFN‐γ treatment, but cannot on its own explain their growth inhibition. © 1995 Wiley‐Liss, Inc.
Expression of members of the bcl-2 gene family in the immature rat ovary: equine chorionic gonadotropin-mediated inhibition of granulosa cell apoptosis is associated with decreased bax and constitutive bcl-2 and bcl-xlong messenger ribonucleic acid levels.

The loss of ovarian follicles through atresia, which accounts for greater than 99% of postnatal female germ cell depletion, is mediated through apoptotic cell death. Although recent data have shown that apoptosis in granulosa cells of ovarian follicles can be hormonally manipulated, the molecular mechanisms responsible for transducing external signals remain to be elucidated. Herein we have characterized changes in the expression of the bcl-2 protooncogene (an inhibitor of apoptosis), the bax gene (an inducer of apoptosis), and the bcl-x gene (which encodes both bcl-xlong, an inhibitor of apoptosis, and bcl-xshort, an inducer of apoptosis) during gonadotropin-stimulated follicular development in vivo and during atresia of antral follicles incubated in vitro. Complementary DNA fragments corresponding to rat bcl-2, rat bax, and rat bcl-x coding sequences were obtained by the reverse transcription-polymerase chain reaction (RT-PCR) technique using total RNA prepared from immature rat ovaries. Northern blot analysis of steady-state bcl-2, bax, and bcl-x messenger RNA (mRNA) levels in total RNA prepared from ovaries of immature rats before and after in vivo priming with 10 IU equine CG (eCG) revealed that eCG-induced follicular growth and survival were associated with a relatively constitutive level of bcl-2 and bcl-x expression but markedly reduced levels of bax mRNA (29 +/- 5% of saline-treated control animals). Using the RT-PCR technique coupled with Southern blot hybridization analysis to distinguish the long vs. short forms of bcl-x (which differ in size by 189 base pairs), it was determined that bcl-xlong was the predominant message expressed by granulosa cells of eCG-primed ovaries. The eCG-mediated decrease in bax expression, coupled with a maintenance of bcl-2 and bcl-xlong mRNA levels, were associated with a pronounced reduction in the extent of granulosa cell apoptosis. In contrast, the induction of apoptosis in a homogeneous population of healthy antral follicles by incubation in vitro without tropic support was associated with an significant increase in bax mRNA levels to 220 +/- 10% of those detected in freshly isolated, healthy follicles. Moreover, bcl-xlong message levels were significantly reduced in follicles incubated for 24 h to 69 +/- 4% of those levels detected in freshly isolated, healthy follicles. However, no significant change in the level of bcl-2 mRNA was detected. (ABSTRACT TRUNCATED AT 250 WORDS)
Abnormal Excitability and Episodic Low-Frequency Oscillations in the Cerebral Cortex of the tottering Mouse

The Ca2+ channelopathies caused by mutations of the CACNA1A gene that encodes the pore-forming subunit of the human Cav2.1 (P/Q-type) voltage-gated Ca2+ channel include episodic ataxia type 2 (EA2). Although, in EA2 the emphasis has been on cerebellar dysfunction, patients also exhibit episodic, nonmotoric abnormalities involving the cerebral cortex. This study demonstrates episodic, low-frequency oscillations (LFOs) throughout the cerebral cortex of tottering (tg/tg) mice, a widely used model of EA2. Ranging between 0.035 and 0.11 Hz, the LFOs in tg/tg mice can spontaneously develop very high power, referred to as a high-power state. The LFOs in tg/tg mice are mediated in part by neuronal activity as tetrodotoxin decreases the oscillations and cortical neuron discharge contain the same low frequencies. The high-power state involves compensatory mechanisms because acutely decreasing P/Q-type Ca2+ channel function in either wild-type (WT) or tg/tg mice does not induce the high-power state. In contrast, blocking l-type Ca2+ channels, known to be upregulated in tg/tg mice, reduces the high-power state. Intriguingly, basal excitatory glutamatergic neurotransmission constrains the high-power state because blocking ionotropic or metabotropic glutamate receptors results in high-power LFOs in tg/tg but not WT mice. The high-power LFOs are decreased markedly by acetazolamide and 4-aminopyridine, the primary treatments for EA2, suggesting disease relevance. Together, these results demonstrate that the high-power LFOs in the tg/tg cerebral cortex represent a highly abnormal excitability state that may underlie noncerebellar symptoms that characterize CACNA1A mutations.
The relationship between national well-being and xenophobia in a divided society: The case of South Africa

Personal well-being surveys have increased their coverage on the African continent in recent years, but detailed research on subjective national wellbeing is less common. The link between national well-being and xenophobic sentiments has not been adequately tested in an African context. In order to better understand (and correspondingly counter) xenophobic sentiments in sub- Saharan Africa, this article tests the correlation of National Well-being Index (NWI) with attitudes towards immigrants in a sub-Saharan country. South Africa was chosen as the research site for this study and data were used from the 2012 South African Social Attitudes Survey (SASAS), a nationally representative opinion poll of 2 521 respondents. In 2012 the six items that constitute the NWI were included in this survey, measuring public evaluations of the country’s economic, natural, governmental, social and security environment. This allowed the construction of the NWI, a composite score that provides a more precise measurement of sociotropic concerns. The findings of this study show that, even when controlling for individual well-being and socio-economic status, the NWI had a statistically significant relationship with attitudes towards immigrants. The lower the reported NWI, the more likely an individual will be to believe negative stereotypes about immigrants. This suggests the importance of studying and measuring subjective national well-being on the African continent.
New records of resupinate, non-poroid agaricomycetous fungi from India.

Nine species of corticioid fungi are newly reported from India. Amethicium luteoincrustatum, Athelidium aurantiacum, Dendrothele commixta, Erythricium hypnophilum, Gloeodontia columbiensis, Peniophorella incrustatissima, Scytinostroma ahmadii, S. corneri and Tretomyces lutescens are described and illustrated, based on collections made from different localities of Punjab and the adjoining area of Chandigarh.
Quantitative assessment of posture stability using computerised dynamic posturography in type 2 diabetic patients with neuropathy and its relation to glycaemic control.

INTRODUCTION Patients with diabetic neuropathy have an imbalance, which comes with a higher risk of falls. The aim of this study was to assess posture stability using computerised dynamic posturography in type 2 diabetics mellitus patients with neuropathy as well as its relation to glycaemic control. METHODS 54 type 2 diabetics mellitus patients with peripheral neuropathy were recruited, together with 18 type 2 diabetics mellitus patients without peripheral neuropathy acting as the control group. The first group was divided into two subgroups according to glycaemic control assessed by HbA1c (A1c), the first subgroup comprising 24 patients had good glycaemic control with A1c less than or equal to seven percent and the second subgroup with 30 patients had poor glycaemic control with A1c more than 7 percent. The postural stability was evaluated using dynamic posturography. RESULTS The composite equilibrium score, sensory organisation test 1, 2 and 3 conditions were significantly lower in the neuropathic group as compared to the non-neuropathic group (p-value is less than 0.001). A1c was significantly correlated with the composite equilibrium score in the neuropathic group with poor glycaemic control (r-value equal to -0.395) but not correlated in the neuropathic group with good glycaemic control (r-value equal to 0.151). CONCLUSION Posture instability in type 2 diabetic patients with peripheral neuropathy reflects an impairment of the somatosensory system; also, poor glycaemic control resulted in more posture instability. The early detection of imbalance using dynamic posturography and achieving good glycaemic control may be of great help in the prevention of falls in such patients.
Ensemble of Part Detectors for Simultaneous Classification and Localization

Part-based representation has been proven to be effective for a variety of visual applications. However, automatic discovery of discriminative parts without object/part-level annotations is challenging. This paper proposes a discriminative mid-level representation paradigm based on the responses of a collection of part detectors, which only requires the image-level labels. Towards this goal, we first develop a detector-based spectral clustering method to mine the representative and discriminative mid-level patterns for detector initialization. The advantage of the proposed pattern mining technology is that the distance metric based on detectors only focuses on discriminative details, and a set of such grouped detectors offer an effective way for consistent pattern mining. Relying on the discovered patterns, we further formulate the detector learning process as a confidence-loss sparse Multiple Instance Learning (cls-MIL) task, which considers the diversity of the positive samples, while avoid drifting away the well localized ones by assigning a confidence value to each positive sample. The responses of the learned detectors can form an effective mid-level image representation for both image classification and object localization. Experiments conducted on benchmark datasets demonstrate the superiority of our method over existing approaches.