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1.
Spec Care Dentist ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654464

RESUMO

INTRODUCTION: Parkinson's disease (PKD) is neurodegenerative disorder marked by tremors, bradykinesia, muscle rigidity and reduction in precise hand movements which could lead to improper oral hygiene and Periodontal disease. Current systematic review aims to review existing literature and provide assessment of periodontal health in PKD patients through a meta-analysis METHODS: Review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and registered in PROSPERO-CRD42023451700. Databases were searched for studies having sufficient data on periodontal health in patients with PKD compared to healthy controls and reporting outcomes in terms of various periodontal parameters of probing depth (PD), plaque index (PI), clinical attachment level (CAL), presence of bleeding on probing and gingivitis. Quality assessment of included was evaluated using Newcastle Ottawa Scale (NOS). RESULTS: Eleven studies fulfilled the eligibility criteria, of which ten studies were suitable for meta-analysis. Pooled estimate through the SMD showed that all periodontal parameters were altered and significantly deteriorated in PKD compared to controls but this group differences were statistically insignificant (p > 0.05). Publication bias through the funnel plot showed symmetric distribution with absence of systematic heterogeneity. CONCLUSION: Parkinson's disease could be a possible factor in deterioration of periodontal health.

2.
JAMA Ophthalmol ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38573612

RESUMO

Importance: Telehealth has the potential to improve health for older adults, but many access disparities exist, including for those with vision impairment (VI). Objective: To examine the associations between VI and digital technology access measures in US older adults. Design, Setting, and Participants: This was a cross-sectional study that included Medicare beneficiaries 65 years and older. Beneficiary data were obtained from the National Health and Aging Trends Study (NHATS) 2021; data collection was conducted from June 2020 through January 2021. Data were analyzed September 2023. Exposure: VI, measured on categorical (distance and near VI [>0.30 logMAR], contrast sensitivity impairment [CSI; <1.55 logCS], and any VI [distance VI, near VI, or CSI]), and continuous (distance and near acuity [logMAR] and contrast sensitivity [logCS]) scales. Main Outcomes: Self-reported outcomes of digital technology access from the technological environment component of the NHATS. Results: Of the 2822 Medicare beneficiaries (mean [SD] age, 78.5 [5.6] years; 1605 female [54.7%]) included in this study, patients self-identified with the following race and ethnicity categories (weighted percentages): 575 non-Hispanic Black (8.0%), 132 Hispanic (7.0%), 2019 non-Hispanic White (81.7%), and 63 non-Hispanic other race (3.4%), which included American Indian, Alaska Native, Asian, multiracial, Native Hawaiian, Pacific Islander, or other specified race. A total of 1077 of 2822 patients (32.3%) had any VI. In multivariable logistic regression models, older adults with any VI had lower odds of having or knowing how to use a cellphone (odds ratio [OR], 0.58; 95% CI, 0.38-0.88), computer (OR, 0.61; 95% CI, 0.47-0.79), or tablet (OR, 0.68, 95% CI = 0.54-0.85) than peers without VI. In other models, near VI was associated with lower odds of having and knowing how to use a phone (OR, 0.56; 95% CI, 0.36-0.87), computer (OR, 0.57; 95% CI, 0.44-0.75), or tablet (OR, 0.65; 95% CI, 0.52-0.81) compared with no near VI. CSI was associated with lower odds of having and knowing how to use a phone (OR, 0.66; 95% CI, 0.45-0.99) or computer (OR, 0.72; 95% CI, 0.55-0.93) compared with no CSI. Distance VI was only associated with lower odds of having and knowing how to use a cellphone (OR, 0.63; 95% CI, 0.41-0.95). Any VI and individual categorical VI measures were not associated with other outcomes of digital health- and nonhealth-related experiences. Similar associations were noted when vision was examined on a continuous scale. However, worse distance acuity (per 0.1 logMAR) was associated with being less likely to visit with family or friends on a video call (OR, 0.91; 95% CI, 0.84-0.98) and to order or refill prescriptions online (OR, 0.90; 95% CI, 0.83-0.97). Conclusions and Relevance: Results suggest that older US adults with VI were less likely to have access to digital technology than peers without VI, although no differences were noted in the report of digital health- and nonhealth-related activities. These findings highlight the potential for inequities that may arise in telehealth for older adults with VI and the necessity to develop strategies to improve accessibility of telemedicine for all.

4.
J Immunother Cancer ; 12(2)2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38309723

RESUMO

BACKGROUND: Comprehensive profiling of autoantibodies (AAbs) in metastatic urothelial cancer (mUC) has not been performed to date. This may aid in diagnosis of UC, uncover novel therapeutic targets in this disease as well as identify associations between AAbs and response and toxicity to systemic therapies. METHODS: We used serum from patients with mUC collected prior to and after systemic therapy (immune checkpoint inhibitor (ICI) or platinum-based chemotherapy (PBC)) at Dana-Farber Cancer Institute. 38 age-matched and sex-matched healthy controls (HCs) from healthy blood donors were also evaluated. The SeroTag immuno-oncology discovery array (Oncimmune) was used, with quantification of the AAb reactivity toward 1132 antigens. Bound AAbs were detected using an anti-immunoglobulin G-specific detection antibody conjugated to the fluorescent reporter dye phycoerythrin. The AAb reactivity was reported as the median fluorescence intensity for each color and sample using a Luminex FlexMAP3D analyzer. Clinical outcomes of interest included radiographic response and development of immune-related adverse events (irAEs). Significance analysis of microarray was used to compare mUC versus HC and radiographic response. Associations with irAE were evaluated using a logistic regression model. P<0.05 was considered statistically significant. RESULTS: 66 patients were included with a median age of 68 years; 54 patients (82%) received ICI and 12 patients (18%) received PBC. Compared with HCs, AAbs against the cancer/testis antigens (CTAG1B, CTAG2, MAGEB18), HSPA1A, TP53, KRAS, and FGFR3 were significantly elevated in patients with mUC. AAbs against BRCA2, TP53, and CTNBB1 were associated with response, and those against BICD2 and UACA were associated with resistance to ICI therapy. AAbs against MITF, CDH3, and KDM4A were associated with development of irAEs in patient who received an ICI. A higher variance in pre-to-post treatment fold change in AAb levels was seen in patients treated with ICI versus PBC and was associated with response to ICI. CONCLUSIONS: This is the first report of comprehensive AAb profiling of patients with mUC and identified key AAbs that were elevated in patients with mUC versus HCs as well as AAbs associated with therapeutic response to ICI. These findings are hypothesis generating and further mechanistic studies evaluating humoral immunity in UC are required.


Assuntos
Autoanticorpos , Carcinoma de Células de Transição , Masculino , Humanos , Idoso , Antígenos de Neoplasias , Proteínas de Membrana , Histona Desmetilases com o Domínio Jumonji
5.
Artigo em Inglês | MEDLINE | ID: mdl-38100771

RESUMO

PURPOSE: This study aimed to investigate the potential link between methamphetamine use and infectious syphilitic uveitis through a retrospective chart review of four patients with both conditions. METHODS: A retrospective chart review was conducted on four patients with a prior history of methamphetamine use and presented with vision loss at an emergency room or clinic that was ultimately diagnosed as syphilitic uveitis. RESULTS: The average age of the four patients was 41.5 ± 9.8 years old, and each presented with symptoms of blurry vision after an average of 3 weeks. Clinical and serologic examinations revealed variable severity of syphilitic uveitis in each patient, and a confirmed history of methamphetamine use was found on a review of social history. Each patient had worsening visual outcomes after the initial presentation and diagnosis. CONCLUSION: Syphilitic uveitis is a challenging diagnosis due to its similarity with other ocular pathologies. This case series highlights the importance of maintaining a high level of suspicion for syphilis in patients with a history of methamphetamine use and uveitis to enable rapid treatment and prevent visual decline. The poor visual outcomes observed in these four patients underscore the significance of identifying and treating syphilitic uveitis promptly in this population and the barriers to treatment completion.

6.
BMJ Case Rep ; 16(11)2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-37989326

RESUMO

A woman in her 50s presented with suspected open globe injury (OGI) of the right eye after being hit with a high velocity piece of plastic. Visual acuity at the time of presentation was counting fingers in the affected eye. Slit lamp examination revealed a full thickness laceration of the cornea and a traumatic cataract. Primary corneal repair was performed and the patient was left aphakic after cataract removal. Secondary intraocular lens placement was deferred for 2 years, after which time a scleral-fixated intraocular lens was implanted using the Yamane technique. Postoperative visual acuity of 20/50 was achieved, with the vision limited by persistent diabetic macular oedema. Thus, this case of successful implantation of a secondary lens using the Yamane technique in a patient with prior corneal laceration and traumatic cataract highlights that the Yamane technique can result in visual improvement in patients with prior OGI.


Assuntos
Extração de Catarata , Catarata , Lesões da Córnea , Lacerações , Cristalino , Lentes Intraoculares , Feminino , Humanos , Catarata/complicações , Lesões da Córnea/cirurgia , Implante de Lente Intraocular/métodos , Cristalino/lesões , Estudos Retrospectivos , Pessoa de Meia-Idade
7.
Microb Genom ; 9(10)2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37902186

RESUMO

Catheter-associated urinary tract infections (CAUTIs) represent one of the major healthcare-associated infections, and Pseudomonas aeruginosa is a common Gram-negative bacterium associated with catheter infections in Egyptian clinical settings. The present study describes the phenotypic and genotypic characteristics of 31 P. aeruginosa isolates recovered from CAUTIs in an Egyptian hospital over a 3 month period. Genomes of isolates were of good quality and were confirmed to be P. aeruginosa by comparison to the type strain (average nucleotide identity, phylogenetic analysis). Clonal diversity among the isolates was determined; eight different sequence types were found (STs 244, 357, 381, 621, 773, 1430, 1667 and 3765), of which ST357 and ST773 are considered to be high-risk clones. Antimicrobial resistance (AMR) testing according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines showed that the isolates were highly resistant to quinolones [ciprofloxacin (12/31, 38.7 %) and levofloxacin (9/31, 29 %) followed by tobramycin (10/31, 32.5 %)] and cephalosporins (7/31, 22.5 %). Genotypic analysis of resistance determinants predicted all isolates to encode a range of AMR genes, including those conferring resistance to aminoglycosides, ß-lactamases, fluoroquinolones, fosfomycin, sulfonamides, tetracyclines and chloramphenicol. One isolate was found to carry a 422 938 bp pBT2436-like megaplasmid encoding OXA-520, the first report from Egypt of this emerging family of clinically important mobile genetic elements. All isolates were able to form biofilms and were predicted to encode virulence genes associated with adherence, antimicrobial activity, anti-phagocytosis, phospholipase enzymes, iron uptake, proteases, secretion systems and toxins. The present study shows how phenotypic analysis alongside genomic analysis may help us understand the AMR and virulence profiles of P. aeruginosa contributing to CAUTIs in Egypt.


Assuntos
Pseudomonas aeruginosa , Infecções Urinárias , Humanos , Pseudomonas aeruginosa/genética , Egito , Filogenia , Genômica , Antibacterianos/farmacologia , Catéteres
8.
Proc (Bayl Univ Med Cent) ; 36(6): 722-727, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37829212

RESUMO

Purpose: To compare the lobbying expenditures and political action committee (PAC) campaign finance activities of the American Academy of Ophthalmology (AAO), American Society of Cataract and Refractive Surgery (ASCRS), and American Optometric Association (AOA) from 2015 to 2022. Methods: Financial data were collected from the Federal Election Commission and OpenSecrets database. Analysis was performed to characterize and compare financial activity among the organizations. P < 0.05 was considered significant and all analyses were two-sided. Results: From 2015 to 2022, the AAO, ASCRS, and AOA spent $6,745,000, $5,354,406, and $13,335,000 on lobbying, respectively. The AOA's annual lobbying expenditure (median, $1,725,000) was significantly greater than AAO's ($842,500, P = 0.03) and ASCRS's ($694,289, P < 0.001). In PAC donations, OPHTHPAC, affiliated with AAO, received $3,221,737 from 2079 donors (median, $900); eyePAC, affiliated with ASCRS, received $506,255 from 349 donors ($500); and AOA-PAC received $6,642,588 from 3641 donors ($825). Compared to eyePAC, median donations to OPHTHPAC (P = 0.01) and AOA-PAC (P = 0.04) were significantly higher. In campaign spending, OPHTHPAC contributed $2,728,500 to 326 campaigns (median, $5000), eyePAC contributed $293,500 to 58 campaigns ($3000), and AOA-PAC contributed $5,128,673 to 617 campaigns ($5500). eyePAC's median campaign contribution was significantly lower than the AOA's (P < 0.001) and AAO's (P = 0.007). Every PAC directed most of its contributions toward Republican campaigns; eyePAC donated the highest proportion (64.9%). Conclusions: AOA was more assertive in shaping policy by increasing lobbying expenditures, fundraising, and donating to a greater number of election campaigns.

10.
Access Microbiol ; 5(7)2023.
Artigo em Inglês | MEDLINE | ID: mdl-37601440

RESUMO

We present the first complete genome sequence of the species Staphylococcus casei . Strain DSM 15096 was sequenced with a hybrid approach using Oxford Nanopore Technologies long-read sequencing and Illumina short-read sequencing. The assembled sequences produced a 2 808 898 bp chromosomal molecule containing 2705 predicted genes, plus eight plasmids.

11.
Sci Adv ; 9(32): eadg9832, 2023 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-37556531

RESUMO

Histone H2A lysine 119 (H2AK119Ub) is monoubiquitinated by Polycomb repressive complex 1 and deubiquitinated by Polycomb repressive deubiquitinase complex (PR-DUB). PR-DUB cleaves H2AK119Ub to restrict focal H2AK119Ub at Polycomb target sites and to protect active genes from aberrant silencing. The PR-DUB subunits (BAP1 and ASXL1) are among the most frequently mutated epigenetic factors in human cancers. How PR-DUB establishes specificity for H2AK119Ub over other nucleosomal ubiquitination sites and how disease-associated mutations of the enzyme affect activity are unclear. Here, we determine a cryo-EM structure of human BAP1 and the ASXL1 DEUBAD in complex with a H2AK119Ub nucleosome. Our structural, biochemical, and cellular data reveal the molecular interactions of BAP1 and ASXL1 with histones and DNA that are critical for restructuring the nucleosome and thus establishing specificity for H2AK119Ub. These results further provide a molecular explanation for how >50 mutations in BAP1 and ASXL1 found in cancer can dysregulate H2AK119Ub deubiquitination, providing insight into understanding cancer etiology.


Assuntos
Proteínas de Drosophila , Neoplasias , Humanos , Histonas/genética , Nucleossomos , Lisina , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo , Proteínas do Grupo Polycomb/genética , Proteínas de Drosophila/genética , Neoplasias/genética , Proteínas Repressoras/genética , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
12.
J Med Microbiol ; 72(6)2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37294289

RESUMO

Introduction. Helicobacter pylori is highly polymorphic, and some strains are much more likely to cause disease than others. Biofilm formation can help bacteria to survive antibiotic treatment, immune attack and other stresses, promoting persistent infection.Hypothesis/Gap Statement. We hypothesized that H. pylori isolates from patients with more severe H. pylori-associated disease would be better at forming biofilms than isolates from patients with less severe disease.Aim. We initially aimed to determine whether or not the biofilm-forming ability of H. pylori isolates was associated with disease in the UK-based patients from whom the bacteria were isolated.Methodology. Biofilm-forming ability of H. pylori isolates was determined using a crystal violet assay on glass coverslips. The complete genome sequence of strain 444A was generated by hybrid assembly of Nanopore MinION and Illumina MiSeq data.Results. Although we found no associations between biofilm-forming ability of H. pylori and disease severity in patients, we discovered that strain 444A had particularly high biofilm-forming ability. This strain had been isolated from a patient with gastric ulcer disease and moderate to severe scores for H. pylori-induced histopathology. Analysis of the genome of the high biofilm-forming H. pylori strain 444A revealed that it possesses numerous biofilm- and virulence-associated genes and a small cryptic plasmid encoding a type II toxin-antitoxin system.Conclusion. There is substantial variation in biofilm-forming ability in H. pylori, but this was not significantly associated with disease severity in our study. We identified and characterized an interesting strain with high biofilm-forming ability, including generation and analysis of the complete genome.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Humanos , Biofilmes , Antibacterianos/farmacologia , Infecções por Helicobacter/microbiologia
13.
Vaccine ; 41(23): 3564-3576, 2023 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-37164820

RESUMO

BACKGROUND: Genital human papillomavirus (HPV) infection is the most prevalent sexually transmitted infection among young adults ages 15-25 years in the United States (US). Although HPV vaccines are recommended for individuals ages through 26 years, vaccine completion rates remain substantially low. METHODS: Accordingly, our study utilized a comprehensive - Theoretical Domains Framework (TDF) of behavior change to systematically identify facilitators and barriers to catch-up HPV vaccinations. Five databases - Medline, Embase, CINAHL, ERIC, and PsycINFO were searched from January 2009 to July 2019 for empirical studies using quantitative and qualitative methods to assess HPV vaccine uptake among males ages 18-26 years within US college and university settings. The TDF analytic process included a content analysis using the mixed deductive-inductive approach to extract, analyze and categorize data into TDF domains/themes and sub-themes. RESULTS: Overall, 17 studies were selected for data extraction. We identified eleven key TDF domains that influenced HPV vaccination behavior among college male students: 'knowledge' (82% of included studies), 'environmental context and resources' (53%), 'beliefs about consequences' (53%), 'unrealistic optimism' (50%) and 'pessimism' (6%), 'emotion' (50%), 'social influences' (50%), 'beliefs about capabilities' (41%), 'intention' (24%), 'reinforcement' (18%), 'social professional role and identity'(12%), and 'behavioral regulation' (12%). Barriers influencing HPV vaccine uptake included lack of knowledge and awareness regarding HPV infections, HPV vaccine safety, effectiveness, side effects, and costs; absence of health providers' recommendations; lack of healthcare and health insurance; low levels of perceived susceptibility and severity for HPV infections; HPV vaccine misinformation; as well as social stigma and peer influences regarding HPV vaccinations. Enablers for HPV vaccine uptake included high levels of perceived benefits for HPV vaccines. DISCUSSION: Our study theoretically identified factors influencing HPV vaccinations. This could inform the efficient planning, support, and implementation of interventions that facilitate catch-up HPV vaccination practices among high-risk males within college/university settings.


Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Adulto Jovem , Humanos , Masculino , Estados Unidos , Infecções por Papillomavirus/prevenção & controle , Atenção à Saúde , Vacinação/métodos , Estudantes , Conhecimentos, Atitudes e Prática em Saúde
14.
Radiat Oncol J ; 41(1): 12-22, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37013414

RESUMO

PURPOSE: There has been limited work assessing the use of re-irradiation (re-RT) for local failure following stereotactic spinal radiosurgery (SSRS). We reviewed our institutional experience of conventionally-fractionated external beam radiation (cEBRT) for salvage therapy following SSRS local failure. MATERIALS AND METHODS: We performed a retrospective review of 54 patients that underwent salvage conventional re-RT at previously SSRS-treated sites. Local control following re-RT was defined as the absence of progression at the treated site as determined by magnetic resonance imaging. RESULTS: Competing risk analysis for local failure was performed using a Fine-Gray model. The median follow-up time was 25 months and median overall survival (OS) was 16 months (95% confidence interval [CI], 10.8-24.9 months) following cEBRT re-RT. Multivariable Cox proportional-hazards analysis revealed Karnofsky performance score prior to re-RT (hazard ratio [HR] = 0.95; 95% CI, 0.93-0.98; p = 0.003) and time to local failure (HR = 0.97; 95% CI, 0.94-1.00; p = 0.04) were associated with longer OS, while male sex (HR = 3.92; 95% CI, 1.64-9.33; p = 0.002) was associated with shorter OS. Local control at 12 months was 81% (95% CI, 69.3-94.0). Competing risk multivariable regression revealed radioresistant tumors (subhazard ratio [subHR] = 0.36; 95% CI, 0.15-0.90; p = 0.028) and epidural disease (subHR = 0.31; 95% CI, 0.12-0.78; p =0.013) were associated with increased risk of local failure. At 12 months, 91% of patients maintained ambulatory function. CONCLUSION: Our data suggest that cEBRT following SSRS local failure can be used safely and effectively. Further investigation is needed into optimal patient selection for cEBRT in the retreatment setting.

15.
Dig Dis Sci ; 68(6): 2379-2388, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37022601

RESUMO

BACKGROUND: Post-operative cardiac complications occur infrequently but contribute to mortality after liver transplantation (LT). Artificial intelligence-based algorithms based on electrocardiogram (AI-ECG) are attractive for use during pre-operative evaluation to screen for risk of post-operative cardiac complications, but their use for this purpose is unknown. AIMS: The aim of this study was to evaluate the performance of an AI-ECG algorithm in predicting cardiac factors such as asymptomatic left ventricular systolic dysfunction or potential for developing post-operative atrial fibrillation (AF) in cohorts of patients with end-stage liver disease either undergoing evaluation for transplant or receiving a liver transplant. METHODS: A retrospective study was performed in two consecutive adult cohorts of patients who were either evaluated for LT or underwent LT at a single center between 2017 and 2019. ECG were analyzed using an AI-ECG trained to recognize patterns from a standard 12-lead ECG which could identify the presence of left ventricular systolic dysfunction (LVEF < 50%) or subsequent atrial fibrillation. RESULTS: The performance of AI-ECG in patients undergoing LT evaluation is similar to that in a general population but was lower in the presence of prolonged QTc. AI-ECG analysis on ECG in sinus rhythm had an AUROC of 0.69 for prediction of de novo post-transplant AF. Although post-transplant cardiac dysfunction occurred in only 2.3% of patients in the study cohorts, AI-ECG had an AUROC of 0.69 for prediction of subsequent low left ventricular ejection fraction. CONCLUSIONS: A positive screen for low EF or AF on AI-ECG can alert to risk of post-operative cardiac dysfunction or predict new onset atrial fibrillation after LT. The use of an AI-ECG can be a useful adjunct in persons undergoing transplant evaluation that can be readily implemented in clinical practice.


Assuntos
Fibrilação Atrial , Transplante de Fígado , Disfunção Ventricular Esquerda , Adulto , Humanos , Inteligência Artificial , Fibrilação Atrial/complicações , Transplante de Fígado/efeitos adversos , Estudos Retrospectivos , Volume Sistólico , Função Ventricular Esquerda , Eletrocardiografia , Disfunção Ventricular Esquerda/complicações , Medição de Risco
16.
bioRxiv ; 2023 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-36865140

RESUMO

The maintenance of gene expression patterns during metazoan development is achieved by the actions of Polycomb group (PcG) complexes. An essential modification marking silenced genes is monoubiquitination of histone H2A lysine 119 (H2AK119Ub) deposited by the E3 ubiquitin ligase activity of the non-canonical Polycomb Repressive Complex 1. The Polycomb Repressive Deubiquitinase (PR-DUB) complex cleaves monoubiquitin from histone H2A lysine 119 (H2AK119Ub) to restrict focal H2AK119Ub at Polycomb target sites and to protect active genes from aberrant silencing. BAP1 and ASXL1, subunits that form active PR-DUB, are among the most frequently mutated epigenetic factors in human cancers, underscoring their biological importance. How PR-DUB achieves specificity for H2AK119Ub to regulate Polycomb silencing is unknown, and the mechanisms of most of the mutations in BAP1 and ASXL1 found in cancer have not been established. Here we determine a cryo-EM structure of human BAP1 bound to the ASXL1 DEUBAD domain in complex with a H2AK119Ub nucleosome. Our structural, biochemical, and cellular data reveal the molecular interactions of BAP1 and ASXL1 with histones and DNA that are critical for remodeling the nucleosome and thus establishing specificity for H2AK119Ub. These results further provide a molecular explanation for how >50 mutations in BAP1 and ASXL1 found in cancer can dysregulate H2AK119Ub deubiquitination, providing new insight into understanding cancer etiology. One Sentence Summary: We reveal the molecular mechanism of nucleosomal H2AK119Ub deubiquitination by human BAP1/ASXL1.

18.
Front Med (Lausanne) ; 9: 992703, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36250077

RESUMO

Liver disease such as cirrhosis is known to cause changes in the composition of volatile organic compounds (VOC) present in patient breath samples. Previous studies have demonstrated the diagnosis of liver cirrhosis from these breath samples, but studies are limited to a handful of discrete, well-characterized compounds. We utilized VOC profiles from breath samples from 46 individuals, 35 with cirrhosis and 11 healthy controls. A deep-neural network was optimized to discriminate between healthy controls and individuals with cirrhosis. A 1D convolutional neural network (CNN) was accurate in predicting which patients had cirrhosis with an AUC of 0.90 (95% CI: 0.75, 0.99). Shapley Additive Explanations characterized the presence of discrete, observable peaks which were implicated in prediction, and the top peaks (based on the average SHAP profiles on the test dataset) were noted. CNNs demonstrate the ability to predict the presence of cirrhosis based on a full volatolomics profile of patient breath samples. SHAP values indicate the presence of discrete, detectable peaks in the VOC signal.

19.
Microbiol Resour Announc ; 11(9): e0051822, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35946951

RESUMO

Here, we present the complete genome sequence of Staphylococcus edaphicus strain CCM 8731, which was originally isolated from Ross Island, Antarctica. The 2,749,487-bp sequence contains 2,709 predicted genes, with a G+C content of 33.4%. The complete genome was assembled using a hybrid approach with Oxford Nanopore Technologies long-read sequencing and Illumina short-read sequencing.

20.
Urology ; 166: 241-245, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35643112

RESUMO

Fetus in fetu is a rare phenomenon of infancy, separate from conjoined twins, teratomas, and acardiac twins. The pathogenesis is not well understood but has been theorized to originate from either the involution of a twin or the differentiation of a teratoma. While the majority of these are found in the retroperitoneum, the presence of a fetus in fetu within the scrotum is exceedingly rare. We present the diagnosis and management of a case of fetus in fetu in the scrotum of a newborn male including radiologic imaging and pathologic examination.


Assuntos
Teratoma , Gêmeos Unidos , Abdome , Feto/diagnóstico por imagem , Feto/patologia , Humanos , Recém-Nascido , Masculino , Escroto/diagnóstico por imagem , Escroto/patologia , Teratoma/diagnóstico por imagem , Teratoma/cirurgia
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