Explore the vast range of titles available.

Long non-coding RNAs (lncRNAs) play pivotal roles in regulating immune responses, immune cell differentiation, activation, and inflammatory processes. In cancer, they are gaining prominence as potential therapeutic targets due to their ability to regulate immune checkpoint molecules and immune-related factors, suggesting avenues for bolstering anti-tumor immune responses. Here, we explore the mechanistic insights into lncRNA-mediated immune modulation, highlighting their impact on immunity. Additionally, we discuss their potential to enhance cancer immunotherapy, augmenting the effectiveness of immune checkpoint inhibitors and adoptive T cell therapies. LncRNAs as therapeutic targets hold the promise of revolutionizing cancer treatments, inspiring further research in this field with substantial clinical implications.

Recently, mRNA-expression signature enriched in LSCs was used to create a 17-gene leukemic stem cell (LSC17) score predictive of prognosis in adult AML. By fitting a Cox-LASSO regression model to the clinical outcome and gene-expression levels of LSC enriched genes in 163 pediatric participants of the AML02 multi-center clinical trial (NCT00136084), we developed a six-gene LSC score of prognostic value in pediatric AML (pLSC6). In the AML02 cohort, the 5-year event-free survival (EFS) of patients within low-pLSC6 group (n = 97) was 78.3 (95% CI = 70.5–86.9%) as compared with 34.5(95% CI = 24.7–48.2 %) in patients within high-pLSC6 group (n = 66 subjects), p < 0.00001. pLSC6 remained significantly associated with EFS and overall survival (OS) after adjusting for induction 1-MRD status, risk-group, FLT3-status, WBC-count at diagnosis and age. pLSC6 formula developed in the AML02 cohort was validated in the pediatric AML-TARGET project data (n = 205), confirming its prognostic value in both single-predictor and multiple-predictor Cox regression models. In both cohorts, pLSC6 predicted outcome of transplant patients, suggesting it as a useful criterion for transplant referrals. Our results suggest that pLSC6 score holds promise in redefining initial risk-stratification and identifying poor risk AML thereby providing guidance for developing novel treatment strategies.

PURPOSE: To evaluate the effects of femtosecond laser small incision lenticule extraction (SMILE) on treating unilateral myopic anisometropia in children with spectacles or contact lens intolerance. METHODS: This was a retrospective study that included children with unilateral myopic anisometropic amblyopia who underwent a SMILE procedure at Alpha Vision Center, Zagazig, Egypt, from January 2014 to December 2016. RESULTS: One hundred twenty-four eyes of 124 patients were included in this study. The postoperative corrected distance visual acuity (CDVA) at the 3-month and 1-, 2-, 3-, and 4-year follow-up visits improved significantly (P < .05) compared to the preoperative CDVA, indicating the safety of the procedure. At the 3-month postoperative visit, 23% of cases showed improvement of one or more lines of CDVA, whereas only 2% of cases showed a decline of only one line. Moreover, the postoperative uncorrected distance visual acuity compared favorably to the preoperative CDVA, denoting the efficacy of the refractive correction. The spherical equivalent was within ±0.50 diopters of the intended correction in 75% of the cases and within ±1.00 diopters in 89% of the cases. The intraoperative complications were scarce and relatively innocuous. CONCLUSIONS: SMILE is a safe and effective alternative method for correcting myopic anisometropic amblyopia in children with spectacles or contact lens intolerance with good refractive results. A larger study with longer follow-up periods is necessary to determine the long-term effects of SMILE. [J Refract Surg. 2021;37(8):510–515.]

The swelling phenomenon of expansive soil is considered one of the most serious problems that face geotechnical engineers. The principal purpose of this study is to investigate the effectiveness of geogrid for reinforcing sand cushion on the heave of isolated footing resting on a top of a sand cushion underlined by highly active expansive clay using the large-scale box model. An artificial case study was imposed to prove the cost-effectiveness of using geogrid reinforcement with sand cushion. After performing experiments, there are many important conclusions that have been extracted from this study, for instance, using biaxial geogrid leads to control the heave of swelling soil due to the tension developed in geogrid. As well, the heave of the footing decreases slightly when the thickness of the sand cushion layer is changed from 0.75B to B.

Background Triple-Negative Breast Cancer (TNBC) is a lethal subtype of breast cancer with limited treatment options. The purpose of this Network Meta-Analysis (NMA) is to compare the efficacy and safety of inhibitors of programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in treating TNBC. Methods Our search strategy was used in six databases: PubMed, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature database, Embase, Scopus, and Web of Science up to November 2nd, 2022, as well as a thorough search in the most used trial registries. We included phase II and III randomized controlled trials that looked at the efficacy of PD-1/PD-L1 inhibitors in the treatment of TNBC and reported either Overall Survival (OS), Progression-Free Survival (PFS), or pathological Complete Response (pCR). The risk of bias was assessed utilizing Cochrane's risk of bias 2 tool, and the statistical analysis was performed using a frequentist contrast-based method for NMA by employing standard pairwise meta-analysis applying random effects model. Results 12 trials (5324 patients) were included in our NMA including seven phase III trials. Pembrolizumab in a neoadjuvant setting achieved a pooled OS of 0.82 (95% Confidence Interval (CI) 0.65 to 1.03), a PFS of 0.82 (95% CI 0.71 to 0.94) and a pCR 2.79 (95% CI 1.07 to 7.24) compared to Atezolizumab’s OS of 0.92 (95% CI 0.74 to 1.15), PFS of 0.82 (95% CI 0.69 to 0.97), and pCR of 1.94 (95% CI 0.86 to 4.37). Atezolizumab had less grade ≥ 3 adverse events (OR 1.48, 95% CI 0.90 to 2.42) than Pembrolizumab (OR 1.90, 95% CI 1.08 to 3.33) in the neoadjuvant setting. Conclusions PD-1/PD-L1 inhibitors exhibited varying efficacy in terms of OS, PFS, and pCR. They were associated with an increase in immune-related adverse effects. When used early in the course of TNBC, PD-1/PD-L1 inhibitors exert their maximum benefit. Durvalumab as a maintenance treatment instead of chemotherapy has shown promising outcomes. Future studies should focus on PD-L1 expression status and TNBC subtypes, since these factors may contribute to the design of individualized TNBC therapy regimens. Systematic review registration PROSPERO Identifier: CRD42022380712.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Here, using whole-genome, exome and transcriptome sequencing of 2,754 childhood patients with ALL, we find that, despite a generally low mutation burden, ALL cases harbor a median of four putative somatic driver alterations per sample, with 376 putative driver genes identified varying in prevalence across ALL subtypes. Most samples harbor at least one rare gene alteration, including 70 putative cancer driver genes associated with ubiquitination, SUMOylation, noncoding transcripts and other functions. In hyperdiploid B-ALL, chromosomal gains are acquired early and synchronously before ultraviolet-induced mutation. By contrast, ultraviolet-induced mutations precede chromosomal gains in B-ALL cases with intrachromosomal amplification of chromosome 21. We also demonstrate the prognostic significance of genetic alterations within subtypes. Intriguingly, DUX4 - and KMT2A -rearranged subtypes separate into CEBPA/FLT3 - or NFATC4 -expressing subgroups with potential clinical implications. Together, these results deepen understanding of the ALL genomic landscape and associated outcomes. A genomic and transcriptomic analysis of 2,754 childhood acute lymphoblastic leukemias identifies 376 putative driver genes, and associations between disease subtypes and prognosis.

Many long noncoding RNAs have been implicated in tumorigenesis and chemoresistance; however, the underlying mechanisms are not well understood. We investigated the role of PRKAR1B-AS2 long noncoding RNA in ovarian cancer (OC) and chemoresistance and identified potential downstream molecular circuitry underlying its action. Analysis of The Cancer Genome Atlas OC dataset, in vitro experiments, proteomic analysis, and a xenograft OC mouse model were implemented. Our findings indicated that overexpression of PRKAR1B-AS2 is negatively correlated with overall survival in OC patients. Furthermore, PRKAR1B-AS2 knockdown-attenuated proliferation, migration, and invasion of OC cells and ameliorated cisplatin and alpelisib resistance in vitro. In proteomic analysis, silencing PRKAR1B-AS2 markedly inhibited protein expression of PI3K-110α and abrogated the phosphorylation of PDK1, AKT, and mTOR, with no significant effect on PTEN. The RNA immunoprecipitation detected a physical interaction between PRKAR1B-AS2 and PI3K-110α. Moreover, PRKAR1B-AS2 knockdown by systemic administration of 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine nanoparticles loaded with PRKAR1B-AS2–specific small interfering RNA enhanced cisplatin sensitivity in a xenograft OC mouse model. In conclusion, PRKAR1B-AS2 promotes tumor growth and confers chemoresistance by modulating the PI3K/AKT/mTOR pathway. Thus, targeting PRKAR1B-AS2 may represent a novel therapeutic approach for the treatment of OC patients.

To describe a new technique for transconjunctival intrascleral fixation of Cionni CTR using double-flanged polypropylens suture. This is a prospective interventional case series which included 7 cases with severe (more than 180 degrees) zonular dialysis. Three cases were hereditary lens subluxation (Marfan syndrome), 2 cases with traumatic subluxation and 2 cases with pseudo-exfoliation syndrome. All cases achieved a good postoperative stable and centered IOL with good visual results. No postoperative complications were recorded apart from PCO in 3 cases and mild bleeding during needle passage in one case. This described technique is a simple, time sparing and minimally invasive method for achieving good bag centration. It eliminates the need of conjunctival peritomy, subconjunctival vessels cautery and scleral fashioning of a flap, pocket or a groove. The use of 6/0 polypropylene theoretically can achieve better longevity.

This study aims to evaluate fetal lung development through volumetric measurements and Doppler assessments of the main pulmonary artery, thereby correlating these findings with neonatal respiratory distress and Apgar score. The study recruited 170 healthy third-trimester pregnant women, excluding those with multiple pregnancies (twins or higher-order), chronic maternal illnesses (e.g., hypertension, diabetes, cardiac disease), fetal congenital anomalies, or maternal substance abuse. Ultrasound was used to measure fetal lung volumes (via Moeglin's and Araujo's formulas) and pulmonary artery Doppler indices, which were then correlated with neonatal respiratory distress and Apgar scores. Out of 169 pregnancies, neonatal RDS occurred in 12.4%, with incidence decreasing at higher gestational ages. Fetal lung volume predicted RDS, with Moeglin's formula offering higher specificity (77%) and Araujo's higher sensitivity (95.2%). Doppler parameters, specifically AT and ET, were shorter in RDS cases and provided fair predictive accuracy, which improved when combined with lung volume. Multivariate analysis identified low estimated fetal weight and reduced lung volume as independent predictors, while right lung width negatively correlated with outcomes and with both PI and AT, indicating a relationship with pulmonary vascular resistance. Combining fetal pulmonary artery Doppler indices with 2D ultrasound lung volume measurements improves prediction of neonatal respiratory distress. Estimated fetal weight and lung volume were confirmed as independent predictors, emphasizing the value of integrating functional and structural assessments for better early risk identification in prenatal care.

Detection of meat adulteration is a critical issue in food labeling procedures and a serious concern related to food fraud, authenticity, and religious beliefs. The current work detected and quantified adulteration of raw ground beef with pork, donkey, and dog meat based on fatty acid profiles using GC-MS/MS. The study design incorporated pork, donkey, or dog meat with beef meat; negative and positive controls were used for the different meat species. Results demonstrated several significant differences (p < 0.05) in fatty acid contents between mixed/adulterated meat and pure beef. In addition, higher total saturated fatty acid levels in ground beef (57.91%) compared to dog fat (46.44%), donkey (38.71%), and pork fat (lard) (40.23%). High total unsaturated fatty acids content was observed in donkey (61.92%), pork (59.77%), and dog (53.56%) fats compared to beef fat (42.09%). On the other hand, total unsaturated and monounsaturated fatty acids in beef meat were lower than in pork, donkey, and dog meat. Moreover, the highest trans-fatty acid content was found in pork compared to the other meat types. All incorporated samples correlated positively with pure ground beef concerning the fatty acid profiles. Therefore, alteration of the mixed beef fatty acid profiles was a potential indicator for adulteration since a marked decrease in total saturated fatty acid content and an increase in unsaturated fatty acids was observed in the substituted samples. We concluded that GC-MS/MS-based fatty acid profiling is a promising technique that can be used to detect meat adulteration.