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- Hirsch, S. D., et al.
(författare)
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The role of CDHR3 in susceptibility to otitis media
- 2021
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Ingår i: Journal of Molecular Medicine. - : Springer Nature. - 0946-2716 .- 1432-1440. ; 99:11, s. 1571-1583
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Tidskriftsartikel (refereegranskat)abstract
- Abstract: Otitis media (OM) is common in young children and can cause hearing loss and speech, language, and developmental delays. OM has high heritability; however, little is known about OM-related molecular and genetic processes. CDHR3 was previously identified as a locus for OM susceptibility, but to date, studies have focused on how the CDHR3 p.Cys529Tyr variant increases epithelial binding of rhinovirus-C and risk for lung or sinus pathology. In order to further delineate a role for CDHR3 in OM, we performed the following: exome sequencing using DNA samples from OM-affected individuals from 257 multi-ethnic families; Sanger sequencing, logistic regression and transmission disequilibrium tests for 407 US trios or probands with OM; 16S rRNA sequencing and analysis for middle ear and nasopharyngeal samples; and single-cell RNA sequencing and differential expression analyses for mouse middle ear. From exome sequence data, we identified a novel pathogenic CDHR3 splice variant that co-segregates with OM in US and Finnish families. Additionally, a frameshift and six missense rare or low-frequency variants were identified in Finnish probands. In US probands, the CDHR3 p.Cys529Tyr variant was associated with the absence of middle ear fluid at surgery and also with increased relative abundance of Lysobacter in the nasopharynx and Streptomyces in the middle ear. Consistent with published data on airway epithelial cells and our RNA-sequence data from human middle ear tissues, Cdhr3 expression is restricted to ciliated epithelial cells of the middle ear and is downregulated after acute OM. Overall, these findings suggest a critical role for CDHR3 in OM susceptibility. Key messages: • Novel rare or low-frequency CDHR3 variants putatively confer risk for otitis media. • Pathogenic variant CDHR3 c.1653 + 3G > A was found in nine families with otitis media. • CDHR3 p.Cys529Tyr was associated with lack of effusion and bacterial otopathogens. • Cdhr3 expression was limited to ciliated epithelial cells in mouse middle ear. • Cdhr3 was downregulated 3 h after infection of mouse middle ear.
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| 3. |
- Fawzy, N. A., et al.
(författare)
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Incidence and factors associated with burnout in radiologists : A systematic review
- 2023
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Ingår i: European Journal of Radiology Open. - : Elsevier BV. - 2352-0477. ; 11
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Forskningsöversikt (refereegranskat)abstract
- Rationale and objectives: Burnout among physicians has a prevalence rate exceeding 50%. The radiology department is not immune to the burnout epidemic. Understanding and addressing burnout among radiologists has been a subject of recent interest. Thus, our study aims to systematically review studies reporting the prevalence of burnout in physicians in the radiology department while providing an overview of the factors associated with burnout among radiologists. Materials and methods: The search was conducted from inception until November 13th, 2022, in PubMed, Embase, Education Resources Information Center, PsycINFO, and psycArticles. Studies reporting the prevalence of burnout or any subdimensions among radiology physicians, including residents, fellows, consultants, and attendings, were included. Data on study characteristics and estimates of burnout syndrome or any of its subdimensions were collected and summarized. Results: After screening 6379 studies, 23 studies from seven countries were eligible. The number of participants ranged from 26 to 460 (median, 162; interquartile range, 91–264). In all, 18 studies (78.3%) employed a form of the Maslach Burnout Inventory. In comparison, four studies (17.4%) used the Stanford Professional Fulfillment Index, and one study (4.3%) used a single-item measure derived from the Zero Burnout Program survey. Overall burnout prevalence estimates were reported by 14 studies (60.9%) and varied from 33% to 88%. High burnout prevalence estimates were reported by only five studies (21.7%) and ranged from 5% to 62%. Emotional exhaustion and depersonalization prevalence estimates were reported by 16 studies (69.6%) and ranged from 11%−100% and 4%−97%, respectively. Furthermore, 15 studies (65.2%) reported low personal accomplishment prevalence, ranging from 14.7% to 84%. There were at least seven definitions for overall burnout and high burnout among the included studies, and there was high heterogeneity among the cutoff scores used for the burnout subdimensions. Conclusion: Burnout in radiology is increasing globally, with prevalence estimates reaching 88% and 62% for overall and high burnout, respectively. A myriad of factors has been identified as contributing to the increased prevalence. Our data demonstrated significant variability in burnout prevalence estimates among radiologists and major disparities in burnout criteria, instrument tools, and study quality.
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- Memon, M. A., et al.
(författare)
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Aetiology and associations of halitosis : A systematic review
- 2023
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Ingår i: Oral Diseases. - : Wiley. - 1354-523X .- 1601-0825. ; 29:4, s. 1432-1438
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Forskningsöversikt (refereegranskat)abstract
- Halitosis is a term that refers to an unpleasant or foul odour originating from the oral cavity that can be caused by either intra-oral or extra-oral factors. Despite the fact that halitosis has multifactorial aetiology, intra-oral factors play a significant role in the majority of cases. This systematic review assesses halitosis's intra-oral and extra-oral associations. An electronic search through MEDLINE (PubMed), Google Scholar and the Wiley Online Library was conducted to identify relevant manuscripts. A keywords-based search was performed, using the terms ‘halitosis’, ‘bad-breath’, and ‘oral malodour causes and aetiology’. Articles published from January 2014 to December 2020 were included. We selected studies evaluating the intra-oral and extra-oral factors that induce oral malodour, as well as the factors associated with systemic diseases. Eighty to ninety percent of halitosis is caused by intra-oral factors, with coated tongue, periodontal diseases and poor oral hygiene practices being the principal factors. Ten to twenty percent of halitosis is induced by extra-oral factors associated with systemic diseases. Multiple factors can cause halitosis, but most of the aetiology is intra-oral. Increased medical awareness is needed to determine the actual pathophysiological process of oral malodour in otherwise healthy individuals.
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- Paulus, A, et al.
(författare)
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Coinhibition of the deubiquitinating enzymes, USP14 and UCHL5, with VLX1570 is lethal to ibrutinib- or bortezomib-resistant Waldenstrom macroglobulinemia tumor cells
- 2016
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Ingår i: Blood cancer journal. - : Springer Science and Business Media LLC. - 2044-5385. ; 6:11, s. e492-
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Tidskriftsartikel (refereegranskat)abstract
- The survival of Waldenstrom macroglobulinemia (WM) tumor cells hinges on aberrant B-cell receptor (BCR) and MYD88 signaling. WM cells upregulate the proteasome function to sustain the BCR-driven growth while maintaining homeostasis. Clinically, two treatment strategies are used to disrupt these complementary yet mutually exclusive WM survival pathways via ibrutinib (targets BTK/MYD88 node) and bortezomib (targets 20 S proteasome). Despite the success of both agents, WM patients eventually become refractory to treatment, highlighting the adaptive plasticity of WM cells and underscoring the need for development of new therapeutics. Here we provide a comprehensive preclinical report on the anti-WM activity of VLX1570, a novel small-molecule inhibitor of the deubiquitinating enzymes (DUBs), ubiquitin-specific protease 14 (USP14) and ubiquitin carboxyl-terminal hydrolase isozyme L5 (UCHL5). Both DUBs reside in the 19 S proteasome cap and their inhibition by VLX1570 results in rapid and tumor-specific apoptosis in bortezomib- or ibrutinib-resistant WM cells. Notably, treatment of WM cells with VLX1570 downregulated BCR-associated elements BTK, MYD88, NFATC, NF-κB and CXCR4, the latter whose dysregulated function is linked to ibrutinib resistance. VLX1570 administered to WM-xenografted mice resulted in decreased tumor burden and prolonged survival (P=0.0008) compared with vehicle-treated mice. Overall, our report demonstrates significant value in targeting USP14/UCHL5 with VLX1570 in drug-resistant WM and carries a high potential for clinical translation.
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| 6. |
- Hashim, Ahmed, et al.
(författare)
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Pattern of novel psychoactive substance use among patients presented to the poison control centre of Ain Shams University Hospitals, Egypt : A cross-sectional study
- 2022
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Ingår i: Heliyon. - : Elsevier BV. - 2405-8440. ; 8:8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Novel psychoactive substances (NPSs) are relatively new substances in the illicit drug market, notpreviously listed in the United Nations Office on Drugs and Crime (UNDOC). Strox and Voodoo are consideredsome of the most popular blends of NPS in the Egyptian drug market.Objectives: The current study was conducted to assess NPS's use pattern: Voodoo and Strox among acutelyintoxicated patients presented to the poison control center of Ain Shams University Hospitals (PCC- ASUH).Methods: A single center based cross-sectional study was carried out in the PCC-ASUH among acutely intoxicatedpatients presenting to the emergency department (ED) over four months (from January–April 2019. using apreviously adopted and validated Fahmy and El-Sherbini socioeconomic scale (SES). Data were presented asmean, median and range as appropriate. Both smoking and crowding indexes were calculated and presented aspreviously reported.Results: Fifty-one patients were presented to the ED of PCC-ASUH during the study period. A total of 96.1% (n ¼49) were males. The mean age was 25 7.5 years. The most common NPS used was Strox: 54.9% (n ¼ 28),followed by Voodoo: 27.4% (n ¼ 14). Neurological and gastrointestinal (GI) symptoms were the most frequentpresentations. The most common motive behind NPS use was the desire to give a trial of new psychoactivesubstances. The mean SES score was 35.1 13.17. Most patients have the preparatory as the highest education36.0% (n ¼ 18).Conclusions: NPS use is common among young males in preparatory education from different social classes,starting it most commonly as a means to experiencing a new high. Neurological and GI manifestations are themost common presenting symptoms of NPS intoxication.
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| 10. |
- Yousaf, M., et al.
(författare)
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Evaluation of rare earth (Yb, La) doped (Sm3Fe5O12) garnet ferrite membrane for LT-SOFC
- 2020
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Ingår i: International journal of hydrogen energy. - : Elsevier Ltd. - 0360-3199 .- 1879-3487.
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Tidskriftsartikel (refereegranskat)abstract
- Rare earth element doping is a popular methodology for improving the electrical and electrochemical properties of materials. Inspired by this ideology, garnet ferrite material Sm3Fe5O12 (SFO) doped by rare earth (Yb, La) metal ions to form Sm3-0.5Yb0.5Fe5O12 (SYFO) and Sm3-0.5La0·5Fe5O12 (SLFO). The samples are synthesized by sol gel auto combustion and have been applied as electrolyte membrane for the first time in low temperature solid oxide fuel cell (LT-SOFC). The results indicate that the as-prepared materials have triple charge transport (H+/O−2/e−) carrier which promotes the hydrogen oxidation reaction (HOR) and oxygen reduction reactions (ORR) in SOFC at triple phase boundary region (TPB). Electrochemical impedance spectroscopy (EIS) reveals that the polarization resistance of SLFO membrane significantly reduces from 0.92 Ω-cm2 to 0.45 Ω-cm2 and the power output improve from 310 mW/cm2 to 650 mW/cm2 at 550 °C temperature in comparison with that of SYFO and SFO electrolyte supported cells. UV-vis diffused spectroscopy explains the semiconducting nature of the prepared materials due to the existence of optical bandgap in the semiconductor region. The further investigation also verifies the protonic conduction of SLFO membrane by constructing oxygen ion blocking fuel cell with configuration of Ni-NCAL/BZCY/SLFO/BZCY/Ni-NCAL having 427.94 mW/Cm2 fuel cell performance with 1.03 OCV at 550 °C temperature.
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| 11. |
- Bootpetch, TC, et al.
(författare)
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Multi-omic studies on missense PLG variants in families with otitis media
- 2020
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 15035-
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Tidskriftsartikel (refereegranskat)abstract
- Otitis media (OM), a very common disease in young children, can result in hearing loss. In order to potentially replicate previously reported associations between OM and PLG, exome and Sanger sequencing, RNA-sequencing of saliva and middle ear samples, 16S rRNA sequencing, molecular modeling, and statistical analyses including transmission disequilibrium tests (TDT) were performed in a multi-ethnic cohort of 718 families and simplex cases with OM. We identified four rare PLG variants c.112A > G (p.Lys38Glu), c.782G > A (p.Arg261His), c.1481C > T (p.Ala494Val) and c.2045 T > A (p.Ile682Asn), and one common variant c.1414G > A (p.Asp472Asn). However TDT analyses for these PLG variants did not demonstrate association with OM in 314 families. Additionally PLG expression is very low or absent in normal or diseased middle ear in mouse and human, and salivary expression and microbial α-diversity were non-significant in c.1414G > A (p.Asp472Asn) carriers. Based on molecular modeling, the novel rare variants particularly c.782G > A (p.Arg261His) and c.2045 T > A (p.Ile682Asn) were predicted to affect protein structure. Exploration of other potential disease mechanisms will help elucidate how PLG contributes to OM susceptibility in humans. Our results underline the importance of following up findings from genome-wide association through replication studies, preferably using multi-omic datasets.
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| 12. |
- Frank, DN, et al.
(författare)
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Otitis media susceptibility and shifts in the head and neck microbiome due to SPINK5 variants
- 2021
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Ingår i: Journal of medical genetics. - : BMJ. - 1468-6244 .- 0022-2593. ; 58:7, s. 442-452
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Tidskriftsartikel (refereegranskat)abstract
- Otitis media (OM) susceptibility has significant heritability; however, the role of rare variants in OM is mostly unknown. Our goal is to identify novel rare variants that confer OM susceptibility.MethodsWe performed exome and Sanger sequencing of >1000 DNA samples from 551 multiethnic families with OM and unrelated individuals, RNA-sequencing and microbiome sequencing and analyses of swabs from the outer ear, middle ear, nasopharynx and oral cavity. We also examined protein localisation and gene expression in infected and healthy middle ear tissues.ResultsA large, intermarried pedigree that includes 81 OM-affected and 53 unaffected individuals cosegregates two known rare A2ML1 variants, a common FUT2 variant and a rare, novel pathogenic variant c.1682A>G (p.Glu561Gly) within SPINK5 (LOD=4.09). Carriage of the SPINK5 missense variant resulted in increased relative abundance of Microbacteriaceae in the middle ear, along with occurrence of Microbacteriaceae in the outer ear and oral cavity but not the nasopharynx. Eight additional novel SPINK5 variants were identified in 12 families and individuals with OM. A role for SPINK5 in OM susceptibility is further supported by lower RNA counts in variant carriers, strong SPINK5 localisation in outer ear skin, faint localisation to middle ear mucosa and eardrum and increased SPINK5 expression in human cholesteatoma.ConclusionSPINK5 variants confer susceptibility to non-syndromic OM. These variants potentially contribute to middle ear pathology through breakdown of mucosal and epithelial barriers, immunodeficiency such as poor vaccination response, alteration of head and neck microbiota and facilitation of entry of opportunistic pathogens into the middle ear.
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| 14. |
- Rasool, Shahzad, et al.
(författare)
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Insight of proton transport phenomena in semiconductor ionic materials
- 2024
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Ingår i: Journal of Power Sources. - : Elsevier BV. - 0378-7753 .- 1873-2755. ; 598
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Forskningsöversikt (refereegranskat)abstract
- Semiconductor ionic materials (SIM) have recently gained broad attention due to their unique structural and chemical properties that enable efficient proton transport, making them promising materials for advanced fuel cell applications. This mini-review provides an overview of the proton transport phenomena in SIM and discusses their significance and future perspectives. We discuss the different types of SIMs, their proton transport mechanisms, and the factors that affect their performance. Furthermore, we emphasize the correlation between traditional perovskite oxides and SIMs and how this can be leveraged to improve the development of more advanced proton conductors for fuel cells. Also, we have highlighted the Proton-coupled electron transfer (PCET) mechanism in SIM. This mini-review provides a comprehensive overview of the current state of this emerging field, including its scientific foundations, future prospects, and applicable materials, technologies, devices, and basics for proton ceramic fuel cells (PCFCs).
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