bluuebunny/crossref_metadata_2025 huggingface dataset:
Geranylgeranyl diphosphate synthase inhibition impairs osteoclast differentiation, morphology, and resorptive activity
Authors: Muehlebach Molly E , Haney Staci L , Chhonker Yashpal S , Rashid Mamunur , Murry Daryl J , Talmon Geoffrey , Holstein Sarah A
Published: October 2024

Nitrogen bisphosphonates, such as zoledronic acid, target the enzyme farnesyl diphosphate synthase (FDPS) in the isoprenoid biosynthetic pathway (IBP), and are the frontline treatment for osteolytic bone diseases. A strong affinity of these agents for bone limits their distribution out of the skeleton. Geranylgeranyl diphosphate synthase (GGDPS) is directly downstream to FDPS in the IBP and novel GGDPS inhibitors such as RAM2061 have been shown to have key drug-like features including prolonged half-life, metabolic stability, and systemic distribution. Furthermore, RAM2061 exerts anti-neoplastic benefits in mouse models of multiple myeloma and Ewing sarcoma. Therefore, we are interested in determining the potential impact of RAM2061 on osteoclast biology and bone remodeling. Studies utilizing undifferentiated RAW264.7 cells demonstrated that treatment with RAM2061 depletes cells of geranylgeranyl diphosphate, impairs protein geranylgeranylation, and induces markers of the unfolded protein response pathway and apoptosis. Differentiation of RAW264.7 cells to mature osteoclasts is disrupted by RAM2061, resulting in decreased numbers of mature osteoclasts, altered morphology, and decreased tartrate-resistant acid phosphatase activity. Treatment of fully differentiated RAW264.7 cells with RAM2061 led to decreased resorptive activity. Confocal microscopy studies revealed that RAM2061 disrupts Cdc42 localization, inhibiting proper actin ring formation in osteoclasts. No significant impact on bone turnover markers or bone histomorphology was observed following a 3-week treatment of CD-1 mice with RAM2061, although decreased numbers of osteoclasts were observed. Liquid chromatography-tandem mass spectrometry studies confirmed accumulation of RAM2061 in bone from the in vivo studies as well as hydroxyapatite binding in vitro. In conclusion, these studies are the first to demonstrate the anti-osteoclastic activity of GGDPS inhibitor treatment and support future studies exploring the therapeutic benefit of this novel therapy in the setting of pathological bone remodeling.
Comparative ecological analysis and predictive modeling of tick-borne pathogens
Authors: Manley William , Tran Tam , Prusinski Melissa , Brisson Dustin
Published: October 2024

Tick-borne diseases constitute the predominant vector-borne health threat in North America. Recent observations have noted a significant expansion in the range of the black-legged tick (Ixodes scapularis Say, Acari: Ixodidae), alongside a rise in the incidence of diseases caused by its transmitted pathogens: Borrelia burgdorferi Johnson (Spirochaetales: Spirochaetaceae), Babesia microti Starcovici (Piroplasmida: Babesiidae), and Anaplasma phagocytophilium Zhu (Rickettsiales: Anaplasmataceae), the causative agents of Lyme disease, babesiosis, and anaplasmosis, respectively. Prior research identified environmental features that influence the ecological dynamics of I. scapularis and B. burgdorferi that can be used to predict the distribution and abundance of these organisms, and thus Lyme disease risk. In contrast, there is a paucity of research into the environmental determinants of B. microti and A. phagocytophilium. Here, we use over a decade of surveillance data to model the impact of environmental features on the infection prevalence of these increasingly common human pathogens in ticks across New York State (NYS). Our findings reveal a consistent northward and westward expansion of B. microti in NYS from 2009 to 2019, while the range of A. phagocytophilum varied at fine spatial scales. We constructed biogeographic models using data from over 650 site-year visits and encompassing more than 250 environmental variables to accurately forecast infection prevalence for each pathogen to a future year that was not included in model training. Several environmental features were identified to have divergent effects on the pathogens, revealing potential ecological differences governing their distribution and abundance. These validated biogeographic models have applicability for disease prevention efforts.
Impacts of nitrogen deposition on Zanthoxylum bungeanum and intercropped plants: assessing growth, chlorophyll fluorescence and yields across diverse cultivation systems
Authors: Li Zilong , Pan Kaiwen , Li Xiyang , Wang Sizhong , Tan Xue , Huang Dan
Published: October 2024

The study aimed to thoroughly investigate the effects of nitrogen deposition on the growth, chlorophyll fluorescence and yield of Zanthoxylum bungeanum Maxim. in both monoculture and intercropping systems with Capsicum annuum L. and Glycine max. The research provided a detailed evaluation of how nitrogen deposition influenced soil and plant parameters within these intercropping systems. Key findings include: (i) In the Z. bungeanum monoculture, nitrogen deposition led to a 346.5% increase in soil NO3− levels, significantly affecting chlorophyll fluorescence parameters and decreasing soil pH. (ii) In the Z. bungeanum–C. annuum intercropping system, nitrogen deposition influenced the growth and chlorophyll fluorescence of both crops and resulted in a 261.5% increase in the root length of C. annuum. (iii) In the Z. bungeanum–G. max system, nitrogen deposition negatively impacted the chlorophyll fluorescence of G. max, reduced Z. bungeanum yields by 89.3% and altered its chlorophyll fluorescence parameters. These changes likely hindered the nitrogen-fixing capacity of G. max due to altered soil conditions. Overall, the Z. bungeanum–C. annuum system showed superior performance by enhancing soil NO3−-N content. In contrast, the Z. bungeanum–G. max system experienced reduced yields due to the adverse effects of nitrogen deposition on symbiotic nitrogen fixation. These findings are crucial for developing agricultural strategies aimed at improving crop adaptability and yield in response to environmental changes.
Studying Chinese immigrants’ spatial distribution in the Raleigh–Durham area by linking survey and commercial data using romanized names
Authors: Bai Eric A , Ju Botao , Beckner Madeleine , Reiter Jerome P , Merli M Giovanna , Mouw Ted
Published: October 2024

Many population surveys do not provide information on respondents’ residential addresses, instead offering coarse geographies like zip code or higher aggregations. However, fine resolution geography can be beneficial for characterizing neighbourhoods, especially for relatively rare populations such as immigrants. One way to obtain such information is to link survey records to records in auxiliary databases that include residential addresses by matching on variables common to both files. We present an approach based on probabilistic record linkage that enables matching survey participants in the Chinese Immigrants in Raleigh–Durham Study to records from InfoUSA, an information provider of residential records. The two files use different Chinese name romanization practices, which we address through a novel and generalizable strategy for constructing records’ pairwise comparison vectors for romanized names. Using a fully Bayesian record linkage model, we characterize the geospatial distribution of Chinese immigrants in the Raleigh–Durham area of North Carolina.
ECBD: European chemical biology database
Authors: Škuta Ctibor , Müller Tomáš , Voršilák Milan , Popr Martin , Epp Trevor , Skopelitou Katholiki E , Rossella Federica , Herzog Katja , Stechmann Bahne , Gribbon Philip , Bartůněk Petr
Published: October 2024

The European Chemical Biology Database (ECBD, https://ecbd.eu) serves as the central repository for data generated by the EU-OPENSCREEN research infrastructure consortium. It is developed according to FAIR principles, which emphasize findability, accessibility, interoperability and reusability of data. This data is made available to the scientific community following open access principles. The ECBD stores both positive and negative results from the entire chemical biology project pipeline, including data from primary or counter-screening assays. The assays utilize a defined and diverse library of over 107 000 compounds, the annotations of which are continuously enriched by external user supported screening projects and by internal EU-OPENSCREEN bioprofiling efforts. These compounds were screened in 89 currently deposited datasets (assays), with 48 already being publicly accessible, while the remaining will be published after a publication embargo period of up to 3 years. Together these datasets encompass ∼4.3 million experimental data points. All public data within ECBD can be accessed through its user interface, API or by database dump under the CC-BY 4.0 license.
20 years of the Bio-Analytic Resource for Plant Biology
Authors: Sullivan Alexander , Lombardo Michael N , Pasha Asher , Lau Vincent , Zhuang Jian Yun , Christendat Ashley , Pereira Bruno , Zhao Tianhui , Li Youyang , Wong Rachel , Qureshi Faisal Z , Provart Nicholas J
Published: October 2024

The Bio-Analytic Resource for Plant Biology (‘the BAR’, at https://bar.utoronto.ca) is celebrating its 20th year in operation in 2025. The BAR encompasses and provides visualization tools for large ‘omics data sets from plants. The BAR covers data from Arabidopsis, tomato, wheat, barley and 29 other plant species (with data for 2 others to be released soon). These data include nucleotide and protein sequence data, gene expression data, protein-protein and protein–DNA interactions, protein structures, subcellular localizations, and polymorphisms. The data are stored in more than 200 relational databases holding 186 GB of data and are presented to the researchers via web apps. These web apps provide data analysis and visualization tools. Some of the most popular tools are eFP (‘electronic fluorescent pictograph’) Browsers, ePlants and ThaleMine (an Arabidopsis-specific instance of InterMine). The BAR was designated a Global Core Biodata Resource in 2023. Like other GCBRs, the BAR has excellent operational stability, provides access without login requirement, and provides an API for researchers to be able to access BAR data programmatically. We present in this update a new overarching search tool called Gaia that permits easy access to all BAR data, powered by machine learning and artificial intelligence.
MicrobiomeNet: exploring microbial associations and metabolic profiles for mechanistic insights
Authors: Lu Yao , Hui Fiona , Zhou Guangyan , Xia Jianguo
Published: October 2024

The growing volumes of microbiome studies over the past decade have revealed a wide repertoire of microbial associations under diverse conditions. Microbes produce small molecules to interact with each other as well as to modulate their environments. Their metabolic profiles hold the key to understanding these association patterns for translational applications. Based on this concept, we developed MicrobiomeNet, a comprehensive database that integrates microbial associations with their metabolic profiles for mechanistic insights. It currently contains a total of ∼5.8 million known microbial associations, coupled with >12 400 genome-scale metabolic models (GEMs) covering ∼6000 microbial species. Users can intuitively explore microbial associations and compare their corresponding metabolic profiles. Our case studies show that MicrobiomeNet can provide mechanistic insights that are consistent with the literature. MicrobiomeNet is freely available at https://www.microbiomenet.com/.
Nutritional Psychology: Review the Interplay Between Nutrition and Mental Health
Authors: Horovitz Omer
Published: October 2024

Nutritional psychology is a burgeoning field that examines the intricate relationship between nutrition and mental health. This concept, its historical development, and its current significance in understanding the complex interplay between diet and psychological well-being are explored in this article. The influence of various nutrients on mental health, the role of dietary patterns, and the impact of nutrition on specific mental disorders are examined. Highlighted are the potential mechanisms underlying the nutrition-mental health connection, and the implications for clinical practice and public health interventions are discussed. The discussion in this article underscores the importance of considering nutrition as essential in mental health promotion and treatment.
26 Culturally informed developmental paediatric care: A qualitative study
Authors: McLeod Scott , Huie Michelle , Francois Katilyn
Published: October 2024

Background

Paediatricians provide developmental care through developmental surveillance, identification and management of specific developmental disorders, and health advocacy. Despite being one of the most common reasons to visit a paediatrician, the provision of care in this field is challenging as it intersects with medical, mental health, and educational systems. Additionally, the rise of international migration, inequities in health systems, and unique culturally based concepts of child development require paediatricians to have unique skills for culturally informed care provision in this area.

Objectives

A qualitative study was conducted to describe the perceptions of paediatricians on providing culturally informed developmental paediatric care to diverse populations.

Design/Methods

Semi-structured interviews were completed with paediatricians who primarily provide developmental care to understand the challenges, opportunities, and potential educational enhancements to improve culturally informed care for developmental paediatrics. Thematic analysis was used to analyze the transcribed interviews using inductive and deductive approaches.

Results

Three major themes emerged from 18 individual semi-structured interviews. The first theme, “cultural translation,” described language differences, interpretation, and trust-building between discordant physician/family dyads. The second theme, “inequity,” described systemic barriers that diverse populations experience, power distance in healthcare relationships, and pandemic-related amplifications of inequity. The third theme, “educational opportunities,” highlighted reflective practice opportunities, immersive experiences in diverse settings, and building a community of practice for paediatricians to build their knowledge base. Paediatricians practicing developmental paediatric care highlighted unique elements to the practice which may benefit from practice changes and curricular reform. Integration of meaningful training in the use of interpretation services, multicultural health brokers, and care coordination teams is a recommended intervention which is transferable to many disciplines. Peer-mentorship from colleagues of differing cultural backgrounds may help reduce race-based stereotypes and enhance perspective taking.

Conclusion

Paediatricians had a variety of perspectives on the provision of developmental paediatric care to diverse populations within Canada. There were a range of perceived opportunities for improvements in care noted on individual and systems levels. The development of infrastructure to build capacity in culturally informed developmental paediatric care to reduce culturally based health gaps is a needed future direction for developmental paediatrics.
59 Enhancing career development in paediatrics residency: A needs assessment
Authors: Cooper Jessica , Veale Pamela
Published: October 2024

Background

Mentorship is a cornerstone of professional growth within medical training, yet the role of formal mentorship in career advising for medical residents remains understudied. In 2020, our Paediatrics Residency program introduced the role of faculty advisors as part of the Competence by Design framework, with a mission to guide academic growth, professional development, and excellence in patient care. However, it is unclear to what extent career advising is occurring in this advisor-advisee relationship.

Objectives

The primary aim of this study was to complete a needs assessment for Paediatric residents to inform faculty advisor roles and responsibilities and effectively support paediatric residents in their career development. This included examination of the current state, identification of the ideal state, followed by a gap analysis and recommendations to create a comprehensive advising program.

Design/Methods

This study utilized a mixed methods approach, using quantitative and qualitative survey methodologies. The survey questions (n=20) were designed from background literature and pilot testing. An anonymous survey was administered through the Qualtrics platform to the Paediatrics residents (n=59). The protocol was submitted for REB review and was granted an exemption as a quality improvement project. Thematic analysis of the qualitative content was completed by two investigators, utilizing the Braun & Clarke six-phase framework.

Results

The response rate for the survey reached 34% (n=20) with the final sample including 16% PGY1, 42% PGY2, 16% PGY3, and 26% PGY4 residents. Alarmingly, most residents (63%) did not have a well-defined plan for monitoring career goals. No residents claimed to have sufficient career mentorship at present (0%), with majority (84%) expressing their interest in regular career planning sessions. A significant proportion (79%) also underscored the importance of considering life context when setting career goals. Our thematic analysis revealed that career advising currently follows a non-formal, self-initiated process, with time constraints as the primary obstacle. Primary themes elicited emphasized career exploration (n=15), networking (n=7) including discussions around life context (n=6), mentorship (n=6), and advisor role clarity (n=6).

Conclusion

Our findings affirm a compelling need for enhanced career development within our Paediatrics Residency program. In response, we propose a multi-faceted approach advocating for structured formal career development. This entails scheduled information sessions, resident goal setting, and formal mentorship. We recommend creating opportunities for networking to enable personalized career development considerations. Exploring an adjunctive role to faculty advisors may be necessary to ensure the success of these recommendations in optimizing resident career education.
77 Antenatal MgS04 in very preterm babies is not related to improved 36 month neurodevelopmental outcomes once accounting for neonatal interventions
Authors: Arumugarasan Arthiga , Selvanathan Thiviya , Charlton Julia K , Au-Young Stephanie , Guo Ting , Branson Helen , Synnes Anne , Ly Linh G , Kelly Edmond , Grunau Ruth Eckstein , Miller Steven Paul , Chau Vann
Published: October 2024

Background

Magnesium Sulphate (MgSO4) has become a standard practice for fetal neuroprotection prior to delivery of very-preterm babies due to an association with MgSO4 and reduction of cerebral palsy at 2 years of age in randomized clinical trials.

Objectives

In a prospective cohort of very preterm babies, we aimed to define the association between antenatal MgSO4 administration and neurodevelopmental outcome.

Design/Methods

We included a prospective cohort of 265 infants born ≤ 32 weeks’ gestation recruited at three tertiary neonatal intensive care units (NICU). Infants underwent two brain MRIs, one in the initial weeks after birth and one at term-equivalent age. Neurodevelopmental follow-up assessments were completed using the Bayley-3 at 3 years. Univariate analysis was undertaken to determine whether MgSO4 was associated with outcome. Multiple maternal and neonatal factors were analyzed according to their relationship with outcome. Gestational age was accounted for in all models. Maternal factors associated with MgSO4 administration were hypertension, multiple births and antenatal corticosteroid administration. Neonatal factors were sex, neonatal resuscitation, major surgery, and moderate-severe white matter injury (volume >40mm3). Multivariable linear regression models of maternal and neonatal risk factors were used to account for potential confounders based on those factors that were significantly (p<0.05) associated in univariate analysis.

Results

On univariate analysis, MgSO4 administration was inversely associated with 36-month motor scores (p<0.05). On the multivariable analysis, no maternal confounders had an impact on the relationship between MgSO4 and outcome (Table 2). MgS04 was no longer statistically related to any Bayley outcomes after adjusting for confounders at 36 months (Table 2). Neonatal surgery was related to poorer 36-month motor and cognitive outcomes.

Conclusion

Antenatal MgSO4 exposure was not associated with improved measures on the Bayley scales at 3 years after adjusting for potential confounders. However, neonatal interventions remained significant risk factors for poorer neurodevelopmental outcome.
Knowing (in) organizations: calculative cultures and paradigmatic learning in the case of the World Bank
Authors: Bandola-Gill Justyna
Published: October 2024

This paper explores the evidence culture in one of the key global knowledge institutions—the World Bank. Framing itself as a “Knowledge Ban,” the World Bank is a leading organization in data and evidence provision around poverty and inequalities, and as such, it shapes the broader evidentiary standards and knowledge infrastructures around the world. Drawing on a rich qualitative study of 46 semistructured interviews with experts working on poverty knowledge as well as document analysis of the key reports and strategic documents, this paper explores the manner in which the calculative evidence culture of the World Bank mediates the production of evidence and expertise within the institution. This paper explores the collectively formulated interpretative lenses that guide formative questions such as what counts as (good) evidence, how it is used in decision-making, and how to deal with uncertainty with data and evidence. By doing so, this paper makes two contributions to the literature on evidence-based policymaking. First, it provides a cultural lens to the production and use of evidence in policymaking, a lens that is significantly underdeveloped in the existing scholarship. Second, it addresses the question of evolving evidentiary standards and learning within knowledge organizations. By exploring how institutions “change their mind,” this paper provides a dynamic account of the evolving politics of knowledge within organizations.
The Causal Effect of Candidate Extremity on Citizens’ Preferences: Evidence from Conjoint Experiments
Authors: Amsalem Eran , Zoizner Alon
Published: October 2024

Previous studies demonstrate that politicians’ issue positions and rhetorical style have grown increasingly extreme. It remains unclear, however, whether extremity pays off electorally. Using two preregistered conjoint experiments conducted in the United States (N = 2,006) and Israel (N = 1,999), we investigate whether citizens reward or penalize candidates for taking extreme positions (i.e., proposing radical solutions to societal problems) and using an extreme rhetorical style (i.e., communicating in a way that signals rigidity and dogmatism). The results are consistent in showing that extremity is costly for candidates. Across countries, citizens penalize both in-party and out-party candidates for both extreme positions and an extreme rhetorical style, and the average penalty for being extreme is a 16-percentage-point decrease in candidate support. Our results are in line with scholarship demonstrating that citizens disapprove of elite extremity. They also indicate that citizens react independently to elites’ substantive policy positions and their communication style.
Partisanship and Older Americans’ Engagement with Dubious Political News
Authors: Lyons Benjamin , Montgomery Jacob M , Reifler Jason
Published: October 2024

Studies based on digital trace data show that older Americans visit and share dubious news sources far more often than younger cohorts, tendencies often attributed to lower levels of digital literacy. At the same time, survey experiments show that older Americans are no worse, if not better, at discerning between false and accurate news. If older Americans can identify misleading news content equally well, why are they still more likely to engage with it in observational settings? In this article, we combine survey measures and digital trace data for three nationally representative samples (N = 9,944) to argue that the existing literature overemphasizes the importance of factors like digital literacy relative to standard political variables such as political interest and partisanship, factors known to increase across the lifespan. Calcified partisanship in particular makes older Americans vulnerable to hyperpartisan news—which is highly slanted but not verified as explicitly false. High rates of engagement with this category of content, which has been examined in survey studies of older citizens less regularly in the literature, may partially explain the high rates of engagement with dubious news domains in behavioral trace data. In all, our findings have important implications for how we understand—and might intervene to reduce—high engagement among this cohort with dubious news.
The basic statistical concepts and their interrelationships in diagnostic research
Authors: Mao Yitao , Xiao Juxiong , Zhu Liping , Zhang Yu , Leng Yueshuang , Li Qingling , Li Ying , Liu Chuyi , Zhao Luqing
Published: October 2024

Background

Many medical postgraduate students exhibit a lack of clarity in their understanding of relevant statistical concepts during the conduct of diagnostic studies.

Methods

This article, grounded in research practice, delves into the role of understanding statistical concepts in diagnostic research. It includes an exploration of sensitivity, specificity, types of statistical errors, and their interrelationships, as well as a discussion on statistical power—an often-overlooked but crucial concept in research.

Results

The article elucidates these important concepts with specific examples and illustrations, and addresses an issue of inconsistency related to the receiver operating characteristic curve in research practice.

Conclusion

By drawing analogies between basic concepts in diagnostic tests and concepts in statistics, this article helps to enhance researchers' abilities in designing and interpreting clinical diagnostic studies, thereby improving the quality of clinical diagnostic research.
Determination of the ambient dose equivalent H*(10) at high-altitude cities using a NaI(Tl) scintillator
Authors: Nina Choque Carlos Lorenzo , Rivera Bretel Hugo Marcelo
Published: October 2024

The ambient dose equivalent rate H*(10) was determined at various locations in the metropolitan area of the cities of La Paz and El Alto in Bolivia. A NaI(Tl) scintillation detector was employed to infer the gamma-ray fluence, and the fluence was transformed in dose rates by means of the appropriate coefficients. In this paper, a full methodology for the estimation of dose rates associated with gamma rays emitted from the ground (terrestrial radiation) and the atmosphere is developed from measurements made with the scintillator instrument. The energy calibration and resolution of the apparatus are presented, followed by the estimation of its response and efficiency by means of Monte Carlo simulations. Lastly, the definition of H*(10) is used to determine the conversion coefficients needed to transform gamma-ray fluence in dose rates. With this methodology, rates for H*(10) around 123 ± 8 nSv/h were estimated using data collected in three city districts: Mallasa (3320 m a.s.l.), San Antonio (3620 m a.s.l.), and Zona Sur (3400 m a.s.l.). The dose rates are believed to be representative of the terrestrial radiation fields encountered in the highlands of Bolivia.
Genetic variants associated with chronic fatigue syndrome predict population-level fatigue severity and actigraphic measurements
Authors: Liu Patrick Z , Raizen David M , Skarke Carsten , Brooks Thomas G , Anafi Ron C
Published: October 2024

Study Objectives

The diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (CFS) is based on a constellation of symptoms which center around fatigue. However, fatigue is commonly reported in the general population by people without CFS. Does the biology underlying fatigue in patients with CFS also drive fatigue experienced by individuals without CFS?

Methods

We used UK Biobank actigraphy data to characterize differences in physical activity patterns and daily temperature rhythms between participants diagnosed with CFS compared to controls. We then tested if single nucleotide variants (SNVs) previously associated with CFS are also associated with the variation of these actigraphic CFS correlates and/or subjective fatigue symptoms in the general population.

Results

Participants diagnosed with CFS (n = 295) had significantly decreased overall movement (Cohen’s d = 0.220, 95% CI of −0.335 to −0.106, p-value = 2.42 × 10−15), lower activity amplitudes (Cohen’s d = -0.377, 95% CI of −0.492 to −0.262, p-value = 1.74 × 10−6), and lower wrist temperature amplitudes (Cohen’s d = −0.173, 95% CI of -0.288 to -0.059, p-value = .002) compared to controls (n = 63,133). Of 30 tested SNVs associated in the literature with CFS, one was associated in the control population with subjective fatigue and one with actigraphic measurements (FDR < 0.05).

Conclusions

The genetic overlap of CFS risk with actigraphy and subjective fatigue phenotypes suggests that some biological mechanisms underlying pathologic fatigue in patients with CFS also underlie fatigue symptoms at a broader population level. Therefore, understanding the biology of fatigue in general may inform our understanding of CFS pathophysiology.
Effects of microgravity on human iPSC-derived neural organoids on the International Space Station
Authors: Marotta Davide , Ijaz Laraib , Barbar Lilianne , Nijsure Madhura , Stein Jason , Pirjanian Nicolette , Kruglikov Ilya , Clements Twyman , Stoudemire Jana , Grisanti Paula , Noggle Scott A , Loring Jeanne F , Fossati Valentina
Published: October 2024

Research conducted on the International Space Station (ISS) in low-Earth orbit (LEO) has shown the effects of microgravity on multiple organs. To investigate the effects of microgravity on the central nervous system, we developed a unique organoid strategy for modeling specific regions of the brain that are affected by neurodegenerative diseases. We generated 3-dimensional human neural organoids from induced pluripotent stem cells (iPSCs) derived from individuals affected by primary progressive multiple sclerosis (PPMS) or Parkinson’s disease (PD) and non-symptomatic controls, by differentiating them toward cortical and dopaminergic fates, respectively, and combined them with isogenic microglia. The organoids were cultured for a month using a novel sealed cryovial culture method on the International Space Station (ISS) and a parallel set that remained on Earth. Live samples were returned to Earth for analysis by RNA expression and histology and were attached to culture dishes to enable neurite outgrowth. Our results show that both cortical and dopaminergic organoids cultured in LEO had lower levels of genes associated with cell proliferation and higher levels of maturation-associated genes, suggesting that the cells matured more quickly in LEO. This study is continuing with several more missions in order to understand the mechanisms underlying accelerated maturation and to investigate other neurological diseases. Our goal is to make use of the opportunity to study neural cells in LEO to better understand and treat neurodegenerative disease on Earth and to help ameliorate potentially adverse neurological effects of space travel.
Pilot Study: Use of Stem Cell Therapy and Diced Cartilage in Secondary Rhinoplasty Cases Clinical Outcomes: The Golden Turkish Delight
Authors: Unlu Ramazan Erkin , Ozmut Ozer , Ergani Hasan Murat , Yasar Burak , Yildirim Furkan
Published: October 2024

Background:

Although many techniques in the secondary rhinoplasty field have been developed in recent years, there are debates regarding achieving results with a high satisfaction rate. We aimed to share the surgical use technique in secondary rhinoplasty patients by enriching the Turkish delight technique with mesenchymal stem cells, which we described as the golden Turkish delight (GTD) technique, and the long-term patient satisfaction results.

Methods:

The study was planned as prospective research, and 30 secondary rhinoplasty patients who presented to our service for rhinoplasty were included. The GTD technique was applied to these patients. The patient’s satisfaction with the surgical procedure was evaluated at least 9–12 months after the surgery, and the Global Aesthetic Improvement Scale (GAIS) was used as a measurement tool.

Results:

Of the participants, the satisfaction levels of 30 patients were evaluated with a 1-year follow-up on average, and the rate of those who improved was found to be 80% using the GAIS score. The rate of those with high GAIS scores and those with high satisfaction levels was approximately 56%. Twenty percent of the patients were not satisfied with the result.

Conclusions:

When we evaluate the postoperative 1-year results of our patients in terms of satisfaction and complications, we may state that the absorption that may occur in the Turkish delight technique over time could give better results with the GTD technique. In addition to GTD and fat graft support, regenerative medicine products such as stromal vascular fraction are very effective in obtaining favorable results.
The relative contribution of hemodynamic parameters to blood pressure decrease in classical orthostatic hypotension
Authors: Gagaouzova Boriana S. , van der Stam Amber , Johansson Madeleine , Van Rossum Ineke A. , Kerkhof Fabian I. , Reijntjes Robert , van Houwelingen Marc , Thijs Roland D. , Fedorowski Artur , van Dijk J. Gert
Published: October 2024

Purpose:

We studied the relative contributions of total peripheral resistance (TPR), stroke volume (SV) and heart rate (HR) to low blood pressure in classical orthostatic hypotension (cOH) on group and individual levels.

Methods:

We retrospectively analyzed tilt test records from cOH patients and age/sex-matched controls. We quantified relative effects of HR, SV and TPR on mean arterial pressure (MAP) with the log-ratio method. We studied relations of changes of HR, SV or TPR with the change of MAP across patients and variability of contributions of HR, SV and TPR to MAP. We also explored neurogenic vs. nonneurogenic causes.

Results:

MAP responded to tilt with a decrease in patients (n = 80) and an increase in controls (n = 80). A too small TPR-increase contributed most to cOH, followed by a too large SV-decrease; both effects were partially corrected by a larger increase of HR. Only TPR changes consistently affected MAP change in patients and controls. TPR decreased almost exclusively in patients, most in those with severe cOH. Contributions of HR, SV and TPR to MAP did not differ between probable neurogenic and nonneurogenic causes.

Conclusion:

HR, SV and TPR all contributed to cOH, with a key role for TPR; a decrease of TPR was almost unique to patients and may be due to hyperventilation. The lack of differences between neurogenic and nonneurogenic causes needs further study.
FLUID RESOLUTION WITHOUT SHORTENING INJECTION INTERVAL DURING SUBRETINAL FLUID–TOLERATING TREATMENT IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION
Authors: Lee Ji Hyun , Park Sang Min , Kim Jae Hui
Published: October 2024

Purpose:

To investigate the incidence and factors associated with subretinal fluid (SRF) resolution during SRF-tolerating treatment in patients with neovascular age-related macular degeneration.

Methods:

This retrospective study included patients diagnosed with neovascular age-related macular degeneration who exhibited fovea-involving residual SRF persisting for at least 6 months during aflibercept treatment. Patients who showed SRF resolution despite maintaining the injection intervals were included in the resolution group, while those who exhibited persisting SRF throughout the study period were included in the nonresolution group. The incidence and associated factors of SRF resolution without reducing the injection interval were evaluated. Furthermore, the frequency of successfully extending the injection intervals while maintaining SRF resolution was identified.

Results:

In total, 65 patients with neovascular age-related macular degeneration were included (32 and 33 in the resolution and nonresolution groups, respectively). When compared with the nonresolution group, the resolution group showed a lower mean height of SRF (67.7 ± 33.4 vs. 109.9 ± 44.9 µm, P < 0.001) and a lower maximum height of SRF (138.3 ± 88.6 vs. 176.2 ± 76.9 µm, P = 0.034). In multivariate analysis, the mean SRF height (P = 0.001), maximum SRF height (P = 0.006), and interval of anti–vascular endothelial growth factor injections (P = 0.023) were significantly associated with the resolution of SRF. In the resolution group, 14 patients (43.8%) successfully expanded the injection interval.

Conclusion:

During SRF-tolerating treatment for neovascular age-related macular degeneration, a substantial proportion of patients exhibited resolution of fluid without shortening the injection interval. Patients with lesser residual SRF during treatment were more likely to achieve fluid resolution. After SRF resolution, injection intervals can be extended in more than 40% of patients.
Socioeconomic and Racial Disparities in Primary Open Angle Glaucoma in the United States
Authors: Downs Carolyn S. , Percelay Paul J. , Williams Brandon , Goedecke Patricia J. , Wesberry Jess M. , Mandal Nawajes
Published: October 2024

Précis:

Socioeconomic status is a potentially significant, although difficult to isolate, factor in determining glaucoma severity.

Purpose:

To analyze the level of glaucoma severity (mild, moderate, or severe) based on demographic factors, including age, gender, ethnicity, insurance profile, and zip code, and to use this data to extrapolate the effect of socioeconomic status (SES) and race on glaucoma severity at the community level in Memphis, TN.

Patients and Methods:

Totally, 2913 patients from a tertiary care center with 3 clinic locations in Memphis, TN who had been given the diagnosis of primary open angle glaucoma (POAG) through use of the ICD-10 codes for mild (H40.1111, H40.1121, H40.1131), moderate (H40.1112, H40.1122, H40.1132), and severe (H40.1113, H40.1123, H40.1133) POAG between January 2016 and July 2021 were included in this study. Diagnoses were made after a complete glaucoma workup consisting of Snellen visual acuity, applanation IOP measurement, gonioscopy, automated Humphreys visual fields (10-2 and 24-2), and optic nerve OCT. Demographic information, including age, gender, ethnicity, insurance profile, and zip code, was also collected with disease severity for each patient. SES was approximated using zip code-level census poverty data and insurance profiles. Statistical analyses were performed, including descriptive, multivariable ordinal logistic modeling, and stepwise multivariable linear modeling.

Results:

Glaucoma severity was shown to increase with poverty rate (OR=1.089, P<0.0071), age (OR=1.030, P<0.0001), male sex (OR=1.374, P<0.0001), and Black race (OR=1.896, P<0.0001). Severity was shown to be decreased in patients with private insurance compared with Medicare (OR=0.895, P<0.093) and those from Shelby County compared with other counties (OR=0.703, P<0.0001).

Conclusions:

Our findings indicate that worsening glaucoma severity was associated with higher poverty rates in our patient population. However, isolating socioeconomic status (SES) as an independent factor influencing the incidence and severity of glaucoma remains challenging, given the strong correlation between race and SES.
Blast Exposure, Tinnitus, Hearing Loss, and Postdeployment Quality of Life in U.S. Veterans: A Longitudinal Analysis
Authors: Mohammed Hoda A.O. , Reavis Kelly M. , Thapa Samrita , Thielman Emily J. , Helt Wendy J. , Carlson Kathleen F. , Hughes Charlotte K.
Published: October 2024

Objective

Examine the association between military blast exposure and functional status among veterans with a focus on functional disability as a proxy for quality of life and explore the potential modifying effect of hearing loss on this association.

Study Design

Prospective cohort.

Setting

Multi-institutional tertiary referral centers.

Patients

540 veterans.

Exposure

Self-reported military blast exposure with and without tinnitus; high-frequency hearing loss (yes/no).

Main Outcome Measure

WHO Disability Assessment Schedule 2.0 questionnaires at baseline and annually over 5 years. The odds of membership into three functional disability trajectory groups: low functional disability, moderate functional disability, and high functional disability.

Results

Of 540 veterans, 197 (36.5%) self-reported a blast exposure history, and 106 of 197 (53.8%) reported tinnitus as a direct result of the blast. Blast exposure without tinnitus increased the odds of moderate functional disability compared with low functional disability (odds ratio [OR] = 1.5; 95% confidence interval [CI], 0.92–2.51), which strengthened among those with blast with tinnitus (OR, 3.6; 95% CI, 2.1–6.1). Blast exposure without tinnitus also increased the odds of membership to high functional disability versus low functional disability (OR, 2.2; 95% CI, 1.1–4.8). Hearing loss further increased the odds of reporting functional disability. The probability of low functional disability was approximately 60% if there was no history of blast or hearing loss, dropping to 20% if there was blast, tinnitus, and hearing loss history.

Conclusions

Blast exposure negatively affects the quality of life of veterans, especially when compounded with tinnitus and hearing loss.
Chronic traumatic encephalopathy in athletes, players, boxers and military: systematic review
Authors: de Sena Barbosa Mateus Gonçalves , Francisco Ghaspar Gomes de Oliveira Alves , de Souza Rafaela Luiza Vilela , de Souza João Marcos Alcântara , Almeida Carneiro Rafael , Rabelo Nicollas Nunes , Chaurasia Bipin
Published: October 2024

The objective of the study was to demonstrate whether athletes, players, boxers and military personnel can really be victims of Chronic traumatic encephalopathy (CTE), and to elucidate this pathology. In 53 articles, 14 were selected for qualitative synthesis in the results table that addresses CTE in football, soccer and rugby players, boxers and the military. Neuropathologically, CTE shows cerebral atrophy, a pelvic septum cavity with fenestrations, dense diffuse immunoreactive inclusions and a TDP-43 proteinopathy. Microscopically, there are extensive neurofibrillary tangles and spindle-shaped neurites throughout the brain. Thus, CTE is characterized by being a distinct tauopathy and with a clear environmental etiology. American football players, boxers and the military are more likely to trigger CET, due to the constant mechanical shocks from their heads. The most frequent clinical manifestations were: headache, aggressiveness, dementia, executive dysfunction and suicide. CET is definitely diagnosed only at autopsy, there is no specific treatment for it, but support and safety measures can help the patient. Advances to definitively diagnose CTE in living people and specific treatment for this disease are needed.
Contrast-Enhanced Digital Mammography for the Diagnosis and Determination of Extent of Disease in Invasive Lobular Carcinoma: Our Experience and Literature Review
Authors: Johansson Lipinski Margaret , Friehmann Tal , Tamir Shlomit , Atar Eli , Grubstein Ahuva
Published: October 2024

Objective

Contrast-enhanced imaging, including magnetic resonance imaging and, more recently, contrast-enhanced digital mammography (CEM), is indicated for the precise diagnosis of invasive lobular carcinoma (ILC). The aim of our study was to further validate the use of CEM for evaluation of extent of disease in ILC cases, with digital breast tomosynthesis (DBT) as an adjunct.

Methods

A retrospective, institutional review board approved study was conducted in a tertiary medical center. All CEM examinations performed on ILC patients between 2017 and 2023 were reread by 2 dedicated breast radiologists. Clinical data and pathology reports were retrieved from electronic medical records. The longest diameter of the enhancing lesion was correlated to pathology findings. In addition, for each case, the readers provided brief commentary on the added value of DBT.

Results

Twenty-four CEM examinations were evaluated. The subjects in the study cohort were on average older than expected for ILC patients (74 vs 63 years) and were unable to undergo breast magnetic resonance imaging due to advanced age and comorbidities. Three subjects were treated with neoadjuvant therapy and thus were excluded from the correlation to pathology analysis. Enhancing lesions, ranging from 4–75 mm, strongly correlated to pathology results, with statistical significance. This was demonstrated for mass and nonmass lesions (r = 0.94, P < 0.001 and r = 0.99, P = 0.002, respectively). For most lesions (17/24, 71%), readers remarked that the addition of DBT allowed for improved characterization of lesion margins, mainly detecting architectural distortion.

Conclusions

When compared with the pathology findings, ILC was accurately diagnosed and assessed using CEM. The addition of DBT was reported by the interpreting radiologists as a valuable adjunct for margin analysis.
Evaluation of Splenic Involvement in Lymphomas Using Extracellular Volume Fraction Computed Tomography
Authors: Xu Suqin , Cao Meimei , Chen Longlan , Shi Jinfang , Wang Xiaoxia , Li Lan , Wang Lu , Zhang Jiuquan
Published: October 2024

Objective

To evaluate whether the extracellular volume (ECV) fraction can be used to identify splenic involvement in lymphoma patients and whether it can be used to improve the diagnostic performance of conventional computed tomography (CT) in the diagnosis of splenic diffuse involvement.

Methods

Consecutive patients with newly diagnosed lymphoma who underwent abdomen contrast-enhanced CT and 18F-fluorodeoxyglucose positron emission tomography/CT for diagnosis or staging were retrospectively enrolled. Patients were divided into the splenic involvement (diffuse or focal) and noninvolvement groups. The ECV fraction was obtained in all patients. In the splenic diffuse involvement and noninvolvement groups, spleen vertical length (SVL) >13 cm and obliteration of normal heterogeneous enhancement of the spleen in arterial phase were recorded. Receiver operating characteristic curve was used to analyze the diagnostic performance, and area under the curve (AUC) comparison was performed using the Delong test.

Results

A total of 135 patients were included, 56 patients with splenic involvement (36 diffuse and 20 focal) and 79 patients with noninvolvement. Splenic involvement can be identified via the ECV fraction (AUC = 0.839). In distinguishing splenic diffuse involvement, the AUC of the ECV fraction was superior to the SVL >13 cm (0.788 vs 0.627, P = 0.007) and obliteration of normal heterogeneous enhancement of the spleen (0.788 vs 0.596, P = 0.001). The combination of ECV fraction and SVL >13 cm demonstrated superior diagnostic performance, with an AUC of 0.830, surpassing all other parameters.

Conclusion

The ECV fraction can be used to identify splenic involvement. The ECV fraction combined with SVL >13 cm is recommended for the prediction of splenic diffuse involvement.