Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 55.985
Filter
Add more filters








Publication year range
1.
Lab Anim ; 58(5): 419-426, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39365005

ABSTRACT

Blinding and randomisation are important methods for increasing the robustness of pre-clinical studies, as incomplete or improper implementation thereof is recognised as a source of bias. Randomisation ensures that any known and unknown covariates introducing bias are randomly distributed over the experimental groups. Thereby, differences between the experimental groups that might otherwise have contributed to false positive or -negative results are diminished. Methods for randomisation range from simple randomisation (e.g. rolling a dice) to advanced randomisation strategies involving the use of specialised software. Blinding on the other hand ensures that researchers are unaware of group allocation during the preparation, execution and acquisition and/or the analysis of the data. This minimises the risk of unintentional influences resulting in bias. Methods for blinding require strong protocols and a team approach. In this review, we outline methods for randomisation and blinding and give practical tips on how to implement them, with a focus on animal studies.


Subject(s)
Animal Experimentation , Random Allocation , Research Design , Animals , Animal Experimentation/standards , Bias
2.
J Prev Alzheimers Dis ; 11(5): 1418-1425, 2024.
Article in English | MEDLINE | ID: mdl-39350389

ABSTRACT

INTRODUCTION: Metrics of a participant's socioeconomic status (SES) are not routinely collected or standardized in clinical trials. This omission limits the ability to evaluate the generalizability of trial results and restricts clinicians from confidently interpreting the efficacy of new treatments across important sub-populations. METHODS: We adapted an SES measure of social disparity; the Hollingshead Two Factor Index of Social Position, which combines education and occupation into a single metric. We modernized the 1965 occupations to reflect the 2017 careers tabulated by the US Bureau of Labor Statistics. We currently use this adapted measure in Alzheimer's Clinical Trials Consortium studies. RESULTS: We present the revised table of occupations. We found that the collection of SES data using the modified Hollingshead was feasible in a multi-site clinical trial and scores were distributed across all SES strata. DISCUSSION: The modified Hollingshead provides a standardized method for collecting SES information, enabling data aggregation, monitoring, and reporting.


Subject(s)
Alzheimer Disease , Social Class , Humans , Clinical Trials as Topic , Occupations , Educational Status , Female
3.
J Prev Alzheimers Dis ; 11(5): 1435-1444, 2024.
Article in English | MEDLINE | ID: mdl-39350391

ABSTRACT

BACKGROUND: Advances in plasma biomarkers to detect Alzheimer's disease (AD) biology allows researchers to improve the efficiency of participant recruitment into preclinical trials. Recently, protein levels of plasma amyloid-beta and tau proteins have been shown to be predictive of elevated amyloid in brain. Online registries, such as the Alzheimer's Prevention Trials (APT) Webstudy, include and follow participants using remote assessments to facilitate efficient screening and enrollment of large numbers of individuals who may be at higher risk for AD. OBJECTIVES: The AlzMatch Pilot Study investigated the feasibility of recruiting individuals from an online registry for blood sample collection at community-based phlebotomy centers and plasma biomarker quantification to assess an individual's eligibility for AD preclinical trials. DESIGN: Pilot feasibility study with co-primary outcomes. SETTING: This pilot feasibility study included participants from the APT Webstudy, the remote assessment arm of the Trial-ready cohort for Preclinical and Prodromal AD (TRC-PAD) Platform. Novel design included collection of electronic consent, use of community laboratories for plasma collection, mass spectrometry-based biomarker assay, and telephone communication of plasma biomarker screening eligibility. PARTICIPANTS: Participants invited to the AlzMatch pilot feasibility study were active in the APT Webstudy, 50 years of age or older, resided within 50 miles of both a Quest Diagnostics Patient Services Center (a national diagnostic laboratory with convenient locations for sample collection and processing) and one of six TRC-PAD vanguard clinical trial sites, had no self-reported dementia diagnosis, were able to communicate in English and engaged with the APT Webstudy within the prior 6 months. MEASUREMENTS: Primary feasibility outcomes were completion of electronic consent (e-consent) for invited participants and collection of usable blood samples. Additional feasibility outcomes included invitation response rate, plasma biomarker eligibility status (based on amyloid beta-42/40 [Aß42/40] concentration ratio), ApoE proteotype, and trial inclusion criterion), and completion of telephone contact to learn eligibility to screen for a study. RESULTS: 300 APT Webstudy participants were invited to consent to the AlzMatch study. The AlzMatch e-consent rate was 39% (n=117) (95% CI of 33.5%-44.5%) overall, which was higher than the expected rate of 25%. Similar consent rates were observed across participants based on self-defined sex (41% Female (n=75), 37% Male (n=42)) and race and ethnicity (37% from underrepresented groups (URG) (n=36), 40% not from URG (n=79)). Among those that consented (n=117), plasma was successfully collected from 74% (n=87) (95% CI of 66%-82%), with similar rates across sex (76% Female (n=57), 71% Male (n=30)) and race and ethnicity (75% URG (n=27) and 75% not from URG (n=59)). 60% (n=51) of participants with plasma biomarker results were eligible to screen for future preclinical AD trials. CONCLUSION: Electronic consent of participants through an online registry, blood sample collection at community-based centers, plasma biomarker quantification and reporting, and biomarker assessments for study eligibility were all feasible with similar engagement rates across demographic groups. Although this pilot was a small and selective sample, participants engaged and consented at higher than expected rates. We conclude that collecting blood at community laboratories for biomarker analyses may improve accessibility beyond research, and may facilitate broader access for clinical use of AD plasma biomarkers. Based on our results, an expanded version of the AlzMatch study is underway, which involves expanding invitations to additional APT Webstudy participants and clinical trial sites.


Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Biomarkers , Feasibility Studies , Humans , Alzheimer Disease/blood , Alzheimer Disease/diagnosis , Pilot Projects , Biomarkers/blood , Female , Male , Aged , Amyloid beta-Peptides/blood , tau Proteins/blood , Blood Specimen Collection/methods , Patient Selection , Prodromal Symptoms , Middle Aged , Registries , Clinical Trials as Topic
4.
Sci Transl Med ; 16(768): eado3022, 2024 Oct 09.
Article in English | MEDLINE | ID: mdl-39383244

ABSTRACT

Increased plasma creatine concentrations are associated with the risk of type 2 diabetes, but whether this alteration is associated with or causal for impairments in metabolism remains unexplored. Because skeletal muscle is the main disposal site of both creatine and glucose, we investigated the role of intramuscular creatine metabolism in the pathophysiology of insulin resistance in type 2 diabetes. In men with type 2 diabetes, plasma creatine concentrations were increased, and intramuscular phosphocreatine content was reduced. These alterations were coupled to reduced expression of sarcomeric mitochondrial creatine kinase 2 (CKMT2). In C57BL/6 mice fed a high-fat diet, neither supplementation with creatine for 2 weeks nor treatment with the creatine analog ß-GPA for 1 week induced changes in glucose tolerance, suggesting that increased circulating creatine was associated with insulin resistance rather than causing it. In C2C12 myotubes, silencing Ckmt2 using small interfering RNA reduced mitochondrial respiration, membrane potential, and glucose oxidation. Electroporation-mediated overexpression of Ckmt2 in skeletal muscle of high-fat diet-fed male mice increased mitochondrial respiration, independent of creatine availability. Given that overexpression of Ckmt2 improved mitochondrial function, we explored whether exercise regulates CKMT2 expression. Analysis of public data revealed that CKMT2 content was up-regulated by exercise training in both humans and mice. We reveal a previously underappreciated role of CKMT2 in mitochondrial homeostasis beyond its function for creatine phosphorylation, independent of insulin action. Collectively, our data provide functional evidence for how CKMT2 mediates mitochondrial dysfunction associated with type 2 diabetes.


Subject(s)
Creatine Kinase, Mitochondrial Form , Diabetes Mellitus, Type 2 , Insulin , Muscle, Skeletal , Animals , Humans , Male , Mice , Middle Aged , Creatine/metabolism , Creatine Kinase, Mitochondrial Form/metabolism , Diabetes Mellitus, Type 2/metabolism , Diet, High-Fat , Glucose/metabolism , Insulin/metabolism , Insulin Resistance , Mice, Inbred C57BL , Mitochondria/metabolism , Mitochondria, Muscle/metabolism , Muscle, Skeletal/metabolism
5.
Clin Oral Investig ; 28(11): 586, 2024 Oct 10.
Article in English | MEDLINE | ID: mdl-39387911

ABSTRACT

BACKGROUND: Little is known about factors associated with the severity of cleft lip with or without cleft palate (CL/P) especially during the COVID-19 pandemic with its dramatic changes. OBJECTIVES: The aim of this multi-national study is to measure the association between CL/P severity, COVID-19 infection, and fear of COVID-19 in five Arab countries. METHODS: This cross-sectional study took place in major governmental hospitals in five Arab countries from November 2020 to April 2023. Participants were infants born with CL/P and their mothers who were in their 1st trimester during the COVID-19 pandemic. Clinical examination was carried out, and CL/P cases were grouped according to phenotype: cleft lip and palate (CLP) versus cleft lip (CL), cleft extension (incomplete versus complete), and site (unilateral versus bilateral) to assess severity. Information on maternal COVID-19 infection and fear of COVID-19 were gathered. RESULTS: The study recruited 273 CL/P infants. Maternal COVID-19 infection during one-month pre-gestation and 1st trimester was significantly associated with higher odds of CL/P severity (AOR = 2.707; P = 0.002) than mothers without the COVID-19 infection. Using supplements during pregnancy showed a protective effect (AOR = 0.573; P = 0.065). CONCLUSION: Mothers infected with COVID-19 before and during pregnancy had more than twofold higher odds of having an infant with a more severe CL/P phenotype.


Subject(s)
COVID-19 , Cleft Lip , Cleft Palate , Pregnancy Complications, Infectious , Humans , COVID-19/epidemiology , Female , Cross-Sectional Studies , Cleft Lip/epidemiology , Pregnancy , Cleft Palate/epidemiology , Adult , Pregnancy Complications, Infectious/epidemiology , SARS-CoV-2 , Infant, Newborn , Middle East/epidemiology , Severity of Illness Index , Male
6.
Theriogenology ; 231: 21-28, 2024 Oct 08.
Article in English | MEDLINE | ID: mdl-39393108

ABSTRACT

South American beef production varies due to diverse climates, environmental conditions, animal breeds (Bos indicus, Bos taurus and crossbreeds), management strategies, and nutritional sources. Applying technology in the South American beef production system can significantly enhance efficiency, sustainability, and profitability. Reproductive efficiency is a significant challenge, especially in cow-calf operation systems conducted under adverse conditions. Consequently, implementing effective assisted reproduction technologies (ART) can make a significant contribution. In the last two decades, the development of fixed-time artificial insemination (FTAI) protocols permitted the widespread application of artificial insemination for breeding management and genetic improvement in beef herds in South America. Nowadays, FTAI is being applied in South America in large-scale programs, with around 20 % of heifers and cows receiving this technology every year. This results in a greater calving rate and significant genetic gain occurring in this territory. Also, in vitro embryo production, mainly using sex-selected sperm has been widely applied in this region, leading to significant improvements in herd genetics and productivity. Recently, 94 % of all embryo transfers in South America consist of in vitro-produced embryos (41,429 being in vivo-derived and 650,782 being in vitro-produced embryos), mainly using fixed-time embryo transfer technology (FTET). Genomic selection combined with in vitro embryo production with oocytes from heifer calves provides a powerful technology platform to reduce generation interval and significantly increase the rate of genetic gain in beef cattle. Emerging biotechnologies, such as genome editing via the CRISPR/Cas system, are being developed to enhance productivity, confer resilience to adverse environmental conditions, increase disease resistance, and control pest species that affect livestock. Finally, while all these technologies offer significant potential, further progresses are needed to transform livestock production. The vast geographical scale and diverse climates of South America make regional knowledge crucial for aligning beef production with sustainability goals and supporting global food security.

7.
J Dent Res ; : 220345241272017, 2024 Oct 09.
Article in English | MEDLINE | ID: mdl-39382100

ABSTRACT

Cisplatin resistance is one of the major causes of treatment failure in head and neck squamous cell carcinoma (HNSCC). There is an urgent need to uncover the underlying mechanism for developing effective treatment strategies. A quantitative proteomics assay was used to identify differential proteins in cisplatin-resistant cells. Mitochondrial topoisomerase I (TOP1MT) localization was determined using laser confocal microscopy and nucleocytoplasmic separation assay. Chromatin immunoprecipitation sequencing, dual-luciferase reporter assay, and RNA immunoprecipitation were used to identify the interaction between pseudogenes, miRNAs, and real genes. In vivo experiments verified the interaction between TOP1MT and pseudogenes on cisplatin resistance. TOP1MT was identified as a driving factor of cisplatin resistance in vitro, in vivo, and in HNSCC patients. Moreover, TOP1MT exceptionally translocated to the nucleus in cisplatin-resistant HNSCC cells in a signal peptide-dependent manner. Nuclear TOP1MT (nTOP1MT) transcriptionally regulated the mitochondrial functional pseudogene MTATP6P1, which bound to miR-137 and miR-491-5p as a competing endogenous RNA (ceRNA) and promoted the expression of MTATP6. An increase in MTATP6 enhanced mitochondrial oxidative phosphorylation (OXPHOS), which conferred cisplatin resistance in HNSCC. Our findings revealed that nTOP1MT transcriptionally activated MTAPT6P1 and increased MTATP6 expression via ceRNA, which facilitated OXPHOS and cisplatin resistance. These results provide novel insight for overcoming cisplatin resistance in HNSCC.

8.
J Endocrinol Invest ; 2024 Oct 09.
Article in English | MEDLINE | ID: mdl-39382627

ABSTRACT

PURPOSE: Understanding the relationship between antithyroperoxidase antibodies (TPOAb) and carotid intima-media thickness (cIMT) could provide insights into the mechanisms linking thyroid autoimmunity and cardiovascular disease. We aimed to explore the association of multiple categories of TPOAb with the increased cIMT at baseline and at follow-up in participants from the ELSA-Brasil Study. METHODS: This prospective cohort study analyzed data from 9,264 participants (51.5 ± 8.9 years old, 55.9% women) without a history of cardiovascular disease. Fasting serum TPOAb levels were determined. Values of cIMT equal to or above one deviation standard of the sample's mean were classified as increased cIMT at baseline. The increased cIMT after the 8-year follow-up was calculated after excluding participants with increased cIMT at baseline. Multivariate analyses were done using binary logistic and Poisson regression models. RESULTS: The increased cIMT was prevalent in 14.3% of the participants at baseline and its development occurred in 16.8% participants during the cohort. After adjustment for all confounder variables, TPOAb detectability (OR = 1.84, 95%CI = 1.21-2.79), and low detectable (OR = 1.81, 95%CI = 1.18-2.75), high detectable (OR = 2.01, 95%CI = 1.29-3.11) and positive (OR = 1.70, 95%CI = 1.07-2.70) TPOAb were positively associated with increased cIMT at baseline. The associations of low and high detectable TPOAb and increased cIMT at baseline were consistent when excluding those with thyroid dysfunction. There was no statistically significant association between TPOAb levels and increased cIMT at follow-up (p > 0.05), neither for all sample nor for euthyroid individuals. CONCLUSION: Different levels of TPOAb, including its detectability, were associated with increased cIMT at baseline in the studied sample. We highlight that may be relevant to consider the levels of TPOAb detectability as possible marker of increased cardiovascular risk.

9.
Int J Biol Macromol ; 281(Pt 1): 136190, 2024 Oct 02.
Article in English | MEDLINE | ID: mdl-39366605

ABSTRACT

Current study provides insight on the feasibility of polylactic acid (PLA) integrated with (1:1 ratio) of essential oils belonging to Ocimum gratissimum (OG) and Mentha spicata (MS) for prevention of major stored insect pests (Sitophilus oryzae and Oryzophilus surinamensis) in Sorghum and Pearl millet. A combination of OG and MS essential oils (1:1) was incorporated into the PLA polymer matrix. Further, SPME analysis of synthesized PLA showed the presence of volatiles corresponding to carvone (6.44 %) and thymol (6.22 %). Synthesized PLA composites were tested against S. oryzae and O. surinamensis using Sorghum and Pearl millets, and insect mortality was equivalent to commercial super bags (CSB). The head space oxygen decreased significantly in CSB and slightly in PLA bags. Thickness of EO blended PLA composite was increased (99 µm), tensile strength (23.94 MPa), WVTR (1.42 g/m2.hr) analysis, significant folding ability, and swelling capacity (0.24 %) showed slight reduction in composite film. TGA showed good thermal stability (334˚C) and XRD displayed the increased crystallinity (38.35 %) in PLAOM films, SEM and FTIR analysis of the synthesized composite films revealed complete homogenization of EO and PLA matrix. In addition, SEM analysis of insects (control & treated) revealed less topology changes in the elytra. Biodegradability study confirmed the weight loss in PLA films. Hence, current approach of using composite EO's with PLA offers sustainable solution for prevention of infestation during storage of millets.

10.
Sci Rep ; 14(1): 23355, 2024 10 07.
Article in English | MEDLINE | ID: mdl-39375382

ABSTRACT

Canine vector-borne infections (CVBIs) are a global health problem. The military working dogs of Sri Lanka die at an early age, and CVBIs have been a leading speculated cause. We examined CVBIs in the working dogs of the Sri Lanka air force (SLAF) and free-roaming dogs (FRDs) and privately owned dogs (PODs) country-wide. Giemsa-stained smears were prepared and conventional PCR-positive DNA was subjected to sequencing and phylogeny. Of the 668 dogs sampled, 212 (31.7%) had one or more CVBIs. The prevalence of infections among the FRDs (40.0%) was significantly higher than SLAF working dogs (30.0%; χ2 = 10.5216; p = 0.0012) and PODs (26.2%; χ2 = 5.3414, p = 0.0208) but not between SLAF dogs and PODs (χ2 = 1.7655, p = 0.1838). Many infected dogs were asymptomatic (57.4%), which was higher among the FRDs. Seven infectious agents were identified: Babesia gibsoni, B. canis, Ehrlichia canis, Anaplasma platys, Leishmania sp., Hepatozoon canis, and filaria worms. The most common infection was B. gibsoni (13.8%), followed by E. canis (9.9%). Three tick species: Rhipicephalus linneai, Rhipicephalus haemaphysaloides and Haemophysalis bispinosa were found infesting the dogs. The SLAF dogs were thoroughly quarantined upon arrival, but the infection prevalence was similar to PODs.


Subject(s)
Dog Diseases , Vector Borne Diseases , Animals , Dogs , Sri Lanka/epidemiology , Dog Diseases/epidemiology , Dog Diseases/parasitology , Dog Diseases/microbiology , Vector Borne Diseases/epidemiology , Working Dogs , Prevalence , Male , Female , Phylogeny
13.
Ter Arkh ; 96(8): 751-756, 2024 Sep 14.
Article in Russian | MEDLINE | ID: mdl-39404719

ABSTRACT

AIM: To systematize data on the prevalence of gastroesophageal reflux disease (GERD) in the adult population of Russia. MATERIALS AND METHODS: The search for studies was conducted in the electronic databases MEDLINE/PubMed, EMBASE, and RSCI (Russian Science Citation Index) from January 2000 to December 2022. The review included relevant publications in peer-reviewed periodicals in English or Russian, publications with data from cross-sectional epidemiological studies assessing the prevalence of GERD in the Russian population, studies on adult patients with GERD, and publications with detailed descriptive statistics that allow using the data in the meta-analysis. RESULTS: The final analysis included 6 studies involving 34,192 subjects. The overall prevalence of GERD (prevalence of heartburn ± regurgitation once a week or more frequently) in the analyzed studies was 25.605% (95% confidence interval [CI] 17.913-34.147). The analysis used a random effect model, as there was significant heterogeneity between the results in both groups (I2=99.63%; p<0.0001). The overall mean age of GERD patients in the study population was 48.14 (95% CI 32.25-4.03) years. The prevalence of GERD in the male population was 23.653% (95% CI 13.351-35.832) and 25.457% (95% CI 17.094-34.849) in females. CONCLUSION: This meta-analysis demonstrated that GERD is a common esophageal disease in the Russian population, affecting approximately one in four country residents.


Subject(s)
Gastroesophageal Reflux , Humans , Gastroesophageal Reflux/epidemiology , Russia/epidemiology , Prevalence
14.
J Psychiatr Res ; 179: 388-395, 2024 Sep 23.
Article in English | MEDLINE | ID: mdl-39383644

ABSTRACT

Adjustment disorder is frequently used as a diagnostic category for work-related stress disorders in Denmark. However, the diagnostic category is poorly delineated in ICD-10 which has hampered clinical practice as well as research studying the development of work-related adjustment disorders. In ICD-11, the diagnostic category of adjustment disorder has been refined and a new self-report measure is available to operationalize symptoms. The aim of the current study is to translate the International Adjustment Disorder Questionnaire (IADQ) to Danish and test the psychometric properties of the scale in a sample of social educators. A total of 609 social educators in current employment participated in an online survey including the IADQ and data was analyzed using confirmatory factor analysis. Findings suggested that a two-factor model reflecting the distinction between preoccupation and failure to adapt as part of the diagnostic criterion fitted the data best, although strong factor correlations and one cross-factor loading suggests that differentiating between the dimensions of preoccupation and failure to adapt is difficult. Relationships to burnout, posttraumatic stress and general distress support the validity of the Danish translation of the IADQ. Further research should explore the structure of adjustment disorder among other working populations.

16.
Heliyon ; 10(19): e38569, 2024 Oct 15.
Article in English | MEDLINE | ID: mdl-39397987

ABSTRACT

Unmanned aerial vehicle (UAV) pesticide application in recent years owing to its importance such as time saving, reduction in human drudgery and also reduction in pesticides application rate. UAV has a great potential to address the problem involved in manual chemicals spraying in tall crops like coconut plantation where at present operation performed by manual climbing involves lots of drudgery and life risk. The current study aimed to understand the most influencing spraying parameters, such as spray height and spray time of the UAV sprayer on droplet characteristics such as spray droplet size, spray coverage and spray deposition at different layers (spindle, middle and bottom) of coconut tree canopy. The selected spray height (1, 2 and 3 m) and spray time (5, 8 and 11 s) significantly affects (p < 0.05) the droplet size (µm), spray coverage (%) and spray deposition (µl cm-2). In spray droplet size, the treatment T4, T5, T7 and T8 were recorded recommended droplet size of 50-400 µm in all layer of the coconut tree canopy. In spray coverage, the nearest value for recommended spray coverage of 10-20 % was observed for T1 and T5 treatment in all layer of the coconut tree canopy. The maximum penetration efficiency of 34.41 % had achieved at spray height of 2m and spray time of 8s (treatment T5). Based on performance of selected parameter, the spray height of 2 m and spray time of 8 s (treatment T5) was found best for spraying operation using UAV in coconut tree. The results showed the performance of the UAV offers best alternative for spraying operation on coconut tree and also this system will drastically reduce application time, labour requirement and improved the safety of coconut farmers.

17.
ESMO Open ; 9(11): 103930, 2024 Oct 11.
Article in English | MEDLINE | ID: mdl-39395265

ABSTRACT

BACKGROUND: The Dual Erb B Inhibition in Oesophago-gastric Cancer (DEBIOC) trial reported an acceptable safety profile for neoadjuvant oxaliplatin and capecitabine (Xelox) ± AZD8931 in oesophageal adenocarcinoma (OAC) but limited efficacy. We evaluated the impact of neoadjuvant Xelox ± AZD8931, a novel small-molecule inhibitor with equipotent activity against epidermal growth factor receptor (EGFR), human epidermal growth factor receptor (HER)2 and HER3, on biological pathways using a unique software-driven solution. PATIENTS AND METHODS: Transcriptomic profiles from 25 pre-treatment formalin-fixed paraffin-embedded OAC biopsies and 18 matched resection specimens, treated with Xelox + AZD8931 (n = 16) and Xelox alone (n = 9), were analysed using the Almac claraT total mRNA report analysing 92 gene signatures, 100 unique single-gene drug targets and 7337 single genes across 10 hallmarks of cancer. Gene-set enrichment analysis (GSEA) was utilised to investigate pathways governing pathological response. Tumour-infiltrating lymphocytes (TILs) were assessed digitally using the QuPath software. RESULTS: Hierarchical clustering identified three molecular subgroups classified by activation of innate immune signalling. The immune-high subgroup was associated with HER2 positivity, increased pathological response and a marked reduction in immune signalling and TILs following neoadjuvant therapy. The immune-low cluster was predominantly HER2/EGFR-negative, and EGFR positivity was associated with the immune-mixed subgroup. Treatment with neoadjuvant therapy induced common resistance mechanisms, such as angiogenesis and epithelial-mesenchymal transition signalling, and a reduction in DNA repair signatures. Addition of AZD8931 was associated with reduction of expression of EGFR, HER2 and AKT pathways and also promoted an immunosuppressive microenvironment. GSEA showed that patients with a pathological response to treatment had increased immune signalling, whereas non-responders to neoadjuvant therapy were enriched for nucleotide repair and cellular growth through the action of E2F transcription factors. CONCLUSION: OAC may be subdivided into three immune-related subgroups which undergo modulation in response to neoadjuvant therapy with marked suppression of the immune microenvironment in HER2-positive/immune-high tumours.

18.
Curr Probl Cardiol ; : 102880, 2024 Oct 10.
Article in English | MEDLINE | ID: mdl-39395644

ABSTRACT

BACKGROUND: Direct Oral Anticoagulants (DOACs) are the first line anticoagulation for patients with non-valvular atrial fibrillation (NVAF). Percutaneous Left Atrial Appendage Occlusion (LAAO) has emerged as a new therapy and its safety and effectiveness compared with DOACs are still controversial. METHODS: A systematic review of randomized controlled trials and observational studies was conducted, focusing on patients with NVAF. Outcomes analyzed included: (1) all-cause mortality; (2) cardiovascular (CV) mortality; (3) thromboembolic events; (4) stroke or transient ischemic attack (TIA); (5) bleeding events; and a (6) composite of death, hemorrhagic, and thromboembolic events. We performed a subgroup analysis of major bleeding according to different definitions, according to (1) Bleeding Academic Research Consortium (BARC); (2) International Society on Thrombosis and Haemostasis (ISTH); and (3) other definitions. RESULTS: Ten studies involving 18,507 patients were included, with 42.35% undergoing LAAO. In pooled analysis, LAAO was associated with lower rates of all-cause mortality (HR 0.63; 95% CI 0.50-0.80), cardiovascular mortality (HR 0.56; 95% CI 0.45-0.70), and of the composite outcome (HR 0.73; 95% CI 0.58-0.92). A trend towards lower stroke/TIA events was observed but not statistically significant. Overall bleeding events did not significantly differ between groups, using the ISTH definition, LAAO showed significantly lower incidence of bleeding events (HR 0.63; 95% CI 0.43-0.91). No significant difference was found in thromboembolic events. CONCLUSION: LAAO was associated with a significantly lower all-cause mortality and cardiovascular mortality, as well as the composite of death, hemorrhagic or thromboembolic events, as compared with DOACs.

20.
Sensors (Basel) ; 24(19)2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39409219

ABSTRACT

This study develops a hybrid machine learning (ML) algorithm integrated with IoT technology to improve the accuracy and efficiency of soil monitoring and tomato crop disease prediction in Anakapalle, a south Indian station. An IoT device collected one-minute and critical soil parameters-humidity, temperature, pH values, nitrogen (N), phosphorus (P), and potassium (K), during the vegetative growth stage, which are essential for assessing soil health and optimizing crop growth. Kendall's correlations were computed to rank these parameters for utilization in hybrid ML techniques. Various ML algorithms including K-nearest neighbors (KNN), support vector machines (SVM), decision tree (DT), random forest (RF), and logistic regression (LR) were evaluated. A novel hybrid algorithm, 'Bayesian optimization with KNN', was introduced to combine multiple ML techniques and enhance predictive performance. The hybrid algorithm demonstrated superior results with 95% accuracy, precision, and recall, and an F1 score of 94%, while individual ML algorithms achieved varying results: KNN (80% accuracy), SVM (82%), DT (77%), RF (80%), and LR (81%) with differing precision, recall, and F1 scores. This hybrid ML approach proved highly effective in predicting tomato crop diseases in natural environments, underscoring the synergistic benefits of IoT and advanced ML techniques in optimizing agricultural practices.


Subject(s)
Algorithms , Machine Learning , Soil , Solanum lycopersicum , Solanum lycopersicum/growth & development , Soil/chemistry , India , Support Vector Machine , Plant Diseases/prevention & control , Internet of Things , Crops, Agricultural/growth & development
SELECTION OF CITATIONS
SEARCH DETAIL