Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of Molecular Subtypes of Paget Disease of the Breast Using Immunohistochemistry and In Situ Hybridization.

CONTEXT. — Paget disease of the breast, in most cases, represents intraepidermal spread of ductal carcinoma in situ. Molecular subtypes of invasive carcinoma of the breast have prognostic and therapeutic significance and show characteristic distribution. Little is known about the distribution of molecular subtypes in Paget disease of the breast. OBJECTIVES. — To examine the distribution of molecular subtypes in Paget disease of the breast and to compare them to concurrent invasive carcinoma of the breast, if present. DESIGN. — We examined 48 cases of Paget disease of the breast with immunohistochemistry and antibodies against estrogen and progesterone receptors, human epidermal growth factor receptor 2 (HER2), and Ki-67, as well as HER2 chromogenic in situ hybridization, to classify the cases into molecular subtypes. Then, we compared the results to the molecular subtypes of associated invasive carcinoma of the breast, if present. RESULTS. — The HER2 subtype was the most common found in Paget disease of the breast, followed by the luminal B subtype and 2 cases of the triple-negative subtype. The associated invasive carcinoma cases were most often of the luminal B subtype, followed by the HER2 subtype and the triple-negative subtype. The molecular subtype of Paget disease and invasive carcinoma was congruent in most of the cases. CONCLUSIONS. — Molecular subtypes of invasive carcinoma of the breast can already be detected in Paget disease. The distribution of molecular subtypes of Paget disease and of Paget disease-associated invasive carcinoma differs from invasive carcinoma without associated Paget disease, with the HER2 subtype overrepresented in Paget disease and associated invasive carcinoma and the luminal and triple-negative subtypes underrepresented.
Review article Is it time to shed some light on the black box of health policies regarding the inhabitants of the high background radiation areas of Ramsar

*Corresponding author: Prof. Seyed Mohammad Javad Mortazavi, Department of Medical Physics and Medical Engineering, School of Medicine, and the Center for Research in Radiation Sciences (CRRS), Shiraz University of Medical Sciences, Shiraz, Iran. Fax: + 98 711 2349332 E-mail: mmortazavi@sums.ac. ir Although there are substantial experimental, epidemiological and clinical evidences that high doses of ionizing radiation cause cancer and other detrimental biological effects, the health effects of human exposure to chronic low dose radiation exposures are still poorly known. People in some areas around the world live in dwellings with radiation and radon levels as much as more than 200 times the global average. Inhabited areas with high levels of natural radiation are found in different areas around the world including Yangjiang, China; Kerala, India; Guarapari, Brazil and Ramsar, Iran. Ramsar in northern Iran is among the world’s well-known areas with highest levels of natural radiation. Annual exposure levels in areas with elevated levels of natural radiation in Ramsar are up to 260 mGy y-1 and average exposure rates are about 10 mGy y-1 for a population of about 2000 residents. Due to the local geology, which includes high levels of radium in rocks, soils, and groundwater, Ramsar residents are also exposed to high levels of alpha activity in the form of ingested radium and radium decay progeny as well as very high radon levels in their dwellings. Based on the findings obtained by studies on the health effect of high levels of natural radiation in Ramsar, as well as other high background radiation areas, no consistent detrimental effect has been detected so far. Further research is needed to clarify if the regulatory authorities should set limiting regulations to protect the inhabitants against such extraordinary elevated levels of natural radiation. Iran. J. Radiat. Res., 2012; 10 (3‐4): 111‐116
Prevalence and associated factors of Helicobacter pylori Infection among HIV positive adults on Anti-retroviral Therapy

Human immunodeficiency virus (HIV) and Helicobacter pylori (H. pylori) infections are worldwide healthcare burdens. This study aimed to assess the prevalence and associated factors of H. pylori infection among HIV patients at Southern-Ethiopia. A Hospital based cross-sectional study was conducted at Hawassa University comprehensive specialized hospital on 390 HIV infected adults on antiretroviral therapy from September to November 2017. All vital data were collected by designed questionnaires and stool samples were collected using appropriate sample cap for H. pylori stool antigen diagnosis. The overall prevalence of H. pylori infection of HIV infected patients was 17.9%. About 42.6% of the participants had a history of dyspepsia and of them, 4.3% were positive for H. pylori infection. In addition, 48.9% of patients were using either aqua tablet (67 mg-Trocloresene sodium) or water filters for drinking water, of them 11.5% were positive for H. pylori infection. Having a history of dyspepsia: the adjusted odds ratio [AOR (95% CI): 4.8 (1.6–14.7)], and age ≤30 years [AOR (95% CI):3.7(1.6–8.8)] were associated factors of H. pylori infection. Moreover, the association of H. pylori infection ≤ 30 years old and history of dyspepsia indicates the need of further large-scale and cohort type studies to determine the other possible associated factors for the infection. Key words: Helicobacter Pylori, HIV, stool antigen test, South-Ethiopia.
Concise Review: Pancreas Regeneration: Recent Advances and Perspectives

The replacement of functional pancreatic β‐cells is seen as an attractive potential therapy for diabetes, because diabetes results from an inadequate β‐cell mass. Inducing replication of the remaining β‐cells and new islet formation from progenitors within the pancreas (neogenesis) are the most direct ways to increase the β‐cell mass. Stimulation of both replication and neogenesis have been reported in rodents, but their clinical significance must still be shown. Because human islet transplantation is limited by the scarcity of donors and graft failure within a few years, efforts have recently concentrated on the use of stem cells to replace the deficient β‐cells. Currently, embryonic stem cells and induced pluripotent stem cells achieve high levels of β‐cell differentiation, but their clinical use is still hampered by ethical issues and/or the risk of developing tumors after transplantation. Pancreatic epithelial cells (duct, acinar, or α‐cells) represent an appealing alternative to stem cells because they demonstrate β‐cell differentiation capacities. Yet translation of such capacity to human cells after significant in vitro expansion has yet to be achieved. Besides providing new β‐cells, cell therapy also has to address the question on how to protect the transplanted cells from destruction by the immune system via either allo‐ or autoimmunity. Encouraging developments have been made in encapsulation and immunomodulation techniques, but many challenges still remain. Herein, we discuss recent advances in the search for β‐cell replacement therapies, current strategies for circumventing the immune system, and mandatory steps for new techniques to be translated from bench to clinics.
Embryonic Stem Cell‐Based Cardiopatches Improve Cardiac Function in Infarcted Rats

Pluripotent stem cell‐seeded cardiopatches hold promise for in situ regeneration of infarcted hearts. Here, we describe a novel cardiopatch based on bone morphogenetic protein 2‐primed cardiac‐committed mouse embryonic stem cells, embedded into biodegradable fibrin matrices and engrafted onto infarcted rat hearts. For in vivo tracking of the engrafted cardiac‐committed cells, superparamagnetic iron oxide nanoparticles were magnetofected into the cells, thus enabling detection and functional evaluation by high‐resolution magnetic resonance imaging. Six weeks after transplantation into infarcted rat hearts, both local (p < .04) and global (p < .015) heart function, as well as the left ventricular dilation (p < .0011), were significantly improved (p < .001) as compared with hearts receiving cardiopatches loaded with iron nanoparticles alone. Histological analysis revealed that the fibrin scaffolds had degraded over time and clusters of myocyte enhancer factor 2‐positive cardiac‐committed cells had colonized most of the infarcted myocardium, including the fibrotic area. De novo CD31‐positive blood vessels were formed in the vicinity of the transplanted cardiopatch. Altogether, our data provide evidence that stem cell‐based cardiopatches represent a promising therapeutic strategy to achieve efficient cell implantation and improved global and regional cardiac function after myocardial infarction.
Adipose‐Derived Mesenchymal Stromal Cells From Aged Patients With Coronary Artery Disease Keep Mesenchymal Stromal Cell Properties but Exhibit Characteristics of Aging and Have Impaired Angiogenic Potential

Tissue regeneration is impaired in aged individuals. Adipose‐derived mesenchymal stromal cells (ADSCs), a promising source for cell therapy, were shown to secrete various angiogenic factors and improve vascularization of ischemic tissues. We analyzed how patient age affected the angiogenic properties of ADSCs. ADSCs were isolated from subcutaneous fat tissue of patients with coronary artery disease (CAD; n = 64, 43–77 years old) and without CAD (n = 31, 2–82 years old). ADSC phenotype characterized by flow cytometry was CD90+/CD73+/CD105+/CD45−/CD31− for all samples, and these cells were capable of adipogenic and osteogenic differentiation. ADSCs from aged patients had shorter telomeres (quantitative reverse transcription polymerase chain reaction) and a tendency to attenuated telomerase activity. ADSC‐conditioned media (ADSC‐CM) stimulated capillary‐like tube formation by endothelial cells (EA.hy926), and this effect significantly decreased with the age of patients both with and without CAD. Angiogenic factors (vascular endothelial growth factor, placental growth factor, hepatocyte growth factor, angiopoetin‐1, and angiogenin) in ADSC‐CM measured by enzyme‐linked immunosorbent assay significantly decreased with patient age, whereas levels of antiangiogenic factors thrombospondin‐1 and endostatin did not. Expression of angiogenic factors in ADSCs did not change with patient age (real‐time polymerase chain reaction); however, gene expression of factors related to extracellular proteolysis (urokinase and its receptor, plasminogen activator inhibitor‐1) and urokinase‐type plasminogen activator receptor surface expression increased in ADSCs from aged patients with CAD. ADSCs from aged patients both with and without CAD acquire aging characteristics, and their angiogenic potential declines because of decreasing proangiogenic factor secretion. This could restrict the effectiveness of autologous cell therapy with ADSCs in aged patients.
Effects of leaf and berry extracts of Phytolacca dioica L. on haematological and weight parameters of Wistar rats

The effect of aqueous leaf and berry extracts of Phytolacca dioica administered at 50, 100 and 200 mg/kg body weight for 14 days was investigated on haematology and weight parameters of Wistar rats. The extracts at all doses had no significant effect on the red blood cells (RBC), haemoglobin (HB), parked cell volume (PCV), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC) when compared with the animals in the control group. In contrast, the extracts at all doses caused a progressive significant reduction in the serum levels of platelets, white blood cells (WBC), neutrophils and monocytes. Also, there was dose-dependent significant increase in the serum levels of lymphocytes and a reduction in the level of eosinophils. Administration of the extracts at all doses investigated led to a significant reduction in the body weight, absolute organ weight and organ-body weight ratio. These observable alterations in some parameters were indications that the leaf and berry extracts of P. dioica possess slight toxicity. Therefore, the crude extracts from the leaf and berry may not be completely safe as oral remedies. Key words: Phytolacca dioica, haematology, weight parameters, slight toxicity, oral remedy.
Concise Review: Cell‐Based Strategies in Bone Tissue Engineering and Regenerative Medicine

Cellular strategies play an important role in bone tissue engineering and regenerative medicine (BTE/RM). Variability in cell culture procedures (e.g., cell types, cell isolation and expansion, cell seeding methods, and preculture conditions before in vivo implantation) may influence experimental outcome. Meanwhile, outcomes from initial clinical trials are far behind those of animal studies, which is suggested to be related to insufficient nutrient and oxygen supply inside the BTE/RM constructs as some complex clinical implementations require bone regeneration in too large a quantity. Coculture strategies, in which angiogenic cells are introduced into osteogenic cell cultures, might provide a solution for improving vascularization and hence increasing bone formation for cell‐based constructs. So far, preclinical studies have demonstrated that cell‐based tissue‐engineered constructs generally induce more bone formation compared with acellular constructs. Further, cocultures have been shown to enhance vascularization and bone formation compared with monocultures. However, translational efficacy from animal studies to clinical use requires improvement, and the role implanted cells play in clinical bone regeneration needs to be further elucidated. In view of this, the present review provides an overview of the critical procedures during in vitro and in vivo phases for cell‐based strategies (both monoculture and coculture) in BTE/RM to achieve more standardized culture conditions for future studies, and hence enhance bone formation.
Preliminary Study of Autologous Bone Marrow Nucleated Cells Transplantation in Children With Spinal Cord Injury

The objective of this study was to assess the safety and efficacy of transplanting bone marrow nucleated cells (BMNCs) to treat children with complete interruption of spinal cord (SC) continuity. The present study was conducted from 2005 to 2011. The inclusion criteria were a magnetic resonance imaging‐confirmed complete interruption of SC continuity and no improvement in neurological status within 6 months after standard therapy. Bone marrow was isolated from the iliac ala and submitted to BMNC isolation. Subsequently, the cell suspension was administered into the SC cavity and intravenously. In total, 18 of 19 intraspinal and intravenous BMNC transplantation procedures performed caused no adverse events. One case was connected with transient bradycardia. The experimental therapy showed no late complications in the 1‐ to 6‐year follow‐up evaluation period. Neurological improvement was observed in two patients who received multiple implantations. One patient demonstrated improved superficial sensation from Th3 to Th12/L1 and a restored bladder‐filling sensation. In the other case, superficial sensation was improved from C2 to C5, and the respiratory drive, the swallowing reflex, and tongue movements were restored. Spasticity and quality of life were improved in three of five patients. In addition, skin pressure ulcers healed and did not recur. Our preliminary results demonstrate the safety and feasibility of BMNC transplantation in children with complete SC injury. The results indicate that a certain degree of neurological and quality‐of‐life improvement can be attained by children with chronic complete SC injury who receive multiple BMNC implantations.
Stable Enhanced Green Fluorescent Protein Expression After Differentiation and Transplantation of Reporter Human Induced Pluripotent Stem Cells Generated by AAVS1 Transcription Activator‐Like Effector Nucleases

Human induced pluripotent stem (hiPS) cell lines with tissue‐specific or ubiquitous reporter genes are extremely useful for optimizing in vitro differentiation conditions as well as for monitoring transplanted cells in vivo. The adeno‐associated virus integration site 1 (AAVS1) locus has been used as a “safe harbor” locus for inserting transgenes because of its open chromatin structure, which permits transgene expression without insertional mutagenesis. However, it is not clear whether targeted transgene expression at the AAVS1 locus is always protected from silencing when driven by various promoters, especially after differentiation and transplantation from hiPS cells. In this paper, we describe a pair of transcription activator‐like effector nucleases (TALENs) that enable more efficient genome editing than the commercially available zinc finger nuclease at the AAVS1 site. Using these TALENs for targeted gene addition, we find that the cytomegalovirus‐immediate early enhancer/chicken β‐actin/rabbit β‐globin (CAG) promoter is better than cytomegalovirus 7 and elongation factor 1α short promoters in driving strong expression of the transgene. The two independent AAVS1, CAG, and enhanced green fluorescent protein (EGFP) hiPS cell reporter lines that we have developed do not show silencing of EGFP either in undifferentiated hiPS cells or in randomly and lineage‐specifically differentiated cells or in teratomas. Transplanting cardiomyocytes from an engineered AAVS1‐CAG‐EGFP hiPS cell line in a myocardial infarcted mouse model showed persistent expression of the transgene for at least 7 weeks in vivo. Our results show that high‐efficiency targeting can be obtained with open‐source TALENs and that careful optimization of the reporter and transgene constructs results in stable and persistent expression in vitro and in vivo.
NG2+ Progenitors Derived From Embryonic Stem Cells Penetrate Glial Scar and Promote Axonal Outgrowth Into White Matter After Spinal Cord Injury

The glial scar resulting from spinal cord injury is rich in chondroitin sulfate proteoglycan (CSPG), a formidable barrier to axonal regeneration. We explored the possibility of breaching that barrier by first examining the scar in a functional in vitro model. We found that embryonic stem cell‐derived neural lineage cells (ESNLCs) with prominent expression of nerve glial antigen 2 (NG2) survived, passed through an increasingly inhibitory gradient of CSPG, and expressed matrix metalloproteinase 9 (MMP‐9) at the appropriate stage of their development. Outgrowth of axons from ESNLCs followed because the migrating cells sculpted pathways in which CSPG was degraded. The degradative mechanism involved MMP‐9 but not MMP‐2. To confirm these results in vivo, we transplanted ESNLCs directly into the cavity of a contused spinal cord 9 days after injury. A week later, ESNLCs survived and were expressing both NG2 and MMP‐9. Their axons had grown through long distances (>10 mm), although they preferred to traverse white rather than gray matter. These data are consistent with the concept that expression of inhibitory CSPG within the injury scar is an important impediment to regeneration but that NG2+ progenitors derived from ESNLCs can modify the microenvironment to allow axons to grow through the barrier. This beneficial action may be partly due to developmental expression of MMP‐9. We conclude that it might eventually be possible to encourage axonal regeneration in the human spinal cord by transplanting ESNLCs or other cells that express NG2.
Tissue-Specific Progenitor and Stem Cells Comparative Study of Autologous Stromal Vascular Fraction and Adipose-Derived Stem Cells for Erectile Function Recovery in a Rat Model of Cavernous Nerve Injury

The abilities of intracavernous injection of autologous stromal vascular fraction (SVF) and adiposederived stem cells (ADSCs) to facilitate recovery of erectile function in a ratmodel of cavernous nerve (CN) injurywere compared. Fortymale Sprague-Dawley ratswere randomly divided into four groups: sham and control groups (intracavernous injection of phosphate-buffered saline), SVF group (intracavernous injection of SVF), and ADSC group (intracavernous injection of ADSCs). Rats in the latter three groups underwent bilateral CN injury prior to injection. The evaluation of erectile function and histomorphometric studies were performed 4 weeks after injection. The ratio of maximal intracavernous pressure to mean arterial pressure was significantly lower in the control group than in the sham group (0.18 vs. 0.56, p < .001). Intracavernous injection of SVF (0.36, p = .035) significantly improved erectile function compared with that in the control group, whereas the ADSC group (0.35, p = .052) showedmarginally significant improvement. The smoothmuscle/collagen ratio, smoothmuscle content, number of neuronal nitric-oxide synthase-positive nerve fibers, and expression of von Willebrand factor were significantly higher in the SVF and ADSC groups than in the control group. Expression of endothelial nitric-oxide synthasewas significantly increased in the SVF group. The increases in the smoothmuscle/collagen ratio and vonWillebrand factor expression were larger in the SVF group than in the ADSC group. Intracavernous injection of SVF or ADSCs was equally effective in recovering penile erection in a rat model of CN injury. STEM CELLS TRANSLATIONAL MEDICINE 2015;4:351–358
Treatment Outcome of Surgical Complications of Pleuropulmonary Tuberculosis in Niger Delta Region of Nigeria

AIM: Although essentially a medical condition, ignorance, non-compliance with treatment and late presentation encourage development of complications that require surgical intervention. This study aimed to investigate the clinico-pathologic characteristics of our pleuropulmonary tuberculosis patients with surgical complications and the outcome of surgical treatment offered. METHODS: Case files of pleuropulmonary tuberculosis patients who were surgically treated for complications of their disease in the cardiothoracic surgery unit of the University of Uyo Teaching Hospital between November 2006 and October 2008 were retrospectively studied. Data on demography, socio economic parameters, clinical presentation, radiological/investigation findings, diagnosis, treatment and outcome were collated for analysis. RESULTS: Out of 156 patients with pleuropulmonary tuberculosis diagnosed and treated by the Directly Observed Therapy Unit of the Hospital during the study period, 33 (21.2%) of them suffered surgically treated complications. The patients consisted of 19 males and 14 females (M:F = 1.3:1) with age range 2-68 years and mean 36.3 years. Seven types of surgically treated complications of pleuro-pulmonary tuberculosis were encountered including pleural effusion in 39.4%, broncho-pleural fistula (spontaneous pneumothorax) in 21%, empyema thoracis in 12%, emphysematous bulla (9.1%), lung abscess (6.1%), haemoptysis (9.1%), and a case of destroyed lung syndrome (3.0%) Surgical treatment given to the patients included closed tube thoracostomy drainage (69.7%), Monaldi tube decompression (9.1%), and thoracotomy and decortication (3.0%). CONCLUSION: The prevalence of surgically treated complications of pulmonary tuberculosis in this study is 21.2%, and we recommend a high index of suspicion, contact tracing and strict adherence to the modus operandi of directly observed continuous combined anti-tuberculous chemotherapy for pleuropulmonary tuberculosis.