Miracle-dz/UniFAR-FTUs huggingface dataset:
Actions of brain‐derived neurotrophic factor on evoked and spontaneous EPSCs dissociate with maturation of neurones cultured from rat visual cortex

1 To address the question of whether brain‐derived neurotrophic factor (BDNF) directly enhances excitatory synaptic transmission, we recorded excitatory postsynaptic currents (EPSCs) from solitary neurones cultured on glial microislands for 7–38 days, and observed changes in EPSCs after the application of BDNF. In this preparation the possible action of BDNF on GABAergic inhibition was not involved, and evoked and spontaneous (miniature) EPSCs were derived from the same group of synapses (autapses). 2 The application of BDNF at a concentration of 200 ng ml−1 rapidly enhanced the frequency of miniature EPSCs (mEPSCs) in almost all the neurones tested. On the other hand, the amplitude of mEPSCs did not change at all, suggesting that the site of BDNF action is presynaptic. 3 In contrast to the enhanced frequency of mEPSCs, evoked EPSCs were not potentiated in 61 % of the cells tested. Most of these BDNF‐insensitive EPSCs had a peak amplitude larger than 1 nA, while most of the other BDNF‐sensitive EPSCs had a smaller amplitude. The former EPSCs had smaller coefficients of variation (CVs) of amplitude, while the latter had larger CVs, suggesting the possibility that the presynaptic release probability for the former groups of EPSCs might have beeen saturated so that the BDNF action was occluded. 4 To test this possibility we applied a low Ca2+ solution to 17 cells and reduced the amplitude of their evoked EPSCs to less than or near to 1 nA. It was found, however, that BDNF did not enhance these EPSCs. Rather, evoked EPSCs of almost all the cells cultured for less than 15 days were enhanced by BDNF, while those of most of the cells cultured for longer than 16 days were not enhanced. 5 These results suggest that BDNF enhances transmitter release from presynaptic sites through its action on the release machinery, which can be differentiated into a BDNF‐insensitive form for evoked release and a BDNF‐sensitive form for spontaneous release with maturation of synapses.
A preliminary study of dopamine D4 receptor genotype and structural brain alterations in adults with ADHD

An emerging literature has demonstrated an association between the dopamine D4 receptor (DRD4) gene and volumetric brain abnormalities in children with ADHD. However, these results have not been extended to adults and have not addressed the impact of comorbidity. Our objective was to examine the DRD4 7R gene and volumetric brain abnormalities in adults with ADHD while accounting for comorbidity with bipolar disorder (BPD). Subjects were male and female adult outpatient referrals stratified into two diagnostic groups: 24 with ADHD, 19 with ADHD and BPD, as well as 20 male and female adult community controls without ADHD or BPD. We measured volumes (cm3) of a priori selected brain regions (superior frontal, middle frontal, anterior cingulate, and cerebellum cortices) by structural magnetic resonance imaging. Among adults with ADHD, subjects with the 7‐repeat allele of the DRD4 gene had a significantly smaller mean volume in the superior frontal cortex and cerebellum cortex compared to subjects without this allele. In contrast, no such effects were detected in the adults with ADHD + BPD or controls. Our findings suggest that volumetric abnormalities in the dorsolateral prefrontal cortex and cerebellum may represent an intermediate neuroanatomical phenotype between DRD4 genotype and the clinical expression of ADHD in adults, but only in ADHD subjects without comorbid BPD. These result support the heterogeneity of ADHD and provides insights as to its underlying pathophysiology. © 2008 Wiley‐Liss, Inc.
Smoking, Occupational Risk Factors, and Bronchial Tumor Location: A Possible Impact for Lung Cancer Computed Tomography Scan Screening

Introduction: The aim of this study was to describe associations between lung tumor location and smoking as well as selected occupational exposures. In the context of lung cancer screening by computed tomography scan, tumor location may have an interest. Computed tomography scan is known to better detect more peripheral tumors. Methods: Lung cancer cases diagnosed in two French University hospitals between 1997 and 2009 were included. Tumors visible on white-light bronchoscopy were defined as central. Occupational exposures were assessed by the same expert. Data were analyzed by case-case comparisons using unconditional logistic regressions. Results: A total of 1701 cases were included, comprising mainly men (86.3%), current smokers (52.8%), or former smokers (42.8%). Main histological subtypes of cancer were adenocarcinomas (33.8%) and squamous cell carcinomas (32.6%). The tumor location was found to be central in 61% of cases, and never smokers and women had more often peripheral tumors. Exposure to asbestos was significantly associated with central location with dose-response relationship (odds ratio [OR] for peripheral tumors = 0.45, 95% confidence interval [CI] 0.29–0.70) for the highest level of exposure. Exposure to silica dust was significantly associated with peripheral tumor (OR for peripheral tumors = 3.28, 95%CI 1.50–7.17) for the highest level of exposure. Exposure to welding fumes was associated with central location (OR for peripheral tumors = 0.51, 95% CI 0.26–0.96) for the first level of exposure). Conclusions: Smoking characteristics and occupational exposures have to be considered to define more accurately high-risk populations suitable for lung cancer screening or early detection programs.
Harmony in a non-harmonic language: word order learning in French children

Recent studies using artificial language learning have argued that the cross-linguistic frequency of harmonic word order patterns–in which heads are ordered consistently before or after dependents across syntactic categories–reflects a cognitive bias (Culbertson, Smolensky, & Legendre, 2012; Culbertson & Newport, 2015a). These studies suggest that English speaking adults and children favor harmonic orders of nouns and different nominal modifiers (adjectives, numerals). However, because they target English learners, whose native language is harmonic in the nominal domain (Num-Adj-N), this preference may be based on transfer rather than a universal bias for harmony. We present new evidence from French-speaking children, whose native language is non-harmonic in this domain (Num-N-Adj). Our results reveal clear effects of native language transfer, but also evidence that a harmonic pattern is favored even in this population of learners.
Immediate or deferred androgen deprivation for patients with prostate cancer not suitable for local treatment with curative intent: European Organisation for Research and Treatment of Cancer (EORTC) Trial 30891.

PURPOSE This study (EORTC 30891) attempted to demonstrate equivalent overall survival in patients with localized prostate cancer not suitable for local curative treatment treated with immediate or deferred androgen ablation. PATIENTS AND METHODS We randomly assigned 985 patients with newly diagnosed prostate cancer T0-4 N0-2 M0 to receive androgen deprivation either immediately (n = 493) or on symptomatic disease progression or occurrence of serious complications (n = 492). RESULTS Baseline characteristics were well balanced in the two groups. Median age was 73 years (range, 52 to 81). At a median follow-up of 7.8 years, 541 of 985 patients had died, mostly of prostate cancer (n = 193) or cardiovascular disease (n = 185). The overall survival hazard ratio was 1.25 (95% CI, 1.05 to 1.48; noninferiority P > .1) favoring immediate treatment, seemingly due to fewer deaths of nonprostatic cancer causes (P = .06). The time from randomization to progression of hormone refractory disease did not differ significantly, nor did prostate-cancer specific survival. The median time to the start of deferred treatment after study entry was 7 years. In this group 126 patients (25.6%) died without ever needing treatment (44% of the deaths in this arm). CONCLUSION Immediate androgen deprivation resulted in a modest but statistically significant increase in overall survival but no significant difference in prostate cancer mortality or symptom-free survival. This must be weighed on an individual basis against the adverse effects of life-long androgen deprivation, which may be avoided in a substantial number of patients with a deferred treatment policy.
FIBRE HETEROGENEITY IN THE CLOSER AND OPENER MUSCLES OF CRAYFISH WALKING LEGS

1. The closer and opener muscles in the third walking legs of the three crayfish Pacifastacus leniusculus, Procambarus clarkii and Astacus leptodactylus are composed of fibres which differ in histochemistry, electrophysiology and morphology. Three major groups of fibres (A, B and C) were distinguished. 2. Group A fibres react weakly to histochemical stains for myofibrillar ATPase (mATPase) activity characteristic of fibres with slow shortening speeds. In the opener muscle, they are innervated by the opener excitor (OE) and the specific opener inhibitor (OI). In the closer muscle, group A fibres are innervated by the common inhibitory neurone (CI) in addition to single (slow closer excitor, SCE) or double excitatory (SCE and fast closer excitor, FCE) innervation. Group A fibres have the largest excitatory junction potentials (EJPs), the longest membrane time constants (tau) and the longest sarcomeres. They are located at the very distal and proximal ends of both muscles. 3. Group B fibres show higher mATPase activity than group A fibres. In the opener muscle, they are innervated by OE and OI; in the closer muscle, they receive double excitatory (SCE and FCE) and CI innervation. Single SCE and OE EJPs are small; those caused by FCE are larger. tau is shorter than in the other two fibre groups. Sarcomere lengths lie between those of group A and C fibres. Group B fibres are found along the entire lengths of both muscles. 4. Group C fibres exhibit the highest mATPase activity (characteristic of fibres with fast shortening velocity) which, in contrast to the ATPase of group B fibres, is not resistant to alkaline preincubation at pH 10.05. In the closer, these fibres lack innervation by CI, otherwise the innervation pattern is identical to that of group B fibres. EJP size is similar to that of group B fibres; tau ranges between values for group A and B fibres. Sarcomere lengths are the shortest of all the fibre types. Group C fibres constitute the majority of the fibres in the two muscles and mainly occupy the central regions.
How the structure of Wikipedia articles influences user navigation

In this work we study how people navigate the information network of Wikipedia and investigate (i) free-form navigation by studying all clicks within the English Wikipedia over an entire month and (ii) goal-directed Wikipedia navigation by analyzing wikigames, where users are challenged to retrieve articles by following links. To study how the organization of Wikipedia articles in terms of layout and links affects navigation behavior, we first investigate the characteristics of the structural organization and of hyperlinks in Wikipedia and then evaluate link selection models based on article structure and other potential influences in navigation, such as the generality of an article's topic. In free-form Wikipedia navigation, covering all Wikipedia usage scenarios, we find that click choices can be best modeled by a bias towards article structure, such as a tendency to click links located in the lead section. For the goal-directed navigation of wikigames, our findings confirm the zoom-out and the homing-in phases identified by previous work, where users are guided by generality at first and textual similarity to the target later. However, our interpretation of the link selection models accentuates that article structure is the best explanation for the navigation paths in all except these initial and final stages. Overall, we find evidence that users more frequently click on links that are located close to the top of an article. The structure of Wikipedia articles, which places links to more general concepts near the top, supports navigation by allowing users to quickly find the better-connected articles that facilitate navigation. Our results highlight the importance of article structure and link position in Wikipedia navigation and suggest that better organization of information can help make information networks more navigable.
Cyclophosphamide-induced ovarian failure.

Abstract Twenty-two women receiving cyclophosphamide for either progressive glomerulonephritis (20) or rheumatoid arthritis (two) were studied to define more closely the nature of menstrual abnormalities known to occur with this drug. The patients were studied by assay of urinary estrogens and total gonadotrophins and, when possible, by ovarian biopsy. Seventeen patients had definite or probable ovarian failure after cyclophosphamide. No patient on whom ovarian biopsy was performed showed normal follicular maturation, and ova were seen in only two. One patient judged clinically and biochemically to have ovarian failure regained normal ovarian function 10 months after cessation of cyclophosphamide therapy. (N Engl J Med 289:1159–1162, 1973)
A double-blind comparison of 0.125% ropivacaine with sufentanil and 0.125% bupivacaine with sufentanil for epidural labor analgesia.

BACKGROUND This study intends to evaluate the benefits of the administration of intermittent bolus doses of ropivacaine (0.125%) compared with bupivacaine (0.125%) after addition of sufentanil for analgesia during labor. METHODS One hundred thirty American Society of Anesthesiologists physical status 1 or 2 parturients were studied. The 90 initial patients were assigned randomly to receive 10 ml bupivacaine, 0.125%, plus 7.5 microg sufentanil (initial bupivacaine 0.125% group) or ropivacaine, 0.125%, plus 7.5 microg sufentanil (ropivacaine 0.125% group). Forty additional patients were recruited and received 0.125% bupivacaine plus 7.5 microg sufentanil (additional bupivacaine 0.125% group) or 0.100% bupivacaine plus 7.5 microg sufentanil (additional bupivacaine 0.100% group). The duration of analgesia, visual analogue scores for pain, motor blockade (using a six-point modified Bromage scale), patient satisfaction scores, nausea, pruritus, heart rate, and blood pressure were recorded. RESULTS Bupivacaine 0.125% and ropivacaine 0.125% coadministered with sufentanil provided rapid and complete analgesia. Onset of analgesia occurred after +/-15 min and lasted +/-90 min. After the third epidural injection, patients in the ropivacaine group experienced significantly less severe motor blockade than patients in the initial bupivacaine 0.125% group. At this point, 93% of the patients in the ropivacaine group were free from motor impairment versus 66% in the bupivacaine group (P<0.05). Comparable levels of motor blockade were obtained in both additional groups. Patients' evaluation of their analgesia was worst in the bupivacaine 0.100% group. CONCLUSIONS Ropivacaine 0.125% with sufentanil affords reliable analgesia with minimal motor blockade.
Weakly Submodular Maximization Beyond Cardinality Constraints: Does Randomization Help Greedy?

Submodular functions are a broad class of set functions, which naturally arise in diverse areas. Many algorithms have been suggested for the maximization of these functions. Unfortunately, once the function deviates from submodularity, the known algorithms may perform arbitrarily poorly. Amending this issue, by obtaining approximation results for set functions generalizing submodular functions, has been the focus of recent works. One such class, known as weakly submodular functions, has received a lot of attention. A key result proved by Das and Kempe (2011) showed that the approximation ratio of the greedy algorithm for weakly submodular maximization subject to a cardinality constraint degrades smoothly with the distance from submodularity. However, no results have been obtained for maximization subject to constraints beyond cardinality. In particular, it is not known whether the greedy algorithm achieves any non-trivial approximation ratio for such constraints. In this paper, we prove that a randomized version of the greedy algorithm (previously used by Buchbinder et al. (2014) for a different problem) achieves an approximation ratio of $(1 + 1/\gamma)^{-2}$ for the maximization of a weakly submodular function subject to a general matroid constraint, where $\gamma$ is a parameter measuring the distance of the function from submodularity. Moreover, we also experimentally compare the performance of this version of the greedy algorithm on real world problems against natural benchmarks, and show that the algorithm we study performs well also in practice. To the best of our knowledge, this is the first algorithm with a non-trivial approximation guarantee for maximizing a weakly submodular function subject to a constraint other than the simple cardinality constraint. In particular, it is the first algorithm with such a guarantee for the important and broad class of matroid constraints.
Antagonistic Interactions between Yeast Chaperones Hsp104 and Hsp70 in Prion Curing

ABSTRACT The maintenance of [PSI], a prion-like form of the yeast release factor Sup35, requires a specific concentration of the chaperone protein Hsp104: either deletion or overexpression of Hsp104 will cure cells of [PSI]. A major puzzle of these studies was that overexpression of Hsp104 alone, from a heterologous promoter, cures cells of [PSI] very efficiently, yet the natural induction of Hsp104 with heat shock, stationary-phase growth, or sporulation does not. These observations pointed to a mechanism for protecting the genetic information carried by the [PSI] element from vicissitudes of the environment. Here, we show that simultaneous overexpression of Ssa1, a protein of the Hsp70 family, protects [PSI] from curing by overexpression of Hsp104. Ssa1 protein belongs to the Ssa subfamily, members of which are normally induced with Hsp104 during heat shock, stationary-phase growth, and sporulation. At the molecular level, excess Ssa1 prevents a shift of Sup35 protein from the insoluble (prion) to the soluble (cellular) state in the presence of excess Hsp104. Overexpression of Ssa1 also increases nonsense suppression by [PSI] when Hsp104 is expressed at its normal level. In contrast,hsp104 deletion strains lose [PSI] even in the presence of overproduced Ssa1. Overproduction of the unrelated chaperone protein Hsp82 (Hsp90) neither cured [PSI] nor antagonized the [PSI]-curing effect of overproduced Hsp104. Our results suggest it is the interplay between Hsp104 and Hsp70 that allows the maintenance of [PSI] under natural growth conditions.
Children's experiences about a structured assessment of health-related quality of life during a patient encounter.

BACKGROUND It has been stated that care for children with chronic health conditions tends to focus on condition-specific issues rather than how these children experience their health and everyday life functioning. AIM The aim of this study was to explore children's experiences about a structured assessment of health-related quality of life applied during a patient encounter. METHODS Prior to the start of the study, a clinical intervention based on the questionnaire DISABKIDS Chronic Generic Measure (DCGM-37) was performed. A qualitative explorative design was chosen, and 25 children between 10-17 years of age were interviewed after the consultation at four different paediatric outpatient clinics. Data were analysed according to qualitative content analysis. RESULTS The results were twofold: children experienced that the assessment was providing them with insights about their health, which motivated them to make lifestyle changes. When outcomes were discussed and requested, the children felt encouraged. CONCLUSIONS The use of an assessment of health-related quality of life may promote insights about health and encourage children with chronic health conditions to discuss their outcomes with healthcare professionals.
Women with intellectual disabilities--a study of sexuality, sexual abuse and protection skills.

BACKGROUND Sexual abuse and abusive relationships are known to be especially common in people with intellectual disability. This study explored how women with intellectual disability understand sex, relationships and sexual abuse, the effects of sexual abuse on their lives, and how successfully they protect themselves from abuse. METHODS Semistructured narrative interviews with nine women with mild intellectual disability in Queensland, Australia. Interviews were audio recorded, transcribed, coded and analysed qualitatively. RESULTS Major themes that emerged were: sexual knowledge and sources of knowledge; negotiating sexual relationships; declining unwanted sexual contact; self protection strategies; sexual abuse experiences; and sequelae of sexual abuse. DISCUSSION Most participants reported unwanted or abusive sexual experiences. They described sequelae such as difficulties with sex and relationships, and anxiety and depression. They described themselves as having inadequate self protection skills and difficulty reporting abuse and obtaining appropriate support. Their understanding of sex was limited and they lacked the literacy and other skills to seek information independently. It is important for general practitioners to be aware of the possibility of sexual abuse against women with intellectual disability, and to offer appropriate interventions.
A Rorschach Investigation of Incarcerated Female Offenders With Antisocial Personality Disorder

Although male psychopathy has been linked to histrionic, narcissistic, and antisocial personality disorders (ASPD), less is known about female psychopathy. The Psychopathy Checklist-Revised (PCL-R) and the Rorschach were used to explore the personality functioning of 45 incarcerated female offenders with ASPD delineated by their psychopathy level. Psychopaths (PCL-R ≥ 30) and nonpsychopaths (PCL-R < 24) were compared on Rorschach measures of self-perception, interpersonal relatedness, and reality testing. Compared to female offenders with ASPD who were nonpsychopathic, female offenders with ASPD who were psychopathic exhibited marked disturbances in self-perception, interpersonal relatedness, and reality testing. Our findings highlight the heterogeneity of the ASPD diagnosis in women, support the utility of the psychopathy construct with female offenders, and implicate important differences between men and women with ASPD. These gender differences have relevance to the evaluation (PCL-R scoring) and treatment of female offenders. Our findings are discussed within the context of the female psychopath’s hypothesized hysterical character style.