bluuebunny/crossref_metadata_2025_split huggingface dataset:
Good practice in needs-based post-diagnostic support for people with young onset dementia: findings from the Angela Project
Authors: Stamou Vasileios , Oyebode Jan , La Fontaine Jenny , O'Malley Mary , Parkes Jacqueline , Carter Janet 
Published: January 2023

AbstractEvidence on post-diagnostic support for people with young onset dementia is scarce. Previous studies have employed a problem-focused approach; however, evidence on ‘what works’ in real-life practice is essential to develop recommendations for service design and delivery. This study aimed to provide insight into ‘what works’ from the perspectives of people with young onset dementia and their supporters. We gathered free-text responses on positive service experiences via a UK cross-sectional survey. Inductive thematic analysis was used to identify the objectives of positive services and the needs these met. Follow-up interviews enabled in-depth insights from people with diverse diagnoses, ages and social situations. These were analysed using a template drawn from the survey. The 233 survey respondents gave 856 examples of positive support. Analysis of 24 follow-up interviews led to 16 themes clustered under three superordinate themes: ‘maintaining autonomy’, ‘being myself’ and ‘togetherness’. We found that positive services address the disruptions to sense of agency, selfhood and meaningful relationships that are experienced by those with young onset dementia. The study provides an in-depth understanding of the needs met by positive services for younger people with dementia. Our nuanced findings on good practice can inform age-specific guidelines for young onset dementia and indicate how personalisation can work in practice to help people with young onset dementia to maintain identity, autonomy and connections.
Multiplicative extended Kalman filter ignoring initial conditions for attitude estimation using vector observations
Authors: Chang Lubin 
Published: January 2023

AbstractIn this paper, the well-known multiplicative extended Kalman filter (MEKF) is re-investigated for attitude estimation using vector observations. From the Lie group theory, it is shown that the attitude estimation model is group-affine and its error state model should be trajectory-independent. Moreover, with such a trajectory-independent error state model, the linear Kalman filter is still effective for large initialisation errors. However, the measurement model of the traditional MEKF is dependent on the attitude prediction, which is therefore trajectory-dependent. This is also the main reason why the performance of traditional MEKF is degraded for large initialisation errors. Through substitution of the attitude prediction related term with vector observations in the body frame, a trajectory-independent measurement model is derived for MEKF. Meanwhile, MEKFs with reference attitude error definition and with global state formulating on special Euclidean group have also been studied, with the main focus on derivation of the trajectory-independent measurement models. Extensive Monte Carlo simulations of spacecraft attitude estimation implementations demonstrate that the performance of MEKFs can be much improved with trajectory-independent measurement models.
Cognitive behavioural therapy and medication for treatment of adolescent depression: a network meta-analysis
Authors: Dardas Latefa Ali , Xu Hanzhang , Franklin Michelle Scotton , Scott Jewel , Vance Ashlee , van de Water Brittney , Pan Wei 
Published: January 2023

AbstractBackground:Cognitive behavioural therapy (CBT) and medication are widely accepted and useful interventions for individuals with depression. However, a gap remains in our current understanding of how CBT directly benefits adolescents with depression.Aims:The purpose of this study was to examine the short- and long-term effectiveness of CBT only, CBT+Medication, or Medication alone in reducing the duration of major depressive episodes, lessening internalizing and externalizing symptoms and improving global functioning.Methods:Data were extracted from 14 unique studies with a total of 35 comparisons. Network meta-analysis was conducted and p-scores, a measure of the extent of certainty that one treatment is better than another, were used to rank treatments.Results:There was no significant difference between any two treatments for depression, nor internalizing or externalizing symptoms. For global functioning, CBT had significantly greater effect at the longest follow-up than CBT+Medication. CBT+Medication had the highest p-score for depression, short- and long-term effects, and internalizing and externalizing symptoms long-term effects. No indication of publication bias was found.Conclusions:Neither modality, CBT nor medication, is superior for treating adolescent depression. However, CBT was superior in improving global functioning, which is essential for meeting developmental goals.
On the Scale‐Dependence of Fault Surface Roughness
Authors: Beeler N. M. 
Published: January 2023

AbstractDefining roughness as the ratio of height to length, the standard approach to characterize amplitudes of single fault, joint and fracture surfaces is to measure average height as a function of profile length. Empirically, this roughness depends strongly on scale. The ratio is approximately 0.01 at a few mm but 10× smaller at a few tens of meters. Surfaces are rougher at small scales. However, these conclusions are metric‐dependent. If instead height is averaged over wavelength, roughness is nearly Brown spatial noise, having almost scale‐independent apparent surface height to wavelength ratio. The small deviation from scale‐independence is of the opposite sense than found using the standard metric; surfaces are slightly rougher at long wavelengths. Some natural surfaces may be Brownian within the measurement uncertainties. These contradictions are curiosities of surfaces that have Hurst exponents between 0.5 and 1, as natural fault surfaces do. The wavelength‐based analysis of roughness and how it changes with scale are straight‐forward; a normalized Fourier transform approximately preserves amplitude and its scale dependence in the wavelength domain. Among the conclusions from reconsideration of scale dependence are that the scale dependence is weak and much smaller than that of other fault and shear zone properties. Background and aftershock seismicity, jogs and step‐overs indicate strong localization (smoothing) with slip and scale. The lack of strong scale dependence to surface roughness suggests it is not the dominant control on brittle shear zone evolution.
Two Phases of Crustal Shortening in Northeastern Tibet as a Result of a Stronger Qaidam Lithosphere During the Cenozoic India–Asia Collision
Authors: Xie Renxian , Chen Lin , Yin An , Xiong Xiong , Chen Yongshun John , Guo Zhen , Wang Kai 
Published: January 2023

AbstractAlthough two phases of Cenozoic crustal deformation in the Qilian Shan thrust belt of northeastern Tibet has been documented, their dynamic causes remain unclear. To address this issue, we investigate whether the mechanical strength of the Qaidam Basin, which is located between the Eastern Kunlun Range and the Qilian Shan, was a controlling factor for the observed deformation history by performing 2‐D thermal–mechanical simulations. Our models consider the division of the Tibetan terranes (i.e., Qilian arc, Kunlun‐Qaidam, Songpan‐Ganzi, Qiangtang, and Lhasa, from north to south) bounded by suture zones. Simulation results show that weak suture zones in central Tibet can lead to peeling off and sinking of the mantle lithosphere beneath the Qiangtang and Songpan–Ganzi terranes. After lithospheric delamination, varying north‐south width, thickness and strength of the Qaidam crust creates three end‐member model results: (a) the mantle lithosphere of the Lhasa terrane delaminates while the mantle lithosphere beneath Eastern Kunlun‐Qaidam terrane and the Qilian Shan thrust belt (KQQ) remains undeformed, (b) the Lhasa mantle lithosphere moves northward while the KQQ mantle lithosphere subducts southward, and (c) the Lhasa mantle lithosphere moves northward while lithospheric thickening occurs north of the Qaidam Basin. Our simulations show that pre‐existing weaknesses in northeastern Tibet can be activated and deformed shortly after the onset of collision, and a second wave of deformation sweeps across northeastern Tibet after lithospheric delamination in northern Tibet.
USP15 promotes pulmonary vascular remodeling in pulmonary hypertension in a YAP1/TAZ-dependent manner
Authors: Wu Zhuhua , Zhu Li , Nie Xinran , Wei Li , Qi Yong 
Published: January 2023

AbstractPulmonary hypertension (PH) is a life-threatening cardiopulmonary disease characterized by pulmonary vascular remodeling. Excessive growth and migration of pulmonary artery smooth muscle cells (PASMCs) are believed to be major contributors to pulmonary vascular remodeling. Ubiquitin-specific protease 15 (USP15) is a vital deubiquitinase that has been shown to be critically involved in many pathologies. However, the effect of USP15 on PH has not yet been explored. In this study, the upregulation of USP15 was identified in the lungs of PH patients, mice with SU5416/hypoxia (SuHx)-induced PH and rats with monocrotaline (MCT)-induced PH. Moreover, adeno-associated virus-mediated functional loss of USP15 markedly alleviated PH exacerbation in SuHx-induced mice and MCT-induced rats. In addition, the abnormal upregulation and nuclear translocation of YAP1/TAZ was validated after PH modeling. Human pulmonary artery smooth muscle cells (hPASMCs) were exposed to hypoxia to mimic PH in vitro, and USP15 knockdown significantly inhibited cell proliferation, migration, and YAP1/TAZ signaling in hypoxic hPASMCs. Rescue assays further suggested that USP15 promoted hPASMC proliferation and migration in a YAP1/TAZ-dependent manner. Coimmunoprecipitation assays indicated that USP15 could interact with YAP1, while TAZ bound to USP15 after hypoxia treatment. We further determined that USP15 stabilized YAP1 by inhibiting the K48-linked ubiquitination of YAP1. In summary, our findings reveal the regulatory role of USP15 in PH progression and provide novel insights into the pathogenesis of PH.
Specific RNA m6A modification sites in bone marrow mesenchymal stem cells from the jawbone marrow of type 2 diabetes patients with dental implant failure
Authors: Yan Wanhao , Lin Xiao , Ying Yiqian , Li Jun , Fan Zhipeng 
Published: January 2023

AbstractThe failure rate of dental implantation in patients with well-controlled type 2 diabetes mellitus (T2DM) is higher than that in non-diabetic patients. This due, in part, to the impaired function of bone marrow mesenchymal stem cells (BMSCs) from the jawbone marrow of T2DM patients (DM-BMSCs), limiting implant osseointegration. RNA N6-methyladenine (m6A) is important for BMSC function and diabetes regulation. However, it remains unclear how to best regulate m6A modifications in DM-BMSCs to enhance function. Based on the “m6A site methylation stoichiometry” of m6A single nucleotide arrays, we identified 834 differential m6A-methylated genes in DM-BMSCs compared with normal-BMSCs (N-BMSCs), including 43 and 790 m6A hypermethylated and hypomethylated genes, respectively, and 1 gene containing hyper- and hypomethylated m6A sites. Differential m6A hypermethylated sites were primarily distributed in the coding sequence, while hypomethylated sites were mainly in the 3′-untranslated region. The largest and smallest proportions of m6A-methylated genes were on chromosome 1 and 21, respectively. MazF-PCR and real-time RT-PCR results for the validation of erythrocyte membrane protein band 4.1 like 3, activity-dependent neuroprotector homeobox (ADNP), growth differentiation factor 11 (GDF11), and regulator of G protein signalling 2 agree with m6A single nucleotide array results; ADNP and GDF11 mRNA expression decreased in DM-BMSCs. Furthermore, gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses suggested that most of these genes were enriched in metabolic processes. This study reveals the differential m6A sites of DM-BMSCs compared with N-BMSCs and identifies candidate target genes to enhance BMSC function and improve implantation success in T2DM patients.
MANF ameliorates DSS-induced mouse colitis via restricting Ly6ChiCX3CR1int macrophage transformation and suppressing CHOP-BATF2 signaling pathway
Authors: Yang Lin , Shen Wen-wen , Shao Wei , Zhao Qing , Pang Gao-zong , Yang Yi , Tao Xiao-fang , Zhang Wei-ping , Mei Qiong , Shen Yu-xian 
Published: January 2023

AbstractMesencephalic astrocyte-derived neurotrophic factor (MANF), an endoplasmic reticulum stress-inducible secreting protein, has evolutionarily conserved immune-regulatory function that contributes to the negative regulation of inflammation in macrophages. In this study, we investigated the profiles of MANF in the macrophages of the patients with active inflammatory bowel disease (IBD) and the mice with experimental colitis, which was induced in both myeloid cell-specific MANF knockout mice and wild-type mice by 3% dextran sodium sulfate (DSS) for 7 days. We found that MANF expression was significantly increased in intestinal macrophages from both the mice with experimental colitis and patients with active IBD. DSS-induced colitis was exacerbated in myeloid cell-specific MANF knockout mice. Injection of recombinant human MANF (rhMANF, 10 mg·kg–1·d–1, i.v.) from D4 to D6 significantly ameliorated experimental colitis in DSS-treated mice. More importantly, MANF deficiency in myeloid cells resulted in a dramatic increase in the number of Ly6ChiCX3CRintproinflammatory macrophages in colon lamina propria of DSS-treated mice, and the proinflammatory cytokines and chemokines were upregulated as well. Meanwhile, we demonstrated that MANF attenuated Th17-mediated immunopathology by inhibiting BATF2-mediated innate immune response and downregulating CXCL9, CXCL10, CXCL11 and IL-12p40; MANF functioned as a negative regulator in inflammatory macrophages via inhibiting CHOP-BATF2 signaling pathway, thereby protecting against DSS-induced mouse colitis. These results suggest that MANF ameliorates colon injury by negatively regulating inflammatory macrophage transformation, which shed light on a potential therapeutic target for IBD.
A pooled analysis of outcomes according to cytogenetic abnormalities in patients receiving ixazomib- vs placebo-based therapy for multiple myeloma
Authors: Chng Wee-Joo , Lonial Sagar , Morgan Gareth J. , Iida Shinsuke , Moreau Philippe , Kumar Shaji K. , Twumasi-Ankrah Philip , Villarreal Miguel , Dash Ajeeta B. , Vorog Alexander , Zhang Xiaoquan , Suryanarayan Kaveri , Labotka Richard , Dimopoulos Meletios A. , Rajkumar S. Vincent 
Published: January 2023

AbstractSome cytogenetic abnormalities (CAs) are associated with poorer prognosis in multiple myeloma (MM); proteasome inhibitors appear to benefit patients with high-risk CAs. We evaluated 2247 MM patients from the TOURMALINE-MM1/-MM2/-MM3/-MM4 trials to assess the PFS benefit of ixazomib plus lenalidomide-dexamethasone (Rd) vs placebo-Rd (TOURMALINE-MM1/-MM2) or ixazomib vs placebo (TOURMALINE-MM3/-MM4) in specific high-risk CAs. After a pooled median follow-up of 25.6 months, the hazard ratio (HR) for PFS with ixazomib- vs placebo-based therapy for high-risk patients was 0.74 (95% confidence interval [CI]: 0.59–0.93; median PFS [mPFS] 17.8 vs 13.2 months), and 0.70 (95% CI: 0.62–0.80; mPFS 26.3 vs 17.6 months) for complementary standard-risk patients. The HR for expanded high-risk patients was 0.75 (95% CI: 0.64–0.87; mPFS 18.1 vs 14.1 months), and 0.71 (95% CI: 0.59–0.85; mPFS 36.1 vs 21.4 months) for complementary standard-risk patients. The HR for PFS with ixazomib- vs placebo-based therapy was 0.68 in patients with t(4;14) (95% CI: 0.48–0.96; mPFS 22.4 vs 13.2 months), and 0.77 for patients with amp1q21 (95% CI: 0.63–0.93; mPFS 18.8 vs 14.5 months). A PFS benefit was demonstrated with ixazomib- vs placebo-based therapy regardless of cytogenetic status, with greatest benefit observed in patients with t(4;14) and amp1q21.
NCBP2 and TFRC are novel prognostic biomarkers in oral squamous cell carcinoma
Authors: Arora Rahul , Haynes Logan , Kumar Mehul , McNeil Reid , Ashkani Jahanshah , Nakoneshny Steven C. , Matthews T. Wayne , Chandarana Shamir , Hart Robert D. , Jones Steven J. M. , Dort Joseph C. , Itani Doha , Chanda Ayan , Bose Pinaki 
Published: January 2023

AbstractThere are few prognostic biomarkers and targeted therapeutics currently in use for the clinical management of oral squamous cell carcinoma (OSCC) and patient outcomes remain poor in this disease. A majority of mutations in OSCC are loss-of-function events in tumour suppressor genes that are refractory to conventional modes of targeting. Interestingly, the chromosomal segment 3q22-3q29 is amplified in many epithelial cancers, including OSCC. We hypothesized that some of the 468 genes located on 3q22-3q29 might be drivers of oral carcinogenesis and could be exploited as potential prognostic biomarkers and therapeutic targets. Our integrative analysis of copy number variation (CNV), gene expression and clinical data from The Cancer Genome Atlas (TCGA), identified two candidate genes: NCBP2, TFRC, whose expression positively correlates with worse overall survival (OS) in HPV-negative OSCC patients. Expression of NCBP2 and TFRC is significantly higher in tumour cells compared to most normal human tissues. High NCBP2 and TFRC protein abundance is associated with worse overall, disease-specific survival, and progression-free interval in an in-house cohort of HPV-negative OSCC patients. Finally, due to a lack of evidence for the role of NCBP2 in carcinogenesis, we tested if modulating NCBP2 levels in human OSCC cell lines affected their carcinogenic behaviour. We found that NCBP2 depletion reduced OSCC cell proliferation, migration, and invasion. Differential expression analysis revealed the upregulation of several tumour-promoting genes in patients with high NCBP2 expression. We thus propose both NCBP2 and TFRC as novel prognostic and potentially therapeutic biomarkers for HPV-negative OSCC.
CircRNA MBOAT2 promotes intrahepatic cholangiocarcinoma progression and lipid metabolism reprogramming by stabilizing PTBP1 to facilitate FASN mRNA cytoplasmic export
Authors: Yu Xiaopeng , Tong Huanjun , Chen Jialu , Tang Chenwei , Wang Shuqing , Si Yu , Wang Shouhua , Tang Zhaohui 
Published: January 2023

AbstractThe carcinogenic role of FASN by regulating lipid metabolism reprogramming has been well-established in multiple tumors. However, whether mechanisms during intrahepatic cholangiocarcinoma (ICC) progression, such as circRNAs, regulate FASN expression remains unknown. Here we demonstrate a lipid metabolism-related circRNA, circMBOAT2 (hsa_circ_0007334 in circBase), frequently upregulated in ICC tissues, and positively correlated with ICC malignant features. CircMBOAT2 knockdown inhibits the growth and metastasis of ICC cells. Mechanistically, circMBOAT2 combines with PTBP1 and protects PTBP1 from ubiquitin/proteasome-dependent degradation, impairing the function of PTBP1 to transfer FASN mRNA from the nucleus to the cytoplasm. Moreover, circMBOAT2 and FASN have the same effect on fatty acid profile, unsaturated fatty acids instead of saturated fatty acids are primarily regulated and associated with malignant behaviors of ICC cells. The levels of lipid peroxidation and ROS were significantly higher when FASN was knocked down and recovered when circMBOAT2 was overexpressed. Our results identified that circMBOAT2 was upregulated in ICC and promoted progression by stabilizing PTBP1 to facilitate FASN mRNA cytoplasmic export, which altered lipid metabolic profile and regulated redox homeostasis in ICC, suggesting that circMBOAT2 may serve as an available therapeutic target for ICC with active lipid metabolism.
Microglia and meningeal macrophages depletion delays the onset of experimental autoimmune encephalomyelitis
Authors: Montilla Alejandro , Zabala Alazne , Er-Lukowiak Marco , Rissiek Björn , Magnus Tim , Rodriguez-Iglesias Noelia , Sierra Amanda , Matute Carlos , Domercq María 
Published: January 2023

AbstractIn multiple sclerosis and the experimental autoimmune encephalomyelitis (EAE) model, both resident microglia and infiltrating macrophages contribute to demyelination as well as spontaneous remyelination. Nevertheless, the specific roles of microglia versus macrophages are unknown. We investigated the influence of microglia in EAE using the colony stimulating factor 1 receptor (CSF-1R) inhibitor, PLX5622, to deplete microglial population andCcr2RFP/+fmsEGFP/+mice, to distinguish blood-derived macrophages from microglia. PLX5622 treatment depleted microglia and meningeal macrophages, and provoked a massive infiltration of CCR2+macrophages into demyelinating lesions and spinal cord parenchyma, albeit it did not alter EAE chronic phase. In contrast, microglia and meningeal macrophages depletion reduced the expression of major histocompatibility complex II and CD80 co-stimulatory molecule in dendritic cells, macrophages and microglia. In addition, it diminished T cell reactivation and proliferation in the spinal cord parenchyma, inducing a significant delay in EAE onset. Altogether, these data point to a specific role of CNS microglia and meningeal macrophages in antigen presentation and T cell reactivation at initial stages of EAE.
Hippo pathway dysregulation in gastric cancer: from Helicobacter pylori infection to tumor promotion and progression
Authors: Messina Beatrice , Lo Sardo Federica , Scalera Stefano , Memeo Lorenzo , Colarossi Cristina , Mare Marzia , Blandino Giovanni , Ciliberto Gennaro , Maugeri-Saccà Marcello , Bon Giulia 
Published: January 2023

AbstractThe Hippo pathway plays a critical role for balancing proliferation and differentiation, thus regulating tissue homeostasis. The pathway acts through a kinase cascade whose final effectors are the Yes-associated protein (YAP) and its paralog transcriptional co‑activator with PDZ‑binding motif (TAZ). In response to a variety of upstream signals, YAP and TAZ activate a transcriptional program that modulates cellular proliferation, tissue repair after injury, stem cell fate decision, and cytoskeletal reorganization. Hippo pathway signaling is often dysregulated in gastric cancer and in Helicobacter pylori-induced infection, suggesting a putative role of its deregulation since the early stages of the disease. In this review, we summarize the architecture and regulation of the Hippo pathway and discuss how its dysregulation fuels the onset and progression of gastric cancer. In this setting, we also focus on the crosstalk between Hippo and other established oncogenic signaling pathways. Lastly, we provide insights into the therapeutic approaches targeting aberrant YAP/TAZ activation and discuss the related clinical perspectives and challenges.
Genetic conversion of a split-drive into a full-drive element
Authors: Terradas Gerard , Bennett Jared B. , Li Zhiqian , Marshall John M. , Bier Ethan 
Published: January 2023

AbstractThe core components of CRISPR-based gene drives, Cas9 and guide RNA (gRNA), either can be linked within a self-contained single cassette (full gene-drive, fGD) or be provided in two separate elements (split gene-drive, sGD), the latter offering greater control options. We previously engineered split systems that could be converted genetically into autonomous full drives. Here, we examine such dual systems inserted at the spo11 locus that are recoded to restore gene function and thus organismic fertility. Despite minimal differences in transmission efficiency of the sGD or fGD drive elements in single generation crosses, the reconstituted spo11 fGD cassette surprisingly exhibits slower initial drive kinetics than the unlinked sGD element in multigenerational cage studies, but then eventually catches up to achieve a similar level of final introduction. These unexpected kinetic behaviors most likely reflect differing transient fitness costs associated with individuals co-inheriting Cas9 and gRNA transgenes during the drive process.