Miracle-dz/UniFAR-FTUs huggingface dataset:
Long‐lasting synaptic loss after repeated induction of LTD: independence to the means of LTD induction

Short‐ and long‐lasting synaptic plasticity is assumed to be the cellular basis of short‐ and long‐lasting memory, respectively. However, the cellular consequences leading to the long‐lasting synaptic plasticity, assumed to include the processes of synapse formation and elimination, remain unknown. Using hippocampal slices maintained stably in culture, we found previously that the repeated induction of long‐term potentiation (LTP) triggered a slowly developing long‐lasting enhancement in synaptic transmission strength accompanied by synapse formation, which was separate from LTP itself. We recently reported a phenomenon apparently of a mirror‐image effect. The repeated activations of metabotropic glutamate receptor (mGluR), which induces long‐term depression (LTD), triggered a long‐lasting reduction in synaptic strength accompanied by synapse elimination. To clarify whether the reported long‐lasting effect was specific to the drugs used previously and whether the effect was specific to mGluR‐mediated LTD, we exposed the cultured slices repeatedly to another Group I metabotropic glutamate receptor (mGluR) agonist, an N‐methyl‐d‐aspartate receptor agonist, and a Na+/K+‐pump inhibitor. All these treatments resulted in an equivalent long‐lasting synaptic reduction/elimination when repeated three times, indicating that the repeated LTD induction leads to synapse elimination. The independence of synapse elimination to the means of LTD induction suggests that the signals leading to short‐term plasticity and long‐term plasticity are independent. Detailed inspections in the representative case of mGluR activation revealed that the reduction in synaptic strength developed with a ∼1‐week delay from the decrease in the number of synaptic structures. This synapse elimination should be unique as it is activity‐dependent rather than inactivity‐dependent.
Novel oral combination chemotherapy in the treatment of intermediate-grade and high-grade AIDS-related non-Hodgkin's lymphoma.

PURPOSE To determine the toxicity, response, and survival rate of orally administered combination chemotherapy in patients with AIDS-related intermediate- and high-grade non-Hodgkin's lymphoma. Secondary objectives included prospective quality-of-life assessment and quantitation of cell-associated p24 antigen (p24 Ag) by flow cytometry. PATIENTS AND METHODS Eighteen patients with biopsy-proven lymphoma were treated with oral chemotherapy consisting of lomustine (CCNU) 100 mg/m2 on day 1, etoposide 200 mg/m2 on days 1 through 3; cyclophosphamide 100 mg/m2 on days 22 through 31, and procarbazine 100 mg/m2 on days 22 through 31 at 6-week intervals. A variety of clinical assessments were performed: prospective quality-of-life assessment using the Functional Living Index-Cancer (FLIC) and Brief Symptom Inventory (BSI) instruments; indirect immunofluorescence with flow cytometry to measure cell-associated p24 antigen; and price of the oral regimen compared with two other intravenous combination chemotherapy regimens. RESULTS The overall objective response rate using Eastern Cooperative Oncology Group (ECOG) criteria was 61% (95% confidence interval, 39% to 84%), with seven complete remissions (39%) and four partial remissions (22%). The median survival duration was 7 months, with a range of 11 days to 36 months. The treatment-related mortality rate was 11%. One patient developed CNS progression. Myelosuppression was the most frequent and severe toxicity encountered. Predictor variables of performance status (PS), prior history of thrush, and CD4 lymphocyte count were found to be of prognostic value. In a separate analysis, scores on the three subscales of the BSI were also found to be predictive of complete response. The price of this regimen is several thousand dollars less than that of other intravenous combination chemotherapy regimens. CONCLUSION This regimen is active in patients with AIDS-related non-Hodgkin's lymphoma. Because it is important to design systemic cytotoxic chemotherapy regimens that are cost-effective, considerate of quality-of-life issues, and efficacious in this patient population, this approach should be compared with standard intravenous combination chemotherapy regimens in randomized controlled clinical trials.
A comparison of three different sources of data in assessing the frequencies of adverse reactions to amiodarone.

AIMS To compare the frequencies of adverse drug reactions (ADRs) to amiodarone from three separate datasets: (i) a meta-analysis of clinical trials, (ii) spontaneous reports published in medical journals, and (iii) spontaneous reports sent to the World Health Organization (WHO). METHODS We classified the ADRs into eight categories, based on the site involved, and built a rank order of the ADRs by category (from most to least commonly reported) for each dataset. We also calculated the relative proportions for all eight ADR categories within each dataset, in order to be able to compare the distributions of ADR frequencies: we assigned an index value of 1.0 to the frequency of respiratory toxicity in each set and calculated values for the other ADRs relative to respiratory toxicity. RESULTS Thyroid disorders were the most commonly reported ADRs in the WHO dataset. In contrast, published case reports showed a preponderance of respiratory disorders, while in the meta-analysis cardiac conduction problems were the most frequent. The rank orders of ADRs differed among the three datasets, as did the index values of specific ADR categories with respect to the respiratory category. CONCLUSIONS The distributions of ADR rank order and relative frequencies are dissimilar among the three datasets, as each dataset compiles information in a different way. Nevertheless, each dataset has its own specific strengths, and all three should be used together in obtaining a complete picture of a drug's safety profile. Important therapeutic and regulatory decisions should not simply be based on one source of data.
Endoscope-Assisted Repair of Pediatric Trapdoor Fractures of the Orbital Floor: Characterization and Management

Background: The mechanism of injury, the clinical presentation, the natural history, and the indications for the treatment of orbital fractures in the pediatric population are less well described than they are in adults. The purpose of this study was to describe the specific characteristics and management of trapdoor fractures of the orbital floor in the pediatric population. Methods: We enrolled 18 pediatric patients younger than 13 years who underwent endoscopic reconstruction of trapdoor fractures of the orbital floor between March 2000 and October 2006 at the Gil Medical Center and the Ansan Hospital, Korea University. Causes, locations, and clinical characteristics such as restriction of extraocular muscle movement were reviewed retrospectively. Results: Ten of 18 patients (55.6%) exhibited nausea and vomiting, which rapidly resolved after surgery. Surgery was undertaken within 2 weeks after injury (82.3%), and most of the extraocular muscle movement restrictions improved within 2 months postoperatively. Temporary postoperative hypertropia occurred in 5 floor fractures (5/16, 31.2%). Conclusions: Trapdoor fractures of the orbital floor revealed a high incidence of persistent diplopia associated with extraocular muscle and soft tissue entrapment in the pediatric population, but actual entrapment of the muscle belly was confirmed in only 27.8% of patients endoscopically. Temporary hypertropia (31.2%) occurred in trapdoor fractures of the orbital floor but improved after 2 months of follow-up in every patient. Marked motility restriction and nausea/vomiting are predictive of trapdoor fractures. Prompt surgical intervention is needed in patients with such symptoms.
Survival of Salmonella in peanut butter and peanut butter spread

In 1996, the first documented outbreak of salmonellosis associated with the consumption of peanut butter was reported. This study was undertaken to determine survival characteristics of high (5·68 log10 cfu g−1) and low (1·51 log10 cfu g−1) inocula of a five‐serotype mixture of Salmonella in five commercial peanut butters and two commercial peanut butter spreads. Populations in samples inoculated with 5·68 log10 cfu g−1 and stored for 24 weeks at 21 or 5 °C decreased 4·14–4·50 log10 cfu g−1 and 2·86–4·28 log10 cfu g−1, respectively, depending on the formulation. The order of retention of viability was: peanut butter spreads > traditional (regular) and reduced sugar, low‐sodium peanut butters > natural peanut butter. Differences in rates of inactivation are attributed to variation in product composition as well as size and stability of water droplets in the colloidal matrix, which may influence nutrient availability. With the exception of natural peanut butter, products initially inoculated with 1·51 log10 cfu of Salmonella g−1 (32 cfu g−1) were positive for the pathogen after storage for 24 weeks at 5 °C. At 21 °C, however, with the exception of one peanut butter spread, all products were negative for Salmonella after storage for 24 weeks. Post‐process contamination of peanut butters and spreads with Salmonella may to result in survival in these products for the duration of their shelf life at 5 °C and possibly 21 °C, depending on the formulation.
Adolescence and the Trajectory of Alcohol Use: Basic to Clinical Studies

Abstract: Emerging findings from developmentally focused research indicates subtle but important neurocognitive disadvantages among adolescents with alcohol‐use disorders (AUD) as compared to teens without AUD. Even after 3 weeks of abstinence AUD youth display a 10% decrement in delayed memory functions. Neuropsychological testing of youth followed at 4 and 8 years demonstrates that heavy drinking during adolescence is associated with diminished retrieval of verbal and nonverbal material, and poorer performance on tests requiring attention skills. Alcohol withdrawal over the teen years appears to uniquely contribute to deterioration in functioning in visuospatial tasks. Brain imaging studies suggest reduced hippocampal volumes, white matter microstructure irregularities, brain response abnormalities while performing challenging cognitive tasks, and enhanced brain response when viewing alcohol cues (i.e., alcohol advertisements) among adolescents with AUD. Family characteristics such as history of alcoholism and socioeconomic status as well as personal features, including adolescent psychopathology, gender, and age of onset must be carefully considered when investigating the influence of teenage drinking on neurocognition. Further research is needed to understand how age at onset of drinking and duration of abstinence at the time of assessment affect cognitive findings. Longitudinal studies are needed to clarify neuromaturational changes associated with early alcohol exposure and patterns of resiliency. Although the magnitude of alcohol‐related effects observed in adolescents' neurocognition is relatively modest, the implications are major given the prevalence of alcohol involvement, and the important educational, occupational, and social transitions that occur during adolescence.
The structure and organization of the human heavy neurofilament subunit (NF‐H) and the gene encoding it.

Genomic clones for the largest human neurofilament protein (NF‐H) were isolated, the intron/exon boundaries mapped and the entire protein‐coding regions (exons) sequenced. The predicted protein contains a central region that obeys the structural criteria identified for alpha‐helical ‘rod’ domains typically present in all IF protein components: it is approximately 310 amino acids long, shares amino acid sequence homology with other IF protein rod domains and displays the characteristic heptad repeats of apolar amino acids which facilitate coiled‐coil interaction. Nevertheless, anomalies are noted in the structure of the NF‐H rod which could explain observations of its poor homopolymeric assembly in vitro. The protein segment on the carboxy‐terminal side of the human NF‐H rod is uniquely long (greater than 600 amino acids) compared to other IF proteins and is highly charged (greater than 24% Glu, greater than 25% Lys), rich in proline (greater than 12%) and impoverished in cysteine, methionine and aromatic amino acids. Its most remarkable feature is a repetitive sequence that covers more than half its length and includes the sequence motif, Lys‐Ser‐Pro (KSP) greater than 40 times. Together with the recent identification of the serine in KSP as the main target for NF‐directed protein kinases in vivo, this repetitive character explains the massive phosphorylation of the NF‐H subunit that can occur in axons. The human NF‐H gene has three introns, two of which interrupt the protein‐coding sequence at identical points to introns in the genes for the two smaller NF proteins, NF‐M and NF‐L. (ABSTRACT TRUNCATED AT 250 WORDS)
Stability from Variation: The Case of Face Recognition the M.D. Vernon Memorial Lecture

A theme running through M.D. Vernon's discussions of visual perception was the key question of how we perceive a stable world despite continuous variation. The central problem in face identification is how we build stable representations from exemplars that vary, both rigidly and non-rigidly, from instant to instant and from encounter to encounter. Experiments reveal that people are rather poor at generalizing from one exemplar of a face to another (e.g. from one photograph to another showing a different view or expression) yet highly accurate at encoding precise details of faces within the range shown by several slightly different exemplars. Moreover, provided instructions do not encourage subjects explicitly to attend to the way that different exemplars vary, faces are retained in a way that enhances familiarity of the prototype of the set, even if this was not presented for study. It is suggested that our usual encounters with continuous variations of facial expressions, angles, and lightings provide the conditions necessary to establish stable representations of individuals within an overall category (the face) where all members share the same overall structure. These observations about face recognition would probably not have come as any great surprise to Maggie Vernon, many of whose more general observations about visual perception anticipated such conclusions.
Genetic and Immunologic Considerations in Autism

According to recent epidemiological surveys, autistic spectrum disorders have become recognized as common childhood psychopathologies. These life-lasting conditions demonstrate a strong genetic determinant consistent with a polygenic mode of inheritance for which several autism susceptibility regions have been identified. Parallel evidence of immune abnormalities in autistic patients argues for an implication of the immune system in pathogenesis. This review summarizes advances in the molecular genetics of autism, as well as recently emerging concerns addressing the disease incidence and triggering factors. The neurochemical and immunologic findings are analyzed in the context of a neuroimmune hypothesis for autism. Studies of disorders with established neuroimmune nature indicate multiple pathways of the pathogenesis; herein, we discuss evidence of similar phenomena in autism.
Security Coordinated Economic Dispatch for Joint Energy and Reserve Markets

In power markets, SO can maintain system security by preventively restraining the energy transactions or, if having procured sufficient reserves, by dispatching the reserves correctively after any contingency happens. The traditional security constrained unit commitment (SCUC) or economic dispatch (SCED), being with all the contingency constraints, probably leads to lower market efficiency. In this paper, a security coordinated economic dispatch (SCoED) model is presented for day-ahead energy and reserve joint market, which is formulated as a Stackelberg leader-follower problem, the upper level determining the energy and reserve procurement schedules subjecting to only the normal constraints while in the lower level, economic dispatch of the procured reserves is executed for every possible N-l contingency to maintain system security. A numerical example is carried out on a 6-bus system to compare the energy market efficiency and reserve procurement cost under the traditional SCED and the SCoED.
The pontine REM switch: past and present

Rapid eye movement (REM) sleep is a behavioural state characterized by activation of the cortical and hippocampal EEG, rapid eye movements and muscle atonia. For the past 30 years, the most widely accepted neural circuitry model for the regulation of REM sleep has emphasized reciprocal inhibitory interactions between pontine brainstem monoaminergic and cholinergic neurons. In general support of the reciprocal interaction model, neuropharmacological studies have shown that cholinergic agonists promote REM sleep and muscarinic antagonists and monoamines inhibit REM sleep. It has nevertheless proven difficult to reconcile both the theoretical framework of this model and the pharmacological data with the fact that selective lesions of either cholinergic or monoaminergic (noradrenergic, serotoninergic or dopaminergic) nuclei in the brainstem have relatively limited effects on REM sleep. Recent work by our laboratory has revealed the presence of non‐cholinergic and non‐monoaminergic mutually inhibitory REM‐off and REM‐on areas in the mesopontine tegmentum that may form the neuroanatomical basis of the switching circuitry for REM sleep. These findings posit a REM switching circuitry model that is analogous to an electronic ‘flip‐flop’ switch. In this flip‐flop switch arrangement, GABAergic REM‐on neurons (located in the sublaterodorsal tegmental nucleus (SLD)) inhibit GABAergic REM‐off neurons (located in the ventrolateral periaqueductal grey matter (vlPAG) and lateral pontine tegmentum (LPT)) and vice versa. In the REM‐on area are two populations of glutamatergic neurons, the first of which projects to the basal forebrain and regulates EEG components of REM sleep and the second of which projects to the ventromedial medulla and spinal cord and regulates atonia during REM sleep. Our findings demonstrating independent pathways mediating atonia and the EEG components of REM provide a basis for their occasional dissociation in pathological states, e.g. REM sleep behaviour disorder.
Pierre Robin Sequence in Denmark: A Retrospective Population-Based Epidemiological Study

Objective To give an epidemiological description of the clinical entity given the name Pierre Robin sequence, defined by retro- and micrognathia, cleft palate, and respiratory distress and describe other malformations and possible intrauterine impairment. Methods Using the inclusion criteria of micrognathia, cleft palate, and neonatal respiratory distress, a retrospective population-based study of all Danish live births during 1990 through 1999 were carried out. We found 50 children, 25 boys and 25 girls, fulfilling the inclusion criteria, giving an incidence of 1 in 14,000 live births. Results Two-thirds (n = 33) of the children had the classical U-shaped cleft palate. More than one-third (n = 19) had one or several other malformations, and in five patients the triad of Pierre Robin was a minor feature of a complex syndrome. The most common noncomplex syndrome was the Stickler syndrome found in 6 of the 50 patients. More than one-fourth (n = 17) had some kind of intrauterine impairment, with no specific obstetric diagnosis predominant. Consistent with this, the average birth weight was well below normal. Conclusions Several authors have stated that the triad of Pierre Robin is not a nosological entity, in that it has diverse etiology and diverse pathogenesis. We conclude that the triad of Pierre Robin still can be regarded as a clinical entity, readily defined at birth, experiencing the same neonatal problems in varying degrees and hence the possibility of designing treatment protocols for later scientific evaluation.
The 2013 Canadian Forces Mental Health Survey

Objective: The 2013 Canadian Forces Mental Health Survey (CFMHS) collected detailed information on mental health problems, their impacts, occupational and nonoccupational determinants of mental health, and the use of mental health services from a random sample of 8200 serving personnel. The objective of this article is to provide a firm scientific foundation for understanding and interpreting the CFMHS findings. Methods: This narrative review first provides a snapshot of the Canadian Armed Forces (CAF), focusing on 2 key determinants of mental health: the deployment of more than 40,000 personnel in support of the mission in Afghanistan and the extensive renewal of the CAF mental health system. The findings of recent population-based CAF mental health research are reviewed, with a focus on findings from the very similar mental health survey done in 2002. Finally, key aspects of the methods of the 2013 CFMHS are presented. Results: The findings of 20 peer-reviewed publications using the 2002 mental health survey data are reviewed, along with those of 25 publications from other major CAF mental health research projects executed over the past decade. Conclusions: More than a decade of population-based mental health research in the CAF has provided a detailed picture of its mental health and use of mental health services. This knowledge base and the homology of the 2013 survey with the 2002 CAF survey and general population surveys in 2002 and 2012 will provide an unusual opportunity to use the CFMHS to situate mental health in the CAF in a historical and societal perspective.
Signal transducer and activator of transcription 4 limits the development of adaptive regulatory T cells

Summary T‐cell responses to a cytokine milieu instruct the development of multiple effector phenotypes. While transforming growth factor‐β1 (TGF‐β1) inhibits the development of T helper type 1 (Th1) and Th2 cells, we demonstrate that like interleukin‐6 (IL‐6) and IL‐4, IL‐12 can inhibit the development of TGF‐β1‐induced Foxp3‐expressing adaptive T regulatory (aTreg) cells. Signal transducer and activator of transcription 4 (STAT4) is critical for the response to IL‐12, although there is a parallel pathway involving T box expressed in T cells (T‐bet), and cells from mice double‐deficient in STAT4 and T‐bet are refractory to the inhibition of aTreg‐cell development by IL‐12. While the ability of these cytokines to promote Th differentiation may contribute to this effect, we observe that culture with IL‐12, or other instructive cytokines, results in an increase in repressive chromatin modifications at the Foxp3 locus that limit STAT5 binding to Foxp3, without observed effects on IL‐2 signalling pathways. In a model of allergic lung inflammation there are increased percentages of Treg cells in the lungs of Stat4−/− mice, compared with wild‐type mice, and increases in Treg cells correlate with decreased allergic inflammation. Overall, these results suggest an important role for STAT4 in regulating Treg‐cell development.