bluuebunny/crossref_metadata_2025_split huggingface dataset:
Victims of human trafficking and exploitation in the healthcare system: a retrospective study using a large multi-state dataset and ICD-10 codes
Authors: Gutfraind Alexander , Sokat Kezban Yagci , Muscioni Guido , Alahmadi Sami , Hudlow Jonathan , Hershow Ronald , Norgeot Beau 
Published: May 2022

AbstractBackgroundTrafficking and exploitation for sex or labor affects millions of persons worldwide. To improve healthcare for these patients, in late 2018 new ICD-10 medical diagnosis codes were implemented in the US.MethodsHere we report on a database search of a large US health insurer that contained approximately 47.1 million patients and 0.9 million provider organizations, not limited to large medical systems. We reported on any diagnosis with the new codes between 2018-09-01 and 2022-09-01.ResultsThe dataset was found to contain 5,262 instances of the ICD-10 codes. Regression analysis of the codes found a 5.8% increase in the uptake of these codes per year, representing a decline relative to 6.7% annual increase in the data. The codes were used by 1,810 different providers (0.19% of total) for 2,793 patients. Of the patients, 1,248 were recently trafficked, while the remainder had a personal history of exploitation. Of the recent cases, 86% experienced sexual exploitation, 14% labor exploitation and 0.8% both types. These patients were predominantly female (83%) with a median age of 20 (interquartile range: 15-35). The patients were characterized by persistently high prevalence of mental health conditions (including anxiety - 21%, post-traumatic stress disorder - 20%, major depression - 18%), sexually-transmitted infections, and high utilization of the emergency department (ED). The first report of trafficking occurred most often outside of a hospital or emergency setting (55%), primarily during primary care and psychiatric visits.ConclusionsOur study strengthens the case for expanding the use of the new ICD-10 codes and studying the barriers to their implementation.
Leishmania allelic selection during experimental sand fly infection correlates with mutational signatures of oxidative DNA damage
Authors: Bussotti Giovanni , Li Blaise , Pescher Pascale , Vojtkova Barbora , Louradour Isabelle , Pruzinova Katerina , Sadlova Jovana , Volf Petr , Späth Gerald F. 
Published: May 2022

ABSTRACTTrypanosomatid pathogens are transmitted by blood-feeding insects, causing devastating human infections. Survival of these parasites in their vertebrate and invertebrate hosts relies on their capacity to differentiate into distinct stages that are the result of a co-evolutionary process. These stages show in addition important phenotypic shifts that often impacts infection, affecting for example parasite pathogenicity, tissue tropism, or drug susceptibility. Despite their clinical relevance, the evolutionary mechanisms that allow for the selection of such adaptive phenotypes remain only poorly investigated. Here we use Leishmania donovani as a trypanosomatid model pathogen to shed first light on parasite evolutionary adaptation during experimental sand fly infection. Applying a comparative genomics approach on hamster- isolated amastigotes and derived promastigotes before (input) and after (output) infection of Phlebotomus orientalis revealed a strong bottleneck effect on the parasite population as judged by principal component and phylogenetic analyses of input and output parasite DNA sequences. Despite random genetic drift caused by the bottleneck effect, our analyses revealed various genomic signals that seem under positive selection given their convergence between independent biological replicates. While no significant fluctuations in gene copy number were revealed between input and output parasites, convergent selection was observed for karyotype, haplotype and allelic changes during sand fly infection. Our analyses further uncovered signature mutations of oxidative DNA damage in the output parasite genomes, suggesting that Leishmania suffers from oxidative stress inside the insect digestive tract. Our results propose a new model of Leishmania genomic adaptation during sand fly infection, where oxidative DNA damage and DNA repair processes drive haplotype and allelic selection. The experimental and computational framework presented here provides a useful blueprint to assess evolutionary adaptation of other eukaryotic pathogens inside their insect vectors, such as Plasmodium spp, Trypanosoma brucei and Trypanosoma cruzi.
Axl contributes to efficient migration and invasion of melanoma cells
Authors: Shao Hanshuang , Teramae Diana , Wells Alan 
Published: May 2022

AbstractAxl, a member of the TAM receptor family has been broadly suggested to play a key role in tumor metastasis. However, the function of Axl in the invasion and metastasis of melanoma, the most lethal skin cancer, remains largely unknown. In the present study, we found that melanoma cell lines present variable protein levels of Axl and Tyro3; interestingly, MerTK is not noted at detectable levels in any of tested MGP (metastatic growth phase) cell lines. Treatment with recombinant human Gas6 significantly activates Akt in the Axl-expressing WM852 and IgR3 lines but just slightly in WM1158. IgR3, WM852 and WM1158 demonstrate different autocrine signaling. Knockdown of Axl by siRNA or the treatment with Axl-specific inhibitor R428 dramatically inhibits the migration and invasion of both IgR3 and WM852 in vitro. These findings suggest that Axl enhances the invasion of melanoma cells.
Mechanically primed cells transfer memory to fibrous matrices for persistent invasion
Authors: Almeida José , Mathur Jairaj , Lee Ye Lim , Sarker Bapi , Pathak Amit 
Published: May 2022

AbstractIn disease and development, cells sense and migrate across mechanically dissimilar environments. We investigated whether mechanical memory of past environments empowers cells to navigate new, three-dimensional environments. Here, we show that cells primed by stiff matrices apply higher forces, compared to soft-primed cells, to accumulate and align collagen fibers towards sustained invasion. This priming advantage persists in dense or stiffened collagen. Through an energy-minimization model, we elucidate how memory-laden cells overcome mechanosensing of softer or challenging environments via a cell-matrix transfer of memory. Consistent with model predictions, depletion of α-catenin and YAP hamper coordinated forces and cellular memory required for collagen remodeling before invasion. We release tension in collagen fibers via laser ablation and disable fiber remodeling by lysyl-oxidase inhibition; both of which disrupt cell-to-matrix transfer of memory and reduce invasion. These results have implications for cancer, fibrosis, and aging, where potential matrix memory may generate prolonged cellular response.One-Sentence SummaryCell invasion across mechanically dissimilar environments is mediated by force-based storage and extraction of cell and matrix memory.
A Phytophthora nucleolar effector, Pi23226, targets to host ribosome biogenesis for necrotrophic cell death
Authors: Lee Soeui , Kim Jaehwan , Kim Myung-Shin , Min Cheol Woo , Kim Sun Tae , Choi Sang-Bong , Lee Joo Hyun , Choi Doil 
Published: May 2022

AbstractPathogen effectors target diverse subcellular organelles to manipulate the plant immune system. Although nucleolus has been emerged as a stress marker, and several effectors are localized in the nucleolus, the roles of nucleolar-targeted effectors remain elusive. In this study, we showed Phytophthora infestans infection of Nicotiana benthamiana results in nucleolar inflation during the transition from biotrophic to necrotrophic phase. Multiple P. infestans effectors were localized in the nucleolus: Pi23226 induced cell death in Nicotiana benthamiana and nucleolar inflation similar to that observed in the necrotrophic stage of infection, whereas its homolog Pi23015 and a deletion mutant (Pi23226ΔC) did not induce cell death or affect nucleolar size. RNA immunoprecipitation and iCLIP-seq analysis indicated that Pi23226 bound to the 3′-end of 25S rRNA precursors, resulting in the accumulation of unprocessed 27S pre-rRNAs. The nucleolar stress marker NAC082 was strongly upregulated under Pi23226-expressing conditions. Pi23226 subsequently inhibited global protein translation in host cells by interacting with ribosomes. Pi23226 enhanced P. infestans pathogenicity, indicating that Pi23226-induced ribosome malfunction and cell death was beneficial for pathogenesis in the host. Our results provide evidence for the molecular mechanism underlying RNA-binding effector activity in host ribosome biogenesis, and lead to new insights into the nucleolar action of effectors in pathogenesis.
Pleiotrophin drives a pro-metastatic immune niche within the breast tumor microenvironment
Authors: Ganguly Debolina , Schmidt Marcel O. , Coleman Morgan , Ngo Tuong-Vi , Sorrelle Noah , Dominguez Adrian TA. , Toombs Jason E. , Lewis Cheryl , Fang Yisheng , Mora Fatima Valdes , Gallego-Ortega David , Wellstein Anton , Brekken Rolf A. 
Published: May 2022

AbstractMetastatic cancer cells adapt to thrive in secondary organs. To investigate metastatic adaptation, we performed transcriptomic analysis of metastatic and non-metastatic murine breast cancer cells. We found that pleiotrophin (PTN), a neurotrophic cytokine, is a metastasis-associated factor that is expressed highly by aggressive breast cancers. Moreover, elevated PTN in plasma correlated significantly with metastasis and reduced survival of breast cancer patients. Mechanistically, we find that PTN activates NF-kB in cancer cells leading to altered cytokine production, subsequent neutrophil recruitment and an immune suppressive microenvironment. Consequently, inhibition of PTN, pharmacologically or genetically, reduces the accumulation of tumor associated neutrophils and reverts local immune suppression resulting in increased T cell activation and attenuated metastasis. Furthermore, inhibition of PTN significantly enhanced the efficacy of immune checkpoint blockade + chemotherapy in reducing metastatic burden in mice. These findings establish PTN as a previously unrecognized driver of a pro-metastatic immune niche and thus represents a promising therapeutic target for the treatment of metastatic breast cancer.
Convergence on reduced aggression through shared behavioral traits in multiple populations of Astyanax mexicanus
Authors: Rodriguez-Morales Roberto , Gonzalez-Lerma Paola , Yuiska Anders , Han Ji Heon , Guerra Yolanda , Crisostomo Lina , Keene Alex C. , Duboue Erik R. , Kowalko Johanna 
Published: May 2022

AbstractAggression is a complex behavior that is observed across the animal kingdom, and plays roles in resource acquisition, defense, and reproductive success. While there are many individual differences in propensity to be aggressive within and between populations, the mechanisms underlying differences in aggression between individuals in natural populations are not well understood. We addressed this using the Mexican tetra, Astyanax mexicanus, a powerful model organism to understand behavioral evolution. A. mexicanus exists in two forms: a river-dwelling surface form and multiple populations of a blind cave form. We characterized aggression in surface fish and cavefish in a resident/intruder assay through quantifying multiple behaviors occurring during social interactions. Surface fish, which are aggressive, display multiple social behaviors in this context, which we characterized into two types of behaviors: aggression- associated and escape-associated behaviors. The majority of these behaviors were reduced or lost in Pachón cavefish. Further, both aggression-associated and escape-associated behaviors were not dependent on the presence of light, and both surface fish and cavefish remained aggressive or non-aggressive, respectively, when opposed to fish from a different population. Additionally, we found that within populations, levels of stress response were not correlated with aggression- or escape-associated behaviors. Finally, when we compared aggression- and escape- associated behaviors across four cavefish populations, we found that both types of behaviors are reduced in three cave populations, while still present in one. Together, these results reveal that multiple cavefish populations have repeatedly evolved reduced aggression through shared behavioral components, while other cavefish have retained aggression.Summary StatementComparison of aggression between surface fish and cavefish demonstrates that multiple complex behaviors compose aggression in surface fish and reveals heterogeneity in loss of aggression in cave populations.
Discovery and structure of a widespread bacterial ABC transporter specific for ergothioneine
Authors: Zhang Yifan , Gonzalez-Gutierrez Giovanni , Legg Katherine A. , Edmonds Katherine A. , Giedroc David P. 
Published: May 2022

ABSTRACTErgothioneine (ET) is the 2-thiourea derivative of trimethylhistidine that is biosynthesized only by select fungi and bacteria, notablyMycobacterium tuberculosis, and functions as a potent scavenger of reactive oxygen species. Although ET is obtained in the diet and accumulates in vertebrate cells via an ET-specific transporter, the extent to which ET broadly functions in bacterial cells unable to synthesize it is unknown. Here we show thatspd_1642-1643inStreptococcus pneumoniaeD39, a Gram-positive respiratory pathogen, encodes a novel ergothioneine uptake ATP-binding cassette (ABC) transporter, which we designate EgtUV. EgtU is a permease-solute binding domain (SBD) fusion protein, and the SBD binds ET with high affinity and exquisite specificity in the cleft between the two subdomains, with cation-π interactions engaging the betaine moiety and a water-mediated hydrogen bonding network surrounding the C2-sulfur-containing imidazole ring. Bioinformatics studies reveal that EgtUV is uniquely strongly conserved among known quaternary amine-specific transporters and widely distributed in firmicutes, including the human pathogensListeria monocytogenes, as BilEB,Enterococcus faecalisandStaphylococcus aureus. This discovery significantly diversifies the LMW thiol pool in Gram-positive human pathogens that may contribute to antioxidant defenses in the infected host.
Disrupting the ciliary gradient of active Arl3 affects rod photoreceptor nuclear migration
Authors: Travis Amanda M. , Manocha Samiya , Willer Jason R. , Wessler Timothy S. , Skiba Nikolai P. , Pearring Jillian N. 
Published: May 2022

ABSTRACTThe small GTPase Arl3 is important for the enrichment of lipidated proteins to primary cilia, including the outer segment of photoreceptors. Human mutations in the small GTPase Arl3 cause both autosomal recessive and dominant inherited retinal dystrophies. We discovered that dominant mutations result in increased active G-protein—Arl3-D67V has constitutive activity and Arl3-Y90C is fast cycling—and their expression in mouse rods resulted in a displaced nuclear phenotype due to an aberrant Arl3-GTP gradient. Using multiple strategies, we go on to show that removing or restoring the Arl3-GTP gradient within the cilium is sufficient to rescue the nuclear migration defect. Together, our results reveal that a Arl3 ciliary gradient is involved in proper positioning of photoreceptor nuclei during retinal development.
Chromosome-level Genomes Reveal the Genetic Basis of Descending Dysploidy and Sex Determination in Morus Plants
Authors: Xia Zhongqiang , Dai Xuelei , Fan Wei , Liu Changying , Zhang Meirong , Bian Peipei , Zhou Yuping , Li Liang , Zhu Baozhong , Liu Shuman , Li Zhengang , Wang Xiling , Yu Maode , Xiang Zhonghuai , Jiang Yu , Zhao Aichun 
Published: May 2022

AbstractMultiple plant lineages have independently evolved sex chromosomes and variable karyotypes to maintain their sessile lifestyles through constant biological innovation. Morus notabilis, a dioecious mulberry species, has the fewest chromosomes among Morus spp., but the genetic basis of sex determination and karyotype evolution in this species have not been identified. Three high-quality genome assemblies generated of Morus spp. (including those of dioecious M. notabilis and Morus yunnanensis) were within the range 301-329 Mb in size which were grouped into six pseudochromosomes. Using a combination of genomic approaches, we showed that the putative ancestral karyotype of Morus was close to 14 protochromosomes, and that several chromosome fusion events resulted in descending dysploidy (2n = 2x = 12). We also characterized a ∼6.2-Mb sex-determining region on chromosome 3. The four potential male-specific genes, including a partially duplicated DNA helicase gene orthologue (named MSDH) and three Ty3_Gypsy long terminal repeat retrotransposons (named MSTG), were solely identified in the Y-linked area and considered to be strong candidate genes for sex determination or differentiation. Population genomic analysis showed that Guangdong accessions in China were genetically similar to Japanese accessions of mulberry. In addition, genomic areas containing selective sweeps that distinguish domesticated mulberry trees from wild populations in terms of flowering and disease resistance were identified. Our findings provide an important genetic resource for sex identification and molecular breeding in mulberry.
CaV1 and CaV2 calcium channels mediate the release of distinct pools of synaptic vesicles
Authors: Mueller Brian D. , Merrill Sean A. , Watanabe Shigeki , Liu Ping , Singh Anish , Maldonado-Catala Pablo , Cherry Alex , Silva Malan , Maricq Andres Villu , Wang Zhao-Wen , Jorgensen Erik M. 
Published: May 2022

AbstractActivation of voltage-gated calcium channels at synapses leads to local increases in calcium and the fusion of synaptic vesicles. However, presynaptic output will be determined by the density of calcium channels, the dynamic properties of the channel, the distance to docked vesicles, and the release probability at the docking site. We demonstrate that at C. elegans neuromuscular junctions two different classes of voltage-gated calcium channels, CaV2 and CaV1, mediate the release of distinct pools of synaptic vesicles. CaV2 channels are concentrated in densely packed clusters ∼300 nm in diameter with the active zone proteins Neurexin, α-Liprin, SYDE, ELKS/CAST, RIM-BP, α-Catulin, and MAGI1. CaV2 channels mediate the fusion of vesicles docked adjacent to the dense projection and are colocalized with the synaptic vesicle priming protein UNC-13L. By contrast, CaV1 channels are dispersed in the synaptic varicosity and are coupled to internal calcium stores via the ryanodine receptor. CaV1 and ryanodine receptor mediate the fusion of vesicles docked broadly in the synaptic varicosity and are colocalized with the vesicle priming protein UNC-13S. Distinct synaptic vesicle pools, released by different calcium channels, could be used to tune the speed, voltage-dependence, and quantal content of neurotransmitter release.
Students' attitudes on the use of Zoom in higher educational institutes of Sri Lanka
Authors: Mohamed Riyath Mohamed Ismail , Muhammed Rijah Uthuma Lebbe , Rameez Aboobacker 
Published: May 2022

PurposeThere is a significant decrease in students' attendance in Zoom classes compared to traditional classes. This paper investigates the factors that affect students' attitudes, behavioral intentions and actual use of Zoom for online classes at higher educational institutions (HEIs) in Sri Lanka.Design/methodology/approachThis research uses the technology acceptance model (TAM) as a theoretical model. The data are collected from HEI students via an online survey form. The hypotheses between constructs in the model are tested using partial least squared–structural equation model.FindingsThe analysis shows that computer self-efficacy (CSE) affects perceived usefulness (PU) and perceived ease of use (PEU), which affects attitude (ATT) and behavioral intention (BI) and actual use (AU) of Zoom in a chain reaction. Further, PEU affects PU, which, in turn, affects BI. Furthermore, the effect size of PU to BI is larger than ATT to BI.Practical implicationsStudents' attendance for Zoom classes mainly depends on CSE, PU and PEU. Therefore, HEIs should promote Zoom with interactive training before teaching online. Further, officials should revise the curriculum in schools to upsurge the CSE of students.Originality/valueDuring coronavirus-19, no research was published on students' use of Zoom for online classes in the Sri Lankan context. Moreover, the TAM model has been modified by including CSE as an external variable.
Procurement innovation as a vehicle for sustainable change – a case study of the Danish model of strategic partnerships
Authors: Berg Jakob Brinkø , Thuesen Christian , Jensen Per Anker 
Published: May 2022

Purpose
Efficient and effective knowledge transfer is important in complex building renovation projects. The addition of sustainability requirements in building renovation adds complexity. This paper aims to investigate the development of innovative public procurement schemes to support sustainable building renovation projects. These blueprints for procurement innovation can support similar efforts in other countries.

Design/methodology/approach
This study is based on a longitudinal case study using interviews with primary stakeholders and workshops with industry practitioners to supplement the analysis of public tender documents from the Danish public building clients.

Findings
The key tenants of the Danish model for strategic partnerships are a single strategic partner, systematic conflict resolution, framework agreements, risk management and joint educational programs. Three phases in the development of the procurement scheme are identified: experiment, definition and replication.

Originality/value
Strategic partnerships and other types of relational contract schemes are not very prevalent in most countries. How these contracts are developed and defined is not well understood. This paper shows how one such contracting scheme is developed, how it is defined and replicated.