Miracle-dz/UniFAR-FTUs huggingface dataset:
Interplay between paracrine signaling and gap junctional communication in ovarian follicles

Intercellular communication is required for ovarian folliculogenesis. This is apparent in mice lacking connexin43 (Cx43, a gap junction protein strongly expressed in granulosa cells), or growth/differentiation factor-9 (GDF9, an oocyte-specific growth factor that stimulates granulosa cell proliferation and differentiation), or in mice expressing a mutant form of Kit ligand (KITL, a paracrine factor that, in the ovary, is secreted by granulosa cells to stimulate oocyte growth). In all of these mutant lines, follicle growth is impaired suggesting a possible interaction between paracrine signaling and gap junctional communication. To assess this possibility, we analyzed gene expression in mutant ovaries. Despite the lack of gap junctional coupling between granulosa cells of Cx43 null mutant ovaries, expression of the genes encoding KITL and its receptor, KIT, is maintained. Furthermore, GDF9 expression is maintained. In GDF9 null mutant ovaries, there is no apparent change in Cx43 expression and, correspondingly, the granulosa cells remain coupled. There is also no increase in granulosa cell apoptosis in ovaries lacking Cx43 or GDF9. Staining for proliferating cell nuclear antigen (PCNA) revealed that the granulosa cells of Cx43 null mutant ovaries have a reduced frequency of DNA synthesis. Using both radiolabeled thymidine incorporation and PCNA staining in vitro, we showed that recombinant GDF9 could restore the proliferation of coupling-deficient granulosa cells to the level of control cells. These results indicate that impaired folliculogenesis in mice lacking Cx43 is due at least in part to reduced responsiveness of granulosa cells to oocyte-derived GDF9, indicating an interaction between these two modes of intercellular communication.
A description of a peer-run supervised injection site for injection drug users

Owing to the ongoing health crisis among injection drug users in Vancouver, Canada, there have been repeated calls for the establishment of supervised injection sites (SIS) since the early 1990s. In April 2003, a group of advocates and drug users opened an unsanctioned SIS in Vancouver’s Downtown Eastside. The “327 SIS” operated for 184 days. During the operation of the SIS, volunteers supervised over 3,000 injections by a bigh-risk injection drug using population. The SIS provided a sterile environment for injection drug use without measured negative consequences and demonstrated the feasibility of a peer-driven low-threshold SIS.
The crystal structure of human UDP-glucuronosyltransferase 2B7 C-terminal end is the first mammalian UGT target to be revealed: the significance for human UGTs from both the 1A and 2B families

Human UDP-glucuronosyltransferases (EC 2.4.1.17) (UGTs) are major phase II metabolism enzymes that detoxify a multitude of endo- and xenobiotics through the covalent addition of a glucuronic acid moiety. UGTs are promiscuous enzymes that regulate the levels of numerous important endobiotics in a range of tissues, and inactivate most therapeutic compounds in concert with phase I enzymes. In spite of the importance of these enzymes, we have only a limited understanding of the molecular mechanisms governing their substrate specificity and catalytic activity. Until recently, no three-dimensional structural information was available for any mammalian UGT. The 1.8-å resolution apo crystal structure of the UDP-glucuronic acid binding domain of human UGT2B7 (2B7CT) is the only structure of a mammalian UGT target determined to date. In this review, we summarize what has been learned about human UGT function from the analysis of this and other related glycosyltransferase (GT) crystal structures.
SELF-BRAND OVERLAP AND DISSOCIATION

Consumer researchers have long accepted that consumption can serve as a tool in the creation, maintenance, and expression of consumers’ identities. And brands, in particular, may be important to the consumer self, even potentially serving as relationship partners. This dissertation explores how brands that are important to consumers may impact their identities at a cognitive level. Specifically, I apply Aron et al.'s (1991) “including others in the self” paradigm from interpersonal relationship research, which finds that people’s cognitive representations of close others overlap the psychological self, to studying the impact of brands on the self. I provide evidence that consumers’ mental representations of loved brands, which may be perceived as relationship partners, overlap the psychological self in memory. I refer to this as self-brand overlap. I also consider the relevance of disliked brands to the consumer self, providing evidence that consumers’ mental representations of disliked brands are dissociated from the psychological self in memory. I refer to this as self-brand dissociation. In two studies I demonstrate and replicate the self-brand overlap and dissociation effects. And, study 2 further explores these constructs, providing evidence that self-brand overlap and dissociation are the cognitive representations of positive and negative, respectively, consumer-brand relationships. This dissertation also includes three further studies that aim to identify boundary conditions of these effects. However, no conclusive support is found for a role of any of the explored moderators. Specifically, studies 3 through 5 find the self-brand dissociation effect in every condition, in every study, suggesting that self-brand dissociation is impervious to the boundary conditions
Revisiting linearized one-dimensional tidal propagation

In this paper we extend the validity of the classical linear solution for tidal hydrodynamics including the effects of width and depth convergence. Reworking such a solution in the light of externally defined, dimensionless parameters we are able to provide simple relationships to predict the most relevant features of the tidal wave at the estuary mouth (velocity amplitude, phase lag, wavelength, and damping) and to reproduce the main dynamics of tidal wave propagation along finite and infinite length channels. We also highlight the need for an accurate treatment of the linearized bed shear stress by exploiting an iterative procedure, and we show the improvement that can be reached by subdividing the entire estuary in shorter reaches. Different versions of the analytical solution are compared with numerical results, highlighting the strengths and weaknesses of the linear model.
Long bone fractures identified in the Joseon Dynasty human skeletons of Korea

Fracture is one of the pathological signs most frequently encountered in archaeologically obtained bones. To expand the paleopathological knowledge on traumatic injuries, it is desirable to secure data on long bone fractures from as wide a geographic and temporal range as possible. We present, for the first time, evidence of long bone fractures in a 16th-18th century Joseon skeletal series (n=96). In this study, we found 3 Colles' fractures of the radius in 2 individual cases. The pattern of fractures was unique. Although previous reports show that the ulna is broken more often than the radius, ulnar fracture associated with fending off a blunt attack was rare in our series (1/7 cases). Transverse fractures, typically caused by intentional violence, were also very rare (1/7 cases) in this study. These results may reflect the relatively tranquil lives of the Joseon people in 16th-18th century Korea. We also found post-fracture complications such as deformations, bone length shortening, and osteomyelitis. The present study would be of interest to medical scientists in related fields because it is one of the few studies conducted on long bone fractures among pre-modern societies in East Asian countries, thus far.
Molecular genetic approaches to the study of primate behavior, social organization, and reproduction.

In the past several decades, the development of novel molecular techniques and the advent of noninvasive DNA sampling, coupled with the ease and speed with which molecular analyses can now be performed, have made it possible for primatologists to directly examine the fitness effects of individual behavior and to explore how variation in behavior and social systems influences primate population genetic structure. This review describes the theoretical connections between individual behavior and primate social systems on the one hand and population genetic structure on the other, discusses the kinds of molecular markers typically employed in genetic studies of primates, and summarizes what primatologists have learned from molecular studies over the past few decades about dispersal patterns, mating systems, reproductive strategies, and the influence of kinship on social behavior. Several important conclusions can be drawn from this overview. First, genetic data confirm that, in many species, male dominance rank and fitness are positively related, at least over the short term, though this relationship need not simply be a reflection of male-male contest competition over mates. More importantly, genetic research reveals the significance of female choice in determining male reproductive success, and documents the efficacy of alternative mating tactics among males. Second, genetic data suggest that the presumed importance of kinship in structuring primate social relationships needs to be evaluated further, at least for some taxa such as chimpanzees in which demographic factors may be more important than relatedness. I conclude this paper by offering several suggestions of additional ways in which molecular techniques might be employed in behavioral and ecological studies of primates (e.g., for conducting "molecular censuses" of unhabituated populations, for studying disease and host-parasite interactions, or for tracking seed fate in studies of seed dispersal) and by providing a brief introduction to the burgeoning field of nonhuman primate behavioral genetics.
Efficient composite pattern finding from monad patterns

Automatically identifying frequent composite patterns in DNA sequences is an important task in bioinformatics, especially when all the basic elements (or monad patterns) of a composite pattern are weak. In this paper, we compare one straightforward approach to assemble the monad patterns into composite patterns to two other rather complex approaches. Both our theoretical analysis and empirical results show that this overlooked straightforward method can be several orders of magnitude faster. Furthermore, different from the previous understandings, the empirical results show that the runtime superiority among the three approaches is closely related to the insignificance of the monad patterns.
Production of Polysaccharide by Rahnella aquatilis with Whey Feedstock

The rates were monitored on biomass Increase, polysaccharide production and viscosity development of whey broth and a control synthetic broth during fermentation by Rahnella aquatills and organic acids, lactose, peptides and free amino acids were measured. Growth curves were simllar and characterized by maximum specific growth rates of 0.61 h -1 for whey and 0.63 h -1 for synthetic medium. The yields of polysaccharide were 0.59 g/g lactose for the synthetic medium and 0.56 for whey. Small peptides (<4,000 Da) and most free amino acids in both fermentation media were consumed within 24h.
Entecavir and Hepatitis B Immune Globulin in Patients Undergoing Liver Transplantation for Chronic Hepatitis B

For patients undergoing liver transplantation (LT) for hepatitis B virus (HBV)–related liver disease, the current standard of care for preventing reinfection of the allograft is nucleoside analogue therapy combined with hepatitis B immune globulin (HBIG). Entecavir has demonstrated high efficacy and a favorable safety profile for chronic hepatitis B (CHB) treatment, but data for patients undergoing HBV‐related LT are limited. This study assessed the safety and efficacy of entecavir combined with various HBIG regimens after CHB‐related LT. In this phase 3b, single‐arm, open‐label study, 65 patients undergoing LT for CHB‐related liver disease with an HBV DNA load <172 IU/mL at LT received entecavir (1.0 mg daily) for 72 weeks after LT. The primary endpoint was the proportion of evaluable patients (treated for ≥4 weeks) with virological recurrence (HBV DNA level ≥50 IU/mL) through week 72. Concomitant HBIG therapy was received by 64 of the 65 enrolled patients, and 44% of these patients received high‐dose HBIG (any HBIG dose in the specified interval ≥10,000 IU). Through week 72, all 61 patients evaluable for the efficacy analysis had undetectable HBV DNA. The Kaplan‐Meier estimate of patients without hepatitis B surface antigen (HBsAg) recurrence at week 72 was 0.9655. Two patients experienced a reappearance of HBsAg, but both remained HBV DNA− until the last follow‐up. The frequency and nature of adverse events were consistent with those expected for this patient population. Serum creatinine increments ≥0.3 mg/dL and ≥0.5 mg/dL occurred in 62% and 39% of the patients, respectively, and all of these patients received calcineurin inhibitor therapy. In conclusion, in this population of patients treated with entecavir after CHB‐related LT, entecavir was well tolerated and effective in maintaining viral suppression, even in individuals who experienced a reappearance of HBsAg. Liver Transpl 19:887–895, 2013. © 2013 AASLD.
Alterations in Energy Metabolism, Neuroprotection and Visual Signal Transduction in the Retina of Parkinsonian, MPTP-Treated Monkeys

Parkinson disease is mainly characterized by the degeneration of dopaminergic neurons in the central nervous system, including the retina. Different interrelated molecular mechanisms underlying Parkinson disease-associated neuronal death have been put forward in the brain, including oxidative stress and mitochondrial dysfunction. Systemic injection of the proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to monkeys elicits the appearance of a parkinsonian syndrome, including morphological and functional impairments in the retina. However, the intracellular events leading to derangement of dopaminergic and other retinal neurons in MPTP-treated animal models have not been so far investigated. Here we have used a comparative proteomics approach to identify proteins differentially expressed in the retina of MPTP-treated monkeys. Proteins were solubilized from the neural retinas of control and MPTP-treated animals, labelled separately with two different cyanine fluorophores and run pairwise on 2D DIGE gels. Out of >700 protein spots resolved and quantified, 36 were found to exhibit statistically significant differences in their expression levels, of at least ±1.4-fold, in the parkinsonian monkey retina compared with controls. Most of these spots were excised from preparative 2D gels, trypsinized and subjected to MALDI-TOF MS and LC-MS/MS analyses. Data obtained were used for protein sequence database interrogation, and 15 different proteins were successfully identified, of which 13 were underexpressed and 2 overexpressed. These proteins were involved in key cellular functional pathways such as glycolysis and mitochondrial electron transport, neuronal protection against stress and survival, and phototransduction processes. These functional categories underscore that alterations in energy metabolism, neuroprotective mechanisms and signal transduction are involved in MPTP-induced neuronal degeneration in the retina, in similarity to mechanisms thought to underlie neuronal death in the Parkinson’s diseased brain and neurodegenerative diseases of the retina proper.
Influence of Scientific Worldviews on Attitudes toward Organ Transplants: National Survey Data from the United States

Context Public acceptance of routine medical procedures is nearly universal, but controversy over dramatic or invasive procedures like transplants is common. Objectives To assess the distributions and organization of public opinion on organ transplant and to discover the magnitude of the direct and indirect impacts of religion, scientific knowledge, and acceptance of evolution on individuals' support for organ transplant. Participants A representative sample (N = 2069) of the US adult, English-speaking population in 2009. Intervention Participants were administered the International Social Science Survey/USA 2009. Results Organ transplants were warmly endorsed by most Americans in 2009, as earlier, but support is not universal. Confirmatory factor analysis shows that Americans' opinions on heart, kidney, and pancreas transplants all reflect the same underlying attitude toward major organ transplants. Structural equation modeling shows that scientific knowledge is the most important influence on these attitudes, with more knowledgeable persons being more supportive. Acceptance of the theory of evolution is the second most important factor, also associated with greater support for transplant. Growing up in a church-going family encourages people to support organ transplant, even after adjusting for other influences. Otherwise denomination and religious belief have only small indirect influences. Demographic differences are small. Conclusions These results provide clues about future trends. A religious revival, were it to occur, would not be likely to alter support for transplants. If public knowledge of science continues to increase, or acceptance of the theory of evolution grows, support for transplant will most likely increase.
Sunitinib in Metastatic Renal Cell Carcinoma: The Pharmacological Basis of the Alternative 2/1 Schedule

Sunitinib is an inhibitor of platelet-derived growth factors receptor (PDGFR) and vascular endothelial growth factor receptor-2 (VEGFR2) tyrosine-kinase activities, and it is registered for the treatment of metastatic renal cell carcinoma (mRCC). Indeed, sunitinib 50mg/day for 28 days every 6 weeks is effective against mRCC and induces significant improvements in progression-free and overall survival (PFS and OS, respectively) with respect to interferon-α and interleukin-2, even in cytokine-resistant tumors (Motzer et al., 2006a,b; Motzer et al., 2007). Moreover, in some patients (30–50%) sunitinib efficacy is counterbalanced by toxicities (Najjar et al., 2014), which are mainly represented by thrombocytopenia (10%), fatigue (9%), asthenia, neutropenia, and hand-foot syndrome (each 7%) (Gore et al., 2015). Toxic effects usually worse between weeks 3 and 4 of therapy, requiring treatment interruption in approximately one-third of patients (van der Veldt et al., 2008; Najjar et al., 2014). The most severe toxicities are associated with low body surface area, older age, and female gender (van der Veldt et al., 2008). Intriguingly, those three factors could be potentially related to increased sunitinib exposure, because the drug is administered as a fixed dose without any adjustment. Indeed, the apparent drug clearance was slightly reduced (approximately 8%) in women with respect to men, while the body weight influenced the apparent volume of distribution (Houk et al., 2009). Those results could be the basis for patients’ stratification, but the individualization of the dose appeared to be difficult because those variables were clinically evident only in combination (i.e., a thin woman) and the inter-patient variability in pharmacokinetic parameters was about 40–60% (Houk et al., 2009). The third obstacle to dose individualization is represented by the non-linear pharmacokinetics of sunitinib, “making dose-response modeling challenging” (Houk et al., 2010). Therefore, the occurrence of moderate-to-severe toxicities seems related to changes/alterations in drug pharmacokinetics in particular subgroups of patients, but dose individualization seems still difficult. In the very recent past, several studies have described a modified schedule for the administration of sunitinib, 50mg/day for 14 days every 3 weeks (2/1 schedule) instead of the standard 4/2 schedule (4 weeks on treatment and 2 weeks of rest). The new schedule has the same dose intensity with respect the classical one, but tolerability has significantly increased (Bracarda et al., 2015). Those evidence and hypothesis find solid pharmacological bases.
Prospective comparison of three predictive rules for assessing severity of community-acquired pneumonia in Hong Kong

Background: Community-acquired pneumonia (CAP) is a leading infectious cause of death throughout the world, including Hong Kong. Aim: To compare the ability of three validated prediction rules for CAP to predict mortality in Hong Kong: the 20 variable Pneumonia Severity Index (PSI), the 6-point CURB65 scale adopted by the British Thoracic Society and the simpler CRB65. Methods: A prospective observational study of 1016 consecutive inpatients with CAP (583 men, mean (SD) age 72 (17) years) was performed in a university hospital in the New Territories of Hong Kong in 2004. The patients were classified into three risk groups (low, intermediate and high) according to each rule. The ability of the three rules to predict 30 day mortality was compared. Results: The overall mortality and intensive care unit (ICU) admission rates were 8.6% and 4.0%, respectively. PSI, CURB65 and CRB65 performed similarly, and the areas under the receiver operating characteristic (ROC) curve were 0.736 (95% CI 0.687 to 0.736), 0.733 (95% CI 0.679 to 0.787) and 0.694 (95% CI 0.634 to 0.753), respectively. All three rules had high negative predictive values but relatively low positive predictive values at all cut-off points. Larger proportions of patients were identified as low risk by PSI (47.2%) and CURB65 (43.3%) than by CRB65 (12.6%). Conclusion: All three predictive rules have a similar performance in predicting the severity of CAP, but CURB65 is more suitable than the other two for use in the emergency department because of its simplicity of application and ability to identify low-risk patients.
Driving and Dementia: A Review of the Literature

The purpose of this article is to review the literature on the ability of individuals with dementia to drive an automobile. Based on a review of the literature, several factors were identified that may be useful in differentiating between people with dementia who presently remain safe drivers from those who have progressed to impaired driving. These factors include disease duration and severity, sex, patient self-assessment, family assessment, neuropsychological measures, findings on road evaluations, and driving simulator testing. The approach of the physician to driving and dementia is addressed, including in-office screening, referral for on-road driving assessments, and the potential for physician reporting to state agencies.
First clinical data of a natural immunomodulator in colorectal cancer.

BACKGROUND/AIMS MSC (trade-name AVEMAR) is a per os applicable complex of multiple, biologically active molecules obtained from fermented wheat-germ extract. Preclinical studies suggest potent anti-metastatic activity and it has a favorable toxicity profile. It has been aimed in a pilot-scale, phase II clinical study to document whether or not MSC as a support to surgery or plus chemotherapy adds any therapeutic benefit compared to the same combination without MSC in colorectal cancer. METHODOLOGY From 1998 to June 1999, 18 control patients and 12 consecutive colorectal cancer patients respectively, were enrolled into this study. All patients underwent curative surgery. The control group (18 patients) received no other therapy or adjuvant chemotherapy alone. The MSC group (12 patients) received MSC alone or plus adjuvant chemotherapy. Until now, the median follow-up has been 9 months. RESULTS Interim data of the study document that in the MSC group no new metastases, neither hepatic nor other, have occurred, so far. On the contrary, several new metastases have developed in the control group. CONCLUSIONS Orally administered MSC is a potent candidate to be regarded as a supportive therapy to surgery or plus chemotherapy for colorectal cancer patients.