bluuebunny/crossref_metadata_2025_split huggingface dataset:
An ethical framework for genetic counseling in the genomic era
Authors: Jamal Leila , Schupmann Will , Berkman Benjamin E. 
Published: December 2019

AbstractThe field of genetic counseling has grown and diversified since the profession emerged in the early 1970s. In the same period, genomic testing has become more complex, profitable, and widespread. With these developments, the scope of ethical considerations relevant to genetic counseling has expanded. In light of this, we find it helpful to revisit how ethical and relational variables are used to inform genetic counseling practice. Our specific focus is on whether, and to what extent, it is ethically acceptable for genetic counselors to make normative recommendations to patients. This article builds on prior literature that has critiqued nondirectiveness, a concept that has influenced and constrained the modern profession of genetic counseling since its origin. In it, we review scholarly efforts to move beyond nondirectiveness, which we believe privilege patient autonomy at the expense of other important values. We then argue that genetic counselors should favor a more explicit commitment to the principles of beneficence and non‐maleficence, as well as a broader understanding of autonomy and the relational variables that impact genetic counseling. Finally, to translate our arguments into practice, we present a framework of six considerations that genetic counselors should take into account when deciding whether it is ethically acceptable, or even desirable, to make recommendations to patients in certain areas of their work.
Epidemiological impact and cost‐effectiveness of providing long‐acting pre‐exposure prophylaxis to injectable contraceptive users for HIV prevention in South Africa: a modelling study
Authors: van Vliet Marjolein M , Hendrickson Cheryl , Nichols Brooke E , Boucher Charles AB , Peters Remco PH , van de Vijver David AMC 
Published: December 2019

AbstractIntroductionAlthough pre‐exposure prophylaxis (PrEP.) is an efficacious HIV prevention strategy, its preventive benefit has not been shown among young women in sub‐Saharan Africa, likely due to non‐adherence. Adherence may be improved with the use of injectable long‐acting PrEP methods currently being developed. We hypothesize that providing long‐acting PrEP to women using injectable contraceptives, the most frequently used contraceptive method in South Africa, could improve adherence to PrEP, result in a reduction of new HIV infections, and be a relatively easy‐to‐reach target population. In this modelling study, we assessed the epidemiological impact and cost‐effectiveness of providing long‐acting PrEP to injectable contraceptive users in Limpopo, South Africa.MethodsWe developed a deterministic mathematical model calibrated to the HIV epidemic in Limpopo. Long‐acting PrEP was provided to 50% of HIV negative injectable contraceptive users in 2018 and scaled‐up over two years. We estimated the number of HIV infections that could be averted by 2030 and the drug price of long‐acting PrEP for which this intervention would be cost‐effective over a time horizon of 40 years, from a healthcare payer perspective. In the base‐case scenario we assumed long‐acting PrEP is 75% effective in preventing HIV infections and 85% of infected individuals are on antiretroviral drug therapy (ART) by 2030. In sensitivity analyses we adjusted PrEP effectiveness and ART coverage. Costs between $519 and $1119 per disability‐adjusted life‐year (DALY) averted were considered potentially cost‐effective, and <$519 as cost‐effective.ResultsWithout long‐acting injectable PrEP, 224,000 (interquartile range 176,000 to 271,000) new infections will occur by 2030; use of long‐acting injectable PrEP could prevent 21,000 (17,000 to 26,000) or 9.8% (8.9% to 10.6%) new HIV infections by 2030 (including 6000 (4000 to 7000) in men). Long‐acting PrEP would prevent 34,000 (29,000 to 39,000) or 12,000 (8000 to 15,000) at 75% and 95% ART coverage by 2030 respectively. To be considered potentially cost‐effective the annual long‐acting PrEP drug price should be <$16, and/or ART coverage remains at <85% in 2030.ConclusionsProviding long‐acting PrEP to injectable contraceptive users in Limpopo is only potentially cost‐effective when long‐acting PrEP drug prices are low. If low prices are not feasible, providing long‐acting PrEP only to women at high risk of HIV infection will become important.
Phenotypes and genotypes of mitochondrial aminoacyl‐tRNA synthetase deficiencies from a single neurometabolic clinic
Authors: Al Balushi Aaisha , Matviychuk Diana , Jobling Rebekah , Salomons Gajja S. , Blaser Susan , Mercimek‐Andrews Saadet 
Published: December 2019

AbstractMitochondrial aminoacyl‐tRNA synthetases play a major role in protein translation, synthesis, and oxidative phosphorylation. We reviewed all patients diagnosed with mitochondrial aminoacyl‐tRNA synthetase deficiencies diagnosed in a single neurometabolic clinic. We report five patients with mitochondrial aminoacyl‐tRNA synthetase deficiencies including DARS2, EARS2, PARS2, and RARS2 deficiencies. Siblings with DARS2 deficiency presented with global developmental delay within the first year of life. DARS2, EARS2, PARS2, and RARS2 deficiencies were identified by whole exome sequencing. We report coagulation factor abnormalities in PARS2 deficiency for the first time. We also report symmetric increased signal intensity in globus pallidi in FLAIR images in brain MRI in EARS2 deficiency for the first time. One patient with RARS2 deficiency had compound heterozygous variants in RARS2. One of those variants was an intronic variant. We confirmed the pathogenicity by mRNA studies. Mitochondrial aminoacyl‐tRNA synthetase deficiencies are diagnosed by molecular genetic investigations. Clinically available non‐invasive biochemical investigations are non‐specific for the diagnosis of mitochondrial aminoacyl‐tRNA synthetase deficiencies. A combination of brain MRI features and molecular genetic investigations should be undertaken to confirm the diagnosis of mitochondrial aminoacyl‐tRNA synthetase deficiencies.
Evaluation of CCR5‐Δ32 mutation among individuals with high risk behaviors, neonates born to HIV‐1 infected mothers, HIV‐1 infected individuals, and healthy people in an Iranian population
Authors: Donyavi Tahereh , Bokharaei‐Salim Farah , Nahand Javid Sadri , Garshasbi Saba , Esghaei Maryam , Sadeghi Mohsen , Jamshidi Sogol , Khanaliha Khadijeh 
Published: December 2019

AbstractOne of the important genetic factors related to resistance to HIV‐1 infection is the presence of the C–C chemokine receptor type 5 delta 32 (CCR5‐Δ32) homozygous genotype (Δ32/Δ32). The aim of this study was to evaluate the CCR5‐Δ32 mutation among individuals with high‐risk behaviors, neonates born to HIV‐1‐infected mothers in the prevention of mother‐to‐child transmission (PMTCT) project, HIV‐1‐infected individuals, and healthy people. The frequency of the CCR5‐Δ32 genotype was assessed in a cross‐sectional survey carried out from March 2014 to March 2019 among four different groups of the Iranian population. Genomic DNA was extracted from peripheral blood mononuclear cells of 140 Iranian healthy people, 84 neonates born to HIV‐1‐infected mothers in the PMTCT project, 71 people with high‐risk behaviors, and 76 HIV‐1‐infected individuals. The polymerase chain reaction method was used for the amplification of the CCR5 gene. The CCR5‐Δ32 heterozygous deletion was detected in five (6.6%) HIV‐1‐infected individuals, four (4.7%) neonates born to HIV‐1 positive mothers, two (1.4%) healthy people, and also three (4.2%) people with high‐risk behaviors whereas the CCR5‐Δ32 homozygous deletion was absent in all the groups (Fisher's exact test, P = .0242). The allele of CCR5‐Δ32 homozygous was not detected in the four study groups, and no significant difference was seen in the frequency of the CCR5Δ32 heterozygous allele between HIV seropositive and seronegative individuals. Therefore, it seems that this allele alone cannot explain the natural resistance to HIV‐1 infection and probably several mechanisms are responsible for these processes and it should be further investigated.
Developmental stages of biofilm and characterization of extracellular matrix of manglicolous fungus Aspergillus niger BSC‐1
Authors: Chatterjee Shreosi , Das Surajit 
Published: December 2019

AbstractFungal biofilm is ubiquitous in natural environment. The major constituent of fungal biofilm other than biomass is the extracellular matrix (ECM), in which fungal hyphae are embedded. Physical properties of biofilms such as attachment, mechanical strength, and antibiotic resistance can be attributed to ECM. The present work probes various stages of biofilm formation by filamentous manglicolous fungus Aspergillus niger BSC‐1. The spectroscopic analysis revealed that with an increase in incubation time the biofilm formation was significantly increased (p < .0001) up to 36 h. Scanning electron micrograph and confocal micrograph depicted the development of fungal biofilm comprising of six stages, that is, (a) adsorption, (b) active attachment, (c) germling and monolayer formation, (d) hyphal development and formation of ECM, (e) maturation of ECM, and (f) dispersal of spores. At maturation stage, thickness of biofilm was observed upto approximately 15 μm. Approximately, 8.1 mg of ECM materials were extracted from 20 ml of broth culture using ethanol precipitation method. Furthermore, attenuated total reflectance Fourier‐transformed infrared spectroscopic analysis exhibited peaks at 3,398, 2,930, 1,571, 1,391, 1,092, 977 cm−1 which confirmed the presence of protein, carbohydrate, and lipid in the biofilm‐associated matrix.
The interpretative value of transformed tephra sequences
Authors: Dugmore Andrew J. , Thompson Polly I. J. , Streeter Richard T. , Cutler Nick A. , Newton Anthony J. , Kirkbride Martin P. 
Published: December 2019

ABSTRACTWe explore developments in tephra science that consider more than chronology, using case studies of morphological transformations of tephra deposits. Volcanic processes and prevailing weather conditions determine the distribution of tephra deposits immediately after an eruption, but as these freshly fallen tephra become part of the stratigraphic record, the thickness, morphology and definition of the layers they form changes, reflecting the interplay of the tephra, climate, Earth surface processes, topography and vegetation structure, plus direct or indirect modification caused by people and animals. Once part of the stratigraphic record, there can be further diagnostic changes to the morphology of tephra layers, such as the creation of over folds by cryoturbation. Thus, tephra layers may contain proxy evidence of both past surface environments and subsurface processes. Transformations of tephra deposits can complicate the reconstruction of past volcanic processes and make the application of classical tephrochronology as pioneered by Thorarinsson (Sigurður Þórarinsson in Icelandic) challenging. However, as Thorarinsson also noted, novel sources of environmental data can exist within transformed tephra sequences that include the spread or removal of tephra, variations in layer thickness and internal structures, the nature of contact surfaces and the orientation of layers.
Dawson tephra, a widespread 29‐ka marker bed, in a marine core from Patton Seamount off the Alaska Peninsula and its potential marine–terrestrial correlation
Authors: Aoki Kaori 
Published: December 2019

ABSTRACTA tephra layer with normal grading in the sub‐bottom depth interval 119–122 cm in marine core SO202‐27‐6 was collected on Patton Seamount in the northeast North Pacific Ocean. Based on the geochemistry of volcanic glass shards determined by a wavelength dispersive electron probe micro‐analyser and an X‐ray fluorescence analyser, this layer is correlated to the Dawson tephra, a widespread late Pleistocene time marker tephra in Alaska and the Yukon. The age of the Dawson tephra in the core is 29.03 ± 0.178 ka (1 sigma) based on a published age model. The Dawson tephra is revealed to have been deposited in the transition from marine isotope stage 3 to 2, i.e. the last stage of Heinrich Stadial 3 derived from the ice‐rafted debris signal. According to the correlation between Greenland (NGRIP ice core) and this core, the Dawson tephra occupies the record immediately before inter stadial 4 in the δ18O stratigraphy of NGRIP. The Dawson tephra on Patton Seamount includes lithic fragments, which suggests that it was deposited not only by fall‐out but also in part via another mechanism, such as icebergs from the Cordilleran ice sheet or seasonal sea ice.
Combinatorial conditioning of adipose derived‐mesenchymal stem cells enhances their neurovascular potential: Implications for intervertebral disc degeneration
Authors: Binch Abbie. L. A. , Richardson Stephen M. , Hoyland Judith A. , Barry Frank P. 
Published: December 2019

ABSTRACTBackgroundMesenchymal stem cells (MSCs) are becoming an increasingly attractive option for regenerative therapies due to their availability, self‐renewal capacity, multilineage potential, and anti‐inflammatory properties. Clinical trials are underway to test the efficacy of stem cell‐based therapies for the repair and regeneration of the degenerate intervertebral disc (IVD), a major cause of back pain. Recently, both bone marrow‐derived MSCs and adipose‐derived stem cells (ASCs) have been assessed for IVD therapy but there is a lack of knowledge surrounding the optimal cell source and the response of transplanted cells to the low oxygen, pro‐inflammatory niche of the degenerate disc. Here, we investigated several neurovascular factors from donor‐matched MSCs and ASCs that may potentiate the survival and persistence of sensory nerve fibers and blood vessels present within painful degenerate discs and their regulation by oxygen tensions and inflammatory cytokines.MethodsDonor‐matched ASCs and MSCs were conditioned with either IL‐1β or TNFα under normoxic (21% O2) or hypoxic (5% O2) conditions. Expression and secretion of several potent neurovascular factors were assessed using qRT‐PCR and human magnetic Luminex assay.ResultsASCs and MSCs expressed constitutive levels of key neurotrophic factors; and stimulation of ASCs with hypoxia triggered increased secretion of both angiogenic factors (Ang‐2 and VEGF‐A) and neurotrophic (NGF and NT‐3) compared to MSCs. We also report increased transcriptional regulation of pain‐associated neuropeptides in hypoxia stimulated ASCs compared to those in normoxic conditions. We demonstrate transcriptional and translational upregulation of NGF, NT‐3, Ang‐1, and FGF‐2 in response to cytokines in ASCs in 21% and 5% O2.ConclusionsThis work highlights fundamental differences between the neurovascular secretome of donor‐matched ASCs and MSCs, demonstrating the importance of cell‐selection for tissue specific regeneration to reduce ectopic sensory nerve and blood vessel survival and improve patient outcomes.
Prevention of Local Tumor Recurrence After Surgery by Thermosensitive Gel‐Based Chemophotothermal Therapy in Mice
Authors: Fan Yanyan , Yu Dujuan , Li Duan , Wang Xue 
Published: December 2019

Background and ObjectivesLocal recurrence of cancer after surgery has long been a tough problem. In the present study, thermosensitive gel‐based chemophotothermal therapy was applied to prevent the recurrence of liver cancer after surgery.Study Design/Materials and MethodsMesoporous silica nanoparticles (MSNs) were used as first‐level carrier to co‐load doxorubicin (DOX) and ICG. Then, the drug‐loaded MSNs (D‐I@MSN) were incorporated into poloxamer gel. A mimic model of liver cancer recurrence after surgery was prepared by subcutaneously injecting H22 cells into the armpit of mice. Then the two‐level composite gel (D‐I@MSN/gel) was also subcutaneously injected at the same site before the formation of tumor, followed by 808 nm laser irradiation.ResultsThe loading efficiency and entrapment efficiency of DOX were as high as 8.85% and 96.9%, and that of ICG were 9.24% and 99.3%, respectively. The results of in vitro cytotoxicity showed that cell viability in D‐I@MSN+Laser group was only 5.8% after being irradiated by 808 nm laser for 5 minutes (0.5 W/cm2). In animal studies, tumor formation (tumor recurrence) was greatly inhibited in D‐I@MSN+Laser group.ConclusionsThe thermosensitive gel‐based chemophotothermal therapy showed excellent safety and efficacy when applied in the prevention of mimic local tumor replase after surgery in mice, presenting its great potential clinically. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.
Temperature Responsive Shape‐Memory Scaffolds with Circumferentially Aligned Nanofibers for Guiding Smooth Muscle Cell Behavior
Authors: Chen Minmin , Li Linlin , Xia Li , Zhang Feng , Jiang Suwei , Hu Hailiang , Li Xingjiang , Wang Hualin 
Published: December 2019

AbstractStructural simulation of the smooth muscle layer plays an important role in tissue engineering of blood vessels for the replacement of damaged arteries. However, it is difficult to construct small‐diameter tubular scaffolds to homogenously locate and align smooth muscle cells (SMCs). In this work, novel temperature responsive shape‐memory scaffolds are designed for SMC culturing. The scaffolds are composed of an outer layer of poly(lactide–glycolide–trimethylene carbonate) (PLGATMC) for programming the deformation from planar to small‐diameter tubular shape and an inner layer of aligned nanofibrous membrane of poly(lactide–glycolide)/chitosan (PLGA/CS) to regulate cell adhesion, proliferation, and morphology. The SMC behaviors and functions are dependent on the PLGA/CS ratios of membranes, and the scaffold with PLGA/CS 7:3 membrane exhibits the most suitable ability to regulate SMC behavior. The PLGA/CS@PLGATMC scaffold can be deformed into a temporary planar at 20 °C for convenient seeding and attachment of SMCs and then immediately self‐rolled into 3D tube at 37 °C. The proposed strategy offers a practical approach for the development of small‐diameter vascular scaffolds from 2D planar into 3D tubular shape by self‐rolling.
Synthesis and Properties of Novel Polyethylene‐Based Antioxidants with Hindered Phenols as Side Groups
Authors: Zhang Yin , Li Huayi , Li Mengru , Liu Weiwei , Li Qian , Hu Youliang 
Published: December 2019

AbstractNovel polyethylene‐based (PE‐based) antioxidants derived from commercially available ethylene‐vinyl acetate copolymer (EVA) with PE as the backbone and hindered phenols as side groups are prepared, and their potential for application as non‐migrating polyolefin stabilizers is investigated. The synthesis route contains the typical hydrolysis of EVA and transesterification reaction between the hydrolysis product and methyl 3‐(3,5‐di‐tert‐butyl‐4‐hydroxyphenyl) propionate. Thermal stabilities of these PE‐based antioxidants (AO‐PE) are studied through thermal analysis under an air atmosphere and shown to be higher than those of antioxidant 1076 and antioxidant 1010 (AO‐1010) due to their macromolecular structures. Antioxidant activities of the AO‐PE are evaluated in polypropylene (PP) by measuring the melt flow index of multiple‐extruded stabilized PP, and the results demonstrate that the antioxidant effectiveness of these antioxidants is strongly related to the molecular weight.
Electrospraying the Triblock Copolymer SEBS: The Effect of Solvent System and the Embedding of Quantum Dots
Authors: Koekoekx Robin , Zawacka Natalia C. , Van den Mooter Guy , Hens Zeger , Clasen Christian 
Published: December 2019

AbstractThis work reports on ABA triblock copolymer microparticles encoded with CdSe/CdS core–shell quantum dots (QDs) realized by electrospraying. This method allows for simple but efficient embedding of QDs in polymer beads while retaining the fluorescent properties of the original QDs. The creation of poly(styrene‐ethylene‐butylene‐styrene) (SEBS) monodisperse spherical microparticles with a tunable morphology for applications of the final QD‐loaded product is attainable via solvent variation. By varying the selectivity of the solvent for one of the distinct blocks in the polymer, the final particle morphology can be selectively altered while maintaining the same overall process conditions, allowing to tailor the particles from homogeneously flat in a nonselective solvent to dense spherical particles in an endblock selective solvent system. The mechanism responsible for this transition in morphology can be related to differences in mass transfer in the droplets and thus solvent evaporation rates arising from particular microphase structures. Finally, fluorescence characteristics of the final QD‐embedded polymer particles and photodegradation stability are investigated by spectrophotometry and are compared to the temporal evolution of the original QDs, indicating significant stability improvement and well‐dispersed QDs in an optimized polymer matrix morphology.
The Reproductive Biology of Female Atlantic Herring in U.S. Waters: Validating Classification Schemes for Assessing the Importance of Spring and Skipped Spawning
Authors: Wuenschel Mark J. , Deroba Jonathan J. 
Published: December 2019

Abstract
Atlantic Herring Clupea harengus are iteroparous (repeat spawners) with group-synchronous oocyte development and determinate fecundity, and they are total spawners. However, they also exhibit plasticity in other aspects of their reproductive biology including spawning seasonality and skipped spawning. Previous studies in other regions have reported skipped spawning and errors in macroscopic classifications of maturity, both of which could bias estimates of reproductive potential, but a critical assessment of these in U.S. waters is lacking. In the Gulf of Maine and Georges Bank, herring are assessed as a single stock complex, where females typically mature as 3 to 4 year olds and may live up to 11 years. To evaluate the magnitude of skipped spawning, we collected the ovaries of Atlantic Herring from fishery-dependent and fishery-independent sources over multiple seasons and evaluated them histologically to assess imminent (indicated by vitellogenic or maturing oocytes) or recent spawning (evidenced by the presence of postovulatory follicles). Gonad histology allowed us to determine spawning seasonality and skipped spawning. Macroscopic maturity classification was more accurate in fall (1–4% incorrect maturity) than in spring (7% incorrect maturity). The spatial distributions of immature and mature fish from both fishery-dependent and fishery-independent sources differed, which affected the estimation of maturity at length and age. We estimated 9–14% spring spawners in the region, but we did not find evidence of skipped spawning. The time series of the macroscopic data that were available (1987–2018) showed increases in spring spawning with latitude, but the proportions have not changed much over recent decades. The effects of up to 30% spring or skipped spawning on a stock assessment of Atlantic Herring were evaluated. Spring spawning had little effect relative to assuming 100% fall spawning (the current assumption), and skipped spawning decreased the scale of spawning stock biomass (SSB) and related reference points, with the degree of change increasing with skipped spawning rates, but it had few consequences otherwise.