bluuebunny/crossref_metadata_2025_split huggingface dataset:
B-cell lymphoma 6 alleviates nonalcoholic fatty liver disease in mice through suppression of fatty acid transporter CD36
Authors: Zhang Hao , Li Yue , Zhang Chao , Huang Kun , Zhao Jing , Le Sheng , Jiang Lang , Liu Hao , Yang Peiwen , Xiao Xiaoyue , Yu Jizhang , Wu Jie , Ye Ping , Xia Jiahong 
Published: April 2022

AbstractNonalcoholic fatty liver disease (NAFLD) is an ubiquitous disease that exists across a wide spectrum ranging from steatosis, steatohepatitis, advanced fibrosis, and liver cirrhosis. Hallmarks of NAFLD are lipid accumulation, insulin resistance, and chronic low-grade inflammation. However, there currently are no medications approved for NAFLD. B-cell lymphoma 6 (BCL6) is a transcriptional inhibitor that is vital for germinal center B-cell formation. Our study identified BCL6 as a critical modulator of hepatic lipid metabolism and appears to contribute to the initiation and progression of NAFLD. In our research, we induced hepatic BCL6 overexpression using adeno-associated virus (AAV), as well as conditional liver-specific BCL6 knockout mice (BCL6-CKO). With these models, we noted that BCL6 overexpression improved insulin resistance and hepatic steatosis in mice models maintained on a HFD diet. Conversely, these parameters worsened in the livers of mice with downregulated BCL6 levels. Mechanistically, the translocase fatty acid CD36 was determined to be a transcriptional target of BCL6 that influences its role in hepatic steatosis. BCL6 bound directly to the CD36 promoter region, restraining CD36 transcription under physiological conditions. We conclude that the hepatocyte BCL6 inhibits the NAFLD progression in mice, including deranged lipid accumulation and glucose metabolism, through a CD36-dependent manner. These results indicate that BCL6 may potentially be targeted in NAFLD treatment.
Bloom syndrome helicase contributes to germ line development and longevity in zebrafish
Authors: Annus Tamás , Müller Dalma , Jezsó Bálint , Ullaga György , Németh Barnabás , Harami Gábor M. , Orbán László , Kovács Mihály , Varga Máté 
Published: April 2022

AbstractRecQ helicases—also known as the “guardians of the genome”—play crucial roles in genome integrity maintenance through their involvement in various DNA metabolic pathways. Aside from being conserved from bacteria to vertebrates, their importance is also reflected in the fact that in humans impaired function of multiple RecQ helicase orthologs are known to cause severe sets of problems, including Bloom, Werner, or Rothmund-Thomson syndromes. Our aim was to create and characterize a zebrafish (Danio rerio) disease model for Bloom syndrome, a recessive autosomal disorder. In humans, this syndrome is characterized by short stature, skin rashes, reduced fertility, increased risk of carcinogenesis, and shortened life expectancy brought on by genomic instability. We show that zebrafish blm mutants recapitulate major hallmarks of the human disease, such as shortened lifespan and reduced fertility. Moreover, similarly to other factors involved in DNA repair, some functions of zebrafish Blm bear additional importance in germ line development, and consequently in sex differentiation. Unlike fanc genes and rad51, however, blm appears to affect its function independent of tp53. Therefore, our model will be a valuable tool for further understanding the developmental and molecular attributes of this rare disease, along with providing novel insights into the role of genome maintenance proteins in somatic DNA repair and fertility.
METTL3-mediated m6A modification of STEAP2 mRNA inhibits papillary thyroid cancer progress by blocking the Hedgehog signaling pathway and epithelial-to-mesenchymal transition
Authors: Zhu Yue , Peng Xinzhi , Zhou Qianlei , Tan Langping , Zhang Cheng , Lin Shaojian , Long Miaoyun 
Published: April 2022

AbstractPapillary thyroid cancer (PTC) is a common endocrine system malignancy all over the world. Aberrant expression of six transmembrane epithelial antigen of the prostate 2 (STEAP2) has been functionally associated with cancer progression in many cancers. Nevertheless, its biological function in PTC is still unclear. Here, we found that PTC tissues had preferentially downregulated STEAP2 as compared with noncancerous tissues. Low STEAP2 expression correlated with aggressive clinicopathological characteristics and dismal prognosis in patients with PTC. We performed gain- and loss-of-function experiments, including cell proliferation assay (Cell Counting Kit-8 assay), EdU (5-ethynyl-2′-deoxyuridine) and colony formation assays, transwell migration, and invasion assays, and constructed a nude mouse xenograft tumor model. The results demonstrated thatSTEAP2overexpression inhibited PTC cell proliferation, migration, and invasion in vitro and inhibited lung metastasis and tumorigenicity in vivo. Conversely, silencingSTEAP2yielded the opposite results in vitro. Mechanistically, bioinformatics analysis combined with validation experiments identifiedSTEAP2as the downstream target of methyltransferase-like 3 (METTL3)-mediated N6-methyladenosine (m6A) modification. METTL3 stabilizedSTEAP2mRNA and regulated STEAP2 expression positively in an m6A-dependent manner. We also showed that m6A-mediatedSTEAP2mRNA translation initiation relied on a pathway dependent on the m6A reader protein YTHDF1. Rescue experiments revealed that silencingSTEAP2partially rescued the tumor-suppressive phenotype induced by METTL3 overexpression. Lastly, we verified that the METTL3–STEAP2 axis functions as an inhibitor in PTC by suppressing epithelial–mesenchymal transition and the Hedgehog signaling pathway. Taken together, these findings strongly suggest that METTL3-mediatedSTEAP2m6A modification plays a critical tumor-suppressive role in PTC progression. The METTL3–STEAP2 axis may be a potential therapeutic molecular target against PTC.
circFAM120B functions as a tumor suppressor in esophageal squamous cell carcinoma via the miR-661/PPM1L axis and the PKR/p38 MAPK/EMT pathway
Authors: Song Huan , Tian Dan , Sun Jian , Mao Xuhua , Kong Weimin , Xu Dian , Ji Ye , Qiu Beibei , Zhan Mengyao , Wang Jianming 
Published: April 2022

AbstractExtensive changes of circRNA expression underscore their essential contributions to multiple hallmarks of cancers; however, their functions and mechanisms of action in esophageal squamous cell carcinoma (ESCC) remain undetermined. Here, we adopted a three-stage approach by first screening for significantly differentially expressed circRNAs in ESCC and performing an external validation study, followed by the functional analyses. The properties of circRNAs were evaluated using Sanger sequencing, RNase R digestion, actinomycin D treatment, subcellular localization analysis, and fluorescence in situ hybridization. Target transcripts were predicted using online tools and verified by dual-luciferase, RNA immunoprecipitation, qRT-PCR, and western blot. Biotin-labeled RNA-protein pull-down, mass spectrometry, and RNA immunoprecipitation were employed to identify proteins interacting with circRNAs. Gain- and loss-of-function experiments were performed to uncover the roles of circRNAs, their target genes, and binding proteins in the proliferation, metastasis, and invasion. We observed that circFAM120B (hsa_circ_0001666) was frequently downregulated in cancer tissues and patient plasma, and its expression level was related to overall survival in ESCC patients. Overexpression of circFAM120B inhibited the proliferation, metastasis, and invasion of ESCC while silencing it enhanced malignant phenotypes. Mechanistically, circFAM120B was predominantly located in the cytoplasm, guarantying its sponging for miR-661 to restore the expression of PPM1L, a tumor suppressor. We observed that circFAM120B could reduce the stability of RNA-dependent protein kinase (PKR) by promoting its ubiquitination-dependent degradation and subsequently regulating the p38 MAPK signaling pathway, resulting in the repression of EMTs in ESCC cells. Our findings suggest that circFAM120B is a promising biomarker of ESCC, which acts as a tumor suppressor via the circFAM120B/miR-661/PPM1L axis and PKR/p38 MAPK/EMT pathway, supporting its significance as a candidate therapeutic target.
An obesogenic feedforward loop involving PPARγ, acyl-CoA binding protein and GABAA receptor
Authors: Anagnostopoulos Gerasimos , Motiño Omar , Li Sijing , Carbonnier Vincent , Chen Hui , Sica Valentina , Durand Sylvère , Bourgin Mélanie , Aprahamian Fanny , Nirmalathasan Nitharsshini , Donne Romain , Desdouets Chantal , Sola Marcelo Simon , Kotta Konstantina , Montégut Léa , Lambertucci Flavia , Surdez Didier , Sandrine Grossetête , Delattre Olivier , Maiuri Maria Chiara , Bravo-San Pedro José Manuel , Martins Isabelle , Kroemer Guido 
Published: April 2022

AbstractAcyl-coenzyme-A-binding protein (ACBP), also known as a diazepam-binding inhibitor (DBI), is a potent stimulator of appetite and lipogenesis. Bioinformatic analyses combined with systematic screens revealed that peroxisome proliferator-activated receptor gamma (PPARγ) is the transcription factor that best explains the ACBP/DBI upregulation in metabolically active organs including the liver and adipose tissue. The PPARγ agonist rosiglitazone-induced ACBP/DBI upregulation, as well as weight gain, that could be prevented by knockout of Acbp/Dbi in mice. Moreover, liver-specific knockdown of Pparg prevented the high-fat diet (HFD)-induced upregulation of circulating ACBP/DBI levels and reduced body weight gain. Conversely, knockout of Acbp/Dbi prevented the HFD-induced upregulation of PPARγ. Notably, a single amino acid substitution (F77I) in the γ2 subunit of gamma-aminobutyric acid A receptor (GABAAR), which abolishes ACBP/DBI binding to this receptor, prevented the HFD-induced weight gain, as well as the HFD-induced upregulation of ACBP/DBI, GABAAR γ2, and PPARγ. Based on these results, we postulate the existence of an obesogenic feedforward loop relying on ACBP/DBI, GABAAR, and PPARγ. Interruption of this vicious cycle, at any level, indistinguishably mitigates HFD-induced weight gain, hepatosteatosis, and hyperglycemia.
Identification of potent inhibitors of NEK7 protein using a comprehensive computational approach
Authors: Aziz Mubashir , Ejaz Syeda Abida , Tamam Nissren , Siddique Farhan , Riaz Naheed , Qais Faizan Abul , Chtita Samir , Iqbal Jamshed 
Published: April 2022

AbstractNIMA related Kinases (NEK7) plays an important role in spindle assembly and mitotic division of the cell. Over expression of NEK7 leads to the progression of different cancers and associated malignancies. It is becoming the next wave of targets for the development of selective and potent anti-cancerous agents. The current study is the first comprehensive computational approach to identify potent inhibitors of NEK7 protein. For this purpose, previously identified anti-inflammatory compound i.e., Phenylcarbamoylpiperidine-1,2,4-triazole amide derivatives by our own group were selected for their anti-cancer potential via detailed Computational studies. Initially, the density functional theory (DFT) calculations were carried out using Gaussian 09 software which provided information about the compounds' stability and reactivity. Furthermore, Autodock suite and Molecular Operating Environment (MOE) software’s were used to dock the ligand database into the active pocket of the NEK7 protein. Both software performances were compared in terms of sampling power and scoring power. During the analysis, Autodock results were found to be more reproducible, implying that this software outperforms the MOE. The majority of the compounds, including M7, and M12 showed excellent binding energies and formed stable protein–ligand complexes with docking scores of − 29.66 kJ/mol and − 31.38 kJ/mol, respectively. The results were validated by molecular dynamics simulation studies where the stability and conformational transformation of the best protein–ligand complex were justified on the basis of RMSD and RMSF trajectory analysis. The drug likeness properties and toxicity profile of all compounds were determined by ADMETlab 2.0. Furthermore, the anticancer potential of the potent compounds were confirmed by cell viability (MTT) assay. This study suggested that selected compounds can be further investigated at molecular level and evaluated for cancer treatment and associated malignancies.
Biochemical abnormalities among patients referred for celiac disease antibody blood testing in a primary health care setting
Authors: Kårhus Line Lund , Kriegbaum Margit , Grand Mia Klinten , Lind Bent Struer , Møllehave Line Tang , Rumessen Jüri J. , Andersen Christen Lykkegaard , Linneberg Allan 
Published: April 2022

AbstractTo investigate possible biochemical abnormalities associated with celiac disease (CD) antibody positivity in a primary health care setting and thereby identify predictors that could potentially reduce diagnostic delay and underdiagnosis of CD. This observational cohort study included measurements of CD antibodies in the Copenhagen Primary Care Laboratory (CopLab) database from 2000 to 2015; CD antibody positivity was defined as tissue transglutaminase antibody IgA or IgG ≥ 7 kU/L and/or deamidated gliadin peptide antibody IgG ≥ 10 kU/L. Individuals with a prior diagnosis of CD were excluded. We examined differences between individuals with positive and negative CD antibody tests regarding the results of biochemical tests performed six months before and one month after the date of the CD antibody test. We identified 76,265 measurements of CD antibodies during 2000–2015, and 57,061 individuals met the inclusion criteria (706 antibody-positive and 56,355 antibody-negative). We found lower ferritin, hemoglobin, cobalamin and folic acid levels and higher levels of transferrin, ALAT (alanine transaminase), and alkaline phosphate among individuals with a positive CD antibody test. Furthermore, we illustrated more measurements below the sex-specific reference intervals for hemoglobin, mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), ferritin, cobalamin and folic acid among individuals with a positive CD antibody test. This study identified several biochemical abnormalities associated with CD antibody positivity among individuals referred to CD antibody testing. The pattern of abnormalities suggested that micronutrient deficiencies were prevalent among CD antibody-positive individuals, confirming malabsorption as a sign of CD. These findings illustrate the possibility of reducing diagnostic delay and underdiagnosis of CD.
The gut microbial metabolite formate exacerbates colorectal cancer progression
Authors: Ternes Dominik , Tsenkova Mina , Pozdeev Vitaly Igorevich , Meyers Marianne , Koncina Eric , Atatri Sura , Schmitz Martine , Karta Jessica , Schmoetten Maryse , Heinken Almut , Rodriguez Fabien , Delbrouck Catherine , Gaigneaux Anthoula , Ginolhac Aurelien , Nguyen Tam Thuy Dan , Grandmougin Lea , Frachet-Bour Audrey , Martin-Gallausiaux Camille , Pacheco Maria , Neuberger-Castillo Lorie , Miranda Paulo , Zuegel Nikolaus , Ferrand Jean-Yves , Gantenbein Manon , Sauter Thomas , Slade Daniel Joseph , Thiele Ines , Meiser Johannes , Haan Serge , Wilmes Paul , Letellier Elisabeth 
Published: April 2022

AbstractThe gut microbiome is a key player in the immunomodulatory and protumorigenic microenvironment during colorectal cancer (CRC), as different gut-derived bacteria can induce tumour growth. However, the crosstalk between the gut microbiome and the host in relation to tumour cell metabolism remains largely unexplored. Here we show that formate, a metabolite produced by the CRC-associated bacterium Fusobacterium nucleatum, promotes CRC development. We describe molecular signatures linking CRC phenotypes with Fusobacterium abundance. Cocultures of F. nucleatum with patient-derived CRC cells display protumorigenic effects, along with a metabolic shift towards increased formate secretion and cancer glutamine metabolism. We further show that microbiome-derived formate drives CRC tumour invasion by triggering AhR signalling, while increasing cancer stemness. Finally, F. nucleatum or formate treatment in mice leads to increased tumour incidence or size, and Th17 cell expansion, which can favour proinflammatory profiles. Moving beyond observational studies, we identify formate as a gut-derived oncometabolite that is relevant for CRC progression.
The Onset–Offset N1–P2 Cortical Auditory Evoked Response in Individuals With High-Frequency Sensorineural Hearing Loss: Responses to High- and Low-Frequency Narrowband Noise
Authors: Gonzalez Jennifer E. , Musiek Frank E. 
Published: April 2022

Purpose:
This study aimed to determine whether onset–offset N1–P2 auditory evoked responses differ in amplitude, latency, and offset-to-onset trough-to-peak N1–P2 amplitude ratios (OOAR) between normal hearing (NH) sensitivity and moderate high-frequency sensorineural hearing loss (HFSNHL) groups when stimuli target regions of peripheral hearing sensitivity where the groups are in the normal range (i.e., 500 Hz) versus where they differ regarding presence of hearing loss (i.e., 4000 Hz).

Method:

Onset–offset N1–P2 auditory evoked responses were measured from 10 participants with normal hearing sensitivity and seven participants with moderate HFSNHL using 500-Hz and 4000-Hz narrowband noise (NBN) stimuli. Stimuli were 2000 ms with 40-ms rise-fall times presented at 50 dB SL referenced to stimulus behavioral thresholds. Amplitudes and latencies were analyzed for N1 and P2 onset and offset components via repeated measures analysis of variance (ANOVA). OOARs were compared between groups using one-way ANOVA and across stimuli per group using paired samples
t
tests.

Results:

Despite dB SPL stimulus presentation differences between groups, there were no significant differences in individual/absolute amplitude and latency waveform components between groups for either stimulus. Derived comparative calculations of OOAR for 4000-Hz NBN were significantly larger (
p
< .025; NH: .39; HFSNHL: .62) for the group with HFSNHL than the group with NH sensitivity; 500-Hz NBN OOAR did not reach significance. OOARs revealed no significant difference between stimuli for the group with normal hearing sensitivity, with .38 OOAR for both stimuli (
p
= .961). OOAR comparisons for the HFSNHL group across stimuli were significant (
p
= .012), with the 4000-Hz NBN OOAR being nearly double the size of the 500-Hz NBN OOAR.

Conclusions:
OOARs may provide insight to the balance of excitatory and inhibitory neural firing in the central auditory nervous system (CANS). Larger OOARs may be a biomarker of reduced CANS inhibition, perhaps indicative of a homeostatic central auditory gain mechanism.
Application of the Behavior Change Wheel Within the Context of Internet-Based Cognitive Behavioral Therapy for Tinnitus Management
Authors: Beukes Eldré W. , Manchaiah Vinaya , Andersson Gerhard , Maidment David W. 
Published: April 2022

Purpose:
Although experiencing tinnitus can lead to many difficulties, these can be reduced by using techniques derived from cognitive behavioral therapy. Internet-based cognitive behavioral therapy (ICBT) has been developed to provide an accessible intervention. The aim of this study was to describe how ICBT can facilitate tinnitus management by identifying the active ingredients of the intervention from the perspective of health behavior change.

Method:
The ICBT intervention was evaluated using the Behavior Change Wheel in eight steps across the following three stages: (1) understanding the behavior, (2) identifying intervention options, and (3) identifying content and implementation options.

Results:
Target behaviors identified to reduce tinnitus distress, as well as additional problems associated with tinnitus, included goal setting, an increased understanding of tinnitus, encouraging deep breathing and progressive muscle relaxation, identifying and restructuring unhelpful thoughts, engaging in positive imagery, and reducing avoidance behaviors. ICBT provided the required components for individuals to be physically and psychologically capable of adapting to tinnitus, providing social and environmental opportunities to manage hearing loss through practice and training, and facilitated automatic and reflective motivation.

Conclusion:
Understanding ICBT in the context of the Behavior Change Wheel has helped identify how its effectiveness can be improved and can be used for future tinnitus intervention planning.

Supplemental Material:

https://doi.org/10.23641/asha.19555213
Analysis and design for constant current/constant voltage multi‐coil wireless power transfer system with high EMF reduction
Authors: Luo Zhichao , Pathmanathan Mehanathan , Han Wei , Nie Shuang , Lehn Peter W. 
Published: April 2022

AbstractThe investigation on the constant current (CC)/constant voltage (CV) charging for the electric vehicle wireless power transfer (WPT) system has been widely conducted. However, the CC/CV performance under misalignment cases has been scarcely studied especially for the multi‐coil WPT system. The resonant tank compensation methodology for the exciter‐quadrature‐repeaters (EQR) transmitter‐based multi‐coil WPT system is studied to achieve high power factor CC/CV charging with low leakage flux over ±150 mm lateral misalignment range. The EQR transmitter consists of one small exciter coil powered by a single full bridge inverter and two larger decoupled quadrature repeater coils which are magnetically coupled to the exciter coil. A variable switched capacitor is applied on the exciter side to maintain a high power factor in the CV mode. A 3‐kW experimental setup with a 200 mm nominal vertical distance was built and a three‐coil WPT system with a single large repeater coil is chosen as a comparison. Experimental results show that the EQR transmitter‐based WPT system achieves 92% coil‐to‐coil efficiency and reduces the leakage flux density by 70% compared with the existing three‐coil system in the CV mode at 150‐mm lateral misalignment.
Light-Emitting Diode (LED) Phototherapy versus Non-LED Phototherapy Devices for Hyperbilirubinemia in Neonates: A Systematic Review and Meta-analysis
Authors: Novoa Rommy H. , Huaman Karen , Caballero Patricia 
Published: April 2022

This review was conducted to evaluate the efficacy of light-emitting diode (LED) phototherapy as compared with the conventional phototherapy in neonates with unconjugated hyperbilirubinemia and their adverse effects. We searched the following databases right from their inception till April, 2021: MEDLINE, EMBASE, Cochrane Library, and LILACS. Randomized clinical trials (RCTs) comparing the LED phototherapy with other light sources, which enrolled newborns (term and preterm) with unconjugated hyperbilirubinemia were included. We included 21 articles in this review. The treatment with the LED light therapy had a lower failure rate as compared with the non-LED one (RR = 0.60, 95% CI: 0.39–0.94). The mean duration of phototherapy was significantly shorter in the group with the LED light source as compared with the one with the non-LED light source (mean difference [hours]: −8.07, 95% CI: −8.45 to −7.68), regardless of the type of non-LED units. However, the rate of bilirubin showed a comparable decline (mean difference [mg/dL/h]: 0.01, 95% CI: −0.00, 0.03) in both the light sources, irrespective of irradiance or distance. No studies reported primary outcomes related to the neurotoxicity effects of hyperbilirubinemia in neonates. The LED light devices caused a significantly higher risk of hypothermia. Neonates were at a lower risk of developing hyperthermia and skin rash with the LED light therapy. Our findings provide support for the use of LED light source phototherapy due to its better clinical efficacy, which is evidenced by its shorter duration and lower rate of treatment failure, as compared with the non-LED light sources.
Key Points