bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pan‐cancer analysis reveals the pro‐oncogenic role of N6‐methyladenosine (m6A)‐regulated NTMT1 in head and neck squamous cell carcinoma
Authors: Zhao Chunhong , Yu Min , Li Yujie 
Published: November 2023

AbstractHead and neck squamous cell carcinoma (HNSC) is a common and fatal tumor with a bleak prognosis, posing a significant threat to human health. N6‐methyladenosine (m6A) modification regulates tumor progression by modulating gene expression post‐transcriptionally. Nevertheless, the specific function of m6A‐modified tumor drivers in HNSC remains largely uncharted. In this study, we revealed the pro‐oncogenic role of m6A‐regulated NTMT1 in HNSC through comprehensive pan‐cancer analysis and experimental validation. By scrutinizing the prognostic and expression profiles of NTMT1 across over 30 cancer types, we observed a significant association between NTMT1 and patient overall survival in ACC, HNSC, LAML, LGG, KIRC, and STAD. Moreover, we find a close correlation between NTMT1 and disease‐free survival in ACC, HNSC, LUSC, UVM, KIRC, and STAD. NTMT1 exhibited dysregulation in 15 cancers, including CESC, CHOL, COAD, DLBC, GBM, HNSC, LGG, LIHC, PAAD, READ, SKCM, THYM, UCS, LAML, and TGCT. Integrated data underscored the critical involvement of NTMT1 in HNSC. Furthermore, the expression of NTMT1 was closely associated with tumor stage and immune infiltration in HNSC. Functionally, NTMT1 deficiency was demonstrated to significantly impede cell proliferation and cell‐cycle progression in HNSC. Mechanistically, METTL3 was elucidated to mediate the epigenetic upregulation of NTMT1 in HNSC in an m6A‐dependent manner, and the overexpression of METTL3 was shown to alleviate the inhibitory impact of downregulated NTMT1 on HNSC proliferation. In conclusion, our findings enhance our understanding of NTMT1's role across various cancer types and offer a rationale for clinically targeting NTMT1 as a therapeutic approach for HNSC.
The impact of COVID‐19 on investor response to earnings and monthly sales news
Authors: Lu Hsueh‐Tien 
Published: November 2023

AbstractThe novel coronavirus (COVID‐19) situation provides new insights into how macroeconomic shocks affect investors’ processing of firm disclosures. This study focuses on the market reactions to mandatory firm disclosures, that is, earnings announcements and the unique practice of monthly sales disclosure in the Taiwanese stock market, and seeks to provide evidence that timely sales information attracts more incremental investor attention than earnings news after a sudden shock. This study finds decreased (increased) market reaction to earnings news (monthly sales news) during the turmoil period of the stock market than during the pre‐ and post‐turmoil periods. I further explore the effects of stock market conditions on the market reaction to the firm disclosures. I observe that a shrinking market leads to lesser (greater) investors’ attention on earnings news (monthly sales news) than a soaring market does. These results imply that the market demand on the earnings or monthly sales news depends on investors’ relative risk aversion. In addition, this study provides evidence that the trade‐off between the market reaction to earnings and monthly sales news seems to be temporary, however, the market reaction to the news had not returned to pre‐crisis levels during the sample period of this study. This paper shows that the increased decision usefulness of timely monthly sales information may supplement the decreased decision usefulness of earnings news during a negative macroeconomic event.
Ab initiostudies of counterion effects in molecular quantum‐dot cellular automata
Authors: Liza Nishattasnim , Coe Daniel J. , Lu Yuhui , Blair Enrique P. 
Published: November 2023

AbstractMolecular quantum‐dot cellular automata (QCA) is a low‐power computing paradigm that may offer ultra‐high device densities and THz‐speed switching at room temperature. A single mixed‐valence (MV) molecule acts as an elementary QCA device known as a cell. Cells coupled locally via the electrostatic field form logic circuits. However, previously‐synthesized ionic MV molecular cells are affected by randomly‐located, nearby neutralizing counterions that can bias device states or change device characteristics, causing incorrect computational results. Thisab initiostudy explores how non‐biasing counterions affect individual molecular cells. Additionally, we model two novel neutral, zwitterionic MV QCA molecules designed to avoid biasing and other undesirable counterionic effects. The location of the neutralizing counterion is controlled by integrating one counterion into each cell at a well‐defined, non‐biasing location. Each zwitterionic QCA candidate molecule presented here has a fixed, integrated counterion, which neutralizes the mobile charges used to encode the device state.
Negative feedback‐seeking in depression: The moderating roles of rumination and interpersonal life stress
Authors: Gallagher Anna G. , Washburn Dustin , Jacobson Jill A. , Harkness Kate L. 
Published: November 2023

AbstractObjectivesSwann's self‐verification theory proposes that negative feedback seeking (NFS)—the solicitation of negative feedback from others that confirms one's self‐views—works in a negative cycle to maintain and exacerbate depression in the face of interpersonal stress. We propose a cognitive‐interpersonal integration account of NFS such that this maladaptive behavior prospectively predicts depression only among those with a trait tendency to ruminate on the causes and consequences of depressed mood and stress.MethodParticipants included 91 young adults who were over‐sampled for a lifetime history of a unipolar depressive disorder (age 17–33; 69% women; 67% lifetime depressive disorder). At baseline, participants completed a structured diagnostic interview and self‐report measures of NFS, rumination, and depression symptoms. In addition, participants engaged in an interpersonal rejection task (the Yale Interpersonal Stressor) followed by a behavioral measure of NFS. At a 3‐month follow‐up, depression symptoms were again assessed by self‐report and exposure to stressful interpersonal life events in the intervening period were assessed with a rigorous contextual interview and independent rating system.ResultsControlling for baseline depression severity, greater self‐reported, and behaviorally assessed NFS predicted greater follow‐up depression severity, but only among those with higher trait tendency to ruminate. For self‐reported NFS, this association was further moderated by level of interpersonal, but not noninterpersonal, life events experienced over follow‐up.ConclusionThese findings suggest that rumination may represent a modifiable intervention target that could break the vicious interpersonal cycle of depression and, thus, mitigate the depressogenic effects of NFS.
Pharmacokinetic and Pharmacodynamic Analysis of Acetaminophen and Ibuprofen Dual Therapy for Patent Ductus Arteriosus Closure in Preterm Neonates at Less Than 29 Weeks of Gestation
Authors: Almoslem Mohammed , Shah Sanket D. , Vozmediano Valvanera , Guzy Serge , Kim Sarah , Hudak Mark L. , Schmidt Stephan 
Published: November 2023

AbstractPatent ductus arteriosus (PDA) is a blood vessel that critically supports fetal circulation. The ductus naturally closes within a few days after birth. However, it can stay open in premature neonates for an extended period of time, which is associated with increased mortality and various co‐morbidities. Ibuprofen and indomethacin are currently the only 2 drugs approved for inducing PDA closure, but both have been associated with adverse renal and bleeding events. Clinical evidence suggests that combining acetaminophen (APAP) and ibuprofen treatments can decrease the need for surgical ligation. The objective of this study was to establish a disease–drug–trial model to characterize and predict PDA closure following single and combination drug therapy with ibuprofen and/or APAP in children at less than 29 weeks of gestation. The model was informed by a comprehensive literature review. The results of our analysis suggest that ibuprofen and APAP achieve therapeutic synergy. They further suggest that the younger the preterm neonates, the higher the treatment benefit. A 5‐day oral dosing regimen consisting of ibuprofen (20 mg/kg Q24h on day 1, followed by 10 mg/kg Q24h on days 2‐5) plus APAP (15 mg/kg Q6h) was deemed appropriate to achieve at least 90% PDA in all preterm neonates evaluated within 1 month of life. The model can now be used to design prospective pediatric trials to evaluate optimal drug combinations for PDA closure in preterm neonates and to refine optimal dosing regimens in cohorts of differing gestational age.
Trying too hard or not hard enough: How effort shapes status
Authors: Warren Nathan B. , Warren Caleb 
Published: November 2023

AbstractIs trying to earn status effective or self‐defeating? We show that whether effort increases or decreases admiration and respect (i.e., status) depends on how the person is trying to earn status. Groups evaluate people along multiple status dimensions (e.g., wealth, coolness). Each dimension is associated with a different ideology, or set of beliefs, that ascribe status to behaviors that contribute to the group's goals. Whether behaviors, including effort, increase status, thus, depends on the ideologies that people use to interpret if a behavior contributes to the group. Four experiments demonstrate that people earn more status when they try to become wealthy compared to when they are effortlessly wealthy, but earn less status when they try to become cool compared to when they are effortlessly cool. Effort increases status when directed at wealth but not at coolness because contemporary ideologies suggest that people who gain wealth through effort contribute more to society, whereas people who gain coolness through effort contribute less.
Handelin alleviates cachexia‐ and aging‐induced skeletal muscle atrophy by improving protein homeostasis and inhibiting inflammation
Authors: Zhang Hui‐Jie , Wang Ben‐Hui , Wang Xiang , Huang Chun‐Ping , Xu Si‐Man , Wang Jia‐Li , Huang Tian‐E , Xiao Wan‐Li , Tian Xiao‐Li , Lan Xin‐Qiang , Wang Qi‐Quan , Xiang Yang 
Published: November 2023

AbstractBackgroundHandelin is a bioactive compound from Chrysanthemum indicum L. that improves motor function and muscle integrity during aging in Caenorhabditis elegans. This study aimed to further evaluate the protective effects and molecular mechanisms of handelin in a mouse muscle atrophy model induced by cachexia and aging.MethodsA tumour necrosis factor (TNF)‐α‐induced atrophy model was used to examine handelin activity in cultured C2C12 myotubes in vitro. Lipopolysaccharide (LPS)‐treated 8‐week‐old model mice and 23‐month‐old (aged) mice were used to examine the therapeutic effects of handelin on cachexia‐ and aging‐induced muscle atrophy, respectively, in vivo. Protein and mRNA expressions were analysed by Western blotting, ELISA and quantitative PCR, respectively. Skeletal muscle mass was measured by histological analysis.ResultsHandelin treatment resulted in an upregulation of protein levels of early (MyoD and myogenin) and late (myosin heavy chain, MyHC) differentiation markers in C2C12 myotubes (P < 0.05), and enhanced mitochondrial respiratory (P < 0.05). In TNF‐α‐induced myotube atrophy model, handelin maintained MyHC protein levels, increased insulin‐like growth factor (Igf1) mRNA expression and phosphorylated protein kinase B protein levels (P < 0.05). Handelin also reduced atrogin‐1 expression, inhibited nuclear factor‐κB activation and reduced mRNA levels of interleukin (Il)6, Il1b and chemokine ligand 1 (Cxcl1) (P < 0.05). In LPS‐treated mice, handelin increased body weight (P < 0.05), the weight (P < 0.01) and cross‐sectional area (CSA) of the soleus muscle (P < 0.0001) and improved motor function (P < 0.05). In aged mice, handelin slightly increased the weight of the tibialis anterior muscle (P = 0.06) and CSA of the tibialis anterior and gastrocnemius muscles (P < 0.0001). In the tibialis anterior muscle of aged mice, handelin upregulated mRNA levels of Igf1 (P < 0.01), anti‐inflammatory cytokine Il10 (P < 0.01), mitochondrial biogenesis genes (P < 0.05) and antioxidant‐related enzymes (P < 0.05) and strengthened Sod and Cat enzyme activity (P < 0.05). Handelin also reduced lipid peroxidation and protein carbonylation, downregulated mRNA levels of Fbxo32, Mstn, Cxcl1, Il1b and Tnf (P < 0.05), and decreased IL‐1β levels in serum (P < 0.05). Knockdown of Hsp70 or using an Hsp70 inhibitor abolished the ameliorating effects of handelin on myotube atrophy.ConclusionsHandelin ameliorated cachexia‐ and aging‐induced skeletal muscle atrophy in vitro and in vivo, by maintaining homeostasis of protein synthesis and degradation, possibly by inhibiting inflammation. Handelin is a potentially promising drug candidate for the treatment of muscle wasting.
Proteome and immune responses of extracellular vesicles derived from macrophages infected with the periodontal pathogen Tannerella forsythia
Authors: Lim Younggap , Kim Hyun Young , Han Dohyun , Choi Bong‐Kyu 
Published: November 2023

AbstractPeriodontitis is a chronic inflammatory disease caused by periodontal pathogens in subgingival plaque and is associated with systemic inflammatory diseases. Extracellular vesicles (EVs) released from host cells and pathogens carry a variety of biological molecules and are of interest for their role in disease progression and as diagnostic markers. In the present study, we analysed the proteome and inflammatory response of EVs derived from macrophages infected with Tannerella forsythia, a periodontal pathogen. The EVs isolated from the cell conditioned medium of T. forsythia‐infected macrophages were divided into two distinct vesicles, macrophage‐derived EVs and T. forsythia‐derived OMVs, by size exclusion chromatography combined with density gradient ultracentrifugation. Proteome analysis showed that in T. forsythia infection, macrophage‐derived EVs were enriched with pro‐inflammatory cytokines and inflammatory mediators associated with periodontitis progression. T. forsythia‐derived OMVs harboured several known virulence factors, including BspA, sialidase, GroEL and various bacterial lipoproteins. T. forsythia‐derived OMVs induced pro‐inflammatory responses via TLR2 activation. In addition, we demonstrated that T. forsythia actively released OMVs when T. forsythia encountered macrophage‐derived soluble molecules. Taken together, our results provide insight into the characterisation of EVs derived from cells infected with a periodontal pathogen.
Massive open online courses (MOOCs) in genomic variant interpretation: An innovative education strategy for the growing genetic counselor workforce
Authors: Coad Beth , Joekes Katherine , Rudnicka Alicja , Frost Amy , Tatton‐Brown Katrina , Snape Katie 
Published: November 2023

AbstractThe growth in genomic testing in healthcare requires a highly trained specialist workforce to ensure evidence based clinical germline variant interpretation. Genetic counselors form a core part of the clinical genomics multidisciplinary team (MDT) and represent a growing workforce participating in variant interpretation from data analysis to the patient consultation. Standardized, high‐quality variant interpretation training for Genetic Counselors has historically been ad hoc and variable, with existing programs lacking capacity to reach the entire workforce. To address the requirement for scalable variant interpretation training for genomics healthcare professionals (HCPs), two Massive Open Online Courses (MOOCs) were developed. We analyzed the data from 17 Genetic counselors, as part of an evaluation cohort completing the first run of these MOOCs. Overall genetic counselors enjoyed the courses, felt they were clinically relevant and would recommend them to colleagues. Common challenges amongst the genetic counseling workforces included utilizing relevant databases and finding time in the workday to complete training. These findings suggest MOOCs could be an acceptable option to ensure a consistent and transferrable high standard of training, complimentary to existing curricula. They also hold the potential to facilitate large‐scale education to update the genetic counseling workforce when changes in variant interpretation guidance occur.
Discussions of personal identity in genetic counseling supervision
Authors: Peplow Katherine , He Hua , Rivers Bryana , Wusik Katie , Yager Geoffrey , Atzinger Carrie 
Published: November 2023

AbstractFieldwork supervision is integral to genetic counseling students' training and has the potential to impact how included students feel in the genetic counseling field. For example, in related counseling fields, when supervisees and supervisors discuss their personal similarities or differences in ethnicity, supervisees report a stronger supervisory working alliance (SWA) (Journal of Multicultural Counseling and Development, 2001, 29, 102–113). However, the application of these studies on identity discussions to the genetic counseling field is currently unknown. The objective of this cross‐sectional questionnaire‐based study was to investigate (a) if genetic counseling students report having discussions of personal identity during fieldwork supervision, (b) who initiated any such discussions, (c) if there was a difference in the supervisory relationship between those who did and did not have discussions of personal identity, and (d) how students perceived the inclusivity of the genetic counseling profession and their genetic counseling programs. Discussions of personal identity were defined in this study as “discussions happening during supervision regarding how one or more aspects of personal identity impacts the provision of genetic counseling services and/or professional interactions” where personal identity included the student or supervisor's gender, sexual orientation, race, ethnicity, religion, disability status or other aspect of identity. Almost 40% of the participants (N = 190) reported discussing personal identity with their supervisor. For students identifying as white, discussions of personal identity were related to a stronger SWA (p = 0.014). However, for those with minoritized identities there was no relationship between the SWA and discussions of personal identity. Therefore, it is unclear from the current research whether discussions of personal identity can be an effective tool in improving inclusivity in the field of genetic counseling. Additional research is needed to explore the direct impact of identity discussions on the supervisory working alliance in genetic counseling supervision.
Arylhydrazine salt‐selenium: A novel and efficient reagent system for arylselenenylation of unprotected uracil and its derivatives
Authors: Wu Yi , Peng Qi‐Yun , He Yan‐Ling , Zheng Xiao‐He , Chen Yan‐Qin , Wang Hai‐Bo , Wang Bing , Xie Jun , Tang Lei , Wang Cong 
Published: November 2023

AbstractA convenient and efficient reagent system of arylhydrazine salt‐selenium was developed to directly selenizing uracil preparation of 5‐selenium uracil. In the presence of this reagent, a variety of uracil/pyrimidine converts to their corresponding 5‐arylselanyluracils/5‐selenopyrimidine with good yield and high regioselectivity. Elemental selenium of commercially accessible, stable, affordable, and easy to use was used as the selenization reagent. This reaction is attractive and practical since there are no catalysts or ligands needed, and a wide range of functional groups can be tolerated.
Severe neuromuscular forms of glycogen storage disease type IV: Histological, clinical, biochemical, and molecular findings in a large French case series
Authors: Lefèvre Charles R. , Collardeau‐Frachon Sophie , Streichenberger Nathalie , Berenguer‐Martin Sophie , Clémenson Alix , Massardier Jérôme , Prieur Fabienne , Laurichesse Hélène , Laffargue Fanny , Acquaviva‐Bourdain Cécile , Froissart Roseline , Pettazzoni Magali 
Published: November 2023

AbstractGlycogen storage disease type IV (GSD IV), also called Andersen disease, or amylopectinosis, is a highly heterogeneous autosomal recessive disorder caused by a glycogen branching enzyme (GBE, 1,4‐alpha‐glucan branching enzyme) deficiency secondary to pathogenic variants on GBE1 gene. The incidence is evaluated to 1:600 000 to 1:800 000 of live births. GBE deficiency leads to an excessive deposition of structurally abnormal, amylopectin‐like glycogen in affected tissues (liver, skeletal muscle, heart, nervous system, etc.). Diagnosis is often guided by histological findings and confirmed by GBE activity deficiency and molecular studies. Severe neuromuscular forms of GSD IV are very rare and of disastrous prognosis. Identification and characterization of these forms are important for genetic counseling for further pregnancies. Here we describe clinical, histological, enzymatic, and molecular findings of 10 cases from 8 families, the largest case series reported so far, of severe neuromuscular forms of GSD IV along with a literature review. Main antenatal features are: fetal akinesia deformation sequence or arthrogryposis/joint contractures often associated with muscle atrophy, decreased fetal movement, cystic hygroma, and/or hydrops fetalis. If pregnancy is carried to term, the main clinical features observed at birth are severe hypotonia and/or muscle atrophy, with the need for mechanical ventilation, cardiomyopathy, retrognathism, and arthrogryposis. All our patients were stillborn or died within 1 month of life. In addition, we identified five novel GBE1 variants.
Blockage of the fractalkine pathway reduces hyperalgesia and prevents morphological glial alterations—Comparison between inflammatory and neuropathic orofacial pain in male rats
Authors: Lisboa Mario Roberto Pontes , Pereira Anamaria Falcão , Alves Bruno Wesley de Freitas , Dias Diego Bernarde Souza , Alves Luiza Clertiani Vieira , da Silva Cristiane Maria Pereira , Lima‐Júnior Roberto César Pereira , Gondim Delane Viana , Vale Mariana Lima 
Published: November 2023

AbstractThis study aimed to evaluate the effects of inhibitors of the fractalkine pathway in hyperalgesia in inflammatory and neuropathic orofacial pain in male rats and the morphological changes in microglia and satellite glial cells (SGCs). Rats were submitted to zymosan‐induced arthritis of the temporomandibular joint or infraorbital nerve constriction, and treated intrathecally with a P2X7 antagonist, a cathepsin S inhibitor or a p‐38 mitogen‐activated protein kinase (MAPK) inhibitor. Mechanical hyperalgesia was evaluated 4 and 6 h following arthritis induction or 7 and 14 days following nerve ligation. The expression of the receptor CX3CR1, phospho‐p‐38 MAPK, ionized calcium‐binding adapter molecule‐1 (Iba‐1), and glutamine synthetase and the morphological changes in microglia and SGCs were evaluated by confocal microscopy. In both inflammatory and neuropathic models, untreated animals presented a higher expression of CX3CR1 and developed hyperalgesia and up‐regulation of phospho‐p‐38 MAPK, which was prevented by all drugs (p < .05). The number of microglial processes endpoints and the total branch length were lower in the untreated animals, but the overall immunolabeling of Iba‐1 was altered only in neuropathic rats (p < .05). The mean area of SGCs per neuron was significantly altered only in the inflammatory model (p < .05). All morphological alterations were reverted by modulating the fractalkine pathway (p < .05). In conclusion, the blockage of the fractalkine pathway seemed to be a possible therapeutic strategy for inflammatory and neuropathic orofacial pain, reducing mechanical hyperalgesia by impairing the phosphorylation of p‐38 MAPK and reverting morphological alterations in microglia and SGCs.