Coastal Flood risk assessment using ensemble multi-criteria decision-making with machine learning approaches.

Coastal areas are at a higher risk of flooding, and novel changes in the climate are induced to raise the sea level. Flood acceleration and frequency have increased recently because of unplanned infrastructural conveniences and anthropogenic activities. Therefore, the assessment of flood susceptibility mapping is considered the most significant flood management model. In this paper, flood susceptibility identification is performed by applying the innovative Multi-criteria decision-making model (MCDM) called Analytical Hierarchy Process (AHP) by ensembles with Support vector machine (AHP-SVM) and Decision Tree (AHP-DT). This model combines two Representation concentration pathway (RCP) scenarios such as RCP 2.6 & RCP 8.5. The factors influencing the coastal flooding in Bandar Abbas, Iran, identified through Flood susceptibility mapping. Multi-criteria decision-making (MCDM) has been applied to evaluate the Coastal flood conditioning factors, and ensemble machine learning (ML) approaches are employed for Coastal risk factor (CRF) prediction and classification. The statistical variances are measured through Friedman and Wilcoxon signed rank tests and statistical metrics such as Accuracy, sensitivity, and specificity. Among the models, AHP-DT obtained an improved AUC value of ROC as 0.95. After applying the ML models, the northern and western park of Raidak Basin River recognises very low and low flood susceptibility because of their topographic characteristics. The eastern part of the middle section fell very high and high CFSM. Observed from this result analysis, the people living nearer to the coastline are distributed by the low to medium exposure in the region of the west and middle of the considered study area. The results of this study can help decision-makers take necessary risk reduction approaches in the high-risk flooding zones of the coastal system.

Evaluating the initial impact of the Riyadh Epilepsy Awareness Campaign.

OBJECTIVE: We determine the impact of an educational awareness campaign on the level of knowledge and the attitude of the Saudi population in Riyadh, Saudi Arabia in an attempt to improve the awareness and reduce the social stigma associated with epilepsy. METHODS: The Saudi Epilepsy Society organized a citywide awareness campaign in 2013. A survey consisting of 11 questions pertaining to epilepsy awareness was distributed to Saudi citizens living in Riyadh, aged 15 years and above, in malls, health clubs, mosques, universities, and schools during that campaign. The same questionnaire was administered before and after the awareness campaign to the same individuals on the same day to assess the impact of the campaign (n=2118). RESULTS: The epilepsy awareness campaign significantly raised the general knowledge about epilepsy: 1519 before vs. 1944 after (P<0.001) would allow their children to interact with an individual who had epilepsy; 1567 before vs. 688 after (P<0.001) would not want their children to marry an individual with epilepsy. Eight hundred twenty six before vs. 47 after (P<0.001) thought that epilepsy is untreatable. Regarding the causes of epilepsy, 1663 before vs. 896 after (P<0.001) believed that epilepsy is caused by supernatural powers, and 1224 before vs. 1874 after (P<0.001) chose brain disease as a cause of epilepsy. CONCLUSION: These findings suggest that epilepsy awareness campaigns can close knowledge gaps. A long-term reevaluation may be needed to assess awareness sustainability.

Obstructive Jaundice Caused by Metastatic Neuroendocrine Tumor of the Ampulla of Vater in a Young Adult: A Case Report.

Introduction: Ampullary neuroendocrine tumors (NETs) are usually diagnosed in the 5th-6th decades of life, and no cases were reported in <20 years of age. We report a rare case, presenting at a very young age, of well-differentiated NET involving the ampulla of Vater with lymph node metastasis. Case Presentation: An 18-year-old man presented with a 3-month history of upper abdominal pain and jaundice. Abdominal ultrasound showed a dilated common bile duct, and endoscopic retrograde cholangiopancreatography revealed two duodenal polypoid lesions, one of them overlying the ampulla of Vater, with an erythematous and ulcerated surface. Histopathological examination confirmed the diagnosis of NET grade 1. Octreotide scan revealed 2 para-aortic lymph nodes with intense radiotracer uptake. The patient had undergone Whipple surgery with para-aortic lymph node dissection. Histopathological examination of the surgical specimens was confirmatory of NET grade 2 and paraganglioma in a few of the dissected lymph nodes. Postoperatively, the patient was kept on monthly intramuscular octreotide. Follow-up gallium-68 DOTATATE is unremarkable apart from an avid left para-aortic lymph node which is showing stability over 12 months of follow-up. Conclusion: This case demonstrates that NETs of the ampulla of Vater can present at a very young age. Radical surgical excision with extended lymph node dissection and postoperative octreotide is associated with better patient outcomes and survival.

The Relationship Between Breast Density and Breast Cancer Surgical Outcomes: A Systematic Review.

This study aims to investigate the relationship between mammographic breast density and the surgical outcomes of breast cancer. PubMed, SCOPUS, Web of Science, Science Direct, and the Wiley Library were systematically searched for relevant literature. Rayyan QRCI was employed throughout this comprehensive process. Our results included ten studies with a total of 5017 women diagnosed with breast cancer. The follow-up duration ranged from 1 year to 15.1 years. Eight out of the twelve included studies reported that low mammographic breast density was significantly associated with no local recurrence, metachronous contralateral breast cancer, and fewer challenges in the preoperative and intraoperative phases. On the other hand, four studies reported that mammographic breast density is not linked to disease recurrence, survival, re-excision, or an incomplete clinical and pathological response. There is a significant association between low mammographic breast density and reduced challenges in the preoperative and intraoperative phases, as well as no local recurrence and fewer mastectomy cases. However, the link between mammographic breast density and disease recurrence, survival, re-excision, and incomplete clinical and pathological response is less clear, with some studies reporting no significant association. The findings suggest that mammographic breast density may play a role in certain aspects of breast cancer outcomes, but further research is needed to fully understand its impact.

Salivary interleukin-17A and interleukin-18 levels in patients with celiac disease and periodontitis.

Background: An increased level of interleukin-17A and interleukin-18 in the serum and intestinal mucosa of celiac disease patients reflecting the severity of villous atrophy and inflammation was documented. Thus, the objective of this study was to evaluate the concentrations of salivary-17A, interleukin-1 beta, and interleukin-18 in patients with celiac disease who are on a gluten-free diet, both with and without periodontitis, and to compare these levels with those in healthy individuals. Methods: The study involved 23 participants with serologically confirmed celiac disease (CD) and 23 control subjects. The CD patients had been following a gluten-free diet (GFD) for a minimum of 1 year and had no other autoimmune disorders. The research involved collecting demographic data, conducting periodontal examinations, gathering unstimulated whole saliva, and performing enzyme-linked immunosorbent assays to measure salivary interleukin-17A, interleukin-1 beta, and interleukin-18 levels. Spearman's correlation analysis was utilized to explore the relationships between CD markers in patients on a GFD and their periodontal clinical findings. Results: The periodontal findings indicated significantly lower values in celiac disease patients adhering to a gluten-free diet compared to control subjects (p = 0.001). No significant differences were found in salivary IL-17A, IL-18, and IL-1B levels between celiac disease patients and control subjects. Nevertheless, the levels of all interleukins were elevated in periodontitis patients in both the celiac and control groups. The IL-1 Beta level was significantly higher in periodontitis patients compared to non-periodontitis patients in the control group (p = 0.035). Significant negative correlations were observed between serum IgA levels and plaque index (r = -0.460, p = 0.010), as well as gingival index (r = -0.396, p = 0.030) in CD patients on a gluten-free diet. Conclusion: Celiac disease patients on gluten-free diet exhibited better periodontal health compared to control subjects. However, increased levels of salivary IL-17A, IL-18 and IL-1B levels were associated with periodontitis. Additionally, serum IgA level was significantly inversely associated with periodontitis clinical manifestations and with salivary inflammatory mediators in CD patients on GFD.

A novel metaheuristics with adaptive neuro-fuzzy inference system for decision making on autonomous unmanned aerial vehicle systems.

Recently, autonomous systems have received considerable attention amongst research communities and academicians. Unmanned aerial vehicles (UAVs) find useful in several applications like transportation, surveillance, disaster management, and wildlife monitoring. One of the important issues in the UAV system is energy efficiency, which can be resolved by the use of clustering approaches. In addition, high resolution remote sensing images need to be classified for effective decision making using deep learning (DL) models. Though several models are available in the literature, only few approaches have focused on the clustering and classification processes in UAV networks. In this aspect, this paper designs a novel metaheuristic with an adaptive neuro-fuzzy inference system for decision making named MANFIS-DM technique on autonomous UAV systems. The proposed MANFIS-DM technique intends to effectively organize the UAV networks into clusters and then classify the images into appropriate class labels. The proposed MANFIS-DM technique encompasses two major stages namely quantum different evolution based clustering (QDE-C) technique and ANFIS based classification technique. Primarily, the QDE-C technique involves the design of a fitness function involving three parameters namely average distance, distance to UAVs, and UAV degree. Besides, the image classification model involves a set of subprocesses namely DenseNet based feature extraction, Adadelta based hyperparameter optimization, and ANFIS based classification. The design of QDE-C algorithm with classification model for autonomous UAV systems show the novelty of the work. The experimental result analysis of the MANFIS-DM method is carried out against benchmark dataset and the results ensured the enhanced performance of the MANFIS-DM technique over the other methods with the maximum accuy of 99.13%.

Clinical Characteristics and Outcomes of Vaccinated VS Non-Vaccinated Critically Ill COVID-19 Patients: Retrospective Observation Study.

Objective: We aim to identify the clinical characteristics and outcome of vaccine breakthrough infection in critically ill COVID-19 patients and to compare the clinical course of disease between vaccinated and non-vaccinated patients. Methods: A retrospective review of all adult patients aged ≥18 years admitted to the ICU in King Fahd Hospital of the University in Saudi Arabia with positive COVID-19 RT-PCR test between the period of January 1st to August 31st, 2021, were included. The recruited patients were grouped in to "vaccinated and non-vaccinated group" based on their immunization status. The demographic data, co-morbidities, modality of oxygen support, ICU length of stay (ICU LOS) and mortality were collected and analyzed. Results: A total of 167 patients were included. Seventy-two patients (43%) were vaccinated. Cardiovascular diseases were higher among the vaccinated group (33.3% vs 12.6%, p value <0.001). Requirements of Non-invasive ventilation was significantly lower in vaccinated group compared to non-vaccinated group (73.6% vs 91.6%, p value <0.011). The rates of intubation were similar between both groups. The total intubation days was longer in non-vaccinated patients compared to vaccinated patients and the median duration of intubation was 8 days vs 2 days, respectively (p value 0.027). In subgroup analysis, the P/F ratio was significantly higher in patients who received two doses of vaccine compared to single dose (p value <0.002). Conclusion: In critically ill COVID-19 patients, the vaccinated group has significantly less need for Non-invasive ventilation, fewer intubation days and less hypoxia compared to non-vaccinated patients. We recommend more policies and public education nationwide and worldwide to encourage vaccination and raise awareness of the general population.

Is Sacral Neuromodulation a Treatment Option for Primary Bladder Neck Obstruction?

Here, we present the first reported case that used sacral neuromodulation as a treatment option for bladder neck obstruction in a 48-year-old man who presented with a long-standing history of lower urinary tract symptoms such as storage and voiding symptoms unresponsive to conservative and medical treatments, including chemodenervation. The patient was diagnosed with primary bladder neck obstruction (PBNO) using a urodynamic study, voiding cystourethrography, and cystoscopy. Sacral neuromodulation was used because the patient refused bladder neck incision because of the risk of retrograde ejaculation. The patient reported significant improvement in symptoms with no obstructive pattern on follow-up uroflowmetry after six months. The use of alpha-blockers, bladder neck incision, and Botox injection into the bladder neck to treat PBNO has been reported. The successful use of sacral neuromodulation to treat PBNO has not been reported before.

Outcomes and surgical nuances in management of giant pituitary adenomas: a review of 108 cases in the endoscopic era.

OBJECTIVE: Giant (maximum diameter ≥ 4 cm) pituitary macroadenomas are complex tumors that require resection for decompression of optic nerves, relief of mass effect, and symptom improvement. Given the lack of surgical accessibility, the lateral extent of the lesions, and the invasion of the cavernous sinus, management presents a significant challenge. Transsphenoidal, transcranial, and combined approaches have been viable options for resection. The authors present their findings from a large series of patients to characterize giant pituitary adenomas, document outcomes, and outline surgical nuances in resection of these tumors. METHODS: The authors reviewed 887 consecutive patients who underwent resection of pituitary adenomas at a single institution. From this group, 108 patients with giant pituitary adenomas who underwent resection between January 1, 2002, and December 31, 2020, were identified for inclusion in the study. The patient demographics, clinical presentation, tumor imaging characteristics, surgical approaches, and postoperative outcomes were analyzed using descriptive statistics. RESULTS: The mean preoperative tumor diameter in this cohort was 4.6 ± 0.8 cm, with a mean volume of 25.9 ± 19.2 cm3. Ninety-seven patients underwent transsphenoidal approaches only, 3 underwent transcranial resection, and 8 patients underwent a combined approach. Gross-total resection was achieved in 42 patients. Tumor stability without a need for additional therapy was achieved in 77 patients, with 26 patients undergoing subsequent adjuvant radiotherapy. Among 100 patients with sufficient follow-up, 14 underwent adjuvant therapy-repeat operation and/or adjuvant radiation therapy-because of recurrence or tumor progression. Six patients with recurrence were observed without additional treatment. Overall, the morbidity associated with removal of these lesions was 11.1%; the most common morbidities were cerebrospinal fluid leak (5 patients, 4.6%) and hydrocephalus (4 patients, 3.7%). One death due to postoperative pituitary apoplexy of the residual tumor and malignant cerebral edema occurred in this cohort. CONCLUSIONS: Giant pituitary tumors still represent a surgical challenge, with significant morbidity. Gross-total resection occurs in a minority of patients. Surgical goals for removal of giant pituitary tumors should include attempts at removal of most tumor tissue to minimize the risk of residual tumor apoplexy by tailoring the approach along the major axis of the tumor. Experience with both transsphenoidal and multiple transcranial techniques is necessary for minimizing complications and improving outcomes.

E-cigarettes and Vaping: A Smoking Cessation Method or Another Smoking Innovation?

The prevalence of using e-cigarettes (vaping) has risen rapidly since its introduction in 2007, mostly among male youth. Although research on the health risks of e-cigarettes is still limited, there is growing evidence of debilitating pulmonary conditions and general immune weakness from e-cigarettes, leading to various infections. Moreover, there are concerns that vaping could be used as a new model of cannabis consumption, increasing cannabis addiction among adolescents. With well-known health risks from traditional smoking, e-cigarettes are viewed as a safe way of smoking, appealing more to youth. Additionally, extensive e-cigarette marketing boosted by the internet and fame has resulted in worries that e-cigarettes can lead to a renormalization of cigarette smoking and can be used as a new method to consume vaporized drugs. Although the concern that e-cigarettes are as harmful as traditional smoking has been raised, youth and most healthcare providers remain relatively unaware. Therefore, this review explored the association between e-cigarettes and traditional smoking. With the introduction of e-cigarettes in the last two decades, the topic is still new and less studied. Therefore, this review will help us understand the topic to better care for e-cigarette smokers and reduce the increasing public health burden from vaping.

Primary Renal Synovial Sarcoma Presenting as Haemorrhagic Shock: A Rare Presentation.

Primary synovial sarcoma (PSS) of the kidney is considered the rarest type of all renal sarcomas with specific chromosomal translocation t (X; 18) (p11.2; q11.2). We report the case of a 65-year-old man with no medical conditions who presented to the emergency department with sudden severe right flank pain associated with haemodynamic instability and haemorrhagic shock. Computed tomography (CT) of the abdomen and pelvis revealed a right renal mass. A right open radical nephrectomy was performed. Histopathology revealed a monophasic synovial sarcoma. The patient received six cycles of docetaxel and gemcitabine as adjuvant chemotherapy. No sign of recurrence was seen on a follow-up CT urogram. This rare tumour often presents atypically, and clear guidelines regarding appropriate treatment are lacking. Our case showed that treatment with docetaxel/gemcitabine after an open radical nephrectomy is promising.

Extended DOAC therapy in patients with VTE and potential risk of recurrence: A systematic review and meta-analysis.

BACKGROUND: Guidelines recommend at least 3 months of anticoagulation for venous thromboembolism (VTE). Evidence supporting indefinite anticoagulation exists in certain conditions; however, for many patients, uncertainty regarding when to discontinue anticoagulation persists. OBJECTIVE: We aimed to investigate the efficacy and safety of extended direct oral anticoagulants (DOAC) therapy in patients with VTE and clinical uncertainty regarding extended anticoagulation. METHODS: We searched EMBASE, MEDLINE, PubMed, and Cochrane Central Register of Controlled Trials databases for randomized control trials examining extended anticoagulation with DOACs as compared to non-extended therapy for the treatment of VTE. RESULTS: Of 560 citations identified by the search, three studies were eligible. Extended anticoagulation reduced VTE recurrence (relative risk [RR] 0.18, 95% confidence interval [CI] 0.12 to 0.25), and mortality (RR 0.39, 95% CI 0.19 to 0.80) with a low total number of deaths in the DOAC group (n = 12) versus placebo (n = 18). Extended anticoagulation increased clinically relevant non-major bleedings (RR 2.51, 95% CI 1.37 to 4.59). There was no difference in rates of major bleeding (RR 1.87, 95% CI 0.19 to 17.85); however, there was a low number of major bleeding events in both DOAC (n = 9) and placebo groups (n = 4). The results were mostly driven by one study (AMPLIFY-EXT), with significant heterogeneity between studies noticed when assessing bleeding outcomes. CONCLUSION: Extended DOAC therapy for 1 year in patients with clinical uncertainty for ongoing anticoagulation can reduce VTE recurrence and mortality; however, it could increase clinically relevant non-major bleeding events.

Lhermitte-Duclos Disease with Cervical Arteriovenous Fistula.

Lhermitte-Duclos disease is a rare condition with less than 250 cases reported in the literature. It was considered a neoplastic or hamartomatous growth in the cerebellum. It commonly presents with symptoms of high intracranial pressure or obstructive hydrocephalus. Surgical resection is often curative. The lesion is associated with PTEN gene mutation, and it is considered to be one of the diagnostic criteria of Cowden's syndrome. Vascular tumors are reported in this syndrome, including glioblastomas and meningiomas. Furthermore, central nervous system vascular lesions were also reported in Lhermitte-Duclos disease, such as deep venous anomalies and brain arteriovenous fistulas. A report of an asymptomatic spinal cervical AVF in a patient with Lhermitte-Duclos disease was published in 2006. We present the second case of Lhermitte-Duclos disease associated with an asymptomatic spinal cervical AVF in a 17-year-old young woman with literature review of central nervous system vascular lesions in Lhermitte-Duclos disease.

Socioeconomic Factors and Severity of Coronary Artery Disease in Patients Undergoing Coronary Angiography: A Multicentre Study of Arabian Gulf States.

INTRODUCTION: Coronary artery disease (CAD) is a leading cause of death worldwide. The association of socioeconomic status with CAD is supported by numerous epidemiological studies. Whether such factors also impact the number of diseased coronary vessels and its severity is not well established. MATERIALS AND METHODS: We conducted a prospective multicentre, multi-ethnic, cross sectional observational study of consecutive patients undergoing coronary angiography (CAG) at 5 hospitals in the Kingdom of Saudi Arabia and the United Arab Emirates. Baseline demographics, socioeconomic, and clinical variables were collected for all patients. Significant CAD was defined as ≥70% luminal stenosis in a major epicardial vessel. Left main disease (LMD) was defined as ≥50% stenosis in the left main coronary artery. Multi-vessel disease (MVD) was defined as having >1 significant CAD. RESULTS: Of 1,068 patients (age 59 ± 13, female 28%, diabetes 56%, hypertension 60%, history of CAD 43%), 792 (74%) were from urban and remainder (26%) from rural communities. Patients from rural centres were older (61 ± 12 vs 58 ± 13), and more likely to have a history of diabetes (63 vs 54%), hypertension (74 vs 55%), dyslipidaemia (78 vs 59%), CAD (50 vs 41%) and percutaneous coronary intervention (PCI) (27 vs 21%). The two groups differed significantly in terms of income level, employment status and indication for angiography. After adjusting for baseline differences, patients living in a rural area were more likely to have significant CAD (adjusted OR 2.40 [1.47, 3.97]), MVD (adjusted OR 1.76 [1.18, 2.63]) and LMD (adjusted OR 1.71 [1.04, 2.82]). Higher income was also associated with a higher risk for significant CAD (adjusted OR 6.97 [2.30, 21.09]) and MVD (adjusted OR 2.49 [1.11, 5.56]), while unemployment was associated with a higher risk of significant CAD (adjusted OR 2.21, [1.27, 3.85]). CONCLUSION: Communal and socioeconomic factors are associated with higher odds of significant CAD and MVD in the group of patients referred for CAG. The underpinnings of these associations (e.g. pathophysiologic factors, access to care, and system-wide determinants of quality) require further study.

Oral Nystatin Versus Intravenous Fluconazole as Neonatal Antifungal Prophylaxis: Non-inferiority Trial.

BACKGROUND: Fluconazole has shown to be effective in reducing both colonization and invasive Candida infection (ICI) in ELBW neonates; we conducted a randomized trial to compare oral nystatin with intravenous fluconazole for prophylaxis against invasive Candidiasis in high risk neonates. MATERIALS AND METHODS: By using SPSS, preterm less than 30 weeks gestation and/or birth weight 1200 grams or less assigned to receive either intravenous Fluconazole (6 mg/kg q72 hr for 1(st) week then q48 h for 6 wks) or oral Nystatin (100,000 unit q8 hr for 6 wks). The medications commenced at one week of age after obtaining the base line investigations and check for Candida colonization by urine culture and rectal swab; subsequently all lab work and the clinical data were monitered regularly. Risk factors were assessed. The data collected prospectively looking for primary end point the invasive Candida infection (ICI) and 2 ndry outcomes include medication safety, tolerance and cost. RESULTS: 65 neonate randomly assigned however only 57 neonates comleted the study 33/57 (57%) to intravenous fluconazole group and 24/57 (42%) to oral nystatin group. No differences in birth weights Nystatin (1.15 Kg) Fluconazole (1.01 Kg), gender males (26/57), female (32/57), Gestational age (29.28 vs l28.22) or risk factors between the two groups. Rectal swab Colonization occurred in 2/24 (8%) in Nystatin group and 4/33 (12%) in the Fluconazole group, but none of the neonates developed ICI or side effects, although in the Fluconazole group transient transaminase elevation 2SD standard deviation above the mean was observed. Central line duration was 2 SD above the mean for fluconazole group, The cost of the Fluconazole treated group (7,581 SAR) 106.4 US/pt double the cost of Nystatin treated group (3,375 SAR) 50 US/pt. CONCLUSION: Intravenous Fluconazole and oral Nystatin at the prophylactic doses are equally effective and safe in preventing (ICI) in preterm neonates, however oral Nystatin is readily available, easily administered with lower cost per neonate.

Glomerular changes in microscopic haematuria, studied by quantitative immunoelectron microscopy and in situ zymography.

BACKGROUND: Haematuria of glomerular origin, even if mild, implies the development of defects in the glomerular basement membrane (GBM). In diseases where there is no infiltration of leukocytes into the glomerulus-such as thin basement membrane disease (TBMD) and histologically mild cases of IgA nephropathy (IgAN)-the mechanism by which such defects form is unclear. METHODS: Frozen renal tissue from 18 cases of TBMD, 18 of mild IgAN and 18 cases with no detectable abnormality were studied: (i) by quantitative in situ zymography, to estimate the activity of glomerular collagenases; and (ii) by quantitative immunoelectron microscopy to estimate the amount of major basement membrane proteins per unit length and per unit area of glomerular basement membrane. RESULTS: Cases of IgAN showed considerably more glomerular collagenase activity than normal (P=0.001). Thin basement membrane disease showed no difference in collagenase activity. A count of LCA-positive cells in glomeruli confirmed that the IgAN cases did not show glomerular leukocyte infiltration. Conversely, cases of IgAN showed no difference in GBM composition from normal, nor was any difference in GBM thickness detected in this group. However, cases of TBMD showed considerably less laminin (P=0.0008), fibronectin (P=0.002) and type VI collagen (P=0.0005) per unit length of basement membrane. Collagen IV showed a smaller reduction per unit length (P=0.01), but unlike the other protein studies it appeared to be present in higher concentration per unit area (P=0.03), suggesting that it is more 'compact' in TBMD disease. CONCLUSIONS: Two distinct mechanisms of haematuria seem to be involved in these two conditions. In IgAN there is increased activity of enzymes that can degrade GBM, probably reflecting mesangial cell activation. In TBMD an abnormal composition of the thinned GBM is confirmed. When considered with published reports of genetic abnormalities in TBMD, these results raise the possibility of an abnormal interaction between collagen IV and laminin.