Miracle-dz/UniFAR-FTUs huggingface dataset:
An Empirical Model of Joint Stock Company Births , Greece : 1840-1939 by Ioanna

This paper investigates the forces driving JSC births in Greece from 1840 to 1939. For this purpose, we combine historical descriptive statistics analysis with the construction of a negative binomial regression model in which the determinants are GDP indicators and other economic variables based on the work of other scholars in the fields of: economic growth, entrepreneurial and joint stock company history, primarily: Kuznets (1966, 1971); Hausman (2005); Broberg (2008); Ruiz and Perez-Amaral (2013); Sylla and Wright (2013); Pavese and Toninelli (2014). We have compiled a unique data base of JSC births (derived from published charters in the Greek Government Gazette and the National Bank of Greece Registry of JSC births) and of selected macro indicators (derived from Kostelenos et al, 2007; Dertilis, 2011 and others). Our main findings are that: 1) After a long hesitant gestation period incorporation embarked on a Take-off (1917-1936); 2) GDP and other macro indicators impacted on JSC births as expected by the international literature; 3) In 1913, there was a structural break. In the long period before this, there had developed a strong sensitivity/response of incorporation to fluctuations to GDP per capita (the standard of living); 4) From the structural break onwards it was real interest rates that had a stronger impact on JSC births; 5) Last but not least, though throughout the century the impact of nonagriculture was more important for incorporation than industry, after 1913 the impact of industry increased. We aspire through this study to contribute to the more general debate about the relationship between incorporation and economic growth and open a dialogue with other national case studies. JEL: N13, N14, N83, N84, C22.
Robust Post-Matching Inference

Abstract Nearest-neighbor matching is a popular nonparametric tool to create balance between treatment and control groups in observational studies. As a preprocessing step before regression, matching reduces the dependence on parametric modeling assumptions. In current empirical practice, however, the matching step is often ignored in the calculation of standard errors and confidence intervals. In this article, we show that ignoring the matching step results in asymptotically valid standard errors if matching is done without replacement and the regression model is correctly specified relative to the population regression function of the outcome variable on the treatment variable and all the covariates used for matching. However, standard errors that ignore the matching step are not valid if matching is conducted with replacement or, more crucially, if the second step regression model is misspecified in the sense indicated above. Moreover, correct specification of the regression model is not required for consistent estimation of treatment effects with matched data. We show that two easily implementable alternatives produce approximations to the distribution of the post-matching estimator that are robust to misspecification. A simulation study and an empirical example demonstrate the empirical relevance of our results. Supplementary materials for this article are available online.
Complete Sequences of Multiple-Drug Resistant IncHI2 ST3 Plasmids in Escherichia coli of Porcine Origin in Australia

IncHI2 ST3 plasmids are known carriers of multiple antimicrobial resistance genes. Complete plasmid sequences from multiple drug resistant Escherichia coli circulating in Australian swine is however limited. Here we sequenced two related IncHI2 ST3 plasmids, pSDE-SvHI2 and pSDC-F2_12BHI2, from phylogenetically unrelated multiple-drug resistant Escherichia coli strains SvETEC (CC23:O157:H19) and F2_12B (ST93:O7:H4) from geographically disparate pig production operations in New South Wales, Australia. Unicycler was used to co-assemble short read (Illumina) and long read (PacBio SMRT) nucleotide sequence data. The plasmids encoded three drug-resistance loci, two of which carried class 1 integrons. One integron, hosting drfA12-orfF-aadA2, was within a hybrid Tn1721/21, with the second residing within a copper/silver resistance transposon, comprising part of an atypical sul3-associated structure. The third resistance locus was flanked by IS15DI and encoded neomycin resistance (neoR). An oqx-encoding transposon (quinolone resistance), similar in structure to Tn6010, was identified only in pSDC-F2_12BHI2. Both plasmids showed high sequence identity to plasmid pSTM6-275, recently described in Salmonella enterica serotype 1,4,[5],12:i:- that has risen to prominence and become endemic in Australia. IncHI2 ST3 plasmids circulating in commensal and pathogenic E. coli from Australian swine belong to a lineage of plasmids often in association with sul3 and host multiple complex antibiotic and metal resistance structures, formed in part by IS26.
Human TLR8 Senses RNA From Plasmodium falciparum-Infected Red Blood Cells Which Is Uniquely Required for the IFN-γ Response in NK Cells

During blood-stage malaria, the innate immune system initiates the production of pro-inflammatory cytokines, including IFN-γ, that are critical to host defense and responsible for severe disease. Nonetheless, the innate immune pathways activated during this process in human malaria remain poorly understood. Here, we identify TLR8 as an essential sensor of Plasmodium falciparum-infected red blood cells (iRBC). In human immune cells, iRBC and RNA purified from iRBC were detected by TLR8 but not TLR7 leading to IFN-γ induction in NK cells. While TLR7 and 9 have been shown to lead to IFN-γ in mice, our data demonstrate that TLR8 was the only TLR capable of inducing IFN-γ release in human immune cells. This unique capacity was mediated by the release of IL-12p70 and bioactive IL-18 from monocytes, the latter via a hitherto undescribed pathway. Altogether, our data are the first reported activation of TLR8 by protozoan RNA and demonstrate both the critical role of TLR8 in human blood-stage malaria and its unique functionality in the human immune system. Moreover, our study offers important evidence that mouse models alone may not be sufficient to describe the human innate immune response to malaria.
Blocking VEGF by Bevacizumab Compromises Electrophysiological and Morphological Properties of Hippocampal Neurons

A hallmark of glioblastoma multiforme (GBM) is neoangiogenesis, mediated by the overexpression of vascular endothelial growth factor (VEGF). Anti-VEGF antibodies, like bevacizumab, prolong progression-free survival in GBM, however, this treatment has been reported to be associated with a decline in neurocognitive function. Therefore, this study focused on the effects of bevacizumab on neuronal function and plasticity. We analyzed neuronal membrane properties and synaptic plasticity in rat hippocampal slices, as well as spine dynamics in dissociated hippocampal neurons, to examine the impact of bevacizumab on hippocampal function and viability. VEGF inhibition resulted in profound impairments in hippocampal synaptic plasticity as well as reductions in dendritic spine number and length. Physiological properties of hippocampal neurons were also affected. These effects of VEGF blockade on hippocampal function may play a role in compromising memory and information processing and thus, may contribute to neurocognitive dysfunction in GBM patients treated with bevacizumab.
Stress Hyperglycemia in Critically Ill Patients: Insight Into Possible Molecular Pathways

Severe sepsis, systemic inflammatory response syndrome (SIRS), and traumatic brain injury are frequently associated with hyperglycemia in non-diabetic patients. In patients suffering from any of these conditions, hyperglycemia at admission to an intensive care unit (ICU) is directly correlated with increased mortality or morbidity. Although there was initial enthusiasm for insulin treatment to blood glucose levels below 110 mg/dL in these patients, recent understanding suggests that the potential for hypoglycemic complications make this approach potentially dangerous. More moderate glucose control seems to be more beneficial than the aggressive glucose lowering initially suggested. An important publication has shown that hyperlactatemia accompanying hyperglycemia could be the real culprit in bad outcomes. This suggests that coupling moderate glucose lowering with therapeutic agents which might treat the underlying metabolic disturbances in these conditions may be a better strategy. The key metabolic disturbance in these three conditions seems to be persistent glycolysis as an energy source even in the presence of adequate tissue oxygenation (the Warburg Effect). We look at recent advances in understanding aerobic glycolysis and possibly the action of DPP4 on incretins resulting in insulin dysregulation and suggest key metabolic pathways involved in hyperglycemia regulation.
Efficacy of Central Neck Dissection for Clinically Node-Negative Papillary Thyroid Carcinoma: Propensity Scoring Matching

Objectives: The utility of prophylactic central neck dissection (pCND) for papillary thyroid carcinoma (PTC) is still controversial. Although the procedure may reduce locoregional recurrence, it is associated with a high rate of postoperative complications. The aim of this study was to evaluate the role of pCND in patients with PTC. Materials and Methods: From January 1995 to April 2011, the records of 477 patients who underwent total thyroidectomy with or without pCND for clinically node-negative PTC measuring < 4 cm were retrospectively reviewed. Of these, 341 patients had undergone pCND with total thyroidectomy and 136 patients did not undergo pCND. The clinicopathologic characteristics, surgical outcomes, complications, recurrence, and survival were analyzed using propensity score matching, using age, sex, tumor size, extrathyroidal extension, and radioactive iodine ablation as covariates to minimize selection bias. Results: At baseline, there was no significant difference in sex, age, and multiplicity and bilaterality of the cancer between the two groups. However, extrathyroidal extension was more common and tumor size larger in patients who underwent pCND. For the propensity score-matched analysis, two matched groups, each comprising 135 patients, were generated. After propensity score matching, the significant differences observed at baseline between the two groups disappeared. The postoperative complication rate did not differ between the two groups. Recurrence occurred in 4 patients (2.96%) who had undergone pCND and in 2 patients (1.48%) who did not undergo pCND (P = 0.684). The recurrence-free survival curves did not differ between the two groups. Conclusion: The efficacy of pCND in total thyroidectomy for clinically node-negative PTC is limited, and pCND is not recommended for these patients.
Sirtuins and Type 2 Diabetes: Role in Inflammation, Oxidative Stress, and Mitochondrial Function

The rising incidence of type 2 diabetes mellitus (T2DM) is a major public health concern, and novel therapeutic strategies to prevent T2DM are urgently needed worldwide. Aging is recognized as one of the risk factors for metabolic impairments, including insulin resistance and T2DM. Inflammation, oxidative stress, and mitochondrial dysfunction are closely related to both aging and metabolic disease. Calorie restriction (CR) can retard the aging process in organisms ranging from yeast to rodents and delay the onset of numerous age-related disorders, such as insulin resistance and diabetes. Therefore, metabolic CR mimetics may represent new therapeutic targets for insulin resistance and T2DM. Sirtuin 1 (SIRT1), the mammalian homolog of Sir2, was originally identified as a nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase. The activation of SIRT1 is closely associated with longevity under CR, and it is recognized as a CR mimetic. Currently, seven sirtuins have been identified in mammals. Among these sirtuins, SIRT1 and SIRT2 are located in the nucleus and cytoplasm, SIRT3 exists predominantly in mitochondria, and SIRT6 is located in the nucleus. These sirtuins regulate metabolism through their regulation of inflammation, oxidative stress and mitochondrial function via multiple mechanisms, resulting in the improvement of insulin resistance and T2DM. In this review, we describe the current understanding of the biological functions of sirtuins, especially SIRT1, SIRT2, SIRT3, and SIRT6, focusing on oxidative stress, inflammation, and mitochondrial function, which are closely associated with aging.
Key Mechanistic Features in Palladium-Catalyzed Methylcyclopropanation of Norbornenes With Vinyl Bromides: Insights From DFT Calculations

DFT calculations were performed to elucidate mechanistic details of an unusual palladium-catalyzed methylcyclopropanation from [2 + 1] cycloadditions of (Z)-2-bromovinylbenzene and endo-N-(p-tolyl)-norbornenesuccinimide. The reaction proceeds via oxidative addition (OA), intermolecular alkene insertion, deprotonation/protonation, intramolecular alkene insertion, β-H elimination and reductive elimination (RE). Protonation is the rate-limiting step and requires an overall barrier of 28.5 kcal/mol. The sources of two protons for protonation and exchange have also been clarified and the calculations agree with experimental observations.
Overlooked Parrot Seed Dispersal in Australia and South America: Insights on the Evolution of Dispersal Syndromes and Seed Size in Araucaria Trees

While Psittaciformes (parrots and allies) are well recognized as highly-mobile seed predators, their role as seed dispersers has been overlooked until very recently. It remains to be determined whether this role is anecdotic or is a key mutualism for some plant species. We recently found that the large nut-like seeds of the two South American Araucaria tree species (A. araucana in Andean forests and A. angustifolia in Atlantic forests, weighing c. 3.5 and 7g, respectively) are frequently dispersed, and to long distances, by parrots. Moreover, both observational and experimental work demonstrated that dispersed seeds can germinate faster after partial predation by parrots. Here, we hypothesized that a third, even larger-seeded (17.5g) congeneric Australian species (A. bidwillii) is also dispersed by parrots. We surveyed 52 A. bidwillii and 42 A. cunninghamii (a sympatric species with small winged seeds, c. 0.2g) during the seeding period. We found that sulphur-crested cockatoos (Cacatua galerita) consumed large amounts of seeds from all of the A. bidwillii trees surveyed. Cockatoos dispersed ca. 30% of the seeds they removed from the mother tree, carrying the seeds to distant perches for handling or dropped them while flying. Dispersal distances ranged between 10 and 153 m (mean = 61m). Most seeds handled for consumption (93%) were fully eaten but others were dropped intact (3%) or only partially eaten (4%), and germination was confirmed for both intact and partially-eaten dispersed seeds. Moreover, seeds dropped by cockatoos facilitated secondary seed dispersal by conspecifics and another three bird species. We found no evidence of other primary dispersal species for A. bidwillii, while the small, winged seeds of A. cunninghamii were just dispersed through barochory and anemochory. The seed weight of the three Araucaria species dispersed by zoochory is strongly related to the body mass of their main seed-dispersing parrot species. These results support a role for parrots as key dispersers of the three large-seeded Araucaria species around the world, and suggest that large seeds may have evolved–at least partially–as an adaptation that allows trees to attract parrots, satiate them, and benefit from their long-distance seed dispersal services.
Radiomics and Machine Learning for Radiotherapy in Head and Neck Cancers

Introduction: An increasing number of parameters can be considered when making decisions in oncology. Tumor characteristics can also be extracted from imaging through the use of radiomics and add to this wealth of clinical data. Machine learning can encompass these parameters and thus enhance clinical decision as well as radiotherapy workflow. Methods: We performed a description of machine learning applications at each step of treatment by radiotherapy in head and neck cancers. We then performed a systematic review on radiomics and machine learning outcome prediction models in head and neck cancers. Results: Machine Learning has several promising applications in treatment planning with automatic organ at risk delineation improvements and adaptative radiotherapy workflow automation. It may also provide new approaches for Normal Tissue Complication Probability models. Radiomics may provide additional data on tumors for improved machine learning powered predictive models, not only on survival, but also on risk of distant metastasis, in field recurrence, HPV status and extra nodal spread. However, most studies provide preliminary data requiring further validation. Conclusion: Promising perspectives arise from machine learning applications and radiomics based models, yet further data are necessary for their implementation in daily care.
Simultaneous Capture and Detumble of a Resident Space Object by a Free-Flying Spacecraft-Manipulator System

A maneuver to capture and detumble an orbiting space object using a chaser spacecraft equipped with a robotic manipulator is presented. In the proposed maneuver, the capture and detumble objectives are integrated into a unified set of terminal constraints. Terminal constraints on the end-effector's position and velocity ensure a successful capture, and a terminal constraint on the chaser's momenta ensures a post-capture chaser-target system with zero angular momentum. The manipulator motion required to achieve a smooth, impact-free grasp is gradually stopped after capture, equalizing the momenta across all bodies, rigidly connecting the two vehicles, and completing the detumble of the newly formed chaser-target system without further actuation. To guide this maneuver, an optimization-based approach that enforces the capture and detumble terminal constraints, avoids collisions, and satisfies actuation limits is used. The solution to the guidance problem is obtained by solving a collection of convex programming problems, making the proposed guidance approach suitable for onboard implementation and real-time use. This simultaneous capture and detumble maneuver is evaluated through numerical simulations and hardware-in-the-loop experiments. Videos of the numerically simulated and experimentally demonstrated maneuvers are included as Supplementary Material.
Music-Enhanced Analgesia and Antiseizure Activities in Animal Models of Pain and Epilepsy: Toward Preclinical Studies Supporting Development of Digital Therapeutics and Their Combinations With Pharmaceutical Drugs

Digital therapeutics (software as a medical device) and mobile health (mHealth) technologies offer a means to deliver behavioral, psychosocial, disease self-management and music-based interventions to improve therapy outcomes for chronic diseases, including pain and epilepsy. To explore new translational opportunities in developing digital therapeutics for neurological disorders, and their integration with pharmacotherapies, we examined analgesic and antiseizure effects of specific musical compositions in mouse models of pain and epilepsy. The music playlist was created based on the modular progression of Mozart compositions for which reduction of seizures and epileptiform discharges were previously reported in people with epilepsy. Our results indicated that music-treated mice exhibited significant analgesia and reduction of paw edema in the carrageenan model of inflammatory pain. Among analgesic drugs tested (ibuprofen, cannabidiol (CBD), levetiracetam, and the galanin analog NAX 5055), music intervention significantly decreased paw withdrawal latency difference in ibuprofen-treated mice and reduced paw edema in combination with CBD or NAX 5055. To the best of our knowledge, this is the first animal study on music-enhanced antinociceptive activity of analgesic drugs. In the plantar incision model of surgical pain, music-pretreated mice had significant reduction of mechanical allodynia. In the corneal kindling model of epilepsy, the cumulative seizure burden following kindling acquisition was lower in animals exposed to music. The music-treated group also exhibited significantly improved survival, warranting further research on music interventions for preventing Sudden Unexpected Death in Epilepsy (SUDEP). We propose a working model of how musical elements such as rhythm, sequences, phrases and punctuation found in K.448 and K.545 may exert responses via parasympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis. Based on our findings, we discuss: (1) how enriched environment (EE) can serve as a preclinical surrogate for testing combinations of non-pharmacological modalities and drugs for the treatment of pain and other chronic diseases, and (2) a new paradigm for preclinical and clinical development of therapies leading to drug-device combination products for neurological disorders, depression and cancer. In summary, our present results encourage translational research on integrating non-pharmacological and pharmacological interventions for pain and epilepsy using digital therapeutics.
A Delay Learning Algorithm Based on Spike Train Kernels for Spiking Neurons

Neuroscience research confirms that the synaptic delays are not constant, but can be modulated. This paper proposes a supervised delay learning algorithm for spiking neurons with temporal encoding, in which both the weight and delay of a synaptic connection can be adjusted to enhance the learning performance. The proposed algorithm firstly defines spike train kernels to transform discrete spike trains during the learning phase into continuous analog signals so that common mathematical operations can be performed on them, and then deduces the supervised learning rules of synaptic weights and delays by gradient descent method. The proposed algorithm is successfully applied to various spike train learning tasks, and the effects of parameters of synaptic delays are analyzed in detail. Experimental results show that the network with dynamic delays achieves higher learning accuracy and less learning epochs than the network with static delays. The delay learning algorithm is further validated on a practical example of an image classification problem. The results again show that it can achieve a good classification performance with a proper receptive field. Therefore, the synaptic delay learning is significant for practical applications and theoretical researches of spiking neural networks.