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Journal For Immunotherapy of Cancer May 2024Artificial intelligence (AI) chatbots have become a major source of general and medical information, though their accuracy and completeness are still being assessed....
BACKGROUND
Artificial intelligence (AI) chatbots have become a major source of general and medical information, though their accuracy and completeness are still being assessed. Their utility to answer questions surrounding immune-related adverse events (irAEs), common and potentially dangerous toxicities from cancer immunotherapy, are not well defined.
METHODS
We developed 50 distinct questions with answers in available guidelines surrounding 10 irAE categories and queried two AI chatbots (ChatGPT and Bard), along with an additional 20 patient-specific scenarios. Experts in irAE management scored answers for accuracy and completion using a Likert scale ranging from 1 (least accurate/complete) to 4 (most accurate/complete). Answers across categories and across engines were compared.
RESULTS
Overall, both engines scored highly for accuracy (mean scores for ChatGPT and Bard were 3.87 vs 3.5, p<0.01) and completeness (3.83 vs 3.46, p<0.01). Scores of 1-2 (completely or mostly inaccurate or incomplete) were particularly rare for ChatGPT (6/800 answer-ratings, 0.75%). Of the 50 questions, all eight physician raters gave ChatGPT a rating of 4 (fully accurate or complete) for 22 questions (for accuracy) and 16 questions (for completeness). In the 20 patient scenarios, the average accuracy score was 3.725 (median 4) and the average completeness was 3.61 (median 4).
CONCLUSIONS
AI chatbots provided largely accurate and complete information regarding irAEs, and wildly inaccurate information ("hallucinations") was uncommon. However, until accuracy and completeness increases further, appropriate guidelines remain the gold standard to follow.
Topics: Humans; Artificial Intelligence; Immunotherapy; Neoplasms; Drug-Related Side Effects and Adverse Reactions
PubMed: 38816231
DOI: 10.1136/jitc-2023-008599 -
BMJ Open May 2024To analyse the HIV-1 subtypes and molecular transmission characteristics of HIV-infected older individuals aged 50 and above in Huzhou City, and provide a scientific...
OBJECTIVE
To analyse the HIV-1 subtypes and molecular transmission characteristics of HIV-infected older individuals aged 50 and above in Huzhou City, and provide a scientific basis for prevention and treatment strategies for them.
DESIGN
A cross-sectional study with clustered molecular transmission network cases was performed, and basic epidemiological information was retrieved from the Chinese Centres for Disease Prevention and Control (CDC) Information System.
SETTING AND PARTICIPANTS
A molecular epidemiological study was conducted in 899 newly diagnosed HIV-infected individuals from January 2019 and March 2023 in Huzhou city, Zhejiang province, Eastern China. Out of these, HIV sequences were successfully obtained from 673 individuals, including 274 who were older individuals aged 50 and above.
PRIMARY AND SECONDARY OUTCOMES
Reverse transcription-polymerase chain reaction (PCR) and nested PCR were used to amplify the polymerase gene of HIV-1, and gene sequencing was performed. We used univariate and multivariate logistic regression to describe the association of clustered molecular transmission network cases.
RESULTS
In total, 274 valid HIV sequences of older individuals were obtained, which revealed 14 subtypes. Circulating recombinant forms (CRF) 07_BC accounted for 55.8% and CRF01_AE accounted for 20.1% of the subtypes. Data of 150 older individuals were included in the molecular transmission network, and the proportion of elderly individuals in clustered cases is 52.26% (150/287). The results of multivariable logistic regression analysis showed that the older age group (60-82 years) and CRF07_BC subtype were associated with case clustering (transmission risk).
CONCLUSIONS
The key high-risk transmission network was mainly composed of the older age group (60-82 years) and CRF07_BC subtype. It is necessary to further strengthen AIDS health promotion and education for individuals aged 60 years and above, as well as for patients with the CRF07_BC subtype, to reduce HIV transmission and clustering risk.
Topics: Humans; China; Cross-Sectional Studies; HIV Infections; Male; Female; Middle Aged; Aged; HIV-1; Aged, 80 and over; Molecular Epidemiology
PubMed: 38816041
DOI: 10.1136/bmjopen-2024-085646 -
The Journal of Biological Chemistry May 2024GRETCHEN HAGEN 3 (GH3) acyl acid amido synthetases conjugate amino acids to acyl acid hormones to either activate or inactivate the hormone molecule. The largest...
GRETCHEN HAGEN 3 (GH3) acyl acid amido synthetases conjugate amino acids to acyl acid hormones to either activate or inactivate the hormone molecule. The largest sub-group of GH3 proteins modify the growth-promoting hormone auxin (indole-3-acetic acid; IAA) with the second largest class activating the defense hormone jasmonic acid (JA). The two-step reaction mechanism of GH3 proteins provides a potential proofreading mechanism to ensure fidelity of hormone modification. Examining pyrophosphate release in the first-half reaction of Arabidopsis GH3 proteins that modify IAA (AtGH3.2/YDK2, AtGH3.5/WES1, AtGH3.17/VAS2), JA (AtGH3.11/JAR1), and other acyl acids (AtGH3.7, AtGH3.12/PBS3) indicates that acyl acid-AMP intermediates are hydrolyzed into acyl acid and AMP in the absence of the amino acid, a typical feature of pre-transfer editing mechanisms. Single-turnover kinetic analysis of AtGH3.2/YDK2 and AtGH3.5/WES1 shows that non-cognate acyl acid-adenylate intermediates are more rapidly hydrolyzed than the cognate IAA-adenylate. In contrast, AtGH3.11/JAR1 only adenylates JA, not IAA. While some of the auxin conjugating GH3 proteins in Arabidopsis (i.e., AtGH3.5/WES1) accept multiple acyl acid substrates others, like AtGH3.2/YDK2, are specific for IAA; however, both these proteins share similar active site residues. Biochemical analysis of chimeric variants of AtGH3.2/YDK2 and AtGH3.5/WES1 indicates that the C-terminal domain contributes to selection of cognate acyl acid substrates. These findings suggest that the hydrolysis of non-cognate acyl acid-adenylate intermediates, or proofreading, proceeds via a slowed structural switch that provides a checkpoint for fidelity before the full reaction proceeds.
PubMed: 38815865
DOI: 10.1016/j.jbc.2024.107421 -
Acta Pharmaceutica (Zagreb, Croatia) Jun 2024This umbrella review examined systematic reviews of deprescribing studies by characteristics of intervention, population, medicine, and setting. Clinical and humanistic... (Review)
Review
This umbrella review examined systematic reviews of deprescribing studies by characteristics of intervention, population, medicine, and setting. Clinical and humanistic outcomes, barriers and facilitators, and tools for deprescribing are presented. The Medline database was used. The search was limited to systematic reviews and meta-analyses published in English up to April 2022. Reviews reporting deprescribing were included, while those where depre-scribing was not planned and supervised by a healthcare professional were excluded. A total of 94 systematic reviews (23 meta--analyses) were included. Most explored clinical or humanistic outcomes (70/94, 74 %); less explored attitudes, facilitators, or barriers to deprescribing (17/94, 18 %); few focused on tools (8/94, 8.5 %). Reviews assessing clinical or humanistic outcomes were divided into two groups: reviews with (39/70, 56 %; 16 reviewing specific deprescribing interventions and 23 broad medication optimisation interventions), and reviews with (31/70, 44 %). Deprescribing was feasible and resulted in a reduction of inappropriate medications in reviews with . Complex broad medication optimisation interventions were shown to reduce hospitalisation, falls, and mortality rates. In reviews of a higher frequency of adverse drug withdrawal events underscores the importance of prioritizing patient safety and exercising caution when stopping medicines, particularly in patients with clear and appropriate indications.
Topics: Deprescriptions; Humans; Systematic Reviews as Topic; Drug-Related Side Effects and Adverse Reactions; Inappropriate Prescribing; Polypharmacy
PubMed: 38815201
DOI: 10.2478/acph-2024-0011 -
PloS One 2024Preeclampsia (PE) is characterized by hypertension and proteinuria mostly after 20 weeks of gestation. It affects 2-8% of pregnancies worldwide, with detrimental...
BACKGROUND AND AIM
Preeclampsia (PE) is characterized by hypertension and proteinuria mostly after 20 weeks of gestation. It affects 2-8% of pregnancies worldwide, with detrimental consequences for both mother and foetus. Evidence, suggests that genetic factors, including vitamin D receptor (VDR) gene polymorphisms, could contribute to PE complexity. However, their role in the Ghanaian population remains underexplored. We assessed the interplay between Vitamin D, VDR gene variants and preeclampsia risk in Ghanaian women.
METHODS
This unmatched case-control study was conducted at Kumasi South Hospital, Ghana, from June to November 2022. A total of 162 participants consisting of 62 PE cases and 100 normotensive controls were enrolled. Clinical and obstetric data were collected. Blood samples were also collected for DNA extraction and vitamin D assay. Genotyping of VDR Fok1 and Bsm1 gene variants was performed using Polymerase Chain Reaction (PCR) and Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) analysis whereas Vitamin D levels were estimated using sandwich ELISA. Statistical analyses were computed with SPSS version 25 and GraphPad prism version 8.0. A p-value of < 0.05 was considered statistically significant.
RESULTS
Vitamin D concentration were significantly lower in the PE group (p < 0.0001). Vitamin D deficiency (aOR = 3.311, 95% CI: 1.584-6.921, p = 0.0010) was significantly associated with a three-fold increase in preeclampsia risk, whilst VDR gene variants, particularly the "bb" genotype (cOR = 0.227, 95% CI: 0.055-0.944, p = 0.0410) was associated with reduced risk of PE. There was no association between the distribution of Fok1 genotypes and PE.
CONCLUSION
This study highlights a significant association between vitamin D deficiency and an increased risk of PE among Ghanaian women. However, the VDR gene variant, "bb", genotype, for Bsm1 reduces the risk of PE.
Topics: Humans; Female; Receptors, Calcitriol; Pre-Eclampsia; Pregnancy; Ghana; Adult; Case-Control Studies; Vitamin D; Genetic Predisposition to Disease; Genotype; Vitamin D Deficiency; Polymorphism, Single Nucleotide; Young Adult; Risk Factors
PubMed: 38814968
DOI: 10.1371/journal.pone.0303778 -
Blood Transfusion = Trasfusione Del... May 2024Anaphylaxis after blood transfusion is a feared complication accounting for severe morbidity. A retrospective study was performed at Haukeland University Hospital,...
BACKGROUND
Anaphylaxis after blood transfusion is a feared complication accounting for severe morbidity. A retrospective study was performed at Haukeland University Hospital, Bergen, Norway, to investigate the rate and features of transfusion-associated anaphylaxis (TAA) occurring between 2002-2021.
MATERIALS AND METHODS
Identified cases of TAA were studied by an immunologist and an allergist to extract information about general characteristics, amplifying factors, co-morbidity, treatment, and treatment responses. TAA was reported as perioperative or non-perioperative.
RESULTS
We identified 29 cases of TAA: 13 perioperative and 16 non-perioperative. Allergic transfusion reaction had an incidence rate of 34/100,000 transfusions and TAA a rate of 7/100,000 transfusions. The incidence of allergic reactions and TAA increased 2.6- and 6.4-fold during the study period. The first perioperative TAA was discovered 12 years into the study period but was equally frequent as non-perioperative transfusion-associated anaphylaxis in the last five years of the study period. 52% of the TAA cases had relevant co-morbidity and 100% of them had amplifying factors. Although only 38% of the non-perioperative patients received epinephrine as treatment, 94% of them had a good treatment response to their total treatment regimen. Poorer treatment response was observed with higher age, more cardiovascular- and respiratory disease, higher use of amplifying and sedating medications and a higher severity score.
DISCUSSION
Our findings indicate that TAA, especially in the perioperative setting, is underdiagnosed. The increased incidence of TAA in our study is temporally related to the introduction of a national hemovigilance program, introduction of standardized laboratory testing for anaphylaxis and increased multidisciplinary focus on the condition. In conclusion, increased awareness of TAA, and especially in the perioperative setting, is needed. A multidisciplinary approach is necessary to improve identification and reporting of TAA.
PubMed: 38814882
DOI: 10.2450/BloodTransfus.738 -
PLoS Neglected Tropical Diseases May 2024Human cystic echinococcosis (CE) is a parasitic infection caused by the larval stage of the tapeworm Echinococcus granulosus sensu lato, primarily affecting the liver...
Human cystic echinococcosis (CE) is a parasitic infection caused by the larval stage of the tapeworm Echinococcus granulosus sensu lato, primarily affecting the liver and lungs. Although the heart is affected in only 0.02-2% of all CE cases, a considerable number of cases have been, and continue to be, published. However, due to the rare occurrence of cardiac CE and the resulting lack of clinical trials, knowledge about various aspects of the disease remains limited. To obtain a clearer picture of anatomical, clinical, diagnostic as well as therapeutic aspects of cardiac CE, we systematically reviewed the literature published between 1965 and 2022. The anatomical pattern of the affected cardiac structures follows the extension of the supplying capillary bed. The majority of patients (82.7%) are symptomatic and present with prolonged non-specific symptoms such as dyspnoea, chest pain and palpitations. Acute complications generally derive from cyst rupture, occur in 18.3% of cases and manifest as embolism, pericardial tamponade, or anaphylactic reaction in 83.2%, 17.8% and 10.9% of these cases, respectively. As for CE cysts localized in other organs, the diagnosis of cardiac CE is made by imaging. Serology plays a minor role due to its limited sensitivity. Unlike abdominal CE cysts, cardiac CE cysts are usually resected independent of their stage (active/inactive), because their presence impairs cardiac performance and carries the risk of long-term sequelae. More than 80% of patients are treated with a single surgical intervention. We found a disease-related case fatality rate of 11.1%. Since local recurrence was reported up to 108 months and secondary CE up to 72 months after surgery, patients should be followed up for a minimum of 10 years.
Topics: Humans; Echinococcosis; Animals; Heart Diseases; Echinococcus granulosus; Heart
PubMed: 38814859
DOI: 10.1371/journal.pntd.0012183 -
MMWR. Morbidity and Mortality Weekly... May 2024
Topics: Humans; United States; Aged; Respiratory Syncytial Virus Vaccines; Middle Aged; Respiratory Syncytial Virus Infections; Female; Male; Aged, 80 and over; Adverse Drug Reaction Reporting Systems
PubMed: 38814851
DOI: 10.15585/mmwr.mm7321a3 -
Microbiology Spectrum May 2024Two patients with acute gastroenteritis tested positive for Shiga toxin-producing (STEC) by polymerase chain reaction (PCR), and both strains carried the Shiga toxin 2...
UNLABELLED
Two patients with acute gastroenteritis tested positive for Shiga toxin-producing (STEC) by polymerase chain reaction (PCR), and both strains carried the Shiga toxin 2 encoding gene. Since routine culture using CHROMagar STEC failed to recover these isolates, immunomagnetic separation (IMS) targeting the top six non-O157:H7 serotypes was used for isolate recovery. After two subsequent IMS runs, the STEC strains were isolated from trypticase soy broth with and without overnight enrichment for runs 1 and 2, respectively. Serotyping based on whole-genome sequencing revealed that both patients carried the strain O166:H15 STEC with the gene. Hence, the magnetic beads used in IMS appeared to have cross-reactivity with other serotypes. When the STEC isolates from both stools were cultured on CHROMagar STEC and sheep blood agar (BAP), two distinct colony sizes were apparent after overnight incubation. The small and large colonies were picked and separately cultured on both media, and colony growth was observed for 2 weeks at room temperature after an initial overnight incubation at 37°C. After 1 week, the colonies showed concentric ring structures with a darker center and a lighter surrounding on CHROMagar STEC and a "fried egg"-resembling structure with a raised circular center and a flat surrounding on BAP. Both colony types remained morphologically different on CHROMagar STEC throughout the 15 days. However, on BAP, their appearance was comparable by day 7.
IMPORTANCE
Shiga toxin-producing (STEC) infections can lead to severe complications such as bloody diarrhea and hemolytic uremic syndrome (HUS), especially in young children and the elderly. Strains that carry the shiga toxin 2 gene (), such as O157:H7, have been mostly linked with severe disease outcomes. In recent years, outbreaks caused by non-O157:H7 strains have increased. O166:H15 has been previously reported causing a gastroenteritis outbreak in 1996 as a non-STEC strain, however the O166:H15 serotype we recovered carried the gene. It was particularly challenging to isolate this strain from stools by culture. Consequently, we tested immunomagnetic separation for the STEC recovery, which was a novel approach on clinical stools. Virulence genes were included for the characterization of these isolates.
PubMed: 38814093
DOI: 10.1128/spectrum.00098-24 -
Disease Models & Mechanisms May 2024Evidence suggests the presence of microglial activation and microRNA (miRNA) dysregulation in amyotrophic lateral sclerosis (ALS), the most common form of adult motor...
Evidence suggests the presence of microglial activation and microRNA (miRNA) dysregulation in amyotrophic lateral sclerosis (ALS), the most common form of adult motor neuron disease. However, few studies have investigated whether the miRNA dysregulation originates from microglia. Furthermore, TDP-43 (encoded by TARDBP), involved in miRNA biogenesis, aggregates in tissues of ∼98% of ALS cases. Thus, this study aimed to determine whether expression of the ALS-linked TDP-43M337V mutation in a transgenic mouse model dysregulates microglia-derived miRNAs. RNA sequencing identified several dysregulated miRNAs released by transgenic microglia and a differential miRNA release by lipopolysaccharide-stimulated microglia, which was more pronounced in cells from female mice. We validated the downregulation of three candidate miRNAs, namely, miR-16-5p, miR-99a-5p and miR-191-5p, by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and identified their predicted targets, which primarily include genes involved in neuronal development and function. These results suggest that altered TDP-43 function leads to changes in the miRNA population released by microglia, which may in turn be a source of the miRNA dysregulation observed in the disease. This has important implications for the role of neuroinflammation in ALS pathology and could provide potential therapeutic targets.
Topics: Microglia; Amyotrophic Lateral Sclerosis; MicroRNAs; Animals; Female; Mice, Transgenic; Male; Mutation; Sex Characteristics; DNA-Binding Proteins; Mice; Extracellular Space; Humans; Lipopolysaccharides; Gene Expression Regulation
PubMed: 38813848
DOI: 10.1242/dmm.050638