Evaluation of Group Genetic Counseling Sessions via a Metaverse-based Application.

Background: Group genetic counseling has been implemented to meet growing demand. A metaverse platform, in which a society is built and activities are carried out in the virtual world, has not yet been implemented in group genetic counseling. We investigated whether a metaverse platform could be an alternative service-delivery model for group genetic counseling. Methods: Participants (N=131) were divided into three groups: patient (N=45), family (N= 43), and interested (N=43) groups. Participants entered the metaverse through a link sent to their mobile phones and attended a 20-min group genetic counseling session reviewing hereditary breast cancer, followed by a 10-min question-and-answer period. Results: The overall median score of post-educational knowledge (9.0, range 8.0-10.0) significantly increased compared to that of pre-educational knowledge (6.0, range 3.0-8.0) (P<0.001). There was no significant difference in the pre- and post-educational knowledge scores among the three groups (P>0.05). Most participants (95%) responded that their understanding of hereditary breast cancer had increased after the group genetic counseling session and that their satisfaction was high. The main advantage noted with metaverse was no limit of space and location while attending the session (97%), and the main disadvantage was a possibility of missing content due to an unstable internet connection (67%). Conclusions: The metaverse platform would be acceptable as an alternative group genetic counseling service. More studies are needed to investigate how, for whom, and in what circumstances metaverse can be effectively utilized.

Severe bradycardia induced by postoperative nausea and vomiting: A case report.

INTRODUCTION: Postoperative nausea and vomiting is a common complication for patients after anesthesia and surgery, which may result in increased parasympathetic activity, such as diaphoresis, pallor, or bradycardia. However, few cases of fatal bradycardia induced by postoperative nausea and vomiting have been reported before. Clinicians generally attribute bradycardia to certain anesthetics, instead of postoperative nausea or vomiting. PATIENT CONCERNS: A fifty-year-old female with a history of well-controlled hypertension underwent elective radical mastectomy. When recovering from anesthesia in the post-anesthesia care unit, the patient experienced severe bradycardia accompanied by hypotension and unconsciousness, shortly after nausea and vomiting. INTERVENTIONS: The patient received cardiopulmonary resuscitation immediately. OUTCOMES: Five minutes later, She recovered sinus rhythm and her vital sings tended to be stable. Three hours later, blood tests showed the N-terminal pro-B-type natriuretic peptide 127 pg/mL and cardiac troponin I 0.44 ng/mL, which peaked to 2.65 ng/mL 10 hours after the emergency. Electrocardiography revealed sinus rhythm, ST-segment depression in the inferior and anterior lateral leads, QTc prolongation, and left ventricular high voltage. Her serum cTnI continued to decline to 0.27 ng/mL on the 3rd day after surgery. She was discharged from the hospital on the fifth day and had no sequelae. CONCLUSION: Although postoperative nausea and vomiting occurs frequently, it should be kept in mind as a potential cause to blame for severe bradycardia or even life-threatening situations.

Investigation of the causal relationship between breast cancer and autoimmune diseases: A bidirectional mendelian randomization study.

A clear bidirectional relationship exists between malignant cancers including breast cancer and different autoimmune diseases. However, none of the studies have assessed whether this association is causal and none have used Mendelian randomization for determining this relationship. This study therefore investigated the causal relationship between autoimmune diseases and breast cancer using the Mendelian randomization approach. Summary statistical data were obtained from genome-wide association studies to investigate the causal relationship between different autoimmune diseases including Graves' disease, Sjögren's syndrome, Crohn disease, systemic sclerosis, and psoriasis and breast cancer risk. The results revealed no strong evidence to support the causal relationship between Graves disease (odds ratio [OR] = 0.9958; 95% confidence interval [CI]: 0.9982-1.0035), Sjögren's syndrome (OR = 1.0018; 95% CI: 0.9950-1.0087), Crohn disease (OR = 2.1195, 95% CI: 0.1872-23.9978), systemic sclerosis (OR = 1.0024; 95% CI: 0.997-1.0079), and psoriasis (OR = 1.0016; 95% CI: 0.9913-1.0121) to breast cancer risk. A similar result was obtained in the reverse Mendelian randomization analysis. Our study provides evidence that autoimmune diseases might not have a causal relationship with breast cancer risk in the European population and concludes that shared genetic effects or environmental confounders.

CDK9 Inhibitor Induces Apoptosis, Autophagy, and Suppression of Tumor Growth in Adult T-Cell Leukemia/Lymphoma.

Adult T-cell leukemia/lymphoma (ATL) is a hematopoietic malignancy with a poor prognosis that develops in approximately 5% of human T-cell leukemia virus type 1 (HTLV-1) carriers. Cyclin-dependent kinase 9 (CDK9), together with Cyclin T, forms a transcription elongation factor, positive transcription elongation factor b (P-TEFb). P-TEFb promotes transcriptional elongation by phosphorylating the second serine (Ser2) of the seven amino acid repeat sequence in the C-terminal domain of RNA polymerase II (RNAP II). CDK9 inhibitors suppress cell proliferation by inducing apoptosis in chronic lymphocytic leukemia and breast cancer but there are no reports on autophagy of CDK9 inhibitors. Here, we investigated the effect of LY2857785, a novel CDK9 selective inhibitor, on cell death in ATL-related cell lines in vitro, freshly isolated cells from ATL patients ex vivo, and on ATL tumor xenografts in NOD/SCID mice in vivo. LY2857785 significantly reduced cell viability and induced apoptosis, as shown by annexin V-positive cells, cleaved poly(ADP-ribose) polymerase (PARP), and cleaved caspase-3, and suppressed the levels of anti-apoptotic protein myeloid cell leukemia-1 (MCL-1). LY2857785 decreased RNAP II Ser2 phosphorylation and downstream c-Myc protein levels. Interestingly, LY2857785 also increased microtubule-associated proteins 1A/1B light chain 3B (LC3)-II binding to autophagosome membranes. Furthermore, LY2857785 decreased the viability of freshly isolated ATL cells and induced apoptosis. Finally, LY2857785 significantly decreased the growth of ATL tumor xenografts. These results suggest that LY2857785 induces cell death of ATL cells by MCL-1-dependent apoptosis and autophagy and has anti-tumor activity.

[Access to breast cancer screening among females in China: a focus report on screening rate and composition].

Objective: To systematically integrate and analyze the breast cancer screening rates among females in China and to estimate the composition of different screening service types. Methods: Based on core literature, relevant official websites, projects/survey reports, and information on breast cancer screening rates of Chinese females were extracted and analyzed, and the screening rates for 40-69 years old and 35-64 years old were standardized and compared using 2010 China's population structure. The literature review method was used to retrieve the journal literature related to the composition of breast cancer screening services types (organized screening, physical examination and opportunistic screening). The number of detected literature and the median sample size of individual screening people of the three screening service types were analyzed, and used them as weights to estimate the composition of screening service types. Results: A total of 6 related national surveys on breast cancer screening rate were identified, including 2 from the National Health Service Surveys (broader definition of "breast screening" in 2013, 2018) and 4 from the chronic disease monitoring system of China CDC (the exact definition of "breast cancer screening" in 2010, 2013 and twice in 2015). The age-standardized analysis indicated that 1-year, 2-year and 3-year breast cancer screening rates in 2015 among females in China aged 40-69 years old were 16.9%, 20.2% and 21.4%, respectively. The ever-breast cancer-screened rates were 21.1% in 2013 and 23.5% in 2015 among females aged 40-69, and the corresponding rates were 23.3% and 25.7%, respectively, among females aged 35-64. When taking the literature published in 2015 for further literature review, 130 articles were included, in which the proportions of numbers of reports on organized screening, physical examination, and opportunistic screening were 71.0%, 23.7%, and 5.3%, respectively. Along with the extracted data on median sample sizes (shown in the main text) by breast cancer screening types, it was estimated that the individual service volume of corresponding screening types accounted for 88.0%, 11.2% and 0.8% among all the screened females in China in 2015. Conclusions: The breast cancer screening rates among females of appropriate age in China in 2015 are higher than those in 2013. The literature review analysis preliminarily suggested that the current breast cancer screening service type in China is mainly organized screening service.

Effect of Dexmedetomidine and Two Different Doses of Esketamine Combined Infusion on the Quality of Recovery in Patients Undergoing Modified Radical Mastectomy for Breast Cancer - A Randomised Controlled Study.

Purpose: This study evaluated the effect of a combined infusion of dexmedetomidine and esketamine on the quality of recovery in patients undergoing modified radical mastectomy. Methods: A total of 135 patients were randomly divided into three groups: dexmedetomidine group (group D) received dexmedetomidine (0.5 µg/kg loading, 0.4 µg/kg/h infusion), dexmedetomidine plus low-dose esketamine group (group DE1) received dexmedetomidine (0.5 µg/kg loading, 0.4 µg/kg/h infusion) and esketamine (0.5 mg/kg loading, 2 µg/kg/min infusion), dexmedetomidine plus high-dose esketamine group (group DE2) received dexmedetomidine (0.5 µg/kg loading, 0.4 µg/kg/h infusion) and esketamine (0.5 mg/kg loading, 4 µg/kg/min infusion). The primary outcome was the overall quality of recovery-15 (QoR-15) scores at 1 day after surgery. The secondary endpoints were total QoR-15 scores at 3 days after surgery, propofol and remifentanil requirement, awaking and extubation time, postoperative visual analogue scale (VAS) pain scores, rescue analgesic, nausea and vomiting, bradycardia, excessive sedation, nightmares, and agitation. Results: The overall QoR-15 scores were much higher in groups DE1 and DE2 than in groups D 1 and D 3 days after surgery (P < 0.05). VAS pain scores at 6, 12, 24 h postoperatively, propofol and remifentanil requirements were significantly lower in groups DE1 and DE2 than in group D (P < 0.05). Compared with group D, awaking time, extubation time, and post-anesthesia care unit (PACU) stay were significantly prolonged in groups DE1 and DE2 (P < 0.05) and were much longer in group DE2 than in group DE1 (P < 0.05). The proportion of postoperative rescue analgesics and bradycardia was higher and the incidence of excessive sedation was lower in group D than in groups DE1 and DE2 (P < 0.05). Conclusion: Dexmedetomidine plus esketamine partly improved postoperative recovery quality and decreased the incidence of bradycardia but prolonged awaking time, extubation time, and PACU stay, especially dexmedetomidine plus 4 µg/kg/min esketamine.

Effects of an intravenous lidocaine bolus before tracheal extubation on recovery after breast surgery - Lidocaine at the End (LATE) study: a randomized controlled clinical trial.

AIM: To investigate whether IV lidocaine improves emergence, early recovery, and late recovery after general anesthesia in women who undergo breast surgery. METHODS: Sixty-seven women with American Society of Anesthesiologists physical status I-II, scheduled for breast surgery were randomized to receive an IV lidocaine 1.5 mg/kg bolus (n=34) or saline placebo (n=33) before tracheal extubation. Anesthesia was induced with thiopental, vecuronium, and fentanyl, and maintained with sevoflurane~1 MAC and 50% nitrous-oxide in oxygen. No postoperative nausea and vomiting (PONV) prophylaxis was given. Time to extubation, bucking before extubation, and quality of emergence, as well as early and late recovery (coughing post-extubation, sore throat, PONV, and pain scores) within 24 hours postoperatively were evaluated. Diclofenac and meperidine were used for the treatment of pain and metoclopramide for PONV. RESULTS: The groups did not significantly differ in demographics, intraoperative data, or PONV risk scores. Extubation was~8 minutes in both groups. Patients who received IV lidocaine had significantly smoother recovery, both statistically and clinically; they had better extubation quality scores (1.5 [1-3] vs 3 [1-5], P<0.001), less bucking before extubation (38% vs 91%, P<0.001), less coughing after extubation (at 1 min 18% vs 42%, P=0.026; and at 24 hours 9% vs 27%, P=0.049), and less sore throat (6% vs 48%, P<0.001). Late PONV decreased (3% vs 24%, P=0.013). There were no differences in pain scores and treatment. CONCLUSION: In women who underwent breast surgery, IV lidocaine bolus administered just before extubation attenuated bucking, cough and sore throat, and PONV for 24 hours after general anesthesia, without prolonging the emergence.

Neoadjuvant palbociclib plus either giredestrant or anastrozole in oestrogen receptor-positive, HER2-negative, early breast cancer (coopERA Breast Cancer): an open-label, randomised, controlled, phase 2 study.

BACKGROUND: The development of more potent selective oestrogen receptor antagonists and degraders (SERDs) that can be orally administered could help to address the limitations of current endocrine therapies. We report the primary and final analyses of the coopERA Breast Cancer study, designed to test whether giredestrant, a highly potent, non-steroidal, oral SERD, would show a stronger anti-proliferative effect than anastrozole after 2 weeks for oestrogen receptor-positive, HER2-negative, untreated early breast cancer. METHODS: In this open-label, randomised, controlled, phase 2 study, postmenopausal women were eligible if they were aged 18 years or older; had clinical T stage (cT)1c to cT4a-c (≥1·5 cm within cT1c) oestrogen receptor-positive, HER2-negative, untreated early breast cancer; an Eastern Cooperative Oncology Group performance status of 0-1; and baseline Ki67 score of at least 5%. The study was conducted at 59 hospital or clinic sites in 11 countries globally. Participants were randomly assigned (1:1) to giredestrant 30 mg oral daily or anastrozole 1 mg oral daily on days 1-14 (window-of-opportunity phase) via an interactive web-based system with permuted-block randomisation with block size of four. Randomisation was stratified by cT stage, baseline Ki67 score, and progesterone receptor status. A 16-week neoadjuvant phase comprised the same regimen plus palbociclib 125 mg oral daily on days 1-21 of a 28-day cycle, for four cycles. The primary endpoint was geometric mean relative Ki67 score change from baseline to week 2 in patients with complete central Ki67 scores at baseline and week 2 (window-of-opportunity phase). Safety was assessed in all patients who received at least one dose of study drug. The study is registered with ClinicalTrials.gov (NCT04436744) and is complete. FINDINGS: Between Sept 4, 2020, and June 22, 2021, 221 patients were enrolled and randomly assigned to the giredestrant plus palbociclib group (n=112; median age 62·0 years [IQR 57·0-68·5]) or anastrozole plus palbociclib group (n=109; median age 62·0 [57·0-67·0] years). 15 (7%) of 221 patients were Asian, three (1%) were Black or African American, 194 (88%) were White, and nine (4%) were unknown races. At data cutoff for the primary analysis (July 19, 2021), the geometric mean relative reduction of Ki67 from baseline to week 2 was -75% (95% CI -80 to -70) with giredestrant and -67% (-73 to -59) with anastrozole (p=0·043), meeting the primary endpoint. At the final analysis (data cutoff Nov 24, 2021), the most common grade 3-4 adverse events were neutropenia (29 [26%] of 112 in the giredestrant plus palbociclib group vs 29 [27%] of 109 in the anastrozole plus palbociclib group) and decreased neutrophil count (17 [15%] vs 16 [15%]). Serious adverse events occurred in five (4%) patients in the giredestrant plus palbociclib group and in two (2%) patients in the anastrozole plus palbociclib group. There were no treatment-related deaths. One patient died due to an adverse event in the giredestrant plus palbociclib group (myocardial infarction). INTERPRETATION: Giredestrant offers encouraging anti-proliferative and anti-tumour activity and was well tolerated, both as a single agent and in combination with palbociclib. Results justify further investigation in ongoing trials. FUNDING: F Hoffmann-La Roche.

The apoptotic effect of the Lycopodium clavatum extracts on MCF-7 human breast cancer cells.

Breast cancer is a significant health problem worldwide, and the search for effective treatments is critical. Side effects of cancer treatments such as surgery, radiotherapy, and chemotherapy reduce the patient's standard of living. Recently, natural compounds from plants have gained attention as potential anticancer agents due to their safety, low toxicity, and potential efficacy. Lycopodium Clavatum (LC) is an herb abundant in tropical regions and Europe and is known for its various medicinal properties. In this study, we investigated the cytotoxic and apoptotic effects of LC Water Extract (LC-WE) and LC Ethanol Extract (LC-EE) plant extracts on MCF-7 human breast cancer cells. Our results showed that LC treatment led to a dose and time-dependent cytotoxic effect on MCF-7 cells, indicating its potential as an anticancer agent against human breast cancer. Additionally, we observed that LC treatment activated apoptosis-related proteins, including BAX, Caspase-3, and Caspase-9. These results suggest that LC may induce apoptosis as a mechanism underlying its cytotoxic effect on MCF-7 human breast cancer cells. Previous studies have shown the anti-cancer potential of LC against different types of cancer. However, the anti-cancer effect of LC on human breast cancer cells has not been investigated to date. Therefore, our study provides novel insights into the potential of LC as an anti-cancer agent against breast cancer. Overall, our results highlight the potential of LC as a promising natural compound for breast cancer treatment.

FBXW7 in breast cancer: mechanism of action and therapeutic potential.

Breast cancer is one of the frequent tumors that seriously endanger the physical and mental well-being in women. F-box and WD repeat domain-containing 7 (FBXW7) is a neoplastic repressor. Serving as a substrate recognition element for ubiquitin ligase, FBXW7 participates in the ubiquitin-proteasome system and is typically in charge of the ubiquitination and destruction of crucial oncogenic proteins, further performing a paramount role in cell differentiation, apoptosis and metabolic processes. Low levels of FBXW7 cause abnormal stability of pertinent substrates, mutations and/or deletions in the FBXW7 gene have been reported to correlate with breast cancer malignant progression and chemoresistance. Given the lack of an effective solution to breast cancer's clinical drug resistance dilemma, elucidating FBXW7's mechanism of action could provide a theoretical basis for targeted drug exploration. Therefore, in this review, we focused on FBXW7's role in a range of breast cancer malignant behaviors and summarized the pertinent cellular targets, signaling pathways, as well as the mechanisms regulating FBXW7 expression. We also proposed novel perspectives for the exploitation of alternative therapies and specific tumor markers for breast cancer by therapeutic strategies aiming at FBXW7.

Liquid biopsy in breast carcinoma: Are we there yet?

Breast carcinoma is the most common malignancy among women worldwide. Liquid biopsy is a method of obtaining tumour-derived material from blood and body fluid. This includes the assessment of circulating tumour cells (CTCs), circulating tumour deoxyribose nucleic acid (ctDNA), tumour educated platelets (TEPs) and exosomes. Detection of CTCs and ctDNA in liquid biopsy has been shown to have prognostic and predictive value in both early and metastatic breast carcinoma. The study of CTCs could also advance our understanding of aspects of tumour biology, including epithelial mesenchymal transition. ctDNA can be used to assess and monitor the molecular profile of breast carcinoma. It may help detect new genetic alterations in tumours and predict disease progression before the onset of clinical features or radiological evidence. TEPs and exosomes are also emerging as diagnostic, prognostic and predictive markers of breast carcinoma. Thus, liquid biopsy provides a non-invasive, repeatable method for the dynamic assessment of the tumour. Many methods have been used for the detection of CTCs and ctDNA. Most of these are still in the research stage and only the CellSearch method for the detection of CTCs and Therascreen PIK3CA RGQ polymerase chain reaction (PCR) assay for the detection of PIK3CA (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha) mutations in liquid biopsy have approval of the United States, Food and Drug Administration. However, their high costs, lack of standardized procedures, and a long and complicated detection process have limited their use. Despite its limitations, liquid biopsy is a useful tool in clinical decision making and has the potential to play an increasingly important role in the management of breast carcinoma in the future as we move toward more personalized cancer care.

Profiling extracellular vesicle surface proteins with 10 µL peripheral plasma within 4 h.

Extracellular vesicle (EV) surface proteins, expressed by primary tumours, are important biomarkers for early cancer diagnosis. However, the detection of these EV proteins is complicated by their low abundance and interference from non-EV components in clinical samples. Herein, we present a MEmbrane-Specific Separation and two-step Cascade AmpLificatioN (MESS2CAN) strategy for direct detection of EV surface proteins within 4 h. MESS2CAN utilises novel lipid probes (long chains linked by PEG2K with biotin at one end, and DSPE at the other end) and streptavidin-coated magnetic beads, permitting a 49.6% EV recovery rate within 1 h. A dual amplification strategy with a primer exchange reaction (PER) cascaded by the Cas12a system then allows sensitive detection of the target protein at 10 EV particles per microliter. Using 4 cell lines and 90 clinical test samples, we demonstrate MESS2CAN for analysing HER2, EpCAM and EGFR expression on EVs derived from cells and patient plasma. MESS2CAN reports the desired specificity and sensitivity of EGFR (AUC = 0.98) and of HER2 (AUC = 1) for discriminating between HER2-positive breast cancer, triple-negative breast cancer and healthy donors. MESS2CAN is a pioneering method for highly sensitive in vitro EV diagnostics, applicable to clinical samples with trace amounts of EVs.

Identification of an optimized glycolytic-related risk signature for predicting the prognosis in breast cancer using integrated bioinformatic analysis.

Aberrant metabolic disorders and significant glycolytic alterations in tumor tissues and cells are hallmarks of breast cancer (BC) progression. This study aims to elucidate the key biomarkers and pathways mediating abnormal glycolysis in breast cancer using bioinformatics analysis. Differential genes expression analysis, gene ontology analysis, Kyoto encyclopedia of genes and genomes analysis, gene set enrichment analyses, and correlation analysis were performed to explore the expression and prognostic implications of glycolysis-related genes. We effectively integrated 4 genes to construct a prognostic model of shorter survival in the high-risk versus low-risk group. The prognostic model showed promising predictive value and may be an integral part of the prognosis of BC. The survival analysis and receiver operating characteristic curves suggested that the signature showed a good predictive performance in both the The Cancer Genome Atlas training set and 2 gene expression omnibus validation sets. Multivariable analysis demonstrated that the 4-gene signature had an independent prognostic value. Furthermore, all calibration curves exhibited robust validity in prognostic prediction. We established an optimized 4-gene signature to clarify the connection between glycolysis and BC, and offered an attractive platform for risk stratification and prognosis predication of BC patients.

Ultrasonographic assessment of rectus abdominis muscle adaptation after deep inferior epigastric artery perforator (DIEP) flap surgery: Single institution retrospective study.

The impact of deep inferior epigastric artery perforator (DIEP) flap on abdominal wall integrity has been the topic of an ongoing debate with previous studies having reported conflicting results using various imaging modalities. Ultrasonography is a noninvasive, cost-effective, and readily available method for evaluating the changes to the rectus muscle after DIEP flap surgery. In the present study, we aimed to compare rectus abdominis muscle thickness between the operated and non-operated sides using ultrasound imaging. The muscle thickness was measured at the cross point of the midclavicular line and the level of the umbilicus and anterior superior iliac spine using real-time B-mode ultrasonography. The muscle anteroposterior diameters of the pedicle-dissected side and the control side were compared using paired t test. In total 31 patients with a mean follow-up of 70.18 weeks were included. The mean diameters at the level of the umbilicus of the operated and non-operated sides were 8.16 ±â€…1.83 and 8.14 ±â€…1.43 mm, respectively (P = .94). The mean thicknesses at the anterior superior iliac spine level were 7.74 ±â€…1.85 on the flap harvested side and 8.04 ±â€…1.84 mm on the control side (P = .35). There was no statistically significant difference between the 2 groups. Ultrasonography can be a reliable, inexpensive, and easily usable modality for evaluating donor site complication following DIEP flap. DIEP flap seems to have minimal impact on the abdominal donor site, and it may be safe and versatile to reconstruct the breast after mastectomy.

Novel insights into DNA methylation-based epigenetic regulation of breast tumor angiogenesis.

Breast tumors are highly vascularized and dependent on angiogenesis for growth, progression and metastasis. Like other solid tumors, vasculature in breast tumors also display leaky and tortuous phenotype and hence inhibit immune cell infiltration, show reduced efficacy to anticancer drugs and radiotherapy. Epigenetic reprogramming including significant alterations in DNA methylation in tumor and stromal cells generate an imbalance in expression of pro- and anti-angiogenic factors and subsequently lead to disordered angiogenesis. Hence, understanding DNA methylation-based regulation of angiogenesis in breast tumors may open new avenues for designing therapeutic targets. Our present review manuscript summarized contemporary knowledge of influence of DNA methylation in regulating angiogenesis. Further, we identified novel set of pro-angiogenic genes enriched in endothelial cells which are coregulated with DNMT isoforms in breast tumors and harboring CpG islands. Our analysis revealed promoters of pro-angiogenic genes were hypomethylated and anti-angiogenic genes were hypermethylated in tumors and further reflected on their expression patterns. Interestingly, promoter DNA methylation intensities of novel set of pro-angiogenic genes significantly correlated to patient survival outcome.