bluuebunny/crossref_metadata_2025 huggingface dataset:
Photodynamic therapy and laser‐assisted drug delivery and R0 excision in the treatment of an immunosuppressed patient showing multiple actinic keratosis and recurrent squamous cell carcinoma: A case report
Authors: Bigge Bianca , Ungerechts Gerd , Bigge Stefan
Published: March 2020

We report on a 73‐year‐old male patient with granulomatosis with polyangiitis (Wegener's granulomatosis) who developed increasingly growing lesions of actinic keratosis (AK) and squamous cell carcinoma (SCC) of the scalp under systemic immunomodulatory therapy with azathioprine for more than 8 years. The patient underwent a first‐line surgical therapy resulting in histologically confirmed R0 resection status followed by topical imiquimod treatment and cryotherapy. However, recurrence of AK/SCC progression could not be stopped sufficiently. Therefore, due to the difficult localization of the lesions at the head and the limitation of further surgical procedures, the patient was presented to our laser medicine department in order to consider complementary therapy options. The therapy approach was combining photodynamic therapy (PDT) with laser‐assisted drug delivery (LADD). PDT has been successful in treating field cancerization for decades, but it has limitations in the treatment of hyperkeratotic lesions. Pre‐treatment with LADD can be used to optimize the penetration depth of the prodrug 5‐aminolevulinic acid (BF‐200 ALA, Ameluz) and significantly increase the bioavailability as well as inducing an inflammatoric reaction. Following this therapeutic approach, we were able to achieve a stable disease over a follow‐up period of 2 years after six sessions of combined LADD + PDT.
Poisonous substances used to capture and kill the greater cane rat (Thryonomys swinderianus)
Authors: Essuman Edward K. , Duah Kingsley K.
Published: March 2020

The greater cane rat, as it is commonly known, is often called grasscutter (in Ghana, Nigeria and other regions of West Africa). Even though is highly patronized as a delicacy by a majority of Ghanaians (akrantie—Twi language) mostly in the rural areas, the persistent reports on people being poisoned as a result of eating food prepared with grasscutter which has been captured/killed by the use of poison are deterring people from consuming the grasscutter meat despite its high protein content. The objective of this study was, therefore, to investigate the actual ingredients that are used in the formulation of poison to capture grasscutter for human consumption. Questionnaires were administered to participants (farmers) who are involved in grasscutter hunting to solicit the ingredient they formulate to poison the grasscutter in their hunting. To prove the activeness of these ingredients, the main ingredient used in formulating the poison to capture the grasscutters were tested on two male grasscutters and these were yellow oleander root (Cascabela thevetia; syn: Thevetia peruviana) powder and carbofuran. The findings of the experimental trial revealed that the grasscutter that was fed with yellow oleander root powder did not die but showed some signs of intoxication and staggered each time it tried to move. However, the grasscutter fed with carbofuran died within 10 hr of being poisoned. Majority of the participants attested to the fact that the use of poison increases their chance of capturing the grasscutter, especially in the dry season since the poison is not washed away by the rainwater. However, consuming grasscutter poisoned with either yellow oleander root power or carbofuran could be detrimental to human health.
On generalized Q-systems
Authors: Bajnok Zoltán , Granet Etienne , Jacobsen Jesper Lykke , Nepomechie Rafael I.
Published: March 2020

Abstract

We formulate Q-systems for the closed XXZ, open XXX and open quantum- group-invariant XXZ quantum spin chains. Polynomial solutions of these Q-systems can be found efficiently, which in turn lead directly to the admissible solutions of the corresponding Bethe ansatz equations.
One-loop universality of holographic codes
Authors: Dong Xi , Marolf Donald
Published: March 2020

Abstract

Recent work showed holographic error correcting codes to have simple universal features at O(1/G). In particular, states of fixed Ryu-Takayanagi (RT) area in such codes are associated with flat entanglement spectra indicating maximal entanglement between appropriate subspaces. We extend such results to one-loop order (O(1) corrections) by controlling both higher-derivative corrections to the bulk effective action and dynamical quantum fluctuations below the cutoff. This result clarifies the relation between the bulk path integral and the quantum code, and implies that i) simple tensor network models of holography continue to match the behavior of holographic CFTs beyond leading order in G, ii) the relation between bulk and boundary modular Hamiltonians derived by Jafferis, Lewkowycz, Maldacena, and Suh holds as an operator equation on the code subspace and not just in code-subspace expectation values, and iii) the code subspace is invariant under an appropriate notion of modular flow. A final corollary requires interesting cancelations to occur in the bulk renormalization-group flow of holographic quantum codes. Intermediate technical results include showing the Lewkowycz-Maldacena computation of RT entropy to take the form of a Hamilton-Jacobi variation of the action with respect to boundary conditions, corresponding results for higher-derivative actions, and generalizations to allow RT surfaces with finite conical angles.
Microwave Ablation in the Proximity of Surgical Clips: Is there a Safety Issue?
Authors: Liebl Martin , Schulze-Hagen Maximilian , Zimmermann Markus , Pedersoli Federico , Kuhl Christiane , Bruners Philipp , Isfort Peter
Published: March 2020

Purpose

The purpose of this study was to evaluate the heat generation of surgical clips within the target area of MWA and the influences on the ablation volume.

Materials and Methods

In bovine liver tissue, 42 ex vivo microwave ablations (60 W; 180 s) were performed. During ablation, the temperature was measured continuously at 4 points of interest (POI), in a distance of 7.5 and 15 mm on each side of the microwave antenna, with a titanium surgical placed at one 7.5-mm POI. Ablation volumes containing large vessels (n = 10) were excluded. For every POI, the mean temperature of 32 ablations was calculated. The mean temperatures were compared between the 4 POI and statistically analyzed using the Student’s t test.

Results

The mean maximum temperatures at the side of the clip were 88.76 °C/ 195 s and 52.97 °C/ 195 s and at the side without clip 78.75 °C/ 195 s and 43.16 °C/ 195 s, respectively, at POI 7.5 mm and POI 15 mm. The maximum difference of mean temperatures for POI 7.5 mm was 12.91 °C at 84 s (p = 0.022) and for POI 15 mm 9.77 °C at 195 s (p = 0.009). No significant changes in size and shape of the ablation zone could be determined.

Conclusions

Our study demonstrated significantly higher temperatures adjacent to surgical clips. Also, the temperatures distal to the titanium clip were higher compared to the control location without clip. These findings suggest an increased risk of thermal damage to surrounding tissues during MWA, especially in case of immediate contact to surgical clips.
Phase 1 study of napabucasin, a cancer stemness inhibitor, in patients with advanced solid tumors
Authors: Kawazoe Akihito , Kuboki Yasutoshi , Bando Hideaki , Fukuoka Shota , Kojima Takashi , Naito Yoichi , Iino Shuichi , Yodo Yasuhide , Doi Toshihiko , Shitara Kohei , Yoshino Takayuki
Published: March 2020

Purpose

Napabucasin is a cancer stemness inhibitor that targets a number of oncogenic pathways, including signal transducer and activator of transcription 3 (STAT3). Phase 1/2 studies suggest tolerability and anti-tumor activity in various types of cancer; a Phase 3 study of napabucasin plus standard therapy in colorectal cancer is ongoing. This is a Phase 1 dose-escalation study in patients with advanced solid tumors, and the first study of napabucasin in Japanese patients.

Methods

Patients received napabucasin 480, 960, or 1440 mg daily in 28-day cycles until disease progression or intolerable toxicity. Primary objectives were to determine dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and the pharmacokinetic (PK) profile of napabucasin. Blood samples were taken for PK analysis on Days 1, 2, 8, and 15 of Cycle 1, and Days 29 and 30 of Cycle 2. Secondary objectives were to assess napabucasin antitumor activity, and the relationship between biomarkers and antitumor activity. JapicCTI-No: JapicCTI-132152.

Results

Enrolled were 14 patients (480 mg [n = 3], 960 mg [n = 4], 1440 mg [n = 7]). One patient experienced a DLT (Grade 3, anorexia). MTD was 1440 mg/day. Most common drug-related adverse events were diarrhea (n = 9), nausea (n = 4), vomiting (n = 3), and anorexia (n = 3). Napabucasin showed a similar PK profile to previous studies and no abnormal accumulation was observed. Following treatment, two patients had stable disease; the remaining 12 had progressive disease.

Conclusion

Napabucasin was well-tolerated at doses up to 1440 mg/day in Japanese patients with advanced solid tumors; the PK profile was comparable to that reported previously.
Fungal Kti12 proteins display unusual linker regions and unique ATPase p-loops
Authors: Krutyhołowa Rościsław , Reinhardt-Tews Annekathrin , Chramiec-Głąbik Andrzej , Breunig Karin D. , Glatt Sebastian
Published: March 2020

Kti12 (Kluyveromyces lactis toxin insensitive 12) is an evolutionary highly conserved ATPase, crucial for the tRNA-modification activity of the eukaryotic Elongator complex. The protein consists of an N-terminal ATPase and a C-terminal tRNA-binding domain, which are connected by a flexible linker. The precise role of the linker region and its involvement in the communication between the two domains and their activities remain elusive. Here, we analyzed all available Kti12 protein sequences and report the discovery of a subset of Kti12 proteins with abnormally long linker regions. These Kti12 proteins are characterized by a co-occurring lysine to leucine substitution in their Walker A motif, previously thought to be invariable. We show that the K14L substitution lowers the affinity to ATP, but does not affect the catalytic activity of Kti12 at high ATP concentrations. We compare the activity of mutated variants of Kti12 in vitro with complementation assays in vivo in yeast. Ultimately, we compared Kti12 to other known p-loop ATPase family members known to carry a similar deviant Walker A motif. Our data establish Kti12 of Eurotiomycetes as an example of eukaryotic ATPase harboring a significantly deviating but still functional Walker A motif.
Caloric restriction induces anabolic resistance to resistance exercise
Authors: Murphy Chaise , Koehler Karsten
Published: March 2020

Purpose

Weight loss can result in the loss of muscle mass and bone mineral density. Resistance exercise is commonly prescribed to attenuate these effects. However, the anabolic endocrine response to resistance exercise during caloric restriction has not been characterized.

Methods

Participants underwent 3-day conditions of caloric restriction (15 kcal kg FFM−1) with post-exercise carbohydrate (CRC) and with post-exercise protein (CRP), and an energy balance control (40 kcal kg FFM−1) with post-exercise carbohydrate (CON). Serial blood draws were taken following five sets of five repetitions of the barbell back squat exercise on day 3 of each condition.

Results

In CRC and CRP, respectively, growth hormone peaked at 2.6 ± 0.4 and 2.5 ± 0.9 times the peak concentrations observed during CON. Despite this, insulin-like growth factor-1 concentrations declined 18.3 ± 3.4% in CRC and 27.2 ± 3.8% in CRP, which was greater than the 7.6 ± 3.6% decline in CON, over the subsequent 24 h. Sclerostin increased over the first 2 days of each intervention by 19.2 ± 5.6% in CRC, 21.8 ± 6.2% in CRP and 13.4 ± 5.9% in CON, but following the resistance exercise bout, these increases were attenuated and no longer significant.

Conclusion

During caloric restriction, there is considerable endocrine anabolic resistance to a single bout of resistance exercise which persists in the presence of post-exercise whey protein supplementation. Alternative strategies to restore the sensitivity of insulin-like growth factor-1 to growth hormone need to be explored.
Role of hyaluronan in regulating self-renewal and osteogenic differentiation of mesenchymal stromal cells and pre-osteoblasts
Authors: Asparuhova Maria B. , Chappuis Vivianne , Stähli Alexandra , Buser Daniel , Sculean Anton
Published: March 2020

Objectives

The aim of the study was to investigate the impact of two hyaluronan (HA) formulations on the osteogenic potential of osteoblast precursors.

Materials and methods

Proliferation rates of HA-treated mesenchymal stromal ST2 and pre-osteoblastic MC3T3-E1 cells were determined by 5-bromo-20-deoxyuridine (BrdU) assay. Expression of genes encoding osteogenic differentiation markers, critical growth, and stemness factors as well as activation of downstream signaling pathways in the HA-treated cells were analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunoblot techniques.

Results

The investigated HAs strongly stimulated the growth of the osteoprogenitor lines and enhanced the expression of genes encoding bone matrix proteins. However, expression of late osteogenic differentiation markers was significantly inhibited, accompanied by decreased bone morphogenetic protein (BMP) signaling. The expression of genes encoding transforming growth factor-β1 (TGF-β1) and fibroblast growth factor-1 (FGF-1) as well as the phosphorylation of the downstream signaling molecules Smad2 and Erk1/2 were enhanced upon HA treatment. We observed significant upregulation of the transcription factor Sox2 and its direct transcription targets and critical stemness genes, Yap1 and Bmi1, in HA-treated cells. Moreover, prominent targets of the canonical Wnt signaling pathway showed reduced expression, whereas inhibitors of the pathway were considerably upregulated. We detected decrease of active β-catenin levels in HA-treated cells due to β-catenin being phosphorylated and, thus, targeted for degradation.

Conclusions

HA strongly induces the growth of osteoprogenitors and maintains their stemness, thus potentially regulating the balance between self-renewal and differentiation during bone regeneration following reconstructive oral surgeries.

Clinical relevance

Addition of HA to deficient bone or bony defects during implant or reconstructive periodontal surgeries may be a viable approach for expanding adult stem cells without losing their replicative and differentiation capabilities.
Relationship between serum calcium or phosphate levels and mortality stratified by parathyroid hormone level: an analysis from the MBD-5D study
Authors: Asada Shinji , Yokoyama Keitaro , Miyakoshi Chisato , Fukuma Shingo , Endo Yuichi , Wada Michihito , Nomura Takanobu , Onishi Yoshihiro , Fukagawa Masafumi , Fukuhara Shunichi , Akizawa Tadao
Published: March 2020

Introduction

There is limited evidence about the association between calcium and phosphate levels and mortality stratified by intact parathyroid hormone (iPTH) level.

Methods

We investigated whether differences in iPTH level affect the relationship between calcium and phosphate levels and all-cause mortality in hemodialysis patients with secondary hyperparathyroidism (SHPT). Calcium and phosphate levels were categorized as low (< 8.5 mg/dL, < 4.0 mg/dL), medium (≥ 8.5–< 9.5 mg/dL, ≥ 4.0–< 7.0 mg/dL), and high (≥ 9.5 mg/dL, ≥ 7.0 mg/dL), respectively. iPTH levels were grouped into < 300 or ≥ 300 pg/mL. Adjusted incidence rate ratios (aIRRs) were analyzed by weighted Poisson regression.

Results

For calcium, patients with higher iPTH (≥ 300 pg/mL) had significantly higher all-cause mortality rates in the high than in the medium category (aIRR 1.99, 95% confidence interval [CI] 1.16–3.42), and tended to have a higher mortality rate in the low category (aIRR 2.04, 95% CI 0.94–4.42). Patients with lower iPTH (< 300 pg/mL) had higher mortality rates in the high than in the medium category (aIRR 1.65, 95% CI 1.39–1.96). For phosphate, the mortality rate was significantly higher in the high than in the medium category in patients with higher and lower iPTH (aIRR 3.23, 95% CI 1.63–6.39 for iPTH ≥ 300 pg/mL; aIRR 1.58, 95% CI 1.06–2.36 for iPTH < 300 pg/mL).

Conclusion

High calcium and phosphate levels were associated with increased risk of mortality irrespective of iPTH level.
Nonproteinuric diabetic kidney disease
Authors: Yamanouchi Masayuki , Furuichi Kengo , Hoshino Junichi , Ubara Yoshifumi , Wada Takashi
Published: March 2020

Proteinuria has been considered to be the hallmark of diabetic kidney disease and to precede renal function loss. However, it has become clear that a substantial proportion of patients either with type 1 diabetes or type 2 diabetes have renal function loss without proteinuria, known as nonproteinuric diabetic kidney disease. Despite increasing recognition of the prevalence of nonproteinuric diabetic kidney disease, data on this phenotype of diabetic kidney disease is sparse. This review describes ever known clinical and pathological manifestations, renal prognosis, and mortality in patient with nonproteinuric diabetic kidney disease.
The Melatonin Receptor Agonist Ramelteon Induces Cardioprotection that Requires MT2 Receptor Activation and Release of Reactive Oxygen Species
Authors: Stroethoff Martin , Goetze Lukas , Torregroza Carolin , Bunte Sebastian , Raupach Annika , Heinen André , Mathes Alexander , Hollmann Markus W. , Huhn Ragnar
Published: March 2020

Purpose

The melatonin receptor (MT) agonist ramelteon has a higher affinity to MT1 than for MT2 receptors and induces cardioprotection by involvement of mitochondrial potassium channels. Activation of mitochondrial potassium channels leads to release of free radicals. We investigated whether (1) ramelteon-induced cardioprotection is MT2 receptor specific and (2) if free radicals are involved in ramelteon-induced cardioprotection.

Methods

Hearts of male Wistar rats were randomized, placed on a Langendorff system, and perfused with Krebs-Henseleit buffer at a constant pressure of 80 mmHg. All hearts were subjected to 33 min of global ischemia and 60 min of reperfusion. Before ischemia hearts were perfused with ramelteon (Ram) with or without the MT2 receptor inhibitor 4-phenyl-2-propionamidotetralin (4P-PDOT+Ram, 4P-PDOT). In subsequent experiments, ramelteon was administered together with the radical oxygen species (ROS) scavenger N-2-mercaptopropionylglycine (MPG+Ram). To determine whether the blockade of ramelteon-induced cardioprotection can be restored, we combined ramelteon and MPG with mitochondrial permeability transition pore (mPTP) inhibitor cyclosporine A (CsA) at different time points. Infarct size was determined by triphenyltetrazolium chloride (TTC) staining.

Results

Ramelteon-induced infarct size reduction was completely blocked by 4P-PDOT and MPG. Ramelteon and MPG combined with CsA before ischemia were not cardioprotective but CsA at the onset of reperfusion could restore infarct size reduction.

Conclusions

This study shows for the first time that despite the higher affinity to MT1 receptors, (1) ramelteon-induced cardioprotection involves MT2 receptors, (2) cardioprotection requires ROS release, and (3) inhibition of the mPTP can restore infarct size reduction.
Distributed multi-munition cooperative guidance based on clock synchronization for switching and noisy networks
Authors: Yi Sheng , She Xiaoyu , Guo Dong , Zhao Tong , Yang Chengwei , Li Jie
Published: March 2020

This paper proposes a novel three-dimensional guidance method based on clock synchronization algorithms, creatively solving the problems of randomized change, non-connection and even communication outage caused by packet loss and delay in the co-guidance of loitering munitions. The proposed method is characterized by fast convergence of the aspect angle rate in the longitudinal plane, and the attack time constrains in the lateral plane. Normal accelerations on the two sub-planes are thereby calculated, so as to control the munitions’ co-attack. Simulation experiments show that the proposed method can ensure reliable and stable asymptotic agreement of attack time expectation for the cooperative multiple munitions under the switching and noisy networks.
Isolation and structural analysis of the Bx6 and Bx7 genes controlling the biosynthesis of benzoxazinoids in rye (Secale cereale L.)
Authors: Bakera Beata , Rakoczy-Trojanowska Monika
Published: March 2020

Benzoxazinoids (BXs) are plant secondary metabolites, first discovered in the 1950s, which are synthesized in many monocotyledonous species from the Poaceae family and in several dicotyledonous plants. They constitute a significant element of the plant’s defence mechanism against both biotic (pests and diseases) and abiotic (elevated salinity, heavy metals) stresses. The aim of this research was to gain more information on the genetic background of BXs biosynthesis in rye (Secale cerealeL.) by isolating and sequencing theScBx6L318andScBx7L318genes encoding 2-oxoglutarate-dependent dioxygenase and 7-O-methyltransferase, respectively. Using the modified Amplicon Express method, BAC clones containing theScBx6L318andScBx7L318genes were isolated and sequenced. The similarity between theScBx6L318andZmBx6genes were, correspondingly, 78% and 68% in the coding sequence (cds) and the amino acid sequence (AA). A lesser similarity was found between theScBx7L318andZmBx7genes (72% and 45% at thecdsand AA levels, respectively).
Die Relevanz eines kohärenten forensischen Beurteilungs- und Behandlungsprozesses
Authors: Borchard Bernd , Gerth Juliane
Published: March 2020

Das Ziel einer therapeutischen Maßnahme bei Straftätern ist gemäß Gesetzesgrundlage die Reduktion der Gefahr erneuter „erheblicher rechtswidriger Taten“ (§§ 63 und 64 StGB, Deutschland) bzw. mit dem „Zustand des Täters in Zusammenhang stehender Taten“ (Art. 59 und 63 bzw. Art. 60 für Abhängigkeiten StGB, Schweiz). Um dieses Ziel zu erreichen, ist ein kohärenter Prozess notwendig, der die Fallkonzeption (inkl. Diagnostik und Hypothese zum Deliktmechanismus), Behandlungsplanung und -Behandlungsevaluation umfasst. Im Rahmen des ersten Schrittes muss herausgearbeitet werden, ob überhaupt eine Behandlungsbedürftigkeit des Straftäters vorliegt. Diese ergibt sich aus dem Risiko für erneute schwerwiegende Taten sowie aus den Behandlungsmöglichkeiten der damit zusammenhängenden forensisch relevanten Auffälligkeiten des Straftäters. Aus einer breiten wissenschaftlichen Befundlage geht hervor, dass solch eine Behandlungsbedürftigkeit mitnichten nur im allgemeinpsychiatrischen Sinne psychisch Kranke und schon gar nicht ausschließlich schuldunfähige Straftäter aufweisen. Vielmehr können weitere deliktrelevante persönlichkeitsnahe Risikofaktoren, die einer wirksamen Behandlung grundsätzlich zugänglich sind, kausal im Zusammenhang mit Delinquenz und Rückfälligkeit stehen.

In der aktuellen Rechtsprechung in Deutschland und der Schweiz spiegelt sich diese Erkenntnis nicht wider. Im Gegenteil: Voraussetzung für die Anordnung einer therapeutischen Maßnahme ist das Vorliegen einer „schweren psychischen Störung“ gemäß ICD/DSM und in Deutschland zusätzlich die verminderte Schuldfähigkeit oder Schuldunfähigkeit.

Diese Eingrenzung blendet die Behandlungsbedürftigkeit eines bedeutsamen Teils der Straftäterpopulation aus und untergräbt damit, was die Forensik zu leisten im Stande wäre: differenziert deliktorientiert zu therapieren. Verfahren wie das Forensische Operationalisierte Therapie-Risiko-Evaluationssystem (FOTRES 3) können gegenüber allgemeinpsychiatrischen Kriterienkatalogen einen inkrementellen Beitrag zur dafür notwendigen forensischen Diagnostik liefern. Erste empirische Befunde dazu werden im Artikel vorgestellt.
Impact of wind speed and apartment ventilation on indoor concentrations of PM10 and PM2.5 in Kraków, Poland
Authors: Ścibor Monika , Bokwa Anita , Balcerzak Bartosz
Published: March 2020

In the period 2013–2015, PM2.5 and PM10 outdoor and indoor concentrations were measured on 23 days in cold half-year periods, in Kraków, Poland. Air pollution is still a serious health hazard for the inhabitants as Kraków is located in a concave landform and smog episodes occur often in the city during the heating periods, due to poor natural ventilation and frequent air temperature inversions. The PM10 and PM2.5 concentrations were studied for very good and very poor weather conditions concerning air pollution. Each subgroup was further divided into cases when the apartments’ windows were kept open or closed. Daily courses of PM10 and PM2.5 concentrations were very dynamic. Weather pattern, in particular wind speed and atmospheric stability, largely determined the concentrations of PM10 in ambient air. The share of PM2.5 in PM10 indoor concentrations reached around 70% for both types of weather conditions. The share of indoor PM10 and PM2.5 mean concentrations in the outdoor values was higher during good than during poor weather conditions by about 10%.
Evaluation of test results and ranking criteria for Varestraint testing of an austenitic high-temperature alloy
Authors: Johansson Mikael M. , Stenvall Peter , Karlsson Leif , Andersson Joel
Published: March 2020

Varestraint testing is commonly used to evaluate hot cracking susceptibility of materials. In this paper, the dependence of operators and evaluation technique on test results is studied for a high-temperature austenitic stainless steel (UNS S31035). Samples were tested at six different strain levels ranging from 0.7 to 3.8%. Four different operators evaluated the same samples following the same instructions on how to measure the cracks manually in an optical microscope at × 25 magnification. The largest variation among operators evaluation was found for low strain levels where small and few cracks were found. In addition, one of the four operators used image analysis to evaluate the samples at × 50 magnification. The average total crack length and total number of cracks in fusion zone and heat-affected zone were approximately 1.5 times higher when using image analysis compared with manual evaluation. Image analysis at × 50 made it possible to detect smaller cracks compared with manual evaluation at × 25 magnification, contributing to an increased number of cracks detected.

The maximum crack length using image analysis at × 50 was similar to manual evaluation made at × 25 magnification and was the criterion that showed the least variation in this study. However, further comparisons using other magnifications are needed to verify the agreement between manual evaluation and image analysis found in this study. An advantage with evaluation using image analysis is that it provides traceable results. A harmonized standard for Varestraint testing, and especially for evaluation, would decrease the variation among operators and laboratories.
Quality of life for older patients with cancer: a review of the evidence supporting melatonin use
Authors: Ginzac Angeline , Dubois Sophie , Hager Marie-Odile , Kwiatkowski Fabrice , Passildas Judith , Biau Julian , Abrial Catherine , Mouret-Reynier Marie-Ange , Thivat Emilie , Durando Xavier
Published: March 2020

Purpose

The proportion of older populations living with cancer is on the increase. Maintaining or improving their quality of life (QoL) has become an important goal in the treatment of cancer and has become an endpoint in clinical trials. Melatonin regulates a wide variety of physiological functions and is involved in the initiation of sleep and the improvement of QoL. With age, the secretion of melatonin decreases and could lead to a deterioration in QoL.

Methods

Literature searches were conducted using the PubMed database. The search terms and derivatives of “metastatic cancer”, “older patients”, “quality of life” and “melatonin” were used. Titles and abstracts were screened to identify whether studies were relevant for full-text screening.

Results

There is major concern about the symptoms older cancer patients encounter during treatment because they can impact their QoL. Melatonin supplementation presents several benefits for older patients: improvement in survival, decrease in symptoms induced by cancer and cancer treatment, and also improvements in quality of life.

Conclusion

It therefore seems appropriate to study the impact of melatonin supplementation during cytotoxic therapy on QoL among elderly patients with metastatic cancer. The use of melatonin as a therapeutic strategy seems particularly suitable for elderly patients, a population known to secrete significantly less melatonin. However, to date, no studies have been conducted in this population.
Improving ant colony optimization algorithm with epsilon greedy and Levy flight
Authors: Liu Yahui , Cao Buyang , Li Hehua
Published: March 2020

Ant colony optimization (ACO) algorithm is a meta-heuristic and reinforcement learning algorithm, which has been widely applied to solve various optimization problems. The key to improving the performance of ACO is to effectively resolve the exploration/exploitation dilemma. Epsilon greedy is an important and widely applied policy-based exploration method in reinforcement learning and has also been employed to improve ACO algorithms as the pseudo-stochastic mechanism. Levy flight is based on Levy distribution and helps to balance searching space and speed for global optimization. Taking advantage of both epsilon greedy and Levy flight, a greedy–Levy ACO incorporating these two approaches is proposed to solve complicated combinatorial optimization problems. Specifically, it is implemented on the top of max–min ACO to solve the traveling salesman problem (TSP) problems. According to the computational experiments using standard TSPLIB instances, greedy–Levy ACO outperforms max–min ACO and other latest TSP solvers, which demonstrates the effectiveness of the proposed methodology.
Multiplex networks reveal geographic constraints on illicit wildlife trafficking
Authors: Arroyave Felber J. , Petersen Alexander M. , Jenkins Jeffrey , Hurtado Rafael
Published: March 2020

Illicit wildlife trafficking poses a threat to the conservation of species and ecosystems, and represents a fundamental source of biodiversity loss, alongside climate change and large-scale land degradation. Despite the seriousness of this issue, little is known about various socio-cultural demand sources underlying trafficking networks, for example the forthright consumption of endangered species on different cultural contexts. Our study illustrates how wildlife trafficking represents a wicked problem at the intersection of criminal enforcement, cultural heritage and environmental systems management. As with similar network-based crimes, institutions are frequently ineffective at curbing wildlife trafficking, partly due to the lack of information detailing activities within illicit trading networks. To address this shortcoming, we leverage official government records documenting the illegal trade of reptiles in Colombia. As such, our study contributes to the understanding of how and why wildlife trafficking persists across robust trafficking networks, which are conduits for a broader range of black-market goods. Leveraging geo-spatial data, we construct a multiplex representation of wildlife trafficking networks, which facilitates identifying network properties that are signatures of strategic trafficker behavior. In particular, our results indicate that traffickers’ actions are constrained by spatial and market customs, a result which is apparent only within an integrated multiplex representation. Characteristic levels of sub-network coupling further indicate that traffickers strategically leverage knowledge of the entire system. We argue that this multiplex representation is essential for prioritizing crime enforcement strategies aimed at disrupting robust trade networks, thereby enhancing the effectiveness and resources allocation of institutions charged with curbing illicit trafficking. We develop a generalizable model of multiplex criminal trade networks suitable for communicating with policy makers and practitioners, thereby facilitating rapid translation into public policy and environmental conservation efforts.
Mechanosensitive Vaginal Epithelial Adenosine Triphosphate Release and Pannexin 1 Channels in Healthy, in Type 1 Diabetic, and in Surgically Castrated Female Mice
Authors: Harroche Jessica , Urban-Maldonado Marcia , Thi Mia M. , Suadicani Sylvia O.
Published: March 2020

Background

Distension of hollow organs is known to release adenosine triphosphate (ATP) from the lining epithelium, which triggers local responses and activates sensory nerves to convey information to the central nervous system. However, little is known regarding participation of ATP and mediators of ATP release, such as Pannexin 1 (Panx1) channels, in mechanisms of vaginal mechanosensory transduction and of changes imposed by diabetes and menopause, conditions associated with vaginal dysfunction and risk for impaired genital arousal.

Aim

To investigate if intravaginal mechanical stimulation triggers vaginal ATP release and if (a) this response involves Panx1 channels and (b) this response is altered in animal models of diabetes and menopause.

Methods

Diabetic Akita female mice were used as a type 1 diabetes (T1D) model and surgical castration (ovariectomy [OVX]) as a menopause model. Panx1-null mice were used to evaluate Panx1 participation in mechanosensitive vaginal ATP release. Vaginal washes were collected from anesthetized mice at baseline (non-stimulated) and at 5 minutes after intravaginal stimulation. For the OVX and Sham groups, samples were collected before surgery and at 4, 12, 22, 24, and 28 weeks after surgery. ATP levels in vaginal washes were measured using the luciferin-luciferase assay. Panx1 mRNA levels in vaginal epithelium were quantified by quantitative polymerase chain reaction.

Outcomes

The main outcome measures are quantification of mechanosensitive vaginal ATP release and evaluation of impact of Panx1 deletion, OVX, and T1D on this response.

Results

Intravaginal mechanical stimulation–induced vaginal ATP release was 84% lower in Panx1-null (P < .001) and 76% lower in diabetic (P < .0001) mice compared with controls and was reduced in a progressive and significant manner in OVX mice when compared with Sham. Panx1 mRNA expression in vaginal epithelium was 44% lower in diabetics than that in controls (P < .05) and 40% lower in OVX than that in the Sham (P < .05) group.

Clinical Translation

Panx1 downregulation and consequent attenuation of mechanosensitive vaginal responses may be implicated in mechanisms of female genital arousal disorder, thereby providing potential targets for novel therapies to manage this condition.

Strengths & Limitations

Using animal models, we demonstrated Panx1 involvement in mechanosensitive vaginal ATP release and effects of T1D and menopause on this response and on Panx1 expression. A limitation is that sex steroid hormone levels were not measured, precluding correlations and insights into mechanisms that may regulate Panx1 expression in the vaginal epithelium.

Conclusions

Panx1 channel is a component of the vaginal epithelial mechanosensory transduction system that is essential for proper vaginal response to mechanical stimulation and is targeted in T1D and menopause.
Responsibility and the Problem of So-Called Marginal Agents
Authors: SVIRSKY LARISA
Published: March 2020

Philosophical views of responsibility often identify responsible agency with capacities such as rationality and self-control. Yet in ordinary life, we frequently hold individuals responsible who are deficient in these capacities, such as children or people with mental illness. The existing literature that addresses these cases has suggested that we merely pretend to hold these agents responsible or that they are responsible to a diminished degree. In this paper, I demonstrate that neither of these approaches is satisfactory, and I offer an alternative focused on the role relationships play in determining whether it is appropriate to hold someone responsible. I argue that relationships are sources of normative expectations about how parties in that relationship ought to behave and that we can be responsible in virtue of being subject to these norms. This is so not only for those who are impaired or immature, but for all of us.
Epidemiological Characteristics on the Clustering Nature of COVID-19 in Qingdao City, 2020: A Descriptive Analysis
Authors: Jia Jing , Hu Xiaowen , Yang Feng , Song Xin , Dong Liyan , Zhang Jingfei , Jiang Fachun , Gao Ruqin
Published: March 2020

Objectives:

As an emerging infectious disease, COVID-19 has involved many countries and regions. With the further development of the epidemic, the proportion of clusters has increased.

Methods:

In our study, we collected information on COVID-19 clusters in Qingdao City. The epidemiological characteristics and clinical manifestations were analyzed.

Results:

Eleven clusters of COVID-19 were reported in Qingdao City between January 29, and February 23, 2020, involving 44 confirmed cases, which accounted for 73.33% of all confirmed cases. From January 19 to February 2, 2020, the cases mainly concentrated in the district that had many designated hospitals. Patients aged 20-59 y old accounted for the largest proportion (68.18%) of cases; the male-to-female sex ratio was 0.52:1. Three cases were infected from exposure to confirmed cases. The average incubation period was 6.28 d. The median number of cases per cluster was 4, and the median duration time was 6 d. The median cumulative number of exposed persons was 53.

Conclusion:

More attention should be paid to the epidemic of clusters in prevention and control of COVID-19. In addition to isolating patients, it is essential to track, screen, and isolate those who have come in close contact with patients. Self-isolation is the key especially for healthy people in the epidemic area.
Probing the relationship between BTBD9 and MEIS1 in C. elegans and mouse
Authors: Lyu Shangru , Doroodchi Atbin , Sheng Yi , DeAndrade Mark P. , Yang Youfeng , Liu Yuning , Miller Michael A. , Xiao Rui , Li Yuqing
Published: March 2020

Restless legs syndrome (RLS) is a neurological disorder characterized by an urge to move and uncomfortable sensations. Genetic studies have identified polymorphisms in up to 19 risk loci, including MEIS1 and BTBD9. Rodents deficient in either homolog show RLS-like phenotypes. However, whether MEIS1 and BTBD9 interact in vivo is unclear. Here, with C. elegans, we observed that the hyperactive egg-laying behavior caused by loss of BTBD9 homolog was counteracted by knockdown of MEIS1 homolog. This was further investigated in mutant mice with Btbd9, Meis1, or both knocked out. The double knockout mice showed an earlier onset of the motor deficit in a wheel running test but did not have increased sensitivity to heat stimuli as observed in single knock outs. Meis1 protein level was not influenced by Btbd9 deficiency, and Btbd9 transcription was not affected by Meis1 haploinsufficiency. Our results demonstrate that MEIS1 and BTBD9 do not regulate each other.
SANOM-HOBBIT: simulated annealing-based ontology matching on HOBBIT platform
Authors: Mohammadi Majid , Hofman Wout , Tan Yao-Hua
Published: March 2020

Ontology alignment is an important and inescapable problem for the interconnections of two ontologies stating the same concepts. Ontology alignment evaluation initiative (OAEI) has been taken place for more than a decade to monitor and help the progress of the field and to compare systematically existing alignment systems. As of 2018, the evaluation of systems is partly transitioned to the HOBBIT platform. This paper contains the description of our alignment system, simulated annealing-based ontology matching (SANOM), and its adaption into the HOBBIT platform. The outcomes of SANOM on the HOBBIT for several OAEI tracks are reported, and the results are compared with other competing systems in the corresponding tracks.
Meningococcal carriage in Norwegian teenagers: strain characterisation and assessment of risk factors
Authors: Watle S. V. , Caugant D. A. , Tunheim G. , Bekkevold T. , Laake I. , Brynildsrud O. B. , Næss L. M.
Published: March 2020

Teenagers have a higher risk of invasive meningococcal disease (IMD) than the general population. This cross-sectional study aimed to characterise strains of Neisseria meningitidis circulating among Norwegian teenagers and to assess risk factors for meningococcal carriage. Oropharyngeal swabs were collected from secondary-school students in southeastern Norway in 2018–2019. Meningococcal isolates were characterised using whole genome sequencing. Risk factors for meningococcal carriage were assessed from questionnaire data. Samples were obtained from 2296 12–24-year-olds (majority 13–19-year-olds). N. meningitidis was identified in 167 (7.3%) individuals. The highest carriage rate was found among 18-year-olds (16.4%). Most carriage isolates were capsule null (40.1%) or genogroup Y (33.5%). Clonal complexes cc23 (35.9%) and cc198 (32.3%) dominated and 38.9% of carriage strains were similar to invasive strains currently causing IMD in Norway. Use of Swedish snus (smokeless tobacco) (OR 1.56, 95% CI 1.07–2.27), kissing >two persons/month (OR 2.76, 95% CI 1.49–5.10) and partying >10 times/3months (OR 3.50, 95% CI 1.45–8.48) were associated with carriage, while age, cigarette smoking, sharing of drinking bottles and meningococcal vaccination were not. The high meningococcal carriage rate among 18-year-olds is probably due to risk-related behaviour. Use of Swedish snus is possibly a new risk factor for meningococcal carriage. Almost 40% of circulating carriage strains have invasive potential.
Risk of bacteremia in patients presenting with shaking chills and vomiting - a prospective cohort study
Authors: Holmqvist M. , Inghammar M. , Påhlman L. I. , Boyd J. , Åkesson P. , Linder A. , Kahn F.
Published: March 2020

Chills and vomiting have traditionally been associated with severe bacterial infections and bacteremia. However, few modern studies have in a prospective way evaluated the association of these signs with bacteremia, which is the aim of this prospective, multicenter study. Patients presenting to the emergency department with at least one affected vital sign (increased respiratory rate, increased heart rate, altered mental status, decreased blood pressure or decreased oxygen saturation) were included. A total of 479 patients were prospectively enrolled. Blood cultures were obtained from 197 patients. Of the 32 patients with a positive blood culture 11 patients (34%) had experienced shaking chills compared with 23 (14%) of the 165 patients with a negative blood culture, P = 0.009. A logistic regression was fitted to show the estimated odds ratio (OR) for a positive blood culture according to shaking chills. In a univariate model shaking chills had an OR of 3.23 (95% CI 1.35–7.52) and in a multivariate model the OR was 5.9 (95% CI 2.05–17.17) for those without prior antibiotics adjusted for age, sex, and prior antibiotics. The presence of vomiting was also addressed, but neither a univariate nor a multivariate logistic regression showed any association between vomiting and bacteremia. In conclusion, among patients at the emergency department with at least one affected vital sign, shaking chills but not vomiting were associated with bacteremia.
Czech Stalemate? The Role of Party Organization for the Communist Party of Bohemia and Moravia since 2010
Authors: Bankov Petar
Published: March 2020

Almost three decades after the regime change in Central and Eastern Europe, some of the political parties that were successors of the communists continue to enjoy important electoral support. This article makes an attempt to understand why this happens and focuses on the role of the party organization. It includes a qualitative analysis on the typical case of the Communist Party of Bohemia and Moravia (KSČM) based on a series of semi-structured interviews with party cadres and independent researchers. These interviews reveal that the stable territorial distribution of their performance amidst significant electoral volatility since 2010 highlights an organizational impasse within the party.
French-speaking Intellectuals and Culture in Some Key Works of Edward Said
Authors: Hart Jonathan Locke
Published: March 2020

Edward Said, who is a key intellectual figure in the theory and interpretation of western European colonization and decolonization, sees criticism as personal engagement and a matter of character and not simply scholarship. He is highly influential in the fields of colonialism, postcolonialism, representation and interpretation. Of the many influences Said in turn has undergone, those in French deserve specific exploration. This article explores some of these influences, but it also looks at some of Said’s own representations of French and French-speaking culture. To this end I will examine how Said in some of his key works addresses, among other things, the role of the intellectual, Orientalism, colonialism, and literary theory. My approach is chronological. I will first turn to the role the French-speaking world plays in Said’s first published book, Joseph Conrad and the Fiction of Autobiography (1966), and then to a couple of Said’s most celebrated works: Orientalism (1978) and Culture and Imperialism (1993).
Clinical characteristics and factors influencing the prognosis of Behçet’s disease complicated with vascular involvement
Authors: Lin Chen-Hong , Luo Dan , Ma Hai-Fen , Shen Yan , Zou Jun , Guan Jian-Long
Published: March 2020

Summary: Background: Vascular Behçet's disease (VBD) might involve all sizes of arterial and venous vessels. Major vascular involvement caused the primary death in Behçet's syndrome (BS). We aimed to investigate the clinical characteristics and factors influencing the prognosis of VBD. Patients and methods: A retrospective analysis of the prospectively collected data of the Shanghai BS database from October 2012 to October 2018 was conducted. Patients who were diagnosed with BS and merged with venous thrombosis, arterial aneurysms, and arterial stenosis/occlusions were enrolled. Results: There were 47 patients with vascular involvement among 836 BS patients, 38 males and 9 females. The numbers of patients with venous thrombosis, arterial aneurysm, and arterial stenosis/occlusion were 25 (53.2 %), 21 (44.7 %), and 12 (25.5 %), respectively. Nearly half of the venous thromboses were located in limbs (n = 22, 46.8 %). Arterial aneurysm was the main form of arterial lesion. Most of the patients (93.6 %) were treated with corticosteroids and immunosuppressants. Late onset of BS or with arterial involvement had lower treatment response. Therapy with biological agents had significantly better results than that in the group without biological treatment (94.1 % vs. 80 %, P = 0.005). Conclusions: VBD showed a male preponderance and more than half of the patients presented with venous thrombosis. Late onset and arterial involvement were associated with poor prognosis. Therapy with biological agents is a viable alternative treatment to improve the prognosis.