The Relationship Development and Learning Organization Dimensions.

This research examined the relationship among learning organization dimensions, leadership development, employee development, and their interactions with two demographic variables (gender and ethnicity) in the context of libraries. The researchers conducted a multivariate analysis of the variance to assess the differences by leadership training groups (low training hours vs. high training hours), or by gender; and by workplace training groups (low vs. high), or by ethnicity (white vs. all others) on a linear combination of the seven dimensions of the learning organization. A conclusive summary is provided along with contributive discussion. Implications and contributions to librarians are discussed in addition to future research recommendations. Also included are conclusive final thoughts accompanied by the limitations of this research

Ack1 is a dopamine transporter endocytic brake that rescues a trafficking-dysregulated ADHD coding variant

The dopamine (DA) transporter (DAT) facilitates high-affinity presynaptic DA reuptake that temporally and spatially constrains DA neurotransmission. Aberrant DAT function is implicated in attention-deficit/hyperactivity disorder and autism spectrum disorder. DAT is a major psychostimulant target, and psychostimulant reward strictly requires binding to DAT. DAT function is acutely modulated by dynamic membrane trafficking at the presynaptic terminal and a PKC-sensitive negative endocytic mechanism, or endocytic brake, controls DAT plasma membrane stability. However, the molecular basis for the DAT endocytic brake is unknown, and it is unknown whether this braking mechanism is unique to DAT or common to monoamine transporters. Here, we report that the cdc42-activated, nonreceptor tyrosine kinase, Ack1, is a DAT endocytic brake that stabilizes DAT at the plasma membrane and is released in response to PKC activation. Pharmacologic and shRNA-mediated Ack1 silencing enhanced basal DAT internalization and blocked PKC-stimulated DAT internalization, but had no effects on SERT endocytosis. Both cdc42 activation and PKC stimulation converge on Ack1 to control Ack1 activity and DAT endocytic capacity, and Ack1 inactivation is required for stimulated DAT internalization downstream of PKC activation. Moreover, constitutive Ack1 activation is sufficient to rescue the gain-of-function endocytic phenotype exhibited by the ADHD DAT coding variant, R615C. These findings reveal a unique endocytic control switch that is highly specific for DAT. Moreover, the ability to rescue the DAT(R615C) coding variant suggests that manipulating DAT trafficking mechanisms may be a potential therapeutic approach to correct DAT coding variants that exhibit trafficking dysregulation

PSMA PET as a predictive tool for sub-regional importance estimates in the parotid gland

Objective: Xerostomia (subjective dry mouth) and radiation-induced salivary gland dysfunction remain a common side effect for head-and-neck radiotherapy patients, and attempts have been made to quantify the intra-parotid dose response. Here, we aim to compare several models of parotid gland regional importance with prostate specific membrane antigen (PSMA) positron emission tomography (PET), which has high concentrations of uptake in salivary glands and has been previously suggested to relate to gland functionality. Furthermore, we develop a predictive model of Clark et al.'s relative importance using radiomic features, and demonstrate a methodology for predicting patient-specific importance deviations from the population. Approach: Intra-parotid uptake was compared with four regional importance models using [18F]DCFPyL PSMA PET images. The correlation of uptake and importance was ascertained when numerous non-overlapping sub-regions were defined, while a paired t-test was used when binary regions were defined. Radiomic PSMA PET/CT features within Clark et al.'s sub-regions were used to develop a predictive model of population importance. Main Results: Clark et al.'s relative importance regions were significantly (p < 0.02) anti-correlated with PSMA PET uptake. Van Luijk et al.'s critical regions had significantly lower (p < 0.01) uptake than in non-critical regions. Kernel Ridge Regression with principal component analysis feature selection performed best over test sets (Mean Absolute Error = 0.08. Deblurring PSMA PET images with neural blind deconvolution strengthened correlations and improved model performance. Significance: This study suggests that regions of relatively low PSMA PET concentration in parotid glands may exhibit relatively high dose-sensitivity. We've demonstrated the ability of PSMA PET radiomic features for predicting relative importance within the parotid glands.Comment: 9 Figures, 7 Table

Neural blind deconvolution for simultaneous partial volume correction and super-sampling of PSMA PET images

Objective: We aimed to simultaneously mitigate partial volume effects (PVEs) in prostate-specific membrane antigen (PSMA) positron emission tomography (PET) images while performing super-sampling. Approach: Blind deconvolution is a method of estimating the hypothetical "deblurred" image along with the blur kernel (related to the point spread function) simultaneously. Traditional maximum a posteriori blind deconvolution methods require stringent assumptions and suffer from convergence to a trivial solution. A promising method of modelling the deblurred image and kernel with independent neural networks, called "neural blind deconvolution" was demonstrated on 2D natural images in 2020. In this work, we adapt neural blind deconvolution for PVE correction of PSMA PET images, along with simultaneous super-sampling. We compare this methodology with several interpolation methods, using blind image quality metrics, and test the model's ability to predict kernels by re-running the model after applying artificial "pseudo-kernels" to deblurred images. Main Results: Our results demonstrate improvements in image quality over other interpolation methods in terms of blind image quality metrics and visual assessment. Predicted kernels were similar between patients, and the model accurately predicted several artificially-applied pseudo-kernels, Significance: The intrinsically low spatial resolution of PSMA PET leads to PVEs which negatively impact uptake quantification in small regions. The proposed method can be used to mitigate this issue, and can be straightforwardly adapted for other medical imaging modalities.Comment: 10 Figures, 4 Tables, 19 page

Dopamine transporter endocytic trafficking in striatal dopaminergic neurons: differential dependence on dynamin and the actin cytoskeleton

Dopaminergic signaling profoundly impacts rewarding behaviors, movement, and executive function. The presynaptic dopamine (DA) transporter (DAT) recaptures released DA, thereby limiting synaptic DA availability and maintaining dopaminergic tone. DAT constitutively internalizes and PKC activation rapidly accelerates DAT endocytosis, resulting in DAT surface loss. Longstanding evidence supports PKC-stimulated DAT trafficking in heterologous expression studies. However, PKC-stimulated DAT internalization is not readily observed in cultured dopaminergic neurons. Moreover, conflicting reports implicate both classic and nonclassic endocytic mechanisms mediating DAT trafficking. Prior DAT trafficking studies relied primarily upon chronic gene disruption and dominant-negative protein expression, or were performed in cell lines and cultured neurons, yielding results difficult to translate to adult dopaminergic neurons. Here, we use newly described dynamin inhibitors to test whether constitutive and PKC-stimulated DAT internalization are dynamin-dependent in adult dopaminergic neurons. Ex vivo biotinylation studies in mouse striatal slices demonstrate that acute PKC activation drives native DAT surface loss, and that surface DAT surprisingly partitions between endocytic-willing and endocytic-resistant populations. Acute dynamin inhibition reveals that constitutive DAT internalization is dynamin-independent, whereas PKC-stimulated DAT internalization is dynamin-dependent. Moreover, total internal reflection fluorescence microscopy experiments demonstrate that constitutive DAT internalization occurs equivalently from lipid raft and nonraft microdomains, whereas PKC-stimulated DAT internalization arises exclusively from lipid rafts. Finally, DAT endocytic recycling relies on a dynamin-dependent mechanism that acts in concert with the actin cytoskeleton. These studies are the first comprehensive investigation of native DAT trafficking in ex vivo adult neurons, and reveal that DAT surface dynamics are governed by complex multimodal mechanisms

Acceptability of and barriers to human papillomavirus vaccination in China:A systematic review of the Chinese and English scientific literature

INTRODUCTION: Widespread adoption of the human papillomavirus (HPV) vaccine will require population acceptance and tailoring of immunisation services to community needs and preferences. We examined peer‐reviewed publications on the acceptability of and barriers to the HPV vaccine across China. METHODS: We searched English (MEDLINE, Embase, and Web of Science) and Chinese (CNKI, VIP, Wanfang data) databases between 1 January 2006 and 31 December 2017. We adopted a narrative approach for data synthesis. RESULTS: We identified 73 studies. The overall median acceptability of HPV vaccine was 71.8% (Q1–Q3: 58.6%–81%). Low levels of acceptability (90%) and urban eastern regions (all <35%). Despite these regional variations, common barriers to HPV vaccine acceptance were concerns about vaccine safety, uncertainty over vaccine effectiveness, low perceived risk of cervical cancer and the price of the vaccine. The level of willingness to pay for the HPV vaccine (over 153 US dollars) was very low (<7%). CONCLUSION: The acceptability of and attitudes towards HPV vaccine vary by regions and populations across China. HPV vaccination programmes will need to tailor service delivery as well as information materials to take account of regional concerns

The Dopamine Transporter Recycles via a Retromer-Dependent Postendocytic Mechanism: Tracking Studies Using a Novel Fluorophore-Coupling Approach

Presynaptic reuptake, mediated by the dopamine (DA) transporter (DAT), terminates DAergic neurotransmission and constrains extracellular DA levels. Addictive and therapeutic psychostimulants inhibit DA reuptake and multiple DAT coding variants have been reported in patients with neuropsychiatric disorders. These findings underscore that DAT is critical for DA neurotransmission and homeostasis. DAT surface availability is regulated acutely by endocytic trafficking, and considerable effort has been directed toward understanding mechanisms that govern DAT\u27s plasma membrane expression and postendocytic fate. Multiple studies have demonstrated DAT endocytic recycling and enhanced surface delivery in response to various stimuli. Paradoxically, imaging studies have not detected DAT targeting to classic recycling endosomes, suggesting that internalized DAT targets to either degradation or an undefined recycling compartment. Here, we leveraged PRIME (PRobe Incorporation Mediated by Enzyme) labeling to couple surface DAT directly to fluorophore, and tracked DAT\u27s postendocytic itinerary in immortalized mesencephalic cells. Following internalization, DAT robustly targeted to retromer-positive endosomes, and DAT/retromer colocalization was observed in male mouse dopaminergic somatodendritic and terminal regions. Short hairpin RNA-mediated Vps35 knockdown revealed that DAT endocytic recycling requires intact retromer. DAT also targeted rab7-positive endosomes with slow, linear kinetics that were unaffected by either accelerating DAT internalization or binding a high-affinity cocaine analog. However, cocaine increased DAT exit from retromer-positive endosomes significantly. Finally, we found that the DAT carboxy-terminal PDZ-binding motif was required for DAT recycling and exit from retromer. These results define the DAT recycling mechanism and provide a unifying explanation for previous, seemingly disparate, DAT endocytic trafficking findings. SIGNIFICANCE STATEMENT The neuronal dopamine (DA) transporter (DAT) recaptures released DA and modulates DAergic neurotransmission, and a number of DAT coding variants have been reported in several DA-related disorders, including infantile parkinsonism, attention-deficit/hyperactivity disorder and autism spectrum disorder. DAT is also competitively inhibited by psychostimulants with high abuse potential. Therefore, mechanisms that acutely affect DAT availability will likely exert significant impact on both normal and pathological DAergic homeostasis. Here, we explore the cellular mechanisms that acutely control DAT surface expression. Our results reveal the intracellular mechanisms that mediate DAT endocytic recycling following constitutive and regulated internalization. In addition to shedding light on this critical process, these findings resolve conflict among multiple, seemingly disparate, previous reports on DAT\u27s postendocytic fate

Evaluation of portable colposcopy and human papillomavirus testing for screening of cervical cancer in rural China

OBJECTIVE: To evaluate the use of a portable, rechargeable colposcope combined with human papillomavirus (HPV) testing, as compared with HPV testing alone, for screening of cervical cancer and pre-cancerous lesions. METHODS: This was a cross-sectional study among 488 women in Baoshan County, Yunnan. The women underwent HPV testing followed by Gynocular portable colposcopy with visual inspection with acetic acid. Obvious lesions were biopsied. If portable colposcopy testing was negative but HPV testing was positive, the women underwent follow-up testing with thin-prep cytology and traditional colposcopy. Cervical biopsies were performed for any abnormalities. Histopathology was followed up with diagnosis and treatment. RESULTS: Among 488 women screened with portable colposcopy, 24 women underwent biopsy based on positive colposcopy screening. Of these 24 women, three were HPV positive and 21 were HPV negative. Five women had cervical intra-epithelial neoplasia (CIN) I and one had advanced cervical cancer. Forty-six women tested positive for HPV. Three of these women had screened positive on preliminary colposcopy, with one positive for CIN III/squamous cell carcinoma and one woman with CIN I. Forty-three women underwent follow-up testing with thin-prep cytology. Two women had atypical squamous cells of undetermined significance and five had low-grade squamous intra-epithelial lesions and were biopsied; three women had CIN I, one had CIN II and one had CIN III. HPV testing and portable colposcopy was more sensitive but slightly less specific than portable colposcopy or HPV testing alone. CONCLUSION: While HPV testing has high sensitivity and specificity for the detection of pre-cancerous and cancerous lesions and portable colposcopy has lower specificity, both methods of detection have low positive predictive value and high negative predictive value. In tandem, HPV testing and portable colposcopy had higher sensitivity for detection among women who underwent biopsies. In clinical practice, portable colposcopy was an effective, easy and affordable tool to transport to villages where cytology is not currently feasible