bluuebunny/crossref_metadata_2025_split huggingface dataset:
‘Finally, I could breathe’: the utility and impact of a diagnosis of obsessive compulsive disorder
Authors: Hughes Finn , Kinderman Peter 
Published: January 2023

AbstractBackground:The diagnosis of obsessive compulsive disorder (OCD) is characterised by intrusive thoughts leading to compulsions to alleviate anxiety. However, research is lacking on impact post-diagnosis. Some research suggests diagnosis may benefit treatment access, but potentially leads to higher levels of stigma and altered self-identity.Aims:The present study assessed the utility (treatment access and problem identification) and impact (stigma, personal wellbeing or social identity) of receiving a diagnosis of OCD.Method:Semi-structured interviews with 12 individuals who had received a diagnosis of OCD were conducted between February and April 2020, then transcribed and analysed using theoretical thematic analysis.Results:Participants reported positive impacts of diagnosis on both ‘utility’ and ‘impact’.Conclusions:The diagnosis of OCD was helpful for participants in making their symptoms tangible, providing relief and hope for recovery. Non-diagnostic or alternative frameworks should aim to meet this need. Future research may wish to identify how this understanding of disorders vary between different diagnoses, especially in terms of stigma and personal wellbeing.
Continent‐Continent Collision Between the South and North China Plates Revealed by Seismic Refraction and Reflection at the Southern Segment of the Tanlu Fault Zone
Authors: Li Haipeng , Li Junlun , Luo Song , Bem Terhemba Shadrach , Yao Huajian , Huang Xianliang 
Published: January 2023

AbstractThe Tanlu Fault Zone (TFZ) is considered as a suture of the intra‐continental collision between the South and North China plates, and it has attracted considerable geological, geochemistry, and geophysical investigations. However, its deep structures still lack clear delineation and the related tectonic processes are still debated without a clear consensus. To better characterize the TFZ as a plate boundary in east China, a 2‐D land seismic survey extending 87 km was conducted across its southern segment to investigate the underlying complex structures. Acoustic full‐waveform inversion (FWI) is applied to the early arrivals of the land seismic data to reconstruct the high‐resolution P‐wave velocity model of the upper crust (above ∼3.5 km). Structures of the crust and the uppermost mantle are further constrained through deep seismic profiling (DSP). The integrated geological interpretation from the FWI and DSP results suggests massive magma upwelling activities, characterized by the reflection‐free zone revealed by DSP and the high‐velocity anomaly recovered by FWI. The TFZ in the study area is found to be a deeply seated fault system with a positive flower structure at its shallow part, which suggests it has undergone a transpression regime. Also, the DSP result provides evidence for the subduction of the South China plate under the North China plate. Finally, a three‐stage model including the compression, transpression, and extension stages is proposed based on the new seismic results to better constrain the tectonic evolution of the southern segment of the TFZ.
Pyrocumulonimbus Events Over British Columbia in 2017: An Ensemble Model Study of Parameter Sensitivities and Climate Impacts of Wildfire Smoke in the Stratosphere
Authors: Lee Hsiang‐He , Lundquist Katherine A. , Tang Qi 
Published: January 2023

AbstractThe Pyrocumulonimbus (pyroCb) events over British Columbia in 2017 were observed in the lower stratosphere for about 8–10 months after the smoke injections. Several previous studies used global climate models to investigate the physical parameters for the 2017 pyroCb events, but the conclusions show strong model dependency. In this study, we use the Energy Exascale Earth System Model (E3SM) and complete an ensemble of runs exploring three injection parameters: smoke aerosol mass, the percentage of black carbon within the smoke aerosols, and plume injection height. Additionally, we consider the heterogeneous reaction of ozone and primary organic matter. According to the satellite daily observed aerosol optical depth (AOD), we find that the best ensemble member is the simulation with 0.4 Tg of smoke, 3% of which is black carbon, a 13.5 km smoke injection height, and a 10−5 probability factor of the heterogeneous reaction. Besides AOD, we examine the ensemble score based on the metrics used in previous studies: the metrics of the extinction coefficient at 18 km altitude and the maximum plume height. The conclusion of the best estimate of the injection parameters for 2017 pyroCb events shows strong not only model but also evaluation metric dependency. We use the Random Forest machine learning technique to quantify the relative importance of each parameter in accurately simulating the 2017 pyroCb events and find that the injection height is the most critical feature, no matter which metric is used to score the ensemble members.
Storm Surge Modeling as an Application of Local Time‐Stepping in MPAS‐Ocean
Authors: Lilly Jeremy R. , Capodaglio Giacomo , Petersen Mark R. , Brus Steven R. , Engwirda Darren , Higdon Robert L. 
Published: January 2023

AbstractThis paper presents the first practical application of local time‐stepping (LTS) schemes in the Model for Prediction Across Scales‐Ocean (MPAS‐O). We use LTS schemes in a single‐layer, global ocean model that predicts the storm surge around the eastern coast of the United States during Hurricane Sandy. The variable‐resolution meshes used are of unprecedentedly high resolution in MPAS‐O, containing cells as small as 125 m wide in Delaware Bay. It is shown that a particular, third‐order LTS scheme (LTS3) produces sea‐surface height solutions that are of comparable quality to solutions produced by the classical four‐stage, fourth‐order Runge‐Kutta method (RK4) with a uniform time step on the same meshes. Furthermore, LTS3 is up to 35% faster in the best cases considered, where the number of cells using the coarse time‐step relative to those using the fine time‐step is as low as 1:1. This shows that LTS schemes are viable for use in MPAS‐O with the added benefit of substantially less computational cost. The results of these performance experiments inform us of the requirements for efficient mesh design and configuration of LTS regions for LTS schemes. In particular, we see that for LTS to be efficient on a given mesh, it is important to have enough cells using the coarse time‐step relative to those using the fine time‐step, typically at least 1:5 to see an increase in performance.
Porphyromonas gingivalis bacteremia increases the permeability of the blood-brain barrier via the Mfsd2a/Caveolin-1 mediated transcytosis pathway
Authors: Lei Shuang , Li Jian , Yu Jingjun , Li Fulong , Pan Yaping , Chen Xu , Ma Chunliang , Zhao Weidong , Tang Xiaolin 
Published: January 2023

AbstractBacteremia induced by periodontal infection is an important factor for periodontitis to threaten general health. P. gingivalis DNA/virulence factors have been found in the brain tissues from patients with Alzheimer’s disease (AD). The blood-brain barrier (BBB) is essential for keeping toxic substances from entering brain tissues. However, the effect of P. gingivalis bacteremia on BBB permeability and its underlying mechanism remains unclear. In the present study, rats were injected by tail vein with P. gingivalis three times a week for eight weeks to induce bacteremia. An in vitro BBB model infected with P. gingivalis was also established. We found that the infiltration of Evans blue dye and Albumin protein deposition in the rat brain tissues were increased in the rat brain tissues with P. gingivalis bacteremia and P. gingivalis could pass through the in vitro BBB model. Caveolae were detected after P. gingivalis infection in BMECs both in vivo and in vitro. Caveolin-1 (Cav-1) expression was enhanced after P. gingivalis infection. Downregulation of Cav-1 rescued P. gingivalis-enhanced BMECs permeability. We further found P. gingivalis-gingipain could be colocalized with Cav-1 and the strong hydrogen bonding between Cav-1 and arg-specific-gingipain (RgpA) were detected. Moreover, P. gingivalis significantly inhibited the major facilitator superfamily domain containing 2a (Mfsd2a) expression. Mfsd2a overexpression reversed P. gingivalis-increased BMECs permeability and Cav-1 expression. These results revealed that Mfsd2a/Cav-1 mediated transcytosis is a key pathway governing BBB BMECs permeability induced by P. gingivalis, which may contribute to P. gingivalis/virulence factors entrance and the subsequent neurological impairments.
The histone demethylase KDM5C functions as a tumor suppressor in AML by repression of bivalently marked immature genes
Authors: Trempenau Mette Louise , Schuster Mikkel Bruhn , Pundhir Sachin , Pereira Mafalda Araujo , Kalvisa Adrija , Tapia Marta , Su Jinyu , Ge Ying , de Boer Bauke , Balhuizen Alexander , Bagger Frederik Otzen , Shliaha Pavel , Sroczynska Patrycja , Walfridsson Julian , Grønbæk Kirsten , Theilgaard-Mönch Kim , Jensen Ole N. , Helin Kristian , Porse Bo T. 
Published: January 2023

AbstractEpigenetic regulators are frequently mutated in hematological malignancies including acute myeloid leukemia (AML). Thus, the identification and characterization of novel epigenetic drivers affecting AML biology holds potential to improve our basic understanding of AML and to uncover novel options for therapeutic intervention. To identify novel tumor suppressive epigenetic regulators in AML, we performed an in vivo short hairpin RNA (shRNA) screen in the context of CEBPA mutant AML. This identified the Histone 3 Lysine 4 (H3K4) demethylase KDM5C as a tumor suppressor, and we show that reduced Kdm5c/KDM5C expression results in accelerated growth both in human and murine AML cell lines, as well as in vivo in Cebpa mutant and inv(16) AML mouse models. Mechanistically, we show that KDM5C act as a transcriptional repressor through its demethylase activity at promoters. Specifically, KDM5C knockdown results in globally increased H3K4me3 levels associated with up-regulation of bivalently marked immature genes. This is accompanied by a de-differentiation phenotype that could be reversed by modulating levels of several direct and indirect downstream mediators. Finally, the association of KDM5C levels with long-term disease-free survival of female AML patients emphasizes the clinical relevance of our findings and identifies KDM5C as a novel female-biased tumor suppressor in AML.
A paradigm shift in translational psychiatry through rodent neuroethology
Authors: Shemesh Yair , Chen Alon 
Published: January 2023

AbstractMental disorders are a significant cause of disability worldwide. They profoundly affect individuals’ well-being and impose a substantial financial burden on societies and governments. However, despite decades of extensive research, the effectiveness of current therapeutics for mental disorders is often not satisfactory or well tolerated by the patient. Moreover, most novel therapeutic candidates fail in clinical testing during the most expensive phases (II and III), which results in the withdrawal of pharma companies from investing in the field. It also brings into question the effectiveness of using animal models in preclinical studies to discover new therapeutic agents and predict their potential for treating mental illnesses in humans. Here, we focus on rodents as animal models and propose that they are essential for preclinical investigations of candidate therapeutic agents’ mechanisms of action and for testing their safety and efficiency. Nevertheless, we argue that there is a need for a paradigm shift in the methodologies used to measure animal behavior in laboratory settings. Specifically, behavioral readouts obtained from short, highly controlled tests in impoverished environments and social contexts as proxies for complex human behavioral disorders might be of limited face validity. Conversely, animal models that are monitored in more naturalistic environments over long periods display complex and ethologically relevant behaviors that reflect evolutionarily conserved endophenotypes of translational value. We present how semi-natural setups in which groups of mice are individually tagged, and video recorded continuously can be attainable and affordable. Moreover, novel open-source machine-learning techniques for pose estimation enable continuous and automatic tracking of individual body parts in groups of rodents over long periods. The trajectories of each individual animal can further be subjected to supervised machine learning algorithms for automatic detection of specific behaviors (e.g., chasing, biting, or fleeing) or unsupervised automatic detection of behavioral motifs (e.g., stereotypical movements that might be harder to name or label manually). Compared to studies of animals in the wild, semi-natural environments are more compatible with neural and genetic manipulation techniques. As such, they can be used to study the neurobiological mechanisms underlying naturalistic behavior. Hence, we suggest that such a paradigm possesses the best out of classical ethology and the reductive behaviorist approach and may provide a breakthrough in discovering new efficient therapies for mental illnesses.
Serum complement proteins rather than inflammatory factors is effective in predicting psychosis in individuals at clinical high risk
Authors: Zhang TianHong , Zeng JiaHui , Ye JiaYi , Gao YuQing , Hu YeGang , Xu LiHua , Wei YanYan , Tang XiaoChen , Liu HaiChun , Chen Tao , Li ChunBo , Wan ChunLing , Wang JiJun 
Published: January 2023

AbstractImmunological/inflammatory factors are implicated in the development of psychosis. Complement is a key driver of inflammation; however, it remains unknown which factor is better at predicting the onset of psychosis. This study aimed to compare the alteration and predictive performance of inflammation and complement in individuals at clinical high risk (CHR). We enrolled 49 individuals at CHR and 26 healthy controls (HCs). Twenty-five patients at CHR had converted to psychosis (converter) by the 3-year follow-up. Inflammatory cytokines, including interleukin (IL)-1β, 6, 8, 10, tumor necrosis factor-alpha (TNF-alpha), macrophage colony-stimulating factor levels, and complement proteins (C1q, C2, C3, C3b, C4, C4b, C5, C5a, factor B, D, I, H) were measured by enzyme-linked immunosorbent assay at baseline. Except for TNF- alpha, none of the inflammatory cytokines reached a significant level in either the comparison of CHR individuals and HC or between CHR-converters and non-converters. The C5, C3, D, I, and H levels were significantly lower (C5, p = 0.006; C3, p = 0.009; D, p = 0.026; I, p = 0.016; H, p = 0.019) in the CHR group than in the HC group. Compared to non-converters, converters had significantly lower levels of C5 (p = 0.012) and C5a (p = 0.007). None of the inflammatory factors, but many complement factors, showed significant correlations with changes in general function and symptoms. None of the inflammatory markers, except for C5a and C5, were significant in the discrimination of conversion outcomes in CHR individuals. Our results suggest that altered complement levels in the CHR population are more associated with conversion to psychosis than inflammatory factors. Therefore, an activated complement system may precede the first-episode of psychosis and contribute to neurological pathogenesis at the CHR stage.
Effects of tuberculosis and/or HIV-1 infection on COVID-19 presentation and immune response in Africa
Authors: du Bruyn Elsa , Stek Cari , Daroowala Remi , Said-Hartley Qonita , Hsiao Marvin , Schafer Georgia , Goliath Rene T. , Abrahams Fatima , Jackson Amanda , Wasserman Sean , Allwood Brian W. , Davis Angharad G. , Lai Rachel P.-J. , Coussens Anna K. , Wilkinson Katalin A. , de Vries Jantina , Tiffin Nicki , Cerrone Maddalena , Ntusi Ntobeko A. B. ,   HIATUS consortium, Abrahams Fatimah , Allwood Brian , Aziz Saalikha , Bangani Nonzwakazi , Black John , Blumenthal Melissa , Bremer Marise , Burgers Wendy , Ciko Zandile , Coussens Anna K. , Daroowala Remy , du Bruyn Elsa , Esmail Hanif G. , Gordon Siamon , Harley Yolande X. R. , Hsiao Marvin , Lai Rachel P.-J. , Lakay Francisco , Martinez-Estrada Fernando-Oneissi , Meintjes Graeme , Mendelson Marc S. , Ntusi Ntobeko , Papavarnavas Tari , Proust Alize , Ruzive Sheena , Schafer Georgia , Serole Keboile , Whitaker Claire , Wilkinson Katalin A. , Wilkinson Robert J. , Zvinairo Kennedy , Riou Catherine , Wilkinson Robert J. 
Published: January 2023

AbstractFew studies from Africa have described the clinical impact of co-infections on SARS-CoV-2 infection. Here, we investigate the presentation and outcome of SARS-CoV-2 infection in an African setting of high HIV-1 and tuberculosis prevalence by an observational case cohort of SARS-CoV-2 patients. A comparator group of non SARS-CoV-2 participants is included. The study includes 104 adults with SARS-CoV-2 infection of whom 29.8% are HIV-1 co-infected. Two or more co-morbidities are present in 57.7% of participants, including HIV-1 (30%) and active tuberculosis (14%). Amongst patients dually infected by tuberculosis and SARS-CoV-2, clinical features can be typical of either SARS-CoV-2 or tuberculosis: lymphopenia is exacerbated, and some markers of inflammation (D-dimer and ferritin) are further elevated (p < 0.05). Amongst HIV-1 co-infected participants those with low CD4 percentage strata exhibit reduced total, but not neutralising, anti-SARS-CoV-2 antibodies. SARS-CoV-2 specific CD8 T cell responses are present in 35.8% participants overall but undetectable in combined HIV-1 and tuberculosis. Death occurred in 30/104 (29%) of all COVID-19 patients and in 6/15 (40%) of patients with coincident SARS-CoV-2 and tuberculosis. This shows that in a high incidence setting, tuberculosis is a common co-morbidity in patients admitted to hospital with COVID-19. The immune response to SARS-CoV-2 is adversely affected by co-existent HIV-1 and tuberculosis.
kHz-precision wavemeter based on reconfigurable microsoliton
Authors: Niu Rui , Li Ming , Wan Shuai , Sun Yu Robert , Hu Shui-Ming , Zou Chang-Ling , Guo Guang-Can , Dong Chun-Hua 
Published: January 2023

AbstractThe mode-locked microcomb offers a unique and compact solution for photonics applications, ranging from the optical communications, the optical clock, optical ranging, the precision spectroscopy, novel quantum light source, to photonic artificial intelligence. However, the photonic micro-structures are suffering from the perturbations arising from environment thermal noises and also laser-induced nonlinear effects, leading to the frequency instability of the generated comb. Here, a universal mechanism for fully stabilizing the microcomb is proposed and experimentally verified. By incorporating two global tuning approaches and the autonomous thermal locking mechanism, the pump laser frequency and repetition rate of the microcomb can be controlled independently in real-time without interrupting the microcomb generation. The high stability and controllability of the microcomb frequency enables its application in wavelength measurement with a precision of about 1 kHz. The approach for the full control of comb frequency could be applied in various microcomb platforms, and improve their performances in timing, spectroscopy, and sensing.
Quantifying propagation of DNA methylation and hydroxymethylation with iDEMS
Authors: Stewart-Morgan Kathleen R. , Requena Cristina E. , Flury Valentin , Du Qian , Heckhausen Zoe , Hajkova Petra , Groth Anja 
Published: January 2023

AbstractDNA methylation is a critical epigenetic mark in mammalian cells. Many aspects of DNA methylation maintenance have been characterized; however, the exact kinetics of post-replicative methylation maintenance remain a subject of debate. Here we develop isolation of DNA by 5-ethynyl-deoxyuridine labelling for mass spectrometry (iDEMS), a highly sensitive, quantitative mass spectrometry-based method for measuring DNA modifications on metabolically labelled DNA. iDEMS reveals an unexpectedly hemi-methylated landscape on nascent DNA. Combining iDEMS with metabolic labelling reveals that methylation maintenance is outpaced by cell division in mouse embryonic stem cells. Our approach shows that hydroxymethylation is perpetually asymmetric between sister strands in favour of the parental, template strand. iDEMS can be coupled with immunoprecipitation of chromatin proteins, revealing features of DNA methylation–histone modification crosstalk and suggesting a model for interplay between methylation and nucleosome assembly. iDEMS therefore elucidates long-standing questions about DNA modification propagation and provides an important orthogonal technology to understanding this process in dynamic cellular contexts.
Liquid crystal defect structures with Möbius strip topology
Authors: Zhao Hanqing , Tai Jung-Shen B. , Wu Jin-Sheng , Smalyukh Ivan I. 
Published: January 2023

AbstractTopological solitons commonly appear as energy-minimizing field configurations, but examples of stable, spatially localized objects with coexisting solitonic structures and singular defects are rare. Here we use a nonpolar chiral liquid crystal system to show how twist domain walls can co-self-assemble with vortices to form spatially localized topological objects with spontaneous folding. These soliton–vortex assemblies, which we call ‘möbiusons’, have a topology of the molecular alignment field resembling that of the Möbius strip’s surface and package localized field excitations into folded structures within a confinement-frustrated uniform far-field background. Upon supplying energy in the form of electric pulses, möbiusons with different overall symmetries of structure exhibit folding-dependent rotational and translational motions, as well as topological cargo-carrying abilities that can be controlled by tuning the amplitude and frequency of the applied fields. We demonstrate on-demand transformations between various möbiusons and show examples of encoding information by manipulating folds in such structures. A model based on the energetics of solitons and vortices provides insights into the origins of the folding instability, whereas minimization of the Landau–de Gennes free energy closely reproduces details of their internal structure. Our findings may provide a route towards topology-enabled light-steering designs.
Primates facing climate crisis in a tropical forest hotspot will lose climatic suitable geographical range
Authors: Pinto Míriam Plaza , Beltrão-Mendes Raone , Talebi Maurício , de Lima Adriana Almeida 
Published: January 2023

AbstractGlobal climate changes affect biodiversity and cause species distribution shifts, contractions, and expansions. Climate change and disease are emerging threats to primates, and approximately one-quarter of primates’ ranges have temperatures over historical ones. How will climate changes influence Atlantic Forest primate ranges? We used habitat suitability models and measured potential changes in area and distributions shifts. Climate change expected in 2100 may change the distribution area of Atlantic Forest primates. Fourteen species (74%) are predicted to lose more than 50% of their distribution, and nine species (47%) are predicted to lose more than 75% of their distribution. The balance was negative, indicating a potential future loss, and the strength of the reduction in the distribution is related to the severity of climate change (SSP scenarios). Directional shifts were detected to the south. The projected mean centroid latitudinal shift is ~ 51 km to the south for 2100 SSP5-8.5 scenario. The possibility of dispersal will depend on suitable routes and landscape configuration. Greenhouse gas emissions should be urgently reduced. Our results also emphasize that no more forest loss is acceptable in Atlantic Forest, and restoration, canopy bridges, friendly agroecosystems, and monitoring of infrastructure projects are urgent to enable dealing with climate change.