Biological Profile Research Articles

Identification of disease phenotypes in acetylcholine receptor-antibody myasthenia gravis using proteomics-based consensus clustering

The clinical heterogeneity of myasthenia gravis (MG), an autoimmune disease defined by antibodies (Ab) directed against the postsynaptic membrane, constitutes a challenge for patient stratification and treatment decision making. Novel strategies are needed to classify patients based on their biological phenotypes aiming to improve patient selection and treatment outcomes. For this purpose, we assessed the serum proteome of a cohort of 140 patients with anti-acetylcholine receptor-Ab-positive MG and utilised consensus clustering as an unsupervised tool to assign patients to biological profiles. For in-depth analysis, we used immunogenomic sequencing to study the B cell repertoire of a subgroup of patients and an invitro assay using primary human muscle cells to interrogate serum-induced complement formation. This strategy identified four distinct patient phenotypes based on their proteomic patterns in their serum. Notably, one patient phenotype, here named PS3, was characterised by high disease severity and complement activation as defining features. Assessing a subgroup of patients, hyperexpanded antibody clones were present in the B cell repertoire of the PS3 group and effectively activated complement as compared to other patients. In line with their disease phenotype, PS3 patients were more likely to benefit from complement-inhibiting therapies. These findings were validated in a prospective cohort of 18 patients using a cell-based assay. Collectively, this study suggests proteomics-based clustering as a gateway to assign patients to a biological signature likely to benefit from complement inhibition and provides a stratification strategy for clinical practice. CN and CBS were supported by the Forschungskommission of the Medical Faculty of the Heinrich Heine University Düsseldorf. CN was supported by the Else Kröner-Fresenius-Stiftung (EKEA.38). CBS was supported by the Deutsche Forschungsgemeinschaft (DFG-German Research Foundation) with a Walter Benjamin fellowship (project 539363086). The project was supported by the Ministry of Culture and Science of North Rhine-Westphalia (MODS, "Profilbildung 2020" [grant no. PROFILNRW-2020-107-A]).

Anthropometric Comparative Study of Nasal Morphology between Malaysian and Indonesian Populations

Nasal morphology is one of the most crucial anthropometric characteristics of the human face. Furthermore, the nose is a pivotal feature in constructing a biological profile. In this cross-sectional study, we examined the nasal morphology of 103 Malaysian and 109 Indonesians, totaling 212 individuals from both groups. A comprehensive analysis involved the measurement of 12 nasal morphological features. The statistical tool employed for the analysis was a t-test, which revealed significant differences in various parameters between Malaysians and Indonesians (p<0.05). These findings demonstrate the statistical importance of nasal morphology in discerning racial and ethnic differences. This research suggests that nose measurements could be instrumental in resolving identity mysteries, making them valuable for forensic examination.

Epidemiological, clinical, biological and evolutionary profile of scorpion envenomed children under one year to 15 years in the Souss Massa region of Morocco

Morocco is one of the main countries affected in North African with the scorpion envenomations. Faced with the threat, significant morbidity and a major risk of death especially in children, a detailed identification of scorpionic profile of stings remains important for health authorities at national or even regional level. The current study aims to establish the epidemiological, clinical, biological and evolutionary data of the scorpionism by analyzing 383 cases of scorpion stings in children from three age groups (<1 year, 1–5 years and >5 years), admitted at the Regional Hospital Hassan II-Agadir in the Souss Massa region during the period of 9 years and 10 months from January 2013 to October 2022. Our results showed that patients under 1 year of age presented the most severe cases and had the highest mortality rate. However, the clinical signs and symptoms observed illustrated severe damages to vital systems, particularly the cardiovascular, neurological and pulmonary systems, although the signs associated with the latter were present only in cases admitted in grades 2 and 3 for the three age categories studied. Fluctuations in vital constants (temperature and peripheral oxygen saturation, blood pressure, heart rate and respiratory rate), biochemical parameters (ASAT, ALAT, urea and blood creatine, as well as blood sugar) and CBC results revealed major functional disturbances in vital organs, especially in envenomated cases admitted in grade 3. A positive correlation was mentioned between the state of evolution and the various epidemiological parameters, digestive symptoms, as well as signs and symptoms linked to hemodynamic state, general and neurological state. The main interest is to illustrate the seriousness of scorpion envenomations, especially in the high-risk population, for whom an improved therapeutic approach in health centers will undoubtedly be reinforced, and the admission of immunotherapy, as a fundamental part of the treatment, remains important.

Reactive hemophagocytic lymphohistiocytosis: Epidemiological, clinico-biological and etiological profile

Hemophagocytic lymphohistiocytosis (HLH) is an hyperinflammatory state resulting from increased secretion of proinflammatory cytokines, which are responsible for clinical, biological and cytological manifestations. ObjectiveThe aim of our study is to describe the epidemiological, clinical, biological, etiological and evolutionary profile of HLH in Tunisia. MethodsA retrospective study that involved patients, with images of hemophagocytosis in myelograms analyzed at the laboratory of biological hematology of the University Hospital "Hédi-Chaker" of Sfax-Tunisia, followed at these departments: hematology, internal medicine, department of infectious-diseases and department of gastroenterology, (June2017- May2021). First, we identified all patients with hemophagocytosis images. Secondly, we selected the patients who fulfilled the diagnostic criteria of the HLH-2004-score. ResultsNineteen patients were included in this study. Nine men and 10 women with a mean age of 37.95 years. Fever was present in all patients. Organomegaly was described in 74% of cases. The most frequent cytopenia was anemia (100%). Hypertriglyceridemia was noted in 79% of cases and hyperferritinemia (> 500 ng/mL) was ubiquitous. In myelogram, 68% of patients had slides showing numerous or very numerous images of hemophagocytosis. The infectious pathology was the most common cause of HLH (42%). No cause was found in 10% of cases. The corticosteroid therapy at a dose of 1 mg/kg/day was prescribed in 89% of our patients. The overall evolution was favorable in 58% of cases. The mortality was not associated with the causal pathology (p=0.218). ConclusionSecondary HLH is likely to be under-recognized, which contributes to its high morbidity and mortality. Early recognition is crucial for any reasonable attempt at curative therapy.

Multimechanism biological profiling of tetrahydro-β-carboline analogues as selective HDAC6 inhibitors for the treatment of Alzheimer's disease

With the intensive research on the pathogenesis of Alzheimer's disease (AD), inhibition of HDAC6 appears to be a potential therapeutic approach for AD. In this paper, a series of tetrahydro-β-carboline derivatives with hydroxamic acid group were fast synthesized. Among all, the most potent 15 selectively inhibited HDAC6 with IC50 of 15.2 nM and markedly increased acetylated alpha-tubulin levels. In cellular assay, 15 showed excellent neurotrophic effect by increasing the expression of GAP43 and Beta-3 tubulin markers. Besides, 15 showed neuroprotective effects in PC12 or SH-SY5Y cells against H2O2 and 6-OHDA injury through activation of Nrf2, catalase and Prx II, and significantly reduced H2O2-induced reactive oxygen species (ROS) production. In vivo, 15 significantly attenuated zebrafish anxiety-like behaviour and memory deficits in a SCOP-induced zebrafish model of AD. To sum up, multifunctional 15 might be a good lead to develop novel tetrahydrocarboline-based agents for the treatment of AD.

Deep learning in sex estimation from photographed human mandible using the Human Osteological Research Collection

Sex estimation is a necessary part of forensic and osteological analyses of skeletal human remains in the construction of a biological profile. Several skeletal traits are sexually dimorphic and used for skeletal sex estimation. The human mandible and morphological traits therein have been long used for sex estimation, but the validity of using the mandible in this purpose has become a concern. In this study, we examined the potential of artificial intelligence (AI) and especially deep learning (DL) to provide accurate sex estimations from the mandible. We used 193 modern South African mandibles from the Human Osteological Research Collection (HORC) in the Sefako Makgatho Health Sciences university with known sex to conduct our study. All mandibles were photographed from the same angle and the photographs were analyzed with an open-source DL software. The best-performing DL algorithm estimated the sex of males with 100% accuracy and females with 76.9% accuracy. However, further studies with a higher number of specimens could provide more reliable validity for using AI when building the biological profile from skeletal remains.

Silicon or Calcium Doping Coordinates the Immunostimulatory Effects of Aluminum Oxyhydroxide Nanoadjuvants in Prophylactic Vaccines.

Aluminum salts still remain as the most popular adjuvants in marketed human prophylactic vaccines due to their capability to trigger humoral immune responses with a good safety record. However, insufficient induction of cellular immune responses limits their further applications. In this study, we prepare a library of silicon (Si)- or calcium (Ca)-doped aluminum oxyhydroxide (AlOOH) nanoadjuvants. They exhibit well-controlled physicochemical properties, and the dopants are homogeneously distributed in nanoadjuvants. By using Hepatitis B surface antigen (HBsAg) as the model antigen, doped AlOOH nanoadjuvants mediate higher antigen uptake and promote lysosome escape of HBsAg through lysosomal rupture induced by the dissolution of the dopant in the lysosomes in bone marrow-derived dendritic cells (BMDCs). Additionally, doped nanoadjuvants trigger higher antigen accumulation and immune cell activation in draining lymph nodes. In HBsAg and varicella-zoster virus glycoprotein E (gE) vaccination models, doped nanoadjuvants induce high IgG titer, activations of CD4+ and CD8+ T cells, cytotoxic T lymphocytes, and generations of effector memory T cells. Doping of aluminum salt-based adjuvants with biological safety profiles and immunostimulating capability is a potential strategy to mediate robust humoral and cellular immunity. It potentiates the applications of engineered adjuvants in the development of vaccines with coordinated immune responses.

An updated review of the pharmacological effects and potential mechanisms of hederagenin and its derivatives.

Hederagenin (HG) is a natural pentacyclic triterpenoid that can be isolated from various medicinal herbs. By modifying the structure of HG, multiple derivatives with superior biological activities and safety profiles have been designed and synthesized. Accumulating evidence has demonstrated that HG and its derivatives display multiple pharmacological activities against cancers, inflammatory diseases, infectious diseases, metabolic diseases, fibrotic diseases, cerebrovascular and neurodegenerative diseases, and depression. Previous studies have confirmed that HG and its derivatives combat cancer by exerting cytotoxicity, inhibiting proliferation, inducing apoptosis, modulating autophagy, and reversing chemotherapy resistance in cancer cells, and the action targets involved mainly include STAT3, Aurora B, KIF7, PI3K/AKT, NF-κB, Nrf2/ARE, Drp1, and P-gp. In addition, HG and its derivatives antagonize inflammation through inhibiting the production and release of pro-inflammatory cytokines and inflammatory mediators by regulating inflammation-related pathways and targets, such as NF-κB, MAPK, JAK2/STAT3, Keap1-Nrf2/HO-1, and LncRNA A33/Axin2/β-catenin. Moreover, anti-pathogen, anti-metabolic disorder, anti-fibrosis, neuroprotection, and anti-depression mechanisms of HG and its derivatives have been partially elucidated. The diverse pharmacological properties of HG and its derivatives hold significant implications for future research and development of new drugs derived from HG, which can lead to improved effectiveness and safety profiles.

The Relevance of Sr–O–C Isotope Analysis on Burnt Human Skeletal Remains in Archeological and Forensic Contexts: A Review and Future Directions

AbstractRecovery and identification of heavily burnt and fragmented skeletal remains pose significant challenges in fire and arson investigations. The ability to identify individuals is crucial in such cases, prompting extensive research into various techniques to aid in the identification process, including isotopic analysis. Although direct personal identification is not achievable through isotopic analysis of skeletal remains, it serves as a valuable tool for obtaining chemical elements of the biological profile. Strontium (Sr), oxygen (O), and carbon (C) isotope analyses have been widely used in archeological contexts but are relatively new approaches in the medicolegal domain. Oxygen isotope analysis, for instance, offers insights into the burning temperature, while strontium isotope analysis provides valuable information for tracing the individual's movement across geologically distinct landscapes. Consequently, the investigation of the impact of heat on the biogenic isotope composition of human bones in forensic contexts has gained significant attention. This article presents a comprehensive overview of the key archeological and forensic questions addressed by Sr–O–C isotope analysis of burnt skeletal remains. By examining the current state of the art and prospects, we aim to contribute to a broader understanding and potential advancements in the field of forensic isotope research.This article is categorized under: Forensic Biology &gt; Interpretation of Biological Evidence Forensic Anthropology &gt; Trauma Analysis

Therapy-related myeloid neoplasms with single-hit TP53 mutations share the clinical, molecular, and survival characteristics of their multi-hit counterparts

Recent updates in the classification of myeloid neoplasms (MNs) recognize the poor prognostic impact of TP53 mutations, with particular emphasis on the TP53 allele status. Studies on the effect of TP53 allele status exclusively in therapy-related MNs (t-MNs) are lacking. We compared the clinicopathologic and survival characteristics of t-MNs with single-hit (SH) and multi-hit (MH) TP53 mutations. A total of 71 TP53-mutated t-MNs were included, including 56 (78.9%) MH and 15 (21.1%) SH. Both groups showed comparable genetic profiles with an excess of high-risk karyotypes and a paucity of other co-mutated genes. TP53 was the sole detectable mutation in 73.3% of SH and 75.0% of MH cases. The overall survival (OS) of SH TP53-mutated t-MNs was not significantly different from MH cases (median survival: 233 vs.273 days, p = 0.70). Our findings suggest that t-MNs with SH TP53 mutations share the poor prognostic and biologic profile of their MH counterparts.

Synthesis, molecular docking and molecular dynamics simulations, drug-likeness studies, ADMET prediction and biological evaluation of novel pyrazole-carboxamides bearing sulfonamide moiety as potent carbonic anhydrase inhibitors.

Pyrazoles are unique bioactive molecules with a versatile biological profile and they have gained an important place on pharmaceutical chemistry. Pyrazole compounds containing sulfonamide nuclei also attract attention as carbonic anhydrase (CA) inhibitors. In this study, a library of pyrazole-carboxamides were synthesized and the structures of the synthesized molecules were characterized using FT-IR, 1H-NMR, 13C-NMR and HRMS. Then the inhibition effects of newly synthesized molecules on human erythrocyte hCA I and hCA II isoenzymes were investigated. Ki values of the compounds were in the range of 0.063-3.368µM for hCA I and 0.007-4.235µM for hCA II. Molecular docking studies were performed between the most active compounds 6a, 6b and the reference inhibitor, acetazolamide (AAZ) and the hCA I and hCA II receptors to investigate the binding mechanisms between the compounds and the receptors. These compounds showed better interactions than the AAZ. ADMET analyzes were performed for the compounds and it was seen that the compounds did not show AMES toxicity. The stability of the molecular docking results over time was analysed by 50ns molecular dynamics simulations. Molecular dynamics simulations revealed that 6a and 6b exhibited good stability after docking to the binding sites of hCA I and hCA II receptors, with minor conformational changes and fluctuations.

Preparation and biological evaluation of coumarin amide derivatives bearing fluorine as potential fungicides and anticancer agents

In order to find new potential fungicides and anticancer agents, a series of new coumarin amide derivatives bearing fluorine were synthesized and characterized spectroscopically. Compounds A6, B11, C2 and C7 were confirmed by X-ray diffraction further. The antifungal bioassays against five typical pathogenic fungi showed that compound C5 exhibited more remarkable fungicidal activities against Alternaria alternata (EC50 = 11.5 μg/mL), Colletotrichum gloeosporioides (EC50 = 18.0 μg/mL), Pyricularia grisea (EC50 = 33.8 μg/mL), surpassing kresoxim-methyl. Molecular docking result indicated that C5 displayed high binding affinity to chitinase, which plays crucial role in degradation and remodeling of fungal cell walls. In addition, the anticancer bioassays against three cancer cells demonstrated that compound A4 displayed excellent growth inhibitory effect against Hela cells with IC50 value of 8.13 μM, and low cytotoxicity against human normal cells BEAS-2B. Flow cytometric analysis further demonstrated that A4 significantly arrested cell cycle at the S phase and trigger apoptosis. With the above interesting biological profile, these coumarin derivatives could be used as anfungicides and anticancer candidates.

A novel single-cell model reveals ferroptosis-associated biomarkers for individualized therapy and prognostic prediction in hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) is a prevalent malignancy with a pressing need for improved therapeutic response and prognosis prediction. This study delves into a novel predictive model related to ferroptosis, a regulated cell death mechanism disrupting metabolic processes.ResultsSingle-cell sequencing data analysis identified subpopulations of HCC cells exhibiting activated ferroptosis and distinct gene expression patterns compared to normal tissues. Utilizing the LASSO-Cox algorithm, we constructed a model with 10 single-cell biomarkers associated with ferroptosis, namely STMN1, S100A10, FABP5, CAPG, RGCC, ENO1, ANXA5, UTRN, CXCR3, and ITM2A. Comprehensive analyses using these biomarkers revealed variations in immune infiltration, tumor mutation burden, drug sensitivity, and biological functional profiles between risk groups. Specific associations were established between particular immune cell subtypes and certain gene expression patterns. Treatment response analyses indicated potential benefits from anti-tumor immune therapy for the low-risk group and chemotherapy advantages for the high-risk group.ConclusionsThe integration of this single-cell level model with clinicopathological features enabled accurate overall survival prediction and effective risk stratification in HCC patients. Our findings illuminate the potential of ferroptosis-related genes in tailoring therapy and prognosis prediction for HCC, offering novel insights into the intricate interplay among ferroptosis, immune response, and HCC progression.

Discovery and biological profile of pyridachlometyl

AbstractPyridachlometyl is a novel tubulin dynamics modulator fungicide developed by Sumitomo as a new agent designed to tackle fungicide resistance. Pyridachlometyl is being developed as a first‐in‐class molecule with an anti‐tubulin mode of action, the chemical structure of which is characterized by a unique tetrasubstituted pyridazine ring. The first commercial product ‘Fuseki flowable’ received initial registration in 2023 in Japan. The concepts of the discovery project, optimization of chemical structures, and biological profiles are reviewed herein. © 2024 The Author(s). Pest Management Science published by John Wiley &amp; Sons Ltd on behalf of Society of Chemical Industry.

What Can Be Learned from the Partitioning Behavior of Proteins in Aqueous Two-Phase Systems?

This review covers the analytical applications of protein partitioning in aqueous two-phase systems (ATPSs). We review the advancements in the analytical application of protein partitioning in ATPSs that have been achieved over the last two decades. Multiple examples of different applications, such as the quality control of recombinant proteins, analysis of protein misfolding, characterization of structural changes as small as a single-point mutation, conformational changes upon binding of different ligands, detection of protein-protein interactions, and analysis of structurally different isoforms of a protein are presented. The new approach to discovering new drugs for a known target (e.g., a receptor) is described when one or more previous drugs are already available with well-characterized biological efficacy profiles.

Comparing Nutritional Values and Bioactivity of Kefir from Different Types of Animal Milk.

The growing interest in fermented dairy products is due to their health-promoting properties. The use of milk kefir grains as a starter culture made it possible to obtain a product with a better nutritional and biological profile depending on the type of milk. Cow, buffalo, camel, donkey, goat, and sheep milk kefirs were prepared, and the changes in sugar, protein, and phenol content, fatty acid composition, including conjugated linoleic acids (CLAs), as well as antioxidant activity, determined by ABTS and FRAP assays, were evaluated and compared. The protein content of cow, buffalo, donkey, and sheep milk increased after 24 h of fermentation. The fatty acid profile showed a better concentration of saturated and unsaturated lipids in all fermented milks, except buffalo milk. The highest content of beneficial fatty acids, such as oleic, linoleic, and C18:2 conjugated linoleic acid, was found in the cow and sheep samples. All samples showed a better antioxidant capacity, goat milk having the highest value, with no correlation to the total phenolic content, which was highest in the buffalo sample (260.40 ± 5.50 μg GAE/mL). These findings suggested that microorganisms living symbiotically in kefir grains utilize nutrients from different types of milk with varying efficiency.

Chromatographic descriptors in QSAR examination of the N, N-disubstituted chloroacetamides’ bioactivity

The main goal of this study was the assessment of the N, N-disubstituted-2-chloroacetamides’ biological profile by chromatographic and in silico approach. Preliminary, their drug-like as well as lead-like properties and the bioactivity scores were analyzed. By applying reversed phase thin-layer chromatography as the simulator of compound’s distribution across biological membranes, the assumed bioactivity descriptors of the studied chloroacetamides were obtained. The compliance between obtained chromatographic parameters (R M,0 m) and relevant software lipophilicity/pharmacokinetic/ecotoxicity predictors of studied derivatives were examined by linear regression and additionally supported by more detailed relations established by multivariate methods. Also, it was confirmed that the studied bioactivity properties of the given chloroacetamides are conditioned by the type of the present hydrocarbon substituents (number, arrangement and binding of C atoms).

Deep mapping of the cytokine release syndrome inflammatory continuum: Comprehensive grade-specific profiling and differentiation from sepsis in patients receiving immune checkpoint therapy.

12129 Background: The delineation of cytokine release syndrome (irCRS) from sepsis and its transition to compensatory anti-inflammatory response syndrome (irCARS) is crucial during ICI therapy for personalized care. Methods: We conducted an extensive biological and immune profiling on PBMC and serum from 38 oncology patients with various irCRS grades, including immune-related hemophagocytic lymphohistiocytosis irHLH (n=9) and sepsis during ICI treatment (n=8). Results: Our results show a dominant Th1 response in irCRS. Early markers of irCRS increased progressively with clinical severity in different grades, especially CXCL9, CXCL10 and IFN-γ levels. Starting with low-grade (G) (G1 and 2), a concomitant irCARS response was detected, characterized by an initial increase in IL-1RA and a significant upregulation of IL-10 specifically in G4. 3 subclusters with different overall survival (OS) and cytokine profiles were identified using routine biomarkers. Cluster 1 (C1, n=7) and Cluster 2 (C2, n=17) showed a 2-year OS of 100% and 48.49%, respectively (HR=4.025 [95% CI = 1.052-15.39], p=0.0419) and differed with higher levels of CCL3/11, CXCL10 and Il-1RA. Cluster 3 (C3, n=3) had the lowest OS, 6-month OS of 0%, and a distinct biological profile with highest levels of CXCL8/12/13, IL1-RA, IL-6, IL-21, HGF, significantly different from C1 (HR=111.4 [95% CI=6.63-1871], p=0.0011) and C2 (HR=30.04 [95% CI=2.686-335.9], p=0.0256). In 12 patients with severe irCRS (G3 and 4) and refractory to steroids, treatment with tocilizumab (TCZ) resulted in 100% resolution. In irHLH patients (n=9), the clusters retained their prognostic impact. Similarly, in irHLH with poor prognosis (irHLH cluster 3, n=3), high levels of CXCL8/12/13, IL-6 and IL-21 were identified. 13 patients with sepsis-like symptoms (irHLH, n=8; or sepsis during ICI, n=5) showed distinct cytokine and immune cell profiles. irHLH showed elevated IL-1-RA, IL-10, IL-18, IFN-γ, CXCL9/10, CCL2/3/4 while sepsis was characterized by increased IL-7. In irHLH, higher HLA-DR+/CD38+ populations were seen in T cells, monocytes, DCs and NK cells. There was significant CD62L downregulation in neutrophils during sepsis. Our decision tree using ferritin, EGF, IL-6 and leukocytes effectively discriminated irHLH from sepsis and G3 irCRS. High CXCL-9 levels predicted the diagnosis and severity of irHLH more accurately than the conventional HScore. Conclusions: We've identified a panel of biomarkers associated with OS. CXCL9 emerges as a superior marker, outperforming HScore. The successful treatment with TCZ underscores the importance of targeted interventions. Our decision tree enhances diagnostic accuracy for sepsis-like symptoms, aiding in the differentiation between irCRS, irHLH, and sepsis. This supports the optimal implementation of personalized strategies.

Association between patient tumour characteristics and five-year survival in Nigerian patients with breast cancer.

e13504 Background: Breast cancer is a heterogeneous disease. The sociodemographic features and biological profile of breast cancer differ globally, especially in women of African descent. In Nigeria, limited studies explore the impact of these breast cancer-related factors on survival. This study evaluated the association between patients' tumour characteristics and survival in breast cancer patients in three regional tertiary cancer treatment centres across Nigeria. Methods: Data were extracted from patients' case files with a histopathologic diagnosis of breast cancer from January 1, 2005 - January 1, 2019. Patients' sociodemographic and clinical features were presented, and survival probabilities were reported; the Log-rank test was used to determine the association between time to death and categorical variables. Results: The study included 1020 patients across the three centres. Five-year survival probability was 0.65; 95% C.I: 0.60- 0.69. Most patients were between ages 30 and 49, and 49% presented with left-sided breast cancer. Patients aged&gt;70 had significantly better survival. Only 40% had Immunohistochemistry (IHC) done, out of which HR+ breast cancer accounted for 43% while triple-negative breast cancer was 30%. Patients who received Herceptin and had molecular subtyping (immunohistochemistry) done had a higher survival probability. Conclusions: Most breast cancer patients in Nigeria present at earlier ages with advanced disease. Regardless of patient tumour characteristics, 5-year survival rates are lower than global rates. Only a few patients have access to optimal breast cancer management, molecular subtyping and targeted treatment inclusive. There is an urgent need to fund the National Cancer Control program to aid in implementing its strategic framework for breast cancer screening and management to improve access to cancer care in Nigeria.

Biological alterations associated with the orthodontic treatment with conventional appliances and aligners: A systematic review of clinical and preclinical evidence

Background&objectivesMechanical forces applied during an orthodontic tooth movement (OTM) propel several biochemical and molecular responses in the periodontal ligament and alveolar bone. Here, we compile the existing clinical and preclinical evidence on these biological changes, aiming to provide a comprehensive discussion on the influence of the mechanical parameters of the OTM in the biological profile of the periodontium. Material and methodsThis systematic integrative review was conducted according to PICOS strategy and PRISMA guidelines. A bibliographic search was performed in three electronic databases (PubMed, Scopus, and Web of Science) to find research articles published until 2023 and written in English. This search resulted in a total of 2279 publications, which were independently assessed by two evaluators using appropriate tools. ResultsForty-six studies were selected for this review. These revealed that compression, and stretching of the periodontal ligament fibers and cells are observed in the initial phase of the OTM. Specifically, on the tension side, high levels of IL-1β, OPG, and TIMPs are identified. On the compression side, an increase of RANKL, RANK, and MMPs levels predominate. ConclusionThis paper describes the release profile of common biomarkers according to the orthodontic protocol, suggesting the most appropriate parameters to keep the teeth and their supporting structures healthy. Overall, this manuscript provides a better understanding of the OTM-associated biological phenomena, also highlighting the importance of early evaluation of oral health, and thus it contributes as a fundamental basis for the development of more effective and safe orthodontic treatments with conventional appliances and aligners.