Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of a UL49-Null Mutant: VP22 of Herpes Simplex Virus Type 1 Facilitates Viral Spread in Cultured Cells and the Mouse Cornea

ABSTRACT Herpes simplex virus type 1 (HSV-1) virions, like those of all herpesviruses, contain a proteinaceous layer termed the tegument that lies between the nucleocapsid and viral envelope. The HSV-1 tegument is composed of at least 20 different viral proteins of various stoichiometries. VP22, the product of the UL49 gene, is one of the most abundant tegument proteins and is conserved among the alphaherpesviruses. Although a number of interesting biological properties have been attributed to VP22, its role in HSV-1 infection is not well understood. In the present study we have generated both a UL49-null virus and its genetic repair and characterized their growth in both cultured cells and the mouse cornea. While single-step growth analyses indicated that VP22 is dispensable for virus replication at high multiplicities of infection (MOIs), analyses of plaque morphology and intra- and extracellular multistep growth identified a role for VP22 in viral spread during HSV-1 infection at low MOIs. Specifically, VP22 was not required for either virion infectivity or cell-cell spread but was required for accumulation of extracellular virus to wild-type levels. We found that the absence of VP22 also affected virion composition. Intracellular virions generated by the UL49-null virus contained reduced amounts of ICP0 and glycoproteins E and D compared to those generated by the wild-type and UL49-repaired viruses. In addition, viral spread in the mouse cornea was significantly reduced upon infection with the UL49-null virus compared to infection with the wild-type and UL49-repaired viruses, identifying a role for VP22 in viral spread in vivo as well as in vitro.
Accuracy of emphysema quantification performed with reduced numbers of CT sections.

OBJECTIVE The purpose of this study was to assess the accuracy of emphysema measurements obtained from systematic samples of evenly spaced CT images compared with measurements obtained from the entire scan. MATERIALS AND METHODS Evenly spaced transverse sections from the CT studies of 136 heavy smokers who underwent screening for lung cancer in the National Lung Screening Trial and of 112 subjects who underwent imaging before lung volume reduction surgery were sampled retrospectively. The samples were acquired both by selection of specific numbers of evenly spaced images and by selection of images at specific distance intervals. The percentage of lung pixels with attenuation below specific thresholds was used as an emphysema index. The image sample error was determined as the difference in emphysema index between the image samples and the entire scan. RESULTS The largest absolute image sample errors in the National Lung Screening Trial cohort with image sample sizes of five, 10, and 20 were 2.2, 0.8, and 0.5 index percentage points, respectively, at 1-mm section thickness (-960 HU threshold), and 2.6, 1.1, and 0.5 index percentage points at 5-mm section thickness (-930 HU threshold). The largest errors in the lung volume reduction surgery cohort for image sample sizes of five and 10 were 5.6 and 2.3 index percentage points at 8- to 10-mm section thickness (-900 HU threshold). Image sample errors were equivalent for the two sampling methods. CONCLUSION Systematic sampling resulted in very small errors in emphysema quantification and may be useful for decreasing radiation exposure in clinical research studies of emphysema.
The Superior Temporal Sulcus Is Causally Connected to the Amygdala: A Combined TBS-fMRI Study

Nonhuman primate neuroanatomical studies have identified a cortical pathway from the superior temporal sulcus (STS) projecting into dorsal subregions of the amygdala, but whether this same pathway exists in humans is unknown. Here, we addressed this question by combining theta burst transcranial magnetic stimulation (TBS) with fMRI to test the prediction that the STS and amygdala are functionally connected during face perception. Human participants (N = 17) were scanned, over two sessions, while viewing 3 s video clips of moving faces, bodies, and objects. During these sessions, TBS was delivered over the face-selective right posterior STS (rpSTS) or over the vertex control site. A region-of-interest analysis revealed results consistent with our hypothesis. Namely, TBS delivered over the rpSTS reduced the neural response to faces (but not to bodies or objects) in the rpSTS, right anterior STS (raSTS), and right amygdala, compared with TBS delivered over the vertex. By contrast, TBS delivered over the rpSTS did not significantly reduce the neural response to faces in the right fusiform face area or right occipital face area. This pattern of results is consistent with the existence of a cortico-amygdala pathway in humans for processing face information projecting from the rpSTS, via the raSTS, into the amygdala. This conclusion is consistent with nonhuman primate neuroanatomy and with existing face perception models. SIGNIFICANCE STATEMENT Neuroimaging studies have identified multiple face-selective regions in the brain, but the functional connections between these regions are unknown. In the present study, participants were scanned with fMRI while viewing movie clips of faces, bodies, and objects before and after transient disruption of the face-selective right posterior superior temporal sulcus (rpSTS). Results showed that TBS disruption reduced the neural response to faces, but not to bodies or objects, in the rpSTS, right anterior STS (raSTS), and right amygdala. These results are consistent with the existence of a cortico-amygdala pathway in humans for processing face information projecting from the rpSTS, via the raSTS, into the amygdala. This conclusion is consistent with nonhuman primate neuroanatomy and with existing face perception models.
Attention and biased competition in multi-voxel object representations

The biased-competition theory accounts for attentional effects at the single-neuron level: It predicts that the neuronal response to simultaneously-presented stimuli is a weighted average of the response to isolated stimuli, and that attention biases the weights in favor of the attended stimulus. Perception, however, relies not on single neurons but on larger neuronal populations. The responses of such populations are in part reflected in large-scale multivoxel fMRI activation patterns. Because the pooling of neuronal responses into blood-oxygen-level-dependent signals is nonlinear, fMRI effects of attention need not mirror those observed at the neuronal level. Thus, to bridge the gap between neuronal responses and human perception, it is fundamental to understand attentional influences in large-scale multivariate representations of simultaneously-presented objects. Here, we ask how responses to simultaneous stimuli are combined in multivoxel fMRI patterns, and how attention affects the paired response. Objects from four categories were presented singly, or in pairs such that each category was attended, unattended, or attention was divided between the two. In a multidimensional voxel space, the response to simultaneously-presented categories was well described as a weighted average. The weights were biased toward the preferred category in category-selective regions. Consistent with single-unit reports, attention shifted the weights by ≈30% in favor of the attended stimulus. These findings extend the biased-competition framework to the realm of large-scale multivoxel brain activations.
Transmitted Raltegravir Resistance in An HIV-1 Crf_Ag-Infected Patient

Here, we describe an HIV-infected patient with pre-treatment resistance to raltegravir, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors, and the ultimate ability to achieve viral suppression. Pretreatment integrase resistance testing is not routinely performed because transmitted integrase mutations conferring resistance to raltegravir are currently thought to be negligible. We suggest obtaining a pretreatment integrase genotype in patients with transmitted multiclass drug resistance in order to create an optimal first regimen and increase the chance for virological suppression.
Endoscopic screening for precancerous lesions of the esophagus in a high risk area in Northern Iran.

BACKGROUND Esophageal squamous cell carcinoma (ESCC) is a major health problem in many developing countries including Iran. ESCC has a very poor prognosis, largely due to late diagnosis. As a first step in developing an early detection and treatment program, we conducted a population-based endoscopic screening for ESCC and its precursor lesion, esophageal squamous dysplasia (ESD) in asymptomatic adults from Golestan Province, northern Iran, a high-risk area for ESCC, to evaluate the feasibility of such a program and to document the prevalence and risk factor correlates of ESD. METHODS This cross-sectional study was conducted among participants of the Golestan Cohort Study (GCS), a population-based cohort of 50,000 adults in eastern Golestan Province. Randomly selected GCS participants were invited by telephone. Those who accepted were referred to a central endoscopy clinic. Eligible subjects were consented and then asked to fill in a brief questionnaire. Detailed information about selected risk factors was obtained from the GCS main database. Endoscopic examination with Lugol's iodine staining was performed, biopsies were taken from unstained lesions as well as the normally stained mucosa of the esophagus, and the biopsies were diagnosed by expert pathologists according to previously described criteria. RESULTS In total, 1906 GCS subjects were invited, of whom only 302 subjects (15.8%) were successfully enrolled. Esophagitis (29.5%) and ESD (6.0%) were the most common pathological diagnoses. Turkmen ethnicity (adjusted OR = 8.61; 95%CI: 2.48-29.83), being older than the median age (OR = 7.7; 95% CI: 1.99-29.87), and using deep frying cooking methods (OR = 4.65; 95%CI: 1.19-18.22) were the strongest predictors for ESD. There were significant relationships between esophagitis and smoking (p-value<0.001), drinking hot tea (P value = 0.02) and lack of education (P value = 0.004). CONCLUSION We observed a low rate for participation in endoscopic screening. Overall prevalence of ESD was 6.0%. Developing non-endoscopic primary screening methods and screening individuals with one or more risk factors may improve these rates.
Mixed Formulation of Conventional and Pegylated Meglumine Antimoniate-Containing Liposomes Reduces Inflammatory Process and Parasite Burden in Leishmania infantum-Infected BALB/c Mice

ABSTRACT Pentavalent antimonial has been the first choice treatment for visceral leishmaniasis; however, it has several side effects that leads to low adherence to treatment. Liposome-encapsulated meglumine antimoniate (MA) arises as an important strategy for chemotherapy enhancement. We evaluated the immunopathological changes using the mixture of conventional and pegylated liposomes with MA. The mice were infected with Leishmania infantum and a single-dose treatment regimen. Comparison was made with groups treated with saline, empty liposomes, free MA, and a liposomal formulation of MA (Lipo MA). Histopathological analyses demonstrated that animals treated with Lipo MA showed a significant decrease in the inflammatory process and the absence of granulomas. The in vitro stimulation of splenocytes showed a significant increase of gamma interferon (IFN-γ) produced by CD8+ T cells and a decrease in interleukin-10 (IL-10) produced by CD4+ and CD8+ T cells in the Lipo MA. Furthermore, the Lipo MA group showed an increase in the IFN-γ/IL-10 ratio in both CD4+ and CD8+ T cell subsets. According to the parasite load evaluation using quantitative PCR, the Lipo MA group showed no L. infantum DNA in the spleen (0.0%) and 41.4% in the liver. In addition, we detected a low positive correlation between parasitism and histopathology findings (inflammatory process and granuloma formation). Thus, our results confirmed that Lipo MA is a promising antileishmanial formulation able to reduce the inflammatory response and induce a type 1 immune response, accompanied by a significant reduction of the parasite burden into hepatic and splenic compartments in treated animals.
Targeted Prostate Biopsy Gleason Score Heterogeneity and Implications for Risk Stratification

Objectives: To quantify Gleason score (GS) heterogeneity within multiparametric magnetic resonance imaging (MRI)-targeted prostate biopsies and to determine impact on National Comprehensive Cancer Network (NCCN) risk stratification. Methods: An Institutional Review Board-approved retrospective study was performed on men who underwent Artemis (MRI-transrectal–ultrasound fusion) targeted biopsy (TB) for suspected prostate cancer between 2012 and 2015. Intratarget heterogeneity was defined as a difference in GS between 2 cores within a single target in patients with ≥2 positive cores. Prostate specific antigen, maximum tumor diameter, apparent diffusion coefficient, MRI suspicion score, prostate volume, systematic biopsy (SB) GS, and T-stage were analyzed for correlation with heterogeneity. Changes in NCCN risk based on high versus low GS on TB, SB alone, and SB+TB were compared. Results: Fifty-three patients underwent TB of 73 suspected lesions. Seventy percent (51/73) had ≥2 positive cores, thus meeting inclusion criteria for heterogeneity analysis. Fifty-five percent (28/51) of qualifying targets showed GS heterogeneity. None of the evaluated factors showed a significant relationship with heterogeneity. NCCN low-risk, intermediate-risk, and high-risk groups were 30%, 49%, and 21%, respectively, with SB alone. Adding low GS TB to SB resulted in 17%, 55%, 28% in each risk group, while using high GS+SB resulted in 4%, 54%, and 42%. Overall, the addition of TB resulted in higher NCCN risk groups in 38% of cases. Conclusions: Over half of multiparametric MRI-defined targets demonstrated GS heterogeneity. The addition of high GS from TB leads to risk inflation compared with using SB alone. Further research is needed on how to integrate these findings into current risk stratification models and clinical practice.
Capturing the temporal evolution of choice across prefrontal cortex

Activity in prefrontal cortex (PFC) has been richly described using economic models of choice. Yet such descriptions fail to capture the dynamics of decision formation. Describing dynamic neural processes has proven challenging due to the problem of indexing the internal state of PFC and its trial-by-trial variation. Using primate neurophysiology and human magnetoencephalography, we here recover a single-trial index of PFC internal states from multiple simultaneously recorded PFC subregions. This index can explain the origins of neural representations of economic variables in PFC. It describes the relationship between neural dynamics and behaviour in both human and monkey PFC, directly bridging between human neuroimaging data and underlying neuronal activity. Moreover, it reveals a functionally dissociable interaction between orbitofrontal cortex, anterior cingulate cortex and dorsolateral PFC in guiding cost-benefit decisions. We cast our observations in terms of a recurrent neural network model of choice, providing formal links to mechanistic dynamical accounts of decision-making. DOI: http://dx.doi. org/10.7554/eLife.11945. 001
Examining the Effects of Scattered Site Supportive Housing on the Social and Economic Integration of Men Who Are Formerly Homeless and Primarily Black/African American

Housing dispersal strategies (scattered sites) have its roots in efforts to construct public housing in more ethnically diverse and affluent communities as a result of the overrepresentation of Blacks/African Americans living in public housing developments with concentrated poverty and racial segregation. Today, the use of scattered site housing is more indicative of nonprofit housing providers seeking to end homelessness. Comparable with the demographics of public housing residents, Blacks/African Americans are severely overrepresented in homeless populations across America. This study examined the impact of scattered site supportive housing, located in an affluent and predominately White/European American community to determine any reductions in social isolation and any levels of improved socio-economic status of men who were formerly homeless and primarily Black/African American. This study used five variables identified from earlier studies thought to influence socio-economic well-being: resident satisfaction, a sense of community, impact on income, neighbor opposition or not-in-my-own backyard (NIMBY) attitudes, and impact of scattered site housing on property values. The results showed that the respondents were, on average, more satisfied with the buildings where they lived than their landlord relations or external neighbors. Furthermore, the study found very little neighbor opposition based on race or class and no negative impact on property values from nearby scattered site developments. Based on these findings, recommendations to continue implementing housing dispersal strategies are offered. In addition, directions for future research are provided.
Science Teaching Beliefs and Reported Approaches Within a Research University: Perspectives from Faculty, Graduate Students, and Undergraduates

This study explores and compares the perspectives of three populations (faculty members, graduate students, and undergraduates) toward science teaching in the College of Chemical and Life Sciences at a research-intensive university. In particular, we investigate the role of faculty professional development in reforming undergraduate science education. In Spring 2011, we collected data through an online survey of 71 faculty members, 99 graduate teaching assistants, and 288 undergraduates in their senior year. We used mixed mode data analysis to examine the perceived importance of skills for undergraduates as viewed by the three populations and the reported practices used by faculty and experienced by students. We found that across all three groups most of the respondents placed a high value on active learning and conceptual understanding, which is consistent with national recommendations. However, when comparing reported beliefs with reported practices, we found that faculty members do not always incorporate active learning techniques. In order to bridge this gap, we suggest providing faculty with professional development opportunities, moral support from peers, and instructional support from science education and instructional technology specialists. Our findings support this recommendation, as faculty who were in teaching-focused communities reported using innovative practices more than those not in communities. This study examines the perspectives of three populations (faculty members, graduate students, and undergraduates) toward science teaching in a researchintensive university to investigate the role of faculty professional development in reforming undergraduate science education. We aimed to determine (1) what skills the three populations believed were most important for undergraduates to acquire; (2) what teaching approaches faculty members believed were most important; (3) what teaching approaches faculty members reported using; (4) what teaching approaches students reported experiencing, and if these were consistent with faculty reports; and (5) what professional development opportunities faculty believed
Psychopathic Traits in Early Childhood: Further Validation of the Child Problematic Traits Inventory

The aim was to further test the reliability and validity of a newly developed instrument designed to assess psychopathic personality traits in children, the Child Problematic Traits Inventory (CPTI). Data from the Preschool Twin Study in Sweden were used, a national general population study of 5-year-old twins (n = 1,188, 50.3% girls). Both preschool teachers and parents were used as informants. Confirmatory factor analysis replicated the intended three-factorial structure of the 28 items of the CPTI. Overall, our findings demonstrated good internal consistency and convergent validity, with all the teacher-rated CPTI scores being associated with teacher and parent ratings of externalizing psychopathology, aggressive behavior, fearlessness, and prosocial peer involvement. In conclusion, the CPTI hold promise as a teacher-rated tool for assessing psychopathic traits in childhood, though more research is needed to see if these findings can be generalized to other countries, settings, and older children.
Prospective evaluation of surgical management of sliding hiatal hernia and gastroesophageal reflux in dogs

OBJECTIVE To evaluate response to surgical management of sliding hiatal hernia (SHH) and gastroesophageal reflux (GER) in dogs using standardized clinical scoring, videofluoroscopic swallow studies, and impedance planimetry. STUDY DESIGN Prospective clinical trial. ANIMALS A total of 17 client-owned dogs. METHODS Dogs were included if they had clinical signs and videofluoroscopic evidence of SHH and/or GER. Owners were asked to complete a standardized canine dysphagia assessment tool (CDAT) preoperatively and postoperatively. Conscious videofluoroscopic swallowing studies and impedance planimetry (IP) were used to evaluate esophageal function and lower esophageal sphincter location and geometry preoperatively and in a subsection of dogs postoperatively. RESULTS Preoperatively, 13/17 dogs included in the study had a history of regurgitation, and 4/17 had radiographic evidence of aspiration pneumonia. Postprandial regurgitation improved in 8/10 dogs with preoperative regurgitation, and for which completed preoperative and postoperative CDAT questionnaires were available (P < .01). The hiatal hernia severity score improved postoperatively (P = .046) in dogs with preoperative and postoperative videofluoroscopic swallowing studies (n = 12). However, hernia frequency score (P = .2) and IP parameters did not differ significantly between time points. CONCLUSION Clinical signs of SHH generally improved with surgery but did not consistently resolve. Videofluoroscopic studies provide evidence that GER and SHH can persist postoperatively in some patients. Based on IP findings, clinical improvement may be attributed to a mechanism independent of lower esophageal sphincter attenuation.