bluuebunny/crossref_metadata_2025 huggingface dataset:
How do engineered Yarrowia lipolytica strains secrete free fatty acids: hints from comparative transcriptomics
Authors: Salvador López José Manuel , Vidal Lea , Adiutama Michelle Patricia , Van Nieuwerburgh Filip , Deforce Dieter , Nicaud Jean-Marc , Van Bogaert Inge Noëlle Adrienne
Published: May 2023

Yarrowia lipolytica has been considered one of the most promising platforms for the microbial production of fatty acids and derived products. The deletion of the faa1 gene coding for an acyl-CoA synthetase leads to the accumulation and secretion of free fatty acids (FFAs) into the extracellular space. The secretion of products is beneficial for the development of microbial cell factories to avoid intracellular inhibitory effects and reduce downstream processing costs. However, the mechanism behind the secretion of fatty acids is not well known. As a starting point, we compared the transcriptome of this mutant showing FFA secretion to a wildtype-like strain not showing this phenotype. The 12 most upregulated genes were evaluated for involvement in FFA secretion by the creation of deletion and overexpression mutants, among them MCH2, YMOH, three cell wall proteins CWP3, CWP4, and CWP11, M12B, and three proteins with unknown functions YUP1, YUP2, and YUP3. None of these proteins take a clear or isolated role in FFA export. As the transcriptomic data revealed an overrepresentation of cell wall-related proteins, some of them were further examined on a theoretical and experimental way. Surprisingly, overexpression of Ygpi led to the production of FFAs in the wildtype-like genetic background. Finally, some of the evaluated genes showed involvement in resistance to FFA toxicity.
Feasibility of the Implementation of LESS-CHRON in Clinical Practice: A Pilot Intervention Study in Older Patients With Multimorbidity
Authors: Mejías-Trueba Marta , Rodríguez-Pérez Aitana , Hernández-Quiles Carlos , Ollero-Baturone Manuel , Nieto-Martín María Dolores , Sánchez-Fidalgo Susana
Published: May 2023

Background and Objectives

Potentially inappropriate medication refers to the prescription of drugs whose risks outweigh the benefits. There are different pharmacotherapeutic optimization strategies to detect and avoid potentially inappropriate medications (PIMs), namely deprescription. The List of Evidence-Based Deprescribing for Chronic Patients (LESS-CHRON) criteria were designed as a tool to systematize the deprescribing process. LESS-CHRON has established itself as one of the most suitable to be applied in older (≥65 years) multimorbid patients. However, it has not been applied to these patients, to measure the impact on their treatment. For this reason, a pilot study was conducted to analyze the feasibility of implementing this tool in a care pathway.

Research Design and Methods

A pre–post quasi-experimental study was conducted. Older outpatients with multimorbidity from the Internal Medicine Unit of a benchmark Hospital were included. The main variable was feasibility in clinical practice, understood as the likelihood that the deprescribing intervention recommended by the pharmacist would be applied to the patient. Success rate, therapeutic, and anticholinergic burden, and other variables related to health care utilization were analyzed.

Results

A total of 95 deprescribing reports were prepared. Forty-three were evaluated by the physician who assessed the recommendations made by pharmacists. This translates into an implementation feasibility of 45.3%. The application of LESS-CHRON identified 92 PIMs. The acceptance rate was 76.7% and after 3 months 82.7% of the stopped drugs remained deprescribed. A reduction in anticholinergic burden and enhanced adherence was achieved. However, no improvement was found in clinical or health care utilization variables.

Discussion and Implications

The implementation of the tool in a care pathway is feasible. The intervention has achieved great acceptance and deprescribing has been successful in a not insignificant percentage. Future studies with a larger sample size are necessary to obtain more robust results in clinical and health care utilization variables.
Siglec cis-ligands and their roles in the immune system
Authors: Tsubata Takeshi
Published: May 2023

Sialic acid-binding immunoglobulin-like lectins are a family of membrane molecules primarily expressed in immune cells. Most of them are inhibitory receptors containing immunoreceptor tyrosine-based inhibition motifs in the cytoplasmic tail. On the cell surface, sialic acid-binding immunoglobulin-like lectins are mostly bound by sialylated glycans on membrane molecules expressed in the same cell (cis-ligands). Although ligands of sialic acid-binding immunoglobulin-like lectins are not efficiently identified by conventional methods such as immunoprecipitation, in situ labeling including proximity labeling is useful in identifying both cis-ligands and the sialylated ligands expressed by other cells (trans-ligands) of sialic acid-binding immunoglobulin-like lectins. Interaction of the inhibitory sialic acid-binding immunoglobulin-like lectins with cis-ligands including both those with and without signaling function modulates the inhibitory activity of sialic acid-binding immunoglobulin-like lectins by multiple different ways. This interaction also modulates signaling function of the cis-ligands. So far, little is known about the role of the interaction between sialic acid-binding immunoglobulin-like lectins and the cis-ligands. Nonetheless, recent studies showed that the inhibitory activity of CD22 (also known as Siglec-2) is regulated by endogenous ligands, most likely cis-ligands, differentially in resting B cells and those in which B-cell antigen receptor is ligated. This differential regulation plays a role in quality control of signaling-competent B cells and also partial restoration of B-cell antigen receptor signaling in immunodeficient B cells.
Multivariate Models of Animal Sex: Breaking Binaries Leads to a Better Understanding of Ecology and Evolution
Authors: McLaughlin J F , Brock Kinsey M , Gates Isabella , Pethkar Anisha , Piattoni Marcus , Rossi Alexis , Lipshutz Sara E
Published: May 2023

Synopsis

“Sex” is often used to describe a suite of phenotypic and genotypic traits of an organism related to reproduction. However, these traits—gamete type, chromosomal inheritance, physiology, morphology, behavior, etc.—are not necessarily coupled, and the rhetorical collapse of variation into a single term elides much of the complexity inherent in sexual phenotypes. We argue that consideration of “sex” as a constructed category operating at multiple biological levels opens up new avenues for inquiry in our study of biological variation. We apply this framework to three case studies that illustrate the diversity of sex variation, from decoupling sexual phenotypes to the evolutionary and ecological consequences of intrasexual polymorphisms. We argue that instead of assuming binary sex in these systems, some may be better categorized as multivariate and nonbinary. Finally, we conduct a meta-analysis of terms used to describe diversity in sexual phenotypes in the scientific literature to highlight how a multivariate model of sex can clarify, rather than cloud, studies of sexual diversity within and across species. We argue that such an expanded framework of “sex” better equips us to understand evolutionary processes, and that as biologists, it is incumbent upon us to push back against misunderstandings of the biology of sexual phenotypes that enact harm on marginalized communities.
Avian Heterothermy: A Review of Patterns and Processes
Authors: McKechnie Andrew E , Freeman Marc T , Brigham R Mark
Published: May 2023

Synopsis

Many birds reduce rest-phase energy demands through heterothermy, physiological responses involving facultative, reversible reductions in metabolic rate and body temperature (Tb). Here, we review the phylogenetic distribution and ecological contexts of avian heterothermy. Heterothermy has been reported in 140 species representing 15 orders and 39 families. Recent work supports the view that deep heterothermy is most pronounced in phylogenetically older taxa whereas heterothermy in passerines and other recently diverged taxa is shallower and confined to minimum Tb > 20°C. The reasons why deep heterothermy is absent in passerines remain unclear; we speculate an evolutionary trade-off may exist between the capacity to achieve low heterothermic Tb and the tolerance of hyperthermic Tb. Inter- and intraspecific variation in heterothermy is correlated with factors including foraging ecology (e.g., territoriality and defense of food resources among hummingbirds), food availability and foraging opportunities (e.g., lunar phase predicts torpor use in caprimulgids), and predation risk. Heterothermy also plays a major role before and during migration. Emerging questions include the magnitude of energy savings associated with heterothermy among free-ranging birds, the role phylogenetic variation in the capacity for heterothermy has played in evolutionary radiations into extreme habitats, and how the capacity for heterothermy affects avian vulnerability to rapid anthropogenic climate change.
Skeletal dosimetry in a microCT image-based rat model for external photon irradiation
Authors: Zhang Xiaomin , Xu Xu , Ning Jing , Yuan Yong , Li Dawei , Ji Yunlong
Published: May 2023

Human skeletal dosimetry has experienced great developments in radiation protection in recent years by using the heterogeneous skeletal model. While for the rats experimentally used in radiation medicine, the investigation on skeletal dosimetry were mainly based on the homogeneous skeletal model, leading to inaccurate assessments of dose to radiosensitive tissues of red bone marrow (RBM) and bone surface. The purpose of this study is to develop a rat model with heterogeneous skeletal system and to investigate the dose difference in bone tissues for external photon irradiation. The high resolution of microCT images of a rat weighing 335 g were segmented into bone cortical, bone trabecular, bone marrow as well as other organs to construct the rat model. The absorbed dose to bone cortical, bone trabecular and bone marrow were calculated respectively by using Monte Carlo simulation for 22 external monoenergetic photon beams between 10 keV and 10 MeV under four different irradiation geometries conditions (left lateral [LL], right lateral [RL], dorsal–ventral [DV], ventral–dorsal [VD]). The calculated absorbed dose data were expressed as dose conversion coefficients and presented in this article, and the effect of irradiation conditions, photon energies and bone tissues density on the skeletal dose was discussed. The results showed that the dose conversion coefficients varying the photon energy for bone cortical, bone trabecular and bone marrow exhibit different trends and have the same sensitivity to irradiation conditions. The dose difference in bone tissues indicated that bone cortical and bone trabecular have significant attenuation effect on the energy deposition in bone marrow and bone surface for photon energies below 0.2 MeV. The set of dose conversion coefficients in this work can be used to determine the absorbed dose to skeletal system for external photon irradiation and to supplement the rat skeletal dosimetry.
Seasonality and Climatic Factors Associated With Human Rhinovirus/Enterovirus Nasopharyngeal Sample Positivity on Oahu, Hawai’i, 2016-2019
Authors: Marcelo Raymundo Z , Lustik Michael B , Jones Milissa U
Published: May 2023

Introduction

Globally, human rhinoviruses/enteroviruses (HRVs/ENTs), indistinguishable on many widely available molecular platforms, are among the leading causes of the common cold. Geographic and climatic factors impact the peak activity of these viruses. In temperate climates, the peak activity of HRV occurs during autumn and spring whereas that of ENT occurs during autumn and summer. Both viruses are thought to peak during the rainy season in tropical climates like Hawai’i; however, data remain limited. We describe HRV/ENT seasonality and evaluate the climatic factors associated with peak activity among respiratory viral samples processed on Oahu, Hawai’i.

Materials and Methods

We conducted a retrospective analysis of all respiratory specimens submitted to Tripler Army Medical Center for multiplex polymerase chain reaction testing between May 2016 and May 2019. Among HRV/ENT-positive samples, we recorded the month and year of positivity. Summative monthly positive detection was calculated with peak months above the mean. Associations between temperature, precipitation levels, relative humidity, and wind speed by week and the number of positive samples for HRV/ENT were evaluated using Poisson regression. This analysis was conducted via IRB exempt protocol number 19R18.

Results

During our study period, there were 7,143 nasopharyngeal respiratory samples sent for multiplex polymerase chain reaction testing, with 1,572 positive for HRV/ENT (22%). Nineteen percent of respiratory samples positive for HRV/ENT were additionally positive for one or more respiratory pathogens. The majority of HRV/ENT-positive samples arose from children < 5 years of age (n = 959, 61%). Peak months were February, March, May, August, November, and December. After controlling for lagged count and year, average wind speed was the only climatic factor significantly associated with HRV/ENT sample positivity.

Conclusions

The peak monthly activity of HRV/ENT was similar to temperate climates with the exception of peak activity in February. Unlike other tropical climates, lower wind speed was associated with increased weekly HRV/ENT positivity and should be further explored as a transmission factor. Our study contributes to understanding the annual variability of HRV/ENT activity in tropical environments, which can inform clinician expectations regarding respiratory viral symptomatology in this region.
Codon Optimization Improves the Prediction of Xylose Metabolism from Gene Content in Budding Yeasts
Authors: Nalabothu Rishitha L , Fisher Kaitlin J , LaBella Abigail Leavitt , Meyer Taylor A , Opulente Dana A , Wolters John F , Rokas Antonis , Hittinger Chris Todd
Published: May 2023

Xylose is the second most abundant monomeric sugar in plant biomass. Consequently, xylose catabolism is an ecologically important trait for saprotrophic organisms, as well as a fundamentally important trait for industries that hope to convert plant mass to renewable fuels and other bioproducts using microbial metabolism. Although common across fungi, xylose catabolism is rare within Saccharomycotina, the subphylum that contains most industrially relevant fermentative yeast species. The genomes of several yeasts unable to consume xylose have been previously reported to contain the full set of genes in the XYL pathway, suggesting the absence of a gene–trait correlation for xylose metabolism. Here, we measured growth on xylose and systematically identified XYL pathway orthologs across the genomes of 332 budding yeast species. Although the XYL pathway coevolved with xylose metabolism, we found that pathway presence only predicted xylose catabolism about half of the time, demonstrating that a complete XYL pathway is necessary, but not sufficient, for xylose catabolism. We also found that XYL1 copy number was positively correlated, after phylogenetic correction, with xylose utilization. We then quantified codon usage bias of XYL genes and found that XYL3 codon optimization was significantly higher, after phylogenetic correction, in species able to consume xylose. Finally, we showed that codon optimization of XYL2 was positively correlated, after phylogenetic correction, with growth rates in xylose medium. We conclude that gene content alone is a weak predictor of xylose metabolism and that using codon optimization enhances the prediction of xylose metabolism from yeast genome sequence data.
MAGUS: machine learning and graph theory assisted universal structure searcher
Authors: Wang Junjie , Gao Hao , Han Yu , Ding Chi , Pan Shuning , Wang Yong , Jia Qiuhan , Wang Hui-Tian , Xing Dingyu , Sun Jian
Published: May 2023

Crystal structure predictions based on first-principles calculations have gained great success in materials science and solid state physics. However, the remaining challenges still limit their applications in systems with a large number of atoms, especially the complexity of conformational space and the cost of local optimizations for big systems. Here, we introduce a crystal structure prediction method, MAGUS, based on the evolutionary algorithm, which addresses the above challenges with machine learning and graph theory. Techniques used in the program are summarized in detail and benchmark tests are provided. With intensive tests, we demonstrate that on-the-fly machine-learning potentials can be used to significantly reduce the number of expensive first-principles calculations, and the crystal decomposition based on graph theory can efficiently decrease the required configurations in order to find the target structures. We also summarized the representative applications of this method on several research topics, including unexpected compounds in the interior of planets and their exotic states at high pressure and high temperature (superionic, plastic, partially diffusive state, etc.); new functional materials (superhard, high-energy-density, superconducting, photoelectric materials), etc. These successful applications demonstrated that MAGUS code can help to accelerate the discovery of interesting materials and phenomena, as well as the significant value of crystal structure predictions in general.
Chemically bonded multi-nanolayer inorganic aerogel with a record-low thermal conductivity in a vacuum
Authors: Yu Hongxuan , Li Menglin , Deng Yuanpeng , Fu Shubin , Guo Jingran , Zhao Han , Zhang Jianing , Dang Shixuan , Zhang Pengyu , Zhou Jian , Liu Dizhou , Wang Duola , Zhang Chuanwei , Hao Menglong , Xu Xiang
Published: May 2023

Inorganic aerogels have exhibited many superior characteristics with extensive applications, but are still plagued by a nearly century-old tradeoff between their mechanical and thermal properties. When reducing thermal conductivity by ultralow density, inorganic aerogels generally suffer from large fragility due to their brittle nature or weak joint crosslinking, while enhancing the mechanical robustness by material design and structural engineering, they easily sacrifice thermal insulation and stability. Here, we report a chemically bonded multi-nanolayer design and synthesis of a graphene/amorphous boron nitride aerogel to address this typical tradeoff to further enhance mechanical and thermal properties. Attributed to the chemically bonded interface and coupled toughening effect, our aerogels display a low density of 0.8 mg cm−3 with ultrahigh flexibility (elastic compressive strain up to 99% and bending strain up to 90%), and exceptional thermostability (strength degradation <3% after sharp thermal shocks), as well as the lowest thermal conductivities in a vacuum (only 1.57 mW m−1 K−1 at room temperature and 10.39 mW m−1 K−1 at 500°C) among solid materials to date. This unique combination of mechanical and thermal properties offers an attractive material system for thermal superinsulation at extreme conditions.
SHORT ROOT and INDETERMINATE DOMAIN family members govern PIN-FORMED expression to regulate minor vein differentiation in rice
Authors: Liu Qiming , Teng Shouzhen , Deng Chen , Wu Suting , Li Haoshu , Wang Yanwei , Wu Jinxia , Cui Xuean , Zhang Zhiguo , Quick William Paul , Brutnell Thomas P , Sun Xuehui , Lu Tiegang
Published: May 2023

C3 and C4 grasses directly and indirectly provide the vast majority of calories to the human diet, yet our understanding of the molecular mechanisms driving photosynthetic productivity in grasses is largely unexplored. Ground meristem cells divide to form mesophyll or vascular initial cells early in leaf development in C3 and C4 grasses. Here we define a genetic circuit composed of SHORT ROOT (SHR), INDETERMINATE DOMAIN (IDD), and PIN-FORMED (PIN) family members that specifies vascular identify and ground cell proliferation in leaves of both C3 and C4 grasses. Ectopic expression and loss-of-function mutant studies of SHR paralogs in the C3 plant Oryza sativa (rice) and the C4 plant Setaria viridis (green millet) revealed the roles of these genes in both minor vein formation and ground cell differentiation. Genetic and in vitro studies further suggested that SHR regulates this process through its interactions with IDD12 and 13. We also revealed direct interactions of these IDD proteins with a putative regulatory element within the auxin transporter gene PIN5c. Collectively, these findings indicate that a SHR–IDD regulatory circuit mediates auxin transport by negatively regulating PIN expression to modulate minor vein patterning in the grasses.
Bridging the “consent gap”: mechanisms of legitimization in a cross-border megaproject
Authors: Lucciarini Silvia , Galdini Rossana
Published: May 2023

In the recent debate on megaprojects (MPs), greater attention is devoted to the functioning of the interorganizational and multiactor networks that are one of the most innovative features in recent years. The complexity of these structures brings out governability issues for an MP’s management. Mutual recognition and consent become elements capable of inaugurating more collaborative processes and practices to reduce organizational and management criticalities in MPs. This paper focuses on a neglected relational dimension, namely legitimacy. We argue that legitimacy is instead the central dimension that attributes effectiveness and capacity for action to the organizations involved. Legitimacy regulates the relationship between various organizations—and especially—between organizations and the public sphere. Institutionalist theory assigns a central role to legitimacy in the construction of social processes, defining it as a generalized form of social acceptance toward an actor, an idea, or a project. In this paper, we hypothesize that the legitimacy attributed and “held” by the stakeholders is a crucial element in countering three critical aspects of MPs, namely the uncertainty, complexity, and conflict acting on the construction of public consensus and the quality of relationships between the participating stakeholders. We verify our hypothesis by analyzing a cross-border MP, the Fehmarnbelt Fixed Link between Germany and Denmark. The paper concentrates on the mechanisms with which stakeholders can acquire legitimacy using the Eriksen discursive legitimation scheme. These mechanisms are different (evidence-based, public participation, and legislators’ command) and produce different outcomes in terms of increasing or containing these three criticalities.
Sea-Level Rise Exposure and Municipal Bond Yields
Authors: Goldsmith-Pinkham Paul , Gustafson Matthew T , Lewis Ryan C , Schwert Michael
Published: May 2023

Municipal bond markets began pricing sea-level rise (SLR) exposure risk in 2013, coinciding with upward revisions to worst-case SLR projections and accompanying uncertainty around these projections. The effect is larger for long-maturity bonds and not solely driven by near-term flood risk. We use a structural model of credit risk to quantify the implied economic impact and distinguish between the effects of underlying asset values and of uncertainty. The SLR exposure premium exhibits a trend different from house prices and is unaffected by house price controls. Together, our results highlight the importance of climate uncertainty in driving municipal bond prices.

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online
Through the looking glass: the neural basis of self-concept in young adults with antisocial trajectories
Authors: van de Groep Ilse H , G N Bos Marieke , Jansen Lucres M C , Popma Arne , Crone Eveline A
Published: May 2023

Self-concept is shaped by social experiences, but it is not yet well understood how the neural and behavioral development of self-concept is influenced by a history of antisocial behavior. In this pre-registered study, we examined neural responses to self-evaluations in young adults who engaged with antisocial behavior in childhood and either desisted or persisted in antisocial behavior. A self-concept task was performed by 94 young adults (age range 18–30 years). During the task, participants with a persistent or desistent antisocial trajectory (n = 54) and typically developing young adults (n = 40) rated whether positive and negative traits in different domains (prosocial and physical) described themselves. We examined both the effects of a history of antisocial behavior as well as current heterogeneity in psychopathic traits on self-concept appraisal and its neural underpinnings. Participants endorsed more positive trait statements than negative across domains, which did not differ between antisocial-history groups. However, current psychopathic traits were negatively associated with prosocial self-concept and medial prefrontal cortex activity during self-evaluation. Together, these findings suggest that antisocial tendencies might indeed be reflected in self-concept development of young adults, specifically in the prosocial domain.
Liberty for Us, Limits for Them: Christian Nationalism and Americans’ Views on Citizens’ Rights
Authors: Davis Joshua T , Perry Samuel L , Grubbs Joshua B
Published: May 2023

Americans are often split along partisan and religious lines regarding which claims they consider “rights,” as well as which of these rights they prioritize over others. Beyond standard political and religious characteristics, we propose that a pervasive ideology that centers conservative religious ethno-culture within America’s deep story and future—Christian nationalism—plays a central role in shaping how Americans evaluate “rights.” Analyses drawn from a nationally representative sample of U.S. adults show Christian nationalism is a leading predictor that Americans prioritize gun rights, religious freedom, and states’ rights, but deprioritize freedom of speech, the press, right to a speedy and fair trial, and protection from unlawful searches or seizures. Further analyses indicate Christian nationalism is the strongest predictor that Americans view voting as a privilege, not a right. Findings suggest Christian nationalism may incline Americans to support rights more suited to the continuance of the current social order and maintenance of power structures, while also making them less likely to support rights traditionally associated with challenging these structures.
Effect of sprouted whole pearl millet on growth performance, intestinal development, bacterial count, and blood indices of broiler chickens
Authors: Olasehinde Oluwakemi , Aderemi Foluke
Published: May 2023

This study investigated the effects of varying levels of sprouted whole grain pearl millet (SPM) on growth performance, intestinal morphology, microbial count, and blood indices of broiler chickens. A maize–soybean meal basal diet was formulated and fed to broiler chickens as starter (0 to 21 d) and finisher (22 to 42 d) diets. The diets comprised of 0%, 25%, 50%, 75%, and 100% of SPM incorporated as whole grain. On 0 d, 180 unsexed broiler chickens were allocated to experimental diets in a completely randomized design. Each treatment was replicated three times; each replicate had 12 chicks. All diets were isonitrogenous and isocaloric to meet the nutrient requirements of broiler chickens. Diets and water were provided ad libitum for 42 d.

Results showed that the body weight gain (BWG) of broiler chickens on SPM compared favorably with those on the control diet. BWG showed trends in increment (P < 0.10) while FCR showed decreased trends (P < 0.10) with partial inclusion of SPM at 42 d and 0 to 42 d. The drumstick weight showed quadratic effect (P = 0.044) while the wing weight showed linear effect (P = 0.047) to treatment diets at 21 d. The liver weights of broiler chickens showed linear response (P = 0.018) at 21 d and (P = 0.004) at 42 d to SPM inclusion in diets. Sprouted whole PM consistently increased low-density lipoprotein concentration and mean corpuscular hemoglobin concentration (P < 0.05). Length and weight of small intestine and ceca showed decreasing trends on SPM levels in the treatment diets. Digesta pH assessment revealed that pH in the crop was lower (P < 0.05) on partial SPM while pH in proventriculus was reduced (P < 0.05) with inclusion of SPM in treatment diets. Lactobacilli count decreased linearly (P = 0.010) with SPM inclusion. This study suggests that SPM could be used as an alternative source of energy in production of broiler chickens. Therefore, partial replacement of maize with SPM in broiler diet had no negative effect on performance, physiological status, and overall health of broiler chickens.
Academic Practice Partnerships
Authors: Bordelon Curry , Poe Terri , Moneyham Linda , Holland Aimee , Polancich Shea
Published: May 2023

Doctor of nursing practice (DNP) projects with impactful health system outcomes can be a challenge for graduate students and graduate program faculty to develop. Rigorous DNP projects address patient and health system needs, meet programmatic requirements, and result in a portfolio of sustainable scholarship for DNP graduates. A strong academic-practice partnership may result in a greater likelihood of successful and impactful DNP projects. Our academic-practice partnership leaders developed a strategic approach to align health system priorities with DNP student project needs. This partnership has resulted in project innovation, increased clinical application, improved outcomes within the community, and enhanced project quality.
Intraoperative Pancreatoscopy During Robotic Pancreatoduodenectomy and Robotic Distal Pancreatectomy for Intraductal Papillary Mucinous Neoplasm with Involvement of the Main Pancreatic Duct
Authors: Fong Zhi Ven , Zwart Maurice J.W. , Gorris Myrte , Voermans Rogier P. , van Wanrooij Roy L.J. , Wielenga Thijs , del Chiaro Marco , Arnelo Urban , Daams Freek , Busch Olivier R. , Besselink Marc G.
Published: May 2023

Background:

Intraductal papillary mucinous neoplasm (IPMN) with involvement of the main pancreatic duct usually requires surgical resection. Consensus is lacking whether to partially or completely resect the pancreatic portion with a dilated main pancreatic duct. Intraoperative pancreatoscopy may be useful to determine the extent of IPMN to tailor surgical resection and was recently studied in a large prospective international study. IPMN is increasingly utilized using a robotic approach. Studies describing the technical approach to intraoperative pancreatoscopy in robotic pancreatoduodenectomy and robotic distal pancreatectomy are lacking.

Methods:

During robotic pancreatoduodenectomy, pancreatoscopy is performed once the pancreas neck is transected. The scope is advanced via a laparoscopic port into the left and right-sided pancreatic duct, guided by robotic graspers. During robotic distal pancreatectomy, pancreatoscopy is performed before complete parenchymal transection. The scope is advanced through an anterior ductotomy to examine the duct and guide the pancreatic transection line. Tips and tricks how to perform the procedure efficiently without complications are detailed.

Results:

In total, 28 robot-assisted pancreatoscopies were performed during robotic pancreatoduodenectomy and robotic distal pancreatectomy. No intraoperative complications resulting from the intraoperative pancreatoscopy were noted. In the 2 described procedures, the added time required to perform the pancreatoscopy was 6 and 17 minutes, respectively. Both patients recovered without complication and were discharged on postoperative day 5 for the robotic pancreatoduodenectomy and day 6 for the robotic distal pancreatectomy.

Conclusions:

Intraoperative pancreatoscopy can be safely performed during both robotic pancreatoduodenectomy and robotic distal pancreatectomy for IPMN with the involvement of the main pancreatic duct. An international prospective study has recently been completed with this technique.
EVALUATION OF THE INCLUSION OF SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY IN A TELEMEDICINE DIABETIC RETINOPATHY SCREENING PROGRAM: A REAL CLINICAL PRACTICE
Authors: Arruabarrena Carolina , Rodríguez-Miguel Antonio , Allendes Germán , Vera Carlos , Son Beatriz , Teus Miguel A.
Published: May 2023

Purpose:

To evaluate whether combining spectral-domain optical coherence tomography (SD-OCT) with monoscopic fundus photography using a non-mydriatic camera (MFP-NMC) improves the accuracy of diabetic macular edema (DME) referrals in a teleophthalmology diabetic retinopathy screening program.

Methods:

We conducted a cross-sectional study with all diabetic patients aged ≥18 years who attended screening from September 2016 to December 2017. We assessed DME according to the three MFP-NMC and the four SD-OCT criteria. The sensitivity and specificity obtained for each criterion were estimated by comparing them with the ground truth of DME.

Results:

This study included 3918 eyes (1925 patients; median age, 66 years; interquartile range, 58–73; females, 40.7%; once-screened, 68.1%). The prevalence of DME ranged from 1.22% to 1.83% and 1.54% to 8.77% on MFP-NMC and SD-OCT, respectively. Sensitivity barely reached 50% in MFP-NMC and less for the quantitative criteria of SD-OCT. When macular thickening and anatomical signs of DME were considered, sensitivity increased to 88.3%, and the false DMEs and non-gradable images were reduced.

Conclusions:

Macular thickening and anatomical signs showed the highest suitability for screening, with a sensitivity of 88.3% and a specificity of 99.8%. Notably, MFP-NMC alone missed half of the true DMEs that lacked indirect signs.
An International External Quality Assessment Scheme to Assess the Diagnostic Performance of Polymerase Chain Reaction Detection of Acanthamoeba Keratitis
Authors: Sarink Maarten J. , Koelewijn Rob , Stelma Foekje , Kortbeek Titia , van Lieshout Lisette , Smit Pieter W. , Tielens Aloysius G. M. , van Hellemond Jaap J.
Published: May 2023

Purpose:

The purpose of this study was to assess the variation in methods and to determine whether an External Quality Assessment Scheme (EQAS) for polymerase chain reaction (PCR) detection of Acanthamoeba keratitis is valuable for the diagnostic process.

Methods:

A multicenter EQAS was introduced, covering 16 diagnostic laboratories. Using Acanthamoeba castellanii ATCC strain 30010, 3 sets of samples were prepared, containing different amounts of DNA, cysts, or trophozoites. Samples were masked and sent to the participants with instructions for use and a questionnaire concerning the applied methodologies. Special attention in this questionnaire was given to the used pretreatment methods to assess existing variations in these procedures.

Results:

A large variation in the methodologies and substantial differences in the diagnostic performance were found between participants. In contrast to the DNA samples where all participants had a perfect score, several false negative results were reported for the samples containing cysts or trophozoites. Only 9 participants had an optimal score, whereas one participant reported all samples as negative, one participant reported failures due to inhibition, and the other 5 reported in total 7 false negative results. A clear correlation was noticed between the PCR detection rate and the number of cysts or trophozoites in the sample.

Conclusions:

The results indicate that a pretreatment procedure can be a risky step in PCR-based detections of Acanthamoeba, but it improves the sensitivity and reliability, especially of samples containing cysts. Therefore, participation in an EQAS is informative for routine diagnostic laboratories and can assist in improving the laboratory procedures used for the diagnosis of Acanthamoeba keratitis.
A Description of Telehealth Use Among Sexually Transmitted Infection Providers in the United States, 2021
Authors: Pearson William S. , Chan Philip A. , Habel Melissa A. , Haderxhanaj Laura T. , Hogben Matthew , Aral Sevgi O.
Published: May 2023

Background

Telehealth offers one approach to improving access to sexually transmitted infection (STI) prevention and care services. Therefore, we described recent telehealth use among those providing STI-related care and identified opportunities for improving STI service delivery.

Materials and Methods

Using the DocStyles Web-based, panel survey conducted by Porter Novelli from September 14 to November 10, 2021, 1500 healthcare providers were asked about their current telehealth usage, demographics, and practice characteristics, and compared STI providers (≥10% of time spent on STI care and prevention) to non-STI providers.

Results

Among those whose practice consisted of at least 10% STI visits (n = 597), 81.7% used telehealth compared with 75.7% for those whose practice consisted of less than 10% STI visits (n = 903). Among the providers with at least 10% STI visits in their practice, telehealth use was highest among obstetrics and gynecology specialists, those practicing in suburban areas, and those practicing in the South. Among providers whose practice consisted of at least 10% STI visits and who used telehealth (n = 488), the majority were female and obstetrics and gynecology specialists practicing in suburban areas of the South. After controlling for age, gender, provider specialty, and geographic location of their practice, providers whose practice consisted of at least 10% STI visits had increased odds (odds ratio, 1.51; 95% confidence interval, 1.16–1.97) of using telehealth compared with providers whose visits consisted of less than 10% STI visits.

Conclusions

Given the widespread use of telehealth, efforts to optimize delivery of STI care and prevention via telehealth are important to improve access to services and address STIs in the United States.
Balancing Data Provision and Data Protection: A Natural Experiment With HIV and Syphilis Surveillance Data in the United States
Authors: Delcher Chris , Wang Yanning , Gusovsky Amanda V. , Benitez Joseph
Published: May 2023

Background

Public release of health data typically requires statistical disclosure limitation (SDL), but scant research demonstrates how real-world SDL affects data usability. Recent changes of federal data re-release policy allow a pseudo-counterfactual comparison of HIV and syphilis data suppression rules.

Methods

Incident counts (2019) of HIV and syphilis infections by county for Black and White populations were downloaded from the US Centers for Disease Control and Prevention. We quantified and compared suppression status by disease and county between Black and White populations and calculated incident rate ratios for counties with statistically reliable counts.

Results

Approximately 50% of US counties have incident HIV counts suppressed for Black and White populations compared with only 5% for syphilis, which has an alternative suppression strategy. The county population sizes protected by a numerator disclosure rule (<4) spans several orders of magnitude. Calculations of incident rate ratios, used as a measure of health disparity, were impossible in the 220 counties most susceptible to an HIV outbreak.

Conclusions

Balancing tradeoffs between providing and protecting data are key to health initiatives worldwide. We encourage an increase in empirical research on the impact of SDL, especially in the context of health disparities, and recommend new approaches to avoid the “oppression of data suppression.”
Prevalence of postoperative pain after hospital discharge: systematic review and meta-analysis
Authors: Park Rex , Mohiuddin Mohammed , Arellano Ramiro , Pogatzki-Zahn Esther , Klar Gregory , Gilron Ian
Published: May 2023

Assessment and management of postoperative pain after hospital discharge is very challenging. We conducted a systematic review to synthesize available evidence on the prevalence of moderate-to-severe postoperative pain within the first 1 to 14 days after hospital discharge. The previously published protocol for this review was registered in PROSPERO. MEDLINE and EMBASE databases were searched until November 2020. We included observational postsurgical pain studies in the posthospital discharge setting. The primary outcome for the review was the proportion of study participants with moderate-to-severe postoperative pain (eg, pain score of 4 or more on a 10-point Numerical Rating Scale) within the first 1 to 14 days after hospital discharge. This review included 27 eligible studies involving a total of 22,108 participants having undergone a wide variety of surgical procedures. The 27 studies included ambulatory surgeries (n = 19), inpatient surgeries (n = 1), both ambulatory and inpatient surgeries (n = 4), or was not specified (n = 3). Meta-analyses of combinable studies provided estimates of pooled prevalence rates of moderate-to-severe postoperative pain ranging from 31% 1 day after discharge to 58% 1 to 2 weeks after discharge. These findings suggest that moderate-to-severe postoperative pain is a common occurrence after hospital discharge and highlight the importance of future efforts to more effectively evaluate, prevent, and treat postsurgical pain in patients discharged from the hospital.
CIRC_0001818 TARGETS MIR-136-5P TO INCREASE LIPOPOLYSACCHARIDE-INDUCED HK2 CELL INJURIES BY ACTIVATING TXNIP/NLRP3 INFLAMMASOME PATHWAY
Authors: Kuang Feng , Wang Baiqi , You Ting , Liu Yu , Li Pei , Wang Jian , Peng Liangshan
Published: May 2023

Background: The implication of circular RNAs (circRNAs) in sepsis-related complications arouses much attention, which provides additional treatment options for sepsis-related complications. The purpose of this study is to unveil the function and functional mechanism of circ_0001818 in cell models of septic acute kidney injury (AKI). Methods: Septic AKI cell models were constructed using HK2 cells treated with lipopolysaccharide (LPS). The expression levels of circ_0001818, miR-136-5p, and thioredoxin interacting protein (TXNIP) mRNA were examined by quantitative real-time polymerase chain reaction. Cell viability and death were explored by CCK-8 and flow cytometry assays. The activity of oxidative stress-related markers was examined using commercial kits. The secretion of inflammatory factors was examined using ELISA kits. The binding between miR-136-5p and circ_0001818 or TXNIP was validated by dual-luciferase reporter test and pull-down assay. The receiver operating characteristic curve was depicted to assess the diagnostic value of circ_0001818, miR-136-5p, and TXNIP in serumal exosomes from patients with septic AKI. Results: Circ_0001818 expression was elevated in LPS-treated HK2 cells. Loss-of-function assays displayed that circ_0001818 downregulation alleviated LPS-induced HK2 cell death, oxidative stress, inflammatory release, and inflammasome activation. MiR-136-5p was targeted by circ_0001818, and inhibition of miR-136-5p attenuated the effects of circ_0001818 downregulation, thus recovering LPS-induced HK2 cell injuries. MiR-136-5p targeted the downstream TXNIP, and circ_0001818 dysregulation could affect TXNIP expression via targeting miR-136-5p. Overexpression of TXNIP overturned the effects of circ_0001818 downregulation. Moreover, circ_0001818, miR-136-5p, and TXNIP in serumal exosomes had diagnostic values. Conclusions: Circ_0001818 targets miR-136-5p to activate TXNIP expression, leading to the contribution of LPS-induced HK2 cell injury.
DANGER Signals Activate G-Protein Receptor Kinases Suppressing Neutrophil Function and Predisposing to Infection After Tissue Trauma
Authors: Kim Hyo In , Park Jinbong , Gallo David , Shankar Sidharth , Konecna Barbora , Han Yohan , Banner-Goodspeed Valerie , Capers Krystal R. , Ko Seong-Gyu , Otterbein Leo E. , Itagaki Kiyoshi , Hauser Carl J.
Published: May 2023

Objective:

Surgery injures tissue and predisposes to local and systemic infections. We studied injury-induced immune dysfunction seeking novel means to reverse such predisposition.

Background:

Injury mobilizes primitive ‘DANGER signals’ (DAMPs) activating innate immunocyte (neutrophils, PMN) signaling and function. Mitochondrial (mt) formyl peptides (FP) activate G-protein coupled receptors (GPCR) like FPR1. mtDNA and heme activate toll-like receptors (TLR9, TLR2/4). GPCR kinases (GRKs) can regulate GPCR activation.

Methods:

We studied human and mouse PMN signaling elicited by mtDAMPs (GPCR surface expression; protein phosphorylation or acetylation; Ca2+ flux) and antimicrobial functions (cytoskeletal reorganization, chemotaxis (CTX), phagocytosis, bacterial killing) in cellular systems and clinical injury samples. Predicted rescue therapies were assessed in cell systems and mouse injury-dependent pneumonia models.

Results:

mtFPs activate GRK2, internalizing GPCRs and suppressing CTX. mtDNA suppresses CTX, phagocytosis and killing via TLR9 through a novel, non-canonical mechanism that lacks GPCR endocytosis. Heme also activates GRK2. GRK2 inhibitors like paroxetine restore functions. GRK2 activation via TLR9 prevented actin reorganization, implicating histone deacetylases (HDACs). Actin polymerization, CTX, bacterial phagocytosis and killing were also rescued therefore by the HDAC inhibitor valproate. Trauma repository PMN showed GRK2 activation and cortactin deacetylation which varied with severity and was most marked in patients developing infections. Either GRK2 or HDAC inhibition prevented loss of mouse lung bacterial clearance, but only the combination rescued clearance when given post-injury.

Conclusions:

Tissue injury-derived DAMPs suppress antimicrobial immunity via canonical GRK2 activation and a novel TLR-activated GRK2 pathway impairing cytoskeletal organization. Simultaneous GRK2/HDAC inhibition rescues susceptibility to infection after tissue injury.
Effects of a Virtually Delivered Reading and Embedded Mindset Intervention on Reading Performance for Fourth-Grader Struggling Readers
Authors: Al Otaiba Stephanie , Wanzek Jeanne , Petscher Yaacov , Fluhler Sally , Rivas Brenna , Russell Freudenthal Dayna
Published: May 2023

The purpose of this study was to examine the effects of a virtual intensive reading intervention embedded with mindset training compared with typical reading instruction in a business-as-usual (BAU) condition delivered to fourth-grade students with or at risk for reading disabilities. After screening, the 59 participants were stratified and assigned randomly to condition. Highly trained interventionists delivered the intervention one-to-one with high fidelity and student engagement during the intensive intervention. Classroom teachers delivered the BAU. We examined the effects of the intervention on a variety of standardized timed and untimed measures of word reading and decoding, reading fluency, comprehension, and mindset. We addressed two research questions: What are the effects of intensive virtual reading intervention embedded with mindset training relative to a BAU comparison on the reading outcomes of fourth-grade students with or at risk for reading disabilities? Was initial mindset related to student response to intervention? Data analyses examined the main effect and moderation using linear mixed effects models. Significant differences in reading favored the virtual treatment condition for letter and word identification (g = 0.38). No other significant effects were observed. We note limitations in our study and offer directions for future research, including the need to explore additional moderators.