bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early life stress and body-mass-index modulate brain connectivity in alcohol use disorder
Authors: Agarwal Khushbu , Joseph Paule V. , Zhang Rui , Schwandt Melanie L. , Ramchandani Vijay A. , Diazgranados Nancy , Goldman David , Momenan Reza 
Published: January 2024

AbstractEarly life stress (ELS) significantly increases susceptibility to alcohol use disorder (AUD) by affecting the interplay between the executive and the salience networks (SNs). The link between AUD and higher body-mass index (BMI) is known, but we lack understanding of how BMI impacts the relationship between ELS and brain connectivity in individuals with AUD. To bridge this gap, we investigated the main and interaction effects of ELS and BMI on brain connectivity in individuals with AUD compared to non-AUD participants (n = 77 sex-matched individuals per group). All participants underwent resting-state functional magnetic resonance imaging, revealing intriguing positive functional connectivity between SN seeds and brain regions involved in somatosensory processing, motor coordination and executive control. Examining the relationship of brain connectivity with ELS and BMI, we observed positive associations with the correlations of SN seeds, right anterior insula (RAIns) and supramarginal gyrus (SMG) with clusters in motor [occipital cortex, supplementary motor cortex]; anterior cingulate cortex (ACC) with clusters in frontal, or executive, control regions (middle frontal gyrus; MFG, precentral gyrus) that reportedly are involved in processing of emotionally salient stimuli (all |β | > 0.001, |p | < 0.05). Interestingly, a negative association of the interaction effect of ELS events and BMI measures with the functional connectivity of SN seeds ACC with decision-making (MFG, precentral gyrus), RAIns and RSMG with visuo-motor control regions (occipital cortex and supplementary motor cortex) (all |β | = −0.001, |p | < 0.05). These findings emphasize the moderating effect of BMI on ELS-associated SN seed brain connectivity in AUD. Understanding the neural mechanisms linking BMI, ELS and AUD can guide targeted interventions for this population.
Genetic evidence for the causal relations between metabolic syndrome and psychiatric disorders: a Mendelian randomization study
Authors: Gao Xue , Qin Yi , Jiao Shu , Hao Junhui , Zhao Jian , Wang Jiale , Wen Yanchao , Wang Tong 
Published: January 2024

AbstractEmerging evidence reveals associations between metabolic syndrome (MetS) and psychiatric disorders (PDs), although causality remains uncertain. Consequently, we conducted Mendelian randomization (MR) to systematically evaluate the causality between MetS and PDs. Linkage disequilibrium score regression estimated the heritability of PDs and their genetic correlations with MetS. In primary analyses, the main model employed inverse variance weighting method, with sensitivity analyses using various MR models to ensure robustness. Replication MR analyses, involving cohorts distinct from those in the primary analyses, were performed to validate the generalizability of the findings. Multivariable MR analyses were carried out to account for genetically predicted body mass index (BMI). As a result, genetic correlations of MetS with attention-deficit/hyperactivity disorder(ADHD), anorexia nervosa(ANO), major depressive disorder(MDD), and schizophrenia were identified. Causal effects of MetS on ADHD (OR: 1.59 [95% CI:1.45–1.74]), ANO (OR: 1.42 [95% CI:1.25–1.61]), MDD(OR: 1.23 [95% CI: 1.13–1.33]), and the effects of ADHD (OR: 1.03 [95% CI: 1.02–1.04]) and ANO (OR: 1.01 [95% CI: 1.01–1.02]) on MetS were observed in primary analyses. Results from sensitivity analyses and replication analyses were generally consistent with the primary analyses, confirming the robustness and generalizability of the findings. Associations between MetS and ADHD, as well as ANO persisted after adjusting for BMI, whereas the statistical significance of the association between MetS and MDD was no longer observable. These results contribute to a deeper understanding of the mechanisms underlying PDs, suggesting potential modifiable targets for public prevention and clinical intervention in specific PDs related to metabolic pathways.
LUBAC-mediated M1 Ub regulates necroptosis by segregating the cellular distribution of active MLKL
Authors: Weinelt Nadine , Wächtershäuser Kaja Nicole , Celik Gulustan , Jeiler Birte , Gollin Isabelle , Zein Laura , Smith Sonja , Andrieux Geoffroy , Das Tonmoy , Roedig Jens , Feist Leonard , Rotter Björn , Boerries Melanie , Pampaloni Francesco , van Wijk Sjoerd J. L. 
Published: January 2024

AbstractPlasma membrane accumulation of phosphorylated mixed lineage kinase domain-like (MLKL) is a hallmark of necroptosis, leading to membrane rupture and inflammatory cell death. Pro-death functions of MLKL are tightly controlled by several checkpoints, including phosphorylation. Endo- and exocytosis limit MLKL membrane accumulation and counteract necroptosis, but the exact mechanisms remain poorly understood. Here, we identify linear ubiquitin chain assembly complex (LUBAC)-mediated M1 poly-ubiquitination (poly-Ub) as novel checkpoint for necroptosis regulation downstream of activated MLKL in cells of human origin. Loss of LUBAC activity inhibits tumor necrosis factor α (TNFα)-mediated necroptosis, not by affecting necroptotic signaling, but by preventing membrane accumulation of activated MLKL. Finally, we confirm LUBAC-dependent activation of necroptosis in primary human pancreatic organoids. Our findings identify LUBAC as novel regulator of necroptosis which promotes MLKL membrane accumulation in human cells and pioneer primary human organoids to model necroptosis in near-physiological settings.
DNA polymerase beta connects tumorigenicity with the circadian clock in liver cancer through the epigenetic demethylation of Per1
Authors: Chen Siyu , Zhang Wenxiang , Li Xiao , Cao Zhengyu , Liu Chang 
Published: January 2024

AbstractThe circadian-controlled DNA repair exhibits a strong diurnal rhythm. Disruption in circadian clock and DNA repair is closely linked with hepatocellular carcinoma (HCC) progression, but the mechanism remains unknown. Here, we show that polymerase beta (POLB), a critical enzyme in the DNA base excision repair pathway, is rhythmically expressed at the translational level in mouse livers. Hepatic POLB dysfunction dampens clock homeostasis, whereas retards HCC progression, by mediating the methylation of the 4th CpG island on the 5′UTR of clock gene Per1. Clinically, POLB is overexpressed in human HCC samples and positively associated with poor prognosis. Furthermore, the hepatic rhythmicity of POLB protein expression is orchestrated by Calreticulin (CALR). Our findings provide important insights into the molecular mechanism underlying the synergy between clock and food signals on the POLB-driven BER system and reveal new clock-dependent carcinogenetic effects of POLB. Therefore, chronobiological modulation of POLB may help to promote precise interventions for HCC.
CYB561 promotes HER2+ breast cancer proliferation by inhibiting H2AFY degradation
Authors: Zhao Ting , Wang Chaomin , Zhao Na , Qiao Ge , Hua Jialei , Meng Donghua , Liu Liming , Zhong Benfu , Liu Miao , Wang Yichao , Bai Changsen , Li Yueguo 
Published: January 2024

AbstractBreast cancer (BRCA) has a high incidence and mortality rate among women. Different molecular subtypes of breast cancer have different prognoses and require personalized therapies. It is imperative to find novel therapeutic targets for different molecular subtypes of BRCA. Here, we demonstrated for the first time that Cytochromeb561 (CYB561) is highly expressed in BRCA and correlates with poor prognosis, especially in HER2-positive BRCA. Overexpression of CYB561 could upregulate macroH2A (H2AFY) expression in HER2-positive BRCA cells through inhibition of H2AFY ubiquitination, and high expression of CYB561 in HER2-positive BRCA cells could promote the proliferation and migration of cells. Furthermore, we have demonstrated that CYB561 regulates H2AFY expression, thereby influencing the expression of NF-κB, a downstream molecule of H2AFY. These findings have been validated through in vivo experiments. In conclusion, we propose that CYB561 may represent a novel therapeutic target for the treatment of HER2-positive BRCA.
The explanation of educational disparities in adiposity by lifestyle, socioeconomic and mental health mediators: a multiple mediation model
Authors: Bartoskova Polcrova Anna , Ksinan Albert J. , González-Rivas Juan P. , Bobak Martin , Pikhart Hynek 
Published: January 2024

Abstract
Background
The inverse association between education and obesity was previously found in numerous studies. This study aims to assess several possible mediators in the educational disparities in adiposity. We hypothesize the potential mediating role of lifestyle, socioeconomic, and mental health factors in the association between education and adiposity.

Methods
Cross-sectional population-based sample from Czechia included 2,154 25-64 years old subjects (54.6% women). Education was classified as high, middle, and low. Adiposity was assessed as a latent variable based on body fat percentage, BMI, waist circumference, and visceral fat. The mediation potential of unhealthy dietary behavior, alcohol intake, smoking, sedentary behaviors, income, stress, depression, and quality of life was assessed in age-adjusted sex-specific multiple mediation models.

Results
The negative direct effect of education on adiposity was statistically significant at 5% level of significance in both sexes. For men, the indirect effect was statistically significant via sedentary behavior (β = 0.041; 95% CI [0.025–0.062]) with a mediation ratio of 23.7%. In women, the indirect effect was statistically significant via dietary risk (β = −0.023, 95% CI [−0.037, −0.013]), alcohol intake (β = −0.006; 95% CI [−0.014, −0.001]), sedentary behavior (β = 0.012, 95% CI [0.004,0.023]), income (β = −0.022; 95% CI [−0.041, −0.004]), and mental health (β = −0.007; 95% CI [−0.019, −0.001]). The total mediation ratio in women was 30.5%.

Conclusions
Sedentary behaviors had mediating role in the association between education and adiposity in both sexes, with more important role in men. In addition, unhealthy diet and lower income partially mediated the educational gradient in adiposity in women.
Reliability and accuracy of artificial intelligence ChatGPT in providing information on ophthalmic diseases and management to patients
Authors: Cappellani Francesco , Card Kevin R. , Shields Carol L. , Pulido Jose S. , Haller Julia A. 
Published: January 2024

Abstract
Purpose
To assess the accuracy of ophthalmic information provided by an artificial intelligence chatbot (ChatGPT).

Methods
Five diseases from 8 subspecialties of Ophthalmology were assessed by ChatGPT version 3.5. Three questions were asked to ChatGPT for each disease: what is x?; how is x diagnosed?; how is x treated? (x = name of the disease). Responses were graded by comparing them to the American Academy of Ophthalmology (AAO) guidelines for patients, with scores ranging from −3 (unvalidated and potentially harmful to a patient’s health or well-being if they pursue such a suggestion) to 2 (correct and complete).

Main outcomes
Accuracy of responses from ChatGPT in response to prompts related to ophthalmic health information in the form of scores on a scale from −3 to 2.

Results
Of the 120 questions, 93 (77.5%) scored ≥ 1. 27. (22.5%) scored ≤ −1; among these, 9 (7.5%) obtained a score of −3. The overall median score amongst all subspecialties was 2 for the question “What is x”, 1.5 for “How is x diagnosed”, and 1 for “How is x treated”, though this did not achieve significance by Kruskal-Wallis testing.

Conclusions
Despite the positive scores, ChatGPT on its own still provides incomplete, incorrect, and potentially harmful information about common ophthalmic conditions, defined as the recommendation of invasive procedures or other interventions with potential for adverse sequelae which are not supported by the AAO for the disease in question. ChatGPT may be a valuable adjunct to patient education, but currently, it is not sufficient without concomitant human medical supervision.
Origin of the multi-phasic quenching dynamics in the BLUF domains across the species
Authors: Zhou Yalin , Tang Siwei , Chen Zijing , Zhou Zhongneng , Huang Jiulong , Kang Xiu-Wen , Zou Shuhua , Wang Bingyao , Zhang Tianyi , Ding Bei , Zhong Dongping 
Published: January 2024

AbstractBlue light using flavin (BLUF) photoreceptors respond to light via one of nature’s smallest photo-switching domains. Upon photo-activation, the flavin cofactor in the BLUF domain exhibits multi-phasic dynamics, quenched by a proton-coupled electron transfer reaction involving the conserved Tyr and Gln. The dynamic behavior varies drastically across different species, the origin of which remains controversial. Here, we incorporate site-specific fluorinated Trp into three BLUF proteins, i.e., AppA, OaPAC and SyPixD, and characterize the percentages for the Wout, WinNHin and WinNHout conformations using 19F nuclear magnetic resonance spectroscopy. Using femtosecond spectroscopy, we identify that one key WinNHin conformation can introduce a branching one-step proton transfer in AppA and a two-step proton transfer in OaPAC and SyPixD. Correlating the flavin quenching dynamics with the active-site structural heterogeneity, we conclude that the quenching rate is determined by the percentage of WinNHin, which encodes a Tyr-Gln configuration that is not conducive to proton transfer.
Macro CD5L+ deteriorates CD8+T cells exhaustion and impairs combination of Gemcitabine-Oxaliplatin-Lenvatinib-anti-PD1 therapy in intrahepatic cholangiocarcinoma
Authors: Lu Jia-Cheng , Wu Lei-Lei , Sun Yi-Ning , Huang Xiao-Yong , Gao Chao , Guo Xiao-Jun , Zeng Hai-Ying , Qu Xu-Dong , Chen Yi , Wu Dong , Pei Yan-Zi , Meng Xian-Long , Zheng Yi-Min , Liang Chen , Zhang Peng-Fei , Cai Jia-Bin , Ding Zhen-Bin , Yang Guo-Huan , Ren Ning , Huang Cheng , Wang Xiao-Ying , Gao Qiang , Sun Qi-Man , Shi Ying-Hong , Qiu Shuang-Jian , Ke Ai-Wu , Shi Guo-Ming , Zhou Jian , Sun Yi-Di , Fan Jia 
Published: January 2024

AbstractIntratumoral immune status influences tumor therapeutic response, but it remains largely unclear how the status determines therapies for patients with intrahepatic cholangiocarcinoma. Here, we examine the single-cell transcriptional and TCR profiles of 18 tumor tissues pre- and post- therapy of gemcitabine plus oxaliplatin, in combination with lenvatinib and anti-PD1 antibody for intrahepatic cholangiocarcinoma. We find that high CD8 GZMB+ and CD8 proliferating proportions and a low Macro CD5L+ proportion predict good response to the therapy. In patients with a poor response, the CD8 GZMB+ and CD8 proliferating proportions are increased, but the CD8 GZMK+ proportion is decreased after the therapy. Transition of CD8 proliferating and CD8 GZMB+ to CD8 GZMK+ facilitates good response to the therapy, while Macro CD5L+–CD8 GZMB+ crosstalk impairs the response by increasing CTLA4 in CD8 GZMB+. Anti-CTLA4 antibody reverses resistance of the therapy in intrahepatic cholangiocarcinoma. Our data provide a resource for predicting response of the combination therapy and highlight the importance of CD8+T-cell status conversion and exhaustion induced by Macro CD5L+ in influencing the response, suggesting future avenues for cancer treatment optimization.
Shifting patterns of dengue three years after Zika virus emergence in Brazil
Authors: Pinotti Francesco , Giovanetti Marta , de Lima Maricelia Maia , de Cerqueira Erenilde Marques , Alcantara Luiz C. J. , Gupta Sunetra , Recker Mario , Lourenço José 
Published: January 2024

AbstractIn 2015, the Zika virus (ZIKV) emerged in Brazil, leading to widespread outbreaks in Latin America. Following this, many countries in these regions reported a significant drop in the circulation of dengue virus (DENV), which resurged in 2018-2019. We examine age-specific incidence data to investigate changes in DENV epidemiology before and after the emergence of ZIKV. We observe that incidence of DENV was concentrated in younger individuals during resurgence compared to 2013-2015. This trend was more pronounced in Brazilian states that had experienced larger ZIKV outbreaks. Using a mathematical model, we show that ZIKV-induced cross-protection alone, often invoked to explain DENV decline across Latin America, cannot explain the observed age-shift without also assuming some form of disease enhancement. Our results suggest that a sudden accumulation of population-level immunity to ZIKV could suppress DENV and reduce the mean age of DENV incidence via both protective and disease-enhancing interactions.
Using big sequencing data to identify chronic SARS-Coronavirus-2 infections
Authors: Harari Sheri , Miller Danielle , Fleishon Shay , Burstein David , Stern Adi 
Published: January 2024

AbstractThe evolution of SARS-Coronavirus-2 (SARS-CoV-2) has been characterized by the periodic emergence of highly divergent variants. One leading hypothesis suggests these variants may have emerged during chronic infections of immunocompromised individuals, but limited data from these cases hinders comprehensive analyses. Here, we harnessed millions of SARS-CoV-2 genomes to identify potential chronic infections and used language models (LM) to infer chronic-associated mutations. First, we mined the SARS-CoV-2 phylogeny and identified chronic-like clades with identical metadata (location, age, and sex) spanning over 21 days, suggesting a prolonged infection. We inferred 271 chronic-like clades, which exhibited characteristics similar to confirmed chronic infections. Chronic-associated mutations were often high-fitness immune-evasive mutations located in the spike receptor-binding domain (RBD), yet a minority were unique to chronic infections and absent in global settings. The probability of observing high-fitness RBD mutations was 10-20 times higher in chronic infections than in global transmission chains. The majority of RBD mutations in BA.1/BA.2 chronic-like clades bore predictive value, i.e., went on to display global success. Finally, we used our LM to infer hundreds of additional chronic-like clades in the absence of metadata. Our approach allows mining extensive sequencing data and providing insights into future evolutionary patterns of SARS-CoV-2.
Discovery of a peripheral 5HT2A antagonist as a clinical candidate for metabolic dysfunction-associated steatohepatitis
Authors: Pagire Haushabhau S. , Pagire Suvarna H. , Jeong Byung-kwan , Choi Won-Il , Oh Chang Joo , Lim Chae Won , Kim Minhee , Yoon Jihyeon , Kim Seong Soon , Bae Myung Ae , Jeon Jae-Han , Song Sungmin , Lee Hee Jong , Lee Eun Young , Goughnour Peter C. , Kim Dooseop , Lee In-Kyu , Loomba Rohit , Kim Hail , Ahn Jin Hee 
Published: January 2024

AbstractMetabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is currently the leading cause of chronic liver disease worldwide. Metabolic Dysfunction-Associated Steatohepatitis (MASH), an advanced form of MASLD, can progress to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Based on recent findings by our team that liver 5HT2A knockout male mice suppressed steatosis and reduced fibrosis-related gene expression, we developed a peripheral 5HT2A antagonist, compound 11c for MASH. It shows good in vitro activity, stability, and in vivo pharmacokinetics (PK) in rats and dogs. Compound 11c also shows good in vivo efficacy in a diet-induced obesity (DIO) male mice model and in a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) male mice model, effectively improving histologic features of MASH and fibrosis. According to the tissue distribution study using [14C]-labeled 11c, the compound was determined to be a peripheral 5HT2A antagonist. Collectively, first-in-class compound 11c shows promise as a therapeutic agent for the treatment of MASLD and MASH.
Cryo- EM structure of the mycobacterial 70S ribosome in complex with ribosome hibernation promotion factor RafH
Authors: Kumar Niraj , Sharma Shivani , Kaushal Prem S. 
Published: January 2024

AbstractRibosome hibernation is a key survival strategy bacteria adopt under environmental stress, where a protein, hibernation promotion factor (HPF), transitorily inactivates the ribosome. Mycobacterium tuberculosis encounters hypoxia (low oxygen) as a major stress in the host macrophages, and upregulates the expression of RafH protein, which is crucial for its survival. The RafH, a dual domain HPF, an orthologue of bacterial long HPF (HPFlong), hibernates ribosome in 70S monosome form, whereas in other bacteria, the HPFlong induces 70S ribosome dimerization and hibernates its ribosome in 100S disome form. Here, we report the cryo- EM structure of M. smegmatis, a close homolog of M. tuberculosis, 70S ribosome in complex with the RafH factor at an overall 2.8 Å resolution. The N- terminus domain (NTD) of RafH binds to the decoding center, similarly to HPFlong NTD. In contrast, the C- terminus domain (CTD) of RafH, which is larger than the HPFlong CTD, binds to a distinct site at the platform binding center of the ribosomal small subunit. The two domain-connecting linker regions, which remain mostly disordered in earlier reported HPFlong structures, interact mainly with the anti-Shine Dalgarno sequence of the 16S rRNA.
Microwave quantum diode
Authors: Upadhyay Rishabh , Golubev Dmitry S. , Chang Yu-Cheng , Thomas George , Guthrie Andrew , Peltonen Joonas T. , Pekola Jukka P. 
Published: January 2024

AbstractThe fragile nature of quantum circuits is a major bottleneck to scalable quantum applications. Operating at cryogenic temperatures, quantum circuits are highly vulnerable to amplifier backaction and external noise. Non-reciprocal microwave devices such as circulators and isolators are used for this purpose. These devices have a considerable footprint in cryostats, limiting the scalability of quantum circuits. As a proof-of-concept, here we report a compact microwave diode architecture, which exploits the non-linearity of a superconducting flux qubit. At the qubit degeneracy point we experimentally demonstrate a significant difference between the power levels transmitted in opposite directions. The observations align with the proposed theoretical model. At − 99 dBm input power, and near the qubit-resonator avoided crossing region, we report the transmission rectification ratio exceeding 90% for a 50 MHz wide frequency range from 6.81 GHz to 6.86 GHz, and over 60% for the 250 MHz range from 6.67 GHz to 6.91 GHz. The presented architecture is compact, and easily scalable towards multiple readout channels, potentially opening up diverse opportunities in quantum information, microwave read-out and optomechanics.
Hydrogen-bonded organic frameworks in solution enables continuous and high-crystalline membranes
Authors: Yin Qi , Pang Kuan , Feng Ya-Nan , Han Lili , Morsali Ali , Li Xi-Ya , Liu Tian-Fu 
Published: January 2024

AbstractHydrogen-Bonded organic frameworks (HOFs) are a type of emerging porous materials. At present, little research has been conducted on their solution state. This work demonstrates that HOFs fragment into small particles while maintaining their original assemblies upon dispersing in solvents, as confirmed by Cryo-electron microscopy coupled with 3D electron diffraction technology. 1D and 2D-Nuclear Magnetic Resonance (NMR) and zeta potential analyses indicate the HOF-based colloid solution and the isolated molecular solution have significant differences in intermolecular interactions and aggregation behavior. Such unique solution processibility allows for fabricating diverse continuous HOF membranes with high crystallinity and porosity through solution-casting approach on various substrates. Among them, HOF-BTB@AAO membranes show high C3H6 permeance (1.979 × 10−7 mol·s−1·m−2·Pa−1) and excellent separation performance toward C3H6 and C3H8 (SF = 14). This continuous membrane presents a green, low-cost, and efficient separation technology with potential applications in petroleum cracking and purification.