bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mass cytometry and type 1 diabetes research in the age of single-cell data science
Authors: Rahman Adeeb H. , Homann Dirk 
Published: June 2020

Purpose of review
New single-cell tec. hnologies developed over the past decade have considerably reshaped the biomedical research landscape, and more recently have found their way into studies probing the pathogenesis of type 1 diabetes (T1D). In this context, the emergence of mass cytometry in 2009 revolutionized immunological research in two fundamental ways that also affect the T1D world: first, its ready embrace by the community and rapid dissemination across academic and private science centers alike established a new standard of analytical complexity for the high-dimensional proteomic stratification of single-cell populations; and second, the somewhat unexpected arrival of mass cytometry awoke the flow cytometry field from its seeming sleeping beauty stupor and precipitated substantial technological advances that by now approach a degree of analytical dimensionality comparable to mass cytometry.

Recent findings
Here, we summarize in detail how mass cytometry has thus far been harnessed for the pursuit of discovery studies in T1D science; we provide a succinct overview of other single-cell analysis platforms that already have been or soon will be integrated into various T1D investigations; and we briefly consider how effective adoption of these technologies requires an adjusted model for expense allocation, prioritization of experimental questions, division of labor, and recognition of scientific contributions.

Summary
The introduction of contemporary single-cell technologies in general, and of mass cytometry, in particular, provides important new opportunities for current and future T1D research; the necessary reconfiguration of research strategies to accommodate implementation of these technologies, however, may both broaden research endeavors by fostering genuine team science, and constrain their actual practice because of the need for considerable investments into infrastructure and technical expertise.
Plant-based diets and bone health: sorting through the evidence
Authors: Hsu Emory 
Published: June 2020

Purpose of reviewAn increase in awareness of vegetarian and vegan (plant-based) diets has brought forth numerous studies on their effects on health. The study of nutrition-based factors affecting bone health is difficult, given the length of time before clinical effects are evident. Furthermore, population-based studies must account for strong confounding influences as effects may be because of association, not causality. Yet, it is highly plausible that dietary factors affect bone remodeling in multiple ways. Plant-based diets may alter macronutrient and micronutrient balance, may cause differences in prebiotic and probiotic effects on gut microbiota, and may subtly change the inflammatory and immune response.Recent findingsSeveral recent studies have looked at plant-based nutrition and markers of bone health, using measures such as bone turnover markers, bone mineral density, or fracture rates. Although population based and cross-sectional studies can be prone to confounding effects, a majority did not show differences in bone health between vegetarians/vegans and omnivores as long as calcium and vitamin D intake were adequate. A few prospective cohort or longitudinal studies even demonstrate some benefit to a plant-based diet, but this claim remains unproven.SummaryThere is no evidence that a plant-based diet, when carefully chosen to maintain adequate calcium and vitamin D levels, has any detrimental effects on bone health. Theoretical findings suggest a long-term plant-based diet may reduce the risk of osteoporosis, through mechanisms that are currently speculative.
Advances in facial nerve management in the head and neck cancer patient
Authors: Crawford Kayva L. , Stramiello Joshua A. , Orosco Ryan K. , Greene Jacqueline J. 
Published: June 2020

Purpose of review
The purpose of this review is to summarize best practices in facial nerve management for patients with head and neck cancer. In addition, we provide a review of recent literature on novel innovations and techniques in facial reanimation surgery.

Recent findings
Although recommended when tumor ablation surgery requires facial nerve sacrifice, facial reanimation procedures are not always performed. Concurrent dynamic facial reanimation with masseteric nerve transfers and cable graft repair can preserve native facial muscle function. Static suspension can provide facial support and immediate resting symmetry for patients. Eyelid weight and eye care should not be delayed, particularly in patients with trigeminal sensory deficits. Choice of neural source to innervate a gracilis-free muscle transfer for smile reanimation remains controversial; however, new techniques, such as dual innervation and multivector muscle transfer, may improve aesthetic and functional outcomes.

Summary
Management of the facial nerve in the setting of head and neck cancer presents unique challenges. When possible, simultaneous oncologic resection and facial reanimation is ideal given the open surgical field, newly dissected and electrically stimulatable facial nerve branches, as well as minimizing postoperative healing time to prevent postsurgical treatment delays. A coordinated approach to facial nerve management with a multidisciplinary surgical team may help provide optimal, comprehensive care.
Radiation Dose to the Fetus From Computed Tomography of Pregnant Patients—Development and Validation of a Web-Based Tool
Authors: Saltybaeva Natalia , Platon Alexandra , Poletti Pierre-Alexandre , Hinzpeter Ricarda , Merce Marta Sans , Alkadhi Hatem 
Published: June 2020

Objective
Estimations of radiation dose absorbed by the fetus from computed tomography (CT) in pregnant patients is mandatory, but currently available methods are not feasible in clinical routine. The aims of this study were to develop and validate a tool for assessment of fetal dose from CT of pregnant patients and to develop a user-friendly web interface for fast fetal dose calculations.

Methods
In the first study part, 750 Monte Carlo (MC) simulations were performed on phantoms representing pregnant patients at various gestational stages. The MC code simulating vendor-independent dose distributions was validated against CT dose index (CTDI) measurements performed on CT scanners of 2 vendors. The volume CTDI–normalized fetal dose values from MC simulations were used for developing the computational algorithm enabling fetal dose assessments from CT of various body regions at different exposure settings. In the institutional review board–approved second part, the algorithm was validated against patient-specific MC simulations performed on CT data of 29 pregnant patients (gestational ages 8–35 weeks) who underwent CT. Furthermore, the tool was compared with a commercially available software. A user-friendly web-based interface for fetal dose calculations was created.

Results
Weighted CTDI values obtained from MC simulations were in excellent agreement with measurements performed on the 2 CT systems (average error, 4%). The median fetal dose from abdominal CT in pregnant patients was 2.7 mGy, showing moderate correlation with maternal perimeter (r = 0.69). The algorithm provided accurate estimates of fetal doses (average error, 11%), being more accurate than the commercially available tool. The web-based interface (www.fetaldose.org) enabling vendor-independent calculations of fetal doses from CT requires the input of gestational age, volume CTDI, tube voltage, and scan region.

Conclusions
A tool for fetal dose assessments from CT of pregnant patients was developed and validated being freely available on a user-friendly web interface.
Surgical Decision-Making in Microvascular Reconstruction of Composite Scalp and Skull Defects
Authors: Vargo James D. , Przylecki Wojciech , Andrews Brian T. 
Published: June 2020

Objectives:
Microvascular reconstruction of composite scalp and skull defects requires careful planning of both cranial bone and soft-tissue coverage. The current body of literature has yet to identify a “best practice” approach to achieve these goals.

Methods:
A retrospective chart review was performed. Patients with composite defects who underwent combined microvascular surgery of the scalp and skull were included over a 6-year period. Reconstructions were classified by: microvascular flap, cranioplasty, timing of cranioplasty (primary or delayed), and exposure to radiation.

Results:
Forty-five microvascular flaps were performed for 36 patients. Fasciocutaneous flaps were more likely to experience complications than other microvascular flaps (50.0% versus 8.6%, P = 0.008). Forty of the 50 patients (80%) underwent cranioplasty, including 19 autogenous and 21 alloplastic reconstructions. There were 8 total complications: partial flap loss with implant exposure (n = 5), cranioplasty infection (n = 2), and wound dehiscence (n = 1). Alloplastic implants experienced more frequent complications than autologous reconstructions (33.3% versus 5.3%, P = 0.046). Titanium implants demonstrated the higher rates of complications than other groups (P = 0.014). Titanium implants also had more complications relative to poly-ether-ether-ketone implants (60.0% versus 9.1%, P = 0.024). Immediate alloplastic cranioplasty was associated with a significant increase in complications relative to autogenous reconstruction (54.5% versus 5.5%, P = 0.027), and no significant difference in the delayed group (10% versus 0%, P = 0.740).

Conclusion:
According to authors’ knowledge, myofascial flaps yield the lowest complication rate and when possible, autologous cranioplasty is preferred. When defects are too large to accommodate autogenous bone, the authors prefer delayed prefabricated poly-ether-ether-ketone implant reconstruction.
Analysis of Frontal Sinus Fracture Management and Resource Utilization
Authors: Firouzbakht Peter K. , Mohiuddin Ismail S. , Varman Rahul M. , Heinrich Matthew P. , Saa Lisa , Cordero Joehassin 
Published: June 2020

Abstract
Frontal sinus fractures require a large amount of force and often occur in the context of a major trauma. Many patients with these fractures are assessed in an emergent setting where stabilization takes precedence. Delayed diagnosis and treatment of a sinus fracture can result in life-threatening conditions, such as a cerebrospinal fluid (CSF) leak. A number of different treatment algorithms have been proposed, highlighting the complexity of frontal sinus fracture management. The goal of this study is to determine how patients with frontal sinus fractures were treated at Texas Tech University Health Sciences Center and what complications arose as a result of the fracture and subsequent management strategy. Over 9 years, there were 69 reported cases. A total of 63 of these occurred in males (91.3%) versus 6 (8.7%) in females. The majority occurred after a motor vehicle collision (MVC) or a motorcycle collision (MCC). A total of 51 cases were unilateral fractures and 18 were bilateral fractures. Five patients (7.2%) had CSF leakage and 64 (92.8%) did not have CSF leakage. One patient with CSF leakage (20.0%) was managed operatively. Of the 64 patients without CSF leakage, 4 (6.3%) were managed operatively. All operative patients were managed by cranialization. Complications included vision changes, facial pressure, anosmia, facial paresthesia, pneumocephalus, and mucus retention cysts. Vision changes were the most common complication. There did not appear to be any significant difference in complications between the CSF leakage groups, indicating that non-operative management remains a viable option in the management of frontal sinus fractures.
Nicotinamide Riboside supplementation does not alter whole-body or skeletal muscle metabolic responses to a single bout of endurance exercise
Authors: Stocks Ben , Ashcroft Stephen P. , Joanisse Sophie , Elhassan Yasir S. , Lavery Gareth G. , Dansereau Linda C. , Philp Ashleigh M. , Wallis Gareth A. , Philp Andrew 
Published: June 2020

AbstractOral supplementation of the NAD+precursor Nicotinamide Riboside (NR) has been reported to increase Sirtuin (SIRT) signalling, mitochondrial biogenesis and endurance capacity in rodent skeletal muscle. However, whether NR supplementation can elicit a similar response in human skeletal muscle is unclear. This study aimed to assess the effect of 7-day NR supplementation on exercise-induced transduction and transcriptional responses in skeletal muscle of young, healthy, recreationally active human volunteers. In a double-blinded, randomised, counter-balanced, crossover design, eight male participants (age: 23 ± 4 years, VO2peak: 46.5 ± 4.4 mL·kg-1·min-1) received one week of NR or cellulose placebo (PLA) supplementation (1000 mg·d-1) before performing one hour of cycling at 60% Wmax. Muscle biopsies were collected prior to supplementation and pre-, immediately and three-hours post-exercise from the medial vastus lateralis, whilst venous blood samples were collected throughout the trial. Global acetylation, auto-PARylation of PARP1, acetylation of p53Lys382and MnSODLys122were unaffected by NR supplementation or exercise. Exercise led to an increase in AMPKThr172(1.6-fold), and ACCSer79(4-fold) phosphorylation, in addition to an increase in PGC-1α (∼5-fold) and PDK4 (∼10-fold) mRNA expression, however NR had no additional effect on this response. There was also no effect of NR supplementation on substrate utilisation at rest or during exercise or on skeletal muscle mitochondrial respiration. Finally, NR supplementation blunted the exercise induced activation of skeletal muscle NNMT mRNA expression, but had no effect on mRNA expression of NMRK1, NAMPT or NMNAT1, which were not significantly affected by NR supplementation or exercise. In summary, one week of NR supplementation does not augment skeletal muscle signal transduction pathways implicated in mitochondrial adaptation to endurance exercise.
Efficient Cas9 multiplex editing using unspaced gRNA arrays engineering in aPotato virus Xvector
Authors: Uranga Mireia , Aragonés Verónica , Selma Sara , Vázquez-Vilar Marta , Orzáez Diego , Daròs José-Antonio 
Published: June 2020

SummarySystems based on the clustered, regularly interspaced, short palindromic repeat (CRISPR) and CRISPR associated proteins (Cas) have revolutionized genome editing in many organisms, including plants. Most CRISPR-Cas strategies in plants rely on genetic transformation usingAgrobacterium tumefaciensto supply the gene editing reagents, such as the Cas nucleases or the guide RNA (gRNA). While the Cas nucleases are constant elements in editing approaches, gRNAs are target-specific and a screening process is usually required to identify those most effective. Plant virus-derived vectors are an alternative for the fast and efficient delivery of gRNAs into adult plants, due to the virus capacity for genome amplification and systemic movement, a strategy known as virus-induced genome editing (VIGE). In this work, we engineeredPotato virus X(PVX) to build a vector able to easily express one or more gRNAs in adult solanaceous plants. Using the PVX-based vector,Nicotiana benthamianagenes were efficiently targeted, producing nearly 80% indels in a transformed line that constitutively expressedStreptococcus pyogenesCas9. Interestingly, results showed that the PVX vector allows expression of arrays of unspaced gRNAs achieving highly efficient multiplex editing in a few days in adult plant tissues. We also demonstrate that genome modifications are inherited in plants regenerated from infected tissues. In sum, the new PVX VIGE vector allows easy, fast and efficient expression of gRNAs arrays for multiplex CRISPR-Cas genome editing and will be a useful tool for functional gene analysis and precision breeding across diverse plant species, particularly in important crops of the familySolanaceae.
Phasic activation of dorsal raphe serotonergic neurons increases pupil-linked arousal
Authors: Cazettes Fanny , Reato Davide , Morais João P. , Renart Alfonso , Mainen Zachary F. 
Published: June 2020

SUMMARYVariations in pupil size under constant luminance are closely coupled to changes in arousal state [1–5]. It is assumed that such fluctuations are primarily controlled by the noradrenergic system [6–9]. Phasic activity of noradrenergic axons precedes pupil dilations associated with rapid changes in arousal [7,9], and is believed to be driven by unexpected uncertainty [1,10–16]. However, the role of other modulatory pathways in the control of pupil-linked arousal has not been as thoroughly investigated, but evidence suggests that noradrenaline may not be alone [7,17,18]. Administration of serotonergic drugs seems to affect pupil size [19–23], but these effects have not been investigated in detail. Here, we show that transient serotonin (5-HT) activation, like noradrenaline, causes pupil-size changes. We used phasic optogenetic activation of 5-HT neurons in the dorsal raphe nucleus (DRN) in head-fixed mice locomoting in a foraging task. 5-HT-driven modulations of pupil size were maintained throughout the photostimulation period and sustained for several seconds after the end of the stimulation. The activation of 5-HT neurons increased pupil size additively with locomotor speed, suggesting that 5-HT transients affect pupil-linked arousal independently from locomotor states. We found that the effect of 5-HT on pupil size depended on the level of environmental uncertainty, consistent with the idea that 5-HT may report a salience or surprise signal [24]. Together, these results challenge the classic view of the neuromodulatory control of pupil-linked arousal, revealing a tight relationship between the activation of 5-HT neurons and changes in pupil size.
Healthy aging interventions reduce non-coding repetitive element transcripts
Authors: Wahl Devin , Cavalier Alyssa N. , Smith Meghan , Seals Douglas R. , LaRocca Thomas J. 
Published: June 2020

ABSTRACTTranscripts from non-coding repetitive elements (RE) in the genome may be involved in aging. However, they are often ignored in transcriptome studies on healthspan and lifespan, and their role in healthy aging interventions has not been characterized. Here, we analyze RE in RNA-seq datasets from mice subjected to robust healthspan- and lifespan-increasing interventions including calorie restriction, rapamycin, acarbose, 17-α-estradiol, and Protandim. We also examine RE transcripts in long-lived transgenic mice, and in mice subjected to high-fat diet, and we use RNA-seq to investigate the influence of aerobic exercise on RE transcripts with aging in humans. We find that: 1) healthy aging interventions/behaviors globally reduce RE transcripts, whereas aging and age-accelerating treatments increase RE expression; and 2) reduced RE expression with healthy aging interventions is associated with biological/physiological processes mechanistically linked with aging. Thus, RE transcript dysregulation and suppression are likely novel mechanisms underlying aging and healthy aging interventions, respectively.
Effects of H2A.B incorporation on nucleosome structures and dynamics
Authors: Kohestani Havva , Wereszczynski Jeff 
Published: June 2020

ABSTRACTThe H2A.B histone variant is an epigenetic regulator involved in transcriptional upregulation, DNA synthesis, and splicing that functions by replacing the canonical H2A histone in the nucleosome core particle. Introduction of H2A.B results in less compact nucleosome states with increased DNA unwinding and accessibility at the nucleosomal entry and exit sites. Despite being well characterized experimentally, the molecular mechanisms by which H2A.B incorporation alters nucleosome stability and dynamics remain poorly understood. To study the molecular mechanisms of H2A.B, we have performed a series of conventional and enhanced sampling molecular dynamics simulation of H2A.B and canonical H2A containing nucleosomes. Results of conventional simulations show that H2A.B weakens protein/protein and protein/DNA interactions at specific locations throughout the nucleosome. These weakened interactions result in significantly more DNA opening from both the entry and exit sites in enhanced sampling simulations. Furthermore, free energy profiles show that H2A.B containing nucleosomes have significantly broader free wells, and that H2A.B allows for sampling of states with increased DNA breathing, which are shown to be stable on the hundreds of nanoseconds timescale with further conventional simulations. Together, our results show the molecular mechanisms by which H2A.B creates less compacted nucleosome states as a means of increasing genetic accessibility and gene transcription.SIGNIFICANCENature has evolved a plethora of mechanisms for altering the physical and chemical properties of chromatin fibers as a means of controlling gene expression. These epigenetic processes may serve to increase or decrease DNA accessibility, manage the recruitment of remodeling factors, or tune the stability of the nucleosomes that make up chromatin. Here, we have used both conventional and enhanced sampling molecular dynamics simulations to understand how one of these epigenetic mechanisms, the substitution of canonical H2A proteins with the H2A.B variant, exerts its influence on the structures and dynamics of the nucleosome. Results show at the molecular level how this variant alters inter-molecular interactions to increase DNA accessibility as a means of increasing genetic accessibility and gene transcription.
Evaluation of Seed or Grain Storage Technologies from Indian Farming Societies Using A Hybrid and Multi-Attribute Approach
Authors: Maity Aniruddha , Mukherjee Anirban , Ray Mrinmoy , Pramanik Pragati , Parmar Sanjay S , Manjunatha N , Kumar Sanjay , Wasnik Vinod Kumar , Shubha Kumari 
Published: June 2020

AbstractSoon after the introduction of green revolution, a parallel increment in percent food grain production and losses has been reported in India, which impedes the mission of achieving food security in India. In parts, among the major causes of these losses are the reluctance among farmers, especially of small holding, towards adoption of scientific storage methods/technologies and inability of the national agencies to meet the challenges imposed by the supply of surplus grains to them by the farmers. Although sets of traditional and improved grain storage technologies exist among Indian farming communities, a controversial account about their effectiveness and performance is available in the literature which negatively impacts the endeavour of bringing rapid developmental in the farming society. In a developing nation like India, a large section of farmers is often either unaware of the modern technologies or cannot logistically access them. They often rely on the traditional or semi-modern technologies without having a comprehensive account of the benefit and economic feasibility of the modern technologies. This impedes the vision of rapid development of the farmers and the process of infusing emerging technologies in the society. In order to develop an informative argument about the performance of the existing technologies, a nearly comprehensive study has been undertaken to compare the different traditional and improved grain storage structures used by Indian farmers. Both qualitative and quantitative parameters were compared individually and simultaneously to achieve their effect on performance individually and in unison. Another objective of the study was to test the applicability of hybrid and multi-attribute approach, based on Analytic Hierarchy Process (AHP) and the Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) for the performance evaluation and ranking of the attributes and structures. Finally, based on analysis and ideas borrowed out of literature a set of theoretical and conceptual guidelines to assist improvement in these structures was brought in. The study will help understand the status of grain storage technologies in the developing, resource-poor society and also increase the adoption and access of farmers to better post-harvest seed storage technologies.