Cancer is a leading cause of morbidity and mortality worldwide, yet much is still unknown about its mechanism of establishment and destruction. Recently, studies had shown that tumor cells cannot survive under the high temperature conditions. This treatment technique is called Hyperthermia. This report presents the case of radiative microwave heating of hyperthermia therapy on breast cancer in a porous medium. In this study, the steady state is solved analytically while unsteady state is solved using semi-implicit finite difference to get a more accurate prediction of blood temperature distributions within the breast tissues. A moderate temperature hyperthermia treatment is apply which results into cell death due to an increase in the level of cell sensitivity to radiation therapy and blood flow in tumor and oxygen. The results show that by applying metabolic heat generation rate of $3.97 X 10^{5}Wm^{-3}$, it takes upto 2 minutes for the tumor cells to get the require therapeutic temperature point.

Background: KDM5 enzymes are H3K4 specific histone demethylases involved in transcriptional regulation and DNA repair. These proteins are over-expressed in different kinds of cancer, including breast, prostate and bladder carcinoma, with positive effects on cancer proliferation and chemo-resistance. For these reasons, these enzymes are potential therapeutic cancer targets. Methods: In the present study, we analyzed the effects of three different inhibitors of KDM5 enzymes in MCF-7 breast cancer cells over-expressing JARID1B. In particular we tested H3K4 demethylation (western blot); target gene transcription (RNAseq and real time PCR); radio-sensitivity (citoxicity and clonogenic assays) and damage accumulation (kinetics of H2AX phosphorylation). Results: we show that two compounds with completely different chemical structure can selectively inhibit KDM5 enzymes and that both compounds are capable of increasing sensitivity of breast cancer cells to ionizing radiation and H2AX phosphorylation. Conclusions: These findings confirm the involvement of H3K4 specific demethylases in DNA damage signaling and repair and suggest new strategies for the therapeutic use of their inhibitors.

The HER2-targeted antibody-drug conjugates (ADCs) trastuzumab emtansine (T-DM1) and Trastuzumab deruxtecan (T-DXd) improved outcomes in breast cancer. Novel combinations and sequential approaches are under investigation to overcome resistance to T-DM1 and T-DXd. Furthermore, the landscape of HER2-targeted therapy is rapidly advancing with the development of ADCs designed to attack cancer cells with greater precision and reduced toxicity. Disitamab Vedotin (RC48) incorporates a HER2 antibody with unique binding epitope and a potent microtubule inhibitor as its cytotoxic moiety. ARX-788 comprises a non-cleavable linker and a novel maytansinoid derivative as the cytotoxic drug, engineered for increased stability and a higher drug-to-antibody ratio. SYD985, a duocarmycin-based ADC, is designed to be activated only in the acidic environment of the tumor, thus reducing off-target effects. BL-M0701 targets a different epitope on the HER2 protein, which might be beneficial in circumventing resistance that affects the binding of other ADCs and incorporate a camptothecin derivative as its payload. Zanidatamab zovodotin (ZW25) is an ADC that binds to two different HER2 epitopes simultaneously, enhancing the internalization and delivery of its cytotoxic payload. These and other ADCs in phase I trials hold the potential to improve outcomes for HER2-positive and HER2-Low breast cancer and possibly other solid tumors.

Abstract: Background: In 2021, two randomized controlled trials (RCTs), TheraP and VISION, demonstrated that 177Lu-PSMA-617 as monotherapy was more effective for enhancing the decline of PSA than the comparator third-line treatments. Methods: Our review summarizes new RCTs that add to the use of radioligand therapy (RLT) for patients with high-risk prostate cancer (PCa). Results: Five past and present RCTs include 1139 patients. A RCT, ENZA-p, studied first-line treatment of patients with metastatic castration-resistant PCa (mCRPC). A combination of enzalutamide (ENZA) and 177Lu-PSMA-617 gave longer progression-free survival than ENZA as monotherapy. Other RCTs of patients with mCRPC, including the PSMAfore, and SPLASH trials, showed 177Lu-PSMA-617 as second-line treatment gave better progression-free survival than androgen receptor pathway inhibitors (combined p value 6 x 10-8). Conclusion: Patients with PCa may gain if they are given PSMA-RLT early in the treatment of PCa and as part of combination therapies.

Familial Mediterranean fever (FMF) is a systemic autoinflammatory disorder caused by inherited mutations in the MEFV (Mediterranean FeVer) gene located on chromosome 16 (16p13.3) and coding pyrin protein. Despite the existing data on MEFV mutations, the exact mechanism of their effect on the development of pathological processes leading to autoinflammation observed in FMF, remains unclear. Induced pluripotent stem cells (iPSCs) are considered an important tool for studying the molecular genetic mechanisms of various diseases due to their ability to differentiate into any cell type, including macrophages, which contribute to the development of FMF. In this study, we developed iPSCs of an Armenian patient with FMF having M694V, p.(Met694Val) (c.2080A>G, rs61752717) pathogenic mutation in exon 10 of the MEFV gene. As a result of direct differentiation, macrophages expressing CD14 and CD45 surface markers were obtained. In addition, we found that the morphology of patient macrophages derived from iPSCs with MEFV mutation was significantly different from that of differentiated from iPSCs of a healthy donor carrying wild-type MEFV gene.

Cathinone is a natural stimulant found in Catha edulis and commonly used in new psychoactive substances. The objective of this study was to examine the disposition kinetics and metabolic profile of cathinone and its metabolite cathine through a single oral dose of cathinone administration in rats. Cathine and cathinone concentrations were identified and quantified using ion trap liquid chromatography (LC-IT/MS), while the metabolic profile was determined using the quadrupole time of flight UPLC-QTOF/MS method in the serum, brain, lung, liver, kidney, and heart over a period of 0, 0.5, 2.5, 6, 12, 24, 48, and 72 hours. The findings revealed a dynamic interplay between the pharmacokinetics of cathinone and its impact on organ-specific biomarkers. The distribution of cathinone and cathine was determined in serum, brain, heart, lung, kidney, and liver. The highest concentration of cathinone was found in the kidney at 1438.6 ug/L. It gradually decreased to 1.97 within 48 hours and disappeared after 72 hours. Within half an hour, cathinone levels in the lungs, liver, and heart were found to be 859, 798.9, and 385.8 ug/L, respectively. However, within 2.5 hours, these levels decreased to 608.1, 429.3, and 309.1 ug/L and kept decreasing until they became undetectable after 24 hours. The concentration of cathinone in the rat brain reduces quickly, dropping to undetectable levels within six hours, with levels decreasing from 712.7 ug/L after just 30 minutes. In the brain and serum, cathine reached its highest levels at 2.5 hours, while in other organs, it peaked at 0.5 hours. This indicates that the conversion of cathinone to cathine is slower in the brain and serum. The study found that cathinone's pharmacokinetics have a significant impact on organ-specific biomarkers. After administering the cathinone, there was a sharp change in biomarker levels, particularly in the liver and brain, during the initial hours. It is essential to investigate the correlation between the changes in biomarkers found in the brain and the levels of cathinone and cathine. The results have significant implications for drug development, pharmacovigilance, and clinical practices involving cathinone. In conclusion, this comprehensive analysis of cathinone's impact on organ-specific biomarkers provides a basis for informed decision-making in medical practices and further research into the cathinone's pharmacological properties.

Background: We aimed to evaluate the impact of two different phytotherapeutic agents on the decision making regarding prostate biopsy in patients with higher-than-normal prostate-specific antigen (PSA) levels. Methods: From June 2022 to May 2023, all patients attending two urological institutions due to higher-than-normal PSA levels were randomized to receive either oral capsules of Curcuma Longa, Boswellia, Pinus pinaster and Urtica dioica (Group A) or Serenoa Repens 320 mg (Group B), for 3 months. At the follow-up visit after 3 months all patients underwent PSA test and multiparametric magnetic resonance imaging (mpMRI). Results: In the per-protocol analysis, data from 66 patients in Group A and 76 in Group B were analyzed. Fifty patients in Group A (75.7%) showed a significant reduction of total PSA compared to 49 in Group B (64.4%) (p<0.001). Twenty-eight patients had PI-RADS III or higher at mpMRI: 12 in Group A and 14 in Group B. Twenty-three patients (34.8%) in Group A underwent prostate biopsy based on mpMRI findings and PSA values and 59 (77.6%) in Group B (p<0.001). Three patients in Group A showed a significant reduction of total PSA value while having positive findings at mpMRI (6%) compared with 9 in Group B (19.5%) (p<0.001). On the contrary, 7 patients in Group A did not show a significant reduction of total PSA value and had negative findings at mpMRI (43%) compared to 22 in Group B (81.4%) (p&lt;0.001). Conclusions: In conclusion, a three-month course of a combination of Curcuma Longa, Boswellia, Pinus pinaster, and Urtica dioica seems an interesting tool to avoid unnecessary prostate biopsies in men with higher-than-normal PSA levels.

Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disorder characterized by marked clinical and genetic heterogeneity. Ethnic groups underrepresented in studies may have distinctive characteristics. We sought to evaluate the clinical and genetic landscape of Russian HCM patients. A total of 193 patients (52% male; 95% Eastern Slavic origin; median age 56 years) were clinically evaluated, including genetic testing, and prospectively followed to document outcomes. As a result, 48% had obstructive HCM, 25% had HCM in family, 21% were asymptomatic, and 68% had comorbidities. During 2.8 years of follow-up, the all-cause mortality rate was 2.86%/year. A total of 5.7% received an implantable cardioverter-defibrillator (ICD), 21% septal reduction therapy. Sequencing analysis of 176 probands identified 64 causative variants in 66 patients (38%); recurrent variants were MYBPC3 p.Q1233* (8), MYBPC3 p.R346H (2), MYH7 p.A729P (2), TPM1 p.Q210R (3) and FLNC p.H1834Y (2); 10 were multiple variant carriers (5.7%); 5 had non-sarcomeric HCM, ALPK3, TRIM63 and FLNC; thin filament variant carriers had a worse prognosis for heart failure (HR = 7.9, p=0.007). In conclusion, in the Russian HCM population, the low use of ICD and relatively high mortality should be noted by clinicians; some distinct recurrent variants are suspected to have a founder effect; family studies on some rare variants enriched the worldwide knowledge in HCM.

Sedimentation processes have negative socioeconomic and environmental consequences, ranging from eutrophication phenomena, loss of water quality in surface water bodies, effects on the potential for hydroelectric generation, etc. Frequently, anthropic activity is the main cause that enhances these processes through changes in land use that can lead to landscape modifications. Therefore, it is relevant to evaluate this phenomenon and to be able to discriminate the influence of different land uses on the contributions to sediment loads at different scales. The novel Compound Specific Stable Isotopes technique allows the evaluation of sediment inputs associated with different land use changes in a study region. In the present work this technique was used in the Alhajuela Lake sub-basin, within the Panama Canal Watershed. The contribution levels of three (3) representative land uses (forest, pasture and sediment) in the study area were evaluated for the sediments present in sixteen (16) selected mixing points. The main contributions of the sources to the sediments present in the main rivers and tributaries flowing into Alhajuela Lake, in the sub-basin of the same name, were identified. The results obtained are consistent with observations and measurements of sedimentation in the study area.

This paper addresses the grammatical challenges associated with the development of clause complexity, focusing on the performance of a group of monolingual Spanish-speaking schoolchildren with Specific Language Impairment/Developmental Language Disorder (SLI/DLD) in a longitudinal corpus of oral narrative samples. The study examines the presence of interclause relations of subordination and equivalence (hypotaxis and parataxis) in language samples of two groups: an experimental group made up of 24 schoolchildren with SLI/DLD and a control group made up of 24 schoolchildren with typical development (TD). The results show that while both groups use parataxis as the most common relation between clauses in all school grades, there is a significant decrease in paratactic relations and a significant increase in hypotactic relations from first to fourth grade of primary education. Although the development patterns are highly similar, the SLI/DLD group shows greater difficulties in mastering more complex (hypotactic) relations in fourth grade compared to the control group, indicating that they are less sophisticated in the use of these types of complex relations. These findings suggest that focused support on the most complex structures is needed towards the fourth grade of primary education, given the demands of the school academic register from 6 and 7 years of age, and the potential problems that the development of clause complexity can cause in school-age children.

Kidney fibrosis is a complex polyetiological progressive disease manifesting as an intraorgan proliferation of the connective tissue with the appearance of cicatricial changes. However, pathogenetic mechanisms of renal fibrosis remain poorly understood. The paper highlights features of the protease phenotype and histotopography of mast cells (MCs) found in the kidney, as the key players in extracellular matrix remodeling in nephrofibrosis, detected in a patient diagnosed with "nephrosclerosis with the non-functioning upper pole of the duplex right kidney in the junction of refluxing megaureter of the upper pole of the duplex right kidney". The highest content of MCs was found in the kidney areas with fibrotic changes. MCs were actively involved in the development of inflammatory and fibrotic changes in limited loci of the specific tissue microenvironment of the kidney through targeted secretion of tryptase, chymase, and carboxypeptidase A3 to the vascular endothelium, nephron epithelium, interstitium cells, and components of the intercellular substance. The formation of a profibrotic environment in the kidney interstitium was facilitated by epigenetic effects of tryptase promoting epithelial-mesenchymal transition (EMT) of the nephron epithelium. A selectively increased number and targeted secretory activity of MCs in limited loci of the kidney parenchyma without visible pathological changes evidence a trigger pathogenetic role of specific proteases in the formation of a local microenvironment with a profibrogenic metabolic profile. Thus, MCs are actively involved in the mechanisms of formation and evolution of fibrogenic niches in the kidney; this fact can be used to develop new strategies for therapeutic options of tubulointerstitial fibrosis resulted from chronic kidney injury. Further study of the molecular phenotype of mast cells reveals new fundamental mechanisms of fibrosis pathogenesis being a significant tool for personalized therapy in nephrology.

Laboratory experiments and natural phenomena investigations in this research series experimentally revealed the existence of gravitational repulsion force dependent on thermal energy content, pervading our surroundings both microscopically and macroscopically. This paper presents an alternative mathematical model of both gravitational repulsion and attraction forces between two gaseous molecules, validated by experimental data. The model is self-standing and independent of existing models built on idealistic assumptions. While existing models considered gravitational interaction as a single force, the presented experimental model considers it the resultant of two distinct forces: gravitational repulsion and attraction. When established experimental data on nitrogen, hydrogen, oxygen, water vapor, carbon monoxide and carbon dioxide were applied, the model performed, both analytically and experimentally: (1) confirming the existence of both gravitational repulsion and attraction forces among gas molecules, (2) demonstrating that the two forces follow Inverse-Cube relationship with the distance between molecules, (3) revealing that repulsion force is linearly proportional to the absolute temperature, thus filling the critical gap between energy and fundamental forces. Orders of magnitude of gravitational repulsion and attraction forces are very large compared to the gravitational force between gas molecules calculated according to the classical theory, enabling manipulation to achieve hitherto unknown outcomes and developments.

Background: The currently advised follow-up scheme of PSA-testing after robot-assisted radical prostatectomy (RARP) is strict and might pose a burden to our healthcare system. We aimed to optimize the 1-year follow-up scheme for patients who undergo RARP. Methods: All patients with histologically-proven prostate cancer (PCa) who underwent RARP between 2018 and August 2022 in the Prostate Cancer Network the Netherlands were retrospectively evaluated. We excluded patients who underwent salvage RARP and patients who had &lt;1 year of PSA follow-up. Postoperative PSA-values were collected. Biochemical persistence (BCP) was defined as PSA-level &gt;0.10 ng/mL at 0-4 months after RARP, whereas biochemical recurrence (BCR) was defined as PSA-level &gt;0.2 ng/mL at any time point after RARP. We aimed to identify a group of patients who had a very low risk of BCR at different time-points after surgery. Results: Of all 1155 patients, BCP was observed in 151 (13%), of whom 79 (6.8%) had PSA ≥0.2 ng/mL. BCR further developed in 51 (4.7%), and 37 (3.4%) patients at 5-8 and 9-12 months after RARP, respectively. In 12 patients, BCR was found at 5-8 months after RARP in absence of BCP. These patients represented 1.2% (12/1004) of the entire group. In other words, 98.8% (992/1004) of patients who had an unmeasurable PSA-level at 0-4 months after RARP also had unmeasurable PSA-level 5-8 months after surgery. Limitations are the retrospective design and incomplete follow-up. Conclusions: Patients with an unmeasurable PSA-level at 3-4 months after RARP may not need to be retested until 12 months of follow-up as almost 100% of patients will not have biochemically recurrent disease at 5-8 months of follow-up. This will reduce PSA-testing substantially at the costs of hardly any missed patients with recurrent disease.

The Musa textilis var. Abuab has high fiber quality (FQ) but has low resistance against abaca bunchy top virus (AbBTV); the Musa balbisiana var. Pacol, has low FQ but high resistance against AbBTV. Their backcrosses (BC2 and BC3) possess both desirable traits. Analysis using RNA-seq showed that the regulatory divergence of Abuab and Pacol is largely explained by cis differences with 27.4% and 22.3% if we are to assess it using BC2 and BC3, respectively. Cis differences between the two genotypes are significantly reduced from BC2 to BC3 due to changes in genomic constitution. Trans, on the other hand, is robust to changes in allelic composition. All these are attributed to the loss of heterozygosity in the BC3 relative to BC2. Further analysis showed that both backcrosses exhibited genome-wide preferential expression of Pacol- over Abuab-specific alleles, despite the wider genetic presence of the latter in the hybrids. The ratio of the two genotype-specific expressed transcripts and the ratio of their corresponding genetic make-up are significantly disproportionate, a phenomenon which we refer here as “genome–transcriptome incongruence”. We also observed preferential expression switching in which several genes prefer Abuab- (or Pacol-) specific allele in the BC2 but switched to Pacol- (or Abuab-) specific allele in the BC3 genome.

Podoplanin (PDPN) is a cell-surface mucin-like glycoprotein that plays a critical role in tumor development and normal development of the lung, kidney, and lymphatic vascular systems. PDPN is overexpressed in several tumors and is involved in their malignancy. PDPN induces platelet aggregation through binding to platelet receptor C-type lectin-like receptor 2. Furthermore, PDPN modulates signal transductions that regulate cell proliferation, differentiation, migration, invasion, epithelial to mesenchymal transition, and stemness, all of which are crucial for the malignant progression of tumor. In the tumor microenvironment (TME), PDPN expression is up-regulated in the tumor stroma, including cancer-associated fibroblasts (CAFs) and immune cells. CAFs play significant roles in the extracellular matrix remodeling and the development of immunosuppressive TME. Additionally, PDPN functions as a co-inhibitory molecule on T cells, indicating the involvement with immune evasion. In this review, we describe the mechanistic basis and diverse roles of PDPN in malignant progression of tumor and discuss the possibility of the clinical application of PDPN-targeted cancer therapy, including cancer-specific monoclonal antibodies, and chimeric antigen receptor T technologies.

The current study investigated whether a domain-specific intervention targeting maths and executive functions of primary school children with a Roma background would be effective in improving their scholastic performance and executive functioning. In total, 122 students attending Grade 4 of elementary school took part in the project. The study concerned a pretest-intervention-training experimental design with three conditions: the experimental condition, an active and a passive control group. The results suggested that both maths performance and executive functions improved over time, with no significant differences between the three conditions. An additional correlational analysis indicated that pretest performance was not related to posttest performance for the children in the experimental and active control group.

Staphylococcus aureus is a high-priority pathogen causing severe infections with high morbidity and mortality worldwide. Many S. aureus strains are methicillin-resistant (MRSA) or even multi-drug resistant. It is one of the most successful and prominent modern pathogens. An effective fight against S. aureus infections requires novel targets for antimicrobial and antistaphylococcal therapies. Recent advances in whole-genome sequencing and high-throughput techniques facilitate the generation of genome-scale metabolic models (GEMs). Among the multiple applications of GEMs is drug-targeting in pathogens. Hence, comprehensive and predictive metabolic reconstructions of S. aureus could facilitate the identification of novel targets for antimicrobial therapies. This review aims at giving an overview of all available GEMs of multiple S. aureus strains. We downloaded all 114 available GEMs of S. aureus for further analysis. The scope of each model was evaluated, including the number of reactions, metabolites, and genes.Furthermore, all models were quality-controlled using Mᴇᴍᴏᴛᴇ, an open-source application with standardized metabolic tests. Growth capabilities and model similarities were examined. This review should lead as a guide for choosing the appropriate GEM for a given research question. With the information about the availability, the format, and the strengths and potentials of each model, one can either choose an existing model or combine several models to create models with even higher predictive values. This facilitates model-driven discoveries of novel antimicrobial targets to fight multi-drug resistant S. aureus strains.

Tough and antimicrobial dual-crosslinked poly((trimethylamino)ethyl methacrylate chloride)-phytic acid hydrogel (pTMAEMA-PA) has been synthesized by adding chemical crosslinker and docking physical crosslinker of multivalent phytic acid into a cationic polyelectrolyte network. By increasing the loading concentration of PA, the tough hydrogel exhibits compressive stress of >1 MPa, along with high elasticity and fatigue-resistant properties. The enhanced mechanical properties of pTMAEMA-PA were stem from multivalent ion effect of PA via the formation of ion bridges within polyelectrolytes. In addition, a comparative study for a series of pTMAEMA-counterion complexes was conducted to elaborate the relationship between swelling ratio and mechanical strength. The study also revealed secondary factors, such as ion valency, ion specificity and hydrogen bond formation, holding crucial roles in tuning mechanical properties of the polyelectrolyte hydrogel. Furthermore, in bacteria attachment and disk diffusion tests, pTMAEMA-PA exhibits superior fouling resistance and antibacterial capability. The results reflect the fact that PA enables chelating strongly with divalent metal ions, hence, disrupting the outer membrane of bacteria, as well as dysfunction of organelles, DNA and protein. Overall, the work demonstrated a novel strategy for preparation of tough polyelectrolyte with antibacterial capability via docking PA to open up the potential use of PA in medical application.

Activated carbons can be produced from biomass in a thermal process either in a direct carbonization-activation process or by first carbonizing the biomass and later on activating the biochars into activated carbons. The properties of the ACs are dependent on the type of process used for production. In this study, the properties of activated carbons produced in a one-stage and a two-stage process are considered. Activated carbons were produced by physical activation of two types of starting materials, bio chars produced from spruce and birch chips in a commercial carbonization plant and from the corresponding raw chips. The activated carbons produced were characterized regarding specific surfaces, pore volumes and pore size distributions. The un-activated bio chars had some degree of surface area 190 and 140 m²g^-1 for spruce and birch and pore volumes of 0.067 and 0.092 cm³g^-1. According to the results obtained, two slightly different types of activated carbons are produced depending if a one-stage or a two-stage carbonization and activation process is used. The ACs produced in the one-stage process had higher specific surface areas compared to the ones produced in a two-stage process (761-940 m²g^-1 vs. 540-650 m²g^-1) . In addition, total pore volumes were higher in one-stage process but development of micropores is greater compared to two-stage process. There was no significant difference in total carbon content between one-stage and two-stage process.

We previously described a model of deep intrinsic resistance of breast cancer wherein we used a function-based approach to selection of cancer cells that can survive a variety of challenges in prolonged but reversible quiescence. Our experimental results suggested that resistant cancer cells possess a variety of mechanisms, including modifications of the epigenome and transcriptome, for generating a high degree of cellular heterogeneity. In the present study, we evaluated JIB-04, a small-molecule epigenetic inhibitor initially discovered to inhibit cancer growth, to determine its ability to affect deep intrinsic resistance in our breast cancer model. We found that long pretreatment with JIB-04 sensitized resistant triple-negative inflammatory breast cancer cells and their parental cell line SUM149 to the chemotherapeutic drugs doxorubicin and paclitaxel. Resistant cancer cells derived from another inflammatory breast cancer cell line, FC-IBC02, were considerably more sensitive to JIB-04 than was the parental cell line. Investigating a mechanism of sensitization, we found that JIB-04 exposure increased the expression of PD-L1 in resistant cells, suggesting that JIB-04 may also sensitize resistant breast cancer cells to anti-PD-L1 immune therapy. Finally, these results support the usefulness of our experimental strategy for evaluating anticancer agents such as JIB-04 that may halt cancer evolution and prevent development of cancer resistance to currently used therapies.

Breast cancer is the most common cause of death for women worldwide. Thus, the ability of artificial intelligence systems to predict and classify breast cancer is very important. In this paper, a hybrid ensemble method classification mechanism is proposed based on a majority voting mechanism. First, the performance of different state-of-the-art machine learning classification algorithms for the Wisconsin Breast Cancer Dataset (WBCD) were evaluated. The three best classifiers were then selected based on their F3 score. F3 score is used to emphasize the importance of false negatives (recall) in breast cancer classification. Then, these three classifiers, simple logistic Regression learning, stochastic gradient descent learning and multilayer perceptron network, are used for ensemble classification using a voting mechanism. We also evaluated the performance of hard and soft voting mechanism. For hard voting, majority-based voting mechanism was used and for soft voting we used average of probabilities, product of probabilities, maximum of probabilities and minimum of probabilities-based voting methods. The hard voting (majority-based voting) mechanism shows better performance with 99.42% as compared to the state-of-the-art algorithm for WBCD.

Timely screening for breast cancer plays a pivotal role in early detection and treatment; however, Afghan refugee females face significant barriers that hinder their access to these life-saving screening services. Cultural norms, socioeconomic factors, proficiency with the English language, and the challenges of navigating foreign healthcare systems contribute to low screening rates within this population. The current review article seeks to identify barriers to breast cancer screening in the Afghan refugee population in the United States (US) and address possible measures to overcome these challenges.

The prospect of drinking water serving as a conduit for gut bacteria, artificially selected by disinfection strategies and lack of monitoring at the point of use, is concerning. Certain opportunistic pathogens, notably some nontuberculous mycobacteria (NTM), often exceed coliform bacteria levels in drinking water, posing safety risks. NTM and other microbiota resist chlorination and thrive in plumbing systems. When inhaled, opportunistic NTM can infect the lungs of immunocompromised or chronically ill patients, and the elderly, primarily postmenopausal women. When ingested with drinking water, NTM often survive stomach acidity, reach the intestines, migrate to other organs using immune cells as vehicles, potentially colonizing tumor tissue, including in breast cancer. The link between the microbiome and cancer is not new, yet the recognition of intratumoral microbiomes is a recent development. Breast cancer risk rises with age, and NTM infections emerged as a concern among breast cancer patients. In addition to studies hinting at a potential association between chronic NTM infections and lung cancer, NTM have also been detected in breast tumors at levels higher than normal adjacent tissue. Evaluating the risks of continued ingestion of contaminated drinking water is paramount, especially given the ability of various bacteria to migrate from the gut to breast tissue via entero-mammary pathways. This underscores a pressing need to revise water safety monitoring guidelines and delve into hormonal factors, which includes addressing the disproportionate impact of NTM infections and breast cancer on women and examining the potential health risks posed by the cryptic and unchecked microbiota from drinking water.

Even with 100% certainty of a complete cure for breast cancer (BC), there is still a long way to go toward more efficient treatment. This requires sensitive and timely detection and accurate pre/post-clinical characterizations. Despite the availability of advanced diagnostic tools, many cancer patients lack access to efficient diagnostics that are both highly reliable and affordable. The fluorescence-based optical technique aims to make another significant leap forward in improving patient safety. It offers a convenient operation that reduces healthcare costs compared to visual examination tools (VETs). The primary and metastatic stages of BC consider different cancerous cell lines (MDAs), meaning the highest number of cells in this research (up to 300,000) represents the metastatic stages of BC, and 50,000 represents the primary level of BC developments have been studied based on fluorescence-enhanced photodynamic characterizations. The ability to characterize the fluorescence caused by MDA with 50,000 cells compared to the dominant radiation of MDA with 300,000 cells is emphatic proof of the high potential of fluorescence technique in timely BC detections, specifically before it spreads to the axillary lymph nodes. The specific cell numbers of 50,000 and 300,000 were chosen arbitrarily based on the cultivation of common biological limitations. Comparing the outcomes between 50,000 and 300,000 cells allows for evaluating the fluorescence technique’s diagnostic capability across various stages of breast cancer. This assessment provides valuable insights into the effectiveness of the fluorescence-based characterizing approach in detecting cancerous cells at different stages of the disease. Here, we have assessed fluorescence’s spectral shift and intensity difference as a diagnostic approach to distinguish between cancerous and normal breast cells. This study also presents a two-way structure of the 5-aminolevulinic acid (5-ALA) prodrug and Fluorescein Sodium (FS) effect in BC cell characterization from the perspective of photodynamical procedures and the detection side. 5-ALA induces an accumulation of protoporphyrin IX (PpIX) photosensitizer through a biosynthetic pathway, leading to red radiation of fluorescence measurements depending on different factors, such as temperature, incubation time, added glucose of the culturing medium, as well as photosynthesis processes. The presence and progression of breast cancer can be indicated by elevated levels of Reactive Oxygen Species (ROS), which are associated with the production of PpIX in cells following the administration of 5-ALA. Also, nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) fluorophores are recognized as the main factors for fluorescence emissions at around 420-580 nm emission intervals. Considering the MDA’s high metastatic potential, the impact of 5-ALA on MDA’s cellular morphology and viability has been investigated. The molecular fluorophores are the primary probes to MDA’s cellular photodynamic considerations, allowing this widespread pre/post-clinical approach. The fluorescence signal reduction due to decreased cell viability and increased MDA’s cellular death rate after 24 hours of the 5-ALA-induced staining corresponds to the changes in lipid metabolism enzymes of MDAs cultured at different doses, which could be known as a cell death inducer function. Furthermore, statistical concerns have been studied using PCA multivariate component analysis to differentiate MDA cell lines administrated by 5-ALA.

Background: Methotrexate (MTX) displayed cytotoxic properties against some cancer cells. However, there is very limited data about the possible anti-tumoral potential of them in breast cancer (BC) cells. We aimed to determine the effects of MTX, which is widely used in clinical practice, on cell viability, Hypoxia-inducible factor (HIF) -1α, HIF-2α and prolyl 4-hydroxylase-transmembrane (P4H-TM) in BC cells (MCF-7) and health breast cell (HTERT-HME1) treated with MTX. Methods: Human healthy breast cells (HTERT-HME1) and BC cells (MCF-7) treated with MTX for 24 h, 48h, and 72 h, the effects of MTX on cell viability. Results: The cell viability and with half-maximal inhibitory concentration (IC50) values of of MTX treatment in healthy breast cells were determined to be higher than in MCF-7 cells. MTX showed higher cytotoxicity against MCF-7 cells. MTX significantly reduced cell viability values in HTERT-HME1 and MCF-7 cells. HIF-1α, HIF-2α, and P4H-TM levels was significantly higher in the MCF-7 group than the other groups. Morever, there was a moderate significant correlation between HIF-1α and HIF-2α levels and between HIF-1α and P4H-TM. Conclusions: MTX will show a further decrease in cell viability in long-term treatments of 48 and 72 hours, it is predicted that short-term use may be more appropriate. P4H-TM may be a novel regulator of hypoxia in BC cells. HIF-1α, a key protein responsible for the molecular mechanism of hypoxia in cells, is a key mediator between P4H-TM and hypoxia in MTX-treated cells. HIF-1α, HIF-2α, and P4H-TM values may be markers that can be used as a panel to differentiate BC from healthy women.

Background: This study aimed to investigate the impact of the COVID-19 pandemic on breast reconstruction trends in the United States, focusing on implant-based and autologous techniques, as well as the timing of reconstruction (immediate vs. delayed). Methods: A retrospective analysis of data from the American Society of Plastic Surgeons' National Plastic Surgery Statistics from 2015 to 2022 was conducted. Annual trends in breast reconstruction procedures were analyzed, comparing the pre-pandemic (2015-2019) and pandemic (2020-2022) periods. Results: The total number of breast reconstructions increased from 106,338 in 2015 to 151,641 in 2022. The proportion of implant-based reconstructions decreased from 81.41% pre-pandemic to 76.51% during the pandemic (p < 0.001), with a notable rise in direct-to-implant procedures from 10.37% to 19.12% (p < 0.001). Autologous reconstructions increased from 18.59% to 23.49% (p < 0.001). Among autologous techniques, DIEP flaps remained the most popular. Immediate reconstruction rates increased from 72.61% pre-pandemic to 75.57% during the pandemic, while delayed recon-struction rates decreased from 27.39% to 24.43% (p < 0.001). Conclusions: The COVID-19 pandemic has significantly influenced breast reconstruction trends in the United States, with a shift towards autologous techniques, particularly DIEP flaps, and an in-crease in immediate reconstructions. These changes may reflect adaptations in surgical practice and decision-making processes in response to the unique challenges posed by the pandemic. Further research is needed to assess the long-term outcomes and patient satisfaction associated with these trends.

Breast cancer is the second most common cancer worldwide, primarily affecting women, while histopathological image analysis is one of the possibilities used to determine tumor malignancy. Regarding image analysis, the application of deep learning has become increasingly prevalent in recent years. However, a significant issue is the unbalanced nature of available datasets, with some classes having more images than others, which may impact the performance of the models due to poorer generalisability. A possible strategy to avoid this problem is downsampling the class with the most images to create a balanced dataset. Nevertheless, this approach is not recommended for small datasets as it can lead to poor model performance. Instead, techniques such as data augmentation are traditionally used to address this issue. These techniques apply simple transformations, such as translation or rotation, to the images to increase variability in the dataset. Recently, Generative Adversarial Networks (GANs) have emerged, which can generate images from a relatively small training set. This work aims to enhance the model’s performance in classifying histopathological images by applying data augmentation using GANs instead of traditional techniques.

Abstract: Exercise has been repeatedly shown to be safe and beneficial for cancer survivors. However, there is no normative guideline for exercise prescription, and it is under exploration. Therefore, this literature review aims to provide some advice for the formulation of exercise prescriptions for patients with breast cancer-related lymphedema (BCRL) from the perspective of reducing lymphedema severity. A review of relevant studies published before November 2023 was conducted using three scientific databases PubMed, Embase, and Scopus. A total of 2696 articles were found. Eventually, 13 studies fulfilled the inclusion criteria and were included in this literature review. We concluded daily, or nearly daily exercise at home can be recommended. Moreover, reduced lymphedema severity may not be maintained after ceasing the exercise program, so exercise should be a lifelong practice.

DIEP-based breast reconstruction necessitates wide undermining at the abdominal donor-site, creating large wound areas. Flap harvesting is usually conducted using electrosurgical dissection devices. This study sought to compare the clinical outcomes in patients after using the PEAK PlasmaBlade (PPB) versus monopolar electrocautery (MPE). This retrospective cohort study included 128 patients with DIEP-based breast reconstruction. Patient characteristics as well as information on the postoperative course were collected and a comparative evaluation was conducted. The MPE group exhibited significantly (p* = 0.0324) higher abdominal drainage volume (351.11 ± 185.96 ml) compared to the PPB group (279.38 ± 183.38 ml). Subgroup analysis demonstrated that PPB significantly reduced postoperative wound fluid in patients with BMI > 30 kg/m² (p* = 0.0284), without prior neoadjuvant chemotherapy (p** = 0.0041), and among non-smokers (p = 0.0046). Furthermore, postoperative pain was significantly (p**** < 0.0001) lower in the PPB cohort. This study confirms the non-inferiority of the PEAK PlasmaBlade to conventional electrocautery for abdominal flap harvesting. The PPB demonstrated advantages, notably reduced drainage volume and lower postoperative pain levels. Recognizing patient subsets that benefit more from the PPB highlights the importance of personalized device selection based on patient characteristics.

Breast cancer brain metastasis (BCBM) is a challenging condition with limited treatment options and poor prognosis. Understanding the interactions between tumor cells and the blood-brain barrier (BBB) is critical for developing novel therapeutic strategies. One promising target is estrogen receptor β (ERβ), which promotes the expression of key tight junction proteins, sealing the BBB and reducing its permeability. In this study, we investigated the effects of 17β-estradiol (E2) and the selective ERβ agonist diarylpropionitrile (DPN) on endothelial and cancer cells. Western blot analysis revealed the expression patterns of ERs in these cell lines, and estrogen treatment upregulated claudin-5 expression in brain endothelial cells. Using in vitro models of the BBB, we found that DPN treatment significantly increased BBB tightness about suppressed BBB transmigration activity of representative HER2-positive (BT-474) and triple-negative (MDA-MB-231) breast cancer cell lines. However, the efficacy of DPN treatment decreased when cancer cells were pre-differentiated in the presence of E2. Our results support ERβ as a potential target for the prevention and treatment of BCBM and suggest that targeted vector-based approaches may be effective for future preventive and therapeutic implications.

Breast cancer has become the most diagnosed cancer in women globally with 2.3 million new diagnosis each year. Accurate early staging is essential for improving survival rates with metastatic spread from loco regional to distant metastasis decreasing rates by 50%. Current guidelines do not advice the routine use of Positron Emission Tomography (PET)-Computed Tomography (CT) in staging of early breast cancer in the absence of symptoms. However, there is a growing body of evidence to suggest that PET-CT used in this early stage can benefit the patient by improving staging and as a result treatment and outcome as well as psychological burden without increasing costs to the health service. Ongoing research in PET radiomics and artificial intelligence is showing promising future prospects in its use in diagnosis, staging, prognosticatication and assessing response to treatment in breast cancer. Furthermore ongoing research to address current limitations of PET-CT by improving techniques and tracers is encouraging.

PIEZO1 plays a crucial role in the human body as a mechanosensory ion channel. It has been demonstrated that PIEZO1 is important in tissue development and regulating many essential physiological processes. Studies have suggested that the PIEZO1 ion channel plays a role in invasion and progression in cancer; elevated levels of PIEZO1 have been correlated with increased migration in breast cancer cells, chemo-resistance and invasion in gastric cancer cells, and increased invasion of osteosarcoma cells. In addition, high PIEZO1 expression levels were correlated with a worse prognosis in glioma patients. On the other hand, studies in lung cancer have attributed high PIEZO1 levels to better patient outcomes. However, the clinical impact of PIEZO1 in breast cancer is not well characterized. Therefore, our goal was to determine the clinical relevance of PIEZO1 in breast cancer. Analysis of breast cancer data from The Cancer Genome Atlas (TCGA) was conducted to investigate PIEZO1 expression levels and correlation to survival, followed by validation in an independent dataset, GSE3494. We also performed gene set enrichment analysis (GSEA) and analyzed immune cell levels in breast tumors from TCGA through a CIBERSORT algorithm. Our results demonstrated that PIEZO1 expression levels are higher in hormone receptor (HR) negative than HR positive cohorts. High PIEZO1 expression is correlated with a significant decrease in survival in HR negative cohorts, suggesting that PIEZO1 could be utilized as a prognostic biomarker in HR negative breast cancer. GSEA showed that various signaling pathways associated with more invasive phenotypes and resistance to treatments, including epithelial-mesenchymal transition (EMT), hypoxia, and multiple signaling pathways, are enriched in high PIEZO1 HR negative tumors. Our results also demonstrated a decrease in CD8+ and CD4+ T cell infiltration in high PIEZO1 HR negative tumors. Further investigations are necessary to elucidate the mechanistic roles of PIEZO1 in HR negative breast cancer.

Breast cancer-related lymphedema (BCRL) affects approximately 20% of women after breast cancer therapy. Advances in treatment have increased life expectancy, thus the prevalence of BCRL will continue to rise with the number of cancer survivors. Hence the need to develop strategies to prevent this condition. We provide a systematic review of the literature on primary prevention of BCRL by prophylactic lymphatic surgery (PLS). Between June and August 2022, we conducted a search of PubMed, Google Scholar and Cochrane. In the end a total of eighteen papers were selected. The eleven studies without a control group reported only 15 of 342 patients who developed lymphedema at least six months after PLS (4.59%). The seven studies with a control group included 569 patients, 328 cases and 241 controls. Among the cases, 36 (10%) developed lymphedema. In contrast, the incidence of lymphedema in controls was 40% (98 of 241 patients). Formulation of definite recommendations in favour of PLS is hindered by low-quality studies. There is no consensus on which technique should be preferred, nor on whether adjuvant radiotherapy might affect the efficacy of PLS. Randomized controlled trials are mandatory to conceive evidence-based recommendations.

This narrative review aims to clarify the role of tertiary lymphoid structures in breast cancer. We examine their development, composition, prognostic value and current ways of recognising them. A comprehensive literature review was performed using PubMed/Medline, Scopus and EMBASE databases. A significant area of interest in breast cancer research involves targeting immune checkpoint molecules, particularly in the triple-negative subtype, where treatment options remain limited. However, existing biomarkers have limitations in accurately predicting treatment response.  In this context, tertiary lymphoid structures (TLS) emerge as a prognostic biomarker and also as a promising predictive marker for response. TLS are ectopic lymphoid formations or neo-organogenesis that can develop after prolonged exposure to inflammatory signals mediated by chemokines and cytokines. Their presence is inversely correlated with estrogen receptor (ER) and/or progesterone receptor (PR) expression, but positively associated with a higher pathologic complete response rate and improved overall  survival. In certain scenarios, TLS-positive tumors were associated with improved outcomes regardless of the presence of PDL-1 (programmed cell death ligand 1) expression or and TILs (tumor-infiltrating lymphocytes).

BRCA1 and 2 pathogenic variants increase lifetime risks of breast (50-75%) and ovarian cancer (15-20%). Guidelines recommend breast screening (MRI and mammogram) or risk-reducing mastectomy with salpingo-oophorectomy for ovarian cancer prevention. We sought to 1) characterize the population of BRCA1/2 carriers in Newfoundland and Labrador (NL) 2) evaluate risk-reducing interventions 3) identify factors influencing screening and prevention adherence. Methods: This is a retrospective study from a population-based provincial cohort of BRCA1/2 carriers. Eligibility criteria for risk-reducing interventions were defined for each case and patients were categorized based on their level of adherence with recommended screening or prevention. Chi-squared and regression analyses were used to determine which factors influenced uptake and level of adherence. Results: 276 BRCA1/2 carriers were identified; 156 living NL females composed the study population. Unaffected females were younger at testing than those with a cancer diagnosis (44.4 y versus 51.7 y; p=0.002). Categorized by eligibility, 61.0%, 61.6%, 39.0% and 75.7% of patients underwent MRI, mammogram, risk-reducing mastectomy, and risk-reducing salpingo-oophorectomy, respectively. Individuals with breast cancer were more likely to have risk-reducing mastectomy (64.7% versus 35.3%; p<0.001), and those who attended specialty hereditary cancer clinic were more likely to be adherent with breast/ovarian cancer recommendations (73.2% versus 13.4%; p<0.001) and to undergo risk-reducing salpingo-oophorectomy(84.1% versus 15.9%; p<0.001). Conclusions: Nearly 40% of female BRCA1/2 carriers were not receiving breast surveillance according to evidence-based recommendations. Cancer risk reduction and uptake of breast imaging and prophylactic breast and pelvic surgeries are significantly higher in patients who receive dedicated specialty care. Organized hereditary cancer prevention programs will be a valuable component of Canadian health care systems and have the potential to reduce the burden of disease country-wide.

The present studies were undertaken to address the role of fetuin-A in the growth and invasion potential in a triple negative breast cancer (TNBC) cell line, MDA-MB-468. Basal like TNBC that express high levels of ectopic fetuin-A have poorer prognosis for the patients compared to those that express low levels of the protein. We overexpressed fetuin-A in MDA-MB-468 and then determined the invasive potential of fetuin-A overexpressing cells vs controls transfected with empty vector. We also determined the adhesion and growth potential of the cells in the presence of only fetuin-A in serum free medium and also in complete medium. Our data suggest that fetuin-A overexpression significantly enhances the invasive potential of the cells and also the expression of Toll like receptor 4 (TLR4) on these cells. More importantly, the cells rely on fetuin-A-TLR4 signaling network for growth and invasion because the specific TLR4 inhibitor CLI-095 (resatorvid) abrogates fetuin-A mediated growth and invasion. Taken together, the data suggest that fetuin-A-TLR4 signaling network plays a significant role in the growth and invasion potential of TNBC.

The cancer stem cell hypothesis suggests that neoplastic cells with stem characteristics hierarchically regulate tumor generation and its high cellular heterogeneity. These cells have been detected in all cancer types, and specific signaling pathways give the regulation of self-renewal and differentiation. In prostate cancer, androgen receptor signaling has been extensively studied, and in non-stem cells, it promotes cell proliferation and tumor progression, but in the cancer stem cell population, it negatively regulates processes such as self-renewal. However, in other types of cancer, such as breast and glioblastoma, the androgen receptor seems to favor the maintenance of cancer stem cells, suggesting that androgen signaling has different effects depending on the tumor context. This review discusses the role of androgen receptor in maintaining cancer stem cells by regulating proliferation, self-renewal, and differentiation, as well as the possible signaling pathways involved in these processes.

Background: Muscle wasting is a common phenomenon in oncology and appears to be alleviated by exercise training. This study aims to determine the degree of aggressiveness of cancer-induced muscle wasting in two different phenotypic muscles, and whether exercise training can attenuate this muscle dysfunction. Methods: Fifty Sprague-Dawley rats were randomly assigned to four experimental groups, two control groups (sedentary and exercised) and two breast cancer model groups (sedentary and exercised) induced by 1-methyl-1-nitrosoureia (MNU). After 35 weeks of endurance training the animals were sacrificed and the gastrocnemius and soleus muscles were harvested for morphometric analysis. Results: A significant reduction in cross-sectional area (P < 0.05) was found in both muscles of sedentary tumor-bearing animals. Interstitial fibrosis was significantly higher in the gastrocnemius of sedentary tumor-bearing animals (P < 0.05), but not in the soleus. A shift from large to small fibers was observed in the gastrocnemius of sedentary tumor-bearing animals. Long-term exercise training was able to prevent this cancer-related mus-cle dysfunction. Conclusions: The Gastrocnemius muscle showed a very pronounced reduction in cross-sectional area and marked interstitial fibrosis in sedentary animals with tumors. The soleus muscle showed a less pronounced but significant reduction in cross-sectional area, and collagen deposition did not differ between tumor groups. These contrasting results confirm that can-cer-induced muscle wasting can affect specific fiber types, and specific muscles, namely fast glycolytic muscles, and that exercise training can act to improve it.

(1) Background: Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer that poses unique management challenges. This review aims to synthesize the current literature on IBC, focusing on diagnosis, treatment, and prognosis, while highlighting recent advances and ongoing issues in patient management.; (2) Methods: We outline the typical clinical presentation and diagnostic criteria of IBC. Additionally, we detail the main therapeutic strategies, including neoadjuvant chemotherapy, surgery, radiation therapy, targeted therapies, hormonal therapies, and emerging treatments such as immunotherapy. The review is based on a comprehensive analysis of the existing literature.; (3) Results: Despite advancements in systemic therapy and a better understanding of IBC biology, the prognosis for patients with IBC remains poor. The overall survival rate has shown only marginal improvement over the past few decades. Future research directions, including the identification of novel biomarkers for early detection and personalized medicine strategies, are identified. The need for more high-quality clinical trials to address the challenges in IBC management is emphasized.; (4) Conclusions: Managing IBC is a complex task that necessitates multidisciplinary care and patient-centered communication. This review provides clinicians and researchers with a comprehensive overview of the current challenges and future directions in IBC management. The goal is to guide treatment decisions and inform further research, ultimately improving patient outcomes and prognosis.

(1) Background: Breast cancer is a frequent heterogeneous disorder diagnosed in woman and is a high cause of mortality of them in reason to rapid metastasis and disease recurrence. Ferroptosis can inhibit breast cancer cell growth, improve the sensitivity of chemotherapy and radiotherapy and inhibit distant metastases so potentially acts on tumor micro-environment; (2) Methods: Ferroptosis/Extracellular matrix remodeling literature text-mining results were integrated in breast cancer transcriptome cohort according their distant relapse free survival (DRFS) under adjuvant therapy (anthracyclin+taxanes) and also in MDA-MB-231 transcriptome functional experiments with ferroptosis activations (GSE173905); (3) Results: Ferroptosis/Extracellular matrix remodeling text-mining identified 910 associated genes in at list 10 articles. Univariate Cox analyses censored on breast cancer (GSE25066) selected 252 individual significant genes and 171 of them found with an adverse expression. Functional enrichment of these 171 adverse genes predicted basal breast cancer signatures. By text-mining some ferroptosis significant adverse selected genes shared citations in domain of ECM remodeling such as: TNF, IL6, SET, CDKN2A, EGFR, HMGB1, KRAS, MET, LCN2, HIF1A, TLR4. A molecular score based on expression the eleven genes was found predictive of worst prognosis breast cancer at univariate level: basal subtype, short DRFS, high grade values 3 and 4, estrogen and progesterone receptors negative and nodal stages 2 and 3. This eleven gene signature was validated as regulated by ferroptosis inductors (erastin and RSL3) in triple negative breast cancer cellular model MDA-MB-231.; (4) Conclusions: Crosstalk between ECM remodeling-Ferroptosis functionalities allowed to define a molecular score which have been characterized as an independent adverse parameter in prognosis of breast cancer patients. Gene signature of this molecular score have been validated to be regulated by erastin/RSL3 ferroptosis activators. This molecular score could be promising to evaluate ECM impact of ferroptosis target therapies in breast cancer.

The antibody Trastuzumab (Tz) targeting ERBB2 has improved the prognosis of patients with breast cancer (BCa) that overexpress this receptor. Resistance to Tz negatively impacts prognosis. Several mechanisms have been reported to cause Tz resistance. The objective of this study was to identify common mechanisms in in vitro models of acquired BCa Tz resistance. In particular, we used three widely available ERBB2+ BCa cell lines adapted to grow in Tz. We performed several analyses to address possible changes in phenotype, proliferation, and ERBB2 membrane expres-sion common to the three Tz-R cell lines compared to wt, but none was found. High-resolution mass spectrometry analysis identified, instead, a common set of differentially expressed proteins (DEPs) in Tz-R vs. wt cells. Furthermore, bioinformatic tools revealed that all three Tz-R cell models shared a modulation of proteins involved in the metabolism of lipids, organophosphate biosynthetic process, and macromolecule methylation. Ultrastructural analysis confirmed altera-tion of lipid droplets in resistant cells. Our data strongly support the hypothesis that complex metabolic adaptation, including lipid metabolism, protein phosphorylation, and possibly chro-matin remodeling, may fuel Tz resistance. The identification of a common set of 10 DEPs in all three TZ-resistant cell lines may provide novel targets for therapeutic intervention.

A recently identified broiler myopathy known as wooden breast (WB) is predominantly found in the pectoralis major muscle of fast-growing broiler hybrids and is causing significant losses to the poultry industry. The aim of this study was to investigate the effects of WB syndrome on raw meat texture, purge loss and thermal properties of intramuscular connective tissue of pectoralis major muscle in the early post-mortem period. Results showed that WB muscles at 1d postmortem was associated with significantly increased stiffness and significantly increased purge loss compared to normal muscles (NB). However, at 3d postmortem, these parameters did not differ between the two groups. Insoluble and total collagen content was significantly higher in WB muscles compared to NB muscles, and the extractability of intramuscular connective tissue (IMCT) was also higher and remained stable in the early postmortem period. These were coincided with significantly lower protein content in the sarcoplasmic protein fraction and myofibrillar protein fraction of WB muscles compared to NB muscles (P < 0.05). The IMCT of these two groups showed different thermal properties, as the enthalpy of denaturation (ΔH) was significantly lower in WB muscles compared to NB muscles. The WB syndrome had a great effect on the texture and connective tissue properties of the meat compared to normal muscle, with a tendency for having a lower water holding capacity and higher raw meat hardness

Background: Liquid biopsy is widely recognised as an efficient diagnostic method in oncology for disease detection and monitoring. Though examination of circulating tumor cell (CTC) is mostly implemented for assessment of genomic aberrations, need of complex methodologies for their detection has impeded its acceptance in low resource settings. We evaluated the cell free DNA (cfDNA) as a liquid biopsy tool and investigated its utility in breast cancer patients. Methods: Total cell free DNA was extracted from plasma of breast cancer patients (n=167) with median follow up of more than 5 years, at various stages of the disease. Quantitative PCR was performed to estimate the copy numbers of two fractions of ALU repetitive elements (ALU 115 and ALU 247) and DNA Integrity (DI) was calculated as the ratio of ALU 247/115. Mutations in TP53 and PIK3CA in the cfDNA was estimated by next-gen sequencing (NGS) in a subset of samples. Association of the levels of both the ALU fragments with various clinico-pathological factors and disease-free survival at various stages were examined. Nomogram models were constructed with clinical variables and ALU 247 levels to predict disease-free survival and best performing model was evaluated by decision curve analysis. Results: DI and ALU 247 levels were significantly lower (p<0.0001) in the post-operative plasma when compared to their pre-surgery levels. DI and ALU 247 were found to be significantly higher in patients with metastasis (p<0.05). Patients with higher levels of ALU 247 in their post-operative plasma had significantly poor disease-free survival (p=0.005). Higher level of ALU 247 in circulation also correlated with low tumor-infiltrating lymphocytes (TIL) within their primary tumors in the ER-negative breast cancer subtype (p=0.01). Cox proportional hazard analysis confirmed ALU 247 as an independent variable of disease-free survival both in univariate and multivariate analysis [HR 1.3 (95% CI 1.047 to 1.613, p= 0.017)]. Nomogram model showed addition of ALU 247 with other variables significantly improved (C-index-0.823) the predictive ability of the model. Conclusion: Our results confirm the utility of cfDNA as an evolving liquid biopsy tool for molecular analysis. Evaluation of larger fragment of cfDNA estimated through ALU 247 can provide vital information concurrent with the pathological process of disease evolution in breast cancer and warrants expansion to other cancer types.

Breast cancer prevention is very important for a woman's health worldwide. We have demonstrated a correlation between mammography and ultrasound with diagnoses using passive microwave radiometry (MWR) and a miRNA oncopanel. While mammography screening dynamics could be completed in 3-6 months, MWR will provide us with a prediction in a matter of weeks or even days with the potential for complementary miRNA diagnostics. An early breast cancer diagnosis may be accomplished using either one of these novel techniques alone or in conjunction with more established techniques

Lifestyle has been associated with breast cancer risk through different pathways, including oxidative stress. Antioxidant enzymes are endogenous defense mechanisms against oxidative stress damage, and this response might be modulated by the genetic variation in these enzyme-codifying genes. This study aimed to analyze the synergistic effect of an antioxidant Healthy Lifestyle Index (HeLiX) composed of principal components of Western dietary pattern, alcohol consumption, smoking and physical activity, and genetic polymorphisms in the first-line antioxidant response family genes SOD, GPX, and CAT on breast cancer risk. We included 176 SNPs, and only CAT rs554576 remained significant after correction for multiple comparisons. Breast cancer odds were reduced at the highest (T3) and medium (T2) tertiles of the HeLiX. When stratified by HeLiX, we observed a reduced risk of breast cancer with at least one T-allele, and the effect increased in a dose-dependent manner. Compared to the reference category (HeLiX T1 and AA genotype), women at the HeLiX T3 with AT and TT genotypes in postmenopausal women showed an OR = 0.15 (95% CI 0.07–0.32). For HeLiX T2 and AT genotype OR = 0.26 (95% CI 0.13–0.54); for TT genotype OR = 0.24 (95% CI 0.12–0.45). For premenopausal women, at the HeLiX T3 and AT genotype OR = 0.29 (95% CI 0.13–0.62); for the TT genotype OR = 0.21 (95% CI 0.08–0.51). We also observed an inverse association for HeLiX T2 and TT genotype (OR 0.39 95% CI 0.17–0.87). Our study shows a significant synergistic gene-environment interaction on an additive scale, contributing to understanding pathways involved in breast cancer etiology and prevention.

This study aimed to determine the feasibility of the development of an over-the-counter (OTC) screening model using machine learning for breast cancer screening in the Asian women population. Data were retrospectively collected from women who came to the Hospital Universiti Sains Malaysia, Malaysia. Five screening models were developed based on machine learning methods; random forest, artificial neural network (ANN), support vector machine (SVM), elastic-net logistic regression and extreme gradient boosting (XGBoost). Features used for the development of the screening models were limited to information from the patients’ registration form. The model performance was assessed across the dense and non-dense groups. SVM had the best sensitivity while elastic-net logistic regression had the best specificity. In terms of precision, both random forest elastic-net logistic regression had the best performance, while, in terms of PR-AUC, XGBoost had the best performance. Additionally, SVM had a more balanced performance in terms of sensitivity and specificity across the mammographic density groups. The three most important features were age at examination, weight and number of children. In conclusion, OTC models developed from machine learning methods can improve the prognostic process of breast cancer in Asian women.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by the lack of estrogen receptors (ER), progesterone receptors, and HER-2 receptors. Thus, TNBC tumours do not benefit from the current therapies targeting ER or HER-2. Therefore, there is an urgent need to develop novel treatment for this subtype of breast cancer. Marijuana is a common name given to Cannabis plants, a group of plants in the Cannabis genus of the Cannabaceae family. Cannabis plants are among the oldest cultivated crops, traced back at least 12,000 years and are well known for their multi-purpose usage, including medicinal purposes. The main active compounds extracted from Cannabis plants are 21-carbon-containing terpenophenolics, which are referred to as phytocannabinoids. Of these, the tetrahydrocannabinol (THC) group contains highly potent cannabinoids, including delta-9-tetrahydrocannabinol (∆9-THC) and delta-8-tetrahydrocannabinol (∆8-THC), which are the most abundant THCs and are largely responsible for psychological and physiological effects of marijuana. The use of Cannabis plants for medicinal purposes was first recorded in 2337 BC in China, where Cannabis plants were used to treat pains, rheumatism, and gout. Recently, several cannabinoids have been approved for a number of treatments, one of which is the treatment of nausea and vomiting caused by chemotherapy in cancer patients. Furthermore, increasing evidence shows that cannabinoids not only attenuate side effects due to cancer treatment, but might also potentially possess direct antitumor effects in several cancer types, including breast cancer. However, anti-tumour activity of marijuana has been variable in different studies and even promoted tumour growth in some cases. In addition, the mechanisms of cannabinoid action in cancer remain unclear. This review summarizes evidence about the mixed actions of cannabinoids in cancer in general and triple-negative breast cancer in particular.

We studied the prognostic impact of tumor immunoglobulin kappa C (IGKC) mRNA expression as a marker of the humoral immune system in the FinHer trial patient population, where 1,010 patients with early breast cancer were randomly allocated to either docetaxel-containing or vinorelbine-containing adjuvant chemotherapy. HER2-positive patients were additionally allocated to either trastuzumab or no trastuzumab. Hormone receptor-positive patients received tamoxifen. IGKC was evaluated in 909 tumors using quantitative real-time polymerase chain reaction, and the influence on distant disease-free survival (DDFS) was examined using univariable and multivariable Cox regression and Kaplan-Meier estimates. Interactions were analyzed using Cox regression. IGKC expression, included as continuous variable, was independently associated with DDFS in a multivariable analysis including also age, molecular subtype, grade, and pT and pN stage (HR 0.930, 95% CI 0.870 – 0.995, P = 0.034). An independent association with DDFS was also found in a subset analysis of triple-negative breast cancers (TNBC) (HR 0.843, 95% CI 0.724 – 0.983, P = 0.029), but not in luminal (HR 0.957, 95% CI 0.867 – 1.056, P = 0.383) or HER2-positive (HR 0.933, 95% CI 0.826 – 1.055, P = 0.271) cancers. No significant interaction between IGKC and chemotherapy or trastuzumab administration was detected (Pinteraction = 0.855 and 0.684, respectively). These results show that humoral immunity beneficially influences the DDFS of patients with early TNBC.

Triple negative breast cancer (TNBC) is an aggressive subtype of the disease with poor clinical outcomes and limited therapeutic options. Immune checkpoint blockade (CP) has surged to the forefront of cancer therapies with widespread clinical success in a variety of cancer types. However, the percentage of TNBC patients that benefit from CP as a monotherapy is low and clinical trials have shown the need for combined therapeutic modalities. Specifically, there has been interest in combining CP therapy with radiation therapy where clinical studies primarily with external beam have suggested their therapeutic synergy, contributing to the development of anti-tumor immunity. Here, we have developed a therapeutic platform combining radionuclide therapy (RT) and immunotherapy utilizing a radiolabelled biomolecule and CP in an E0771 murine TNBC tumor model. Survival studies show that while neither monotherapy is able to improve therapeutic outcomes, the combination of RT + CP extended overall survival. Histologic analysis showed that RT + CP increased necrotic tissue within the tumor and decreased levels of F4/80+ macrophages. Flow cytometry analysis of the peripheral blood also showed that RT + CP suppressed macrophages and myeloid-derived suppressive cells, both of which actively contribute to immune escape and tumor relapse.

Chemotherapy is a standard therapeutic option for triple-negative breast cancer (TNBC); however, its effectiveness is often compromised by drug-related toxicity and resistance development. Herein, we aimed to evaluate whether an improved antineoplastic effect could be achieved in vitro and in vivo in TNBC by combining dovitinib, a multi-kinase inhibitor, with calcitriol, a natural anti-cancer hormone. In vitro, cell proliferation and cell-cycle distribution were studied by sulforhodamine B-assays and flow cytometry. In vivo, dovitinib/calcitriol effects on tumor growth, angiogenesis and endothelium activation were evaluated in xenografted mice by caliper measures, Itgb3-immunohistochemistry and 99mTc-RGD2-tumor uptake. The drug combination elicited a synergistically improved antiproliferative effect in TNBC-derived cells, which allowed a 7-fold dovitinib dose-reduction. Mechanistically, the co-treatment induced cell death and accumulation in S and G2/M phases, while inhibited tumor growth to a greater extent than each compound alone. Tumor uptake of 99mTc-RGD2 was reduced by dovitinib, suggesting angiogenesis inhibition, which was corroborated by decreased endothelial cell growth and tumor vessel density. In summary, calcitriol synergized dovitinib anticancer effects in vitro and in vivo, allowing for a significant dose-reduction of dovitinib, while maintaining its antiproliferative potency. Our results suggest the beneficial convergence of independent antitumor mechanisms of dovitinib and calcitriol to inhibit TNBC-tumor growth.

Recently, two chicken breast fillet abnormalities, termed Wooden Breast (WB) and Spaghetti Meat (SM), have become a challenge for the chicken meat industry. The two abnormalities share some overlapping morphological features, including myofiber necrosis, intramuscular fat deposition, and collagen fibrosis, but display very different textural properties. WB has a hard, rigid surface, while the SM has a soft and stringy surface. Connective tissue is affected in both WB and SM, and accordingly, this study's objective was to investigate the major component of connective tissue, collagen. The collagen structure was compared with normal (NO) fillets using histological methods and Fourier transform infrared (FTIR) microspectroscopy and imaging. The histology analysis demonstrated an increase in the amount of connective tissue in the chicken abnormalities, particularly in the perimysium. The WB displayed a mixture of thin and thick collagen fibers, whereas the collagen fibers in SM were thinner, fewer, and shorter. For both, the collagen fibers were oriented in multiple directions. The FTIR data showed that WB contained more β-sheets than the NO and the SM fillets, whereas SM fillets expressed the lowest mature collagen fibers. This insight into the molecular changes can help to explain the underlying causes of the abnormalities.

Signaling from estrogen receptor alpha (ER) and its ligand estradiol (E2) is critical for growth of ~70% of breast cancers. Therefore, several drugs that inhibit ER functions are in clinical use for decades and new classes of anti-estrogens are continuously being developed. Although a significant number of ER+ breast cancers respond to anti-estrogen therapy, ~30% of these breast cancers recur, sometimes even after 20 years of initial diagnosis. Mechanism of resistance to anti-estrogens is one of the intensely studied disciplines in breast cancer. Several mechanisms have been proposed including mutations in ESR1, crosstalk between growth factor and ER signaling, and interplay between cell cycle machinery and ER signaling. ESR1 mutations as well as crosstalk with other signaling networks lead to ligand independent activation of ER thus rendering anti-estrogens ineffective, particularly when treatment involved anti-estrogens that do not degrade ERa. As a result of these studies, several therapies that combine anti-estrogens that degrade ER with PI3K/AKT/mTOR inhibitors targeting growth factor signaling or CDK4/6 inhibitors targeting cell cycle machinery are used clinically to treat recurrent ER+ breast cancers. In this review, we discuss nexus between ER-PI3K/AKT/mTOR pathways and how understanding of this nexus has helped to develop combination therapies.

Translational medicine requires facile experimental systems to replicate the dynamic biological systems of diseases. Drug approval continues to lag, partly due to incongruencies in the research pipeline that traditionally involve 2D models, which could be improved with 3D models. The bone marrow (BM) poses challenges to harvest as an intact organ making it difficult to study disease processes such as breast cancer (BC) survival in BM, and to effective evaluation of drug response in BM. Furthermore, it is a challenge to develop 3D BM structures due to its weak physical properties, and complex hierarchical structure and cellular landscape. To address this, we leveraged 3D bioprinting to create a BM structure with varied methylcellulose (M):alginate (A) ratios. We selected hydrogels containing 4% (w/v) M and 2% (w/v) A, which recapitulates rheological and ultrastructural features of the BM while maintaining stability in culture. This hydrogel sustained the culture of two key primary BM microenvironmental cells found at the perivascular region, mesenchymal stem cells and endothelial cells. More importantly, the scaffold showed evidence of cell autonomous dedifferentiation of BC cells to cancer stem cell properties. This scaffold could be the platform to create BM models for various disease and also for drug screening.

Triple negative breast cancers (TNBCs) are molecularly heterogeneous, and the link between their aggressiveness with African ancestry is not established. We investigated primary TNBCs for gene expression among self-reported race (SRR) groups of African American (AA, n=42) and European American (EA, n=33) women. Using The Cancer Genome Atlas (TCGA) approaches, we analyzed RNA sequencing data to measure changes in genome-wide expression and used logistic regressions to identify ancestry-associated gene expression signatures. To determine global ancestry, GATK best practices were followed for variant calling, and used the 1000 Genomes Project as reference data. We identified >150 African ancestry-associated genes and found that, compared to SRR, quantitative genetic analysis was a more robust method to identify racial/ethnic-specific genes that were differentially expressed. A subset of African ancestry-specific genes that were upregulated in TNBCs of our AA patients were validated in TCGA data. In AA patients, there was a higher incidence of basal-like 2 tumors and altered TP53, NFB1, and AKT pathways. The distinct distribution of TNBC subtypes and altered oncologic pathways show that the ethnic variations in TNBCs are driven by shared genetic ancestry. Thus, to appreciate the molecular diversity of TNBCs, tumors from patients of various ancestral origins should be evaluated.

Breast cancer (BC) is the most frequent form of malignancy and the second only to lung cancer as common cause of cancer-causing deaths in women. Notwithstanding many progresses in the field, metastatic BC has a very poor prognosis. As therapies are becoming more personalized to meet patients‘ needs, a better knowledge of the molecular biology leading to the disease unfolds the possibility to project more precise compounds or antibodies targeting definite alteration at the molecular level expressed in cancer cells of patients or as antigens on the surface of cell membranes. Fibroblast growth factor receptor (FGFR) is a druggable target -which is activated by its own ligands -namely the Fibroblast Growth Factors (FGFs). This pathway provides a vast range of interesting molecular targets pursued at different levels of clinical investigation. Herein we provide an update on the knowledge on genetic alterations of the receptors in breast cancer, their role in tumorigenesis and the most recent drugs against this particular receptor to treat the disease.

Though Moracin D derived from Morus alba was known to have anti-inflammatory and antioxidant activities, the underlying antitumor mechanism of Moracin D was never unveiled so far. Thus, in the recent study, the apoptotic mechanism of Moracin D was elucidated in breast cancer cells. Herein, Moracin D exerted significant cytotoxicity in MDA-MB231 and MCF7 cells. Also, Moracin D increased sub G1 population, cleaved poly (ADP-ribose) polymerase (PARP) and attenuated the expression of pro-cysteine aspartyl-specific protease (procaspase 3), c-Myc, cyclin D1, B-cell lymphoma 2 (Bcl-2),and X-linked inhibitor of apoptosis protein (XIAP) in MDA-MB231 cells. Of note, Moracin D reduced expression of Forkhead box M1 (FOXM1), β-catenin, Wnt3a, and upregulated glycogen synthase kinase 3 beta (GSK 3β) on Tyr216 along with disturbed binding of FOXM1 with β-catenin in MDA-MB-231 cells. Conversely, GSK3β inhibitor SB216763 reversed the apoptotic ability of Moracin D to reduce expression of FOXM1, β-catenin, pro-caspase3 and pro-PARP in MDA-MB-231 cells. Overall, these findings provide novel insight that Moracin D inhibits proliferation and induces apoptosis via suppression of Wnt3a/FOXM1/β-catenin signaling and activation of caspase and GSK3β

Bronchopulmonary dysplasia (BPD) is the most common complication after preterm birth. Pasteurized donor human milk (DHM) has increasingly become the standard of care for very preterm infants over the use of preterm formula (PF) if mother’s own milk (MOM) is unavailable. Studies have reported beneficial effects of DHM on BPD. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies on the effects of DHM on BPD and other respiratory outcomes. Eighteen studies met the inclusion criteria. Meta-analysis of RCT’s could not demonstrate that supplementation of MOM with DHM reduced BPD when compared to PF (3 studies, risk ratio [RR] 0.89, 95% confidence interval [CI] 0.60–1.32). However, meta-analysis of observational studies showed that DHM supplementation reduced BPD (8 studies, RR 0.78, 95% CI 0.67–0.90). An exclusive human milk diet reduced the risk of BPD, compared to a diet with PF and/or bovine milk-based fortifier (3 studies, RR 0.80, 95% CI 0.68–0.95). Feeding raw MOM, compared to feeding pasteurized MOM, protected against BPD (2 studies, RR 0.77, 95% CI 0.62–0.96). In conclusion, our data suggest that DHM protects against BPD in very preterm infants, but pasteurization of human milk reduces the benefit.

This study aims to quantify carotenoids and tocopherols in human milk from healthy Chinese women, and to explore their associations with region, lactation stage, and maternal socio-economic and obstetric factors. Human milk was obtained from 509 healthy mothers and the compounds of carotenoids and tocopherols were analyzed by high-performance liquid chromatography after mild saponification and solvent extraction. Socio-economic and obstetric characteristics of the mothers and their dietary intakes through a single 24-hour dietary recall were evaluated. The median content of each component [μg/100mL, median (interquartile range)] in colostrum and mature milk was, respectively, β-carotene 8.0 (4.7-15.2) and 1.8 (1.4-2.7), β-cryptoxanthin 6.2 (2.4-12.9) and 1.8 (1.1-3.4), lutein 5.7 (2.9-10.2) and 3.4 (1.5-6.0), lycopene 6.3 (4.0-9.9) and 1.4 (1.1-2.0), zeaxanthin 1.0 (0.6-1.5) and 1.0 (0.6-1.4), α-tocopherol 645 (388-1176) and 211 (131-321), γ-tocopherol 68 (48-121) and 77 (45-120). The levels of all those vitamins presented regional differences, and decreased as lactation stage increased except for zeaxanthin and γ-tocopherol. Associations of carotenoid contents with maternal education, delivery mode, and present body mass index were found in multivariate analyses. These results suggest that some region, lactation stage, obstetric and socio-economic factors are associated with human milk concentrations of carotenoids and tocopherols in healthy Chinese mothers.

Genetic testing allows for identification of germline DNA variations which are associated with a significant increase in risk of developing breast and ovarian cancer. Detection of a BRCA1 or BRCA2 pathogenic variant triggers several clinical management actions, which may include increased surveillance and prophylactic surgery for healthy carriers or treatment with PARP inhibitor therapy for carriers diagnosed with cancer. Thus, standardized validated criteria for annotation of BRCA1 and BRCA2 variants according to their pathogenicity are necessary to support clinical decision making and ensure improved outcomes. Upon detection, variants whose pathogenicity can be inferred by the genetic code are typically classified as pathogenic, likely pathogenic, likely benign, or benign. Variants whose impact on function cannot be directly inferred by the genetic code are labeled as Variants of Uncertain Clinical Significance (VUS) and are evaluated by multifactorial likelihood models that use personal and family history of cancer, segregation data, prediction tools, and co-occurrence with a pathogenic BRCA variant. Missense variants, coding alterations that replace a single amino acid residue with another, are a class of variants for which determination of clinical relevance is particularly challenging. Here, we discuss current issues in variant classification by following a typical life cycle of a BRCA1 missense variant through detection, annotation and information dissemination. Advances in massively parallel sequencing have led to a substantial increase in VUS findings. Although comprehensive assessment and classification of missense variants according to their pathogenicity remains the bottle neck, new developments in functional analysis, high throughput assays, data sharing, and statistical models are rapidly changing this scenario.

New homogeneous bilayer membranes with a thin anion-exchange layer have been developed based on the copolymer of N,N-diallyl-N,N-dimethylammonium chloride (DADMAC) and ethyl methacrylate (EMA) on the surface of a membrane substrate made from polyfluorosulfonic acid (PFSA). The overall and partial current-voltage characteristics, as well as external and internaldiffusion limiting currents, were theoretically and experimentally investigated. Parameters such as specific conductivity, sorption, and diffusion permeability of individual membrane layers were determined, along with effective transport numbers and specific permselectivity of the bilayer homogeneous membranes in mixed solutions of calcium chloride and sodium chloride. It was found that applying a thin anion-exchange layer of DADMAC and EMA to the homogeneous membrane allows for the creation of a charge-selective bilayer membrane with enhanced selectivity towards monovalent metal cations. The specific selectivity of the bilayer membrane for sodium cations increases more than 6-fold (from 0.8 to 4.8). Verification of the obtained experimental data was performed within a four-layer mathematical model with quasi-equilibrium boundary conditions for the diffusion layer (I)/modifying layer (II)/membrane substrate (III)/diffusion layer (IV) in ternary NaCl+CaCl2 solutions.

Balsam fir trees are a specialty agricultural species that are largely used as Christmas trees. Soil or tissue sampling is seldom performed to assess balsam fir nutrition needs, which can contribute to over or under fertilization and subsequent environmental challenges. Remote sensing to determine the normalized difference vegetation index (NDVI) has had strong relationships with nutrition in other plants. This research aimed to determine whether there is a relationship between NDVI and nutrition in balsam fir. A random sample of 45 trees was selected in autumn of 2021 and then another 70 trees selected in spring of 2022. Soil and needle tissue samples were analyzed for N, P, K, Ca, Mg, S, Fe, Zn, Mn, B, and Cu. An uncrewed aerial vehicle equipped with a multispectral camera was flown over the orchard to determine the NDVI for each tree. Nutrition and NDVI were analyzed for correlations through all sampled trees. Separate correlation analyses were repeated for mature trees (greater than 5 years old) and young trees (less than 5 years old). Soil nutrients N, P, K had a significant relationship with NDVI in autumn sampling. Only N was correlated consistently in both autumn and spring, with R2 of 37% and 33% respectively. Relationships were much stronger when only mature trees were considered, increasing to 60% and 51% respectively. NDVI was found to offer predictive power for tissue N that can be useful to producers to help optimize fertilizer input. However, further work is needed to refine these relationships.

Extracellular vesicles (EVs), a diverse group of cell-derived exocytosed particles, are pivotal in mediating intercellular communication due to their ability to selectively transfer biomolecules to specific cell types. EVs, composed of proteins, nucleic acids, and lipids, are taken up by cells to affect a variety of signaling cascades. Research in the field has primarily focused on stem-cell derived EVs, with a particular focus on mesenchymal stem cells, for their potential therapeutic benefits. Recently, tissue specific EVs or cell type specific extracellular vesicles (CTS-EVs), have garnered attention for their unique biogenesis and molecular composition because they enable highly targeted cell-specific communication. Various studies have outlined the roles that CTS-EVs play in signaling for physiological function and maintenance of homeostasis, including immune modulation, tissue regeneration, and organ development. These properties are also exploited for disease propagation, such as in cancer, neurological disorders, infectious diseases, autoimmune conditions, and more. The insights gained from analyzing CTS-EVs in different biological roles not only enhance our understanding of intercellular signaling and disease pathogenesis, but also open new avenues for innovative diagnostic biomarkers and therapeutic targets for a wide spectrum of medical conditions. This review comprehensively outlines current understanding of CTS-EV origins, function within normal physiology, and implications in diseased states.

This study investigated whether reciprocal collaborative pedagogy significantly impacts Indonesian electrical engineering polytechnic students in reducing reading anxiety and improving self-efficacy in ESP reading comprehension skills. Fifty Polytechnic students were equally assigned to two groups. Control groups learned in the traditional reciprocal teaching method individually. Experimental group engaged in reciprocal collaborative pedagogy. Each group received a 6-week reading strategy training. E-learning platforms were used in this study as a complementary tool to distribute ESP reading materials, announcements, and the experiment details being taught. The quantitative and qualitative results demonstrated that the tasks in reciprocal collaborative pedagogy positively affects Indonesian electrical engineering polytechnic students' learning experience and outcomes. This pedagogy promotes a productive learning environment through peer interaction, active engagement, and peer group discussions of the whole learning activities, reducing feelings of anxiety and building confidence in ESP-specialized text.

This study focuses on the modification of ion-exchange membranes by incorporating phosphorylated dendrimer into sulfonated polytetrafluoroethylene membranes to enhance specific selectivity between mono-/divalent ions, using the Ca2+/Na+ pair as an example. The research employs mechanical, physico-chemical, and electrochemical analyses to explore the effects of P-H20 incorporation on membrane properties. Bulk modification significantly increases membrane selectivity towards calcium ions (specific permselectivity coefficient rises from 1.5 to 7.2), while maintaining the same level of the limiting current density. Other findings indicate that bulk modification significantly changes the transport-channel structure of the membrane and alters the mechanism of over-limiting mass transfer. The over-limiting current for the pristine membrane is mainly due to non-equilibrium electroconvection, while modified membranes actively participate in the water-splitting reaction, leading to the suppression of the electroconvection. Despite this drawback, the decrease of the over-limiting potential drop results in a decrease in specific energy consumption from 0.11 to 0.07 kWh/mol. In the under-limiting current mode, the specific energy consumption for all studied membranes remains within the same limits of 0.02-0.03 kWh/mol.

Key thermophysical properties necessary for the successful design and use of CoCrFeNi alloy in thermophysical applications have been measured experimentally, and the results have been compared with literature values and results previously obtained for commercial Ni-Cr alloys and equiatomic CoCrFeNi alloy. In particular, the thermal diffusivity, coefficient of thermal expansion (CTE), and specific heat capacity were measured for the as-cast and homogenized equiatomic CoCrFeNi alloy over a temperature range allowing the thermal conductivity to be calculated up to 1173 K. The thermal conductivity and thermal diffusivity of the equiatomic CoCrFeNi alloy were found to deviate from monotonic behavior in the temperature range from 773 to 1100 K. Such a deviation was previously observed in the behavior of the temperature dependence of CTE and specific heat capacity of the equiatomic CoCrFeNi alloy. The non-linear behavior is primarily the result of order/disorder phenomena for the as-cast and homogenized sample, as well as additionally for the as-cast sample, non-equilibrium solidification under arc melting conditions. The measured data of thermophysical properties are provided for thermally differently treated samples, and it is shown that there is a difference in the behavior of the temperature dependences of CTE, thermal diffusivity, and heat capacity.

A comparative study of the physicochemical properties of natural bentonite clays of Pogodayevо (Republic of Kazakhstan, mod.1) and Dash-Salakhli (Republic of Azerbaijan, mod.2) deposits and modification of the bentonite clay with polyhydroxocations of iron (III) and aluminium (III). It-wasestablished that the modification of natural bentonitesusing polyhydroxocations of iron (III) and aluminium(III) by the method of "co-precipitation" leads to a change in their chemical composition, structural and sorption properties. The results showed that hydroxy-aluminum cations ([Al3O4(OH)24(H2O)12]7+) and poly-hydroxyl-Fe or polyoxo-Fe were intercalated into clay layers, which led to an increase in the values of d001 and specific surface areas compared to those of the original bentonite, from 37 to 120 for the Pogodaevo bentonite and from 51 to 172 respectively for bentonite from the Dash-Salakhli deposit. It is shown that modified sorbents based on natural bentonite are finely porous objects with a predominance of pores of 1.5−6.0 nm in size. As a result, there is a significant increase in the specific surface area of sorbents. Modification of bentonite with polyhydroxocations of iron (III) and aluminium (III) by the "co-precipitation" method also leads to an increase in the sorption capacity of the sorbents obtained with respect to nickel (II) cations. Modified bentonites were used for the adsorption of Ni (II) ions from the model solution. Ni (II) was absorbed in a neutral pH solution. The study of equilibrium adsorption showed that the data are in good agreement with the Langmuir isotherm model. The maximum adsorption capacity of the Ni (II) monolayer obtained from the Langmuir equation was 25.0 mg/g (mod. 1_Al_5-c), 18.2 mg/g (mod. 2_Al_5-c) for Al-bentonite and 16.7 mg/g (mod. 1_Fe_5-c), 10.1 (mod. 2_Fe_5-c) for Fe-bentonite. The kinetics of adsorption is considered. The high content of Al-OH anion exchange centresin them determines the higher sorption activity of Al-modified bentonites.

A reduced ability to work with information contained in a text is usually registered in low-achieving students. One important internal factor influencing reading comprehension concerns the child’s executive functioning. The current study investigated whether the domain-specific intervention ExeFun-READ targeting language abilities related to reading comprehension and executive functioning in primary school children would be effective in improving their scholastic performance in their reading domain and executive functioning. ExeFun-READ is designed to address the relations between domain-specific versus thinking-skill-oriented (domain-general) instruction. A child’s active learning is focused on semantic, phonetic, morphological and syntactical comprehension of linguistic material. In total, 151 students attending grade four from seven elementary schools took part in the project. The study concerned a pretest-intervention-posttest experimental design with three conditions: the experimental condition, an active, and a passive control group. To assess the children’s level of EF, the Delis–Kaplan Executive Function System test battery was used; to assess children’s language ability in reading domain, the Cognitive Abilities Test (the verbal battery, Thorndike &amp; Hagan, 1986 [1]), was used. In the current study, the intervention led to improved language abilities related to reading comprehension, but in terms of executive functioning the improvement only extended to switching fluency. Regarding the effects of the ExeFun-READ intervention on children’s reading abilities, specified as language abilities related to reading comprehension, significant improvements were found in vocabulary, completion of sentences, and classification of terms in the group of children that received the ExeFun-READ intervention.

Prostate-specific membrane antigen (PSMA) has been identified as a target for the development of theranostic agents. In our current work, we describe the design and synthesis of novel N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-(S)-L-lysine (DCL) urea-based PSMA inhibitors with a chlorine-substituted aromatic fragment at the lysine ε-nitrogen atom, a dipeptide as peptide fragment of the linker, including two phenylalanine residues in the L-configuration, and 3- or 4-(tributylstannyl)benzoic acid as prosthetic group in their structures for radiolabeling. The standard compounds ([127I]PSMA-m-IB and [127I]PSMA-p-IB) for comparative and characterization studies were firstly synthesized using two alternative synthetic approaches. An important advantage of the alternative synthetic approach in which the prosthetic group (NHS-activated esters of compounds) is first conjugated with the polypeptide sequence, followed by replacement of the Sn(Bu)3 group with radioiodine, is that the radionuclide is introduced in the final step of synthesis, thereby minimizing operating time with iodine-123 during the radiolabeling process. The obtained DCL urea-based PSMA inhibitors were radiolabeled with iodine-123. The radiolabeling optimization results showed that the radiochemical yield of [123I]PSMA-p-IB was higher than those of [123I]PSMA-m-IB, which were 74.9± 1.0% and 49.4 ± 1.2%, respectively. The radiochemical purity of [123I]PSMA-p-IB after purification was greater than 99.50%. The initial preclinical evaluation of [123I]PSMA-p-IB demonstrated a considerable affinity and specific binding to PC-3 PIP (PSMA-expressing cells) in vitro. The in vivo biodistribution of this new radioligand [123I]PSMA-p-IB showed less accumulation than [177Lu]Lu-PSMA-617 in several normal organs (liver, kidney and bone). These results warrants further preclinical development including toxicology evaluation and experiments in tumor-bearing mice.

The Lewis basicity of selected organic bases, modeled by the enthalpies of adduct formation between gaseous BF3 and the bases in dichloromethane (DCM) solution, is critically examined. Although experimental enthalpies for a large number of molecules have been reported in the literature, it may be desirable to estimate missing or uncertain data for important Lewis bases. We have decided to use high-level ab initio procedures, combined with a polarized continuum solvation model, in which the solvated species are the clusters formed by specific hydrogen bonding of DCM with the Lewis base and the Lewis base/BF3 adduct. This mode of interaction with DCM corresponds to a specific solvation model (SSM). The results actually show that the enthalpy of BF3 adduct formation in DCM solution is clearly influenced by specific interactions, DCM acting as hydrogen-bonding donor (HBD) molecule in two ways: base/DCM and adduct/DCM, confirming that specific solvation is an important contribution to experimentally determined Lewis basicity scales. This analysis allows us to conclude that there are reasons to suspect some gas-phase values to be in error by more than the stated experimental uncertainty. Some experimental values in DCM solution that were uncertain because of identified reasons can be complemented by the computed values.

Soil water loss by evaporation influences the sodium adsorption ratio (SAR) of irrigation drainage water. Evaporation concentrates sodium and magnesium but calcite precipitation has a more complicated effect on soluble calcium and alkalinity. Here we propose a revised sodicity hazard assessment that quantifies the impact of evaporative water loss and calcite precipitation on drainage water SAR. This paper shows sodicity hazard is determined by the initial composition of irrigation water as originally suggested by previous researchers, and provide a simple, accurate way to identify the potential sodicity hazard of any irrigation water. In particular, the initial equivalent concentration of alkalinity and calcium determine the salinization pathway followed during evaporation. If the irrigation water alkalinity exceeds soluble calcium expressed as equivalent concentrations, drainage water SAR approaches an upper limit determined by the initial relative concentration of sodium and magnesium. If irrigation water alkalinity is less than soluble calcium, drainage water SAR approaches a lower limit determined by the initial calcium, magnesium and sodium. In both cases the SAR is scaled by the square root of the concentration factor √Fc quantifying soil water loss. To assess the impact of evaporation and calcite precipitation on the SAR and test the accuracy of the new sodicity hazard assessment, we evaluated data from previously published lysimeter studies. We plotted water composition boundaries for each source water, comparing these boundaries to the drainage water composition recorded in the lysimeter studies. As salinity increased by evaporation, each drainage water followed a distinct salinization path.

Breast cancer is the most common cancer in women globally, often necessitating mastectomy and subsequent breast reconstruction. Silicone mammary implants (SMIs) play a pivotal role in breast reconstruction, yet their interaction with the host immune system and microbiome remains poorly understood. This study investigates the impact of SMI surface topography on host antimicrobial responses, wound proteome dynamics, and microbial colonization. Biological samples were col-lected from ten human patients undergoing breast reconstruction with SMIs. Mass spectrometry profiles were analyzed for acute and chronic wound proteomes, revealing a nuanced interplay between topography and antimicrobial respondseproteins. 16S rRNA sequencing assessed mi-crobiome dynamics, unveiling topography-specific variations in microbial composition. Surface topography alterations influenced wound proteome composition. Microbiome analysis revealed heightened diversity around rougher SMIs, emphasizing topography-dependent microbial inva-sion. In vitro experiments confirmed staphylococcal adhesion, growth, and biofilm formation on SMI surfaces, with increased texture correlating positively with bacterial colonization. This comprehensive investigation highlights the intricate interplay between SMI topography, wound proteome dynamics, and microbial transmission. The findings contribute to understanding host-microbe interactions on SMI surfaces, essential for optimizing clinical applications and minimizing complications in breast reconstruction.

Background: There are limited evidence-based data to guide treatment recommendations for breast cancer (BC) patients ≥ 80 years (P80+). Identifying and addressing unmet needs are critical. Aims: Advocate-BREAST80+ compared the needs of P80+ vs. patients < 80 years (P80-). Methods: In 12/2021, a REDCap survey was circulated electronically to 6,918 persons enrolled in the Mayo Clinic Breast Disease Registry. The survey asked about concerns and satisfaction with multiple aspects of BC care. Results: 2,437 participants responded (35 % response rate); 202 (8.3%) were P80+. P80+ were less likely to undergo local regional and systemic therapies vs. P80- (p

Introduction: Neoadjuvant chemotherapy in breast cancer offers the possibility to facilitate breast and axillary surgery, it is a test of chemosensibility in vivo with significant prognostic value and may tailor adjuvant treatment according to response. Material and Methods: a retrospective single institution of 482 stage II and III breast cancer patients treated with neoadjuvant chemotherapy based on anthracycline and taxans plus antiHEr2 in those Her2 positive cases. Survival was calculated at 5 and 10 years. Kaplan Meier with log rank test were calculated for difference according to TNM, pathological and molecular surrogated subtype, TILs cut-off 20%, response to chemotherapy and the presence of vascular invasion. Results: In the univariate those factors that influenced long-term patient outcome were TNM (p=0.000); pathologic subtype (p=0.003); Tils cut off 20%; achieving pCR (p=0.000), RCB (p=0.000) and vascular invasion (p=0.000). After a mean follow up of 126 months, Luminal tumors presented a substantial difference of survival rates calculated at 5 or 10 years (81.2% compared to 74.7%) whereas for TNBC was 75.3 and 73.5, respectively. The greatest difference was seen according to response those patients with pCR presented a 10yDDFS of 95.5 vs 72.4% for those patients without pCR. This difference was especially meaningful in TNBC were 10y DDFS according to the RCB 0 to 3 was 100%, 80.6%, 69% and 49.2% respectively. Patients with a special bad prognosis in our series were lobular carcinomas with 10y DDFS of 42.9% vs 79.7%, p= 0.001 for ductal carcinomas; and those patients with vascular invasion at the surgical specimen with a 10yDDFS of 59.2% vs 83.6, p=0.,000 for those patients without vascular invasion. Conclusion: long-term outcomes after neoadjuvant chemotherapy can help patient and clinician make well-informed decisions.

PgRMC1 (progesterone receptor membrane component 1) is a progesterone-binding protein highly expressed in various cancer cells. Its expression has been associated with cancer development, chemoresistance, and poor prognosis in breast cancer through the regulation of drug and sterol metabolism, cell cycle, and apoptosis. However, the precise functions of PgRMC1 remain unclear. We examined PgRMC1 expression in breast cancer tissues and analyzed its correlation with clinicopathological characteristics and treatment response (n=112). PgRMC1 expression was detected in breast cancer tissue, while no immunoreactivity for PgRMC1 was observed in normal breast tissue. Notably, PgRMC1 expression levels were high in the HER2 subtype. Among patients treated with neoadjuvant chemotherapy, those with a poor pathological response had significantly higher PgRMC1 expression than those with a good response. PgRMC1 overexpression in breast cancer cell lines reduced chemosensitivity. Real-time qPCR analyses revealed that PgRMC1 induced the expression of differentiation markers, including CDH1 and KRT19, indicating that PgRMC1 is involved in the suppression of epithelial-mesenchymal transition and mammary luminal epithelial differentiation. Our findings suggest that PgRMC1 may contribute to chemoresistance and serve as a putative biomarker for assessing neoadjuvant chemotherapy sensitivity.

In the most cases, invasive ductal carcinoma (IDC) of the breast is identifiable when they present with classic infiltrative growth pattern. However, subset of IDC can occur in a very sneaky way, significantly mimicking the appearance of ductal carcinoma in situ (DCIS). In this condition, it’s much easier to miss the invasive component without pulling ancillary staining when morphologic findings are extremely compatible with DCIS, especially the diagnosis of DCIS was made on the previous biopsy. Here, we reported a 55 year-old female who was noted to have microcalcification at the 11:00 o’clock of the right posterior breast on routine mammographic examination in 09/2023. Biopsy of the calcification area in 10/2023 reported high grade DCIS (ER+ PR-). Histologic examination of subsequent mastectomy specimen showed two separate DCIS-looking areas (Figure 1A-D and Figure 2). Immunohistochemical (IHC) staining showed that myoepithelial markers, smooth muscle myosin heavy chain (SMMHC), p63, CK5/6 and S100, were retained at the periphery of all the expanded acini in one area (Figure 1E-H). Unexpectedly and surprisingly, myoepithelial markers were completely lost at the periphery of part of the DCIS-looking acini in another area (Figure 3A-H), immunohistochemically compatible with the diagnosis of invasive ductal carcinoma admixed with DCIS. Knowing that invasive ductal carcinoma of the breast can present as DCIS-looking morphology, especially given the condition that the diagnosis of DCIS was rendered on the previous biopsy, will enhance awareness of pathologists to recognize DCIS-looking invasive ductal carcinoma. In turn, this will prevent misdiagnosis and under-treatment of patients with invasive ductal carcinoma of the breast.

Purpose To investigate the effects of intra-articular glenohumeral joint triamcinolone injection in treating secondary adhesive capsulitis after breast cancer surgery.Methods This study prospectively enrolled 37 participants, 22 of the breast cancer surgery group and 15 of the idiopathic group. All participants received intra-articular glenohumeral joint injection in the affected shoulder joint and received physiotherapy for 12 week. The clinical assessment evaluated before, and 1, 3, and 6 months after the intervention. The primary outcome was the change in the Shoulder Pain and Disability Index (SPADI).Results The total SPADI(%) in both groups showed significant decrease from baseline to 1, 3, and 6 months after the intervention. There was no significant difference in the differences of the total SPADI from baseline to 1, 3, and 6 months between two groups. However, the improvement in the SPADI pain subscale and the PROM of abduction at 3 and 6 months post-injection in the breast cancer group were inferior to the idiopathic group.Conclusion Intra-articular triamcinolone injection for adhesive capsulitis after breast cancer surgery significantly improved in significant improvements of pain, shoulder function and the PROM. The effects were similar to idiopathic adhesive capsulitis, but in the breast cancer surgery group, appropriate pain and ROM management and monitoring are required even 3 months after injection. With a standardized injection protocol, intra-articular triamcinolone injection could be an effective and safe treatment option for secondary adhesive capsulitis after breast cancer surgery.

Developing clinically meaningful nanomedicines for cancer therapy requires the drugs to be effective, safe, simple, cheap, and easy to store. In the present work, we report that a simple cationic Fe(III)-rich salt of [FeIIICl(TMPPH2)][FeIIICl4]2 (Fe-TMPP) exhibits a superior anticancer performance toward a broad spectrum of cancer cell lines, including breast, colorectal cancer, liver, pancreatic, prostate, and gastric cancers, with half maximal inhibitory concentration (IC50) values in the range of 0.098−3.97 μM (0.066−2.68 μg mL−1), and comparable to the best-reported medicines. Fe-TMPP can forms stand-alone nanoparticles in water without the need for extra surface modification or organic-solvent-assisted antisolvent precipitation. Critically, Fe-TMPP is TME-responsive (TME = tumor microenvironment), and can only elicit its function in the TME with overexpressed H2O2, converting H2O2 to the cytotoxic •OH to oxidize the phospholipid of the cancer cell membrane, causing ferroptosis, a programmed cell death process of cancer cells.

Auger electrons (AEs) represent an intriguing topic in the field of radionuclide therapy. They are emitted by several radionuclides commonly used in nuclear medicine (indium-111, iodine-123, iodine-125), allowing for highly localized energy deposition and thus exerting a radiotoxic effect on specific cellular and sub-cellular targets. However, due to their short range in matter, AEs have had limited use in therapeutic applications so far. In recent years, the synthesis of various radiopharmaceuticals capable of binding to the enzyme poly(ADP-ribose) polymerase 1 has reignited interest in this type of therapy, laying the groundwork for a theranostic approach based on radionuclides emitting AEs. The enzyme PARP-1 operates enzymatically in close proximity to DNA that represents the prime target of radionuclide therapies. Following this trend, several PARP-targeted radiopharmaceuticals for AE-based theranostics have been developed. We provide an updated overview of preclinical studies focused on the applications of this new theranostic approach in glioblastoma, breast, prostate and ovarian carcinoma, and pancreatic adenocarcinoma.

It is known that breastfeeding difficulties are often seen in the first weeks of the postpartum period and that various factors are effective in the mother's early cessation of breastfeeding. Mothers' self-efficacy and perception of insufficient milk are among these factors. This study aimed to examine the effect of hot application applied to the breast with the help of Thera Pearl in the postpartum period on milk perception and postpartum breastfeeding self-efficacy. This is a randomized controlled study. The study was completed with a total of 64 puerperal mothers, 31 of whom were control and 33 were experimental. Personal Information Form, Breastfeeding Observation Form, Breastfeeding Self-Efficacy Scale and Insufficient Milk Perception Scale were used to collect data. As a result, self-efficacy and milk perception are important factors affecting breastfeeding. In this study, we found that Thera pearl application increased breastfeeding self-efficacy, but did not affect milk perception.

Background: So far, vaccination has been considered the most crucial defense against viral infection, including SARS-CoV-2. Numerous reports have demonstrated the effectiveness of the above vaccines in oncology patients. It has also been proven that, apart from vaccinations and oncological therapy, the course of the cancer process itself influences the magnitude of the humoral response, especially in people after infection with SARS-CoV-2. Objective: This study aimed to answer the question about the impact of the cancer process on the humoral response in oncological patients vaccinated against SARS-CoV-2 infection and in patients after COVID-19. Material and methods: 1,668 people were observed. Over two years, 5,082 SARS-CoV-2 IgG and IgM antibody samples were determined. The concentration of antibodies was assessed in three groups of oncological patients: those undergoing anticancer therapy after contracting COVID-19 and those after vaccination against the SARS-CoV-2 infection. Results: The obtained results indicate a naturally more significant humoral response in oncological patients who have not been vaccinated and have not undergone anticancer therapy, such as radiotherapy, chemotherapy, or surgical intervention. The above observation applies to patients with breast, lung, and colon cancer, although the response varies significantly depending on the type of cancer. Summary: The size of the humoral response and the presence of specific antibodies directed against the SARS-CoV-2, IgM, and IgG, in response to the supply of the vaccine antigen or assessed after COVID-19, is an indicator of adequate immune protection against reinfection. This study highlights for the first time the phenomenon of increased humoral response in response to a viral infection in patients with certain types of cancer that are assumed to be sensitive to oncological therapy, the initiation of which, according to generally accepted principles, was blocked by infection with the SARS-CoV-2. The phenomenon we observe seems to confirm the presence of a "natural" defence potential in a cancer patient's body, in this case, directed against infection with a viral pathogen. A "stronger" antiviral response also seems to explain the asymptomatic course of SARS-CoV-2 infection in some of the above patients. It remains an open question to what extent the SARS-CoV-2 infection weakened the "natural" potential of the anticancer response in these patients.

Locally Advanced Breast Cancer (LABC) is a complex disease that requires a multidisciplinary approach. Neoadjuvant Chemotherapy (NAC) is usually performed in order to achieve loco-regional radical resection; although its importance in the multidisciplinary approach to LABC is well recognised, a small number of patients show Progressive Disease (PD). No standard Salvage Treatment (ST) has been defined and different strategies can be adopted, such as second line systemic therapies, radiation therapy, and surgery. Herein a case of LABC in PD during NAC is reported with a literature review, with the aim of highlighting the importance of a tailored multidisciplinary treatment in each patient.

(1) Background: Breast cancer (BC) is the second largest cause of mortality in female worldwide. Besides from basic risk factors, there are several hereditary variables that contribute to BC. Breast cancer has been linked to a variety of nuclear DNA changes as well as mitochondrial DNA alterations. The aim of this study was to analysis the association of mitochondrial tRNA leucine2 gene with BC. (2) Material and methods: In the current study, 24 samples have been collected from various families in Peshawar. DNA was extracted from Blood. PCR was used to amplify the mitochondrial tRNA MT-TL2 gene, and 22 samples were sequenced. The sequence was compared with accession #NC-012920.1 of the revised Cambridge Reference Sequence (rCRS). (3) Results: The results (Chromatograph, nucleotide sequence and rCRS alignment) shows mutations in mitochondrial tRNA MT-TL2 gene in our participants is not the cause of Breast cancer. (4) Conclusion: Yet, a significant number of BC patients must be studied, and their full mitochondrial DNA must be analyzed. This will provide an indication of the potential DNA marker that might be used to prevent BC deaths at the earliest stages.

Breast cancer (BCa) is the most frequently diagnosed malignant tumor in women and is also one of the leading causes of cancer-related death. Most breast tumors are hormone-dependent and estrogen signaling plays a critical role in promoting the survival and malignant behaviors of these cells. Estrogen signaling involves ligand-activated cytoplasmic estrogen receptors that translocate to the nucleus with various co-regulators such as steroid receptor co-activator (SRC) family members, and bind to the promoters of target genes and regulate their expression. SRC-3 is a member of this family that interacts with, and enhances the transcriptional activity of the ligand activated estrogen receptor. Although SRC-3 has important roles in normal homeostasis and developmental processes, it has been shown to be amplified and overexpressed in breast cancer and to promote malignancy. The malignancy-promoting potential of SRC-3 is diverse and involves both promoting malignant behavior of tumor cells and creating a tumor microenvironment that has an immunosuppressive phenotype. SRC-3 also inhibits the recruitment of tumor-infiltrating lymphocytes with effector function and promotes stemness. Furthermore, SRC-3 is also involved in the development of resistance to hormone therapy and immunotherapy during breast cancer treatment. The versatility of SRC-3 in promoting breast cancer malignancy in this way makes it a good target, and methodical targeting of SRC-3 probably will be important for the success of breast cancer treatment.

Background: The target volume for post-mastectomy radiation therapy (PMRT) in breast cancer patients with reconstruction has been a subject of debate. This study aimed to assess the radiation dose distribution and treatment outcomes associated with different chest wall (CW) delineation according to ESTRO ACROP guideline for patients underwent implant-based reconstruction. Methods: We conducted a retrospective review of breast cancer patients who underwent mastectomy followed by two-stage implant-based breast reconstruction and adjuvant radiation therapy (RT) between 2007 and 2022. The expanders/implants were positioned retropectorally. The chest wall target volumes were categorized into two groups: the prepectoral group, which excluded the deep lymphatic plexus, and the whole expander group. Results: The study included 26 patients, 15 in prepectoral group and 11 in whole expander group. No significant differences were observed in normal organs exposure between the two groups. There was a trend toward a lower ipsilateral lung mean dose in the prepectoral group (10.2 vs. 11.1 Gy, p=0.06). Both groups exhibited limited instances of reconstruction failure and local recurrence. Conclusions: For patients undergoing two-stage expander-implant retropectoral breast reconstruction and PMRT, our data have provided comparable outcomes and normal organs exposure for those omitting the deep lymphatic plexus.

Breast cancer stands as the prevailing malignancy across all six Gulf Cooperation Council (GCC) nations. In this literature review, we highlighted the incidence and trend of BC in the GCC. Most of the studies reported a consistent increase in BC incidence over the past decades, which was particularly attributed to the adoption of a westernized lifestyle in the region and the implications of emerging risk factors and other environmental and societal factors, the increase in screening uptake, as well as the improvement in data collection and reporting in the GCC. The data about BC risk factors in GCC was limited. In this geographic region, breast cancer frequently manifests with distinctive characteristics, including an early onset, typically occurring before the age of 50, an advanced stage at presentation, and a higher pathological grade. Additionally, it often exhibits more aggressive features such as human epidermal growth factor receptor 2 (HER2) positivity or the presence of triple-negative (TN) attributes, particularly among younger patients. Despite the growing body of literature on breast cancer in the GCC, data pertaining to survival rates are, regrettably, meager. Reports on breast cancer survival rates emanating from the GCC region are largely confined to Saudi Arabia and the United Arab Emirates (UAE). In the UAE, predictive modeling reveals 2-year and 5-year survival rates of 97% and 89%, respectively, for the same period under scrutiny. These rates, when compared to Western counterparts such as Australia (89.5%) and Canada (88.2%), fall within the expected range. Conversely, Saudi Arabia reports a notably lower 5-year survival rate, standing at 72%. This disparity in survival rates underscores the need for further research directed towards elucidating risk factors and barriers that hinder early detection and screening. Additionally, there is a pressing need for expanded data reporting on survival outcomes within the GCC. In sum, a more comprehensive and nuanced understanding of breast cancer dynamics in this region is imperative to inform effective strategies for prevention, early detection, and improved patient outcomes.

Cancer metastasis accounts for approximately 90% of cancer deaths, and elucidating markers in metastasis is the first step in its prevention. To characterize metastasis marker genes of breast cancer (MGs), XGBoost models that classify metastasis status were trained with gene expression profiles from TCGA. Then, a metastasis score (MS) was assigned to each gene by calculating the inner product between the feature importance and AUC performance of the models. As a result, the 54, 202, and 357 genes with the highest MS were characterized as MGs by empirical P-value cutoffs of 0.001, 0.005, and 0.01, respectively. The three sets of MGs were compared with those from existing metastasis marker databases, which provided significant results in most comparisons. We noticed that the set of MGs with the median EP cutoff showed better performance than the other two sets, suggesting the importance of the cutoff used in determining MGs. They were also significantly enriched in biological processes associated to breast cancer metastasis. The MGs that could not be identified by statistical analysis (e.g., GOLM1, ELAVL1, UBP1, and AZGP1) as well as the MGs with the highest MS (e.g., ZNF676, FAM163B, LDOC2, IRF1, and STK40) were verified via the literature. Additionally, we checked how close the MGs are located to each other in the protein–protein interaction networks. We expect that the characterized markers will help understand and prevent breast cancer metastasis.

In recent years, there has been a notable rise in the incidence of breast cancer among young patients, who exhibit worse survival outcomes and distinct characteristics compared to the intermediate and elder patients. Therefore, it’s imperative to identify identify the specific features unique to young patients, which could offer insights into potential therapeutic strategies and improving survival outcomes. In our study, we performed an integrative analysis of bulk transcriptional and genomic data from extensive clinical cohorts to identify prognostic factors. Additionally, we analyzed the single-cell transcriptional data and conducted in vitro experiments. Our work confirmed that young patients exhibited higher grading, worse disease-free survival (DFS), a higher frequency of mutations in TP53 and BRCA1, a lower frequency of mutations in PIK3CA, and upregulation of eight metabolic pathways. Notably, galactose metabolism pathway showed upregulation in young patients and was associated with worse DFS. Further analysis and experiments indicated that galactose metabolism pathway may regulate the stemness of cancer cells and ultimately contribute to worse survival outcomes. In summary, our finding identified distinct clinicopathological, transcriptional, and genomics features and revealed a correlation between galactose metabolism pathway, stemness, and poor disease-free survival of breast cancer in young patients.

Vasculogenic mimicry (VM), a process in which aggressive cancer cells form tube-like structures, plays a crucial role in providing nutrients and escape routes. Highly plastic tumor cells, such as those with triple-negative breast cancer (TNBC) phenotype, can develop VM. However, little is known about the interplay between cellular components of the tumor microenvironment upon TNBC cells VM-capacity. In this study, we analyzed the ability of endothelial and stromal cells to induce VM when interacting with TNBC cells, and analyzed the involvement of the FGFR/PI3K/Akt pathway in this process. VM was corroborated using fluorescently‐labeled TNBC cells. Only endothelial cells triggered VM formation, suggesting a predominant role of paracrine/ juxtacrine factors from an endothelial origin in VM development. By immunocytochemistry, qPCR and secretome analyses, we determined increased expression of proangiogenic factors as well as stemness markers in VM-forming cancer cells. Similarly, endothelial cells primed by TNBC cells showed upregulation of proangiogenic molecules, including FGF, VEGFA, and several inflammatory cytokines. The endothelium-dependent TNBC-VM formation was prevented by AZD4547 or LY294002, strongly suggesting the involvement of the FGFR/PI3K/Akt axis in this process. Given that VM is associated with poor clinical prognosis, targeting FGFR/PI3K/Akt pharmacologically may hold promise for treating and preventing VM in TNBC tumors.

Abstract: (1) Background: Cancer immune escape is associated with the metabolic reprogramming of TME, and combining metabolic targets with immunotherapy has great potential to improve clinical outcomes. Among all metabolic processes, lipid metabolism, especially fatty acid (FA) metabolism, has a huge role in cancer cell survival, migration, and proliferation, but its mechanism and role in the tumor immune microenvironment remain to be investigated. (2) Methods: We comprehensively analyzed 309 fatty acid-related genes, screened 121 different genes, and used one-way COX regression to select 15 genes with prognostic impact. Systematically evaluated the correlation between FMGs modification patterns and Tumor Microenvironment Infiltration, prognosis, and Immunotherapy. The FMGs-Score was constructed to quantify the FMGs modification patterns using principal component analysis. (3) Results: Three clusters based on FMGs-related genes were demonstrated in breast cancer, with three patterns of distinct immune cell infiltration and biological behavior. An FMGsScore signature was constructed to reveal that patients with a low FMGsScore had higher immune checkpoint expression, higher immune checkpoint inhibitor (ICI) scores, increased immune microenvironment infiltration, better survival advantage, and were more sensitive to immunotherapy than those with a high FMGsScore. Finally, the expression and function of the signature key gene NDUFAB1 were examined by in vitro experiments. (4) Conclusions: This study significantly demonstrates the non-negligible role of FMGs in the immune microenvironment of breast cancer, and that FMGsScores can be used to guide the prediction of immunotherapy in breast cancer patients. In in vitro experiments, knockdown of the NDUFAB1 gene resulted in reduced proliferation and migration of MCF-7 cell lines.

Breast cancer pathogenesis, treatment, and patient outcomes are shaped by tumor-intrinsic genomic alterations that divide breast tumors into molecular subtypes. These molecular subtypes often dictate viable therapeutic interventions, and ultimately, patient outcomes. However, heterogeneity of therapeutic response may be a result of underlying epigenetic features that may further stratify breast cancer patient outcomes. In this review we examine non-genetic mechanisms that drive functional changes to chromatin in breast cancer to contribute to cell and tumor fitness, and highlight how epigenetic activity may inform therapeutic response. We conclude by providing perspectives on the future of therapeutic targeting of epigenetic enzymes, an approach which holds untapped potential to improve breast cancer patient outcomes.

The employment of breast silicone implants, both in aesthetic and reconstructive medicine, is widespread thanks to their recognized biocompatibility and durability. Some critical situations, as for example in case of accidental impacts, may however induce concerns by potential patients about their use. Experimental data is collected by means of static compressive and tensile tests. Aging at 37, 60, 75° and 90° Celsius is performed in a physiological saline solution (0,9% NaCl). Impact dynamic tests are carried out using a Hybrid II anthropomorphic test dummy with the prostheses implanted. Mechanical tensile and compressive tests show mechanical degradation of the prostheses characteristics after aging. Impact dynamic tests show a great probability of breast implant rupture at speeds up to 90 km/h. Accidental events like car crashes or bad falls, are con-firmed as possible causes of significant damages to implanted prostheses. In addition, the possi-ble long-term aging of the silicone shell, although of limited relevance in terms of body compati-bility or reaction, can lead to some degradation of mechanical properties, rendering the outcome of accidental events even more worthy of attention.

Standard of care for triple negative breast cancer (TNBC) involves the use of microtubule poisons like paclitaxel, which are proposed to work by inducing lethal levels of aneuploidy in tumor cells. While these drugs are initially effective in treating cancer, dose-limiting peripheral neuropathies are common. Unfortunately, patients often relapse with drug resistant tumors. Identifying agents against targets that limit aneuploidy may be a valuable approach for therapeutic development. One potential target is the microtubule depolymerizing kinesin, MCAK, which limits aneuploidy by regulating microtubule dynamics during mitosis. Using publicly available datasets, we found that MCAK is upregulated in triple negative breast cancer and is associated with poorer prognoses. Knockdown of MCAK in tumor-derived cell lines caused a two- to five-fold reduction in the IC50 for paclitaxel, without affecting normal cells. Using FRET and image-based assays, we screened compounds from the ChemBridge 50k library and discovered three putative MCAK inhibitors. These compounds reproduced the aneuploidy-inducing phenotype of MCAK loss, reduced clonogenic survival of TNBC cells regardless of taxane-resistance, and the most potent of the three, C4, sensitized TNBC cells to paclitaxel. Collectively, our work shows promise that MCAK may serve as both a biomarker of prognosis and as a therapeutic target.

(1) Background: Breast cancer is the second leading cause of cancer death among women. The accurate prediction of survival intervals will help physicians make informed decisions on treatment strategies or the use of palliative care for patients; (2) Methods: The gene expression is predictive and correlates to patient prognosis. To establish a reliable prediction tool, we collected the RNA-seq data of breast cancer patients, a total of 1187 RNA-seq data (median age 58 years), in FPKM format from the TCGA database. Among them, 144 RNA-seq data with date of death information was selected to establish the SaBrcada-AD dataset. We first normalized the SaBrcada-AD dataset to transcripts per million (TPM) to build survival prediction model SaBrcada. After normalization and dimension raising, the differential gene expression data were used for testing eight different deep learning architectures. Among them, GoogLeNet performed the best. Considering the effect of age on prognosis, we examined all ages between the lower and upper quartiles of patient age for a stratified random sampling test; (3) Results: Stratifying by age based on a cut-off of 61 years of age improved the accuracy of SaBrcada compared to previous findings, resulting in an accuracy of 0.798. We also built a free website tool to provide 5 kinds of predicted survival period information for clinician reference; (4) Conclusions: We established a breast cancer survival analysis prediction model, SaBrcada, and a website tool with the same name. Through this highly reliable survival analysis model and website tool, information on survival intervals will be provided for clinicians as part of precision medicine.

Early detection of breast cancer, one of the most common cancers in women worldwide, raises survival rates and lowers the cost of treatment. Although breast cancer detection and classification (CAD) tools have improved, some issues and restrictions still require further research. The creation of breast cancer CAD systems, particularly with deep learning models, was significantly impacted by recent advancements in machine learning and image processing techniques. The current deep learning-based CAD system to identify and categorize masses in mammography is presented in a structured manner in this survey. The survey provides the most popular breast cancer CAD system evaluation metrics, publicly available mammographic datasets, and current image modalities. The survey examines the available literature, emphasizing its strengths and limitations. The survey also emphasizes the difficulties and drawbacks of the current methods for classifying and detecting breast cancer. We point out research gaps and make suggestions for further study. This systematic review may be beneficial for clinicians using CAD systems to diagnose breast cancer early on and for researchers looking for knowledge gaps and making more contributions to the field.

(1) Background: Breast cancer-associated lymphedema (BCRL) is a major complication of breast cancer treatment, affects the quality of life of breast cancer survivors who develop it. Manual lymphatic drainage has a beneficial result in combating lymphedema in patients who have undergone breast cancer surgery. The hypothesis consists in complete decongestive therapy reduces the lymphedema at the level of the upper limb on the side of mastectomy. (2) Methods: Twenty-five patients with radical mastectomy and upper limb lymphedema on the mastectomy side were included in this study. Upper limb circumferences were measured with a tape measure at the following levels: metacarpophalangeal joint; distal radioulnar joint; 10 cm distal to lateral epicondyle; 5 cm proximal to elbow joint; 10 cm proximal to lateral epicondyle. (3) Results: Patients received twice weekly manual lymphatic drainage, multi-layer compression bandaging and upper limb muscle stimulation exercises on the mastectomy side twice weekly. The circumference assessed at the level of the metacarpophalangeal joints and distal radio-carpal joint decreased at the final evaluation. Forearm perimetery - 5 and 10 cm distal to the lateral epicondyle the circumference decreased at the final assessment. (4) Conclusions: Patients with breast cancer-related lymphedema should receive comprehensive decongestive therapy in the early stage of lymphedema to achieve rapid clinical results and improved quality of life

Antimicrobial edible coatings could eliminate pathogen contamination risk on the surface of meat and poultry products during storage. In this study, the edible coating (EC) based on wheat gluten, Pistacia vera L. tree resin (PVR), and essential oil (EO) of PVR were applied on chicken breast fillets (CBF) by dipping method to prevent the growth of Salmonella Typhimurium and Listeria monocytogenes. The samples were packed in foam trays wrapped with low-density polyethylene stretch film and stored at 8°C for 12 days to observe antimicrobial effects and sensory properties. The total bacteria count (TBC), L. monocytogenes, and S. Typhimurium were reported during the storage. All samples coated with EC containing 0.5, 1, 1.5, and 2% v/v EO (ECEO) decreased microbial growth significantly compared to control samples. The growth of TBC, L. monocytogenes, and S. Typhimurium was suppressed by 4.6, 3.2, and 1.6 logs, respectively, at the end of 12 days on the samples coated by ECEO (2%) compared to uncoated controls (p&lt;0.05). Coating with ECEO (2%) also preserved appearance, smell, and general acceptance parameters better than uncoated raw chicken (p&lt;0.05) on the 5th day of storage. In grilled chicken samples, ECEO (2%) did not significantly change the sensory properties of appearance, smell, and texture but had increased taste and general acceptance scores (p&gt;0.05). So, ECEO (2%) can be a feasible and reliable alternative to preserve chicken breast fillets without affecting their sensory properties adversely during the shelf life.

During the progression from ductal carcinoma in situ (DCIS) to invasive breast cancer (IBC), cells have to overcome the physically restraining basement membrane (BM) which compartmentalizes the epithelium from the stroma. Since the extracellular matrix (ECM) of the epithelial and stromal compartment is biochemically and physically distinct from one another, the progression demands a certain degree of cellular plasticity being essentially required for a primary tumor to become invasive. The Epithelial-to-Mesenchymal Transition depicts such a cell program equipping cancer cells with features allowing for dissemination from the epithelial entity and stromal invasion on the single-cell level. Here, we investigated the reciprocal interference between an altering tumor microenvironment and the EMT-phenotype in vitro. BM-typical collagen IV and stroma-typical collagen I coatings were applied as provisional 2-D matrices. Pro-inflammatory growth factors were introduced to improve tissue mimicry. Whereas the growth on coated surfaces did only slightly affect the EMT-phenotype, the combinatorial action of collagen with growth factor TGF-β1 induced prominent phenotypic changes. However, the EMT-induction was independent of the collagen type and cellular accessibility for EMT-like changes was strongly cell line dependent. Summarizing the entire body of data, we computed an EMT-phenotyping model that was used to decide on cellular EMT-status and estimate EMT-like changes. We confirmed that miR200c-mediated reversion of mesenchymal MDA-MB-231 cells is reflected by our EMT-phenotype model emphasizing its potential to predict the therapeutic efficacy of EMT-targeting drugs in the future.

HAX1 is a multifunctional protein involved in the antagonism of apoptosis in cellular response to oxidative stress. In the present study we identified HAX1 as novel binding partner for Che-1/AATF, a pro-survival factor which plays a crucial role in fundamental processes, including response to multiple stresses and apoptosis. HAX1 and Che-1 proteins show extensive colocalization in mitochondria and we demonstrated that their association is strengthened after oxidative stress stimuli. Interestingly, in MCF-7 cells, resembling luminal estrogen receptor (ER) positive breast cancer, we found that Che-1 depletion correlates with decreased HAX1 mRNA and protein levels, and this event is not significantly affected by oxidative stress induction. Furthermore, we observed an enhancement of the previously reported interaction between HAX1 and estrogen receptor alpha (ERα) upon H2O2 treatment. These results indicate the two anti-apoptotic proteins HAX1 and Che-1 as coordinated players in cellular response to oxidative stress with a potential role in estrogen sensitive breast cancer cells.

Two related tumor suppressor genes, Brca1 and Brca2, attract a lot of attention from both fundamental and clinical points of view. Oncogenic hereditary mutations in these genes are firmly linked to the early onset of breast and ovarian cancers. However, the molecular mechanisms that drive extensive mutagenesis in these genes are not known. In this review we hypothesize that one of the potential mechanisms behind this phenomenon can be mediated by Alu mobile genomic elements. Linking mutations in the BRCA1 and BRCA2 genes to the general mechanism(s) of genome stability and DNA repair is critical to ensure the rationalized choice of anti-cancer therapy. Accordingly, we review the literature available on mechanisms of DNA damage repair where these proteins are involved in and how the inactivating mutations in these genes (BRCAness) can be exploited in anti-cancer therapy. We also propose a hypothesis that explains why breast and ovarian epithelial tissues are preferentially susceptible to mutations in BRCA genes. Finally, we discuss perspectives of novel therapeutic approaches for treating BRCAness cancers.

Nearly 15 million patients undergo cosmetic surgery in the United States each year, with breast augmentations such as implants, lifts, or reductions being some of the most common procedures. The most common complications of these procedures are scarring and infection at the incision site, which often necessitates expensive corrective surgery. After significant weight loss, the patient in this study underwent an elective lower body lift in conjunction with a breast reduction and nipple-areolar transplant. An autologous skin graft was used at the transplant donor site. The skin graft unfortunately necrosed, warranting the need for rapid wound closure to avoid further pain and infection. The patient was treated for eight weeks with conservative measures. After eight weeks of failed attempts to close her wound, she was referred for specialist care. Upon initial examination, the donor site wound measured 3.5 cm x 3.5 cm with no sign of epithelialization. The patient received a single dose of Wharton’s jelly flowable perinatal tissue allograft and five hyperbaric oxygen therapy treatments over seven weeks. Upon inspection at the final examination, the wound was closed entirely with 100% epithelialization overlying granulation tissue. This case study demonstrates a precedent for the application of Wharton’s jelly flowable allografts in complicated cosmetic post-surgical wounds. Future efforts will be directed at applying Wharton’s jelly allografts on a preventative basis. Preventative applications could be in stage 2 pressure sores or intra-operatively to decrease potential patient suffering, prevent emotional distress, and reduce unnecessary healthcare expenses.