bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapamycin Reduces Arterial Mineral Density and Promotes Beneficial Vascular Remodeling in a Murine Model of Severe Medial Arterial Calcification
Authors: Behzadi Parya , Cuevas Rolando A. , Crane Alex , Wendling Andrew A , Chu Claire C. , Moorhead William J , Wong Ryan , Brown Mark , Tamakloe Joshua , Suresh Swathi , Salehi Payam , Jaffe Iris Z. , Kuipers Allison L. , Lukashova Lyudmila , Verdelis Konstantinos , St. Hilaire Cynthia
Published: August 2024

Peripheral artery disease (PAD) is the narrowing of the arteries that carry blood to the lower extremities. PAD has been traditionally associated with atherosclerosis. However, recent studies have found that medial arterial calcification (MAC) is the primary cause of chronic limb ischemia below the knee. MAC involves calcification of the elastic fibers surrounding smooth muscle cells (SMCs) in arteries. Matrix GLA protein (MGP) inhibits vascular calcification by binding circulating calcium and preventing hydroxyapatite crystal deposition, while also modulating osteogenic signaling by blocking BMP-2 activation of RUNX2.Mgp−/−mice develop severe MAC and die around 8 weeks after birth due to aortic rupture or heart failure. We previously discovered a rare genetic disease Arterial Calcification due to Deficiency in CD73 (ACDC) in which patients present with extensive MAC in their lower extremity arteries. Using a patient-specific induced pluripotent stem cell model we found that rapamycin inhibited calcification. Here we investigated whether rapamycin could reduce MAC in vivo using theMgp−/−murine model.Mgp+/+andMgp−/−mice received 5mg/kg rapamycin or vehicle. Calcification content was assessed via microCT, and vascular morphology and extracellular matrix content assessed histologically. Immunostaining and western blot analysis were used to examine SMC phenotype and extracellular matrix content. Rapamycin prolongedMgp−/−mice lifespan, decreased mineral density in the arteries, maintained SMC contractile phenotype, and improved vessel structure, however, calcification volume was unchanged.Mgp−/−mice with SMC-specific deletion of Raptor or Rictor, did not recapitulate treatment with rapamycin. These findings suggest rapamycin promotes beneficial vascular remodeling in vessels with MAC.
Systems-level reconstruction of kinase phosphosignaling networks regulating endothelial barrier integrity using temporal data
Authors: Wei Ling , Aitchison John D. , Kaushansky Alexis , Mast Fred D.
Published: August 2024

Phosphosignaling networks control cellular processes. We built kinase-mediated regulatory networks elicited by thrombin stimulation of brain endothelial cells using two computational strategies: Temporal Pathway Synthesizer (TPS), which uses phosphoproteomics data as input, and Temporally REsolved KInase Network Generation (TREKING), which uses kinase inhibitor screens. TPS and TREKING predicted overlapping barrier-regulatory kinases connected with unique network topology. Each strategy effectively describes regulatory signaling networks and is broadly applicable across biological systems.
Light quality affects chlorophyll biosynthesis and photosynthetic performance in Antarctic Chlamydomonas
Authors: Poirier Mackenzie C. , Fugard Kassandra , Cvetkovska Marina
Published: August 2024

The perennially ice-covered Lake Bonney in Antarctica has been deemed a natural laboratory for studying life at the extreme. Photosynthetic algae dominate the lake food webs and are adapted to a multitude of extreme conditions including perpetual shading even at the height of the austral summer. Here we examine how the unique light environment in Lake Bonney influences the physiology of twoChlamydomonasspecies.Chlamydomonas priscuiiis found exclusively in the deep photic zone where is receives very low light levels biased in the blue part of the spectrum (400-500 nm). In contrast,Chlamydomonassp. ICE-MDV is represented at various depths within the water column (including the bright surface waters), and it receives a broad range of light levels and spectral wavelengths. The close phylogenetic relationship and psychrophilic character of both species makes them an ideal system to study the effects of light quality and quantity on chlorophyll biosynthesis and photosynthetic performance in extreme conditions. We show that the shade-adaptedC. priscuiiexhibits a decreased ability to accumulate chlorophyll and severe photoinhibition when grown under red light compared to blue light. These effects are particularly pronounced under red light of higher intensity, suggesting a loss of capability to acclimate to varied light conditions. In contrast, ICE-MDV has retained the ability to synthesize chlorophyll and maintain photosynthetic efficiency under a broader range of light conditions. Our findings provide insights into the mechanisms of photosynthesis under extreme conditions, and have implications on algal survival in changing conditions of Antarctic ice-covered lakes.
MRI-based quantification of cardiac-driven brain biomechanics for early detection of neurological disorders
Authors: Diorio Tyler C. , Abderezzai Javid , Nauman Eric , Kurt Mehmet , Tong Yunjie , Rayz Vitaliy L.
Published: August 2024

We present a pipeline to quantify biomechanical environment of the brain using solely MRI-derived data in order to elucidate the role of biomechanical factors in neurodegenerative disorders. Neurological disorders, like Alzheimer’s and Parkinson’s diseases, are associated with physical changes, including the accumulation of amyloid-β and tau proteins, damage to the cerebral vasculature, hypertension, atrophy of the cortical gray matter, and lesions of the periventricular white matter. Alterations in the external mechanical environment of cells can trigger pathological processes, and it is known that AD causes reduced stiffness in the brain tissue during degeneration. However, there appears to be a significant lag time between microscale changes and macroscale obstruction of neurological function in the brain. Here, we present a pipeline to quantify the whole brain biomechanical environment to bridge the gap in understanding how underlying brain changes affect macroscale brain biomechanics. This pipeline enables image-based quantification of subject-specific displacement field of the whole brain to subject-specific strain, strain rate, and stress across 133 labeled functional brain regions. We have focused our development efforts on utilizing solely MRI-derived data to facilitate clinical applicability of our approach and have emphasized automation in all aspects of our methods to reduce operator dependance. Our pipeline has the potential to improve early detection of neurological disorders and facilitate the identification of disease before widespread, irreversible damage has occurred.
Individualized Cerebellar Damage Predicts the Behavioral Disorders in Children with Brainstem Tumors
Authors: Jia Heyuan , Wang Kaikai , Zhang Mingxin , Gu Guocan , Mai Yiying , Wu Xia , Chu Congying , Yin Xuntao , Zhang Peng , Fan Lingzhong , Zhang Liwei
Published: August 2024

Background and Purpose

Brainstem tumors are rare but cause enduring behavioral issues, challenging patients and surgeons. Research on cerebellar changes in these patients limited, despite symptoms similar to cerebellar injuries. This study aims to investigate cerebellar damage pattern resulting from brainstem tumors and its association with behavioral disorders.

Methods

In this study, a U-Net-based segmentation algorithm was used to divide the cerebellum into 26 lobules, which were then used to build a normative model for assessing individual structural deviations. Furthermore, a behavior prediction model was developed using the total outlier count (tOC) index and brain volume as predictive features.

Results

Most patients were found to have negative deviations in cerebellar regions, particularly in anterior lobules like Left V. Higher tOC was significantly associated with severe social problems (r = 0.31, p = 0.001) and withdrawal behavior (r = 0.28, p = 0.001). Smaller size of cerebellar regions strongly correlated with more pronounced social problems (r = 0.27, p = 0.007) and withdrawal behavior (r = 0.25, p = 0.015). Notably, lobules Right X, V, IV, VIIB, Left IX, VIII, and X influenced social problems, while Left V, Right IV, Vermis VI, and VIII impacted withdrawal behavior.

Conclusions

Our study revealed cerebellar damage patterns in patients with brainstem tumors, emphasizing the role of both anterior and posterior cerebellar lobes in social problems and withdrawal behavior. This research sheds light on the brain mechanisms underlying complex behavioral disorders in brainstem tumor patients.
Compatibility of time-lapse dry incubator onin vitroproduction of bovine embryos
Authors: Tsuji Haruhisa , Nagai Hiroki , Kobinata Sayaka , Koyama Hinata , Khurchabilig Atchalalt , Fukunaga Noritaka , Asada Yoshimasa , Sugimura Satoshi
Published: August 2024

Embryo culture is crucial to achieve successful outcomes in assisted reproductive technology (ART) for cattle. This study explored the innovative use of dry incubators integrated with time-lapse monitoring systems for bovine embryo culture, building on their advantages in human medicine, such as reduced contamination risk, stable temperature control, and lower gas consumption. Our research demonstrates the feasibility of this approach, showing that although the osmotic pressure gradually increases over the culture period, it remains below the critical threshold for developmental impairment. Embryos cultured in dry incubators exhibited morphokinetics comparable to those cultured in conventional humidified time-lapse incubators. Furthermore, RNA-seq revealed that the transcriptomic profiles of blastocysts cultured in dry incubators closely matched those of blastocysts cultured in humidified incubators. These findings highlight the significant potential of dry incubators with time-lapse monitoring systems for the in vitro production of bovine embryos, marking a promising advancement in assisted reproductive technologies for the livestock industry and research setting.
Fetal Gene Regulatory Gene Deletions are Associated with Poor Cognition and Altered Cortical Morphology in Schizophrenia and Community-Based Samples
Authors: Forsyth Jennifer K. , Zhu Jinhan , Chavannes Ariana S. , Trevorrow Zachary H. , Hyat Mahnoor , Sievertsen Sam A. , Ferreira-Ianone Sophie , Conomos Matthew P. , Nuechterlein Keith H. , Asarnow Robert F. , Green Michael F. , Karlsgodt Katherine H. , Perkins Diana O. , Cannon Tyrone D. , Addington Jean M. , Cadenhead Kristen S. , Cornblatt Barbara A. , Keshavan Matcheri S. , Mathalon Daniel H. , Stone William S. , Tsuang Ming T. , Walker Elaine F. , Woods Scott W. , Narr Katherine L. , McEwen Sarah C. , Schleifer Charles H. , Yee Cindy M. , Diehl Caroline K. , Guha Anika , Miller Gregory A. , Alexander-Bloch Aaron F. , Seidlitz Jakob , Bethlehem Richard A. I. , Ophoff Roel A. , Bearden Carrie E.
Published: August 2024

Schizophrenia spectrum disorders (SSDs) are characterized by substantial clinical and genetic heterogeneity. Multiple recurrent copy number variants (CNVs) increase risk for SSDs; however, how known risk CNVs and broader genome-wide CNVs influence clinical variability is unclear. The current study examined associations between borderline intellectual functioning or childhood-onset psychosis, known risk CNVs, and burden of deletions affecting genes in 18 previously validated neurodevelopmental gene-sets in 618 SSD individuals. CNV associations were assessed for replication in 235 SSD relatives and 583 controls, and 9,930 youth from the Adolescent Brain Cognitive Development (ABCD) Study. Known SSD- and neurodevelopmental disorder (NDD)-risk CNVs were associated with borderline intellectual functioning in SSD cases (odds ratios (OR) = 7.09 and 4.57, respectively); NDD-risk deletions were nominally associated with childhood-onset psychosis (OR = 4.34). Furthermore, deletion of genes involved in regulating gene expression during fetal brain development was associated with borderline intellectual functioning across SSD cases and non-cases (OR = 2.58), with partial replication in the ABCD cohort. Exploratory analyses of cortical morphology showed associations between fetal gene regulatory gene deletions and altered gray matter volume and cortical thickness across cohorts. Results highlight contributions of known risk CNVs to phenotypic variability in SSD and the utility of a neurodevelopmental framework for identifying mechanisms that influence phenotypic variability in SSDs, as well as the broader population, with implications for personalized medicine approaches to care.
Tinnitus risk factors and its evolution over time: a cohort study
Authors: Hobeika L. , Fillingim M. , Tanguay-Sabourin C. , Roy M. , Londero A. , Samson S. , Vachon-Presseau E.
Published: August 2024

Background

Subjective tinnitus is an auditory percept unrelated to an external sound source. The lack of curative treatments and limited understanding of its risk factors complicate the prevention and management of this distressing symptom. This study seeks to identify socio-demographic, psychological, and health-related risk factors predicting tinnitus presence (how often individuals perceive tinnitus) and severity separately, and their evolution over time.

Methods

Using the UK Biobank dataset which encompasses data on the socio-demographic, physical, mental and hearing health from more than 170,000 participants, we trained two distinct machine learning models to identify risk scores predicting tinnitus presence and severity separately. These models were used to predict tinnitus over time and were replicated in 463 individuals from the Tinnitus Research Initiative database.

Finding

Machine learning based approach identified hearing health as a primary risk factor for the presence and severity of tinnitus, while mood, neuroticism, hearing health, and sleep only predicted tinnitus severity. Only the severity model accurately predicted the evolution over nine years, with a large effect size for individuals developing severe tinnitus (Cohen’sd= 1.10, AUC-ROC = 0.70). To facilitate its clinical applications, we simplified the severity model and validated a five-item questionnaire to detect individuals at risk of developing severe tinnitus.

Interpretation

This study is the first to clearly identify risk factors predicting tinnitus presence and severity separately. Hearing health emerges as a major predictor of tinnitus presence, while mental health plays a crucial role in its severity. The successful prediction of the evolution of tinnitus severity over nine years based on socio-emotional, hearing and sleep factors suggests that modifying these factors could mitigate the impact of tinnitus. The newly developed questionnaire represents a significant advancement in identifying individuals at risk of severe tinnitus, for which early supportive care would be crucial.

Funding

Horizon Europe Marie Slodowska-Curie Actions, the Fondation des gueules cassées, the Fondation pour l’Audition, the Louise and Alan Edwards Foundation, the Canadian Institutes Health Research, the Institut TransMedTech and the Canada First Research Excellence Fund.
Transitions in lung microbiota landscape associate with distinct patterns of pneumonia progression
Authors: Sumner Jack T. , Pickens Chiagozie I. , Huttelmaier Stefanie , Moghadam Anahid A. , Abdala-Valencia Hiam ,   NU SCRIPT Study Investigators, Hauser Alan R , Seed Patrick C. , Wunderink Richard G. , Hartmann Erica M.
Published: August 2024

The precise microbial determinants driving clinical outcomes in severe pneumonia are unknown. Competing ecological forces produce dynamic microbiota states in health; infection and treatment effects on microbiota state must be defined to improve pneumonia therapy. Here, we leverage our unique clinical setting, which includes systematic and serial bronchoscopic sampling in patients with suspected pneumonia, to determine lung microbial ecosystem dynamics throughout pneumonia therapy. We combine 16S rRNA gene amplicon, metagenomic, and transcriptomic sequencing with bacterial load quantification to reveal clinically-relevant pneumonia progression drivers. Microbiota states are predictive of pneumonia category and exhibit differential stability and pneumonia therapy response. Disruptive forces, like aspiration, associate with cohesive changes in gene expression and microbial community structure. In summary, we show that host and microbiota landscapes change in unison with clinical phenotypes and that microbiota state dynamics reflect pneumonia progression. We suggest that distinct pathways of lung microbial community succession mediate pneumonia progression.Graphical Abstract 1.

Determining landscape dynamics of lung microbial ecosystems with multiomics.
Associations between prenatal adversity and neonatal white matter microstructure on language outcomes at age 2 years
Authors: Bjork Jacob , Kenley Jeanette K. , Gardner Caleb , Latham Aidan , Smyser Tara A. , Miller J. Philip , Shimony Joshua J. , Neil Jeffrey J. , Warner Barbara , Luby Joan , Barch Deanna M. , Rogers Cynthia E. , Smyser Christopher D. , Lean Rachel E.
Published: August 2024

Background

Early life adversity is associated with microstructural alterations in white matter regions that subserve language. However, the mediating and moderating pathways between adversities experiencedin uteroand key neonatal white matter tracts including the corpus callosum (CC), superior longitudinal fasciculus (SLF), arcuate fasciculus (AF), inferior fronto- occipital fasciculus (IFOF), and uncinate on early language outcomes remains unknown.

Methods

This longitudinal study includes 160 neonates, oversampled for prenatal exposure to adversity, who underwent diffusion MRI (dMRI) in the first weeks of life. dMRI parameters were obtained using probabilistic tractography in FSL. Maternal Social Disadvantage and Psychosocial Stress was assessed throughout pregnancy. At age 2 years, the Bayley Scales of Infant and Toddler Development-III evaluated language outcomes. Linear regression, mediation, and moderation assessed associations between prenatal adversities and neonatal white matter on language outcomes.

Results

Prenatal exposure to Social Disadvantage (p<.001) and Maternal Psychosocial Stress (p<.001) were correlated with poorer language outcomes. When Social Disadvantage and maternal Psychosocial Stress were modeled simultaneously in relation to language outcomes, only Social Disadvantage was significant (p<.001). Independent of Social Disadvantage (p<.001), lower neonatal CC fractional anisotropy (FA) was related to poorer global (p=.02) and receptive (p=.02) language outcomes. CC FA did not mediate the association between Social Disadvantage and language outcomes (indirect effect 95% CIs -0.96-0.15), and there was no interaction between Social Disadvantage and CC FA on language outcomes (p>.05). Bilateral SLF/AF, IFOF, and uncinate were not significant (p>.05).

Conclusions

Prenatal exposure to Social Disadvantage and neonatal CC FA were independently related to language problems by age 2, with no evidence of mediating or moderating associations with language outcomes. These findings elucidate the early neural underpinnings of language development and suggest that the prenatal period may be an important time to provide poverty- reducing support to expectant mothers to promote offspring neurodevelopmental outcomes.
A comprehensive atlas of testicular interstitium reveals Cd34+/Sox4+mesenchymal cells as potential Leydig cell progenitors
Authors: Huang Xiaojia , Xia Kai , Yang Meiling , Hong Mengzhi , Jiang Meihua , Li Weiqiang , Lei Zhenmin , Peng Xiang Andy , Zhao Wei
Published: August 2024

The declining rates of male fertility pose a significant clinical challenge, primarily due to our limited understanding of the testicular interstitium, which is crucial for male reproductive health. Here, we conducted a comprehensive analysis of the single-cell transcriptomic landscape of the murine testicular interstitium across the postnatal lifespan. Our investigation unveiled a previously unrecognized population of Cd34+/Sox4+mesenchymal cells nestled within the interstitium, hinting at their potential as Leydig cell progenitors. During the aging process of Cd34+/Sox4+mesenchymal cells, we observed a decline in glutathione levels within the testicular interstitium. Remarkably, these Cd34+/Sox4+mesenchymal cells exhibited clonogenic self-renewal capacity and an impressive propensity to differentiate into Leydig cells. Intriguingly, when transplanted into Leydig cell-disrupted or failure models, Cd34+/Sox4+cells efficiently colonized the testicular interstitium, resulting in a notable increase in testosterone production. Exploring the epigenetic landscape, we identified critical transcription factors, most notably Sox4, governing the stem cell fate of Cd34+/Sox4+mesenchymal cells. Overall, this comprehensive reference atlas of lifespan testicular Leydig cells presents significant findings that may guide the development of cell-based strategies for treating testicular hypogonadism in elderly individuals.
Minimally invasive activation of spared interneurons alleviates local CA1 hypersynchrony and behavioral deficits in a model of temporal lobe epilepsy
Authors: Matringhen Célanie , Vigier Alexandre , Bourtouli Nikoleta , Marissal Thomas
Published: August 2024

Background

Temporal lobe epilepsy (TLE) is associated with severe cognitive impairments including memory deficits. The dysfunction of hippocampal inhibitory neurons is proposed as a key mechanism and possible target for therapeutic approaches. However, the nature and extent of alterations in hippocampal inhibitory neurons remain unclear, as does their impact on behavioral impairments associated with TLE.

Methods

We investigated the role of inhibitory neurons from the CA1 hippocampal region on memory deficits associated with TLE, considering both the survival and changes in the activity of a large population of interneurons. To this end, we used a combination of immunolabelling, calcium imaging, electrophysiology, human-applicable chemogenetic tools, and behavioral testing on a reliable mouse pilocarpine TLE model.

Results

We show that in TLE mice with severely disturbed spatial behavior, CA1 major interneuron populations are spared from histological damages that affect the epileptic hippocampus (e.g., sclerosis). However, CA1 interneurons fire less in epileptic than in control conditions, resulting in increased synchronization and activity of the epileptic CA1 network in vitro. Restoring CA1 interneuron discharge using a chemogenetic strategy rescued CA1 activity and synchronization in vitro. In vivo, the minimally invasive chemogenetic activation of hippocampal interneurons does not affect generalized seizures but reduces behavioral alterations.

Conclusions

Our data suggest that rescuing CA1 local network dynamics using interneurons as a lever could be sufficient to decrease behavioral deficits related to TLE.
A genome-wide genetic screen identified targets for destabilizing the parasitophorous vacuole ofChlamydia trachomatis
Authors: Babu Sait Mohammed Rizwan , Jachmann Lana H. , Milivojevic Milica , Llorente-Sáez Celia , Dhanjal Soniya , Schumacher Fabian , Henriksson Sara , Gayathri Vegesna Naga Venkata , Chaban Anastasiia , Mohanty Partha , Ölander Magnus , Muraleedharan Samada , Azadeh Sepideh Farmand , Kleuser Burkhard , Schmierer Bernhard , Sixt Barbara S.
Published: August 2024

The bacterial pathogenChlamydia trachomatisemploys the effector CpoS to suppress a host defense response that aborts intracellular bacterial growth by inducing host cell death. While conducting a CRISPR knock-out screen for genes contributing to this response, we uncovered a mutant deficient for CpoS to display a markedly increased reliance on host cellular ceramide synthesis, compensating for its diminished ability to acquire sphingolipids via modulating membrane trafficking. Employing the power of the just recently established molecular genetic toolbox forChlamydia, we developed an innovative microscopic reporter system that revealed the mutant to thrive in unstable parasitophorous vacuoles (inclusions), characterized initially by the release of individual bacteria from otherwise intact-appearing vacuoles. CpoS-deficient inclusions were further destabilized by disruptions in ceramide synthesis, while supplementation of sphingoid bases stabilized them, also preventing the defensive host cell death response. Notably, early inclusion destabilization, achieved by simultaneous disruption of two transport routes, caused infection clearance without damaging the host cells. Overall, this study highlights the inclusion’s role as a refuge, demonstrates CpoS to maintain inclusion integrity by ensuring sphingolipid supply, and provides directions for a future therapeutic exploitation.

SIGNIFICANCE

A wide range of clinically significant microbes evolved to hide from the intrinsic defenses of their host cells by thriving within membrane-enclosed pathogen-containing vacuoles. This raises the intriguing possibility that such vacuoles could be targeted therapeutically. The bacterial pathogenChlamydia trachomatiscould be an exceptionally well-suited target for such innovative medicines given its medical importance and strict dependence on host cells. However, progress has been stalled by the lack of sensitive tools for detecting inclusion damage. Here, we resolved this major technical roadblock and uncovered the pathogen to employ the secreted effector CpoS, a modulator of membrane trafficking, to stabilize its vacuole by ensuring adequate sphingolipid supply. These methodological advances and mechanistic insights should promote the development of vacuole-destabilizing therapeutics.
LONG-TERM ECOLOGICAL MONITORING IN INDIA: A SYNTHESIS
Authors: Tiruvaimozhi Yadugiri V , Borah Jimmy , Kala Chandra Prakash , Kunte Krushnamegh , Patel Bharati , Sreejith K A , Thadani Rajesh , Osuri Anand M , Ghosh-Harihar Mousumi
Published: August 2024

Long-term ecological monitoring (LTEM) is crucial for understanding ecological processes and responses to environmental change, informing management of natural resources, and biodiversity conservation. Systematic LTEM efforts began in India in the mid-1900s, but there is a lack of comprehensive synthesis of LTEM efforts in the country. Here, we use a wide-ranging questionnaire survey of ecologists coupled with a survey of published literature on LTEM efforts in India to synthesise their thematic and geographical spread, and types of data being collected, and identify key challenges to the establishment and maintenance of LTEM projects in the country. Studies monitor 77 unique subjects across 272 LTEM efforts in India. LTEM efforts are more often located in the Western Ghats and Eastern Himalaya, focused on forest vegetation, and monitoring factors such as abundance, distribution, species richness, and biomass. Regions such as North-Eastern, Eastern, Central, and North-Western India, ecosystems such as grasslands, deserts and wetlands, organisms such as macrofungi, amphibians, and reptiles (other than turtles) are underrepresented. Short turnover times of funding and permits were most frequently reported as hurdles in sustaining LTEM efforts. Data from LTEM efforts have been largely used to produce academic outputs such as journal articles, but have also found use for on-the-ground conservation efforts. Overall, this synthesis can help draw attention to the need for systematic long-term ecological monitoring, help efficient utilisation of existing long-term ecological data, identify regions, species and ecosystem components that are underrepresented in Indian LTEM efforts, foster collaborations, and serve as a starting point to address challenges in sustaining LTEM efforts in India.
A Framework to Identify Opportunities to Address Socioscientific Issues in the Elementary School Curricula: A Case Study from England, Italy, and Portugal
Authors: Pessoa Patrícia , de Lima Joelyn , Piacentini Valentina , Realdon Giulia , Jeffries Alex , Ometto Lino , Lopes J. Bernardino , Zeidler Dana L. , Fonseca Maria João , Sousa Bruno , Pinto Alexandre , Sá-Pinto Xana
Published: August 2024

Scientific literacy is crucial to address important and complex societal problems, both current and future. Teaching using a socioscientific issues (SSI) approach is a potential strategy to develop students’ scientific literacy, although teachers have reported concerns about its implementation, such as the inability to add additional distinct requirements to already demanding curricula. To facilitate this task, we describe the development of a valid and reliable instrument for curricula analysis, called “Framework for Identifying Opportunities to implement an SSI approach in science school curricula” (FIOSSI), and use it to identify opportunities to implement the SSI approach in the elementary school science curriculum of three European countries (England, Italy and Portugal). The framework categorizes SSI opportunities into three areas: 1) awareness of the issue; 2) socioscientific reasoning; and 3) socioscientific identity. Our analyses of the three countries’ elementary curricula reveal that the current versions have significant opportunities to explore awareness of SSI (especially relating to environmental and human health issues), promote the development of socioscientific reasoning, and foster socioscientific identity. FIOSSI can be a useful tool for education research and practice, and our results can help inform future research and guide educational policies.
Assessing The Relationship Between Demand And Accessibility For Pediatric Ophthalmology Services By State In The United States
Authors: Chuter Benton , Lieu Alexander C. , Huynh Justin , Bu Jennifer J. , Zangwill Linda M.
Published: August 2024

Purpose

To investigate the relationship between public demand for pediatric ophthalmology services and the accessibility of such services on a statewide basis in the United States, focusing on strabismus care.

Methods

Using Google Trends data, search volumes for “strabismus” were analyzed from January 2014 to December 2023. Pediatric ophthalmologist availability was assessed via the American Academy of Ophthalmology directory, normalized for state population size to create a relative demand index. Additional metrics from the United States Census Bureau and Centers for Disease Control and Prevention provided socioeconomic and health data. Correlation coefficients were used to explore relationships between search volumes, specialist availability, vision screening, socioeconomics, and demographic factors.

Results

The data revealed variability in public interest in pediatric ophthalmology across states, with Alaska showing the highest relative search volume for strabismus. The data also indicated notable disparities in pediatric ophthalmologist density, with North Dakota, Vermont, and Wyoming having no pediatric ophthalmologists. A significant correlation was identified between pediatric ophthalmologist availability and vision screening (R = 0.486, p < 0.001). Negative correlations were observed between the relative demand index and urbanization (R = −0.388, p = 0.007), as well as the strabismus prevalence (R = −0.455, p = 0.001), indicating that urbanization and specialist distribution influence eyecare demand and access.

Conclusion

The findings highlight disparities in accessibility and demand for pediatric ophthalmology services across the US, influenced by urbanization and distribution of healthcare professionals. The study underscores the need for targeted interventions to improve access to care and bridge gaps in pediatric ophthalmology service provision.
Synthetic And Natural Face Identity Processing Share Common Mechanisms
Authors: Uittenhove Kim , Otroshi Shahreza Hatef , Marcel Sébastien , Ramon Meike
Published: August 2024

Recent developments in generative AI offer the means to create synthetic identities, or deepfakes, at scale. As deepfake faces and voices become indistinguishable from real ones, they are considered as promising alternatives for research and development to enhance fairness and protect humans’ rights to privacy. Notwithstanding these efforts and intentions, a basic question remains unanswered: Are natural faces and facial deepfakes perceived and remembered in the same way? Using images created via professional photography on the one hand, and a state-of-the-art generative model on the other, we investigated the most studied process of face cognition: perceptual matching and discrimination of facial identity. Our results demonstrate that identity discrimination of naturalandsynthetic faces is governed by the same underlying perceptual mechanisms: objective stimulus similarity and observers’ ability level. These findings provide empirical support both for the societal risks associated with deepfakes, while also underscoring the utility of synthetic identities for research and development.
Urinary extracellular vesicles in healthy individuals: positive correlation between podocyte and tubular vesicles independent of kidney function
Authors: Wu Liang , Baan Carla C. , Reijerkerk Derek , Hesselink Dennis A. , Boer Karin
Published: August 2024

Urinary extracellular vesicles (uEVs) are promising non-invasive biomarkers for assessing renal physiology and disease. Focusing specifically on kidney-derived uEVs (kd-uEVs) rather than the overall uEV population may offer a more precise insight into kidney health. However, research distinguishing single kd-uEVs from various nephron segments and their relationship with kidney biology remains limited. Imaging flow cytometry (IFCM) can identify single kd-uEVs by labeling them with CD63 (a uEV marker) in combination with PODXL (a podocyte marker) or AQP2 (a tubular marker). This study investigated the correlations between CD63+ AQP2+ or PODXL+ kd-uEVs and kidney function. CD63+ AQP2+ and CD63+ PODXL+ uEVs were detected in urine compared to negative controls, including urine with detergent treatment or isotype staining and reagent-containing PBS. While no significant association was found between CD63+ AQP2+ or PODXL+ uEV concentration and kidney function, a significant correlation was observed between AQP2+ and PODXL+ uEV concentrations (Rho = 0.789, p < 0.001). This correlation could be explained by the colocalization of AQP2 and PODXL on CD63+ uEVs. In conclusion, our study is the first to demonstrate the colocalization of podocyte and tubular proteins on uEVs.
Serum protein biomarkers for degenerative cervical myelopathy: a prospective pilot study
Authors: Vedantam Aditya , Rahman Mahmudur , Salam Sakib , Banerjee Anjishnu , Satkunendrarajah Kajana , Budde Matthew D. , Meier Timothy B.
Published: August 2024

Introduction

Diagnosis of degenerative cervical myelopathy (DCM) is primarily based on clinical evaluation and evidence of cervical spinal cord compression on conventional MRI. However, delays in diagnosis are common in DCM and there is a need for additional objective assessments of spinal cord structure and function. Serum proteins are increasingly being used as biomarkers for neurological disorders and are promising targets for biomarker discovery in DCM. The objective of this study was to profile serum protein biomarkers in DCM and determine if serum proteins can aid diagnosis and prognosis in DCM.

Methods

Patients with a clinical diagnosis of DCM and scheduled to undergo decompressive surgery were prospectively enrolled from July 2022 to August 2023. Serum was obtained prior to surgery and at 3 months after surgery. Serum neuronal and inflammatory proteins were quantified using ultrasensitive single-molecular array technology. Serum biomarker concentrations were compared between DCM patients and age- and sex-matched healthy controls. Robust logistic regression was used to determine the panel of serum biomarkers that best differentiated DCM and controls. Serum biomarkers were also related to pre- and post-surgical functional measurements using linear regression.

Results

Twenty DCM patients (median age 70 years, 10 females) and 10 healthy controls (median age 65 years, 5 females) were enrolled. Pre-surgical NfL (30.2 vs 11.2 pg/ml, p=0.01) and IL-6 (2.9 vs 1.2, p=0.003) was significantly higher in DCM patients compared to controls. Pre-surgical NfL, IL-6 and BDNF best differentiated DCM and controls (p<0.001). At 3 months after surgery, significant increase in serum BDNF (p=0.001), AB-42 (p=0.042) and TNFa (p=0.007) were noted. Pre-surgical serum NfL was significantly associated improvement in pinch strength after surgery (p<0.05). Inflammatory biomarkers were linked to improvement in the neck pain-related disability and upper limb function assessed by the QuickDASH.

Conclusion

A pre-surgical serum panel of NfL, IL-6 and BDNF may aid in the diagnosis of DCM. Serum NfL is elevated in DCM and is associated with improvement in post-surgical objective measures of upper limb function. Pre-surgical serum neuronal and inflammatory biomarkers predict early post-surgical functional outcomes in DCM.
Opposite white matter abnormalities in post-infectious vs. gradual onset chronic fatigue syndrome revealed by diffusion MRI
Authors: Yu Qiang , Kwiatek Richard A. , Fante Peter Del , Bonner Anya , Calhoun Vince D. , Bateman Grant A. , Yamamura Takashi , Shan Zack Y.
Published: August 2024

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex and debilitating illness with an unknown pathogenesis. Although post-infectious (PI-ME/CFS) and gradual onset ME/CFS (GO-ME/CFS) manifest similar symptoms, it has long been suspected that different disease processes underlie them. However, the lack of biological evidence has left this question unanswered. In this study, we recruited PI-ME/CFS and GO-ME/CFS patients based on consensus diagnoses made by two experienced clinicians and compared their diffusion MRI features with those of rigorously matched healthy controls (HCs) with sedentary lifestyles. PI-ME/CFS patients showed significantly higher axial diffusivities (ADs) in several association and projection fibres compared to HCs. Higher AD values in PI-ME/CFS were significantly related to worse physical summary scores. In contrast, GO-ME/CFS patients exhibited significantly decreased ADs in the corpus callosum. Lower AD values in GO- ME/CFS patients were significantly associated with lower mental summary scores in commissural and projection fibres. Distinct patterns of AD alterations in PI-ME/CFS and GO- ME/CFS provide neurophysiological evidence of different disease processes and highlight the heterogeneities of ME/CFS. These results also help explain inconsistent findings in previous ME/CFS studies and guide future intervention design.
Multiscale heterogeneity of white matter morphometry in psychiatric disorders
Authors: Segal Ashlea , Smith Robert E , Chopra Sidhant , Oldham Stuart , Parkes Linden , Aquino Kevin M , Kia Seyed Mostafa , Wolfers Thomas , Franke Barbara , Hoogman Martine , Beckmann Christian F , Westlye Lars T , Andreassen Ole A , Zaleskey Andrew , Ben Harrison J , Davey Christopher G , Soriano-Mas Carles , Cardoner Narcis , Tiego Jeggan , Yucel Murat , Braganza Leah , Suo Chao , Berk Michael , Cotton Sue , Bellgrove Mark A , Marquand Andre F , Fornito Alex
Published: August 2024

Background: Interindividual variability in neurobiological and clinical characteristics in mental illness is often overlooked by classical group mean case control studies. Studies using normative modelling to infer person specific deviations of grey matter volume have indicated that group means are not representative of most individuals. The extent to which this variability is present in white matter morphometry, which is integral to brain function, remains unclear. Methods: We applied Warped Bayesian Linear Regression normative models to T1 weighted magnetic resonance imaging data and mapped interindividual variability in person specific white matter volume deviations in 1,294 cases (58% male) diagnosed with one of six disorders (attention-deficit/hyperactivity, autism, bipolar, major depressive, obsessive compulsive and schizophrenia) and 1,465 matched controls (54% male) recruited across 25 scan sites. We developed a framework to characterize deviation heterogeneity at multiple spatial scales, from individual voxels, through inter-regional connections, specific brain regions, and spatially extended brain networks. Results: The specific locations of white matter volume deviations were highly heterogeneous across participants, affecting the same voxel in fewer than 8% of individuals with the same diagnosis. For autism and schizophrenia, negative deviations (i.e., areas where volume is lower than normative expectations) aggregated into common tracts, regions and large scale networks in up to 35% of individuals. Conclusions: The prevalence of white matter volume deviations was lower than previously observed in grey matter, and the specific location of these deviations was highly heterogeneous when considering voxelwise spatial resolution. Evidence of aggregation within common pathways and networks was apparent in schizophrenia and autism but not other disorders.
Cryo-EM phase-plate images reveal unexpected levels of apparent specimen damage
Authors: Remis Jonathan , Petrov Petar N. , Zhang Jessie T , Axelrod Jeremy J. , Cheng Hang , Sandhaus Shahar , Mueller Holger , Glaeser Robert M.
Published: August 2024

Apoferritin (apoF) is commonly used as a test specimen in single-particle electron cryo-microscopy (cryo-EM), since it consistently produces density maps that go to 3 Å resolution or higher. When we imaged apoF with a laser phase plate (LPP), however, we observed more severe particle-to-particle variation in the images than we had previously thought to exist. Similarly, we found that images of ribulose bisphosphate carboxylase/oxygenase (rubisco) also exhibited a much greater amount of heterogeneity than expected. By comparison to simulations of images, we verified that the heterogeneity is not explained by the known features of the LPP, shot noise, or differences in particle orientation. We also demonstrate that our specimens are comparable to those previously used in the literature, based on using the final-reconstruction resolution as the metric for evaluation. All of this leads us to the hypothesis that the heterogeneity is due to damage that has occurred either during purification of the specimen or during preparation of the grids. It is not, however, our goal to explain the causes of heterogeneity; rather, we report that using the LPP has made the apparent damage too obvious to be ignored. In hindsight, similar heterogeneity can be seen in images of apoF and the 20S proteasome which others had recorded with a Volta phase plate. We therefore conclude that the increased contrast of phase-plate images (at low spatial frequencies) should also make it possible to visualize, on a single-particle basis, various forms of biologically functional heterogeneity in structure that had previously gone unnoticed.

GRAPHICAL ABSTRACT

HIGHLIGHTS

Phase plates recover low-frequency information with significantly improved SNR

Laser phase-plate images reveal unexpected amounts of structural heterogeneity

In retrospect, similar heterogeneity can also be seen in Volta phase-plate images

Particle heterogeneity produces “structural noise”, which may diminish map quality
Exploring the impact of an artificial intelligence-based intraoperative image navigation system in laparoscopic surgery on clinical outcomes: A protocol for a multicenter randomized controlled trial
Authors: Kitaguchi Daichi , Fuse Nozomu , Wakabayashi Masashi , Kosugi Norihito , Ishikawa Yuto , Hayashi Kazuyuki , Hasegawa Hiro , Takeshita Nobuyoshi , Ito Masaaki
Published: August 2024

Background

In the research field of artificial intelligence (AI) in surgery, there are many open questions that must be clarified. Well-designed randomized controlled trials (RCTs) are required to explore the positive clinical impacts by comparing the use and non-use of AI-based intraoperative image navigation. Therefore, herein, we propose the “ImNavi” trial, a multicenter RCT, to compare the use and non-use of an AI-based intraoperative image navigation system in laparoscopic surgery.

Methods

The ImNavi trial is a Japanese multicenter RCT involving 1:1 randomization between the use and non-use of an AI-based intraoperative image navigation system in laparoscopic colorectal surgery. The participating institutions will include three high-volume centers with sufficient laparoscopic colorectal surgery caseloads (>100 cases/year), including one national cancer center and two university hospitals in Japan. Written informed consent will be obtained from all patients. Patients aged between 18 and 80 years scheduled to undergo laparoscopic left-sided colorectal resection will be included in the study. The primary outcome is the time required for each target organ, including the ureter and autonomic nerves, to be recognized by the surgeon after its initial appearance on the monitor. Secondary outcomes include intraoperative target organ injuries, intraoperative complications, operation time, blood loss, duration of postoperative hospital stay, postoperative complications within 30 days, postoperative male sexual dysfunction 1 month after surgery, surgeon’s confidence in recognizing each target organ, and the postoperative fatigue of the primary surgeon.

Discussion

The impact of AI-based surgical applications on clinical outcomes beyond numerical expression will be explored from a variety of viewpoints while evaluating quantitative items, including intraoperative complications and operation time, as secondary endpoints. We expect that the findings of this RCT will contribute to advancing research in the domain of AI in surgery.

Trial registration

The trial was registered at the University Hospital Medical Information Network Center (https://www.umin.ac.jp/ctr/index-j.html) on March 28th, 2023 under trial ID: UMIN000050701.
Multimodal prehabilitation enhances innate antitumor immunity via NK cell recruitment
Authors: Feng Lixuan , Gordon Benjamin , Su Xin , Brassard Ariane , Dhoparee-Doomah Iqraa , Leo Sabrina , Awasthi Rashami , Bourdeau France , Giannias Betty , Gill Heather , Minnella Enrico , Ferri Lorenzo , Najmeh Sara , Spicer Jonathan , Carli Francesco , Cools-Lartigue Jonathan
Published: August 2024

BACKGROUND

While the clinical benefits of multimodal prehabilitation in cancer patients are well defined, the underlying immune modulations have not been studied. The objective of this study was to examine how prehabilitation can alter lung cancer immunity.

METHODS

Newly diagnosed lung cancer patients were referred to the prehabilitation clinic for preoperative personalized multimodal intervention (exercise training, nutritional optimization, and anxiety reduction) and blood samples were collected at baseline and surgery. Tumor samples were collected at surgery and compared to matched control samples from patients who did not receive prehabilitation. An animal model was used to study prehabilitation and tumor growth kinetics.

RESULTS

Twenty-eight lung cancer patients who underwent multimodal prehabilitation were included (McGill University Health Centre Research Ethics Board #2023-9005). After prehabilitation, patient-isolated peripheral blood mononuclear cells (PBMCs) showed significantly increased cytotoxicity against cancer cells (p< 0.0001) and significantly increased circulating natural killer (NK) cells in cohort (p= 0.0290) and paired analyses (p= 0.0312). Compared to matched controls, patients who received prehabilitation had significantly more intra-tumor NK cells (p= 0.0172).In vivo, we observed a significant increase in circulating NK cells (p= 0.0364) and slower tumor growth (p= 0.0396) with prehabilitation. When NK cells were depleted in prehabilitated mice, we observed a decrease in the protective effects of prehabilitation (p= 0.0314) and overall, we observed a significant correlation between circulating NK cells and reduced tumor volume (p= 0.0203, r = -0.5143).

CONCLUSIONS

Multimodal prehabilitation may play a role in antitumor immunity by increasing peripheral and tumour-infiltrating NK cells leading to a reduced cancer burden. Future studies on the protective effect of prehabilitation on postoperative immunity should be conducted.