bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adipose-Derived Stem Cells Therapy for Radiation-Induced Skin Injury
Authors: Huayllani Maria T. , Ruiz-Garcia Henry , Boczar Daniel , Avila Francisco R. , Lu Xiaona , Rinker Brian D. , Moran Steven L. , Sarabia-Estrada Rachel , Quiñones-Hinojosa Alfredo , Forte Antonio J. 
Published: November 2021

Background
Radiation-induced skin injuries have been treated with different medical therapies and have shown diverse outcomes. We aim to evaluate the effect of adipose-derived stem cells (ADSCs) therapy on radiation-induced skin injury.

Methods
We performed a review by querying PubMed, Ovid MEDLINE, and EMBASE databases from inception to April 2020 following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. The MeSH terms “adipose-derived stem cells,” “wound healing,” “radiation,” and synonyms in combinations determined our search strategy. Experimental peer-reviewed articles describing the protocol and comparing the results with controls were included. Non-English studies were excluded.

Results
Our search recorded a total of 137 articles. Only 8 studies met our inclusion criteria and were included in this review. Five studies evaluated the use of ADSC alone, whereas the others evaluated the efficacy of ADSC seeded in scaffolds. Adipose-derived stem cell–based therapies, either alone or seeded in scaffolds, were shown to improve wound healing in most studies when compared with controls.

Conclusions
There is evidence supporting the positive benefits from ADSC-based therapies in radiation-induced skin injury. However, further studies are needed to standardize the method of ADSC extraction, radiation-induced skin injury experimental model, and increase the time of follow-up to evaluate the results accurately.
Multiplex PCR Assays for Identifying All Major SARS-CoV-2 Variants
Authors: Dikdan Ryan J. , Marras Salvatore AE , Field Amanda P. , Brownlee Alicia , Cironi Alexander , Hill D. Ashley , Tyagi Sanjay 
Published: October 2021

AbstractVariants of Concern (VOC) of SARS-CoV-2, including Alpha, Beta, Gamma, Delta, and Omicron threaten to prolong the pandemic leading to more global morbidity and mortality. Genome sequencing is the mainstay of tracking the development and evolution of the virus, but is costly, slow, and not easily accessible. A multiplex qRT-PCR assay for SARS-CoV-2 was developed, which identifies all VOC as well as other mutations of interest in the viral genome, eight mutations total, using single nucleotide discriminating molecular beacons in a two-tube assay. The presented variant molecular beacon assay showed a limit of detection of five copies of the viral RNA, with 100% specificity. Twenty-six SARS-CoV-2 positive patient samples were blinded and tested using this assay. When testing patient samples, the assay was in full agreement with results from deep sequencing with a sensitivity and specificity of 100% (26/26). We have used our design methodology to rapidly design an assay which detects the new Omicron variant. This Omicron assay was used to accurately identify this variant in 17 of 33 additional patient samples. These qRT-PCR assays identify all currently circulating VOC of SARS-CoV-2 as well as other important mutations in its Spike protein coding sequence. These assays can be easily implemented on broadly available five-color thermal cyclers and will help track the spread of these variants.
Clinical sequencing of soft tissue and bone sarcomas delineates diverse genomic landscapes and potential therapeutic targets
Authors: Nacev Benjamin A. , Sanchez-Vega Francisco , Smith Shaleigh A. , Antonescu Cristina R. , Rosenbaum Evan , Shi Hongyu , Tang Cerise , Socci Nicholas D. , Rana Satshil , Gularte-Mérida Rodrigo , Zehir Ahmet , Gounder Mrinal M. , Bowler Timothy G. , Luthra Anisha , Jadeja Bhumika , Okada Azusa , Strong Jonathan A. , Stoller Jake , Chan Jason E. , Chi Ping , D’Angelo Sandra P. , Dickson Mark A. , Kelly Ciara M. , Keohan Mary Louise , Movva Sujana , Thornton Katherine , Meyers Paul A. , Wexler Leonard H. , Slotkin Emily K. , Glade Bender Julia L. , Shukla Neerav N. , Hensley Martee L. , Healey John H. , La Quaglia Michael P. , Alektiar Kaled M. , Crago Aimee M. , Yoon Sam S. , Untch Brian R. , Chiang Sarah , Agaram Narasimhan P. , Hameed Meera R. , Berger Michael F. , Solit David B. , Schultz Nikolaus , Ladanyi Marc , Singer Samuel , Tap William D. 
Published: October 2021

AbstractThe genetic, biologic, and clinical heterogeneity of sarcomas poses a challenge for the identification of therapeutic targets, clinical research, and advancing patient care. Because there are > 100 sarcoma subtypes, in-depth genetic studies have focused on one or a few subtypes. Herein, we report a comparative genetic analyses analysis of 2,138 sarcomas representing 45 pathological entities. This cohort was prospectively analyzed using targeted sequencing to characterize subtype-specific somatic alterations in targetable pathways, rates of whole genome doubling, mutational signatures, and subtype-agnostic genomic clusters. The most common alterations were in cell cycle control andTP53, receptor tyrosine kinases/PI3K/RAS, and epigenetic regulators. Subtype-specific associations includedTERTamplification in intimal sarcoma and SWI/SNF alterations in uterine adenosarcoma. Tumor mutational burden, while low compared to other cancers, varied between and within subtypes. This resource will improve sarcoma models, motivate studies of subtype-specific alterations, and inform investigations of genetic factors and their correlations with treatment response.
The integrity of the antimicrobial supply chain in Bangladesh: assessing the regulatory environment and contextual challenges
Authors: Orubu Ebiowei S.F. , Samad Mohammed A. , Rahman Md. Tanvir , Zaman Muhammad H. , Wirtz Veronika J. 
Published: October 2021

AbstractPoor-quality medicines lead to large individual, health systems and national economic losses. Most low- and middle-income countries (LMICs) lack the robust regulatory quality assurance system necessary to contain the spread of poor-quality medicines. Innovations in regulatory systems strengthening are needed to protect public health. In this study, we assessed the integrity of the antimicrobial supply chain in Bangladesh and suggest innovations. We employed a qualitative methodology comprising a policy content analysis, and literature and database reviews. Bangladesh was chosen as a model LMIC because of its pharmaceuticals production capacity. Using a framework modified from the World Health Organization’s and the United States Pharmacopoeia’s, the Bangladesh National Drug Policy (BNDP) was evaluated for provisions on quality assurance mechanisms that match regulatory functions. Newspaper, peer-reviewed and post-marketing surveillance reports were used to assess the extent of poor-quality antimicrobials in circulation. There are provisions for quality assurance in the BNDP. Newspaper reports identified the circulation of substandard antimicrobials and reported on actions by the government to seize fraudulent/falsified and expired products. Only six peer-review studies testing antimicrobial product quality were identified; the three studies with the larger sample size (over 10 samples tested) reported results of out-of-specifications products. This assessment found evidence of regulatory actions against poor-quality antimicrobials as well as news reports and studies suggesting quality concerns, but no current rigorous assessment of the extent in Bangladesh. We suggest a multi-pronged approach to regulatory system strengthening comprising three strategies: community-based surveillance, task-shifting, and technology-enabled consumer participation.
Vaccination of COVID-19 Convalescent Plasma Donors Increases Binding and Neutralizing Antibodies Against SARS-CoV-2 Variants
Authors: Germanio Clara Di , Simmons Graham , Thorbrogger Chloe , Martinelli Rachel , Stone Mars , Gniadek Thomas , Busch Michael P 
Published: October 2021

ABSTRACTBackgroundCOVID-19 convalescent plasma (CCP) was widely used as passive immunotherapy during the first waves of SARS-CoV-2 infection in the US. However, based on observational studies and randomized controlled trials, beneficial effects of CCP were limited, and its use was virtually discontinued early in 2021, in concurrence with increased vaccination rates and availability of monoclonal antibody (mAb) therapeutics. However, as new variants of the SARS-CoV-2 spread, interest in CCP derived from vaccine-boosted CCP donors is resurging. The effect of vaccination of previously infected CCP donors on antibodies against rapidly spreading variants of concern (VOC) is still under investigation.Study Design/MethodsIn this study, paired samples from 11 CCP donors collected before and after vaccination were tested to measure binding antibodies levels and neutralization activity against the ancestral and SARS-CoV-2 variants (Wuhan-Hu-1, B.1.1.7, B.1.351, P.1, D614G, B.1.617.2, B.1.427) on the Ortho Vitros Spike Total Ig and IgG assays, the MSD V-PLEX SARS-CoV-2 Panel 6 arrays for IgG binding and ACE2 inhibition, and variant-specific Spike Reporter Viral Particle Neutralization (RVPN) assays.Results/FindingsBinding and neutralizing antibodies were significantly boosted by vaccination, with several logs higher neutralization for all the variants tested post-vaccination compared to the pre-vaccination samples, with no difference found among the individual variants.DiscussionVaccination of previously infected individuals boosts antibodies including neutralizing activity against all SARS-CoV-2 VOC, including the current spreading delta (B.1.617.2) variant. Animal model and human studies to assess clinical efficacy of vaccine boosted CCP are warranted, especially since 15-20% of current donations in the US are from previously infected vaccine-boosted donors.
Identification of COVID-19 and COPD common key genes and pathways using a protein-protein interaction approach
Authors: Thambiraja Thiviya S. , Karuppanan Kalimuthu , Subramaniam Gunasekaran , Kumar Suresh 
Published: October 2021

ABSTRACTCoronavirus disease (COVID-19) is an extremely contagious and cognitive disease that could cause immense hypoxemia. The rise in critically ill patients in epidemic regions has put enormous pressure on hospitals. There is a need to define extreme COVID-19 clinical determinants to optimize clinical diagnosis and the management system is strong. Chronic obstructive pulmonary disease (COPD) is linked to a rapidly increasing risk of death rates in population pneumonia. In this research, a network of protein-protein interaction (PPI) was developed using constructed datasets of COVID-19 and COPD genes to define the interrelationship between COVID-19 and COPD, how it affects each other, and the genes that are responsible for the process. The PPI network shows the top 10 common overlapping genes, which include IL10, TLR4, TNF, IL6, CXCL8, IL4, ICAM1, IFNG, TLR2, and IL18. These are the genes that COVID-19 and high-risk COPD patients are known to be expressed. These important genes shared by COVID-19 and COPD are involved in pathways such as malaria, African trypanosomiasis, inflammatory bowel disease, Chagas disease, influenza, and tuberculosis.
Optimal Design of Stochastic DNA Synthesis Protocols based on Generative Sequence Models
Authors: Weinstein Eli N. , Amin Alan N. , Grathwohl Will , Kassler Daniel , Disset Jean , Marks Debora S. 
Published: October 2021

AbstractGenerative probabilistic models of biological sequences have widespread existing and potential applications in analyzing, predicting and designing proteins, RNA and genomes. To test the predictions of such a model experimentally, the standard approach is to draw samples, and then synthesize each sample individually in the laboratory. However, often orders of magnitude more sequences can be experimentally assayed than can affordably be synthesized individually. In this article, we propose instead to use stochastic synthesis methods, such as mixed nucleotides or trimers. We describe a black-box algorithm for optimizing stochastic synthesis protocols to produce approximate samples from any target generative model. We establish theoretical bounds on the method’s performance, and validate it in simulation using held-out sequence-to-function predictors trained on real experimental data. We show that using optimized stochastic synthesis protocols in place of individual synthesis can increase the number of hits in protein engineering efforts by orders of magnitude, e.g. from zero to a thousand.
Intracellular pH dynamics regulates intestinal stem cell lineage specification
Authors: Liu Yi , Reyes Efren , Castillo-Azofeifa David , Klein Ophir D. , Barber Diane L. , Nystul Todd 
Published: October 2021

SummaryIntracellular pH (pHi) dynamics is increasingly recognized to regulate myriad cell behaviors, including proliferation, migration, differentiation, and transformation. Here we report a new finding that pHi dynamics also regulates adult stem cell lineage specification. In mouse small intestinal organoids, we identify a pHi gradient along the crypt axis, lower at the crypt base and higher toward the villus, and find that dissipating this gradient by inhibiting Na+-H+exchanger 1 (NHE1) activity genetically or pharmacologically abolishes crypt budding. Using single-cell RNA sequencing and lineage tracing we demonstrate that pHi dynamics acts downstream of ATOH1, with increased pHi promoting differentiation toward the secretory lineage, while reduced pHi biases differentiation into the absorptive lineage. Consistent with these results, disrupting the pHi gradient blocks new Paneth cell differentiation. Paneth cells provide an essential WNT signal to ISCs in organoids, and we find that the loss of crypt budding with inhibiting NHE1 activity is rescued with exogenous WNTs. Our findings indicate that pHi dynamics is tightly regulated in the ISC lineage and that an increase in pHi is required for the specification of secretory lineage, including Paneth cell differentiation that contributes to crypt maintenance. These observations reveal a previously unreported role for pHi dynamics in cell fate decisions within an adult stem cell lineage.
Generating and testing the efficacy of transgenic Cas9 inTribolium castaneum
Authors: Rylee Johnathan C. , Nin-Velez Alexandra , Mahato Simpla , Helms Kennedy J. , Wade Michael J. , Zentner Gabriel E. , Zelhof Andrew C. 
Published: October 2021

AbstractCRISPR/Cas9 genome editing has now expanded to many insect species, includingTribolium castaneum. However, compared toDrosophila melanogaster, the CRISPR toolkit ofT. castaneumis limited. A particularly apparent gap is the lack of Cas9 transgenic animals, which generally offer higher editing efficiency. We address this by creating and testing transgenic beetles expressing Cas9. We generated two different constructs bearing basal heat shock promoter-driven Cas9, two distinct 3’ UTRs, and one containing Cas9 fused to EGFP by a T2A peptide. For each construct, we were able to generate a line that is homozygous viable, though variable reductions in reproductive success with each construct were noted. Analyses of Cas9 activity in each transgenic line demonstrated that both designs are capable of inducing CRISPR-mediated changes in the genome in the absence of heat induction. Overall, these resources enhance the accessibility of CRISPR/Cas9 genome editing for theTriboliumresearch community and provide a benchmark against which to compare future transgenic Cas9 lines.
Systems-based approach for optimization of a scalable bacterial ST mapping assembly-free algorithm
Authors: Pavlovikj Natasha , Gomes-Neto Joao Carlos , Deogun Jitender S. , Benson Andrew K. 
Published: November 2021

AbstractEpidemiological surveillance of bacterial pathogens requires real-time data analysis with a fast turn-around, while aiming at generating two main outcomes: 1) Species level identification; and 2) Variant mapping at different levels of genotypic resolution for population-based tracking, in addition to predicting traits such as antimicrobial resistance (AMR). With the recent advances and continual dissemination of whole-genome sequencing technologies, large-scale population-based genotyping of bacterial pathogens has become possible. Since bacterial populations often present a high degree of clonality in the genomic backbone (i.e., low genetic diversity), the choice of genotyping scheme can even facilitate the understanding of ancestral relationships and can be used for prediction of co-inherited traits such as AMR. Multi-locus sequence typing (MLST) fits that purpose and can identify sequence types (ST) based on seven ubiquitous genome-scattered loci that aid in genotyping isolates beneath the species level. ST-based mapping also standardizes genotyping across laboratories and is used by laboratories worldwide. However, algorithms for inferring ST from Illumina paired-end sequencing data typically rely on genome assembly prior to classification. Genome assembly is computationally intensive and is a bottleneck for speed and scalability, which are important aspects of genomic epidemiology. The stringMLST program uses an assembly-free, kmer-based algorithm for inferring STs, which can overcome the speed and scalability bottlenecks. Here we have systematically studied the accuracy and scalability of stringMLST relative to the standard MLST program across a wide array of phylogenetically divergent Public Health-relevant bacterial pathogens. Our data shows that optimal kmer length for stringMLST is species-specific and that genome-intrinsic and -extrinsic features can affect performance and accuracy of the program. While suitable parameters could be identified for most organisms, there were a few instances where this program may not be directly deployable in its current format. More importantly, we integrated stringMLST into our freely available and scalable hierarchical-based population genomics platform, ProkEvo, and further demonstrated how the implementation facilitates automated, reproducible bacterial population analysis. The ProkEvo implementation provides a rapidly deployable genomic epidemiology tool for ST mapping along with other pan-genomic data mining strategies, while providing specific guidance on how to optimize stringMLST performance for a wide variety of bacterial pathogens.
Elevated Hoxb5b expands vagal neural crest pool and blocks enteric neuronal development in zebrafish
Authors: Adam Howard Aubrey G. , Nguyen Aaron C. , Tworig Joshua , Ravisankar Priya , Singleton Eileen W. , Li Can , Kotzur Grayson , Waxman Joshua S. , Uribe Rosa. A. 
Published: October 2021

AbstractNeural crest cells (NCCs) are a migratory, transient, and multipotent stem cell population essential to vertebrate embryonic development, contributing to numerous cell lineages in the adult organism. While great strides have been made in elucidating molecular and cellular events that drive NCC specification, comprehensive knowledge of the genetic factors that orchestrate NCC developmental programs is still far from complete. We discovered that elevated Hoxb5b levels promoted an expansion of zebrafish NCCs, which persisted throughout multiple stages of development. Correspondingly, elevated Hoxb5b also specifically expanded expression domains of the vagal NCC markers foxd3 and phox2bb. Increases in NCCs were most apparent after pulsed ectopic Hoxb5b expression at early developmental stages, rather than later during differentiation stages, as determined using a novel transgenic zebrafish line. The increase in vagal NCCs early in development led to supernumerary Phox2b+ enteric neural progenitors, while leaving many other NCC-derived tissues without an overt phenotype. Surprisingly, these NCC-derived enteric progenitors failed to expand properly into sufficient quantities of enterically fated neurons and stalled in the gut tissue. These results suggest that while Hoxb5b participates in vagal NCC development as a driver of progenitor expansion, the supernumerary, ectopically localized NCC fail to initiate expansion programs in timely fashion in the gut. All together, these data point to a model in which Hoxb5b regulates NCCs both in a tissue specific and temporally restricted manner.
Analytical Accuracy and Clinical Agreement of a Novel Internet of Things and AI-based Point-of-Care Testing Laboratory
Authors: Malucelli Lucca Centa , Neves Alves Gabriele Luise , Rank Filho Claucio Antonio , Correa Rafaela Fortes , Albano Vanessa Hintz , Rocha Saldanha Anita Leme da , Fakhouri Tereza Bellincanta , Santos Carolina Melchioretto dos , Severo Matheus Gonçalves , Ribeiro Victor Henrique Alves , de Almeida Bernardo Montesanti Machado , Klosovski Caio Corsi , Rocha Martinez Tania Leme da , Scartezini Marileia , Mazega Figueredo Marcus Vinícius 
Published: October 2021

ABSTRACTPoint-of-care testing (POCT) offers several advantages over conventional laboratory testing. Nonetheless, a faster turnaround time, with less invasive procedures, is not enough if not associated with an acceptable level of accuracy. Here, we show the analytical validation behind the Hilab Flow (HiF), a multi-analyte POCT analyzer. HiF quantitative and qualitative tests for 6,175 clinical samples were compared to gold-standard methods from College of American Pathologists accredited laboratories. The compatibility between methods was evaluated in terms of association and clinical agreement. The established approval criteria was a kappa agreement > 0.8. A strong concordance was observed for the 27 analytes tested. Accuracy was greater than 90% for all HiF exams, indicating a good clinical agreement to gold standard laboratory testing. Results indicate that all quantitative and qualitative tests are suitable for POCT and present a reliable performance. HiF stands as a useful tool to aid decision-making in the clinical setting, with potential to contribute to healthcare solutions in diagnostic medicine worldwide.
Synchrony-Division Neural Multiplexing: An Encoding Model
Authors: Rezaei Mohammad R. , Popovic Milos R. , Prescott Steven A , Lankarany Milad 
Published: October 2021

AbstractCortical neurons receive mixed information from collective spiking activities of primary sensory neurons in response to a sensory stimulus. A recent study demonstrated that the time underlying the onset-offset of a tactile stimulus and its varying intensity can be respectively represented by synchronous and asynchronous spikes of S1 neurons in rats. This evidence capitalized on the ability of an ensemble of homogeneous neurons to multiplex, a coding strategy that was referred to as synchrony division multiplexing (SDM). Although neural multiplexing can be conceived by distinct functions of individual neurons in a heterogeneous neural ensemble, the extent to which nearly identical neurons in a homogeneous neural ensemble encode multiple features of a mixed stimulus remains unknown. Here, we present a computational framework to provide a system level understanding on how an ensemble of homogeneous neurons enable SDM. First, we simulate SDM with an ensemble of homogeneous conductance-based model neurons receiving a mixed stimulus comprising slow and fast features. Using feature estimation techniques, we show that both features of the stimulus can be inferred from the generated spikes. Second, we utilize linear nonlinear (LNL) cascade models and calculate temporal filters and static nonlinearities of differentially synchronized spikes. We demonstrate that these filters and nonlinearities are distinct for synchronous and asynchronous spikes. Finally, we develop an augmented LNL cascade model as an encoding model for the SDM by combining individual LNLs calculated for each type of spike. The augmented LNL model reveals that a homogeneous neural ensemble can perform two different functions, namely, temporal- and rate-coding, simultaneously.