-
Seizure May 2024Cognitive behavioural therapy (CBT) and other psychological approaches have a growing evidence base for treating Non-Epileptic Seizures (NES). However, communication... (Review)
Review
BACKGROUND
Cognitive behavioural therapy (CBT) and other psychological approaches have a growing evidence base for treating Non-Epileptic Seizures (NES). However, communication about the diagnosis can be difficult for clinicians and is not always well received. It is thought that Psychoeducation about NES may improve engagement with treatment such as CBT and may contribute to reductions in the frequency of seizures and improvements in health related quality of life. However, psychoeducational components of treatment are often not evaluated in isolation meaning the specific benefit to patients is not currently well understood.
AIMS
The researchers aimed to examine the outcomes associated with psychoeducational interventions and the content of these programmes for NES.
METHOD
A scoping review was undertaken across four databases with seventeen eligible studies identified which were charted to analyse the data.
RESULTS
Findings revealed that components and modalities of interventions varied as did methods of evaluating the interventions. A number of different outcome measures were used and not all studies reported the significance of findings. Results across studies were inconsistent; however, there was a general trend across the studies of symptom reduction and improvement in mental health.
CONCLUSIONS
Findings illustrate that psychoeducation has potential benefits as an intervention in its own right. However, it may be best placed as a second step in a stepped care model, between initial diagnosis and further psychological treatment. The present literature needs replication and more robust studies for more certain conclusions to be drawn.
PubMed: 38889520
DOI: 10.1016/j.seizure.2024.05.013 -
MedComm Jul 2024The association between Hepatitis B virus (HBV) infection and colorectal liver metastases (CRLM) remains ambiguous in current population-based evidence. To clarify this,...
The association between Hepatitis B virus (HBV) infection and colorectal liver metastases (CRLM) remains ambiguous in current population-based evidence. To clarify this, we present a retrospective analysis of 5871 colorectal cancer (CRC) patients. Propensity score matching (PSM) was applied to harmonize age and sex disparities within HBV+ ( = 1696) and HBV- ( = 4175) groups and further within HBV+ subgroups of chronic (CHB, = 474) and occult (OHB, = 1222) infections. Our initial results indicated a significant association between HBV infection and synchronous colorectal liver metastasis (SYN-CRLM); however, this association dissipated after PSM was employed to adjust for confounding variables. No significant association was observed between HBV infection and metachronous colorectal liver metastases (MET-CRLM) both before and after PSM. Further analysis revealed that HBV replication status did not influence the incidence of CRLM. However, HBV+ participants demonstrated an increased incidence of metachronous extrahepatic metastases, particularly to the lungs. Our findings imply that neither past nor present HBV infection is significantly correlated with the occurrence of SYN-CRLM or MET-CRLM. The absence of an association between HBV replication status and CRLM incidence highlights the importance of incorporating a broader range of factors in the clinical management of CRLM beyond the status of HBV infection.
PubMed: 38887467
DOI: 10.1002/mco2.584 -
Journal of the American College of... Jun 2024Patients hospitalized for COVID-19 frequently develop hypoxemia and acute respiratory distress syndrome (ARDS) after admission. In non-COVID-19 ARDS studies, admission...
OBJECTIVES
Patients hospitalized for COVID-19 frequently develop hypoxemia and acute respiratory distress syndrome (ARDS) after admission. In non-COVID-19 ARDS studies, admission to hospital wards with subsequent transfer to intensive care unit (ICU) is associated with worse outcomes. We hypothesized that initial admission to the ward may affect outcomes in patient with COVID-19 ARDS.
METHODS
This was a retrospective study of consecutive adults admitted for COVID-19 ARDS between March 2020 and March 2021 at Stanford Health Care. Mortality scores at hospital admission (Coronavirus Clinical Characterization Consortium Mortality Score [4C score]) and ICU admission (Simplified Acute Physiology Score III [SAPS-III]) were calculated, as well as ROX index for patients on high flow nasal oxygen. Patients were classified by emergency department (ED) disposition (ward-first vs. ICU-direct), and 28- and 60-day mortality and highest level of respiratory support within 1 day of ICU admission were compared. A second cohort (April 2021‒July 2022, = 129) was phenotyped to validate mortality outcome.
RESULTS
A total of 157 patients were included, 48% of whom were first admitted to the ward ( = 75). Ward-first patients had more comorbidities, including lung disease. Ward-first patients had lower 4C and similar SAPS-III score, yet increased mortality at 28 days (32% vs. 17%, hazard ratio [HR] 2.0, 95% confidence interval [95% CI] 1.0‒3.7, = 0.039) and 60 days (39% vs. 23%, HR 1.83, 95% CI 1.04‒3.22, = 0.037) compared to ICU-direct patients. More ward-first patients escalated to mechanical ventilation on day 1 of ICU admission (36% vs. 14%, = 0.002) despite similar ROX index. Ward-first patients who upgraded to ICU within 48 h of ED presentation had the highest mortality. Mortality findings were replicated in a sensitivity analysis.
CONCLUSION
Despite similar baseline risk scores, ward-first patients with COVID-19 ARDS had increased mortality and escalation to mechanical ventilation compared to ICU-direct patients. Ward-first patients requiring ICU upgrade within 48 h were at highest risk, highlighting a need for improved identification of this group at ED admission.
PubMed: 38887225
DOI: 10.1002/emp2.13192 -
Retrovirology Jun 2024An essential regulatory hub for retroviral replication events, the 5' untranslated region (UTR) encodes an ensemble of cis-acting replication elements that overlap in a... (Review)
Review
An essential regulatory hub for retroviral replication events, the 5' untranslated region (UTR) encodes an ensemble of cis-acting replication elements that overlap in a logical manner to carry out divergent RNA activities in cells and in virions. The primer binding site (PBS) and primer activation sequence initiate the reverse transcription process in virions, yet overlap with structural elements that regulate expression of the complex viral proteome. PBS-segment also encompasses the attachment site for Integrase to cut and paste the 3' long terminal repeat into the host chromosome to form the provirus and purine residues necessary to execute the precise stoichiometry of genome-length transcripts and spliced viral RNAs. Recent genetic mapping, cofactor affinity experiments, NMR and SAXS have elucidated that the HIV-1 PBS-segment folds into a three-way junction structure. The three-way junction structure is recognized by the host's nuclear RNA helicase A/DHX9 (RHA). RHA tethers host trimethyl guanosine synthase 1 to the Rev/Rev responsive element (RRE)-containing RNAs for m7-guanosine Cap hyper methylation that bolsters virion infectivity significantly. The HIV-1 trimethylated (TMG) Cap licenses specialized translation of virion proteins under conditions that repress translation of the regulatory proteins. Clearly host-adaption and RNA shapeshifting comprise the fundamental basis for PBS-segment orchestrating both reverse transcription of virion RNA and the nuclear modification of m7G-Cap for biphasic translation of the complex viral proteome. These recent observations, which have exposed even greater complexity of retroviral RNA biology than previously established, are the impetus for this article. Basic research to fully comprehend the marriage of PBS-segment structures and host RNA binding proteins that carry out retroviral early and late replication events is likely to expose an immutable virus-specific therapeutic target to attenuate retrovirus proliferation.
Topics: Virus Replication; RNA, Viral; Humans; HIV-1; 5' Untranslated Regions; Binding Sites; Gene Expression Regulation, Viral; Reverse Transcription; Retroviridae
PubMed: 38886829
DOI: 10.1186/s12977-024-00646-x -
The EMBO Journal Jun 2024Mutational patterns caused by APOBEC3 cytidine deaminase activity are evident throughout human cancer genomes. In particular, the APOBEC3A family member is a potent...
Mutational patterns caused by APOBEC3 cytidine deaminase activity are evident throughout human cancer genomes. In particular, the APOBEC3A family member is a potent genotoxin that causes substantial DNA damage in experimental systems and human tumors. However, the mechanisms that ensure genome stability in cells with active APOBEC3A are unknown. Through an unbiased genome-wide screen, we define the Structural Maintenance of Chromosomes 5/6 (SMC5/6) complex as essential for cell viability when APOBEC3A is active. We observe an absence of APOBEC3A mutagenesis in human tumors with SMC5/6 dysfunction, consistent with synthetic lethality. Cancer cells depleted of SMC5/6 incur substantial genome damage from APOBEC3A activity during DNA replication. Further, APOBEC3A activity results in replication tract lengthening which is dependent on PrimPol, consistent with re-initiation of DNA synthesis downstream of APOBEC3A-induced lesions. Loss of SMC5/6 abrogates elongated replication tracts and increases DNA breaks upon APOBEC3A activity. Our findings indicate that replication fork lengthening reflects a DNA damage response to APOBEC3A activity that promotes genome stability in an SMC5/6-dependent manner. Therefore, SMC5/6 presents a potential therapeutic vulnerability in tumors with active APOBEC3A.
PubMed: 38886582
DOI: 10.1038/s44318-024-00137-x -
BioRxiv : the Preprint Server For... Apr 2024Viral internal ribosomal entry sites (IRESs) form several classes that use distinct mechanisms to mediate end-independent initiation of translation. The origin of viral...
Viral internal ribosomal entry sites (IRESs) form several classes that use distinct mechanisms to mediate end-independent initiation of translation. The origin of viral IRESs is a longstanding question. The simplest IRESs comprise tandem pseudoknots and occur in the intergenic region (IGR) of genomes (order ). Larger IGR IRESs contain additional elements that determine specific properties such as binding to the head of the ribosoma l 40S subunit. Metagenomic analyses reported here identified novel groups of structurally distinct IGR-like IRESs. The smallest of these (∼120nt long) comprise three pseudoknots and bind directly to the ribosomal P site. Others are up to 260nt long: insertions occurred at specific loci, possibly reflecting non-templated nucleotide insertion during replication. Various groups can be arranged in order, differing by the cumulative addition of single structural elements, suggesting an accretion mechanism for the structural elaboration of IRESs. Identification of chimeric IRESs implicates recombinational exchange of domains as a second mechanism for the diversification of IRES structure. Recombination likely also accounts for the presence of IGR-like IRESs at the 5'-end of some dicistrovirus-like genomes (e.g. Hangzhou dicistrovirus 3) and in the RNA genomes of (order ), (order s), and the 'Ripiresk' picorna-like clade (order s).
PubMed: 38883778
DOI: 10.1101/2024.04.17.590008 -
ArXiv Jun 2024Electrical waves in the heart form rotating spiral or scroll waves during life-threatening arrhythmias such as atrial or ventricular fibrillation. The wave dynamics are...
Electrical waves in the heart form rotating spiral or scroll waves during life-threatening arrhythmias such as atrial or ventricular fibrillation. The wave dynamics are typically modeled using coupled partial differential equations, which describe reaction-diffusion dynamics in excitable media. More recently, data-driven generative modeling has emerged as an alternative to generate spatio-temporal patterns in physical and biological systems. Here, we explore denoising diffusion probabilistic models for the generative modeling of electrical wave patterns in cardiac tissue. We trained diffusion models with simulated electrical wave patterns to be able to generate such wave patterns in unconditional and conditional generation tasks. For instance, we explored the diffusion-based i) parameter-specific generation, ii) evolution and iii) inpainting of spiral wave dynamics, including reconstructing three-dimensional scroll wave dynamics from superficial two-dimensional measurements. Further, we generated arbitrarily shaped bi-ventricular geometries and simultaneously initiated scroll wave patterns inside these geometries using diffusion. We characterized and compared the diffusion-generated solutions to solutions obtained with corresponding biophysical models and found that diffusion models learn to replicate spiral and scroll waves dynamics so well that they could be used for data-driven modeling of excitation waves in cardiac tissue. For instance, an ensemble of diffusion-generated spiral wave dynamics exhibits similar self-termination statistics as the corresponding ensemble simulated with a biophysical model. However, we also found that diffusion models {produce artifacts if training data is lacking, e.g. during self-termination,} and `hallucinate' wave patterns when insufficiently constrained.
PubMed: 38883235
DOI: No ID Found -
Frontiers in Public Health 2024Chat Generative Pre-trained Transformer (ChatGPT) is a new machine learning tool that allows patients to access health information online, specifically compared to...
BACKGROUND
Chat Generative Pre-trained Transformer (ChatGPT) is a new machine learning tool that allows patients to access health information online, specifically compared to Google, the most commonly used search engine in the United States. Patients can use ChatGPT to better understand medical issues. This study compared the two search engines based on: (i) frequently asked questions (FAQs) about Femoroacetabular Impingement Syndrome (FAI), (ii) the corresponding answers to these FAQs, and (iii) the most FAQs yielding a numerical response.
PURPOSE
To assess the suitability of ChatGPT as an online health information resource for patients by replicating their internet searches.
STUDY DESIGN
Cross-sectional study.
METHODS
The same keywords were used to search the 10 most common questions about FAI on both Google and ChatGPT. The responses from both search engines were recorded and analyzed.
RESULTS
Of the 20 questions, 8 (40%) were similar. Among the 10 questions searched on Google, 7 were provided by a medical practice. For numerical questions, there was a notable difference in answers between Google and ChatGPT for 3 out of the top 5 most common questions (60%). Expert evaluation indicated that 67.5% of experts were satisfied or highly satisfied with the accuracy of ChatGPT's descriptions of both conservative and surgical treatment options for FAI. Additionally, 62.5% of experts were satisfied or highly satisfied with the safety of the information provided. Regarding the etiology of FAI, including cam and pincer impingements, 52.5% of experts expressed satisfaction or high satisfaction with ChatGPT's explanations. Overall, 62.5% of experts affirmed that ChatGPT could serve effectively as a reliable medical resource for initial information retrieval.
CONCLUSION
This study confirms that ChatGPT, despite being a new tool, shows significant potential as a supplementary resource for health information on FAI. Expert evaluations commend its capacity to provide accurate and comprehensive responses, valued by medical professionals for relevance and safety. Nonetheless, continuous improvements in its medical content's depth and precision are recommended for ongoing reliability. While ChatGPT offers a promising alternative to traditional search engines, meticulous validation is imperative before it can be fully embraced as a trusted medical resource.
Topics: Humans; Cross-Sectional Studies; Femoracetabular Impingement; Search Engine; Internet; Machine Learning; Male; Female; Adult
PubMed: 38883198
DOI: 10.3389/fpubh.2024.1412063 -
Biochemia Medica Jun 2024Glycomics, focusing on the role of glycans in biological processes, particularly their influence on the folding, stability and receptor interactions of glycoconjugates...
INTRODUCTION
Glycomics, focusing on the role of glycans in biological processes, particularly their influence on the folding, stability and receptor interactions of glycoconjugates like antibodies, is vital for our understanding of biology. Changes in immunoglobulin G (IgG) N-glycosylation have been associated with various physiological and pathophysiological conditions. Nevertheless, time-consuming manual sample preparation is one of the limitations in the glycomics diagnostic implementation. The study aimed to develop an automated method for sample preparation on the Tecan Freedom Evo 200 platform and compare its efficiency and precision with the manual counterpart.
MATERIALS AND METHODS
The initial method development included 32 pooled blood plasma technical replicates. An additional 24 pooled samples were used in the method comparison along with 78 random duplicates of plasma samples collected from 10,001 Dalmatians biobank to compare the manual and automated methods.
RESULTS
The development resulted in a new automated method. For the automated method, glycan peaks comprising 91% of the total sample glycan showed a variation of less than 5% while 92% of the total sample showed a variation of less than 5% for the manual method. The results of the Passing-Bablok regression indicated no differences between the automated and manual methods for 12 glycan peaks (GPs). However, for 8 GPs systematic difference was present, while both systematic and proportional differences were present for four GPs.
CONCLUSIONS
The developed automated sample preparation method for IgG glycan analysis reduced exposure to hazardous chemicals and offered a simplified workflow. Despite slight differences between the methods, the new automated method showed high precision and proved to be highly comparable to its manual counterpart.
Topics: Humans; Glycosylation; Immunoglobulin G; Polysaccharides; Glycomics; High-Throughput Screening Assays; Automation; Glycoproteins
PubMed: 38882586
DOI: 10.11613/BM.2024.020708 -
Virus Research Jun 2024Although it is generally believed that large DNA viruses capture genes by horizontal gene transfer (HGT), the detailed manner of such transfer has not been fully...
Although it is generally believed that large DNA viruses capture genes by horizontal gene transfer (HGT), the detailed manner of such transfer has not been fully elucidated. Here, we searched for genes in the coleopteran entomopoxvirus (EV) Anomala cuprea entomopoxvirus (ACEV) that might have been gained by ACEV by HGT. We classified the potential source organisms for HGT into three categories: the host A. cuprea; other organisms, including viruses unrelated to EVs; and organisms with uncertain host attribution. Of the open reading frames (ORFs) of the ACEV genome, 2.1 % were suggested to have been gained from the host by ACEV or its recent ancestor via HGT; 8.7 % were possibly from organisms other than the host, and 3.7 % were possibly from the third category of organisms via HGT. The analysis showed that ACEV contains some interesting ORFs obtained by HGT, including a large ATP-binding cassette protein (ABC transporter) ORF and a tenascin ORF (IDs ACV025 and ACV123, respectively). We then performed a detailed analysis of the HGT of the ACEV large ABC transporter ORF-the largest of the ACEV ORFs. mRNA sequences obtained by RNA-seq from fat bodies-sites of ACEV replication-and midgut tissues-sites of initial infection-of the virus's host A. cuprea larvae were subjected to BLAST analysis. One type of ABC transporter ORF from the fat bodies and two types from the midgut tissues, one of which was identical to that in the fat bodies, had the greatest identity to the ABC transporter ORF of ACEV. The two types from the host had high levels of identity to each other (approximately 95 % nucleotide sequence identity), strongly suggesting that the host ABC transporter group consisting of the two types was the origin of ACV025. We then determined the sequence (12,381 bp) containing a full-length gene of the A. cuprea ABC transporter. It turned out to be a transcription template for the abovementioned mRNA found in both tissues. In addition, we determined a large part (ca. 6.9 kb) of the template sequence for the mRNA found only in the midgut tissues. The results showed that the ACEV ABC transporter ORF is missing parts corresponding to introns of the host ABC transporter genes, indicating that the ORF was likely acquired by HGT in the form of mRNA. The presence of definite duplicated sequences adjacent to the ACEV ABC transporter genes-a sign of LINE-1 retrotransposon-mediated HGT-was not observed. An approximately 2-month ACV025 transcription experiment suggested that the transporter sequence is presumed to be continuously functional. The amino acid sequence of ACV025 suggests that its product might function in the regulation of phosphatide in the host-cell membranes.
PubMed: 38880337
DOI: 10.1016/j.virusres.2024.199418