bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative Assessment of Parental Somatic Mosaicism for Copy‐Number Variant (CNV) Deletions
Authors: Liu Qian , Grochowski Christopher M. , Bi Weimin , Lupski James R. , Stankiewicz Paweł 
Published: March 2020

AbstractAs genome sequencing methodologies have become more sensitive in detecting low‐frequency rare‐variant events, the link between post‐zygotic mutagenesis and somatic mosaicism in the etiology of several human genetic conditions other than cancers has become more clear. Given that current clinical‐genomics diagnostic methods have limited detection sensitivity for mosaic events, a copy‐number variant (CNV) deletion inherited from a parent with low‐level (<10%) mosaicism can be erroneously interpreted in the proband to represent a de novo germline event. Here, we describe three sensitive, precise, and cost‐efficient methods that can quantitatively assess the potential degree of parental somatic mosaicism levels for CNV deletions: droplet digital PCR (ddPCR), PCR amplicon–based next‐generation sequencing (NGS), and quantitative PCR. ddPCR using the EvaGreen fluorescent dye protocol can specifically quantify the deleted or non‐deleted alleles by analyzing the number of droplets positive for a fluorescent signal for each event. PCR amplicon–based NGS assesses the allele frequencies of a heterozygous single‐nucleotide polymorphism within a deletion region. The difference in number of reads between the two genotypes indicates the level of somatic mosaicism for the CNV deletion. Quantitative PCR can be applied where the relative quantity of the deletion junction–specific product represents the level of mosaicism. Clinical implementation of these quantitative variant‐detection methods enables potentially more accurate assessment of disease recurrence risk in family‐based genetic counseling, allowing couples to engage in more informed family planning. © 2020 by John Wiley & Sons, Inc.Basic Protocol: Droplet digital PCR (ddPCR)Alternate Protocol 1: PCR amplicon–based next‐generation sequencingAlternate Protocol 2: Quantitative real‐time PCR (qPCR)
Engineering the Morphology and Crystal Phase of 3 D Hierarchical TiO2 with Excellent Photochemical and Photoelectrochemical Solar Water Splitting
Authors: Chandra Moumita , Pradhan Debabrata 
Published: March 2020

AbstractOwing to their unique characteristics, hierarchical TiO2 nanostructures have several advantages in solar‐fuel production. In this work, a single‐step approach has been developed to control both the crystal phase and morphology of TiO2 with 3 D urchin‐like structure via a surfactant‐free solvothermal route. The growth of 3 D hierarchical structure with phase‐engineered band alignment, the role of the H2O/HCl ratio, and fine‐tuning of the reaction parameters are investigated systematically. An optimum ratio of anatase (41 %) to rutile (59 %) in the mixed‐phase TiO2 (AR‐2) results in excellent photocatalytic H2 generation activity of 5753 μmol g−1 after 5 h of irradiation with apparent quantum yields of 20.9 % at 366 nm and 4.5 % at 420 nm. The superior performance of AR‐2, attributed to efficient separation of charge carriers through the phase junction, is apparent from the transient photocurrent response and photoluminescence studies. The 3 D urchin‐like pure rutile TiO2 (R‐1) composed of nanorods shows enhanced photocatalytic activity compared with pure anatase and pure rutile TiO2 nanoparticles, and this demonstrates the role of morphology. The best‐performing mixed‐phase 3 D TiO2 shows excellent durability up to 25 h and is shown to produce 3522 μmol g−1 of H2 under natural sunlight, which highlights its potential for long‐term application.
Effectiveness of offloading interventions to heal foot ulcers in persons with diabetes: a systematic review
Authors: Lazzarini Peter A. , Jarl Gustav , Gooday Catherine , Viswanathan Vijay , Caravaggi Carlo F. , Armstrong David G. , Bus Sicco A. 
Published: March 2020

AbstractBackgroundOffloading interventions are commonly used in clinical practice to heal foot ulcers. The aim of this updated systematic review is to investigate the effectiveness of offloading interventions to heal diabetic foot ulcers.MethodsWe updated our previous systematic review search of PubMed, EMBASE, and Cochrane databases to also include original studies published between July 29, 2014 and August 13, 2018 relating to four offloading intervention categories in populations with diabetic foot ulcers: (a) offloading devices, (b) footwear, (c) other offloading techniques, and (d) surgical offloading techniques. Outcomes included ulcer healing, plantar pressure, ambulatory activity, adherence, adverse events, patient‐reported measures, and cost‐effectiveness. Included controlled studies were assessed for methodological quality and had key data extracted into evidence and risk of bias tables. Included non‐controlled studies were summarised on a narrative basis.ResultsWe identified 41 studies from our updated search for a total of 165 included studies. Six included studies were meta‐analyses, 26 randomised controlled trials (RCTs), 13 other controlled studies, and 120 non‐controlled studies. Five meta‐analyses and 12 RCTs provided high‐quality evidence for non‐removable knee‐high offloading devices being more effective than removable offloading devices and therapeutic footwear for healing plantar forefoot and midfoot ulcers. Total contact casts (TCCs) and non‐removable knee‐high walkers were shown to be equally effective. Moderate‐quality evidence exists for removable knee‐high and ankle‐high offloading devices being equally effective in healing, but knee‐high devices have a larger effect on reducing plantar pressure and ambulatory activity. Low‐quality evidence exists for the use of felted foam and surgical offloading to promote healing of plantar forefoot and midfoot ulcers. Very limited evidence exists for the efficacy of any offloading intervention for healing plantar heel ulcers, non‐plantar ulcers, and neuropathic ulcers with infection or ischemia.ConclusionStrong evidence supports the use of non‐removable knee‐high offloading devices (either TCC or non‐removable walker) as the first‐choice offloading intervention for healing plantar neuropathic forefoot and midfoot ulcers. Removable offloading devices, either knee‐high or ankle‐high, are preferred as second choice over other offloading interventions. The evidence bases to support any other offloading intervention is still weak and more high‐quality controlled studies are needed in these areas.
An Overview on Electrochemical Determination of Cholesterol
Authors: Amiri Mandana , Arshi Simin 
Published: March 2020

AbstractCholesterol detection is of great significance in biomedical applications because it is a crucial biomarker for some diseases. It is the precursor of different biological compounds such as vitamin D, hormones, and bile acid, etc. The cholesterol level in blood correlated to various diseases such as hypolipoproteinaemia, septicaemia, malnutrition hypertension, anaemia, brain thrombosis and arteriosclerosis for instance its levels in the blood of more than 200 mg/dL, increase the risk of heart disease. It is also found in foods from animal origin such as milk, meat, cheese, egg and seafood. With respect to dietary reference value for cholesterol intake, most of food safety authorities recommended maximum intake 300 mg per day for adults. Consequently, cholesterol is considered as a critical indicator of clinical biochemistry and so introducing new techniques for determination of it in biological samples and food is important. In this review, Principles, methods and recent developments in electrochemical cholesterol sensors are reviewed. Special attention is given to the discussion on some problems and bottlenecks in areas of enzymatic cholesterol sensing and new advances in non‐enzymatic sensors.
Lipid accumulation capability of typical non‐acclimated activated sludge microbial consortia using methane gas as secondary carbon source
Authors: Fortela Dhan Lord B. , Sharp Wayne , Revellame Emmanuel , Chistoserdov Andrei , Holmes William , Gang Daniel , Hernandez Rafael , Zappi Mark E. 
Published: March 2020

AbstractThis work experimentally demonstrates that wastewater activated sludge microbial consortia can utilize methane resulting in lipid content enhancement. Activated sludge was cultivated using a synthetic wastewater as culture media. After initial purging with air, analytical grade methane gas was added in the culture headspace. The cultures were cultivated in batch‐mode for 120 hours at 25°C in 500‐mL bioreactors with 125‐mL working liquid volume. Results indicate that methane gas was utilized by activated sludge microbial consortia under a similar pattern of microbial respiration as the control cultivated only with air. The activated sludge in the methane‐purged bioreactors showed lipid enhancement (0.123 ± 0.037 mg lipid per mg biomass) and biomass growth (0.626 ± 0.163 mg biomass per mg glucose plus methane), which were higher than those in the control runs (0.009 ± 0.034 mg lipid per mg biomass and 0.225 ± 0.133 mg biomass per mg glucose).
Tanycyte ablation in the arcuate nucleus and median eminence increases obesity susceptibility by increasing body fat content in male mice
Authors: Yoo Sooyeon , Cha David , Kim Soohyun , Jiang Lizhi , Cooke Patrick , Adebesin Mobolanie , Wolfe Andrew , Riddle Ryan , Aja Susan , Blackshaw Seth 
Published: March 2020

AbstractTanycytes are radial glial cells located in the mediobasal hypothalamus. Recent studies have proposed that tanycytes play an important role in hypothalamic control of energy homeostasis, although this has not been directly tested. Here, we report the phenotype of mice in which tanycytes of the arcuate nucleus and median eminence were conditionally ablated in adult mice. Although the cerebrospinal fluid‐hypothalamic barrier was rendered more permeable following tanycyte ablation, neither the blood‐hypothalamic barrier nor leptin‐induced pSTAT3 activation in hypothalamic parenchyma were affected. We observed a significant increase in visceral fat distribution accompanying insulin insensitivity in male mice, without significant effect on either body weight or food intake. A high‐fat diet tended to accelerate overall body weight gain in tanycyte‐ablated mice, but the development of visceral adiposity and insulin insensitivity was comparable to wildtype. Thermoneutral housing exacerbated fat accumulation and produced a shift away from fat oxidation in tanycyte‐ablated mice. These results clarify the extent to which tanycytes regulate energy balance, and demonstrate a role for tanycytes in regulating fat metabolism.
MicroRNA miR‐204 regulates proliferation and differentiation of oligodendroglia in culture
Authors: Wittstatt Jan , Weider Matthias , Wegner Michael , Reiprich Simone 
Published: March 2020

AbstractOligodendrocytes wrap and physically shield axons of the central nervous system with myelin sheaths, resulting in rapid signal transduction and accurate neuronal function. The complex oligodendroglial development from immature oligodendrocyte precursor cells (OPCs) to myelinating oligodendrocytes (OLs) is profoundly dependent on the activity of transcription factors of the Sox protein family. Target genes of the crucial regulator Sox10 have recently been expanded to microRNAs. Here, we report miR‐204 as a novel transcriptional target of Sox10. Regulatory regions of miR‐204 show responsiveness to and binding of Sox10 in reporter gene assays and electromobility shift assays. Once expressed, miR‐204 inhibits OPC proliferation and facilitates differentiation into OLs in the presence of Sox10 as evident from overexpression in primary rat and mouse oligodendroglial cultures. Phenotypes are at least in part caused by miR‐204‐dependent repression of the pro‐proliferative Ccnd2 and the differentiation inhibiting Sox4. These findings argue that the transcriptional activator Sox10 forces oligodendroglial cells to exit the cell cycle and start differentiation by gene inhibition via miR‐204 induction.
Critical roles of astrocytic‐CCL2‐dependent monocyte infiltration in a DJ‐1 knockout mouse model of delayed brain repair
Authors: Choi Dong‐Joo , Yang Hajie , Gaire Sushil , Lee Keon Ah , An Jiawei , Kim Byung Gon , Jou Ilo , Park Sang Myun , Joe Eun‐Hye 
Published: March 2020

AbstractMonocyte‐derived macrophages play a role in the repair of the injured brain. We previously reported that a deficiency of the Parkinson's disease (PD)‐associated gene DJ‐1 delays repair of brain injury produced by stereotaxic injection of ATP, a component of damage‐associated molecular patterns. Here, we show that a DJ‐1 deficiency attenuates monocyte infiltration into the damaged brain owing to a decrease in C‐C motif chemokine ligand 2 (CCL2) expression in astrocytes. Like DJ‐1‐knockout (KO) mice, CCL2 receptor (CCR2)‐KO mice showed defects in monocyte infiltration and delayed recovery of brain injury, as determined by 9.4 T magnetic resonance imaging analysis and immunostaining for tyrosine hydroxylase and glial fibrillary acid protein. Notably, transcriptome analyses showed that genes related to regeneration and synapse formation were similarly downregulated in injured brains of DJ‐1‐KO and CCR2‐KO mice compared with the injured wild‐type brain. These results indicate that defective astrogliosis in DJ‐1‐KO mice is associated with decreased CCL2 expression and attenuated monocyte infiltration, resulting in delayed repair of brain injury. Thus, delayed repair of brain injury could contribute to the development of PD.Main PointsA DJ‐1 deficiency attenuates infiltration of monocytes owing to a decrease in CCL2 expression in astrocytes, which in turn led to delay in repair of brain injury.
Behind the internationalization of family SMEs: A strategy tripod synthesis
Authors: Lahiri Somnath , Mukherjee Debmalya , Peng Mike W. 
Published: March 2020

AbstractResearch SummaryWe review and synthesize the growing literature concerning the internationalization of small and medium‐sized family enterprises (family SMEs) around a strategy tripod framework. In doing so, we identify various resource‐based, institution‐based, and industry‐based factors that contribute to family SME internationalization endeavors. We also pinpoint possible home‐country‐level and host‐country‐level institutional and industry‐based structural–cultural contingencies that may interact with family SME resource‐based factors to accentuate or impede their internationalization. Moreover, we highlight different behavioral orientations as crucial missing links that characterize the family SME internationalization scholarship. Overall, our comprehensive synthesis of the literature sheds light on how internationalization strategies of family SMEs vary based on important drivers and contextual influences captured in our tripod framework.Managerial SummaryFamily SMEs are distinct in that they possess the attributes of family businesses (family ownership and control) as well as those of SMEs (smallness, flexibility, and resource constraints). Managing these attributes may be difficult when it comes to executing important strategies such as internationalization. Family SMEs, therefore, need to be cognizant of various factors that can potentially impact their internationalization planning and success. The strategy tripod framework that we develop can provide guidance to managers in considering how resource‐based, institution‐based, and industry‐based factors drive family SME internationalization. Our integrative framework endeavors to help managers realize how their internationalization strategies and the resultant outcomes will vary depending on how they manage the three factors.
Elbasvir and grazoprevir for hepatitis C virus genotype 1 infection in people with recent injecting drug use (DARLO‐C): An open‐label, single‐arm, phase 4, multicentre trial
Authors: Grebely Jason , Read Phillip , Cunningham Evan B. , Weltman Martin , Matthews Gail V. , Dunlop Adrian , Montebello Mark , Martinello Marianne , Gilliver Rosie , Marks Philippa , Applegate Tanya L. , Dore Gregory J. ,   the DARLO‐C Study Group
Published: March 2020

AbstractBackground and AimsDirect‐acting antiviral therapy for hepatitis C virus (HCV) is effective, but few prospective studies among people with ongoing injecting drug use exist. This study evaluated the efficacy of elbasvir/grazoprevir in people with HCV genotype 1/4 (G1/4) infection and recent injecting drug use. An exploratory aim evaluated the feasibility of fingerstick point‐of‐care HCV RNA testing prior to and following treatment.MethodsDARLO‐C (ClinicalTrials.gov: NCT02940691) is an open‐label phase 4 trial. Participants were recruited between May 2017 and March 2018 from two drug treatment clinics, two hospital clinics, and one community clinic in Australia. Inclusion criteria included recent injection drug use (previous 6 months) and HCV G1/4 infection. Exclusion criteria included prior HCV treatment and decompensated liver disease. Participants received elbasvir/grazoprevir once‐daily for 12 weeks. The primary endpoint was undetectable HCV RNA 12 weeks post‐treatment (SVR). Fingerstick whole‐blood samples were tested using the Xpert HCV Viral Load Fingerstick (Xpert HCV VL Fingerstick) assay and compared to the Aptima HCV Quant Dx Assay on plasma samples.ResultsOf a planned 150 participants, 32 were enrolled due to slower than anticipated recruitment [median age 46 years, 10 (31%) female, 29 (91%) G1a]. Eighteen (56%) were receiving opioid agonist therapy and 29 (91%) injected in the previous month. Twenty‐six (81%) of 32 completed treatment (lost to follow‐up, n = 5; incarceration, n = 1). There were no virological failures. Twenty‐four (75%, 95% CI 59%‐91%) of 32 achieved SVR. Two participants who completed treatment did not have SVR (loss to follow‐up, n = 1; refused test, n = 1). Among paired samples (n = 36), sensitivity of the Xpert HCV VL Fingerstick assay for HCV RNA detection was 100.0% (95% CI 75.3%‐100.0%) and specificity was 95.7% (95% CI 78.1%‐99.9%).ConclusionElbasvir/grazoprevir is effective among people with HCV G1 with recent injecting drug use. Implementation of point‐of‐care HCV RNA testing was feasible, but the high error rate requires investigation.
Magnetic nanoparticles of Ga‐substituted ε‐Fe2O3 for biomedical applications: Magnetic properties, transverse relaxivity, and effects of silica‐coated particles on cytoskeletal networks
Authors: Královec Karel , Havelek Radim , Koutová Darja , Veverka Pavel , Kubíčková Lenka , Brázda Petr , Kohout Jaroslav , Herynek Vít , Vosmanská Magda , Kaman Ondřej 
Published: March 2020

AbstractMagnetic nanoparticles of ε‐Fe1.76Ga0.24O3 with the volume‐weighted mean size of 17 nm were prepared by thermal treatment of a mesoporous silica template impregnated with metal nitrates and were coated with silica shell of four different thicknesses in the range 6–24 nm. The bare particles exhibited higher magnetization than the undoped compound, 22.4 Am2 kg−1 at 300 K, and were characterized by blocked state with the coercivity of 1.2 T at 300 K, being thus the very opposite of superparamagnetic iron oxides. The relaxometric study of the silica‐coated samples at 0.47 T revealed promising properties for MRI, specifically, transverse relaxivity of 89–168 s−1 mmol(f.u.)−1 L depending on the shell thickness was observed. We investigated the effects of the silica‐coated nanoparticles on human A549 and MCF‐7 cells. Cell viability, proliferation, cell cycle distribution, and the arrangement of actin cytoskeleton were assessed, as well as formation and maturation of focal adhesions. Our study revealed that high concentrations of silica‐coated particles with larger shell thicknesses of 16–24 nm interfere with the actin cytoskeletal networks, inducing thus morphological changes. Consequently, the focal adhesion areas were significantly decreased, resulting in impaired cell adhesion.
Treatment with bisphosphonates to mitigate calcification of elastin‐containing bioprosthetic materials
Authors: Zhuravleva Irina Y. , Polienko Yuliya F. , Karpova Elena V. , Timchenko Tatyana P. , Vasilieva Maria B. , Baratova Ludmila A. , Shatskaya Svetlana S. , Kuznetsova Elena V. , Nichay Nataliya R. , Beshchasna Natalia , Bogachev‐Prokophiev Alexander V. 
Published: March 2020

AbstractThis study evaluated the ability of bisphosphonates (BPAs) of different molecular structures to mitigate the calcification of porcine aortic wall (PAW) and bovine jugular vein wall (BJVW). Tissues cross‐linked with glutaraldehyde (GA) or diepoxide (DE) were modified with pamidronic acid (PAM), alendronic acid (ALE), neridronic acid (NER) (type 1 BPAs); 2‐(2′‐carboxyethylamino)ethylidene‐1,1‐bisphosphonic acid (CEABA), 2‐(5‐carboxypentylamino)ethylidene‐1,1‐bisphosphonic acid (CPABA) (type 2); and zoledronic acid (ZOL) (type 3). After implanting the tissue samples subcutaneously in 100 rats, calcification was examined using atomic absorption spectrophotometry (60‐day explants) and light microscopy after von Kossa staining (10‐ and 30‐day explants). The calcium contents in GA‐BJVW and GA‐ and DE‐PAW increased up to 100–120 mg/g after 60 days, while being 3 times lower in DE‐BJVW. In modified and nonmodified PAW samples, calcium phosphates appeared by day 10 and were associated with elastic fibers and devitalized cellular elements. In all groups of BJVW samples, mineralization began in elastic fibers near the subendothelial layer. In addition, calcified collagen was found in the GA‐BJVW samples. Minimal calcification was found in GA‐PAW treated with type 1 BPAs and CEABA. For DE‐PAW and GA‐BJVW, the calcium level significantly decreased with PAM and CEABA. Meanwhile, ALE and NER were effective for DE‐BJVW.
A Comparison of Bone-Targeted Exercise Strategies to Reduce Fracture Risk in Middle-Aged and Older Men with Osteopenia and Osteoporosis: LIFTMOR-M Semi-Randomized Controlled Trial
Authors: Harding Amy T , Weeks Benjamin K , Lambert Conor , Watson Steven L , Weis Lisa J , Beck Belinda R 
Published: March 2020

ABSTRACT
The Lifting Intervention For Training Muscle and Osteoporosis Rehabilitation for Men (LIFTMOR-M) trial examined efficacy and safety of two novel exercise programs in older men with low BMD. Men with low hip and/or LS BMD were randomized to high-intensity progressive resistance and impact training (HiRIT) or machine-based isometric axial compression (IAC) and compared to a nonrandomized matched control (CON). Outcomes included: hip and LS BMD; calcaneal ultrasound parameters; anthropometry; body composition; function (timed up-and-go [TUG], five-times sit-to-stand [FTSTS]); back extensor strength (BES); leg extensor strength (LES); compliance and adverse events. Ninety-three men (67.1 ± 7.5 years; 82.1 ± 11.6 kg; 175.2 ± 6.7 cm; FN T-score −1.6 ± 0.6) were randomized to HiRIT (n = 34) or IAC (n = 33), or allocated to CON (n = 26). HiRIT improved trochanteric BMD (2.8 ± 0.8%; −0.1 ± 0.9%, p = .024), LS BMD (4.1 ± 0.7%; 0.9 ± 0.8%, p = .003), BUA (2.2 ± 0.7%; −0.8 ± 0.9%, p = .009), stiffness index (1.6 ± 0.9%; −2.0 ± 1.1%, p = .011), lean mass (1.5 ± 0.8%; −2.4 ± 0.9%, p = .002), TUG, FTSTS, BES, and LES (p &lt; .05) compared with CON. IAC improved lean mass (0.8 ± 0.8%; −2.4 ± 0.9%, p = .013) and FTSTS (−4.5 ± 1.6%; 7.5 ± 2.0%, p &lt; .001) compared with CON. HiRIT improved LS BMD (4.1 ± 0.7%; 2.0 ± 0.7%, p = .039), stiffness index (1.6 ± 0.9%; −1.3 ± 0.9%, p = .025), and FTSTS (−10.7 ± 1.6%; −4.5 ± 1.7%, p = .010) compared with IAC. Exercise compliance was high (HiRIT 77.8 ± 16.6%; IAC 78.5 ± 14.8%, p = .872). There were five minor adverse events (HiRIT, 2; IAC, 3). HiRIT was well-tolerated and improved bone, function and fracture risk more than CON or IAC. © 2020 American Society for Bone and Mineral Research.