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  1. Abubakar M. Umar, Tham, Lik Gin, Natarajan Perumal, Nur Adeela Yasid, Hassan Mohd Daud, Mohd Yunus Shukor
    MyJurnal
    Acetylcholinesterase (AChE) is usually used as an inhibitive assay for insecticides. A lesserknown
    property of AChE is its inhibition by heavy metals. In this work, we evaluate an AChE
    from brains of Clarias batrachus (catfish) exposed to wastes from aquaculture industry as an
    inhibitive assay for heavy metals. We discovered that the AChE was inhibited completely by
    Hg2+, Ag2+, Pb2+, Cu2+, Cd2+, Cr6+ and Zn2+ during initial screening. When tested at various
    concentrations, the heavy metals exhibited exponential decay type inhibition curves. The
    calculated IC50 (mg/L) for the heavy metals Ag2+, Cu2+, Hg2+, Cr6+ and Cd2+ were 0.088, 0.078,
    0.071, 0.87 and 0.913, respectively. The IC50 for these heavy metals are comparable, and some
    are lower than the IC50 values from the cholinesterases from previously studied fish. The assay
    can be carried out in less than 30 minutes at ambient temperature.
  2. Abubakar M. Umar, Tham, Lik Gin, Natarajan Perumal, Nur A. Yasid, Hassan Mohd Daud, Mohd Y. Shukor
    MyJurnal
    In this work we assess the potential of acetylcholinesterase (AChE) from Oreochromis
    mossambicus (Toman) as a sensitive test for the presence of insecticides. The partial purification
    and characterization of a soluble AChE from Oreochromis mossambicus brain tissues using
    affinity chromatography gel (procainamide–Sephacryl S-1000) showed that the partially purified
    AChE was most active on acetylthiocholine (ATC) but had low activities on
    propionylthiocholine (PTC) and butyrylthiocholine (BTC), indicating that the partially purified
    fraction was predominantly AChE. Soluble AChE was partially purified 9.27-fold with a 91.12%
    yield. The partially purified AChE displayed the highest activity on ATC at pH 7 and at 30oC
    using 0.1 M Tris buffer. The enzyme exhibited Michaelis-Menten kinetic constants, Km, for
    ATC, BTC and PTC at 36, 77 and 250 μM, respectively, and the maximum velocities, Vmax, were
    18.75, 0.12 and 0.05 μmol/min/mg protein, respectively. Moreover, the AChE from
    Oreochromis mossambicus presented comparable sensitivity to carbamates and
    organophosphates insecticides than that from Electrophorus electricus and many other fish
    AChE by comparing half maximal inhibitory concentration values. Therefore, the enzyme is a
    valuable source for insecticides detection in Malaysian waters at lower cost.
  3. Abubakar MB, Gan SH
    Niger J Physiol Sci, 2017 Dec 30;32(2):219-225.
    PMID: 29485645
    Although anastrozole (Anas) plays a key role in the management of endocrine sensitive post-menopausal (PM) breast cancer (BC), there is much variability in its efficacy and tolerability. Anas-associated musculoskeletal symptoms (MS) and other adverse reactions, such as hot flashes (HF) and vaginal dryness/dyspareunia (VDD), are common and can affect the quality of life of BC patients, even sometimes leading to treatment withdrawal. The aim of this study was to determine the clinical and demographic factors associated with these adverse events. This is a cross-sectional study in estrogen receptor (ER) positive PM women (n = 92) with stages I to III BC receiving Anas. Multivariate analyses were performed to investigate the factors associated with Anas-induced adverse effects such as MS, HF and VDD. A serum estradiol concentration was undetectable (< 36.7 pmol/L) in 68.1% of patients but was detectable within a normal range (>36.7-88.1 pmol/L) in the other 31.9% of patients, and this group was found to have a lower odds of having at least one adverse effect (AE) compared to those with undetectable levels [adjusted odds ratio (AOR) 0.12, 95% confidence interval (CI) 0.02 to 0.64, p = 0.013]. Women with grades II and III tumors and a family history of BC had a higher odds of AE (grade II: AOR 12.22, CI 1.48 to 100.80, p = 0.020; grade III: AOR 12.95, CI 1.25 to 134.33, p = 0.032) and VDD (AOR 5.99, CI 1.30 to 27.52, p = 0.021), respectively. Patients who received Anas treatment for more than one year had a higher odds of VDD (one to three years: AOR 34.57, CI 3.86, 309.50, p = 0.002; more than 3 years: AOR 27.90, CI 2.21 to 351.84, p = 0.010). Advanced age also lowered the odds of HF (AOR 0.90, CI 0.83 to 1.00, p = 0.049). In conclusion, patients' hormonal environments and durations of Anas treatment may play a role in developing Anas-induced adverse effects.
  4. Abubakar MB, Aini I, Omar AR, Hair-Bejo M
    J Biomed Biotechnol, 2011;2011:414198.
    PMID: 21541235 DOI: 10.1155/2011/414198
    Avian influenza (AI) is a highly contagious and rapidly evolving pathogen of major concern to the poultry industry and human health. Rapid and accurate detection of avian influenza virus is a necessary tool for control of outbreaks and surveillance. The AI virus A/Chicken/Malaysia/5858/2004 (H5N1) was used as a template to produce DNA clones of the full-length NS1 genes via reverse transcriptase synthesis of cDNA by PCR amplification of the NS1 region. Products were cloned into pCR2.0 TOPO TA plasmid and subsequently subcloned into pPICZαA vector to construct a recombinant plasmid. Recombinant plasmid designated as pPICZαA-NS1 gene was confirmed by PCR colony screening, restriction enzyme digestion, and nucleotide sequence analysis. The recombinant plasmid was transformed into Pichia pastoris GS115 strain by electroporation, and expressed protein was identified by SDS-PAGE and western blotting. A recombinant protein of approximately ~28 kDa was produced. The expressed protein was able to bind a rabbit polyclonal antibody of nonstructural protein (NS1) avian influenza virus H5N1. The result of the western blotting and solid-phase ELISA assay using H5N1 antibody indicated that the recombinant protein produced retained its antigenicity. This further indicates that Pichia pastoris could be an efficient expression system for a avian influenza virus nonstructural (NS1).
  5. Abubakar M, Mohamed SB, Abd Halim AA, Tayyab S
    PMID: 36868020 DOI: 10.1016/j.saa.2023.122543
    This study explores the plausible molecular interaction between a potent hepatitis C virus inhibitor, PSI-6206 (PSI), and human serum albumin (HSA), a primary transporter in blood plasma. Results obtained from both computational viz. molecular docking and molecular dynamics (MD) simulation and wet lab techniques such as UV absorption, fluorescence, circular dichroism (CD), and atomic force microscopy (AFM) complemented each other. While docking results identified PSI binding to subdomain IIA (Site I) of HSA by forming six hydrogen bonds, MD simulations signified the complex stability throughout the 50,000 ps. A consistent cutback in the Stern-Volmer quenching constant (Ksv) along with rising temperatures supported the static mode of fluorescence quenching in response to PSI addition and implied the development of the PSI-HSA complex. This discovery was backed by the alteration of the HSA UV absorption spectrum, a larger value (>1010 M-1.s-1) of the bimolecular quenching rate constant (kq) and the AFM-guided swelling of the HSA molecule, in the presence of PSI. Moreover, the fluorescence titration results revealed a modest binding affinity (4.27-6.25×103 M-1) in the PSI-HSA system, involving hydrogen bonds, van der Waals and hydrophobic interactions, as inferred from ΔS = + 22.77 J mol-1 K-1 and ΔH = - 11.02 KJ mol-1values. CD and 3D fluorescence spectra reminded significant adjustment in the 2° and 3° structures and modification in the Tyr/Trp microenvironment of the protein in the PSI-bound state. The results obtained from drug competing experiments also advocated the binding location of PSI in HSA as Site I.
  6. Abubakar M, Mohamad SB, Abd Halim AA, Tayyab S
    J Biomol Struct Dyn, 2024 Feb 05.
    PMID: 38315445 DOI: 10.1080/07391102.2024.2311331
    Molecular docking, molecular dynamics (MD) simulation, atomic force microscopy (AFM) and multi-spectroscopic techniques were selected to unveil the molecular association between the hepatitis B virus (HBV) inhibitor, entecavir (ETR), and the major blood plasma transporter, human serum albumin (HSA). The entire docking and simulation analyses recognized ETR binding to subdomain IIA (Site I) of HSA through hydrogen bonds, hydrophobic and van der Waals forces while maintaining the complex's stability throughout the 100 ns. A gradual lessening in the Stern-Volmer quenching constant (Ksv) with rising temperatures registered ETR-induced quenching of HBV fluorescence as static quenching, thus advising complexation between ETR and HSA. The further advocation of this conclusion was seen from a larger value of the biomolecular quenching rate constant ((kq) > 1010 M-1s-1), changes in the spectra (UV-Vis absorption) of HSA following ETR inclusion and ETR-induced swelling of HSA in the AFM results. The ETR appeared to bind to HSA with moderate affinity (Ka=1.87-1.19×104 M-1) at 290, 300 and 310 K. Significant alterations in the protein's secondary and tertiary structures, including changes in the protein's Tyr/Trp microenvironment, were also detected by circular dichroism and three-dimensional fluorescence spectra when the protein was bound to ETR. The findings of the drug displacement study backed the docking results of Site I as ETR's preferred binding site in HSA.Communicated by Ramaswamy H. Sarma.
  7. Bala AA, Jatau AI, Yunusa I, Mohammed M, Mohammed AH, Isa AM, et al.
    Ther Adv Drug Saf, 2020;11:2042098620935721.
    PMID: 32944213 DOI: 10.1177/2042098620935721
    Introduction: Snakebite envenoming (SBE) is an important occupational and public health hazard especially in sub-Saharan Africa. For optimum management of SBE, adequate knowledge of Snake antivenom (SAV) is very critical among the healthcare practioners in this region. Information related to the knowledge of SAV use in the management of SBE, as well as SAV logistics is scarce among the Health Care Professionals (HCPs) in Nigeria, particularly in the northern region. We therefore aimed to develop, validate and utilize a tool to assess the SAV knowlegde among HCPs in northern Nigeria. We also sought to implement and evaluate an intervention that could improve the SAV knowledge among the HCPs.

    Methods: The proposed study will be conducted in three phases: Phase I will involve the development of the item-pool to be included in the tool, followed by a face, content validity and construct validity. The tool reliability, readability and difficulty index will be determined. Phase II will involve the utilization of the tool to assess baseline SAV knowledge among the HCPs followed by an educational intervention. Multiple Linear Regression analysis will be used to determine the factors associated with SAV knowledge among the HCPs. Lastly, Phase III which will be a repeat of Phase II to assess and evaluate the knowledge after the intervention.

    Discussion: The study design and findings may guide future implementation and streamline the intervention of improving SAV knowledge in HCPs training and practice.

    Lay Summary: Knowledge assessment and educational intervention of snake antivenom among healthcare practitioners in northern Nigeria: a study protocol Snakebite envenoming (SBE) is an important occupational and public health hazard especially in sub-Saharan Africa. For optimum management of SBE, adequate knowledge of snake antivenom (SAV) is very critical among the healthcare practitioners. The baseline knowledge SAV dosage, mode of administration, availability, and logistics is very relevant among healthcare professionals, particularly those that are directly involved in its logistics. It is paramount that SAV is handled and used appropriately. The efforts and advocacy for the availability for more SAV will be in vain if not handled appropriately before they are used. This study protocol aims to develop a tool, to assess SAV knowledge and effects of educational interventions among healthcare professionals (HCPs) in northern Nigeria. This protocol suggests conducting studies in three phases: (a) Development and validation of SAV knowledge assessment tool, (b) Baseline assessment of SAV knowledge assessment tool among HCPs, and (c) Development, implementation and evaluation of an educational intervention to improve SAV knowledge among HCPs in northern Nigeria.

  8. Bala AA, Jatau AI, Yunusa I, Mohammed M, Mohammed AH, Isa AM, et al.
    Toxicon X, 2020 Dec;8:100064.
    PMID: 33319211 DOI: 10.1016/j.toxcx.2020.100064
    Antisnake venom (ASV) is the only specific and standard treatment for snakebite envenoming worldwide. The knowledge of antivenom dosage, mode of administration, availability, and logistics is essential to the healthcare practitioners (HCPs) in the management of snakebites. It is vital for the HCPs involved in the handling of ASVs to have its basic knowledge. The ASV contains proteins and can, therefore, easily get denatured if not handled appropriately, leading to poor therapeutic outcome. It is also essential for clinicians to be aware of the tendency of ASV to cause a severe life-threatening hypersensitivity reaction. There is currently no validated tool for assessing the knowledge of ASV among HCPs. Therefore, we developed and validated a tool for evaluating the HCPs knowledge of ASV. The items included in the tool were first generated from a comprehensive literature review. Face validity were conducted by presenting the drafted tool to ten experts on the subject matter. A validation study was conducted among doctors, pharmacists, nurses, pharmacy technicians, and the general public. The objectives of the study were to test the tool for content validity using the content validity index (CVI), construct validity using contrast group approach, difficulty index, readability, and reliability test using the test-retest method. We developed and validated a final tool containing thirty-three items. The tool was valid for face validity and had a scale-level (average) content validity (S-CVI/Ave) of 0.91. The ASV knowledge of pharmacists was higher than that of doctors, pharmacy technicians, nurses, and the general public (p 
  9. Bala AA, Jatau AI, Yunusa I, Mohammed M, Mohammed AH, Isa AM, et al.
    Ther Adv Infect Dis, 2021 08 19;8:20499361211039379.
    PMID: 34434552 DOI: 10.1177/20499361211039379
    Introduction: Anti-snake venom (ASV) is the standard therapy for the management of snakebite envenoming (SBE). Therefore, the knowledge of ASV among healthcare practitioners (HCPs) is essential for achieving optimal clinical outcomes in snakebite management. This study aimed to assess knowledge of ASV among the HCPs in northern Nigeria.

    Methods: We conducted a cross-sectional study involving eligible HCPs from different healthcare settings in northern Nigeria. The participants were recruited into the study using a combination of online (via Google Form) and face-to-face paper-based survey methods. The ASV knowledge of the respondents was measured using a validated anti-snake venom knowledge assessment tool (AKAT). Inadequate overall knowledge of ASV was defined as scores of 0-69.9%, and 70-100% were considered adequate overall knowledge scores. The predictors of ASV knowledge were determined using multiple logistic regression.

    Results: Three hundred and thirty-one (331) eligible HCPs were included in the study analysis (310 from online and 21 from paper-based survey). Overall, an estimated 12.7% of the participants had adequate knowledge of ASV. Adequate ASV knowledge was higher among physicians compared with other HCPs (21.7%; χ2 = 8.1; p = 0.04). Those without previous training on ASV (adjusted odds ratio [aOR], 0.37; 95% confidence interval [CI], 0.18-0.73; p = 0.004) and who have not previously administered/dispensed ASV (aOR, 0.31; 95% CI, 0.15-0.63; p 

  10. Abubakar M, Sung H, Bcr D, Guida J, Tang TS, Pfeiffer RM, et al.
    Breast Cancer Res, 2018 09 18;20(1):114.
    PMID: 30227867 DOI: 10.1186/s13058-018-1033-8
    BACKGROUND: Limited evidence, mostly from studies in Western populations, suggests that the prognostic effects of lifestyle-related risk factors may be molecular subtype-dependent. Here, we examined whether pre-diagnostic lifestyle-related risk factors for breast cancer are associated with clinical outcomes by molecular subtype among patients from an understudied Asian population.

    METHODS: In this population-based case series, we evaluated breast cancer risk factors in relation to 10-year all-cause mortality (ACM) and 5-year recurrence by molecular subtype among 3012 women with invasive breast cancer in Sarawak, Malaysia. A total of 579 deaths and 314 recurrence events occurred during a median follow-up period of ~ 24 months. Subtypes (luminal A-like, luminal B-like, HER2-enriched, triple-negative) were defined using immunohistochemical markers for hormone receptors and human epidermal growth factor receptor 2 (HER2) in conjunction with histologic grade. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between risk factors and ACM/recurrence were estimated in subtype-specific Cox regression models.

    RESULTS: We observed heterogeneity in the relationships between parity/breastfeeding, age at first full-term pregnancy (FFP), family history, body mass index (BMI), and tumor subtype (p value  30 vs 

  11. Rehman F, Abubakar M, Ridzwan NFW, Mohamad SB, Abd Halim AA, Tayyab S
    PMID: 38061108 DOI: 10.1016/j.saa.2023.123641
    The binding mode of antineoplastic antimetabolite, floxuridine (FUDR), with human serum albumin (HSA), the leading carrier in blood circulation, was ascertained using multi-spectroscopic, microscopic, and computational techniques. A static fluorescence quenching was established due to decreased Ksv values with rising temperatures, suggesting FUDR-HSA complexation. UV-vis absorption spectral results also supported this conclusion. The binding constant, Ka values, were found within 9.7-7.9 × 103 M-1 at 290, 300, and 310 K, demonstrating a moderate binding affinity for the FUDR-HSA system. Thermodynamic data (ΔS = +46.35 J.mol-1.K-1 and ΔH = -8.77 kJ.mol-1) predicted the nature of stabilizing forces (hydrogen-bonds, hydrophobic, and van der Waals interactions) for the FUDR-HSA complex. Circular dichroism spectra displayed a minor disruption in the protein's 2° and 3° structures. At the same time, atomic force microscopy images proved variations in the FUDR-HSA surface morphology, confirming its complex formation. The protein's microenvironment around Trp/Tyr residues was also modified, as judged by 3-D fluorescence spectra. FUDR-bound HSA showed better resistance against thermal stress. As disclosed from ligand displacement studies, the FUDR binding site was placed in subdomain IIA (Site I). Further, the molecular docking analysis corroborated the competing displacement studies. Molecular dynamics evaluations revealed that the complex achieved equilibrium during simulations, confirming the FUDR-HSA complex's stability.
  12. Abubakar M, Ahmad N, Ghafoor A, Latif A, Ahmad I, Atif M, et al.
    Front Pharmacol, 2021;12:640555.
    PMID: 33867989 DOI: 10.3389/fphar.2021.640555
    Background: The current study is conducted with the aim to the fill the gap of information regarding treatment outcomes and variables associated with unsuccessful outcome among XDR-TB patients from Pakistan. Methods: A total of 404 culture confirmed XDR-TB patients who received treatment between 1st May 2010 and June 30, 2017 at 27 treatment centers all over Pakistan were retrospectively followed until their treatment outcomes were reported. A p-value <0.05 reflected a statistical significant association. Results: The patients had a mean age 32.9 ± 14.1 years. The overall treatment success rate was 40.6% (95% confidence interval [CI]:35.80-45.60%). A total of 155 (38.4%) patients were declared cured, 9 (2.2%) completed treatment, 149 (36.9%) died, 60 (14.9%) failed treatment and 31 (7.7%) were lost to follow up (LTFU). The results of the multivariate binary logistic regression analysis revealed that the patients' age of >60 years (OR = 4.69, 95%CI:1.57-15.57) and receiving high dose isoniazid (OR = 2.36, 95%CI:1.14-4.85) had statistically significant positive association with death, whereas baseline body weight >40 kg (OR = 0.43, 95%CI:0.25-0.73) and sputum culture conversion in the initial two months of treatment (OR = 0.33, 95%CI:0.19-0.58) had statistically significant negative association with death. Moreover, male gender had statistically significant positive association (OR = 1.92, 95%CI:1.04-3.54) with LTFU. Conclusion: The treatment success rate (40.6%) of XDR-TB patients in Pakistan was poor. Providing special attention and enhanced clinical management to patients with identified risk factors for death and LTFU in the current cohort may improve the treatment outcomes.
  13. Kankia MU, Baloo L, Danlami N, Samahani WN, Mohammed BS, Haruna S, et al.
    Materials (Basel), 2021 Oct 22;14(21).
    PMID: 34771834 DOI: 10.3390/ma14216308
    In the industries of petroleum extraction, a large volume of oily sludge is being generated. This waste is usually considered difficult to dispose of, causing environmental and economic issues. This study presented the novel experimental method of manufacturing mortar used in civil construction by cement and oily sludge ash (OSA). The defined method was described with a logical experimental study conducted to examine a feasible manufacturing method for casting cement-based mortars by partially replacing cement with OSA. Replacement concentrations for OSA ranged from 0 to 20 percent by cement weight, while the water-to-cement (w/c) ratio was varied from 0.4 to 0.8, and the amount of sand was kept constant. The strengths and absorption rate of the mortar were monitored for 28 days. The OSA contains a crystalline structure with packs of angular grains. Because of OSA in the cement-based mortar mixtures and water-to-cement ratios, the mechanical strength was improved significantly. However, the water absorption trend increased linearly. Using variance analysis, the influence of OSA and w/c ratio on the behavior of mortar was acquired. The developed models were significant for all p-value reactions of <5%. Numerical optimization results showed that the best mixture can be obtained by replacing 8.19 percent cement with OSA and 0.52 as a ratio of w/c.
  14. Rizwi FA, Abubakar M, Puppala ER, Goyal A, Bhadrawamy CV, Naidu VGM, et al.
    PMID: 37522565 DOI: 10.1615/JEnvironPatholToxicolOncol.2023045403
    According to the World Health Organization (WHO), cancer is the second-highest cause of mortality worldwide, killing nearly 9.6 million people annually. Despite the advances in diagnosis and treatment during the last couple of decades, it remains a serious concern due to the limitations of currently available cancer management strategies. Therefore, alternative strategies are highly required to overcome these glitches. In addition, many etiological factors such as environmental and genetic factors initiate the activation of the Janus kinase (JAK)-signal transducer and activator of the transcription (STAT) pathway. This aberrant activation of the JAK-STAT pathway has been reported in various disease states, including inflammatory conditions, hematologic malignancies, and cancer. For instance, many patients with myeloproliferative neoplasms carry the acquired gain-of-function JAK2 V617F somatic mutation. This knowledge has dramatically improved our understanding of pathogenesis and has facilitated the development of therapeutics capable of suppressing the constitutive activation of the JAK-STAT pathway. Our aim is not to be expansive but to highlight emerging ideas towards preventive therapy in a modern view of JAK-STAT inhibitors. A series of agents with different specificities against different members of the JAK family of proteins is currently undergoing evaluation in clinical trials. Here we give a summary of how JAK-STAT inhibitors function and a detailed review of current clinical drugs for managing cancer as a new therapeutic approach.
  15. Murphy N, Cross AJ, Abubakar M, Jenab M, Aleksandrova K, Boutron-Ruault MC, et al.
    PLoS Med, 2016 Apr;13(4):e1001988.
    PMID: 27046222 DOI: 10.1371/journal.pmed.1001988
    BACKGROUND: Obesity is positively associated with colorectal cancer. Recently, body size subtypes categorised by the prevalence of hyperinsulinaemia have been defined, and metabolically healthy overweight/obese individuals (without hyperinsulinaemia) have been suggested to be at lower risk of cardiovascular disease than their metabolically unhealthy (hyperinsulinaemic) overweight/obese counterparts. Whether similarly variable relationships exist for metabolically defined body size phenotypes and colorectal cancer risk is unknown.

    METHODS AND FINDINGS: The association of metabolically defined body size phenotypes with colorectal cancer was investigated in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Metabolic health/body size phenotypes were defined according to hyperinsulinaemia status using serum concentrations of C-peptide, a marker of insulin secretion. A total of 737 incident colorectal cancer cases and 737 matched controls were divided into tertiles based on the distribution of C-peptide concentration amongst the control population, and participants were classified as metabolically healthy if below the first tertile of C-peptide and metabolically unhealthy if above the first tertile. These metabolic health definitions were then combined with body mass index (BMI) measurements to create four metabolic health/body size phenotype categories: (1) metabolically healthy/normal weight (BMI < 25 kg/m2), (2) metabolically healthy/overweight (BMI ≥ 25 kg/m2), (3) metabolically unhealthy/normal weight (BMI < 25 kg/m2), and (4) metabolically unhealthy/overweight (BMI ≥ 25 kg/m2). Additionally, in separate models, waist circumference measurements (using the International Diabetes Federation cut-points [≥80 cm for women and ≥94 cm for men]) were used (instead of BMI) to create the four metabolic health/body size phenotype categories. Statistical tests used in the analysis were all two-sided, and a p-value of <0.05 was considered statistically significant. In multivariable-adjusted conditional logistic regression models with BMI used to define adiposity, compared with metabolically healthy/normal weight individuals, we observed a higher colorectal cancer risk among metabolically unhealthy/normal weight (odds ratio [OR] = 1.59, 95% CI 1.10-2.28) and metabolically unhealthy/overweight (OR = 1.40, 95% CI 1.01-1.94) participants, but not among metabolically healthy/overweight individuals (OR = 0.96, 95% CI 0.65-1.42). Among the overweight individuals, lower colorectal cancer risk was observed for metabolically healthy/overweight individuals compared with metabolically unhealthy/overweight individuals (OR = 0.69, 95% CI 0.49-0.96). These associations were generally consistent when waist circumference was used as the measure of adiposity. To our knowledge, there is no universally accepted clinical definition for using C-peptide level as an indication of hyperinsulinaemia. Therefore, a possible limitation of our analysis was that the classification of individuals as being hyperinsulinaemic-based on their C-peptide level-was arbitrary. However, when we used quartiles or the median of C-peptide, instead of tertiles, as the cut-point of hyperinsulinaemia, a similar pattern of associations was observed.

    CONCLUSIONS: These results support the idea that individuals with the metabolically healthy/overweight phenotype (with normal insulin levels) are at lower colorectal cancer risk than those with hyperinsulinaemia. The combination of anthropometric measures with metabolic parameters, such as C-peptide, may be useful for defining strata of the population at greater risk of colorectal cancer.

  16. Grootes I, Keeman R, Blows FM, Milne RL, Giles GG, Swerdlow AJ, et al.
    Eur J Cancer, 2022 Sep;173:178-193.
    PMID: 35933885 DOI: 10.1016/j.ejca.2022.06.011
    BACKGROUND: Predict Breast (www.predict.nhs.uk) is an online prognostication and treatment benefit tool for early invasive breast cancer. The aim of this study was to incorporate the prognostic effect of progesterone receptor (PR) status into a new version of PREDICT and to compare its performance to the current version (2.2).

    METHOD: The prognostic effect of PR status was based on the analysis of data from 45,088 European patients with breast cancer from 49 studies in the Breast Cancer Association Consortium. Cox proportional hazard models were used to estimate the hazard ratio for PR status. Data from a New Zealand study of 11,365 patients with early invasive breast cancer were used for external validation. Model calibration and discrimination were used to test the model performance.

    RESULTS: Having a PR-positive tumour was associated with a 23% and 28% lower risk of dying from breast cancer for women with oestrogen receptor (ER)-negative and ER-positive breast cancer, respectively. The area under the ROC curve increased with the addition of PR status from 0.807 to 0.809 for patients with ER-negative tumours (p = 0.023) and from 0.898 to 0.902 for patients with ER-positive tumours (p = 2.3 × 10-6) in the New Zealand cohort. Model calibration was modest with 940 observed deaths compared to 1151 predicted.

    CONCLUSION: The inclusion of the prognostic effect of PR status to PREDICT Breast has led to an improvement of model performance and more accurate absolute treatment benefit predictions for individual patients. Further studies should determine whether the baseline hazard function requires recalibration.

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