Miracle-dz/UniFAR-FTUs huggingface dataset:
Treatment-refractory anxiety; definition, risk factors, and treatment challenges

A sizable proportion of psychiatric patients will seek clinical evaluation and treatment for anxiety symptoms reportedly refractory to treatment. This apparent lack of response is either due to “pseudo-resistance” (a failure to have received and adhered to a recognized and effective treatment or treatments for their condition) or to true “treatment resistance. ” Pseudo-resistance can be due to clinician errors in selecting and delivering an appropriate treatment effectively, or to patient nonadherence to a course of treatment. True treatment resistance can be due to unrecognized exogenous anxiogenic factors (eg, caffeine overuse, sleep deprivation, use of alcohol or marijuana) or an incorrect diagnosis (eg, atypical bipolar illness, occult substance abuse, attention deficit-hyperactivity disorder). Once the above factors are eliminated, treatment should focus on combining effective medications and cognitive behavioral therapy, combining several medications (augmentation), or employing novel medications or psychotherapies not typically indicated as first-line evidence-based anxiety treatments.
Correlates and predictors of loneliness in older-adults: a review of quantitative results informed by qualitative insights

ABSTRACT Background: Older persons are particularly vulnerable to loneliness because of common age-related changes and losses. This paper reviews predictors of loneliness in the older population as described in the current literature and a small qualitative study. Methods: Peer-reviewed journal articles were identified from psycINFO, MEDLINE, and Google Scholar from 2000–2012. Overall, 38 articles were reviewed. Two focus groups were conducted asking older participants about the causes of loneliness. Results: Variables significantly associated with loneliness in older adults were: female gender, non-married status, older age, poor income, lower educational level, living alone, low quality of social relationships, poor self-reported health, and poor functional status. Psychological attributes associated with loneliness included poor mental health, low self-efficacy beliefs, negative life events, and cognitive deficits. These associations were mainly studied in cross-sectional studies. In the focus groups, participants mentioned environmental barriers, unsafe neighborhoods, migration patterns, inaccessible housing, and inadequate resources for socializing. Other issues raised in the focus groups were the relationship between loneliness and boredom and inactivity, the role of recent losses of family and friends, as well as mental health issues, such as shame and fear. Conclusions: Future quantitative studies are needed to examine the impact of physical and social environments on loneliness in this population. It is important to better map the multiple factors and ways by which they impact loneliness to develop better solutions for public policy, city, and environmental planning, and individually based interventions. This effort should be viewed as a public health priority.
Two new 3′ PML Breakpoints in t(15;17)(q22;q21)‐positive acute promyelocytic leukemia

In the present article, two new types of PML/RARA junctions are described. Both were identified in diagnostic samples from two t(15;17)(q22;q21)‐positive acute promyelocytic leukemia (APL) patients who failed to achieve complete remission. By using different sets of primers, reverse transcriptase polymerase chain reaction (RT‐PCR) of PML/RARA junctions showed atypical larger bands compared with those generated from the three classical PML breakpoints already described. Sequence analysis of the fusion region of the amplified cDNAs allowed us to determine the specificity of these fragments in both patients. This analysis showed two new hybrid transcripts that were 53 and 306 base pairs (bp) longer than that expressed by the NB4 cell line (PML breakpoint within intron 6), and are the result of the direct joining of RARA exon 3 with PML exon 7a (patient 2) or the 5′ portion of PML exon 7b (patient 1), respectively. In patient 1, RT‐PCR analysis of the reciprocal RARA/PML junction showed a smaller transcript than that expected in bcr1 cases, while in patient 2 no amplified fragment was obtained. Cytogenetic analysis and/or fluorescence in situ hybridization (FISH) showed that both patients had the t(15;17) translocation. The clinical and hematological profiles expressed by the two patients carrying these unexpected types of PML/RARA rearrangement did not differ significantly from that commonly seen in other APLs with the exception of the poor outcome. Genes Chromosomes Cancer 27:35–43, 2000. © 2000 Wiley‐Liss, Inc.
Adenovirus Serotype 7 Retention in a Late Endosomal Compartment prior to Cytosol Escape Is Modulated by Fiber Protein

ABSTRACT The intracellular trafficking of adenovirus (Ad) subgroup B (e.g., Ad7) differs from that of subgroup C (e.g., Ad5) in that Ad5 rapidly escapes from endocytic compartments following infection whereas Ad7 accumulates in organelles. To assess the hypothesis that Ad7 is targeted to the lysosomal pathway, Ad7 and Ad5 were conjugated with fluorophores and their trafficking in A549 epithelial cells was analyzed by fluorescence microscopy. Within 1 h after infection, Ad7, but not Ad5, accumulated in the cytoplasm of A549 cells. The pH in the environment of Ad5 was nearly neutral (pH 7), while Ad7 occupied acidic compartments (pH 5) over the first 2 h with a gradual shift toward neutrality by 8 h. Ad7 partially colocalized with α2-macroglobulin and late endosomal and lysosomal marker proteins, including Rab7, mannose-6-phosphate receptor, and LAMP-1. The pH optimum for membrane lysis by Ad7, as well as a chimeric Ad5 capsid that expressed the Ad7 fiber (Ad5fiber7), was pH 5.5, while that for lysis by Ad5 was pH 6.0. Thus, the native trafficking pathway for Ad7 involves residence in late endosomes and lysosomes, with information encoded in the Ad7 fiber acting as a pH-dependent trigger for membrane lysis and escape to the cytosol.
H(+)-ATPases of renal cortical and medullary endosomes are differentially sensitive to Sch-28080 and omeprazole.

Adenosinetriphosphatase (ATPase) activity stimulated by K+ and inhibited by Sch-28080 (SCH), omeprazole (OME), and vanadate has been measured in microsomes from mammalian renal medulla and attributed to a kidney isoform of the H(+)-K(+)-ATPase. To determine whether the H(+)-K(+)-ATPase inhibitors could also inhibit the vacuolar (V)-type H(+)-adenosinetriphosphatase (H(+)-ATPase, i.e., H+ pump) in mammalian intracellular vesicles, we examined their effects on bafilomycin-sensitive acidification in renal cortical vesicles (CEV) and medullary endocytic vesicles (MEV). Rats were injected with fluorescein isothiocyanate-labeled dextran, and labeled endosomes were enriched from kidney tissue homogenates by differential and Percoll density gradient centrifugation. In the CEV, the V-type H+ pump was inhibited 25% by SCH and 30% by OME (100 microM each). Whereas the inhibition by OME was concentration and time dependent, the inhibition by SCH was only concentration dependent. Inhibition by these compounds was similar in the presence of 50 mM K+ (in = out) and in the complete absence of K+, thus ruling out a significant involvement of H(+)-K(+)-ATPase-mediated acidification. Inhibition, however, was not observed with 10 microM SCH and OME. The sensitivity of the V-type H+ pump to 100 microM SCH and OME in CEV was confirmed by the comparable inhibitions of intravesicular acidification observed in acridine orange fluorescence quench studies and by inhibition of Pi liberation in an ATPase assay. We also found that the V-type H+ pump in isolated rat liver endosomes is sensitive to 100 microM SCH and OME to a similar degree. In the MEV, acidification was only weakly affected by 100 microM SCH and OME, thus suggesting that H(+)-ATPases in endosomes from cortical and medullary tubules are different, possibly due to a previously described selective expression of subunit isoforms. Our finding indicates the importance of using low concentrations (< 10 microM) of OME and SCH in studies of H(+)-K(+)-ATPase in nongastric tissues to avoid misinterpretation of the data due to nonspecific inhibition of V-type H(+)-ATPases.
Member Checking: Can Benefits Be Gained Similar to Group Therapy?

Member checking continues to be an important quality control process in qualitative research as during the course of conducting a study, participants receive the opportunity to review their statements for accuracy and, in so doing; they may acquire a therapeutic benefit. The authors of this article suggest that this benefit is similar to some of the components of group therapy, especially in normalizing the phenomenon being experienced. Even if the participants never meet, they can feel a sense of relief that their feelings are validated and that they are not alone.
Behavioral and intelligence outcome in 8- to 16-year-old born small for gestational age

Purpose We investigated behavioral problems, attention problems, and cognitive function in children and adolescents born small for gestational age (SGA). Methods Forty-six SGA children born at term and 46 appropriate for gestational age (AGA) children born at term were compared. Psychiatric symptoms were examined with reference to the Korean-Child Behavior Checklist, Korean-Youth Self Report, and Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS). Cognitive function was estimated using the Wechsler Intelligence Scale. Sociodemographic data were recorded from interviews. Results SGA children had high scores on delinquent behavior, aggressive behavior, and the externalizing scale, and they also showed a propensity for anxiety and depression. The SGA group had a higher mean ADHD-RS score than the AGA group (10.52±8.10 vs.9.93±7.23), but the difference was not significant. The SGA group had a significantly lower verbal intelligence quotient (IQ) than the AGA group, but the mean scores of both groups were within normal limits. Conclusion This study indicates marked behavioral problems, such as delinquency, aggressiveness, and anxiety and depression, as well as low verbal IQ in the SGA group than in the AGA group. Even in cases in which these symptoms are not severe, early detection and proper treatment can help these children adapt to society.
The Role of Endothelin‐1 in Cardiovascular Development a

Endothelin-1 (ET-1) is a peptide consisting of 21 amino acids. It was originally isolated from media conditioned by cultured vascular endothelial cells. ' Three isopeptides (ET-1, 2, and 3) encoded by different gene loci constitute a gene family2 and act on two distinct G protein-coupled receptors (ETA and ETs) with different affinit ie~. ~? ~ In addition to vasoconstrictive effects on vascular smooth muscle cells, ET-1 has a diverse set of biological activities, such as proliferative effects on various cells, stimulation of hormone release, and modulation of central nervous a~t iv i ty . ~ ET-1 also acts on endothelial cells in an autocrine manner and stimulates NO and prostacyclin release.6 These effects of ET-1 suggest that ET-1 may participate in the regulation of cardiovascular homeostasis and the pathogenesis of cardiovascular disease, such as hypertension, vasospasm, and atheroscler~sis. ~-~ However, there has been little consensus about the physiological and pathophysiological importance of ET-I. Recently, we disrupted the mouse Ednl locus encoding ET-1 by gene targeting.I0 The resultant mice homozygous for ET1 null mutation represent morphological abnormalities of the pharyngeal arch-derived craniofacial tissues and organs, indicating that ET-1 is essential to normal embryonic development. In mammalian craniofacial morphogenesis, mesenchyme constituting the pharyngeal arches stems mainly from neural crest cells. Cranial neural crest cells migrate to the pharyngeal arch region and differentiate into ectomesenchymal cells, Neural crestderived ectomesenchymal cells interact with surface ectoderm, resulting in further differentiation into various tissues such as cartilage and dentine of the In situ hybridization detected ET-I gene expression in the epithelium of pharyngeal arches,1° suggesting that ET-1 may be involved in this epithelialmesenchymal interaction. Neural crest cells are also required for normal cardiovascular de~elopment. '~'~ Ectomesenchymal cells derived from cardiac neural crest migrate to pharyngeal arches 3,4, and 6 and contribute to the aortic arch development and aorticopulmonary septation. Thus, we speculated that ET-I may participate not only in the craniofacial development but also in the cardiovascular development. In
Citrate bridges between mineral platelets in bone

Significance Bone contains ∼2% wt citrate; however, its role in bone remains a much-debated question. We propose a new structure for bone mineral in which citrate in hydrated layers forms bridges between mineral platelets, which can explain a number of observations at odds with previous models. The incorporation of citrate between mineral platelets can explain the flat, plate-like morphology of bone mineral platelets and may be important in controlling the crystallinity of bone mineral, which in turn, is highly relevant to the mechanical properties of bone. We provide evidence that citrate anions bridge between mineral platelets in bone and hypothesize that their presence acts to maintain separate platelets with disordered regions between them rather than gradual transformations into larger, more ordered blocks of mineral. To assess this hypothesis, we take as a model for a citrate bridging between layers of calcium phosphate mineral a double salt octacalcium phosphate citrate (OCP-citrate). We use a combination of multinuclear solid-state NMR spectroscopy, powder X-ray diffraction, and first principles electronic structure calculations to propose a quantitative structure for this material, in which citrate anions reside in a hydrated layer, bridging between apatitic layers. To assess the relevance of such a structure in native bone mineral, we present for the first time, to our knowledge, 17O NMR data on bone and compare them with 17O NMR data for OCP-citrate and other calcium phosphate minerals relevant to bone. The proposed structural model that we deduce from this work for bone mineral is a layered structure with thin apatitic platelets sandwiched between OCP-citrate–like hydrated layers. Such a structure can explain a number of known structural features of bone mineral: the thin, plate-like morphology of mature bone mineral crystals, the presence of significant quantities of strongly bound water molecules, and the relatively high concentration of hydrogen phosphate as well as the maintenance of a disordered region between mineral platelets.
Nontubulation Repair of Peripheral Nerve Gap Using Heparin/Alginate Gel Combined with b-FGF

Summary: All artificial nerve grafts have a tubular structure, and they guide axonal regrowth through the tube from the proximal side toward the peripheral side. Based on the results of our experimental study using animals, we used alginate gel without a tubular structure as an artificial nerve graft for digital nerve repair and evaluated peripheral nerve regeneration. In 2 patients, a gap due to digital nerve injury was bridged with controlled-release heparin/alginate gel combined with basic fibroblast growth factor, and restoration of the sensory function was serially evaluated. In both patients, Tinel’s sign appeared 3–4 weeks after the operation, and sensory recovery to the fingertip was achieved at 6 months postoperatively. Our results suggest that even gel without a tubular structure provides a site for peripheral nerve regeneration.
darkNoC: Designing energy-efficient network-on-chip with multi-Vt cells for dark silicon

In this paper, we propose a novel NoC architecture, called dark-NoC, where multiple layers of architecturally identical, but physically different routers are integrated, leveraging the extra transistors available due to dark silicon . Each layer is separately optimized for a particular voltage-frequency range by the adroit use of multi-Vt circuit optimization. At a given time, only one of the network layers is illuminated while all the other network layers are dark. We provide architectural support for seamless integration of multiple network layers, and a fast inter-layer switching mechanism without dropping in-network packets. Our experiments on a 4 × 4 mesh with multi-programmed real application workloads show that darkNoC improves energy-delay product by up to 56% compared to a traditional single layer NoC with state-of-the-art DVFS. This illustrates darkNoC can be used as an energy-efficient communication fabric in future dark silicon chips.
Rapid Plasma Membrane-Endosomal Trafficking of the Lymph Node Sinus and High Endothelial Venule Scavenger Receptor/Homing Receptor Stabilin-1 (Feel-1/Clever-1)*

The sinusoidal endothelia of liver, spleen, and lymph node are major sites for uptake and recycling of waste macromolecules through promiscuous binding to a disparate family of scavenger receptors. Among the most complex is stabilin-1, a large multidomain protein containing tandem fasciclin domains, epidermal growth factor-like repeats, and a C-type lectin-like hyaluronan-binding Link module, which functions as an endocytic receptor for acetylated low density lipoprotein and advanced glycation end products. Intriguingly, stabilin-1 has also been reported to mediate both homing of leukocytes across lymph node high endothelial venules and adhesion of metastatic tumor cells to peritumoral lymphatic vessels. Currently, however, it is not clear how stabilin-1 mediates these distinct functions. To address the issue, we have investigated the tissue and subcellular localization of stabilin-1 in detail and assessed the functional status of its Link module. We show that stabilin-1 is almost entirely intracellular in lymph node high endothelial venules, lymphatic sinus endothelium, and cultured endothelial cells but that a finite population, detectable only by fluorescent antibody or fluorescein-labeled (Fl)-acetylated low density lipoprotein uptake, cycles rapidly between the plasma membrane and EEA-1+ve (early endosome antigen 1) early endosomes. In addition, we show using full-length stabilin-1 cDNA and a stabilin-1/CD44 chimera in HeLa cells that intracellular targeting is influenced by the transmembrane domain/cytoplasmic tail, which contains a putative dileucine (DXXLL) Golgi to endosomal sorting signal. Finally, we provide evidence that the stabilin-1 Link domain binds neither hyaluronan nor other glycosaminoglycans. These properties support a role for stabilin-1 as a rapidly recycling scavenger receptor and argue against a role in cell adhesion or lymphocyte homing.
CD44v6: a potential marker of malignant transformation in intestinal metaplasia of the stomach? An immunohistochemical study using tissue microarrays

Objective Intestinal metaplasia is a well-established risk factor in the development of stomach cancer. However, since the specificity is low it would be of great practical value to find a marker to separate cases of intestinal metaplasia into low and high risk for progression to dysplasia/carcinoma. So far this has not been achieved. CD44 is a cell surface molecule involved in cell–cell and cell–matrix interactions, and the spliced variant 6 has been shown to play a role in the progression of gastric carcinoma. The aim of this study was therefore to evaluate CD44v6 as a marker of increased cancer risk in intestinal metaplasia. Methods The current study investigated immunohistochemical CD44v6 expression in biopsies of normal gastric mucosa (n = 154) and gastric mucosa with intestinal metaplasia (n = 127). A third group consisted of cancer gastrectomies (n = 117) in which both tumour and uninvolved mucosa was studied. Proximal (cardia) and distal (corpus/antrum) locations were noted in all cases. Results There was a significant sequential increase in CD44v6 expression from normal mucosa and mucosa showing intestinal metaplasia to uninvolved mucosa adjacent to cancers without and with intestinal metaplasia to tumour. The most striking increase was from ‘normal’ to intestinal metaplastic mucosa adjacent to cancers. There were no differences between proximal and distal cases in any group. Conclusion These findings strongly suggest that CD44v6 expression is a late phenomenon in the transformation of intestinal metaplasia to dysplasia/cancer. It may therefore be a useful marker of cancer risk in patients with intestinal metaplasia.
Improvement in SAR Image Classification using Adaptive Stack Filters

Stack filters are a special case of non-linear filters. They have a good performance for filtering images with different types of noise while preserving edges and details. A stack filter decomposes an input image into several binary images according to a set of thresholds. Each binary image is filtered by a Boolean function. The Boolean function that characterizes an adaptive stack filter is optimal and is computed from a pair of images consisting of an ideal noiseless image and its noisy version. In this work the behavior of adaptive stack filters is evaluated for the classification of synthetic aperture radar (SAR) images, which are affected by speckle noise. With this aim it was carried out experiment in which simulated and real images are generated and then filtered with a stack filter trained with one of them. The results of their maximum likelihood classification are evaluated and then are compared with the results of classifying the images without previous filtering.
Cholinergic axons in the rat ventral tegmental area synapse preferentially onto mesoaccumbens dopamine neurons

Cholinergic afferents to the ventral tegmental area (VTA) contribute substantially to the regulation of motivated behaviors and the rewarding properties of nicotine. These actions are believed to involve connections with dopamine (DA) neurons projecting to the nucleus accumbens (NAc). However, this direct synaptic link has never been investigated, nor is it known whether cholinergic inputs innervate other populations of DA and γ‐aminobutyric acid (GABA) neurons, including those projecting to the prefrontal cortex (PFC). We addressed these questions by using electron microscopic analysis of retrograde tract‐tracing and immunocytochemistry for the vesicular acetylcholine transporter (VAChT) and for tyrosine hydroxylase (TH) and GABA. In tissue labeled for TH, VAChT+ terminals frequently synapsed onto DA mesoaccumbens neurons but only seldom contacted DA mesoprefrontal cells. In tissue labeled for GABA, one‐third of VAChT+ terminals innervated GABA‐labeled dendrites, including both mesoaccumbens and mesoprefrontal populations. VAChT+ synapses onto DA and mesoaccumbens neurons were more commonly of the asymmetric (presumed excitatory) morphological type, whereas VAChT+ synapses onto GABA cells were more frequently symmetric (presumed inhibitory or modulatory). These findings suggest that cholinergic inputs to the VTA mediate complex synaptic actions, with a major portion of this effect likely to involve an excitatory influence on DA mesoaccumbens neurons. As such, the results suggest that natural and drug rewards operating through cholinergic afferents to the VTA have a direct synaptic link to the mesoaccumbens DA neurons that modulate approach behaviors. J. Comp. Neurol. 494:863–875, 2006. © 2005 Wiley‐Liss, Inc.