bluuebunny/crossref_metadata_2025 huggingface dataset:
FIGURE 3 from Gigaxonin Suppresses Epithelial-to-Mesenchymal Transition of Human Cancer Through Downregulation of Snail
Authors: Veena Mysore S. , Gahng Jungmo J. , Alani Mustafa , Ko Albert Y. , Basak Saroj K. , Liu Isabelle Y. , Hwang Kimberly J. , Chatoff Jenna R. , Venkatesan Natarajan , Morselli Marco , Yan Weihong , Ali Ibraheem , Kaczor-Urbanowicz Karolina Elżbieta , Gowda Bhavani Shankara , Frost Patrick , Pellegrini Matteo , Moatamed Neda A. , Wilczynski Sharon P. , Bomont Pascale , Wang Marilene B. , Shin Daniel Sanghoon , Srivatsan Eri S.
Published: March 2024

Enhanced in vitro cell growth and higher expression of EMT markers in GAN edited clones. A, Map of the gRNAs used in CRISPR-Cas9 assay. B, TspGW1 digested DNAs of puromycin-resistant clones of gRNAs 2 and 4 transfected ME180 cells show the presence of 287 and 155/132 bp PCR products (T and C alleles, respectively) compared with the presence of 287 bp (T/T alleles) in the parental ME180 cells. C, Representative morphology of GAN edited clones of gRNA4, C4.15.1, 15.3 in comparison with ME180 cells. D, Exon 8 PCR product sequencing shows conversion of T/T with C/C alleles in the GAN edited clone C4.15.1. Sequencing data show exon 8 SNP site containing T allele in ME180 and C allele in both the GAN edited clones C4.15.1 and C4.15.3. E, Western blot data show decreased expression of gigaxonin and e-cadherin in these clones in comparison with ME180 cells. However, there is increased expression of EMT markers, Snail, Twist, and n-cadherin in GAN edited clones. F, Incucyte growth assay shows faster growth of GAN edited clones C4.15.1 and C4.15.3 in comparison with parental ME180 cells. Cisplatin sensitivity is also reduced in these clones.
Early Organ Metastasis in Granulomatous Mycosis Fungoides: A Systematic Review
Authors: Motamedi Melika , Xiao Maggie Z.X. , Deschenes Jean , Hardin Jori , Sterrett Russell , Street Lesley , Taparia Minakshi , Mahe Etienne , Ferrara Giovanni , Barrie James R. , Gniadecki Robert
Published: March 2024

Background: Granulomatous mycosis fungoides (GMF) is a rare form of cutaneous T-cell lymphoma characterized by a granulomatous inflammatory infiltrate. Objective: The impact of granulomatous inflammation on the prognosis of the disease remains controversial as there have been both favorable and unfavorable outcomes documented. Methods: We performed a systematic review of 116 GMF cases previously described in the literature. Results: In contrast to the classic Alibert-Bazin type of mycosis fungoides (MF), cutaneous lesions in GMF tend to involve distal extremities (lower legs, feet, hands) early in the disease course. In the literature, 30% of GMF patients developed organ metastasis, most frequently to the lung. The median time to stage progression was 25 months. Conclusion: GMF is an aggressive form of MF. Therefore, screening for distant metastases should be considered at presentation and repeated during follow-up.
Upregulated Genes in Atrial Fibrillation Blood and the Left Atrium
Authors: Kamihara Takahiro , Kinoshita Tomoyasu , Kawano Reo , Tanaka Seiya , Toda Ayano , Ohara Fumiya , Hirashiki Akihiro , Kokubo Manabu , Shimizu Atsuya
Published: March 2024

Introduction: Atrial fibrillation (AF) is a common arrhythmia associated with aging. Many known risk factors are associated with AF, but many senior individuals do not develop AF despite having multiple risk factors. This finding suggests that other factors may be involved in AF onset. This study aimed to identify upregulated genes in the peripheral blood and left atrium of patients with AF. These genes may serve as potential biomarkers to predict AF onset risk and its complications. Methods: Gene expression data were analyzed from blood (n = 3) and left atrial samples (n = 15) of patients with AF and sinus rhythm. We evaluated the significant genes identified using p value analysis of weighted average difference to confirm their rankings. We created figures for the genes using GeneMANIA and performed a functional analysis using Cytoscape3.10.1. Hub and bottleneck genes were identified based on degree and betweenness centrality. We used reference expression (RefEx) to confirm the organs in which the extracted genes were expressed. Heatmaps and Gene ontology term evaluation were performed to further elucidate the biological functions of the genes. Results: We identified 12 upregulated genes (CAST, ASAH1, MAFB, VCAN, DDIT4, FTL, HEXB, PROS1, BNIP3L, PABPC1, YBX3, and S100A6) in both the blood and left atrium of patients with AF. We analyzed the gene functions using GeneMANIA and Cytoscape. The identified genes were involved in a variety of pathways, including lysosomal function and lipid and sphingolipid catabolism. Next, we investigated whether the 12 identified genes identified were systemically expressed or had high organ specificity. Finally, RefEx was used to analyze the gene expression levels in various tissues. Four genes, FTL, ASAH1, S100A6, and PABPC1, were highly expressed in the normal heart tissue. Finally, we evaluated the expression levels of the 12 genes in the blood of patients with AF using a heatmap. Our findings suggest that the 12 genes identified in this study, especially the lysosome-related genes (FTL and ASAH1), may be involved in AF pathogenesis. Conclusion: Lysosome-related genes may be important to understand the AF pathophysiology and to develop AF-related future studies.
Medullary Sponge Kidney and Its Relationship with Primary Distal Renal Tubular Acidosis: Case Reports and a Comprehensive Genetics-First Approach
Authors: van den Berg Gerrit , Claus Laura R. , van der Zwaag Bert , Lakeman Phillis ,   Genomics England Research Consortium, Kaasenbrood Lotte , Sayer John A. , Lilien Marc R. , van Eerde Albertien M.
Published: March 2024

Medullary sponge kidney (MSK) is a description of radiographic features. However, the pathogenesis of MSK remains unclear. MSK is supposed to be the cause of secondary distal renal tubular acidosis (dRTA), although there are case reports suggesting that MSK is a complication of primary dRTA. In addition to these reports, we report 3 patients with metabolic acidosis and MSK, in whom primary dRTA is confirmed by molecular genetic analyses of SLC4A1 and ATP6V1B1 genes. With a comprehensive genetics-first approach using the 100,000 Genomes Rare Diseases Project dataset, the association between MSK and primary dRTA is examined. We showed that many patients with MSK phenotypes are genetically tested with a gene panel which does not contain dRTA-associated genes, revealing opportunities for missed genetic diagnosis. Our cases highlight that the radiological description of MSK is not a straightforward disease or clinical phenotype. Therefore, when an MSK appearance is noted, a broader set of causes should be considered including genetic causes of primary dRTA as the underlying reason for medullary imaging abnormalities.
The Complement C3a and C5a Signaling in Renal Diseases: A Bridge between Acute and Chronic Inflammation
Authors: Buelli Simona , Imberti Barbara , Morigi Marina
Published: March 2024

The complement system, a cornerstone of the innate immune defense, typically confers protection against pathogens. However, in various clinical scenarios the complement’s defensive actions can harm host cells, exacerbating immune and inflammatory responses. The central components C3 and C5 undergo proteolytic cleavage during complement activation, yielding small active fragments C3a and C5a anaphylatoxins. Traditionally, these fragments were associated with inflammation via the specific receptors C3a receptor (R), C5aR1 and C5aR2. Recent insights, however, spotlight the excessive C3a/C3aR and C5a/C5aR1 signaling as culprits in diverse disorders of inflammatory and autoimmune etiology. This is particularly true for several kidney diseases, where the potential involvement of anaphylatoxins in renal damage is supported by the enhanced renal expression of their receptors and the high levels of C3a and C5a in both plasma and urine. Furthermore, the production of complement proteins in the kidney, with different renal cells synthesizing C3 and C5, significantly contributes to local tissue injury. In the present review, we discuss the different aspects of C3a/C3aR and C5a/C5aR signaling in acute and chronic kidney diseases and explore the therapeutic potential of emerging targeted drugs for future clinical applications.
Multi-Ethnic Study of Atherosclerosis Early Heart Failure Study: Rationale, Design, and Baseline Characteristics
Authors: Beussink-Nelson Lauren , Freed Benjamin H. , Chirinos Julio A. , Brubaker Peter H. , Kitzman Dalane W. , Yeboah Joseph , Rosas Sylvia E. , Hu Mo , Lima João A.C. , Pandit Jay , Bertoni Alain G. , Shah Sanjiv J.
Published: March 2024

Background:

Current prevalence estimates of heart failure (HF) are primarily based on self-report or HF hospitalizations. There is an unmet need to define the prevalence and pathogenesis of early symptomatic HF, which may be undiagnosed and precedes HF hospitalization.

Methods:

The MESA (Multi-Ethnic Study of Atherosclerosis) Early HF study was conducted during MESA exam 6 to determine the prevalence of early HF and investigate the transition from risk factors to early HF in a diverse population-based cohort of older adults. Between 2016 and 2018, 3285 MESA participants from 6 field centers underwent comprehensive speckle-tracking echocardiography with passive leg raise maneuver, Kansas City Cardiomyopathy Questionnaire, 6-minute walk test, arterial stiffness assessment, and proteomics (including NT-proBNP [N-terminal pro-B-type natriuretic peptide]).

Results:

Median age was 73 (25th–75th percentile 67–81) years, 53.2% were female, 25.6% were Black, 12.8% were Chinese, and 40.0% were White. The prevalence of HF risk factors was high: hypertension, 61.9%; former or current smoking, 53.7%; obesity 34.8%; diabetes; 24.7%; and chronic kidney disease; 22%. Overt cardiovascular disease, which ranged from 2.1% (HF) to 13.6% (atrial fibrillation), was less common. Of the 3285 participants, 96% underwent proteomics, 94% Kansas City Cardiomyopathy Questionnaire, 93% speckle-tracking echocardiography with passive leg raise, 82% arterial stiffness exam, and 77% 6-minute walk test. Feasibility of resting speckle-tracking echocardiography (87%–99% across cardiac chambers) and passive leg raise Doppler/speckle-tracking echocardiography (>84%) measurements was high. A total of 120 unique echocardiographic indices were measured.

Conclusions:

The MESA Early HF study is a key resource for cardiovascular researchers who are interested in improving the epidemiological and phenotypic characterization of early HF.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT00005487.
Characterizing the Causal Pathway From Childhood Adiposity to Right Heart Physiology and Pulmonary Circulation Using Lifecourse Mendelian Randomization
Authors: Leyden Genevieve M. , Urquijo Helena , Hughes Alun D. , Davey Smith George , Richardson Tom G.
Published: March 2024

Background

Observational epidemiological studies have reported an association between childhood adiposity and altered cardiac morphology and function in later life. However, whether this is due to a direct consequence of being overweight during childhood has been difficult to establish, particularly as accounting for other measures of body composition throughout the lifecourse can be exceptionally challenging.

Methods and Results

In this study, we used human genetics to investigate this using a causal inference technique known as lifecourse Mendelian randomization. This approach allowed us to evaluate the effect of childhood body size on 11 measures of right heart and pulmonary circulation independent of other anthropometric traits at various stages in the lifecourse. We found strong evidence that childhood body size has a direct effect on an enlarged right heart structure in later life (eg, right ventricular end‐diastolic volume: β=0.24 [95% CI, 0.15–0.33];
P
=3×10
−7
) independent of adulthood body size. In contrast, childhood body size effects on maximum ascending aorta diameter attenuated upon accounting for body size in adulthood, suggesting that this effect is likely attributed to individuals remaining overweight into later life. Effects of childhood body size on pulmonary artery traits and measures of right atrial function became weaker upon accounting for adulthood fat‐free mass and childhood height, respectively.

Conclusions

Our findings suggest that, although childhood body size has a long‐term influence on an enlarged heart structure in adulthood, associations with the other structural components of the cardiovascular system and their function may be largely attributed to body composition at other stages in the lifecourse.
Use of Sodium‐Glucose Cotransporter‐2 Inhibitors and Angiotensin Receptor‐Neprilysin Inhibitors in Patients With Atrial Fibrillation and Heart Failure From 2021 to 2022: An Analysis of Real‐World Data
Authors: Alonso Alvaro , Morris Alanna A. , Naimi Ashley I. , Alam Aniqa B. , Li Linzi , Subramanya Vinita , Chen Lin Yee , Lutsey Pamela L.
Published: March 2024

Background

Contemporary use of sodium‐glucose cotransporter‐2 inhibitors (SGLT2i) and angiotensin receptor‐neprilysin inhibitors (ARNi) in patients with atrial fibrillation (AF) and heart failure (HF) has not been described.

Methods and Results

We analyzed the MarketScan databases for the period January 1, 2021 to July 30, 2022. Validated algorithms were used to identify patients with AF and HF, and to classify patients into HF with reduced ejection fraction (HFrEF) or HF with preserved ejection fraction (HFpEF). We assessed the prevalence of SGLT2i and ARNi use overall and by HF type. Additionally, we explored correlates of lower use, including demographics and comorbidities. The study population included 60 927 patients (mean age, 75 years; 43% women) diagnosed with AF and HF (85% with HFpEF, 15% with HFrEF). Prevalence of ARNi use was 11% overall (30% in HFrEF, 8% in HFpEF), whereas the corresponding figure was 6% for SGLT2i (13% in HFrEF, 5% in HFpEF). Use of both medications increased over the study period: ARNi from 9% to 12% (22%–29% in HFrEF, 6%–8% in HFpEF), and SGLT2i from 3% to 9% (6%–16% in HFrEF, 2%–7% in HFpEF). Female sex, older age, and specific comorbidities were associated with lower use of these 2 medication types overall and by HF type.

Conclusions

Use of ARNi and SGLT2i in patients with AF and HF is suboptimal, particularly among women and older individuals, though use is increasing. These results underscore the need for understanding reasons for these disparities and developing interventions to improve adoption of evidence‐based therapies among patients with comorbid AF and HF.
Toward Improving the Generation Quality of Autoregressive Slot VAEs
Authors: Emami Patrick , He Pan , Ranka Sanjay , Rangarajan Anand
Published: March 2024

Unconditional scene inference and generation are challenging to learn jointly with a single compositional model. Despite encouraging progress on models that extract object-centric representations (“slots”) from images, unconditional generation of scenes from slots has received less attention. This is primarily because learning the multiobject relations necessary to imagine coherent scenes is difficult. We hypothesize that most existing slot-based models have a limited ability to learn object correlations. We propose two improvements that strengthen object correlation learning. The first is to condition the slots on a global, scene-level variable that captures higher-order correlations between slots. Second, we address the fundamental lack of a canonical order for objects in images by proposing to learn a consistent order to use for the autoregressive generation of scene objects. Specifically, we train an autoregressive slot prior to sequentially generate scene objects following a learned order. Ordered slot inference entails first estimating a randomly ordered set of slots using existing approaches for extracting slots from images, then aligning those slots to ordered slots generated autoregressively with the slot prior. Our experiments across three multiobject environments demonstrate clear gains in unconditional scene generation quality. Detailed ablation studies are also provided that validate the two proposed improvements.
Jesus: A Life in Class Conflict
Authors: Wines Megan
Published: March 2024

This essay is a review of Jesus: A Life in Class Conflict by James Crossley and Robert J. Myles, a historical materialist exploration of what we know about the life of Jesus and the Jesus movement in first-century Roman Palestine. This review focuses particularly on the ways in which Crossley and Myles engage with considerations of gender and masculinity as part of their engagement with the historical materials.
Jesus, the Crowds, and Historical Agency
Authors: Elliott Neil
Published: March 2024

Crossley and Myles’s Jesus: A Life in Class Struggle offers an innovative and accessible reading of the movement around Jesus in terms of class struggle. The authors combine a breadth of knowledge about first-century realities, acumen in exegesis of the Gospel texts, and contemporary crowd theory to reach new conclusions regarding Jesus and his disciples, especially in his last days, and regarding the ‘failure’ of their movement. This review examines their understanding of the ‘Jesus movement’ and its relationship to the Galilean peasantry and their methodology in extrapolating from the Gospels; and proposes a more thorough Marxist theorization of the Gospels’ role in producing the ‘failure’ they describe.
Young Chinese’s Modern Arranged Marriage and Mosaic Familialism in Shanghai
Authors: Ji Yingchun , Lin Zeyu , Liu Yue , Kang Rui
Published: March 2024

With rapid socio-economic development over the past four decades, a unique tapestry of Chinese society has unfolded into a mosaic of rapid modernization and resurgent patriarchal tradition. Within this complex temporality, parents still remain salient in young Chinese’ love and marital life. This study uses data from semi-structured interviews with recently married young people and their parents to investigate how young adults and their parents are involved in the marriage formation process. We found that in this joint process of intergenerational cooperative marriage arrangement, young people and their parents play different roles, as accommodating decision-makers and respectful advisers, respectively. They agreed that a modern marriage based on individual, romantic love was also a union between two families and welcomed their parents’ involvement. Moreover, they considered getting married and taking their parents’ opinions and preferences into account in their marriage decision as part of their filial piety towards their parents. We have also found that mothers played a salient and significant role in facilitating the transformation of the traditional and distant patriarchal intergenerational relationship into a warm and supportive family union. There are two sides to the mother’s role: the entrenchment of the traditional gender roles and the elevation of women’s status in the family.
Digital Work, Emotion Commodification, and Moral Legitimacy: Transnational Bloggers on Chinese Social Media Platforms
Authors: Liu Yuting
Published: March 2024

Transnational bloggers, a rising breed of digital workers, foster emotional connections with followers, expand their influence through diverse digital interactions, and generate income through commercial activities. However, the commodification of emotions is met with resistance from select Chinese netizens, raising moral questions. This article explores how transnational bloggers integrate emotion and commerce within China’s platform economy. Our findings show that these bloggers establish positive emotional connections with Chinese followers, characterized by friendship, support, and sharing, which are crucial for sustaining their careers. In their quest for moral legitimacy in transnational digital commerce, they employ various strategies, including posting techniques, marketing strategies, and moral self-negotiation. This article encourages further research on emerging digital workers in the global platform economy, shedding light on their resources, actions, and competencies.
Confucian Liberalism With/out Mou Zongsan: On Roy Tseng’s Confucian Liberalism
Authors: Kim Sungmoon
Published: March 2024

In his recent book, Roy Tseng provides one of the most systematic accounts of modern Confucianism that is liberal and moderately perfectionist. Tseng also offers a comprehensive analysis of Mou Zongsan’s political philosophy with special attention to its Hegelian-liberal dimension. This paper critically examines whether Tseng’s constructive and interpretive goals are integrated seamlessly. Its central claim is that while Tseng has succeeded in developing a morally attractive vision of Confucian liberalism through the creative reinterpretation of Confucianism in communication with Hegelian idealism, it is dubious that his extensive investigation of Mou’s political philosophy was necessary for achieving this goal. More specifically, it challenges Tseng’s claim that the idea of Confucian democratic civility is the central component of Mou’s vision of Confucian liberalism by showing that Mou never committed himself to the distinction between moral virtue and civic virtue, the baseline assumption for the possibility of Confucian democratic civility.
6. Journalism and Authorship
Authors: Howsam Leslie
Published: March 2024

A further aspect of Eliza Orme’s public life in the 1870s, 1880s, and 1890s was her eloquent, engaged, authorship—some of it signed but much of it published anonymously. This chapter situates her as a journalist and editor as well as a lawyer and politician. In more or less chronological order, sections include: ‘Contributions to The Examiner, Englishwoman’s Review and Longman’s (and an index)’ (these comprised her important essays ‘Sound-Minded Women’ and ‘How Poor Ladies Live’ as well as a work of legal scholarship that took the form of indexing Savill Vaizey’s book on marriage settlements); ‘Leaders for the Weekly Dispatch’ (an important aspect of Orme’s life that puts her among a handful of powerful women journalists, but still awaits further research); The Women’s Gazette and the Royal Commission (whatever the political or official purposes of these activities, the editing of the Women’s Gazette was journalism and the several reports of the Royal Commission report constituted authorship); ‘A Trial in India, a literary labour of love, and more’ (Orme’s editing of The Trial of Shama Charan Pal and her biography, Lady Fry of Darlington); ‘National Biography’ (Orme’s three contributions to the 1901 supplementary volume of the Dictionary of National Biography).

This chapter is shaped significantly by Leslie Howsam’s research interests in the history of the book, and of the periodical press, in nineteenth-century Britain.
Potential Predictability of Two-Year Droughts in the Missouri River Basin
Authors: Hoell Andrew , Quan Xiao-Wei , Robinson Rachel , Hoerling Martin
Published: March 2024

Potential predictability of 2-yr droughts indicated by low runoff in the consecutive April–September seasons in the upper Missouri River basin (UMRB) and lower Missouri River basin (LMRB) is examined with observed estimates and climate models. The majority of annual runoff is generated in April–September, which is also the main precipitation and evapotranspiration season. Physical features related to low April–September runoff in both UMRB and LMRB include a dry land surface state indicated by low soil moisture, low snowpack indicated by low snow water equivalent, and a wave train across the Pacific–North American region that can be generated internally by the atmosphere or forced by the La Niña phase of El Niño–Southern Oscillation. When present in March, these features increase the risk of low runoff in the following April–September warm seasons. Antecedent low soil moisture significantly increases low runoff risks in each of the following two April–September, as the dry land surfaces decrease runoff efficiency. Initial low snow water equivalent, especially in the Missouri River headwaters of Montana, generates less runoff in the subsequent warm season. La Niña increases the risk of low runoff during the warm seasons by suppressing precipitation via dynamically induced atmospheric circulation anomalies. Model simulations that differ in their radiative forcing suggest that climate change increases the predictability of 2-yr droughts in the Missouri River basin related to La Niña. The relative risk of low runoff in the second April–September following a La Niña event in March is greater in the presence of stronger radiative forcing.

Significance Statement

Drought spanning consecutive years in the upper Missouri River basin (UMRB) and lower Missouri River basin (LMRB) poses threats to a region whose economy depends on reliable water quantity to support transportation and recreation, adequate water supply for irrigated agriculture, and sufficient streamflow to generate hydroelectric power. We examined physical features in March related to low runoff in the following April–September—low soil moisture, low snow water equivalent, and La Niña events—and examined their effect on the risk of 2-yr drought occurrences. These physical features lead to sustained impacts on the surface water balance. Low snow water equivalent generates less runoff, low soil moisture reduces the runoff efficiency of converting precipitation into runoff, and La Niña inhibits warm-season precipitation and runoff via atmospheric circulation anomalies.
Forecasting High Wind Events in the HRRR Model over Wyoming and Colorado. Part II: Sensitivity of Surface Wind Speeds to Model Resolution and Physics
Authors: Collins Ethan , Lebo Zachary J. , Cox Robert , Hammer Christopher , Brothers Matthew , Geerts Bart , Capella Robert , McCorkle Sarah
Published: March 2024

Strong wind events can cause severe economic loss and societal impacts. Peak winds over Wyoming and Colorado occur during the wintertime months, and in the first part of this two-part series, it was shown that the High-Resolution Rapid Refresh (HRRR) model displays large negative biases with respect to strong wind events. In this part of the study, we address two questions: 1) does increasing the horizontal resolution improve the representation of strong wind events over this region, and 2) are the biases in HRRR-forecasted winds related to the selected planetary boundary layer (PBL), surface layer (SL), and/or land surface model (LSM) parameterizations? We conduct Weather Research and Forecasting (WRF) Model simulations to address these two main questions. Increasing the horizontal resolution leads to a small improvement in the simulation of strong wind speeds over the complex terrain of Wyoming and Colorado. In general, changes in the PBL, SL, and LSM parameterizations show much larger changes in simulated wind speeds compared to increasing the model resolution alone. Specifically, changing from the Mellor–Yamada–Nakanishi–Niino scheme to the Mellor–Yamada–Janjić PBL and SL schemes results in nearly no change in the r2 values, but there is a decrease in the magnitude of the strong wind speed bias (from −12.52 to −10.16 m s−1). We attribute these differences to differences in the diagnosis of surface wind speeds and mixing in the boundary layer. Further analysis is conducted to determine the value of 1-km forecasts of strong winds compared with wind speed diagnostics commonly used by the National Weather Service.

Significance Statement

Motivated by prior studies showing low skill in the prediction of strong winds using state-of-the-art weather forecast models, in this study, we aim to investigate two questions: 1) does increasing the horizontal resolution improve the prediction of strong wind events over the complex terrain of Wyoming and Colorado, and 2) are the biases in High-Resolution Rapid Refresh (HRRR) forecasted winds related to the selected planetary boundary layer, surface layer, and/or land surface model parameterizations? We find that increasing the horizontal resolution provides a slight improvement in the prediction of strong winds. Further, considerable improvement in the prediction of strong winds is found for varying boundary layer, surface layer, and land surface parameterizations.
Screening of genes characteristic of pancreatic cancer by LASSO regression combined with support vector machine and recursive feature elimination, and immune correlation analysis
Authors: Zeng Longhui , Chen Zheng
Published: March 2024

Background

Pancreatic cancer is a malignant tumor of the digestive tract that shows increased mortality, recurrence, and morbidity year on year.

Methods

Differentially expressed genes between pancreatic cancer and healthy tissues were first analyzed from four datasets within the Gene Expression Omnibus (GEO). Gene ontology, disease ontology, and gene set enrichment analysis of differentially expressed genes were performed, and genes identified as characteristic of pancreatic cancer were screened using LASSO regression combined with support vector machine and recursive feature elimination (SVM–RFE). Differential analysis and receiver operating characteristic curve analysis were performed on the identified eigengenes, and validation was carried out using another dataset from the GEO database. Differences and correlations between characteristic pancreatic cancer genes and immune cells were analyzed.

Results

A total of 90 differentially expressed genes were identified by screening, and six genes characteristic of pancreatic cancer were obtained by taking the intersection of two characteristic genes identified by machine learning. Immunoassays yielded multiple immune cells associated with pancreatic cancer signature genes.

Conclusion

The six characteristic genes screened by a combination of LASSO regression and SVM–RFE are potential new biomarkers for the early diagnosis and prognosis of pancreatic cancer, and could be a novel therapeutic target.
Masks wearing off: Changing effects of face masks on trustworthiness over time
Authors: Oldmeadow Julian A. , Gogan Taylor
Published: March 2024

During the global COVID-19 pandemic, the wearing of face masks became a common practice, raising questions about how masks affect perceptions of and behaviour towards others. Numerous studies have explored the impact of face masks on perceptions of trustworthiness, but results have been mixed and it remains unclear whether masks influence perceptions via their social meaning or their effects on facial appearance. In this study, Australian participants ( N = 363) rated a series of faces which were either masked, unmasked, or occluded by a non-mask object (computer) in terms of perceived trustworthiness in 2020, 2022, or 2023. The apparent trustworthiness of unmasked faces remained stable across years, but masked faces were rated significantly more trustworthy in 2020 compared to 2022 and 2023. Furthermore, ratings of masked faces, but not unmasked faces, were correlated with participants’ attitudes towards wearing masks. Faces occluded by a non-mask object were perceived to be less trustworthy than masked faces. Together, results strongly suggest the increase in perceived trustworthiness of masked faces reported in numerous studies conducted during COVID-19 were driven by positive social meanings around mask wearing rather than by their effect on facial appearance.
Calprotectin as a new inflammatory marker of abdominal aortic aneurysm: A pilot study
Authors: Plana Emma , Oto Julia , Herranz Raquel , Medina Pilar , Cana Fernando , Miralles Manuel
Published: March 2024

Introduction:

Abdominal aortic aneurysm (AAA) is a relevant clinical problem due to the risk of rupture of progressively dilated infrarenal aorta. It is characterized by degradation of elastic fibers, extracellular matrix, and inflammation of the arterial wall. Though neutrophil infiltration is a known feature of AAA, markers of neutrophil activation are scarcely analyzed; hence, the main objective of this study.

Methods:

Plasma levels of main neutrophil activation markers were quantified in patients with AAA and a double control group (CTL) formed by healthy volunteers (HV) and patients with severe atherosclerosis submitted for carotid endarterectomy (CE). Calprotectin, a cytoplasmic neutrophil protein, was quantified, by Western blot, in arterial tissue samples from patients with AAA and organ donors. Colocalization of calprotectin and neutrophil elastase was assessed by immunofluorescence.

Results:

Plasma calprotectin and IL-6 were both elevated in patients with AAA compared with CTL ( p ⩽ 0.0001) and a strong correlation was found between both molecules ( p < 0.001). This difference was maintained when comparing with HV and CE for calprotectin but only with HV for IL-6. Calprotectin was also elevated in arterial tissue samples from patients with AAA compared with organ donors ( p < 0.0001), and colocalized with neutrophils in the arterial wall.

Conclusions:

Circulating calprotectin could be a specific AAA marker and a potential therapeutical target. Calprotectin is related to inflammation and neutrophil activation in arterial wall and independent of other atherosclerotic events.
Understanding autism diagnosis in primary care: Rates of diagnosis from 2004 to 2019 and child age at diagnosis
Authors: Smith Jessica V , Menezes Michelle , Brunt Sophie , Pappagianopoulos Jessica , Sadikova Eleonora , O Mazurek Micah
Published: March 2024

The capacity of the workforce lags behind the current demand for timely autism diagnostic assessment. Primary care providers (PCPs) are well-positioned to diagnose autism at earlier ages than providers from other disciplines. Thus, bolstering PCPs’ diagnostic capabilities has been the focus of many recent capacity-building initiatives. Using data from the National Survey of Children’s Health, this study aimed to evaluate whether diagnosis of autism in primary care has changed over time and whether diagnosis in primary care relates to age at autism diagnosis. Results indicated that the likelihood of being diagnosed with autism by a PCP decreased by about 2% with every passing year from 2004 to 2019 when controlling for demographic characteristics. PCPs diagnosed children approximately 1 year earlier than non-PCPs (e.g., psychiatrists and psychologists), which supports the critical role PCPs can play in timely diagnosis. Further research is needed to understand why the proportion of children diagnosed by PCPs has decreased over time; however, these findings suggest that capacity-building initiatives have not yet reached community practice. Future research should focus on the dissemination and implementation of training initiatives in community-based primary care practices.

Lay abstract

The current demand for autism diagnostic services exceeds the ability of the workforce to assess and diagnose children in a timely manner. One solution may be to equip primary care providers (PCPs) with the tools and expertise needed to diagnose autism within their practice. PCPs are often trusted professionals who have many touchpoints with children during early development, in which they can identify early signs of autism. Recent initiatives have focused on bolstering PCPs’ diagnostic capabilities; however, no studies have examined how the rates of autism diagnosis in primary care have changed over time. We aimed to evaluate whether autism diagnosis in primary care has changed over time and how diagnosis in primary care relates to a child’s age at the time of diagnosis. We found that the likelihood of a child being diagnosed by a PCP decreased by about 2% with every passing year from 2004 to 2019 when accounting for demographic characteristics. In our sample, PCPs diagnosed children approximately 1 year earlier than non-PCPs (e.g., psychologists and psychiatrists). Further research is needed to understand why the proportion of children diagnosed by PCPs decreases over time. However, this decrease suggests more work is needed to get capacity-building initiatives into community primary care practice. Though we must continue to find effective ways to build community PCPs’ ability to diagnose autism, the present findings support the crucial role PCPs can play in early autism diagnosis.
The silicon future
Authors: Cheney-Lippold John
Published: March 2024

This article proposes the concept of the silicon future—a privileged temporal position that functionally precedes the present—to argue for an increased focus on temporality and the role it plays in technodeterminist discourse. By interpreting how Silicon Valley firms employ this silicon future as an inevitability that they themselves have already reached, the article describes a temporal paternalism—a claim to authority that validates itself not according to arguments or facts, but to temporal supremacy—that executives and venture capitalists rely on to justify their actions and investments. In kind, this article shows how this idea of an already-existing future is used by big tech to frame its own inventions as inevitable, unregulatable, and beyond critique. Using news reports and other publicfacing technophilic materials, it traces the temporal forms that underwrite the power of Silicon Valley’s technodeterminism.
Environmental outlook of ASEAN-5 through the lens of green bonds, environmental technologies and financialization
Authors: Tran Ngoc Thanh , Nguyen Hai-Tuan , Tran Trung Kien , Diep Gia Luat , Nguyen Thi Huong Nhai , Tran Thai Ha Nguyen
Published: March 2024

Sustainable development goals call for urgent action with an aim to spur socio-economic growth along with the protection of the environment and resources. However, these goals are difficult to be achieved when finances are not mobilized to mitigate harmful resources. In return, numerous green bond manifestations appeared in the market, which are viewed as a bridge to have successful implementation of sustainable development goals. Therefore, the study is aimed to explore the relevance of green bonds, financialization, and sustainable environmental change mitigation technologies for environmental change in ASEAN economies. The initial outcomes confirm the long-run cointegration association between study variables and also explore the slope heterogeneity and cross-sectional dependencies. To explore the causal connections between the study variables, the current study employs CS-ARDL technique. The study finds significant contributions of sustainable environmental change mitigation technologies and green bonds in the reduction of pollution, hence improving climate quality. The short-run infers similar results with relatively lower magnitudes of coefficients as compared to the long-run. Negative error correction terms are used to confirm the stability of the model, which implies sustained convergence towards “steady-state equilibrium” in case of expected deviations. The results offer practical implications and recommendations.
Neonatal Graves disease with persistent hypoglycemia: A case report
Authors: Fine Samantha , Gottschalk Michael , Marc-Aurele Krishelle
Published: March 2024

Neonatal Graves disease is the most common cause of hyperthyroidism during the newborn period. Maternal Graves disease increases the risk of intrauterine growth restriction, small for gestational age, and neonatal Graves disease. Intrauterine growth restriction and small for gestational age are associated with hypoglycemia and transient neonatal hyperinsulinism. Neonatal Graves disease with severe persistent hypoglycemia has not been well described. We present the case of a female patient born at 34 weeks and 3 days with a birth weight of 1.6 kg (fifth percentile) to a mother with recent treatment for Graves disease. Prenatal ultrasounds were significant for intrauterine growth restriction and small for gestational age. The mother did not begin hyperthyroidism medical therapy until 23 weeks and 2 days of gestation. After the infant was born, the infant not only had symptoms of hyperthyroidism such as tachycardia and abnormal thyroid values but also had persistent hypoglycemia, which could be due to maternal propranolol usage, prematurity, IUGR, increased metabolism due to neonatal Graves, and transient stress-induced hyperinsulinism. The infant was started on methimazole for hyperthyroidism and propranolol for tachycardia. She was also started on diazoxide for persistent hypoglycemia. By 6 months of age, the hyperthyroidism and hypoglycemia had resolved. This is an interesting case of neonatal Graves disease with severe persistent hypoglycemia which we suspect is due to transient neonatal hyperinsulinism induced by multiple stress responses.
Greening the gentrification process: Insights and engagements from practitioners
Authors: Quinton Jessica , Nesbitt Lorien , Sax Daniel , Harris Leila
Published: March 2024

Green gentrification implicates urban greening as a driver of neighbourhood ‘upgrading’ and subsequent displacement. However, it is unclear whether the concept resonates with, or supports the work of, those responsible for much of the greening occurring in cities – urban green planners/practitioners. We interviewed 33 planners/practitioners in Canada to refine our understanding of the relationships between urban greening and gentrification. We found that greening is closely tied to development, with funding/space for greening often provided through development requirements/incentives. Thus, rather than greening causing gentrification (as described in current literature), here greening is often a requirement and direct outcome of new development – contributing to what we describe as a broader greening of the gentrification process that is facilitated by various political-economic factors. Many interviewees stated that their current work focuses on addressing existing inequities rather than strategizing to limit future gentrification. However, they had mixed opinions about whether knowledge of green gentrification as a concept can help them promote equitable urban greening due to their lack of power over where/how urban greening occurs, along with the finding that greening is not causing gentrification. The uneven power dynamics between urban green practitioners/planners, developers, and elected officials also influenced views on whether gentrification is an intended outcome of greening. We conclude that relying on new development to provide urban greening is antithetical to addressing existing green inequities and is likely to exacerbate inequities through associating greening with gentrification. Recent measures to improve housing affordability (i.e. the removal of developer greening requirements) will disrupt the current development-greening relationship but are unlikely to address the issue of inequitable greening. Increased and ongoing collaboration between those working in urban greening, housing, and planning is paramount and should focus on affordability and equity across urban systems – attending to the interplay between greening, housing, affordability, and sustainability.
AMPK activation attenuates central sensitization in a recurrent nitroglycerin-induced chronic migraine mouse model by promoting microglial M2-type polarization
Authors: Lu Guangshuang , Xiao Shaobo , Meng Fanchao , Zhang Leyi , Chang Yan , Zhao Jinjing , Gao Nan , Su Wenjie , Guo Xinghao , Liu Yingyuan , Li Chenhao , Tang Wenjing , Zou Liping , Yu Shengyuan , Liu Ruozhuo
Published: March 2024

Background

Energy metabolism disorders and neurogenic inflammation play important roles in the central sensitization to chronic migraine (CM). AMP-activated protein kinase (AMPK) is an intracellular energy sensor, and its activation regulates inflammation and reduces neuropathic pain. However, studies on the involvement of AMPK in the regulation of CM are currently lacking. Therefore, this study aimed to explore the mechanism underlying the involvement of AMPK in the central sensitization to CM.

Methods

Mice with recurrent nitroglycerin (NTG)-induced CM were used to detect the expression of AMPK protein in the trigeminal nucleus caudalis (TNC). Following intraperitoneal injection of the AMPK activator 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR) and inhibitor compound C, the mechanical pain threshold, activity level, and pain-like behaviors in the mice were measured. The expression of calcitonin gene-related peptide (CGRP) and cytokines, M1/M2 microglia, and NF-κB pathway activation were detected after the intervention.

Results

Repeated NTG injections resulted in a gradual decrease in AMPK protein expression, and the negative regulation of AMPK by increased ubiquitin-like plant homeodomain and RING finger domain 1 (UHRF1) expression may counteract AMPK activation by increasing ADP/ATP. AICAR can reduce the hyperalgesia and pain-like behaviors of CM mice, improve the activity of mice, reduce the expression of CGRP, IL-1β, IL-6, and TNF-α in the TNC region, and increase the expression of IL-4 and IL-10. Moreover, AMPK in TNC was mainly located in microglia. AICAR could reduce the expression of inducible NO synthase (iNOS) in M1 microglia and increase the expression of Arginase 1 (Arg1) in M2 microglia by inhibiting the activation of NF-κB pathway.

Conclusions

AMPK was involved in the central sensitization of CM, and the activation of AMPK reduced neuroinflammation in NTG-induced CM mice. AMPK may provide new insights into interventions for energy metabolism disorders and neurogenic inflammation in migraine.
Efficient and scalable gene delivery method with easily generated cationic carbon dots
Authors: Algarra Manuel , Gonzalez-Muñoz Elena
Published: March 2024

Gene delivery is a complex process with several challenges when attempting to incorporate genetic material efficiently and safely into target cells. Some of the key challenges include not only efficient cellular uptake and endosomal escape to ensure that the genetic material can exert its effect but also minimizing the toxicity of the delivery system, which is vital for safe gene delivery. Of importance, if gene delivery systems are intended for biomedical applications or clinical use, they must be scalable and easy and affordable to manufacture to meet the demand. Here, we show an efficient gene delivery method using a combination of carbon dots coated by PEI through electrostatic binding to easily generate cationic carbon dots. We show a biofunctional approach to generate optimal cationic carbon dots (CCDs) that can be scaled up to meet specific transfection demands. CCDs improve cell viability and increase transfection efficiency four times over the standard of PEI polyplexes. Generated CCDs enabled the challenging transfection protocol to produce retroviral vectors via cell cotransfection of three different plasmids into packing cells, showing not only high efficiency but also functionality of the gene delivery, tested as the capacity to produce infective retroviral particles.