bluuebunny/crossref_metadata_2025 huggingface dataset:
The benefit of reduced serum phosphate levels depends on patient characteristics: a nationwide prospective cohort study
Authors: Goto Shunsuke , Hamano Takayuki , Fujii Hideki , Taniguchi Masatomo , Abe Masanori , Nitta Kosaku , Nishi Shinichi
Published: October 2024

Background

In cohort studies of hyperphosphatemic hemodialysis patients, reduced serum phosphate levels have been linked to a lower mortality risk. To investigate whether this benefit is influenced by patient characteristics, we calculated the number needed to be exposed (NNE), stratified by patient characteristics.

Methods

In this 9-year prospective cohort study using the nationwide Japanese registry, we enrolled 78 256 hemodialysis patients aged 18 years or older. We investigated the relationship between time-averaged (TA) phosphate levels and mortality due to cardiovascular disease (CVD) using Cox proportional models. We estimated the 1-year NNE for CVD death in patients with baseline serum phosphate levels ≥6.0 mg/dL and exposure to TA phosphate levels decreasing to 3.5–<5.0 mg/dL using mixed-effects Poisson models.

Results

The hazard ratio of CVD mortality decreased linearly with lower serum TA phosphate levels in those with prior atherosclerotic CVD (ACVD) or diabetic nephropathy (DN) but plateaued with serum phosphate <5.0 mg/dL in those without. The hazard ratios (95% confidence interval) for phosphate ≥7.0 mg/dL compared with 3.5–<3.9 mg/dL were 1.58 (1.38–1.81) in those with prior ACVD, 1.91 (1.68–2.17) in those without, 1.87 (1.63–2.16) in those with DN and 1.65 (1.46–1.87) in those without. However, the NNE for one more person to benefit (NNEB) for CVD death was lower in patients with a history of ACVD than in those without (61 vs 118). Patients with DN had lower NNEB than those without (69 vs 113). In patients with TA albumin ≥3.8 g/dL, older patients had lower NNEB, while patients with TA albumin <3.45 g/dL showed no benefit in some groups, including the elderly.

Conclusions

The benefit of intensive phosphate management may be pronounced in patients with a history of ACVD or DN. A comprehensive approach that considers both age and nutritional status may be necessary when managing serum phosphate levels.
Crohn’s Disease and Ulcerative Colitis Share 2 Molecular Subtypes With Different Mechanisms and Drug Responses
Authors: Wang Jing , Guay Heath , Chang Dan
Published: October 2024

Background and Aims

Several therapies have been approved to treat Crohn’s disease (CD) and ulcerative colitis (UC), indicating that both diseases may share the same molecular subtypes. The aim of this study is to identify shared patient subtypes with common molecular drivers of disease.

Methods

Five public datasets with 406 CD and 421 UC samples were integrated to identify molecular subtypes. Then, the patient labels from 6 independent datasets and 8 treatment datasets were predicted for validating subtypes and identifying the relationship with response status of corticosteroids, infliximab, vedolizumab, and ustekinumab.

Results

Two molecular subtypes were identified from the training datasets, in which CD and UC patients were relatively evenly represented in each subtype. We found 6 S1-specific gene modules related to innate/adaptive immune responses and tissue remodeling and 9 S1-specific cell types (cycling T cells, Tregs, CD8+ lamina propria, follicular B cells, cycling B cells, plasma cells, inflammatory monocytes, inflammatory fibroblasts, and postcapillary venules). Subtype S2 was associated with 3 modules related to metabolism functions and 4 cell types (immature enterocytes, transit amplifying cells, immature goblet cells, and WNT5B+ cells). The subtypes can be replicated in 6 independent datasets based on a 20-gene classifier. Furthermore, response rates to 4 treatments in subtype S2 were significantly higher than those in subtype S1.

Conclusions

This study discovered and validated a robust transcriptome-based molecular classification shared by CD and UC and built a 20-gene classifier. Because 2 subtypes have different molecular mechanisms and drug response, our classification may aid interpretation of heterogeneous molecular and clinical information in inflammatory bowel disease patients.
Preformed mincle dimers stabilized by an interchain disulfide bond in the neck region
Authors: Liu Yu , Drickamer Kurt , Taylor Maureen E
Published: October 2024

The sugar-binding receptor mincle stimulates macrophages when it encounters surface glycans on pathogens, such as trehalose dimycolate glycolipid in the outer membrane of mycobacteria. Binding of oligosaccharide ligands to the extracellular C-type carbohydrate-recognition domain (CRD) in mincle initiates intracellular signaling through the common Fc receptor γ (FcRγ) adapter molecule associated with mincle. One potential mechanism for initiation of signaling involves clustering of receptors, so it is important to understand the oligomeric state of mincle. Affinity purification of mincle from transfected mammalian cells has been used to show that mincle exists as a pre-formed, disulfide-linked dimer. Deletion of cysteine residues and chemical crosslinking further demonstrate that the dimers of mincle are stabilized by a disulfide bond between cysteine residues in the neck sequence that links the CRD to the membrane. In contrast, cysteine residues in the transmembrane region of mincle are not required for dimer formation or association with FcRγ. A protocol has been developed for efficient production of a disulfide-linked extracellular domain fragment of mincle in a bacterial expression system by appending synthetic dimerization domains to guide dimer formation in the absence of the membrane anchor.
Perceptions and Concerns About Misinformation on Facebook in Canada, France, the US, and the UK
Authors: Boulianne Shelley , Hoffmann Christian P
Published: October 2024

Across the globe, people are concerned about misinformation despite evidence suggesting actual exposure is limited and specific to subgroups. We examine the extent to which concerns about misinformation on Facebook are related to perceived exposure to misinformation on the platform (misinformation perceptions), political experiences on Facebook, and country context. Using survey data gathered in February 2021 in four countries (Canada, France, UK, and the US), we find a strong positive correlation between perceptions of and concerns about misinformation on Facebook. We explain that this concern about misinformation is rational in that it is rooted in personal experience of perceived exposure. Seeing political content and observing uncivil political discussions on Facebook also relate to concerns about misinformation. We explain heightened concerns about misinformation in terms of views about the virality of misinformation on Facebook as well as the presumed influence of misinformation on others (third-person effects), which makes misinformation a perceived threat to democracy and society. The observed relationships are supported in three of the four countries, but France tends to be an exception. Understanding citizens’ concerns about misinformation is important for understanding support for interventions, including platform regulation.
From Reflection to Action: Enhancing Workplace Well-Being Through Digital Solutions
Authors: van Berkel Niels , Visuri Aku , Shalawadi Sujay , Evans Madeleine R , Tag Benjamin , Hosio Simo
Published: October 2024

Despite the widely acknowledged importance of well-being, our well-being can regularly be under pressure from external sources. Work is often attributed as a source of stress and dissatisfaction, so, unsurprisingly, extensive efforts are made to measure and improve our well-being in this context. This paper examines opportunities to better design supportive digital solutions through two complementary studies. In the first study, we present a longitudinal assessment of a well-being-focused self-report application deployed in two organizations. Through an analysis of one year of application usage across 219 users, we find both established and novel patterns of application usage and well-being evaluation. While prior work has highlighted substantial dropout rates and daily well-being fluctuations that peak in the morning and early evening, our results highlight that substantial breaks in usage are common, suggesting that users choose to engage with well-being applications mainly when they need them. In the second study, we expand on the topic of well-being reflection at work and the use of technology for this purpose. Through a survey involving 100 participants, we identify current practices in increasing well-being at work, obstacles to sharing and discussing mental well-being states, opportunities for digital well-being solutions and reflections on transparency and communication. Our combined results highlight opportunities for HCI research and practice to address the ongoing challenges of maintaining well-being in today’s work environments.
Association of genomically enhanced residual feed intake with performance, feed efficiency, feeding behavior, gas flux, and nutrient digestibility in growing Holstein heifers
Authors: O’Reilly Keara , Carstens Gordon E , Johnson Jocelyn R , Deeb Nader , Ross Pablo
Published: October 2024

Residual feed intake (RFI), a metric of feed efficiency, is moderately heritable and independent of body size and productivity, making it an ideal trait for investigation as a selection criterion to improve the feed efficiency of growing cattle. The objective of this study was to examine the differences in performance, feed efficiency, feeding behavior, gas flux, and nutrient digestibility in Holstein heifers with divergent genomically enhanced breeding values for RFI (RFIg). Holstein heifers (n = 55; BW = 352 ± 64 kg) with low (n = 29) or high (n = 26) RFIg were selected from a contemporary group of 453 commercial Holstein heifers. Heifers were rotated between 1 of 2 pens, each equipped with 4 electronic feed bunks and 1 pen with a GreenFeed emissions monitoring (GEM) system. Individual dry matter intake (DMI) and feeding behavior data were collected for 84-d. Body weight (BW) was measured weekly and spot fecal samples were collected at weighing. Phenotypic RFI (RFIp) was calculated as the residual from the regression of DMI on average daily gain (ADG) and mid-test metabolic BW (BW0.75). A mixed model including the fixed effect of RFIg classification and the random effect of group was used to evaluate the effect of RFIg classification on response variables. There were no differences (P > 0.05) in BW and ADG for heifers with divergent RFIg; however, low RFIg heifers consumed 7.5% less (P < 0.05) feed per day. Consequently, low RFIg heifers exhibited a more favorable (P < 0.05) RFIp compared to high RFIg heifers (−0.196 vs 0.222 kg/d, respectively). Low RFIg heifers had 8.7% fewer (P < 0.05) bunk visit events per day and tended to have an 11.2% slower (P < 0.10) eating rate. Low RFIg heifers had 7.7% lower (P < 0.05) methane (CH4) emissions (g/d), 6.1% lower (P ≤ 0.05) carbon dioxide (CO2) production (g/d), and 5.6% lower (P ≤ 0.05) heat production (Mcal/d) than high RFIg heifers. However, CH4 yield and CO2 yield (g/kg DMI), and heat production per unit DMI (Mcal/kg DMI) did not differ (P > 0.05) between heifers with divergent RFIg. Dry matter (DM) and nutrient digestibility did not differ (P > 0.05) between heifers with divergent RFIg. Results suggest that selection based on RFIg provides opportunities to select cattle with favorable feed efficiency phenotypes to increase the economic and environmental sustainability of the cattle industry.
Environmental Enforceable Undertakings: An Innovative Tool to Repair and Prevent Environmental Harm
Authors: Forsyth Miranda , Tepper Felicity
Published: October 2024

This article identifies an emerging form of sanction for addressing environmental harm: the environmental enforceable undertaking (EEU). Currently used for environmental protection in Australia and the UK, the EEU is a cooperative, timely, and accountable regulatory instrument targeted at encouraging offenders to voluntarily invest in repairing and preventing harm, frequently going beyond basic regulatory compliance. We identify four regulatory objectives met by EEUs (strategic; responsive; deterrent; and preventative) before discussing how EEUs might contribute to the environmental regulation landscape, exploring examples primarily from Australia, but also the UK. Finally, we discuss how EEUs can benefit not only the regulator and regulated but can also involve the community in environmental regulation. We then assert a fifth regulatory objective: they can serve as a restorative form of regulation.
Anti-liver cancer therapeutic targets and safety of usenamine A in experimental liver cancer
Authors: He Xiaoqiong , Zhou Zhangping , Wang Jing , Zhao Qing , Fan Shirui , Yao Qian , Lian Wenjing , You Yutong
Published: October 2024

Background

Liver cancer is highly heterogeneous with poor drug response. Usenamine A has anticancer activity. Usnic acid has hepatocytotoxicity.

Objectives

As a derivative of usnic acid, if usenamine A can be safely used in treatment for liver cancer is unknown.

Methods

MTT and clone formation assays assessed cell viability and proliferation. Tumor growth was determined using a xenograft model. Flow cytometry was used to detect the cell cycle. mRNA transcriptome sequencing investigated differential gene expression. Safety was evaluated in mice.

Key findings

Usenamine A inhibited proliferation and clone formation of HepG2 cells and xenograft tumor growth through cell cycle arrest at G0/G1. Usenamine A altered gene expression in a direction supporting anticancer activity. IL24, JUN, DUSP4, and DUSP5 were upregulated while PRKACA, PRKCB, TP53, WNT6, E2F3, LGR4, GPR78, and MAPK4 were downregulated. Ten of above genes overlapped in the KEGG enriched non-small cell lung cancer/glioma/cytokine–cytokine receptor interaction/Wnt/MAPK pathway network. Usenamine A has a strong binding affinity for PRKACA and PRKCB proteins. Usenamine A showed minimal toxicity in mice.

Conclusions

Usenamine A is a safe anticancer agent against hepatocellular carcinoma. Regulation of 12 cancer-associated genes and the correlated pathway network are its therapeutic targets.
The U-shaped association between hemoglobin concentrations and all-cause death risk in patients with community-acquired pneumonia
Authors: Xu Yilin , Fang Jianhua , Kang Xiuhua , Xiang Tianxin
Published: October 2024

Background

The prevalence of anemia in patients with community-acquired pneumonia (CAP) has been well described. However, few studies have explored its association with short-term and long-term mortality risk in CAP patients.

Aim

We aimed to investigate the associations between hemoglobin concentrations at baseline and 14-day and 1-year mortality risk in a CAP population with a large sample size. Our data originated from the Dryad database, including a dataset from the study “Incidence rate of community-acquired pneumonia in adults: a population-based prospective active surveillance study in 3 cities in South America.” A total of 1463 study samples with follow-up data from the dataset were enrolled for our analysis.

Results

During the follow-up period of 3 years, the 14-day risk and 1-year mortality risk were 206 (14.08%) and 401 (27.41%), respectively, among these CAP patients. Curve analysis indicated a strong U-shaped relationship between blood hemoglobin concentrations and 14-day mortality (r = –0.191, P < .001) and 1-year mortality (r = –0.220, P < .001). The blood hemoglobin level with the lowest point of mortality risk was 14.5 g/dL, suggesting that an increased hemoglobin concentration contributed to reduced 14-day and 1-year mortality risk in CAP patients when hemoglobin does not exceed 14.5 g/dL even if it is within the normal clinical range. In addition, we also observed significant associations of hemoglobin with 14-day mortality risk (odds ratio [OR] = 0.817; 95% CI, 0.742-0.899 P < .001) and 1-year mortality risk (OR = 0.834; 95% CI, 0.773-0.900; P < .001), but only in participants without risk factors for health care–associated pneumonia (HCAP) rather than in participants with risk factors for HCAP.

Conclusion

The greatest discovery is that our findings indicated a significant U-shaped relationship between hemoglobin levels and 14-day and 1-year mortality risk in CAP patients. However, a significant relationship was only discovered in subjects without risk factors for HCAP. More evidence is needed to support this finding.
The geometry of conchiferan shell evolution: origins of coiling and bivalved morphologies
Authors: Roopnarine Peter D , Goodwin David H
Published: October 2024

The unifying theme of conchiferan shell morphology, including near-logarithmic expansion of a coiling cone, has led to the development of numerous descriptive mathematical models. Here, we develop and demonstrate a simple geometric model, based on minimal assumptions of ontogenetic development and mantle activity, that seeks to explain several fundamental features, including the origin of coiling, lateral compression and both pseudobivalved and true bivalved morphologies in the Diasoma. Coiling is hypothesized to have been facilitated by a genetically controlled asymmetry in the rate of mineralization around the growing margin of early Cambrian univalved taxa that adhered to an epibenthic life mode. Coiling would have been advantageous, and still is, for increase of size, internal volume expansion and protection against hydrodynamic and biotic forces. Three hypotheses are tested for the origin of Rostroconchia and Bivalvia. The first is an existing hypothesis of descent from laterally compressed helcionellid taxa. The other two are novel hypotheses, the first involving a bifurcation of the mineralizing asymmetry of the shell field along the anterior–posterior axis of symmetry, and the second proposes a bifurcation of the shell field itself, rendering each bivalve valve homologous with the univalve shell. Both hypotheses generate model shells consistent with rostroconch and bivalve morphologies respectively, and it is suggested that the proliferation of laterally compressed conchiferans in the late Cambrian is at least partially a result of multiple independent, and evolutionarily convergent invasions of organic and algae rich soft sediment environments.
Selective degradation of phage RNAs by the Csm6 ribonuclease provides robust type III CRISPR immunity in Streptococcus thermophilus
Authors: Johnson Katie A , Garrett Sandra C , Noble-Molnar Christopher , Elgarhi Hanna A , Woodside Walter T , Cooper Clare , Zhang Xinfu , Olson Sara , Catchpole Ryan J , Graveley Brenton R , Terns Michael P
Published: October 2024

Type III CRISPR immune systems bind viral or plasmid RNA transcripts and activate Csm3/Cmr4 and Cas10 nucleases to uniquely cleave both invader RNA and DNA, respectively. Additionally, type III effector complexes generate cyclic oligoadenylate (cOA) signaling molecules to activate trans-acting, auxiliary Csm6/Csx1 ribonucleases, previously proposed to be non-specific in their in vivo RNA cleavage preference. Despite extensive in vitro studies, the nuclease requirements of type III systems in their native contexts remain poorly understood. Here we systematically investigated the in vivo roles for immunity of each of the three Streptococcus thermophilus (Sth) type III-A Cas nucleases and cOA signaling by challenging nuclease defective mutant strains with plasmid and phage infections. Our results reveal that RNA cleavage by Csm6 is both sufficient and essential for maintaining wild-type levels of immunity. Importantly, Csm6 RNase activity leads to immunity against even high levels of phage challenge without causing host cell dormancy or death. Transcriptomic analyses during phage infection indicated Csm6-mediated and crRNA-directed preferential cleavage of phage transcripts. Our findings highlight the critical role of Csm6 RNase activity in type III immunity and demonstrate specificity for invader RNA transcripts by Csm6 to ensure host cell survival upon phage infection.
Light Color Regulation of Photosynthetic Antennae Biogenesis in Marine Phytoplankton
Authors: Kehoe David M , Biswas Avijit , Chen Bo , Dufour Louison , Grébert Théophile , Haney Allissa M , Joseph Kes Lynn , Kumarapperuma Indika , Nguyen Adam A , Ratin Morgane , Sanfilippo Joseph E , Shukla Animesh , Garczarek Laurence , Yang Xiaojing , Schluchter Wendy M , Partensky Frédéric
Published: October 2024

Photosynthesis in the world’s oceans is primarily conducted by phytoplankton, microorganisms that use many different pigments for light capture. Synechococcus is a unicellular cyanobacterium estimated to be the second most abundant marine phototroph, with a global population of 7 × 1026 cells. This group’s success is partly due to the pigment diversity in their photosynthetic light harvesting antennae, which maximize photon capture for photosynthesis. Many Synechococcus isolates adjust their antennae composition in response to shifts in the blue:green ratio of ambient light. This response was named type 4 chromatic acclimation (CA4). Research has made significant progress in understanding CA4 across scales, from its global ecological importance to its molecular mechanisms. Two forms of CA4 exist, each correlated with the occurrence of one of two distinct but related genomic islands. Several genes in these islands are differentially transcribed by the ambient blue:green light ratio. The encoded proteins control the addition of different pigments to the antennae proteins in blue versus green light, altering their absorption characteristics to maximize photon capture. These genes are regulated by several putative transcription factors also encoded in the genomic islands. Ecologically, CA4 is the most abundant of marine Synechococcus pigment types, occurring in over 40% of the population oceanwide. It predominates at higher latitudes and at depth, suggesting that CA4 is most beneficial under sub-saturating photosynthetic light irradiances. Future CA4 research will further clarify the ecological role of CA4 and the molecular mechanisms controlling this globally important form of phenotypic plasticity.
Comprehensive analysis of aging-related gene expression patterns and identification of potential intervention targets
Authors: Yang Sha , Song Jianning , Deng Min , Cheng Si
Published: October 2024

Purpose

This study aims to understand the molecular mechanisms underlying the aging process and identify potential interventions to mitigate age-related decline and diseases.

Methods

This study utilized the GSE168753 dataset to conduct comprehensive differential gene expression analysis and co-expression module analysis. Machine learning and Mendelian randomization analyses were employed to identify core aging-associated genes and potential drug targets. Molecular docking simulations and mediation analysis were also performed to explore potential compounds and mediators involved in the aging process.

Results

The analysis identified 4164 differentially expressed genes, with 1893 upregulated and 2271 downregulated genes. Co-expression analysis revealed 21 modules, including both positively and negatively correlated modules between older age and younger age groups. Further exploration identified 509 aging-related genes with distinct biological functions. Machine learning and Mendelian randomization analyses identified eight core genes associated with aging, including DPP9, GNAZ, and RELL2. Molecular docking simulations suggested resveratrol, folic acid, and ethinyl estradiol as potential compounds capable of attenuating aging through modulation of RELL2 expression. Mediation analysis indicated that eosinophil counts and neutrophil count might act as mediators in the causal relationship between genes and aging-related indicators.

Conclusion

This comprehensive study provides valuable insights into the molecular mechanisms of aging and offers important implications for the development of anti-aging therapeutics.

Key Messages What is already known on this topic – Prior research outlines aging’s complexity, necessitating precise molecular targets for intervention. What this study adds – This study identifies novel aging-related genes, potential drug targets, and therapeutic compounds, advancing our understanding of aging mechanisms. How this study might affect research, practice, or policy – Findings may inform targeted therapies for age-related conditions, influencing future research and clinical practices.
Gappy action and murder
Authors: Melamed Noam
Published: October 2024

This paper explores the form of persistence distinctive of intentional actions. Unlike entities whose progression through time is typically continuous, our actions often have parts separated in time by a gap in our own activity. The way in which their coherence is understood thus affects their attribution to us. I present a theory of agency at the gaps that accounts for such phenomena and passes two touchstones. It solves the puzzle of the time of a killing in a new way and provides a support to the assessment of moral agency.
Bringing Capacity Back In: Paradiplomacy and Sub-State Government Internationalization in the Global Economy
Authors: Kovacikova Lucia
Published: October 2024

Why do some sub-state governments establish offices abroad for international economic development, while others do not? This article focuses on the paradiplomatic policy of sub-state government internationalization (SGI) that allows sub-state governments to build international networks abroad to promote greater trade, investment, and tourism within their borders. Moving away from autonomy-focused explanations, this article develops three capacity-based hypotheses about the adoption and size of sub-state internationalization. Using an original dataset of the 517 sub-state governments within the Organization for Economic Co-operation and Development (OECD), the analysis reveals that revenue, human capital, and information capacities are significant in predicting SGI. These findings help paint a novel picture of sub-state internationalization in the globalized economy, showcasing a new methodological and theoretical approach for the study of paradiplomacy and sub-state decision-making.
Exploring genetic and immune cell dynamics in systemic lupus erythematosus patients with Epstein–Barr virus infection via machine learning
Authors: Gui Jiajun , Fang Mengyuan , Tu Jianxin , Chen Xiaowei , Sun Li
Published: October 2024

Objectives

EBV is a widespread virus implicated in various diseases, including SLE. However, the specific genes and pathways altered in SLE patients with EBV infection remain unclear. We aimed to identify key genes and immune cells in SLE patients with EBV infection.

Methods

The datasets of SLE (GSE50772 and GSE81622) and EBV infection (GSE85599 and GSE45918) were obtained from the Gene Expression Omnibus (GEO) database. Next, differential gene expression (DEGs) analyses were conducted to identify overlapping DEGs, and then enrichment analysis was performed. Machine learning was applied to identify key genes. Validation was conducted using receiver operating characteristic (ROC) curve analysis and expression level verification in test datasets and single-cell RNA sequencing. Immune cell infiltration patterns were analysed using CIBERSORTx, and clinical data were reviewed for SLE patients.

Results

We identified 58 overlapping DEGs enriched in IFN-related pathways. Five overlapping DEGs (IFI27, TXK, RAPGEF6, PIK3IP1 and PSENEN) were selected as key genes by machine-learning algorithms, with IFI27 showing the highest diagnostic performance. The expression level of IFI27 was found to be higher in CD4 CTL, CD8-naïve and various B cell subsets of SLE patients with EBV infection. IFI27 showed significant correlation with B intermediate and CD4 CTL cells. Clinical data showed lower CD4 T cell proportions in SLE patients with EBV infection.

Conclusion

This study identified IFI27 as a key gene for SLE patients with EBV infection, influencing CD4 CTL and B cell subtypes. These findings enhance the understanding of the molecular mechanisms linking SLE and EBV infection, providing potential targets for diagnostic and therapeutic strategies.
Two different mirror neuron pathways for social and non-social actions? A meta-analysis of fMRI studies
Authors: Zhao Minghui , Li Rui , Xiang Sijia , Liu Ning
Published: October 2024

Mirror neurons (MNs) represent a class of neurons that are activated when performing or observing the same action. Given their role in social cognition and previous research in patients with psychiatric disorders, we proposed that the human MN system (MNS) might display different pathways for social and non-social actions. To examine this hypothesis, we conducted a comprehensive meta-analysis of 174 published human functional magnetic resonance imaging studies. Our findings confirmed the proposed hypothesis. Our results demonstrated that the non-social MN pathway exhibited a more classical pattern of frontoparietal activation, whereas the social MN pathway was activated less in the parietal lobe but more in the frontal lobe, limbic lobe, and sublobar regions. Additionally, our findings revealed a modulatory role of the effector (i.e. face and hands) within this framework: some areas exhibited effector-independent activation, while others did not. This novel subdivision provides valuable theoretical support for further investigations into the neural mechanisms underlying the MNS and its related disorders.
Emotion Processing and Its Relationship to Social Functioning and Symptoms in Psychotic Disorder: A Systematic Review and Meta-analysis
Authors: Murrihy Sean , Filia Kate , Cotton Sue , Phillips Lisa , Youn Sarah , Jayasinghe Anuradhi , Wrobel Anna , Bastawy Eslam M , Allott Kelly , Watson Amity
Published: October 2024

Background

Emotion processing (EP) is impaired in individuals with psychosis and associated with social functioning; however, it is unclear how symptoms fit into this relationship. The aim of this systematic review and meta-analysis was to examine interrelationships between EP, symptoms, and social functioning, test whether different symptom domains mediate the relationship between EP and social functioning, and examine the moderating effects of illness stage and EP task type.

Study Design

MEDLINE, Embase, and PsycINFO databases were searched for studies that included individuals with psychosis and reported correlations between EP, symptom domains (positive, negative, depressive, and disorganization), and social functioning. Random effects meta-analyses determined the strength of correlations, and subgroup analyses included illness stage and EP task type (lower- vs higher-level processing). Meta-analytic structural equation models tested whether symptom domains mediated the relationship between EP and social functioning.

Results

There was a small relationship (r = .18) between EP and social functioning. Positive, negative, and disorganization symptoms mediated this relationship, although indirect effects were small. Higher-level EP tasks were more strongly associated with negative symptoms than lower-level tasks. Relationships between EP and both social functioning and positive symptoms were smaller in the first episode of psychosis than in established illness.

Conclusions

The mediating relationship suggests that EP not only influences social dysfunction directly but contributes to negative and disorganization symptoms, which in turn impair social functioning. This pathway suggests that targeting negative and disorganization symptoms may ultimately improve social outcomes for individuals with psychosis. Future research, particularly in early psychosis, is needed to determine other factors impacting these interrelationships.
Dose-dependent effects of silver nanoparticles on cell death modes in mouse blastocysts induced via endoplasmic reticulum stress and mitochondrial apoptosis
Authors: Lee Cheng-Kai , Wang Fu-Ting , Huang Chien-Hsun , Chan Wen-Hsiung
Published: October 2024

In view of the rapidly expanding medical and commercial applications of silver nanoparticles (AgNPs), their potential health risks and environmental effects are a significant growing concern. Earlier research by our group uncovered the embryotoxic potential of AgNPs, showing detrimental impacts of these nanoparticles on both pre- and post-implantation embryonic development. In the current study, we showed that low (50–100 μM) and high (200–400 μM) dose ranges of AgNPs trigger distinct cell death programs affecting mouse embryo development and further explored the underlying mechanisms. Treatment with low concentrations of AgNPs (50–100 μM) triggered ROS generation, in turn, inducing mitochondria-dependent apoptosis, and ultimately, harmful effects on embryo implantation, post-implantation development, and fetal development. Notably, high concentrations of AgNPs (200–400 μM) evoked more high-level ROS generation and endoplasmic reticulum (ER) stress-mediated necrosis. Interestingly, pre-incubation with Trolox, a strong antioxidant, reduced ROS generation in the group treated with 200–400 μM AgNPs to the level induced by 50–100 μM AgNPs, resulting in switching of the cell death mode from necrosis to apoptosis and a significant improvement in the impairment of embryonic development. Our findings additionally indicate that activation of PAK2 is a crucial step in AgNP-triggered apoptosis and sequent detrimental effects on embryonic development. Based on the collective results, we propose that the levels of ROS generated by AgNP treatment of embryos serve as a critical regulator of cell death type, leading to differential degrees of damage to embryo implantation, post-implantation development and fetal development through triggering apoptosis, necrosis or other cell death signaling cascades.
Transcriptomic analysis reveals transcription factors implicated in radon-induced lung carcinogenesis
Authors: Liu Xing , Peng Yuting , Chen Ruobing , Zhou Yueyue , Zou Xihuan , Xia Mingzhu , Wu Xinyi , Yu Meng
Published: October 2024

Background

Radon, a potent carcinogen, is a significant catalyst for lung cancer development. However, the molecular mechanisms triggering radon-induced lung cancer remain elusive.

Methods

Utilizing a radon exposure concentration of 20,000 Bq/m3 for 20 min/session, malignant transformation was induced in human bronchial epithelial cells (BEAS-2B).

Results

Radon-exposed cells derived from passage 25 (BEAS-2B-Rn) exhibited enhanced proliferation and increased colony formation. Analysis of differential gene expression (DEG) through transcription factors revealed 663 up-regulated and 894 down-regulated genes in radon-exposed cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed significant alterations in the malignant transformation pathway of cells, including those related to cancer and the PI3K/AKT signaling pathway. A PPI network analysis indicated a significant association of oncogenes, such as CCND1, KIT, and GATA3, with lung cancer among differentially expressed genes. In addition, the stability of the housekeeping gene was determined through RT-qPCR analysis, which also confirmed the results of transcriptome analysis.

Conclusions

The results suggest that transcription factors may play a pivotal role in conferring a survival advantage to radon-exposed cells. This is achieved by malignant transformation of human bronchial epithelial cells into lung carcinogenesis cell phenotypes.
Axon guidance genes are regulated by TDP‐43 and RGNEF through long‐intron removal
Authors: Abbassi Yasmine , Cappelli Sara , Spagnolo Eugenio , Gennari Alice , Visani Giulia , Barattucci Simone , Paron Francesca , Stuani Cristiana , Droppelmann Cristian A. , Strong Michael J. , Buratti Emanuele
Published: October 2024

Rho guanine nucleotide exchange factor (RGNEF) is a guanine nucleotide exchange factor (GEF) mainly involved in regulating the activity of Rho‐family GTPases. It is a bi‐functional protein, acting both as a guanine exchange factor and as an RNA‐binding protein. RGNEF is known to act as a destabilizing factor of neurofilament light chain RNA (NEFL) and it could potentially contribute to their sequestration in nuclear cytoplasmic inclusions. Most importantly, RGNEF inclusions in the spinal motor neurons of ALS patients have been shown to co‐localize with inclusions of TDP‐43, the major well‐known RNA‐binding protein aggregating in the brain and spinal cord of human patients. Therefore, it can be hypothesized that loss‐of‐function of both proteins following aggregation may contribute to motor neuron death/survival in ALS patients. To further characterize their relationship, we have compared the transcriptomic profiles of neuronal cells depleted of TDP‐43 and RGNEF and show that these two factors predominantly act in an antagonistic manner when regulating the expression of axon guidance genes. From a mechanistic point of view, our experiments show that the effect of these genes on the processivity of long introns can explain their mode of action. Taken together, our results show that loss‐of‐function of factors co‐aggregating with TDP‐43 can potentially affect the expression of commonly regulated neuronal genes in a very significant manner, potentially acting as disease modifiers. This finding further highlights that neurodegenerative processes at the RNA level are the result of combinatorial interactions between different RNA‐binding factors that can be co‐aggregated in neuronal cells. A deeper understanding of these complex scenarios may lead to a better understanding of pathogenic mechanisms occurring in patients, where more than one specific protein may be aggregating in their neurons.
A New Tool for Estimating the Number of Pregnant People in the United States
Authors: Strid Penelope , Simeone Regina M. , Hall Rebecca , Meeker Jessica R. , Ellington Sascha R.
Published: October 2024

BACKGROUND:

Knowing the approximate number of women of reproductive age (ie, 15–49 years) who are pregnant at a point in time in the United States can aid in emergency preparedness resource allocation. The Centers for Disease Control and Prevention (CDC) released a pregnancy estimator toolkit in 2012, which could be used to estimate the number of pregnant people in a geographic area at a point in time. This original toolkit did not account for pregnancy losses before 20 weeks of gestation; however, an updated toolkit released by the CDC in May 2024 uses a ratio of live births to estimate the number of pregnancy losses before 20 weeks at a point in time for improved estimation of total pregnant people at a point in time.

INSTRUMENT:

We used the CDC's updated reproductive health tool, “Estimating the Number of Pregnant Women in a Geographic Area.”

EXPERIENCE:

Using publicly available data for 2020, we gathered the necessary input values, including total births, fetal deaths, and induced abortions, and applied the equation available in the CDC toolkit to estimate the number of pregnant people in the United States at any point in time in 2020.

CONCLUSION:

In 2020, there were 75,582,028 women of reproductive age in the United States, and we estimate that approximately 2,962,052 or 3.9% of women of reproductive age were pregnant at any point in time in the United States
Effective preexposure prophylaxis in young women and girls, a key population for HIV prevention
Authors: Rousseau Elzette , Bennin Fiona , Bekker Linda-Gail
Published: October 2024

Purpose of review

Although there is substantial momentum to scale up preexposure prophylaxis (PrEP) for HIV prevention in adolescent girls and young women (AGYW) at risk of HIV acquisition, this key population has demonstrated difficulty in sustained PrEP use. Despite being a user-controlled and discreet prevention option, effective oral PrEP use requires a series of complex daily decisions in the life of the PrEP user. In this review, we describe how the number of decisions AGYW have to execute for effective and continued PrEP use may potentially be reduced by providing simplified, integrated, differentiated sexual and reproductive health services that include PrEP, and introducing a choice of PrEP products, including less frequently dosed, longer acting and/or multipurpose prevention technology (MPT) products.

Recent findings

PrEP uptake and effective use are enhanced when AGYW experience PrEP service delivery channels as convenient, integrated with their other sexual and reproductive health needs and matching their experiences (including limited autonomy) and lifestyle. Longer acting or less frequently dosed PrEP products or MPTs may reduce the cognitive burden associated with prevention decision-making and is, therefore, likely more suitable for the majority of AGYW who struggle with daily pill adherence.

In the scaling up of HIV prevention for AGYW, implementers are encouraged to consider both PrEP products and PrEP delivery outlet preferences. Understanding and responding to AGYW's different needs will allow for preferred PrEP delivery outlets and choice in PrEP products, leading to a greater likelihood of effective PrEP use in this key population.
Correction of the Manubriosternal Angle: The Missing Link in the Diagnosis and Management of Anterior Chest Wall “Pectus” Deformities
Authors: El Oakley Reida
Published: October 2024

A normal manubriosternal angle (MSA) varies between 157 and 161 degrees, and it is either increased (in pectus carinatum) or decreased (in pectus excavatum). Measurements of the MSA can accurately define the severity of both deformities and gauge the degree of response to therapeutic intervention(s). Correction of the MSA during repair of pectus deformity by complete upper transverse sternotomy seems necessary. We found no report of complete upper transverse sternotomy in repairing pectus deformities. Similarly, the MSA was never used in defining the severity of pectus deformity. We describe a novel technique in repairing anterior chest wall deformity (pectus carinatum, MSA = 172) in a young man. Under general anesthesia and complete aseptic precautions, through a midline presternal incision, bilateral pectoral flaps were mobilized, and complete transverse sternotomy at the level of the second intercostal space and bilateral intrapericondrium excision of the costal cartilages (3–7) were performed. The wound was closed in layers after insertion of two, 9-mm subpectoral Redivac drains. The patient had an uneventful recovery with satisfactory cosmetic appearance. Magnetic resonance imaging of the chest 4 months postoperatively showed reduction of the MSA by 8 degrees, which is 78% (8 of 11) progress toward reaching the upper limit of normal MSA values. In correcting pectus deformity, complete transaction of the sternum at the level of the second intercostal space enhances recovery and allows for normalization of the MSA. Using the MSA in assessing the severity and response to treatment of pectus deformity is recommended.
The Controversy over Price Transparency: Patients and Plastic Surgeons Disagree
Authors: Rai Parul , Pareek Priyasha , Vilas Caitlyn L. , Kaplan Jonathan L.
Published: October 2024

Background:

The No Surprises Act (NSA) went into effect on January 1, 2022. This federal law is designed to minimize surprise bills for emergency care, out of network (OON) care, and care for uninsured or self-pay individuals. To achieve these goals, the NSA relies heavily on physicians providing cost estimates to patients prior to administering care. Because healthcare is often price-opaque, this study was conducted to assess physician and patient attitudes toward price transparency in plastic surgery and aesthetic/self-pay medicine.

Methods:

Two cohorts of providers received a survey asking whether and how their practice offers pricing information prior to a consultation and their views regarding the NSA. Patients who had previously used an online price estimator tool also received a survey regarding their experience and accuracy of estimates received online.

Results:

Most surveyed providers do not share the costs of their services online, whereas patients had a positive experience when receiving estimates of medical services before consultation. Although many providers cited the inaccuracy of price estimator tools as a reason not to incorporate them into their website, most patients reported that their final cost of service was close to (or even less than) the estimate received online prior to the consultation.

Conclusions:

This study suggests that price transparency is a patient satisfier. Therefore, plastic surgeons should exercise price transparency to be compliant with federal law and to gain a competitive advantage in the market, as the decision to implement price transparency can be mutually beneficial to patients and providers.
Severe Clinical Outcomes Due to Human Adenoviral Respiratory Infections in Hospitalized Immunocompetent Adults
Authors: Legakis Luke P. , Nguyen Duc , Bandaranayake Thilinie D.
Published: October 2024

Background

Human adenoviral infections typically result in upper respiratory tract infections, conjunctivitis, and gastroenteritis that is classically self-limiting but can be life-threatening in immunocompromised individuals. In relatively rare cases, adenovirus infections in immunocompetent patients can result in hospitalizations and severe outcomes that include need for critical care or death. The risk factors that are associated with severe adenoviral infections in immunocompetent hosts have not been thoroughly investigated and are currently poorly understood.

Methods

Retrospective cohort of 78 patients with ages ranging from 18–85 years who were admitted to Yale New Haven-affiliated hospitals over a period of 2 years with positive adenovirus tests on a nasopharyngeal respiratory viral panel. Immunocompromised patients were excluded from the study. Patient charts were reviewed to obtain demographic information, comorbid conditions, smoking history, and clinical outcomes.

Results

Of the 78 patients admitted, 15 (19.2%) were admitted as observation, 44 (56.4%) were admitted to the hospital for over 48 hours, 15 (19.2%) required critical care, and 4 (5.1%) expired during hospitalization. Pulmonary disease as a comorbidity in the form of asthma (33.3%) or chronic obstructive pulmonary disease (12.8%), and smoking history (59.0%) were more common in those with severe adenoviral infections. With severe disease, 13 (16.7%) required mechanical ventilation, 10 (12.8%) required pressor support, and 2 (2.6%) required extracorporeal membrane oxygenation.

Conclusions

This retrospective study characterizes severity of adenoviral infections in adult immunocompetent patients, highlights the lack of treatment available, and identifies potential risk factors for severe disease, including asthma, smoking, absence of fever, and presence of coinfection.