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Fulltext Multiple Linear Regression for Reconstruction of Gene Regulatory Networks in Solving Cascade Error Problems

Salleh FH, Zainudin S, Arif SM

Adv Bioinformatics, 2017;2017:4827171.
PMID: 28250767 DOI: 10.1155/2017/4827171

Gene regulatory network (GRN) reconstruction is the process of identifying regulatory gene interactions from experimental data through computational analysis. One of the main reasons for the reduced performance of previous GRN methods had been inaccurate prediction of cascade motifs. Cascade error is defined as the wrong prediction of cascade motifs, where an indirect interaction is misinterpreted as a direct interaction. Despite the active research on various GRN prediction methods, the discussion on specific methods to solve problems related to cascade errors is still lacking. In fact, the experiments conducted by the past studies were not specifically geared towards proving the ability of GRN prediction methods in avoiding the occurrences of cascade errors. Hence, this research aims to propose Multiple Linear Regression (MLR) to infer GRN from gene expression data and to avoid wrongly inferring of an indirect interaction (A → B → C) as a direct interaction (A → C). Since the number of observations of the real experiment datasets was far less than the number of predictors, some predictors were eliminated by extracting the random subnetworks from global interaction networks via an established extraction method. In addition, the experiment was extended to assess the effectiveness of MLR in dealing with cascade error by using a novel experimental procedure that had been proposed in this work. The experiment revealed that the number of cascade errors had been very minimal. Apart from that, the Belsley collinearity test proved that multicollinearity did affect the datasets used in this experiment greatly. All the tested subnetworks obtained satisfactory results, with AUROC values above 0.5.
Fulltext Utility of alpha-blockade in a hypotensive pheochromocytoma patient with myocardial infarction

Wahab NA, Zainudin S, AbAziz A, Kamaruddin NA

Med Princ Pract, 2015;24(1):96-8.
PMID: 25428406 DOI: 10.1159/000369021

OBJECTIVE: The aim of this case study is to emphasize the importance of α-blockade in managing a rare complication of an untreated pheochromocytoma.
CLINICAL PRESENTATION AND INTERVENTION: A 41-year-old man with previous bilateral pheochromocytoma presented with chest pain. He was suffering from cardiac failure and persistent hypotension requiring an inotrope. Cardiac markers, an electrocardiogram and an echocardiogram confirmed acute myocardial infarct with poor ejection fraction and global hypokinesia. An (18)F-fluorodeoxyglucose PET/CT scan showed progressive left suprarenal and organ of Zuckerkandl pheochromocytomas. Blood pressure stabilisation proved challenging but was achieved by titrating an incremental dose of α-blocker against a tapering inotropic dose.
CONCLUSION: This case showed the efficacy of an α-blocker despite persistent hypotension in a patient with pheochromocytoma-induced cardiomyopathy.
Adrenal involvement in histoplasmosis

Wahab NA, Mohd R, Zainudin S, Kamaruddin NA

EXCLI J, 2013;12:1-4.
PMID: 27047312

Histoplasmosis infection is endemic in Asia and disseminated histoplasmosis (DH) is one form of its presentation (Benevides et al., 2007[1]). DH commonly affects both adrenal glands. We describe a case of disseminated histoplasmosis complicated with hypercalcaemia in a 75-year-old immunosuppressed patient who presented with bilateral adrenal masses. The fine needle aspiration cytology of the adrenal mass was positive for Histoplasma capsulatum.
Reconstructing gene regulatory networks from knock-out data using Gaussian Noise Model and Pearson Correlation Coefficient

Mohamed Salleh FH, Arif SM, Zainudin S, Firdaus-Raih M

Comput Biol Chem, 2015 Dec;59 Pt B:3-14.
PMID: 26278974 DOI: 10.1016/j.compbiolchem.2015.04.012

A gene regulatory network (GRN) is a large and complex network consisting of interacting elements that, over time, affect each other's state. The dynamics of complex gene regulatory processes are difficult to understand using intuitive approaches alone. To overcome this problem, we propose an algorithm for inferring the regulatory interactions from knock-out data using a Gaussian model combines with Pearson Correlation Coefficient (PCC). There are several problems relating to GRN construction that have been outlined in this paper. We demonstrated the ability of our proposed method to (1) predict the presence of regulatory interactions between genes, (2) their directionality and (3) their states (activation or suppression). The algorithm was applied to network sizes of 10 and 50 genes from DREAM3 datasets and network sizes of 10 from DREAM4 datasets. The predicted networks were evaluated based on AUROC and AUPR. We discovered that high false positive values were generated by our GRN prediction methods because the indirect regulations have been wrongly predicted as true relationships. We achieved satisfactory results as the majority of sub-networks achieved AUROC values above 0.5.
Fulltext Acute renal failure following the use of rosiglitazone in a chronic kidney disease patient

Abdul Ghani R, Zainudin S, Kamaruddin NA, Kong NC

Singapore Med J, 2009 Jan;50(1):e32-4.
PMID: 19224067

Drug-induced acute interstitial nephritis is a well-recognised and important reversible cause of acute renal failure. Peroxisome-proliferator activated receptor-gamma agonists, such as rosiglitazone, have been proven to be safe in chronic kidney disease patients. We describe a 65-year-old man with long-standing diabetes mellitus and hypertension, presenting with a five-day history of fluid overload and uraemic symptoms. There was no ingestion of analgesics, alternative medicine and other nephrotoxic drugs, the only new prescription being rosiglitazone, which was commenced during his last clinic follow-up two weeks prior to presentation. He required haemodialysis with minimal improvement in renal profile, despite cessation of the offending drug. Renal biopsy revealed findings consistent with acute interstitial nephritis. An episode of upper gastrointestinal bleeding with bleeding duodenal ulcer limited the use of steroids. He was treated with a course of mycophenolate mofetil which showed good gradual response and he remained stable with residual renal impairment.
Fulltext De Garengeot hernia: a rare case in an elderly woman and a review of operative approaches

Zainudin S, Hayati F, Arumugam T, Ho KY

BMJ Case Rep, 2021 Apr 16;14(4).
PMID: 33863769 DOI: 10.1136/bcr-2020-240557

De Garengeot hernia is a rare finding of the vermiform appendix inside a femoral hernia sac. We report this occurrence in a 73-year-old woman who presented in the acute setting. There are no standardised surgical approaches and many different techniques have been described in case reports in the literature. We conducted a literature review of and found a total of 113 cases with addition of our case 114 unique cases were included for analysis. Inguinal incision was most cited (n=89). Concomitant laparotomy was needed in 13 patients, however, the association between type of incision and additional laparotomy was not significant (p>0.05). Laparoscopic surgery alone was performed in eight patients. Nine patients had hybrid surgery. The most common hernia repair was through suture technique with non-absorbable material (n=31). Mesh repair was used in 28 cases. More laparoscopic surgeries were done when the disease was diagnosed preoperatively (7/39, p<0.05).
Intravenous calcitriol versus paricalcitol in haemodialysis patients with severe secondary hyperparathyroidism

Abdul Gafor AH, Saidin R, Loo CY, Mohd R, Zainudin S, Shah SA, et al.

Nephrology (Carlton), 2009 Aug;14(5):488-92.
PMID: 19298641 DOI: 10.1111/j.1440-1797.2008.01058.x

Secondary hyperparathyroidism (SHPT) is common among haemodialysis patients. Intensive treatment with calcitriol is often complicated by hypercalcaemia, hyperphosphataemia and elevated calcium phosphorus (Ca X PO(4)) product. Paricalcitol is a vitamin D analogue developed to overcome some of the limitations of calcitriol therapy. The study objectives were to compare the response of intact parathyroid hormone (iPTH) and the incidence of hypercalcaemia, hyperphosphataemia and elevated Ca X PO(4) product in patients with severe SHPT treated with either i.v. calcitriol or i.v. paricalcitol.
Fulltext Extragonadal germ cell tumor presenting in a woman with systemic lupus erythematosus: a case report

Shahrir M, Halim A, Zainudin S, Mohamad R, Yuen LC, Saidin R, et al.

J Med Case Rep, 2010;4:97.
PMID: 20338049 DOI: 10.1186/1752-1947-4-97

Germ cell tumor of the pituitary gland is a very rare occurrence.
Fulltext Multi-Target Approach to Metastatic Adrenal Cell Carcinoma

Wahab NA, Zainudin S, AbAziz A, Mustafa N, Sukor N, Kamaruddin NA

Arch Iran Med, 2016 Sep;19(9):671-3.
PMID: 27631184 DOI: 0161909/AIM.0012

Adrenal cell carcinoma is a rare tumor and more than 70% of patients present with advanced stages. Adrenal cell carcinoma is an aggressive tumor with a poor prognosis. Surgical intervention is the gold standard treatment and mitotane is the only drug approved for the treatment of adrenal cell carcinoma. Until recently in 2012, the etoposide, doxorubicin, cisplatin plus mitotane are approved as first-line therapy based on response rate and progression-free survival. This case illustrates a case of advanced adrenal cell carcinoma in a young girl who presented with huge adrenal mass with inferior vena cava thrombosis and pulmonary embolism. Multi-approach of therapy was used to control the tumor size and metastasis. Therefore, it may prolong her survival rate for up to 5 years and 4 months.
Fulltext Relative adrenal insufficiency amongst hospitalized mild to moderate acute ischemic stroke patients

Wahab NA, Razak NZ, Sukor N, Zainudin S, Razali AM, Mustafa N, et al.

Arch Iran Med, 2015 Feb;18(2):89-93.
PMID: 25644796 DOI: 015182/AIM.006

Acute ischemic stroke is a stressful condition where there is marked increase in the production of cortisol. In the past, adrenal insufficiency in critically ill patients had been shown to be associated with significant morbidity and mortality. To date, there have been no studies performed to determine its prevalence among patients with acute ischemic stroke.
The influence of fenofibrate on lipid profile, endothelial dysfunction, and inflammatory markers in type 2 diabetes mellitus patients with typical and mixed dyslipidemia

Ghani RA, Bin Yaakob I, Wahab NA, Zainudin S, Mustafa N, Sukor N, et al.

J Clin Lipidol, 2013 Sep-Oct;7(5):446-53.
PMID: 24079286 DOI: 10.1016/j.jacl.2013.04.004

BACKGROUND: Type 2 diabetes is associated with early development of endothelial dysfunction. Patients present with typical dyslipidemia (predominantly high levels of triglycerides [TG] and low levels of high-density lipoprotein cholesterol [HDL-C]) or mixed hypercholesterolemia (high levels of low-density lipoprotein cholesterol [LDL-C] and TG with low HDL-C). Normal levels include LDL-C < 100 mg/dL, TG < 135 mg/dL, and HDL-C > 40 mg/dL for men and >50 mg/dL for women.
OBJECTIVE: To determine the effects of 8 weeks' administration of fenofibrate on inflammatory markers, metabolic parameters, and endothelial dysfunction.
METHODS: We administered micronized fenofibrate (Laboratories Fourneir S.A Dijon, France) daily for 8 weeks to 40 dyslipidemic, type 2 diabetes patients with equal numbers in each arm of the typical or mixed dyslipidemia groups. Noninvasive endothelial function assessments were performed and serum inflammatory markers obtained before and after treatment.
RESULTS: The typical group demonstrated significantly greater TG reduction and HDL-C increment, ie, 56% vs, 21.3% (P < .005) and 21% vs. 7.6% (P = .001), respectively, compared with the mixed group. There was greater LDL-C reduction within the mixed group compared with the typical group 21.0% vs. 2.2% (P < .05). Endothelial dysfunction was present in both groups at baseline. After treatment, the typical group demonstrated significant improvement in resting brachial diameter (3.9 mm [interquartile range {IQR} 3.3-4.7] to 4.2 mm [IQR 3.4-4.8], P = .001) compared with no change within the mixed group (3.6 mm [IQR 3.1-5.4] to 3.7 mm [IQR 3.1-5.3], P = .26). Flow-mediated diameter improved significantly in both groups. The mixed group had significantly greater levels of hs-CRP at baseline but no changes throughout the study. The mixed group demonstrated an increase in vascular adhesion molecule-1 from 706 ng/mL (IQR 566-1195) to 845 ng/mL (637-1653; P = .01), a reduction of tumor necrosis factor-α from 7.0 pg/mL (IQR 1.0-43.5) to 2.5 pg/mL (IQR 1.5-13.5; P = .04) throughout the study.
CONCLUSIONS: We effectively compared 8 weeks of fenofibrate therapy in type 2 diabetics with contrasting lipid abnormalities. The typical dyslipidemia group showed significantly greater lipid improvements compared with the mixed dyslipidemia group. Both groups had improvements in endothelial functions that were independent of the lipid levels. We concluded that fibrate therapy in type 2 diabetics is beneficial, especially those with typical dyslipidemia and extends beyond its lipid lowering properties.
KEYWORDS: Endothelial dysfunction; Fenofibrate; High-density lipoprotein cholesterol; Low density lipoprotein; Noninvasive endothelial function assessments; Triglyceride; Vascular cell adhesion molecule-1; hsCRP
Serum IL-6 and IL-1-ra with sequential organ failure assessment scores in septic patients receiving high-volume haemofiltration and continuous venovenous haemofiltration

Ghani RA, Zainudin S, Ctkong N, Rahman AF, Wafa SR, Mohamad M, et al.

Nephrology (Carlton), 2006 Oct;11(5):386-93.
PMID: 17014550

Sepsis is characterized by an uncontrolled release of pro-inflammatory and anti-inflammatory mediators leading to immunoparalysis, cellular and humoral dysfunction, multiorgan dysfunction and death. This study evaluated the efficacy of high-volume haemofiltration (HVHF) compared with continuous venovenous haemofiltration (CVVH) in removing these inflammatory mediators. Clinical responses were assessed with the sequential organ failure assessment (SOFA) score.
An oncological curiosity of a male patient with a huge leiomyoma of the terminal ileum

Zainudin S, Rajanthran SK, Azizan N, Hayati F, Ginawoi J, Suhaimi KA, et al.

Oxf Med Case Reports, 2020 Oct;2020(10):omaa086.
PMID: 33133619 DOI: 10.1093/omcr/omaa086

Leiomyoma is a smooth muscle tumour that can arise in any part of the body especially the uterus. Even though it is traditionally linked with hormonal influence, it can also develop in extrauterine organs with a slight female predominance. It is indistinguishable with gastrointestinal stromal tumour (GIST) histologically. We report a case of a 30-year-old gentleman who presented with a huge painful mass in the right iliac fossa. Computed tomography revealed a 10 × 10 cm homogeneous mass arising from the terminal ileum; he subsequently underwent an open right hemicolectomy. Histology showed a well-circumscribed lesion composed of interlacing bundles of smooth muscle fibres of the submucosa with positive smooth muscle actin and H-Caldesmon stains but negative for DOG-1 and CD117 (c-kit) stains which were consistent with leiomyoma. Despite its rarity, this hormone-related tumour needs to be considered regardless of gender. Immunohistochemistry is paramount as it is histologically identical to GIST.
Diabetes and Ramadan: Practical guidelines 2021

Hassanein M, Afandi B, Yakoob Ahmedani M, Mohammad Alamoudi R, Alawadi F, Bajaj HS, et al.

Diabetes Res Clin Pract, 2022 Jan 08.
PMID: 35016991 DOI: 10.1016/j.diabres.2021.109185

Fasting during Ramadan is one of the five pillars of Islam and is obligatory for all healthy Muslims from the age of puberty. Though individuals with some illness and serious medical conditions, including some people with diabetes, can be exempted from fasting, many will fast anyway. It is of paramount importance that people with diabetes that fast are given the appropriate guidance and receive proper care. The International Diabetes Federation (IDF) and Diabetes and Ramadan (DaR) International Alliance have come together to provide a substantial update to the previous guidelines. This update includes key information on fasting during Ramadan with type 1 diabetes, the management of diabetes in people of elderly ages and pregnant women, the effects of Ramadan on one's mental wellbeing, changes to the risk of macrovascular and microvascular complications, and areas of future research. The IDF-DAR Diabetes and Ramadan Practical Guidelines 2021 seek to improve upon the awareness, knowledge and management of diabetes during Ramadan, and to provide real-world recommendations to health professionals and the people with diabetes who choose to fast.
The ChoCO-W prospective observational global study: Does COVID-19 increase gangrenous cholecystitis?

De Simone B, Abu-Zidan FM, Chouillard E, Di Saverio S, Sartelli M, Podda M, et al.

World J Emerg Surg, 2022 Dec 16;17(1):61.
PMID: 36527038 DOI: 10.1186/s13017-022-00466-4

BACKGROUND: The incidence of the highly morbid and potentially lethal gangrenous cholecystitis was reportedly increased during the COVID-19 pandemic. The aim of the ChoCO-W study was to compare the clinical findings and outcomes of acute cholecystitis in patients who had COVID-19 disease with those who did not.
METHODS: Data were prospectively collected over 6 months (October 1, 2020, to April 30, 2021) with 1-month follow-up. In October 2020, Delta variant of SARS CoV-2 was isolated for the first time. Demographic and clinical data were analyzed and reported according to the STROBE guidelines. Baseline characteristics and clinical outcomes of patients who had COVID-19 were compared with those who did not.
RESULTS: A total of 2893 patients, from 42 countries, 218 centers, involved, with a median age of 61.3 (SD: 17.39) years were prospectively enrolled in this study; 1481 (51%) patients were males. One hundred and eighty (6.9%) patients were COVID-19 positive, while 2412 (93.1%) were negative. Concomitant preexisting diseases including cardiovascular diseases (p

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