Miracle-dz/UniFAR-FTUs huggingface dataset:
Immunohistochemical evaluation of phosphorylated SMAD2/SMAD3 and the co-activator P300 in human glomerulonephritis: correlation with renal injury

Background: Smad2 and Smad3 are transcription factors that mediate transforming growth factor beta (TGF‐β) signals. Upon their activation, phosphorylated Smad2/Smad3 (pSmad2/Smad3), translocate to the nucleus and associate with co‐activators such as p300, regulating the transcription of genes that contribute to the fibrotic processes. Methods: We investigated the immunohistochemical expression of pSmad2/Smad3 and the co‐activator p300 in 152 renal biopsy specimens from patients with various types of glomerulonephritides (GNs) and in 15 normal kidney specimens. Patients’ clinical data (serum creatinine level and proteinuria) had been collected. Results: There was a dramatic increase in the expression of pSmad2/3 and p300 in all glomerular cell types in all GNs. pSmad2/3 expression was increased in all tubular segments (except for the proximal tubules in nonproliferative GNs), while p300 expression was significantly increased only in the proximal tubular cells in all GNs. Glomerular and tubular pSmad2/Smad3 and p300 were significantly increased in proliferative GNs (compared to the nonproliferative), particularly in the secondary group. The expression profile of p300 correlated positively with the expression of pSmad2/Smad3 in the diseased glomeruli and proximal tubules. pSmad2/3 and p300 were very often detected in segmental hyperplastic lesions, cellular crescents, microadhesions and segmental or global sclerotic areas. Glomerular and proximal tubular pSmad2/Smad3 was positively correlated with serum creatinine levels, while distal and collecting tubular pSmad2/3 and p300 correlated positively with tubular atrophy. Glomerular and proximal tubular pSmad2/3 expression and glomerular p300 expression correlated positively with lupus nephritis activity. Conclusion: Our results suggest that pSmad2/3‐p300 pathway may play a pivotal role in the pathogenesis and progression of human glomerulonephritis.
The Acid Test of Fluoride: How pH Modulates Toxicity

Background It is not known why the ameloblasts responsible for dental enamel formation are uniquely sensitive to fluoride (F−). Herein, we present a novel theory with supporting data to show that the low pH environment of maturating stage ameloblasts enhances their sensitivity to a given dose of F−. Enamel formation is initiated in a neutral pH environment (secretory stage); however, the pH can fall to below 6.0 as most of the mineral precipitates (maturation stage). Low pH can facilitate entry of F− into cells. Here, we asked if F− was more toxic at low pH, as measured by increased cell stress and decreased cell function. Methodology/Principal Findings Treatment of ameloblast-derived LS8 cells with F− at low pH reduced the threshold dose of F− required to phosphorylate stress-related proteins, PERK, eIF2α, JNK and c-jun. To assess protein secretion, LS8 cells were stably transduced with a secreted reporter, Gaussia luciferase, and secretion was quantified as a function of F− dose and pH. Luciferase secretion significantly decreased within 2 hr of F− treatment at low pH versus neutral pH, indicating increased functional toxicity. Rats given 100 ppm F− in their drinking water exhibited increased stress-mediated phosphorylation of eIF2α in maturation stage ameloblasts (pH<6.0) as compared to secretory stage ameloblasts (pH∼7.2). Intriguingly, F−-treated rats demonstrated a striking decrease in transcripts expressed during the maturation stage of enamel development (Klk4 and Amtn). In contrast, the expression of secretory stage genes, AmelX, Ambn, Enam and Mmp20, was unaffected. Conclusions The low pH environment of maturation stage ameloblasts facilitates the uptake of F−, causing increased cell stress that compromises ameloblast function, resulting in dental fluorosis.
Elevational variation in density dependence in a subtropical forest

Density-dependent mortality has been recognized as an important mechanism that underpins tree species diversity, especially in tropical forests. However, few studies have attempted to explore how density dependence varies with spatial scale and even fewer have attempted to identify why there is scale-dependent differentiation. In this study, we explore the elevational variation in density dependence. Three 1-ha permanent plots were established at low and high elevations in the Heishiding subtropical forest, southern China. Using data from 1200 1 m2 seedling quadrats, comprising of 200 1 m2 quadrats located in each 1-ha plot, we examined the variation in density dependence between elevations using a generalized linear mixed model with crossed random effects. A greenhouse experiment also investigated the potential effects of the soil biota on density-dependent differentiation. Our results demonstrated that density-dependent seedling mortality can vary between elevations in subtropical forests. Species found at a lower elevation suffered stronger negative density dependence than those found at a higher elevation. The greenhouse experiment indicated that two species that commonly occur at both elevations suffered more from soilborne pathogens during seed germination and seedling growth when they grew at the lower elevation, which implied that soil pathogens may play a crucial role in density-dependent spatial variation.
Audiovisual Temporal Processing and Synchrony Perception in the Rat

Extensive research on humans has improved our understanding of how the brain integrates information from our different senses, and has begun to uncover the brain regions and large-scale neural activity that contributes to an observer’s ability to perceive the relative timing of auditory and visual stimuli. In the present study, we developed the first behavioral tasks to assess the perception of audiovisual temporal synchrony in rats. Modeled after the parameters used in human studies, separate groups of rats were trained to perform: (1) a simultaneity judgment task in which they reported whether audiovisual stimuli at various stimulus onset asynchronies (SOAs) were presented simultaneously or not; and (2) a temporal order judgment task in which they reported whether they perceived the auditory or visual stimulus to have been presented first. Furthermore, using in vivo electrophysiological recordings in the lateral extrastriate visual (V2L) cortex of anesthetized rats, we performed the first investigation of how neurons in the rat multisensory cortex integrate audiovisual stimuli presented at different SOAs. As predicted, rats (n = 7) trained to perform the simultaneity judgment task could accurately (~80%) identify synchronous vs. asynchronous (200 ms SOA) trials. Moreover, the rats judged trials at 10 ms SOA to be synchronous, whereas the majority (~70%) of trials at 100 ms SOA were perceived to be asynchronous. During the temporal order judgment task, rats (n = 7) perceived the synchronous audiovisual stimuli to be “visual first” for ~52% of the trials, and calculation of the smallest timing interval between the auditory and visual stimuli that could be detected in each rat (i.e., the just noticeable difference (JND)) ranged from 77 ms to 122 ms. Neurons in the rat V2L cortex were sensitive to the timing of audiovisual stimuli, such that spiking activity was greatest during trials when the visual stimulus preceded the auditory by 20–40 ms. Ultimately, given that our behavioral and electrophysiological results were consistent with studies conducted on human participants and previous recordings made in multisensory brain regions of different species, we suggest that the rat represents an effective model for studying audiovisual temporal synchrony at both the neuronal and perceptual level.
Improved detection of individual nodal involvement in squamous cell carcinoma of the esophagus by FDG PET.

UNLABELLED Because both the number and location of metastatic lymph nodes and the N stage influence survival in esophageal cancer, accurate noninvasive evaluation of individual lymph node groups for the presence of metastasis is essential for therapeutic planning. Therefore, we investigated the accuracy of FDG PET for evaluating individual lymph groups in esophageal cancer patients and compared the results with those of CT and endoscopic sonography (ES). METHODS Sixty-one consecutive patients with histologically proven primary esophageal carcinoma were studied prospectively with FDG PET. Thirteen patients who were treated nonsurgically were excluded from data analysis. The remaining 48 patients underwent esophagectomy and lymph node dissection. All 48 patients underwent CT scanning, including the lower neck, thorax, and upper abdomen, with intravenous administration of contrast medium. ES was performed in 45 of the patients but was incomplete in 12 patients because of esophageal stenosis. The accuracies of FDG PET, CT, and ES were compared with histologic findings. RESULTS During surgery, a total of 382 lymph node groups were dissected in 48 patients, of which 100 node groups in 32 patients were malignant on histologic examination. For assessing metastasis to individual groups, FDG PET showed 57% sensitivity, 97% specificity, and 86% accuracy, whereas CT showed 18% sensitivity (P < 0.0001), 99% specificity (P = 0.033), and 78% accuracy (P = 0.003). For N staging, FDG PET was correct in 83% (40/48) of the patients, whereas CT and ES were correct in 60% (29/48; P = 0.006) and 58% (26/45; P = 0.003), respectively. CONCLUSION FDG PET is more accurate than is CT or ES for evaluating metastasis to individual lymph node groups and for N staging in esophageal cancer and thus may be helpful in determining the therapeutic plan.
Marking text documents

Summary form only given. Electronic documents are more easily copied and redistributed than paper documents. This is a major impediment to electronic publishing. Illegal redistribution can be discouraged by placing unique marks in each copy and registering the copy with the original recipient. If an illegal copy is discovered, the original recipient can be identified. We describe several invisible techniques for encoding information in text documents. We also describe a marking system, for electronic publishing, that is scalable to large numbers of users.
Incidence and Risk Factors for Vertebral Fracture in Women and Men: 25‐Year Follow‐Up Results From the Population‐Based Framingham Study

This study evaluates baseline characteristics of 704 women and men in the Framingham Study with respect to long‐term risk of incident vertebral fracture. Incidence was 24% in women and 10% in men. Few factors in middle‐aged persons, except prevalent (moderate) fracture and alcohol consumption (in men), predicted long‐term incidence of vertebral fracture.
Environmental variation, vegetation distribution, carbon dynamics and water/energy exchange at high latitudes

Abstract The responses of high latitude ecosystems to global change involve complex interactions among environmental variables, vegetation distribution, carbon dynamics, and water and energy exchange. These responses may have important consequences for the earth system. In this study, we evaluated how vegetation distribution, carbon stocks and turnover, and water and energy exchange are related to environmental variation spanned by the network of the IGBP high latitude transects. While the most notable feature of the high latitude transects is that they generally span temperature gradients from southern to northern latitudes, there are substantial differences in temperature among the transects. Also, along each transect temperature co-varies with precipitation and photosynthetically active radiation, which are also variable among the transects. Both climate and disturbance interact to influence latitudinal patterns of vegetation and soil carbon storage among the transects, and vegetation distribution appears to interact with climate to determine exchanges of heat and moisture in high latitudes. Despite limitations imposed by the data we assembled, the analyses in this study have taken an important step toward clarifying the complexity of interactions among environmental variables, vegetation distribution, carbon stocks and turnover, and water and energy exchange in high latitude regions. This study reveals the need to conduct coordinated global change studies in high latitudes to further elucidate how interactions among climate, disturbance, and vegetation distribution influence carbon dynamics and water and energy exchange in high latitudes.
Hypergeometric language models for republished article finding

Republished article finding is the task of identifying instances of articles that have been published in one source and republished more or less verbatim in another source, which is often a social media source. We address this task as an ad hoc retrieval problem, using the source article as a query. Our approach is based on language modeling. We revisit the assumptions underlying the unigram language model taking into account the fact that in our setup queries are as long as complete news articles. We argue that in this case, the underlying generative assumption of sampling words from a document with replacement, i.e., the multinomial modeling of documents, produces less accurate query likelihood estimates. To make up for this discrepancy, we consider distributions that emerge from sampling without replacement: the central and non-central hypergeometric distributions. We present two retrieval models that build on top of these distributions: a log odds model and a bayesian model where document parameters are estimated using the Dirichlet compound multinomial distribution. We analyse the behavior of our new models using a corpus of news articles and blog posts and find that for the task of republished article finding, where we deal with queries whose length approaches the length of the documents to be retrieved, models based on distributions associated with sampling without replacement outperform traditional models based on multinomial distributions.
The Association Between Obesity and Low Back Pain and Disability Is Affected by Mood Disorders

AbstractLow back pain (LBP) and obesity are major public health problems; however, the relationship between body composition and low back pain in men is unknown. This study aims to examine the association between body composition and LBP and disability in a population-based sample of men, as well as the factors that may affect this relationship.Nine hundred seventy-eight male participants from the Geelong Osteoporosis Study were invited to participate in a follow-up study in 2006. Participants completed questionnaires on sociodemographics and health status. Low back pain was determined using the validated Chronic Back Pain Grade Questionnaire and the presence of an emotional disorder was assessed using the Hospital Anxiety Depression Scale. Body composition was measured using dual energy x-ray absorptiometry.Of the 820 respondents (84% response rate), 124 (15%) had high-intensity low back pain and/or disability (back pain). Low back pain was associated with higher body mass index (28.7 ± 0.4 vs 27.3 ± 0.2 kg/m2, P = 0.02) and waist–hip ratio (0.97 ± 0.006 vs 0.96 ± 0.006, P = 0.04), with increased tendency toward having a higher fat mass index (8.0 vs 7.6 kg/m2, P = 0.08), but not fat-free mass index (P = 0.68). The associations between back pain and measures of obesity were stronger in those with an emotional disorder, particularly for waist–hip ratio (P = 0.05 for interaction) and fat mass index (P = 0.06 for interaction). In a population-based sample of men, high-intensity LBP and/or disability were associated with increased levels of obesity, particularly in those with an emotional disorder. This provides evidence to support a biopsychosocial interaction between emotional disorders and obesity with low back pain.
Occupational Cultures of Information Systems Personnel and Managerial Personnel: Potential Conflicts

Management scholars have articulated the importance of occupational cultures in understanding employee behaviors in organizations. In keeping with this theme, Information Systems (IS) scholars have begun examining the occupational culture of IS personnel. It is generally argued that culture is important because cultural differences lead to conflicts and thus to dysfunctional interactions. A comparison of the occupational cultures of two groups can help identify potential conflicts that could ensue when the members from the two groups interact. In the current study, we interviewed IS personnel and management personnel to identify their respective cultural beliefs along group and grid dimensions proposed in Trice’s theoretical framework for characterizing occupational cultures. Based on these interviews, we have analyzed the belief systems of the two groups and highlighted the potential for conflict.
Design of a peptide-based vector, PepFect6, for efficient delivery of siRNA in cell culture and systemically in vivo

While small interfering RNAs (siRNAs) have been rapidly appreciated to silence genes, efficient and non-toxic vectors for primary cells and for systemic in vivo delivery are lacking. Several siRNA-delivery vehicles, including cell-penetrating peptides (CPPs), have been developed but their utility is often restricted by entrapment following endocytosis. Hence, developing CPPs that promote endosomal escape is a prerequisite for successful siRNA implementation. We here present a novel CPP, PepFect 6 (PF6), comprising the previously reported stearyl-TP10 peptide, having pH titratable trifluoromethylquinoline moieties covalently incorporated to facilitate endosomal release. Stable PF6/siRNA nanoparticles enter entire cell populations and rapidly promote endosomal escape, resulting in robust RNAi responses in various cell types (including primary cells), with minimal associated transcriptomic or proteomic changes. Furthermore, PF6-mediated delivery is independent of cell confluence and, in most cases, not significantly hampered by serum proteins. Finally, these nanoparticles promote strong RNAi responses in different organs following systemic delivery in mice without any associated toxicity. Strikingly, similar knockdown in liver is achieved by PF6/siRNA nanoparticles and siRNA injected by hydrodynamic infusion, a golden standard technique for liver transfection. These results imply that the peptide, in addition to having utility for RNAi screens in vitro, displays therapeutic potential.
Peer Instruction: Ten years of experience and results

We report data from ten years of teaching with Peer Instruction (PI) in the calculus- and algebra-based introductory physics courses for nonmajors; our results indicate increased student mastery of both conceptual reasoning and quantitative problem solving upon implementing PI. We also discuss ways we have improved our implementation of PI since introducing it in 1991. Most notably, we have replaced in-class reading quizzes with pre-class written responses to the reading, introduced a research-based mechanics textbook for portions of the course, and incorporated cooperative learning into the discussion sections as well as the lectures. These improvements are intended to help students learn more from pre-class reading and to increase student engagement in the discussion sections, and are accompanied by further increases in student understanding.
Oxidative Stress in Immature Brain after Traumatic Brain Injury

High oxygen demand along with the abundance of readily oxidizable substrates yielding productive oxidative metabolism are required for the normal function of the brain. This necessitates the existence of the complex and multicomponent antioxidant system in the brain for protection against oxidative damage. However, during development, individual components of the antioxidant system are not equally expressed and not always sufficient to fulfill their tasks in a coordinated way. As a result, the developing brain may be more vulnerable to oxidative insults than the adult brain. Traumatic brain injury is one of the damaging acute impacts that challenge the brain antioxidant reserves by exposing them to a number of decompartmentalized prooxidant molecules. This review focuses on the sources and assessment of oxidative stress and the link between oxidative stress and cell death pathways in the immature brain after experimental and clinical traumatic brain injury.
Development of extraintestinal manifestations in pediatric patients with inflammatory bowel disease

Background: Extraintestinal manifestations (EIMs) in pediatric patients with inflammatory bowel disease (IBD) are poorly characterized. We examined the prevalence of EIMs at diagnosis, subsequent incidence, and risk factors for EIMs. Methods: Data for 1649 patients from the PediIBD Consortium Registry, diagnosed with IBD before 18 years of age (1007 [61%] with Crohn's disease, 471 [29%] with ulcerative colitis, and 171 [10%] with indeterminate colitis), were analyzed using logistic regression, Kaplan–Meier, log rank tests, and Cox models. Results: EIMs were reported prior to IBD diagnosis in 97 of 1649 patients (6%). Older children at diagnosis had higher rates compared with younger children, and arthritis (26%) and aphthous stomatitis (21%) were most common. Among the 1552 patients without EIM at diagnosis, 290 developed at least 1 EIM. Kaplan–Meier estimates of cumulative incidence were 9% at 1 year, 19% at 5 years, and 29% at 15 years after diagnosis. Incidence did not differ by IBD type (P = 0.20), age at diagnosis (P = 0.22), or race/ethnicity (P = 0.24). Arthritis (17%) and osteopenia/osteoporosis (15%) were the most common EIMs after IBD diagnosis. Conclusions: In our large cohort of pediatric IBD patients, 6% had at least 1 EIM before diagnosis of IBD. At least 1 EIM will develop in 29% within 15 years of diagnosis. The incidence of EIMs both before and after diagnosis of IBD differs by type of EIM and may be slightly higher in girls, but is independent of the type of IBD, age at diagnosis, and race/ethnicity.
An embodied conversational agent in a mobile health coaching application

Sedentary lifestyles are increasingly common in modern day society. This is becoming a serious problem, as a lack of physical activity can not only lead to overweight and obesity, but also increases the risk of many other health problems. In order to increase their physical activity levels, most people can bene�t from some form of guidance or coaching. Many digital systems designed to provide such coaching are currently being developed, including systems for mobile hardware platforms. In an attempt to increase the e�ectiveness of such mobile health coaching systems, we have integrated an Embodied Conversational Agent (ECA) into one such system. A user experiment was performed where participants used the system for two weeks, with the system employing plain text messages to deliver feedback during one of the weeks, and delivering feedback through the ECA during the other. Participants completed several surveys and an interview, and activity data was recorded and stored by the system. This data was then analyzed to try and �nd di�erences between the two feedback delivery methods. Analysis of the collected data did not reveal a signi�cant advantage of the ECA feedback version over the text feedback version. In fact, the text version received signi�cantly higher scores on several items. Participants' responses during the interviews indicated that the lack of glanceability of the ECA feedback, combined with the predictability of the feedback message contents, had a strong negative in uence on the evaluations of the ECA feedback version.