bluuebunny/crossref_metadata_2025 huggingface dataset:
66 A Recurrent Pattern of Posterior Vermis-Predominant Cerebellar Hypoplasia (Not Dandy-Walker) Occurring with Psychosis-Schizophrenia
Authors: Leslie Alison C. , Dobyns William B. , Ward Mitchell P.
Published: December 2023

Objective:

Schizophrenia (SCZ) is a neuropsychiatric disorder with strong genetic heritability and predicted genetic heterogeneity, but limited knowledge regarding the underlying genetic risk variants. Classification into phenotype-driven subgroups or endophenotypes is expected to facilitate genetic analysis. Here, we report a teen boy with chronic psychosis and cerebellar hypoplasia (CBLH) and analyze data on 16 reported individuals with SCZ or chronic psychosis not otherwise specified associated with cerebellar hypoplasia to look for shared features.

Participants and Methods:

We evaluated an 18-year-old boy with neurodevelopmental deficits from early childhood and onset of hallucinations and other features of SCZ at 10 years who had mild vermis-predominant CBLH on brain imaging. This prompted us to review prior reports of chronic psychosis or SCZ with cerebellar malformations using paired search terms including (1) cerebellar hypoplasia, Dandy-Walker malformation, Dandy-Walker variant, or mega-cisterna magna with (2) psychosis or SCZ. We found reports of 16 affected individuals from 13 reports. We reviewed clinical features focusing on demographic information, prenatal-perinatal history and neuropsychiatric and neurodevelopmental phenotypes, and independently reviewed brain imaging features.

Results:

All 17 individuals had classic psychiatric features of SCZ or chronic psychosis as well as shared neurodevelopmental features not previously highlighted including a downward shift in IQ of about 20 points, memory impairment, speech-language deficits, attention deficits and sleep disturbances. The brain imaging findings among these individuals consistently showed posterior vermis predominant CBLH with variable cerebellar hemisphere hypoplasia and enlarged posterior fossa (a.k.a. mega-cisterna magna). None had features of classic DWM.

Conclusions:

In 17 individuals with chronic psychosis or SCZ and cerebellar malformation, we found a high frequency of neurodevelopmental disorders, a consistent brain malformation consisting of posterior vermis-predominant (and usually symmetric) CBLH, and no evidence of prenatal risk factors. The consistent phenotype and lack of prenatal risk factors for CBLH leads us to hypothesize that psychosis or schizophrenia associated with vermis predominant CBLH comprises a homogeneous subgroup of individuals with chronic psychosis/schizophrenia that is likely to have an underlying genetic basis. No comprehensive targeted gene panel for CBLH has yet been defined, leading us to recommend trio-based exome sequencing for individuals who present with this combination of features.
15 Construct Validity of the Stroop Interference task in Youth and the Contribution of Effort
Authors: Flowers Julius H , Steinbaugh Ashlynn , Forbes Bradley , Talamahe’a Tarah , Vang Lillian , Baldini Daniel , Hirst Rayna
Published: December 2023

Objective:

Previous literature has studied the cognitive processes that contribute to performance on the Stroop interference condition in adults and found that the Stroop task performance (i.e., color-word interference) is comprised of multiple cognitive skills, including speed of visual search, working memory, and conflict monitoring (Perianez et al. 2020). However, the relationship of these cognitive processes to Stroop interference in youth remains understudied. Moreover, no studies have examined the contribution of effort measurement to the interference condition in healthy youth.

Participants and Methods:

Golden Stroop Test interference performance was examined in healthy youth athletes (n=174) aged 8-16 years (mean age=12.07) who participated in a baseline neuropsychological evaluation as part of a clinical research program on sports concussion. Predictor variables included speed of visual search, working memory, processing speed, verbal fluency effort (i.e., validity tests), visuospatial abilities, visual processing, and executive functioning skills such as cognitive flexibility and reasoning.

Results:

Speed of visual search as measured by Trail Making Test visual scanning time (p<0.00), and effort as measured by Reliable Digit Span and Trail Making Test ratio (p=0.03; p<0.00, respectively) significantly contributed to Stroop interference performance in healthy youth. We provided three validity measures; however, only those requiring higher-order cognitive processes predicted Stroop performance: Reliable Digit Span (p=0.03) and the Trail Making Test ratio (p<0.00). The standalone validity measure (TOMM) was not a significant predictor of Stroop performance (p>0.05).

Conclusions:

In contrast to adults, working memory and processing speed did not significantly predict Stroop performance, while visual search speed did predict Stroop interference. Furthermore, two embedded validity indicator (EVI) measures predicted Stroop interference, in contrast to a standalone validity measure requiring lower cognitive processes, which did not predict Stroop performance. Therefore, EVI’s that include an executive functioning component may not accurately represent effort in youth, perhaps due to their less developed executive functioning relative to adults (Lezak et al., 2012; Shanmugan & Satterthwaite, 2017). Overall, understanding the cognitive processes contributing to Stroop performance in healthy youth will allow clinicians to better detect deficits in those cognitive processes and understand how they may impact Stroop performance. This would lead to a better understanding of executive functioning and the accurate measurement of effort in healthy youth.
18 Nightmares Independently Predict Neurobehavioral Symptoms in Adults with mTBI
Authors: Faerman Afik , Nabasny Andrew , Wright Brittany , Juengst Shannon B.
Published: December 2023

Objective:

To investigate the informative value of nightmares on neurobehavioral functioning in individuals with mild traumatic brain injury (mTBI) beyond general sleep disturbance.

Participants and Methods:

A sample of 146 adults with mTBI (mean age = 45.1±16.0), recruited from a specialized concussion treatment center, underwent an assessment of neurobehavioral functioning using the Behavioral Assessment Screening Tool (BAST), self-reported habitual sleep disturbance and quality (via the Pittsburgh Sleep Quality Index; PSQI), and reported nightmare frequency in the past two weeks.

Results:

Nightmare frequency was the strongest predictor of negative affect (ß = .362, p <.001), anxiety (ß = .332, p <.001), and impulsivity (ß = .270, p <.001) after controlling for sex and age. Sleep disturbance accounted for the greatest variance in depression (ß = .493, p <.001), burden from concussion (ß = .477, p <.001), and fatigue (ß = .449, p <.001) after controlling for sex and age.

Conclusions:

Nightmares independently associate with neurobehavioral symptoms and likely have differential etiology from reported sleep disturbance. Nightmare frequency was more strongly related to positive neurobehavioral symptoms (i.e., added factors that impact functioning, e.g., anxiety), while general sleep disturbance was associated with negative neurobehavioral symptoms (i.e., factors taken away that impact functioning, e.g., lack of energy). Our findings suggest that neuropsychological evaluations of individuals with mTBI should assess for sleep disturbance and nightmare frequency as risk factors for neurobehavioral barriers to functioning.
37 'A Rollercoaster of Emotions': Adults' Reflections on Epilepsy in Childhood
Authors: Sherlock Clara , Linehan Christine , Madigan Cathy , Downes Michelle
Published: December 2023

Objective:

Epilepsy is one of the most common neurological disorders affecting young people globally. While up to 60% of seizures experienced during childhood will resolve, childhood epilepsy can give rise to long-lasting neuropsychological effects which extend far beyond those attributed to seizure activity. While these effects have been explored extensively using quantitative methodologies, little research has examined the lived experience of epilepsy in childhood. The aim of the present study was to capture adults' retrospective insights into the impact of epilepsy throughout their schooling years.

Participants and Methods:

Participants consisted of Irish adults between 18 and 35 years, who had their first seizure on or before the age of 16 years. Participants were recruited from epilepsy support agencies and social media, and self-referred to the study. A bespoke semi-structured interview protocol was developed in collaboration with a patient expert which explored learning experiences, relations with peers, and participants' understanding and support of epilepsy during childhood. The methodology adopted a fully qualitative approach to reflexive thematic analysis. Therefore, patterns across the data were examined whilst taking into consideration the wider social context in which the data were generated. Latent assumptions that may have underpinned participants' experiences were prioritised and data was interpreted using pre existing theories and/or concepts. Interviews were completed following the original abstract deadline, and data analysed thereafter.

Results:

Thirteen adults who experienced epilepsy during childhood in Ireland were interviewed. Three primary themes and 14 subthemes were generated from the data. The primary themes were that of (1) disenfranchised grief, (2) the need to belong and (3) meeting the child where they're at. Adults reflected that, as children, the diagnosis of epilepsy evoked feelings typically associated with bereavement or loss. Although adults described childhood epilepsy as isolating, these feelings were countered by the support of friends, family and others with epilepsy, as participants recalled finding their tribe. Participants also called for developmentally appropriate practice when dealing with children and their families, across clinical and educational settings, in order to facilitate more comprehensive understandings of epilepsy and its consequences.

Conclusions:

Retrospective qualitative research offers a unique opportunity to explore changes in perception those with childhood epilepsy over time. The present study highlights the need for developmentally appropriate practice, which takes the child's neuropsychological and developmental standing into consideration, when supporting for young people with epilepsy. Given the dearth of research in this field, further retrospective research is needed to fully comprehend the impact of epilepsy in childhood globally.
47 Assessing the Feasibility of Cardiorespiratory Exercise During Functional MRI
Authors: Cloud J A , Hiersche K J , Hasselbach A N , Shin A N , Williams V J , Salat D , Hayes S M
Published: December 2023

Objective:

To examine the feasibility of implementing a cardiorespiratory exercise stimulus during functional Magnetic Resonance Imaging (fMRI).

Participants and Methods:

12 young adults (age: 18-22 years) completed progressive maximal exercise testing and a brain MRI scan. During scanning, participants completed three runs of functional MRI (volumes = 619; TR = 800 ms; multiband = 4; voxel size = 3 mm3). During each 8 minute fMRI run, participants completed an exercise challenge consisting of alternating blocks of exercise and rest. Exercise was implemented with a cardiostepper, an MRI-compatible device (similar to a Stairmaster) capable of generating a cardiorespiratory exercise stimulus. During exercise blocks, participants stepped at a rate of 60 Hz with pedal resistance determined by participants' fitness level. Heart rate and respiration data were collected during MRI. fMRI data were processed and analyzed using FMRIB Software Library (FSL). The ARtifact Detection Toolbox (ART) software was also used to identify volumes with significant artifact, and ICA-AROMA was used to remove motion-related BOLD signal components.

Results:

During exercise blocks, heart rate increased (mean = 131 beats per minute) compared to rest (mean = 87 beats per minute; t(34) = 4.3; p < .001). The mean heart rate during exercise blocks corresponds to an exercise intensity in the light to moderate intensity range for this age group. Motion (median framewise displacement) was significantly higher during exercise (mean = .53 mm) than rest (mean = .36 mm). Across all blocks, ART classified 19.8% of brain volumes as artifact-containing outliers, with 69% of the outliers occurring during exercise blocks. Although greater head motion was observed during exercise, the use of ICA-AROMA reduced the impact of motion considerably, recovering an additional 25% of the task-related signal, relative to noise. Comparison of fMRI activity during exercise versus rest revealed significant associations with primary and supplementary motor cortices, hippocampus, and the insula, among other regions.

Conclusions:

The current study demonstrates the feasibility of eliciting light to moderate intensity cardiorespiratory exercise (using a lower body stepping exercise) during functional MRI. Although increased head motion was observed during exercise compared to rest, the degree of head motion was roughly approximate to the values published in previous fMRI studies and post image acquisition processing improved task-related signal. During exercise, increased brain activation was observed in regions associated with the central command network, which regulates autonomic nervous system and musculoskeletal function during exercise.
53 Working Memory Network Load Engagement in Schizophrenia
Authors: Duffy John R. , Thomas Michael L
Published: December 2023

Objective:

Cognitive deficits in patients diagnosed with schizophrenia are a core feature of the disorder. There are currently no treatments for these cognitive deficits. Our aim was to examine and compare patterns of increased versus decreased activity in the central executive network (CEN), salience network (SN), and default mode network (DMN) between healthy controls (HCs) and patients diagnosed with schizophrenia (SZs) as well as to explore the influence of task load on these networks between HCs and SZs.

Participants and Methods:

Analyses focused on a secondary dataset comprising Blood Oxygen-Level Dependent (BOLD) data collected from 25 HCs and 27 SZs who completed a working memory (WM) task (N-back) with 5 load conditions while undergoing functional magnetic resonance imaging (fMRI). Region of interest (ROI) data were analyzed using linear mixed-effects models.

Results:

Group activation differences were found in the posterior salience network (pSN), default mode network (DMN), dorsal default mode network (dDMN), and ventral default mode network (vDMN) showing greater activity for SZs. Specifically, pSN, DMN, dDMN, and vDMN all showed increased activity in SZs compared to HCs. The curve of brain activity was consistent between HCs and SZs with the exception of the vDMN, where HCs show greater activation at modest mental workload (quadratic curve) and SZs showed greater brain activation at lower mental workload (linear). In the CEN, there were no group differences, and the response curve was the same for both groups.

Conclusions:

These group differences demonstrate network difference between HCs and SZs and could show value in treatments targeting cognitive deficits in SZs from a large-scale brain network connectivity perspective. Future studies are needed to confirm these results with larger sample size in order to examine potential subtleties of interactions between these networks.
56 Outcome Probability Task: Association with Safety Behaviors and Avenues for Future Imaging Research
Authors: Rech Madeline A. , Anderson Page L.
Published: December 2023

Objective:

Probability bias—overestimation of the likelihood that feared social outcomes will occur—is a mechanism targeted for symptom reduction in cognitive behavioral therapy for social anxiety. Safety behaviors (i.e., the conscious and unconscious actions taken to reduce discomfort in feared social situations) are related to cognitive biases and can be manipulated to reduce probability bias. The purpose of this research was to test the hypothesis that scores from a newly developed computer task to measure probability bias, the Outcome Probability Task (OPT; Draheim & Anderson, 2022) would be associated with self-reported safety behaviors during a speech task.

Participants and Methods:

Participants (N=90) included diverse students from a university in a southern, metropolitan area. Individuals reported an average age of 20.74 (SD=3.57) and self-identified as 'Woman’ (69%), 'Man’ (30%), 'Transgender’ (1%), or 'Non-binary/Agender’ (1%), and 'African American or Black’ (52%), 'Asian or Asian American’ (19%), 'White’ (16%), 'Multi-racial’ (7%), 'Hispanic or Latine’ (5%), or 'Middle Eastern’ (1%). Participants viewed social images and imagined themselves in the scenarios, then rated the likelihood that they would be negatively evaluated on a 0-100% scale (higher ratings indicate greater probability bias), gave a speech, and completed a standardized self-report measure of safety behaviors to rate how often they engaged in avoidant safety behaviors during the speech.

Results:

Results from a linear regression indicated that OPT scores (ß=.43) were positively associated with self-reported safety behaviors during a speech task, R2 = .19, F(1, 88) = 20.02, p < .001, 95% CI [0.170, 0.443].

Conclusions:

Negatively biased expectations about fear-relevant social situations—measured by a digital imagery task, the OPT—may contribute to increased engagement in avoidant safety behaviors during a speech task among a convenience sample. Outcome probability bias has previously only been measured through self-report, and the OPT is a promising new measure to multi-modally assess this aspect of social cognition. This task could be used along with imaging techniques to better understand the functional brain activity involved in outcome probability bias. Future studies could explore how activity in the orbitofrontal cortex, which is associated with the anticipation of negative outcomes, relates to responses on the OPT. If there is a connection, this brain region could be an indicator of improvement following intervention, such as cognitive behavioral therapy, for probability biases involved in social anxiety.
The Long Shadows of Brexit: Implications for African Countries
Authors: Salamat Usama , Ali Salamat
Published: December 2023

The exit of the United Kingdom from the European Union (EU) single market and customs union has adversely affected trade prospects of many developing economies that depended on the UK market for their exports. This paper investigates the impact of Brexit on African countries' exports to the UK. The comparison is based upon trade between the set of African countries which export most to the UK and the EU. It provides a quantitative assessment of the trade effect through the use of descriptive analysis and empirical estimations by employing the difference-in-difference (DID) estimation approach. The descriptive analysis finds that the share of African exports sent to the UK has declined since the Brexit announcement in 2016. The empirical estimations using the DID approach also demonstrate a drop of 20–30% in African countries exports to the UK relative to the EU-27 in this period. These results hold to a battery of robustness checks, including the use of an alternative estimation approach, varying sample size, and the use of alternative counterfactuals. We further show that the trade flows started to drop immediately after the announcement of the Brexit referendum in 2015 but the main drop came after the Brexit referendum results became evident. These findings imply the need for policy intervention and support for African countries to revitalize their trade flows and alleviate the unintended effects of this trade shock.
Diversity and structure assessment of the genetic resources in a germplasm collection from a vanilla breeding programme in Madagascar
Authors: Rasoamanalina Rivo Onisoa Léa , Mirzaei Khaled , El Jaziri Mondher , Ramirez Ramirez Angel Rafael , Bertin Pierre
Published: December 2023

A breeding programme of aromatic vanilla, dating back to 1944, was conducted in Ambohitsara, Antalaha, SAVA (Sambava, Antalaha, Vohemara, Andapa) – Madagascar. Imported, local, wild and cultivated vanillas were used as progenitors and thousands of hybrids were generated. However, this germplasm has not undergone any genetic evaluation, and it appears that these valuable genetic resources have been dispersed or lost after the end of the programme (2000). This study aims to investigate the genetic diversity and structure of rescued genotypes currently held in a local collection in Antalaha. Double digest restriction associated-site (RAD)-seq (ddRAD)-seq protocol was applied, providing 865 million read sequences from 56 accessions. The ddRAD sequences have been deposited to the SRA archive of NCBI. From the data, 23,701 filtered concordant common Single Nucleotide Polymorphisms (SNPs) were identified using the three widely used tools (Stacks, BCFtools, Genome Analysis ToolKit - GATK) for short-read library sequencing. These SNPs were used for germplasm evaluation. Clustering analysis segregated samples into five genetic groups: Vanilla planifolia, Vanilla pompona, hybrid Tsitaitra, Vanille Banane and the phenotype Tsivaky. Our analysis revealed distinct subgroups within V. pompona and Tsitaitra, emphasizing the importance of further characterization to accurately reflect the genetic diversity and facilitate better utilization of these accessions in future research and germplasm management. The presence of private alleles in all groups (from 487 to 2866) indicated that populations were diverging and represented a large gene pool that could be useful for future breeding efforts. The genetic data obtained from this study offers valuable insights into the genetic diversity and structure of the vanilla population, with potential applications in breeding and conservation efforts.
Automatic Extraction of Surface Wave Dispersion Curves Using Unsupervised Learning and High‐Resolution Tau‐p Transform
Authors: Yao Hai , Cao Weiping , Huang Xuri , Li Luo , Wu Bin
Published: December 2023

Dispersion curves for surface wave recordings are required input for many surface wave inversion methods to image subsurface shear wave velocity distribution, while the conventional extraction of dispersion curves requires significant amount of human interaction. This step impedes efficiency enhancement of surface wave analysis and its automation. In this paper, we present an unsupervised learning scheme to achieve efficient automatic picking of dispersion curves of the fundamental mode for surface wave gathers. This scheme is composed of four major steps: computing a frequency velocity(f‐v) spectrum for the surface wave gather using a high‐resolution Tau‐p transform improved by the iteratively shrinkage Thresholding algorithm (ISTA) algorithm, generating clusters points along the dispersion energy in the f‐v spectrum via a weighted Kmeans algorithm, filtering these cluster points by principal component analysis (PCA) and Local Outlier Factor (LOF) algorithms to remove the erroneous clusters, and fitting the remaining clusters to form the dispersion curve. Tests with synthetic and field noisy surface wave recordings demonstrated the effectiveness of this approach and its potential in automatic processing of noisy surface wave data sets.
ITRF2020 Plate Motion Model
Authors: Altamimi Z. , Métivier L. , Rebischung P. , Collilieux X. , Chanard K. , Barnéoud J.
Published: December 2023

A tectonic Plate Motion Model (PMM) is essential for geodetic applications, while contributing to the understanding of geodynamic processes affecting the Earth's surface. We introduce a PMM derived from the horizontal velocities of 518 sites extracted from the ITRF2020 solution. These sites were chosen away from plate boundaries, Glacial Isostatic Adjustment regions, and other deforming zones. Unlike the ITRF2014‐PMM, which showed no significant Origin Rate Bias (ORB), velocities used to determine the ITRF2020‐PMM exhibit a statistically significant ORB (0.74 ± 0.09 mm/yr along the Z‐component). Users are advised to add the estimated ORB to the horizontal velocities predicted by the ITRF2020‐PMM rotation poles for full consistency with the ITRF2020. However, the predicted vertical velocities resulting from the addition of the ORB should be discarded. The overall precision with which the ITRF2020 velocity field is represented by the rigid ITRF2020‐PMM is at the level of 0.25 mm/yr WRMS.
Global Observations of Tropospheric Bromine Monoxide (BrO) Columns From TROPOMI
Authors: Chen Yuyang , Liu Song , Zhu Lei , Seo Sora , Richter Andreas , Li Xicheng , Ding Ao , Sun Wenfu , Shu Lei , Wang Xuan , Valks Pieter , Hendrick Francois , Koenig Theodore K. , Volkamer Rainer , Bai Bin , Wang Dakang , Pu Dongchuan , Sun Shuai , Li Juan , Zuo Xiaoxing , Fu Weitao , Li Yali , Zhang Peng , Yang Xin , Fu Tzung‐May
Published: December 2023

Bromine monoxide (BrO) plays an important role in tropospheric chemistry. The state‐of‐the‐science TROPOspheric Monitoring Instrument (TROPOMI) offers the potential to monitor atmospheric composition with a fine spatial resolution of up to 5.5 × 3.5 km2. We present here the retrieval of tropospheric BrO columns from TROPOMI. We implement a stratospheric correction scheme using a climatological approach based on the latest GEOS‐Chem High Performance chemical transport model, and improve the tropospheric air mass factor calculation with TROPOMI surface albedo data accounting for the geometrical dependency. Our product presents a good level of consistency in comparison with measurements from ground‐based zenith‐sky differential optical absorption spectroscopy (r = 0.67), aircrafts (r = 0.46), and satellites (similar spatial distributions of BrO columns). Furthermore, our retrieval captures BrO enhancements in the polar springtime with values up to 7.8 × 1013 molecules cm−2 and identifies small‐scale emission sources such as volcanoes and salt marshes. Based on TROPOMI data, we probe a blowing snow aerosol bromine mechanism in which the snow salinity is reduced to better match simulation and observation. Our TROPOMI tropospheric BrO product contributes high‐resolution global information to studies investigating atmospheric bromine chemistry.
Interindividual variability in appetitive sensations and relationships between appetitive sensations and energy intake
Authors: Cheon Eunjin , Mattes Richard D.
Published: December 2023

Background

Appetitive sensations (AS) are signals that guide eating behaviors. Marked short-term inter-individual variability in AS has been reported but the long-term stability of individual ratings and their dietary implications are not well characterized.

Objectives

This study explored the stability of inter-individual ratings of hunger, fullness and thirst for 17 weeks; determined the relationships between these sensations, eating patterns and energy intake (EI); as well as the associations between ratings and selected individual characteristics (age, gender, BMI).

Methods

A 17-week observational study collected hourly appetitive ratings and dietary intake data from 97 (90 completers, 7 partial completers) healthy adults at weeks 1, 9, and 17.

Results

There were marked and stable inter-individual differences over the 17 weeks for hunger (week 1 vs. week 9, r = 0.72 (p < 0.001); week 1 vs. week 17, r = 0.67 (p < 0.001); week 9 vs. week 17, r = 0.77 (p < 0.001)); fullness (week 1 vs. week 9 r = 0.74 (p < 0.001); week 1 vs. week 17, r = 0.71 (p < 0.001); week 9 vs. week 17, r = 0.81 (p < 0.001)); and thirst (week 1 vs. week 9 r = 0.82 (p < 0.001); week 1 vs. week 17, r = 0.81 (p < 0.001); week 9 vs. week 17, r = 0.88 (p < 0.001)). Cross-correlation functions revealed EI and eating pattern exerted stronger effects on AS than the reverse. However, the absolute effect sizes were small. Path analyses also indicated that there were weak relationships between AS and EI. No robust effects of the studied individual characteristics were observed.

Conclusion

This study found that acute and chronic sensations of hunger, fullness and thirst are relatively stable within individuals but vary markedly between individuals. In addition, the present data indicate AS are poorly associated with dietary patterns or with EI under conditions of relatively stable energy balance.
SPHK1 potentiates colorectal cancer progression and metastasis via regulating autophagy mediated by TRAF6-induced ULK1 ubiquitination
Authors: Chen Da , Wu Jiangni , Qiu Xinze , Luo Shibo , Huang Shanpei , Wei Erdan , Qin Mengbin , Huang Jiean , Liu Shiquan
Published: December 2023

A sphingolipid metabolite regulator, sphingosine kinase 1 (SPHK1), plays a critical role in the development of colorectal cancer (CRC). Studies have demonstrated that invasion and metastasis of CRC are promoted by SPHK1-driven autophagy. However, the exact mechanism of SPHK1 drives autophagy to promote tumor progression remains unclear. Here, immunohistochemical detection showed the expression of SPHK1 and tumor necrosis factor receptor-associated factor-6 (TRAF6) in human CRC tissues was stronger than in adjacent normal tissues, they were both associated with distance metastasis. It was discovered that knockdown of SPHK1 reduced the expression of TRAF6, inhibited autophagy, and inhibited the growth and metastasis of CRC cells in vitro. Moreover, the effects of SPHK1-downregulating were reversed by overexpression of TRAF6 in CRC cells transfected by double-gene. Overexpression of SPHK1 and TRAF6 promoted the expression of autophagy protein LC3 and Vimentin, while downregulated the expression of autophagy protein P62 and E-cadherin. The expression of autophagy-related ubiquitination protein ULK1 and Ubiquitin protein were significantly upregulated in TRAF6-overexpressed CRC cells. In addition, autophagy inhibitor 3-methyladenine (3MA) significantly inhibited the metastasis-promoting effect of SPHK1 and TRAF6, suppressed the expression of LC3 and Vimentin, and promoted the expression of P62 and E-cadherin, in CRC cells. Immunofluorescence staining showed SPHK1 and TRAF6 were co-localized in HT29 CRC cell membrane and cytoplasm. Immunoprecipitation detection showed SPHK1 was efficiently combined with the endogenous TRAF6, and the interaction was also detected reciprocally. Additionally, proteasome inhibitor MG132 treatment upregulated the expression of TRAF6 and the level of Ubiquitin protein, in SPHK1-downregulating CRC cells. These results reveal that SPHK1 potentiates CRC progression and metastasis via regulating autophagy mediated by TRAF6-induced ULK1 ubiquitination. SPHK1-TRAF6-ULK1 signaling axis is critical to the progression of CRC and provides a new strategy for the therapeutic control of CRC.
A small molecule iCDM-34 identified by in silico screening suppresses HBV DNA through activation of aryl hydrocarbon receptor
Authors: Furutani Yutaka , Hirano Yoshinori , Toguchi Mariko , Higuchi Shoko , Qin Xian-Yang , Yanaka Kaori , Sato-Shiozaki Yumi , Takahashi Nobuaki , Sakai Marina , Kongpracha Pornparn , Suzuki Takehiro , Dohmae Naoshi , Kukimoto-Niino Mutsuko , Shirouzu Mikako , Nagamori Shushi , Suzuki Harukazu , Kobayashi Kaoru , Masaki Takahiro , Koyama Hiroo , Sekiba Kazuma , Otsuka Motoyuki , Koike Kazuhiko , Kohara Michinori , Kojima Soichi , Kakeya Hideaki , Matsuura Tomokazu
Published: December 2023

IFN-alpha have been reported to suppress hepatitis B virus (HBV) cccDNA via APOBEC3 cytidine deaminase activity through interferon signaling. To develop a novel anti-HBV drug for a functional cure, we performed in silico screening of the binding compounds fitting the steric structure of the IFN-alpha-binding pocket in IFNAR2. We identified 37 compounds and named them in silico cccDNA modulator (iCDM)-1–37. We found that iCDM-34, a new small molecule with a pyrazole moiety, showed anti-HCV and anti-HBV activities. We measured the anti-HBV activity of iCDM-34 dependent on or independent of entecavir (ETV). iCDM-34 suppressed HBV DNA, pgRNA, HBsAg, and HBeAg, and also clearly exhibited additive inhibitory effects on the suppression of HBV DNA with ETV. We confirmed metabolic stability of iCDM-34 was stable in human liver microsomal fraction. Furthermore, anti-HBV activity in human hepatocyte-chimeric mice revealed that iCDM-34 was not effective as a single reagent, but when combined with ETV, it suppressed HBV DNA compared to ETV alone. Phosphoproteome and Western blotting analysis showed that iCDM-34 did not activate IFN-signaling. The transcriptome analysis of interferon-stimulated genes revealed no increase in expression, whereas downstream factors of aryl hydrocarbon receptor (AhR) showed increased levels of the expression. CDK1/2 and phospho-SAMHD1 levels decreased under iCDM-34 treatment. In addition, AhR knockdown inhibited anti-HCV activity of iCDM-34 in HCV replicon cells. These results suggest that iCDM-34 decreases the phosphorylation of SAMHD1 through CDK1/2, and suppresses HCV replicon RNA, HBV DNA, and pgRNA formation.
Hemozoin in malaria eradication—from material science, technology to field test
Authors: Rathi Ashutosh , Chowdhry Z. , Patel Anand , Zuo Siming , Veettil Thulya Chakkumpulakkal Puthan , Adegoke John A. , Heidari Hadi , Wood Bayden R. , Bhallamudi Vidya Praveen , Peng Weng Kung
Published: December 2023

Malaria continues to be among the most lethal infectious diseases. Immediate barriers include the detection of low-parasitemia levels in asymptomatic individuals, which act as a reservoir for future infections, and the emergence of multidrug-resistant strains in malaria-endemic, under-resourced regions. The development of technologies for field-deployable devices for early detection and targeted drugs/vaccines is an ongoing challenge. In this respect, the identification of hemozoin during the Plasmodium growth cycle presents a unique opportunity as a biomarker for malaria infection. The last decade has witnessed the development of numerous opto-/magnetic- based ultrasensitive hemozoin sensing technologies with tremendous potential of rapid and accurate malaria diagnosis and drug testing. The unique information in hemozoin formation can also shed light on the development of targeted drugs. Here, we present a comprehensive perspective on state-of-the-art hemozoin-based methodologies for detecting and studying malaria. We discuss the challenges (and opportunities) to expedite the translation of the technology as a point-of-site tool to assist in the global eradication of malaria infection.
The role of ion migration, octahedral tilt, and the A-site cation on the instability of Cs1-xFAxPbI3
Authors: Li Weilun , Hao Mengmeng , Baktash Ardeshir , Wang Lianzhou , Etheridge Joanne
Published: December 2023

Organic-inorganic hybrid perovskites are promising materials for the next generation photovoltaics and optoelectronics; however, their practical application has been hindered by poor structural stability mainly caused by ion migration and external stimuli. Understanding the mechanism(s) of ion migration and structure decomposition is thus critical. Here we observe the sequence of structural changes at the atomic level that precede structural decomposition in the technologically important Cs1-xFAxPbI3 using ultralow dose transmission electron microscopy. We find that these changes differ, depending upon the A-site composition. Initially, there is a random loss of FA+, complemented by the loss of I-. The remaining FA+ and I- ions then migrate, unit cell by unit cell, into an ordered and more stable phase with a √2 x √2 superstructure. Further ion loss is accompanied by A-site dependent octahedral tilt modes and associated tetragonal phases with different stabilities. These observations of the loss of FA+/I- ion pairs, ion migration, octahedral tilt modes, and the role of the A-cation, provide insights into the atomic-scale structural mechanisms that drive and block ion loss and ion migration, opening pathways to inhibit ion loss, migration and improve structural stability.
Differential responses of the gut microbiome and resistome to antibiotic exposures in infants and adults
Authors: Li Xuanji , Brejnrod Asker , Thorsen Jonathan , Zachariasen Trine , Trivedi Urvish , Russel Jakob , Vestergaard Gisle Alberg , Stokholm Jakob , Rasmussen Morten Arendt , Sørensen Søren Johannes
Published: December 2023

Despite their crucial importance for human health, there is still relatively limited knowledge on how the gut resistome changes or responds to antibiotic treatment across ages, especially in the latter case. Here, we use fecal metagenomic data from 662 Danish infants and 217 young adults to fill this gap. The gut resistomes are characterized by a bimodal distribution driven by E. coli composition. The typical profile of the gut resistome differs significantly between adults and infants, with the latter distinguished by higher gene and plasmid abundances. However, the predominant antibiotic resistance genes (ARGs) are the same. Antibiotic treatment reduces bacterial diversity and increased ARG and plasmid abundances in both cohorts, especially core ARGs. The effects of antibiotic treatments on the gut microbiome last longer in adults than in infants, and different antibiotics are associated with distinct impacts. Overall, this study broadens our current understanding of gut resistome dynamics and the impact of antibiotic treatment across age groups.
Co-adjuvanting DDA/TDB liposomes with a TLR7 agonist allows for IgG2a/c class-switching in the absence of Th1 cells
Authors: Zimmermann Julie , van Haren Simon D. , Diray-Arce Joann , Adriawan Ignatius Ryan , Wørzner Katharina , Krog Ricki T. , Guleed Safia , Hu Tu , Mortensen Rasmus , Dietrich Jes , Solbak Sara M. Ø. , Levy Ofer , Christensen Dennis , Pedersen Gabriel K.
Published: December 2023

Class-switching to IgG2a/c in mice is a hallmark response to intracellular pathogens. T cells can promote class-switching and the predominant pathway for induction of IgG2a/c antibody responses has been suggested to be via stimulation from Th1 cells. We previously formulated CAF®01 (cationic liposomes containing dimethyldioctadecylammonium bromide (DDA) and Trehalose-6,6-dibehenate (TDB)) with the lipidated TLR7/8 agonist 3M-052 (DDA/TDB/3M-052), which promoted robust Th1 immunity in newborn mice. When testing this adjuvant in adult mice using the recombinant Chlamydia trachomatis (C.t.) vaccine antigen CTH522, it similarly enhanced IgG2a/c responses compared to DDA/TDB, but surprisingly reduced the magnitude of the IFN-γ+Th1 response in a TLR7 agonist dose-dependent manner. Single-cell RNA-sequencing revealed that DDA/TDB/3M-052 liposomes initiated early transcription of class-switch regulating genes directly in pre-germinal center B cells. Mixed bone marrow chimeras further demonstrated that this adjuvant did not require Th1 cells for IgG2a/c switching, but rather facilitated TLR7-dependent T-bet programming directly in B cells. This study underlines that adjuvant-directed IgG2a/c class-switching in vivo can occur in the absence of T-cell help, via direct activation of TLR7 on B cells and positions DDA/TDB/3M-052 as a powerful adjuvant capable of eliciting type I-like immunity in B cells without strong induction of Th1 responses.
Effects of calibrated blue–yellow changes in light on the human circadian clock
Authors: Blume Christine , Cajochen Christian , Schöllhorn Isabel , Slawik Helen C. , Spitschan Manuel
Published: December 2023

Evening exposure to short-wavelength light can affect the circadian clock, sleep and alertness. Intrinsically photosensitive retinal ganglion cells expressing melanopsin are thought to be the primary drivers of these effects. Whether colour-sensitive cones also contribute is unclear. Here, using calibrated silent-substitution changes in light colour along the blue–yellow axis, we investigated whether mechanisms of colour vision affect the human circadian system and sleep. In a 32.5-h repeated within-subjects protocol, 16 healthy participants were exposed to three different light scenarios for 1 h starting 30 min after habitual bedtime: baseline control condition (93.5 photopic lux), intermittently flickering (1 Hz, 30 s on–off) yellow-bright light (123.5 photopic lux) and intermittently flickering blue-dim light (67.0 photopic lux), all calibrated to have equal melanopsin excitation. We did not find conclusive evidence for differences between the three lighting conditions regarding circadian melatonin phase delays, melatonin suppression, subjective sleepiness, psychomotor vigilance or sleep.

The Stage 1 protocol for this Registered Report was accepted in principle on 9 September 2020. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.13050215.v1.
Unsupervised machine learning to investigate trajectory patterns of COVID-19 symptoms and physical activity measured via the MyHeart Counts App and smart devices
Authors: Gupta Varsha , Kariotis Sokratis , Rajab Mohammed D. , Errington Niamh , Alhathli Elham , Jammeh Emmanuel , Brook Martin , Meardon Naomi , Collini Paul , Cole Joby , Wild Jim M. , Hershman Steven , Javed Ali , Thompson A. A. Roger , de Silva Thushan , Ashley Euan A. , Wang Dennis , Lawrie Allan
Published: December 2023

Previous studies have associated COVID-19 symptoms severity with levels of physical activity. We therefore investigated longitudinal trajectories of COVID-19 symptoms in a cohort of healthcare workers (HCWs) with non-hospitalised COVID-19 and their real-world physical activity. 121 HCWs with a history of COVID-19 infection who had symptoms monitored through at least two research clinic visits, and via smartphone were examined. HCWs with a compatible smartphone were provided with an Apple Watch Series 4 and were asked to install the MyHeart Counts Study App to collect COVID-19 symptom data and multiple physical activity parameters. Unsupervised classification analysis of symptoms identified two trajectory patterns of long and short symptom duration. The prevalence for longitudinal persistence of any COVID-19 symptom was 36% with fatigue and loss of smell being the two most prevalent individual symptom trajectories (24.8% and 21.5%, respectively). 8 physical activity features obtained via the MyHeart Counts App identified two groups of trajectories for high and low activity. Of these 8 parameters only ‘distance moved walking or running’ was associated with COVID-19 symptom trajectories. We report a high prevalence of long-term symptoms of COVID-19 in a non-hospitalised cohort of HCWs, a method to identify physical activity trends, and investigate their association. These data highlight the importance of tracking symptoms from onset to recovery even in non-hospitalised COVID-19 individuals. The increasing ease in collecting real-world physical activity data non-invasively from wearable devices provides opportunity to investigate the association of physical activity to symptoms of COVID-19 and other cardio-respiratory diseases.
Distribution and genomic variation of ammonia-oxidizing archaea in abyssal and hadal surface sediments
Authors: Trouche Blandine , Schauberger Clemens , Bouderka Feriel , Auguet Jean-Christophe , Belser Caroline , Poulain Julie , Thamdrup Bo , Wincker Patrick , Arnaud-Haond Sophie , Glud Ronnie N , Maignien Loïs
Published: December 2023

Ammonia-oxidizing archaea of the phylum Thaumarchaeota play a central role in the biogeochemical cycling of nitrogen in benthic sediments, at the interface between pelagic and subsurface ecosystems. However, our understanding of their niche separation and of the processes controlling their population structure in hadal and abyssal surface sediments is still limited. Here, we reconstructed 47 AOA metagenome-assembled genomes (MAGs) from surface sediments of the Atacama and Kermadec trench systems. They formed deep-sea-specific groups within the family Nitrosopumilaceae and were assigned to six amoA gene-based clades. MAGs from different clades had distinct distribution patterns along oxygen-ammonium counter gradients in surface sediments. At the species level, MAGs thus seemed to form different ecotypes and follow deterministic niche-based distributions. In contrast, intraspecific population structure, defined by patterns of Single Nucleotide Variants (SNV), seemed to reflect more complex contributions of both deterministic and stochastic processes. Firstly, the bathymetric range had a strong effect on population structure, with distinct populations in abyssal plains and hadal trenches. Then, hadal populations were clearly separated by trench system, suggesting a strong isolation-by-topography effect, whereas abyssal populations were rather controlled by sediment depth or geographic distances, depending on the clade considered. Interestingly, genetic variability between samples was lowest in sediment layers where the mean MAG coverage was highest, highlighting the importance of selective pressure linked with each AOA clade’s ecological niche. Overall, our results show that deep-sea AOA genome distributions seem to follow both deterministic and stochastic processes, depending on the genomic variability scale considered.
Natural Epoxy Oil (Euphorbia Oil) Polymerization in Liquid Carbon Dioxide–Green Solvents
Authors: Shah Shailesh N. , Liu Zengshe
Published: December 2023

Aside from being renewable, non-toxic, non-polluting, biodegradable and environmentally friendly, vegetable oils also possess renewable properties. Due to these properties, vegetable oils have been used in a variety of industrial applications, such as plastics, lubricants, adhesives, inks, fuels/biodiesel, coatings, printing inks, varnish solvents and surfactants. Many researchers have reported the production of polymers from vegetable oils, specifically from epoxidized soybean oil (ESO). However, ESO must be synthesized using conventional synthetic routes and some of the synthesized epoxide rings can degrade during the process. Plant oils with an epoxidized ring have been investigated to overcome this shortcoming. One such plant oil is euphorbia oil (EuO). This chapter discusses the ring-opening polymerization of EuO in a liquid carbon dioxide–green solvent using the boron trifluoride diethyl etherate (BF3·OEt2) catalyst. A variety of analytical techniques have been used to characterize the material, including FTIR, 1H-NMR, 13C-NMR, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and gel permeation chromatography (GPC). Using subcritical carbon dioxide (CO2) and a pressure of 65.5 bar, the ring-opening polymerization of euphorbia oil (RPEuO) was carried out under mild conditions, such as at room temperature. It was found that the cross-linked polymers formed by RPEuO had glass transition temperatures ranging from −15.0 °C to −22.7 °C. RPEuO polymers were thermally stable below 220 °C, and decomposition occurred above 340 °C, according to the TGA results.
Plant Oil-based Polyurethanes
Authors: Zhang Chaoqun
Published: December 2023

Polyurethanes have become the fifth largest polymeric materials and have been widely used in various fields. Until now, most of the monomers for the production of polyurethane products have been generally derived from non-renewable fossil feedstock. With the increasing global concerns about the depletion of fossil fuels associated with environmental impacts, developing bio-based chemicals and monomers from renewable resources for bio-based polyurethanes has attracted much attention. Plant oils are one of the promising options for such purposes due to their abundant production, biodegradability, and renewable origin. In this chapter, the transformation of plant oils into bio-based chemicals, including polyols, internal emulsifiers, chain extenders, and isocyanates, is reviewed. Furthermore, the general method and performance of different types of polyurethanes (solvent-based, waterborne, and non-isocyanate) are summarized. Finally, the potential applications of these plant oil-based chemicals and polyurethanes are discussed.