bluuebunny/crossref_metadata_2025 huggingface dataset:
Conditional Lower Bounds for All-Pairs Max-Flow
Authors: Krauthgamer Robert , Trabelsi Ohad
Published: August 2018

We provide evidence that computing the maximum flow value between every pair of nodes in a
directed
graph on
n
nodes,
m
edges, and capacities in the range [1‥
n
], which we call the All-Pairs Max-Flow problem, cannot be solved in time that is significantly faster (i.e., by a polynomial factor) than
O
(
n
3
) even for sparse graphs, namely
m
=
O
(
n
); thus for general
m
, it cannot be solved significantly faster than
O
(
n
2
m
). Since a single maximum
st
-flow can be solved in time Õ(
m
√
n
) [Lee and Sidford, FOCS 2014], we conclude that the all-pairs version might require time equivalent to Ω
˜
(
n
3/2
) computations of maximum
st
-flow, which strongly separates the directed case from the undirected one. Moreover, if maximum
st
-flow can be solved in time Õ(
m
), then the runtime of Ω
˜
(
n
2
) computations is needed. This is in contrast to a conjecture of Lacki, Nussbaum, Sankowski, and Wulff-Nilsen [FOCS 2012] that All-Pairs Max-Flow in general graphs can be solved faster than the time of
O
(
n
2
) computations of maximum
st
-flow.

Specifically, we show that in sparse graphs
G
= (
V
,
E
,
w
), if one can compute the maximum
st
-flow from every
s
in an input set of sources
S
⊆
V
to every
t
in an input set of sinks
T
⊆
V
in time
O
((|
S
||
T
|
m
)
1−ε
), for some |
S
|, |
T
| and a constant ε > 0, then MAX-CNF-SAT (maximum satisfiability of conjunctive normal form formulas) with
n
′ variables and
m
′ clauses can be solved in time
m
′

O
(1)

2

(1−δ)
n
′

for a constant δ(ε) > 0, a problem for which not even 2

n
′

/
poly
(
n
′) algorithms are known. Such running time for MAX-CNF-SAT would in particular refute the Strong Exponential Time Hypothesis (SETH). Hence, we improve the lower bound of Abboud, Vassilevska-Williams, and Yu [STOC 2015], who showed that for every fixed ε > 0 and |
S
| = |
T
| =
O
(√
n
), if the above problem can be solved in time
O
(
n
3/2−ε
), then some incomparable (and intuitively weaker) conjecture is false. Furthermore, a larger lower bound than ours implies strictly super-linear time for maximum
st
-flow problem, which would be an amazing breakthrough.

In addition, we show that All-Pairs Max-Flow in
uncapacitated
networks with every edge-density
m
=
m
(
n
) cannot be computed in time significantly faster than
O
(
mn
), even for acyclic networks. The gap to the fastest known algorithm by Cheung, Lau, and Leung [FOCS 2011] is a factor of
O
(
m
ω−1
/
n
), and for acyclic networks it is
O
(
n
ω−1
), where ω is the matrix multiplication exponent.

Finally, we extend our lower bounds to the version that asks only for the maximum-flow values below a given threshold (over all source-sink pairs).
Device-Free Motion & Trajectory Detection via RFID
Authors: Liang Xiaoxuan , Huang Zhangqin , Yang Shengqi , Qiu Lanxin
Published: August 2018

Compared with traditional methods that employ inertial sensors or wireless sensors, device-free approaches do not require that people carry devices, and they are considered a useful technique for indoor navigation and posture recognition. However, few existing methods can detect the trajectory and movements of humans at the same time. In this study, we propose a scheme called PADAR for addressing these two problems simultaneously by using passive radio frequency identification (RFID) tags but without attaching them to the human body. The idea is based on the principle of radio tomographic imaging, where the variance in a tag’s backscattered radio frequency signal strength is influenced by human movement. We integrated a commodity off-the-shelf RFID reader with a two-dimensional phased array antenna and a matrix of passive tags to evaluate the performance of our scheme. We conducted experiments in a simulated indoor environment. The experimental results showed that PADAR achieved an accuracy of over 70%.
QMLE
Authors: Wang Weikun , Casale Giuliano , Kattepur Ajay , Nambiar Manoj K.
Published: August 2018

Estimating the demands placed by services on physical resources is an essential step for the definition of performance models. For example, scalability analysis relies on these parameters to predict queueing delays under increasing loads. In this article, we investigate maximum likelihood (ML) estimators for demands at load-independent and load-dependent resources in systems with parallelism constraints. We define a likelihood function based on state measurements and derive necessary conditions for its maximization. We then obtain novel estimators that accurately and inexpensively obtain service demands using only aggregate state data. With our approach, and also thanks to approximation methods for computing marginal and joint distributions for the load-dependent case, confidence intervals can be rigorously derived, explicitly taking into account both topology and concurrency levels of the services. Our estimators and their confidence intervals are validated against simulations and real system measurements for two multi-tier applications, showing high accuracy also in models with load-dependent resources.
Efficient Evaluation and Static Analysis for Well-Designed Pattern Trees with Projection
Authors: Barceló Pablo , Kröll Markus , Pichler Reinhard , Skritek Sebastian
Published: August 2018

Conjunctive queries (CQs) fail to provide an answer when the pattern described by the query does not exactly match the data. CQs might thus be too restrictive as a querying mechanism when data is semistructured or incomplete. The semantic web therefore provides a formalism—known as
(projected) well-designed pattern trees
(pWDPTs)—that tackles this problem: pWDPTs allow us to formulate queries that match parts of the query over the data if available, but do not ignore answers of the remaining query otherwise. Here we abstract away the specifics of semantic web applications and study pWDPTs over arbitrary relational schemas. Since the language of pWDPTs subsumes CQs, their evaluation problem is intractable. We identify structural properties of pWDPTs that lead to (fixed-parameter) tractability of various variants of the evaluation problem. We also show that checking if a pWDPT is equivalent to one in our tractable class is in 2EXPTIME. As a corollary, we obtain fixed-parameter tractability of evaluation for pWDPTs with such good behavior. Our techniques also allow us to develop a theory of approximations for pWDPTs.
Mechanisms Underlying Muscle Protein Imbalance Induced by Alcohol
Authors: Kimball Scot R. , Lang Charles H.
Published: August 2018

Both acute intoxication and longer-term cumulative ingestion of alcohol negatively impact the metabolic phenotype of both skeletal and cardiac muscle, independent of overt protein calorie malnutrition, resulting in loss of skeletal muscle strength and cardiac contractility. In large part, these alcohol-induced changes are mediated by a decrease in protein synthesis that in turn is governed by impaired activity of a protein kinase, the mechanistic target of rapamycin (mTOR). Herein, we summarize recent advances in understanding mTOR signal transduction, similarities and differences between the effects of alcohol on this central metabolic controller in skeletal muscle and in the heart, and the effects of acute versus chronic alcohol intake. While alcohol-induced alterations in global proteolysis via activation of the ubiquitin-proteasome pathway are equivocal, emerging data suggest alcohol increases autophagy in muscle. Further studies are necessary to define the relative contributions of these bidirectional changes in protein synthesis and autophagy in the etiology of alcoholic myopathy in skeletal muscle and the heart.
Nonselective autophagy reduces mitochondrial content during starvation in Caenorhabditis elegans
Authors: Hibshman Jonathan D. , Leuthner Tess C. , Shoben Chelsea , Mello Danielle F. , Sherwood David R. , Meyer Joel N. , Baugh L. Ryan
Published: August 2018

Starvation significantly alters cellular physiology, and signs of aging have been reported to occur during starvation. Mitochondria are essential to the regulation of cellular energetics and aging. We sought to determine whether mitochondria exhibit signs of aging during starvation and whether quality control mechanisms regulate mitochondrial physiology during starvation. We describe effects of starvation on mitochondria in the first and third larval stages of the nematode Caenorhabditis elegans. When starved, C. elegans larvae enter developmental arrest. We observed fragmentation of the mitochondrial network, a reduction in mitochondrial DNA (mtDNA) copy number, and accumulation of DNA damage during starvation-induced developmental arrest. Mitochondrial function was also compromised by starvation. Starved worms had lower basal, maximal, and ATP-linked respiration. These observations are consistent with reduced mitochondrial quality, similar to mitochondrial phenotypes during aging. Using pharmacological and genetic approaches, we found that worms deficient for autophagy were short-lived during starvation and recovered poorly from extended starvation, indicating sensitivity to nutrient stress. Autophagy mutants unc-51/Atg1 and atg-18/Atg18 maintained greater mtDNA content than wild-type worms during starvation, suggesting that autophagy promotes mitochondrial degradation during starvation. unc-51 mutants also had a proportionally smaller reduction in oxygen consumption rate during starvation, suggesting that autophagy also contributes to reduced mitochondrial function. Surprisingly, mutations in genes involved in mitochondrial fission and fusion as well as selective mitophagy of damaged mitochondria did not affect mitochondrial content during starvation. Our results demonstrate the profound influence of starvation on mitochondrial physiology with organismal consequences, and they show that these physiological effects are influenced by autophagy.
Revascularization and endothelial progenitor cells in stroke
Authors: Esquiva Gema , Grayston Alba , Rosell Anna
Published: August 2018

Stroke is one of the leading causes of death and disability worldwide. Tremendous improvements have been achieved in the acute care of stroke patients with the implementation of stroke units, thrombolytic drugs, and endovascular trombectomies. However, stroke survivors with neurological deficits require long periods of neurorehabilitation, which is the only approved therapy for poststroke recovery. With this scenario, more treatments are urgently needed, and only the understanding of the mechanisms of brain recovery might contribute to identify new therapeutic agents. Fortunately, brain injury after stroke is counteracted by the birth and migration of several populations of progenitor cells towards the injured areas, where angiogenesis and vascular remodeling play a key role providing trophic support and guidance during neurorepair. Endothelial progenitor cells (EPCs) constitute a pool of circulating bone-marrow derived cells that mobilize after an ischemic injury with the potential to incorporate into the damaged endothelium, to form new vessels, or to secrete trophic factors stimulating vessel remodeling. The circulating levels of EPCs are altered after stroke, and several subpopulations have proved to boost brain neurorepair in preclinical models of cerebral ischemia. The goal of this review is to discuss the current state of the neuroreparative actions of EPCs, focusing on their paracrine signaling mechanisms thorough their secretome and released extracellular vesicles.
Rodent models of leptin receptor deficiency are less sensitive to amylin
Authors: Duffy Sonya , Lutz Thomas A. , Boyle Christina N.
Published: August 2018

The pancreatic hormone amylin is released from beta cells following nutrient ingestion and contributes to the control of body weight and glucose homeostasis. Amylin reduces food intake by activating neurons in the area postrema (AP). Amylin was also shown to synergize with the adipokine leptin, with combination therapy producing greater weight loss and food intake reduction than either hormone alone. Although amylin and leptin were initially thought to interact downstream of the AP in the hypothalamus, recent findings show that the two hormones can act on the same AP neurons, suggesting a more direct relationship. The objective of this study was to determine whether amylin action depends on functional leptin signaling. We tested the ability of amylin to induce satiation and to activate its primary target neurons in the AP in two rodent models of LepR deficiency, the db/db mouse and the Zucker diabetic fatty (ZDF) rat. When compared with wild-type (WT) mice, db/db mice exhibited reduced amylin-induced satiation, reduced amylin-induced Fos in the AP, and a lower expression of calcitonin receptor (CTR) protein, the core component of all amylin receptors. ZDF rats also showed no reduction in food intake following amylin treatment; however, unlike the db/db mice, levels of amylin-induced Fos and CTR in the AP were no different than WT rats. Our results suggest that LepR expression is required for the full anorexic effect of amylin; however, the neuronal activation in the AP seems to depend on the type of LepR mutation.
Influence of dietary protein on Dahl salt-sensitive hypertension: a potential role for gut microbiota
Authors: Abais-Battad Justine M. , Mattson David L.
Published: August 2018

High blood pressure affects 1.39 billion adults across the globe and is the leading preventable cause of death worldwide. Hypertension is a multifaceted disease with known genetic and environmental factors contributing to its progression. Our studies utilizing the Dahl salt-sensitive (SS) rat have demonstrated the remarkable influence of dietary protein and maternal environment on the development of hypertension and renal damage in response to high salt. There is growing interest in the relationship between the microbiome and hypertension, with gut dysbiosis being correlated to a number of pathologies. This review summarizes the current literature regarding the interplay among dietary protein, the gut microbiota, and hypertension. These studies may provide insight into the effects we have observed between diet and hypertension in Dahl SS rats and, we hope, lead to new perspectives where potential dietary interventions or microbiota manipulations could serve as plausible therapies for hypertension.
Faster processing of moving compared with flashed bars in awake macaque V1 provides a neural correlate of the flash lag illusion
Authors: Subramaniyan Manivannan , Ecker Alexander S. , Patel Saumil S. , Cotton R. James , Bethge Matthias , Pitkow Xaq , Berens Philipp , Tolias Andreas S.
Published: August 2018

When the brain has determined the position of a moving object, because of anatomical and processing delays the object will have already moved to a new location. Given the statistical regularities present in natural motion, the brain may have acquired compensatory mechanisms to minimize the mismatch between the perceived and real positions of moving objects. A well-known visual illusion—the flash lag effect—points toward such a possibility. Although many psychophysical models have been suggested to explain this illusion, their predictions have not been tested at the neural level, particularly in a species of animal known to perceive the illusion. To this end, we recorded neural responses to flashed and moving bars from primary visual cortex (V1) of awake, fixating macaque monkeys. We found that the response latency to moving bars of varying speed, motion direction, and luminance was shorter than that to flashes, in a manner that is consistent with psychophysical results. At the level of V1, our results support the differential latency model positing that flashed and moving bars have different latencies. As we found a neural correlate of the illusion in passively fixating monkeys, our results also suggest that judging the instantaneous position of the moving bar at the time of flash—as required by the postdiction/motion-biasing model—may not be necessary for observing a neural correlate of the illusion. Our results also suggest that the brain may have evolved mechanisms to process moving stimuli faster and closer to real time compared with briefly appearing stationary stimuli.

NEW & NOTEWORTHY We report several observations in awake macaque V1 that provide support for the differential latency model of the flash lag illusion. We find that the equal latency of flash and moving stimuli as assumed by motion integration/postdiction models does not hold in V1. We show that in macaque V1, motion processing latency depends on stimulus luminance, speed and motion direction in a manner consistent with several psychophysical properties of the flash lag illusion.
“Restauraciones de lesiones cervicales no cariosas: un protocolo de revisión sistemática para la práctica clínica”.
Authors: Ortuño Borroto Duniel Ricardo , Mellado Beatriz , Prado Sebastián , Vargas Juan Pablo , Rada Gabriel
Published: August 2018

Introducción: Las lesiones cervicales no cariosas son condiciones patológicas no bacterianas localizadas en el límite amelocementario de los dientes. Los principales biomateriales descritos para el tratamiento restaurador de estas lesiones son: vidrios ionómeros, vidrios ionómeros modificados con resinas, compómeros y resinas compuestas. El objetivo de este protocolo, consiste en establecer los elementos metodológicos de una revisión sistemática que evaluará el comportamiento clínico de restauraciones cervicales realizadas con estos biomateriales. Métodos: El protocolo fue diseñado, y será reportado, en línea con Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P 2015). Se realizará una búsqueda sensible en MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials y ClinicalTrials.gov, sin restricción por lenguaje o publicación, para identificar ensayos controlados aleatorizados que comparen dos o más tratamientos restauradores en lesiones cervicales no cariosas. Los desenlaces a evaluar serán la retención de las restauraciones y caries secundaria, según criterios RYGE/USPHS. Al menos dos investigadores realizarán de manera independiente la selección de los ensayos y la extracción de los datos. El riesgo de sesgo será evaluado utilizando la herramienta recomendada por la colaboración Cochrane. Si es posible, se realizará un metanálisis y los datos serán presentados en tablas de resúmenes de resultados mediante el método Grading of Recommendations Assesment, Development and Evaluation (GRADE). Fortalezas y debilidades: Esta revisión sistemática entregará evidencia actualizada sobre el comportamiento de cuatro biomateriales en el tratamiento de lesiones cervicales no cariosas. La principal limitación proviene de la baja cantidad o deficiencias metodológicas de los estudios primarios. Número de registro (PROSPERO): CRD42017071114.
Utilidad de factores pronósticos antenatales en pacientes con hernia diafragmática congénita aislada
Authors: Ferrer Márquez Fernando Andres , Vera Claudio , Parrao Guillermo , Coronado Paula , Urbano Norma , Vargas Paula , Theodor Mónica , Robles Carolina , Duran Ruth , Tsunekawa Harumi , Luco Matías , Belmar Cristian , Poblete José Andrés
Published: August 2018

Introducción: La Hernia Diafragmática Congénita (HDC) corresponde a una malformación del diafragma por la cual los órganos abdominales protruyen hacia la cavidad torácica durante el desarrollo intrauterino. Los recién nacidos afectados presentan grados variables de insuficiencia respiratoria e hipertensión pulmonar, asociándose a una alta morbilidad y mortalidad. Materiales y métodos: Se revisaron los casos de HDC controlados en los períodos pre y post-natal en el Hospital Clínico UC durante el período 2012-2016. Se analizaron los resultados perinatales según distintos factores pronósticos. Resultados: Fueron analizadas 26 embarazadas con diagnóstico de HDC. La sobrevida global fue de un 77% (20/26). La mortalidad global de las pacientes con herniación hepática fue de un 45% (5/11) versus  7% (1/15) en los fetos con hígado no herniado. La mortalidad neonatal fue de un 14% (3/21) en las pacientes con la  relación pulmón cabeza (LHR), (observado/ esperado) o/e ≥ a 45% y 60% (3/5) cuando el LHR o/e es < 45%. De las pacientes con LHR o/e ≥ 45%, la necesidad de ECMO fue de un 33% (8/21) mientras que un LHR o/e < 45% fue de un 20% (1/5). Conclusión: La obtención antenatal de un LHR o/e ≥ 45% y ausencia de herniación hepática, son buenos predictores de sobrevida neonatal. La medición de LHR o/e no es capaz de discriminar que pacientes desarrollarán morbilidad respiratoria grave, por lo que debemos buscar nuevos y mejores modelos que permitan seleccionar que pacientes requerirán nacer en un centro con disponibilidad de terapias de soporte vital avanzado como el ECMO neonatal.
p53–Pirh2 Complex Promotes Twist1 Degradation and Inhibits EMT
Authors: Yang-Hartwich Yang , Tedja Roslyn , Roberts Cai M. , Goodner-Bingham Jamie , Cardenas Carlos , Gurea Marta , Sumi Natalia J. , Alvero Ayesha B. , Glackin Carlotta A. , Mor Gil
Published: August 2018

Epithelial–mesenchymal transition (EMT) is a critical process involved in cancer metastasis and chemoresistance. Twist1 is a key EMT-inducing transcription factor, which is upregulated in multiple types of cancers and has been shown to promote tumor cell invasiveness and support tumor progression. Conversely, p53 is a tumor suppressor gene that is frequently mutated in cancers. This study demonstrates the ability of wild-type (WT) p53 to promote the degradation of Twist1 protein. By forming a complex with Twist1 and the E3 ligase Pirh2, WT p53 promotes the ubiquitination and proteasomal degradation of Twist1, thus inhibiting EMT and maintaining the epithelial phenotype. The ability of p53 to induce Twist1 degradation is abrogated when p53 is mutated. Consequently, the loss of p53-induced Twist1 degradation leads to EMT and the acquisition of a more invasive cancer phenotype.

Implication: These data provide new insight into the metastatic process at the molecular level and suggest a signaling pathway that can potentially be used to develop new prognostic markers and therapeutic targets to curtail cancer progression.
Suctioning Minimally Invasive Percutaneous Nephrolithotomy with a Patented System Is Effective to Treat Renal Staghorn Calculi: A Prospective Multicenter Study
Authors: Du Chuance , Song Leming , Wu Xiaoyuan , Fan Difu , Zhu Lunfeng , Liu Shengfeng , Deng Xiaolin , Liu Tairong , Yang Zhongsheng , Peng Zuofeng , Hu Min , Liu Qigui , Pan Tiejun , Chen Zhiqiang , Ye Zhangqun
Published: August 2018

Objectives: To investigate the safety, efficacy, and practicability of minimally invasive percutaneous nephrolithotomy (MPCNL) with the aid of a patented irrigation clearance system in treating renal staghorn calculi. Methods: From August 2009 to July 2014, 4 hospitals had executed a prospective multicenter study with a total of 912 cases. The patients were randomly divided into 3 groups: suctioning MPCNL, standard percutaneous nephrolithotomy (PCNL), and traditional MPCNL groups. Multiple operative and perioperative parameters were compared. Results: Blood loss and intrapelvic pressure in the suctioning MPCNL group were significantly less than those in the standard PCNL group. The average operation time, intrapelvic pressure, and amount of bleeding in the suctioning MPCNL group were better than those in the traditional MPCNL group. The suctioning MPCNL used one tract more frequently and 2 or 3 tracts less frequently than the standard MPCNL and traditional MPCNL groups. The stone-free rate by one surgery in the suctioning MPCNL group was significantly higher than that in standard PCNL and traditional MPNCL groups. Conclusions: Suctioning MPCNL using our patented system shows several advantages in treating renal staghorn calculi, including minimal invasion, shorter operation time, lower intrapelvic pressure, less bleeding and the need for a smaller number of ­percutaneous tracts, and higher stone clearance rate by one ­surgery.
Prevalence of Atopy following Mass Drug Administration with Albendazole: A Study in School Children on Flores Island, Indonesia
Authors: Staal Steven L. , Hogendoorn Sarika K.L. , Voets Sophie A. , Tepper Rebecca C. , Veenstra Mirte , de Vos Ivo I. , van Son Koen C. , Gool Jari K. , Paramitha Antonia C. , Aristyo Kevin , Wildan Ardy , Pratiwi Chici , van Ree Ronald , Yazdanbakhsh Maria , Supali Taniawati , Djuardi Yenny , Labuda Lucja A. , Tahapary Dicky L. , Sartono Erliyani
Published: August 2018

Background: In many rural areas of tropical countries such as Indonesia, the prevalence of soil-transmitted helminths (STH) infections remains high. At the same time, the burden of allergic disorders in such rural areas is reported to be low and inversely associated with helminth infections. To reduce the morbidity and transmission of helminth infections, the world health organization recommends preventive treatment of school children by providing mass drug administration (MDA) with albendazole. Here, we had an opportunity to evaluate the prevalence of skin reactivity to allergens before and after albendazole treatment to get an indication of the possible impact of MDA on allergic sensitization. Methods: A study was conducted among 150 school children living in an area endemic for STH infections. Before and 1 year after anthelminthic treatment with albendazole, stool samples were examined for the presence of STH eggs, skin prick tests (SPT) for cockroach and house dust mites were performed, blood eosinophilia was assessed, and total immunoglobulin E (IgE) and C-reactive protein (CRP) were measured in plasma. Results: Anthelminthic treatment significantly reduced the prevalence of STH from 19.6 before treatment to 6% after treatment (p < 0.001). Levels of total IgE (estimate: 0.30; 95% CI 0.22–0.42, p < 0.0001), CRP (estimate: 0.60; 95% CI 0.42–0.86, p = 0.006), and eosinophil counts (estimate: 0.70; 95% CI 0.61–0.80, p < 0.001) decreased significantly. The prevalence of SPT positivity increased from 18.7 to 32.7%. Multivariate analysis adjusted for confounding factors showed an increased risk of being SPT positive to any allergen (OR 3.04; 95% CI 1.338–6.919, p = 0.008). Conclusions: This study indicates that 1 year of MDA with albendazole was associated with a reduced prevalence of STH infections. This study shows that the prevalence of allergic sensitization increases after 1 year of albendazole treatment. Placebo-controlled and larger studies are needed to further substantiate a role of deworming treatment in an increased risk of allergic sensitization.
Efficacy and Safety of Infliximab Tolerance Induction in Patients with Inflammatory Bowel Diseases who Experienced Acute Infusion Reactions
Authors: Pauchard Isabelle , Nancey Stéphane , Hacard Florence , Williet Nicolas , Roblin Xavier , Moussata Driffa , Bérard Frédéric , Flourié Bernard , Boschetti Gilles
Published: August 2018

Background and Aims: One of the reasons for the failure of infliximab (IFX) is immediate hypersensitivity reactions (IHR). We aimed to report the efficacy and safety of a tolerance induction protocol in inflammatory bowel diseases (IBD) patients who had previously experienced IHR during IFX infusions. Patients and Methods: We reported all cases of IBD patients who had previously experienced IHR due to IFX and who were submitted to a standardized protocol of tolerance induction to IFX from 2010 to 2015. Results: IHR occurred in a majority of patients (69%) during the first 3 infusions and for half of them after a period of IFX withdrawn. Skin prick tests were negative and only 2 intradermal tests were positive. Basophil activation tests and antidrug antibody measurements were performed in 8 out of 16 patients and were positive in 3 and 4 patients respectively. Induction of tolerance was successful in 69% of patients and IFX was pursued with clinical efficacy > 1 year in 7 patients (44%). Allergologic investigations were not predictive of tolerance induction success. Conclusion: A majority of IHR to IFX infusions occurred during the beginning or restarting of treatment and was related to a nonallergic hypersensitivity. Induction of tolerance to IFX is feasible and effective and may safely allow retreatment of IFX in almost 70% of IBD patients.
Maternal High-Fat Diet Modifies the Immature Hippocampus Vulnerability to Perinatal Asphyxia in Rats
Authors: Isac Sebastian , Panaitescu Anca Maria , Iesanu Mara , Grigoras Ioana Florentina , Totan Alexandra , Udriste Amalia , Cucu Natalia , Peltecu Gheorghe , Zagrean Leon , Zagrean Ana-Maria
Published: August 2018

Background: High-fat diet (HFD) is a detrimental habit with harmful systemic consequences, including low-grade, long-lasting inflammation. During pregnancy, HFD can induce developmental changes. Moreover, HFD-related maternal obesity might enhance the risk of peripartum complications including hypoxic-ischemic encephalopathy secondary to perinatal asphyxia (PA). Objectives: Following our previous results showing that PA increases neuroinflammation and neuronal injury in the immature hippocampus and modifies hippocampal epigenetic programming, we further aimed to establish the impact of maternal HFD on offspring hippocampus response to PA. Methods: We assessed hippocampal tumor necrosis factor alpha (TNFα), interleukin 1 beta ­(IL-1b) and S-100B protein (S-100B), 24–48 h after PA exposure in postnatal day 6 Wistar rats, whose mothers received either the standard diet or HFD. The expression of small non-coding microRNA species miR124, miR132, miR134, miR146, and miR15a, as epigenetic markers for the maternal dietary influence on immature hippocampus response after PA, was determined 24 h after asphyxia exposure. Metabolic activity was measured using resazurin test in hippocampal cell suspension obtained 24 h after PA. Results: Our results indicate that maternal HFD additionally increases hippocampal TNFα, IL-1b, and S-100B after PA. Also, PA associated with maternal HFD induces miR124 upregulation and miR132 downregulation relative to PA only. Metabolic activity was increased in hippocampal cells from pups whose mothers received HFD. Conclusion: HFD increases the PA-induced neuroinflammation and neuronal injury, and epigenetically influences homeostatic synaptic plasticity and neuronal tolerance to asphyxia, processes associated with a higher hippocampal cellular metabolism.
Long-Term Outcomes after Performing Tympanoplasty without Mastoidectomy for Active and Inactive Noncholesteatomatous Chronic Otitis Media
Authors: Huang Jie , Li Zeqing , Wu Kunmin , Wang Wuqing
Published: August 2018

Objective: This study aimed to assess long-term outcomes after performing tympanoplasty without mastoidectomy (TWOM) for active and inactive noncholesteatomatous chronic otitis media (COM) and to estimate the optimal time for surgery. Methods: The patients were placed into an active ear group (group A) and an inactive ear group (group B). All patients were followed up for 5 years after TWOM. Results: Ninety-two cases among 113 achieved dry ears in half a month to 1 month. The tympanic pressure gradually improved 3–6 months after the operation. A total of 69/72 ears achieved dry ears in the active ear group, and 37 ears had effective hearing improvement. In all, 40/41 ears achieved dry ears in the inactive ear group, and 20 ears had effective hearing improvement. There was no difference in the recurrence rate or hearing improvement in the two groups. Conclusion: With good quality control of the surgical treatment of TWOM, there are no differences in long-term outcomes in noncholesteatomatous COM in different chronic infection conditions.
A 6-Month Follow-Up Study of the Relation between Apolipoprotein E Gene Polymorphism and Major Adverse Cardiovascular Events in Patients with Acute Coronary Syndrome
Authors: Xia Jinggang , Hu Shaodong , Yin Chunlin , Xu Dong
Published: August 2018

Objectives: This study aimed to investigate the relation between ApoE gene polymorphisms and major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS) during a 6-month follow-up. Methods: From October 2016 to July 2017, 211 patients were admitted to a cardiology clinic with a diagnosis of ACS. Blood samples were obtained from all patients on the first day. The primary end point was a 6-month incidence of MACE. ApoE gene polymorphism was genotyped by real-time PCR using TaqMan® SNP Genotyping Assay. Results: The patients with the E4 allele were associated with higher low-density lipoprotein (LDL) cholesterol and total cholesterol (TC) levels compared with the patients without the E4 allele (p = 0001 and p = 0.001). The patients with the E4 allele were associated with a higher rate of MACE compared with the patients without the E4 allele (ApoE4 allele(+) 23.1% vs. ApoE4 allele(−) 9.3%; p = 0.03). Multivariable analysis suggested that E4 allele carriers showed an 85% risk increment of 6-month MACE (odds ratio 2.48, 95% confidence interval 2.37–5.95; p = 0.01). Conclusions: The trial shows that E4 allele carriers were correlated with not only higher LDL cholesterol and TC levels, but also with a higher incidence of MACE during a 6-month follow-up.
Estimating Survival Probabilities of Advanced Gastric Cancer Patients in the Second-Line Setting: The Gastric Life Nomogram
Authors: Pietrantonio Filippo , Barretta Francesco , Fanotto Valentina , Park Se Hoon , Morano Federica , Fucà Giovanni , Niger Monica , Prisciandaro Michele , Silvestris Nicola , Bergamo Francesca , Fornaro Lorenzo , Bordonaro Roberto , Rimassa Lorenza , Santini Daniele , Tomasello Gianluca , Antonuzzo Lorenzo , Noventa Silvia , Avallone Antonio , Leone Francesco , Faloppi Luca , Di Donato Samantha , de Braud Filippo , Lee Jeeyun , De Vita Ferdinando , Di Bartolomeo Maria , Miceli Rosalba , Aprile Giuseppe
Published: August 2018

Objective: We built and externally validated a nomogram for predicting the overall survival (OS) probability of advanced gastric cancer patients receiving second-line treatment. Methods: The nomogram was developed on a set of 320 Italian patients and validated on two independent sets (295 Italian and 172 Korean patients). Putative prognostic variables were selected using a random forest model and included in the multivariable Cox model. The nomogram’s performance was evaluated by calibration plot and C index. Results: ECOG performance status, neutrophils to lymphocytes ratio, and peritoneal involvement were selected and included into the multivariable model. The C index was 0.72 (95% CI 0.68–0.75) in the development set, 0.69 (95% CI 0.65–0.73) in the Italian validation set, but only 0.57 (95% CI 0.52–0.62) in the Korean set. While Italian calibrations were quite good, the Korean one was poor. Regarding 6-month OS predictions, calibration was best in both Caucasian cohorts and worst the in Asian one. Conclusions: Our nomogram may be a useful tool to predict 3- or 6-month OS in Caucasian gastric cancer patients eligible for second-line therapy. Based on three easy-to-collect variables, the Gastric Life nomogram may help clinicians improve patient selection for second-line treatments and assist in clinical trial enrollment.
Antidermatophytic Activity and Skin Retention of Clotrimazole Microemulsion and Microemulsion-Based Gel in Comparison to Conventional Cream
Authors: Kaewbanjong Jarika , Amnuaikit Thanaporn , Souto Eliana B. , Boonme Prapaporn
Published: August 2018

Aim: Antifungal activity, skin permeation and skin retention of water-in-oil microemulsion (ME) and microemulsion-based gel (MBG) containing clotrimazole (CTZ) were evaluated in comparison to a conventional CTZ cream. Methods: CTZ-ME and CTZ-MBG containing 1% w/w of CTZ were produced. Antifungal activity against Trichophyton mentagrophytes was assessed by the agar diffusion method. Pig skin was used in the in vitro penetration study using modified Franz diffusion cells. Drug amounts which permeated into the receptor fluid, retained in the skin membrane and remained in the donor compartment were analyzed by a validated HPLC technique. Results: CTZ-ME and CTZ-MBG exhibited inhibition zones against T. mentagrophytes whereas the conventional cream did not reveal any inhibition zone in the assay. While no CTZ was detected in the receptor fluid up to 24 h following the in vitro penetration study from all tested formulations, the amount of CTZ retained in the skin membrane when applying CTZ-ME and CTZ-MBG was remarkably higher than that when applying the cream. Conclusion: Results revealed the capacity of ME and MBG in improving skin bioavailability of CTZ while reducing the risk of systemic side effects. Thereby, ME and MBG could increase the efficacy of CTZ for dermatophytosis treatment in comparison to conventional cream.
The Association between Male Asthma and Lower Urinary Tract Symptoms Evaluated by the International Prostate Symptom Score: A Population-Based Study
Authors: Han Chang Hoon , Kim Seung Jun , Chung Jae Ho
Published: August 2018

Objectives: We explored the association between asthma severity and lower urinary tract symptoms (LUTS) using the International Prostate Symptom Score in a population-based study of males (aged ≥19 years) and evaluated voiding and urine storage symptoms. Methods: This was a cross-sectional study of 101,848 males, 2,544 of whom had asthma, who participated in the 2011 Korean Community Health Survey. All subjects were assessed in terms of sociodemographic data, pre-existing conditions, and the presence of LUTS. Logistic regression was used to identify risk factors for LUTS in asthmatics. Results: Urine storage symptoms (frequency, urgency, and nocturia) and voiding symptoms (straining, a weak stream, intermittency, and incomplete emptying) were significantly higher in the asthma group than in the non­asthma group (all p < 0.001). Moderate and severe LUTS were significantly more common in the asthma group (moderate, 24.3%; severe, 22.5%) than in the nonasthma group (moderate, 9.5%; severe, 2.9%). Compared to the mild LUTS group, the odds ratio (OR) for asthma was 2.21 (95% confidence interval [CI] 1.99–2.46) in the moderate LUTS group, and 3.04 (95% CI 2.64–3.51) in the severe LUTS group. In a model evaluating multiple variables, the OR for asthma in the moderate LUTS group was 1.95 (95% CI 1.74–2.16) and that in the severe LUTS group was 2.17 (95% CI 1.87–2.53). Asthma was associated with both voiding and storage symptoms. Conclusions: Male asthma was associated with moderate-to-severe LUTS. More aggressive urological diagnosis and treatment are needed for patients with asthma.
The Levels of T Lymphocyte Subsets in Immune Thrombocytopenia Associated with Anti-GPIIb/IIIa- and/or Anti-GPIbα-Mediated Responses Are Differentially Sensitive to Dexamethasone
Authors: Chen Yang , Xie Yanyan , Ruan Min , Shi Jinning
Published: August 2018

Objective: The aim of this work was to investigate the influence of T lymphocyte subsets and platelet-specific autoantibodies on immune thrombocytopenia (ITP) with dexamethasone therapy. Methods: The samples were obtained from patients before therapy. T lymphocyte subsets were measured by flow cytometry, and platelet-specific autoantibodies were evaluated by modified monoclonal antibody immobilization of platelet antigen assay. Results: A total of 50 ITP patients were involved in the study. Twenty-three were anti-GPIbα antibody positive and were treated with dexamethasone, with a response rate of 47.8%. Twenty-seven cases were anti-GPIbα antibody negative, with a response rate of 77.8%. A significant difference was detected (p < 0.05). The level of CD4+ T lymphocytes in ITP patients was lower compared with the control group (p < 0.05). The level of CD8+ T lymphocytes was higher than that in the normal controls (p < 0.05). Additionally, the patients with a higher level of CD8+ T lymphocytes and lower level of CD4+ T lymphocytes were more likely to respond to dexamethasone treatment. Moreover, we observed that ITP patients associated with anti-GPIIb/IIIa antibodies had lower levels of CD4+ T lymphocytes and higher CD8+ T lymphocyte levels. Conclusions: There was insensitivity to dexamethasone treatment in ITP patients who were anti-GPIbα antibody positive. The detection of T lymphocyte subsets is useful in ITP patients for forecasting the outcome of dexamethasone treatment. There were some relationships between the different antibodies and the levels of T lymphocyte subsets.
Real-World Outcomes of Vedolizumab Therapy in Ulcerative Colitis and Crohn’s Disease at a Tertiary Referral Center
Authors: Hoffmann Peter , Krisam Johannes , Stremmel Wolfgang , Gauss Annika
Published: August 2018

Background: Vedolizumab was approved for the therapy of ulcerative colitis and Crohn’s disease in mid-2014. Real-world treatment data are necessary for a balanced assessment of its position among other therapeutic options. Summary: Patients with ulcerative colitis or Crohn’s disease, initiating vedolizumab therapy at the outpatient clinic for inflammatory bowel diseases at the University Hospital ­Heidelberg between June 1, 2014 and August 31, 2016, were recruited based on electronic medical records. The primary study endpoint was response at week 30, while the secondary endpoints were the need for surgery and discontinuation of therapy due to inadequate response, or adverse events. Twenty-five patients with ulcerative colitis (40% anti-tumor necrosis factor α [TNFα] naive) and 28 patients with Crohn’s disease (10.7% anti-TNFα naive, 53.6% having undergone at least one intestinal surgery) were enrolled. Among the ulcerative colitis patients, 20% achieved remission, 32% partial response, and 48% were non-responders to vedolizumab. In Crohn’s disease, 14.3% of the patients achieved remission, 46.4% partial response, and 39.4% were non-responders. Two patients discontinued vedolizumab therapy due to suspected side effects. Key Message: In a relatively treatment-refractory cohort of inflammatory bowel disease patients, vedolizumab was efficacious in achieving response. However, the majority of the patients were not satisfactorily treated, as they did not reach remission.
Increased Risk-Taking Behaviour and Brain-Derived Neurotrophic Factor Val66Met Polymorphism Correlates to Decreased Serum Brain-Derived Neurotrophic Factor Level in Heroin Users
Authors: Roviš Darko , Černelič Bizjak Maša , Vasiljev Marchesi Vanja , Petelin Ana , Jenuš Tina , Vidic Suzana , Drevenšek Gorazd , Jenko Pražnikar Zala
Published: August 2018

Background: This study has examined the relationships and interactions between serum brain-derived neurotrophic factor (BDNF) levels, BDNF Val66Met polymorphism and self-reported risk-taking behaviour in individuals with a history of heroin use undergoing outpatient treatment in comparison to healthy individuals. Methods: We enrolled 167 heroin users and 86 healthy subjects and examined serum BDNF levels, Val66Met polymorphism, and personal characteristics using Connor Davidson Resilience Scale, Risk-taking (RT) propensity questionnaire, and Personality Assessment Inventory. Results: Heroin users had significantly higher serum BDNF levels than controls. In addition, serum BDNF levels were significantly higher in Val/Val carriers than in Met/Val or Met/Met in all recruited subjects. Furthermore, a stepwise multiple regression analysis of serum BDNF levels as a dependent variable with related factors showed that in heroin users, Alcohol Use Disorder Identification Test score, anxiety and RT score were found as independent contributors to serum BDNF levels. When performing gene-environment interaction it was additionally found that heroin users with self-reported high risk-taking behaviour had significantly lower levels of serum BDNF among heroin users with the Met allele. Conclusions: These results indicate that genetic variant Met66 decreased the serum BDNF levels in combination with self-reported risk-taking propensity among heroin users. If results of future work confirm the influence of this combined effect between neurotrophic genotype and risk-taking behaviour, 66Met carriers might require higher levels of intervention to overcome their drug use pattern and risky behaviour.
Inhibition of MicroRNA-96 Ameliorates Cognitive Impairment and Inactivation Autophagy Following Chronic Cerebral Hypoperfusion in the Rat
Authors: Liu Peifang , Liu Peijia , Wang Zhiyong , Fang Shaohong , Liu Yuting , Wang Jinhua , Liu Wenjuan , Wang Ning , Chen Lixia , Wang Jianjian , Zhang Huixue , Wang Lihua
Published: August 2018

Background/Aims: Chronic cerebral hypoperfusion (CCH) is a high-risk factor for vascular dementia and Alzheimer’s disease. Autophagy plays a critical role in the initiation and progression of CCH. However, the underlying mechanisms remain unclear. In this study, we identified the effect of a microRNA (miR) on autophagy under CCH. Methods: A CCH rat model was established by two-vessel occlusion (2VO). Learning and memory abilities were assessed by the Morris water maze. The protein levels of LC3, beclin-1, and mTOR were detected by western blotting and immunofluorescence assays, miR-96 expression was assessed by real-time PCR, luciferase assays were used to determine the effect of miR-96 on the 3′ untranslated region (UTR) of mTOR, and the number of autophagosomes was examined by electron microscopy. Results: The level of miR-96 was significantly increased in 2VO rats, and inhibition of miR-96 ameliorated the cognitive impairment induced by 2VO. Furthermore, the number of LC3- and beclin-1-positive autophagosomes was increased in 2VO rats, and was decreased after miR-96 antagomir injection. However, the protein level of mTOR was reduced in 2VO rats, and it was down-regulated by miR-96 overexpression and up-regulated by miR-96 inhibition in 2VO rats and primary culture cells. Moreover, the luciferase activity of the 3′-UTR of mTOR was suppressed by miR-96, which was relieved by mutation of the miR-96 binding sites. Conclusion: Our study demonstrated that miR-96 may play a key role in autophagy under CCH by regulating mTOR; therefore, miR-96 may represent a potential therapeutic target for CCH.
A contribuição dos Jogos Paralímpicos para a promoção da inclusão social: o discurso midiático como um obstáculo
Authors: Marques Renato Francisco Rodrigues
Published: August 2018

A inclusão social de pessoas com deficiência é um processo que perpassa tanto pelo empoderamento quanto por transformações da sociedade, de modo a proporcionar oportunidades de participação social plena. Sua efetividade está intimamente atrelada à transformação de paradigmas, estereótipos e preconceitos. Isso é possível por meio da educação formal, da mídia e de fenômenos socioculturais capazes de contribuir para modificar ou reforçar valores morais, como o esporte. O objetivo geral deste ensaio é propor uma reflexão a respeito da maneira como atletas paralímpicos são retratados pela mídia durante os Jogos Paralímpicos e o produto dessa forma de interação com os espectadores. Conclui-se que os atletas querem ser reconhecidos como pessoas produtivas e eficientes assim como qualquer outro cidadão.
Long slide holders for microscope stages
Authors: Klisz Marcin , Miodek Adam , Kojs Paweł , Gärtner Holger
Published: August 2018

The use of automated techniques for image analysis of microscopic wood specimens together with new procedures for the preparation of stained xylem tissue support the use of quantitative wood anatomy. These techniques and procedures are especially useful in the studies of retrospective analysis of xylem phenology, reaction(s) of trees to stressful conditions of growth, or reconstruction of long-term growth trends. The unresolved technical problems during the digitalization of cross sections from entire increment cores were stabilization and precise shifting of long microscopic specimens onto the optical microscope stage. For this reason, we have developed a long slide holder for microscope stages in two versions: the basic one allowing stabilization and manual shifting, and the advanced one for stabilization and mechanical shifting. Both versions of the adapter speed up the work with long slides, improving the quality of panoramic images of microscopic specimens.