bluuebunny/crossref_metadata_2025 huggingface dataset:
A Design & Innovation‐Driven Growth Model For Micro, Small, And Medium Enterprises
Authors: James Anand
Published: February 2024

For a developing economy like India's, the creative industries can help the economy flourish and grow.

India's fast growing furniture industry is used to illustrate the link between strategy, design, and entrepreneurial thinking as a growth engine model—adding value to the design management process.
Sustainable Development Competencies in Design Education
Authors: Persov Elad
Published: February 2024

…there is a gap between the complexity and scale of climate and sustainability challenges and the professional competencies currently taught in most design education programs.

Designers are expected to have a key role in addressing looming problems like climate change and sustainability. Examining current curricula and finding gaps in competencies provides a starting point to ensuring that future designers have the skills necessary for the job.
Repairing a Relationship: The Fall of Design Thinking and What We Can Learn from It
Authors: Mittersinker Gregor
Published: February 2024

Design increasingly finds itself in the crosshairs and is held accountable for not delivering the miraculous solutions businesses desperately seek and design consultants promise.

OPINION | A creative director shares his thoughts about what steps should be taken to repair design's relationship with businesses that feel design hasn't delivered on its promises.
Noninvasive minimal residual disease assessment in relapsed/refractory large B‐cell lymphoma using digital droplet PCR
Authors: Heger Jan‐Michel , d'Hargues Yannick , Kleinert Fanni , Mattlener Julia , Weiss Jonathan , Franzen Fabian , Becker Christian , Becker Kerstin , Gödel Philipp , Schmiel Marcel , Meinel Jörn , Flümann Ruth , Simon Florian , Reinhardt H. Christian , Borchmann Peter , Borchmann Sven , Balke‐Want Hyatt , Knittel Gero , von Tresckow Bastian
Published: February 2024

Although several promising approaches for the treatment of relapsed/refractory diffuse large B‐cell lymphoma (rrDLBCL) have been approved recently, it remains unclear which patients will ultimately achieve long‐term responses. Circulating tumor (ct)DNA sequencing has emerged as a valuable tool to assess minimal residual disease (MRD). Correlations between MRD and outcomes have been shown in previously untreated DLBCL, but data on the repeated assessment of MRD in the dynamic course of rrDLBCL is limited. Here, we present an approach leveraging cost‐ and time‐sensitivity of digital droplet (dd)PCR to repeatedly assess MRD in rrDLBCL and present proof‐of‐principle for its ability to predict outcomes.
Dopamine activity in the nigrostriatal pathway alters cue‐induced risky choice patterns in female rats
Authors: Hathaway Brett A. , Li Andrew , Brodie Hannah G. , Silveira Mason M. , Tremblay Melanie , Seo Yeon Soo , Winstanley Catharine A.
Published: February 2024

Deficits in cost/benefit decision making is a critical risk factor for gambling disorder. Reward‐paired cues may play an important role, as these stimuli can enhance risk preference in rats. Despite extensive research implicating the dorsal striatum in the compulsive aspects of addiction, the role of nigrostriatal dopaminergic activity in cue‐induced risk preference remains unclear, particularly in females. Accordingly, we examined the effects of manipulating the dopaminergic nigrostriatal pathway on cue‐induced risky choice in female rats. TH:Cre rats were trained on the cued version of the rat Gambling Task. This task was designed such that maximal reward is attained by avoiding the high‐risk, high‐reward options and instead favouring the options associated with lower per‐trial gains, as they feature less frequent and shorter time‐out penalties. Adding reward‐paired audiovisual cues to the task leads to greater risky choice on average. To assess the role of the nigrostriatal pathway, a viral vector carrying either Cre‐dependent inhibitory or excitatory DREADD was infused into the substantia nigra. Rats then received clozapine‐N‐oxide either during task acquisition or after a stable performance baseline was reached. Inhibition of this pathway accelerated the development of risk preference in early sessions and increased risky choice during performance, but long‐term inhibition actually improved decision making. Activation of this pathway had minimal effects. These results provide evidence for the involvement of the dopaminergic nigrostriatal pathway in cue‐induced risk preference in females, therefore shedding light on its role in cost/benefit decision‐making deficits and expanding our knowledge of the female dopaminergic system.
Mutation of novel ethanol‐responsive lncRNAGm41261 impacts ethanol‐related behavioral responses in mice
Authors: Plasil S. L. , Farris S. P. , Blednov Y. , Mayfield R. D. , Mangieri R. A. , Nwokeji U. J. , Aziz H. C. , Lambeth P. S. , Harris R. A. , Homanics G. E.
Published: February 2024

Chronic alcohol exposure results in widespread dysregulation of gene expression that contributes to the pathogenesis of Alcohol Use Disorder (AUD). Long noncoding RNAs are key regulators of the transcriptome that we hypothesize coordinate alcohol‐induced transcriptome dysregulation and contribute to AUD. Based on RNA‐Sequencing data of human prefrontal cortex, basolateral amygdala and nucleus accumbens of AUD versus non‐AUD brain, the human LINC01265 and its predicted murine homolog Gm41261 (i.e., TX2) were selected for functional interrogation. We tested the hypothesis that TX2 contributes to ethanol drinking and behavioral responses to ethanol. CRISPR/Cas9 mutagenesis was used to create a TX2 mutant mouse line in which 306 base‐pairs were deleted from the locus. RNA analysis revealed that an abnormal TX2 transcript was produced at an unchanged level in mutant animals. Behaviorally, mutant mice had reduced ethanol, gaboxadol and zolpidem‐induced loss of the righting response and reduced tolerance to ethanol in both sexes. In addition, a male‐specific reduction in two‐bottle choice every‐other‐day ethanol drinking was observed. Male TX2 mutants exhibited evidence of enhanced GABA release and altered GABAA receptor subunit composition in neurons of the nucleus accumbens shell. In C57BL6/J mice, TX2 within the cortex was cytoplasmic and largely present in Rbfox3+ neurons and IBA1+ microglia, but not in Olig2+ oligodendrocytes or in the majority of GFAP+ astrocytes. These data support the hypothesis that TX2 mutagenesis and dysregulation impacts ethanol drinking behavior and ethanol‐induced behavioral responses in mice, likely through alterations in the GABAergic system.
Multi‐ecosystem services differently affected by over‐canopy and understory nitrogen additions in a typical subtropical forest
Authors: Tian Yang , Zhou Peng , Zhou Lang , Zhang Lei , Lin Yongbiao , Wang Yanjia , Wang Jun , Hui Dafeng , Ren Hai , Lu Hongfang
Published: February 2024

Obtaining a holistic understanding of the impacts of atmospheric nitrogen deposition on multiple ecosystem services of forest is essential for developing comprehensive and sustainable strategies, particularly in heavy N deposition regions such as subtropical China. However, such impacts remain incompletely understood, with most previous studies focus on individual ecosystem function or service via understory N addition experiments. To address this knowledge gap, we quantified the effects of over‐canopy and understory N additions on multiple ecosystem services based on a 7‐year large‐scale field experiment in a typical subtropical forest. Our results showed continued over‐canopy N addition with 50 kg ha−1 year−1 over a period of 4–7 years significantly increased plant nutrient retention, but did not affect the services of soil nutrient accumulation, water yield, C sequestration (in plants and soil), or oxygen release. There were trade‐offs between the soil and plant on providing the services of nutrient accumulation/retention and C sequestration under over‐canopy N addition. However, without uptake and retention of tree canopy, the trade‐off between soil and plant were more weaken under the understory N addition with 50 kg ha−1 year−1, and their relationships were even synergetic under the understory N addition with 25 kg ha−1 year−1. The results suggest that understory N addition cannot accurately simulate the effects of atmospheric N deposition on multiple services, along with mutual relationships. Interestingly, the services of plant N, P retention, and C sequestration exhibited a synergetic increase under the over‐canopy N addition but a decrease under the understory N addition. Our results also found tree layer plays a primary role in providing plant nutrient retention service and is sensitive to atmospheric N deposition. Further studies are needed to investigate the generalized effects of forest canopy processes on alleviating the threaten of global change factors in different forest ecosystems.
Growth responses to waterlogging stress among cool‐season grass species
Authors: Braun Ross C. , Patton Aaron J.
Published: February 2024

Urban grasslands span climates and topography in soils with variable water infiltration and drainage rates that result in occasional waterlogging stress, while data on grass species tolerance to waterlogging stress is scant. Whole plant responses to waterlogging stress among cool‐season grass species were quantified in a controlled environment. The following grasses were grown in well‐drained vs. waterlogged soil for 55 d: strong creeping red fescue (Festuca rubra ssp. rubra), slender creeping red fescue (F. rubra ssp. littoralis), Chewings fescue (F. rubra ssp. commutata), hard fescue (F. brevipila), tall fescue (F. arundinacea syn. Schedonorus arundinaceus), Kentucky bluegrasses (Poa pratensis), annual bluegrass (P. annua), rough bluegrass (P. trivialis), creeping bentgrass (Agrostis stolonifera), perennial ryegrass (Lolium perenne), and alkaligrass (Puccinellia distans). Five cultivars of each fine fescue (Festuca spp.) taxon were included for comparison. When grown in waterlogged soil compared to well‐drained conditions, relative differences generally ranged from −3% to −26% (shoots) and −13% to −33% (roots) for creeping bentgrass, tall fescue, and Kentucky bluegrass indicating higher waterlogging stress tolerance. The relative differences ranged from −18% to −43% in shoots and −3% to −34% in roots for annual bluegrass and perennial ryegrass indicating fair performance under waterlogging stress. Fine fescues, rough bluegrass, and alkaligrass exhibited the poorest performance during waterlogging stress with plant responses ranging from −12% to −64% (shoots) and −17% to −73% (roots). Negative whole plant responses among cultivars of four fine fescue taxa were similar. The selection of grasses tolerant to waterlogging stress will be important in developing resilient landscapes.
Electronic monitoring of working time and labour market outcomes: Evidence from Brazil
Authors: Lira Ísis F. , de Carvalho Schiavon Laura , da Silva Freguglia Ricardo
Published: February 2024

This study analyses the dynamics of registered firms after implementing a new law (2009) in the Brazilian labour market. The law proposed the electronic monitoring of working time to provide more efficiency and security by standardizing the equipment used for control and avoiding manipulation. As stricter monitoring may increase costs, this paper seeks to analyse whether there have been changes in the dynamics of firms adapting to the new regulation. There are two potential mechanisms as a reference: increasing wages and decreasing workers (or contracted hours), and increasing labour force and decreasing contracted hours per worker (and therefore the monthly wage). Using Brazilian employee–employer data and the difference‐in‐differences approach as an empirical strategy, our main findings suggest that firms that adapt to the new electronic workday control had a general reduction in the number of hours hired, an increase in wages for companies with 10–50 employees and a decrease in workplace accidents in firms with 50 or more employees.
A configurational theory of digital disruption
Authors: Huang Sha , Burton‐Jones Andrew , Xu Dongming
Published: February 2024

Digital Disruption (DD) has become a hot topic in recent years, yet detailed research is surprisingly lacking. The literature offers almost no insights into how DD occurs at the industry level and what industry factors influence it. This paper advances knowledge of DD by developing and testing a configurational theory. Using a multi‐method research design, we identify two types of DD and four industry factors (downstream DD, digitally enabled structural conflict, transferability of core competitive elements, and industry player size) that contingently lead to the different types of DD. We integrate those findings into a configurational theory that describes causal recipes of how these factors or conditions combine to produce the outcome of transformational DD and destructive DD. The theory offers important implications for researchers and practitioners. The research also contributes methodologically by demonstrating the merits of combining grounded theory with qualitative comparative analysis (QCA) to expand the theory‐building potential of QCA.
Effects of water on cold‐sintered highly dense dicalcium phosphate anhydrous bioceramic using its hydrate
Authors: Wang Xu , Zhang Hexin , Yu Xiao , Mo Xiumei , Gao Jie , Hu Yunfeng , Min Jie , Ding Qi , Fan Yuchi , Jiang Wan
Published: February 2024

The dicalcium phosphate anhydrous (DCPA, CaHPO4) bioceramic has long been difficult to prepare by conventional sintering techniques due to its weak thermal stability. Here, the DCPA ceramic is prepared at 250°C by cold sintering process (CSP) using the dicalcium phosphate dihydrate (DCPD, CaHPO4·2H2O) as the starting powder. It is found that the dehydration temperature of DCPD powder is greatly reduced during CSP, which facilitates the densification even without additive water. However, the ceramic only reaches a relatively low density of around 90% without additive water, which can be ascribed to the lack of particle rearrangement and the readily loss of dehydration water during sintering. In comparison, a high relative density of 95% can be obtained when the DCPD hydrate is densified with additive water, in which both hydration water and additive water play important roles. The obtained DCPA ceramic with high density exhibits a flexural strength of 46.17 MPa and Young's modulus closer to human bones compared with hydroxyapatite. Combined with the low cytotoxicity, the DCPA bioceramic has great potential to be applied for bone tissue engineering.
Which pedagogical approaches are more effective in mobile learning? A meta‐analysis and research synthesis
Authors: Tlili Ahmed , Salha Soheil , Garzón Juan , Denden Mouna , Kinshuk  , Affouneh Saida , Burgos Daniel
Published: February 2024

Background Study

Several meta‐analysis studies have investigated the effects of mobile learning on learning performance. However, limited attention has been paid to pedagogy in mobile learning, making quantitative evidence of the effects of pedagogical approaches on learning performance in mobile learning scarce. Filling this gap can therefore help stakeholders understand which mobile pedagogical approaches might work or not under which learning conditions, hence achieving better learning experience and performance.

Objectives

To address this gap, this study conducted a meta‐analysis and research synthesis of the effects of integrated pedagogical approaches on students' learning performance in mobile learning. Additionally, this study analysed the field of education, level of education, learning setting, sample size, and mobile device as moderating variables of the effect of pedagogical approaches.

Methods

The software Comprehensive Meta‐Analysis V.3 was used for this meta‐analysis, where Hedges' g was calculated for the effect sizes. Specifically, 70 quantitative studies (N = 5575 participants) were coded and analysed.

Results

The results indicate that pedagogical approaches in mobile learning have a large effect on students' learning performance (g = 0.93, p < 0.001). The most effective pedagogical approach was project‐based learning (huge effect), while collaborative learning, situated learning and game‐based learning had large effects. Finally, cognitive theory of multimedia learning and inquiry‐based learning had medium effects. The results also indicate that the effect is moderated by the field of education, the level of education, the learning setting, the sample size, and the mobile device. Finally, it is found that study quality might influence the overall effect size.

Conclusions

The findings of this study can be beneficial to both researchers and practitioners as they highlight and discuss which pedagogical approaches could be more effective in mobile learning under specific conditions. Further research, on the other hand, should focus on covering additional moderators of learning performance like mobile device type and screen size which is one of the limitations of this study.
The impact of genomic distance on enhancer‐promoter interactions at the CFTR locus
Authors: Kerschner Jenny L. , Meckler Frederick , Coatti Giuliana C. , Vaghela Nirbhayaditya , Paranjapye Alekh , Harris Ann
Published: February 2024

We identified and characterized multiple cell‐type selective enhancers of the CFTR gene promoter in previous work and demonstrated active looping of these elements to the promoter. Here we address the impact of genomic spacing on these enhancer:promoter interactions and on CFTR gene expression. Using CRISPR/Cas9, we generated clonal cell lines with deletions between the −35 kb airway enhancer and the CFTR promoter in the 16HBE14o− airway cell line, or between the intron 1 (185 + 10 kb) intestinal enhancer and the promoter in the Caco2 intestinal cell line. The effect of these deletions on CFTR transcript abundance, as well as the 3D looping structure of the locus was investigated in triplicate clones of each modification. Our results indicate that both small and larger deletions upstream of the promoter can perturb CFTR expression and −35 kb enhancer:promoter interactions in the airway cells, though the larger deletions are more impactful. In contrast, the small intronic deletions have no effect on CFTR expression and intron 1 enhancer:promoter interactions in the intestinal cells, whereas larger deletions do. Clonal variation following a specific CFTR modification is a confounding factor particularly in 16HBE14o− cells.
Corticosteroid‐triggered acute skeletal muscle loss in lipodystrophy: A case report
Authors: Sasako Takayoshi , Suzuki Ken , Odawara Sara , Suwanai Hirotsugu , Akuta Naoko , Kubota Naoto , Ueki Kohjiro , Kadowaki Takashi , Yamauchi Toshimasa
Published: February 2024

The potential liability to hypercatabolism in lipodystrophy remains to be fully elucidated. Here we report a 28‐year‐old Japanese woman with acquired generalized lipodystrophy, who presented with recurrence of panniculitis and anemia. After corticosteroid treatment was started, she showed rapid reductions in body weight and lean mass by 15% at maximum, accompanied by an elevated urea nitrogen/creatinine ratio, which recovered almost fully as the corticosteroid treatment was tapered and discontinued. She had multiple risk factors for hypercatabolism: lack of metabolic reserves, insulin resistance, and hyperglycemia due to lipodystrophy, lowered daily activity due to anemia, persistent inflammation, and wasting associated with panniculitis, and relatively insufficient energy and protein intake during hospitalization. More attention should be paid to the potential liability to hypercatabolism in patients with lipodystrophy, and to skeletal muscle loss as an adverse effect of corticosteroid treatment in patients at high risk, such as those with diabetes or decreased metabolic reserves.
TET1 inhibits liver fibrosis by blocking hepatic stellate cell activation
Authors: Wang Jingjie , Zhang Yitong , Ma Yanyun , Zhao Suhan , Wang Jiucun , Chen Hongtan , Zhang Jun , Liu Jie
Published: February 2024

Hepatic stellate cells (HSCs) are critical regulator contributing to the onset and progression of liver fibrosis. Chronic liver injury triggers HSCs to undergo vast changes and trans‐differentiation into a myofibroblast HSCs, the mechanism remains to be elucidated. This study investigated that the involvement of hydroxymethylase TET1 (ten–eleven translocation 1) in HSC activation and liver fibrosis. It is revealed that TET1 levels were downregulated in the livers in mouse models of liver fibrosis and patients with cirrhosis, as well as activated HSCs in comparison to quiescent HSCs. In vitro data showed that the inhibition of TET1 promoted the activation HSC, whereas TET1 overexpression inhibited HSC activation. Moreover, TET1 could regulate KLF2 (Kruppel‐like transcription factors) transcription by promoting hydroxymethylation of its promoter, which in turn suppressed the activation of HSCs. In vivo, it is confirmed that liver fibrosis was aggravated in Tet1 knockout mice after CCl4 injection, accompanied by excessive activation of primary stellate cells, in contrast to wild‐type mice. In conclusion, we suggested that TET1 plays a significant role in HSC activation and liver fibrosis, which provides a promising target for anti‐fibrotic therapies.
Perspectives of Certified Nurse‐Midwives and Physicians on the Structural and Institutional Barriers that Contribute to the Reproductive Inequities of Black Birthing People in the San Francisco Bay Area
Authors: Nelson Tamara J. , Butcher Brittany D. Chambers , Delgado Ana , McLemore Monica R.
Published: February 2024

Introduction

Black birthing people in the United States disproportionately endure inequitable experiences and outcomes during pregnancy and childbirth via structural, interpersonal, and obstetric racism. In this study, the researchers explore provider perspectives of how racism is perpetuated in institutional perinatal and reproductive health care.

Methods

Critical Race Theory, Reproductive Justice, and midwifery theory were operationalized through secondary thematic analysis of existing qualitative data from the Community Racial Equity and Training Interventions and Evaluation of Current and Future Healthcare Clinicians Study. Twenty‐four perinatal providers (certified nurse‐midwives [n = 7] and physicians [n = 17]) voluntarily participated in interviews. A comparative approach was used to determine how professional identity and model of care influence physicians’ and certified nurse‐midwives’ perceptions of equity.

Results

Thematic analysis produced 5 themes: racism as a comorbidity, health care systems’ inability to address the needs of Black birthing people, health care systems prioritizing providers over patients are failed systems, patients are the experts in the optimal health care model, and benefits of interprofessional teams grounded in Reproductive Justice. Additionally, both physicians and midwives expressed a need for a new care model.

Discussion

With these findings, our team proposes a modification of the midwifery model for application by all provider types that could radically shift the experience and outcomes of perinatal and reproductive health care and reduce mortality. Using a human rights approach to care, a Reproductive Justice–Public Health Critical Race praxis–informed midwifery model may be operationalized by all perinatal and reproductive health care providers. This novel model reflects an iterative process that may offer institutions and providers methods to build on past research supporting midwifery‐centered care for improving outcomes for all patients by specifically focusing on improving care of Black birthing people. The implications of this work offer broad application in current clinical practice, quality improvement, research, technology, and patient resources.
Lipid imaging of Alzheimer's disease pathology
Authors: Hanrieder Jörg
Published: February 2024

Alzheimer's disease (AD) affects one in eight individuals over 65 and poses an immense societal challenge. AD pathology is characterized by the formation of beta‐amyloid plaques and Tau tangles in the brain. While some disease‐modifying treatments targeting beta‐amyloid are emerging, the exact chain of events underlying the pathogenesis of this disease remains unclear. Brain lipids have long been implicated in AD pathology, though their role in AD pathogenesis remains not fully resolved. Significant advancements in mass spectrometry imaging (MSI) allow to detail spatial lipid regulations in biological tissues at the low um scale. In this issue, Huang et al. resolve spatial lipid patterns in human AD brain and genetic mouse models using desorption electrospray ionization (DESI)‐based MSI integrated with other spatial techniques such as imaging mass cytometry of correlative protein signatures. Those spatial multiomics experiments identify plaque‐associated lipid regulations that are dependent on progressing plaque pathology in both mouse models and the human brain. Of those lipid species, particularly pro‐inflammatory lysophospholipids have been implicated in AD pathology through their interaction with both aggregating Aβ and microglial activation through lipid sensing surface receptors. Together, this study provides further insight into how brain lipid homeostasis is linked to progressing AD pathology, and thereby highlights the potential of MSI‐based spatial lipidomics as an emerging spatial biology technology for biomedical research.
A phylogenetic framework to study desirable traits in the wild relatives of Theobroma cacao (Malvaceae)
Authors: Bossa‐Castro Ana M. , Colli‐Silva Matheus , Pirani José R. , Whitlock Barbara A. , Morales Mancera Laura T. , Contreras‐Ortiz Natalia , Cepeda‐Hernández Martha L. , Di Palma Federica , Vives Martha , Richardson James E.
Published: February 2024

Crop wild relatives (CWRs) of cultivated species may provide a source of genetic variation that can contribute to improving product quantity and quality. To adequately use these potential resources, it is useful to understand how CWRs are related to the cultivated species and to each other to determine how key crop traits have evolved and discover potentially usable genetic information. The chocolate industry is expanding and yet is under threat from a variety of causes, including pathogens and climate change. Theobroma cacao L. (Malvaceae), the source of chocolate, is a representative of the tribe Theobromateae that consists of four genera and c. 40 species that began to diversify over 25 million years ago. The great diversity within the tribe suggests that its representatives could exhibit advantageous agronomic traits. In this study, we present the most taxonomically comprehensive phylogeny of Theobromateae to date. DNA sequence data from WRKY genes were assembled into a matrix that included 56 morphological characters and analyzed using a Bayesian approach. The inclusion of a morphological data set increased resolution and support for some branches of the phylogenetic tree. The evolutionary trajectory of selected morphological characters was reconstructed onto the phylogeny. This phylogeny provides a framework for the study of morphological and physiological trait evolution, which can facilitate the search for agronomically relevant traits.
A daytime nap with REM sleep is linked to enhanced generalization of emotional stimuli
Authors: Reichardt Richárd , Király Anna , Szőllősi Ágnes , Racsmány Mihály , Simor Péter
Published: February 2024

How memory representations are shaped during and after their encoding is a central question in the study of human memory. Recognition responses to stimuli that are similar to those observed previously can hint at the fidelity of the memories or point to processes of generalization at the expense of precise memory representations. Experimental studies utilizing this approach showed that emotions and sleep both influence these responses. Sleep, and more specifically rapid eye movement sleep, is assumed to facilitate the generalization of emotional memories. We studied mnemonic discrimination by the emotional variant of the Mnemonic Separation Task in participants (N = 113) who spent a daytime nap between learning and testing compared with another group that spent an equivalent time awake between the two sessions. Our findings indicate that the discrimination of similar but previously not seen items from previously seen ones is enhanced in case of negative compared with neutral and positive stimuli. Moreover, whereas the sleep and the wake groups did not differ in memory performance, participants entering rapid eye movement sleep exhibited increased generalization of emotional memories. Our findings indicate that entering into rapid eye movement sleep during a daytime nap shapes emotional memories in a way that enhances recognition at the expense of detailed memory representations.
A contactless cure: Leveraging telehealth to improve hepatitis C treatment at a safety‐net hospital
Authors: Frye Krysta , Davis Andrew , Darby Rapheisha , McDaniel Kathryn , Quairoli Kristi , Liu Zhanxu , Miller Lesley S. , Fluker Shelly‐Ann
Published: February 2024

Hepatitis C virus (HCV) causes significant mortality worldwide. HCV is highly curable but access to care is limited for many patients. The Grady Liver Clinic (GLC), a primary care‐based HCV clinic, utilizes a multidisciplinary team to provide comprehensive care for a medically underserved patient population in Atlanta, Georgia. The GLC added a telehealth option for HCV treatment at the start of the COVID‐19 pandemic. We describe the outcomes of utilizing telehealth in this population. We performed a retrospective chart review of patients who initiated HCV treatment from March 2019 to February 2020 (pre‐pandemic) and March 2020 to February 2021 (pandemic). Charts were abstracted for patient demographics and characteristics, treatment regimen, and treatment outcomes. Our primary outcome was HCV cure rate of the pre‐pandemic compared to the pandemic cohorts and within the different pandemic cohort visit types. We performed an intention‐to‐treat (ITT) analysis for all patients who took at least one dose of a direct‐acting antiviral (DAA) regardless of therapy completion, and a per‐protocol (PP) analysis of those who completed treatment and were tested for HCV cure. SVR12 rates were >95% on ITT analysis, with no significant difference between pre‐pandemic and pandemic cohorts. There was also no significant difference within the pandemic group when treatment was provided traditionally, via telehealth, or via a hybrid of these. Our findings support the use of telehealth as a tool to expand access to HCV treatment in a medically underserved patient population.
Bacteriophage lambda site‐specific recombination
Authors: Van Duyne Gregory D. , Landy Arthur
Published: February 2024

The site‐specific recombination pathway of bacteriophage λ encompasses isoenergetic but highly directional and tightly regulated integrative and excisive reactions that integrate and excise the vial chromosome into and out of the bacterial chromosome. The reactions require 240 bp of phage DNA and 21 bp of bacterial DNA comprising 16 protein binding sites that are differentially used in each pathway by the phage‐encoded Int and Xis proteins and the host‐encoded integration host factor and factor for inversion stimulation proteins. Structures of higher‐order protein–DNA complexes of the four‐way Holliday junction recombination intermediates provided clarifying insights into the mechanisms, directionality, and regulation of these two pathways, which are tightly linked to the physiology of the bacterial host cell. Here we review our current understanding of the mechanisms responsible for regulating and executing λ site‐specific recombination, with an emphasis on key studies completed over the last decade.
Factors influencing health‐related quality of life in women with endometriosis: A cross‐sectional study
Authors: Wu Yueh‐Hsiang , Lu Yu‐Ying , Liu Kuei Fen
Published: February 2024

This study aimed to assess the health‐related quality of life and identify its associated factors in women with endometriosis. A cross‐sectional correlation study design and convenience sampling were conducted in the gynecological outpatient clinic of a teaching hospital in northern Taiwan. A total of 216 women with endometriosis were recruited. The data were collected using structured questionnaires and analyzed using descriptive and inferential statistics. Participants reported a moderate level of health‐related quality of life. The most significant impact of endometriosis on health‐related quality of life was emotional well‐being, followed by feeling of control or powerless, pain, social support, and self‐image. Educational attainment, menstrual cycle, period length, perceived menstrual flow, symptom distress, and self‐management strategies explained 66% of the variance in health‐related quality of life. Factors influencing health‐related quality of life in women with endometriosis play a key role in promoting women's well‐being. Interventions based on these related factors should be developed and taken into practice to effectively manage the disease‐related symptoms for women with endometriosis and thereby improve their overall health‐related quality of life.
Ciliary muscle and anterior segment characteristics in pre‐presbyopic adults with Down syndrome
Authors: Vinuela‐Navarro Valldeflors , Baker Fiona Jane , Woodhouse J. Margaret , Sheppard Amy L.
Published: February 2024

Purpose

Previous research has shown that accommodation deficits are common in individuals with Down syndrome (DS), but the origin and mechanisms behind these deficits are still unknown. The aim of this study was to investigate the characteristics of different ocular structures involved in accommodation, in particular the ciliary muscle (CM), in a population of individuals with DS to further understand this deficit and its mechanisms.

Methods

Thirty‐two volunteer participants of pre‐presbyopic age with (n = 16) and without DS (n = 16) were recruited. Temporal and nasal images of the CM were acquired using anterior segment optical coherence tomography (AS‐OCT) while participants fixated an eccentrically located target. Analysis of CM parameters was undertaken using validated semi‐automated software. Axial length, anterior chamber depth, lens thickness and corneal curvature were obtained with the Topcon Aladdin Optical Biometer and Corneal Topographer. Non‐cycloplegic refractive error and accommodative ability were obtained with an open‐field autorefractor and dynamic retinoscopy, respectively. Independent t‐tests were conducted to determine differences in CM and other anterior segment parameters between participants with and without DS.

Results

No significant differences were found in the CM parameters studied between participants with and without DS (p > 0.05). In contrast, significant differences were found in visual acuity (p < 0.001), accommodative response (p < 0.001) and corneal curvature (K1 p = 0.003 and K2 p < 0.001) between participants with and without DS.

Conclusions

Despite having poorer accommodation, pre‐presbyopic adults with DS do not have a different CM morphology to that found in typically developing adults. These findings suggest that the accommodative deficit found in this population is not due to a mechanical deficit of the CM.
Singlet oxygen signalling and its potential roles in plant biotic interactions
Authors: Goggin Fiona L. , Fischer Hillary D.
Published: February 2024

Singlet oxygen (SO) is among the most potent reactive oxygen species, and readily oxidizes proteins, lipids and DNA. It can be generated at the plant surface by phototoxins in the epidermis, acting as a direct defense against pathogens and herbivores (including humans). SO can also accumulate within mitochondria, peroxisomes, cytosol and the nucleus through multiple enzymatic and nonenzymatic processes. However, the majority of research on intracellular SO generation in plants has focused on transfer of light energy to triplet oxygen by photopigments from the chloroplast. SO accumulates in response to diverse stresses that perturb chloroplast metabolism, and while its high reactivity limits diffusion distances, it participates in retrograde signalling through the EXECUTER1 sensor, generation of carotenoid metabolites and possibly other unknown pathways. SO thereby reprogrammes nuclear gene expression and modulates hormone signalling and programmed cell death. While SO signalling has long been known to regulate plant responses to high‐light stress, recent literature also suggests a role in plant interactions with insects, bacteria and fungi. The goals of this review are to provide a brief overview of SO, summarize evidence for its involvement in biotic stress responses and discuss future directions for the study of SO in defense signalling.
Rhizosphere priming promotes plant nitrogen acquisition by microbial necromass recycling
Authors: Pausch Johanna , Holz Maire , Zhu Biao , Cheng Weixin
Published: February 2024

Nitrogen availability in the rhizosphere relies on root‐microorganism interactions, where root exudates trigger soil organic matter (SOM) decomposition through the rhizosphere priming effect (RPE). Though microbial necromass contribute significantly to organically bound soil nitrogen (N), the role of RPEs in regulating necromass recycling and plant nitrogen acquisition has received limited attention. We used 15N natural abundance as a proxy for necromass‐N since necromass is enriched in 15N compared to other soil‐N forms. We combined studies using the same experimental design for continuous 13CO2 labelling of various plant species and the same soil type, but considering top‐ and subsoil. RPE were quantified as difference in SOM‐decomposition between planted and unplanted soils. Results showed higher plant N uptake as RPEs increased. The positive relationship between 15N‐enrichment of shoots and roots and RPEs indicated an enhanced necromass‐N turnover by RPE. Moreover, our data revealed that RPEs were saturated with increasing carbon (C) input via rhizodeposition in topsoil. In subsoil, RPEs increased linearly within a small range of C input indicating a strong effect of root‐released C on decomposition rates in deeper soil horizons. Overall, this study confirmed the functional importance of rhizosphere C input for plant N acquisition through enhanced necromass turnover by RPEs.
Complement receptor 3 is required for maximum in vitro trogocytic killing of the parasite Trichomonas vaginalis by human neutrophil‐like cells
Authors: Trujillo Emma N. , Flores Barbara A. , Romero Isabel V. , Moran Jose A. , Leka Aljona , Ramirez Ashley D. , Ear Jason , Mercer Frances
Published: February 2024

Trichomonas vaginalis (Tv) is a parasite that causes trichomoniasis, a prevalent sexually‐transmitted infection. Neutrophils are found at the site of infection, and can rapidly kill the parasite in vitro, using trogocytosis. However, the specific molecular players in neutrophil killing of Tv are unknown. Here, we show that complement proteins play a role in Tv killing by human neutrophil‐like cells (NLCs). Using CRISPR/Cas9, we generated NLCs deficient in each of three complement receptors (CRs) known to be expressed on human neutrophils: CR1, CR3, and CR4. Using in vitro trogocytosis assays, we found that CR3, but not CR1 or CR4 is required for maximum trogocytosis of the parasite by NLCs, with NLCs lacking CR3 demonstrating ~40% reduction in trogocytosis, on average. We also observed a reduction in NLC killing of Tv in CR3 knockout, but not CR1 or CR4 knockout NLCs. On average, NLCs lacking CR3 had ~50% reduction in killing activity. We also used a parallel approach of pre‐incubating NLCs with blocking antibodies against CR3, which similarly reduced NLC killing of parasites. These data support a model in which Tv is opsonized by the complement protein iC3b, and bound by neutrophil CR3 receptor, to facilitate trogocytic killing of the parasite.
Reduction in creatine metabolites in macrophages exposed to small molecule analogues of the anti‐inflammatory parasitic worm product ES‐62
Authors: Alanazi S. , Doonan J. , Lumb F. E. , Alenzi N. , Jabbar S. , Al‐Riyami L. , Suckling C. J. , Harnett W. , Watson D. G.
Published: February 2024

ES‐62, a protein secreted by Acanthocheilonema viteae, is anti‐inflammatory by virtue of covalently attached phosphorylcholine (PC) residues and thus a library of drug‐like small molecule analogues (SMAs) based on its PC moieties has been designed for therapeutic purposes. Two members, SMAs 11a and 12b, were previously found to suppress production of pro‐inflammatory cytokines by mouse bone marrow‐derived macrophages (BMMs) exposed to cytosine‐phosphate‐guanosine oligodeoxynucleotides (CpG), agonists for Toll‐like receptor 9. In order to explore the mechanism of action underlying such activities, an untargeted mass spectrometry‐based metabolomics screen was undertaken. Stimulation of BMMs with CpG produced significant metabolic changes relating to glycolysis and the TCA cycle but the SMAs had little impact on this. Also, the SMAs did not promote alterations in metabolites known to be associated with macrophage M1/M2 polarization. Rather, BMMs exposed to SMAs 11a or 12b prior to CpG treatment, or even alone, revealed downregulation of metabolites of creatine, a molecule whose major role is in the transport of high energy phosphate from the mitochondria to the cytosol. These data therefore provide insight into a possible mechanism of action of molecules with significant therapeutic potential that has not previously been described for parasitic worm products.
The relative effects of artificial shrubs on animal community assembly
Authors: Zuliani Mario , Ghazian Nargol , MacDonald Suzanne , Lortie Christopher J.
Published: February 2024

Facilitative associations between the foundational shrub species Ephedra californica and local vertebrate species can drive positive interactions within desert ecosystems that influence diversity and assembly processes. These foundational shrubs can contribute to the structural heterogeneity of ecosystems for plants and animals including variation in temperature profiles, refuge from predation, and habitat for foraging. Artificial structures can also influence fine‐scale ecological and micro‐environmental dynamics. We tested the hypothesis that artificial shrubs (mimics) positively influence desert vertebrate association through facilitative interactions, similar to foundational shrub species. Mimics were deployed at four distinct sites within the central deserts of Southern California. A combination of camera traps and temperature pendants were utilized to measure the association patterns of vertebrate species and the microclimatic variation at mimic, open, and shrubs. A total of 21 species were observed in this study. Mimics had a significantly higher vertebrate abundance and richness than open microsites and functioned similarly to shrubs. These findings suggest that mimics can be utilized as a stop‐gap replacement for foundational shrub species as they can act as a novel fine‐scale habitat for many desert vertebrate species.
Next‐generation sequencing identifies four novel HLA class I alleles with nucleotide substitutions in the 3′ UTR
Authors: Niño Ramírez Jairo Eduardo , Gil‐Etayo Francisco Javier , Jiménez Hernaz Isabel , Arroyo‐Sánchez Daniel , Tejeda Velarde Amalia
Published: February 2024

Characterization by next‐generation sequencing of four novel HLA alleles: C*17:03:01:07, C*16:01:01:39, B*15:17:01:07, and B*44:03:01:57.
Characterization of the novel HLA‐DRB1*16:76 allele in a Chinese individual
Authors: Ren Zhixiang , Li Pei‐Heng , Hao Qing , Xu Heng , Shi Yun‐Ying
Published: February 2024

The HLA‐DRB1*16:76 allele differs from HLA‐DRB1*16:02:01 by one nucleotide substitution (A > G) at position 37 in exon 1.
A novel HLA‐C*02:10 variant, HLA‐C*02:10:09, identified in a healthy individual from Brazil
Authors: Stelet Vinícius N. , Romero Matilde , Cita Rafael F. , Binato Renata , Abdelhay Eliana
Published: February 2024

Identification of the novel HLA‐C*02:10:09 allele that differs from HLA‐C*02:10:01:01 at one position in exon 1.
Demushkin groups of uncountable rank
Authors: Bar‐On Tamar , Nikolov Nikolay
Published: February 2024

We extend the theory of countably generated Demushkin groups to Demushkin groups of arbitrary rank. We investigate their algebraic properties and invariants, count their isomorphism classes, and study their realization as absolute Galois group. At the end, we compute their profinite completion and conclude with some results on profinite completion of absolute Galois groups.
Impact of Sources of Damping on the Fragility Estimates of Wind Turbine Towers
Authors: Baisthakur Shubham , Pakrashi Vikram , Bhattacharya Subhamoy , Fitzgerald Breiffni
Published: February 2024

Fragility estimates in wind turbine towers have been investigated but the effect of damping on fragility has not been studied. While damping can often be small, it can come from different sources for a wind turbine. This paper demonstrates that even for small levels of equivalent viscous damping, a combination of sources can have a significant impact on the estimate of the fragility of a wind turbine in operational conditions. The widely studied 5 MW reference wind turbine is considered for this study. The fragility analysis is performed considering the tower fore-aft displacement and acceleration responses. The impact of different sources of damping on fragility is estimated and ranked to qualitatively understand the impact of damping on the lifetime performance of the tower and develop approximate estimates of their quantitative changes.
Calculation and Uncertainty Analysis of Core Parameters of Advanced Lead-Cooled Modular Nuclear Reactor Using New Nuclear Data Libraries
Authors: Vu Thanh Mai , Tran Le Quang Linh , Bui Thi Hong , Pham Nhu Viet Ha
Published: February 2024

A small modular lead-cooled fast spectrum core concept called Advanced lead-cooled modular nuclear reactor (ALMANAR) designed to produce 45 MWth power for 22 years operating without refueling was proposed in a previous study. The neutronics investigation showed its excellent inherent safety features. It could be considered as a candidate for future electricity source for the near future. It is noteworthy that the target accuracy for eigenvalue calculation for keff regardless of spectrum is set to 300 pcm. However, findings in this analysis revealed that the keff uncertainty was larger for the recently released nuclear data libraries (about 800 pcm), mostly from 235U capture cross section (624 pcm) in the case of ENDF/B-VIII.0 and 238U inelastic scattering cross section (437 pcm) in the case of JENDL-5. Selected kinetic parameters of the ALMANAR core and their uncertainty were also evaluated and analyzed. No major impact on the total βeff, leff, and λeff simulation results was found. In order to improve the reliability of criticality calculations of the lead-cooled small fast reactor, the accuracy of capture and fission cross section of 235,238U, the capture cross section of 10B and the elastic scattering cross section of 208Pb at the fast energy range of ENDF/B-VIII.0 should be improved. Furthermore, the inelastic scattering and capture cross section of 238U, fission and capture cross section of 235U and the capture cross section of 10B of JENDL-5 should also be improved.