bluuebunny/crossref_metadata_2025 huggingface dataset:
HIV and pericardial fat are associated with abnormal cardiac structure and function among Ugandans
Authors: Buggey Jonathan , Yun Leo , Hung Chung-Lieh , Kityo Cissy , Mirembe Grace , Erem Geoffrey , Truong Tiffany , Ssinabulya Isaac , Tang W H Wilson , Hoit Brian D , McComsey Grace A , Longenecker Chris T
Published: September 2019

Objectives

To examine the relationship between pericardial fat (PCF) and cardiac structure and function among HIV-infected patients in the sub-Saharan African country of Uganda. People living with HIV (PLHIV) have altered fat distribution and an elevated risk for heart failure. Whether altered quantity and radiodensity of fat surrounding the heart relates to cardiac dysfunction in this population is unknown.

Methods

One hundred HIV-positive Ugandans on antiretroviral therapy were compared with 100 age and sex-matched HIV-negative Ugandans; all were >45 years old with >1 cardiovascular disease risk factor. Subjects underwent ECG-gated non-contrast cardiac CT and transthoracic echocardiography with speckle tracking strain imaging. Multivariable linear and logistic regression models were used to explore the association of PCF with echocardiographic outcomes.

Results

Median age was 55% and 62% were female. Compared with uninfected controls, PLHIV had lower body mass index (27 vs 30, p=0.02) and less diabetes (26% vs 45%, p=0.005). Median left ventricular (LV) ejection fraction was 67%. In models adjusted for traditional risk factors, HIV was associated with 10.3 g/m2higher LV mass index (LVMI) (95% CI 3.22 to 17.4; p=0.005), 0.87% worse LV global longitudinal strain (GLS) (95% CI −1.66 to −0.07; p=0.03) and higher odds of diastolic dysfunction (OR 1.96; 95% CI 0.95 to 4.06; p=0.07). In adjusted models, PCF volume was significantly associated with increased LVMI and worse LV GLS, while PCF radiodensity was associated with worse LV GLS (all p<0.05).

Conclusions

In Uganda, HIV infection, PCF volume and density are associated with abnormal cardiac structure and function.
Next-generation sequencing-based BRCA testing on cytological specimens from ovarian cancer ascites reveals high concordance with tumour tissue analysis
Authors: Fumagalli Caterina , Rappa Alessandra , Casadio Chiara , Betella Ilaria , Colombo Nicoletta , Barberis Massimo , Guerini-Rocco Elena
Published: September 2019

Background

With the approval of the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib for newly diagnosed, breast cancer gene(BRCA)1/2mutated, ovarian cancer women, the assessment ofBRCA1/2tumour status will be shortly required at the time of diagnosis.

Aim

To investigate the feasibility of next-generation sequencing (NGS)-based BRCA tumour test on cytological specimens from ovarian cancer ascites.

Methods

We evaluated theBRCA1/2status on neoplastic ascites and corresponding tumour tissue of 11 patients with ovarian cancer, using the NGS ‘Oncomine BRCA Research Assay’.

Results

The NGS-based BRCA test on cytological samples had a success rate of 100%, with 11 of 11 concordantBRCA1/2results between ascites and tumour tissues analyses, including two wild type samples and nine cases harbouring somatic or germline variants.

Conclusion

BRCA test may be performed on ovarian cancer ascites, reproducingBRCA1/2tumour status and representing a useful tool for clinical decision-making.
Randomised prospective trial to assess the clinical utility of multianalyte assay panel with complement activation products for the diagnosis of SLE
Authors: Wallace Daniel J , Alexander Roberta Vezza , O'Malley Tyler , Khosroshahi Arezou , Hojjati Mehrnaz , Loupasakis Konstantinos , Alper Jeffrey , Sherrer Yvonne , Fondal Maria , Kataria Rajesh , Powell Tami , Ibarra Claudia , Narain Sonali , Massarotti Elena , Weinstein Arthur , Dervieux Thierry
Published: September 2019

Objective

We compared the physician-assessed diagnostic likelihood of SLE resulting from standard diagnosis laboratory testing (SDLT) to that resulting from multianalyte assay panel (MAP) with cell-bound complement activation products (MAP/CB-CAPs), which reports a two-tiered index test result having 80% sensitivity and 86% specificity for SLE.

Methods

Patients (n=145) with a history of positive antinuclear antibody status were evaluated clinically by rheumatologists and randomised to SDLT arm (tests ordered at the discretion of the rheumatologists) or to MAP/CB-CAPs testing arm. The primary endpoint was based on the change in the physician likelihood of SLE on a five-point Likert scale collected before and after testing. Changes in pharmacological treatment based on laboratory results were assessed in both arms. Statistical analysis consisted of Wilcoxon and Fisher’s exact tests.

Results

At enrolment, patients randomised to SDLT (n=73, age=48±2 years, 94% females) and MAP/CB-CAPs testing arms (n=72, 50±2 years, 93% females) presented with similar pretest likelihood of SLE (1.42±0.06 vs 1.46±0.06 points, respectively; p=0.68). Post-test likelihood of SLE resulting from randomisation in the MAP/CB-CAPs testing arm was significantly lower than that resulting from randomisation to SDLT arm on review of test results (−0.44±0.10 points vs −0.19±0.07 points) and at the 12-week follow-up visit (−0.61±0.10 points vs −0.31±0.10 points) (p<0.05). Among patients randomised to the MAP/CB-CAPs testing arm, two-tiered positive test results associated significantly with initiation of prednisone (p=0.034).

Conclusion

Our data suggest that MAP/CB-CAPs testing has clinical utility in facilitating SLE diagnosis and treatment decisions.
Abortion and Ectogenesis: Moral Compromise
Authors: Simkulet William
Published: September 2019

The contemporary philosophical literature on abortion primarily revolves around three seemingly intractable debates, concerning the (1) moral status of the fetus, (2) scope of women’s rights and (3) moral relevance of the killing/letting die distinction. The possibility of ectogenesis—technology that would allow a fetus to develop outside of a gestational mother’s womb—presents a unique opportunity for moral compromise. Here, I argue those opposed to abortion have aprima faciemoral obligation to pursue ectogenesis technology and provide ectogenesis for disconnected fetuses as part of a moral compromise.
Incidence and prevalence of vaccine preventable infections in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD): a systemic literature review informing the 2019 update of the EULAR recommendations for vaccination in adult patients with AIIRD
Authors: Furer Victoria , Rondaan Christien , Heijstek Marloes , van Assen Sander , Bijl Marc , Agmon-Levin Nancy , Breedveld Ferdinand C , D'Amelio Raffaele , Dougados Maxime , Kapetanovic Meliha Crnkic , van Laar Jacob M , Ladefoged de Thurah Annette , Landewé Robert , Molto Anna , Müller-Ladner Ulf , Schreiber Karen , Smolar Leo , Walker Jim , Warnatz Klaus , Wulffraat Nico M , Elkayam Ori
Published: September 2019

Objectives

The aims of this study were to update the evidence on the incidence and prevalence rates of vaccine preventable infections (VPI) in patients with autoimmune inflammatory rheumatic diseases (AIIRD) and compare the data to the general population when available.

Methods

A literature search was performed using Medline, Embase and Cochrane library (October 2009 to August 2018). The primary outcome was the incidence or prevalence of VPI in the adult AIIRD population. Meta-analysis was performed when appropriate.

Results

Sixty-three publications out of 3876 identified records met the inclusion criteria: influenza (n=4), pneumococcal disease (n=7), hepatitis B (n=10), herpes zoster (HZ) (n=29), human papillomavirus (HPV) infection (n=13). An increased incidence of influenza and pneumococcal disease was reported in patients with AIIRD. HZ infection-pooled incidence rate ratio (IRR) was 2.9 (95% CI 2.4 to 3.3) in patients with AIIRD versus general population. Among AIIRD, inflammatory myositis conferred the highest incidence rate (IR) of HZ (pooled IRR 5.1, 95% CI 4.3 to 5.9), followed by systemic lupus erythematosus (SLE) (pooled IRR 4.0, 95% CI 2.3 to 5.7) and rheumatoid arthritis (pooled IRR 2.3, 95% CI 2.1 to 2.6). HPV infection-pooled prevalence ratio was 1.6, 95% CI 0.7 to 3.4 versus general population, based on studies mainly conducted in the SLE population in Latin America and Asia. Pooled prevalence of hepatitis B surface antigen and hepatitis B core antibody in patients with AIIRD was similar to the general population, 3%, 95% CI 1% to 5% and 15%, 95% CI 7% to 26%, respectively.

Conclusion

Current evidence shows an increased risk of VPI in patients with AIIRD, emphasising that prevention of infections is essential in these patients.
Dietary fatty acid content and thickness of plantar pads in gilts
Authors: Grandía Juan , Monteagudo Luis Vicente , Sánchez-Abad Paloma , Tejedor María Teresa
Published: September 2019

The objective of this study was to test a diet enriched in the most abundant components of foot fat pads (oleic and palmitic acid) to increase its thickness in gilts. We evaluated the effects of two oleic and palmitic acid dietary concentrations (control and test) and three treatment durations (35, 45, and 65 d) on 116 gilts (Landrace × Large White), all 180-d-old and slaughtered at the end of the study. Both test and control diets contained 5.9% total fat. The control diet contained 0.9% oleic acid and 0.6% palmitic acid; the test diet contained 1.9% and 1.2%, respectively. Body weight (BW), backfat (BF), lateral, and medial plantar pad thickness from the left rear leg were measured. No significant differences were detected for BW or BF between the test and control groups. The lateral pad was always thicker than the medial one (P < 0.001). No significant difference for plantar pad thickness was detected for the 35 d treatment. For the other treatments, thickness increased with respect to the control group (P < 0.01); the percentage of increase ranged from 20.8% (lateral side, 45 d treatment) to 37.8% (lateral side, 65 d treatment). Its effects on foot health must still be demonstrated.
The effects of gasotransmitters inhibition on biochemical and haematological parameters and oxidative stress in propofol-anaesthetized Wistar male rats
Authors: Djuric M. , Nikolic Turnic T. , Kostic S. , Stankovic S. , Radonjic K. , Djuric D. , Zivkovic V. , Jakovljevic V. , Stevanovic P.
Published: September 2019

This study aimed to investigate the effects of propofol through evaluating its interaction with nitric oxide (NO), hydrogen sulfide (H2S), and carbon monoxide (CO). Wistar male rats were divided in 4 groups: (1) bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.); (2) Nω-nitro-l-arginine methyl ester (L-NAME; NO synthase inhibitor, 60 mg/kg bw, i.p.) + bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.); (3) DL-propargylglycine (DL-PAG; H2S synthase inhibitor, 50 mg/kg bw, i.p.) + bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.); (4) zinc protoporphyrin IX (ZnPPIX; CO synthase inhibitor, 50 μmol/kg bw, i.p.) + bolus injection of propofol (1% 10 mg/mL, 100 mg/kg bw, i.p.). Increased levels of albumins, low-density lipoproteins, alkaline phosphatase, amylase, high-sensitivity Troponin T, and fibrinogen were found in L-NAME + propofol group. Platelet crit, platelet count, total cholesterol, and high-density lipoproteins were elevated in ZnPPIX + propofol group. Hydrogen peroxide was increased in all groups treated with gasotransmitters inhibitors. Reduced glutathione was reduced in all groups, superoxide dismutase activity only in L-NAME + propofol. The effect of propofol on various biochemical, haematological, and oxidative stress markers may be at least in part mediated through interaction with 3 estimated gasotransmitters.
Analytic structure of nonhydrodynamic modes in kinetic theory
Authors: Kurkela Aleksi , Wiedemann Urs Achim
Published: September 2019

How physical systems approach hydrodynamic behavior is governed by the decay of nonhydrodynamic modes. Here, we start from a relativistic kinetic theory that encodes relaxation mechanisms governed by different timescales thus sharing essential features of generic weakly coupled nonequilibrium systems. By analytically solving for the retarded correlation functions, we clarify how branch cuts arise generically from noncollective particle excitations, how they interface with poles arising from collective hydrodynamic excitations, and to what extent the appearance of poles remains at best an ambiguous signature for the onset of fluid dynamic behavior. We observe that processes that are slower than the hydrodynamic relaxation timescale can make a system that has already reached fluid dynamic behavior to fall out of hydrodynamics at late times. In addition, the analytical control over this model allows us to explicitly demonstrate how the hydrodynamic gradient expansion of the correlation function can be resummed such that the complete and exact non-analytic form of the correlation function can be recovered.
Sets of Pictures Avoiding Overlaps
Authors: Anselmo Marcella , Giammarresi Dora , Madonia Maria
Published: September 2019

A string set avoids overlaps if it has the property that the prefix of each string in the set does not coincide with the suffix of any string in the set. The problem of avoiding overlaps in strings is extensively investigated since it plays an important role in the context of string matching and coding. The notion of overlap can be extended naturally to two dimensions; two pictures [Formula: see text] and [Formula: see text] have an overlap if one can put one corner of [Formula: see text] on some position in [Formula: see text] in such a way that all symbols in the common positions coincide. A picture with no self-overlaps is called unbordered and it is a generalization in two dimensions of an unbordered (or bifix-free) string.

We first investigate the problem of generating all unbordered pictures of fixed size. Then, we study particular sets of unbordered pictures that are non-overlapping each others. We show that the frame of the pictures has a special role in defining these sets. In particular, we prove that there exist kinds of synchronization frames that can be put around the pictures of any set to make it non-overlapping. Finally, we present a construction of non-expandable non-overlapping sets of pictures which starts from some property of frame-completeness.
On Average Behaviour of Regular Expressions in Strong Star Normal Form
Authors: Broda Sabine , Machiavelo António , Moreira Nelma , Reis Rogério
Published: September 2019

For regular expressions in (strong) star normal form a large set of efficient algorithms is known, from conversions into finite automata to characterisations of unambiguity. In this paper we study the average complexity of this class of expressions using analytic combinatorics. As it is not always feasible to obtain explicit expressions for the generating functions involved, here we show how to get the required information for the asymptotic estimates with an indirect use of the existence of Puiseux expansions at singularities. We study, asymptotically and on average, the alphabetic size, the size of the [Formula: see text]-follow automaton and of the position automaton, as well as the ratio and the size of these expressions to standard regular expressions.
Most Complex Non-Returning Regular Languages
Authors: Brzozowski Janusz A. , Davies Sylvie
Published: September 2019

A regular language [Formula: see text] is non-returning if in the minimal deterministic finite automaton accepting it there are no transitions into the initial state. Eom, Han and Jirásková derived upper bounds on the state complexity of boolean operations and Kleene star, and proved that these bounds are tight using two different binary witnesses. They derived tight upper bounds for concatenation and reversal using three different ternary witnesses. These five witnesses use a total of six different transformations. We show that for each [Formula: see text], there exists a ternary witness of state complexity [Formula: see text] that meets the bound for reversal, and restrictions of this witness to binary alphabets meet the bounds for star, product, and boolean operations. Hence all of these operations can be handled simultaneously with a single witness, using only three different transformations. We also derive tight upper bounds on the state complexity of binary operations that take arguments with different alphabets. We prove that the maximal syntactic semigroup of a non-returning language has [Formula: see text] elements and requires at least [Formula: see text] generators. We find the maximal state complexities of atoms of non-returning languages. We show that there exists a most complex sequence of non-returning languages that meet the bounds for all of these complexity measures. Furthermore, we prove there is a most complex sequence that meets all the bounds using alphabets of minimal size.
Square on Deterministic, Alternating, and Boolean Finite Automata
Authors: Jirásková Galina , Krajňáková Ivana
Published: September 2019

We investigate the state complexity of the square operation on languages represented by deterministic, alternating, and Boolean automata. For each [Formula: see text] such that [Formula: see text], we describe a binary language accepted by an [Formula: see text]-state deterministic finite automaton with [Formula: see text] final states meeting the upper bound [Formula: see text] on the state complexity of its square. We show that in the case of [Formula: see text], the corresponding upper bound cannot be met. Using the binary deterministic witness for square with [Formula: see text] states where half of them are final, we get the tight upper bounds [Formula: see text] and [Formula: see text] on the complexity of the square operation on alternating and Boolean automata, respectively.
Reset Complexity of Ideal Languages Over a Binary Alphabet
Authors: Maslennikova Marina
Published: September 2019

We prove PSPACE-completeness of checking whether a given ideal language serves as the language of reset words for some automaton with at most four states over a binary alphabet. We compare the reset complexity and the state complexity for languages related to slowly synchronizing automata.
Identifying the number of components in Gaussian mixture models using numerical algebraic geometry
Authors: Shirinkam Sara , Alaeddini Adel , Gross Elizabeth
Published: September 2019

Using Gaussian mixture models for clustering is a statistically mature method for clustering in data science with numerous successful applications in science and engineering. The parameters for a Gaussian mixture model (GMM) are typically estimated from training data using the iterative expectation-maximization algorithm, which requires the number of Gaussian components a priori. In this study, we propose two algorithms rooted in numerical algebraic geometry (NAG), namely, an area-based algorithm and a local maxima algorithm, to identify the optimal number of components. The area-based algorithm transforms several GMM with varying number of components into sets of equivalent polynomial regression splines. Next, it uses homotopy continuation methods for evaluating the resulting splines to identify the number of components that is most compatible with the gradient data. The local maxima algorithm forms a set of polynomials by fitting a smoothing spline to a dataset. Next, it uses NAG to solve the system of the first derivatives for finding the local maxima of the resulting smoothing spline, which represent the number of mixture components. The local maxima algorithm also identifies the location of the centers of Gaussian components. Using a real-world case study in automotive manufacturing and extensive simulations, we demonstrate that the performance of the proposed algorithms is comparable with that of Akaike information criterion (AIC) and Bayesian information criterion (BIC), which are popular methods in the literature. We also show the proposed algorithms are more robust than AIC and BIC when the Gaussian assumption is violated.
Audit Firm Assessments of Cyber-Security Risk: Evidence from Audit Fees and SEC Comment Letters
Authors: Rosati Pierangelo , Gogolin Fabian , Lynn Theo
Published: September 2019

This study investigates the impact of cyber-security incidents on audit fees. Using a sample of 5,687 firms, we find that (i) breached firms are charged 12% higher audit fees, and (ii) firms operating in the same industry of a breached firm are charged 5% higher fees. Finally, using a difference-in-difference regression on a propensity score matched sample, we provide evidence suggesting that auditors do not revise their audit risk assessment following a breach. Overall, these results suggest that the increase in audit fees in the year of a breach is only temporary, and that auditors include cyber-security risk in their audit risk assessment even before an incident occurs. Higher cyber-security risk is ultimately reflected in higher audit fees paid by auditees.
CAN-TM
Authors: Mrabet Manel , Saied Yosra Ben , Saidane Leila Azouz
Published: September 2019

The increasing proliferation of Cloud Services (CSs) has made the reliable CS selection problem a major challenge. To tackle this problem, this article introduces a new trust model called Chain Augmented Naïve Bayes-based Trust Model (CAN-TM). This model leverages the correlation that may exist among QoS attributes to solve many issues in reliable CS selection challenge, such as predicting missing assessments and improving accuracy of trust computing. This is achieved by combining both the n-gram Markov model and the Naïve Bayes model. Experiments are conducted to validate that our proposed CAN-TM outperforms state-of-the-art approaches.
Online Bipartite Matching with Amortized
O
(log
2
n
) Replacements
Authors: Bernstein Aaron , Holm Jacob , Rotenberg Eva
Published: September 2019

In the online bipartite matching problem with replacements, all the vertices on one side of the bipartition are given, and the vertices on the other side arrive one-by-one with all their incident edges. The goal is to maintain a maximum matching while minimizing the number of changes (replacements) to the matching. We show that the greedy algorithm that always takes the shortest augmenting path from the newly inserted vertex (denoted the SAP protocol) uses at most amortized
O
(log
2
n
) replacements per insertion, where
n
is the total number of vertices inserted. This is the first analysis to achieve a polylogarithmic number of replacements for
any
replacement strategy, almost matching the Ω (log
n
) lower bound. The previous best strategy known achieved amortized
O
(√
n
) replacements [Bosek, Leniowski, Sankowski, Zych, FOCS 2014]. For the SAP protocol in particular, nothing better than the trivial
O
(
n
) bound was known except in special cases. Our analysis immediately implies the same upper bound of
O
(log
2
n
) reassignments for the capacitated assignment problem, where each vertex on the static side of the bipartition is initialized with the capacity to serve a number of vertices.

We also analyze the problem of minimizing the maximum server load. We show that if the final graph has maximum server load
L
, then the SAP protocol makes amortized
O
(min {
L
log
2
n
, √
n
log
n
}) reassignments. We also show that this is close to tight, because Ω (min {
L
, √
n
}) reassignments can be necessary.
Offline versus Online Representation Learning of Documents Using External Knowledge
Authors: Tamine Lynda , Soulier Laure , Nguyen Gia-Hung , Souf Nathalie
Published: September 2019

An intensive recent research work investigated the combined use of hand-curated knowledge resources and corpus-driven resources to learn effective text representations. The overall learning process could be run by online revising the learning objective or by offline refining an original learned representation. The differentiated impact of each of the learning approaches on the quality of the learned representations has not been studied so far in the literature. This article focuses on the design of comparable offline vs. online knowledge-enhanced document representation learning models and the comparison of their effectiveness using a set of standard IR and NLP downstream tasks. The results of quantitative and qualitative analyses show that (1) offline vs. online learning approaches have dissimilar result trends regarding the task as well as the dataset distribution counts with regard to domain application; (2) while considering external knowledge resources is undoubtedly beneficial, the way used to express relational constraints could affect semantic inference effectiveness. The findings of this work present opportunities for the design of future representation learning models, but also for providing insights about the evaluation of such models.
The Healing of Oxidative Injuries with Trehalose in UVB-Irradiated Rabbit Corneas
Authors: Cejka Cestmir , Kossl Jan , Hermankova Barbora , Holan Vladimir , Kubinova Sarka , Olmiere Céline , Cejkova Jitka
Published: September 2019

Our previous research revealed that trehalose, a nonreducing disaccharide of glucose and an important stress responsive factor, proved to have anti-inflammatory, antiapoptotic, and particularly antioxidant properties in UVB-irradiated corneas. Trehalose reduced oxidative stress in corneas induced by UVB irradiation, by means of a decrease in the antioxidant/prooxidant imbalance in the corneal epithelium. In this study, we demonstrate that trehalose of 3% or 6% concentration in eye drops directly decreases oxidative stress in UVB-irradiated corneas, by removing the excessive amount of reactive oxygen species (ROS). Trehalose drops applied on corneas during UVB irradiation once daily for four days resulted in a reduction or even absence of the oxidative stress, DNA damage, and peroxynitrite formation (detected by nitrotyrosine residues), seen in buffer-treated corneas. Furthermore, trehalose treatment applied curatively after repeated irradiation for the subsequent fourteen days led to the renewal of corneal transparency and significant suppression or even absence of neovascularization. This was in contrast to buffer-treated irradiated corneas, where the intracorneal inflammation was developed and the untransparent corneas were vascularized. In conclusion, the treatment of UVB-irradiated corneas with trehalose eye drops removed the excessive amount of ROS in the corneal epithelium, leading to the suppression of oxidative stress and favorable corneal healing. The 6% trehalose showed a higher intensive antioxidant effect.
Applicability of Dmax Method on Heart Rate Variability to Estimate the Lactate Thresholds in Male Runners
Authors: Nascimento Eduardo Marcel Fernandes , Antunes Diego , do Nascimento Salvador Paulo Cesar , Borszcz Fernando Klitzke , de Lucas Ricardo Dantas
Published: September 2019

Introduction. The purpose of this study was to evaluate the application of the Dmax method on heart rate variability (HRV) to estimate the lactate thresholds (LT), during a maximal incremental running test (MIRT). Methods. Nineteen male runners performed two MIRTs, with the initial speed at 8 km·h−1 and increments of 1 km·h−1 every 3 minutes, until exhaustion. Measures of HRV and blood lactate concentrations were obtained, and lactate (LT1 and LT2) and HRV (HRVTDMAX1 and HRVTDMAX2) thresholds were identified. ANOVA with Scheffe’s post hoc test, effect sizes (d), the bias ± 95% limits of agreement (LoA), standard error of the estimate (SEE), Pearson’s (r), and intraclass correlation coefficient (ICC) were calculated to assess validity. Results. No significant differences were observed between HRVTDMAX1 and LT1 when expressed for speed (12.1 ± 1.4 km·h−1 and 11.2 ± 2.1 km·h−1; p=0.55; d = 0.45; r = 0.46; bias ± LoA = 0.8 ± 3.7 km·h−1; SEE = 1.2 km·h−1 (95% CI, 0.9–1.9)). Significant differences were observed between HRVTDMAX2 and LT2 when expressed for speed (12.0 ± 1.2 km·h−1 and 14.1 ± 2.5 km·h−1; p=0.00; d = 1.21; r = 0.48; bias ± LoA = −1.0 ± 1.8 km·h−1; SEE = 1.1 km·h−1 (95% CI, 0.8–1.6)), respectively. Reproducibility values were found for the LT1 (ICC = 0.90; bias ± LoA = −0.7 ± 2.0 km·h−1), LT2 (ICC = 0.97; bias ± LoA = −0.1 ± 1.1 km·h−1), HRVTDMAX1 (ICC = 0.48; bias ± LoA = −0.2 ± 3.4 km·h−1), and HRVTDMAX2 (ICC = 0.30; bias ± LoA = 0.3 ± 3.5 km·h−1). Conclusions. The Dmax method applied over a HRV dataset allowed the identification of LT1 that is close to aerobic threshold, during a MIRT.
Role of 24-Hour Intraocular Pressure Monitoring in Glaucoma Management
Authors: Ho Chun Hing , Wong Jasper K. W.
Published: September 2019

Glaucoma is the leading cause of irreversible blindness worldwide and the prevalence is on the rising trend. Intraocular pressure (IOP) reduction is the mainstay of treatment. The current practice of IOP monitoring is based on spot measurements during clinic visits during office hours. However, there are up to 50% of glaucoma patients who had normal initial IOP, while some treated patients continued to have progressive glaucomatous optic nerve damage even with a low IOP. Recent studies have shown that the IOP of glaucoma patients fluctuated during the day with different patterns, and some of them had peak IOP outside office hours. These findings provided us with new insights on the role of 24-hour IOP monitoring in managing normal tension glaucoma and patients with progressive deterioration despite apparently well-controlled IOP. Nevertheless, results to date are rather inconsistent, and there is no consensus yet. In this review, we briefly highlighted the current modalities of 24-hour IOP monitoring and summarized the characteristic 24-hour IOP pattern and the clinical relevance of IOP parameters in predicting glaucomatous progression in different glaucoma subtypes. We also discussed the therapeutic efficacy of current glaucoma treatment modalities with respect to the mentioned 24-hour IOP profiles, so as to strengthen the role of 24-hour IOP monitoring in identifying and stratifying the risks of progression in glaucoma patients, as well as optimizing treatments according to their IOP profiles.
Investigating the Interaction of Nanodiamonds with Human Serum Albumin and Induced Cytotoxicity
Authors: Chen Miaomiao , Zuo Xiaoshuang , Xu Qinqin , Wang Rong , Fan Suhua , Wu Hai
Published: September 2019

Nanodiamonds (NDs) have been recognized as emerging carbon-based delivery vehicles due to their biocompatibility. NDs were reported to be nontoxic and suited for biomedical applications in the complete cell culture medium. However, in this study, the cytotoxicity of NDs in serum-free medium was studied and indicated that serum proteins in cell culture medium played significant effect on the toxicity of NDs. Therefore, the interaction mechanism between NDs and a serum protein (human serum albumin, HSA) was first investigated by fluorescence quenching technique and circular dichroism (CD) spectrometry. The results suggest that HSA strongly bonds on the NDs surface to form “protein corona,” which not only prevents the aggregation of NDs and improves its stability but also inhibits the cytotoxicity of NDs. In serum-free medium, NDs exhibited obvious toxicity toward the human lung epithelial cell line (BEAS-2B) and showed concentration-dependent cytotoxicity. In the presence of bovine serum albumin (BSA), which shares structural homology and similar properties with HSA, toxicity of NDs was apparently inhibited. Therefore, the interaction between serum protein and NDs should be considered in the understanding of the biological effects of NDs exposure in biomedical applications.
Laboratory Markers in the Prediction of Acute Perforated Appendicitis in Children
Authors: Yang Jing , Liu Chong , He Yuxia , Cai Zhangqiao
Published: September 2019

Objective. This study aimed to explore the laboratory markers associated with perforation in children with acute appendicitis.Methods. This retrospective study reviewed 1895 children (3–18 years old) with confirmed acute appendicitis from 2007 to 2017. Clinical (demographic characteristics, symptoms, and signs) and laboratory data (white blood cell count, C-reactive protein (CRP), procalcitonin, D-lactate, platelet count, bilirubin, aspartate aminotransferase, and alanine aminotransferase) were collected and compared between perforated and nonperforated groups. The logistic regression analysis was performed to identify independent risk factors.Results. Of all patients, 613 children were perforated. Children with perforation had significantly longer duration of symptoms, higher white blood cell count, CRP level, and neutrophils percentage, and lower serum sodium level. Elevated white blood cell count with CRP level and elevated neutrophils percentage with CRP level were found to be associated with risk of perforation.Conclusions. White blood cell count with C-reactive protein and neutrophils percentage with CRP are important markers in distinguishing perforated appendicitis from nonperforated appendicitis in pediatric subjects.
Development of a Three‐Dimensional Fully Nonlinear Potential Numerical Wave Tank for a Heaving Buoy Wave Energy Converter
Authors: Kim Sung-Jae , Koo Weoncheol
Published: September 2019

The hydrodynamic performance of a vertical cylindrical heaving buoy‐type floating wave energy converter under large‐amplitude wave conditions was calculated. For this study, a three‐dimensional fully nonlinear potential‐flow numerical wave tank (3D‐FN‐PNWT) was developed. The 3D‐FN‐PNWT was based on the boundary element method with Rankine panels. Using the mixed Eulerian–Lagrangian (MEL) method for water particle movement, nonlinear waves were produced in the PNWT. The PNWT can calculate the wave forces acting on the buoy accurately using an acceleration potential approach. The constant panels and least‐square gradient reconstruction method were applied to regridding of computational boundaries. An artificial damping zone was employed to satisfy the open‐sea conditions at the end free surface boundaries. The diffraction and radiation problems were solved, and their solutions were confirmed by a comparison with previous studies. The interaction of the incident wave, floating body, and power take‐off (PTO) behavior was examined in the time domain using the developed 3D‐FN‐PNWT. From comparison, the difference between the conventional linear analysis and the nonlinear analysis in large‐amplitude waves was examined.
Effective Modulus Estimation Method of QT400‐18 Cast Iron with Repair Welding
Authors: Wei Tao , Liu Wei , Gou Wenxuan , Kou Junqiang
Published: September 2019

Repair welding is an important remediation process for castings with slight defects. In this paper, the tensile behaviors of the QT400‐18 nodular cast iron with different repair welding sizes were experimentally analyzed. Specimens with different diameters of the filler region were prepared by the same welding process. The fracture initiated in the filler region under uniaxial tensile loading. The modulus, strength, and ductility decreased with the weld diameter increase. The postyield hardening phenomenon was not observed in the repaired specimen. The repair region ratio was defined as the proportion of the repair welding area to the cross‐sectional area of the structure. The effective modulus of the repaired specimens decreased with the repair region ratio increase, and the relationship between them was fitted by a negative exponential function. The repair welding region was treated as an inclusion in the matrix of castings, and the volume fraction of inclusion was applied to characterize the repair welding size. Based on the theories of Eshelby tensor and Mori–Tanaka equivalent method, a method for estimating macroscopic effective modulus of repair welding castings was established. The theoretical solutions were in good agreement with the experimental results. The method will be helpful in estimating the safe service limit of repair welded castings.
Optimisation of Cutting Tool and Cutting Parameters in Face Milling of Custom 450 through the Taguchi Method
Authors: Gokce Harun
Published: September 2019

Stainless steels with unique corrosion resistance are used in applications with a wide range of fields, especially in the medical, food, and chemical sectors, to maritime and nuclear power plants. The low heat conduction coefficient and the high mechanical properties make the workability of stainless steel materials difficult and cause these materials to be in the class of hard-to-process materials. In this study, suitable cutting tools and cutting parameters were determined by the Taguchi method taking surface roughness and cutting tool wear into milling of Custom 450 martensitic stainless steel. Four different carbide cutting tools, with 40, 80, 120, and 160 m/min cutting speeds and 0.05, 0.1, 0.15, and 0.2 mm/rev feed rates, were selected as cutting parameters for the experiments. Surface roughness values and cutting tool wear amount were determined as a result of the empirical studies. ANOVA was performed to determine the significance levels of the cutting parameters on the measured values. According to ANOVA, while the most effective cutting parameter on surface roughness was the feed rate (% 50.38), the cutting speed (% 81.15) for tool wear was calculated.
Inflammatory Biomarkers as Predictors of Response to Immunotherapy in Urological Tumors
Authors: Schepisi Giuseppe , Brighi Nicole , Cursano Maria Concetta , Gurioli Giorgia , Ravaglia Giorgia , Altavilla Amelia , Burgio Salvatore Luca , Testoni Sara , Menna Cecilia , Farolfi Alberto , Casadei Chiara , Tonini Giuseppe , Santini Daniele , De Giorgi Ugo
Published: September 2019

Immunotherapy represents the new era of cancer treatment because of its promising results in various cancer types. In urological tumors, the use of the immune-checkpoint inhibitors (ICIs) is increasingly spreading. Although not all patients and not all diseases respond equally well to immunotherapy, there is an increasing need to find predictive markers of response to ICIs. Patient- and tumor-related factors may be involved in primary and secondary resistance to immunotherapy: tumor-derived protein and cytokines, tumor mutational burden, and patient performance status and comorbidities can condition tumor response to ICIs. Recently, some of these factors have been evaluated as potential biomarkers of response, with conflicting results. To date, the expression of programmed death-ligand 1 (PD-L1) and the presence of deficient mismatch repair (dMMR) in tumor tissue are the only biomarkers capable of guiding the clinician’s decision in urothelial cancer and prostate cancer, respectively. In this review, we performed a comprehensive search of the main publications on biomarkers that are predictive of response to ICIs in urological cancers. Our aim was to understand whether existing data have the potential to drive clinical decision-making in the near future.
Safety Threshold Determination for Blasting Vibration of the Lining in Existing Tunnels under Adjacent Tunnel Blasting
Authors: Xue Fei , Xia Caichu , Li Guoliang , Jin Baocheng , He Yongwang , Fu Yapeng
Published: September 2019

The effects of tunnel blast excavation on the lining structures of adjacent tunnels are comprehensively studied for the Xinling highway tunnel project. First, the LS‐DYNA software is applied to obtain the characteristics of vibration velocities and dynamic stresses at different positions of the tunnel liner. The results indicate that the maximum peak particle velocity (PPV) is located on the haunch of the lining facing the blasting source and that the PPV and peak tensile stress decrease with the increase in the surrounding rock grade. Second, a site test on blasting vibration is conducted to verify the simulation results. By using regression analysis of the measured vibration data, the calculation method of maximum charge per delay for optimizing blasting excavation under different surrounding rock grades is obtained. Finally, based on the statistical relationship between crack alteration and PPV on the lining before and after blasting, the safety thresholds of PPV for different portions of the tunnel are determined. The recommended safety threshold of PPV is 10 cm/s for intact lining and for B‐grade and V‐grade linings of the surrounding rock tunnel. However, if the lining crack grade falls between 1A and B, then the recommended safety thresholds of PPV for the III‐grade and IV‐grade surrounding rock tunnel are 5 cm/s and 6 cm/s, respectively. The threshold PPV proposed in this study has been successfully applied to restrict blast‐induced damage during new tunnel excavation of the Xinling tunnel project.
Elevated H2AX Phosphorylation Observed with kINPen Plasma Treatment Is Not Caused by ROS-Mediated DNA Damage but Is the Consequence of Apoptosis
Authors: Bekeschus Sander , Schütz Clarissa S. , Nießner Felix , Wende Kristian , Weltmann Klaus-Dieter , Gelbrich Nadine , von Woedtke Thomas , Schmidt Anke , Stope Matthias B.
Published: September 2019

Phosphorylated histone 2AX (γH2AX) is a long-standing marker for DNA double-strand breaks (DSBs) from ionizing radiation in the field of radiobiology. This led to the perception ofγH2AX being a general marker of direct DNA damage with the treatment of other agents such as low-dose exogenous ROS that unlikely act on cellular DNA directly. Cold physical plasma confers biomedical effects majorly via release of reactive oxygen and nitrogen species (ROS).In vitro, increase ofγH2AX has often been observed with plasma treatment, leading to the conclusion that DNA damage is a direct consequence of plasma exposure. However, increase inγH2AX also occurs during apoptosis, which is often observed with plasma treatment as well. Moreover, it must be questioned if plasma-derived ROS can reach into the nucleus and still be reactive enough to damage DNA directly. We investigatedγH2AX induction in a lymphocyte cell line upon ROS exposure (plasma, hydrogen peroxide, or hypochlorous acid) or UV-B light. Cytotoxicity andγH2AX induction was abrogated by the use of antioxidants with all types of ROS treatment but not UV radiation. H2AX phosphorylation levels were overall independent of analyzing either all nucleated cells or segmentingγH2AX phosphorylation for each cell cycle phase. SB202190 (p38-MAPK inhibitor) and Z-VAD-FMK (pan-caspase inhibitor) significantly inhibitedγH2AX induction upon ROS but not UV treatment. Finally, and despiteγH2AX induction, UV but not plasma treatment led to significantly increased micronucleus formation, which is a functional read-out of genotoxic DNA DSBs. We conclude that plasma-mediated and low-ROSγH2AX induction depends on caspase activation and hence is not the cause but consequence of apoptosis induction. Moreover, we could not identify lasting mutagenic effects with plasma treatment despite phosphorylation of H2AX.
A Review of Potential Beneficial Effects of Honey on Bone Health
Authors: Kamaruzzaman Mohd Amir , Chin Kok-Yong , Mohd Ramli Elvy Suhana
Published: September 2019

Bone remodelling is a complex and tightly regulated process. Disruption of bone remodelling skewing towards resorption will cause osteoporosis and increase the risk of fragility fracture. Honey is a natural product containing various bioactive ingredients with health benefits, especially polyphenols. Therefore, honey may be a novel dietary supplement to prevent osteoporosis. This review aims to summarize the current evidence on the effects of honey on bone health. The evidence reported so far indicates a skeletal-beneficial effect of honey in animal models of osteoporosis. However, the number of studies on humans is limited. Honey can protect the bone via its antioxidant and anti-inflammatory properties, primarily through its polyphenol content that acts upon several signalling pathways, leading to bone anabolic and antiresorptive effects. In conclusion, honey is a potential functional food for bone health, but the dose and the bioactive contents of honey need to be verified prior to its application in humans.
Prostaglandin E2 Reverses the Effects of DNA Methyltransferase Inhibitor and TGFB1 on the Conversion of Naive T Cells to iTregs
Authors: Sahin Mehmet , Sahin Emel
Published: September 2019

Naturally occurring regulatory T cells (nTregs) are produced under thymic (tTregs) or peripherally induced (pTregs) conditions in vivo. On the other hand, Tregs generated from naive T cells in vitro under some circumstances, such as treatment with transforming growth factor-β (TGFB), are called induced Tregs (iTregs). Tregs are especially characterized by FOXP3 expression, which is mainly controlled by DNA methylation. nTregs play important roles in the suppression of immune response and self-tolerance. The prostaglandin E2 (PGE2) pathway was reported to contribute to regulatory functions of tumor-infiltrating nTregs. In this study, we examined whether PGE2 contributes to the formation of iTregs treated with TGFB1 and 5-aza-2′-deoxycytidine (5-aza-dC), which is a DNA methyltransferase inhibitor. We found that the protein and gene expression levels of FOXP3 and IL-10 were increased in 5-aza-dC and TGFB1-treated T cells in vitro. However, the addition of PGE2 to these cells reversed these increments significantly. In CFSE-based cell suppression assays, we demonstrated that PGE2 decreased the suppressive functions of 5-aza-dC and TGFB1-treated T cells.
Intracranial Hemorrhage following Lumbar Puncture in a Patient on Apixaban
Authors: Vijapura Priyanka , Maniaci Michael J.
Published: September 2019

Currently, clinical practice recommendations regarding patients in need of emergent lumbar puncture who are taking direct oral anticoagulants (DOACs) are based upon expert opinion, as evidence-based guidelines are unavailable. We present the case of an 80-year-old Caucasian lady who underwent diagnostic lumbar puncture for presumed meningitis while on therapeutic apixaban for nonvalvular atrial fibrillation. She was subsequently found to have bilateral subdural hematomas. This case report reviews both the current criteria for computerized tomography brain imaging prior to lumbar puncture as well as the bleeding risks of lumbar puncture while on a DOAC.
Therapeutic Modulation of the Immune Response in Arrhythmogenic Cardiomyopathy
Authors: Chelko Stephen P. , Asimaki Angeliki , Lowenthal Justin , Bueno-Beti Carlos , Bedja Djahida , Scalco Arianna , Amat-Alarcon Nuria , Andersen Peter , Judge Daniel P. , Tung Leslie , Saffitz Jeffrey E.
Published: September 2019

Background:

Inflammation is a prominent feature of arrhythmogenic cardiomyopathy (ACM), but whether it contributes to the disease phenotype is not known.

Methods:

To define the role of inflammation in the pathogenesis of ACM, we characterized nuclear factor-κB signaling in ACM models in vitro and in vivo and in cardiac myocytes from patient induced pluripotent stem cells.

Results:

Activation of nuclear factor-κB signaling, indicated by increased expression and nuclear accumulation of phospho-RelA/p65, occurred in both an in vitro model of ACM (expression of

JUP
2157del2

in neonatal rat ventricular myocytes) and a robust murine model of ACM (homozygous knock-in of mutant desmoglein-2 [
Dsg2

mut/mu
t

]) that recapitulates the cardiac manifestations seen in patients with ACM. Bay 11-7082, a small-molecule inhibitor of nuclear factor-κB signaling, prevented the development of ACM disease features in vitro (abnormal redistribution of intercalated disk proteins, myocyte apoptosis, release of inflammatory cytokines) and in vivo (myocardial necrosis and fibrosis, left ventricular contractile dysfunction, electrocardiographic abnormalities). Hearts of
Dsg2
mut/mut
mice expressed markedly increased levels of inflammatory cytokines and chemotactic molecules that were attenuated by Bay 11-7082. Salutary effects of Bay 11-7082 correlated with the extent to which production of selected cytokines had been blocked. Nuclear factor-κB signaling was also activated in cardiac myocytes derived from a patient with ACM. These cells produced and secreted abundant inflammatory cytokines under basal conditions, and this was also greatly reduced by Bay 11-7082.

Conclusions:

Inflammatory signaling is activated in ACM and drives key features of the disease. Targeting inflammatory pathways may be an effective new mechanism-based therapy for ACM.