bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reducing hydrological disturbances in absolute gravity observations by combining global hydrological models with a regional run-off model
Authors: Bramanto B , Breili K , Gerlach C , Ophaug V , Gjevestad J G O 
Published: February 2022

SUMMARYSince the beginning of the 1990s, absolute gravity has been observed at several locations in Norway with FG5-type instruments to investigate the temporal gravity changes due to glacial isostatic adjustment (GIA). Previous work suggests that some of the estimated secular gravity trends may be affected by remaining unmodelled geophysical effects, such as the effect of local hydrology. In this work, we compute hydrological gravity effects from global hydrological models for the far zone and a combination of regional run-off models and modelling of residual hydrological effects for the near zone. The method developed in this paper is first tested at the geodetic observatory in Wettzell, Germany, where both high-resolution superconducting gravimeter data as well as a regional hydrological model are available. Next, the method is transferred to two Norwegian gravity sites (NMBU and TRYC), with long time-series of frequent absolute gravity observations using FG5-226. At these sites, we investigate the impact of the hydrological gravity correction on data variability as well as estimated secular gravity trends. We find that the data variability is reduced by up to 40 per cent when applying the modelled hydrological gravity effect at TRYC. The reduction is less at NMBU where the amplitude of the hydrological signal and in consequence also the signal-to-noise ratio are smaller. We also note that it is challenging to determine the near zone residual hydrological effects without carefully taking into account the hydrogeological setting of the area for modelling such effects. When utilizing the long corrected absolute gravity series to determine the gravity trends, we find that the estimated trends are not significantly different from the uncorrected observations. However, the uncertainty of the estimated trends is reduced significantly for a limited corrected gravity series. We further suggest repeatability analysis of the absolute gravimeter. From the long time-series at NMBU we find a significant step coinciding with hardware replacement. We find that the fit between observed and modelled secular trends improves when introducing the step. Further analysis of gravity rates at other stations is needed to verify the existence of a real instrumental offset.
Engineering CAR-NK cells: how to tune innate killer cells for cancer immunotherapy
Authors: Schmidt Dayane , Ebrahimabadi Sima , Gomes Kauan Ribeiro de Sena , de Moura Aguiar Graziela , Cariati Tirapelle Mariane , Nacasaki Silvestre Renata , de Azevedo Júlia Teixeira Cottas , Tadeu Covas Dimas , Picanço-Castro Virginia 
Published: February 2022

AbstractCell therapy is an innovative approach that permits numerous possibilities in the field of cancer treatment. CAR-T cells have been successfully used in patients with hematologic relapsed/refractory. However, the need for autologous sources for T cells is still a major drawback. CAR-NK cells have emerged as a promising resource using allogeneic cells that could be established as an off-the-shelf treatment. NK cells can be obtained from various sources, such as peripheral blood (PB), bone marrow, umbilical cord blood (CB), and induced pluripotent stem cells (iPSC), as well as cell lines. Genetic engineering of NK cells to express different CAR constructs for hematological cancers and solid tumors has shown promising preclinical results and they are currently being explored in multiple clinical trials. Several strategies have been employed to improve CAR-NK-cell expansion and cytotoxicity efficiency. In this article, we review the latest achievements and progress made in the field of CAR-NK-cell therapy.
Descending colon cancer in a patient with situs inversus totalis: a case report and literature review
Authors: Cheng Long , Feng Yi-Guo , He Lin , Xie Jie-Bin , Zhou Cen-Ji , Liu Jian-Jun , Wang Pan 
Published: February 2022

Abstract
Situs inversus totalis (SIT) is a congenital disorder of anatomical position, and the operation of patients with total visceral inversion often brings great challenges to surgeons. Although there have been previously documented on patients with SIT and colonic cancer, this is the first case report of descending colon cancer in patient with SIT. The current report presents a case of a 67-year-old female patient with descending colon cancer and SIT. After preoperative preparation and discussion, open left hemicolectomy was performed for the patient. The postoperative recovery of the patient was smooth; however, there was a mild lymphatic leakage in the patient, which was cured by conservative treatment for 5 days. The patient was discharged on postoperative Day 10. There was no tumor recurrence or other discomfort in 1 year follow-up period.
Variability of methanol and OH masers in G339.62−0.12
Authors: Seidu Mavis , Goedhart S , van der Walt D J 
Published: February 2022

ABSTRACT
The study of the periodic variability of masers has greatly increased after the discovery of periodic class II methanol (CH3OH) masers. Currently, more than 20 masers associated with various high-mass star-forming regions have shown this interesting behaviour. Since the mainline OH masers are pumped under similar conditions as that of the class II methanol masers, it becomes necessary to also search for periodic behaviour of OH masers. In this paper, we present the results of the 6.7 GHz methanol and mainline OH masers associated with G339.62−0.12 observed using the 26 m HartRAO single-dish and the KAT-7 telescopes, respectively. We find evidence of variability, however, periodic variability is clearly visible for the masers that are blue-shifted from the systemic velocity ($\mathrm{\mathit{ \mathit{V}}_{lsr} = -34.2~km\, s^{-1}}$ ). Using the Lomb–Scargle periodogram, the blue-shifted methanol masers have periods of 208 ± 4 d while the blue-shifted OH 1665 and 1667 MHz masers have average periods of 208 d. Further analysis suggests that the maser profiles are similar, having a delay of 5 d (∼870 au) between the 6.7 GHz methanol maser and the 1667 MHz OH maser, as well as a delay of 15 d (∼2600 au) between the 6.7 GHz methanol maser and the 1665 MHz OH maser. To further interpret the observed periodic behaviour as well as the similarities found in the profiles of these masers will require high-resolution observations of the OH and methanol masers and high-resolution mm/sub-mm observations of the G339.62−0.12 source.
Long-term general relativistic magnetohydrodynamics simulations of magnetic field in isolated neutron stars
Authors: Sur Ankan , Cook William , Radice David , Haskell Brynmor , Bernuzzi Sebastiano 
Published: February 2022

ABSTRACT
Strong magnetic fields play an important role in powering the emission of neutron stars. Nevertheless, a full understanding of the interior configuration of the field remains elusive. In this work, we present general relativistic magnetohydrodynamics (MHD) simulations of the magnetic field evolution in neutron stars lasting ${\sim } {880}\,$ms (∼6.5 Alfvén crossing periods) and up to resolutions of $0.1155\,$km using Athena++. We explore two different initial conditions, one with purely poloidal magnetic field and the other with a dominant toroidal component, and study the poloidal and toroidal field energies, the growth times of the various instability-driven oscillation modes, and turbulence. We find that the purely poloidal setup generates a toroidal field, which later decays exponentially reaching $1{{\ \rm per\ cent}}$ of the total magnetic energy, showing no evidence of reaching equilibrium. The initially stronger toroidal field setup, on the other hand, loses up to 20 per cent of toroidal energy and maintains this state till the end of our simulation. We also explore the hypothesis, drawn from previous MHD simulations, that turbulence plays an important role in the quasi-equilibrium state. An analysis of the spectra in our higher resolution setups reveals, however, that in most cases we are not observing turbulence at small scales, but rather a noisy velocity field inside the star. We also observe that the majority of the magnetic energy gets dissipated as heat increasing the internal energy of the star, while a small fraction gets radiated away as electromagnetic radiation.
Potential of the prognostic nutritional index to determine the risk factor for severe infection in elderly patients with rheumatoid arthritis
Authors: Isoda Kentaro , Tsuji Shigeyoshi , Harada Yoshinori , Yoshimura Maiko , Nakabayashi Akihiko , Sato Megumi , Nagano Hiromichi , Kim Dong-seop , Hashimoto Jun , Ohshima Shiro 
Published: February 2022

ABSTRACTObjectiveTo investigate the influence of nutritional status on severe infection complications in patients with rheumatoid arthritis (RA)MethodsThis retrospective cohort study on 2108 patients with RA evaluated the prognostic nutritional index (PNI) as an index of nutritional status. Patients were classified into the high or low PNI group according to the cutoff PNI value (45.0). Based on propensity score matching analysis, 360 patients in each group were selected for comparing the incidence of serious infection, clinical findings, and PNI scores.ResultsThe incidence of infection was significantly higher in the low PNI group than in the high PNI group (p &lt; 0.001). The occurrence rate of infectious complication at 104 weeks was significantly higher in the low PNI (&lt;45.0) group than in the high PNI group (p &lt; 0.001). The incidence of infection was particularly high in elderly patients (≥65 years) with a low PNI, but the incidence in elderly patients with a high PNI was similar to that in nonelderly patients with a high PNI.ConclusionsPatients with RA and malnutrition had a higher incidence of severe infection; thus, evaluating and managing nutritional status is necessary for the appropriate and safe treatment of elderly patients with RA.
Brief self-exercise education for adults with chronic knee pain: A randomized controlled trial
Authors: Jinnouchi Hiroshige , Kitamura Akihiko , Matsudaira Ko , Kakihana Hironobu , Oka Hiroyuki , Yamagishi Kazumasa , Kiyama Masahiko , Iso Hiroyasu 
Published: February 2022

ABSTRACTObjectivesEffective brief instructions for self-management of chronic knee pain are needed.MethodsForty-six participants with chronic knee pain were randomly allocated into two programmes: material-based education alone or brief self-exercise education (brief-See), which comprised a 100-minute instruction for self-exercise combined with compact pain education. Total function (KOOS4, 4-subscale average of knee injury and osteoarthritis outcome score), pain intensity (NRS, numeric rating scale), self-efficacy (PSEQ, pain self-efficacy questionnaire), and health-related quality of life (EQ-5D, European quality of life-5 dimensions) were evaluated at baseline and 4 and 12 weeks after the initial intervention. A generalized mixed linear model estimated average group differences in changes from baseline and 95% confidence intervals (95% CIs) using intention-to-treat principle.ResultsCompared to material-based education alone, the brief-See provided significant additional improvements of 9.4% (95% CI: 2.3 to 16.4) on the KOOS4 and 5.4 points (0.3 to 10.4) on the PSEQ at 12 weeks but did not on the NRS and EQ-5D. Adherence and satisfaction were favourable in the brief-See without any notable adverse event.ConclusionsAdding the brief-See to material-based education could be more acceptable and restore total function and self-efficacy, which could contribute to the self-management of chronic knee pain in primary care.
A case of TAFRO syndrome maintained in remission for 5 years after discontinuation of tocilizumab
Authors: Yamagami Keiko , Hanioka Yusuke , Yao Shuhei , Nakamura Ryota , Nakamura Tomoyuki , Ishii Naomi , Goto Hitoshi 
Published: February 2022

ABSTRACT
TAFRO syndrome is a subtype of idiopathic multicentric Castleman’s disease (iMCD) that is characterised by thrombocytopenia, generalised oedema, fever, bone marrow fibrosis, renal failure, and organ enlargement and has a poor prognosis. The prognosis of TAFRO syndrome is worse than that of iMCD-not otherwise specified, with a high mortality rate. There are only a few long-term follow-up reports after remission of TAFRO syndrome with tocilizumab (TCZ) treatment in a patient in whom all drugs were discontinued after attaining sustained remission. Here, we report a case in which interleukin-6 negativity was confirmed and remission was maintained without relapse for 5 years after all drug treatments, including TCZ, were discontinued.
Aseptic meningitis as initial presentation of subclinical Sjögren’s syndrome: Could the cerebrospinal fluid anti-Ro/SSA and anti-La/SSB antibody system be the culprit?
Authors: Kurotaki Keigo , Fujita Masashi , Aizawa Tomomi , Tsugawa Koji , Tanaka Hiroshi 
Published: February 2022

Abstract
Aseptic meningitis sometimes occurs as a consequence of central nervous system (CNS) involvement in patients with primary Sjögren’s syndrome (SS), even in paediatric-onset cases. However, little information is available regarding the pathological role of CSF anti-Ro/SSA and anti-La/SSB antibodies in the CNS involvement in patients with primary SS. We experienced an 18-year-old adolescent female with a 7-year history of suspicion of subclinical SS who subsequently developed aseptic meningitis as an initial presentation of probable SS. Her CSF exhibited marked elevation of anti-Ro/SSA and anti-La/SSB antibodies. When compared to her CSF IgG/serum IgG ratio (0.0058), her CSF/serum ratios of anti-Ro/SSA and anti-La/SSB antibody titres were higher (0.448 and 0.068, respectively; these were 77.5 and 11.7 times higher than that of IgG, respectively), suggesting that regional production of these antibodies was attributable, at least partly, to the development of meningitis. After the initiation of prednisolone treatment, her clinical manifestations promptly subsided. Since the clinical and pathological roles of the Ro/SSA antibody system in several autoimmune conditions have been postulated, our clinical observation may add novel insight to this theory.
Depth normalization of small RNA sequencing: using data and biology to select a suitable method
Authors: Düren Yannick , Lederer Johannes , Qin Li-Xuan 
Published: February 2022

Abstract
Deep sequencing has become one of the most popular tools for transcriptome profiling in biomedical studies. While an abundance of computational methods exists for ‘normalizing’ sequencing data to remove unwanted between-sample variations due to experimental handling, there is no consensus on which normalization is the most suitable for a given data set. To address this problem, we developed ‘DANA’—an approach for assessing the performance of normalization methods for microRNA sequencing data based on biology-motivated and data-driven metrics. Our approach takes advantage of well-known biological features of microRNAs for their expression pattern and chromosomal clustering to simultaneously assess (i) how effectively normalization removes handling artifacts and (ii) how aptly normalization preserves biological signals. With DANA, we confirm that the performance of eight commonly used normalization methods vary widely across different data sets and provide guidance for selecting a suitable method for the data at hand. Hence, it should be adopted as a routine preprocessing step (preceding normalization) for microRNA sequencing data analysis. DANA is implemented in R and publicly available at https://github.com/LXQin/DANA.
Discovery of potent and versatile CRISPR–Cas9 inhibitors engineered for chemically controllable genome editing
Authors: Song Guoxu , Zhang Fei , Tian Chunhong , Gao Xing , Zhu Xiaoxiao , Fan Dongdong , Tian Yong 
Published: February 2022

AbstractAnti-CRISPR (Acr) proteins are encoded by many mobile genetic elements (MGEs) such as phages and plasmids to combat CRISPR–Cas adaptive immune systems employed by prokaryotes, which provide powerful tools for CRISPR–Cas-based applications. Here, we discovered nine distinct type II-A anti-CRISPR (AcrIIA24–32) families from Streptococcus MGEs and found that most Acrs can potently inhibit type II-A Cas9 orthologs from Streptococcus (SpyCas9, St1Cas9 or St3Cas9) in bacterial and human cells. Among these Acrs, AcrIIA26, AcrIIA27, AcrIIA30 and AcrIIA31 are able to block Cas9 binding to DNA, while AcrIIA24 abrogates DNA cleavage by Cas9. Notably, AcrIIA25.1 and AcrIIA32.1 can inhibit both DNA binding and DNA cleavage activities of SpyCas9, exhibiting unique anti-CRISPR characteristics. Importantly, we developed several chemically inducible anti-CRISPR variants based on AcrIIA25.1 and AcrIIA32.1 by comprising hybrids of Acr protein and the 4-hydroxytamoxifen-responsive intein, which enabled post-translational control of CRISPR–Cas9-mediated genome editing in human cells. Taken together, our work expands the diversity of type II-A anti-CRISPR families and the toolbox of Acr proteins for the chemically inducible control of Cas9-based applications.
Role of the cellular factor CTCF in the regulation of bovine leukemia virus latency and three-dimensional chromatin organization
Authors: Bellefroid Maxime , Rodari Anthony , Galais Mathilde , Krijger Peter H L , Tjalsma Sjoerd J D , Nestola Lorena , Plant Estelle , Vos Erica S M , Cristinelli Sara , Van Driessche Benoit , Vanhulle Caroline , Ait-Ammar Amina , Burny Arsène , Ciuffi Angela , de Laat Wouter , Van Lint Carine 
Published: February 2022

Abstract
Bovine leukemia virus (BLV)-induced tumoral development is a multifactorial phenomenon that remains incompletely understood. Here, we highlight the critical role of the cellular CCCTC-binding factor (CTCF) both in the regulation of BLV transcriptional activities and in the deregulation of the three-dimensional (3D) chromatin architecture surrounding the BLV integration site. We demonstrated the in vivo recruitment of CTCF to three conserved CTCF binding motifs along the provirus. Next, we showed that CTCF localized to regions of transitions in the histone modifications profile along the BLV genome and that it is implicated in the repression of the 5′Long Terminal Repeat (LTR) promoter activity, thereby contributing to viral latency, while favoring the 3′LTR promoter activity. Finally, we demonstrated that BLV integration deregulated the host cellular 3D chromatin organization through the formation of viral/host chromatin loops. Altogether, our results highlight CTCF as a new critical effector of BLV transcriptional regulation and BLV-induced physiopathology.
AT-hook peptides bind the major and minor groove of AT-rich DNA duplexes
Authors: Garabedian Alyssa , Jeanne Dit Fouque Kevin , Chapagain Prem P , Leng Fenfei , Fernandez-Lima Francisco 
Published: February 2022

AbstractThe mammalian high mobility group protein AT-hook 2 (HMGA2) houses three motifs that preferentially bind short stretches of AT-rich DNA regions. These DNA binding motifs, known as ‘AT-hooks’, are traditionally characterized as being unstructured. Upon binding to AT-rich DNA, they form ordered assemblies. It is this disordered-to-ordered transition that has implicated HMGA2 as a protein actively involved in many biological processes, with abnormal HMGA expression linked to a variety of health problems including diabetes, obesity, and oncogenesis. In the current work, the solution binding dynamics of the three ‘AT-hook’ peptides (ATHPs) with AT-rich DNA hairpin substrates were studied using DNA UV melting studies, fluorescence spectroscopy, native ion mobility spectrometry-mass spectrometry (IMS-MS), solution isothermal titration calorimetry (ITC) and molecular modeling. Results showed that the ATHPs bind to the DNA to form a single, 1:1 and 2:1, ‘key-locked’ conformational ensemble. The molecular models showed that 1:1 and 2:1 complex formation is driven by the capacity of the ATHPs to bind to the minor and major grooves of the AT-rich DNA oligomers. Complementary solution ITC results confirmed that the 2:1 stoichiometry of ATHP: DNA is originated under native conditions in solution.
Determinants of heritable gene silencing for KRAB-dCas9 + DNMT3 and Ezh2-dCas9 + DNMT3 hit-and-run epigenome editing
Authors: O’Geen Henriette , Tomkova Marketa , Combs Jacquelyn A , Tilley Emma K , Segal David J 
Published: February 2022

Abstract
Precision epigenome editing has gained significant attention as a method to modulate gene expression without altering genetic information. However, a major limiting factor has been that the gene expression changes are often transient, unlike the life-long epigenetic changes that occur frequently in nature. Here, we systematically interrogate the ability of CRISPR/dCas9-based epigenome editors (Epi-dCas9) to engineer persistent epigenetic silencing. We elucidated cis regulatory features that contribute to the differential stability of epigenetic reprogramming, such as the active transcription histone marks H3K36me3 and H3K27ac strongly correlating with resistance to short-term repression and resistance to long-term silencing, respectively. H3K27ac inversely correlates with increased DNA methylation. Interestingly, the dependance on H3K27ac was only observed when a combination of KRAB-dCas9 and targetable DNA methyltransferases (DNMT3A-dCas9 + DNMT3L) was used, but not when KRAB was replaced with the targetable H3K27 histone methyltransferase Ezh2. In addition, programmable Ezh2/DNMT3A + L treatment demonstrated enhanced engineering of localized DNA methylation and was not sensitive to a divergent chromatin state. Our results highlight the importance of local chromatin features for heritability of programmable silencing and the differential response to KRAB- and Ezh2-based epigenetic editing platforms. The information gained in this study provides fundamental insights into understanding contextual cues to more predictably engineer persistent silencing.