bluuebunny/crossref_metadata_2025 huggingface dataset:
Food components and abdominal aortic aneurysm
Authors: Sumi Tomoko , Kugo Hirona , Higashihara Mayo , Moriyama Tatsuya , Zaima Nobuhiro
Published: October 2024

Abdominal aortic aneurysm (AAA) is a disease in which the abdominal aorta expands irreversibly and ruptures. At present, no preventive methods are available for this disease. Among potential risk factors, certain foods are considered to play important roles in the development of AAA. Epidemiological studies suggest a close relationship between AAA and dietary habits. Experimental studies have clarified potential suppressive or progressive food components for AAA. In this review, a summary of studies related to nutritional science in the fields of AAA and/or aortic degeneration are provided.
Impact of lesion location and pattern on the prognosis of genital extramammary Paget disease: a retrospective study
Authors: Yasui Yukiko , Kato Hiroshi , Kano Shinji , Yoshimitsu Maki , Nakagawa Yua , Nakamura Motoki , Morita Akimichi
Published: October 2024

Lesion location and pattern are associated with prognosis in extramammary Paget disease. This retrospective study found that nodular and erosive lesions, and lesion areas larger than approximately 70–100 cm2 (roughly equivalent to a palm-sized area of skin), were predictive of a poor prognosis.
Quantitative susceptibility mapping at 7 T in COVID-19: brainstem effects and outcome associations
Authors: Rua Catarina , Raman Betty , Rodgers Christopher T , Newcombe Virginia F J , Manktelow Anne , Chatfield Doris A , Sawcer Stephen J , Outtrim Joanne G , Lupson Victoria C , Stamatakis Emmanuel A , Williams Guy B , Clarke William T , Qiu Lin , Ezra Martyn , McDonald Rory , Clare Stuart , Cassar Mark , Neubauer Stefan , Ersche Karen D , Bullmore Edward T , Menon David K , Pattinson Kyle , Rowe James B
Published: October 2024

Post-mortem studies have shown that patients dying from severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection frequently have pathological changes in their CNS, particularly in the brainstem. Many of these changes are proposed to result from para-infectious and/or post-infection immune responses. Clinical symptoms such as fatigue, breathlessness, and chest pain are frequently reported in post-hospitalized coronavirus disease 2019 (COVID-19) patients. We propose that these symptoms are in part due to damage to key neuromodulatory brainstem nuclei. While brainstem involvement has been demonstrated in the acute phase of the illness, the evidence of long-term brainstem change on MRI is inconclusive. We therefore used ultra-high field (7 T) quantitative susceptibility mapping (QSM) to test the hypothesis that brainstem abnormalities persist in post-COVID patients and that these are associated with persistence of key symptoms.

We used 7 T QSM data from 30 patients, scanned 93–548 days after hospital admission for COVID-19 and compared them to 51 age-matched controls without prior history of COVID-19 infection. We correlated the patients’ QSM signals with disease severity (duration of hospital admission and COVID-19 severity scale), inflammatory response during the acute illness (C-reactive protein, D-dimer and platelet levels), functional recovery (modified Rankin scale), depression (Patient Health Questionnaire-9) and anxiety (Generalized Anxiety Disorder-7).

In COVID-19 survivors, the MR susceptibility increased in the medulla, pons and midbrain regions of the brainstem. Specifically, there was increased susceptibility in the inferior medullary reticular formation and the raphe pallidus and obscurus. In these regions, patients with higher tissue susceptibility had worse acute disease severity, higher acute inflammatory markers, and significantly worse functional recovery.

This study contributes to understanding the long-term effects of COVID-19 and recovery. Using non-invasive ultra-high field 7 T MRI, we show evidence of brainstem pathophysiological changes associated with inflammatory processes in post-hospitalized COVID-19 survivors.
Myelination potential and injury susceptibility of grey versus white matter human oligodendrocytes
Authors: Cui Qiao-Ling , Mohammadnia Abdulshakour , Yaqubi Moein , Weng Chao , Dorion Marie-France , Pernin Florian , Hall Jeffery A , Dudley Roy , Stratton Jo Anne , Kennedy Timothy E , Srour Myriam , Antel Jack P
Published: October 2024

Increasing evidence indicates heterogeneity in functional and molecular properties of oligodendrocyte lineage cells both during development and in pathological conditions. In multiple sclerosis, remyelination of grey matter lesions exceeds that in white matter.

Here, we used cells derived from grey matter versus white matter regions of surgically resected human brain tissue samples to compare the capacities of human A2B5-positive progenitor cells and mature oligodendrocytes to ensheath synthetic nanofibres, and we related differences to the molecular profiles of these cells.

For both cell types, the percentage of ensheathing cells was greater for grey matter versus white matter cells. For both grey matter and white matter samples, the percentage of cells ensheathing nanofibres was greater for A2B5-positive cells versus mature oligodendrocytes. Grey matter A2B5-positive cells were more susceptible than white matter A2B5-positive cells to injury induced by metabolic insults. Bulk RNA sequencing indicated that separation by cell type (A2B5-positive versus mature oligodendrocytes) is more significant than by region, but segregation for each cell type by region is apparent. Molecular features of grey matter- versus white matter-derived A2B5-positive and mature oligodendrocytes were lower expression of mature oligodendrocyte genes and increased expression of early oligodendrocyte lineage genes. Genes and pathways with increased expression in grey matter-derived cells with relevance for myelination included those related to responses to the external environment, cell–cell communication, cell migration and cell adhesion. Immune- and cell death-related genes were upregulated in grey matter-derived cells. We observed a significant number of upregulated genes shared between the stress/injury and myelination processes, providing a basis for these features. In contrast to oligodendrocyte lineage cells, no functional or molecular heterogeneity was detected in microglia maintained in vitro, probably reflecting the plasticity of these cells ex vivo.

The combined functional and molecular data indicate that grey matter human oligodendrocytes have increased intrinsic capacity to myelinate but also increased injury susceptibility, in part reflecting their being at a stage earlier in the oligodendrocyte lineage.
Multilayer network analysis reveals instability of brain dynamics in untreated first-episode schizophrenia
Authors: Gao Ziyang , Xiao Yuan , Zhu Fei , Tao Bo , Zhao Qiannan , Yu Wei , Sweeney John A , Gong Qiyong , Lui Su
Published: October 2024

Although aberrant static functional brain network activity has been reported in schizophrenia, little is known about how the dynamics of neural function are altered in first-episode schizophrenia and are modulated by antipsychotic treatment. The baseline resting-state functional magnetic resonance imaging data were acquired from 122 first-episode drug-naïve schizophrenia patients and 128 healthy controls (HCs), and 44 patients were rescanned after 1-year of antipsychotic treatment. Multilayer network analysis was applied to calculate the network switching rates between brain states. Compared to HCs, schizophrenia patients at baseline showed significantly increased network switching rates. This effect was observed mainly in the sensorimotor (SMN) and dorsal attention networks (DAN), and in temporal and parietal regions at the nodal level. Switching rates were reduced after 1-year of antipsychotic treatment at the global level and in DAN. Switching rates at baseline at the global level and in the inferior parietal lobule were correlated with the treatment-related reduction of negative symptoms. These findings suggest that instability of functional network activity plays an important role in the pathophysiology of acute psychosis in early-stage schizophrenia. The normalization of network stability after antipsychotic medication suggests that this effect may represent a systems-level mechanism for their therapeutic efficacy.
Mpox in People With Human Immunodeficiency Virus: Predictors of Diagnosis, Outcomes, and Vaccine Effectiveness in a Multisite Cohort
Authors: Montaño Michalina , Shapiro Adrienne E , Whitney Bridget M , Bamford Laura , Burkholder Greer , Cachay Edward R , Christopoulos Katerina A , Crane Heidi M , Delaney Joseph A C , Eron Joseph J , Fredericksen Rob J , Hunt Peter W , Jacobson Jeffrey M , Keruly Jeanne C , Kim H Nina , Mayer Kenneth H , Moore Richard D , Napravnik Sonia , Pettit April , Saag Michael S , Yendewa George A , Kitahata Mari M , Bender Ignacio Rachel A
Published: October 2024

Introduction

Since its global reemergence in 2022, monkeypox (mpox) has demonstrated increased incidence and severity among people with human immunodeficiency virus (HIV [PWH]). Predictors of mpox diagnosis, vaccination, and outcomes among PWH are limited.

Methods

We included PWH with primary care visits after 1 January 2022 at 9 US sites participating in the Centers for AIDS Research Network of Integrated Clinic Systems Network. We identified mpox diagnosed between 1 June 2022 and 31 May 2023, through a combination of polymerase chain reaction result, diagnosis code, and/or tecovirimat receipt. We examined validated clinical diagnoses, laboratory results, vaccine data, and patient reported outcomes. We evaluated relative risks (RR) of mpox diagnosis, hospitalization, tecovirimat treatment, and vaccine receipt.

Findings

Among 19 777 PWH in care, 413 mpox cases (all male sex at birth) occurred (2.2 cases/100 person-years). Age <40 years, geographic region, Hispanic/Latine ethnicity, lack of antiretroviral therapy, detectable HIV viral load, and recent bacterial sexually transmitted infection predicted mpox diagnosis. PWH with CD4 200–349 cells/mm3 were most likely to be hospitalized (adjusted RR, 3.20; 95% confidence interval: 1.44–7.09) compared to CD4 ≥500, but half as likely as those with CD4 <200 to receive tecovirimat. Overall, smallpox/mpox vaccine effectiveness of ≥1 vaccine was 71% (adjusted RR, 0.29; 95% confidence interval: .14–.47) at preventing mpox, and 86% or better with CD4 ≥350 or HIV viral suppression. Non-Hispanic Black PWH were less likely to be vaccinated than other racial/ethnic identities.

Interpretation

PWH not on antiretroviral therapy or with unsuppressed HIV were more likely to be diagnosed with, and hospitalized for, mpox. Mpox/smallpox vaccine effectiveness was high, inclusive of those with low CD4 count and HIV viremia.
Comparison of At-Home Versus In-Clinic Receipt of Long-Acting Injectable Cabotegravir/Rilpivirine
Authors: Kirk Stephanie E , Young Christina , Berry Hayley , Hanson Rochelle , Moreland Angela , Fonner Virginia , Gebregziabher Mulugeta , Williams Jamila , Meissner Eric G
Published: October 2024

Background

The need for frequent travel to a clinic could impair access to injectable antiretroviral therapy for persons living with human immunodeficiency virus type 1 (HIV-1) infection. We hypothesized that allowing persons receiving treatment with long-acting injectable cabotegravir plus rilpivirine (LA CAB/RPV) to receive and store the medication in their own refrigerator prior to in-home administration by a healthcare provider would be as safe and effective as receiving treatment in a clinic.

Methods

Persons prescribed LA CAB/RPV in the Infectious Diseases clinic at the Medical University of South Carolina were offered enrollment in this non-randomized, observational study between August 2021 and December 2022. After in-clinic receipt of the initial LA CAB/RPV injection, participants chose to receive each subsequent injection over the following 12-months either in clinic or at home.

Results

The 33 enrolled participants were primarily Black (64%), male (73%), and had a median age of 46. Three participants stopped LA CAB/RPV and transitioned to oral antiretroviral therapy due to allergy (n = 1), loss of virologic suppression (n = 1), and visit adherence (n = 1) concerns. A comparable number of participants received treatment primarily in clinic (n = 18) relative to at home (n = 15). Injection site pain/soreness was common (52% of injections) but did not differ between groups. There were no differences in safety or efficacy between groups and both groups reported high treatment satisfaction. All participants were virologically suppressed and retained in care at the end of the study.

Conclusions

At-home administration of LA CAB/RPV by a healthcare provider was comparably safe, effective, and associated with high participant satisfaction relative to in-clinic administration.
The End of Composite Monarchies: Hugo Grotius’s De iure belli ac pacis and Mid-Seventeenth-Century Iberian Diplomacy
Authors: Jones Corredera Edward
Published: October 2024

This article sheds light on the seventeenth-century Catalan, Portuguese and Castilian uses of Hugo Grotius’s De iure belli ac pacis (1625) and, in particular, his chapters on the matter of monarchical succession. By studying the patterns in the ways that Catalan and Portuguese rebels and Spanish diplomats drew on this source to mediate disputes over succession, the article suggests that, while Grotius’s works may have eroded the rights of possession in the Atlantic and the Pacific by building on classical, biblical and Spanish sources, Iberian authors saw the text as a shared rulebook for discussing a sensitive matter that Spain had traditionally resolved through creative ambiguity, by granting and expanding local privileges under the threat of brute force. The article, in this way, encourages a reconsideration of the practical, diplomatic and high-political uses of Grotius’s ideas in Catholic Europe, a reassessment of a clear-cut binary between Dutch ideas of liberty and Spanish visions of empire, and a reconsideration of the historiographical explanation for the decomposition of composite monarchies.
Dark patterns, dark nudges, sludge and misinformation: alcohol industry apps and digital tools
Authors: Roy-Highley Elliott , Körner Katherine , Mulrenan Claire , Petticrew Mark
Published: October 2024

Many alcohol-industry-funded (AIF) organizations disseminate eHealth/mHealth tools that claim to assist users in making health decisions by monitoring alcohol consumption, e.g. blood alcohol calculators, AUDIT scores, consumption trackers. Previously, AIF materials were found to contain health misinformation that could increase consumption (dark nudges) or make healthy behaviour change more difficult (sludge). The accuracy and functionality of AIF tools have never been analysed, and given the history of AIF materials it is possible they contain misinformation and function as covert marketing channels to promote alcohol-industry-friendly narratives on the causes and possible solutions of alcohol-related harms. We evaluated the information accuracy and framing, behaviour change techniques (BCTs), and functions of AIF digital tools (n = 15, from the UK, Ireland, the USA, Canada, New Zealand, Australia; including Drinkaware, Drinkwise, Educ’alcool and others), compared to a non-industry-funded independent sample (n = 10). We identified misinformation and ‘dark patterns’ (interface design strategies for influencing users against their interest) throughout AIF tools; significantly fewer provided accurate feedback (33% vs 100%), and significantly more omitted information on cancer (67% vs 10%) and cardiovascular disease (80% vs 30%) and promoted industry-friendly narratives (47% vs 0%). AIF tools encouraged consumption through priming nudges (53%) and social norming (40%). AIF tools utilized fewer BCTs, provided users with more limited pre-set options (54%), and fewer drink choices (mean 24 vs 275). Their input structure often impeded their ability to provide guideline advice. We conclude that AIF tools contain pro-industry misinformation strategies and dark patterns that misinform users about their consumption and could ‘nudge’ them towards continuing to drink alcohol—characteristics of ‘Dark Apps’ designs.
CSR and the Constitutive Role of Law: Harnessing Social Norms for Labour Law Enforcement
Authors: Menashe Maayan
Published: October 2024

This article explores how international labour law can harness social norms for the enforcement of international labour standards within private companies. By doing so, it provides a particular take on the ‘constitutive’ role of the law in shaping societal norms and economic activities. Such reliance on societal enforcement mechanisms gains particular relevance in the realm of global labour governance. With the dominance of private compliance initiatives, the law can regain influence by internalising its norms as social norms within companies, even when, strictly speaking, international law is not intended to oblige these actors. Accordingly, the article argues that international labour law holds unique cognitive and normative capacities that can shape actors’ beliefs and expectations, promoting a universal understanding of what shall be considered as the appropriate behaviour in the realm of labour. Once international labour standards become the social benchmark for evaluating companies’ codes of conduct, compliance with these norms becomes key to companies’ reputation and market access. At the same time, the transmission of legal norms to the company level is not straightforward. The article thus puts forward an evolutionary path where international labour law can induce desirable learning processes towards the gradual emergence of a social norm among companies on compliance with its legal requirements.
Immunogenicity, Safety, and Persistence Induced by Triple- and Standard-Strength 4-Dose Hepatitis B Vaccination Regimens in Patients Receiving Hemodialysis
Authors: Yao Tian , Li Yandi , Zhang Yidan , Sun Yangle , Guo Yana , Wang Jianmin , Song Xiaohui , Zhang Wei , Wei Baozhu , Bai Jingen , Wang Hui , Yu Weimin , Wang Huiyuan , Jiao Lu , Diao Yinqiang , Liu Liming , Shi Shuaishuai , Yang Jie , Ren Xiaojun , Liu Wenyuan , Fang Jingai , Liang Xiaofeng , Wang Suping , Feng Yongliang
Published: October 2024

Background

Patients receiving hemodialysis represent a high-risk group for hepatitis B virus (HBV) infection. It is crucial to administer hepatitis B vaccination and stimulate higher and more sustained levels of hepatitis B surface antibodies (anti -HBs). Our aim is to enhance the immunogenicity and persistence by implementing high-dose and prolonged hepatitis B vaccine schedules in patients receiving hemodialysis.

Methods

We conducted this multicenter, randomized, parallel-controlled trial between July 2020 and February 2023 at 11 hospitals in Shanxi province, China. A total of 504 patients receiving hemodialysis were enrolled. All participants were randomly allocated in a ratio of 1:1:1 to receive recombinant HBV vaccine of 3 standard doses (20 μg) at 0, 1, and 6 months (IM20 × 3 group), 4 standard doses at 0, 1, 2, and 6 months (IM20 × 4 group), or 4 triple doses (60 μg) at 0, 1, 2, and 6 months (IM60 × 4 group).

Results

The vaccine-elicited antibody response peaked at month 7. The follow-up from month 7 to 30 revealed that response rates of anti-HBs decreased from 85.9% (134/156) to 33.0% (33/100) in IM20 × 3 group, from 92.5% (135/146) to 53.9% (56/104) in IM20 × 4 group, and from 95.4% (145/152) to 57.3% (55/96) in IM60 × 4 group. The duration of vaccine-induced response with 75% of patients maintained protective antibodies were 21.0 months in IM20 × 3 group, 25.7 months in IM20 × 4 group (vs IM20 × 3 group, P = .056), and 29.2 months in IM60 × 4 group (vs IM20 × 3 group, P = .034). All the adverse reactions were mild.

Conclusions

The triple-strength 4-dose hepatitis B vaccination regimens could enhance the immunogenicity and 2-year duration in patients receiving hemodialysis.

Clinical Trials Registration. NCT03962881.
Insecticide susceptibility in a planthopper pest increases following inoculation with cultured Arsenophonus
Authors: Cai Tingwei , Nadal-Jimenez Pol , Gao Yuanyuan , Arai Hiroshi , Li Chengyue , Su Chunyan , King Kayla C , He Shun , Li Jianhong , Hurst Gregory D D , Wan Hu
Published: October 2024

Facultative vertically transmitted symbionts are a common feature of insects that determine many aspects of their hosts’ phenotype. Our capacity to understand and exploit these symbioses is commonly compromised by the microbes unculturability and consequent lack of genetic tools, an impediment of particular significance for symbioses of pest and vector species. Previous work had established that insecticide susceptibility of the economically important pest of rice, the brown planthopper Nilaparvata lugens, was higher in field-collected lineages that carry Ca. Arsenophonus nilaparvatae. We established Ca. A. nilaparvatae into cell-free culture and used this to establish the complete closed genome of the symbiont. We transformed the strain to express GFP and reintroduced it to N. lugens to track infection in vivo. The symbiont established vertical transmission, generating a discrete infection focus towards the posterior pole of each N. lugens oocyte. This infection focus was retained in early embryogenesis before transition to a diffuse somatic infection in late N. lugens embryos and nymphs. We additionally generated somatic infection in novel host species, but these did not establish vertical transmission. Transinfected planthopper lines acquired the insecticide sensitivity trait, with associated downregulation of the P450 xenobiotic detoxification system of the host. Our results causally establish the role of the symbiont in increasing host insecticide sensitivity with implications for insecticide use and stewardship. Furthermore, the culturability and transformation of this intracellular symbiont, combined with its ease of reintroduction to planthopper hosts, enables novel approaches both for research into symbiosis and into control of insect pest species.
Alliances and Civil War Intervention
Authors: Johnson Jesse C , Leeds Brett Ashley , Savun Burcu
Published: October 2024

Governments have a number of structural advantages over rebel groups in civil wars, one of which is their greater ability to make credible international commitments. Governments can use foreign policy commitments to incentivize other states to provide them military support or deny support to their rebel groups. We analyze international intervention in civil conflicts between 1975 and 2017 and find that some kinds of alliances are associated with pro-government intervention, but all alliances are not equal. Alliances with consultation commitments are associated with interventions that provide materiel, training, intelligence, and/or other forms of non-troop support, while defense pacts are associated with both troop and non-troop support. Members of nonaggression and neutrality pacts are not more likely to intervene to support the government but are less likely to provide support to anti-government forces. We argue that alliances are not simply proxies for common interests; they sometimes involve specific bargains designed to aid a government in defeating rebels. Our evidence suggests that these agreements are successful at incentivizing the intended behavior. Governments use international security policy to protect the status quo domestically as well as internationally, and this affects our understanding both of civil wars and of alliance politics.
Transnationalism and Populist Networks in a Digital Era: Canada and the Freedom Convoy
Authors: Boucher Jean-Christophe , Rutherglen Lauren , Kim So Youn
Published: October 2024

Abstracts

The growth and success of right-wing populist movements globally has been remarkable since the early 2010s. Indeed, populist parties in Europe, Asia, Latin America, and North America have received tremendous electoral success, shaping a movement for the people and by the people within the political sphere. To what extent do populist movements influence other such programs across national borders? Research has suggested that globalization has facilitated the spread of populist ideology. Transnational populism emphasizes the “people” as a “horizontal, membership-based collective with membership premised on an in/out logic between nations, allowing populist national movements to engage and share a global ideological program. This paper seeks to understand and measure to what extent populism has become a transnational movement and identify how populism moves across national borders through online political participation. To explore this question, we collected over 6.7 million digital trace data on X/Twitter during Canada’s January–February 2022 Freedom Convoy movement. Receiving support from thousands of citizens, the Freedom Convoy revealed the ability of populist ideology to move aimlessly across international borders. We used a deep-learning model applied to text analysis to implement a classification task to measure populist narratives during the movement.
Point-of-care tests to manage acute respiratory tract infections in primary care: a systematic review and qualitative synthesis of healthcare professional and patient views
Authors: Hoste Melanie E , Borek Aleksandra J , Santillo Marta , Roberts Nia , Tonkin-Crine Sarah , Anthierens Sibyl
Published: October 2024

Objectives

To review the evidence on healthcare professionals’ (HCPs) and patients’ views of the use of point-of-care tests (POCTs) in the management of acute respiratory tract infections (RTIs) in primary care settings.

Methods

We conducted a systematic review of studies up to 28 April 2023. We included studies that included qualitative methods and results; focused on HCPs’ and/or patients’ views/experiences of POCTs for acute RTIs; and were conducted in primary care settings. We conducted a thematic synthesis to identify how their views on POCTs and interventions can support test use (PROSPERO registration: CRD42019150347).

Results

We included 33 studies, developing 9 categories each for HCP and patient data. We identified 38 factors affecting POCT use: 28 from HCPs and 10 from patients. Factors exist outside and within consultations, and post-consultations, illustrating that some cannot be addressed by HCPs alone. Fourteen interventions were identified that could address factors and support POCT use, with 7 interventions appearing to address the most factors. Some interventions were beyond the scope of HCPs and patients and needed to be addressed at system and organizational levels. Both groups had mixed views on the use of POCTs and highlighted implementation challenges.

Discussion

This review highlights numerous factors affecting POCT use in primary care. Policy-makers planning to implement POCTs are likely to achieve more by providing multi-faceted interventions that target factors outside, within, and post-consultation. Some interventions may need to be already established before POCT introduction. Whilst evidence beyond general practice is limited, similar factors suggest that similar context-tailored interventions would be appropriate.
B-cell interleukin 1 receptor 1 modulates the female adipose tissue immune microenvironment during aging
Authors: Carey Anna , Pitcher Louise E , Jang In Hwa , Nguyen Katie , Cholensky Stephanie , Robbins Paul D , Camell Christina D
Published: October 2024

Myeloid cell production of interleukin-1β (IL-1β) drives inflammaging in visceral white adipose tissue (vWAT) and contributes to the expansion of interleukin-1 receptor 1 (Il1r1)-positive aged adipose B cells (AABs). AABs promote metabolic dysfunction and inflammation under inflammatory challenges. However, whether IL-1β contributes to AAB-associated inflammation during aging is unclear. Using a B-cell-specific knockout of Il1r1 (BKO mice), we characterized old vWAT in the absence of IL-1β–B-cell signaling. In addition to sex-specific metabolic improvements in females, we identified a reduction in the proportion of B cells and a sex-specific increase in the B1/B2 B-cell ratio in BKO vWAT. Using single-cell RNA sequencing of vWAT immune cells, we observed that BKO differentially affected inflammatory signaling in vWAT immune cells. These data suggest that IL-1β–B-cell signaling supports the inflammatory response in multiple cell types and provides insight into the complex microenvironment in aged vWAT.
Mechanisms of fibrinogen trans-activation of the EGFR/Ca2+ signaling axis to regulate mitochondrial transport and energy transfer and inhibit axonal regeneration following cerebral ischemia
Authors: Zhou Shengqiang , Li Bo , Wu Dahua , Chen Yanjun , Zeng Wen , Huang Jia , Tan Lingjuan , Mao Guo , Liu Fang
Published: October 2024

Ischemic stroke results in inhibition of axonal regeneration but the roles of fibrinogen (Fg) in neuronal signaling and energy crises in experimental stroke are under-investigated. We explored the mechanism of Fg modulation of axonal regeneration and neuronal energy crisis after cerebral ischemia using a permanent middle cerebral artery occlusion (MCAO) rat model and primary cortical neurons under low glucose-low oxygen. Behavioral tests assessed neurological deficits; immunofluorescence, immunohistochemistry, and Western-blot analyzed Fg and protein levels. Fluo-3/AM fluorescence measured free Ca2+ and ATP levels were gauged via specific assays and F560nm/F510nm ratio calculations. Mito-Tracker Green labeled mitochondria and immunoprecipitation studied protein interactions. Our comprehensive study revealed that Fg inhibited axonal regeneration post-MCAO as indicated by reduced GAP43 expression along with elevated free Ca2+, both suggesting an energy crisis. Fg impeded mitochondrial function and mediated impairment through the EGFR/Ca2+ axis by trans-activating EGFR via integrin αvβ3 interaction. These results indicate that the binding of Fg with integrin αvβ3 leads to the trans-activation of the EGFR/Ca2+ signaling axis thereby disrupting mitochondrial energy transport and axonal regeneration and exacerbating the detrimental effects of ischemic neuronal injury.
Deciphering farnesol’s anti-arthritic and immunomodulatory potential by targeting multiple pathways: a combination of network pharmacology guided exploration and experimental verification
Authors: Ahmed Shaimaa R , Uttra Ambreen Malik , Usman Muhammad , Qasim Sumera , Jahan Shah , Roman Muhammad , Khojah Hanan , Hendawy Omnia , Rashwan Eman K
Published: October 2024

Objective

Farnesol (FAR), a sesquiterpene alcohol, has documented FAR’s anti-inflammatory and antioxidant activities. Current study was undertaken to assess the efficacy and mechanism of FAR in arthritis by employing network pharmacology and experimental models.

Methods

Two experimental models comprising formaldehyde- and complete Freund’s adjuvant (CFA)-induced arthritis evaluated the efficacy of FAR in treating arthritis. Various parameters were assessed. Then, a network pharmacology approach was applied to gain further insight into the potential mechanism and signaling pathways.

Key findings

FAR significantly reduced paw volume and the arthritic score and improved the hematological and biochemical changes. Radiographic and histological examination showed the anti-arthritic efficacy of FAR, which was associated with down-regulation of pro-inflammatory mediators and upregulation of anti-inflammatory mediators. Network pharmacology analysis revealed that FAR may exert its anti-arthritic effects by targeting specific genes associated with arthritis. Pathway analysis revealed the involvement of three key signaling pathways (IL-17 signaling, TNF signaling, and toll-like receptor signaling) in the development and progression of arthritis.

Conclusions

The results pointed out the protective attributes of farnesol against formaldehyde and CFA-induced arthritis via modulation of multiple targets. This study provides a valuable reference for the development of a new treatment or complementary therapy for arthritis.
Investigation of interfractional range variation owing to anatomical changes with beam directions based on water equivalent thickness in proton therapy for pancreatic cancer
Authors: Kikkawa Yuhei , Ueda Hideaki , Uchinami Yusuke , Katoh Norio , Aoyama Hidefumi , Ito Yoichi M , Yokokawa Kohei , Chen Ye , Matsuura Taeko , Miyamoto Naoki , Takao Seishin
Published: October 2024

To assess the interfractional anatomical range variations (ARVs) with beam directions and their impact on dose distribution in intensity modulated proton therapy, we analyzed water equivalent thickness (WET) from 10 patients with pancreatic cancer. The distributions of the interfractional WET difference ($\Delta{\mathrm{WET}}^{\theta }$) across 360° were visualized using polar histograms. Interfractional ARVs were evaluated using the mean absolute error and ΔWET pass rate, indicating the percentage of $\Delta \mathrm{WE}{\mathrm{T}}^{\theta }$ < thresholds. The impact on dose distribution in proton therapy was evaluated based on two treatment plans for 40 Gy(RBE)/5 fractions: ‘Plan A’, using two beam angles, in which the target was closest to the body surface among four perpendicular directions; and ‘Plan B’, using two beam angles with small ARVs. Analysis revealed individual variations in angular trends of interfractional ARVs. Three distinct trends were identified: Group 1 exhibited small ARVs around posterior directions; Group 2 exhibited small ARVs except ~60°; Group 3 demonstrated minimal ARVs only ~90°. In dose evaluation, while 150° and 210° were selected in Plan B for 9 out of 10 patients, for the remaining patient, 60° and 90° were chosen. Comparing dose volume histogram parameters for all patients, Plan B significantly reduced target coverage loss while maintaining organ-at-risk sparing comparable to Plan A. These results demonstrated that selecting beam angles with small interfractional ARVs for each patient enhances the robustness of dose distribution, reducing target coverage loss.
MRI-Seed-Wizard: combining deep learning algorithms with magnetic resonance imaging enables advanced seed phenotyping
Authors: Plutenko Iaroslav , Radchuk Volodymyr , Mayer Simon , Keil Peter , Ortleb Stefan , Wagner Steffen , Lehmann Volker , Rolletschek Hardy , Borisjuk Ljudmilla
Published: October 2024

Evaluation of relevant seed traits is an essential part of most plant breeding and biotechnology programmes. There is a need for non-destructive, three-dimensional assessment of the morphometry, composition, and internal features of seeds. Here, we introduce a novel tool, MRI-Seed-Wizard, which integrates deep learning algorithms with non-invasive magnetic resonance imaging (MRI) for use in a new domain—plant MRI. The tool enabled in vivo quantification of 23 grain traits, including volumetric parameters of inner seed structure. Several of these features cannot be assessed using conventional techniques, including X-ray computed tomography. MRI-Seed-Wizard was designed to automate the manual processes of identifying, labeling, and analysing digital MRI data. We further provide advanced MRI protocols that allow the evaluation of multiple seeds simultaneously to increase throughput. The versatility of MRI-Seed-Wizard in seed phenotyping is demonstrated for wheat (Triticum aestivum) and barley (Hordeum vulgare) grains, and it is applicable to a wide range of crop seeds. Thus, artificial intelligence, combined with the most versatile imaging modality, MRI, opens up new perspectives in seed phenotyping and crop improvement.
Voters distrust delayed election results, but a prebunking message inoculates against distrust
Authors: Lockhart Mackenzie , Gaudette Jennifer , Hill Seth J , Kousser Thad , Romero Mindy , Uribe Laura
Published: October 2024

Counting and certifying election results in the United States can take days and even weeks following election day. These delays are often linked to distrust in elections but does delay cause distrust? What can election officials do to counteract distrust if counting most ballots and announcing results cannot occur on election night? Using a preregistered survey experiment of nearly 10,000 Americans, this article shows that informing voters about longer-than-expected vote counting time induces a large, significant decrease in trust in the election. However, viewing a “prebunking” video in advance of being informed of the delay in results more than makes up for the delay-induced decrease in election trust. Our findings have two important implications. First, unexpected delays in calling elections induce distrust even without misinformation from third parties. Second, providing voters with information about vote counting and the legitimate reasons for delays increases trust and mitigates the distrust induced by delays.
Perspectives on Anesthesia and Perioperative Patient Safety: Past, Present, and Future
Authors: Kanjia Megha Karkera , Kurth C. Dean , Hyman Daniel , Williams Eric , Varughese Anna
Published: October 2024

During the past 70 years, patient safety science has evolved through four organizational frameworks known as Safety-0, Safety -1, Safety-2, and Safety-3. Their evolution reflects the realization over time that blaming people, chasing errors, fixing one-offs, and regulation would not create the desired patient safety. In Safety-0, the oldest framework, harm events arise from clinician failure; event prevention relies on better staffing, education, and basic standards. In Safety-1, used by hospitals, harm events arise from individual and/or system failures. Safety is improved through analytics, workplace culture, high reliability principles, technology, and quality improvement. Safety-2 emphasizes clinicians’ adaptability to prevent harm events in an everchanging environment, using resilience engineering principles. Safety-3, used by aviation, adds system design and control elements to Safety-1 and Safety-2, deploying human factors, design-thinking, and operational control or feedback to prevent and respond to harm events. Safety-3 represents a potential way for anesthesia and perioperative care to become safer.
Association between Histological Composition and Clinical Symptoms in Lumbar Disc Herniation in Different Age Groups
Authors: Kawaguchi Kenichi , Saiwai Hirokazu , Kobayakawa Kazu , Tarukado Kiyoshi , Yokota Kazuya , Matsumoto Yoshihiro , Harimaya Katsumi , Kato Go , Nakashima Yasuharu
Published: October 2024

Study Design.

Retrospective study of prospectively collected data.

Objective.

To investigate the influence of cartilaginous endplates (CEs) in herniated discs on clinical symptoms and postoperative outcomes in patients with lumbar disc herniation (LDH) in different age groups.

Summary of Background Data.

LDH involving CEs, which are hard and less resorptive, is frequently observed with increasing age and appears to affect the natural course and clinical outcomes following discectomy.

Methods.

Overall, 239 patients who underwent microscopic discectomy were included. Main outcomes were evaluated using motor strength, visual analog scale (VAS) for back and leg pain, and Rolland–Morris Disability Questionnaire. The effects of CEs on clinical variables and postoperative outcomes were compared between two groups (<50 y and ≥50 y). Furthermore, we investigated the characteristics of CE avulsions in each group and examined the association between CE occupancy rate and clinical symptoms.

Results.

CEs were predominantly observed with increasing age and were more frequently detected in patients with Modic changes in both groups (P<0.001). A higher proportion of LDH with a ≥20% occupancy rate was found in patients aged <50 years (P=0.009) and was associated with a decrease in motor strength preoperatively (P=0.007). Postoperative VAS score for low back pain (LBP) was higher in patients with CEs than in those without CEs in the ≥50-year-old group (P<0.001). In multiple regression analysis, the presence of CEs was independently associated with residual LBP at 1 year postoperatively in older patients (β=0.46, P<0.001).

Conclusion.

Avulsion-type herniations in patients aged <50 years had a higher CE occupancy rate, which is a potential cause of preoperative motor weakness. Clinical outcomes following discectomy improved regardless of the presence of CEs, however, cartilaginous herniation in patients aged ≥50 years may affect residual LBP at 1 year.
Association Between Positive Childhood Experiences and Caregiver-Reported ADHD Diagnosis and Severity
Authors: Crouch Elizabeth , Radcliff Elizabeth , Boswell Emma , Brown Monique J. , Hung Peiyin
Published: October 2024

Objective:

Little is known about the prevalence of positive childhood experiences (PCEs), a counter to adverse childhood experiences, in children with an attention-deficit hyperactivity disorder (ADHD) diagnosis. The purpose of this study was to examine the relationship between PCEs and ADHD diagnosis and severity, adjusting for child, family, and household characteristics, using a nationally representative data set.

Methods:

Using the 2020 to 2021 National Survey of Children's Health, our sample included children 6 years of age or older, as this is the age at which PCE questions are asked (n = 56,224). Multivariable logistic regression was used to examine the association between PCE type and ADHD diagnosis and severity, controlling for child and household characteristics.

Results:

In multivariable regression analyses, children who had volunteered in their community had lower odds of a reported ADHD diagnosis than children who had not volunteered in their community (adjusted odds ratio [aOR] 0.83; 95% confidence interval [CI], 0.73–0.95). Children with a connected caregiver had a lower likelihood of ADHD diagnosis than children without a connected caregiver (aOR 0.66; 95% CI, 0.58–0.74). Children reporting moderate to severe ADHD were less likely to report exposure to any of the 7 PCEs examined, when compared with children reporting mild ADHD.

Conclusion:

The findings from this study can be important for clinicians and families to mitigate the negative social and academic outcomes that children with ADHD may face.
The Contribution of Noncommunicable and Infectious Diseases to the Effect of Depression on Mortality: A Longitudinal Causal Mediation Analysis
Authors: Didden Christiane , Egger Matthias , Folb Naomi , Maartens Gary , Rohner Eliane , Kassanjee Reshma , Mesa-Vieira Cristina , Kriel Ayesha , Seedat Soraya , Haas Andreas D.
Published: October 2024

Background:

The increased prevalence of physical diseases among individuals with mental illness contributes to their increased risk of mortality. However, the mediating role of specific diseases in the effect of mental illness on mortality is not well understood.

Method:

We conducted a longitudinal causal mediation analysis using data from beneficiaries of a South African medical insurance scheme from 2011 to 2020. We estimated the overall effect of major depressive disorder (MDD) on mortality and evaluated reductions in this overall effect through hypothetical interventions on the risks of mediating physical diseases using an interventional effects approach. Monte Carlo simulation-based g-computation was used for estimation.

Results:

Among 981,540 individuals, 143,314 (14.6%) were diagnosed with MDD. Mortality risk after 8 years was 6.5% under MDD, and 5.3% under no MDD (risk ratio 1.23, 95% CI = 1.19, 1.26). Overall, 43.4% of this disparity could be attributed to higher rates of physical comorbidities due to MDD. Cardiovascular diseases accounted for 17.8%, followed by chronic respiratory diseases (8.6%), cancers (7.5%), diabetes and chronic kidney disease (5.8%), tuberculosis (4.3%), and HIV (2.7%).

Conclusion:

Within the privately insured population of South Africa, MDD is associated with increased mortality. We found that noncommunicable diseases, rather than infectious diseases, are important mediators of the effect of MDD on mortality.
Prevalence of HCV HVR1 insertions and their role in antibody evasion
Authors: Olesen Christina Holmboe , Collignon Laura , Velázquez-Moctezuma Rodrigo , Fanalista Margherita , Fahnøe Ulrik , Mollerup Sarah , Schneider Uffe V. , Holmbeck Kenn , Bukh Jens , Prentoe Jannick
Published: October 2024

Background and Aims:

Chronic HCV infection afflicts around 50 million people globally, causing ~250,000 deaths yearly. An effective vaccine needs to overcome high viral diversity and HCV’s ability to evade neutralizing antibodies (NAbs). Rapid antigenic drift in the N-terminal motif of envelope protein E2, named HVR1, is critically involved in NAb evasion through an incompletely understood mechanism involving viral entry factors. The canonical length of HVR1 is 27 amino acids, but insertions of 2–4 amino acids were described in patients infected with genotype 1b. We aimed to determine whether HVR1 insertions may be underreported due to extreme HVR1 variability.

Approach and Results:

We observed a 0.7% HVR1 insertion prevalence in routine next-generation sequencing patient contigs. Thus, we performed a direct sequence analysis of E1E2 sequences from 131 patients infected with HCV. Interestingly, we observed that 3% of patients harbored viruses (genotypes 1a, 2b, and 3a) with dominant HVR1 insertions. Insertion of longer noncanonical HVR1s into HCV cell culture recombinants frequently caused loss of fitness. However, culture-viable viruses with HVR1 insertions were fully viable in vivo. Interestingly, in adapted genotype 1b recombinants with HVR1 insertions, we found internal HVR1 deletions that increased antibody sensitivity, which surprisingly correlated more with reduced LDLr than reduced SR-BI dependency, indicating a role of LDLr in NAb evasion. Conversely, HVR1 insertions had no effect on receptor dependency; however, they modulated epitope-specific NAb sensitivity.

Conclusions:

HVR1 insertion prevalence and NAb sensitivity modulation represent a mechanism by which HCV evades emerging NAbs during infection.
Resolution of Macular Confluent Drusen During the Development and Spontaneous Closure of an Eccentric Full-Thickness Macular Hole
Authors: Aoki Shuichiro , Ueda Kohei , Kitamoto Kohdai , Azuma Keiko , Obata Ryo
Published: October 2024

Purpose:

To describe a unique case of drusen resolution accompanying the spontaneous closure of an eccentric full-thickness macular hole (FTMH).

Methods:

This study is a case report.

Results:

A 71-year-old male exhibited confluent drusen in the right eye beneath the fovea. During regular follow-up, an eccentric FTMH developed in the right eye and closed spontaneously. Concurrently, the confluent drusen showed rapid regression without signs of geographic atrophy or macular neovascularization. Visual acuity remained stable throughout the monitoring period.

Conclusion:

This case suggests that drusen regression can occur alongside spontaneous FTMH closure without surgical intervention. This adds to the current understanding of the pathology and treatment for drusen.