Miracle-dz/UniFAR-FTUs huggingface dataset:
Phosphorylation of neuronal Lysine‐Specific Demethylase 1LSD1/KDM1A impairs transcriptional repression by regulating interaction with CoREST and histone deacetylases HDAC1/2

Epigenetic mechanisms play important roles in brain development, orchestrating proliferation, differentiation, and morphogenesis. Lysine‐Specific Demethylase 1 (LSD1 also known as KDM1A and AOF2) is a histone modifier involved in transcriptional repression, forming a stable core complex with the corepressors corepressor of REST (CoREST) and histone deacetylases (HDAC1/2). Importantly, in the mammalian CNS, neuronal LSD1‐8a, an alternative splicing isoform of LSD1 including the mini‐exon E8a, sets alongside LSD1 and is capable of enhancing neurite growth and morphogenesis. Here, we describe that the morphogenic properties of neuronal LSD1‐8a require switching off repressive activity and this negative modulation is mediated in vivo by phosphorylation of the Thr369b residue coded by exon E8a. Three‐dimensional crystal structure analysis using a phospho‐mimetic mutant (Thr369bAsp), indicate that phosphorylation affects the residues surrounding the exon E8a‐coded amino acids, causing a local conformational change. We suggest that phosphorylation, without affecting demethylase activity, causes in neurons CoREST and HDAC1/2 corepressors detachment from LSD1‐8a and impairs neuronal LSD1‐8a repressive activity. In neurons, Thr369b phosphorylation is required for morphogenic activity, converting neuronal LSD1‐8a in a dominant‐negative isoform, challenging LSD1‐mediated transcriptional repression on target genes.
The risk of developing a second cancer after receiving craniospinal proton irradiation

The purpose of this work was to compare the risk of developing a second cancer after craniospinal irradiation using photon versus proton radiotherapy by means of simulation studies designed to account for the effects of neutron exposures. Craniospinal irradiation of a male phantom was calculated for passively-scattered and scanned-beam proton treatment units. Organ doses were estimated from treatment plans; for the proton treatments, the amount of stray radiation was calculated separately using the Monte Carlo method. The organ doses were converted to risk of cancer incidence using a standard formalism developed for radiation protection purposes. The total lifetime risk of second cancer due exclusively to stray radiation was 1.5% for the passively scattered treatment versus 0.8% for the scanned proton beam treatment. Taking into account the therapeutic and stray radiation fields, the risk of second cancer from intensity-modulated radiation therapy and conventional radiotherapy photon treatments were 7 and 12 times higher than the risk associated with scanned-beam proton therapy, respectively, and 6 and 11 times higher than with passively scattered proton therapy, respectively. Simulations revealed that both passively scattered and scanned-beam proton therapies confer significantly lower risks of second cancers than 6 MV conventional and intensity-modulated photon therapies.
A conversation analytic approach to the prediction of leadership in two to six-party audio conferences

When evaluating the Quality of Experience (QoE) of audio conferences the participants talking behaviour is critical for their quality judgement. A dominant person, for instance, who talks and interacts a lot is likely to be more disturbed by conversation-related impairments than a less active person. Social interaction analysis provides reliable nonverbal audio features to predict dominance in face-to-face meetings. However, little is known about pure audio conferences. This is why this study investigates common dominance features for audio-only conferences. In the first part, we look at different group sizes and whether prediction models exist that predict the leader for two-to six-party audio-only conversations. In a second step, we apply the best model to an unknown audio conferencing dataset. Finally, we tested if dominance features are associated to the assigned caller or a particular person in each group and how the callers talking behaviour is related to perceived quality.
Communication dynamics in hospice teams: understanding the role of the chaplain in interdisciplinary team collaboration.

BACKGROUND Hospice chaplains provide a specific expertise to patient and family care, however, individual roles and responsibilities that facilitate the interdisciplinary team environment are less well known. OBJECTIVE The primary aim of this study was to investigate how hospice chaplains perceive their role in interdisciplinary team meetings and to what extent hospice chaplains share common experiences within the interdisciplinary team approach in hospice. METHOD Hospice chaplains within a 10-state region participated in a 39-item phone survey about professional roles, group roles, and structural characteristics that influence their ability to participate in interdisciplinary collaboration. RESULTS Findings revealed that professional role conflict is experienced, primarily with social workers. Informal group task and maintenance roles included team spiritual care advisor and conflict manager, and structural characteristics consisted of extracurricular communication outside of the organization. CONCLUSIONS Although chaplains foster interdisciplinary collaboration within the hospice team, future research needs to address improvements to the chaplain's role within the interdisciplinary team process.
Effect of mental health specialty care on antidepressant length of therapy.

OBJECTIVES Treatment of depression with medications and psychotherapy clearly is efficacious, but not all patients require such intensive therapy. In this report, we examine the costs and effects of dual treatment on a population of employees and their families with depression. We sought to determine the costs and length of medication treatment consequences of providing mental health specialty care to antidepressant-treated individuals. RESEARCH DESIGN AND SUBJECTS A quasi-experimental retrospective design was used to examine the administrative data of 2678 antidepressant users whose insurance claims are included in the MarketScan database. The primary measure used was joint cost-continuity of antidepressant medication. RESULTS Patients receiving concurrent psychotherapy were more likely to achieve length of antidepressant treatment consistent with current recommendations. The cost-consequence ratio for concurrent treatment was $4062/1% improvement in the number of adequately treated individuals. CONCLUSION Adding psychotherapy to treatment with medication appears to improve the efficacy of antidepressant treatment. The incremental costs suggest that it is a valuable addition in most cases and should be considered cost-effective.
Dendritic Cells and Lentiviral Vectors: Mapping the Way to Successful Immunotherapy

Professional antigen presenting cells, in particular dendritic cells (DCs) are central players in the immune response (Steinman & Banchereau 2007). Their function is dual; on the one hand DCs evoke strong immune responses against antigens that are considered hazardous, on the other hand DCs induce tolerance against self-antigens. To that end, DCs need to present antigen-derived peptides in the context of MHC class I or class II molecules to CD8+ and CD4+ T cells, respectively. It is the context in which these peptides are presented that determines the outcome of the immune response, immune activation versus tolerance. Consequently, DCs have become targets for immunotherapy against not only cancer and infectious disease, but also autoimmune diseases and transplantation rejection (Palucka et al.). Key to successful DC-based immunotherapy is the delivery of the antigen of interest, be it cancer, viral or auto-antigens, to DCs, as well as the delivery of molecules that dictate the immune stimulatory capacity of the DCs. Therefore, it is not surprising that much effort has been put in the development of vectors for genetic modification of DCs (Breckpot et al. 2004c). Of these lentiviral vectors (LVs), often derived from human immunodeficiency virus type 1 (HIV-1) are amongst the most efficient gene delivery vehicles, for both in vitro and in vivo modification of DCs (Escors & Breckpot ; Breckpot et al. 2007a). In addition, these LVs were demonstrated to activate the innate immune system through interaction with amongst others Toll-like receptors (TLRs), a characteristic that makes LVs even better suited for immunotherapeutic approaches against cancer and infectious diseases (Breckpot et al. ; Brown et al. 2006a). As immune activation of DCs is critical for the induction of antigenspecific immunity, several strategies have been developed to further strengthen the immune response by introduction of immune modulating molecules or by modulation of wellknown activation pathways such as the nuclear factor-kappaB (NF-κB), mitogen activated protein kinase (MAPK) p38 and MAPK c-Jun N-terminal kinases (JNK) pathways (Breckpot & Escors 2009a). Although LVs inherently activate DCs, they have also been evaluated for their ability to switch of the stimulatory capacity of DCs, thus to generate tolerogenic DCs. The strategies exploited therefore are similar to the strategies employed to activate DCs and include introduction of single inhibitory molecules and modulation of pathways that
Identification and Molecular Diversity of T‐superfamily Conotoxins from Conus lividus and Conus litteratus

The T‐superfamily conotoxins comprise a large and diverse group of biologically active peptides and are widely distributed in venom ducts of all major feeding types of Conus. Six novel T‐superfamily peptides from the two worm‐hunting cone snail species of Conus lividus andConus. litteratus native to Hainan were identified and determined to share a common signal sequence as well as a conserved arrangement of cysteine residues (CC–CC). The predicted mature peptides consist of 11–15 amino acids only. Phylogenetic analyses of new conotoxins from C. lividus andC. litteratus in present study and published homologue T‐superfamily sequences from the other Conus species was systematically performed. Phylogenetic trees, residue substitutions to view evolutionary relationships of the precursors’ signal, propeptide, and mature toxin regions were explored, as well as residue frequency component and cystine codon usage. Percent divergence of the amino acid sequences of the signal‐region exhibited high conservation, whereas the sequences of the mature peptides ranged from high similarity to high divergence between inter‐ and intro‐species. Notably, diversity of pro‐peptide region was also high with intermediate percent divergence between that observed in signal and toxin‐regions. Consensus hydrophobic residues Leu, Val, Ala, Ile and Pro of signal regions were abundant, whereas among propeptides, basic residues Arg and Lys and acidic residue Asp, addition of hydrophilic residues Thr and Ser were abundant. Residue frequency components were hypervariable in mature toxin region except for highly conservative cystine frame residues. The T‐superfamily conotoxins have been previously found mainly in piscivorous and molluscivorous cone snails. The newly identified six T‐superfamily peptides described in this investigation exemplify the first to be found from vermivorousC. lividus andC. litteratus. The elucidated cDNAs of the six toxins will facilitate a better understanding of the relationship between structure and function as well as provide a framework for their further research and development.
vanA and vanB Incorporate into an Endemic Ampicillin-Resistant Vancomycin-SensitiveEnterococcus faecium Strain: Effect on Interpretation of Clonality

ABSTRACT Clonal spread and horizontal transfer in the spread of vancomycin resistance genes were investigated. Multiplex PCR, pulsed-field gel electrophoresis (PFGE), hybridization of enterococcal plasmids with thevanA and vanB probes, and sequencing of a fragment of vanB were used in the analysis. Before May 1996, 12 vancomycin-resistant Enterococcus faecium (VRE) isolates were found in Finland. Between May 1996 and October 1997, 156 VRE isolates were found in the Helsinki area. Between December 1997 and April 1998, fecal samples from 359 patients were cultured for VRE. One new case of colonization with VRE was found. During the outbreak period, 88% (137 of 155) of the VRE isolates belonged to two strains (VRE types I and II), as determined by PFGE. Each VRE type I isolate possessed vanB, and five isolates also hadvanA. Of the 34 VRE type II isolates, 27 possessedvanA and 7 possessed vanB. Fifteen of 21 (71%) ampicillin-resistant, vancomycin-sensitive E. faecium (VSE) isolates found during and after the outbreak period in one ward were also of type II. Two VSE type II isolates were found in the hospital before the outbreak in 1995. By PFGE, the three groups (vanA, vanB, or no van gene) of type II shared the same band differences with the main type of VRE type II with vanA. None of the differences was specific to or determinative for any of the groups. Our material suggests thatvanA and vanB incorporate into an endemic ampicillin-resistant VSE strain.
KNEE Static rotational and sagittal knee laxity measurements after reconstruction of the anterior cruciate ligament

Purpose The goal of the present study was to evaluate static anteroposterior and rotational knee laxity after ACL reconstructions with two noninvasive measurement devices by comparing the measured results of the operated with the contralateral healthy knees of the patients. Methods Fifty-two consecutive patients were reviewed after isolated single-bundle transtibial ACL reconstruction using a BPTB graft. At a mean follow-up of 27 months, sagittal AP laxity was tested using a noninvasive knee measurement system (Genourob) with an applied pressure of 67 N, 89 N and 134 N. Rotational laxity was measured using a noninvasive rotational knee laxity device (Rotameter) with an applied torque of 5, 8 and 10 Nm. The results were compared with the measurements of the patients’ healthy contralateral knees. Tegner, Lysholm and IKDC score were used in order to evaluate the clinical outcome. Results Pivot shift was negative (33) or glide (16) in 49 patients with 12 of 16 (75%) patients having also a pivot glide on the healthy contralateral side; Lachman tests were negative in 50 cases. Subjective assessment of the IKDC score was classified according to category A in 44 patients, B in 5 patients and C in 3 patients. Mean Lysholm score was 94.5 ± 9.5, median Tegner score was 7 (3–9) preoperative and 6 (3–9) at follow-up (n.s.). Anteroposterior knee laxity measurements revealed mean side-to-side differences of 0.6–1.3 mm (P \ 0.0001). Rotational laxity measurements revealed no statistical significant differences between the operated and the contralateral knee (n.s.). The measured differences in the entire rotational range varied from 0.2 to 1 depending on the applied torque. In those 3 patients with a positive pivot shift, differences in the entire rotational range of 4.5 at 5 N, 4.6 at 8 N and 4.1 at 10 N were found. Conclusion Static knee laxity was quantified after ACL surgery using the introduced noninvasive measurement systems by comparing the measured results of the operated with the contralateral healthy knees. Significant differences were found in AP laxity although they were defined as clinically successful according to the IKDC classification. No significant differences were found in rotational knee laxity measurements. Therefore, the used noninvasive masurement devices might offer a high potential for objective quality control in knee ligament injuries and their treatment. Level of evidence Retrospective case series, Level IV.
Alterations in expression of angiopoietins and the Tie-2 receptor in the retina of streptozotocin induced diabetic rats.

PURPOSE The angiopoietin (Ang)/Tie-2 system may play a role in vascular integrity and angiogenesis. In this study, we investigated alterations of the gene expression of Ang-1 and Ang-2 in the retinas of streptozotocin (STZ) induced diabetic rats. METHODS In situ hybridization, reverse transcriptase polymerase chain reaction (RT-PCR) and western blot analyses were performed to determine the mRNA and protein content for Ang-1 and Ang-2 and the Tie2 receptor in the retinas of STZ diabetic and age matched control rats. RESULTS Using in situ hybridization analysis, Ang-1, Ang-2, and Tie2 mRNA expression was observed in the ganglion cell layer (GCL) and the inner nuclear layer (INL). While Ang-2 mRNA expression did not changed after 2 weeks, 1 month, or 3 months of STZ induced diabetes, it was increased in the GCL and slightly elevated in the INL after 6 months of diabetes. In contrast, Ang-1 and Tie2 mRNA expression was stable at every timepoint during 6 months of STZ induced diabetes. RT-PCR and western blot analyses confirmed the increase of Ang-2 expression after 6 months of diabetes. Furthermore, double staining of alpha-smooth muscle actin (alphaSMA) and Ang-2 mRNA demonstrated that the SMA positive cells surrounding Ang-2-expressing cells were decreased in the GCL. CONCLUSIONS Diabetes increases Ang-2 expression in the GCL accompanied by a reduction of alphaSMA positive perivascular cells. These changes may suggest a role for Ang-2 in the mechanism of pericyte loss in diabetic retinopathy.
On Almost Sure Stability of Hybrid Stochastic Systems With Mode-Dependent Interval Delays

This note develops a criterion for almost sure stability of hybrid stochastic systems with mode-dependent interval time delays, which improves an existing result by exploiting the relation between the bounds of the time delays and the generator of the continuous-time Markov chain. The improved result shows that the presence of Markovian switching is quite involved in the stability analysis of delay systems. Numerical examples are given to verify the effectiveness.
Genotype may correlate with liver carcinogenesis and tumor characteristics in cirrhotic patients infected with hepatitis B virus subtype adw

To identify the influence of hepatitis B virus (HBV) genotype on development of hepatocellular carcinoma (HCC) and clinical outcome in chronic HBV infection, 26 consecutive cirrhotic patients infected with HBV subtype adw were investigated prospectively. HBV serology was undertaken using subtype‐specific antibodies against hepatitis B surface antigens. The HBV genotype was determined by sequencing directly the polymerase chain reaction products of the HBV S gene. When HCC occurred, patients underwent transcatheter arterial embolization therapy. If tumor necrosis was incomplete, additional embolization therapy was carried out after a 3‐ to 4‐month interval. At a median follow‐up of 14.1 years (range 2.2 to 31.7), HCC occurred in 9 (35%) of 26 patients. Nineteen patients were infected with genotype B and 7 with genotype C. Four of the 19 genotype B patients (21%) and 5 of the 7 genotype C patients (71%) developed HCC (P = 0.058). Patient age (<45 years or 45 ≤ ) at diagnosis of cirrhosis was the only significant independent factor influencing liver carcinogenesis by multiple logistic regression analysis and Cox's regression analysis (P = 0.0069 and 0.029, respectively). When analysis was limited to the age of 45 years or more at the last visit, genotype was the only contributory factor to HCC development by univariate analysis (P = 0.038). Whereas genotype B patients responded well to embolization therapy and had no recurrence of HCC for a prolonged period of time, genotype C patients showed poor responses and died of hepatic failure due to rapid HCC progression despite embolization therapy. The cumulative incidence of survival was significantly higher in the genotype B group (P = 0.0049). The HBV genotype correlated with the development of HCC, response to embolization therapy, and recurrence of HCC. Determination of HBV genotype may be useful in predicting outcomes in HBV subtype adw‐related cirrhosis. J. Med. Virol. 65:257–265, 2001. © 2001 Wiley‐Liss, Inc.
Financial incentives for cadaver organ donation: an ethical reappraisal1

A panel of ethicists, organ procurement organization executives, physicians, and surgeons was convened by the sponsorship of the American Society of Transplant Surgeons to determine whether an ethically acceptable pilot trial could be proposed to provide a financial incentive for a family to consent to the donation of organs from a deceased relative. An ethical methodology was developed that could be applied to any proposal for monetary compensation to elucidate its ethical acceptability. An inverse relationship between financial incentives for increasing the families’ consent for cadaver donation that clearly would be ethically acceptable (e.g., a contribution to a charity chosen by the family or a reimbursement for funeral expenses) and those approaches that would more likely increase the rate of donation (e.g., direct payment or tax incentive) was evident. The panel was unanimously opposed to the exchange of money for cadaver donor organs because either a direct payment or tax incentive would violate the ideal standard of altruism in organ donation and unacceptably commercialize the value of human life by commodifying donated organs. However, a majority of the panel members supported reimbursement for funeral expenses or a charitable contribution as an ethically permissible approach. The panel concluded that the concept of the organ as a gift could be sustained by a funeral reimbursement or charitable contribution that conveyed the appreciation of society to the family for their donation. Depending on the amount of reimbursement provided for funeral expenses, this approach could be ethically distinguished from a direct payment, by their intrusion into the realm of altruism and voluntariness. We suggest that a pilot project be conducted to determine whether this kind of a financial incentive would be acceptable to the public and successful in increasing organ donation.