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Cancer Research Jun 2024Breast cancer includes several subtypes with distinct characteristic biological, pathological, and clinical features. Elucidating subtype-specific genetic etiology could...
Breast cancer includes several subtypes with distinct characteristic biological, pathological, and clinical features. Elucidating subtype-specific genetic etiology could provide insights into the heterogeneity of breast cancer to facilitate development of improved prevention and treatment approaches. Here, we conducted pairwise case-case comparisons among five breast cancer subtypes by applying a case-case GWAS (CC-GWAS) approach to summary statistics data of the Breast Cancer Association Consortium. The approach identified 13 statistically significant loci and eight suggestive loci, the majority of which were identified from comparisons between triple-negative breast cancer (TNBC) and luminal A breast cancer. Associations of lead variants in 12 loci remained statistically significant after accounting for previously reported breast cancer susceptibility variants, among which two were genome-wide significant. Fine mapping implicated putative functional/causal variants and risk genes at several loci, e.g., 3q26.31/TNFSF10, 8q22.3/NACAP1/GRHL2, and 8q23.3/LINC00536/TRPS1, for TNBC as compared to luminal cancer. Functional investigation further identified rs16867605 at 8q22.3 as a SNP that modulates enhancer activity of GRHL2. Subtype-informative polygenic risk scores (PRS) were derived, and patients with a high subtype-informative PRS had an up to 2-fold increased risk of being diagnosed with TNBC instead of luminal cancers. The CC-GWAS PRS remained statistically significant after adjusting for TNBC PRS derived from traditional case-control GWAS in The Cancer Genome Atlas and the African Ancestry Breast Cancer Genetic Consortium. The CC-GWAS PRS was also associated with overall survival and disease-specific survival among breast cancer patients. Overall, these findings have advanced our understanding of the genetic etiology of breast cancer subtypes, particularly for TNBC.
PubMed: 38832928
DOI: 10.1158/0008-5472.CAN-23-3854 -
Obesity (Silver Spring, Md.) Jul 2024The main objective of this study is to better understand the effects of diet-induced weight loss on brain connectivity in response to changes in glucose levels in...
OBJECTIVE
The main objective of this study is to better understand the effects of diet-induced weight loss on brain connectivity in response to changes in glucose levels in individuals with obesity.
METHODS
A total of 25 individuals with obesity, among whom 9 had a diagnosis of type 2 diabetes, underwent functional magnetic resonance imaging (fMRI) scans before and after an 8-week low-calorie diet. We used a two-step hypereuglycemia clamp approach to mimic the changes in glucose levels observed in the postprandial period in combination with task-mediated fMRI intrinsic connectivity distribution (ICD) analysis.
RESULTS
After the diet, participants lost an average of 3.3% body weight. Diet-induced weight loss led to a decrease in leptin levels, an increase in hunger and food intake, and greater brain connectivity in the parahippocampus, right hippocampus, and temporal cortex (limbic-temporal network). Group differences (with vs. without type 2 diabetes) were noted in several brain networks. Connectivity in the limbic-temporal and frontal-parietal brain clusters inversely correlated with hunger.
CONCLUSIONS
A short-term low-calorie diet led to a multifaceted body response in patients with obesity, with an increase in connectivity in the limbic-temporal network (emotion and memory) and hormone and eating behavior changes that may be important for recovering the weight lost.
Topics: Humans; Obesity; Magnetic Resonance Imaging; Male; Female; Weight Loss; Adult; Caloric Restriction; Middle Aged; Hunger; Brain; Diabetes Mellitus, Type 2; Leptin; Blood Glucose; Eating
PubMed: 38831482
DOI: 10.1002/oby.24046 -
ACS Applied Electronic Materials May 2024We recently identified CaCuP as a potential low cost, low density thermoelectric material, achieving = 0.5 at 792 K. Its performance is limited by a large lattice... (Review)
Review
We recently identified CaCuP as a potential low cost, low density thermoelectric material, achieving = 0.5 at 792 K. Its performance is limited by a large lattice thermal conductivity, , and by intrinsically large p-type doping levels. In this paper, we address the thermal and electronic tunability of CaCuP. Isovalent alloying with As is possible over the full solid solution range in the CaCuPAs series. This leads to a reduction in due to mass fluctuations but also to a detrimental increase in p-type doping due to increasing Cu vacancies, which prevents improvement. Phase boundary mapping, exploiting small deviations from 1:1:1 stoichiometry, was used to explore doping tunability, finding increasing p-type doping to be much easier than decreasing the doping level. Calculation of the Lorenz number within the single parabolic band approximation leads to an unrealistic low for highly doped samples consistent with the multiband behavior in these materials. Overall, CaCuP and slightly Cu-enriched CaCuP yield the best performance, with approaching 0.6 at 873 K.
PubMed: 38828033
DOI: 10.1021/acsaelm.3c00828 -
Community Dentistry and Oral... Jun 2024Expanding HIV testing beyond specialized services has been a key strategic approach to eliminating the transmission of HIV. In recent years, dental settings have been... (Review)
Review
OBJECTIVES
Expanding HIV testing beyond specialized services has been a key strategic approach to eliminating the transmission of HIV. In recent years, dental settings have been identified as offering an opportunity for delivering point of care HIV testing (POCT) interventions. Intervention components and implementation strategies have varied across studies and there is uncertainty about the prevalence of undiagnosed HIV in the dental patient population. Therefore, this systematic review aimed to synthesize the HIV testing outcomes of intervention studies, identify the core components of POCT interventions implemented in dental settings; and understand the barriers and facilitators to intervention implementation.
METHODS
A mixed-methods systematic review was undertaken. Two authors reviewed abstracts and full papers for inclusion and appraised the studies using the Mixed Methods Appraisal Tool. A convergent integrated mixed methods study design underpinned the synthesis. Outcomes were presented using descriptive statistics. Intervention components were mapped to the Template for Intervention Description and Replication (TIDieR) checklist. Barriers and facilitators were described using a narrative thematic analysis.
RESULTS
POCT was offered to 22 146 dental patients, 62.5% accepted POCT. Intervention studies that reported higher uptake of testing utilized a dedicated dental or researcher staff member to provide testing, integrated testing and provided results within the routine dental appointment and adopted a provider-initiated universal approach to offering testing. Six themes emerged that were pertinent to the barriers and facilitators to HIV testing in dental setting.
CONCLUSIONS
POCT uptake in dental settings was comparable with other non-specialized health settings. Key to the operationalization of the intervention were perceptions about its value and relevance to the dental patient population, attitudes toward the intervention, logistical barriers to its implementation, the risk of HIV testing stigma to the patient-practitioner relationship and maximising the fit of the intervention within the constraints of the dental setting.
PubMed: 38822596
DOI: 10.1111/cdoe.12963 -
Nanotoxicology May 2024Synthetic dyes play a crucial role in our daily lives, especially in clothing, leather accessories, and furniture manufacturing. Unfortunately, these potentially... (Review)
Review
Synthetic dyes play a crucial role in our daily lives, especially in clothing, leather accessories, and furniture manufacturing. Unfortunately, these potentially carcinogenic substances are significantly impacting our water systems due to their widespread use. Dyes from various sources pose a serious environmental threat owing to their persistence and toxicity. Regulations underscore the urgency in addressing this problem. In response to this challenge, metal oxide nanoparticles such as titanium dioxide (TiO), zinc oxide (ZnO), and iron oxide (FeO) have emerged as intriguing options for dye degradation due to their unique characteristics and production methods. This paper aims to explore the types of nanoparticles suitable for dye degradation, various synthesis methods, and the properties of nanoparticles. The study elaborates on the photocatalytic and adsorption-desorption activities of metal oxide nanoparticles, elucidating their role in dye degradation and their application potential. Factors influencing degradation, including nanoparticle properties and environmental conditions, are discussed. Furthermore, the paper provides relevant case studies, practical applications in water treatment, and effluent treatment specifically in the textile sector. Challenges such as agglomeration, toxicity concerns, and cost-effectiveness are acknowledged. Future advancements in nanomaterial synthesis, their integration with other materials, and their impact on environmental regulations are potential areas for development. In conclusion, metal oxide nanoparticles possess immense potential in reducing dye pollution, and further research and development are essential to define their role in long-term environmental management.
PubMed: 38821108
DOI: 10.1080/17435390.2024.2349304 -
PloS One 2024Spray drying fruit juice powders poses challenges because sugars and organic acids with low molecular weight and a low glass transition temperature inherently cause...
Enhancing polytetrafluoroethylene (PTFE) coated film for food processing: Unveiling surface transformations through oxygenated plasma treatment and parameter optimization using response surface methodology.
Spray drying fruit juice powders poses challenges because sugars and organic acids with low molecular weight and a low glass transition temperature inherently cause stickiness. This study employed a hydrophobic polytetrafluoroethylene (PTFE) film to mimic the surface of the drying chamber wall. The Central Composite Design (CCD) using response surface methodology investigated the impact of power (X1, Watt) and the duration of oxygenated plasma treatment (X2, minutes) on substrate contact angle (°), reflecting surface hydrophobicity. To validate the approach, Morinda citrofolia (MC) juice, augmented with maltodextrins as drying agents, underwent spray drying on the improved PTFE-coated surface. The spray drying process for MC juice was performed at inlet air temperatures of 120, 140, and 160°C, along with Noni juice-to-maltodextrin solids ratios of 4.00, 1.00, and 0.25. The PTFE-coated borosilicate substrate, prepared at a radio frequency (RF) power of 90W for 15 minutes of treatment time, exhibited a porous and spongy microstructure, correlating with superior contact angle performance (171°) compared to untreated borosilicate glass. Optimization data indicated that the PTFE film attained an optimum contact angle of 146.0° with a specific combination of plasma RF operating power (X1 = 74 W) and treatment duration (X2 = 10.0 minutes). RAMAN spectroscopy indicated a structural analysis with an ID/IG ratio of 0.2, while Brunauer-Emmett-Teller (BET) surface area analysis suggested an average particle size of less than 100 nm for all coated films. The process significantly improved the powder's hygroscopicity, resistance to caking, and moisture content of maltodextrin-MC juice. Therefore, the discovery of this modification, which applies oxygen plasma treatment to PTFE-coated substrates, effectively enhances surface hydrophobicity, contact angle, porosity, roughness, and ultimately improves the efficacy and recovery of the spray drying process.
Topics: Polytetrafluoroethylene; Surface Properties; Food Handling; Oxygen; Fruit and Vegetable Juices; Hydrophobic and Hydrophilic Interactions; Polysaccharides; Plasma Gases
PubMed: 38820420
DOI: 10.1371/journal.pone.0303931 -
The Veterinary Record Jun 2024
Topics: Humans; Animals; Tuberculosis, Bovine; United Kingdom; Veterinarians; Cattle
PubMed: 38819906
DOI: 10.1002/vetr.4365 -
Urology Annals 2024We aimed to study whether using 30 W versus 60 W thulium enucleation of the prostate (ThuLEP) would affect postoperative outcomes in patients with benign prostatic...
INTRODUCTION
We aimed to study whether using 30 W versus 60 W thulium enucleation of the prostate (ThuLEP) would affect postoperative outcomes in patients with benign prostatic hyperplasia (BPH).
MATERIALS AND METHODS
We prospectively identified male patients with moderate or severe lower urinary tract symptoms due to BPH. We randomized patients into 30 W (Group 1) or 60 W (Group 2) thulium yag laser with a 550 μm laser fiber and a 26 Fr continuous flow resectoscope. We collected data related to prostate size, enucleation time, morcellation time, laser time, perioperative complications, and 1-year functional outcomes.
RESULTS
A total of 120 patients were included, with a mean age of 67 years and a mean prostate size of 105 g. The preoperative characteristics were similar across both groups. The mean operative time was shorter in the 60 W group, 74 ± 27 vs. 91 ± 33 min in the 30 W group ( = 0.001), and the mean laser time was 55 ± 20 in 60 W versus 71 ± 25 in 30 W ( = 0.0001). The mean hospital stay was 1 day in both groups and at 1-year follow-up; there was a similar improvement in mean Qmax and International Prostate Symptom Score symptom scores.
DISCUSSION/CONCLUSION
Both 30 and 60 W ThuLEP provided a safe and comparable outcome with a relatively shorter operative time for the 60 W groups. Perhaps using a 30-W setting would be beneficial in the early learning curve or cases with more bleeding capsular perforators; besides, the financial benefit of manufacturing low-cost low-power devices that may help in the widespread of AEEP.
PubMed: 38818432
DOI: 10.4103/ua.ua_159_22 -
Arab Journal of Urology 2024Anatomical endoscopic enucleation of the prostate (AEEP) provides durable management for patients with lower urinary tract symptoms (LUTS) secondary to large-sized...
INTRODUCTION AND OBJECTIVES
Anatomical endoscopic enucleation of the prostate (AEEP) provides durable management for patients with lower urinary tract symptoms (LUTS) secondary to large-sized prostate over other surgical modalities. We aimed to assess the early outcomes of Collins knife-assisted bipolar enucleation (BipolEP) versus Thulium-Yag enucleation (ThuLEP) in a group of patients with LUTS secondary to a prostate larger than 80 grams.
METHODS
We included patients with benign prostatic hyperplasia (BPH) having a prostate volume > 80 grams, international prostate symptom score (IPSS) >7, urine flow (Q-max) <15, and post-void residual (PVR)>150 ml. We excluded those with a history of previous prostatic surgery, stone, or neurogenic bladder. Bipolar enucleation with early apical release was performed using Collins knife at an 80/100-watt setting (Lamidey Noury), while ThuLEP was conducted using 550- micron fiber and 40/15-watt energy (Lisa Laser). Patients were evaluated before then 2 weeks and 3, 6,12 months postoperatively for changes in IPSS, Q- max, PVR, and the incidence of stress incontinence.
RESULT
One hundred and twenty patients were equally randomized with a mean prostate size of 104 ± 25 gram. The mean IPSS score was 25 ± 6, Qmax 7.6 ± 1.3 mL/S, and PVR 225 ± 39. There was no significant difference regarding enucleation time, morcellation time, and enucleated tissue volume. Irrigation volume and post-operative hemoglobin drop were significantly lower in the bipolar group ( = 0.008, = 0.0002), respectively. At the third-month follow-up, IPSS, Q-max, and PVR were comparable across both groups, with stress incontinence at 3.3% in the bipolar group versus 1.6% in the thulium group, showing an insignificant difference ( = 0.5)."
CONCLUSION
Both BipolEP and ThuLEP, with early apical release, provide a safe and effective management of large-size prostate resulting in significant decrease in post-operative stress incontinence incidence during early follow-up. Intraoperative irrigation saline volume, and post-operative hemoglobin drop favored the bipolar group.
PubMed: 38818261
DOI: 10.1080/20905998.2024.2321737 -
Clinical Pharmacokinetics Jun 2024Levetiracetam is an antiseizure medication used for several seizure types in adults and children aged 1 month and older; however, due to a lack of data, pharmacokinetic...
Application of Physiologically Based Pharmacokinetic Modeling to Characterize the Effects of Age and Obesity on the Disposition of Levetiracetam in the Pediatric Population.
BACKGROUND
Levetiracetam is an antiseizure medication used for several seizure types in adults and children aged 1 month and older; however, due to a lack of data, pharmacokinetic (PK) variability of levetiracetam is not adequately characterized in certain populations, particularly neonates, children younger than 2 years of age, and children older than 2 years of age with obesity.
OBJECTIVE
This study aimed to address the gap by leveraging PK data from two prospective standard-of-care pediatric trials (n = 88) covering an age range from 1 month to 19 years, including those with obesity (64%), and applying a physiologically based PK (PBPK) modeling framework.
METHODS
A published PBPK model of levetiracetam for children aged 2 years and older was extended to pediatric patients younger than 2 years of age and patients older than 2 years of age with obesity by accounting for the obesity and age-related changes in PK using PK-Sim software. The prospective pediatric data, along with the literature data for neonates and children younger than 2 years of age, were used to evaluate the extended PBPK models.
RESULTS
Overall, 82.4% of data fell within the 90% interval of model-predicted concentrations, with an average fold error within twofold of the accepted criteria. PBPK modeling revealed that children with obesity had lower weight-normalized clearances (0.053 L/h/kg) on average than children without obesity (0.063 L/h/kg). The effect of maturation was well-characterized, resulting in comparable PBPK-simulated, weight-normalized clearances for neonates and children younger than 2 years of age reported from the literature.
CONCLUSIONS
PBPK modeling simulations revealed that the current US FDA-labeled pediatric dosing regimen listed in the prescribing information can produce the required exposure of levetiracetam in these target populations with dose adjustments for children with obesity aged 4 years to younger than 16 years.
Topics: Humans; Levetiracetam; Child, Preschool; Child; Models, Biological; Infant; Adolescent; Anticonvulsants; Male; Female; Age Factors; Infant, Newborn; Young Adult; Obesity; Prospective Studies; Computer Simulation
PubMed: 38814425
DOI: 10.1007/s40262-024-01367-2