bluuebunny/crossref_metadata_2025_split huggingface dataset:
The structure of psychiatric comorbidity without selection and assortative mating
Authors: Ayorech Ziada , Torvik Fartein Ask , Cheesman Rosa , Eilertsen Espen M. , Valstad Mathias , Bjørndal Ludvig Daae , Røysamb Espen , Havdahl Alexandra , Ystrøm Eivind 
Published: February 2024

AbstractThe widespread comorbidity observed across psychiatric disorders may be the result of processes such as assortative mating, gene-environment correlation, or selection into population studies. Between-family analyses of comorbidity are subject to these sources of bias, whereas within-family analyses are not. Because of Mendelian inheritance, alleles are randomly assigned within families, conditional on parental alleles. We exploit this variation to compare the structure of comorbidity across broad psychiatric polygenic scores when calculated either between-family (child polygenic scores) or within-family (child polygenic scores regressed on parental polygenic scores) in over 25,000 genotyped parent-offspring trios from the Norwegian Mother Father and Child Cohort study (MoBa). We fitted a series of factor models to the between- and within-family data, which consisted of a single genetic p-factor and a varying number of uncorrelated subfactors. The best-fitting model was identical for between- and within-family analyses and included three subfactors capturing variants associated with neurodevelopment, psychosis, and constraint, in addition to the genetic p-factor. Partner genetic correlations, indicating assortative mating, were not present for the genetic p-factor, but were substantial for the psychosis (b = 0.081;95% CI [0.038,0.124]) and constraint (b = 0.257;95% CI [0.075,0.439]) subfactors. When average factor levels for MoBa mothers and fathers were compared to a population mean of zero we found evidence of sex-specific participation bias, which has implications for the generalizability of findings from cohort studies. Our results demonstrate the power of the within-family design for better understanding the mechanisms driving psychiatric comorbidity and their consequences on population health.
Transcriptomic effects of paternal cocaine-seeking on the reward circuitry of male offspring
Authors: Huang Nan , Cui Jian , Fan Guangyuan , Pan Tao , Han Kunxiu , Xu Kailiang , Jiang Changyou , Liu Xing , Wang Feifei , Ma Lan , Le Qiumin 
Published: February 2024

AbstractIt has been previously established that paternal development of a strong incentive motivation for cocaine can predispose offspring to develop high cocaine-seeking behavior, as opposed to sole exposure to the drug that results in drug resistance in offspring. However, the adaptive changes of the reward circuitry have not been fully elucidated. To infer the key nuclei and possible hub genes that determine susceptibility to addiction in offspring, rats were randomly assigned to three groups, cocaine self-administration (CSA), yoked administration (Yoke), and saline self-administration (SSA), and used to generate F1. We conducted a comprehensive transcriptomic analysis of the male F1 offspring across seven relevant brain regions, both under drug-naïve conditions and after cocaine self-administration. Pairwise differentially expressed gene analysis revealed that the orbitofrontal cortex (OFC) exhibited more pronounced transcriptomic changes in response to cocaine exposure, while the dorsal hippocampus (dHip), dorsal striatum (dStr), and ventral tegmental area (VTA) exhibited changes that were more closely associated with the paternal voluntary cocaine-seeking behavior. Consistently, these nuclei showed decreased dopamine levels, elevated neuronal activation, and elevated between-nuclei correlations, indicating dopamine-centered rewiring of the midbrain circuit in the CSA offspring. To determine if possible regulatory cascades exist that drive the expression changes, we constructed co-expression networks induced by paternal drug addiction and identified three key clusters, primarily driven by transcriptional factors such as MYT1L, POU3F4, and NEUROD6, leading to changes of genes regulating axonogenesis, synapse organization, and membrane potential, respectively. Collectively, our data highlight vulnerable neurocircuitry and novel regulatory candidates with therapeutic potential for disrupting the transgenerational inheritance of vulnerability to cocaine addiction.
The effect of salt substitution on frequency and severity of headache: results from the SSaSS cluster-randomised controlled trial of 20,995 participants
Authors: Haghdoost Faraidoon , Gnanenthiran Sonali R. , Shan Sana , Kaistha Prachi , Huang Liping , Tian Maoyi , Liu Yishu , Yin Xuejun , Zhang Xinyi , Hao Zhixin , Wu Yangfeng , Di Tanna Gian Luca , Neal Bruce , Rodgers Anthony 
Published: February 2024

Abstract
Background
Headache is one of the most common neurological symptoms. Headache disorders are associated with a high global burden of disease. Prior studies indicate that short-to-medium term sodium reduction reduces headache symptom. This study evaluated the effects of long-term reduced-sodium, added-potassium salt on headache frequency and severity in rural China.

Methods
The Salt substitute and stroke study (SSaSS) was an open-label cluster-randomised trial in rural China designed to evaluate the effect of salt substitution on mortality and cardiovascular events. Participants included adults with a history of prior stroke and those aged ≥60 years with uncontrolled high blood pressure (BP). Villages were randomly assigned in a 1:1 ratio either to intervention with salt substitute (75% sodium chloride and 25% potassium chloride by mass) or to control with continued use of regular salt (100% sodium chloride). In this pre-specified analysis, between-group differences in headache frequency and severity were evaluated. The study was registered with ClinicalTrials.gov (identifier number: NCT02092090).

Results
A total of 20,995 participants were included in the trial (mean age 64.3 years, 51% female, mean follow-up 4.7 years). At final follow-up at the end of the study, headache outcome data including frequency and severity of headaches was available for 16,486 (98%) of 16,823 living participants. Overall, 4454/16,486 (27%) individuals reported having headache: 27.4% in the intervention group (2301/8386) vs 26.6% in the control group (2153/8100) (RR 1.04, 95% CI: 0.93, 1.16, p = 0.48). There was no difference in headache severity between intervention and control groups (p = 0.90).

Conclusion
Long term salt substitution did not reduce the frequency or severity of headaches in this population.
Bilateral choroid plexus resection in a 9p hexasomy/tetrasomy mosaic patient
Authors: Takada Rei , Tozawa Takenori , Yamanaka Takumi , Moroto Masaharu , Iehara Tomoko , Chiyonobu Tomohiro 
Published: February 2024

Abstract
Previous reports have shown that a gain of the chromosome 9 short arm (9p) is associated with choroid plexus hyperplasia (CPH). Furthermore, CPH can lead to communicating hydrocephalus; however, no cases of CPH with 9p gain requiring choroid plexus resection have been reported. Here, we describe the first case in which a 9p hexasomy/tetrasomy mosaic patient required choroid plexus resection for hydrocephalus. This finding suggested that the 9p copy number is correlated with CPH severity.
T-DOpE probes reveal sensitivity of hippocampal oscillations to cannabinoids in behaving mice
Authors: Kim Jongwoon , Huang Hengji , Gilbert Earl T. , Arndt Kaiser C. , English Daniel Fine , Jia Xiaoting 
Published: February 2024

AbstractUnderstanding the neural basis of behavior requires monitoring and manipulating combinations of physiological elements and their interactions in behaving animals. We developed a thermal tapering process enabling fabrication of low-cost, flexible probes combining ultrafine features: dense electrodes, optical waveguides, and microfluidic channels. Furthermore, we developed a semi-automated backend connection allowing scalable assembly. We demonstrate T-DOpE (Tapered Drug delivery, Optical stimulation, and Electrophysiology) probes achieve in single neuron-scale devices (1) high-fidelity electrophysiological recording (2) focal drug delivery and (3) optical stimulation. The device tip can be miniaturized (as small as 50 µm) to minimize tissue damage while the ~20 times larger backend allows for industrial-scale connectorization. T-DOpE probes implanted in mouse hippocampus revealed canonical neuronal activity at the level of local field potentials (LFP) and neural spiking. Taking advantage of the triple-functionality of these probes, we monitored LFP while manipulating cannabinoid receptors (CB1R; microfluidic agonist delivery) and CA1 neuronal activity (optogenetics). Focal infusion of CB1R agonist downregulated theta and sharp wave-ripple oscillations (SPW-Rs). Furthermore, we found that CB1R activation reduces sharp wave-ripples by impairing the innate SPW-R-generating ability of the CA1 circuit.
Indication of critical scaling in time during the relaxation of an open quantum system
Authors: Wu Ling-Na , Nettersheim Jens , Feß Julian , Schnell Alexander , Burgardt Sabrina , Hiebel Silvia , Adam Daniel , Eckardt André , Widera Artur 
Published: February 2024

AbstractNear continuous phase transitions, universal power-law scaling, characterized by critical exponents, emerges. This behavior reflects the singular responses of physical systems to continuous control parameters like temperature or external fields. Universal scaling extends to non-equilibrium dynamics in isolated quantum systems after a quench, where time takes the role of the control parameter. Our research unveils critical scaling in time also during the relaxation dynamics of an open quantum system. Here we experimentally realize such a system by the spin of individual Cesium atoms dissipatively coupled through spin-exchange processes to a bath of ultracold Rubidium atoms. Through a finite-size scaling analysis of the entropy dynamics via numerical simulations, we identify a critical point in time in the thermodynamic limit. This critical point is accompanied by the divergence of a characteristic length, which is described by critical exponents that turn out to be unaffected by system specifics.
Transient chemical and structural changes in graphene oxide during ripening
Authors: Otsuka Hayato , Urita Koki , Honma Nobutaka , Kimuro Takashi , Amako Yasushi , Kukobat Radovan , Bandosz Teresa J. , Ukai Junzo , Moriguchi Isamu , Kaneko Katsumi 
Published: February 2024

AbstractGraphene oxide (GO)—the oxidized form of graphene—is actively studied in various fields, such as energy, electronic devices, separation of water, materials engineering, and medical technologies, owing to its fascinating physicochemical properties. One major drawback of GO is its instability, which leads to the difficulties in product management. A physicochemical understanding of the ever-changing nature of GO can remove the barrier for its growing applications. Here, we evidencde the presence of intrinsic, metastable and transient GO states upon ripening. The three GO states are identified using a $$\pi -{\pi }^{*}$$
π
−

π

*

transition peak of ultraviolet–visible absorption spectra and exhibit inherent magnetic and electrical properties. The presence of three states of GO is supported by the compositional changes of oxygen functional groups detected via X-ray photoelectron spectroscopy and structural information from X-ray diffraction analysis and transmission electron microscopy. Although intrinsic GO having a $$\pi -{\pi }^{*}$$
π
−

π

*

transition at 230.5 ± 0.5 nm is stable only for 5 days at 298 K, the intrinsic state can be stabilized by either storing GO dispersions below 255 K or by adding ammonium peroxydisulfate.
Circulating tumor cells in early lobular versus ductal breast cancer and their associations with prognosis
Authors: Alkhafaji Silver , Wolf Denise M. , Magbanua Mark Jesus M. , J. van ‘t Veer Laura , Park John W. , Esserman Laura , Mukhtar Rita A. 
Published: February 2024

AbstractThis is a secondary data analysis of the TIPPING study, which included 1,121 patients with stage I-III breast cancer who had enumeration of CTCs (by either CellSearch or immunomagnetic enrichment and flow cytometry [IE/FC]) and disseminated tumor cells (DTCs) at the time of surgical resection between 1999 and 2012. The primary endpoint was mean number of CTCs by histology, taking into account method of detection and treatment type, and evaluation of histology specific prognostic cutpoints. Overall, patients with ILC had significantly higher CTC counts than those with IDC, a finding which persisted in the 382 patients with CTC enumeration by IE/FC method. Additionally, among those with primary surgery, patients with ILC had significantly higher mean CTC counts than those with IDC (mean 2.11 CTCs/mL versus 0.71 CTCs/mL respectively, p < 0.001), which persisted on multivariate analysis. Patients with ILC and CTC-high/DTC-high status trended towards reduced DRFS HR = 9.27, 95% CI 0.95–90.5, p = 0.055) and had significantly decreased BCSS (HR = 10.4, 95% CI 1.07–99.7, P = 0.043) compared with those who were CTC-low/DTC-low. In the IDC group, CTC-high/DTC-high status was not associated with either DRFS or BCSS. In neoadjvuantly treated patients, there was no significant difference in CTC counts in the ILC group versus the IDC group (mean 0.89 CTCs/mL versus 1.06 CTCs/mL respectively, p = 0.82). Our findings contribute to the limited literature on CTCs and DTCs in ILC, and suggest that clinical utility and optimal thresholds for CTC and DTC assays may differ by histologic subtype in early-stage breast cancer.
Genome-scale pan-cancer interrogation of lncRNA dependencies using CasRx
Authors: Montero Juan J. , Trozzo Riccardo , Sugden Maya , Öllinger Rupert , Belka Alexander , Zhigalova Ekaterina , Waetzig Paul , Engleitner Thomas , Schmidt-Supprian Marc , Saur Dieter , Rad Roland 
Published: February 2024

AbstractAlthough long noncoding RNAs (lncRNAs) dominate the transcriptome, their functions are largely unexplored. The extensive overlap of lncRNAs with coding and regulatory sequences restricts their systematic interrogation by DNA-directed perturbation. Here we developed genome-scale lncRNA transcriptome screening using Cas13d/CasRx. We show that RNA targeting overcomes limitations inherent to other screening methods, thereby considerably expanding the explorable space of the lncRNAome. By evolving the screening system toward pan-cancer applicability, it supports molecular and phenotypic data integration to contextualize screening hits or infer lncRNA function. We thereby addressed challenges posed by the enormous transcriptome size and tissue specificity through a size-reduced multiplexed gRNA library termed Albarossa, targeting 24,171 lncRNA genes. Its rational design incorporates target prioritization based on expression, evolutionary conservation and tissue specificity, thereby reconciling high discovery power and pan-cancer representation with scalable experimental throughput. Applied across entities, the screening platform identified numerous context-specific and common essential lncRNAs. Our work sets the stage for systematic exploration of lncRNA biology in health and disease.
Submovement interpersonal coupling is associated to audio-motor coordination performance
Authors: Laroche Julien , Tomassini Alice , Fadiga Luciano , D’Ausilio Alessandro 
Published: February 2024

AbstractActing in concert with others, a key aspect of our social life, requires behavioral coordination between persons on multiple timescales. When zooming in on the kinematic properties of movements, it appears that small speed fluctuations, called submovements, are embedded within otherwise smooth end-point trajectories. Submovements, by occurring at a faster timescale than that of movements, offer a novel window upon the functional relationship between distinct motor timescales. In this regard, it has previously been shown that when partners visually synchronize their movements, they also coordinate the timing of their submovement by following an alternated pattern. However, it remains unclear whether the mechanisms behind submovement coordination are domain-general or specific to the visual modality, and whether they have relevance for interpersonal coordination also at the scale of whole movements. In a series of solo and dyadic tasks, we show that submovements are also present and coordinated across partners when sensorimotor interactions are mediated by auditory feedback only. Importantly, the accuracy of task-instructed interpersonal coordination at the movement level correlates with the strength of submovement coordination. These results demonstrate that submovement coordination is a potentially fundamental mechanism that participates in interpersonal motor coordination regardless of the sensory domain mediating the interaction.
Altered hippocampal neurogenesis in a mouse model of autism revealed by genetic polymorphisms and by atypical development of newborn neurons
Authors: Barón-Mendoza Isabel , Mejía-Hernández Montserrat , Hernández-Mercado Karina , Guzmán-Condado Jessica , Zepeda Angélica , González-Arenas Aliesha 
Published: February 2024

AbstractIndividuals with autism spectrum disorder (ASD) often exhibit atypical hippocampal anatomy and connectivity throughout their lifespan, potentially linked to alterations in the neurogenic process within the hippocampus. In this study, we performed an in-silico analysis to identify single-nucleotide polymorphisms (SNPs) in genes relevant to adult neurogenesis in the C58/J model of idiopathic autism. We found coding non-synonymous (Cn) SNPs in 33 genes involved in the adult neurogenic process, as well as in 142 genes associated with the signature genetic profile of neural stem cells (NSC) and neural progenitors. Based on the potential alterations in adult neurogenesis predicted by the in-silico analysis, we evaluated the number and distribution of newborn neurons in the dentate gyrus (DG) of young adult C58/J mice. We found a reduced number of newborn cells in the whole DG, a higher proportion of early neuroblasts in the subgranular layer (SGZ), and a lower proportion of neuroblasts with morphological maturation signs in the granule cell layer (GCL) of the DG compared to C57BL/6J mice. The observed changes may be associated with a delay in the maturation trajectory of newborn neurons in the C58/J strain, linked to the Cn SNPs in genes involved in adult hippocampal neurogenesis.
Associations between Th1-related cytokines and complicated pediatric appendicitis
Authors: Elliver Matilda , Salö Martin , Roth Bodil , Ohlsson Bodil , Hagander Lars , Gudjonsdottir Johanna 
Published: February 2024

AbstractThe pathogenesis of appendicitis is not understood fully, and the diagnosis can be challenging. Previous research has suggested an association between a T helper (Th) 1-dependent immune response and complicated appendicitis. This prospective cohort study aimed to evaluate the association between serum concentrations of the Th1-associated cytokines interleukin (IL)-1α, IL-1β, IL-2, IL-6, IL-10, IL-17A and tumor necrosis factor beta (TNF-β) and the risk of complicated appendicitis in children. Appendicitis severity was determined through histopathological examination. A total of 137 children < 15 years with appendicitis were included with a median age of 10 years (IQR 8–12); 86 (63%) were boys, and 58 (42%) had complicated appendicitis. Children with complicated appendicitis had significantly higher concentrations of serum IL-6 and IL-10, and lower of TNF-β. After adjustment for age, symptom duration, and presence of appendicolith in a multivariable logistic regression, a higher concentration of IL-6 remained associated with an increased risk of complicated appendicitis (aOR 1.001 [95% CI 1.000–1.002], p = 0.02). Serum concentrations of IL-1α, IL-1β, IL-2, IL-10, IL-17A and TNF-β were not significantly associated with the risk of complicated appendicitis. In conclusion, our results suggests that the systemic inflammatory response in complicated appendicitis is complex and not solely Th1-dependent.
The spectrum of psychological disorders in family members of patients suffering from delirium associated with critical illness: a prospective, observational study
Authors: Kotfis Katarzyna , Maj Patrycja , Szylińska Aleksandra , Pankowiak Maria , Reszka Elżbieta , Ely E. Wesley , Marra Annachiara 
Published: February 2024

AbstractDuring intensive care unit admission, relatives of critically ill patients can experience emotional distress. The authors hypothesized that families of patients who are diagnosed with intensive care unit (ICU) delirium experience more profound depression and anxiety disorders related to stress than do families of patients without delirium. We performed a prospective observational single-center study including families of adult patients (age above 18 years) hospitalized in a 17-bed ICU of a university hospital for at least 48 h who completed research questionnaires at day 2 after admission and day 30 after initial evaluation using dedicated questionnaires (HADS, CECS, IES, PTSD-C). A total of 98 family members of patients hospitalized in the ICU were included in the final analysis (50 family members whose relatives were CAM-ICU positive (DEL+), and 48 family members of patients without delirium (DEL−)). No statistically significant differences in demographics and psychosocial data were found between the groups. In the follow-up 30 days after the first conversation with a family member, the mean PTSD score for the relatives of patients with delirium was 11.02 (Me = 13.0; SD = 5.74), and the mean score for nondelirious patients' family members was 6.42 (Me = 5.5; SD = 5.50; p < 0.001). A statistically significant increase in IES scores for family members of patients with delirium was observed for total PTSD (p = 0.001), IES—intrusion (p < 0.001), and IES—hyperarousal (p = 0.002). The prevalence of anxiety symptoms, depression, and posttraumatic stress disorder (PTSD) was higher in families of patients diagnosed with ICU delirium within 48 h of admission to the ICU. No factors increasing the depth of these disorders in family members of patients with ICU delirium were identified. Taking appropriate actions and thus providing families with appropriate support will contribute to the understanding of unfavorable emotional states, including anxiety, stress, depression, anger, agitation, or avoidance.