Bladder cancer is a common malignancy, and its diagnosis is based on invasive procedures such as cystoscopy. Genetic aberrations play an important role in the development of many diseases, including bladder cancer. As a result, identifying the genetic basis of a disease can provide useful information for early diagnosis and therapy. Cell-free DNA (cfDNA) offers a non-invasive approach to extract genetic information, which could be valuable for establishing the genetic cause of bladder cancer. In this study, we analyzed copy number variations (CNV) in urine cfDNA from 20 patients, with cystoscopy confirmed bladder cancer, sequenced by next-generation sequencing (NGS) and their CNV examined using the whole genome sequence. Statistical analysis of the carcinoma samples included Wilcoxon and Chi-square tests (p ≤ 0.005). Different patterns in CNV were identified in Chromosomes 1, 2, 3, 5, 6, 8, 9, 10, 11, 12, 17, 19, and 20 with the chromosome cytobands showing significant difference in variation patterns in patient parameters, such as smoking habit, number of tumors, grade of the tumors, and invasiveness. The genes that exhibited distinct CNV in each chromosomal cytoband have been associated with the development and progression of various cancers including bladder cancer indicating the clinical significance of CNVs as a useful tool for disease diagnosis. Therefore, this study demonstrates that by using NGS, CNV in urine cfDNA can provide valuable information on the state of blader cancer which can be further utilized to investigate therapies or early diagnosis.

Pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) predicts favorable outcomes in HER2-positive and triple-negative breast cancer (TNBC). While breast and axillary pCR often coexist, some patients with residual breast disease still achieve axillary pCR. This study evaluated axillary pCR rates and factors in this subgroup, and the potential to omit sentinel lymph node biopsy (SLNB) in selected patients.

We retrospectively reviewed 1043 patients with HER2-positive or TNBC who did not achieve breast pCR after NACT and underwent surgery between 2008 and 2021 at a single institution. Clinicopathological features were compared between axillary pCR and non-pCR groups. Logistic regression analyses identified predictors of axillary pCR.

Axillary pCR was observed in 648 (62.1 %) of 1043 patients who did not achieve breast pCR after NACT. The axillary pCR rate was 91.3 % in clinically node-negative (cN0) patients and 55.4 % in cN-positive patients. Axillary pCR rates decreased as the size of the residual breast tumor increased in both cN0 and cN-positive patients. Axillary pCR rates exceeded 94 % in patients with cN0 and residual tumor size of 1 cm or less. Multivariable analysis identified lower clinical N stage, smaller residual breast tumor size, and absence of lymphovascular invasion as independent predictors of axillary pCR.

A substantial proportion of HER2-positive or TNBC patients without breast pCR after NACT achieved axillary pCR, especially those with cN0 status and small residual tumors. These results support the potential omission of SLNB in selected patients and highlight the need for prospective validation and predictive model development.

To investigate the performance of two segmentation algorithms for nodule volumetric classification at participant/scan level in the NELCIN-B3 cohort (Netherlands and China Big-3), a lung cancer screening program (LCS) using low-dose CT (LDCT).

Baseline scans with qualified LDCT images from consecutive NELCIN-B3 participants were included from June 2017 to July 2018. Performance of two software algorithms were independently evaluated by two radiologists: software A (Syngo.via VB30A) by reader 1 and software B (AVIEW v1.1.39.14) by reader 2. According to the NELSON2.0 protocol, nodules with a solid component ≥ 100 mm³ were classified as indeterminate-positive, while all other nodules were classified as negative. Disagreements in classification were resolved by consensus with three senior radiologists. These results served as a reference standard for identifying positive misclassifications (PM) and negative misclassifications (NM).

In total, 300 participants were evaluated comprising 159 women (53.0 %) and 193 (64.3 %) never smokers, with a mean ± standard deviation age of 61.2 ± 7.1 years. There were disagreements in 17 cases: in 11 (11/300, 3.7 %), this was due to differences in nodule selection and nodule type classification between readers; and in 6 (6/300, 2.0 %), this was due to variations in nodule volume metrics between algorithms. Inter-software agreement was almost perfect (κ = 0.88 [95 %CI: 0.83-0.93]). In the consensus read, reader 1/software A generated 12 misclassifications (11 PM, 1 NM), giving a negative predictive value of 99.6 % (95 % CI: 98.9 %-100.0 %). Reader 2/software B generated 5 misclassifications (2 PM, 3 NM), giving a negative predictive value of 98.9 % (95 % CI: 97.7 %-100.0 %).

Two software algorithms (Syngo.via VB30A and AVIEW v1.1.39.14) showed comparable performance for lung nodule volumetric classification at participant/scan level. Further research is needed to confirm the results in other LDCT LCS programs.

Multiple myeloma (MM) is a hematologic cancer affecting plasma cells, characterized by the abnormal proliferation of malignant plasma cells in the bone marrow. Research in recent years has shown that the inhibition of ferroptosis is involved in the pathogenesis of MM. CLEC2 is a C-type lectin receptor family member mainly related to the activation of platelets, which is reported to be lowly expressed in multiple tumors. However, the role of CLEC2 in MM remain unknown. The present study clarified CLEC2's function in MM by exploring its impacts on ferroptosis. Comparing to normal plasma cells (NPCs), CLEC2 was found markedly downregulated in MM cell lines. In CLEC2-overexpressed U266 cells, largely declined cell viability and migrated cell counts, markedly enhanced ROS and MDA levels, and declined SOD activities were observed, accompanied by increased Fe²⁺ levels, upregulated ACSL4, and downregulated GPX4, HIF-1α, and SLC7A11. Moreover, in CLEC2-knockdown OPM-2 cells, greatly increased cell viability and migrated cell counts, sharply repressed ROS and MDA levels, and enhanced SOD activities were observed, along with reduced Fe²⁺ levels, downregulated ACSL4, and upregulated GPX4, HIF-1α, and SLC7A11. In addition, influences of CLEC2 overexpression on proliferation, Fe²⁺ levels, and expressions of ACSL4, GPX4, HIF-1α, and SLC7A11 in U266 cells were remarkably abolished by Fer-1 (an inhibitor of ferroptosis) or HIF-1α overexpression. Collectively, downregulation of CLEC2 in MM facilitated the proliferation and migration of MM cells via regulating HIF-1α-mediated ferroptosis.

Breast cancer is considered to be the most common cancer that affects women worldwide, where it accounts for approximately 38.8% of all cancer cases among females. Luminal subtypes are the most prevalent in Egypt. Small noncoding RNAs also called microRNAs (miRNAs) influence gene expression posttranscriptionally. Since they regulate the epithelial-mesenchymal transition process, which is vital for tumor invasion and metastasis, microRNAs play a critical role in the progression of cancer.

This study has investigated the expression profiles of four microRNAs (miR-101-3p, miR-106a-5p, miR-106b-5p, and miR-130b-5p) and their impacts on genes associated with epithelial-mesenchymal transition (EMT) in luminal breast cancer. Tissue samples from 43 luminal breast cancer patients and 18 controls have been studied via real-time PCR (RT-qPCR). The association between the expression levels was evaluated using the Pearson correlation test. The correlation between the measured variables and numerous clinicopathological characteristics was assessed using the linear regression test.

The results demonstrated that miR-101-3p, miR-106a-5p, and miR-106b-5p were significantly dysregulated, highlighting their possible role as oncogenes or tumor suppressors in the development of breast cancer. EMT markers, especially Twist, SNAI1, and E-cadherin, show significant alterations, indicating the activation of EMT pathways in luminal breast cancer. Correlation analysis showed interactions between miRNAs and EMT-related genes, showing a negative correlation between miR-101-3p and SNAI1, as well as a positive correlation between Twist and miR-106a-5p. Moreover, logistic regression analysis associated expression levels of those miRNAs with clinicopathological characteristics, such as body weight, age, and tumor laterality.

These findings highlight the leading role of miR-101-3p and miR-106b-5p in the progression of luminal breast cancer via interacting with the EMT process and their potential as diagnostic, prognostic, and therapeutic targets.

Acute and chronic exposure to pesticides is associated with several negative effects on human health, such as an increased risk of cancer, including mature B-cell neoplasms such as chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). However, the biological mechanism linking pesticide exposure to the development of CLL and MM has not yet been elucidated. Thus, this study aimed to explore miRNA expression profiles in patients with CLL and MM who were occupationally exposed and not exposed to pesticides. For this purpose, 24 patients with MM and CLL were recruited from a cohort in Brazil and the miRNA expression profiles between the groups were analyzed using Nanostring technology. The study revealed the downregulation of miR-423-3p, miR-1193, miR-576-5p, miR-509-5p, miR-548b-3p, miR-1469, miR-329-3p, and miR-548j-3p, and the upregulation of miR-301b-5p and miR-548ah-5p in patients with CLL and MM were associated with occupational exposure to pesticides. The integrated network analysis of the differentially expressed miRNAs and their target genes in the exposed group demonstrated that miRNAs can participate in the regulation of signaling pathways, such as PI3K/Akt/mTOR and MAPK. Additionally, these miRNAs were found to be associated with an increased risk of developing neurological diseases and various types of cancer. In the present study, we demonstrate, for the first time, altered expression of plasma-derived miRNAs in patients with CLL and MM exposed to pesticides. The plasma miRNAs identified may serve as promising candidates for biomarkers of pesticides effects, potentially contributing to the emerging field of Precision Environmental Health.

Preeclampsia is now acknowledged as a systemic disorder with long-term implications for maternal and offspring health, reframing it as a sentinel event that reveals underlying vulnerabilities and signals future risk of cardiovascular, hypertensive, and kidney diseases in both mother and child. The "children of preeclampsia" should be on our radars as a population warranting early attention, shaping new standards of disease prevention.

Targeted therapies (TT) for non-small cell lung cancer (NSCLC) with actionable genomic alterations (AGA), particularly EGFR-mutant and ALK-rearranged tumors, have become the standard of care across nearly all stages of the disease. However, the arbitrarily defined dose and treatment duration of TT, as well as the financial cost of these drugs, reduce their availability worldwide. Pharmacokinetic and pharmacodynamic properties of TT suggest that doses of some TT are overestimated as there is limited evidence supporting a direct relationship between therapeutic intensity and outcomes. This can lead to overtreatment of patients, resulting in an increased risk of toxicity without enhanced efficacy. Some academic initiatives have been launched aiming to explore de-escalating strategies with TT, either reducing the dose or the duration of these drugs. These approaches can decrease the risk of adverse events positively impacting patients' quality of life, without compromising efficacy, while reducing economic impact. In this review, we summarize current data regarding de-escalating strategies with TT, ongoing trials and challenges of this approach.

Plasma ceramides (Cer) are associated with adverse cardiovascular outcomes in patients with coronary artery disease (CAD). We examined whether a newly developed plasma ceramide-based risk score (CER24 score) performs better than CERT1 risk score in predicting adverse cardiovascular outcomes in patients with known or suspected CAD.

We followed 167 ambulatory patients undergoing stress myocardial perfusion scintigraphy (MPS) for clinical reasons for a median of 6 years. For the CER24 risk score calculation, we measured plasma Cer(d16:1/24:1)/Cer(d16:1/24:0), Cer(d18:0/24:1)/Cer(d18:0/24:0), Cer(d18:1/24:1)/Cer(d18:1/24:0), Cer(d18:2/24:1)/Cer(d18:2/24:0), and Cer(d20:1/24:1)/Cer(d20:1/24:0), both before and after stress MPS, using a targeted liquid chromatography-tandem mass spectrometry assay. Pre-stress CER24 risk categories (high vs. low/moderate risk) at baseline were associated with a ∼3-fold higher risk of developing the primary composite outcome (defined as all-cause mortality or nonfatal myocardial infarction) even after adjustment for age, sex, smoking, diabetes, pre-existing CAD, left ventricular ejection fraction, and stress-induced inducible myocardial ischemia on MPS (adjusted-hazard ratio 3.06, 95 %CI 1.63-5.77; p = 0.001). Post-stress CER24 risk categories yielded similar results. CER24 high-risk category performed better than CERT1 high-risk category in predicting the primary composite outcome (AUCs = 0.647 vs. 0.580; p = 0.048).

The CER24 score is associated with a higher risk of the composite outcome and performs better than CERT1 score in predicting the risk of dying or developing nonfatal cardiovascular events.

A man in his 60s presented with severe abdominal pain, vomiting and obstipation for the last 2 days. His examination revealed a tender abdomen. The contrast-enhanced CT of the abdomen reported superior mesenteric artery thrombosis with ischaemic changes in the bowel. After initial resuscitation, an exploratory laparotomy was done, revealing a gangrenous small bowel of 323 cm, which was resected, and a double-barrel jejuno-ileostomy was performed. Postoperatively, total parenteral nutrition was started and gradually replaced with oral supplements and refeeding of bowel contents. One week after discharge, the patient presented with features of severe dehydration and short bowel syndrome. After resuscitation and stabilisation, restoration of bowel continuity was performed. The patient developed the refeeding syndrome postsurgery, which was managed with micronutrient supplementation. This case highlights the challenges of managing a patient with short bowel syndrome, including timely surgical intervention, postoperative monitoring and appropriate nutritional management for the best outcome.