bluuebunny/crossref_metadata_2025 huggingface dataset:
A comprehensive picture of using standardized nursing languages in long‐term care systems: An integrative review
Authors: Giap Thi‐Thanh‐Tinh , Park Myonghwa , Bui Linh Khanh
Published: July 2024

Purpose

This integrative review was conducted to provide a comprehensive picture of the use of standardized nursing languages (SNLs) in long‐term care (LTC) systems.

Methods

A comprehensive search was performed with terminological variants of “standardized terminology” and “long‐term care” in eight electronic databases up to December 2021. Eligible studies were further identified by screening the reference lists of publications that met the inclusion criteria. The quality of the included studies was appraised using the Joanna Briggs Institute checklists. The study findings were organized into themes, which represent the focus of the study.

Findings

Eighty‐one publications that studied 12 SNLs in 17 countries are presented in this review. The Omaha System, NANDA‐I, NIC, and NOC were the most common SNLs. Study foci were classified into five themes: evaluating the applicability of 10 SNLs (n = 22), characterizing nursing care using six SNLs (n = 16), developing core sets and tools based on seven SNLs (n = 15), documenting nursing care by using four SNLs (n = 14), and implementing intervention programs based on six SNLs (n = 14).

Conclusions and implications for nursing

SNLs can be used for various purposes, and the available evidence supports the expansion of their utilization. Further studies should continue to identify gaps in the existing versions of SNLs to reflect the LTC nursing process in multiple societies. Additionally, the successful use of SNLs requires background knowledge of nursing informatics; therefore, preparation should be started in the nursing curriculum and continued in healthcare facilities, including LTC settings. These research findings will assist healthcare managers, researchers, and policymakers in the LTC field in effectively utilizing SNLs.
Investigating the impact of environmental enrichment on proteome and neurotransmitter‐related profiles in an animal model of Alzheimer's disease
Authors: Nam Yunkwon , Kim Sujin , Park Yong Ho , Kim Byeong‐Hyeon , Shin Soo Jung , Leem Seol Hwa , Park Hyun Ha , Jung Gukhwa , Lee Jeongbeen , Kim Hyung‐Gun , Yoo Doo‐Han , Kim Hak Su , Moon Minho
Published: July 2024

Alzheimer's disease (AD) is a neurodegenerative disorder associated with behavioral and cognitive impairments. Unfortunately, the drugs the Food and Drug Administration currently approved for AD have shown low effectiveness in delaying the progression of the disease. The focus has shifted to non‐pharmacological interventions (NPIs) because of the challenges associated with pharmacological treatments for AD. One such intervention is environmental enrichment (EE), which has been reported to restore cognitive decline associated with AD effectively. However, the therapeutic mechanisms by which EE improves symptoms associated with AD remain unclear. Therefore, this study aimed to reveal the mechanisms underlying the alleviating effects of EE on AD symptoms using histological, proteomic, and neurotransmitter‐related analyses. Wild‐type (WT) and 5XFAD mice were maintained in standard housing or EE conditions for 4 weeks. First, we confirmed the mitigating effects of EE on cognitive impairment in an AD animal model. Then, histological analysis revealed that EE reduced Aβ accumulation, neuroinflammation, neuronal death, and synaptic loss in the AD brain. Moreover, proteomic analysis by liquid chromatography–tandem mass spectrometry showed that EE enhanced synapse‐ and neurotransmitter‐related networks and upregulated synapse‐ and neurotransmitter‐related proteins in the AD brain. Furthermore, neurotransmitter‐related analyses showed an increase in acetylcholine and serotonin concentrations as well as a decrease in polyamine concentration in the frontal cortex and hippocampus of 5XFAD mice raised under EE conditions. Our findings demonstrate that EE restores cognitive impairment by alleviating AD pathology and regulating synapse‐related proteins and neurotransmitters. Our study provided neurological evidence for the application of NPIs in treating AD.
Activation of the hypoxia response in the aging cerebrovasculature protects males against cognitive impairment
Authors: Li Peihu , Bi Xiaoman , Xu Dahua , Meng Yuan , Xia Yucheng , Cai Jiale , Shen Yutong , Wang Jiaqi , Chen Jiazhu , Yin Lamei , Wang Bo , Wu Deng , Li Kongning
Published: July 2024

Alzheimer's disease (AD) is a neurodegenerative disorder with a distinct sex bias. Age‐related vascular alterations, a hallmark of AD onset and progression, are consistently associated with sexual dimorphism. Here, we conducted an integrative meta‐analysis of 335,803 single‐nucleus transcriptomes and 667 bulk transcriptomes from the vascular system in AD and normal aging to address the underlying sex‐dependent vascular aging in AD. All vascular cell types in male AD patients exhibited an activated hypoxia response and downstream signaling pathways including angiogenesis. The female AD vasculature is characterized by increased antigen presentation and decreased angiogenesis. We further confirmed that these sex‐biased alterations in the cerebral vascular emerged and were primarily determined in the early stages of AD. Sex‐stratified analysis of normal vascular aging revealed that angiogenesis and various stress‐response genes were downregulated concurrently with female aging. Conversely, the hypoxia response increased steadily in males upon aging. An investigation of upstream driver transcription factors (TFs) revealed that altered communication between estrogen receptor alpha (ESR1) and hypoxia induced factors during menopause contributes to the inhibition of angiogenesis during normal female vascular aging. Additionally, inhibition of CREB1, a TF that targets estrogen, is also related to female AD. Overall, our study revealed a distinct cerebral vascular profile in females and males, and revealed novel targets for precision medicine therapy for AD.
Evaluation of artificial intelligence‐generated drug therapy communication skill competencies in medical education
Authors: Sridharan Kannan , Sequeira Reginald P.
Published: July 2024

Aims

This study compared three artificial intelligence (AI) platforms' potential to identify drug therapy communication competencies expected of a graduating medical doctor.

Methods

We presented three AI platforms, namely, Poe Assistant©, ChatGPT© and Google Bard©, with structured queries to generate communication skill competencies and case scenarios appropriate for graduating medical doctors. These case scenarios comprised 15 prototypical medical conditions that required drug prescriptions. Two authors independently evaluated the AI‐enhanced clinical encounters, which integrated a diverse range of information to create patient‐centred care plans. Through a consensus‐based approach using a checklist, the communication components generated for each scenario were assessed. The instructions and warnings provided for each case scenario were evaluated by referencing the British National Formulary.

Results

AI platforms demonstrated overlap in competency domains generated, albeit with variations in wording. The domains of knowledge (basic and clinical pharmacology, prescribing, communication and drug safety) were unanimously recognized by all platforms. A broad consensus among Poe Assistant© and ChatGPT© on drug therapy‐related communication issues specific to each case scenario was evident. The consensus primarily encompassed salutation, generic drug prescribed, treatment goals and follow‐up schedules. Differences were observed in patient instruction clarity, listed side effects, warnings and patient empowerment. Google Bard did not provide guidance on patient communication issues.

Conclusions

AI platforms recognized competencies with variations in how these were stated. Poe Assistant© and ChatGPT© exhibited alignment of communication issues. However, significant discrepancies were observed in specific skill components, indicating the necessity of human intervention to critically evaluate AI‐generated outputs.
Myo‐inositol trispyrophosphate prevents right ventricular failure and improves survival in monocrotaline‐induced pulmonary hypertension in the rat
Authors: Oknińska Marta , Paterek Aleksandra , Grzanka Małgorzata , Zajda Karolina , Surzykiewicz Mateusz , Rolski Filip , Zambrowska Zuzanna , Torbicki Adam , Kurzyna Marcin , Kieda Claudine , Piekiełko‐Witkowska Agnieszka , Mączewski Michał
Published: July 2024

Background and Purpose

Pulmonary hypertension (PH) results from pulmonary vasculopathy, initially leading to a compensatory right ventricular (RV) hypertrophy, and eventually to RV failure. Hypoxia can trigger both pulmonary vasculopathy and RV failure. Therefore, we tested if myo‐inositol trispyrophosphate (ITPP), which facilitates oxygen dissociation from haemoglobin, can relieve pulmonary vasculopathy and RV hypoxia, and eventually prevent RV failure and mortality in the rat model of monocrotaline‐induced PH.

Experimental approach

Rats were injected with monocrotaline (PH) or saline (control) and received ITPP or placebo for 5 weeks. Serial echocardiograms were obtained to monitor the disease, pressure‐volume loops were recorded and evaluated, myocardial pO2 was measured using a fluorescent probe, and histological and molecular analyses were conducted at the conclusion of the experiment.

Key Results and Conclusions

ITPP reduced PH‐related mortality. It had no effect on progressive increase in pulmonary vascular resistance, yet significantly relieved intramyocardial RV hypoxia, which was associated with improvement of RV function and reduction of RV wall stress. ITPP also tended to prevent increased hypoxia inducible factor‐1α expression in RV cardiac myocytes but did not affect RV capillary density.

Implications

Our study suggests that strategies aimed at increasing oxygen delivery to hypoxic RV in PH could potentially be used as adjuncts to other therapies that target pulmonary vessels, thus increasing the ability of the RV to withstand increased afterload and reducing mortality. ITPP may be one such potential therapy.
FP‐Flow: Feature pyramid flow model for fabric defect detection
Authors: Wang Yuanfei , Xu Yang , Yu Zhiqi , Sheng Xiaowei
Published: July 2024

Fabric defect detection is a crucial aspect of fabric production. At present, deep learning detection methods mostly rely on supervised learning. To tackle this issue, this study proposes an unsupervised fabric defect detection approach based‐on normalising flow. The method only needs to train the mapping of the feature probability distribution of defect‐free samples to a Gaussian distribution. In the inference process, the location of defects can be determined by testing the distance between the probability distribution of image features and the estimated distribution. To adapt to the complex background and various minor defects of the fabric, a feature pyramid structure is adopted. Moreover, considering the gradient vanishing and network degradation caused by deep layers during training, a residual structure is incorporated into the model. Experimental results demonstrate that the feature pyramid flow model outperforms other methods in defect detection across multiple datasets, with an average score rate of 98.7% and 100% for pixel‐level area under the curve (AUC) receiver operating characteristic and image‐level AUC, respectively, compared to an average score rate of 91.1% and 85.4% for other methods.
Integrating genomic data and simulations to evaluate alternative species distribution models and improve predictions of glacial refugia and future responses to climate change
Authors: Naughtin Sarah R. , Castilla Antonio R. , Smith Adam B. , Strand Allan E. , Dawson Andria , Hoban Sean , Abhainn Everett Andrew , Romero‐Severson Jeanne , Robinson John D.
Published: July 2024

Climate change poses a threat to biodiversity, and it is unclear whether species can adapt to or tolerate new conditions, or migrate to areas with suitable habitats. Reconstructions of range shifts that occurred in response to environmental changes since the last glacial maximum (LGM) from species distribution models (SDMs) can provide useful data to inform conservation efforts. However, different SDM algorithms and climate reconstructions often produce contrasting patterns, and validation methods typically focus on accuracy in recreating current distributions, limiting their relevance for assessing predictions to the past or future. We modeled historically suitable habitat for the threatened North American tree green ash Fraxinus pennsylvanica using 24 SDMs built using two climate models, three calibration regions, and four modeling algorithms. We evaluated the SDMs using contemporary data with spatial block cross‐validation and compared the relative support for alternative models using a novel integrative method based on coupled demographic‐genetic simulations. We simulated genomic datasets using habitat suitability of each of the 24 SDMs in a spatially‐explicit model. Approximate Bayesian computation (ABC) was then used to evaluate the support for alternative SDMs through comparisons to an empirical population genomic dataset. Models had very similar performance when assessed with contemporary occurrences using spatial cross‐validation, but ABC model selection analyses consistently supported SDMs based on the CCSM climate model, an intermediate calibration extent, and the generalized linear modeling algorithm. Finally, we projected the future range of green ash under four climate change scenarios. Future projections using the SDMs selected via ABC suggest only minor shifts in suitable habitat for this species, while some of those that were rejected predicted dramatic changes. Our results highlight the different inferences that may result from the application of alternative distribution modeling algorithms and provide a novel approach for selecting among a set of competing SDMs with independent data.
Neurocognitive performance in functional neurological disorder: A systematic review and meta‐analysis
Authors: Millman L. S. Merritt , Williams Isobel A. , Jungilligens Johannes , Pick Susannah
Published: July 2024

Background and purpose

Cognitive complaints are common in functional neurological disorder (FND), but it is unclear whether objective neurocognitive deficits are present. This systematic review summarized validated/standardized cognitive test performance in FND samples across cognitive domains.

Methods

Embase, PsycInfo and MEDLINE were searched from inception to 15 May 2023, combining terms for FND and cognitive domains (e.g., attention, memory, executive functioning). Studies included a range of FND phenotypes (seizures, motor, cognitive disorder, mixed), compared to healthy or clinical controls. Risk of bias was assessed with the modified Newcastle–Ottawa Scale and a qualitative synthesis/narrative review of cognitive performance in FND was conducted. Test performance scores were extracted, and random effects meta‐analyses were run where appropriate. This review was registered on PROSPERO, CRD42023423139.

Results

Fifty‐six studies including 2260 individuals with FND were eligible. Although evidence for some impairments emerged across domains of executive functioning, attention, memory and psychomotor/processing speed, this was inconsistent across studies and FND phenotypes. Common confounds included group differences in demographics, medication and intellectual functioning. Only 24% of studies objectively assessed performance validity. Meta‐analyses revealed higher scores on tests of naming (g = 0.67, 95% confidence interval [CI] 0.50, 0.84) and long‐term memory (g = 0.43, 95% CI 0.13, 0.74) in functional seizures versus epilepsy, but no significant differences in working (g = −0.08, 95% CI −0.44, 0.29) or immediate (g = 0.25, 95% CI −0.02, 0.53) memory and cognitive flexibility (g = −0.01, 95% CI −0.29, 0.28).

Conclusions

There is mixed evidence for objective cognitive deficits in FND. Future research should control for confounds, include tests of performance validity, and assess relationships between objective and subjective neurocognitive functioning.
Prediction of molecular subclasses of uveal melanoma by deep learning using routine haematoxylin–eosin‐stained tissue slides
Authors: Akram Farhan , de Bruyn Daniël P , van den Bosch Quincy C C , Trandafir Teodora E , van den Bosch Thierry P P , Verdijk Rob M , de Klein Annelies , Kiliç Emine , Stubbs Andrew P , Brosens Erwin , von der Thüsen Jan H
Published: July 2024

Aims

Uveal melanoma has a high propensity to metastasize. Prognosis is associated with specific driver mutations and copy number variations, and these can only be obtained after genetic testing. In this study we evaluated the efficacy of patient outcome prediction using deep learning on haematoxylin and eosin (HE)‐stained primary uveal melanoma slides in comparison to molecular testing.

Methods

In this retrospective study of patients with uveal melanoma, 113 patients from the Erasmus Medical Centre who underwent enucleation had tumour tissue analysed for molecular classification between 1993 and 2020. Routine HE‐stained slides were scanned to obtain whole‐slide images (WSI). After annotation of regions of interest, tiles of 1024 × 1024 pixels were extracted at a magnification of 40×. An ablation study to select the best‐performing deep‐learning model was carried out using three state‐of‐the‐art deep‐learning models (EfficientNet, Vision Transformer, and Swin Transformer).

Results

Deep‐learning models were subjected to a training cohort (n = 40), followed by a validation cohort (n = 20), and finally underwent a test cohort (n = 48). A k‐fold cross‐validation (k = 3) of validation and test cohorts (n = 113 of three classes: BAP1, SF3B1, EIF1AX) demonstrated Swin Transformer as the best‐performing deep‐learning model to predict molecular subclasses based on HE stains. The model achieved an accuracy of 0.83 ± 0.09 on the validation cohort and 0.75 ± 0.04 on the test cohort. Within the subclasses, this model correctly predicted 70% BAP1‐mutated, 61% SF3B1‐mutated and 80% EIF1AX‐mutated UM in the test set.

Conclusions

This study showcases the potential of the deep‐learning methodology for predicting molecular subclasses in a multiclass manner using HE‐stained WSI. This development holds promise for advanced prognostication of UM patients without the need of molecular or immunohistochemical testing. Additionally, this study suggests there are distinct histopathological features per subclass; mainly utilizing epithelioid cellular morphology for BAP1‐classification, but an unknown feature distinguishes EIF1AX and SF3B1.
MIDDLEMEN IN SEARCH EQUILIBRIUM WITH INTENSIVE AND EXTENSIVE MARGINS
Authors: Gong Grace Xun , Wright Randall
Published: July 2024

We study endogenous intermediation activity, the implied transaction pattern—direct trade, indirect trade, or both—and implications for efficiency. Related papers have agents exchanging indivisible goods or assets, capturing only extensive margins (trade frequency). To capture intensive margins, we incorporate divisibility representing quantity or quality. We characterize equilibrium, show how it depends on bargaining powers and costs, and how intensive margins matter—for example, middlemen with high bargaining power may charge more but offer higher quantity/quality, thus improving welfare. A tax‐subsidy policy is designed to achieve efficiency. A monetary version lets us compare money and middlemen and further discuss policy.
Erythropoietin induces tumour progression and CD39 expression on immune cells in a preclinical model of triple‐negative breast cancer
Authors: Bessoles Stéphanie , Chiron Andrada , Sarrabayrouse Guillaume , De La Grange Pierre , Abina Amine M. , Hacein‐Bey‐Abina Salima
Published: July 2024

The adverse effects observed in some cancer patients treated with erythropoiesis‐stimulating agents such as erythropoietin (EPO) might be due to the latter's well‐known immunosuppressive functions. Here, we used a mouse model of syngeneic triple‐negative breast cancer to explore EPO's immunomodulatory role in a tumour setting. Our results showed that EPO treatment promotes tumour growth, exacerbates the ‘immune desert’, and results in a ‘cold tumour’. EPO treatment changed the immune cell distribution in peripheral blood, secondary lymphoid organs, and the tumour microenvironment (TME). Our in‐depth analysis showed that EPO mainly impacts CD4 T cells by accelerating their activation in the spleen and thus their subsequent exhaustion in the TME. This process is accompanied by a general elevation of CD39 expression by several immune cells (notably CD4 T cells in the tumour and spleen), which promotes an immunosuppressive TME. Lastly, we identified a highly immunosuppressive CD39+ regulatory T cell population (ICOS+, CTLA4+, Ki67+) as a potential biomarker of the risk of EPO‐induced tumour progression. EPO displays pleiotropic immunosuppressive functions and enhances mammary tumour progression in mice.
Is gender a factor in socioeconomic disparities in undiagnosed, and untreated hypertension in Bangladesh?
Authors: Kumar Roy Tapan , Rahman Mosiur , Rahman Md. Sohanur , Halder Nityananda , Rashid Md Mamunur
Published: July 2024

Our objectives were to ascertain the following: (1) the prevalence and socioeconomic distribution of hypertension (HTN), undiagnosed for HTN, and untreated cases of HTN‐diagnosed individuals; (2) the relationship between SES and the prevalence of HTN, undiagnosed for HTN, and untreated for HTN; and (3) whether sex moderate this association. Data from the 2017–18 Bangladesh Demographic Health Survey were used. 11,776 participants who were 18 years of age or older responded to our analysis. The age‐adjusted prevalence of HTN, undiagnosed for HTN, and untreated cases was 25.1%, 57.2%, and 12.3%. Compared to females, males were less likely to have HTN but more likely to have undiagnosed HTN. People in the rich SES groups had a higher odd of (adjusted odds ratio [aoR] 1.25; 95% confidence interval [CI] 1.08–3.45) of having HTN compared to those in the poor SES group. When compared to individuals in the poor SES group, those in the rich SES group had lower odds of undiagnosed (aoR 0.57; 95% CI 0.44–0.74) and untreated (aoR 0.56; 95% CI 0.31–0.98) for HTN. Sex moderated the association between SES and HTN prevalence, which showed that men from rich SES were more likely to suffer from HTN than men from poor SES. According to this study, the government and other pertinent stakeholders should concentrate more on developing suitable policy measures to reduce the risk of HTN, particularly for men in rich socioeconomic groups. They should also concentrate on screening and diagnosing HTN in socioeconomically disadvantaged populations, regardless of sex.
Identification of the cytochrome P450s responsible for the biosynthesis of two types of aporphine alkaloids and their de novo biosynthesis in yeast
Authors: Li Qishuang , Jiao Xiang , Li Xinyi , Shi Wenlong , Ma Ying , Tan Xiangmei , Gan Jingyi , Liu Jimei , Yang Jian , Wang Jian , Jin Baolong , Chen Tong , Su Ping , Zhao Yujun , Zhang Yifeng , Tang Jinfu , Cui Guanghong , Chen Yun , Guo Juan , Huang Luqi
Published: July 2024

Aporphine alkaloids have diverse pharmacological activities; however, our understanding of their biosynthesis is relatively limited. Previous studies have classified aporphine alkaloids into two categories based on the configuration and number of substituents of the D‐ring and have proposed preliminary biosynthetic pathways for each category. In this study, we identified two specific cytochrome P450 enzymes (CYP80G6 and CYP80Q5) with distinct activities toward (S)‐configured and (R)‐configured substrates from the herbaceous perennial vine Stephania tetrandra, shedding light on the biosynthetic mechanisms and stereochemical features of these two aporphine alkaloid categories. Additionally, we characterized two CYP719C enzymes (CYP719C3 and CYP719C4) that catalyzed the formation of the methylenedioxy bridge, an essential pharmacophoric group, on the A‐ and D‐rings, respectively, of aporphine alkaloids. Leveraging the functional characterization of these crucial cytochrome P450 enzymes, we reconstructed the biosynthetic pathways for the two types of aporphine alkaloids in budding yeast (Saccharomyces cerevisiae) for the de novo production of compounds such as (R)‐glaziovine, (S)‐glaziovine, and magnoflorine. This study provides key insight into the biosynthesis of aporphine alkaloids and lays a foundation for producing these valuable compounds through synthetic biology.
A digital technique for occlusal design of a posterior full crown based on physiological tooth displacement and occlusion of adjacent teeth
Authors: Chen Ying , Tu Ya , Pu Tingting , Ding Qian , Sun Yuchun , Zhang Lei
Published: July 2024

This article presents a digital technique to construct a virtual occlusion in the maximal intercuspal position (MIP), considering physiological tooth displacement and reducing intermesh penetrations between occlusal surfaces, in order to design more precise and accurate occlusal contacts of a posterior full crown.
Assessment of hard and soft tissue thickness at mandibular symphysis in skeletal Class III patients with different vertical patterns
Authors: Oh Jiyoung , Ham Lyun Kwang , Shin Hyemin , Han Sung‐Hoon , Kim Yoonji
Published: July 2024

Introduction

This study aimed to assess the bony and soft tissue parameters at mandibular symphysis among skeletal Class III patients with different vertical growth patterns, using cone‐beam computed tomography (CBCT).

Materials and Methods

CBCT images of 60 skeletal Class III non‐growing patients were evaluated (mean age 24.9 ± 8.4 years). Study samples were classified into three facial types based on the mandibular plane angle (SN‐MP angle): low, normal, and high angle. The bony and soft tissue parameters at the mandibular symphysis were evaluated.

Results

Among hard tissue variables, symphysis and pogonion width were significantly narrower in the high‐angle group (P < .05). The thickness of the buccal cortex at pogonion was also significantly thinner in subjects with high angles (P < .01). Symphysis height showed an increasing tendency from the low‐angle to the high‐angle group. However, no significant differences were found in chin width and height according to vertical patterns. Across all soft tissue measurements, the low‐angle group exhibited the highest thickness, which gradually decreased in the high‐angle group. Statistically significant differences in soft tissue thickness were observed at Menton (Me) and Gnathion (Gn) (P < .05). A significant negative correlation was observed between the SN‐MP angle and the thickness of both hard and soft tissues.

Conclusions

In skeletal Class III subjects, significant differences existed in both hard and soft tissues at the mandibular symphysis, depending on the vertical patterns. These results provide a comprehensive evaluation of symphyseal area, which can aid clinicians in identifying appropriate treatment approaches, especially for combined orthognathic and orthodontic treatment.
Pyrobacteriopheophorbide‐a derivatives possessing various hydrophilic esterifying groups at the C17‐propionate residues for photodynamic therapy
Authors: Sasaki Shin‐ichi , Morioka Yuto , Maegawa Kohta , Katsuragi Yuya , Nakamura Takashi , Kamemura Kazuo , Tamiaki Hitoshi
Published: July 2024

Aiming at the application to photodynamic therapy, natural bacteriochlorophyll‐a was converted to chemically stable free‐base derivatives possessing different kinds of hydrophilic C17‐propionate residues. These semi‐synthetic bacteriochlorins were found to have self‐assembling ability in an aqueous environment and formed stable J‐type aggregates in a cell culture medium containing 0.2% DMSO. The electronic absorption spectra of all the sensitizers showed Qy absorption maxima at 754 nm in DMSO as their monomeric states, while a drastic shift of the red‐most bands to ca. 880 nm was observed in the aqueous medium. The circular dichroism spectra in the medium showed much intense signals compared to those measured in DMSO, supporting the formation of well‐ordered supramolecular structures. By introducing hydrophilic side chains, the bacteriochlorin sensitizers could be dispersed in the aqueous medium as their J‐aggregates without the use of any surfactants. Cellular uptake efficiencies as well as photodynamic activities were evaluated using human cervical adenocarcinoma HeLa cells. Among the 11 photosensitizers investigated, the best result was obtained for a charged derivative possessing trimethylammonium terminal (17‐CH2CH2COOCH2CH2N+(CH3)3I−) and photocytotoxicity of EC50 = 0.09 μM was achieved by far‐red light illumination of 35 J/cm2 from an LED panel (730 nm).
Unique regulatory network of dragon fruit simultaneously mitigates the effect of vanadium pollutant and environmental factors
Authors: Zaman Qamar U. , Garg Vanika , Raza Ali , Nazir Mian Faisal , Hui Liu , Khan Darya , Khokhar Aamir Ali , Hussain Muhammad Azhar , Wang Hua‐Feng , Varshney Rajeev K.
Published: July 2024

Under changing climatic conditions, plants are simultaneously facing conflicting stresses in nature. Plants can sense different stresses, induce systematic ROS signals, and regulate transcriptomic, hormonal, and stomatal responses. We performed transcriptome analysis to reveal the integrative stress response regulatory mechanism underlying heavy metal stress alone or in combination with heat and drought conditions in pitaya (dragon fruit). A total of 70 genes were identified from 31,130 transcripts with conserved differential expression. Furthermore, weighted gene co‐expression network analysis (WGCNA) identified trait‐associated modules. By integrating information from three modules and protein–protein interaction (PPI) networks, we identified 10 interconnected genes associated with the multifaceted defense mechanism employed by pitaya against co‐occurring stresses. To further confirm the reliability of the results, we performed a comparative analysis of 350 genes identified by three trait modules and 70 conserved genes exhibiting their dynamic expression under all treatments. Differential expression pattern of genes and comparative analysis, have proven instrumental in identifying ten putative structural genes. These ten genes were annotated as PLAT/LH2, CAT, MLP, HSP, PB1, PLA, NAC, HMA, and CER1 transcription factors involved in antioxidant activity, defense response, MAPK signaling, detoxification of metals and regulating the crosstalk between the complex pathways. Predictive analysis of putative candidate genes, potentially governing single, double, and multifactorial stress response, by several signaling systems and molecular patterns. These findings represent a valuable resource for pitaya breeding programs, offering the potential to develop resilient “super pitaya” plants.
Heterogenous Rates of Return on Homes: Do The Rich Do Better?
Authors: Wolff Edward N.
Published: July 2024

Recent work on wealth inequality using the capitalization method wherein aggregate wealth totals are distributed proportionately to property income like dividends motivates concern about whether rates of return on assets vary across the income or wealth distribution. Here I use accrued capital gains and imputed rent on homes estimated from the Survey of Consumer Finances to address this issue. Both capital gains and imputed rent form part of total income. I find strong econometric evidence that returns vary directly with wealth level and are considerably higher for very wealthy compared to poorer households. However, I do not find evidence that higher income households receive higher returns once controlling for overall market house price trends. Returns are also strongly related to overall market house price movements, suggesting that timing the market is a key determinant. However, paradoxically, adding housing returns to baseline household wealth reduces overall wealth inequality.
Quantification of the contribution of individual coagulation factors to haemostasis using a microchip flow chamber system and reconstituted blood from deficient plasma
Authors: Fuchizaki Akihiro , Yasui Kazuta , Hayashi Tomoya , Fujimura Yoshihiro , Oyamada Chiaki , Ohnishi‐Wada Tomoko , Hosokawa Kazuya , Shimogaki Kazushige , Kimura Takafumi , Hirayama Fumiya , Takihara Yoshihiro
Published: July 2024

Background and Objectives

Quantifying the contribution of individual coagulation factors to haemostasis may aid our understanding of the haemostatic function in patients with rare coagulation deficiencies (RCDs) and the exploration of suitable treatments.

Materials and Methods

Reconstituted blood prepared from specific coagulation factor‐deficient plasma (factor [F]II; prothrombin, FV, FVII, FVIII, FIX, FX, FXI or FXII) and red blood cell/platelet products were used to simulate the whole blood of patients with RCD. We prepared in vitro treatment models for patients with prothrombin deficiency using coagulation factor agents and fresh frozen plasma. Haemostatic function was measured using a microchip flow chamber system at 600 s−1.

Results

The haemostatic function was low, especially in blood samples reconstituted with prothrombin‐ and FX‐deficient plasma. In a plasma transfusion model of prothrombin deficiency, haemostatic function recovered after 10% replacement with normal plasma and reached a plateau at ≧60% replacement. A treatment model of prothrombin deficiency with prothrombin complex concentrates revealed dose‐dependent therapeutic effects in the range of 0–50 IU/kg.

Conclusion

Microchip flow chamber system‐based quantification of haemostatic function using reconstituted blood could predict haemostasis and therapeutic effects of treatments in patients with prothrombin deficiency.
Surgical management of brachycephalic obstructive airway syndrome: An update on options and outcomes
Authors: Wallace Mandy L.
Published: July 2024

Dogs with a brachycephalic conformation often experience a collection of abnormalities related to their craniofacial conformation, which can lead to a variety of clinical signs such as stertor, exercise intolerance, respiratory distress, and gastrointestinal signs such as regurgitation, among others. This collection of abnormalities is termed brachycephalic obstructive airway syndrome (BOAS). With the rise in popularity of several brachycephalic breeds, veterinarians and veterinary surgery specialists are seeing these dogs with increasing frequency for surgical and medical treatment of these clinical signs, leading to an increased interest in developing surgical techniques for dogs with BOAS and evaluating objective methods of determining outcome after surgery. Advances in anesthetic management including standardized protocols and use of local nerve blocks to decrease opiate use may decrease postoperative complications. A variety of new or modified surgical techniques to manage hyperplastic soft palate and stenotic nares, among other BOAS components, have been developed and studied in recent years. Newer studies have also focused on risk factors for development of major complications in the postoperative period and on objective measurements that may help determine which patients will receive the most benefit from BOAS surgery. In this review, the newest studies focused on updates in anesthetic management, surgical techniques, and postoperative care will be discussed. Additionally, updated information on complication rates and outcomes for dogs undergoing surgical management of BOAS will be included.
Solving fractional differential equations on a quantum computer: A variational approach
Authors: Leong Fong Yew , Koh Dax Enshan , Kong Jian Feng , Goh Siong Thye , Khoo Jun Yong , Ewe Wei-Bin , Li Hongying , Thompson Jayne , Poletti Dario
Published: July 2024

We introduce an efficient variational hybrid quantum-classical algorithm designed for solving Caputo time-fractional partial differential equations. Our method employs an iterable cost function incorporating a linear combination of overlap history states. The proposed algorithm is not only efficient in terms of time complexity but also has lower memory costs compared to classical methods. Our results indicate that solution fidelity is insensitive to the fractional index and that gradient evaluation costs scale economically with the number of time steps. As a proof of concept, we apply our algorithm to solve a range of fractional partial differential equations commonly encountered in engineering applications, such as the subdiffusion equation, the nonlinear Burgers' equation, and a coupled diffusive epidemic model. We assess quantum hardware performance under realistic noise conditions, further validating the practical utility of our algorithm.
Barriers to Leisure-Time Physical Activity Among Women of Rural Gipuzkoa: A Mixed-Methods Approach
Authors: Eizagirre-Sagastibeltza Olaia , Fernandez-Lasa Uxue , Usabiaga Oidui
Published: July 2024

Background: Women, particularly those with young children, engage in less leisure-time physical activity (LTPA) than men. Additionally, mothers living in rural areas have more difficulty participating in LTPA than those in urban areas. The aim of this study was to analyze the challenges faced by mothers of rural areas of Gipuzkoa in LTPA participation, from a feminist perspective. Methods: A total of 129 mothers (age 41.5 ± 5.9; 45.7% inactive) with young children completed the Gipuzkoa Women’s Physical Activity Questionnaire. Concurrently, four focus groups were organized in four different municipalities, in which 19 mothers of young children participated (13 were inactive). Barriers were classified based on the socioecological perspective. Results: The most frequently mentioned intrapersonal barriers were lack of time due to work and caregiving, age-/pregnancy-/motherhood-related health issues, and a feeling of rejection toward LTPA. The most relevant interpersonal barriers were a lack of partners to do LTPA with and a lack of spouse support. The main environmental barriers were related to the shortage of facilities and activities suited to their needs and the rugged terrain. Conclusions: Mothers of young children living in rural areas face barriers twice over: because they are women and mothers and because they live in a rural environment. It therefore seems important to consider their perceived barriers to design, develop, and implement strategies to promote LTPA among this population group.
Brincidofovir inhibits polyomavirus infection
in vivo
Authors: Butic Arrienne B. , Katz Zoe E. , Jin Ge , Fukushima Koji , Hazama Masatoshi , Lukacher Aron E. , Lauver Matthew D.
Published: July 2024

Polyomaviruses are species-specific DNA viruses that can cause disease in immunocompromised individuals. Despite their role as the causative agents for several diseases, there are no currently approved antivirals for treating polyomavirus infection. Brincidofovir (BCV) is an antiviral approved for the treatment of poxvirus infections and has shown activity against other double-stranded DNA viruses. In this study, we tested the efficacy of BCV against polyomavirus infection
in vitro
and
in vivo
using mouse polyomavirus (MuPyV). BCV inhibited virus production in primary mouse kidney cells and brain cortical cells. BCV treatment of cells transfected with MuPyV genomic DNA resulted in a reduction in virus levels, indicating that viral inhibition occurs post-entry. Although
in vitro
BCV treatment had a limited effect on viral DNA and RNA levels, drug treatment was associated with a reduction in viral protein, raising the possibility that BCV acts post-transcriptionally to inhibit MuPyV infection. In mice, BCV treatment was well tolerated, and prophylactic treatment resulted in a reduction in viral DNA levels and a potent suppression of infectious virus production in the kidney and brain. In mice with chronic polyomavirus infection, therapeutic administration of BCV decreased viremia and reduced infection in the kidney. These data demonstrate that BCV exerts antiviral activity against polyomavirus infection
in vivo
, supporting further investigation into the use of BCV to treat clinical polyomavirus infections.

IMPORTANCE

Widespread in the human population and able to persist asymptomatically for the life of an individual, polyomavirus infections cause a significant disease burden in the immunocompromised. Individuals undergoing immune suppression, such as kidney transplant patients or those treated for autoimmune diseases, are particularly at high risk for polyomavirus-associated diseases. Because no antiviral agent exists for treating polyomavirus infections, management of polyomavirus-associated diseases typically involves reducing or discontinuing immunomodulatory therapy. This can be perilous due to the risk of transplant rejection and the potential development of adverse immune reactions. Thus, there is a pressing need for the development of antivirals targeting polyomaviruses. Here, we investigate the effects of brincidofovir, an FDA-approved antiviral, on polyomavirus infection
in vivo
using mouse polyomavirus. We show that the drug is well-tolerated in mice, reduces infectious viral titers, and limits viral pathology, indicating the potential of brincidofovir as an anti-polyomavirus therapeutic.
Sac1 links phosphoinositide turnover to cryptococcal virulence
Authors: Gaylord Elizabeth A. , Choy Hau Lam , Chen Guohua , Briner Sydney L. , Doering Tamara L.
Published: July 2024

Cryptococcus neoformans
is an environmentally acquired fungal pathogen that causes over 140,000 deaths per year. Cryptococcal infection occurs when infectious particles are deposited into the lung, where they encounter host phagocytic cells.
C. neoformans
may be engulfed by these phagocytes, an important step of infection that leads to outcomes ranging from termination of infection to cryptococcal dissemination. To study this critical process, we screened approximately 4,700 cryptococcal gene deletion mutants for altered uptake, using primary mouse and human phagocytic cells. Among the hits of these two screens, we identified 93 mutants with perturbed uptake in both systems, as well as others with differences in uptake by only one cell type. We further screened the hits for changes in thickness of the capsule, a protective polysaccharide layer around the cell which is an important cryptococcal virulence factor. The combination of our three screens yielded 45 mutants, including one lacking the phosphatidylinositol-4-phosphate phosphatase Sac1. In this work, we implicate Sac1 in both host cell uptake and capsule production. We found that
sac1
mutants exhibit lipid trafficking defects, reductions in secretory system function, and changes in capsule size and composition. Many of these changes occur specifically in tissue culture media, highlighting the role of Sac1 phosphatase activity in responding to the stress of host-like conditions. Overall, these findings show how genome-scale screening can identify cellular factors that contribute to our understanding of cryptococcal biology and demonstrate the role of Sac1 in determining fungal virulence.

IMPORTANCE

Cryptococcus neoformans
is a fungal pathogen with significant impact on global health. Cryptococcal cells inhaled from the environment are deposited into the lungs, where they first contact the human immune system. The interaction between
C. neoformans
and host cells is critical because this step of infection can determine whether the fungal cells die or proliferate within the human host. Despite the importance of this stage of infection, we have limited knowledge of cryptococcal factors that influence its outcome. In this study, we identify cryptococcal genes that affect uptake by both human and mouse cells. We also identify mutants with altered capsule, a protective coating that surrounds the cells to shield them from the host immune system. Finally, we characterize the role of one gene,
SAC1
, in these processes. Overall, this study contributes to our understanding of how
C. neoformans
interacts with and protects itself from host cells.
Multiple levels of transcriptional regulation control glycolate metabolism in
Paracoccus denitrificans
Authors: Schada von Borzyskowski Lennart , Hermann Lucas , Kremer Katharina , Barthel Sebastian , Pommerenke Bianca , Glatter Timo , Paczia Nicole , Bremer Erhard , Erb Tobias J.
Published: July 2024

The hydroxyacid glycolate is a highly abundant carbon source in the environment. Glycolate is produced by unicellular photosynthetic organisms and excreted at petagram scales to the environment, where it serves as growth substrate for heterotrophic bacteria. In microbial metabolism, glycolate is first oxidized to glyoxylate by the enzyme glycolate oxidase. The recently described β-hydroxyaspartate cycle (BHAC) subsequently mediates the carbon-neutral assimilation of glyoxylate into central metabolism in ubiquitous Alpha- and Gammaproteobacteria. Although the reaction sequence of the BHAC was elucidated in
Paracoccus denitrificans
, little is known about the regulation of glycolate and glyoxylate assimilation in this relevant alphaproteobacterial model organism. Here, we show that regulation of glycolate metabolism in
P. denitrificans
is surprisingly complex, involving two regulators, the IclR-type transcription factor BhcR that acts as an activator for the BHAC gene cluster, and the GntR-type transcriptional regulator GlcR, a previously unidentified repressor that controls the production of glycolate oxidase. Furthermore, an additional layer of regulation is exerted at the global level, which involves the transcriptional regulator CceR that controls the switch between glycolysis and gluconeogenesis in
P. denitrificans
. Together, these regulators control glycolate metabolism in
P. denitrificans
, allowing the organism to assimilate glycolate together with other carbon substrates in a simultaneous fashion, rather than sequentially. Our results show that the metabolic network of Alphaproteobacteria shows a high degree of flexibility to react to the availability of multiple substrates in the environment.

IMPORTANCE

Algae perform ca. 50% of the photosynthetic carbon dioxide fixation on our planet. In the process, they release the two-carbon molecule glycolate. Due to the abundance of algae, massive amounts of glycolate are released. Therefore, this molecule is available as a source of carbon for bacteria in the environment. Here, we describe the regulation of glycolate metabolism in the model organism
Paracoccus denitrificans
. This bacterium uses the recently characterized β-hydroxyaspartate cycle to assimilate glycolate in a carbon- and energy-efficient manner. We found that glycolate assimilation is dynamically controlled by three different transcriptional regulators: GlcR, BhcR, and CceR. This allows
P. denitrificans
to assimilate glycolate together with other carbon substrates in a simultaneous fashion. Overall, this flexible and multi-layered regulation of glycolate metabolism in
P. denitrificans
represents a resource-efficient strategy to make optimal use of this globally abundant molecule under fluctuating environmental conditions.