julilili42/papers huggingface dataset:
Overcoming Treatment Resistance in Chronic Depression: A Pilot Study on Outcome and Feasibility of the Cognitive Behavioral Analysis System of Psychotherapy as an Inpatient Treatment Program
2014-12-24

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; The Cognitive Behavioral Analysis System of Psychotherapy (CBASP), initially developed as an outpatient treatment for chronic depression (CD), has been adapted as a multidisciplinary 12-week inpatient program for CD. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Seventy inpatients with CD and treatment resistance were included in a noncontrolled trial. The Hamilton Depression Rating Scale served as the primary outcome measure. Prospective naturalistic follow-up assessments were conducted 6 and 12 months after discharge. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Dropout rate was 7.1%; 90.4% perceived the program as helpful. Pre-post comparisons yielded strong effect sizes; 75.7% of the intention-to-treat sample responded, and 40.0% remitted. Nonremission was associated with experiencing temporary deterioration of symptoms during treatment. After 6 months 75.0% and after 12 months 48.0% of patients sustained response. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; The CBASP program appears as a feasible acute treatment for treatment-resistant CD inpatients with promising outcome. However, the continuation of treatment after discharge should be optimized especially for patients with subjective deterioration during treatment.
Rare-Earth-Metal Allyl Complexes Supported by the [2-(N,N-Dimethylamino)ethyl]tetramethylcyclopentadienyl Ligand: Structural Characterization, Reactivity, and Isoprene Polymerization
2014-12-24

Rare-earth-metal half-sandwich allyl complexes bearing an amino-functionalized cyclopentadienyl ligand (CpNMe2 = 1-[2-(N,N-dimethylamino)ethyl]-2,3,4,5-tetramethylcyclopentadienyl) were synthesized in a two-step salt-metathesis reaction. Treatment of LnCl3(THF)x with LiCpNMe2, followed by an in situ reaction with the Grignard reagent C3H5MgCl, generated the bis(allyl) half-sandwich complexes CpNMe2Ln(η3-C3H5)2 only for the smaller rare-earth metals (Ln = Y, Ho, Lu) in good yields (82–88%). In case of the larger neodymium, the dimeric mono(allyl) chlorido half-sandwich complex [CpNMe2Nd(η3-C3H5)(μ-Cl)]2 was obtained in 68% yield. All complexes show moderate to high activity in isoprene polymerization upon cationization with organoborates [Ph3C][B(C6F5)4] and [PhNMe2H][B(C6F5)4], the yttrium, holmium, and neodymium metal centers yielding mainly 3,4-microstructures (maximum 79%). Addition of 10 equiv of AlMe3 to the catalyst systems CpNMe2Ln(η3-C3H5)2 (Ln = Y, Ho)/[PhNMe2H][B(C6F5)4] and [CpNMe2Nd(η3-C3H5)(μ-Cl)]2/[PhNMe2H][B(C6F5)4] switched the polyisoprene stereoregularity from 3,4-specific to trans-1,4-selective (maximum 85%). The use of AliBu3 instead led to polymers with mainly cis-1,4-microstructure for the monomeric yttrium and holmium complexes (maximum 74%). Treatment of the bis(allyl) complexes with Et2AlCl (as cocatalyst) did not provide active species for isoprene polymerization but led to [allyl] → [Cl] exchange and isolation of the hexameric rare-earth-metal clusters [{(CpNMe2AlEt3)2(CpNMe2)Ln3(μ2-Cl)3(μ3-Cl)2}(μ2-Cl)]2 (Ln = Y, Ho). The complexes CpNMe2Ln(η3-C3H5)2 (Ln = Y, Ho, Lu), [CpNMe2Nd(η3-C3H5)(μ-Cl)]2, and [{(CpNMe2AlEt3)2(CpNMe2)Ln3(μ2-Cl)3(μ3-Cl)2}(μ2-Cl)]2 (Ln = Y, Ho) were analyzed by X-ray crystallography.
Confocal Raman microscopic investigation of the effectiveness of penetration enhancers for procaine delivery to the skin
2014-12-24

A methodology that employs confocal Raman microscopy (CRM) on ex vivo skin samples is proposed for the investigation of drug content and distribution in the skin. To this end, the influence of the penetration enhancers propylene glycol and polyoxyethylene-23-lauryl ether on the penetration and permeation of procaine as a model substance was investigated. The drug content of skin samples that had been incubated with semisolid formulations containing one of these enhancers was examined after skin segmentation. The experiments showed that propylene glycol did not affect the procaine content that was delivered to the skin, whereas polyoxyethylene-23-lauryl ether led to higher procaine contents and deeper penetration. Neither substance was found to influence the permeation rate of procaine. It is thereby shown that CRM can provide additional information on drug penetration and permeation. Furthermore, the method was found to enhance the depth from which Raman spectra can be collected and to improve the depth resolution compared to previously proposed methods.
Midcheek endoscopic anatomy
2014-12-24

ABSTRACT Background Surgical approaches to the midcheek area are challenging. Recent clinical reports have proposed minimally endoscopic approach again, in order to obtain to obtain a correct balance between the operation's safety and the cosmetic and minimally invasive outcome, but none of them provides a careful anatomic description of the midcheek area. The purpose of this study was to provide a new anatomic perception of the midcheek area through a detailed anatomic endoscopic‐assisted dissection. Methods Four freshly injected cadaver heads were dissected to illustrate the endoscopic anatomy of the midcheek region. Results An endoscope provided an excellent surgical window that achieved greater exposure for dissection and at the same time improved magnification of the noble key anatomic elements. Conclusion This study emphasizes the critical role of the transverse facial artery and the facial retaining ligaments as a fundamental endoscopic landmark that allows the identification of key anatomic structures and the creation of safe surgical corridors. © 2015 Wiley Periodicals, Inc. Head Neck 38 : E268–E273, 2016
Persistent Staphylococcus aureus nasal colonization in ambulatory human immunodeficiency virus-infected patients in Nigeria: Risk factors and molecular features
2014-12-24

This longitudinal study on Staphylococcus aureus colonization in Nigerian human immunodeficiency virus patients (n = 187) found a trend towards a higher proportion of persistent S. aureus carriage in patients with advanced human immunodeficiency virus infection, low CD4+ cell counts, and a predominance of isolates belonging to ST8/spa-CC064 in persistent carriers.
Ligand-Independent EPHA2 Signaling Drives the Adoption of a Targeted Therapy–Mediated Metastatic Melanoma Phenotype
2014-12-27

Abstract Many patients with BRAF inhibitor resistance can develop disease at new sites, suggesting that drug-induced selection pressure drives metastasis. Here, we used mass spectrometry–based phosphoproteomic screening to uncover ligand-independent EPHA2 signaling as an adaptation to BRAF inhibitor therapy that led to the adoption of a metastatic phenotype. The EPHA2-mediated invasion was AKT-dependent and readily reversible upon removal of the drug as well as through PI3K and AKT inhibition. In xenograft models, BRAF inhibition led to the development of EPHA2-positive metastases. A retrospective analysis of patients with melanoma on BRAF inhibitor therapy showed that 68% of those failing therapy develop metastases at new disease sites, compared with 35% of patients on dacarbazine. Further IHC staining of melanoma specimens taken from patients on BRAF inhibitor therapy as well as metastatic samples taken from patients failing therapy showed increased EPHA2 staining. We suggest that inhibition of ligand-independent EPHA2 signaling may limit metastases associated with BRAF inhibitor therapy. Significance: This study provides evidence that BRAF inhibition promotes the adoption of a reversible, therapy-driven metastatic phenotype in melanoma. The cotargeting of ligand-independent EPHA2 signaling and BRAF may be one strategy to prevent the development of therapy-mediated disease at new sites. Cancer Discov; 5(3); 264–73. ©2014 AACR. See related article by Miao et al., p. 274 This article is highlighted in the In This Issue feature, p. 213
P2Y2 receptor activation decreases blood pressure via intermediate conductance potassium channels and connexin 37
2014-12-27

Abstract Aims Nucleotides are important paracrine regulators of vascular tone. We previously demonstrated that activation of P 2 Y 2 receptors causes an acute, NO ‐independent decrease in blood pressure, indicating this signalling pathway requires an endothelial‐derived hyperpolarization ( EDH ) response. To define the mechanisms by which activation of P 2 Y 2 receptors initiates EDH and vasodilation, we studied intermediate‐conductance ( KC a3.1, expressed in endothelial cells) and big‐conductance potassium channels ( KC a1.1, expressed in smooth muscle cells) as well as components of the myoendothelial gap junction, connexins 37 and 40 ( C x37, C x40), all hypothesized to be part of the EDH response. Methods We compared the effects of a P 2 Y 2/4 receptor agonist in wild‐type ( WT ) mice and in mice lacking KC a3.1, KC a1.1, C x37 or C x40 under anaesthesia, while monitoring intra‐arterial blood pressure and heart rate. Results Acute activation of P 2 Y 2/4 receptors (0.01–3 mg kg −1 body weight i.v.) caused a biphasic blood pressure response characterized by a dose‐dependent and rapid decrease in blood pressure in WT (maximal response % of baseline at 3 mg kg −1 : −38 ± 1%) followed by a consecutive increase in blood pressure (+44 ± 11%). The maximal responses in KC a3.1 −/− and C x37 −/− were impaired (−13 ± 5, +17 ± 7 and −27 ± 1, +13 ± 3% respectively), whereas the maximal blood pressure decrease in response to acetylcholine at 3 μ g kg −1 was not significantly different ( WT : −53 ± 3%; KC a3.1 −/− : −52 ± 3; C x37 −/− : −53 ± 3%). KC a1.1 −/− and C x40 −/− showed an identical biphasic response to P 2 Y 2/4 receptor activation compared to WT . Conclusions The data suggest that the P 2 Y 2/4 receptor activation elicits blood pressure responses via distinct mechanisms involving KC a3.1 and C x37.
Association Study Indicates a Protective Role of Phosphatidylinositol-4-Phosphate-5-Kinase against Tardive Dyskinesia
2014-12-28

We conclude from this association that PIP5K2A is possibly involved in a mechanism protecting against tardive dyskinesia-inducing neurotoxicity. This corresponds to our hypothesis that tardive dyskinesia is related to neurotoxicity at striatal indirect pathway medium-sized spiny neurons.
Outbreeding effects in an inbreeding insect, Cimex lectularius
2014-12-28

Abstract In some species, populations with few founding individuals can be resilient to extreme inbreeding. Inbreeding seems to be the norm in the common bed bug, Cimex lectularius, a flightless insect that, nevertheless, can reach large deme sizes and persist successfully. However, bed bugs can also be dispersed passively by humans, exposing inbred populations to gene flow from genetically distant populations. The introduction of genetic variation through this outbreeding could lead to increased fitness (heterosis) or be costly by causing a loss of local adaptation or exposing genetic incompatibility between populations (outbreeding depression). Here, we addressed how inbreeding within demes and outbreeding between distant populations impact fitness over two generations in this re‐emerging public health pest. We compared fitness traits of families that were inbred (mimicking reproduction following a founder event) or outbred (mimicking reproduction following a gene flow event). We found that outbreeding led to increased starvation resistance compared to inbred families, but this benefit was lost after two generations of outbreeding. No other fitness benefits of outbreeding were observed in either generation, including no differences in fecundity between the two treatments. Resilience to inbreeding is likely to result from the history of small founder events in the bed bug. Outbreeding benefits may only be detectable under stress and when heterozygosity is maximized without disruption of coadaptation. We discuss the consequences of these results both in terms of inbreeding and outbreeding in populations with genetic and spatial structuring, as well as for the recent resurgence of bed bug populations.
HLA ligandome analysis identifies the underlying specificities of spontaneous antileukemia immune responses in chronic lymphocytic leukemia (CLL)
2014-12-29

Significance Effective cancer immunotherapy relies on specific immune recognition of tumor-associated and tumor-specific antigens. In chronic lymphocytic leukemia (CLL), the highly variable course of disease implicates an underlying mechanism of tumor control by the immune system. In this study, we directly analyzed the landscape of naturally presented CLL antigens and identified targets conveying immune protection. These novel antigens might be valuable both for patient stratification and for inducing therapeutic antitumor immunity. Taken together, we demonstrate that CLL is subject to spontaneous T-cell responses targeting nonmutated antigens, which are associated with improved patient survival and provide novel options for the immunotherapy of CLL.
Search for dark matter annihilation signatures in H.E.S.S. observations of dwarf spheroidal galaxies
2014-12-29

Dwarf spheroidal galaxies of the Local Group are close satellites of the Milky Way characterized by a large mass-to-light ratio and are not expected to be the site of nonthermal high-energy gamma-ray emission or intense star formation. Therefore they are among the most promising candidates for indirect dark matter searches. During the last years the High Energy Stereoscopic System (H.E.S.S.) of imaging atmospheric Cherenkov telescopes observed five of these dwarf galaxies for more than 140 hours in total, searching for TeV gamma-ray emission from annihilation of dark matter particles. The new results of the deep exposure of the Sagittarius dwarf spheroidal galaxy, the first observations of the Coma Berenices and Fornax dwarves and the reanalysis of two more dwarf spheroidal galaxies already published by the H.E.S.S. Collaboration, Carina and Sculptor, are presented. In the absence of a significant signal new constraints on the annihilation cross section applicable to weakly interacting massive particles (WIMPs) are derived by combining the observations of the five dwarf galaxies. The combined exclusion limit depends on the WIMP mass and the best constraint is reached at 1–2 TeV masses with a cross-section upper bound of at a 95% confidence level.
Molecular polygamy: The promiscuity of l‐phenylalanyl‐tRNA‐synthetase triggers misincorporation of meta‐ and ortho‐tyrosine in monoclonal antibodies expressed by Chinese hamster ovary cells
2014-12-29

ABSTRACT In‐depth analytical characterization of biotherapeutics originating from different production batches is mandatory to ensure product safety and consistent molecule efficacy. Previously, we have shown unintended incorporation of tyrosine (Tyr) and leucine/isoleucine (Leu/Ile) at phenylalanine (Phe) positions in a recombinant produced monoclonal antibody (mAb) using an orthogonal MASCOT/SIEVE based approach for mass spectrometry data analysis. The misincorporation could be avoided by sufficient supply of phenylalanine throughout the process. Several non‐annotated signals in the primarily chromatographic peptide separation step for apparently single Phe→Tyr sequence variants (SVs) suggest a role for isobar tyrosine isoforms. Meta‐ and ortho‐ Tyr are spontaneously generated during aerobic fed‐batch production processes using Chinese hamster ovary (CHO) cell lines. Process induced meta ‐ and ortho ‐Tyr but not proteinogenic para ‐Tyr are incorporated at Phe locations in Phe‐starved CHO cultures expressing a recombinant mAb. Furthermore, meta ‐ and ortho ‐Tyr are preferably misincorporated over Leu. Structural modeling of the l‐phenylalanyl‐tRNA‐synthetase (PheRS) substrate activation site indicates a possible fit of non‐cognate ortho ‐Tyr and meta ‐Tyr substrates. Dose‐dependent misincorporations of Tyr isoforms support the hypothesis that meta ‐ and ortho ‐Tyr are competing, alternative substrates for PheRS in CHO processes. Finally, easily accessible at‐line surrogate markers for Phe→Tyr SV formation in biotherapeutic production were defined by the calculation of critical ratios for meta ‐Tyr/Phe and ortho ‐Tyr/Phe to support early prediction of SV probability, and finally, to allow for immediate process controlled Phe→Tyr SV prevention. Biotechnol. Bioeng. 2015;112: 1187–1199. © 2014 Wiley Periodicals, Inc.
Early Modern English again: a corpus study and semantic analysis
2014-12-29

This article investigates uses of the adverb again in Early Modern English (EModE) correspondence. The study collects occurrences of again and analyses their interpretation. It reveals interesting differences in the use of again between EModE and Late Modern English (LModE) as well as Present-day English (PDE). To bring out the grammatical significance of the results, we connect the study methodologically as closely as possible with Beck, Berezovskaya &amp; Pflugfelder's (2009) study of LModE/PDE correspondence. We show that the key diachronic alteration we observe when considering EModE is not just numerical in nature but also qualitatively distinct from the later change at the transition between LModE and PDE. At the heart of our proposal is the finding that while a structural approach to again (Rapp &amp; von Stechow 1999; Beck 2005) is successful for characterizing the transition between LModE and PDE, a uniform analysis for the entire diachronic trajectory is not warranted; a combined theoretical modelling is required instead. Specifically, a lexical analysis relying on counterdirectionality (e.g. Fabricius-Hansen 2001) is required to capture the differences in the EModE data.
Diffuse Galactic gamma-ray emission with H.E.S.S.
2014-12-30

Diffuse -ray emission is the most prominent observable signature of celestial cosmic-ray interactions at high energies. While already being investigated at GeV energies over several decades, assessments of diffuse -ray emission at TeV energies remain sparse. After completion of the systematic survey of the inner Galaxy, the H.E.S.S. experiment is in a prime position to observe large-scale diffuse emission at TeV energies. Data of the H.E.S.S. Galactic Plane Survey are investigated in regions off known -ray sources. Corresponding -ray flux measurements were made over an extensive grid of celestial locations. Longitudinal and latitudinal profiles of the observed -ray fluxes show characteristic excess emission not attributable to known -ray sources. For the first time large-scale -ray emission along the Galactic Plane using imaging atmospheric Cherenkov telescopes has been observed. While the background subtraction technique limits the ability to recover modest variation on the scale of the H.E.S.S. field of view or larger, which is characteristic of the inverse Compton scatter-induced Galactic diffuse emission, contributions of neutral pion decay as well as emission from unresolved -ray sources can be recovered in the observed signal to a large fraction. Calculations show that the minimum -ray emission from -decay represents a significant contribution to the total signal. This detection is interpreted as a mix of diffuse Galactic -ray emission and unresolved sources.
Neolithisation of the Aegean and Southeast Europe during the 6600–6000 calBC period of Rapid Climate Change
2014-12-30

In extension of the recently established ‘Rapid Climate Change (RCC) Neolithisation Model’ (Clare 2013), in the present paper we demonstrate the existence of a remarkable coincidence between the exact (decadel-scale) entry and departure dates of the Neolithic into/from the Aegean (~6600/6050 calBC) with begin/end of RCC-conditions.
Beginnings of the Neolithic in Southeast Europe: the Early Neolithic sequence and absolute dates from Džuljunica-Smărdeš (Bulgaria)
2014-12-30

Investigations of a balk in the centre of the prehistoric settlement of Džuljunica-Smărdeš comprised a sequence of archaeological deposits from the very onset of Neolithisation in South-eastern Europe throughout the end of the Early Neolithic. The arrival of Neolithic lifeways in the region coincides with the end of a period for which palaeoclimate proxies attest to considerable climate fluctuation. In connection with these investigations, the zoological finds were examined, which provide insight into the economy of this key settlement for the entire Balkan region.
Archaeobotanical evidence on the Neolithisation of Northeast Bulgaria in the Balkan-Anatolian context: chronological framework, plant economy and land use
2014-12-30

\\nThe study presents archaeobotanical analyses of four Early Neolithic sites (Koprivets, Orlovets, Dzhulyunitsa, Samovodene) from Northeast Bulgaria. Those archaeobotanical data are linked to comprehensive series of 14C dates for the early Neolithic in northeastern Bulgaria allowing their attribution to high resolution radiocarbon chronology. In the considered sites the dominating cereal crop during the Early Neolithic is hulled barley (Hordeum vulgare var. vulgare), followed by einkorn (Triticum monococcum) and few emmer (Triticum dicoccum) what is a clear difference from the southern parts of Bulgaria where during the early Neolithic the dominating cereal crops are einkorn and emmer. Further principal crops, present from the earliest phases of the Neolithic in the region are lentil - Lens culinaris, pea – Pisum sativum, grass pea – Lathyrus sativus/cicera and flax – Linum usitatissimum. Wide spectrum of finds of gathered plants (at least 11 taxa) reflects the use of the natural vegetation resources. Useful for reconstructing the vegetation and land use in the Neolithic are also wood charcoal identifications, indicating apart of oak forests also presence of open vegetation, riparian forests and wetlands. The relatively open vegetation in the surrounding of the early Neolithic settlements could be one of the reasons why the corresponding locations were chosen by the Neolithic people to settle there. On the other hand this open vegetation could be caused by the Neolithic land use and animal husbandry, which have also led to certain reduction of the forests in the immediate surroundings of the settlements.\\n