bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
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

Abstract

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

AbstractSoft 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

AbstractBackgroundSugar 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.ResultsRhodosporidium 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.ConclusionsRhodosporidium 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

Abstract

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

Abstract
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

Abstract

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

Abstract
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.
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

Abstract
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

AbstractBackgroundTrichoderma 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.ResultsWe 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.ConclusionsDeletion 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.