bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wearable and interactive multicolored photochromic fiber display
Authors: Li Pan , Wang Yuwei , He Xiaoxian , Cui Yuyang , Ouyang Jingyu , Ouyang Ju , He Zicheng , Hu Jiayu , Liu Xiaojuan , Wei Hang , Wang Yu , Lu Xiaoling , Ji Qian , Cai Xinyuan , Liu Li , Hou Chong , Zhou Ning , Pan Shaowu , Wang Xiangru , Zhou Huamin , Qiu Cheng-Wei , Lu Yan-Qing , Tao Guangming 
Published: February 2024

AbstractEndowing flexible and adaptable fiber devices with light-emitting capabilities has the potential to revolutionize the current design philosophy of intelligent, wearable interactive devices. However, significant challenges remain in developing fiber devices when it comes to achieving uniform and customizable light effects while utilizing lightweight hardware. Here, we introduce a mass-produced, wearable, and interactive photochromic fiber that provides uniform multicolored light control. We designed independent waveguides inside the fiber to maintain total internal reflection of light as it traverses the fiber. The impact of excessive light leakage on the overall illuminance can be reduced by utilizing the saturable absorption effect of fluorescent materials to ensure light emission uniformity along the transmission direction. In addition, we coupled various fluorescent composite materials inside the fiber to achieve artificially controllable spectral radiation of multiple color systems in a single fiber. We prepared fibers on mass-produced kilometer-long using the thermal drawing method. The fibers can be directly integrated into daily wearable devices or clothing in various patterns and combined with other signal input components to control and display patterns as needed. This work provides a new perspective and inspiration to the existing field of fiber display interaction, paving the way for future human–machine integration.
Molecular profiling of the hippocampus of children with autism spectrum disorder
Authors: Rexrode Lindsay E. , Hartley Joshua , Showmaker Kurt C. , Challagundla Lavanya , Vandewege Michael W. , Martin Brigitte E. , Blair Estelle , Bollavarapu Ratna , Antonyraj Rhenius B. , Hilton Keauna , Gardiner Alex , Valeri Jake , Gisabella Barbara , Garrett Michael R. , Theoharides Theoharis C. , Pantazopoulos Harry 
Published: February 2024

AbstractSeveral lines of evidence point to a key role of the hippocampus in Autism Spectrum Disorders (ASD). Altered hippocampal volume and deficits in memory for person and emotion related stimuli have been reported, along with enhanced ability for declarative memories. Mouse models have demonstrated a critical role of the hippocampus in social memory dysfunction, associated with ASD, together with decreased synaptic plasticity. Chondroitin sulfate proteoglycans (CSPGs), a family of extracellular matrix molecules, represent a potential key link between neurodevelopment, synaptic plasticity, and immune system signaling. There is a lack of information regarding the molecular pathology of the hippocampus in ASD. We conducted RNAseq profiling on postmortem human brain samples containing the hippocampus from male children with ASD (n = 7) and normal male children (3–14 yrs old), (n = 6) from the NIH NeuroBioBank. Gene expression profiling analysis implicated molecular pathways involved in extracellular matrix organization, neurodevelopment, synaptic regulation, and immune system signaling. qRT-PCR and Western blotting were used to confirm several of the top markers identified. The CSPG protein BCAN was examined with multiplex immunofluorescence to analyze cell-type specific expression of BCAN and astrocyte morphology. We observed decreased expression of synaptic proteins PSD95 (p < 0.02) and SYN1 (p < 0.02), increased expression of the extracellular matrix (ECM) protease MMP9 (p < 0.03), and decreased expression of MEF2C (p < 0.03). We also observed increased BCAN expression with astrocytes in children with ASD, together with altered astrocyte morphology. Our results point to alterations in immune system signaling, glia cell differentiation, and synaptic signaling in the hippocampus of children with ASD, together with alterations in extracellular matrix molecules. Furthermore, our results demonstrate altered expression of genes implicated in genetic studies of ASD including SYN1 and MEF2C.
Key subphenotypes of bipolar disorder are differentially associated with polygenic liabilities for bipolar disorder, schizophrenia, and major depressive disorder
Authors: Song Jie , Jonsson Lina , Lu Yi , Bergen Sarah E. , Karlsson Robert , Smedler Erik , Gordon-Smith Katherine , Jones Ian , Jones Lisa , Craddock Nick , Sullivan Patrick F. , Lichtenstein Paul , Di Florio Arianna , Landén Mikael 
Published: February 2024

AbstractBipolar disorder (BD) features heterogenous clinical presentation and course of illness. It remains unclear how subphenotypes associate with genetic loadings of BD and related psychiatric disorders. We investigated associations between the subphenotypes and polygenic risk scores (PRS) for BD, schizophrenia, and major depressive disorder (MDD) in two BD cohorts from Sweden (N = 5180) and the UK (N = 2577). Participants were assessed through interviews and medical records for inter-episode remission, psychotic features during mood episodes, global assessment of functioning (GAF, function and symptom burden dimensions), and comorbid anxiety disorders. Meta-analyses based on both cohorts showed that inter-episode remission and GAF-function were positively correlated with BD-PRS but negatively correlated with schizophrenia-PRS (SCZ-PRS) and MDD-PRS. Moreover, BD-PRS was negatively, and MDD-PRS positively, associated with the risk of comorbid anxiety disorders. Finally, SCZ-PRS was positively associated with psychotic symptoms during mood episodes. Assuming a higher PRS of certain psychiatric disorders in cases with a positive family history, we further tested the associations between subphenotypes in index BD people and occurrence of BD, schizophrenia, or MDD in their relatives using Swedish national registries. BD patients with a relative diagnosed with BD had: (1) higher GAF and lower risk of comorbid anxiety than those with a relative diagnosed with schizophrenia or MDD, (2) lower risk of psychotic symptoms than those with a relative diagnosed with schizophrenia. Our findings shed light on the genetic underpinnings of the heterogeneity in clinical manifestations and course of illness in BD, which ultimately provide insights for developing personalized approaches to the diagnosis and treatment.
Divergent suicidal symptomatic activations converge on somato-cognitive action network in depression
Authors: Li Jiao , Wang Dajing , Xia Jie , Zhang Chao , Meng Yao , Xu Shuo , Chen Huafu , Liao Wei 
Published: February 2024

AbstractIndividuals with depression have the highest lifetime prevalence of suicide attempts (SA) among mental illnesses. Numerous neuroimaging studies have developed biomarkers from task-related neural activation in depressive patients with SA, but the findings are inconsistent. Empowered by the contemporary interconnected view of depression as a neural system disorder, we sought to identify a specific brain circuit utilizing published heterogeneous neural activations. We systematically reviewed all published cognitive and emotional task-related functional MRI studies that investigated differences in the location of neural activations between depressive patients with and without SA. We subsequently mapped an underlying brain circuit functionally connecting to each experimental activation using a large normative connectome database (n = 1000). The identified SA-related functional network was compared to the network derived from the disease control group. Finally, we decoded this convergent functional connectivity network using microscale transcriptomic and chemo-architectures, and macroscale psychological processes. We enrolled 11 experimental tasks from eight studies, including depressive patients with SA (n = 147) and without SA (n = 196). The heterogeneous SA-related neural activations localized to the somato-cognitive action network (SCAN), exhibiting robustness to little perturbations and specificity for depression. Furthermore, the SA-related functional network was colocalized with brain-wide gene expression involved in inflammatory and immunity-related biological processes and aligned with the distribution of the GABA and noradrenaline neurotransmitter systems. The findings demonstrate that the SA-related functional network of depression is predominantly located at the SCAN, which is an essential implication for understanding depressive patients with SA.
Incubation of methamphetamine craving in punishment-resistant individuals is associated with activation of specific gene networks in the rat dorsal striatum
Authors: Daiwile Atul P. , McCoy Michael T. , Ladenheim Bruce , Subramaniam Jayanthi , Cadet Jean Lud 
Published: February 2024

AbstractMethamphetamine use disorder (MUD) is characterized by loss of control over compulsive drug use. Here, we used a self-administration (SA) model to investigate transcriptional changes associated with the development of early and late compulsivity during contingent footshocks. Punishment initially separated methamphetamine taking rats into always shock-resistant (ASR) rats that continued active lever pressing and shock-sensitive (SS) rats that reduced their lever pressing. At the end of the punishment phase, rats underwent 15 days of forced abstinence at the end of which they were re-introduced to the SA paradigm followed by SA plus contingent shocks. Interestingly, 36 percent of the initial SS rats developed delayed shock-resistance (DSR). Of translational relevance, ASR rats showed more incubation of methamphetamine craving than DSR and always sensitive (AS) rats. RNA sequencing revealed increased striatal Rab37 and Dipk2b mRNA levels that correlated with incubation of methamphetamine craving. Interestingly, Bdnf mRNA levels showed HDAC2-dependent decreased expression in the AS rats. The present SA paradigm should help to elucidate the molecular substrates of early and late addiction-like behaviors.
Targeted inhibition of SCFSKP2 confers anti-tumor activities resulting in a survival benefit in osteosarcoma
Authors: Wang Jichuan , Ferrena Alexander , Zhang Ranxin , Singh Swapnil , Viscarret Valentina , Al-Harden Waleed , Aldahamsheh Osama , Borjihan Hasibagan , Singla Amit , Yaguare Simon , Tingling Janet , Zi Xiaolin , Lo Yungtai , Gorlick Richard , Schwartz Edward L. , Zhao Hongling , Yang Rui , Geller David S. , Zheng Deyou , Hoang Bang H. 
Published: February 2024

AbstractOsteosarcoma(OS) is a highly aggressive bone cancer for which treatment has remained essentially unchanged for decades. Although OS is characterized by extensive genomic heterogeneity and instability, RB1 and TP53 have been shown to be the most commonly inactivated tumor suppressors in OS. We previously generated a mouse model with a double knockout (DKO) of Rb1 and Trp53 within cells of the osteoblastic lineage, which largely recapitulates human OS with nearly complete penetrance. SKP2 is a repression target of pRb and serves as a substrate recruiting subunit of the SCFSKP2 complex. In addition, SKP2 plays a central role in regulating the cell cycle by ubiquitinating and promoting the degradation of p27. We previously reported the DKOAA transgenic model, which harbored a knock-in mutation in p27 that impaired its binding to SKP2. Here, we generated a novel p53-Rb1-SKP2 triple-knockout model (TKO) to examine SKP2 function and its potential as a therapeutic target in OS. First, we observed that OS tumorigenesis was significantly delayed in TKO mice and their overall survival was markedly improved. In addition, the loss of SKP2 also promoted an apoptotic microenvironment and reduced the stemness of DKO tumors. Furthermore, we found that small-molecule inhibitors of SKP2 exhibited anti-tumor activities in vivo and in OS organoids as well as synergistic effects when combined with a standard chemotherapeutic agent. Taken together, our results suggest that SKP2 inhibitors may reduce the stemness plasticity of OS and should be leveraged as next-generation adjuvants in this cancer.
Memory persistence: from fundamental mechanisms to translational opportunities
Authors: Merlo Santiago Abel , Belluscio Mariano Andrés , Pedreira Maria Eugenia , Merlo Emiliano 
Published: February 2024

AbstractMemory persistence is a double edge sword. Persistence of adaptive memories is essential for survival and even determines who we are. Neurodegenerative conditions with significant memory loss such as Alzheimer’s disease, testify how defects of memory persistence have severe and irreversible effects on personality, among other symptoms. Yet, maintenance of overly strong maladaptive memories underlies highly debilitating psychiatric conditions including post-traumatic stress disorder, specific phobia, substance dependence and binge eating disorder. Here we review the neurobiological mechanisms supporting memory formation, persistence, inhibition and forgetting. We then shift the focus to how such mechanisms have been exploited to alter the persistence of laboratory-generated memories in human healthy volunteers as a proof of concept. Finally, we review the effect of behavioural and pharmacological interventions in anxiety and addiction disorder patients, highlighting key findings, gaps, and future directions for basic and translational research.
Pervasive alterations of intra-axonal volume and network organization in young children with a 16p11.2 deletion
Authors: Maillard Anne M. , Romascano David , Villalón-Reina Julio E. , Moreau Clara A. , Almeida Osório Joana M. , Richetin Sonia , Junod Vincent , Yu Paola , Misic Bratislav , Thompson Paul M. , Fornari Eleonora , Gygax Marine Jequier , Jacquemont Sébastien , Chabane Nadia , Rodríguez-Herreros Borja 
Published: February 2024

AbstractReciprocal Copy Number Variants (CNVs) at the 16p11.2 locus confer high risk for autism spectrum disorder (ASD) and other neurodevelopmental disorders (NDDs). Morphometric MRI studies have revealed large and pervasive volumetric alterations in carriers of a 16p11.2 deletion. However, the specific neuroanatomical mechanisms underlying such alterations, as well as their developmental trajectory, are still poorly understood. Here we explored differences in microstructural brain connectivity between 24 children carrying a 16p11.2 deletion and 66 typically developing (TD) children between 2 and 8 years of age. We found a large pervasive increase of intra-axonal volume widespread over a high number of white matter tracts. Such microstructural alterations in 16p11.2 deletion children were already present at an early age, and led to significant changes in the global efficiency and integration of brain networks mainly associated to language, motricity and socio-emotional behavior, although the widespread pattern made it unlikely to represent direct functional correlates. Our results shed light on the neuroanatomical basis of the previously reported increase of white matter volume, and align well with analogous evidence of altered axonal diameter and synaptic function in 16p11.2 mice models. We provide evidence of a prevalent mechanistic deviation from typical maturation of brain structural connectivity associated with a specific biological risk to develop ASD. Future work is warranted to determine how this deviation contributes to the emergence of symptoms observed in young children diagnosed with ASD and other NDDs.
Emerging role of RNA modification and long noncoding RNA interaction in cancer
Authors: Yang Liqiong , Tang Lu , Min Qi , Tian Hua , Li Linwei , Zhao Yueshui , Wu Xu , Li Mingxing , Du Fukuan , Chen Yu , Li Wanping , Li Xiaobing , Chen Meijuan , Gu Li , Sun Yuhong , Xiao Zhangang , Shen Jing 
Published: February 2024

AbstractRNA modification, especially N6-methyladenosine, 5-methylcytosine, and N7-methylguanosine methylation, participates in the occurrence and progression of cancer through multiple pathways. The function and expression of these epigenetic regulators have gradually become a hot topic in cancer research. Mutation and regulation of noncoding RNA, especially lncRNA, play a major role in cancer. Generally, lncRNAs exert tumor-suppressive or oncogenic functions and its dysregulation can promote tumor occurrence and metastasis. In this review, we summarize N6-methyladenosine, 5-methylcytosine, and N7-methylguanosine modifications in lncRNAs. Furthermore, we discuss the relationship between epigenetic RNA modification and lncRNA interaction and cancer progression in various cancers. Therefore, this review gives a comprehensive understanding of the mechanisms by which RNA modification affects the progression of various cancers by regulating lncRNAs, which may shed new light on cancer research and provide new insights into cancer therapy.
Utilizing nullomers in cell-free RNA for early cancer detection
Authors: Montgomery Austin , Tsiatsianis Georgios Christos , Mouratidis Ioannis , Chan Candace S. Y. , Athanasiou Maria , Papanastasiou Anastasios D. , Kantere Verena , Syrigos Nikos , Vathiotis Ioannis , Syrigos Konstantinos , Yee Nelson S. , Georgakopoulos-Soares Ilias 
Published: February 2024

AbstractEarly detection of cancer can significantly improve patient outcomes; however, sensitive and highly specific biomarkers for cancer detection are currently missing. Nullomers are the shortest sequences that are absent from the human genome but can emerge due to somatic mutations in cancer. We examine over 10,000 whole exome sequencing matched tumor-normal samples to characterize nullomer emergence across exonic regions of the genome. We also identify nullomer emerging mutational hotspots within tumor genes. Finally, we provide evidence for the identification of nullomers in cell-free RNA from peripheral blood samples, enabling detection of multiple tumor types. We show multiple tumor classification models with an AUC greater than 0.9, including a hepatocellular carcinoma classifier with an AUC greater than 0.99.
Ethical and social reflections on the proposed European Health Data Space
Authors: Staunton Ciara , Shabani Mahsa , Mascalzoni Deborah , Mežinska Signe , Slokenberga Santa 
Published: February 2024

AbstractThe COVID-19 pandemic demonstrated the benefits of international data sharing. Data sharing enabled the health care policy makers to make decisions based on real-time data, it enabled the tracking of the virus, and importantly it enabled the development of vaccines that were crucial to mitigating the impact of the virus. This data sharing is not the norm as data sharing needs to navigate complex ethical and legal rules, and in particular, the fragmented application of the General Data Protection Regulation (GDPR). The introduction of the draft regulation for a European Health Data Space (EHDS) in May 2022 seeks to address some of these legal issues. If passed, it will create an obligation to share electronic health data for certain secondary purposes. While there is a clear need to address the legal complexities involved with data sharing, it is critical that any proposed reforms are in line with ethical principles and the expectations of the data subjects. In this paper we offer a critique of the EHDS and offer some recommendations for this evolving regulatory space.
The experience of receiving a letter from a cancer genetics clinic about risk for hereditary cancer
Authors: Öfverholm Anna , Karlsson Per , Rosén Anna 
Published: February 2024

AbstractDirect contact may be an option for supporting disclosure in families with hereditary cancer risk. In this qualitative interview study, we explored how healthy at-risk relatives experience receiving a letter with information about hereditary cancer directly from healthcare rather than via a relative. The study is part of an ongoing multicentre randomised clinical trial in Sweden that evaluates the effectiveness of direct letters from cancer genetics clinics to at-risk relatives. After conducting semi-structured interviews with 14 relatives who had received a letter and contacted the clinic, we analysed the data using thematic analysis. The relatives had different levels of prior knowledge about the hereditary cancer assessment. Many had been notified by family that a letter was coming but some had not. Overall, these participants believed healthcare-mediated disclosure could complement family-mediated disclosure. They expressed that the letter and the message raised concerns and a need for counselling, and they wanted healthcare to be accessible and informed when making contact. The participants found the message easier to cope with when they had been notified by a family member beforehand, with a general attitude that notifying relatives was the appropriate step to take. They thought healthcare should help patients with the disclosure process but also guard the right of at-risk relatives to be informed. The findings support a direct approach from healthcare as a possible complement to an established model of family-mediated risk disclosure, but implementation must be made within existing frameworks of good practice for genetic counselling.
Multicenter assessment and longitudinal study of the prevalence of antibodies and related adaptive immune responses to AAV in adult males with hemophilia
Authors: Pabinger Ingrid , Ayash-Rashkovsky Mila , Escobar Miguel , Konkle Barbara A. , Mingot-Castellano María Eva , Mullins Eric S. , Negrier Claude , Pan Luying , Rajavel Kavitha , Yan Brian , Chapin John 
Published: February 2024

AbstractAdeno-associated virus (AAV) based gene therapy has demonstrated effective disease control in hemophilia. However, pre-existing immunity from wild-type AAV exposure impacts gene therapy eligibility. The aim of this multicenter epidemiologic study was to determine the prevalence and persistence of preexisting immunity against AAV2, AAV5, and AAV8, in adult participants with hemophilia A or B. Blood samples were collected at baseline and annually for ≤3 years at trial sites in Austria, France, Germany, Italy, Spain, and the United States. At baseline, AAV8, AAV2, and AAV5 neutralizing antibodies (NAbs) were present in 46.9%, 53.1%, and 53.4% of participants, respectively; these values remained stable at Years 1 and 2. Co-prevalence of NAbs to at least two serotypes and all three serotypes was present at baseline for ~40% and 38.2% of participants, respectively. For each serotype, ~10% of participants who tested negative for NAbs at baseline were seropositive at Year 1. At baseline, 38.3% of participants had detectable cell mediated immunity by ELISpot, although no correlations were observed with the humoral response. In conclusion, participants with hemophilia may have significant preexisting immunity to AAV capsids. Insights from this study may assist in understanding capsid-based immunity trends in participants considering AAV vector-based gene therapy.