Miracle-dz/UniFAR-FTUs huggingface dataset:
Causal Inference Under Network Interference: A Framework for Experiments on Social Networks

No man is an island, as individuals interact and influence one another daily in our society. When social influence takes place in experiments on a population of interconnected individuals, the treatment on a unit may affect the outcomes of other units, a phenomenon known as interference. This thesis develops a causal framework and inference methodology for experiments where interference takes place on a network of influence (i.e. network interference). In this framework, the network potential outcomes serve as the key quantity and flexible building blocks for causal estimands that represent a variety of primary, peer, and total treatment effects. These causal estimands are estimated via principled Bayesian imputation of missing outcomes. The theory on the unconfoundedness assumptions leading to simplified imputation highlights the importance of including relevant network covariates in the potential outcome model. Additionally, experimental designs that result in balanced covariates and sizes across treatment exposure groups further improve the causal estimate, especially by mitigating potential outcome model mis-specification. The true potential outcome model is not typically known in real-world experiments, so the best practice is to account for interference and confounding network covariates through both balanced designs and model-based imputation. A full factorial simulated experiment is formulated to demonstrate this principle by comparing performance across different randomization schemes during the design phase and estimators during the analysis phase, under varying network topology and true potential outcome models. Overall, this thesis asserts that interference is not just a nuisance for analysis but rather an opportunity for quantifying and leveraging peer effects in real-world experiments.
Effect of Omeprazole on Acid Gastroesophageal Reflux and Gastric Acidity in Preterm Infants With Pathological Acid Reflux

Introduction: Proton pump inhibitor (PPI) therapy is increasingly being used to treat premature infants with gastroesophageal reflux disease (GERD); however, the efficacy of PPI on acid production in this population has yet to be assessed in this patient group. The aim of this study was to determine the effect of 0.7 mg/kg/d omeprazole on gastric acidity and acid gastroesophageal reflux in preterm infants with reflux symptoms and pathological acid reflux on 24-h pH probe. Methods: A randomized, double blind, placebo-controlled, crossover design trial of omeprazole therapy was performed in 10 preterm infants (34–40 weeks postmenstrual age). Infants were given omeprazole for 7 d and then placebo for 7 d in randomized order. Twenty-four-hour esophageal and gastric pH monitoring was performed on days 7 and 14 of the trial. Results: Compared to placebo, omeprazole therapy significantly reduced gastric acidity (%time pH <4, 54% vs 14%, P < 0.0005), esophageal acid exposure (%time pH <4, 19% vs 5%, P < 0.01) and number of acid GER episodes (119 vs 60 episodes, P < 0.05). Conclusions: Omeprazole is effective in reducing esophageal acid exposure in premature infants with pathological acid reflux on 24-h pH probe; however, the far more complex issues of safety and efficacy have yet to be addressed.
Psychiatric disorders and stress factors experienced by staff members in cancer hospitals: A preliminary finding from psychiatric consultation service at National Cancer Center Hospitals in Japan

Abstract Objective: The purpose of this study is to identify psychiatric disorders and stress factors experienced by staff members in cancer hospitals who were referred to psychiatric consultation service, and to investigate the association between psychiatric disorders and stress factors. Method: A retrospective descriptive study using clinical practice data on staff members referred to psychiatric consultation service, obtained for 8 years, was conducted at two National Cancer Center Hospitals in Japan. Psychiatric disorders were identified according to DSM-IV. Stress factors were extracted from a chief complaint at the initial visit in medical charts, using a coding approach, and grouped as job stress or personal stress. The frequencies of the stress factors were determined by two coders who were unaware of the categorized procedure. Fisher's exact test was used to determine the association between psychiatric disorders and stress factors. Results: Of 8077 psychiatric consultations, 65 (1%) staff members were referred. The most common psychiatric disorder was adjustment disorder (n = 26, 40%), followed by major depression (n = 17, 26%). Eight stress factors were identified from 76 meaning units and were grouped into five job stresses and three personal stresses. Of the five job stresses, four were most frequently experienced in adjustment disorders, and “failure to adapt to job environmental change” was significantly associated (p = 0.014). Two of the three personal stresses were most frequently experienced in psychiatric disorders other than major depressive disorder and adjustment disorders, and “suffering from mental disease” was significantly associated (p = 0.001). Significance of results: We found that very few staff members were provided with psychiatric consultation service. A comprehensive support system for job stress might be needed to prevent adjustment disorders, as those are suggested to be the most common psychiatric disorders among staff members in cancer hospitals.
The Simulation of Mechanical States of Repaired Articular Cartilage

Though cartilage tissue is susceptible to damage and difficult to self-repair, cartilage tissue engineering provides an ideal way for the treatment of cartilage defects. Mechanical environments have significant effects on the growth and development of cartilage. The research of mechanical states of repaired articular cartilage by tissue engineering has significantly clinical value. According to the physical structure and movement modes of the knee, a model for the treatment of cartilage defects by tissue engineering was established based on the finite element method, with a rolling depression load as the mechanical condition. Defect models of articular cartilage were represented by three different indicators: defect width, depth and the elastic modulus of artificial cartilage implanted. By finite element simulating, we theoretically studied the mechanical states of articular cartilage repaired by tissue engineering. The results show that the mechanical states varied in different parts of the defect, and some stresses in the tissue engineered cartilage or host cartilage deviated obviously from normally physiological conditions of the knee. An artificial cartilage with certain mechanical properties may contribute to the repair of cartilage defects by tissue engineering.
Sodium Bicarbonate for Correction of Metabolic Acidosis in Open‐Heart Surgery

HEN A PUMP oxygenator is employed w for total body perfusion during openheart surgery, metabolic acidosis may occur whether the perfusion flow is low or normal.1-3 In such instances, the effect on the heart may be detrimental, even to the point of fatality.4~5 To offset such effects, we have used sodium bicarbonate to raise the standard bicarbonate content of the blood. Since the body can tolerate a wider range of standard bicarbonate or PaC02 than of pH, we believe that chemotherapy to restore proper acid-base balance is of distinct advantage.
[Factors associated with obesity among adolescents].

INTRODUCTION Obesity during adolescence is considered a strong predictor of adult obesity. The present study assessed the overweight/obesity prevalence and associated factors in middle class adolescents of a school in the city of Niteroi, Rio de Janeiro, Brazil, and evaluated the correlation between body mass index with anthropometric measures of fatness. METHOD The analysis covered 391 students aged from 15 to 17 years. Adolescents had their weight, height, skinfold thickness and upper arm circumference measured at school. A food frequency questionnaire (list of 79 items) and a questionnaire including food habits, parents anthropometric characteristics, physical activity and other factors associated with obesity were filled out by the adolescents at school. RESULTS The proportion of overweight individuals among boys (Body Mass Index (BMI) greater than the 90th percentile of the Brazilian population) was 23.9%, whereas the prevalence among girls was 7.2%. The fact of being on a slimming diet was a relevant factor for the prediction of BMI and was 7 times more frequent among girls than among boys. Among boys, being on a diet, absence of breakfast, and family body appearance were positively associated with BMI. Among girls these variables were also significantly associated, whereas age at menarche was negatively associated with BMI. Hours of watching TV/video/video-game was associated with BMI only among boys. The correlation coefficient between BMI and measures of fatness varied from 0.7 to 0.9 for boys, and from 0.8 to 0.90 for girls. CONCLUSIONS BMI appears to be a good indicator of obesity among adolescents and showed that girls demonstrated an exaggerated preoccupation with body image and stereotyped slim body patterns.
Overexpression of p16 and p14ARF is associated with human papillomavirus infection in cervical squamous cell carcinoma and dysplasia

The CDKN2 gene encodes two structurally different proteins: a cyclin‐dependent kinase inhibitor, p16, which regulates retinoblastoma protein (pRb)‐dependent G1 arrest, and a cell cycle inhibitor, p14ARF, which blocks MDM2‐induced p53 degradation resulting in an increase in p53 levels that leads to cell cycle arrest. Recent studies have revealed that expression of p16 and p14ARF is influenced markedly by the status of pRb and p53, and p16 overexpression has been demonstrated in cervical neoplasia because of functional inactivation of pRb by the human papillomavirus (HPV) E7 protein. To clarify the p14ARF status and the relationship between p16/p14ARF and other cell cycle molecules in cervical carcinogenesis, immunohistochemical analysis of p16, p14ARF, p53 and MDM2 was performed on 65 samples of cervical and genital condylomatous and neoplastic lesions, including nine HPV‐negative tumors. In most cervical cancers and preneoplastic lesions with HPV infection of high and intermediate risk, a marked overexpression of p14ARF as well as the p16 protein (i.e. dotted nuclear immunostaining) was observed. All condyloma acuminata except one and low‐grade dysplasia with HPV infection of low risk, such as HPV 6, immunohistochemically showed completely negative staining for p14ARF, also seen in non‐neoplastic and mesenchymal cells. Our results clearly show that the mode of p14ARF overexpression in cervical neoplastic cells with HPV association differs from that in cancers of other organs without HPV association, and the p14ARF overexpression may be attributable to a negative feedback result in the functional inactivation of the pRb and p53 proteins by HPV oncoproteins.
Phase I clinical and pharmacogenetic trial of irinotecan and raltitrexed administered every 21 days to patients with cancer.

PURPOSE Irinotecan and raltitrexed display schedule-dependent synergy in vitro, which supports the clinical investigation of the combination. Functional polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene result in intracellular redistribution of folate derivatives, which may affect raltitrexed-associated cytotoxicity. PATIENTS AND METHODS Patients with a range of solid cancers and good performance status received irinotecan as a 90-minute infusion on day 1 and raltitrexed as a 15-minute infusion on day 2, repeated every 21 days. Samples were collected for MTHFR C677T genotyping and fasting plasma homocysteine during the first cycle. RESULTS Thirty-nine assessable patients received 127 cycles of therapy. Irinotecan doses ranged from 100 to 350 mg/m(2), and raltitrexed, 1.0 to 4.0 mg/m(2). Raltitrexed doses of more than 3.0 mg/m(2) were not tolerated and were associated with dose-limiting asthenia, diarrhea, and AST/ALT elevation. Irinotecan/raltitrexed doses of 350/3.0 mg/m(2) were well-tolerated; principal toxicities included neutropenia, diarrhea, and fatigue. Two partial responses were observed in patients with pretreated gastroesophageal cancers. Homozygotes with the MTHFR 677 TT polymorphism incurred significantly less raltitrexed-associated toxicity than those with either wild-type or heterozygous genotypes (P = .05). No significant differences were noted in plasma homocysteine values between the genotypic subtypes, and plasma homocysteine levels did not predict the risk of toxicity. CONCLUSION Irinotecan and raltitrexed doses of 350 and 3.0 mg/m(2) are recommended for further study on a day 1, 2 schedule every 21 days. Efficacy results suggest that trials in upper and lower gastrointestinal malignancies are warranted. MTHFR C677T genotypes may be predictive of clinical raltitrexed toxicity.
A relative evaluation of multiclass image classification by support vector machines

Support vector machines (SVMs) have considerable potential as classifiers of remotely sensed data. A constraint on their application in remote sensing has been their binary nature, requiring multiclass classifications to be based upon a large number of binary analyses. Here, an approach for multiclass classification of airborne sensor data by a single SVM analysis is evaluated against a series of classifiers that are widely used in remote sensing, with particular regard to the effect of training set size on classification accuracy. In addition to the SVM, the same datasets were classified using a discriminant analysis, decision tree, and multilayer perceptron neural network. The accuracy statements of the classifications derived from the different classifiers were compared in a statistically rigorous fashion that accommodated for the related nature of the samples used in the analyses. For each classification technique, accuracy was positively related with the size of the training set. In general, the most accurate classifications were derived from the SVM approach, and with the largest training set the SVM classification was significantly (p < 0.05)more accurate (93.75%) than that derived from the discriminant analysis (90.00%) and decision tree algorithms (90.31%). Although each classifier could yield a very accurate classification, > 90% correct, the classifiers differed in the ability to correctly label individual cases and so may be suitable candidates for an ensemble-based approach to classification.
Riplet/RNF135, a RING Finger Protein, Ubiquitinates RIG-I to Promote Interferon-β Induction during the Early Phase of Viral Infection*

RIG-I (retinoic acid-inducible gene-I), a cytoplasmic RNA helicase, interacts with IPS-1/MAVS/Cardif/VISA, a protein on the outer membrane of mitochondria, to signal the presence of virus-derived RNA and induce type I interferon production. Activation of RIG-I requires the ubiquitin ligase, TRIM25, which mediates lysine 63-linked polyubiquitination of the RIG-I N-terminal CARD-like region. However, how this modification proceeds for activation of IPS-1 by RIG-I remains unclear. Here we identify an alternative factor, Riplet/RNF135, that promotes RIG-I activation independent of TRIM25. The Riplet/RNF135 protein consists of an N-terminal RING finger domain, C-terminal SPRY and PRY motifs, and shows sequence similarity to TRIM25. Immunoprecipitation analyses demonstrated that the C-terminal helicase and repressor domains of RIG-I interact with the Riplet/RNF135 C-terminal region, whereas the CARD-like region of RIG-I is dispensable for this interaction. Riplet/RNF135 promotes lysine 63-linked polyubiquitination of the C-terminal region of RIG-I, modification of which differs from the N-terminal ubiquitination by TRIM25. Overexpression and knockdown analyses revealed that Riplet/RNF135 promotes RIG-I-mediated interferon-β promoter activation and inhibits propagation of the negative-strand RNA virus, vesicular stomatitis virus. Our data suggest that Riplet/RNF135 is a novel factor of the RIG-I pathway that is involved in the evoking of human innate immunity against RNA virus infection, and activates RIG-I through ubiquitination of its C-terminal region. We infer that a variety of RIG-I-ubiquitinating molecular complexes sustain RIG-I activation to modulate RNA virus replication in the cytoplasm.
Mornings with art, lessons learned: Feedback regulation, restriction threshold biology, and redundancy govern molecular stress responses

Work from the laboratory of Dr. Arthur B. Pardee has highlighted basic principles that govern cellular and molecular biological processes in living cells. Among the most important governing principles in cellular and molecular responses are: (i) threshold “restriction” responses, wherein a level of response is reached and a “point of no return” is achieved; (ii) feedback regulation; and (iii) redundancy. Lessons learned from the molecular biology of cellular stress responses in mammalian cancer versus normal cells after ionizing radiation (IR) or chemotherapeutic agent exposures reveal similar instances of these guiding principles in mammalian cells. Among these are the: (i) induction of cell death responses by β‐lapachone (β‐lap), a naphthoquinone anti‐tumor agent that kills cancer cells via an NQO1 (i.e., X‐ray‐inducible protein‐3, xip3)‐dependent mechanism; (ii) induction of secretory clusterin (sCLU) in response to TGF‐β1 exposure, and the ability of induced sCLU protein to down‐regulate TGF‐β1 signaling; and (iii) induction of DNA mismatch repair‐dependent G2 cell cycle checkpoint responses after exposure to alkylating agents. We have learned these lessons and now adopted strategies to exploit them for improved therapy. These examples will be discussed and compared to the pioneering findings of researchers in the Pardee laboratory over the years. J. Cell. Physiol. 209: 604–610, 2006. © 2006 Wiley‐Liss, Inc.
Neuroprotective functions of prion protein

The normal function of prion protein (PrP) is usually disregarded at the expense of the more fascinating role of PrP in transmissible prion diseases. However, the normal PrP may play an important role in cellular function in the central nervous system, since PrP is highly expressed in neurons and motifs in the sequence of PrP are conserved in evolution. The finding that prion null mice do not have a significant overt phenotype suggests that the normal function of PrP is of minor importance. However, the absence of PrP in cells or in vivo contributes to an increased susceptibility to oxidative stress or apoptosis‐inducing insults. An alternative explanation is that the PrP normal function is so important that it is redundant. Probing into the characteristics of PrP has revealed a number of features that could mediate important cellular functions. The neuroprotective actions so far identified with PrP are initiated through cell surface signaling, antioxidant activity, or anti‐Bax function. Here, we review the characteristics of the PrP and the evidence that PrP protects against neurodegeneration and neuronal cell death. © 2003 Wiley‐Liss, Inc.
Photosynthesis in Tall Fescue : IV. Carbon Assimilation Pattern in two Genotypes of Tall Fescue Differing in Net Photosynthesis Rates.

We previously reported that the net photosynthetic rate of a decaploid genotype (I-16-2) of tall fescue (Festuca arundinacea Schreb.) was 32 to 41 versus 22 milligrams CO(2) per square decimeter per hour in a hexaploid genotype (V6-802) (Randall, Nelson, Asay Plant Physiol 59: 38-41). The high rate was later correlated with increases in total ribulose 1,5-bisphosphate carboxylase protein (17%) and activity (27%) (Joseph, Randall, Nelson Plant Physiol 68: 894-898). This report characterizes photosynthesis with respect to light saturation and early products of photosynthesis in an attempt to identify regulatory metabolic site(s) in these two genotypes. Analysis of the early products of photosynthesis indicated that both genotypes fixed CO(2) via the Calvin-Benson cycle with phosphoglyceric acid as the initial primary product. Both genotypes had similar (14)C-labeled intermediates. Sucrose was the primary sink of (14)CO(2) assimilation. After 10 min of (14)CO(2) assimilation with attached leaves, sucrose accounted for 89% (decaploid) and 81% (hexaploid) of the total (14)C incorporated. In 10 min, this amounted to 1.3 (decaploid) and 0.8 (hexaploid) mumol [(14)C]sucrose formed g fresh weight(-1) and reflected the observed differences in photosynthetic rates. There was limited labeling of starch (1%) and fructan (1%). Results of total nonstructural carbohydrates and P(i) analysis also demonstrated sucrose was the predominant carbohydrate in fescue leaves. Quantitative differences in sucrose and P(i) between the two genotypes may reflect changes in partitioning and this possibility is discussed.
Sp8 expression in putative neural progenitor cells in guinea pig and human cerebrum

Neural stem/progenitor cells have been characterized at neurogenic sites in adult mammalian brain with various molecular markers. Here it has been demonstrated that Sp8, a transcription factor typically expressed among mature GABAergic interneurons, also labels putative neural precursors in adult guinea pig and human cerebrum. In guinea pigs, Sp8 immunoreactive (Sp8+) cells were localized largely in the superficial layers of the cortex including layer I, as well as the subventricular zone (SVZ) and subgranular zone (SGZ). Sp8+ cells at the SGZ showed little colocalization with mature and immature neuronal markers, but co‐expressed neural stem cell markers including Sox2. Some layer I Sp8+ cells also co‐expressed Sox2. The amount of Sp8+ cells in the dentate gyrus was maintained 2 weeks after X‐ray irradiation, while that of doublecortin (DCX+) cells was greatly reduced. Mild ischemic insult caused a transient increase of Sp8+ cells in the SGZ and layer I, with the subgranular Sp8+ cells exhibited an increased colabeling for the mitotic marker Ki67 and pulse‐chased bromodeoxyuridine (BrdU). Sp8+ cells in the dentate gyrus showed an age‐related decline in guinea pigs, in parallel with the loss of DCX+ cells in the same region. In adult humans, Sp8+ cells exhibited comparable morphological features as seen in guinea pigs, with those at the SGZ and some in cortical layer I co‐expressed Sox2. Together, these results suggested that Sp8 may label putative neural progenitors in guinea pig and human cerebrum, with the labeled cells in the SGZ appeared largely not mitotically active under normal conditions. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 939–955, 2016