bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV, Vascular Risk Factors, and Cognition in the Combination Antiretroviral Therapy Era: A Systematic Review and Meta-Analysis
Authors: McIntosh Elissa C. , Tureson Kayla , Rotblatt Lindsay J. , Singer Elyse J. , Thames April D. 
Published: November 2020

AbstractObjectives:Mounting evidence indicates that vascular risk factors (VRFs) are elevated in HIV and play a significant role in the development and persistence of HIV-associated neurocognitive disorder. Given the increased longevity of people living with HIV (PLWH), there is a great need to better elucidate vascular contributions to neurocognitive impairment in HIV. This systematic review and meta-analysis examine relationships between traditional VRFs, cardiovascular disease (CVD), and cognition in PLWH in the combination antiretroviral therapy era.Methods:For the systematic review, 44 studies met inclusion criteria and included data from 14,376 PLWH and 6,043 HIV-seronegative controls. To better quantify the contribution of VRFs to cognitive impairment in HIV, a robust variance estimation meta-analysis (N = 11 studies) was performed and included data from 2139 PLWH.Results:In the systematic review, cross-sectional and longitudinal studies supported relationships between VRFs, cognitive dysfunction, and decline, particularly in the domains of attention/processing speed, executive functioning, and fine motor skills. The meta-analysis demonstrated VRFs were associated with increased odds of global neurocognitive impairment (odds ratio [OR ]= 2.059, p = .010), which remained significant after adjustment for clinical HIV variables (p = .017). Analyses of individual VRFs demonstrated type 2 diabetes (p = .004), hyperlipidemia (p = .043), current smoking (p = .037), and previous CVD (p = .0005) were significantly associated with global neurocognitive impairment.Conclusions:VRFs and CVD are associated with worse cognitive performance and decline, and neurocognitive impairment in PLWH. Future studies are needed to examine these relationships in older adults with HIV, and investigate how race/ethnicity, gender, medical comorbidities, and psychosocial factors contribute to VRF-associated cognitive dysfunction in HIV.
Blood Biomarkers Relate to Cognitive Performance Years after Traumatic Brain Injury in Service Members and Veterans
Authors: Lippa Sara M. , Gill Jessica , Brickell Tracey A. , French Louis M. , Lange Rael T. 
Published: November 2020

AbstractObjective:This study examines the relationship of serum total tau, neurofilament light (NFL), ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), and glial fibrillary acidic protein (GFAP) with neurocognitive performance in service members and veterans with a history of traumatic brain injury (TBI).Method:Service members (n = 488) with a history of uncomplicated mild (n = 172), complicated mild, moderate, severe, or penetrating TBI (sTBI; n = 126), injured controls (n = 116), and non-injured controls (n = 74) prospectively enrolled from Military Treatment Facilities. Participants completed a blood draw and neuropsychological assessment a year or more post-injury. Six neuropsychological composite scores and presence/absence of mild neurocognitive disorder (MNCD) were evaluated. Within each group, stepwise hierarchical regression models were conducted.Results:Within the sTBI group, increased serum UCH-L1 was related to worse immediate memory and delayed memory (R2Δ = .065–.084, ps < .05) performance, while increased GFAP was related to worse perceptual reasoning (R2Δ = .030, p = .036). Unexpectedly, within injured controls, UCH-L1 and GFAP were inversely related to working memory (R2Δ = .052–.071, ps < .05), and NFL was related to executive functioning (R2Δ = .039, p = .021) and MNCD (Exp(B) = 1.119, p = .029).Conclusions:Results suggest GFAP and UCH-L1 could play a role in predicting poor cognitive outcome following complicated mild and more severe TBI. Further investigation of blood biomarkers and cognition is warranted.
Proton beam radiotherapy of locally advanced or recurrent conjunctival squamous cell carcinoma: experience of the CATANA Centre
Authors: Milazzotto Roberto , Liardo Rocco Luca Emanuele , Privitera Giuseppe , Raffaele Luigi , Salamone Vincenzo , Arena Floriana , Pergolizzi Stefano , Cuttone Giacomo , Cirrone Giuseppe A. P. , Russo Andrea , Avitabile Teresio , Foti Pietro Valerio , Palmucci Stefano , Basile Antonio , Spatola Corrado 
Published: November 2020

AbstractAim:Conjunctival squamous cell carcinoma (SCC) is a rare tumour of the ocular region and microscopic radical surgical is difficult. There are no single guidelines for therapeutic management and the role of radiation therapy is not clearly defined although conventionally photon or electron beams are used. Proton beam radiotherapy (PBRT) is a new option for a conservative approach and allows good sparing of the organs at risk.Materials and methods:After surgical resection, we collected 15 cases treated at our institution with PBRT. The dose delivered was between 48 and 60 Gy relative biological effectiveness (RBE), with fractions of 12–15 Gy RBE.Results:After an average period of 48 months, the patients achieved excellent disease control (overall survival and disease-free survival: 86·6%), with minimal acute and late toxicity.Findings:In this work, we present our experience on the use of PBRT technique in SCC treatment. A larger sample of patients is needed to draw conclusions about the impact of this treatment on disease recurrence and overall survival.
Intercomparisons of High‐Resolution Global Ocean Analyses: Evaluation of A New Synthesis in Tropical Oceans
Authors: Sun Yujuan , Perrie William , Qiao Fangli , Wang Gang 
Published: November 2020

AbstractA new high‐resolution global analysis product is constructed from a fully coupled surface wave‐tide‐circulation Ocean Model developed by the First Institute of Oceanography Coupled Ocean Model (FIO‐COM). The performance of the FIO‐COM analysis data set is assessed based on comparisons with two other widely used high‐resolution global analysis products (Copernicus marine and environment monitoring service and HYbrid isopycnal‐sigma‐pressure coordinate ocean model), and observations in tropical oceans. Through comparison with observations, the FIO‐COM analysis is shown to be able to accurately capture the large‐scale mixed layer depth (MLD) structures in the tropical oceans during all seasons. Seasonal variations of MLDs can exceed ±80% in the southern and northern tropical oceans (10°‐25°S and 10°‐25°N) in both boreal winter and summer, as inferred from observations and FIO‐COM analysis data. Quantitative assessments of the 20°C isothermal depth, temperature at 5°m depth, and temperature and salinity profiles, among the analyses and in situ observations are also conducted. The capability of the FIO‐COM analysis to reflect the observed sea surface temperature variability during the 2015 El Niño episode is further investigated through comparisons with observations from 19 TAO buoys located in the Niño 3.4 region. All indicate the high quality of the new data set.
Highly efficient and safe genome editing by CRISPR-Cas12a using CRISPR RNA with a ribosyl-2′-O-methylated uridinylate-rich 3′-overhang in mouse zygotes
Authors: Ha Dae-In , Lee Jeong Mi , Lee Nan-Ee , Kim Daesik , Ko Jeong-Heon , Kim Yong-Sam 
Published: November 2020

AbstractThe CRISPR-Cas12a system has been developed to harness highly specific genome editing in eukaryotic cells. Given the relatively small sizes of Cas12a genes, the system has been suggested to be most applicable to gene therapy using AAV vector delivery. Previously, we reported that a U-rich crRNA enabled highly efficient genome editing by the CRISPR-Cas12a system in eukaryotic cells. In this study, we introduced methoxyl modifications at C2 in riboses in the U-rich 3′-overhang of crRNA. When mixed with Cas12a effector proteins, the ribosyl-2′-O-methylated (2-OM) U-rich crRNA enabled improvement of dsDNA digestibility. Moreover, the chemically modified U-rich crRNA achieved very safe and highly specific genome editing in murine zygotes. The engineered CRISPR-Cas12a system is expected to facilitate the generation of various animal models. Moreover, the engineered crRNA was evaluated to further improve a CRISPR genome editing toolset.
Targeting TOPK sensitises tumour cells to radiation-induced damage by enhancing replication stress
Authors: Herbert Katharine J. , Puliyadi Rathi , Prevo Remko , Rodriguez-Berriguete Gonzalo , Ryan Anderson , Ramadan Kristijan , Higgins Geoff S. 
Published: November 2020

AbstractT-LAK-originated protein kinase (TOPK) overexpression is a feature of multiple cancers, yet is absent from most phenotypically normal tissues. As such, TOPK expression profiling and the development of TOPK-targeting pharmaceutical agents have raised hopes for its future potential in the development of targeted therapeutics. Results presented in this paper confirm the value of TOPK as a potential target for the treatment of solid tumours, and demonstrate the efficacy of a TOPK inhibitor (OTS964) when used in combination with radiation treatment. Using H460 and Calu-6 lung cancer xenograft models, we show that pharmaceutical inhibition of TOPK potentiates the efficacy of fractionated irradiation. Furthermore, we provide in vitro evidence that TOPK plays a hitherto unknown role during S phase, showing that TOPK depletion increases fork stalling and collapse under conditions of replication stress and exogenous DNA damage. Transient knockdown of TOPK was shown to impair recovery from fork stalling and to increase the formation of replication-associated single-stranded DNA foci in H460 lung cancer cells. We also show that TOPK interacts directly with CHK1 and Cdc25c, two key players in the checkpoint signalling pathway activated after replication fork collapse. This study thus provides novel insights into the mechanism by which TOPK activity supports the survival of cancer cells, facilitating checkpoint signalling in response to replication stress and DNA damage.
LncRNA NEAT1 remodels chromatin to promote the 5-Fu resistance by maintaining colorectal cancer stemness
Authors: Zhu Yihao , Hu Hanqing , Yuan Ziming , Zhang Qian , Xiong Huan , Hu Zhiqiao , Wu Hongyu , Huang Rui , Wang Guiyu , Tang Qingchao 
Published: November 2020

AbstractResistance of chemotherapy is one of causes of recurrence and poor prognosis in patients with colorectal cancer (CRC). The role of differentially expressed long non-coding RNA (lncRNA) in 5-fluorouracil (5-Fu) resistance has not been fully elucidated. Here we observed that lncRNA NEAT1 was associated with 5-Fu resistance in CRC. Our Functional studies showed that NEAT1 promoted 5-Fu resistance in colorectal cells. In addition, A-TAC sequencing and chromatin immunoprecipitation (ChIP) showed that NEAT1 affected chromatin remodeling, increased the acetylation levels of histones, increased their enrichment at the promoters of ALDH1 and c-Myc, and promoted the expression of ALDH1 and c-Myc. Taken together, our study suggested that NEAT1 promoted 5-Fu resistance and cancer stemness by remodeling chromatin. Our finding provides a novel role of NEAT1 and may provide a new strategy for the treatment of CRC 5-Fu resistance.
Pontocerebellar hypoplasia due to bi-allelic variants in MINPP1
Authors: Appelhof Bart , Wagner Matias , Hoefele Julia , Heinze Anja , Roser Timo , Koch-Hogrebe Margarete , Roosendaal Stefan D. , Dehghani Mohammadreza , Mehrjardi Mohammad Yahya Vahidi , Torti Erin , Houlden Henry , Maroofian Reza , Rajabi Farrah , Sticht Heinrich , Baas Frank , Wieczorek Dagmar , Jamra Rami Abou 
Published: November 2020

AbstractPontocerebellar hypoplasia (PCH) describes a group of rare heterogeneous neurodegenerative diseases with prenatal onset. Here we describe eight children with PCH from four unrelated families harboring the homozygousMINPP1(NM_004897.4) variants; c.75_94del, p.(Leu27Argfs*39), c.851 C > A, p.(Ala284Asp), c.1210 C > T, p.(Arg404*), and c.992 T > G, p.(Ile331Ser). The homozygous p.(Leu27Argfs*39) change is predicted to result in a complete absence of MINPP1. The p.(Arg404*) would likely lead to a nonsense mediated decay, or alternatively, a loss of several secondary structure elements impairing protein folding. The missense p.(Ala284Asp) affects a buried, hydrophobic residue within the globular domain. The introduction of aspartic acid is energetically highly unfavorable and therefore predicted to cause a significant reduction in protein stability. The missense p.(Ile331Ser) affects the tight hydrophobic interactions of the isoleucine by the disruption of the polar side chain of serine, destabilizing the structure of MINPP1. The overlap of the above-mentioned genotypes and phenotypes is highly improbable by chance. MINPP1 is the only enzyme that hydrolyses inositol phosphates in the endoplasmic reticulum lumen and several studies support its role in stress induced apoptosis. The pathomechanism explaining the disease mechanism remains unknown, however several others genes of the inositol phosphatase metabolism (e.g.,INPP5K,FIG4,INPP5E,ITPR1) are correlated with phenotypes of neurodevelopmental disorders. Taken together, we presentMINPP1as a novel autosomal recessive pontocerebellar hypoplasia gene.
A generic assay for the identification of splicing variants that induce nonsense-mediated decay in Pompe disease
Authors: Bergsma Atze J. , in ’t Groen Stijn L. M. , Catalano Fabio , Yamanaka Manjiro , Takahashi Satoru , Okumiya Toshika , van der Ploeg Ans T. , Pijnappel W. W. M. Pim 
Published: November 2020

AbstractDNA variants affecting mRNA expression and processing in genetic diseases are often missed or poorly characterized. We previously reported a generic assay to identify variants that affect mRNA expression and splicing in Pompe disease, a monogenic disorder caused by deficiency of acid α-glucosidase (GAA). However, this assay could miss mRNA that is subjected to degradation. Here, we inhibited mRNA degradation using cycloheximide and performed unbiased splicing analysis of all GAA exons using exon flanking RT-PCR and exon internal RT-qPCR. In four patients that were suspected of harboring splicing variants but for which aberrant splicing could not be detected in normally growing cells, we detected a total of 10 novel splicing events in cells treated with cycloheximide. In addition, we found that sequences of GAA introns 6 and 12 were naturally included in a subset of transcripts from patients and healthy controls, indicating inefficient canonical splicing. Identification of aberrant splicing caused by the common Asian variant c.546G>T allowed the development of an antisense oligonucleotide that promoted canonical GAA pre-mRNA splicing and elevated GAA enzymatic activity. Our results indicate that this extended generic splicing assay allows the detection of aberrant splicing in cases of mRNA degradation to enable functional analysis of unknown splicing variants and the development of targeted treatment options.
Reconstitution of prospermatogonial specification in vitro from human induced pluripotent stem cells
Authors: Hwang Young Sun , Suzuki Shinnosuke , Seita Yasunari , Ito Jumpei , Sakata Yuka , Aso Hirofumi , Sato Kei , Hermann Brian P. , Sasaki Kotaro 
Published: November 2020

AbstractEstablishment of spermatogonia throughout the fetal and postnatal period is essential for production of spermatozoa and male fertility. Here, we establish a protocol for in vitro reconstitution of human prospermatogonial specification whereby human primordial germ cell (PGC)-like cells differentiated from human induced pluripotent stem cells are further induced into M-prospermatogonia-like cells and T1 prospermatogonia-like cells (T1LCs) using long-term cultured xenogeneic reconstituted testes. Single cell RNA-sequencing is used to delineate the lineage trajectory leading to T1LCs, which closely resemble human T1-prospermatogonia in vivo and exhibit gene expression related to spermatogenesis and diminished proliferation, a hallmark of quiescent T1 prospermatogonia. Notably, this system enables us to visualize the dynamic and stage-specific regulation of transposable elements during human prospermatogonial specification. Together, our findings pave the way for understanding and reconstructing human male germline development in vitro.
Glass-cutting medical images via a mechanical image segmentation method based on crack propagation
Authors: Huang Yaqi , Hu Ge , Ji Changjin , Xiong Huahui 
Published: November 2020

AbstractMedical image segmentation is crucial in diagnosing and treating diseases, but automatic segmentation of complex images is very challenging. Here we present a method, called the crack propagation method (CPM), based on the principles of fracture mechanics. This unique method converts the image segmentation problem into a mechanical one, extracting the boundary information of the target area by tracing the crack propagation on a thin plate with grooves corresponding to the area edge. The greatest advantage of CPM is in segmenting images involving blurred or even discontinuous boundaries, a task difficult to achieve by existing auto-segmentation methods. The segmentation results for synthesized images and real medical images show that CPM has high accuracy in segmenting complex boundaries. With increasing demand for medical imaging in clinical practice and research, this method will show its unique potential.
Genomic landscape and clonal architecture of mouse oral squamous cell carcinomas dictate tumour ecology
Authors: Sequeira Inês , Rashid Mamunur , Tomás Inês M. , Williams Marc J. , Graham Trevor A. , Adams David J. , Vigilante Alessandra , Watt Fiona M. 
Published: November 2020

AbstractTo establish whether 4-nitroquinoline N-oxide-induced carcinogenesis mirrors the heterogeneity of human oral squamous cell carcinoma (OSCC), we have performed genomic analysis of mouse tongue lesions. The mutational signatures of human and mouse OSCC overlap extensively. Mutational burden is higher in moderate dysplasias and invasive SCCs than in hyperplasias and mild dysplasias, although mutations in p53, Notch1 and Fat1 occur in early lesions. Laminin-α3 mutations are associated with tumour invasiveness and Notch1 mutant tumours have an increased immune infiltrate. Computational modelling of clonal dynamics indicates that high genetic heterogeneity may be a feature of those mild dysplasias that are likely to progress to more aggressive tumours. These studies provide a foundation for exploring OSCC evolution, heterogeneity and progression.
Steering magnonic dynamics and permeability at exceptional points in a parity–time symmetric waveguide
Authors: Wang Xi-guang , Guo Guang-hua , Berakdar Jamal 
Published: November 2020

AbstractTuning the magneto optical response and magnetic dynamics are key elements in designing magnetic metamaterials and devices. This theoretical study uncovers a highly effective way of controlling the magnetic permeability via shaping the magnonic properties of coupled magnetic waveguides separated by a nonmagnetic spacer with strong spin–orbit interaction (SOI). We demonstrate how a spacer charge current leads to enhancement of magnetic damping in one waveguide and a decrease in the other, constituting a bias-controlled magnetic parity–time (PT) symmetric system at the verge of the exceptional point where magnetic gains/losses are balanced. We find phenomena inherent to PT-symmetric systems and SOI-driven interfacial structures, including field-controlled magnon power oscillations, nonreciprocal propagation, magnon trapping and enhancement as well as an increased sensitivity to perturbations and abrupt spin reversal. The results point to a new route for designing magnonic waveguides and microstructures with enhanced magnetic response.
Single-phase perovskite oxide with super-exchange induced atomic-scale synergistic active centers enables ultrafast hydrogen evolution
Authors: Dai Jie , Zhu Yinlong , Tahini Hassan A. , Lin Qian , Chen Yu , Guan Daqin , Zhou Chuan , Hu Zhiwei , Lin Hong-Ji , Chan Ting-Shan , Chen Chien-Te , Smith Sean C. , Wang Huanting , Zhou Wei , Shao Zongping 
Published: November 2020

AbstractThe state-of-the-art active HER catalysts in acid media (e.g., Pt) generally lose considerable catalytic performance in alkaline media mainly due to the additional water dissociation step. To address this issue, synergistic hybrid catalysts are always designed by coupling them with metal (hydro)oxides. However, such hybrid systems usually suffer from long reaction path, high cost and complex preparation methods. Here, we discover a single-phase HER catalyst, SrTi0.7Ru0.3O3-δ (STRO) perovskite oxide highlighted with an unusual super-exchange effect, which exhibits excellent HER performance in alkaline media via atomic-scale synergistic active centers. With insights from first-principles calculations, the intrinsically synergistic interplays between multiple active centers in STRO are uncovered to accurately catalyze different elementary steps of alkaline HER; namely, the Ti sites facilitates nearly-barrierless water dissociation, Ru sites function favorably for OH* desorption, and non-metal oxygen sites (i.e., oxygen vacancies/lattice oxygen) promotes optimal H* adsorption and H2 desorption.
Inhibition of aquaporin-3 in macrophages by a monoclonal antibody as potential therapy for liver injury
Authors: Hara-Chikuma Mariko , Tanaka Manami , Verkman Alan S. , Yasui Masato 
Published: November 2020

AbstractAquaporin 3 (AQP3) is a transporter of water, glycerol and hydrogen peroxide (H2O2) that is expressed in various epithelial cells and in macrophages. Here, we developed an anti-AQP3 monoclonal antibody (mAb) that inhibited AQP3-facilitated H2O2 and glycerol transport, and prevented liver injury in experimental animal models. Using AQP3 knockout mice in a model of liver injury and fibrosis produced by CCl4, we obtained evidence for involvement of AQP3 expression in nuclear factor-κB (NF-κB) cell signaling, hepatic oxidative stress and inflammation in macrophages during liver injury. The activated macrophages caused stellate cell activation, leading to liver injury, by a mechanism involving AQP3-mediated H2O2 transport. Administration of an anti-AQP3 mAb, which targeted an extracellular epitope on AQP3, prevented liver injury by inhibition of AQP3-mediated H2O2 transport and macrophage activation. These findings implicate the involvement of macrophage AQP3 in liver injury, and provide evidence for mAb inhibition of AQP3-mediated H2O2 transport as therapy for macrophage-dependent liver injury.