bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

ABSTRACTWe 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

AbstractBackground and PurposeBrainstem 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.MethodsIn 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.ResultsMost 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.ConclusionsOur 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

AbstractEmbryo 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

ABSTRACTSchizophrenia 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

AbstractBackgroundSubjective 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.MethodsUsing 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.FindingMachine 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.InterpretationThis 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.FundingHorizon 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

SUMMARYThe 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

ABSTRACTBackgroundEarly 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.MethodsThis 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.ResultsPrenatal 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).ConclusionsPrenatal 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

AbstractThe 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

AbstractBackgroundTemporal 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.MethodsWe 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.ResultsWe 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.ConclusionsOur 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

ABSTRACTThe 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.SIGNIFICANCEA 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

AbstractLong-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.