Miracle-dz/UniFAR-FTUs huggingface dataset:
Increased Voluntary Alcohol Consumption in Mice Lacking GABAB(1) Is Associated With Functional Changes in Hippocampal GABAA Receptors

Gamma-aminobutyric acid type B receptor (GABABR) has been extensively involved in alcohol use disorders; however, the mechanisms by which this receptor modulates alcohol drinking behavior remain murky. In this study, we investigate alcohol consumption and preference in mice lacking functional GABABR using the 2-bottle choice paradigm. We found that GABAB(1), knockout (KO), and heterozygous (HZ) mice drank higher amounts of an alcoholic solution, preferred alcohol to water, and reached higher blood alcohol concentrations (BACs) compared to wild-type (WT) littermates. The GABABR agonist GHB significantly reduced alcohol consumption in the GABAB(1) HZ and WT but not in the KO mice. Next, because of a functional crosstalk between GABABR and δ-containing GABAA receptor (δ-GABAAR), we profiled δ subunit mRNA expression levels in brain regions in which the crosstalk was characterized. We found a loss of the alcohol-sensitive GABAAR δ subunit in the hippocampus of the GABAB(1) KO alcohol-naïve mice that was associated with increased ɣ2 subunit abundance. Electrophysiological recordings revealed that these molecular changes were associated with increased phasic inhibition, suggesting a potential gain of synaptic GABAAR responsiveness to alcohol that has been previously described in an animal model of excessive alcohol drinking. Interestingly, voluntary alcohol consumption did not revert the dramatic loss of hippocampal δ-GABAAR occurring in the GABAB(1) KO mice but rather exacerbated this condition. Finally, we profiled hippocampal neuroactive steroids levels following acute alcohols administration in the GABAB(1) KO and WT mice because of previous involvement of GABABR in the regulation of cerebral levels of these compounds. We found that systemic administration of alcohol (1.5 g/kg) did not produce alcohol-induced neurosteroid response in the GABAB(1) KO mice but elicited an expected increase in the hippocampal level of progesterone and 3α,5α-THP in the WT controls. In conclusion, we show that genetic ablation of the GABAB(1) subunit results in increased alcohol consumption and preference that were associated with functional changes in hippocampal GABAAR, suggesting a potential mechanism by which preference for alcohol consumption is maintained in the GABAB(1) KO mice. In addition, we documented that GABAB(1) deficiency results in lack of alcohol-induced neurosteroids, and we discussed the potential implications of this finding in the context of alcohol drinking and dependence.
Substantiating Nexus Between Consumption Values and Sustainable Consumption Behavior: A Way Toward Sustainable Business

The unprecedented economic growth in recent decades has cultivated the exploitation of natural resources and over-consumption, leading to ecological deterioration and sustainability. The ever-increasing consumption in developing countries is creating a significant environmental strain. Thus, the industry and consumers’ environmental issues and their harmful effects on human health have led to concerns among researchers, scientists, academic communities, and policymakers. The present work examines the impact of different consumption value factors on sustainable consumption behavior concerning consumer choice in Pakistan and China. A cross-sectional study is conducted, and data are collected through a primary source questionnaire. A sample of 431 respondents is chosen from different cities in Pakistan, and a sample of 342 respondents is selected from China. Estimation techniques like descriptive statistics, frequency distribution, multicollinearity, R square, independent sample t-test, the coefficient of correlation, and regression analysis are used for the data analysis. The comparative results show that knowledge values (KVs) and emotional values (EMVs) significantly influence the choice behavior of respondents toward environmentally friendly products both in Pakistan and China. In contrast, social values (SVs) and conditional values (CVs) show insignificant influence. Furthermore, functional values (FVs) are significant in Pakistan while insignificant in the context of China, and environmental values (EVs) are significant in China although insignificant in Pakistan with regard to sustainable consumption behavior.
Evaluation of the Radiographic Risk Factors of Postoperative Shoulder Imbalance in Adult Scoliosis

Objective This study aimed to evaluate the radiographic risk factors of postoperative shoulder imbalance (PSI) after adult scoliosis (AS) correction surgery. Methods Seventy-nine patients with AS undergoing correction surgery at a single institution were reviewed. The mean follow-up was 28 months. Patients were divided into two groups based on their radiographic shoulder height (RSH): (1) the balanced group (RSH <10 mm) and (2) the unbalanced group (RSH ≥10 mm). The preoperative and postoperative Cobb angles of the proximal thoracic (PT), main thoracic (MT), thoracolumbar/lumbar (TL/L) and upper instrumented vertebra (UIV) were measured. Results No significant difference was found between the balanced and unbalanced groups when the UIV was T1–2, T3–4, or below T4. Univariate analysis indicated that the unbalanced group had significantly higher postoperative RSH, lower percentage PT correction, and greater percentage MT correction. The classification and regression tree analysis revealed that when the correction percentage of PT curve was more than 55.3%, 84.4% of patients acquired shoulder balance. However, when the correction percentage of PT curve was less than 55.3%, and the correction percentage of MT curve was more than 56%, 65.7% of the patients developed PSI. Conclusions In AS correction surgery, a lower percentage correction of the PT curve and greater percentage correction of the MT curve were independent radiographic risk factors of PSI, regardless of the UIV level. Sufficient PT correction is required to achieve postoperative shoulder balance in AS correction surgery when the MT curve is overcorrected.
Modulation of Iron Import and Metronidazole Resistance in Bacteroides fragilis Harboring a nimA Gene

Bacteroides fragilis is a commensal of the human gut but can also cause severe infections when reaching other body sites, especially after surgery or intestinal trauma. Bacteroides fragilis is an anaerobe innately susceptible to metronidazole, a 5-nitroimidazole drug that is prescribed against the majority of infections caused by anaerobic bacteria. In most of the cases, metronidazole treatment is effective but a fraction of B. fragilis is resistant to even very high doses of metronidazole. Metronidazole resistance is still poorly understood, but the so-called nim genes have been described as resistance determinants. They have been suggested to encode nitroreductases which reduce the nitro group of metronidazole to a non-toxic aminoimidazole. More recent research, however, showed that expression levels of nim genes are widely independent of the degree of resistance observed. In the search for an alternative model for nim-mediated metronidazole resistance, we screened a strain carrying an episomal nimA gene and its parental strain 638R without a nim gene for physiological differences. Indeed, the 638R daughter strain with the nimA gene had a far higher pyruvate-ferredoxin oxidoreductase (PFOR) activity than the parental strain. High PFOR activity was also observed in metronidazole-resistant clinical isolates, either with or without a nim gene. Moreover, the strain carrying a nimA gene fully retained PFOR activity and other enzyme activities such as thioredoxin reductase (TrxR) after resistance had been induced. In the parental strain 638R, these were lost or very strongly downregulated during the development of resistance. Further, after induction of high-level metronidazole resistance, parental strain 638R was highly susceptible to oxygen whereas the daughter strain with a nimA gene was hardly affected. Ensuing RT-qPCR measurements showed that a pathway for iron import via hemin uptake is downregulated in 638R with induced resistance but not in the resistant nimA daughter strain. We propose that nimA primes B. fragilis toward an alternative pathway of metronidazole resistance by enabling the preservation of normal iron levels in the cell.
The Mechanism of Bladder Injury in Fetal Rats With Myelomeningocele

Background Bladder dysfunction has been implicated as a major cause of progressive renal failure in children with neurogenic bladder. However, its pathogenesis remains unclear. This study aimed to compare the expression of proliferation, apoptosis, and neuromuscular-related proteins during the development of the bladder in myelomeningocele fetal rats, and to explore the characteristics of its abnormal development. Methods For the myelomeningocele group, Sprague Dawley pregnant rats were intragastrically injected with retinoic acid on the 10th day of gestation to induce myelomeningocele fetal rats. For the control group, the same amount of olive oil was injected to induce normal fetal rats. Bladders were harvested at embryonic days E16, E18, E20, and E22. Real-time quantitative polymerase chain reaction and western blotting were used to detect the protein levels of proliferating cell nuclear antigen (PCNA), cleaved caspase-3, neuron-specific nuclear-binding protein (NeuN), α-smooth muscle actin (α-SMA), and mRNA at E16–E22; immunohistochemistry was used to detect the expression of cleaved caspase-3 at E22. Results The proliferation of bladder tissue cells was inhibited, with suppressed PCNA expression in myelomeningocele bladder tissue compared with that in control tissue at the early stage (E16). Myelomeningocele bladders showed increased tissue apoptosis in the late embryonic stage, with significantly higher cleaved caspase-3 protein expression than in the control bladders at E20 and E22. NeuN protein expression increased along with embryonic stage, although the expression at E20 and E22 was significantly lower in myelomeningocele bladders than in control bladders. α-SMA protein expression in myelomeningocele bladders increased gradually with the progression of pregnancy, although its expression was lower than that for control bladders at E22. Immunohistochemistry showed abundant positive staining for cleaved caspase-3 in the bladder mucosa and muscle layer of myelomeningocele bladders, and the expression of cleaved caspase-3 was significantly higher in myelomeningocele bladders than in control bladders. Conclusions Bladder dysfunction in myelomeningocele fetal rats is related to the inhibition of proliferation, promotion of apoptosis, and reduction of bladder nerve and smooth muscle-related protein synthesis.
Novel Brain-Stiffness-Mimicking Matrix Gel Enables Comprehensive Invasion Analysis of 3D Cultured GBM Cells

Glioblastoma (GBM) is the most common malignant primary brain tumor in adults, which is fast growing and tends to invade surrounding normal brain tissues. Uncovering the molecular and cellular mechanisms of GBM high invasion potential is of great importance for the treatment and prognostic prediction. However, the commonly used two-dimensional (2D) cell culture and analysis system suffers from lack of the heterogeneity and in vivo property of brain tissues. Here, we established a three-dimensional (3D) cell culture-based analysis system that could better recapitulate the heterogeneity of GBM and mimic the in vivo conditions in the brain. The GBM cell lines, DBTRG and U251, were cultured by hanging drop culture into the GBM multicellular spheroids, which were embedded in the optimized 3D brain-stiffness-mimicking matrix gel (0.5 mg/ml Collagen Ⅰ + 3 mg/ml Matrigel+ 3.3 mg/ml Hyaluronic Acid (HA)). The biochemical composition of the optimized matrix gel is similar to that of the brain microenvironment, and the elastic modulus is close to that of the brain tissue. The dynamics of the GBM spheroids was examined using high-content imaging for 60 h, and four metrics including invasion distance, invasion area, single-cell invasion velocity, and directionality were employed to quantify the invasion capacity. The result showed that DBTRG cells possess higher invasion capacity than U251 cells, which was consistent with the results of the classic transwell test. Transcriptome analysis of both cell lines was performed to explore the underlying molecular mechanisms. Our novel brain-stiffness-mimicking matrix gel enables comprehensive invasion analysis of the 3D cultured GBM cells and provides a model basis for in-depth exploration of the mechanisms regulating GBM invasion including the interaction between GBM cells and brain stroma.
Climate Change Affects Reproductive Phenology in Lianas of Australia’s Wet Tropics

Lianas are increasing in abundance in many tropical forests. This increase can alter forest structure and decrease both carbon storage and tree diversity via antagonistic relationships between lianas and their host trees. Climate change is postulated as an underlying driver of increasing liana abundances, via increases in dry-season length, forest-disturbance events, and atmospheric CO2 concentrations; all factors thought to favour lianas. However, the impact of climate change on liana reproductive phenology, an underlying determinant of liana abundance, has been little studied, particularly outside of Neotropical forests. Over a 15-year period (2000–2014), we examined the phenological patterns of a liana community in intact rainforests of the Wet Tropics bioregion of Australia; a World Heritage Area and hotspot of floral diversity. Specifically, we assessed (1) flowering and fruiting patterns of liana species; (2) potential climate drivers of flowering and fruiting activity; and (3) the influence of El Niño-related climatic disturbances on liana phenology. We found that flowering and fruiting of the studied liana species increased over time. Liana reproduction, moreover, rose in apparent response to higher temperatures and reduced rainfall. Finally, we found flowering and fruiting of the liana species increased following El Niño events. These results suggest that liana reproduction and abundance are likely to increase under predicted future climate regimes, with potentially important impacts on the survival, growth, and reproduction of resident trees and thus the overall health of Australian tropical rainforests.
Meta-Analysis of Human Antibodies Against Plasmodium falciparum Variable Surface and Merozoite Stage Antigens

Concerted efforts to fight malaria have caused significant reductions in global malaria cases and mortality. Sustaining this will be critical to avoid rebound and outbreaks of seasonal malaria. Identifying predictive attributes that define clinical malaria will be key to guide development of second-generation tools to fight malaria. Broadly reactive antibodies against variable surface antigens that are expressed on the surface of infected erythrocytes and merozoites stage antigens are targets of naturally acquired immunity and prime candidates for anti-malaria therapeutics and vaccines. However, predicting the relationship between the antigen-specific antibodies and protection from clinical malaria remains unresolved. Here, we used new datasets and multiple approaches combined with re-analysis of our previous data to assess the multi-dimensional and complex relationship between antibody responses and clinical malaria outcomes. We observed 22 antigens (17 PfEMP1 domains, 3 RIFIN family members, merozoite surface protein 3 (PF3D7_1035400), and merozoites-associated armadillo repeats protein (PF3D7_1035900) that were selected across three different clinical malaria definitions (1,000/2,500/5,000 parasites/µl plus fever). In addition, Principal Components Analysis (PCA) indicated that the first three components (Dim1, Dim2 and Dim3 with eigenvalues of 306, 48, and 29, respectively) accounted for 66.1% of the total variations seen. Specifically, the Dim1, Dim2 and Dim3 explained 52.8%, 8.2% and 5% of variability, respectively. We further observed a significant relationship between the first component scores and age with antibodies to PfEMP1 domains being the key contributing variables. This is consistent with a recent proposal suggesting that there is an ordered acquisition of antibodies targeting PfEMP1 proteins. Thus, although limited, and further work on the significance of the selected antigens will be required, these approaches may provide insights for identification of drivers of naturally acquired protective immunity as well as guide development of additional tools for malaria elimination and eradication.
The Relationship Between Resting Cerebral Blood Flow, Neurometabolites, Cardio-Respiratory Fitness and Aging-Related Cognitive Decline

Older adults typically experience a decline in cognitive function, but improvements in physical health and lifestyle can be neuroprotective across the human lifespan. The primary objective of this study is to advance our basic understanding of how cardiorespiratory fitness and neurophysiological attributes relate to cognitive decline. While cerebral blood flow (CBF) is critical for the supply of nutrients to the tissue, the brain’s major neurotransmitters (i.e., gamma-aminobutyric acid, GABA, and glutamate-glutamine complex, Glx) are closely linked to oxidative metabolism. Within the context of flow-metabolism coupling, the critical question is how these neurophysiological parameters interplay, resulting in cognitive decline. Further, how cardiorespiratory fitness may impact aging neurophysiology and cognition is not well understood. To address these questions, we recruited 10 younger and 12 older cognitively intact participants to collect GABA and Glx using magnetic resonance spectroscopy (MRS), CBF using pseudo-continuous arterial spin labeling Magnetic Resonance Imaging (MRI), VO2max as a measure of cardiorespiratory fitness using the YMCA submax test, and cognitive and motor-cognitive measures using a battery of behavioral assessments. We observed expected differences in GABA+, Glx, and CBF between younger and older participants in pre-SMA, a frontal domain-general region. When GABA+ and Glx were related to CBF via multiple linear regression, Glx was identified as the main contributor to the model. For higher-order executive function (i.e., inhibition versus color naming), GABA*Glx*CBF interaction was critical in younger, while only Glx was involved in older participants. For unimanual motor dexterity, GABA*Glx interaction was the common denominator across both groups, but younger participants’ brain also engages CBF. In terms of selective motor inhibition, CBF from younger participants was the only major neurophysiological factor. In terms of fitness, cardiorespiratory fitness was significantly related to GABA, Glx, and motor performance when combining cohorts, but no group-specific relationships were observed. Taken together, our results indicate that Glx and CBF coupling decreases with aging, perhaps due to altered glial oxidative metabolism. Our data suggest that GABA, Glx, and CBF are engaged and weighted differently for different cognitive measures sensitized to aging, and higher fitness allows for a more efficient metabolic shift that facilitates improved performance on cognitive-motor tasks.
Development and Internal Validation of a Model for Predicting Internet Gaming Disorder Risk in Adolescents and Children

Background The high prevalence of Internet gaming disorder among children and adolescents and its severe psychological, health, and social consequences have become a public emergency. A high efficiency and cost-effective early recognition method are urgently needed. Objective We aim to develop and internally validate a nomogram model for predicting Internet gaming disorder (IGD) risk in Chinese adolescents and children. Methods Through an online survey, 780 children and adolescents aged 7–18 years who participated in the survey from June to August 2021 were selected. The least absolute shrinkage and selection operator regression model was used to filter the factors. Multivariate logistic regression analysis was used to establish the prediction model and generate nomograms and a website calculator. The area under the receiver operating characteristic curve, calibration plot, and decision curve analysis were used to evaluate the model's discrimination, calibration, and clinical utility. Bootstrapping validation was used to verify the model internally. Results Male sex and experience of game consumption were the two most important predictors. Both models exhibited good discrimination, with an area under the curve >0.80. The calibration plots were both close to the diagonal line (45°). Decision curve analyses revealed that two nomograms were clinically useful when the threshold probability for the intervention was set to 5–75%. Conclusion Two prediction models appear to be reliable tools for Internet gaming disorder screening in children and adolescents, which can also help clinicians to personalize treatment plans. Moreover, from the standpoint of simplification and cost, Model 2 appears to be a better alternative.
Identity Integration in Adolescents With Features of Gender Dysphoria Compared to Adolescents in General Population

Adolescence is an important period for identity formation and identity consolidation is one of the main developmental tasks. Gender identity is an essential aspect of identity but so far little is known about its development. Neither has the identity development of adolescents with features of gender dysphoria (GD) been extensively studied so far. However, adolescents with features of GD have been shown to present extensive psychiatric psychopathology and could therefore be assumed also to have more problems with identity development. We set out to compare the identity integration of adolescents with features of GD (n = 215; 186 natal females, 29 natal males) and adolescents from general population (n = 400; 244 females, 154 males and 2 who did not report their sex) using a culture-adapted Finnish version of an assessment tool for adolescents and young adults on identity in terms of personality functioning, the Assessment of Identity Development in Adolescence (AIDA). AIDA is a 58-item self-report questionnaire enabling dimensional differentiation between healthy and impaired identity development. The continuous AIDA total score (sum score) and its subscales were analyzed using MANOVA, and dichotomized T-scores differentiating identity development in impaired and healthy range using cross-tabulations with chi-square statistics. Adolescents with features of GD showed identity development similar to adolescents in general population. The slight differences seen in AIDA scores were in favor of the GD group. The proportion scoring to identity impairment was lowest among gender-referred adolescents assigned males at birth. Identity integration of the gender-referred adolescents was further compared to that of 77 adolescents in specialist level psychiatric outpatient treatment (67 females, 10 males). The adolescent psychiatric outpatients scored much higher toward impaired identity on all AIDA scales than did the adolescents with features of GD. These results suggest that features of GD are not associated with problems in identity development in adolescents at large. Adolescents with features of GD may have been required to process their identity more, thereby advancing further in their identity consolidation process than young people on average.