Miracle-dz/UniFAR-FTUs huggingface dataset:
Vulvar Cancer: Dosimetric Comparison of Advanced 3D Conformal Radiation Therapy Technique with Anteroposterior and Posteroanterior Irradiation Techniques

Introduction: The commonly used technique of radiation therapy for vulvar cancer consists of anteroposterior (AP) and posteroanterior (PA) fields. This is the first study that reports the dosimetric comparison between the AP-PA techniques and the new 3D advanced conformal technique (3D-ACT) based on the multiplicity of treatment fields in patients with squamous cell cancer of the vulva in the postoperative setting. Material and Methods: This comparative planning study was conducted on15 patients with vulvar carcinoma treated with adjuvant radiation therapy at the National Institute of Oncology in Rabat, Morocco. Three treatment plans were performed, corresponding to three techniques, namely photons with source-skin distance inguinal supplement, modified segmental boost technique and 3D advanced conformal technique. For each plan, the dose-volume histogram was used to generate planning target volumes (total and inguinal PTV) and organs at risk (bladder, rectum, bowel and femoral heads) parameters. Results: The 95% isodose volume was significantly reduced with the advanced conformal technique (P<0.0001) without compromising the total PTV coverage (P= 0.94). This technique resulted in the best conformity and homogeneity index. The 3D-ACT decreased significantly the PTVs Dmax and Dmean (P<0.0001), and offered better homogeneity for inguinal PTV (i.e., 1.07±0.01, P<0.0001). The 3D-ACT decreased the rectum absorbed dose, V40 (volume receiving ≥40Gy), V45, and Dmaxto50.21±27.21, 22.81±10.22, and 46.56±1.11, respectively. With regard to femoral heads, the 3D-ACT decreased the Dmax and V45 in comparison to the other two techniques. Conclusion: The 3D-ACT seems to be an alternative to the AP-PA irradiation techniques in postoperative setting when IMRT is unavailable.
Intensive Lipid-Lowering Therapy Ameliorates Asymptomatic Intracranial Atherosclerosis

Statins have proven to exert protective effects in patients with symptomatic intracranial atherosclerotic stenosis (SICAS). It is unclear whether intensive lipid-lowering therapy (ILLT) can ameliorate atherosclerosis in asymptomatic ICAS (AICAS). A single-center, prospective cohort study was performed in 71 AICAS patients with lipid-lowering therapy. Vascular stenoses were evaluated with transcranial color-coded sonography (TCCS) before and after statin treatment. With target therapeutic level of low-density lipoprotein cholesterol (LDL-C) ≤ 1.8 mmol/L or ≥ 50% reduction from baseline after the two years of follow-up, patients were divided into intensive statin treatment (IST) group and standard statin treatment (SST) group. A total of 104 stenotic intracranial arteries were detected in 51 patients belonging to the IST group and 47 arteries in 20 patients of the SST group. In the first year, LDL-C levels were significantly decreased in the IST compared with SST groups (1.48 ± 0.26 vs. 2.20 ± 0.58, P=0.000). However, the ratio of regressed ICAS in IST was not significantly higher than that in SST (26.3% vs. 5.9%, P=0.052). Forty-nine branches in 25 patients of the IST group and 16 branches in 7 patients of the SST group were followed up for two years. The LDL-C level was decreased in the IST compared with SST groups (1.55 ± 0.29 vs. 2.36 ± 0.77, P=0.048). The ratio of regressed ICAS in the IST group was significantly higher than that in SST group (34.7% vs. 6.3%, P=0.017). We concluded that the degree of stenosis in AICAS can be ameliorated with intensive lipid-lowering therapy within two years; target LDL-C level can be reached by moderate-intensity statin treatment for Chinese AICAS patients.
Skeletal muscle regulatory factors with alterations in muscle mass

Given that maintenance of skeletal muscle mass is essential for overall health, functionality and quality of life, it is critical to elucidate the fiindaniental mechanisms underlying the maintenance of muscle mass which likely vary as a function of niuscle status (i.e. healthy or diseased). This thesis examined key skeletal muscle regulatory factors (smRFs) that are known to affect skeletal muscle mass, including components of the PI3KlAkt and MAPK(ERK) pathways, calcineurin, the myogenic regulatory factors and myostntin, following administration of a Pz-adrenergic agonist, Clenbuterol, and with progressive denervation. Although it is I<nown that Clenbuterol induces hypertrophy and attenuates atrophy of skeletal muscle, its mechanism of action is unclear. In this thesis, I have demonstrated that Clenbuterol induces PKA-independent stimulation of sniRFs (CAMP, p-Akt, pERK), and additional phospho-kinases (PKCa, PAK11213. FAK and Pyk2) that are also thought to be involved in regulating muscle mass. These changes occur relatively rapidly, often within 10 minutes of administration. Using a G93A mouse model of progressive denervation, I found an up-regulation of smRFs involved in growthlsulvival (Akt, calcineurin, ERK1/2), and decreases in the myogenic regulatory factor, MyoD, in skeletal muscle of these mice. These alterations occurred in coiijiinction with the onset of later-stage (i.e. severe) symptoms but prior to significant muscle atrophy. I was therefore interested in determining if Clenbuterol would attenuate the onset of disease symptoms and nluscle atrophy acconipanying the progressive denervation by altering these smKFs. Akt and MyoD levels in the G93A mouse were similar to wild-type muscle after six weeks of Clenbuterol treatment. Clenbuterol also attenuated the progression of symptoms in G93A mice which may account for the levels of smRFs observed. Increases in G93A mouse body mass, improved motor coordination (RotoRod) and strength (PaGE, females only) were also observed with Clenbuterol treatment without significant increases in muscle mass. This thesis suggests that alterations in smRFs. including the PI3WAkt and MAPK(ERK) pathways, calcineurin, and the myogenic regulatory factors occur prior to any observable changes in muscle mass. Identification of these muscle-specific factors has clinical relevance for the characterization and treatment of skeletal muscle atrophy associated with chronic diseases.
Prevalence and associated factors of pneumonia among under-five children atpublic hospitals in Jimma zone, South West of Ethiopia, 2018.

Background: Pneumonia is a leading single disease killing under-five children. In Ethiopia, it contributes to 18% deaths of under-five children every year. These deaths are easily preventable and treatable through simple and cost effective interventions. Objective: To assess the prevalence and associated factors of pneumonia among under -five children at public hospitals in Jimma Zone, Ethiopia. Methods: Cross-sectional study design was conducted on 306 systematically selected participants. Data was entered in to EPIDATA version 3.1 and exported to SPSS version 23 for analysis. Variables with p- value less than 0.2 at Bivariate logistic analysis were selected for further analysis by multivariate logistic regression to declare statistically significant association at P value <0.05 Result: Prevalence of pneumonia among under-five children was 28.1%. Use wood as fuel source(P= 0.003, AOR=3.45), cook food in living room(P= 0.008, AOR= 3.34), caring of the child on mothers back or besides the mother during cooking (P= 0.008, AOR= 2.96), absence of windows in the kitchen (P= 0.001, AOR= 2.5), children who unvaccinated (P= 0.004, AOR= 4.6), Vitamin A supplementation (P= 0.002, AOR= 0.168), mixed breast feeding (P= 0.014, AOR= 3.26), moderate acute malnutrition(P= 0.002, AOR= 4) and child history of ARTI(P= 0.004, AOR= 4) were a potential determinates of pneumonia. Conclusion and Recommendations: This study showed that the prevalence of pneumonia was high. Therefore, intervention on potential determinates such as: improved housing conditions, health education on exclusive breastfeeding and nutrition, increase immunization and Vitamin A supplementation and early control of respiratory tract infection were recommended.
The Relationship Between the Level of Parathormone and the Existence and the Degree of Coronary Atherosclerosis

Akdeniz University Faculty of Medicine, Department of Internal Medicine, Antalya, Turkey *Akdeniz University Faculty of Medicine, Department of Cardiology, Antalya, Turkey **Akdeniz University Faculty of Medicine, Department of Biochemistry, Antalya, Turkey ***Akdeniz University Faculty of Medicine, Department of Endocrinology and Metabolism, Antalya, Turkey Original Article Turk J Endocrinol Metab 2018;22:237-243
In vitro interaction studies of rosuvastatin and ACE-inhibitors by HPLC

In present paper in vitro drug interactions of rosuvastatin and ACE inhibitors; lisinopril, captopril and enalapril have been described. Co-administration of statins and ACE inhibitors is quite common since CVDs and anti-hypertensives go side by side, ignoring which may lead to heart attacks and strokes. These studies were carried out at 37oC in different pH environments of simulating human body fluids using HPLC. It was observed that after interaction of rosuvastatin with lisinopril, captopril and enalapril, the % availability values of all drugs were affected indicating formation of hydrogen bonded complexes among respective drugs that were verified by synthesizing their complexes and elucidating from IR and NMR spectroscopic studies. The studies show that co-administration of these drugs with rosuvastatin lower the clinical efficacy of all drugs unless the complexes are not broken down in vivo.
Screening questions for the diagnosis of restless legs syndrome in hemodialysis

Abstract Background Restless legs syndrome (RLS) is common in end-stage renal disease and is associated with reduced health-related quality of life. Simple and accurate screening instruments are needed since RLS is underdiagnosed and treatable. We examined the operating characteristics of screening questions and a disease-specific measurement tool for the diagnosis of RLS in hemodialysis. Methods We conducted a cohort study of prevalent adult hemodialysis patients in Hamilton, Canada. The diagnosis of RLS was made using the 2012 Revised International Restless Legs Syndrome Study Group (IRLSSG) criteria. All participants received three screening instruments: (i) a single screening question for RLS derived from a nondialysis population; (ii) a single question from the Edmonton Symptom Assessment System (ESAS); and (iii) the IRLSSG Rating Scale (IRLS). All instruments were compared with the reference standard using logistic regression from which receiver operating characteristics curves were generated. Cutoffs associated with maximum performance were identified. Results We recruited 50 participants with a mean (SD) age of 64 (12.4) years, of whom 52% were male and 92% were on three times weekly hemodialysis. Using the reference standard, 14 (28%) had a diagnosis of RLS. The single screening question for RLS had an area under the receiver operating curve (AUROC) of 0.72 with a sensitivity of 85.7% and specificity of 58.3%. An ESAS cutoff of ≥1 had the highest AUROC at 0.65 with a sensitivity of 79% and specificity of 56%. An IRLS cutoff of ≥20 had the highest AUROC at 0.75 with a sensitivity of 71% and specificity of 81%. Conclusion IRLS had better specificity than the single question or ESAS for the diagnosis of RLS.
Symptomatic accessory branch of the superficial peroneal nerve identified by ultrasound

commonly associated with SPG 11 or SPG 15 mutations. Clinicogenomic heterogeneity, with recessive and sometimes sporadic mutations, causes HSP, which creates challenges. Distinguishing PLS from HSP on clinical grounds has been difficult. Neurophysiological investigations can provide clues, with reduced lower limb SSEP latencies reported in some patients with HSP, although larger studies have not yet substantiated this finding. Normal levels of motor cortical excitability, measured using transcranial magnetic stimulation, are seen in those with HSP, whereas those with PLS are more likely to have inexcitable motor cortices. NGS is becoming a significant diagnostic resource in the neuromuscular clinic. One helpful resource is the GeneTable of Neuromuscular Disorders, which provides comprehensive and annually updated lists of pathogenic mutations. The early use of NGS may expedite the diagnostic process for those with progressive pyramidal tract disorders.
Production of constitutive and induced secondary metabolites is coordinated with growth and storage in Norway spruce saplings

Abstract A mechanistic understanding of how trees balance the trade-offs between growth, storage and defense is limited but crucial for predicting tree responses to abiotic and biotic stresses. Here we investigated how trees allocate storage of non-structural carbohydrates (NSC) to growth and constitutive and induced secondary metabolites (SM). We exposed Norway spruce (Picea abies) saplings to 5 weeks of complete darkness to induce light and/or carbon limitation and then applied methyl jasmonate (MeJA) to simulate biotic attack. We measured changes in biomass, NSC (sum of soluble sugars and starches), and constitutive and induced SM (sum of phenolic compounds and terpenoids) in current-year developing and previous-year mature needles and branches, as well as volatiles emitted from the canopy. Under darkness, NSC storage was preferentially used for constitutive biosynthesis of monoterpenes rather than biosynthesis of stilbenes and growth of developing organs, while SM stored in mature organs cannot be remobilized and recycled. Furthermore, MeJA-induced production of SM was constrained by low NSC availability in developing organs but not in mature organs grown in the dark. Emissions of volatiles were suppressed in the dark but after 1 h of re-illumination, emissions of both constitutive and induced monoterpene hydrocarbons recovered rapidly, whereas emissions of linalool and sesquiterpene produced via de novo synthesis did not recover. Our results highlight that light and/or carbon limitation may constrain constitutive and JA-induced biosynthesis of SM in coordination with growth, NSC storage and mobilization.
Phosphorylation of myelin regulatory factor by PRKG2 mediates demyelination in Huntington's disease

Demyelination is a common pathological feature of a large number of neurodegenerative diseases including multiple sclerosis and Huntington's disease (HD). Laquinimod (LAQ) has been found to have therapeutic effects on multiple sclerosis and HD. However, the mechanism underlying LAQ's therapeutic effects remains unknown. Using HD mice that selectively express mutant huntingtin in oligodendrocytes and show demyelination, we found that LAQ reduces the Ser259 phosphorylation on myelin regulatory factor (MYRF), an oligodendrocyte‐specific transcription factor promoting the expression of myelin‐associated genes. The reduced MYRF phosphorylation inhibits MYRF's binding to mutant huntingtin and increases the expression of myelin‐associated genes. We also found that PRKG2, a cGMP‐activated protein kinase subunit II, promotes the Ser259‐MYRF phosphorylation and that knocking down PRKG2 increased myelin‐associated protein's expression in HD mice. Our findings suggest that PRKG2‐regulated phosphorylation of MYRF is involved in demyelination and can serve as a potential therapeutic target for reducing demyelination.
EFFECT OF DIETARY EXPOSURE TO ERGOT ALKALOIDS ON CONTRACTILITY OF BOVINE MESENTERIC VASCULATURE AND RUMEN MOTILITY

OF THESIS EFFECT OF DIETARY EXPOSURE TO ERGOT ALKALOIDS ON CONTRACTILITY OF BOVINE MESENTERIC VASCULATURE AND RUMEN MOTILITY Endophyte-infected (E+) tall fescue grass has been associated with fescue toxicosis, a costly syndrome characterized by poor cattle performance and health resulting in significant production losses. The fungal endophyte produces ergot alkaloids, which help the grass thrive in poor conditions but are toxic to mammals. A number of symptoms of fescue toxicosis can be related to vasoconstriction of bovine core, peripheral, and foregut vasculature. The first part of this series of experiments demonstrated ergot alkaloids were also vasoactive in midgut vasculature, with the exception of lysergic acid. Additionally, prior dietary exposure to ergot alkaloids decreased the contractile response of mesenteric vasculature to many of the ergot alkaloids tested. In the second part of this series, a non-invasive method was developed for measuring rumen motility in cannulated cattle. Using this technology without different dietary treatments, it was determined that 8 to 16 h after feeding was the least variable between animals and would provide the best opportunity to measure differences in motility. Application of this technique in the third part of this series investigated the effect of ruminally dosed ergot alkaloids on rumen motility. Treatments were not effective at inducing fescue toxicosis, and no differences in rumen motility variables were detected.
What is the optimal fit-for-purpose design in an oncology first-in-human trial?: 3+3 vs. Bayesian logistic regression model

Primary goals When designing a clinical trial, the goals must be clearly and specifically defined, and this should guide decision making on the details of the study. The goals of phase 1 oncology studies may include: 1) determine maximal tolerated dose (MTD), 2) provide recommended phase 2 dose (RP2D), 3) describe/characterize dose-limiting toxicity (DLT), 4) expand understanding of the investigational product, e.g. pharmacokinetics, efficacy. These goals may be coupled with business/development timeline (e.g., as quickly as possible) and/or cost goals (with fewest possible subjects). For novel targets or mode of action, these many goals are further complicated by limited information about clinical efficacy and toxicity. The ethical dilemma regarding dose selection has evolved from being centered on limiting the number of patients who experience toxicity to also minimize underdosing of patients in need of treatment.
Proteomic analysis of the processes leading to Madurella mycetomatis grain formation in Galleria mellonella larvae

Mycetoma is a neglected chronic and granulomatous infection primarily associated with the fungal pathogen Madurella mycetomatis. Characteristic of this infection is the formation of grains. However, the processes leading to grain formation are not known. In this study, we employed a proteomic approach to characterise M. mycetomatis grain formation in Galleria mellonella larvae and map the processes leading to grain formation over time. For this, at 1 day, 3 days and 7 days post-inoculation, proteins from grains and hemolymph were extracted and analysed by label-free mass spectrometry. A total of 87, 51 and 48 M. mycetomatis proteins and 713, 997, 18 G. mellonella proteins were found in grains on day 1, 3 and 7 post-inoculation respectively. M. mycetomatis proteins were mainly involved in cellular metabolic processes and numerous enzymes were encountered. G. mellonella proteins were primarily involved in the nodulation process. The proteins identified were linked to nodulation and grain formation and four steps of grain formation were identified. The results of this proteomic approach could in the future be used to design novel strategies to interfere with mycetoma grain formation and to combat this difficult to treat infection.
No money, no treatment, no life : the lived experiences of haemodialysis patients in Nigeria

Background: Chronic kidney disease is one of the major health challenges across the world, and a silent killer of Nigerian people because they can’t pay for life saving treatment which has been available for over 30 years. People pay for their own haemodialysis (HD) treatment without any government or healthcare insurance-based support system. Studies have explored the lived experiences of dialysis patients in other parts of the world, where governments support the patients with the cost of care, there is no evidence that reports the lived experiences of what it means to be a dialysis patient in Nigeria. It is important to expose the experiences of HD patients living in a healthcare system where there is unequal access to treatment; where factors such as culture, cost, family and dependents needs influence and affect compliance to treatment. The aim of the study was to explore the experiences of CKD patients receiving HD in Nigeria. Methods: Seventeen eligible HD patients were recruited (5 females and 12 males). A qualitative longitudinal research approach was used in the conduct of the study over a period of seven months. Semi-structured interviews were conducted in three waves (1, 4 and 7 month) while a reflexive journal was kept through the period of the study and was used in the data analysis. All the interview data were analysed using framework analysis approach. Following the first interview, summary of the interview transcripts was sent to the participants for confirmation before the second and the third interviews. The transcripts of the three interviews were analysed and presented as the themes. Findings: This study exposed the unique experiences of people living with ESKD in Nigeria, reported as ‘death sentence’. Those who the money to access dialysis services had survived longer while those who had no money died early. However, that survival came at a price, often the family, friends and even whole villages would sell assets to fund short term dialysis treatment. This was unsustainable and resulted in increased poverty for the families and the dialysis patient, who ultimately died due to irregular and sub-optimum treatment. Decisions to attend dialysis sessions or adhere to treatment regimen was influenced by cultural practices/societal norms, costs issues, geographical barrier, family needs and religion. Lack of accurate information on conservative management (where there would be no financial gain for the health care facility) forced patients to make decisions to commence dialysis, resulting in early death due to inability to sustain the cost of treatment. Conclusion: Healthcare practitioners need to provide accurate information on conservative management to enable patients to make informed choices over their lives. They should be discouraged from selling all they have to pay for treatment, stripping themselves and their families of meagre resources, for very little gain, and health policy should support funded HD programmes.
Total plasma sulfide in mild to moderate diastolic heart dysfunction

Background. Th e early pathophysiological mechanisms of diastolic dysfunction are not understood well. Hydrogen sul fi de is an important endogenous gaseous transmitter that can in fl uence heart remodeling. Th e aim was to determine total plasma sul fi de (TPS) levels, as a surrogate marker of hydrogen sul fi de, in patients with mild diastolic dysfunction. Methods. Total plasma sul fi de and N-terminal pro brain-type natriuretic peptide (NT-proBNP) levels were determined in ambulatory patients with arterial hypertension or diabetes mellitus and echocar-diographically mild to moderate diastolic dysfunction. Results. Twenty-four patients were included: nine with normal diastolic function (Grade 0), eight with an impaired relaxation pattern (Grade 1), and seven with a pseudo-normalized pattern (Grade 2). TPS levels were highest in patients with normal diastolic function (Grade 0), and lowest in patients with Grade 2 diastolic dysfunction, with this di ff erence between Grade 0 and Grade 2 showing statistical signi fi cance (p = 0.017). NT-proBNP levels showed the reverse behavior, with this di ff erence again showing statistical signi fi - cance (p = 0.042). Conclusions. Total plasma sul fi de levels decrease with worsening of diastolic function from normal to moderate diastolic dysfunction.