bluuebunny/crossref_metadata_2025 huggingface dataset:
Skin Ultrasound Measurement as a Potential Marker of Bone Quality: A Prospective Pilot Study of Patients undergoing Lumbar Spinal Fusion
Authors: Salzmann Stephan N. , Okano Ichiro , Rentenberger Colleen , Winter Fabian , Miller Courtney Ortiz , Schadler Paul , Sax Oliver C. , Miller Theodore T. , Shue Jennifer , Boskey Adele L. , Sama Andrew A. , Cammisa Frank P. , Girardi Federico P. , Hughes Alexander P.
Published: August 2019

Bone mineral density (BMD) is not the sole predictor of fracture development. Qualitative markers including bone collagen maturity contribute to bone fragility. Bone and related type I collagen containing connective tissues degenerate in parallel fashion. With aging, changes in skin collagen content and quality have been observed that can be detected on ultrasound (US) as a decrease in dermal thickness and an increase in reticular layer echogenicity. We hypothesized that US dermal thickness and echogenicity correlate with bone collagen maturity. Data of 43 prospectively enrolled patients (mean age 61 years, 24 females), who underwent instrumented, posterior lumbar fusion was analyzed. Besides preoperative quantitative computed tomography (QCT) and skin US measurements, intraoperative bone biopsies were obtained and analyzed with Fourier‐transform infrared spectroscopy. Among men, there was no correlation between US measurements and collagen maturity. Among women, dermal layer thickness correlated negatively with collagen maturity in trabecular bone of the iliac crest (r = −0.51, p = 0.01) and vertebra (r = −0.59, p = 0.01) as well as in cortical bone of the iliac crest (r = −0.50, p = 0.02) and vertebra (r = −0.50, p = 0.04). In addition, echogenicity correlated positively with collagen maturity in trabecular vertebral bone (r = 0.59, p = 0.01). In both genders, US measurements showed no correlation with QCT BMD. In summary, ultrasound skin parameters are associated with bone quality factors such as collagen maturity, rather than bone quantity (BMD). Ultrasound of the skin may thereby be an easy and accessible take off point for diagnosis of bone collagen maturity and connective tissue degeneration in the future. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2508–2515, 2019
Tutorial on Diarrhea and Enteral Nutrition: A Comprehensive Step‐By‐Step Approach
Authors: Pitta Marina Regueira , Campos Franciele Maciel , Monteiro Alline Gonçalves , Cunha Anna Gabriella Ferreira , Porto Juliana Dourado , Gomes Raquel Rodrigues
Published: August 2019

This tutorial suggests a current strategy toward a multiprofessional therapy based upon a comprehensive step‐by‐step approach to the course of intensive care unit diarrhea episodes. Evidence published in the last 10 years, obtained through a database search (PubMed), shows that its prevalence is quite variable. Although multicausal, it is often erroneously associated with the supply of enteral nutrition. Several complications affect not only nutrition status but also the development of skin lesions, which can become the focus of infections, and the length of hospital stay. Here, we propose an early, objective, directed, and multimodal approach, aiming at optimizing care for these patients. In a dynamic walkthrough, the reader will find a guide for the general diagnosis and for colitis resulting from Clostridium difficile infections, as well as current instructions and recommendations for drug treatment and supportive therapy for these 2 modalities. We also bring together ways to prevent and treat associated skin lesions in this setting. Because it is neglected in the critical environment, diarrhea is still a poorly addressed disease, and its complications bring about a significant worsening in quality of life and hospital stay.
Student perceptions of the white coat ceremony in a pharmacy program in Australia
Authors: Mylrea Martina F. , Gupta Tarun Sen , Glass Beverley D.
Published: August 2019

The white coat ceremony (WCC) is an opportunity to welcome students to the profession and highlight the essential characteristics and responsibilities of the pharmacist. After three consecutive years of WCCs, all pharmacy students enrolled at the James Cook University in 2017 were invited to complete an online survey designed to ascertain student perceptions regarding the effect, meaning and timing of the ceremony. The 78 survey respondents (response rate 56%) revealed that students at all levels of the program were positive about the WCC and were proud to receive a white coat (90%). They demonstrated a clear understanding of the role of the ceremony and reported that the preferred timing for the WCC was at the end of the fourth year (43%) of the program. This study revealed that the WCC was perceived positively and represents a worthwhile strategy for enhancing student connection to the profession of pharmacy.
Rhabdomyolysis after Ginkgo biloba and cannabis
Authors: Strain Madisyn L. , Yingling Megan N. , Kraleti Shashank , Thiessen Kaci A.
Published: August 2019

Background

Rhabdomyolysis is a syndrome caused by the death of muscle tissue, which leads to the release of the muscle protein myoglobin into the circulation. The severity of rhabdomyolysis varies widely from asymptomatic to life threatening, and has many possible causes, including a specific classification associated with medications. This report suggests the potential for rhabdomyolysis induction by an interaction between ginkgo (Ginkgo biloba) and cannabis, in addition to recent strenuous exercise. Prompt identification of the aetiology and treatment are crucial in preventing complications and mortality.

Clinical details

A 26‐year‐old African American female presented to the emergency department (ED) with a chief complaint of worsening muscle pain and weakness, 2 days after exercise without adequate hydration. The patient reported recently starting a ginkgo supplement, in addition to her regular medications and confirmed marijuana use. Urinalysis and creatine kinase (CK) data collected in the ED were suggestive of rhabdomyolysis.

Outcomes

The patient was admitted to hospital. After rehydration with intravenous normal saline, her CK levels and symptoms improved.

Conclusion

Ginkgo is an increasingly popular natural supplement with a variety of uses. However, the use of this product, with or without cannabis consumption, may correspond to an increased likelihood for interactions and adverse drug reactions, such as the potential for rhabdomyolysis presented here. It is important for pharmacists and other clinicians to be aware of the prospective risks associated with this supplement in order to properly educate patients and mitigate potential morbidities.
Making the profession attractive for our future and young pharmacists, the game changers for primary health care
Authors: Uzman Nilhan , Kusynova Zuzana , Manikkath Jyothsna , Duggan Catherine
Published: August 2019

The Pharmacy profession has shifted its focus from a traditional medicine‐centred one to an advanced person‐centred one over recent decades. Taking on new services as care providers within an integrated care system and collaborating with other healthcare professionals to positively impact and implement healthcare policies present important and exciting opportunities for the future of the pharmacy profession. The International Pharmaceutical Federation (FIP), as the global leadership body for pharmacy, supports pharmacy students and early career pharmacists in their professional development as well as developing pharmacy as a profession for a future where youth will practice with enthusiasm and compassion within society. By working in collaboration with the International Pharmaceutical Students Federation (IPSF) and creating a platform for early career pharmacists within FIP, the FIP Young Pharmacist Group (FIP YPG) aims to make the profession attractive for our future and young pharmacists. In this article, based on current innovations and future trends, FIP YPG and IPSF have looked at ten reasons to be a pharmacist and with these reasons, we identified what it means to be a pharmacist for future generations.
2D GeP as a Novel Broadband Nonlinear Optical Material for Ultrafast Photonics
Authors: Guo Jia , Huang Dazhou , Zhang Yue , Yao Huizhen , Wang Yunzheng , Zhang Feng , Wang Rui , Ge Yanqi , Song Yufeng , Guo Zhinan , Yang Fumei , Liu Jiefeng , Xing Chenyang , Zhai Tianyou , Fan Dianyuan , Zhang Han
Published: August 2019

A new member of the IV–V compounds, germanium–phosphorus (Ge–P) compounds, has been shown in experiment and theory to have a tunable bandgap (Eg), excellent chemical stability, strong in‐plane anisotropy, and wide‐range optical absorption, all indicating a promising future in electronic and optoelectronic applications. In this work, the application potential of Ge–P compounds as nonlinear optical (NLO) materials in ultrafast photonics is studied for the first time. The strong light–matter interaction, broad and tunable Ep, and broadband and strong optical response make GeP a likely NLO material for photonics, especially in infrared photonic devices. In addition, 2D GeP nanosheets are mixed with poly(vinylidene fluoride) (PVDF) to obtain a GeP@PVDF composite film, which further improves the stability of the GeP and, for the development of organic photonic devices, helps to slow its degradation. From Z‐scan data and fitting results, it is found that GeP has an excellent broadband NLO response. Moreover, using the GeP@PVDF composite film as a saturable absorber, a high‐stability femtosecond laser with a 722 fs pulse width is obtained in the telecommunications band. Preliminarily, Ge–P compounds display excellent optical properties suggesting that they may be used as NLO materials in advanced photonic devices.
Influence of Alkyl Chains of Modified Polysuccinimide‐Based Polycationic Polymers on Polyplex Formation and Transfection
Authors: Kravicz Marcelo H. , Balogh Debora T. , Kar Mrityunjoy , Wedepohl Stefanie , Bentley Maria Vitoria L. B. , Calderón Marcelo
Published: August 2019

The development of polymers with low toxicity and efficient gene delivery remains a significant barrier of nonviral gene therapy. Modification and tuning of chemical structures of carriers is an attractive strategy for efficient nucleic acid delivery. Here, polyplexes consisting of plasmid DNA (pDNA) and dodecylated or non‐dodecylated polysuccinimide (PSI)‐based polycations are designed, and their transfection ability into HeLa cells is investigated by green fluorescent protein (GFP) expressing cells quantification. All cationic polymers show lower cytotoxicity than those of branched polyethyleneimine (bPEI). PSI and bPEI‐based polyplexes have comparable physicochemical properties such as size and charge. Interestingly, a strong interaction between dodecylated polycations and pDNA caused by the hydrophobic moiety is observed in dodecylated PSI derivatives. Moreover, the decrease of GFP expression is associated with lower dissociation of pDNA from polyplexes according to the heparin displacement assay. Besides, a hydrophobization of PSI cationic derivatives with dodecyl side chains can modulate the integrity of polyplexes by hydrophobic interactions, increasing the binding between the polymer and the DNA. These results provide useful information for designing polyplexes with lower toxicity and greater stability and transfection performance.
Quantitative Studies of Block Copolymers and Their Containing Homopolymer Components by Diffusion Ordered Spectroscopy
Authors: Hiller Wolf
Published: August 2019

Several polystyrene‐b‐poly(methyl methacrylate) (PS‐b‐PMMA) and polyisoprene‐b‐PMMA (PI‐b‐PMMA) block copolymers are studied with high‐resolution diffusion ordered spectroscopy (DOSY) in order to quantify the amounts and molar masses of the copolymers and the containing homopolymers. These studies are particularly challenging because these homopolymers and one block of the copolymers consist of the same monomer type with different molar masses and compositions and cause a total overlap of these polymer components in the NMR spectra. However, DOSY can be proven as a powerful tool for separation and quantification of these moieties. Whereas exponential fittings only deliver averaged diffusion data, biexponential fittings of the individual magnetization curves can separate the overlapping polymer parts. This DOSY approach can be successfully tested for different blends of PS as well as PS and PS‐b‐PMMA of different molar masses and weighed compositions. The DOSY separation is also compared to size exclusion chromatography (SEC). In the case of the PS‐b‐PMMA and PI‐b‐PMMA block copolymers, DOSY identifies the contaminations with homopolymers, quantifies their individual amounts as well as determines the molar masses of both the copolymers and homopolymers. Two mathematical evaluations are used for quantifying these homopolymers with DOSY. These results are compared with the online coupling of SEC and NMR.
Rain‐rate estimation algorithm using signal attenuation of Ka‐band cloud radar
Authors: Oh Su‐Bin , Kollias Pavlos , Lee Jeong‐Soon , Lee Seung‐Woo , Lee Yong Hee , Jeong Jong‐Hoon
Published: August 2019

A millimetre‐wave cloud radar has limitations for observing heavy rainfall because the short wavelength leads to strong attenuation from raindrops. However, recent studies have attempted to estimate the rain rate using attenuation, which becomes greater as the rain intensity increases. The rain‐rate‐retrieval algorithm is developed in the present paper using the Ka‐band cloud radar (KaCR) installed at the Boseong Global Standard Observatory (BGSO) in the Republic of Korea. First, rain profiles were identified using the threshold of reflectivity (Z) and Doppler velocity (DV) averaged for the analysis of layer that minimized the effects of the receiver saturation and classified as low or high rain‐rate cases using the averaged DV. The reflectivity and rain‐rate (Z‐R) relationship was then derived for low rain‐rate cases that showed insignificant effects for signal attenuation. On the other hand, the attenuation and rain‐rate (A‐R) relationship was derived using high rain‐rate cases that showed the dominant effects of attenuation. The attenuation was calculated using a reflectivity gradient between the upper and lower boundaries of the attenuated layer. Finally, the rain‐rate‐retrieval algorithm was designed using the derived Z‐R and A‐R relationship and then applied back to the KaCR. The estimated rain rate in the KaCR was a similar trend to the observed rain rate in the optical rain gauge (ORG), but slightly underestimated.
A segmentation procedure of the pervious area of the aorta artery from CT images without contrast medium
Authors: Costarelli Danilo , Seracini Marco , Vinti Gianluca
Published: August 2019

In this paper, we develop an algorithm for the segmentation of the pervious lumen of the aorta artery in computed tomography (CT) images without contrast medium, a challenging task due to the closeness gray levels of the different zones to segment. The novel approach of the proposed procedure mainly resides in enhancing the resolution of the image by the application of the algorithm deduced from the mathematical theory of sampling Kantorovich operators. After the application of suitable digital image processing techniques, the pervious zone of the artery can be distinguished from the occluded one. Numerical tests have been performed using 233 CT images, and suitable numerical errors have been computed and introduced ex novo to evaluate the performance of the proposed method. The above procedure is completely automatic in all its parts after the initial region of interest (ROI) selection. The main advantages of this approach relies in the potential possibility of performing diagnosis concerning vascular pathologies even for patients with severe kidney diseases or allergic problems, for which CT images with contrast medium cannot be achieved.
A broadband beam scanning antenna array based on substrate integrated coaxial line Butler matrix for Q‐band application
Authors: Li Xiuping , Hou Yajing , Zhu Hua , Qi Zihang , Xiao Jun , Cao Cheng
Published: August 2019

In this article, a broadband beam scanning antenna array is proposed in Q‐band attributed to miniaturized size, wideband and high integration. A patch antenna element is utilized with a back cavity, which is formed by metallic via holes and ground plane. A 1 × 4 series fed sub‐array is implemented by the patch element using multilayer PCB. Four symmetrical sub‐arrays and Butler matrix feeding network are used to form the antenna array with high gain and decrease side lobes. The Butler matrix is implemented by substrate integrated coaxial line, which provides low loss of around 0.09 dB/mm from 40 to 50 GHz. The measured antenna array bandwidth is 9.8 GHz (21.8%) under the condition of voltage standing wave ratio less than 2. The main beam of the antenna array in azimuth direction is tilted to −28.5°, −14.1°, 18.4° and 35.6° and the gains are 13.11, 13.88, 14.02 and 11.78 dBi at 45 GHz, respectively. Both the measured and simulated results agree well.
MEMRI‐based imaging pipeline for guiding preclinical studies in mouse models of sporadic medulloblastoma
Authors: Rallapalli Harikrishna , Tan I‐Li , Volkova Eugenia , Wojcinski Alexandre , Darwin Benjamin C. , Lerch Jason P. , Joyner Alexandra L. , Turnbull Daniel H.
Published: August 2019

Purpose

Genetically engineered mouse models of sporadic cancers are critical for studying tumor biology and for preclinical testing of therapeutics. We present an MRI‐based pipeline designed to produce high resolution, quantitative information about tumor progression and response to novel therapies in mouse models of medulloblastoma (MB).

Methods

Sporadic MB was modeled in mice by inducing expression of an activated form of the Smoothened gene (aSmo) in a small number of cerebellar granule cell precursors. aSmo mice were imaged and analyzed at defined time‐points using a 3D manganese‐enhanced MRI‐based pipeline optimized for high‐throughput.

Results

A semi‐automated segmentation protocol was established that estimates tumor volume in a time‐frame compatible with a high‐throughput pipeline. Both an empirical, volume‐based classifier and a linear discriminant analysis‐based classifier were tested to distinguish progressing from nonprogressing lesions at early stages of tumorigenesis. Tumor centroids measured at early stages revealed that there is a very specific location of the probable origin of the aSmo MB tumors. The efficacy of the manganese‐enhanced MRI pipeline was demonstrated with a small‐scale experimental drug trial designed to reduce the number of tumor associated macrophages and microglia.

Conclusion

Our results revealed a high level of heterogeneity between tumors within and between aSmo MB models, indicating that meaningful studies of sporadic tumor progression and response to therapy could not be conducted without an imaging‐based pipeline approach.
High‐resolution intravascular MRI‐guided perivascular ultrasound ablation
Authors: Liu Xiaoyang , Ellens Nicholas , Williams Emery , Burdette Everette C. , Karmarkar Parag , Weiss Clifford R. , Kraitchman Dara , Bottomley Paul A.
Published: August 2019

Purpose

To develop and test in animal studies ex vivo and in vivo, an intravascular (IV) MRI‐guided high‐intensity focused ultrasound (HIFU) ablation method for targeting perivascular pathology with minimal injury to the vessel wall.

Methods

IV‐MRI antennas were combined with 2‐ to 4‐mm diameter water‐cooled IV‐ultrasound ablation catheters for IV‐MRI on a 3T clinical MRI scanner. A software interface was developed for monitoring thermal dose with real‐time MRI thermometry, and an MRI‐guided ablation protocol developed by repeat testing on muscle and liver tissue ex vivo. MRI thermal dose was measured as cumulative equivalent minutes at 43°C (CEM43). The IV‐MRI IV‐HIFU protocol was then tested by targeting perivascular ablations from the inferior vena cava of 2 pigs in vivo. Thermal dose and lesions were compared by gross and histological examination.

Results

Ex vivo experiments yielded a 6‐min ablation protocol with the IV‐ultrasound catheter coolant at 3‐4°C, a 30 mL/min flow rate, and 7 W ablation power. In 8 experiments, 5‐ to 10‐mm thick thermal lesions of area 0.5‐2 cm2 were produced that spared 1‐ to 2‐mm margins of tissue abutting the catheters. The radial depths, areas, and preserved margins of ablation lesions measured from gross histology were highly correlated (r ≥ 0.79) with those measured from the CEM43 = 340 necrosis threshold determined by MRI thermometry. The psoas muscle was successfully targeted in the 2 live pigs, with the resulting ablations controlled under IV‐MRI guidance.

Conclusion

IV‐MRI‐guided, IV‐HIFU has potential as a precision treatment option that could preserve critical blood vessel wall during ablation of nonresectable perivascular tumors or other pathologies.
Responsiveness and interpretability of the Animated Activity Questionnaire for assessing activity limitations of patients with hip or knee osteoarthritis
Authors: Peter Wilfred F. , Poolman Rudolf W. , Scholtes Vanessa A.B. , de Vet Henrika C.W. , Terwee Caroline B.
Published: August 2019

Purpose

The aim of the study was to determine the responsiveness and interpretability of the Animated Activity Questionnaire (AAQ), an online questionnaire in which osteoarthritis patients select animations that best match their performance of daily activities.

Methods

A longitudinal study was carried out, in which 94 patients with hip or knee osteoarthritis were assessed at baseline, and 3 and 6 months after treatment (conservative and surgical). Responsiveness was assessed by means of testing hypotheses about expected correlations between change in AAQ, a Global Rating Scale of change (GRS) and change in the Activities of Daily Living subscale of the Hip disability or Knee injury and Osteoarthritis Outcome Score (H/KOOS), and a combination of performance‐based tests (the 30 s chair‐stand test, the timed up‐and‐go test and the nine‐step stair climbing test). The minimal important change (MIC) was estimated by means of the receiving operating characteristics (ROC) method.

Results

The correlations of the AAQ with the H/KOOS were as expected, but other correlations were lower than anticipated. The area under the ROC curve was 0.74 at 6 months. At 3 months' follow‐up, the correlations were too low to calculate a MIC. A total of 20% of the results at 3 months and 80% of the results at 6 months were in accordance with the hypotheses. The MIC was 9 points at 6 months.

Conclusions

The AAQ was sufficiently responsive at the six‐months follow‐up, but not at the three‐month follow‐up. The MIC at the 6‐month follow‐up (9 points) was slightly lower than the smallest detectable change of 14 points found in a previous study.
Surface modification of cellulose nanofiber aerogels using phthalimide
Authors: Sepahvand Sima , Jonoobi Mehdi , Ashori Alireza , Gauvin Florent , Brouwers H.J.H. , Yu Qingliang
Published: August 2019

The present work studied the possibility of using phthalimide for surface modification of cellulose nanofibers (CNF). The modification was carried out in 96/4 (v/v) water/acetic acid with CNF to phthalimide ratio of 1:0, 1:0.5, 1:1, and 1:1.5 wt%, respectively. Morphological, physical, chemical, and thermal properties of prepared aerogels were characterized by scanning electron microscopy, transmission electron microscopy, X‐ray diffraction spectroscopy, and thermogravimetric analysis. The mechanical characterization such as the stress‐strain behavior was measured by compression testing. The results showed that surface modification and addition of phthalimide increased the surface area and pore volume but decreased the overall pores size. The presence of phthalimide onto CNF was confirmed by attenuated total reflectance‐Fourier transform infrared spectroscopy as the characteristic peaks of NH2, CN, and ester bonding (
COO−) appeared. Since more energy is needed for breaking hydroxyl bonds than ionic bonds, by taking into account the reduced hydrogen bonds as the result of the chemical modification, the thermal stability of the CNF‐Ph is lower than the pure CNF aerogel. Besides, the modulus of elasticity increased that could be due to the high densities.
Anti‐VEGF‐Aptamer Modified C‐Dots—A Hybrid Nanocomposite for Topical Treatment of Ocular Vascular Disorders
Authors: Shoval Asaf , Markus Amos , Zhou Zhixin , Liu Xia , Cazelles Rémi , Willner Itamar , Mandel Yossi
Published: August 2019

The vascular endothelial growth factor (VEGF) induces pathological angiogenetic ocular diseases. It is a scientific challenge to develop carriers for the controlled release of inhibitors for VEGF present in the back of the eye domain. Carbon dots (C‐dots) functionalized with the VEGF aptamer are introduced and the hybrid nanoparticles are used for ocular nanomedicine. The C‐dots are applied as effective carriers of the anti‐VEGF aptamer across the cornea, yielding therapeutic levels upon topical administration. The hybrids show no toxicity for both in vitro and in vivo murine animal model, and further enable noninvasive intraocular concentration monitoring through the C‐dots inherent fluorescence. In addition, the hybrid C‐dots effectively inhibit VEGF‐stimulated angiogenesis in choroidal blood vessels. This inhibition is comparable to two commercially available anti‐VEGF drugs, bevacizumab and aflibercept. The hybrid aptamer‐modified C‐dots provide a versatile nanomaterial to treat age‐related macular degeneration and diabetic retinopathy.
Making Sense of Modeling in Elementary Literacy Instruction
Authors: Schutz Kristine M. , Rainey Emily C.
Published: August 2019

Although modeling is an instructional approach commonly named in literacy education circles, the authors struggled to articulate the essential features of modeling to preservice teachers. This was a problem for them and for the preservice teachers with whom they worked. The problem also represents a larger one in the field, which is that educators are still building that which is the foundation of most other professions: a shared professional language. Efforts to build a shared professional language are important for literacy educators seeking to reflect on and improve their craft, literacy leaders working to make change at the school level, and mentor teachers and teacher educators tasked with preparing the next generation of teachers. The authors describe their efforts to articulate and represent modeling in elementary literacy instruction.
Hypercoagulability After Resection of Thoracic Malignancy: A Prospective Evaluation
Authors: Mulder Michelle B. , Proctor Kenneth G. , Valle Evan J. , Livingstone Alan S. , Nguyen Dao M. , Van Haren Robert M.
Published: August 2019

Background

Rates of venous thromboembolism are increased in thoracic malignancy; however, coagulation patterns are not established. We hypothesize that patients with esophageal and lung malignancy have similar hypercoagulable pre‐ and postoperative profiles as defined by rotational thromboelastometry (ROTEM).

Methods

Prospective study was conducted in 47 patients with esophageal and lung cancer undergoing surgical resection. ROTEM evaluated pre/postoperative coagulation status.

Results

Patients with thoracic malignancy were hypercoagulable by ROTEM, but not by conventional coagulation tests. Preoperative hypercoagulability was higher in lung versus esophageal cancer (64 vs. 16%, p = 0.001). Lung cancer patients that were hypercoagulable preoperatively demonstrated decreased maximum clot firmness (MCF) (p = 0.044) and increased clot time (p = 0.049) after surgical resection, suggesting reversal of hypercoagulability. Resection of esophageal cancer increased hypercoagulability (16 vs. 56%, p = 0.002) via elevated MCF (reflecting platelet activity). Hypercoagulability remained at follow‐up clinic for both lung and esophageal cancer patients.

Conclusions

Hypercoagulability in patients with lung malignancies reversed following complete surgical resection, whereas hypercoagulability occurred only postoperatively in those with esophageal malignancies. In both, hypercoagulability was associated with fibrin and platelet function.
Mathematics and Explanatory Generality: Nothing but Cognitive Salience
Authors: Knowles Robert , Saatsi Juha
Published: August 2019

We demonstrate how real progress can be made in the debate surrounding the enhanced indispensability argument. Drawing on a counterfactual theory of explanation, well-motivated independently of the debate, we provide a novel analysis of ‘explanatory generality’ and how mathematics is involved in its procurement. On our analysis, mathematics’ sole explanatory contribution to the procurement of explanatory generality is to make counterfactual information about physical dependencies easier to grasp and reason with for creatures like us. This gives precise content to key intuitions traded in the debate, regarding mathematics’ procurement of explanatory generality, and adjudicates unambiguously in favour of the nominalist, at least as far as explanatory generality is concerned.
Structural, Electrochemical and Hydrogen Sorption Studies of Nanocrystalline Ti-V-Co and Ti-V-Ni-Co Alloys Synthesized by Mechanical Alloying Method
Authors: Balcerzak M.
Published: August 2019

In this paper, Ti-V-Co and Ti-V-Ni-Co alloys are considered as the hydrogen storage systems and the negative electrodes in Ni-MH
x
secondary batteries. This work shows results of studies that have been made on Ti0.5V1.5−x
Co
x
and Ti0.5V1.4−x
Ni0.1Co
x
nanocrystalline alloys (x = 0, 0.1 0.2, 0.3) synthesized by the mechanical alloying technique. The goal of this study is to determine an effect of partial replacement of V by Co atoms on hydrogen storage and electrochemical properties of Ti-V and Ti-V-Ni alloys. X-ray diffraction studies have proven that 14 h of the ball milling has resulted in crystallization of body-centered-cubic solid solution. Studies performed on high-resolution transmission electron microscope confirm creation of nanocrystalline materials. Hydrogen sorption/desorption measurements that have been performed at 303 K show that Co accelerates the hydrogen sorption process, diminishes hysteresis and ameliorates the hydrogen storage reversibility. Properties of Ti-V-Co alloys, described in this work, originate mainly from structure of these materials. Electrochemical measurements of Ti-V-Co alloys have shown these materials poorly absorb hydrogen in 6 M KOH solution. Ti0.5V1.4−x
Ni0.1Co
x
alloys are characterized by better activation properties and improved cyclability in comparison to Co-free Ti0.5V1.4Ni0.1 alloy.
IBN AL-HAYTHAM, IBN SĪNĀ, AL-ṬŪSĪ : ÉGALITÉ OU CONGRUENCE
Authors: Rashed Roshdi
Published: August 2019

As their greek predecessors, mathematicians and arab-speaking philosophers raised several important epistemological questions. One of those questions concerns the concept of equality and the concept of congruence of geometric magnitudes. What was the meaning of such concepts? How were they related to the idea of movement? Answers to these questions were often combining metric elements and other, philosophical (topological) elements, and I chose to study those of a mathematician, of a philosopher, and of a mathematician-philosopher.
Spray mixture pH as affected by dicamba, glyphosate, and spray additives
Authors: Mueller Thomas C , Steckel Lawrence E
Published: August 2019

The pH of spray mixtures is an important attribute that affects dicamba volatility under field conditions. This report examined the effect of different components added to water sources that ranged in initial pH from 4.6 to 8.4. Commercial products were used, which include formulations of dicamba, glyphosate, the drift retardant Intact, ammonium sulfate (AMS), and several pH modifiers. Adding BAPMA salt of dicamba always increased the mixture pH, whereas diglycolamine + VaporGrip® (DGA+VG) had a mixed response. The addition of AMS decreased pH slightly (usually <0.5 pH unit), whereas the addition of potassium salt of glyphosate (GLY-K) always decreased the measured pH (from 1.0 to 2.1 pH units). A substantial pH change could have profound effects on dicamba volatility. Moreover, the 1.0 to 2.1 pH units would not be consistent with the registrant’s report stating that GLY-K decreased mixtures with DGA+VG pH by only 0.2 to 0.3 units. The drift retardant Intact had no effect on pH. There was no difference in resultant pH when comparing K salt and isopropylamine (IPA) salts of glyphosate. Spray carrier volume, ranging from 94 to 187 L ha–1, had only a minor effect on measured pH after the addition of various spray components. The addition of selected pH modifiers raised the pH above 5.0, which is a critical value according to the latest dicamba application labels. The order of mixing of various pH modifiers, including AMS, had only limited effect on measured spray solution pH.
MLP-deficient human pluripotent stem cell derived cardiomyocytes develop hypertrophic cardiomyopathy and heart failure phenotypes due to abnormal calcium handling
Authors: Li Xiaowei , Lu Wen-Jing , Li Ya’nan , Wu Fujian , Bai Rui , Ma Shuhong , Dong Tao , Zhang Hongjia , Lee Andrew S. , Wang Yongming , Lan Feng
Published: August 2019

Muscle LIM protein (MLP, CSRP3) is a key regulator of striated muscle function, and its mutations can lead to both hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) in patients. However, due to lack of human models, mechanisms underlining the pathogenesis of MLP defects remain unclear. In this study, we generated a knockout MLP/CSRP3 human embryonic stem cell (hESC) H9 cell line using CRISPR/Cas9 mediated gene disruption. CSRP3 disruption had no impact on the cardiac differentiation of H9 cells and led to confirmed MLP deficiency in hESC-derived cardiomyocytes (ESC-CMs). MLP-deficient hESC-CMs were found to develop phenotypic features of HCM early after differentiation, such as enlarged cell size, multinucleation, and disorganized sarcomeric ultrastructure. Cellular phenotypes of MLP-deficient hESC-CMs subsequently progressed to mimic heart failure (HF) by 30 days post differentiation, including exhibiting mitochondrial damage, increased ROS generation, and impaired Ca2+ handling. Pharmaceutical treatment with beta agonist, such as isoproterenol, was found to accelerate the manifestation of HCM and HF, consistent with transgenic animal models of MLP deficiency. Furthermore, restoration of Ca2+ homeostasis by verapamil prevented the development of HCM and HF phenotypes, suggesting that elevated intracellular Ca2+ concentration is a central mechanism for pathogenesis of MLP deficiency. In summary, MLP-deficient hESC-CMs recapitulate the pathogenesis of HCM and its progression toward HF, providing an important human model for investigation of CSRP3/MLP-associated disease pathogenesis. More importantly, correction of the autonomous dysfunction of Ca2+ handling was found to be an effective method for treating the in vitro development of cardiomyopathy disease phenotype.
Aurora-A/ERK1/2/mTOR axis promotes tumor progression in triple-negative breast cancer and dual-targeting Aurora-A/mTOR shows synthetic lethality
Authors: Zhang Wenfeng , Xia Ding , Li Zhangyun , Zhou Tao , Chen Tingting , Wu Zhengping , Zhou Weihua , Li Zilun , Li Longkun , Xu Jie
Published: August 2019

Abstract

Triple-negative breast cancer (TNBC), defined as a tumor subtype that lacks ER, PR, and HER2, shows a poor prognosis due to its aggressive tumor biology and limited treatment options. Deregulation of Aurora kinase A (Aur-A), a member of the mitotic serine/threonine Aurora kinase family, and overactivation of the mTOR pathway commonly occur in multiple cancer types. We previously found that Aur-A activated the mTOR pathway and inhibited autophagy activity in breast cancer cell models. Whether and how Aur-A regulates mTOR in TNBC are still unclear. Here, we found that Aur-A and p-mTOR are highly expressed and positively associated with each other in TNBC cells and tissues. Inhibition or knockdown of Aur-A decreased p-mTOR and suppressed cell proliferation and migration, whereas overexpression of Aur-A increased p-mTOR levels and promoted cell proliferation and migration, which was significantly abrogated by simultaneous silencing of mTOR. Intriguingly, overexpression of Aur-A enhanced the expression of p-mTOR and p-ERK1/2, and silencing or inhibition of ERK1/2 blocked Aur-A-induced p-mTOR. However, silencing or inhibition of mTOR failed to reverse Aur-A-induced ERK1/2, indicating that Aur-A/ERK1/2/mTOR forms an oncogenic cascade in TNBC. We finally found that double inhibition of Aur-A and mTOR showed significant synergistic effects in TNBC cell lines and a xenograft model, indicating that Aur-A and mTOR are potential therapeutic targets in the TNBC subtype.
The NEDD8-activating enzyme inhibitor MLN4924 sensitizes a TNFR1+ subgroup of multiple myeloma cells for TNF-induced cell death
Authors: El-Mesery Mohamed , Rosenthal Tina , Rauert-Wunderlich Hilka , Schreder Martin , Stühmer Thorsten , Leich Ellen , Schlosser Andreas , Ehrenschwender Martin , Wajant Harald , Siegmund Daniela
Published: August 2019

The NEDD8-activating enzyme (NAE) inhibitor MLN4924 inhibits cullin-RING ubiquitin ligase complexes including the SKP1-cullin-F-box E3 ligase βTrCP. MLN4924 therefore inhibits also the βTrCP-dependent activation of the classical and the alternative NFĸB pathway. In this work, we found that a subgroup of multiple myeloma cell lines (e.g., RPMI-8226, MM.1S, KMS-12BM) and about half of the primary myeloma samples tested are sensitized to TNF-induced cell death by MLN4924. This correlated with MLN4924-mediated inhibition of TNF-induced activation of the classical NFκB pathway and reduced the efficacy of TNF-induced TNFR1 signaling complex formation. Interestingly, binding studies revealed a straightforward correlation between cell surface TNFR1 expression in multiple myeloma cell lines and their sensitivity for MLN4924/TNF-induced cell death. The cell surface expression levels of TNFR1 in the investigated MM cell lines largely correlated with TNFR1 mRNA expression. This suggests that the variable levels of cell surface expression of TNFR1 in myeloma cell lines are decisive for TNF/MLN4924 sensitivity. Indeed, introduction of TNFR1 into TNFR1-negative TNF/MLN4924-resistant KMS-11BM cells, was sufficient to sensitize this cell line for TNF/MLN4924-induced cell death. Thus, MLN4924 might be especially effective in myeloma patients with TNFR1+ myeloma cells and a TNFhigh tumor microenvironment.
Robust continuous in vitro culture of the Plasmodium cynomolgi erythrocytic stages
Authors: Chua Adeline C. Y. , Ong Jessica Jie Ying , Malleret Benoit , Suwanarusk Rossarin , Kosaisavee Varakorn , Zeeman Anne-Marie , Cooper Caitlin A. , Tan Kevin S. W. , Zhang Rou , Tan Bee Huat , Abas Siti Nurdiana , Yip Andy , Elliot Anne , Joyner Chester J. , Cho Jee Sun , Breyer Kate , Baran Szczepan , Lange Amber , Maher Steven P. , Nosten François , Bodenreider Christophe , Yeung Bryan K. S. , Mazier Dominique , Galinski Mary R. , Dereuddre-Bosquet Nathalie , Le Grand Roger , Kocken Clemens H. M. , Rénia Laurent , Kyle Dennis E. , Diagana Thierry T. , Snounou Georges , Russell Bruce , Bifani Pablo
Published: August 2019

The ability to culture pathogenic organisms substantially enhances the quest for fundamental knowledge and the development of vaccines and drugs. Thus, the elaboration of a protocol for the in vitro cultivation of the erythrocytic stages of Plasmodium falciparum revolutionized research on this important parasite. However, for P. vivax, the most widely distributed and difficult to treat malaria parasite, a strict preference for reticulocytes thwarts efforts to maintain it in vitro. Cultivation of P. cynomolgi, a macaque-infecting species phylogenetically close to P. vivax, was briefly reported in the early 1980s, but not pursued further. Here, we define the conditions under which P. cynomolgi can be adapted to long term in vitro culture to yield parasites that share many of the morphological and phenotypic features of P. vivax. We further validate the potential of this culture system for high-throughput screening to prime and accelerate anti-P. vivax drug discovery efforts.
Smart machine learning or discovering meaningful physical and chemical contributions through dimensional stacking
Authors: Griffin Lee A. , Gaponenko Iaroslav , Zhang Shujun , Bassiri-Gharb Nazanin
Published: August 2019

Despite remarkable advances in characterization techniques of functional materials yielding an ever growing amount of data, the interplay between the physical and chemical phenomena underpinning materials’ functionalities is still often poorly understood. Dimensional reduction techniques have been used to tackle the challenge of understanding materials’ behavior, leveraging the very large amount of data available. Here, we present a method for applying physical and chemical constraints to dimensional reduction analysis, through dimensional stacking. Compared to traditional, uncorrelated techniques, this approach enables a direct and simultaneous assessment of behaviors across all measurement parameters, through stacking of data along specific dimensions as required by physical or chemical correlations. The proposed method is applied to the nanoscale electromechanical relaxation response in (1 − x)PMN-xPT solid solutions, enabling a direct comparison of electric field- and chemical composition-dependent contributors. A poling-like, and a relaxation-like behavior with a domain glass state are identified, and their evolution is tracked across the phase diagram. The proposed dimensional stacking technique, guided by the knowledge of the underlying physics of correlated systems, is valid for the analysis of any multidimensional dataset, opening a spectrum of possibilities for multidisciplinary use.
Author Correction: Age-associated changes in the impact of sex steroids on influenza vaccine responses in males and females
Authors: Potluri Tanvi , Fink Ashley L. , Sylvia Kristyn E. , Dhakal Santosh , Vermillion Meghan S. , vom Steeg Landon , Deshpande Sharvari , Narasimhan Harish , Klein Sabra L.
Published: August 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
A continuum study of layer analysis for single species ion transport inside double-layered graphene sheets with various separations
Authors: Chan Yue , Saeed Muhammad , Lee Shern-Long , Wylie Jonathan J.
Published: August 2019

We investigate the formation of thin ionic layers driven by electro-osmotic forces, that are commonly found in micro- and nano-channels. Recently, multi-layers have been reported in the literature. However, the relation between classical Debye layers and multi-layers, which is a practically and fundamentally important question, was previously unexplained. Here, we fill this gap by using a continuum approach to investigate the flow of lithium ions inside double-layered graphene sheets. Fluid flow, charge conductivity and thermal stability will be investigated. We show that the separation and strength of forces between the sheets, the external electric field and thermal effects determine the topology of the ionic layers between the graphene sheets.
Strip rotary tillage with a two-year subsoiling interval enhances root growth and yield in wheat
Authors: He Jianning , Shi Yu , Zhao Junye , Yu Zhenwen
Published: August 2019

Excessive tillage and soil compaction threaten the sustainable farmlands in the Huang-Huai-Hai Plains of China. Our study explores tillage practices to improve soil and root ecology and promote productivity in the winter wheat fields. We tested the impact of plowing, rotary, strip rotary tillage and strip rotary tillage with a two-year subsoiling interval (SRS) on wheat yield and root quality. SRS decreased soil bulk density compared with other treatments, resulting in lower soil penetration resistance. Root morphology and weight density decreased with the increased soil depth and was higher in SRS. Moreover, SRS increased the indoleacetic acid and trans zeatin riboside levels corresponding to greater TTC reduction activities, the total and active absorption root area. SRS increased the superoxide dismutase and catalase activities and soluble protein concentration and decreased the malondialdehyde concentration. The first two factors extracted using 11 root attributes in various soil layers through principal component analysis were selected as the integrated indicators for the minimum data set, and their integrated score was calculated to quantify the root quality. Our study suggests that SRS could significantly improve root morphology and enhance the root activity in subsoil layers, thus, delaying root senescence and increasing winter wheat yield.
Genome-wide Identification, Classification, Expression and Duplication Analysis of GRAS Family Genes in Juglans regia L.
Authors: Quan Shaowen , Niu Jianxin , Zhou Li , Xu Hang , Ma Li , Qin Yang
Published: August 2019

Fifty-two GRAS genes are identified in walnut genome. Based on the evolutionary relationship and motif analysis, the walnut GRAS gene family was divided into eight subfamilies, and the sequence features analysis of JrGRAS proteins showed that the JrGRAS protein sequences were both conserved and altered during the evolutionary process. Gene duplication analysis indicated that seven GRAS genes in walnut have orthologous genes in other species, and five of them occurred duplicated events in walnut genome. Expression pattern analysis of the GRAS family genes in walnut showed that two JrGRAS genes (JrCIGRa-b and JrSCL28a) were differentially expressed between flower bud and leaf bud (p < 0.01), and two JrGRAS genes (JrCIGRa-b and JrSCL13b-d) were differentially expressed between the different development stages of flower buds transition (p < 0.01), besides, three hub genes (JrGAIa, JrSCL3f and JrSHRc) were identified by co-expression analysis, which suggested these GRAS genes may play an important role in regulating the development of apical meristem in walnut. This study laid a foundation for further understanding of the function of GRAS family genes in walnut.
Improved culture of fastidious Gemmata spp. bacteria using marine sponge skeletons
Authors: Kaboré Odilon D. , Godreuil Sylvain , Drancourt Michel
Published: August 2019

Gemmata are Planctomycetes bacteria recalcitrant to traditional cultivation in the clinical microbiology laboratory and they have been seldom documented in patients. Based on previously known relationships of Planctomycetes with marine sponges, we designed a new culture medium A incorporating marine sponge skeleton of Spongia sp. to the standard culture medium; and culture medium B incorporating Spongia sp. skeleton heat aqueous filtrate into medium A; and inoculating the three culture media (standard, A and B) with Gemmata obscuriglobus DSM 5831T and Gemmata massiliana DSM 26013T in the presence of negative controls. Cultures were observed by naked eyes for 7 days and bacterial growth was quantified by microscopic observations and culture-based enumerations. Macroscopic observations at day-3 revealed a pink bacterial pellet in medium B tubes while standard medium tubes remained limpid until day-8. Growing Gemmata spp. bacteria in medium A yielded air bubbles released by bacterial respiration, whereas control tubes remained bubble-free. The number of colonies in standard medium (1.363 ± 115 for G. obscuriglobus, 1.288 ± 83 for G. massiliana) was significantly lower than those counted from medium B (2.552 ± 128 for G. obscuriglobus, 1.870 ± 112 for G. massiliana) and from medium A (2.851 ± 137 for G. obscuriglobus, 2.035 ± 163 for G. massiliana) (p < 0.10−4) at day-2 incubation. At day-3 incubation, the number of colonies counted from supplemented media A and B increased up to one log than those counted from the control medium (p < 0.10−4). Along the following day-4–7 incubation, the number of colonies counted from media A and B remained significantly higher compared to standard medium (p < 0.10−4). These data indicate that incorporation of spongin-based marine sponge skeleton and heat aqueous filtrate of sponge skeleton significantly improved growth of Gemmata spp. bacteria. These observations pave the way towards improved isolation and culture of Gemmata spp. from environmental and clinical specimens.