bluuebunny/crossref_metadata_2025_split huggingface dataset:
Iron dysregulation in COVID‐19 and reciprocal evolution of SARS‐CoV‐2: Natura nihil frustra facit
Authors: Gupta Yash , Maciorowski Dawid , Medernach Brian , Becker Daniel P. , Durvasula Ravi , Libertin Claudia R. , Kempaiah Prakasha 
Published: January 2022

AbstractAfter more than a year of the COVID‐19 pandemic, SARS‐CoV‐2 infection rates with newer variants continue to devastate much of the world. Global healthcare systems are overwhelmed with high positive patient numbers. Silent hypoxia accompanied by rapid deterioration and some cases with septic shock is responsible for COVID‐19 mortality in many hospitalized patients. There is an urgent need to further understand the relationships and interplay with human host components during pathogenesis and immune evasion strategies. Currently, acquired immunity through vaccination or prior infection usually provides sufficient protection against the emerging variants of SARS‐CoV‐2 except Omicron variant requiring recent booster. New strains have shown higher viral loads and greater transmissibility with more severe disease presentations. Notably, COVID‐19 has a peculiar prognosis in severe patients with iron dysregulation and hypoxia which is still poorly understood. Studies have shown abnormally low serum iron levels in severe infection but a high iron overload in lung fibrotic tissue. Data from our in‐silico structural analysis of the spike protein sequence along with host proteolysis processing suggests that the viral spike protein fragment mimics Hepcidin and is resistant to the major human proteases. This functional spike‐derived peptide dubbed “Covidin” thus may be intricately involved with host ferroportin binding and internalization leading to dysregulated host iron metabolism. Here, we propose the possible role of this potentially allogenic mimetic hormone corresponding to severe COVID‐19 immunopathology and illustrate that this molecular mimicry is responsible for a major pathway associated with severe disease status. Furthermore, through 3D molecular modeling and docking followed by MD simulation validation, we have unraveled the likely role of Covidin in iron dysregulation in COVID‐19 patients. Our meta‐analysis suggests the Hepcidin mimetic mechanism is highly conserved among its host range as well as among all new variants to date including Omicron. Extensive analysis of current mutations revealed that new variants are becoming alarmingly more resistant to selective human proteases associated with host defense.
Characterization of the first microRNA in human CDH1 that affects cell cycle and apoptosis and indicates breast cancers progression
Authors: Gharbi Sedigheh , Mohammadi Zahra , Dezaki Maryam Saedi , Dokanehiifard Sadat , Dabiri Shahriar , Korsching Eberhard 
Published: January 2022

AbstractThe E‐cadherin protein (Cadherin 1, gene: CDH1), a master regulator of the human epithelial homeostasis, contributes to the epithelial‐mesenchymal transition (EMT) which confers cell migratory features to the cells. The EMT is central to many pathophysiological changes in cancer. Therefore, a better understanding of this regulatory scenario is beneficial for therapeutic regiments. The CDH1 gene is approximately 100 kbp long and consists of 16 exons with a relatively large second intron. Since none microRNA (miRNA) has been identified in CDH1 up to now we screened the CDH1 gene for promising miRNA hairpin structures in silico. Out of the 27 hairpin structures we identified, one stable RNA fold with a promising sequence motive was selected for experimental verification. The exogenous validation of the hairpin sequence was performed by transfection of HEK293T cells and the mature miRNA sequences could be verified by quantitative polymerase chain reaction. The endogenous expression of the mature miRNA provisionally named CDH1‐i2‐miR‐1 could be confirmed in two normal (HEK293T, HUVEK) and five cancer cell lines (MCF7, MDA‐MB‐231, SW480, HT‐29, A549). The functional characterization by the 3‐(4,5‐dimethylthiazol‐2‐yl)−2,5‐diphenyltetrazolium bromide assay showed a suppression of HEK293T cell proliferation. A flow cytometry‐based approach showed the ability of CDH1‐i2‐miR‐1 to arrest transfected cells on a G2/M state while annexin staining exemplified an apoptotic effect. BAX and PTEN expression levels were affected following the overexpression with the new miRNA. The in vivo expression level was assessed in 35 breast tumor tissues and their paired nonmalignant marginal part. A fourfold downregulation in the tumor specimens compared to their marginal controls could be observed. It can be concluded that the sequence of the hub gene CDH1 harbors at least one miRNA but eventually even more relevant for the pathophysiology of breast cancer.
Uncovering Clar's aromatic ‐sextet rule in the Hubbard model using Maximum Probability Domain Partitions
Authors: Van Hende Daria , Lemmens Laurent , De Baerdemacker Stijn , Van Neck Dimitri , Bultinck Patrick , Acke Guillaume 
Published: January 2022

AbstractClar's aromatic ‐sextet rule is a widely used qualitative method for assessing the electronic structure of polycyclic benzenoid hydrocarbons. Unfortunately, many of the quantum chemical concordances for this rule have a limited range of applicability. Here, we show that the fundamental probabilities associated with a distribution of electrons over domain partitions support Clar's rule in both mean‐field and static correlation regimes. In particular, domain partitions that maximize those probabilities reflect the dominance of Clar structures in the electronic structure of these molecules. These findings suggest that extending methods that aim to maximize probabilities by deforming domain partitions could lead to novel quantum chemical underpinnings for many chemical concepts.
Integrated weighted gene co‐expression network analysis reveals biomarkers associated with prognosis of high‐grade serous ovarian cancer
Authors: Wang Bo , Chao Shan , Guo Bo 
Published: January 2022

AbstractBackgroundOvarian cancer is the gynecologic tumor with the highest fatality rate, and high‐grade serous ovarian cancer (HGSOC) is the most common and malignant type of ovarian cancer. One important reason for the poor prognosis of HGSOC is the lack of effective diagnostic and prognostic biomarkers. New biomarkers are necessary for the improvement of treatment strategies and to ensure appropriate healthcare decisions.MethodsTo construct the co‐expression network of HGSOC samples, we applied weighted gene co‐expression network analysis (WGCNA) to assess the proteomic data obtained from the Clinical Proteomic Tumor Analysis Consortium (CPTAC), and module‐trait relationship was then analyzed and plotted in a heatmap to choose key module associated with HGSOC. Subsequently, hub genes with high connectivity in key module were identified by Cytoscape software. Furthermore, the biomarkers were selected through survival analysis, followed by evaluation using the relative operating characteristic (ROC) analysis.ResultsA total of 9 modules were identified by WGCNA, and module‐trait analysis revealed that the brown module was significantly associated with HGSOC (cor = 0.7). Ten hub genes with the highest connectivity were selected by protein‐protein interaction analysis. After survival and ROC analysis, ALB, APOB and SERPINA1 were suggested to be the biomarkers, and their protein levels were positively correlated with HGSOC prognosis.ConclusionWe conducted the first gene co‐expression analysis using proteomic data from HGSOC samples, and found that ALB, APOB and SERPINA1 had prognostic value, which might be applied for the treatment of HGSOC in the future.
Explore the effect of LLY‐283 on the ototoxicity of auditory cells caused by cisplatin: A bioinformatic analysis based on RNA‐seq
Authors: Zhao Bin , Zhang Dongdong , Sun Yixin , Lei Min , Zeng Peiji , Wang Yue , Hong Yongjun , Jiao Yanchao , Cai Chengfu 
Published: January 2022

AbstractBackgroundCisplatin is a commonly used chemotherapeutic drug in clinics, and long‐term application will lead to hearing impairment. LLY‐283, an inhibitor of PRMT5, has not been reported in deafness. Our study aimed to explore the mechanism of LLY‐283 in hearing impairment.Materials and MethodsFirst, we performed RNA‐seq (cisplatin in the experimental group and DMSO in the control group) to obtain the biological processes mainly involved in differentially expressed genes (DEGs). CCK‐8 and LDH experiments were used to observe the effect of LLY‐283 on cisplatin‐induced auditory cell injury. ROS experiment was used to monitor the impact of LLY‐283 on oxidative damage of auditory cells. Effect of LLY‐283 on apoptosis of auditory cells detected by TUNEL experiment. PCR and Western blotting were used to detect the expression of genes and proteins related to auditory cell apoptosis in LLY‐283 cells. Meanwhile, we explored the effect of LLY‐283 on the expression of PRMT5 in cisplatin‐induced hearing impaired cells at RNA and protein levels.ResultsBiological process analysis showed that DEGs were mainly enriched in the apoptotic process involved in morphogenesis (‐Log10 P = 3.71). CCK‐8 and LDH experiments confirmed that LLY‐283 could save cisplatin‐induced auditory cell injury. ROS experiments confirmed that LLY‐283 could rescue cisplatin‐induced oxidative damage to auditory cells. TUNEL experiments confirmed that LLY‐283 could protect cisplatin‐induced apoptosis of auditory cells. Meanwhile, LLY‐283 could inhibit the expression of PRMT5 in auditory cells induced by cisplatin.ConclusionLLY‐283 can rescue cisplatin‐induced auditory cell apoptosis injury. LLY‐283 can inhibit the increase in PRMT5 expression induced by cisplatin.
Proline‐rich transmembrane protein 2 specifically binds to GluA1 but has no effect on AMPA receptor‐mediated synaptic transmission
Authors: Feng Hao‐Yang , Qiao Fengchang , Tan Jianxin , Zhang Xiaozuo , Hu Ping , Shi Yun Stone , Xu Zhengfeng 
Published: January 2022

AbstractBackgroundProline‐rich transmembrane protein 2 (PRRT2) is a neuron‐specific protein associated with seizures, dyskinesia, and intelligence deficit. Previous studies indicate that PRRT2 regulates neurotransmitter release from presynaptic membranes. However, PRRT2 can also bind AMPA‐type glutamate receptors (AMPARs), but its postsynaptic functions remain unclear.Methods and resultsWhole‐exome sequencing used to diagnose a patient with mental retardation identified a nonsense mutation in the PRRT2 gene (c.649C>T; p.R217X). To understand the pathology of the mutant, we cloned mouse Prrt2 cDNA and inserted a premature stop mutation at Arg223, the corresponding site of Arg217 in human PRRT2. In mouse hippocampal tissues, Prrt2 interacted with GluA1/A2 AMPAR heteromers but not GluA2/A3s, via binding to GluA1. Additionally, Prrt2 suppressed GluA1 expression and localization on cell membranes of HEK 293T cells. However, when Prrt2 was overexpressed in individual hippocampal neurons using in utero electroporation, AMPAR‐mediated synaptic transmission was unaffected. Deletion of Prrt2 with the CRIPR/Cas9 technique did not affect AMPAR‐mediated synaptic transmission. Furthermore, deletion or overexpression of Prrt2 did not affect GluA1 expression and distribution in primary neuronal culture.ConclusionsThe postsynaptic functions of Prrt2 demonstrate that Prrt2 specifically interacts with the AMPAR subunit GluA1 but does not regulate AMPAR‐mediated synaptic transmission. Therefore, our study experimentally excluded a postsynaptic regulatory mechanism of Prrt2. The pathology of PRRT2 variants in humans likely originates from defects in neurotransmitter release from the presynaptic membrane as suggested by recent studies.
Evaluating a semi‐nested PCR to support histopathology reports of fungal rhinosinusitis in formalin‐fixed paraffin‐embedded tissue samples
Authors: Ashraf Mohammad Javad , Kord Mohammad , Morovati Hamid , Ansari Saham , Shekarkhar Golsa , Badali Hamid , Pakshir Kayvan , Shamsizadeh Forough , Khademi Bijan , Shishegar Mahmood , Ahmadikia Kazem , Zomorodian Kamiar 
Published: January 2022

AbstractBackgroundFungal rhinosinusitis (FRS) encompasses a various spectrum of diseases. Histopathology is the “reference method” for diagnosing FRS, but it cannot determine the genus and species. Moreover, in more than 50% of the histopathologically proven cases, the culture elicited no reliable results. This study was an attempt to evaluate the diagnostic efficiency of semi‐nested polymerase chain reaction (PCR) from formalin‐fixed paraffin‐embedded (FFPE) functional endoscopic sinus surgery (FESS) in FRS patients.MethodsOne hundred ten specimens were subjected to DNA extraction and histopathology examination. The amplification of the β‐globin gene by conventional PCR was used to confirm the quality of extracted DNA. The semi‐nested PCR was performed using ITS1, ITS2, and ITS4 primers during two steps. Sequencing the internal transcribed spacer region (ITS1‐5.8S‐ITS2) to identify causative agents was performed on PCR products.ResultsSixty‐four out of 110 samples were positive by histopathology evidence, of which 56 samples (87.5%) were positive by PCR. Out of 46 negative samples by histopathological methods, five samples (10.9%) yielded positive results by PCR. Sensitivity, specificity, positive predictive value, and negative predictive value of the semi‐nested PCR method were reported 87.5%, 89.2%, 92.7%, and 85.2%, respectively. The kappa factor between PCR and histopathological methods was 0.76, indicating substantial agreements between these two tests.ConclusionDue to the acceptable sensitivity and specificity of the present method, it might be used to diagnose fungal sinusitis infections along with microscopic techniques. This method is recommended to confirm the diagnose of suspected fungal sinusitis with negative histopathology results.
The association between non‐alcoholic fatty liver disease and serum ferritin levels in American adults
Authors: Yang Naibin , Lu Yi , Cao Liwen , Lu Mingqin 
Published: January 2022

AbstractBackgroundElevated serum ferritin levels (SFLs) was previously reported to be related with hepatic histologic severity and advanced liver fibrosis among non‐alcoholic fatty liver disease (NAFLD) patients. However, whether NAFLD influences SFLs remains uncertain and needs more clinical evidences. This study explored the differences of SFLs in US adults with or without NAFLD.MethodsWe conducted a cross‐sectional study of 3689 participants aged 18–80 years using the National Health and Nutrition Examination Survey (NHANES) 2017–2018 cycle. NAFLD status was confirmed based on controlled attenuation parameter (CAP) values ≥274 dB/m through vibration controlled and transient elastography (VCTE). We performed weighted multivariable logistic regression models to evaluate the associations between NAFLD and SFLs in different age and gender.ResultsThere was a positive association between NAFLD and SFLs in all three models (model 1:β = 23.07, 95% CI: 10.32, 35.81; model 2:β = 23.68, 95% CI: 10.86, 36.50; model 3:β = 13.86, 95% CI: 0.29, 27.43). After adjusting for the covariates, this positive association persisted in females (β = 16.22, 95% CI: 2.81, 29.62). Further, relationships between NAFLD and SFLs were significantly different in various age groups. In the subgroup stratified by gender, their associations further differed. In males, the positive association was more prominent in 50–64 age group (β = 70.89, 95% CI: 25.14, 116.64). In females, this positive association was more prominent in 18–34 age group (β = 20.72, 95% CI: 7.45, 33.99). However, no correlations between severe steatosis, significant fibrosis, advanced fibrosis, cirrhosis, and SFLs in adults with NAFLD were found.ConclusionThis study indicated that US adults suffered with NAFLD had significantly higher SFLs compared with their counterparts in non‐NAFLD group. Moreover, the associations between NAFLD and SFLs further differed by age and gender.
Disability self‐worth relates to lower anxiety and depression in people with visual impairment
Authors: Zapata Mercedes A. , Pearlstein Jennifer G. 
Published: January 2022

AbstractObjectiveVisual impairment (VI) has been associated with depression and anxiety. Although researchers have identified several relevant individual differences associated with risk for depression and anxiety, researchers have not considered the role of personal disability identity (PDI) in depression and anxiety for people with VI. The purpose of this study is to examine the association between two aspects of PDI, perceived self‐worth and personal meaning, and depression and anxiety among people with VI.MethodHierarchical linear regressions assessed the relative contribution of PDI and disability characteristics to anxiety and depression in an international sample of adults with VI (N = 390).ResultsLower disability self‐worth, but not lower personal meaning, was significantly associated with higher depression and anxiety, explaining more variance than demographic or disability‐related factors.ConclusionBy introducing disability self‐worth as a correlate of depression and anxiety in VI, study findings suggest that considering and cultivating PDI for people with VI may be useful for improving clinical outcomes.
Parents matter: Parent acceptance of school‐based executive functions interventions relates to improved child outcomes
Authors: Rothschild Leah B. , Ratto Allison B. , Kenworthy Lauren , Hardy Kristina K. , Verbalis Alyssa , Pugliese Cara , Strang John F. , Safer‐Lichtenstein Jonathan , Anthony Bruno J. , Anthony Laura G. , Guter Madison M. , Haaga David A. F. 
Published: January 2022

AbstractObjectivesSchool‐based interventions with parent‐training components might improve access among lower‐income families to effective help for children with neurodevelopmental disorders. This potential might be realized, however, only if parents perceive the interventions as acceptable and therefore engage with treatment.MethodsParents (N = 124) of 3rd−5th grade students diagnosed with Autism Spectrum Disorder or Attention‐Deficit/Hyperactivity Disorder rated the acceptability of their child's treatment (one of two culturally responsive behavioral interventions). Parent engagement was measured through attendance at parent training sessions and the extent to which they read a corresponding workbook.ResultsEducation and income correlated inversely with parent perceptions of treatment acceptability. Acceptability correlated positively with engagement, more strongly among lower‐income families. Acceptability had an indirect effect on treatment outcome, mediated by parent engagement.ConclusionsTreatment providers should focus on strategies to increase parent acceptability, with particular attention to improving access for lower‐income families.
A systematic review of self‐report measures of generalized shame
Authors: Lear M. Kati , Lee Eric B. , Smith Sarah M. , Luoma Jason B. 
Published: January 2022

AbstractObjectiveShame is a transdiagnostic emotion of strong clinical and research interest. Yet, there is a lack of consensus on the definition and varying methods employed across self‐report measures, potentially affecting our ability to accurately study shame and examine whether clinical interventions to alter shame are effective. This paper offers a systematic review of self‐report measures of generalized shame.MethodsPubMed, PsycInfo, and Web of Science were searched. Studies were included when they were available in English and the primary aim was to evaluate measurement properties of scales or subscales designed to measure generalized shame in adults.ResultsThirty‐six papers examining 19 scales were identified, with measures of trait shame more common than state shame. Construct validity, internal consistency, and structural validity were relative strengths. Development and content validity studies were lacking and suffered from low methodological quality.ConclusionsAll measures evaluated needed additional research to meet criteria for recommended use.
Renal failure suppresses muscle irisin expression, and irisin blunts cortical bone loss in mice
Authors: Kawao Naoyuki , Kawaguchi Miku , Ohira Takashi , Ehara Hiroki , Mizukami Yuya , Takafuji Yoshimasa , Kaji Hiroshi 
Published: January 2022

AbstractBackgroundChronic renal failure induces bone mineral disorders and sarcopenia. Skeletal muscle affects other tissues, including bone, by releasing myokines. However, the effects of chronic renal failure on the interactions between muscle and bone remain unclear.MethodsWe investigated the effects of renal failure on bone, muscle, and myokines linking muscle to bone using a mouse 5/6 nephrectomy (Nx) model. Muscle mass and bone mineral density (BMD) were analysed by quantitative computed tomography 8 weeks after Nx.ResultsNephrectomy significantly reduced muscle mass in the whole body (12.1% reduction, P < 0.05), grip strength (10.1% reduction, P < 0.05), and cortical BMD at the femurs of mice (9.5% reduction, P < 0.01) 8 weeks after surgery, but did not affect trabecular BMD at the femurs. Among the myokines linking muscle to bone, Nx reduced the expression of irisin, a proteolytic product of fibronectin type III domain‐containing 5 (Fndc5), in the gastrocnemius muscles of mice (38% reduction, P < 0.01). Nx increased myostatin mRNA levels in the gastrocnemius muscles of mice (54% increase, P < 0.01). In simple regression analyses, cortical BMD, but not trabecular BMD, at the femurs was positively related to Fndc5 mRNA levels in the gastrocnemius muscles of mice (r = 0.651, P < 0.05). The weekly administration of recombinant irisin to mice ameliorated the decrease in cortical BMD, but not muscle mass or grip strength, induced by Nx (6.2% reduction in mice with Nx vs. 3.3% reduction in mice with Nx and irisin treatment, P < 0.05).ConclusionsThe present results demonstrated that renal failure decreases the expression of irisin in the gastrocnemius muscles of mice. Irisin may contribute to cortical bone loss induced by renal failure in mice as a myokine linking muscle to bone.
Skeletal muscle alterations in patients with acute Covid‐19 and post‐acute sequelae of Covid‐19
Authors: Soares Madu N. , Eggelbusch Moritz , Naddaf Elie , Gerrits Karin H. L. , van der Schaaf Marike , van den Borst Bram , Wiersinga W. Joost , van Vugt Michele , Weijs Peter J.M. , Murray Andrew J. , Wüst Rob C.I. 
Published: January 2022

AbstractSkeletal muscle‐related symptoms are common in both acute coronavirus disease (Covid)‐19 and post‐acute sequelae of Covid‐19 (PASC). In this narrative review, we discuss cellular and molecular pathways that are affected and consider these in regard to skeletal muscle involvement in other conditions, such as acute respiratory distress syndrome, critical illness myopathy, and post‐viral fatigue syndrome. Patients with severe Covid‐19 and PASC suffer from skeletal muscle weakness and exercise intolerance. Histological sections present muscle fibre atrophy, metabolic alterations, and immune cell infiltration. Contributing factors to weakness and fatigue in patients with severe Covid‐19 include systemic inflammation, disuse, hypoxaemia, and malnutrition. These factors also contribute to post‐intensive care unit (ICU) syndrome and ICU‐acquired weakness and likely explain a substantial part of Covid‐19‐acquired weakness. The skeletal muscle weakness and exercise intolerance associated with PASC are more obscure. Direct severe acute respiratory syndrome coronavirus (SARS‐CoV)‐2 viral infiltration into skeletal muscle or an aberrant immune system likely contribute. Similarities between skeletal muscle alterations in PASC and chronic fatigue syndrome deserve further study. Both SARS‐CoV‐2‐specific factors and generic consequences of acute disease likely underlie the observed skeletal muscle alterations in both acute Covid‐19 and PASC.