Tag: pubmed

Biometrics. 2024 Jul 1;80(3):ujae061. doi: 10.1093/biomtc/ujae061.

ABSTRACT

What is the best way to split one stratum into two to maximally reduce the within-stratum imbalance in many covariates? We formulate this as an integer program and approximate the solution by randomized rounding of a linear program. A linear program may assign a fraction of a person to each refined stratum. Randomized rounding views fractional people as probabilities, assigning intact people to strata using biased coins. Randomized rounding is a well-studied theoretical technique for approximating the optimal solution of certain insoluble integer programs. When the number of people in a stratum is large relative to the number of covariates, we prove the following new results: (i) randomized rounding to split a stratum does very little randomizing, so it closely resembles the linear programming relaxation without splitting intact people; (ii) the linear relaxation and the randomly rounded solution place lower and upper bounds on the unattainable integer programming solution; and because of (i), these bounds are often close, thereby ratifying the usable randomly rounded solution. We illustrate using an observational study that balanced many covariates by forming matched pairs composed of 2016 patients selected from 5735 using a propensity score. Instead, we form 5 propensity score strata and refine them into 10 strata, obtaining excellent covariate balance while retaining all patients. An R package optrefine at CRAN implements the method. Supplementary materials are available online.

PMID:38994639 | DOI:10.1093/biomtc/ujae061

Comb Chem High Throughput Screen. 2024 Jul 11. doi: 10.2174/0113862073324077240624094140. Online ahead of print.

ABSTRACT

BACKGROUND: According to current worldwide cancer data, Prostate Cancer (PC) ranks as the second most common type of cancer and is the fifth leading cause of cancer-related mortality among men worldwide. PC in China has the 10th highest number of new cases and the 13th highest fatality rate, both of which show an ongoing annual increase. One of the significant challenges with prostate cancer is the difficulty in early detection, often resulting in diagnosis at intermediate or late stages, complicating treatment. Although hormonal therapy is initially successful in controlling the progression of prostate cancer, almost all tumors that respond to hormones eventually transform into Castration-resistant Prostate Cancer (CRPC) within 18-24 months of hormonal therapy. This poses clinical difficulties due to an absence of successful therapeutic approaches. Therefore, understanding the fundamental mechanisms of prostate cancer development, identifying effective therapeutic targets, and discovering reliable molecular biomarkers are crucial objectives.

METHODS: CircRNA expression in plasma was assessed in 4 samples obtained from patients with Benign Prostatic Hyperplasia (BPH), and PC was detected through microarray probes. Statistical analysis of the expression of circDUSP22 and clinicopathological features was conducted. The investigation of target genes was conducted using luciferase reporter assays and bioinformatics analysis. The expression levels of circDUSP22, miR-18a-5p, and Solute Carrier Family 7 member 11 (SLC7A11) were assessed using a quantitative Real-time Polymerase Chain Reaction (qRT-PCR) assay. Cell invasion, migration, colony formation, and proliferation were evaluated using Transwell, wound healing, colony formation, and CCK-8 assays, respectively. RNA Immunoprecipitation (RIP) and dual-luciferase reporter assays were used to examine the connections among circDUSP22, miR-18a-5p, and SLC7A11. The impact of circDUSP22 on the expression of ferroptosis-related proteins, specifically SLC7A11, as well as its effects on Fe2+ and ROS were also examined.

RESULTS: In both plasma samples and PCa cell lines, there was a substantial elevation of circDUSP22 and SLC7A11 expression and a decline in miR-18a-5p expression. Suppression of circDUSP22 significantly impeded the migration, invasion, and proliferation of PC cells in vitro. The target gene of miR-18a-5p, SLC7A11, was found to be upregulated as an effect of circDUSP22’s competitive binding to miR-18a-5p. Cellular experiments demonstrated that interference with circDUSP22 expression in DU145 and PC-3 cells led to increased ferroptosis and decreased SLC7A11 expression. The modulation of prostate cancer cell proliferation was reversed by either overexpressing SLC7A11 or inhibiting miR-18a-5p in response to the silencing of circDUSP22.

CONCLUSION: The circDUSP22 has been found to have a substantial effect on the development of ferroptosis in PC. It has been observed to influence the formation and evolution of this disorder by affecting the miR-18a-5p/SLC7A11 signaling pathway.

PMID:38994627 | DOI:10.2174/0113862073324077240624094140

Curr Comput Aided Drug Des. 2024 Jul 11. doi: 10.2174/0115734099305382240704071258. Online ahead of print.

ABSTRACT

BACKGROUND: MicroRNA-584-5p (miR-584-5p) plays an important role in certain types of cancer. However, its precise role in head and neck squamous cell carcinoma (HNSC) remains unknown.

OBJECTIVE: Our aim was to investigate how miR-584-5p influences HNSC.

METHODS: The Cancer Genome Atlas (TCGA) provided samples for the study. We use statistical methods to evaluate the diagnostic value, the prognostic value, and the correlation with the clinical features of miR-584-5p. We analyze the target genes and the regulatory network of miR- 584-5p. Quantitative reverse transcriptase PCR (qRT-PCR) confirmed the expression of miR- 584-5p in HNSC cell lines.

RESULTS: MiR-584-5p expression of miR-584-5p varied significantly among different types of cancer. A notable correlation was observed between elevated miR-584-5p expression and gender (p < 0.001) and histological grade (p < 0.001). Furthermore, high levels of miR-584-5p were found to be associated with a decrease in overall survival (HR: 1.44; 95% CI: 1.10-1.88; p = 0.007), progression-free survival (HR: 1.35; 95% CI: 1.02-1.79; p = 0.035) and disease-specific survival (HR: 1.54; 95% CI: 1.09-2.18; p = 0.016) in the context of HNSC. miR-584-5p demonstrated independent prognostic significance in HNSC and potentially contributes to disease progression through multiple pathways, such as dilated cardiomyopathy and hypertrophic cardiomyopathy. In particular, HNSC cell lines exhibited a substantial upregulation of miR-584-5p compared to normal epithelial cells.

CONCLUSIONS: It is possible that miR-584-5p could serve as a promising patent for a therapeutic target and prognostic biomarker for people with HNSC.

PMID:38994617 | DOI:10.2174/0115734099305382240704071258

Euro Surveill. 2024 Jul;29(28). doi: 10.2807/1560-7917.ES.2024.29.28.2300697.

ABSTRACT

BackgroundAs Ireland prepared for an autumn 2023 COVID-19 vaccination booster campaign, there was concern that vaccine fatigue would affect uptake, which has been abating.AimThis study aimed to quantify the direct impact of the COVID-19 vaccination programme in Ireland on averted COVID-19-related outcomes including symptomatic presentations to primary care/community testing centres, emergency department (ED) presentations, hospitalisations, intensive care unit (ICU) admissions and deaths, in individuals aged ≥ 50 years, during Omicron dominance.MethodsWe conducted a retrospective observational COVID-19 vaccine impact study in December 2021-March 2023 in Ireland. We used national data on notified outcomes and vaccine coverage, as well as vaccine effectiveness (VE) estimates, sourced from the World Health Organization’s live systematic review of VE, to estimate the count and prevented fraction of outcomes in ≥ 50-year-olds averted by the COVID-19 vaccination programme in this age group.ResultsThe COVID-19 vaccination programme averted 48,551 symptomatic COVID-19 presentations to primary care/community testing centres (36% of cases expected in the absence of vaccination), 9,517 ED presentations (53% of expected), 102,160 hospitalisations (81% of expected), 3,303 ICU admissions (89% of expected) and 15,985 deaths (87% of expected).ConclusionsWhen Omicron predominated, the COVID-19 vaccination programme averted symptomatic and severe COVID-19 cases, including deaths due to COVID-19. In line with other international vaccine impact studies, these findings emphasise the benefits of COVID-19 vaccination for population health and the healthcare system and are relevant for informing COVID-19 booster vaccination programmes, pandemic preparedness and communicating the reason for and importance of COVID-19 vaccination in Ireland and internationally.

PMID:38994604 | DOI:10.2807/1560-7917.ES.2024.29.28.2300697

Euro Surveill. 2024 Jul;29(28). doi: 10.2807/1560-7917.ES.2024.29.28.2300733.

ABSTRACT

BackgroundBy mid-September 2023, several event notifications related to cryptosporidiosis had been identified from different regions in Spain. Therefore, a request for urgent notification of cryptosporidiosis cases to the National Surveillance Network was launched.AimWe aimed at assessing the extent of the increase in cases, the epidemiological characteristics and the transmission modes and compared to previous years.MethodsWe analysed data on case notifications, outbreak reports and genotypes focusing on June-October 2023 and compared the results to 2016-2022.ResultsIn 2023, 4,061 cryptosporidiosis cases were notified in Spain, which is an increase compared to 2016-2022. The cumulative incidence was 8.3 cases per 100,000 inhabitants in 2023, sixfold higher than the median of 1.4 cases per 100,000 inhabitants 2016-2022. Almost 80% of the cases were notified between June and October. The largest outbreaks were related to contaminated drinking water or swimming pools. Cryptosporidium hominis was the most common species in the characterised samples (115/122), and the C. hominis IfA12G1R5 subtype, previously unusual in Spain, was detected from 76 (62.3%) of the 122 characterised samples.ConclusionsA substantial increase in cryptosporidiosis cases was observed in 2023. Strengthening surveillance of Cryptosporidium is essential for prevention of cases, to better understand trends and subtypes circulating and the impact of adverse meteorological events.

PMID:38994603 | DOI:10.2807/1560-7917.ES.2024.29.28.2300733

Clin Nephrol. 2024 Jul 12. doi: 10.5414/CN111226. Online ahead of print.

ABSTRACT

BACKGROUND: Hyperkalemia is a common complication of chronic kidney disease (CKD). This study aims to investigate the efficacy and safety of sodium zirconium cyclosilicate and calcium polystyrene sulfonate in reducing potassium in patients with acute and severe hyperkalemia in CKD who are not undergoing dialysis.

MATERIALS AND METHODS: A retrospective real-world study was conducted among 73 patients with non-dialysis chronic kidney disease who were hospitalized in the First Affiliated Hospital of Chengdu Medical College from June 2020 to June 2022. 33 patients treated with sodium zirconium cyclosilicate were categorized as SZC group, and the other 40 patients treated with calcium polystyrene sulfonate were categorized as CPS group. Serum potassium, serum sodium, magnesium, calcium, and phosphorus levels were examined. Adverse reactions were recorded during medication.

RESULTS: Significantly decreased serum potassium was observed in both groups, whereas the potassium reduction was higher in the SZC group than in the CPS group at 2, 4, 24, and 48 hours after medication while there was no statistically significant difference in the serum potassium level between the two groups at 72 hours. For those people whose initial potassium exceeded 6 mmol/L, the potassium reduction was more obvious in the SZC group than in the CPS group at 2 and 4 hours after medication. The control rate of hyperkalemia in the SZC group was significantly higher than in the CPS group at 4, 24, and 48 hours. No distinct change was observed in serum sodium, calcium, magnesium, and phosphorus before and 72 hours after medication. No severe adverse reactions occurred.

CONCLUSION: Sodium zirconium cyclosilicate has a more obvious effect on reducing potassium particularly for those patients with moderate to severe hyperkalemia who need rapid potassium reduction.

PMID:38994592 | DOI:10.5414/CN111226

Ann Surg. 2024 Jul 12. doi: 10.1097/SLA.0000000000006404. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to evaluate the association of surgeon self-reported gender on clinical outcomes in contemporary U.S. surgical practice.

SUMMARY BACKGROUND DATA: Previous research has suggested that there are potentially improved surgical outcomes for female surgeons, yet the underlying causal path for this association remains unclear.

METHODS: Using the Vizient® Clinical Database(2016-2021), 39 operations categorized by the CDC’s National Healthcare Safety Network were analyzed. Surgeon self-reported gender was the primary exposure. The primary outcome was a composite of in-hospital death, complications, and/or 30-day readmission. Multivariable logistic regression and propensity score matching was used for risk adjustment.

RESULTS: The analysis included 4,882,784 patients operated on by 11,955 female surgeons(33% of surgeons, performing 21% of procedures) and 23,799 male surgeons(67% of surgeons, performing 79% of procedures). Female surgeons were younger(45±9 vs. males-53±11 y;P<0.0001) and had lower operative volumes. Unadjusted incidence of the primary outcome was 13.6%(10.7%-female surgeons, 14.3%-male surgeons;P<0.0001). After propensity matching, the primary outcome occurred in 13.0% of patients(12.9%-female, 13.0%-male; OR[M vs. F]=1.02, 95%CI 1.01-1.03;P=.001), with female surgeons having small statistical associations with lower mortality and complication rates but not readmissions. Procedure-specific analyses revealed inconsistent or no surgeon-gender associations.

CONCLUSIONS: In the largest analysis to date, surgeon self-reported gender had a small statistical, clinically marginal correlation with postoperative outcomes. The variation across surgical specialties and procedures suggests that the association with surgeon gender is unlikely causal for the observed differences in outcomes. Patients should be reassured that surgeon gender alone does not have a clinically meaningful impact on their outcome.

PMID:38994583 | DOI:10.1097/SLA.0000000000006404

J Clin Endocrinol Metab. 2024 Jul 12:dgae472. doi: 10.1210/clinem/dgae472. Online ahead of print.

ABSTRACT

CONTEXT: Supplemental methotrexate (MTX) may affect the clinical course of Graves’ disease (GD).

OBJECTIVE: Evaluate efficacy of add-on MTX on medical treatment in GD.

DESIGN: Prospective, open-label, randomized supplementation controlled trial.

SETTING: Academic endocrine outpatient clinic.

PATIENTS: One hundred and fifty-three untreated hyperthyroid patients with GD.

INTERVENTION: Patients received MTX 10 mg/d with methimazole (MMI) or MMI only. MTX and MMI were discontinued at months 12-18 in euthyroid patients.

MAIN OUTCOME MEASURES: Discontinuation rate at months 18 in each group.

RESULTS: In the MTX with MMI group, the discontinuation rate was higher than the MMI group at months 15-18 (50.0 vs. 33.3%, P=0.043, 95% CI 1.020 to 3.922; and 55.6 vs 38.9%, P=0.045, 95%CI 1.011 to 3.815, respectively). The decrease in TRAb levels in the MTX with MMI group was significant from baseline to months 6 compared to the MMI alone group [MTX+MMI 67.22% (43.12-80.32), MMI 54.85% (33.18-73.76), P= 0.039) and became more significant from months 9 [MTX+MMI 77.79% (62.27-88.18), MMI 69.55% (50.50-83.22), P= 0.035] to months 18 (P < 0.01 in 15-18 months). A statistically significant difference between the levels of TRAb in the MTX with MMI group and the MMI group at 9-18 months. There were no significant differences in the levels of FT3, FT4 and TSH between two groups. No serious drug-related adverse events were observed in both groups(P=0.771).

CONCLUSIONS: Supplemental MTX with MMI resulted in higher discontinuation rate and improvement in decreased TRAb levels to homeostatic levels faster than methimazole treatment alone at months 12-18.

PMID:38994582 | DOI:10.1210/clinem/dgae472

Spec Care Dentist. 2024 Jul 12. doi: 10.1111/scd.13040. Online ahead of print.

ABSTRACT

BACKGROUND: The number of older individuals with mild cognitive impairment and neurocognitive diseases is increasing, which may rapidly deteriorate oral health and Quality of life. Therefore, removing dental biofilm is essential for maintaining good oral health. The present study aimed to investigate whether introducing a powered toothbrush reduces the presence of dental plaque, bleeding on probing, and periodontal pockets ≥4 mm, leading to maintained or improved oral health and improved Quality of life in a group of older individuals with mild cognitive impairment.

METHODS: Two hundred and thirteen individuals aged 55 or older living without official home care with a Mini-Mental State Examination (MMSE) score between 20 and 28 and a history of memory problems in the previous 6 months were recruited and screened for the study. The individuals received a powered toothbrush and thorough instructions on how to use it. Clinical oral examinations, Quality of life examinations, and MMSE tests were conducted at baseline, 6, 12, and 24 months. The intervention group was compared to control groups at baseline and 24-month examination. It was divided into an MMSE high group with a score of more than 26 and an MMSE low group with a score of 26 and lower or decreasing two steps or more for 12 months.

RESULTS: PI, BOP, and PPD≥4 mm improved continuously in both MMSE groups during the 24 months of the study. The values for QoL-AD deteriorated over time, while the oral health-related Quality of life did not show any statistically significant changes.

CONCLUSIONS: Introducing a powered toothbrush improved PI, BOP, and PPD≥4 mm over 24 months, even among individuals with low or declining MMSE scores. Improved oral health is associated with a preserved OHR-QoL.

PMID:38994574 | DOI:10.1111/scd.13040

Nutr Cancer. 2024 Jul 12:1-11. doi: 10.1080/01635581.2024.2378502. Online ahead of print.

ABSTRACT

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer in the world. Doxorubicin (Dox) is a very useful drug in these patients, however, one of the main adverse effects caused by the use of Dox is cardiotoxicity (CT). Protein-calorie malnutrition (PCM) is a factor that, among others, can influence the development of CT due to Dox. The aim of our study was to associate PCM as a risk factor for CT induced by Dox in Mexican children with ALL. We included 89 children with ALL who were treated with Dox, from October 2018 to July 2023, and of whom 14 developed some type of CT, 15 were underweight and 3 were overweight. The analysis of the association risk of CT due to PCM shows a statistically significant association of risk of developing CT due to PCM. On the other hand, healthy weight was associated with protection for developing CT due to Dox use. Of the total number of girls who presented CT, all had systolic dysfunction, while 6 of them also had diastolic dysfunction. On the other hand, of the total number of boys who presented CT, all of them had systolic dysfunction and only one of them also had diastolic dysfunction. These results show that in patients in which Dox is being administered, special attention is suggested for girls with PCM, since systolic failure is a precursor and occurs before diastolic failure in girls with PCM.

PMID:38994569 | DOI:10.1080/01635581.2024.2378502