Veterinary medicine - Repository of PHD, master's thesis
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Setting research priorities for global pandemic preparedness: An international consensus and comparison with ChatGPT’s output
No full textBackground: In this priority-setting exercise, we sought to identify leading research priorities needed for strengthening future pandemic preparedness and response across countries.
Methods: The International Society of Global Health (ISoGH) used the Child Health and Nutrition Research Initiative (CHNRI) method to identify research priorities for future pandemic preparedness. Eighty experts in global health, translational and clinical research identified 163 research ideas, of which 42 experts then scored based on five pre-defined criteria. We calculated intermediate criterion-specific scores and overall research priority scores from the mean of individual scores for each research idea. We used a bootstrap (n = 1000) to compute the 95% confidence intervals.
Results: Key priorities included strengthening health systems, rapid vaccine and treatment production, improving international cooperation, and enhancing surveillance efficiency. Other priorities included learning from the coronavirus disease 2019 (COVID-19) pandemic, managing supply chains, identifying planning gaps, and promoting equitable interventions. We compared this CHNRI-based outcome with the 14 research priorities generated and ranked by ChatGPT, encountering both striking similarities and clear differences.
Conclusions: Priority setting processes based on human crowdsourcing - such as the CHNRI method - and the output provided by ChatGPT are both valuable, as they complement and strengthen each other. The priorities identified by ChatGPT were more grounded in theory, while those identified by CHNRI were guided by recent practical experiences. Addressing these priorities, along with improvements in health planning, equitable community-based interventions, and the capacity of primary health care, is vital for better pandemic preparedness and response in many settings
Editorial: Cystic kidney diseases in children and adults: from diagnosis to etiology and back
No full textIntegrative analysis in head and neck cancer reveals distinct role of miRNome and methylome as tumour epigenetic drivers
No full textHead and neck cancer is the sixth most common malignancy worldwide, with the relatively low 5-year survival rate, mainly because it is diagnosed at a late stage. Infection with HPV is a well known aetiology, which affects the nature of these cancers and patients’ survival. Besides, it is considered that the main driving force for this type of cancer could be epigenetics. In this study we aimed to find potential epigenetic biomarkers, by integrating miRNome, methylome, and transcriptome analyses. From the fresh head and neck cancer tissue samples, we chose a group for miRNome, methylome and transcriptome profiling, in comparison to adequate control samples. Bioinformatics analyses are performed in R v4.2.2. Count normalisation and group differential expression for mRNA and the previously obtained miRNA count data was performed with DESeq2 v1.36. Gene set enrichment analysis was performed and visualised using gProfiler2 v0.2.1 Identification of miRNA targets was performed by querying in miRTarBase using multiMiR v1.18.0. Annotation of CpG sites merging into islands was obtained from RnBeads.hg19 v1.28.0. package. For the integrative analysis we performed kmeans clustering using stats v4.2.2 package, using 8–12 clusters and nstart 100. We found that transcriptome analysis divides samples into cancers and controls clusters, with no relation to HPV status or cancer anatomical location. Differentially expressed genes (n = 2781) were predominantly associated with signalling pathways of tumour progression. We identified a cluster of genes under the control of the transcription factor
that are significantly underexpressed in cancer tissue, as well as T cell immunity genes and genes related to regulation of transcription. Among overexpressed genes in tumours we found those that belong to cell cycle regulation and vasculature. A small number of genes were found significantly differentially expressed in HPV-positive
HPV-negative tumours (for example
,
,
,
, and
). In this comprehensive study on an overlapping set of samples where the integration of miRNome, methylome and transcriptome analysis were performed for head and neck cancer, we demonstrated that the majority of genes were associated exclusively with miRNome or methylome and, to a lesser extent, under the control of both epigenetic mechanisms
Mobocertinib in Patients with EGFR Exon 20 Insertion-Positive Non-Small Cell Lung Cancer (MOON): An International Real-World Safety and Efficacy Analysis
No full textEGFR exon 20 (EGFR Ex20) insertion mutations in non-small cell lung cancer (NSCLC) are insensitive to traditional EGFR tyrosine kinase inhibitors (TKIs). Mobocertinib is the only approved TKI specifically designed to target EGFR Ex20. We performed an international, real-world safety and efficacy analysis on patients with EGFR Ex20-positive NSCLC enrolled in a mobocertinib early access program. We explored the mechanisms of resistance by analyzing postprogression biopsies, as well as cross-resistance to amivantamab. Data from 86 patients with a median age of 67 years and a median of two prior lines of treatment were analyzed. Treatment-related adverse events (TRAEs) occurred in 95% of patients. Grade ≥3 TRAEs were reported in 38% of patients and included diarrhea (22%) and rash (8%). In 17% of patients, therapy was permanently discontinued, and two patients died due to TRAEs. Women were seven times more likely to discontinue treatment than men. In the overall cohort, the objective response rate to mobocertinib was 34% (95% CI, 24–45). The response rate in treatment-naïve patients was 27% (95% CI, 8–58). The median progression-free and overall survival was 5 months (95% CI, 3.5–6.5) and 12 months (95% CI, 6.8–17.2), respectively. The intracranial response rate was limited (13%), and one-third of disease progression cases involved the brain. Mobocertinib also showed antitumor activity following EGFR Ex20-specific therapy and vice versa. Potential mechanisms of resistance to mobocertinib included amplifications in MET, PIK3CA, and NRAS. Mobocertinib demonstrated meaningful efficacy in a real-world setting but was associated with considerable gastrointestinal and cutaneous toxicity
Management of Mandibular Condyle Fractures in Pediatric Patients: A Multicentric Retrospective Study with 180 Children and Adolescents
No full textBackground: Mandibular condyle fractures in pediatric patients can lead to crippling sequelae such as ankylosis, pain and facial deformity if not managed properly. However, there is no consensus on the best approach for treating these fractures in children. Objective: This study aimed to describe the management of mandibular condyle fractures in growing patients across 14 maxillofacial departments worldwide.
Methods: A retrospective multicenter study was conducted on children and adolescents aged 0 to 16 who had at least one mandibular condyle fracture. This study included patients who underwent expectant, closed, or open management and were treated over an 11-year period.
Results: 180 patients had at least one mandibular condyle fracture, and 37 had a second condylar fracture. One hundred sixteen patients (65%) were males, and 64 (35%) were females (ratio 1.8:1). An expectant strategy was chosen in 51 (28%) patients, a closed treatment—stand-alone maxillomandibular fixation (MMF)—in 47 (26%), and open reduction and internal fixation (ORIF) was performed in 82 (46%) patients. The management varied significantly between the different departments (p < 0.0001). Significant differences were also identified between the fracture type (non-displaced, displaced or comminuted) and the management of the 180 patients with a single condylar fracture. Out of 50 non-displaced fractures, only 3 (6%) had ORIF, 25 (50%) had expectant management, and 22 (44%) had MMF. Out of 129 displaced fractures, 79 (62%) had ORIF, 25 (19%) had a soft diet, and 25 (19%) had MMF.
Conclusions: Expectative management, MMF, and ORIF were all effective in treating pediatric mandibular condyle fractures, with a low incidence of complications and asymmetry
Novel RAI1:c.2736delC Variant in Smith–Magenis Syndrome: Identification by Whole Genome Sequencing and Joint Analysis
No full textSmith–Magenis syndrome is a complex neurobehavioral genetic disorder with a broad phenotypic spectrum. While the etiology of SMS is commonly attributed to one-copy interstitial deletion in the 17p11.2 region (90–95% of cases), variants identified by sequence analysis in RAI1 have also been reported in 5–10% of cases. In this study, we report a 9-year-old male with global cognitive and psychomotor developmental delay, musculoskeletal and cardiovascular abnormalities, and dysmorphic craniofacial features. Joint analysis was performed on the whole-genome sequencing data obtained from the proband, unaffected parents, and unaffected brother. This quad analysis identified the novel de novo RAI1:c.2736delC variant. This is the first report of this variant in the literature. This report highlights the details of genome analysis and the patient’s phenotypic spectrum
A Machine Learning-Driven Virtual Biopsy System For Kidney Transplant Patients
No full textIn kidney transplantation, day-zero biopsies are used to assess organ quality and discriminate between donor-inherited lesions and those acquired post-transplantation. However, many centers do not perform such biopsies since they are invasive, costly and may delay the transplant procedure. We aim to generate a non-invasive virtual biopsy system using routinely collected donor parameters. Using 14,032 day-zero kidney biopsies from 17 international centers, we develop a virtual biopsy system. 11 basic donor parameters are used to predict four Banff kidney lesions: arteriosclerosis, arteriolar hyalinosis, interstitial fibrosis and tubular atrophy, and the percentage of renal sclerotic glomeruli. Six machine learning models are aggregated into an ensemble model. The virtual biopsy system shows good performance in the internal and external validation sets. We confirm the generalizability of the system in various scenarios. This system could assist physicians in assessing organ quality, optimizing allograft allocation together with discriminating between donor derived and acquired lesions post-transplantation
Corticosteroid Dosing Level, Incidence and Profile of Bacterial Blood Stream Infections in Hospitalized COVID-19 Patients
No full textCOVID-19 patients with severe or critical symptoms are often treated with corticosteroids, per contemporary guidelines. Due to their immunosuppressive and immunomodulatory properties, corticosteroids are associated with the development of superinfections. We aimed to retrospectively assess patterns of corticosteroid use and the profiles of bacterial blood stream infections associated with exposure to different dosing levels, in a cohort of 1558 real-life adult COVID-19 patients. A total of 1391 (89.3%) patients were treated with corticosteroids, with 710 (45.6%) patients receiving low, 539 (34.6%) high and 142 (9.1%) very high corticosteroid doses. Bacteremia developed in a total of 178 (11.4%) patients. The risk of bacteremia was of similar magnitude between the no and low-dose corticosteroid treatments (p = 0.352), whereas it progressively increased with high (OR 6.18, 95% CI (2.66–14.38), p < 0.001) and very high corticosteroid doses (OR 8.12, 95% CI (3.29–20.05), p < 0.001), compared to no corticosteroid treatment. These associations persisted after multivariate adjustments and were present independently of sex, comorbidity burden, and mechanical ventilation. The profiles of individual bacterial pathogens differed depending on the used corticosteroid doses. High and very high corticosteroid doses are frequently used for real-life COVID-19 patients with severe and critical clinical presentations and are associated with a higher risk of bacteremia independently of sex, comorbidity burden, and mechanical ventilation use
Cyberchondria, Health Literacy, and Perception of Risk in Croatian Patients with Risk of Sexually Transmitted Infections and HIV—A Cross-Sectional Study
No full textBackground: The perception of the risk of sexually transmitted infections (STIs) is a well-researched phenomenon, but not in relation to cyberchondria and health literacy. Therefore, our aim was to examine the association between the assessment of the risk of sexually transmitted diseases and HIV, cyberchondria, and health literacy.
Materials and methods: This study was conducted in 2020–2021 in Croatia. The experimental group consisted of patients from the Centre for Voluntary Counselling and Testing for HIV (N = 134). The control group consisted of other patients recruited from daily epidemiological practices (N = 171). The instruments that were used were questionnaires that measure the perception of risk of sexually transmitted infections and HIV, health literacy, and cyberchondria.
Results: Out of 305 respondents, 134 (43.9%) were in the STI counselling group, and 171 (56.1%) were in the control group. Generally, the participants in the former perceived the risk of sexually transmitted infections and HIV to be higher (but still low) than those in the latter. There was no difference in health literacy between the STI and control group; the health literacy score was average in both groups. There were differences in almost all the cyberchondria factors, except for Mistrust. Health literacy, belonging to the STI counselling group, and risk behaviours were positively associated with CH in the logistic regression analysis.
Conclusions: People with a risk for STIs tend to minimize this risk, have higher cyberchondria levels, and have average health literacy. Cyberchondria is positively associated with health literacy, and more education about excessive health-related internet research is needed