Miracle-dz/UniFAR-FTUs huggingface dataset:
Emergence of cancer stem cells in the early stages of hepatic carcinogenesis and development of innovative models of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a major public health problem, being the second most lethal cancer with an increasing incidence around the world. The only approved systemic drug is the multikinase inhibitor Sorafenib, which prolongs patients’ survival by only three months. HCC is refractory to known chemotherapeutic drugs and more than 50% of patients relapse after surgical tumor removal. These phenomena are thought to be due to the existence of a population of poorly differentiated cancer cells, largely known as liver cancer stem cells (CSCs). Recent studies revealed that CSCs activate similar pathways as normal stem cells. They are therefore highly resistant to therapies and are thought to be capable of self-renewal and generation of tumor’s heterogeneous cell mass. The understanding of mechanisms proper to liver CSCs should allow the development of innovative drugs with original mechanism of action against liver CSC, likely to improve patients’ outcome. However, the development of new therapies against HCC is penalized by the limited number of experimental models.According to these current challenges in the field of HCC research, my PhD thesis project covers three main axes: Development of novel models of disease (IMODI consortium)The Innovative Models of Disease (IMODI) consortium is mainly dedicated to the development of innovative experimental models for 7 different types of cancer. Our participation to the project concerned 3 main objectives i) development of HCC patient-derived xenografts ii) development of new HCC cell lines and iii) set up a cryoconservation method of primary human hepatocytes (PHHs) in the aim to employ them in humanizing murine livers. 30 patients planned for HCC tumor resection were recruited and their clinicopathological data were collected. Fresh tumor specimens were subcutaneously xenografted in immune-deficient mice and dissociated for in-vitro tumor cell culture. One tumor led to the development of a moderately differentiated HCC PDX model, as confirmed by histological characterization. Several studies showed the importance of PDX models in drug discovery as they recapitulate the drug-sensitivity patterns seen in patients from which they derive but very few models have been described in the literature for HCC. In vitro, primary HCC cells could be maintained in culture for a limited period of time, in average 30 days. No HCC cell lines developed due to cells entering replicative senescence, as previously described
Cardiovascular complications in end stage renal disease in a tertiary hospital in Nepal

Background & Objectives: The cardiovascular complications including morbidity and mortality remains alarmingly high in all stages of chronic kidney disease. Although patients with chronic kidney disease share many of the similar risk factors for cardiovascular disease as the general population, there are a number of uremia related risk factors, such as anemia and alterations in calcium/phosphorus metabolism that also play a role in promoting cardiovascular disease. The objective of the study was to study the cardiovascular complications in end stage renal disease patients on maintenance hemodialysis. Materials & Methods: It is a hospital based cross-sectional observational study conducted at College of Medical Science - teaching Hospital. Hundred patients (n=100) with a diagnosis of end stage renal disease (irrespective of the underlying cause), and those who were on hemodialysis support were studied over a period of one year. Results: One hundred end stage renal disease patients were analyzed. Cardiovascular disease was present in 74% (n=74). the mean age of the patient who had cardiovascular disease was 59.36+14.337 years. The three major causes of end stage renal disease in the study population were hypertension (35%) followed by diabetes(31%) and chronic glomerulonephritis (14%). On electrocardiogram, left ventricular hypertrophy was a major finding 64% (n=64) followed by arrhythmias 30% (n=30). On echocardiography, left ventricular hypertrophy was found in 49% (n=49) followed by left ventricular diastolic dysfunction 38% (n=38). On subgroup analysis, left ventricular hypertrophy was found statistically significant with calcium and phosphorus product > 55 mg2/dl2 (p=0.01). Similarly left ventricular systolic dysfunction, regional wall motion abnormalities and st-t changes was found statistically significant with anemia; p=0.006, p=0.0004 and p=0.02 respectively. Conclusion: Prevalence of cardiovascular complications were common in end stage renal disease patients receiving maintenance hemodialysis. Anemia, calcium and phosphorus product > 55 mg2/dl2 were their independent risk factors.
The Effect of 8 Weeks of Core Stability Muscles Training on Kinetics of Single-Leg Landing

Purpose: Core stability training (CST) has increased among athletes. The study hypothesis is that neuromuscular training and exercises of central area of trunk, pelvis and hip can reduce injury risk, and specifically peak vertical ground reaction forces in drop landing task. Therefore, the objective of this study was to evaluate kinetics during single leg drop landing test following a CST intervention.
Haematemesis and Melaena

Oesophago-gastro-duodenoscopy was successfully performed in 196 of208 patients admitted with haematemesis or melaena, or both. A precise visual diagnosis was made in 80% of all patients and in 96% of those where the final diagnosis lay within the oesophagus, stomach, and first two parts of the duodenum. Bleeding oesophagitis was more common and bleeding duodenal ulcer less common than in other series using mainly radiology. Altogether, 26% of all patients with endoscopically-proved duodenal ulcers were bleeding from another site, and 15.4% of all patients had more than one lesion. This fact, and inability to detect surface lesions limits the value of acute barium radiology, which was performed in only 81 patients. Accurate diagnosis should lead to better understanding of individual lesions and more rational management of individual patients. Where a good service is available oesophago-gastro-duodenoscopy should be performed on all bleeding patients within 24 hours of admission.
Living with Multiple Sclerosis in Europe: Pharmacological Treatments, Cost of Illness and Health Related Quality of Life Across Countries

ABSTRACT More than 700,000 people suffer from multiple sclerosis (MS) in Europe. This implies that more than 1 million people are affected by this disease through their role as caregivers and family members. Given its relevant impact, MS deserves consideration by epidemiologists, clinicians, psychologists, social scientists and other scholars. Such interdisciplinarity is stressed in the present contribution, which focuses on various aspects of socioeconomic burden. Starting from considerations about the epidemiology of the disease in Europe, as outlined by the MS Barometer, a comparative survey based on data collected by the national MS societies and launched in 2008, a brief literature review for each European country mentioned in the report was carried out with the following key terms: “multiple sclerosis,” “cost of illness,” and “health-related quality of life (HRQoL). ” The consideration of the level of assistance provided, the access to rehabilitation centers, and the availability of pharmacological treatments, especially innovative therapies, reveal how there are still huge differences across Europe. Literature contributions are mostly oriented toward HRQoL studies and the impact of new pharmacological treatments. There are less studies focusing on compliance: this may be the consequence of a higher awareness of the disease among the patients and a strengthened cooperation with the physicians. Some suggestions about foreseeable and desirable lines of research conclude the contribution.
Exploring patient and public involvement in motor neuron disease research

Abstract Objectives: Patient and public involvement (PPI) is a relatively new practice whereby researchers involve patients and the public in the conduct of their research. The Sheffield Motor Neurone Disorders Research Advisory Group (SMNDRAG) is one of the first groups to specialise in motor neuron disease (MND). Its members include people living with MND, carers, relatives, volunteers, clinicians, and scientists. Our aim was to explore the experiences of those who participate in, organise and work with the SMNDRAG. Methods: We conducted 13 semi-structured interviews: 10 with members of the SMNDRAG and three with researchers who have worked with the group. We used thematic analysis to identify ways in which the group influenced research and the barriers and enablers to PPI. Results: A number of motivations for participating in the SMNDRAG were reported but the majority were altruistic. The SMNDRAG offered individuals psychosocial and intellectual benefits. The SMNDRAG has overcome a number of practical and psychological barriers to developing a successful and effective collaborative partnership resulting in a positive impact on research and researchers at each stage of the research process. For example, the group identified research priorities which ensured that research was patient-focused. However, several barriers remain, including the lack of diversity within the group and the perception that PPI participation requires a “certain type of person. ” Conclusions: PPI can make a valuable contribution to all aspects of research and can have a positive impact on those involved. We recommend ways in which PPI can and should be incorporated into research.
IUGR Pregnancies - Feto-Maternal Outcome

Intra-uterine fetal growth restriction (IUGR) is an important and common cause of neonatal morbidity and mortality. It is a multifactorial phenomenon including many maternal and fetal factors. This study is a retrospective observational study carried out in tertiary care centre which mainly receives referral cases and patients from poor socio economic background . Our study included the patients who were antenatally diagnosed as having IUGR fetus on basis of ultrasound findings and later delivered a baby weighing less than 2.5 kg. The study assessed the maternal and fetal outcome of IUGR pregnancies. The incidence of Intra-uterine growth restriction in our study was 4%. The pregnancy induced hypertension (PIH) was the most common factor associated with IUGR. The 60% of the IUGR neonates required admission to neonatal ICU. The majority of those admitted to neonatal ICU were born to mothers without adequate antenatal care. We concluded that apart from PIH, anemia, poor weight gain during pregnancy and the poor antenatal period care were major risk factors for IUGR.
Psychiatric Health Care Crisis in Pediatrics: Potential Approaches and Solutions

All articles published in Research Journal of Clinical Pediatrics are the property of SciTechnol, and is protected by copyright laws. Copyright © 2017, SciTechnol, All Rights Reserved. *Corresponding author: Robert M. Post, MD, Clinical Professor of Psychiatry, George Washington University School of Medicine, Bipolar Collaborative Network 5415 W, Cedar Lane Suite 201-B Bethesda, USA, Tel: 3015308245/ 2408881317; Fax: 301-5308247; E-mail: robert.post@speakeasy.net
Attitudes of mental health care professionals toward the provision of tobacco dependence treatment in the transition to a smoke-free mental health unit: An exploratory mixed method study.

3 List of Tables . 7 List of Figures . 8 Glossary . 9 Acknowledgements . 12 Introduction . 13 Significance of Study . 14 Research Questions . 17 Hypothesis . 17 Literature Review. 19 Smoking tobacco prevalence . 19 People with a Mental Illness Who Smoke . 21 Health professionals who smoke . 24 Historical Context and Tobacco Industry . 27 The Tobacco Industry and Smoking . 29 Smoke-free Policy and Tobacco Control . 32 Smoke-free Policy in the Hospital . 33 Smoke-free Policy Inpatient Mental Health Units . 34 Smoke-free Policy (partial ban) . 37 Tobacco Dependence Treatment. 39 Mental Health Settings . 41 Barriers to Tobacco Dependence Treatment and Smoke-free Policy . 45 Provision Tobacco Dependence Treatment Inpatient Mental Health . 48 Attitude Barriers . 51 TTCS Attitude Domains. 54
Development of an ELISA to Detect Folate Receptor alpha (FRα) Autoantibodies, and their Association with Recurrent Miscarriage.

Pregnancy can be a joyous moment in a couple’s life; yet on the other hand it can also bring much heartache to couples that experience any form of pregnancy complication. A significant proportion of pregnancies don’t make full term, in addition, 1% of couples may experience recurrent miscarriage (RM) which can be devastating to the couple (Bansal et al. 2011)…
SENSORY REGRESSION TIME FROM SUBARACHNOID BLOCK WITH HYPERBARIC 0.75% BUPIVACAINE IN THE OBESE PATIENT

S EN SORY REG RESSION T IME FROM SUBARACHNOID BLOCK WITH HYPERBARIC 0.75% BUP IVACA INE IN THE OBESE PAT IENT George L. Hilton, BBA, BSN School of Allied Health Professions, Virginia Commonwealth University, 19 89 Major Director : Charles H. Moore, MS, CRNA The purpose of this study was to determine if obese patients have a different sensory regression time from subarachnoid block than non-obese patients using hyperbaric 0.75% bupivacaine. A quasi-experimental design was used. Twenty patients were separated into two groups; one group was classified as obese, and the other group was classified as non-obese. The data consisting of age, height, weight, sex, and surgical procedure were recorded preoperatively. All the patients received hyperbaric 0.75% bupivacaine via subarachnoid puncture. The levels of spinal anesthesia were recorded at the highest level achieved. The injection time was also recorded. When the surgery was completed, the patient was transferred to the recovery room and levels of sensory blockade were checked by pin-prick with an 18-gauge needle every 10 minutes until complete recovery
Effectiveness of Cardiac Walking on Blood Pressure Among Patients with Acute Coronary Syndrome

Background: Cardiovascular diseases (CVD) are the leading cause of the mortality in urban and rural India and foremost causes of the death worldwide. Hypertension is a major risk condition that plays a pivotal role regarding the complications for those diagnosed with Acute Coronary Syndrome. According to the World Health Organization (2012), hypertension is the number one cause of mortality in the world and it is a major risk factor for cardiac diseases and stroke. Objectives: i) To identify the level of blood pressure (BP) in pre and post test among study and control group of patients with acute coronary syndrome. ii) Determine the effect of cardiac walking on blood pressure among patients with ACS. iii) Associate the selected back ground variables with the level of systolic BP in the post test among study and control group. Methods: A quasi experimental design was adopted for this study. There are 50 Patients diagnosed with ASC admitted for the treatment and attending cardiac OPD were selected by purposive sampling technique of non- probability type. The intervention cardiac walking given for a period of one month to the study group. Findings: The comparison of before and after systolic and diastolic blood pressure (BP) within study group depicted statistically significant difference at **p less than 0.001 but not in control group. The comparison of post systolic and diastolic BP between study and control group inferred that there was statistically significant difference at **p less than 0.001. Conclusion: Cardiac walking is most effective way to stabilize the blood pressure among patients with ACS in order to prevent further complications such as stroke.
Antibody affinity and valency impact brain uptake of transferrin receptor-targeted gold nanoparticles

Rationale: The ability to treat invalidating neurological diseases is impeded by the presence of the blood-brain barrier (BBB), which inhibits the transport of most blood-borne substances into the brain parenchyma. Targeting the transferrin receptor (TfR) on the surface of brain capillaries has been a popular strategy to give a preferential accumulation of drugs or nanomedicines, but several aspects of this targeting strategy remain elusive. Here we report that TfR-targeted gold nanoparticles (AuNPs) can accumulate in brain capillaries and further transport across the BBB to enter the brain parenchyma. Methods: We characterized our targeting strategy both in vitro using primary models of the BBB and in vivo using quantitative measurements of gold accumulation by inductively-coupled plasma-mass spectrometry together with morphological assessments using light microscopy after silver enhancement and transmission electron microscopy with energy-dispersive X-ray spectroscopy. Results: We find that the uptake capacity is significantly modulated by the affinity and valency of the AuNP-conjugated antibodies. Specifically, antibodies with high and low affinities mediate a low and intermediate uptake of AuNPs into the brain, respectively, whereas a monovalent (bi-specific) antibody improves the uptake capacity remarkably. Conclusion: Our findings indicate that monovalent ligands may be beneficial for obtaining transcytosis of TfR-targeted nanomedicines across the BBB, which is relevant for future design of nanomedicines for brain drug delivery.
Role of insulin sensitising agents in altering PSA level in PCOS

4-11% of women of reproductive age group in Indian population suffer from Polycystic Ovarian Syndrome (PCOS), which is the most common endocrine reproductive disorder of females. PCOS manifest as irregular menstrual cycles concurrently with hirsutism and/ or acne and occasionally obesity is associated with it. Insulin resistance with the consequent hyperinsulinemia has a pathogenic role in PCOS. Insulin can promote ovarian androgen production, either directly by stimulating ovarian enzyme complex P450c17α or indirectly by stimulating pituitary luteinizing hormone (LH) secretion. In vitro studies have also suggested amplification of ACTH (Adrenocorticotropic hormone) stimulated adrenal androgen secretion by hyperinsulinemia.
Fluconazole susceptibility of Candida species isolated from cases of Vulvovaginal Candidiasis by using E-test method

Candida vaginitis is one of the most frequently encountered form of superficial candidiasis. The principal agent of vulvovaginal candidiasis is C.albicans , but other species known generally as C.nonalbicans ( C.glabrata, C.tropicalis, C.krusei, C.parapsilosis, C.lusitaniae ) are also isolated. The available therapeutic arsenal for treatment of vulvovaginal candidiasis offer few options and includes the imidazole and trizole agents, in topical and oral form. The E-test has been introduced as an easier testing procedure and an alternative for the NCCLS method. The present study determines the distribution of Candida species and in vitro susceptibilities of fluconazole against the Candida isolated from vulvovaginitis candidiasis using E-test . Methods: Two vaginal swabs from each patient were processed by microscopy and culture to know the prevalence of candidialvulvovaginitis and to study their antifungal susceptibility pattern of fluconazole by E-test. Results: Out of 300 suspected cases of vulvovaginitis, only Candida as a cause of vulvovaginitis was present in 133(44.33%) cases. The most common age group associated with vulvovaginal candidiasis was 20-29 years (43.61%) followed by 30-39 years (30.83%) and greater than 40 years (25.56%). The most common species isolated was C.albicans followed by C.glabrata . By E-test method 92.21% of C.albicans , 60.46% of C.glabrata and all (100%) C.tropicalis was susceptible, that is, showing MIC of fluconazole less than or equal to 8µg/ml and all 100% C.krusei was resistant (MIC 64µg/ml) to fluconazole. Conclusion: For effective treatment of the infection, to prescribe the correct medication and to overcome recurrence, it may be advisable to identify the Candida species routinely from vaginal swabs of infected women. Also, the high growing rate of resistance of non-albicans Candida to azoles confirms the importance of monitoring changes in the distribution of pathogenic Candida species. The major feature of E-test method is that it can allow a quick answer concerning Candida resistance to antifungal agents, preventing unnecessary patients’ drug abuse. Keywords: E- test, Fluconazole, Vulvovaginitis.
SUBCELLULAR LOCALIZATION OF PRORENIN IN THE HOG KIDNEY EXAMINED BY DENSITY-GRADIENT CENTRIEUGATION

Subcellular distribution of renin and prorenin in the hog kidney was examined by density-gradient centrifugation to investigate the subcellular sites where the biosynthetic precursors of renin undergo activation through specific proteolytic cleavages. Trypsinization of the subcellular organelles, separated by continuous density-gradients, revealed the presence of inactive prorenin in renin granules and in microsomal fractions. The trypsin-activated prorenin was inhibited by antibody against hog renal active renin. The renin granule fraction contained less precursor (prorenin) and more product (active renin) than endoplasmic reticulum and Golgi vesicles. These results indicate that the most likely site of the conversion is the Golgi apparatus. The inactive renin in the storage granules may represent the proenzyme that escaped proteolytic activation and is the source of circulating inactive renin. Cell-free translations of polyadenylated mRNA from the mouse kidney have led to identification of an apparent precursor of renin (preprorenin (8, 18, 19, 21)). Affinity chromatographic examinations of kidney extracts have demonstrated the presence of inactive renin which can be activated by limited proteolysis and satisfies several other criteria required for prorenin (16, 23). These observations have led to the hypothesis that renin is biosynthesized from a larger precursor by way of two sequential proteolytic cleavages: preprorenin -—> prorenin -—> renin. However, little is known about where and how these cleavages take place. Plasma has also been shown to contain an inactive form of renin that has characteristics similar to those of kidney prorenin (for review, see references 10, 11, 20, and 22). Since such an inactive renin can be isolated from perfusate of kidney (2), and bilateral nephrectomy causes a marked decrease in both active and inactive renin 1 To whom reprint requests should be made in the blood (7), it is very likely that the kindey is the source of circulating inactive renin. If so, secreting renin granules can be expected to contain prorenin in addition to active renin. To clarify these points, we examined the subcellular localization of prorenin. The results showed that 1) the renin granules contained prorenin, and 2) the ratio of active to inactive renin increases as renin is transported from the site of synthesis (microsomal and Golgi fraction) to the storage site (renin granule fraction). MATERIALS AND METHODS Fractionation of Subceflu/ar Orgcmel/es Hog kidney cortex (2 g) was homogenized in eight volumes of 0.25 M sucrose with a loosefitting Potter-Elvehjem homogenizer and centrifuged at 4°C. The pellet sedimenting between 500 and 15,000 g was suspended in 5 ml of 0.25 M sucrose and layered on the top of a continuous linear gradient of 1.0—1.6 M sucrose which had been formed in a 38-ml centrifuge tube with a Hitachi DGF-U density gradient maker. The