bluuebunny/crossref_metadata_2025 huggingface dataset:
Synchronous aldosterone- and cortisol-producing adrenocortical adenomas diagnosed using CYP11B immunohistochemistry
Authors: Stenman Adam , Shabo Ivan , Ramström Annica , Zedenius Jan , Juhlin Carl Christofer
Published: October 2019

Immunohistochemistry with antibodies targeting enzymes responsible for the final conversion steps of cortisol (CYP11B1) and aldosterone (CYP11B2) is gaining ground as an adjunct tool in the postoperative evaluation of adrenocortical nodules. The method allows the pathologist to visualize hormone production for each lesion, thereby permitting a more exact assessment regarding the distinction between adrenocortical adenomas and adrenocortical hyperplasia, with implications for patient follow-up. We describe how immunohistochemistry facilitated the histopathological diagnosis of twin adenoma (one cortisol- and one aldosterone-producing) from suspected hyperplasia in a patient with hypertension, mild autonomous cortisol secretion and concurrent adrenocorticotropic hormone–producing adrenomedullary hyperplasia. As the nodules were similar in size and displayed rather analogous histology, CYP11B1 and B2 immunohistochemistry was needed to exclude adrenocortical hyperplasia, allowing us to discharge the patient from further surveillance. We conclude that the application of functional immunohistochemistry has direct clinical consequences and advocates the prompt introduction of these markers in clinical routine.
Risk Factor Analysis for Proximal Junctional Kyphosis After Adult Spinal Deformity Surgery: A New Simple Scoring System to Identify High-Risk Patients
Authors: Lafage Renaud , Beyer George , Schwab Frank , Klineberg Eric , Burton Douglas , Bess Shay , Kim Han Jo , Smith Justin , Ames Christopher , Hostin Richard , Khalife Marc , Shaffrey Christopher , Mundis Gregory , Lafage Virginie
Published: October 2019

Study Design:

Retrospective cohort study.

Objective:

Develop a simple scoring system to estimate proximal junctional kyphosis (PJK) risk.

Methods:

A total of 417 adult spinal deformity (ASD) patients (80% females, 57.8 years) with 2-year follow-up were included. PJK was defined as a >10° kyphotic angle between the upper-most instrumented vertebra (UIV) and the vertebrae 2 levels above the UIV (UIV+2). Based on a previous literature review, the following point score was attributed to parameters likely to impact PJK development: age >55 years (1 point), fusion to S1/ilium (1 point), UIV in the upper thoracic spine (UIV-UT: 1 point), UIV in the lower thoracic region (UIV-LT: 2 points), flattening of the thoracic kyphosis (TK) relative to the lumbar lordosis (LL; ie, ▵LL − ▵TK) greater than 10° (1 point).

Results:

At 2 years, the overall PJK rate was 43%. The odds ratios for each risk factor were the following: age >55 years (2.52), fusion to S1/ilium (5.17), UIV-UT (6.63), UIV-LT (8.24), and ▵LL − ▵TK >10° (1.59). Analysis by risk factor revealed a significant impact on PJK (no PJK vs PJK): age >55 years (28% vs 51%, P < .001), LIV S1/ilium (16.3% vs 51.4%, P < .001), UIV in lower thoracic spine (12.0% vs 38.7% vs 52.9%, P < .001), and a >10° surgical reduction in TK relative to LL increase (40.0% vs 51.5%, P < .001). The PJK rate by point score was as follows: 1 = 17%, 2 = 29%, 3 = 40%, 4 = 53%, and 5 = 69%.

Conclusion:

A pragmatic scoring system was developed that is tied to the increasing risk of PJK. These findings are helpful for surgical planning and preoperative counseling.
ECM-enriched alginate hydrogels for bioartificial pancreas: an ideal niche to improve insulin secretion and diabetic glucose profile
Authors: Crisóstomo Joana , Pereira Ana M , Bidarra Sílvia J , Gonçalves Ana C , Granja Pedro L , Coelho Jorge FJ , Barrias Cristina C , Seiça Raquel
Published: October 2019

Introduction:

The success of a bioartificial pancreas crucially depends on ameliorating encapsulated beta cells survival and function. By mimicking the cellular in vivo niche, the aim of this study was to develop a novel model for beta cells encapsulation capable of establishing an appropriate microenvironment that supports interactions between cells and extracellular matrix (ECM) components.

Methods:

ECM components (Arg-Gly-Asp, abbreviated as RGD) were chemically incorporated in alginate hydrogels (alginate-RGD). After encapsulation, INS-1E beta cells outcome was analyzed in vitro and after their implantation in an animal model of diabetes.

Results:

Our alginate-RGD model demonstrated to be a good in vitro niche for supporting beta cells viability, proliferation, and activity, namely by improving the key feature of insulin secretion. RGD peptides promoted cell–matrix interactions, enhanced endogenous ECM components expression, and favored the assembly of individual cells into multicellular spheroids, an essential configuration for proper beta cell functioning. In vivo, our pivotal model for diabetes treatment exhibited an improved glycemic profile of type 2 diabetic rats, where insulin secreted from encapsulated cells was more efficiently used.

Conclusions:

We were able to successfully introduce a novel valuable function in an old ally in biomedical applications, the alginate. The proposed alginate-RGD model stands out as a promising approach to improve beta cells survival and function, increasing the success of this therapeutic strategy, which might greatly improve the quality of life of an increasing number of diabetic patients worldwide.
On the (ir)relevance of religion for human resource management and diversity management: A German perspective
Authors: Alewell Dorothea , Rastetter Daniela
Published: October 2019

From the limited empirical knowledge we have, religion is hardly ever implemented as a dimension of diversity management in German firms. As religion is increasingly important in many areas of law, with regard to world conflicts, the integration of refugees, societal tensions and potentially high religious diversity of employees and customers in globally acting firms, this finding triggers questions why or why not religion is applied as a dimension of diversity management in German companies. We thus discuss pros and cons for considering religion as a dimension of diversity management, arguing that on the one side there are many arguments for employers in favour of considering religion as a diversity dimension, especially arguments grounded on legal regulations, discrimination or effects on performance and resilience of employees. However, on the negative side, attributions of conflict and irrationality connected with religion and employers’ difficulties in collecting a sound database may hamper implementation as a diversity dimension. We conclude with a research outlook.
Effects of chemical reaction and activation energy on a Carreau nanoliquid past a permeable surface under zero mass flux conditions
Authors: Ramesh GK , Kumar K Ganesh , Chamkha Ali J , Gorla Rama Subba Reddy
Published: October 2019

Arrhenius condition has been broadly utilized as a model of the temperature impact on the rate compound responses and organic procedure. Hence, our aim of this article is to examine the effects of chemical reaction and activation energy on a Carreau nanoliquid in a permeable surface. For thermal and mass transport curiosities, the cumulative upgrade of convective type condition and zero mass transition have been considered. The overseeing sets of partial differential equations are rendered into coupled nonlinear ordinary differential equations. The arrangement of the subsequent ordinary differential equations is acquired with the assistance of the Runge-Kutta-Fehlberg-fourth-fifth order (RKF-45) procedure. The influence of relevant parameters and physical quantities is investigated. The results show that the presence of reaction rate and energy activation term decelerates the temperature and concentration gradients.
Terminal deoxynucleotidyl transferase promotes acute myeloid leukemia by priming FLT3-ITD replication slippage
Authors: Borrow Julian , Dyer Sara A. , Akiki Susanna , Griffiths Michael J.
Published: October 2019

These complementary papers by Borrow et al report persuasive but indirect evidence that the lymphoid enzyme terminal deoxynucleotidyl transferase (TdT) is the mutagen responsible for 2 common pathogenic genetic changes in acute myeloid leukemia (AML): FLT3-ITD and NPM1.
Fatty airways: implications for obstructive disease
Authors: Elliot John G. , Donovan Graham M. , Wang Kimberley C.W. , Green Francis H.Y. , James Alan L. , Noble Peter B.
Published: October 2019

Epidemiological studies report that overweight or obese asthmatic subjects have more severe disease than those of a healthy weight. We postulated that accumulation of adipose tissue within the airway wall may occur in overweight patients and contribute to airway pathology. Our aim was to determine the relationship between adipose tissue within the airway wall and body mass index (BMI) in individuals with and without asthma.

Transverse airway sections were sampled in a stratified manner frompost mortemlungs of control subjects (n=15) and cases of nonfatal (n=21) and fatal (n=16) asthma. The relationship between airway adipose tissue, remodelling and inflammation was assessed. The areas of the airway wall and adipose tissue were estimated by point count and expressed as area per mm of basement membrane perimeter (Pbm). The number of eosinophils and neutrophils were expressed as area densities.

BMI ranged from 15 to 45 kg·m−2and was greater in nonfatal asthma cases (p<0.05). Adipose tissue was identified in the outer wall of large airways (Pbm >6 mm), but was rarely seen in small airways (Pbm <6 mm). Adipose tissue area correlated positively with eosinophils and neutrophils in fatal asthma (Pbm >12 mm, p<0.01), and with neutrophils in control subjects (Pbm >6 mm, p=0.04).

These data show that adipose tissue is present within the airway wall and is related to BMI, wall thickness and the number of inflammatory cells. Therefore, the accumulation of airway adipose tissue in overweight individuals may contribute to airway pathophysiology.
Antibiotic efficacy varies based on the infection model and treatment regimen forPseudomonas aeruginosa
Authors: Cigana Cristina , Ranucci Serena , Rossi Alice , De Fino Ida , Melessike Medede , Bragonzi Alessandra
Published: October 2019

Antibiotic discovery and preclinical testing are needed to combat thePseudomonas aeruginosahealth threat. Most frequently, antibiotic efficacy is tested in models of acute respiratory infection, with chronic pneumonia remaining largely unexplored. This approach generates serious concerns about the evaluation of treatment for chronically infected patients, and highlights the need for animal models that mimic the course of human disease.

In this study, the efficacy of the marketed antibacterial drugs tobramycin (TOB) and colistin (COL) was tested in murine models of acute and chronicP. aeruginosapulmonary infection. Different administration routes (intranasal, aerosol or subcutaneous) and treatment schedules (soon or 7 days post-infection) were tested.

In the acute infection model, aerosol and subcutaneous administration of TOB reduced the bacterial burden and inflammatory response, while intranasal treatment showed modest efficacy. COL reduced the bacterial burden less effectively but dampened inflammation. Mice treated soon after chronic infection for 7 days with daily aerosol or subcutaneous administration of TOB showed higher and more rapid body weight recovery and reduced bacterial burden and inflammation than vehicle-treated mice. COL-treated mice showed no improvement in body weight or change in inflammation. Modest bacterial burden reduction was recorded only with aerosol COL administration. When treatment for chronic infection was commenced 7 days after infection, both TOB and COL failed to reduceP. aeruginosaburden and inflammation, or aid in recovery of body weight.

Our findings suggest that the animal model and treatment regimen should be carefully chosen based on the type of infection to assess antibiotic efficacy.
The analgesic efficacy of ultrasound-guided transversus abdominis plane block for retroperitoneoscopic renal surgery: a randomized controlled study
Authors: Li Xue , Xu Zhen-Zhen , Li Xue-Ying , Jiang Ting-Ting , Lin Zeng-Mao , Wang Dong-Xin
Published: October 2019

Background

Ultrasound-guided lateral transversus abdominis plane (TAP) block can provide definite analgesia to the anterior abdominal wall. However, whether this method is useful in renal surgery through the lateral abdominal wall pathway remains unknown. The study aimed to evaluate the analgesic efficacy of lateral TAP block for retroperitoneoscopic partial or radical nephrectomy.

Method

In this prospective, randomized, double-blind, placebo-controlled trial, eligible patients were randomized into two groups. After anaesthesia induction, ultrasound-guided lateral TAP block was performed with either 30 ml of 0.4% ropivacaine (Group T) or an equivalent volume of normal saline (Group C). The primary outcomes were opioid consumption during surgery and in the first 24 h after surgery. Secondary outcomes included postsurgical pain intensity immediately awakening from anaesthesia and at 0.5, 1, 2, 6, 12, and 24 h after surgery, as well as recovery variables including the incidence of postoperative nausea and vomiting (PONV), sleep quality, time to first ambulation, drainage and length of hospital stay.

Results

A total of 104 patients were enrolled and randomized (53 in Group T and 51 in Group C). Laparoscopic surgery was converted to open surgery in one patient of Group T; this patient was excluded from the outcome analysis. The opioid consumption during surgery (intravenous morphine equivalent dose: median 35.0 mg [interquartile range 18.0, 49.6] in Group C vs. 40.3 mg [20.9, 59.0] in Group T, P = 0.281) and in the first 24 h after surgery (10.8 mg [7.8, 21.7] in Group C vs. 13.2 mg [8.0, 26.6] in Group T, P = 0.311) did not differ significantly between groups. There were no significant differences between groups regarding the pain intensity at all time points after surgery and the recovery variables (all P > 0.05).

Conclusions

Our results showed that, in patients undergoing retroperitoneoscopic renal surgery, preoperative lateral TAP did not decrease intra- and postoperative opioid consumption, nor did it relieve pain intensity or promote postoperative recovery in the first 24 h after surgery. However, the trial might be underpowered.

Trial registration

This study was registered on November 4, 2017, in the Chinese Clinical Trail Registry with the identification number ChiCTR-INR-17013244.
Smart polymers for cell therapy and precision medicine
Authors: Huang Hung-Jin , Tsai Yu-Liang , Lin Shih-Ho , Hsu Shan-hui
Published: October 2019

Soft materials have been developed very rapidly in the biomedical field over the past 10 years because of advances in medical devices, cell therapy, and 3D printing for precision medicine. Smart polymers are one category of soft materials that respond to environmental changes. One typical example is the thermally-responsive polymers, which are widely used as cell carriers and in 3D printing. Self-healing polymers are one type of smart polymers that have the capacity to recover the structure after repeated damages and are often injectable through needles. Shape memory polymers are another type with the ability to memorize their original shape. These smart polymers can be used as cell/drug/protein carriers. Their injectability and shape memory performance allow them to be applied in bioprinting, minimally invasive surgery, and precision medicine. This review will describe the general materials design, characterization, as well as the current progresses and challenges of these smart polymers.
Production of galactitol from galactose by the oleaginous yeast Rhodosporidium toruloides IFO0880
Authors: Jagtap Sujit Sadashiv , Bedekar Ashwini Ashok , Liu Jing-Jing , Jin Yong-Su , Rao Christopher V.
Published: October 2019

Background

Sugar alcohols are commonly used as low-calorie sweeteners and can serve as potential building blocks for bio-based chemicals. Previous work has shown that the oleaginous yeastRhodosporidium toruloidesIFO0880 can natively produce arabitol from xylose at relatively high titers, suggesting that it may be a useful host for sugar alcohol production. In this work, we explored whetherR. toruloidescan produce additional sugar alcohols.

Results

Rhodosporidium toruloidesis able to produce galactitol from galactose. During growth in nitrogen-rich medium,R. toruloidesproduced 3.2 ± 0.6 g/L, and 8.4 ± 0.8 g/L galactitol from 20 to 40 g/L galactose, respectively. In addition,R. toruloideswas able to produce galactitol from galactose at reduced titers during growth in nitrogen-poor medium, which also induces lipid production. These results suggest thatR. toruloidescan potentially be used for the co-production of lipids and galactitol from galactose. We further characterized the mechanism for galactitol production, including identifying and biochemically characterizing the critical aldose reductase. Intracellular metabolite analysis was also performed to further understand galactose metabolism.

Conclusions

Rhodosporidium toruloideshas traditionally been used for the production of lipids and lipid-based chemicals. Our work demonstrates thatR. toruloidescan also produce galactitol, which can be used to produce polymers with applications in medicine and as a precursor for anti-cancer drugs. Collectively, our results further establish thatR. toruloidescan produce multiple value-added chemicals from a wide range of sugars.
Participant and study partner prediction and identification of cognitive impairment in preclinical Alzheimer’s disease: study partner vs. participant accuracy
Authors:   for the Alzheimer’s Disease Neuroimaging Initiative, Ryan Mary M. , Grill Joshua D. , Gillen Daniel L.
Published: October 2019

Background

Preclinical Alzheimer’s disease (AD) clinical trials require participants to enroll with a study partner, a person who can attend visits and report changes in the participant’s cognitive ability. Whether study partners, compared to participants themselves, provide added information about participant cognition in preclinical AD trials is an open question. We tested the hypothesis that study partners provide meaningful information related to participant cognition cross-sectionally and longitudinally, and assessed whether amyloid status modified observed effects.

Methods

We assessed participant and study partner Everyday Cognition (ECog) scores and participant Alzheimer’s Disease Assessment Scale 13-item cognitive subscale (ADAS13) data from 335 cognitively normal participant-partner dyads in the AD Neuroimaging Initiative. We used random forest and linear mixed effects (LME) models to predict ADAS13 scores as a function of participant and/or study partner ECog scores over time. LME models were adjusted for potential confounding factors, including APOE4 status, amyloid status, baseline age, years of education, and sex. Random forest models were split into the above factors, as well as race/ethnicity and other available neuropsychological battery test scores.

Results

In random forest models predicting ADAS13 12 months from baseline, we observed no difference in the estimated mean variable importance (eMVI) associated with baseline study partner ECog compared to the baseline participant ECog (eMVI = 0.15, 95%CB 0.13, 0.16 for partner; eMVI = 0.15, 95%CB 0.14, 0.16 for participant). In models predicting ADAS13 48 months after baseline, the eMVI associated with baseline study partner ECog was slightly lower than that associated with baseline participant ECog (eMVI = 0.21, 95%CB 0.20, 0.22 for partner; eMVI = 0.24, 95%CB 0.22, 0.25 for participant). In cross-sectional models, study partner eMVI was twice as large as participant eMVI at 12 months (eMVI = 0.20, 95%CB 0.19, 0.21 for partner; eMVI = 0.09, 95%CB 0.09, 0.10 for participant) and three times as large at 48 months (eMVI = 0.38, 95%CB 0.36, 0.39 for partner; eMVI = 0.13, 95%CB 0.12, 0.14 for participant). We did not observe qualitative differences by amyloid status.

Conclusions

While baseline participant reports reasonably predict subsequent cognitive change, informants perform better at cross-sectionally recognizing cognitive status as observation time grows. The study partner requirement may be essential to ensure trial data integrity, especially in longer trials.
Amyloid β-protein oligomers promote the uptake of tau fibril seeds potentiating intracellular tau aggregation
Authors: Shin Woo Shik , Di Jing , Cao Qin , Li Binsen , Seidler Paul M. , Murray Kevin A. , Bitan Gal , Jiang Lin
Published: October 2019

Background

Repeated failure of drug candidates targeting Alzheimer’s disease (AD) in clinical trials likely stems from a lack of understanding of the molecular mechanisms underlying AD pathogenesis. Recent research has highlighted synergistic interactions between aggregated amyloid-β (Aβ) and tau proteins in AD, but the molecular details of how these interactions drive AD pathology remain elusive and speculative.

Methods

Here, we test the hypothesis that Aβ potentiates intracellular tau aggregation, and show that oligomeric Aβ specifically exacerbates proteopathic seeding by tau. Using tau-biosensor cells, we show that treatment with sub-toxic concentrations of Aβ oligomers, but not monomers or fibrils, “primes” cells, making them more susceptible to tau seeding. The treatment with Aβ oligomers enhances intracellular tau aggregation in a dose-dependent manner when the cells are seeded with either recombinant or brain-derived tau fibrils, whereas little or no aggregation is observed in the absence of Aβ-oligomer priming.

Results

Priming by Aβ oligomers appears to be specific to tau, as α-synuclein seeding is unaffected by this treatment. Aβ oligomer-enhanced tau seeding also occurs in primary mouse neurons and human neuroblastoma cells. Using fluorescently labeled tau seeds, we find that treatment with Aβ oligomers significantly enhances the cellular uptake of tau seeds, whereas a known tau-uptake inhibitor blocks the effect of Aβ on tau uptake.

Conclusion

The ability of Aβ to promote tau seeding suggests a specific and plausible mechanism by which extracellular Aβ initiates a deleterious cascade that is unique to AD. These data suggest that the Aβ-mediated potentiation of tau uptake into cells should also be taken into account when designing Aβ-targeted therapeutics.
Levothyroxine-induced liver injury followed by complete recovery upon cessation of the drug: a case report
Authors: Hlaihel Abbas F. , Al-Khairalla Mudher Z. H.
Published: October 2019

Background

Levothyroxine is a synthetic thyroxine and is the treatment of choice for hypothyroidism. It is a prohormone with minimal intrinsic activity. The drug is de-iodinated in peripheral tissue to form triiodothyronine, which is the active thyroid hormone. On initiation of treatment, levothyroxine is titrated, and usually it is extremely well tolerated in the vast majority of patients. We report a case of a patient with self-limiting levothyroxine-induced liver injury, a rare adverse effect of this drug.

Case presentation

We report a case of a 34-year-old Mediterranean woman diagnosed with post-thyroidectomy hypothyroidism. She was commenced on levothyroxine and developed liver injury confirmed by noninvasive liver investigations. Complete recovery of the patient’s liver tests occurred upon cessation of the drug. Triiodothyronine was an appropriate treatment alternative.

Conclusion

Levothyroxine-induced liver injury is a rare, and in the present case report, a self-limiting, adverse effect. The diagnosis of our patient was confirmed via noninvasive diagnostic methods. Knowledge of this rare adverse effect is important in the differential diagnosis of patients who have commenced on levothyroxine and have deranged liver enzymes in the context of hypothyroidism.
Carnosol induces apoptotic cell death through ROS-dependent inactivation of STAT3 in human melanoma G361 cells
Authors: Choi Seung Mi , Kim Do-Hee , Chun Kyung-Soo , Choi Joon-Seok
Published: October 2019

Melanoma is the leading cause of skin cancer deaths, and the poor prognosis of metastatic melanoma has made needs for a novel pharmacological treatment or efficient intervention. Carnosol, a major polyphenolic compound from Rosmarinus officinalis, has a wide range of biological activities including anti-cancer effect. However, the underlying molecular mechanisms of its anti-cancer effect remain poorly understood in malignant human melanoma cells. In the present study, we investigate the apoptotic effect and the underlying anti-cancer mechanisms of carnosol. Our results revealed that carnosol strongly induced apoptosis against human melanoma G361 cells in a dose- and time-dependent manner, and caused dramatical elevation in cellular reactive oxygen species (ROS) level during apoptosis. In mechanistic studies, carnosol treatment decreased protein level of anti-apoptotic B‑cell lymphoma 2 (Bcl-2) and B cell lymphoma-extra large (Bcl-xL), however, increased level of pro-apoptotic Bcl-2-associated X protein (Bax) protein. Moreover, carnosol escalated cellular level of p53, which was accompanied by a decline of mouse double minute 2 homolog (MDM2) level. Also, carnosol inhibited activation of Src and signal transducer and activator of transcription 3 (STAT3), therefore down-regulated STAT3-dependent gene expression, such as D-series cyclin and survivin. These changes by carnosol were attenuated by pre-treatment of N-acetyl cysteine, and abolished progression of carnosol-induced apoptosis. In conclusion, carnosol induced apoptosis in human melanoma G361 cells through ROS generation and inhibition of STAT3-mediated pathway. Our results provide molecular bases of carnosol-induced apoptosis, and suggest a novel candidate for human melanoma treatment.
Correction to: Retinal pathology in experimental optic neuritis is characterized by retrograde degeneration and gliosis
Authors: Manogaran Praveena , Samardzija Marijana , Schad Anaïs Nura , Wicki Carla Andrea , Walker-Egger Christine , Rudin Markus , Grimm Christian , Schippling Sven
Published: October 2019

In the original publication of this article [1], Fig. 10 contained two panels “C” as panel “F” was accidentally omitted. The incorrect (Fig. 1) and correct (Fig. 2) versions are published in this correction article.
Surface rupture and characteristics of a fault associated with the 2011 and 2016 earthquakes in the southern Abukuma Mountains, northeastern Japan, triggered by the Tohoku-Oki earthquake
Authors: Komura Keitaro , Aiyama Kotaro , Nagata Takahiro , Sato Hiroshi P. , Yamada Akihiro , Aoyagi Yasuhira
Published: October 2019

The 2011 Tohoku-Oki offshore subduction earthquake (Mw 9.0) triggered many normal-type earthquakes inland in northeastern Japan. Among these were two very similar normal-faulting earthquakes in 2011 (Mw 5.8) and 2016 (Mw 5.9), which created surface ruptures along the newly named Mochiyama fault within the southern Abukuma Mountains, northeastern Japan, where no active faults had been previously mapped by interpretation of aerial photographs. We conducted field surveys in this area immediately after both earthquakes, and we performed trench excavations and observations of fault fracture zones after the 2016 event. These activities were complemented by an interferometric synthetic aperture radar analysis that mapped the areas of deformation and locations of surface discontinuities for both events. The combined results document the coseismic behavior of the Mochiyama fault during both events. Subtle tectonic geomorphic features associated with the fault were evident in a lidar digital elevation model of the area, and layered structures of gouge were documented in the field. These lines of evidence indicate repeated activity at shallow crustal levels and the possibility of Quaternary activity. In addition, our trench excavations revealed at least one faulting event before 2011. Our comparison of paleoseismic records on this and two other normal faults in the Abukuma Mountains suggests that great earthquakes in the Japan Trench supercycle of 500–700 years do not consistently trigger ruptures on these faults, and the case of 2011, in which the Tohoku-Oki megathrust earthquake triggered all three faults, is a rare occurrence.
Deletion of the small GTPase rac1 in Trichoderma reesei provokes hyperbranching and impacts growth and cellulase production
Authors: Fitz Elisabeth , Gamauf Christian , Seiboth Bernhard , Wanka Franziska
Published: October 2019

Background

Trichoderma reeseiis widely known for its enormous protein secretion capacity and as an industrially relevant producer of cellulases and hemicellulases. Over the last decades, rational strain engineering was applied to further enhance homologous and heterologous enzyme yields. The introduction of hyperbranching is believed to increase protein secretion, since most exocytosis is located at the hyphal apical tip. There are several genetic modifications which can cause hyperbranching, for example the deletion of the small Rho GTPaserac. Rac plays a crucial role in actin dynamics and is involved in polarisation of the cell during germination and apical extension of the hyphae.

Results

We deletedrac1in aT. reeseistrain with an ectopically overexpressed endoglucanase, CEL12A, under Pcdna1control. This deletion provoked a hyperbranching phenotype and strong apolar growth during germination and in mature hyphae. The strains displayed dichotomous branching and shorter total mycelium length with a larger hyphal diameter. Δrac1strains exhibited a decreased radial growth on solid media. Biomass formation in liquid cultures was carbon source dependent; similar to the reference strain during growth on lactose, increased ond-glucose and slightly enhanced on cellulose. While extracellular cellulase activities remained at parental strain levels ond-glucose and cellulose, the specific activity on lactose cultures was increased up to three times at 72 h accompanied by an upregulation of transcription of the main cellulases. Although the morphology of the Δrac1strains was considerably altered, the viscosity of the culture broth in fed-batch cultivations were not significantly different in comparison to the parental strain.

Conclusions

Deletion of the small Rho GTPaserac1changes the morphology of the hyphae and provokes hyperbranching without affecting viscosity, independent of the carbon source. In contrast, biomass formation and cellulase production are altered in a carbon source dependent manner in the Δrac1strains.
Laboratory and numerical based analysis of floating sand columns in clayey soil
Authors: Naseer S. , Sarfraz Faiz M. , Iqbal S. , Jamil S. M.
Published: October 2019

The inclusion of sand columns results in enhancing the bearing capacity of clayey soil, increase the rate of consolidation, presentation of liquefaction in loose sandy soils and provide lateral resistance against the horizontal movement. This research aims at investigating the effects of floating columns in clayey soil with silty deposits by developing small scale laboratory models. The effects of sand columns on soils of different shear strengths, slenderness ratio (L/D) of columns were investigated. Group effect was also investigated by varying spacing between the columns. Experimental results were compared with the numerical analysis results. A 15-noded triangular mesh was generated using a finite element tool PLAXIS 2D. Finite element analysis was performed using Mohr’s Coulomb’s criterion considering undrained analysis for soft clayey soil and drained analysis for sand columns. It was concluded that the sand columns can significantly increase the ultimate loading capacity of soft soils. Results show that critical length for floating column ranges from 4 to 5.5 times the diameter of the column, beyond which bulging occurs and loading capacity decreased. The effect of group was also investigated and observed that with high spacing between the sand columns, the group efficiency decreased. The axial capacity of sand columns decreases while increasing spacing between the columns.
Aphid vectors impose a major bottleneck on Soybean dwarf virus populations for horizontal transmission in soybean
Authors: Tian Bin , Gildow Frederick E. , Stone Andrew L. , Sherman Diana J. , Damsteegt Vernon D. , Schneider William L.
Published: October 2019

Many RNA viruses have genetically diverse populations in a single host. Important biological characteristics may be related to the levels of diversity, including adaptability, host specificity, and host range. Shifting the virus between hosts might result in a change in the levels of diversity associated with the new host. The level of genetic diversity for these viruses is related to host, vector and virus interactions, and understanding these interactions may facilitate the prediction and prevention of emerging viral diseases. It is known that luteoviruses have a very specific interaction with aphid vectors. Previous studies suggested that there may be a tradeoff effect between the viral adaptation and aphid transmission when Soybean dwarf virus (SbDV) was transmitted into new plant hosts by aphid vectors. In this study, virus titers in different aphid vectors and the levels of population diversity of SbDV in different plant hosts were examined during multiple sequential aphid transmission assays. The diversity of SbDV populations revealed biases for particular types of substitutions and for regions of the genome that may incur mutations among different hosts. Our results suggest that the selection on SbDV in soybean was probably leading to reduced efficiency of virus recognition in the aphid which would inhibit movement of SbDV through vector tissues known to regulate the specificity relationship between aphid and virus in many systems.
Efficiency of the spectral element method with very high polynomial degree to solve the elastic wave equation
Authors: Lyu Chao , Capdeville Yann , Zhao Liang
Published: October 2019

The spectral element method (SEM) has gained tremendous popularity within the seismological community to solve the wave equation at all scales. Classic SEM applications mostly rely on degrees 4–8 elements in each tensorial direction. Higher degrees are usually not considered due to two main reasons. First, high degrees imply large elements, which make the meshing of mechanical discontinuities difficult. Second, the SEM’s collocation points cluster toward the edge of the elements with the degree, degrading the time-marching stability criteria and imposing a small time step and a high numerical cost. Recently, the homogenization method has been introduced in seismology. This method can be seen as a preprocessing step before solving the wave equation that smooths out the internal mechanical discontinuities of the elastic model. It releases the meshing constraint and makes use of very high degree elements more attractive. Thus, we address the question of memory and computing time efficiency of very high degree elements in SEM, up to degree 40. Numerical analyses reveal that, for a fixed accuracy, very high degree elements require less computer memory than low-degree elements. With minimum sampling points per minimum wavelength of 2.5, the memory needed for a degree 20 is about a quarter that of the one necessary for a degree 4 in two dimensions and about one-eighth in three dimensions. Moreover, for the SEM codes tested in this work, the computation time with degrees 12–24 can be up to twice faster than the classic degree 4. This makes SEM with very high degrees attractive and competitive for solving the wave equation in many situations.
Pathophysiological Response to Trauma-Induced Coagulopathy: A Comprehensive Review
Authors: Duque Patricia , Mora Lidia , Levy Jerrold H. , Schöchl Herbert
Published: October 2019

Hypercoagulability can occur after severe tissue injury, that is likely related to tissue factor exposure and impaired endothelial release of tissue plasminogen activator (tPA). In contrast, when shock and hypoperfusion occur, activation of the protein C pathway and endothelial tPA release induce a shift from a procoagulant to a hypocoagulable and hyperfibrinolytic state with a high risk of bleeding. Both thrombotic and bleeding phenotypes are associated with increased mortality and are influenced by the extent and severity of tissue injury and degree of hemorrhagic shock. Response to trauma is a complex, dynamic process in which risk can shift from bleeding to thrombosis depending on the injury pattern, hemostatic treatment, individual responses, genetic predisposition, and comorbidities. Based on this body of knowledge, we will review and consider future directions for the management of severely injured trauma patients.
Computational analysis of size, shape and structure of insect wings
Authors: Salcedo Mary K. , Hoffmann Jordan , Donoughe Seth , Mahadevan L.
Published: October 2019

The size, shape and structure of insect wings are intimately linked to their ability to fly. However, there are few systematic studies of the variability of the natural patterns in wing morphology across insects. We have assembled a dataset of 789 insect wings with representatives from 25 families and performed a comprehensive computational analysis of their morphology using topological and geometric notions in terms of (i) wing size and contour shape, (ii) vein topology, and (iii) shape and distribution of wing membrane domains. These morphospaces are complementary to existing methods for quantitatively characterizing wing morphology and are likely to be useful for investigating wing function and evolution. This Methods and Techniques paper is accompanied by a set of computational tools for open use.

This article has an associated First Person interview with the first author of the paper.
Non-coplanar VMAT plans for lung SABR to reduce dose to the heart: a planning study
Authors: Kim Sang-Tae , An Hyun Joon , Kim Jung-in , Yoo Jae-Ryong , Kim Hak Jae , Park Jong Min
Published: October 2019

Objective:

This study aimed to compare the plan quality of non-coplanar partial arc (NPA) volumetric modulated arc therapy (VMAT) to that of coplanar partial arc (CPA) VMAT for stereotactic ablative radiotherapy (SABR) for lung cancer.

Methods:

A total of 20 patients treated for lung cancer with the SABR VMAT technique and whose lung tumors were close to the heart were retrospectively selected for this study. For the CPA VMAT, three coplanar half arcs were used while two coplanar half arcs and one noncoplanar arc rotating 315°–45° with couch rotations of 315° ± 5° were used for the NPA VMAT. For each patient, identical CT image sets and identical structures were used for both the CPA and NPA VMAT plans. Dose–volumetric parameters of each plan were analyzed.

Results:

For the planning target volume and both lungs, no statistically significant differences between the CPA and NPA VMAT plans were observed in general. For the heart, average values of D0.1cc of the CPA and NPA VMAT plans were 29.42 ± 13.37 and 21.71 ± 9.20 Gy, respectively (p < 0.001). For whole body, the mean dose and the gradient index of the CPA VMAT plans were 1.2 ± 0.5 Gy and 4.356 ± 0.608 while those of the NPA VMAT plans were 1.1 ± 0.5 Gy and 4.111 ± 0.480, respectively (both with p < 0.001).

Conclusion:

The NPA VMAT proposed in this study showed more favorable plan quality than the CPA VMAT plans for lung SABR with tumors located close to the heart.

Advances in knowledge:

For lung SABR, NPA VMAT can reduce doses to the heart as well as whole-body irradiation.
The yield of continuous EEG monitoring in the intensive care unit at a tertiary care hospital in Saudi Arabia: A retrospective study
Authors: Tayeb Haythum O.
Published: October 2019

Background: The practice of continuous EEG monitoring (CEEG) in the intensive care unit (ICU) has spread over the past decade. Building an effective ICU CEEG program demands adequate EEG equipment and human resources. This may not be available in developing healthcare systems. This study sought to shed light on the real-life utility of CEEG at a tertiary healthcare center in the developing healthcare system of Saudi Arabia.

Methods: This is a retrospective review of CEEG findings, along with mortality and duration of hospitalization of patients who had CEEG during a 12-month period at the adult ICU at the King Abdulaziz University Hospital (KAUH) in Jeddah, Saudi Arabia.

Results: A total of 202 CEEG records were identified. A total of 52 records showed non-convulsive seizures (NCS); 10 clearly fulfilled criteria for non-convulsive status epilepticus. There were 120 patients that had clinical seizures upon presentation. Among them, 36 (30%) had NCS on EEG. The proportion of patients who were deceased at 60 days was higher in patients with NCS than those who didn’t have NCS (42% vs 27%, χ 2 = 4.4, df=2, p=0.03). There was no statistically significant association between having rhythmic or periodic patterns without NCS and mortality at 60 days or length of hospital stay.

Conclusion: This retrospective study demonstrates a real-world experience from a tertiary care center in Saudi Arabia, a developing healthcare system. ICU CEEG was found to be effective in detecting potentially harmful subclinical patterns, supporting the need to develop ICU CEEG programs. However, the incurred excesses in morbidity and mortality associated with CEEG patterns were relatively modest. Further studies are needed to delineate how the practice of CEEG may be developed in similar healthcare systems to provide meaningful data to clinicians with regards to patient outcomes.
RCy3: Network biology using Cytoscape from within R
Authors: Gustavsen Julia A. , Pai Shraddha , Isserlin Ruth , Demchak Barry , Pico Alexander R.
Published: October 2019

RCy3 is an R package in Bioconductor that communicates with Cytoscape via its REST API, providing access to the full feature set of Cytoscape from within the R programming environment. RCy3 has been redesigned to streamline its usage and future development as part of a broader Cytoscape Automation effort. Over 100 new functions have been added, including dozens of helper functions specifically for intuitive data overlay operations. Over 40 Cytoscape apps have implemented automation support so far, making hundreds of additional operations accessible via RCy3. Two-way conversion with networks from \textit{igraph} and \textit{graph} ensures interoperability with existing network biology workflows and dozens of other Bioconductor packages. These capabilities are demonstrated in a series of use cases involving public databases, enrichment analysis pipelines, shortest path algorithms and more. With RCy3, bioinformaticians will be able to quickly deliver reproducible network biology workflows as integrations of Cytoscape functions, complex custom analyses and other R packages.
Bodenwertermittlung mit statistischen Methoden
Authors: Kolbe Jens , Schulz Rainer , Wersing Martin , Werwatz Axel
Published: October 2019

Die Besteuerung von Immobilien auf der Grundlage von Marktwerten erfordert eine regelmäßige Bewertung einer Vielzahl von Immobilien. Vor dem Hintergrund der jüngsten Diskussion über die Reform der Grundsteuer in Deutschland wird argumentiert, dass eine wertorientierte Steuer nicht mit vertretbarem Aufwand umgesetzt werden kann. In mehreren anderen Ländern werden Massenbewertungssysteme auf Basis von statistischen Methoden für die Grundsteuerveranlagung eingesetzt. In diesem Beitrag zeigen wir, wie dies in Deutschland grundsätzlich geschehen könnte; mittels Transaktionsdaten zu deren Erhebung die lokalen Sachverständigenkommissionen gesetzlich verpflichtet sind. Wir diskutieren die Regressionsverfahren zur Schätzung von Bodenwerten aus solchen Daten und veranschaulichen sie, indem wir sie auf Daten aus Berlin anwenden. Wir kommen zu dem Ergebnis, dass die Methoden in der Lage sind, Bodenwertschätzungen zu erstellen, die gut mit fachspezifischen Einschätzungen übereinstimmen.
On-site and distance piano teaching: An analysis of verbal and physical behaviours in a teacher, student and parent
Authors: Comeau Gilles , Lu Yuanyuan , Swirp Mikael
Published: October 2019

This study was designed to examine how distance piano teaching might affect the verbal behaviours and physical actions of a teacher, a student and a parent. Weekly 30-minute piano lessons over a year-long period were taught to a 5-and-a-half-year-old on-site student and a 6-year-old distance student. All lessons were delivered by the same teacher who followed the Suzuki programme. All sessions were recorded and then analysed using Simple Computer Recording Interface Behaviour Evaluation (SCRIBE), a video analysis software that provides frequencies and durations of pre-coded events. The observation of recorded lessons showed that distance teaching did not slow down student progress. In addition, behavioural analysis revealed that in most aspects, distance and on-site delivery were remarkably similar. The most striking difference was the interaction between the teacher and the parent. During on-site teaching, most of the teacher’s instructions were directed to the student while the parent was listening and observing attentively; during distance teaching, half of the teacher’s instructions were addressed to the student and the other half to the parent. The distance student also tended to relate more to the parent than to the teacher. In the distance environment, when interacting with a young beginner student, the role of the parent becomes very central to the success of the lessons.
Investigating interpretative models in music through multi-layer representation formats
Authors: Baratè Adriano , Haus Goffredo , Ludovico Luca Andrea , Presti Giorgio
Published: October 2019

Multi-layer formats are becoming increasingly important in the field of music description. Thanks to their adoption, it is possible to embed into a unique digital document different representations of music contents, multiple in number and potentially heterogeneous in media type. Moreover, these descriptions can be mutually synchronized, thus providing different views of the same information entity with a customizable level of granularity. Standard use cases of multi-layer formats for music address information structuring and support to advanced fruition. The goal of the paper is to demonstrate how suitable multi-layer formats can foster analytical activities in the field of interpretative modelling and expressiveness investigation, discussing both the pedagogical roots and the educational implications of this approach. A use case focusing on the incipit of G. Mahler’s Symphony No. 5 will be presented.
Therapy of the climacteric disorders in women with type II diabetes
Authors: Popkov S. A. , Starkova N. T. , Morozova T. P. , Volobuyeva Yu. V.
Published: October 2019

The efficacy of estrogen-gestagen therapy of patients with climacteric syndrome is no longer doubted. Besides reducing the number of hot flashes, hyperhidrosis, etc., such treatment prevents atherosclerosis, osteoporosis, and atrophy of the external genitals. However, hormone replacement therapy of diabetics with climacteric syndrome involves a high risk of deteriorating carbohydrate metabolism. This study was aimed at elucidating the possibility of using Divine (Orion, Finland) for the treatment of patients suffering from climacteric syndrome in the presence of type II diabetes concomitant with coronary heart disease. The results indicate that the divine had a favorable impact on the course of the climacteric syndrome in the named patient population, appreciably improving the patient's quality of life and causing no decompensation of diabetes, which was confirmed by clinical and laboratory findings.