Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of language task demands on the neural response during lexical access: a functional magnetic resonance imaging study

This study examined the effects of linguistic task demands on the neuroanatomical localization of the neural response related to automatic semantic processing of concrete German nouns combining the associative priming paradigm with functional magnetic resonance imaging (fMRI). To clarify the functional role of the inferior frontal gyrus (IFG) for semantic processing with respect to semantic decision making compared to semantic processing per se, we used a linguistic task that involved either a binary decision process (i.e., semantic categorization; Experiment 1) or not (i.e., silently thinking about a word's meaning; Experiment 2). We observed associative priming effects indicated as neural suppression in bilateral superior temporal gyri (STG), anterior cingulate cortex (ACC), occipito‐temporal brain areas, and in medial frontal brain areas independently of the linguistic task. Inferior parietal brain areas were more active for silently thinking about a word's meaning compared to semantic categorization. A conjunction analysis of linguistic task revealed that both tasks activated the same left‐lateralized occipito‐temporo‐frontal network including the IFG. Contrasting neural associative priming effects across linguistic task demands, we found a significant interaction in the right IFG. The present fMRI data give rise to the assumption that activation of the left inferior frontal gyrus (LIFG) in the semantic domain might be important for semantic processing in general and not only for semantic decision making. These findings contrast with a recent study regarding the role of the LIFG for binary decision making in the lexical domain (Wright et al. 2011).
Phosphorylation of Serine 248 of C/EBPα Is Dispensable for Myelopoiesis but Its Disruption Leads to a Low Penetrant Myeloid Disorder with Long Latency

Background Transcription factors play a key role in lineage commitment and differentiation of stem cells into distinct mature cells. In hematopoiesis, they regulate lineage-specific gene expression in a stage-specific manner through various physical and functional interactions with regulatory proteins that are simultanously recruited and activated to ensure timely gene expression. The transcription factor CCAAT/enhancer binding protein α (C/EBPα) is such a factor and is essential for the development of granulocytic/monocytic cells. The activity of C/EBPα is regulated on several levels including gene expression, alternative translation, protein interactions and posttranslational modifications, such as phosphorylation. In particular, the phosphorylation of serine 248 of the transactivation domain has been shown to be of crucial importance for granulocytic differentiation of 32Dcl3 cells in vitro. Methodology/Principal Findings Here, we use mouse genetics to investigate the significance of C/EBPα serine 248 in vivo through the construction and analysis of Cebpa S248A/S248A knock-in mice. Surprisingly, 8-week old Cebpa S248A/S248A mice display normal steady-state hematopoiesis including unaltered development of mature myeloid cells. However, over time some of the animals develop a hematopoietic disorder with accumulation of multipotent, megakaryocytic and erythroid progenitor cells and a mild impairment of differentiation along the granulocytic-monocytic lineage. Furthermore, BM cells from Cebpa S248A/S248A animals display a competitive advantage compared to wild type cells in a transplantation assay. Conclusions/Significance Taken together, our data shows that the substitution of C/EBPα serine 248 to alanine favors the selection of the megakaryocytic/erythroid lineage over the monocytic/granulocytic compartment in old mice and suggests that S248 phosphorylation may be required to maintain proper hematopoietic homeostasis in response to changes in the wiring of cellular signalling networks. More broadly, the marked differences between the phenotype of the S248A variant in vivo and in vitro highlight the need to exert caution when extending in vitro phenotypes to the more appropriate in vivo context.
Mesenchymal stem cells alleviate hypoxia-induced oxidative stress and enhance the pro-survival pathways in porcine islets

Islet transplantation is a promising treatment for selected patients with type 1 diabetes mellitus (T1DM). Hypoxia and oxidative stress are major causes of damage to transplanted islets. Mesenchymal stem cells (MSCs) have been shown to enhance cell survival mainly through paracrine secretion. However, mechanisms of action underlying the protective effects of MSCs on islets have not been fully elucidated. In this study, we investigated whether human umbilical cord-derived MSCs (huc-MSCs) could inhibit hypoxia and ROS-related cell death of neonatal porcine islet cell clusters (NICCs) and further determined the underlying molecular mechanisms. NICCs were cultured in vitro under normoxic and hypoxic (1% O2) conditions with or without MSC-conditioned medium (MSC-CM). Apoptosis of NICCs was evaluated by the AO/EB staining and Annexin V/PI flow cytometry analysis. Total and mitochondrial ROS production was detected by fluorometric assays. Western blot and the ERK pathway inhibitor, PD98059, were used to assess the possible pathways involved. The results showed that MSC-CM suppressed hypoxia-induced oxidative stress and cell death of NICCs. MSC-CM also activated several pro-survival pathways in NICCs under hypoxic conditions. Furthermore, MSC-secreted exosomes and IL-6 partially recapitulated the multifunctional benefits of MSC-CM. This study showed that huc-MSCs protected NICCs from hypoxia-induced cell death by regulating the cell redox state and cell signaling pathways. This increased understanding may enable MSCs to become a more promising adjuvant cell therapy for islet transplantation. Impact statement The utilization of mesenchymal stem cells (MSCs) is a promising approach to serve as adjuvant therapy for islet transplantation. But the inability to translate promising preclinical results into sound therapeutic effects in human subjects indicates a lack of key knowledge of MSC-islet interactions that warrant further research. Hypoxia and oxidative stress are critical factors which lead to a tremendous loss of islet grafts. However, previous studies mainly focused on other aspects of MSC protection such as inducing revascularization, enhancing insulin secretion, and reducing islet apoptosis. In this study, we aim to investigate whether MSC can protect islet cells from hypoxic damage by inhibiting ROS production and the potential underlying pathways involved. We also explore the effects of MSC-derived exosomes and IL-6 on hypoxia-injured islets. Our data provide new molecular targets for developing MSC applications, and this may ultimately promote the efficiency of clinical islet transplantation.
Food Cravings Questionnaire–Trait (FCQ–T) Discriminates Between Obese and Overweight Patients With and Without Binge Eating Tendencies: The Italian Version of the FCQ–T

Food craving (FC) might play an important role in the course of eating disorders and obesity. The question of its measurement has particular importance in relation to the dramatic growth in obesity rates and its relevance for public health. The aim of this study was to investigate the psychometric properties of the Italian version of the Food Cravings Questionnaire–Trait (FCQ–T) in overweight and obese patients who were attending weight loss programs, and its efficiency in discriminating patients with binge eating. Participants were 497 (411 women, 86 men) overweight and obese patients in treatment with low-energy diet therapy. We used structural equation modeling to compare 3 factor models tested in previous studies (a 6-factor model, an 8-factor model, and a 9-factor model), which indicated that the 9-factor model has a better fit over the competing models. The FCQ–T had good internal consistency (Cronbach's α of.96 for the total score, and between.76 and.92 for subfactors), and was able to discriminate patients with clinical-level binge eating from those with probable and without binge eating with an efficiency of.74 (sensitivity =.64, specificity =.78). FCQ–T scores were sensitive to changes associated with treatment only for patients who started dietary restriction between the baseline and the follow-up assessment, but not for patients who were already observing dietary restrictions at the time of the baseline assessment. These results suggest that the FCQ–T could be a potentially useful measure for the screening of binge eating problems in overweight and obese patients while in treatment.
Gelatinous Bone Marrow in an Hiv-Positive Patient

Gelatinous bone marrow transformation has been identified in patients with anorexia, malignancy, malabsorption, and HIV/AIDS. This represents a deposition of gelatinous material within the bone marrow, along with atrophy. We report the case of an HIV-seropositive man who presented with low back pain related to his gelatinous bone marrow changes.
Have protoplanetary discs formed planets

It has recently been noted that many discs around T Tauri stars appear to comprise only a few Jupiter masses of gas and dust. Using millimetre surveys of discs within six local star formation regions, we confirm this result, and find that only a few per cent of young stars have enough circumstellar material to build gas giant planets, in standard core accretion models. Since the frequency of observed exoplanets is greater than this, there is a ‘missing-mass’ problem. As alternatives to simply adjusting the conversion of dust flux to disc mass, we investigate three other classes of solution. Migration of planets could hypothetically sweep up the disc mass reservoir more efficiently, but trends in multiplanet systems do not support such a model, and theoretical models suggest that the gas accretion time-scale is too short for migration to sweep the disc. Enhanced inner-disc mass reservoirs are possible, agreeing with predictions of disc evolution through self-gravity, but not adding to millimetre dust flux as the inner disc is optically thick. Finally, the incidence of massive discs is shown to be higher at the protostellar stages, Classes 0 and I, where discs substantial enough to form planets via core accretion are abundant enough to match the frequency of exoplanets. Gravitational instability may also operate in the Class 0 epoch, where half the objects have potentially unstable discs of ≳30 per cent of the stellar mass. However, recent calculations indicate that forming gas giants inside 50 au by instability is unlikely, even in such massive discs. Overall, the results presented suggest that the canonically ‘protoplanetary’ discs of Class II T Tauri stars have globally low masses in dust observable at millimetre wavelengths, and conversion to larger bodies (anywhere from small rocks up to planetary cores) must already have occurred.
Los valores culturales y el desarrollo socioeconómico: una comparación entre teorías culturales

Resumen Las teorías transculturales de Hofstede (1980), Schwartz (1994), Triandis (1995) e Inglehart (1998) representan en la actualidad las formulaciones más contrastadas sobre las dimensiones culturales de valores. A pesar del interés y popularidad del modelo de Inglehart, no existen trabajos que traten de analizar la validez convergente y discriminante de esta teoría con relación a otras teorías culturales. Este trabajo trata de llenar este hueco comparando la dimensión de Post-materialismo de Inglehart con las dimensiones culturales de Autonomía, Conservación, Jerarquía, Igualitarismo, Armonía y Competencia de Schwartz, para lo cual seguimos varios procedimientos. En primer lugar, estudiamos la relación entre las puntuaciones en las dimensiones culturales de ambos modelos con una muestra de 40 países. A continuación, relacionamos las dimensiones culturales convergentes con variables externas, macrosociales y macroeconómicas, de estas mismas sociedades. Finalmente, analizamos el impacto de la cultura, medida por los valores, y del nivel socioeconómico previo sobre el desarrollo económico y el desarrollo social de las mismas sociedades. Los resultados indican que la similaridad conceptual entre las dos teorías se produce entre las dimensiones culturales del Postmaterialismo, Autonomía Intelectual y Afectiva e Igualitarismo, y que los valores son resultado de una serie de condiciones macroeconómicas y macrosociales. Así, mientras que el crecimiento económico refuerza los valores materiales, el desarrollo humano refuerza valores más solidarios. Ahora bien, la orientación de valores explica gran parte del desarrollo económico y del desarrollo humano posterior.
Limiting Distributions for Sums of Independent Random Products

Let $\{X_{i,j}:(i,j)\in\mathbb N^2\}$ be a two-dimensional array of independent copies of a random variable $X$, and let $\{N_n\}_{n\in\mathbb N}$ be a sequence of natural numbers such that $\lim_{n\to\infty}e^{-cn}N_n=1$ for some $c>0$. Our main object of interest is the sum of independent random products $$Z_n=\sum_{i=1}^{N_n} \prod_{j=1}^{n}e^{X_{i,j}}. $$ It is shown that the limiting properties of $Z_n$, as $n\to\infty$, undergo phase transitions at two critical points $c=c_1$ and $c=c_2$. Namely, if $c>c_2$, then $Z_n$ satisfies the central limit theorem with the usual normalization, whereas for $c c_1$. If the random variable $X$ is Gaussian, we recover the results of Bovier, Kurkova, and L\"owe [Fluctuations of the free energy in the REM and the $p$-spin SK models. Ann. Probab. 30(2002), 605-651].
Students' online shopping behavior: an empirical study

The ever-increasing use of the internet in Malaysia provides a developing prospect for E-marketers. Such marketers' awareness of the factors affecting Malaysian buyers’ attitude can further develop their marketing strategies in converting potential customers into active ones, while maintaining their existent online customers. This paper sets out to examine the factors influencing students’ attitudes towards online shopping in Malaysia through a five-level Likert scale self-administered questionnaire, which was developed based on prior literature. A total of 370 students were randomly selected. The multiple regression analysis demonstrated the most significant determinants of consumers’ attitudes towards online shopping. The results indicated that utilitarian orientation, convenience, price, and a wider selection influenced consumers’ attitudes towards online shopping. Therefore, e-retailers should emphasize a more user-friendly function in order to provide utilitarian customers a way to find what they need efficiently.
Prevalence of gastrointestinal helminths in pastoral sheep and goat flocks in the Cholistan desert of Pakistan.

Small ruminants are a major source of cash for many rural popul ations, especially in semi -arid and arid regions of developing countries. Extensively managed animals often host gastrointestinal parasites, and even chronic infestations lead to economic losses. We evaluated the prevalence of gastrointestinal helminths in sheep and goats of the Cholistan desert, Pakistan, where livestock is the backbone of the regional economy. Fresh faeces (10 - 15 g) were collected from 500 sheep and 500 goats across five different localities. Standard parasitological techniques served t o identify parasite eggs, and copro-culture enabled larval determination of specific nematodes. Overall helminth prevalence was 78.1% across the 1000 animals; pure nematode infestations were most prevalent (37.5%), followed by pure trematode (7.9%), pure cestode (2.6%) and pure protozoa infestations (0.8%). Mixed infestations with nematodes and trematodes occurred in 6.4% of all animals, mixed nematode-cestode infestations in 3.8%, and all three groups were found in 19.1% of the sheep and goats. In goats more males (81.1%) than females (77.0%) were infested, the opposite was found in sheep (73.6% males, 79.5% females). Parasites were especially prevalent in suckling goats (85.2%) and sheep (88.5%) and to a lesser extent in young (goats 80.6%, sheep 79.3%) and adult animals (goats 72.8%, sheep 73.8%). Given the high infestation rates, particular attention should be paid to management of suckling animals. A general means of reducing infestation rates might be the systematic testing of traditional plant -based remedies against helminths for cheap and regular deworming of the herds.
Topotecan given as a 21-day infusion in the treatment of advanced ovarian cancer

A phase II programme was carried out in both Europe and North America to evaluate the activity of topotecan administered as a 21-day continuous intravenous infusion to patients with recurrent ovarian cancer. The European results are reported here. Patients who had failed first line therapy with a platinum-based regimen received topotecan 0.4 mg/m2/day, as a 21-day infusion every 28 days. Patients were only permitted one prior regimen. 35 patients were enrolled and evaluable for response. 3 patients (8.6%) had a partial response to treatment (95% CI 1.8%, 23.1%) with a median time to response of 8.1 weeks and a median duration of response of 17.6 weeks. Response was also evaluated by CA125 and was also found to be 8%. For all 35 patients, median time to progression was 16.1 weeks and median survival was 43.6 weeks. The principal toxicity was myelosuppression although grade 4 neutropenia occurred in only 8.8% of patients (2.1% of courses) and infectious complications were relatively infrequent. Non-haematological toxicity was generally mild and mainly consisted of gastrointestinal events, alopecia and fatigue. A prolonged infusion of topotecan was well tolerated with a low incidence of severe neutropenia. Responses were seen in both North American and European patients. Response rates varied between the 2 studies possibly due to differences in patient demographics. © 2001 Cancer Research Campaign
A cluster of cooperating tumor-suppressor gene candidates in chromosomal deletions

The large chromosomal deletions frequently observed in cancer genomes are often thought to arise as a “two-hit” mechanism in the process of tumor-suppressor gene (TSG) inactivation. Using a murine model system of hepatocellular carcinoma (HCC) and in vivo RNAi, we test an alternative hypothesis, that such deletions can arise from selective pressure to attenuate the activity of multiple genes. By targeting the mouse orthologs of genes frequently deleted on human 8p22 and adjacent regions, which are lost in approximately half of several other major epithelial cancers, we provide evidence suggesting that multiple genes on chromosome 8p can cooperatively inhibit tumorigenesis in mice, and that their cosuppression can synergistically promote tumor growth. In addition, in human HCC patients, the combined down-regulation of functionally validated 8p TSGs is associated with poor survival, in contrast to the down-regulation of any individual gene. Our data imply that large cancer-associated deletions can produce phenotypes distinct from those arising through loss of a single TSG, and as such should be considered and studied as distinct mutational events.
Translating Nanomedicine to Comparative Oncology—the Case for Combining Zinc Oxide Nanomaterials with Nucleic Acid Therapeutic and Protein Delivery for Treating Metastatic Cancer

The unique anticancer, biochemical, and immunologic properties of nanomaterials are becoming a new tool in biomedical research. Their translation into the clinic promises a new wave of targeted therapies. One nanomaterial of particular interest are zinc oxide (ZnO) nanoparticles (NPs), which has distinct mechanisms of anticancer activity including unique surface, induction of reactive oxygen species, lipid oxidation, pH, and also ionic gradients within cancer cells and the tumor microenvironment. It is recognized that ZnO NPs can serve as a direct enzyme inhibitor. Significantly, ZnO NPs inhibit extracellular signal–regulated kinase (ERK) and protein kinase B (AKT) associated with melanoma progression, drug resistance, and metastasis. Indeed, direct intratumoral injection of ZnO NPs or a complex of ZnO with RNA significantly suppresses ERK and AKT phosphorylation. These data suggest ZnO NPs and their complexes or conjugates with nucleic acid therapeutic or anticancer protein may represent a potential new strategy for the treatment of metastatic melanoma, and potentially other cancers. This review focuses on the anticancer mechanisms of ZnO NPs and what is currently known about its biochemical effects on melanoma, biologic activity, and pharmacokinetics in rodents and its potential for translation into large animal, spontaneously developing models of melanoma and other cancers, which represent models of comparative oncology.
In the aftermath of the Fusarium keratitis outbreak: What have we learned?

The 2005–2006 outbreak of Fusarium keratitis associated with soft hydrophilic contact lens wear was both unprecedented and unexpected. More than 250 cases have been reported worldwide that have primarily been associated with Bausch & Lomb ReNu with MoistureLoc and, more recently, with Bausch and Lomb ReNu MultiPlus multipurpose contact lens disinfecting solutions. This article documents the outbreak, presenting the time line and the historical and scientific basis for its occurrence. Underlying causes are explored including likely mechanisms of contamination and subsequent corneal infection. Thorough exploration of this unique occurrence affords the opportunity to examine contact lens and lens care actions and interactions and to develop greater understanding of possible associated risks and ways to minimize them.
Endogenous zinc depresses GABAergic transmission via T-type Ca2+ channels and broadens the time window for integration of glutamatergic inputs in dentate granule cells

• Zinc inhibits ionotropic receptors commonly found at central synapses, as well as a wide variety of voltage‐activated ion channels that modulate neuronal excitability and neurotransmitter release. • We found that zinc chelation facilitated GABAergic signalling in dentate granule cells and that blocking T‐type Ca2+ channel activity abolished this effect. Zinc chelation reduced spike threshold, increased spike width and shifted the input–output relationship in dentate interneurones, which is consistent with increased excitability. • In granule cells, zinc chelation narrowed the window for the integration of glutamatergic inputs originating from perforant path synapses. • These results demonstrate that zinc modulates dentate interneurone function and regulates spike routing to local and hippocampal targets.
A developmental study of the structural integrity of white matter in autism

Diffusion tensor imaging was used to examine developmental changes in the organization of white matter in a large sample of male participants with autism and controls between the ages of 10 and 35 years. Participants with autism had lower fractional anisotropy in areas within and near the corpus callosum and in the right retrolenticular portion of the internal capsule. Only one area, in the posterior limb of the right internal capsule, showed an interaction between age and group. The findings suggest that reductions in the structural integrity of white matter in autism persist into adulthood. These reductions may underlie the behavioral pattern observed in autism, as well as findings of reduced functional connectivity in functional magnetic resonance imaging signal between activating cortical areas.