Miracle-dz/UniFAR-FTUs huggingface dataset:
Health economic evaluation of gene replacement therapies: methodological issues and recommendations

ABSTRACT Objective: To provide recommendations for addressing previously identified key challenges in health economic evaluations of Gene Replacement Therapies (GRTs), including: 1) the assessment of clinical effectiveness; 2) the valuation of health outcomes; 3) the time horizon and extrapolation of effects beyond trial duration; 4) the estimation of costs; 5) the selection of appropriate discount rates; 6) the incorporation of broader elements of value; and 7) affordability. Methods: A literature review on economic evaluations of GRT was performed. Interviews were conducted with 8 European and US health economic experts with experience in evaluations of GRT. Targeted literature reviews were conducted to investigate further potential solutions to specific challenges. Recommendations: Experts agreed on factors to be considered to ensure the acceptability of historical cohorts by HTA bodies. Existing prospective registries or, if not available, retrospective registries, may be used to analyse different disease trajectories and inform extrapolations. The importance of expert opinion due to limited data was acknowledged. Expert opinion should be obtained using structured elicitation techniques. Broader elements of value, beyond health gains directly related to treatment, can be considered through the application of a factor to inflate the quality-adjusted life years (QALYs) or a higher cost-effectiveness threshold. Additionally, the use of cost-benefit analysis and saved young life equivalents (SAVE) were proposed as alternatives to QALYs for the valuations of outcomes of GRT as they can incorporate broader elements of value and avoid problems of eliciting utilities for paediatric diseases. Conclusions: While some of the limitations of economic evaluations of GRT are inherent to limited clinical data and lack of experience with these treatments, others may be addressed by methodological research to be conducted by health economists.
Drill Hole Orientation: Its Role and Importance on the Compression Response of Pure Magnesium

Drilling is used in creating cylindrical through-holes for various applications. While optimizing drilling parameters is widespread, the effect of a drilled through-hole on the structural stability of components is not fully documented. The base material, along with other parameters, such as drill diameter, drill location and its orientation affect structural stability. Since carrying out tests on different base materials can be time consuming, simulation software can instead be used to provide valuable information. However, the comparison between experiments and simulations gets difficult; hence, this study attempts to provide a basis for effective comparison by studying simulations and compression tests, comparing the two, and documenting the role of drill hole orientation on the compressive response of magnesium, a material with immense potential in light-weight components. Simulations and experiments were carried out on three through-hole orientations and were compared to the undrilled scenario. Results demonstrate significant differences in compression behaviour. While the compressive yield strength increased in all three drill orientations, ultimate strength and ductility was reduced in horizontal and angular drill hole orientations. These observations, therefore, provide valuable insight into choosing the right orientation for different applications.
The shape of success in a turbulent world: wave exposure filtering of coral reef herbivory

While environmental filters are well-known factors influencing community assembly, the extent to which these modify species functions, and entire ecosystem processes, is poorly understood. Focusing on a high-diversity system, we ask whether environmental filtering has ecosystem-wide effects beyond community assembly. We characterise a coral reef herbivorous fish community for swimming performance based on ten functional traits derived from fish morphology. We then investigate whether wave exposure modifies the functional make-up of herbivory, and the absolute and relative feeding frequency of distinct feeding functional groups. Herbivorous fish species conformed to either laterally compressed or fusiform body plans, which differ in their morphological design to minimise drag. High wave exposure selectively limited the feeding function of the deepest body shapes with highest caudal thrust efficiency, and favoured fusiform bodies irrespective of pectoral fin shape. Traditionally recognised herbivore feeding functional groups (i.e. grazers–detritivores and scrapers–small excavators) differed in swimming performance, and in their capacity to feed consistently across levels of wave exposure. We therefore emphasise the distinctness of their ecological niche and functional complementarity. Species within the same feeding functional group also had contrasting responses to wave exposure. We thereby reveal a further ecological dimension of niche partitioning, and reiterate the risk of assuming functional redundancy among species with a common feeding mode. Contrasting responses of species within feeding functional roles (i.e. response diversity) allowed the preservation of critical trophic functions throughout the gradient (e.g. macroalgal browsing), and likely explained why overall levels of herbivory were robust to filtering. Whether ecosystem functioning will remain robust under the additive effects of environmental stress and human-induced disturbances remains to be tested. A lay summary is available for this article.
Freeze–thaw processes degrade post‐fire water repellency in wet soils

Wildfires are a cause of soil water repellency (hydrophobicity), which reduces infiltration whilst increasing erosion and flooding from post‐fire rainfall. Post‐fire soil water repellency degrades over time, often in response to repeated wetting and drying of the soil. However, in mountainous fire‐prone forests such as those in the Western USA, the fire season often terminates in a cold and wet winter, during which soils not only wet and dry, but also freeze and thaw. Little is known about the effect of repeated freezing and thawing of soil on the breakdown of post‐fire hydrophobicity. This study characterized the changes in hydrophobicity of Sierra Nevada mountain soils exposed to different combinations of wet–dry and freeze–thaw cycling. Following each cycle, hydrophobicity was measured using the Molarity of Ethanol test. Hydrophobicity declined similarly across all experiments that included a wetting cycle. Repeated freezing and thawing of dry soil did not degrade soil water repellency, but freeze–thaw cycles decreased hydrophobicity in wet soils. Total soil organic matter content was not different between soils of contrasting hydrophobicity. Macroscopic changes such as fissures and cracks were observed to form as soil hydrophobicity decayed. Microscopic changes revealed by scanning electron microscope imagery suggest different levels of soil aggregation occurred in samples with distinct hydrophobicities, although the size of aggregates was not clearly correlated to the change in water repellency due to wet–dry and freeze–thaw cycling. A 9‐year climate and soil moisture record from Providence Critical Zone Observatory was combined with the laboratory results to estimate that hydrophobicity would persist an average of 144 days post‐fire at this well‐characterized, typical mid‐elevation Sierra Nevada site. Most of the breakdown in soil water repellency (79%) under these climate conditions would be attributable to freeze–thaw cycling, underscoring the importance of this process in soil recovery from fire in the Sierra Nevada.
Internal phosphorus loading contributions from deposited and resuspended sediment to the Lake of the Woods

ABSTRACT James WF. 2017. Internal phosphorus loading contributions from deposited and resuspended sediment to the Lake of the Woods. Lake Reserv Manage. 33:347–359. The Lake of the Woods exhibits cyanobacterial blooms despite substantial declines in watershed phosphorus (P) loading since the 1970s, suggesting that internal P loads are contributing to the P budget. A better understanding of internal P loading contributions and dynamics is needed to refine management strategies and water quality goals. Sediment cores were collected from several stations within the US portion to examine potential internal P contributions from deposited and resuspended sediment. Although laboratory-derived diffusive P fluxes were highest under anaerobic conditions (8−12 mg/m2 d), aerobic conditions at the sediment–water interface may regulate in situ diffusive P fluxes due to frequent polymixis. Although much lower under aerobic conditions, modest fluxes of 0.2−0.6 mg/m2 d could play an important role in the P budget. Simulated resuspension indicated that the critical shear stress of deposited sediment was relatively low at 1.3−2.3 dynes/cm2. The wind-exposed long fetches and shallow morphometry of regions of Lake of the Woods could result in frequent resuspension of P-enriched clays and silts that contribute inorganic P to the water column. Resuspended sediments exhibited a low equilibrium P concentration (near zero) and high linear adsorption coefficient (700−3200 L/kg), suggesting they may act more as a sink rather than a source for soluble P. Resuspension could compete with cyanobacterial uptake by sequestering soluble reactive P. Resuspended inorganic P could also constitute a significant portion of the water column total P composition in addition to organic P, incorporated as cyanobacterial biomass, and needs to be considered in the P budget and chlorophyll prediction.
Two Novel Current-Mode CNFET-Based Full Adders Using ULPD as Voltage Regulator

This paper presents two novel current-mode Full Adders based on Carbon Nanotube FET (CNFET). They comprise of three main parts: current-to-voltage converter, threshold detector and voltage-to-current converter. While other designs in the literature use either inverter or current source for detecting threshold, the new designs are based on a heuristic usage of an Ultra Low-Power Diode (ULPD) as voltage regulator. The use of diode does not lengthen the critical path and thereby ensuring high-speed operation. It does not increase power consumption significantly either. Simulation results by HSPICE and 32[Formula: see text]nm CNFET technology file demonstrate at least 19% higher performance in terms of energy consumption for the second proposed Full Adder compared to other traditional and state-of-the-art current-mode and mixed-mode designs.
Differences in the Quantity and Quality of Organic Matter Exported From Greenlandic Glacial and Deglaciated Watersheds

Riverine input of terrestrial dissolved organic matter (DOM) is an important component of the marine carbon cycle and drives net carbon dioxide production in coastal zones. DOM exports to the Arctic Ocean are likely to increase due to melting of permafrost and the Greenland Ice Sheet, but the quantity and quality of DOM exports from deglaciated watersheds in Greenland, as well as expected changes with future melting, are unknown. We compare DOM quantity and quality in Greenland over the melt seasons of 2017–2018 between two rivers directly draining the Greenland Ice Sheet (meltwater rivers) and four streams draining deglaciated catchments that are disconnected from the ice (nonglacial streams). We couple these data with discharge records to compare dissolved organic carbon (DOC) exports. DOM sources and quality differ significantly between watershed types: fluorescence characteristics and organic molar C:N ratios suggest that DOM from deglaciated watersheds is derived from terrestrial vegetation and soil organic matter, while that in glacial watersheds contains greater proportions of algal and/or freshly produced biomass and may be more reactive. DOC specific yield is similar for nonglacial streams (0.1–1.2 Mg/km2/year) compared to a glacial meltwater river (0.2–1.1 Mg/km2/year), despite orders of magnitude differences in instantaneous discharge. Upscaling based on land cover leads to an estimate of total DOC contributions from Greenland between 0.2 and 0.5 Tg/year, much of which is derived from deglaciated watersheds. These results suggest that future warming and ice retreat may increase DOC fluxes from Greenland with consequences for the Arctic carbon cycle.
Neural differentiation of pluripotent stem cells and applications to micropatterned agarose hydrogel for nerve guidance

NEURAL DIFFERENTIATION OF PLURIPOTENT STEM CELLS AND APPLICATIONS TO MICROPATTERNED AGAROSE HYDROGEL FOR NERVE GUIDANCE by Jamila S. Gittens Many central nervous system (CNS) disorders are attributable to damaged oligodendrocytes, the cells that form the myelin sheath of axons. An effective source of human oligodendrocytes is crucial, making pluripotent stem cells, such as embryonic stem (ES) cells, an attractive source for nerve tissue repair and regeneration due to their unlimited capacity for self-renewal and their ability to differentiate into all major cell lineages. Bioengineered 3-D hydrogel culture systems have the potential to elucidate mechanisms required for regeneration of CNS cells. The goals of this study are: (1) to investigate the effects of retinoic acid (RA), sonic hedgehog (shh) agonist, and glucose levels on neural differentiation of mouse embryonic stem cells (mESCs), and (2) to employ micropatterned agarose hydrogels for nerve guidance. A protocol utilizing embryoid body (EB) formation, under both high and low glucose conditions, was devised for RA-induced neural lineage differentiation and RA/shh-induced oligodendrocyte differentiation. EBs exposed to lower glucose concentrations with agonists exemplified a more rapid differentiation. After 8 days in culture, there was a higher expression level of oligodendrocyte precursor cell markers in low glucose conditions. These results illustrate that physiologic glucose concentrations are more conducive to the development of EBs and favor the differentiation of mESCs into neural lineages. In order to fabricate 3-D microchannel hydrogel structures for nerve guidance, agarose solution was poured onto the plastic mold master with gridded microchannels and peeled off after hydrogel formation. An extracellular matrix (ECM) coating, such as collagen, was used to promote cell adhesion and neurite outgrowth limited to the channels. Exploitation of various cell types, including fibroblasts and PC12 cells, to optimize the hydrogel conditions, exhibited good cell and ECM patterns on the microchannels. Further studies using dorsal root ganglion (DRG) neurons, Schwann cells, and differentiating ES cells demonstrated good cell growth and nerve guidance through the micropatterned channels. Micropatterned hydrogels can be used as an in vitro model to replicate complex tissue organization, and to investigate nerve signal propagation and myelination. NEURAL DIFFERENTIATION OF PLURIPOTENT STEM CELLS AND APPLICATIONS TO MICROPATTERNED AGAROSE HYDROGEL FOR NERVE GUIDANCE by Jamila S. Gittens A Thesis Submitted to the Faculty of New Jersey Institute of Technology in Partial Fulfillment of the Requirements for the Degree of Master of Science in Biomedical Engineering Department of Biomedical Engineering
Community Health Worker Training Curricula and Intervention Outcomes in African American and Latinx Communities: A Systematic Review

In recent years, community health workers (CHWs) have emerged as key stakeholders in implementing community-based public health interventions in racially diverse contexts. Yet little is known about the extent to which CHW training curriculums influence intervention effectiveness in marginalized racial and ethnic minority communities. This review summarizes evidence on the relationship between CHW training curricula and intervention outcomes conducted among African American and Latinx populations. We conducted a literature search of intervention studies that focused on CHW public health interventions in African American and Latinx populations using PubMed, PsycINFO, ERIC, CINAHL, EMBASE, and Web of Science databases. Included studies were quantitative, qualitative, and mixed methods studies employed to conduct outcome (e.g., blood pressure and HbA1c) and process evaluations (e.g., knowledge and self-efficacy) of CHW-led interventions. Out of 3,295 articles from the database search, 36 articles met our inclusion criteria. Overall, the strength of evidence linking specific CHW training curricula components to primary intervention health outcomes was weak, and no studies directly linked outcomes to specific characteristics of CHW training. Studies that described training related to didactic sessions or classified as high intensity reported higher percentages of positive outcomes compared to other CHW training features. These findings suggest that CHW training may positively influence intervention effectiveness but additional research using more robust methodological approaches is needed to clarify these relationships.
Genome-Wide Identification and Coexpression Network Analysis of DNA Methylation Pathway Genes and Their Differentiated Functions in Ginkgo biloba L.

DNA methylation plays a vital role in diverse biological processes. DNA methyltransferases (DNMTs) genes and RNA-directed DNA methylation (RdDM)-related genes are key genes responsible for establishing and maintaining genome DNA methylation in plants. In the present study, we systematically identified nine GbDNMTs in Ginkgo biloba, including the three common families of GbMET1a/1b, GbCMT2, and GbDRMa/b/2a/2b/2c, and a fourth family—GbDNMT3—which is absent in most angiosperms. We also identified twenty RdDM-related genes, including four GbDCLs, six GbAGOs, and ten GbRDRs. Expression analysis of the genes showed the different patterns of individual genes, and 15 of 29 genes displayed expression change under five types of abiotic stress. Gene coexpression analysis and weighted gene co-expression network analysis (WGCNA) using 126 public transcriptomic datasets revealed that these genes were clustered into two groups. In group I, genes covered members from all six families which were preferentially expressed in the ovulate strobile and fruit. A gene ontology (GO) enrichment analysis of WGCNA modules indicated that group I genes were most correlated with the biological process of cell proliferation. Group II only consisted of RdDM-related genes, including GbDRMs, GbAGOs, and GbRDRs, but no GbDCLs, and these genes were specifically expressed in the cambium, suggesting that they may function in a dicer-like (DCL)-independent RdDM pathway in specific tissues. The gene module related to group II was most enriched in signal transduction, cell communication, and the response to the stimulus. These results demonstrate that gene family members could be conserved or diverged across species, and multi-member families in the same pathway may cluster into different modules to function differentially. The study provides insight into the DNA methylation genes and their possible functions in G. biloba, laying a foundation for the further study of DNA methylation in gymnosperms.
Plant-Based Natural Fibre Reinforced Composites: A Review on Fabrication, Properties and Applications

The increasing global environmental concerns and awareness of renewable green resources is continuously expanding the demand for eco-friendly, sustainable and biodegradable natural fibre reinforced composites (NFRCs). Natural fibres already occupy an important place in the composite industry due to their excellent physicochemical and mechanical properties. Natural fibres are biodegradable, biocompatible, eco-friendly and created from renewable resources. Therefore, they are extensively used in place of expensive and non-renewable synthetic fibres, such as glass fibre, carbon fibre and aramid fibre, in many applications. Additionally, the NFRCs are used in automobile, aerospace, personal protective clothing, sports and medical industries as alternatives to the petroleum-based materials. To that end, in the last few decades numerous studies have been carried out on the natural fibre reinforced composites to address the problems associated with the reinforcement fibres, polymer matrix materials and composite fabrication techniques in particular. There are still some drawbacks to the natural fibre reinforced composites (NFRCs)—for example, poor interfacial adhesion between the fibre and the polymer matrix, and poor mechanical properties of the NFRCs due to the hydrophilic nature of the natural fibres. An up-to-date holistic review facilitates a clear understanding of the behaviour of the composites along with the constituent materials. This article intends to review the research carried out on the natural fibre reinforced composites over the last few decades. Furthermore, up-to-date encyclopaedic information about the properties of the NFRCs, major challenges and potential measures to overcome those challenges along with their prospective applications have been exclusively illustrated in this review work. Natural fibres are created from plant, animal and mineral-based sources. The plant-based cellulosic natural fibres are more economical than those of the animal-based fibres. Besides, these pose no health issues, unlike mineral-based fibres. Hence, in this review, the NFRCs fabricated with the plant-based cellulosic fibres are the main focus.
Status of the Tibetan Plateau observatory (Tibet-Obs) and a 10-year (2009–2019) surface soil moisture dataset

Abstract. The Tibetan Plateau observatory of plateau scale soil moisture and soil temperature (Tibet-Obs) was established ten years ago, which has been widely used to calibrate/validate satellite- and model-based soil moisture (SM) products for their applications to the Tibetan Plateau (TP). This paper reports on the status of the Tibet-Obs and presents a 10-year (2009–2019) surface SM dataset produced based on in situ measurements taken at a depth of 5 cm collected from the Tibet-Obs that consists of three regional-scale SM monitoring networks, i.e. the Maqu, Naqu, and Ngari (including Ali and Shiquanhe) networks. This surface SM dataset includes the original 15-min in situ measurements collected by multiple SM monitoring sites of the three networks, and the spatially upscaled SM records produced for the Maqu and Shiquanhe networks. Comparisons between four spatial upscaling methods, i.e. arithmetic averaging, Voronoi diagram, time stability and apparent thermal inertia, show that the arithmetic average of the monitoring sites with long-term (i.e. ≥ six years) continuous measurements are found to be most suitable to produce the upscaled SM records. Trend analysis of the 10-year upscaled SM records using the Mann-Kendall method shows that the Maqu network area in the eastern part of the TP is drying while the Shiquanhe network area in the west is getting wet that generally follow the change of precipitation. To further demonstrate the uniqueness of the upscaled SM records in validating existing SM products for long term period (~ 10 years), comparisons are conducted to evaluate the reliability of three reanalysis datasets for the Maqu and Shiquanhe network areas. It is found that current model-based SM products still show deficiencies in representing the trend and variation of measured SM dynamics in the Tibetan grassland (i.e. Maqu) and desert ecosystems (i.e. Shiquanhe) that dominate the landscape of the TP. The dataset would be also valuable for calibrating/validating long-term satellite-based SM products, evaluation of SM upscaling methods, development of data fusion methods, and quantifying the coupling strength between precipitation and SM at 10-year scale. The dataset is available in the 4TU.ResearchData repository at https://doi.org/10.4121/uuid:21220b23-ff36-4ca9-a08f-ccd53782e834 (Zhang et al., 2020).