Miracle-dz/UniFAR-FTUs huggingface dataset:
GABA Concentration in the Left Ventral Premotor Cortex Associates With Sensory Hyper-Responsiveness in Autism Spectrum Disorders Without Intellectual Disability

Individuals with autism spectrum disorder (ASD) often exhibit abnormal processing of sensory inputs from multiple modalities and higher-order cognitive/behavioral response to those inputs. Several lines of evidence suggest that altered γ-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the brain, is a central characteristic of the neurophysiology of ASD. The relationship between GABA in particular brain regions and atypical sensory processing in ASD is poorly understood. We therefore employed 1H magnetic resonance spectroscopy (1H-MRS) to examine whether GABA levels in brain regions critical to higher-order motor and/or multiple sensory functions were associated with abnormal sensory responses in ASD. We evaluated atypical sensory processing with a clinically-validated assessment tool. Furthermore, we measured GABA levels in four regions: one each in the primary visual cortex, the left sensorimotor cortex, the left supplementary motor area (SMA), and the left ventral premotor cortex (vPMC). The latter two regions are thought to be involved in executing and coordinating cognitive and behavioral functions in response to multisensory inputs. We found severer sensory hyper-responsiveness in ASD relative to control participants. We also found reduced GABA concentrations in the left SMA but no differences in other regions of interest between ASD and control participants. A correlation analysis revealed a negative association between left vPMC GABA and the severity of sensory hyper-responsiveness across all participants, and the independent ASD group. These findings suggest that reduced inhibitory neurotransmission (reduced GABA) in a higher-order motor area, which modulates motor commands and integrates multiple sensory modalities, may underlie sensory hyper-responsiveness in ASD.
Utilizing conformational changes for patterning thin films of recombinant spider silk proteins.

Recombinant spider silk proteins mimicking the properties of dragline silk proteins represent a class of materials that hold great potential for future high-performance applications. Here we explore the self-assembly behavior of a recombinantly produced spider silk protein based on the dragline silk of the Araneus diadematus , eADF4 (C16), by selectively patterning its secondary structure using capillary transfer lithography and solvent-assisted microcontact molding. Two conformational transitions were observed, influenced by initial solvent composition: α-helix/random coil conformation to a more densely packed β-sheet conformation (by casting from 1,1,1,3,3,3-hexafluoro-propanol) and moderate initial β-sheet content to higher β-sheet content (casting from formic acid). Furthermore, by using the solvent-assisted microcontact molding technique, we were able to achieve a submicrometer spatial resolution and reveal fine details of morphological and mechanical changes in patterned regions and at interfaces.
Cost analysis of adjunct hypnosis with sedation during outpatient interventional radiologic procedures.

PURPOSE To compare the cost of standard intravenous conscious sedation with that of sedation with adjunct self-hypnotic relaxation during outpatient interventional radiologic procedures. MATERIALS AND METHODS Data were reviewed from a prospective randomized study in which patients undergoing vascular and renal interventional procedures underwent either standard sedation (n = 79) or sedation with adjunct hypnosis (n = 82). These data were used to construct a decision analysis model to compare the cost of standard sedation with the cost of sedation with adjunct hypnosis. Multiple sensitivity analyses were performed to assess the applicability of these results to other institutions with different cost structures with respect to the following variables: cost of the hypnosis provider, cost of room time for interventional radiologic procedure, hours of observation after the procedure, and frequency and cost of complications associated with over- or undersedation. RESULTS According to data from this experience, the cost associated with standard sedation during a procedure was $638, compared with $300 for sedation with adjunct hypnosis, which resulted in a savings of $338 per case with hypnosis. Although hypnosis was known to reduce room time, hypnosis remained more cost-effective even if it added an additional 58.2 minutes to the room time. CONCLUSION Use of adjunct hypnosis with sedation reduces cost during interventional radiologic procedures.
Death Receptor 5 Displayed on Extracellular Vesicles Decreases TRAIL Sensitivity of Colon Cancer Cells

Tumor necrosis factor–related apoptosis inducing ligand (TRAIL) is considered to be a promising antitumor drug because of its selective proapoptotic properties on tumor cells. However, the clinical application of TRAIL is until now limited because of the resistance of several cancer cells, which can occur at various levels in the TRAIL signaling pathway. The role of decoy receptors that can side-track TRAIL, thereby preventing the formation of an activated death receptor, has been extensively studied. In this study, we have focused on extracellular vesicles (EVs) that are known to play a role in cell-to-cell communication and that can be released by donor cells into the medium transferring their components to recipient cells. TRAIL-induced apoptotic signaling is triggered upon the binding of two death receptors, DR4 and DR5. Here, we found that DR5 but not DR4 is present in the conditioned medium (CM)–derived from various cancer cells. Moreover, we observed that DR5 was exposed on EVs and can act as “decoy receptor” for binding to TRAIL. This results in a strongly reduced number of apoptotic cells upon treatment with DR5-specific TRAIL variant DHER in CM. This reduction happened with EVs containing either the long or short isoform of DR5. Taken together, we demonstrated that colon rectal tumor cells can secrete DR5-coated EVs, and this can cause TRAIL resistance. This is to our knowledge a novel finding and provides new insights into understanding TRAIL sensitivity.
Impediments to Screening for Hazardous Alcohol Use and Dependence in General Hospital Psychiatric Inpatients

Objective: The Alcohol Use Disorders Identification Test (AUDIT) has been developed to screen for hazardous and harmful alcohol consumption. It has been used among a variety of primary care, general population and general hospital populations. However, with the exception of one study undertaken by the author and colleagues, the use of the AUDIT in general hospital psychiatric patients has not been reported. This paper reports on a substudy of this larger study whose aim was to determine the frequency of hazardous alcohol use and dependence among patients admitted to the psychiatric units of general hospitals in Perth, Western Australia, and discusses major reasons for non-AUDIT screening among this group. Method: In a 12-month period 990 patients aged 18–64 years and residing in the Perth metropolitan area were admitted to the psychiatric unit of the two hospitals. Using the AUDIT alcohol use in patients with four major types of psychiatric disorder, namely mood, adjustment, anxiety and psychotic disorders, was assessed. Results: Of the 834 admissions targeted for AUDIT screening 263 were not screened. This non-screening represented 27–42% of patients in each of the major diagnostic categories. There was no significant difference in the proportion of patients screened versus not screened for mood, adjustment or schizophrenia/psychosis. There were however, significantly fewer patients with anxiety disorder screened compared with mood disorder. Those non-screened patients in major psychiatric groups had significantly shorter hospital stays than their diagnostic counterparts who were screened. The major reason for non-screening in all groups was due to patients leaving the psychiatric facility before they could be accessed. This included discharge before screening, transfer to another psychiatric facility and short admission. To a lesser extent cognitive dysfunction accounted for non-screening among major diagnostic groups. Conclusions: Failure to screen patients was largely due to short hospital stays. Screening was impeded by the brief window period, commonly 1 or 2 days, between the absence of acute psychiatric sequelae and discharge. This situation contrasts dramatically to the medical or surgical admission where major sequelae are largely resolved in 2–3 days and AUDIT screening can take place over the remaining 3–4 days prior to discharge. To be effective in the general hospital psychiatric setting, alcohol screening needs to be incorporated into the routine ward assessment procedures. The brevity of the AUDIT makes this possible. This would maximize the time available to implement an intervention programme to those found to be consuming alcohol at a hazardous or harmful level.
Review of EEG, ERP, and Brain Connectivity Estimators as Predictive Biomarkers of Social Anxiety Disorder

Social anxiety disorder (SAD) is characterized by a fear of negative evaluation, negative self-belief and extreme avoidance of social situations. These recurrent symptoms are thought to maintain the severity and substantial impairment in social and cognitive thoughts. SAD is associated with a disruption in neuronal networks implicated in emotional regulation, perceptual stimulus functions, and emotion processing, suggesting a network system to delineate the electrocortical endophenotypes of SAD. This paper seeks to provide a comprehensive review of the most frequently studied electroencephalographic (EEG) spectral coupling, event-related potential (ERP), visual-event potential (VEP), and other connectivity estimators in social anxiety during rest, anticipation, stimulus processing, and recovery states. A search on Web of Science provided 97 studies that document electrocortical biomarkers and relevant constructs pertaining to individuals with SAD. This study aims to identify SAD neuronal biomarkers and provide insight into the differences in these biomarkers based on EEG, ERPs, VEP, and brain connectivity networks in SAD patients and healthy controls (HC). Furthermore, we proposed recommendations to improve methods of delineating the electrocortical endophenotypes of SAD, e.g., a fusion of EEG with other modalities such as functional magnetic resonance imaging (fMRI) and magnetoencephalograms (MEG), to realize better effectiveness than EEG alone, in order to ultimately evolve the treatment selection process, and to review the possibility of using electrocortical measures in the early diagnosis and endophenotype examination of SAD.
Detection of β-Thalassemia Mutations Using TaqMan Single Nucleotide Polymorphism Genotyping Assays.

AIMS Sickle-cell anemia and β-thalassemia are two of the most common autosomal recessive disorders in the developing world. The severity of the problem and the pressure it exerts on the health services in the Kingdom of Saudi Arabia forced the introduction of a national premarital screening program to lessen its impact on the society. Furthermore, a significant effort has been exerted in the elucidation of the genetic causes of such diseases to facilitate diagnosis and detection of carriers. METHODS We have designed and validated the use of custom TaqMan(®) genotyping assays for the rapid detection of IVS-I-1 (G>A), IVS-I-5 (G>C), codon 39 (C>T), and IVS-I-110 (G>A) mutations in transfusion-dependent β-thalassemia patients' cohort. RESULTS We demonstrated that IVS-I-5 (rs33915217) is the most common single-nucleotide variant in our cohort, with the variant allele constituting 26% of the total alleles investigated. However, this variant was not found in 352 alleles screened from buccal swab DNA obtained from healthy volunteers. CONCLUSION The TaqMan single nucleotide polymorphism (SNP) genotyping assays are a rapid, accurate, and cost-effective method for the initial screening of β-thalassemia cases, which will minimize the need for direct sequencing of the HBB gene, thus reducing detection costs and increasing throughput.
COLON : TARGETED DRUG DELIVERY SYSTEM – A REVIEW

INTRODUCTION Drug delivery to the colon is beneficial not only f or the oral delivery of proteins and peptide drugs (degraded by digestive enzymes of stomach and small intestine) but also for the delivery of low molecular weight compounds used to treat diseases associated with the colon or large intestine such a s ulcerative colitis, diarrhea, and colon cancer . The colon specific drug delivery system (CDDS) should be capable of protecting the drug en route to the colon i.e. drug release and absorption should not occur in the stomach as well as the small intestine , and neither the bioactive agent should be degraded ABSTRACT The colon is a site where both local and systemic d elivery of drugs can take place . Local delivery all ows topical treatment of inflammatory bowel disease. Ho wever, treatment can be made effective if the drugs can be targeted directly into the colon, thereby reduci ng the systemic side effects. Colon target drug del ivery system has been gained great importance not only fo r the treatment of local diseases but also for the systemic delivery of proteins, therapeutic peptides, anti-as thmatic drugs, antihypertensive drugs and ant diabe tic agents. New systems and technologies have been developed fo r col n targeting and to overcome pervious method’s limitations. Colon targeting holds a great potentia l and still need more innovative work. This review article discusses introduction of colon, need and approache s of colonic drug delivery, factor effecting coloni c transition, colonic diseases and the novel and emer ging technologies for colon targeting.
The Electrophysiological Determinants of Corticospinal Motor Neuron Vulnerability in ALS

The brain is complex and heterogeneous. Even though numerous independent studies indicate cortical hyperexcitability as a potential contributor to amyotrophic lateral sclerosis (ALS) pathology, the mechanisms that are responsible for upper motor neuron (UMN) vulnerability remain elusive. To reveal the electrophysiological determinants of corticospinal motor neuron (CSMN, a.k.a UMN in mice) vulnerability, we investigated the motor cortex of hSOD1G93A mice at P30 (postnatal day 30), a presymptomatic time point. Glutamate uncaging by laser scanning photostimulation (LSPS) revealed altered dynamics especially within the inhibitory circuitry and more specifically in L2/3 of the motor cortex, whereas the excitatory microcircuits were unchanged. Observed microcircuitry changes were specific to CSMN in the motor column. Electrophysiological evaluation of the intrinsic properties in response to the microcircuit changes, as well as the exon microarray expression profiles of CSMN isolated from hSOD1G93A and healthy mice at P30, revealed the presence of a very dynamic set of events, ultimately directed to establish, maintain and retain the balance at this early stage. Also, the expression profile of key voltage-gated potassium and sodium channel subunits as well as of the inhibitory GABA receptor subunits and modulatory proteins began to suggest the challenges CSMN face at this early age. Since neurodegeneration is initiated when neurons can no longer maintain balance, the complex cellular events that occur at this critical time point help reveal how CSMN try to cope with the challenges of disease manifestation. This information is critically important for the proper modulation of UMNs and for developing effective treatment strategies.
Social Media as a Tool to Help Select Tourism Destinations: The Case of Malaysia

ABSTRACT This study modeled use of social media as a tool to select tourism destinations. The findings revealed that perceived usefulness, perceived ease of use, perceived risk, and electronic word-of-mouth (e-WOM) directly influenced the attitude and has an indirect effect on intention with the presence of attitude. The development of tourism marketing and communication strategies should focus on the online context as the factors which are capable of influencing tourists’ behavior in a more efficient way.
Limb bone morphology, bone strength, and cursoriality in lagomorphs

The primary aim of this study is to broadly evaluate the relationship between cursoriality (i.e. anatomical and physiological specialization for running) and limb bone morphology in lagomorphs. Relative to most previous studies of cursoriality, our focus on a size‐restricted, taxonomically narrow group of mammals permits us to evaluate the degree to which ‘cursorial specialization’ affects locomotor anatomy independently of broader allometric and phylogenetic trends that might obscure such a relationship. We collected linear morphometrics and μCT data on 737 limb bones covering three lagomorph species that differ in degree of cursoriality: pikas (Ochotona princeps, non‐cursorial), jackrabbits (Lepus californicus, highly cursorial), and rabbits (Sylvilagus bachmani, level of cursoriality intermediate between pikas and jackrabbits). We evaluated two hypotheses: cursoriality should be associated with (i) lower limb joint mechanical advantage (i.e. high ‘displacement advantage’, permitting more cursorial species to cycle their limbs more quickly) and (ii) longer, more gracile limb bones, particularly at the distal segments (as a means of decreasing rotational inertia). As predicted, highly cursorial jackrabbits are typically marked by the lowest mechanical advantage and the longest distal segments, non‐cursorial pikas display the highest mechanical advantage and the shortest distal segments, and rabbits generally display intermediate values for these variables. Variation in long bone robusticity followed a proximodistal gradient. Whereas proximal limb bone robusticity declined with cursoriality, distal limb bone robusticity generally remained constant across the three species. The association between long, structurally gracile limb bones and decreased maximal bending strength suggests that the more cursorial lagomorphs compromise proximal limb bone integrity to improve locomotor economy. In contrast, the integrity of distal limb bones is maintained with increasing cursoriality, suggesting that the safety factor takes priority over locomotor economy in those regions of the postcranial skeleton that experience higher loading during locomotion. Overall, these findings support the hypothesis that cursoriality is associated with a common suite of morphological adaptations across a range of body sizes and radiations.
Cognitive and Linguistic Predictors of Language Control in Bilingual Children

In order to communicate effectively with a variety of conversation partners and in a variety of settings, bilingual children must develop language control, the ability to control which language is used for production. Past work has focused on linguistic skills as the limiting factor in children’s ability to control their language choice, while cognitive control has been the focus of adult models of language control. The current study examined the effects of both language ability and cognitive control on language control in 4−6 year old Spanish/English bilingual children with a broad range of language skills, including those with low skills in both languages. To measure language control, children participated in an interactive scripted confederate dialogue paradigm in which they took turns describing picture scenes with video partners who presented themselves as monolingual speakers of English or monolingual speakers of Spanish. The paradigm had two conditions: a single-language context, in which children interacted with only one partner, and a dual-language context, in which children needed to switch between languages to address different partners. The Dimensional Change Card Sort (DCCS) indexed cognitive control. The findings revealed an overall effect of language ability, such that children with lower language skills were more likely to produce words in the language not understood by their conversation partner. There was also an effect of cognitive control on children’s ability to adjust to the dual-language context. Based on these findings, we suggest that a model of language control in children should consider both linguistic and cognitive factors. However, language ability appears to be the main limiting factor, with cognitive control playing a more restricted role in adapting to a dual-language context.
Cost analyses of community-acquired pneumonia from the hospital perspective.

STUDY OBJECTIVES Community-acquired pneumonia (CAP) is a widespread disease with important implications for health-care systems worldwide. This study investigated direct costs, treatment patterns, and outcomes associated with two patient cohorts hospitalized with CAP. DESIGN The study design was naturalistic, prospective, and open. PATIENTS The study enrolled 580 patients. Two hundred sixty-one patients were treated initially with IV moxifloxacin (45%, cohort M); the remaining 319 patients received nonstandardized treatment (cohort S). SETTING Twenty-two hospitals in Germany. RESULTS Clinical success rates were similar between treatment groups (cohort M, 242 of 256 patients, 95%; cohort S, 286 of 312 patients, 92%; p = 0.208). Mean +/- SD length of hospital stay was 10.8 +/- 5.2 days, with cohort M having a significantly shorter hospital stay (10.0 +/- 4 days) compared to cohort S (11.5 +/- 6 days; p < 0.001). Median of all direct costs was dollar 1,333 (minimum, dollar 127; maximum, dollar 9,488), with direct costs of dollar 1,250 in cohort M (minimum, dollar 372; maximum, dollar 9,488) and dollar 1,409 in cohort S (minimum, dollar 127; maximum, dollar 9,366) per treated episode of CAP (p = 0.066). CONCLUSIONS Major determinants of costs were length of hospital stay and ICU admission, whereas costs for staff and hotel were major contributors to direct costs. Initial antibiotic therapy with moxifloxacin resulted in similar clinical efficacy and direct costs compared to nonstandardized therapy; however, patients treated with moxifloxacin benefited with an earlier hospital discharge.
Quantification of the N-glycosylated Secretome by Super-SILAC During Breast Cancer Progression and in Human Blood Samples

Cells secrete a large number of proteins to communicate with their surroundings. Furthermore, plasma membrane proteins and intracellular proteins can be released into the extracellular space by regulated or non-regulated processes. Here, we profiled the supernatant of 11 cell lines that are representative of different stages of breast cancer development by specifically capturing N-glycosylated peptides using the N-glyco FASP technology. For accurate quantification we developed a super-SILAC mix from several labeled breast cancer cell lines and used it as an internal standard for all samples. In total, 1398 unique N-glycosylation sites were identified and quantified. Enriching for N-glycosylated peptides focused the analysis on classically secreted and membrane proteins. N-glycosylated secretome profiles correctly clustered the different cell lines to their respective cancer stage, suggesting that biologically relevant differences were detected. Five different profiles of glycoprotein dynamics during cancer development were detected, and they contained several proteins with known roles in breast cancer. We then used the super-SILAC mix in plasma, which led to the quantification of a large number of the previously identified N-glycopeptides in this important body fluid. The combination of quantifying the secretome of cancer cell lines and of human plasma with a super-SILAC approach appears to be a promising new approach for finding markers of disease.