Miracle-dz/UniFAR-FTUs huggingface dataset:
A comparison between methadone and buprenorphine for perioperative analgesia in dogs undergoing ovariohysterectomy

OBJECTIVE To investigate whether preoperative methadone provides superior perioperative analgesia compared to buprenorphine in dogs undergoing ovariohysterectomy. METHODS Eighty female dogs were recruited to an assessor-blinded, randomised, clinical trial. Dogs received a premedication dose of 0·05 mg/kg acepromazine or 10 μg/kg medetomidine combined with either 0·3 mg/kg methadone or 20 μg/kg buprenorphine intramuscularly. Anaesthesia was induced with propofol and maintained with isoflurane. Pain was assessed using two scoring schemes (a dynamic interactive visual analogue scale and the short form of the Glasgow Composite Pain Scale) before premedication, 30 minutes later and every hour for 8 hours after premedication. If indicated, rescue analgesia was provided with methadone. Meloxicam was administered after the final assessment. The area under the curve for change in pain scores over time and the requirement for rescue analgesia were compared between groups. RESULTS Groups premedicated with buprenorphine had significantly higher pain scores than those premedicated with methadone. There was no interaction between opioid and sedative for any outcome measure. Rescue analgesia was required by significantly more dogs premedicated with buprenorphine (45%) than that of methadone (20%). CLINICAL SIGNIFICANCE At the doses investigated, methadone produced superior postoperative analgesia compared to buprenorphine in dogs undergoing ovariohysterectomy.
Proofs and Programs about Open Terms

Formal deductive systems are very common in computer science. They are used to represent logics, programming languages, and security systems. Moreover, writing programs that manipulate them and that reason about them is important and common. Consider proof assistants, language interpreters, compilers and other software that process input described by formal systems. This thesis shows that contextual types can be used to build tools for convenient implementation and reasoning about deductive systems with binders. We discuss three aspects of this: the reconstruction of implicit parameters that makes writing proofs and programs with dependent types easier, the addition of contextual objects to an existing programming language that make implementing formal systems with binders easier, and finally, we explore the idea of embedding the logical framework LF using contextual types in fully dependently typed theory. These are three aspects of the same message: programming using the right abstraction allows us to solve deeper problems with less effort. In this sense we want: easier to write programs and proofs (with implicit parameters), languages that support binders (by embedding a syntactic framework using contextual types), and the power of the logical framework LF with the expressivity of dependent types.
Constrained Sparse Subspace Clustering with Side-Information

Subspace clustering refers to the problem of segmenting high dimensional data drawn from a union of subspaces into the respective subspaces. In some applications, partial side-information to indicate “must-link” or “cannot-link” in clustering is available. This leads to the task of subspace clustering with side-information. However, in prior work the supervision value of the side-information for subspace clustering has not been fully exploited. To this end, in this paper, we present an enhanced approach for constrained subspace clustering with side-information, termed Constrained Sparse Subspace Clustering plus (CSSC+), in which the side-information is used not only in the stage of learning an affinity matrix but also in the stage of spectral clustering. Moreover, we propose to estimate clustering accuracy based on the partial side-information and theoretically justify the connection to the ground-truth clustering accuracy in terms of the Rand index. We conduct experiments on three cancer gene expression datasets to validate the effectiveness of our proposals.
Endurance training alters YKL40, PERM1, and HSP70 skeletal muscle protein contents in men with type 2 diabetes mellitus

ABSTRACT Background: The fight against type 2 diabetes mellitus (T2DM) is tremendously challenging. This pilot study investigates whether endurance training (3 times per week for 3 months, moderate intensity) can change the skeletal muscle protein contents of chitinase-3-like protein-1 (YKL40), peroxisome proliferator-activated receptor y coactivator-1 and estrogen-related receptor-induced regulator in muscle-1 (PERM1) and heat-shock protein-70 (HSP70), which have been discussed as novel therapeutically relevant targets. Methods: Muscle biopsies were obtained from overweight/obese men with T2DM (n = 7, years = 63 ± 9) at T1 (6 weeks pre-training), T2 (1 week pre-training) and T3 (3 to 4 days post-training). The protein levels of YKL40, PERM1, and HSP70 were determined by immunohistochemistry. Results: YKL40, PERM1, and HSP70 were significantly upregulated following endurance training (T2–T3: +103%, +61%, +89%, p = 0.012, p = 0.010, p = 0.028). There was a fiber type-specific distribution of HSP70 with increased protein contents in type I fibers. A significant change in the fiber type distribution with an increase in type I fibers and a decrease in type II fibers was observed post-training. There were no significant differences for YKL40, PERM1, HSP70, or the fiber type distribution between T1 and T2. Conclusion: The training-induced upregulation of YKL40, PERM1, and HSP70 could help manage the diabetic disease and reduce its complications.
Mental health interventions among older adults: A systematic review

Background: The aim of the present study was to conduct a systematic review to identify documented mental health promotion interventions developed and tested among population-based older adults. Methods: A systematic review based on PRISMA guidelines. The literature was searched in PsycINFO and PubMed between June and September 2016. The Effective Public Health Practice Project tool was used to assess the quality of the included study. Results: In total 53 randomized controlled trial studies qualified for the systematic review. Across studies, three types of common conceptual themes emerged for interventions, including: 1) individual characteristics; 2) content and structure of the interventions; and 3) implementation of the interventions. Conclusions: No specific interventions could be recommended on the aforementioned basis. We conclude that a number of factors are of central importance for an intervention to have the desired effect. If these factors are considered, mental health can be successfully promoted among older adults.
A reply to “Ranging Behavior Drives Parasite Richness: A More Parsimonious Hypothesis”

This preprint has been reviewed and recommended by Peer Community In Ecology (https://dx.doi.org/10.24072/pci.ecology.100001). In a recent article, Bicca-Marques and Calegaro-Marques [Bicca-Marques JC, Calegaro-Marques C (2016) Ranging behavior drives parasite richness: A more parsimonious hypothesis. American Journal of Primatology 78: 923–927. ] discussed the putative assumptions related to an interpretation we provided regarding an observed positive relationship between weekly averaged parasite richness of a group of mandrills (Mandrillussphinx) and their daily path lengths (DPL), published earlier in the same journal [Brockmeyer T, Kappeler PM, Willaume E, Benoit L, Mboumba S, Charpentier MJE (2015) Social organization and space use of a wild mandrill (Mandrillussphinx) group. American Journal of Primatology 77: 1036–1048. ]. In our article, we proposed, inter alia, that “the daily travels of mandrills could be seen as a way to escape contaminated habitats on a local scale”. In their article, Bicca-Marques and Calegaro-Marques proposed an alternative mechanism that they considered to be more parsimonious. In their view, increased DPL also increases exposure to novel parasites from the environment. In other words, while we proposed that elevated DPL may be a consequence of elevated parasite richness, they viewed it as a cause. We are happy to see that our study attracted so much interest that it evoked a public comment. We are also grateful to Bicca-Marques and Calegaro-Marques for pointing out an obvious alternative scenario that we failed to discuss and for laying out several key factors and assumptions that should be addressed by future studies examining the links between parasite risk and group ranging. We use this opportunity to advance this discourse by responding to some of the criticisms raised in their discussion of our article. In this reply, we briefly contextualize the main object of criticism. We then discuss the putative parsimony of the two competing scenarios.
Genetic inactivation of alpha-synuclein affects embryonic development of dopaminergic neurons of the substantia nigra, but not the ventral tegmental area, in mouse brain

Lesion of the dopaminergic neurons of the nigrostriatal system is a key feature of Parkinson’s disease (PD). Alpha-synuclein is a protein that is a major component of Lewy bodies, histopathological hallmarks of PD, and is involved in regulation of dopamine (DA) neurotransmission. Previous studies of knockout mice have shown that inactivation of alpha-synuclein gene can lead to the reduction in number of DA neurons in the substantia nigra (SN). DA neurons of the SN are known to be the most affected in PD patients whereas DA neurons of neighboring ventral tegmental area (VTA) are much less susceptible to degeneration. Here we have studied the dynamics of changes in TH-positive cell numbers in the SN and VTA during a critical period of their embryonic development in alpha-synuclein knockout mice. This precise study of DA neurons during development of the SN revealed that not only is the number of DA neurons reduced by the end of the period of ontogenic selection, but that the way these neurons are formed is altered in alpha-synuclein knockout mice. At the same time, DA neurons in the VTA are not affected. Alpha-synuclein exerts a modulating effect on the formation of DA neurons in the SN and has no effect on the formation of DA neurons in VTA, the structure that is much less susceptible to degeneration in a brain with PD, suggesting a potential role of alpha-synuclein in the development of the population of DA neurons in substantia nigra.
Reply to Bamforth

Bamforth contends that research conducted into cation-ratio dating at CA-KER-140 was flawed because of (1) a poorly conceived research design, (2) a lack of site integrity, and (3) misinterpretation of the chemical data. He further argues that processes affecting artifact stability at KER-140 were absent from the IPP sites. As a result, he suggests that the conclusions presented in my earlier article are unsound and irrelevant to the interpretation of previously derived cation-ratio dates. In this article I respond to these assertions. Specifically, I demonstrate that Bamforth has failed to establish grounds for dismissing either the KER-140 research design or the chemical results obtained from that study. In addition, I review descriptions of the IPP sites presented elsewhere by Bamforth and conclude that these descriptions support the interpretation of artifact instability at the IPP sites.
Hippocampal lipidome and transcriptome profile alterations triggered by acute exposure of mice to GSM 1800 MHz mobile phone radiation: An exploratory study

The widespread use of wireless devices during the last decades is raising concerns about adverse health effects of the radiofrequency electromagnetic radiation (RF‐EMR) emitted from these devices. Recent research is focusing on unraveling the underlying mechanisms of RF‐EMR and potential cellular targets. The “omics” high‐throughput approaches are powerful tools to investigate the global effects of RF‐EMR on cellular physiology.
Multi-objective optimization of artificial swimmers

A fundamental understanding of how various biological traits and features provide organisms with a competitive advantage can help us improve the design of several mechanical systems. Numerical optimization can be invaluable for this purpose, by allowing us to scrutinize the evolution of specific biological adaptations. Importantly, the use of numerical optimization can help us overcome limiting constraints that restrict the evolutionary capability of biological species. Thus, we couple high-fidelity simulations of self-propelled swimmers with evolutionary optimization algorithms, to examine peculiar swimming patterns observed in a number of fish species. More specifically, we investigate the intermittent form of locomotion referred to as ‘burst-and-coast’ swimming, which involves a few quick flicks of the fish's tail followed by a prolonged unpowered glide. This mode of swimming is believed to confer energetic benefits, in addition to several other advantages. We discover a range of intermittent-swimming patterns, the most efficient of which resembles the swimming-behaviour observed in live fish. We also discover patterns which lead to a marked increase in swimming-speed, albeit with a significant increase in energy expenditure. Notably, the use of multi-objective optimization reveals locomotion patterns that strike the perfect balance between speed and efficiency, which can be invaluable for use in robotic applications. The analyses presented may also be extended for optimal design and control of airborne vehicles. As an additional goal of the paper, we highlight the ease with which disparate codes can be coupled via the software framework used, without encumbering the user with the details of efficient parallelization.
A retrospective histological comparison of EUS-guided fine-needle biopsy using a novel franseen needle and a conventional end-cut type needle

Background and Objectives: Recently, a 22G Franseen needle for EUS-guided fine-needle biopsy (EUS-FNB) with three novel symmetric heels has been developed to adequately obtain a core tissue. Methods: All 38 consecutive patients with pancreatic masses who underwent EUS-FNB using a Franseen needle were investigated retrospectively to assess the efficacy and safety of EUS-FNB using the Franseen needle. Then, the EUS-FNB outcomes and histological assessments of the tissue obtained by EUS-FNB using the Franseen needle and EUS-FNA using the conventional end-cut type needle for each of the 30 pancreatic ductal adenocarcinoma cases were compared. Results: An accurate histological diagnosis of the Franseen needle was achieved with a mean of 2 passes in 97.4% of patients. Although the accurate histological diagnosis rate of pancreatic ductal adenocarcinoma was not significantly different (96.7% vs. 93.3%, P = 0.55), the mean number of passes in the Franseen needle was significantly less than that in the conventional needle (2.1 ± 0.4 vs. 3.2 ± 0.8, P < 0.001). The presence of desmoplastic fibrosis with neoplastic cellular elements and venous invasion were significantly higher (96.7% vs. 40.0%, P < 0.001 and 23.3% vs. 0%, P < 0.01, respectively) and the amount of obtained tissue was significantly larger with the Franseen needle (2.13 mm2 vs. 0.45 mm2, P < 0.001). Conclusions: EUS-FNB using the Franseen needle enables the acquisition of a larger amount of tissue sample and achieves an accurate histological diagnosis with a smaller number of passes than the conventional end-cut type needle.
Genes Whose Gain or Loss-Of-Function Increases Skeletal Muscle Mass in Mice: A Systematic Literature Review

Skeletal muscle mass differs greatly in mice and humans and this is partially inherited. To identify muscle hypertrophy candidate genes we conducted a systematic review to identify genes whose experimental loss or gain-of-function results in significant skeletal muscle hypertrophy in mice. We found 47 genes that meet our search criteria and cause muscle hypertrophy after gene manipulation. They are from high to small effect size: Ski, Fst, Acvr2b, Akt1, Mstn, Klf10, Rheb, Igf1, Pappa, Ppard, Ikbkb, Fstl3, Atgr1a, Ucn3, Mcu, Junb, Ncor1, Gprasp1, Grb10, Mmp9, Dgkz, Ppargc1a (specifically the Ppargc1a4 isoform), Smad4, Ltbp4, Bmpr1a, Crtc2, Xiap, Dgat1, Thra, Adrb2, Asb15, Cast, Eif2b5, Bdkrb2, Tpt1, Nr3c1, Nr4a1, Gnas, Pld1, Crym, Camkk1, Yap1, Inhba, Tp53inp2, Inhbb, Nol3, Esr1. Knock out, knock down, overexpression or a higher activity of these genes causes overall muscle hypertrophy as measured by an increased muscle weight or cross sectional area. The mean effect sizes range from 5 to 345% depending on the manipulated gene as well as the muscle size variable and muscle investigated. Bioinformatical analyses reveal that Asb15, Klf10, Tpt1 are most highly expressed hypertrophy genes in human skeletal muscle when compared to other tissues. Many of the muscle hypertrophy-regulating genes are involved in transcription and ubiquitination. Especially genes belonging to three signaling pathways are able to induce hypertrophy: (a) Igf1-Akt-mTOR pathway, (b) myostatin-Smad signaling, and (c) the angiotensin-bradykinin signaling pathway. The expression of several muscle hypertrophy-inducing genes and the phosphorylation of their protein products changes after human resistance and high intensity exercise, in maximally stimulated mouse muscle or in overloaded mouse plantaris.
Improving the Correctness of Automated Program Repair

Developers spend much of their time fixing bugs in software programs. Automated program repair (APR) techniques aim to alleviate the burden of bug fixing from developers by generating patches at the source-code level. Recently, Generate-and-Validate (G&V) APR techniques show great potential to repair general bugs in real-world applications. Recent evaluations show that G&V techniques repair 8–17.7% of the collected bugs from mature Java or C open-source projects. Despite the promising results, G&V techniques may generate many incorrect patches and are not able to repair every single bug. This thesis makes contributions to improve the correctness of APR by improving the quality assurance of the automatically-generated patches and generating more correct patches by leveraging human knowledge. First, this thesis investigates whether improving the test-suite-based validation can precisely identify incorrect patches that are generated by G&V, and whether it can help G&V generate more correct patches. The result of this investigation, Opad , which combines new fuzz-generated test cases and additional oracles (i.e., memory oracles), is proposed to identify incorrect patches and help G&V repair more bugs correctly. The evaluation of Opad shows that the improved test-suite-based validation identifies 75.2% incorrect patches from G&V techniques. With the integration of Opad , SPR, one of the most promising G&V techniques, repairs one additional bug. Second, this thesis proposes novel APR techniques to repair more bugs correctly, by leveraging human knowledge. Thus, APR techniques can repair new types of bugs that are not currently targeted by G&V APR techniques. Human knowledge in bug-fixing activities is noted in the forms such as commits of bug fixes, developers’ expertise, and documentation pages. Two techniques (APARE and Priv) are proposed to target two types of defects respectively: project-specific recurring bugs and vulnerability warnings by static analysis. APARE automatically learns fix patterns from historical bug fixes (i.e., originally crafted by developers), utilizes spectrum-based fault-localization technique to identify highly-likely faulty methods, and applies the learned fix patterns to generate patches for developers to review. The key innovation of APARE is to utilize a percentage semantic-aware matching algorithm between fix patterns and faulty locations. For the 20 recurring bugs, APARE generates 34 method fixes, 24 of which (70.6%) are correct; 83.3% (20 out of 24) are identical to the fixes generated by developers. In addition, APARE complements current repair systems by generating 20 high-quality method fixes that RSRepair and PAR cannot generate. Priv is a multi-stage remediation system specifically designed for static-analysis securitytesting (SAST) techniques. The prototype is built and evaluated on a commercial SAST
Propylthiouracil-induced Otitis Media with Antineutrophil Cytoplasmic Antibody-associated Vasculitis

We herein report a case of otitis media with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV) induced by propylthiouracil (PTU). A 30-year-old Japanese woman with Graves’ disease, who was treated with PTU, reported with otitis media with sensorineural hearing loss bilaterally and trigeminal neuralgia on the left side, as well as elevated serum levels of myeloperoxidase-ANCA. Prior treatment with antibiotics was ineffective even after tympanostomy. However, clinical remission was immediately achieved after initiating prednisolone together with PTU withdrawal. These findings suggest that PTU therapy induces localized otological involvement as the concept of OMAAV.
Genetic structure in human populations: implications for the personalized medicine value chain.

John A Fossella Weill Medical College of Cornell University, The Sackler Institute for Developmental Psychobiology, 1300 York Avenue, New York, NY 10021, USA Tel. : +1 212 746 3781; E-mail: jaf2014@ med.cornell. edu; http://sacklerinstitute.org/~ fossella/ ‘As personalized medicines are designed with allele-specific biomarkers in mind, the basic question of how these alleles are distributed in human populations naturally arises. ’
Role of brain‐derived neurotrophic factor in the pathogenesis of distention‐associated abdominal pain in bowel obstruction

Previous studies found that visceral sensitivity is increased in bowel obstruction (BO). We hypothesized that mechanical stress‐induced expression of BDNF in smooth muscle cells (SMC) of the distended bowel plays a critical role in visceral hypersensitivity in BO by altering voltage‐gated K+ channel (Kv) activity in sensory neurons.
The Effect of Intellectual Property Boxes on Innovative Activity & Effective Tax Rates

We investigate whether and to what extent the adoption of an intellectual property box increases innovative activity and the extent to which different types of firms benefit financially. We examine the adoption of the intellectual property box in Belgium because it allows us to cleanly identify the impact on innovative activity and effective tax rates. Our results indicate an overall increase in innovative activity as proxied by patent applications, grants, and highly-skilled employment, at the expense of patent quality. We also provide evidence that firms with patents on average enjoy 7.2% to 7.9% lower effective tax rates, with the greatest financial benefits accruing to multinational firms compared to domestic firms. Within multinational firms, those without income shifting opportunities appear to benefit more than other multinationals with income shifting opportunities.