bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protocol of a randomized, double-blind, placebo-controlled, parallel-group, multicentre study of the efficacy and safety of nicotinamide in patients with Friedreich ataxia (NICOFA)
Authors:   the EFACTS or NICOFA study group, Reetz Kathrin , Hilgers Ralf-Dieter , Isfort Susanne , Dohmen Marc , Didszun Claire , Fedosov Kathrin , Kistermann Jennifer , Mariotti Caterina , Durr Alexandra , Boesch Sylvia , Klopstock Thomas , Rodríguez de Rivera Garrido Francisco Javier , Schöls Ludger , Klockgether Thomas , Pandolfo Massimo , Korinthenberg Rudolf , Lavin Philip , Molenberghs Geert , Libri Vincenzo , Giunti Paola , Festenstein Richard , Schulz Jörg B. 
Published: October 2019

Abstract

Introduction
Currently, no treatment that delays with the progression of Friedreich ataxia is available. In the majority of patients Friedreich ataxia is caused by homozygous pathological expansion of GAA repeats in the first intron of the FXN gene. Nicotinamide acts as a histone deacetylase inhibitor. Dose escalation studies have shown, that short term treatment with dosages of up to 4 g/day increase the expression of FXN mRNA and frataxin protein up to the levels of asymptomatic heterozygous gene carriers. The long-term effects and the effects on clinical endpoints, activities of daily living and quality of life are unknown.

Methods
The aim of the NICOFA study is to investigate the efficacy and safety of nicotinamide for the treatment of Friedreich ataxia over 24 months. An open-label dose adjustment wash-in period with nicotinamide (phase A: weeks 1–4) to the individually highest tolerated dose of 2–4 g nicotinamide/day will be followed by a 2 (nicotinamide group): 1 (placebo group) randomization (phase B: weeks 5–104). In the nicotinamide group, patients will continue with their individually highest tolerated dose between 2 and 4 g/d per os once daily and the placebo group patients will be receiving matching placebo. Safety assessments will consist of monitoring and recording of all adverse events and serious adverse events, regular monitoring of haematology, blood chemistry and urine values, regular measurement of vital signs and the performance of physical examinations including cardiological signs. The primary outcome is the change in the Scale for the Assessment and Rating of Ataxia (SARA) over time as compared with placebo in patients with Friedreich ataxia based on the linear mixed effect model (LMEM) model. Secondary endpoints are measures of quality of life, functional motor and cognitive measures, clinician’s and patient’s global impression-change scales as well as the up-regulation of the frataxin protein level, safety and survival/death.

Perspective
The NICOFA study represents one of the first attempts to assess the clinical efficacy of an epigenetic therapeutic intervention for this disease and will provide evidence of possible disease modifying effects of nicotinamide treatment in patients with Friedreich ataxia.

Trial registration
EudraCT-No.: 2017-002163-17, ClinicalTrials.govNCT03761511.
FOLFOXIRI Plus Panitumumab As First-Line Treatment of RAS Wild-Type Metastatic Colorectal Cancer: The Randomized, Open-Label, Phase II VOLFI Study (AIO KRK0109)
Authors: Modest Dominik P. , Martens Uwe M. , Riera-Knorrenschild Jorge , Greeve Jobst , Florschütz Axel , Wessendorf Swen , Ettrich Thomas , Kanzler Stephan , Nörenberg Dominik , Ricke Jens , Seidensticker Max , Held Swantje , Buechner-Steudel Petra , Atzpodien Jens , Heinemann Volker , Seufferlein Thomas , Tannapfel Andrea , Reinacher-Schick Anke C. , Geissler Michael 
Published: October 2019

PURPOSE This trial investigated the addition of panitumumab to triplet chemotherapy with fluorouracil/folinic acid, oxaliplatin, and irinotecan (FOLFOXIRI) in a two-to-one randomized, controlled, open-label, phase II trial in patients with untreated RAS wild-type (WT) metastatic colorectal cancer. PATIENTS AND METHODS The primary end point was objective response rate (ORR) according to RECIST (version 1.1). The experimental arm (modified FOLFOXIRI [mFOLFOXIRI] plus panitumumab) was considered active if the ORR was ≥ 75%. The experimental ORR was compared with an estimated ORR of 60% based on historical data, verified by a randomized control group (FOLFOXIRI). The power of the trial was 80%, with a potential type I error of 0.05. Secondary end points included secondary resection rate, toxicity, progression-free survival, and overall survival. RESULTS A total of 63 patients were randomly assigned to the experimental arm and 33 patients to the control arm. The ORR of the mFOLFOXIRI plus panitumumab arm exceeded 75% and was higher when compared with that of FOLFOXIRI (87.3% v 60.6%; odds ratio, 4.469; 95% CI, 1.61 to 12.38; P = .004). The secondary resection rate was improved with the addition of panitumumab (33.3% v 12.1%; P = .02). Progression-free survival was similar in the study arms, whereas overall survival showed a trend in favor of the panitumumab-containing arm (hazard ratio for death, 0.67; 95% CI, 0.41 to 1.11; P = .12). CONCLUSION The addition of panitumumab to mFOLFOXIRI in patients with RAS WT metastatic colorectal cancer improved the ORR and rate of secondary resection of metastases and represents a treatment option in selected and fit patients in need of highly active first-line therapy. Future studies should determine whether the addition of panitumumab to mFOLFOXIRI prolongs survival.
Pancreatic Heterotopia Found in the Gastric Antrum Mistaken for Malignancy
Authors: Berry Rani , Rahal Harman K. , Ho Wendy 
Published: October 2019

ABSTRACT
Pancreatic heterotopia is a rare and often incidental finding in clinical practice. The term refers to pancreatic tissue distinct from the normal pancreas and with its own ductal and vascular supply. Usually asymptomatic, ectopic tissue is still prone to infection and may cause clinical complications when mistaken for malignancy or abscess. We describe a 32-year-old woman who presented with epigastric discomfort, initially thought to be a gastric outlet mass concerning for gastric malignancy vs an intraabdominal infection. She was eventually found to have an umbilicated submucosal lesion in the gastric antrum consistent with pancreatic heterotopia. Given the young age and sex of the patient, the differential diagnosis remained broad, underscoring the high risk of mismanagement of pancreatic heterotopia secondary to infrequency of this condition as a presenting diagnosis.
On Some Mutual Positions of Hyperplanes in a Finite-Dimensional Affine Space
Authors: Kharazishvili Alexander 
Published: October 2019

Abstract
Several combinatorial questions and facts connected with certain types of mutual positions of finitely many hyperplanes in a finite-dimensional affine space are considered. An application of one of such facts to a multi-dimensional version of the well-known Sylvester theorem is presented.
Controllability of Sobolev Type Semilinear Functional Differential and Integrodifferential Inclusions with an Unbounded Delay
Authors: Chang Yong-Kui , Li Wan-Tong 
Published: October 2019

Abstract
In this paper, sufficient conditions are established for the controllability of Sobolev type semilinear functional differential and integrodifferential inclusions with an unbounded delay in Banach spaces. The main results are obtained by using the fixed point theorem for condensing maps due to Martelli.
Acupuncture for Chemotherapy-Induced Peripheral Neuropathy in Breast Cancer Survivors: A Randomized Controlled Pilot Trial
Authors: Lu Weidong , Giobbie-Hurder Anita , Freedman Rachel A. , Shin Im Hee , Lin Nancy U. , Partridge Ann H. , Rosenthal David S. , Ligibel Jennifer A. 
Published: October 2019

Abstract

Background
Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most debilitating long-term side effects in breast cancer survivors. We conducted a randomized controlled pilot trial to assess the feasibility, safety, and effects of an acupuncture intervention on CIPN in this population.

Patients and Methods
Women with stage I–III breast cancer with grade 1 or higher CIPN after taxane-containing adjuvant chemotherapy were randomized 1:1 to an immediate acupuncture (IA) arm or to a waitlist control group (CG). Participants in the IA arm received 18 sessions of acupuncture over 8 weeks, then received no additional acupuncture. Patients in the CG arm received usual care over 8 weeks, followed by nine sessions of acupuncture over 8 weeks. Measures including Patient Neurotoxicity Questionnaire (PNQ), Functional Assessment of Cancer Therapy—Neurotoxicity subscale (FACT-NTX), and Brief Pain Inventory—short form (BPI-SF) were collected at baseline and at 4, 8, and 16 weeks after enrollment.

Results
Forty women (median age, 54) were enrolled (20 to IA and 20 to CG), with median time between completion of chemotherapy and enrollment of 14 months (range 1–92). At 8 weeks, participants in the IA arm experienced significant improvements in PNQ sensory score (−1.0 ± 0.9 vs. −0.3 ± 0.6; p = .01), FACT-NTX summary score (8.7 ± 8.9 vs. 1.2 ± 5.4; p = .002), and BPI-SF pain severity score (−1.1 ± 1.7 vs. 0.3 ± 1.5; p = .03), compared with those in the CG arm. No serious side effects were observed.

Conclusion
Women with CIPN after adjuvant taxane therapy for breast cancer experienced significant improvements in neuropathic symptoms from an 8-week acupuncture treatment regimen. Additional larger studies are needed to confirm these findings.
Motor Abilities: Identification of Development Level in Boys Aged 12-14
Authors: Khudolii O. M. , Ivashchenko O. V. , Iermakov S. S. , Veremeenko V. Yu. , Lopatiev A. O. 
Published: October 2019

The study objective is to determine the possibility of identifying the state of strength abilities development in boys aged 12-14, using the methodology of multidimensional statistics.
Materials and methods. The study involved boys: 12 (n =35), 13 (n = 36), 14 (n = 36) years old. The study used the following methods: analysis and collation of scientific and methodological literature, general scientific methods of theoretical level, such as analogy, analysis, synthesis, abstraction, induction, as well as general scientific methods of empirical level: observation, testing, experiment. The testing program included well-known tests.
Results. In identifying the state of motor abilities development in boys aged 12-14, the most important results were obtained in tests: 10 “Squats Test (two legs), quantity of times” (0.519), 9 “Trunk Lift Test, quantity of times” (0.497), 21 “Flamingo Balance Test - single leg balance test” (-0.496), 1 “Pull-Up / Chin Up Test (low crossbar), quantity of times” (0.428), 19 “Hand Tapping Test, sec.” (-0.427), 20 “Seated Forward Bend, cm” (-0.412), 5 “The subject lies in prone position, arms bent at the elbow 90 degrees - hold position in seconds” (0.408). These tests characterize the comprehensive development of motor abilities in boys aged 12-14.
In identifying the state of motor abilities development in boys aged 13-14, the most important results were obtained in tests: 8 “Decline Reverse Crunch on Bench, quantity of times” (-0.989), 11 “Single Leg Squat (SLS) Test - right leg, quantity of times” (0.965), 1 “Pull-Up / Chin Up Test (low crossbar), quantity of times” (0.676), №13 “Single Leg Squat (Pistol) - right leg” (0.682), 17 “Eurofit Sit Up Test (for 30 sec.), quantity of times” (0.454). These tests characterize the development level of relative and static leg strength, strength endurance of abdominal muscles, and dynamic strength of shoulder muscles.
Conclusions. A discriminant analysis made it possible to determine informative indicators for comprehensive control of motor abilities development in boys aged 12-14; to answer the question as to how significantly the states of motor abilities development in boys aged 12, 13 and 14 differ; what motor tests most substantially influence the differentiation of classes; what class the object belongs to based on the values of discriminant variables.
To identify the level of motor abilities development in boys aged 12-14 years, it is necessary to focus on the indicators of relative strength and strength endurance; in boys aged 13 and 14 years – on the indicators of strength endurance of abdominal muscles and endurance of leg muscles.
The source of HLA molecules on platelets: Does platelets adsorb soluble HLA molecules from their environment?
Authors: Dargahi Tahereh , Yari Fatemeh , Rezaei Negar 
Published: October 2019

Background: The origin and function of human leukocyte antigen (HLA) class I molecules on platelets are still highly arguable. Given the differences in the results of the previous studies in this regard, the lack of research in recent years, and the clinical importance of HLA class I molecules, the absorption capacity of platelets for soluble HLA class I molecules was studied in this investigation.
Materials and Methods: In this experimental study, HLA-A2 antigen was purified from a B cell precursor leukemia cell line (Nalm-6) by cell membrane protein solubilization and usage of HLA-A2 affinity column. Platelet concentrates (PCs) were received from Tehran Blood Transfusion Center. Eighteen bags of HLA-A2-negative PCs were prepared randomly and treated with various concentrations of the purified HLA antigen (100, 500, and 1000 ng/ml) for 48 to 72 hours. Subsequently, the HLA-A2 levels were evaluated on platelets by flow cytometery technique. Data were evaluated using repeated measure ANOVA.P-values less than 0.05 were considered significant.
Results: The results of this study showed that the purified protein was an HLA molecule (HLA-A2). After the treatment of platelets and HLA molecules, platelets inability was shown for the attracting of HLA molecules. This finding was true in both media of RPMI and plasma. The differences between the case (HLA-treated platelets) and control (untreated platelets) were not significant (p-values> 0.05).
Conclusion: Platelets were unable to significantly adsorb exogenous HLA antigens from their environment. Further studies are needed to unravel the nature and origin of HLA molecules on platelets.
Predictors of Caregiver Burden among Parents of Children with Cancer
Authors: Ahmadi Mehrnaz , Rassouli Maryam , Gheibizadeh Mahin , Karami Maryam , Poormansouri Saeed 
Published: October 2019

Background: Cancer is one of the most common diseases in children. Cancer in children can cause many problems for parents, and impose heavy care burden on them, which can lead to negative health consequences. The aim of this study was to determine caregiving burden and relevant influential factors among parents of children with cancer.
Materials and Methods: This cross-sectional descriptive study was done on 125 parents of children with cancer in oncology department of Shohada Hospital, Tehran, Iran, during March to August 2017. Caregiving burden was measured using the Caregiver Burden Scale. Descriptive statistics, independent-samples T test, one-way ANOVA, Pearson’s correlation analysis, and multivariate linear regression analysis (stepwise method) were used in data analysis with SPSS software (v.19).
Results: The mean score of parents’ care burden was 52.76 ± 10. Moreover, 17.6%, 71.2% and 11.2% of parents had low, moderate, and high care burden, respectively. Regression analyses indicated that the factors associated with care burden were cancer type (Acute myeloid leukemia (β=0.36, p<0.001) and Ewing sarcoma (β=0.16, p=0.007)), the number of hospitalization (β=0.38, p<0.001), duration of disease (β=-0.31, p<0.001), parent’s age (β=-0.29, p<0.001), parent’s income (β=-0.23, p<0.001), and child’s age (β=0.24, p<0.001). These variables accounted for 65% of the variance in care burden.
Conclusion: The result of this study demonstrated that most of parents of children with cancer had moderate levels of care burden. Different variables increased care burden in parents. Therefore, planning for holistic interventions to reduce care burden in parents and improve quality of care is necessary.
Classification model of funding for research institutions in Armenia
Authors: Sargsyan Sh. A. , Harutyunyan T. S. , Sahakyan V. H. , Haroutiunian S. G. 
Published: October 2019

Improving the efficiency of the use of public funds directed at scientific and technological research and development is one of the urgent problems of our time. Among the possible solutions is scientific organizations funding according to their results. With this aim, a number of countries have implemented evaluation of their scientific organizations productivity at the national level. Evaluation of the effectiveness of organizations engaged in scientific and technical R&D, and the distribution of funding according to the results of such evaluation there are in the UK (the first country to introduce such practices), Italy and Russia. Starting from 2020, the Republic of Armenia is also planning to invest a rating model for financing state scientific organizations.The article presents the model of rating financing of the state scientific organizations in Armenia, developed and proposed by the Committee on science of the Republic of Armenia. The introduction of the model will lead to the formation of additional financial resources and increase the efficiency of budget financing, as it will be done with the account of results of a scientific organization.
Surveying the Prevalence of Lower Urinary Tract Symptoms Based on Individual and Clinical Parameters in Patients with Multiple Sclerosis
Authors: Nazari Fatemeh , Shaygannejad Vahid , Sichani Mehrdad Mohammadi , Gharaagozlou Marjan Mansourian , Hajhashemi Valiollah 
Published: October 2019

Abstract
Background: Most patients with multiple sclerosis (MS) suffer from bladder dysfunction during the course of the disease. This study was conducted to examine the prevalence of these complications among patients with MS.
Methods: This cross-sectional study was performed on 602 patients with MS who referred to the neurology clinics of Kashani and Alzahra Hospitals affiliated to Isfahan University of Medical Sciences, Isfahan, Iran. The sampling was performed by multi-stage random cluster sampling method and the informed consent form was filled in by the subjects. Then, all the data were collected through interviews using the Lower Urinary Tract Symptom Score (LUTSS) developed in accordance with the definitions presented by the International Continence Society (ICS) and the International Prostate Symptom Score (I-PSS). The data were analyzed using descriptive and inferential statistical tests in SPSS.
Results: The prevalence rate of lower urinary tract symptoms (LUTS) was 87.6% among all the subjects, with a similar rate among women (88.0%) and men (86.0%). There was a significant difference between men and women in terms of the prevalence of stress urinary incontinence (SUI), intermittent urine flow, hesitancy, straining, and dribbling (P < 0.050). There was no significant difference between women and men in terms of the prevalence of other symptoms (P > 0.050). There was a significant difference between the degree of LUTS with age, marital status, marriage duration, education, illness duration, clinical course, and disability (P < 0.05). Moreover, logistic regression analysis revealed that there was a higher probability of a urinary problem among patients with MS and high EDSS score [0.67(0.512-0.898), P = 0.007].
Conclusions: A high prevalence of LUTS was found among patients with MS, with similar rates in men and women, and the nature of the LUTS was different among men and women with MS. There was a higher probability of a urinary tract problem among patients with MS and high EDSS score .Therefore, it is recommended that the health system take necessary measures regarding timely detection and treatment of LUTS among these patients in order to prevent secondary outcomes of patients with MS.
Keywords: Multiple sclerosis, prevalence, urinary symptoms
A novel variant of IHH in a Chinese family with brachydactyly type 1
Authors: Yang Qi , Wang Jin , Tian Xiaoxian , Chen Fei , Lan Jing , Zhang Qiang , Fan Xin , Yi Shang , Li Mengting , Shen Yiping 
Published: October 2019

Abstract
Brachydactyly type A1(BDA-1) is an autosomal dominant disorder which is caused by heterozygous pathogenic variants in a specific region of the N-terminal active fragment of Indian Hedgehog ( IHH ). The disorder is mainly characterized by shortening or missing of the middle phalanges. The following study revealed a novel heterozygous missense variant c.299A>G (p.D100G) at the mutational hotspot of IHH gene after performing whole-exome sequencing in the proband of a Chinese family with BDA-1. The variant co-segregated with BDA-1 in the pedigree, showed 100% penetrance for phalange phenotype with variable expressivity. This finding expanded the variants on IHH gene which contribute to the cause of BDA-1.
Multiplexed lipid metabolic tracing using click chemistry mass spectrometric reporter molecules
Authors: Thiele Christoph , Wunderling Klaus , Leyendecker Philipp 
Published: October 2019

Abstract
This protocol provides a method for sensitive multiplexed metabolic tracing. It is based on the combination of alkyne-labeled metabolic precursors and dedicated azido reporter molecules that are optimized for mass spectrometric detection after click reaction. After metabolic incorporation of alkyne fatty acids, sub-picomole to femtomole amounts of labeled material can be detected. Time resolution can be achieved by pulse-chase labeling.
Prevalence of diabetes among homeless and slum dwellers in Accra, Ghana: A survey study
Authors: BAWAH AHMED TIJANI , Yawson Albert Abaka , Seini Mohammed Mustapha , Yeboah Francis Agyemang , Ngala Robert Amadu 
Published: October 2019

Abstract
Objective: This study aimed at determining diabetes status of homeless people in Nima and Agbogbloshie, Accra, Ghana and to evaluate the association between socio-demographic characteristics and diabetes prevalence.
Results: A total of 130 homeless and slum dwellers took part in the study out of which 7 (5.4%) participants were diagnosed with diabetes while 13 (10 %) were considered as having prediabetes. This is slightly lower than what had been reported two decades ago but similar to overall estimates of diabetes prevalence in Africa (5.7%). Diagnosis of normoglycemia, prediabetes and diabetes was based on individual’s hemoglobin A1c (HbA1c) level: ≤5.9%, 6.4–6.0%, and ≥6.5%, respectively. There was no significant association between prevalence of diabetes or prediabetes and the socio-demographic characteristics of the participants. The slightly lower diabetes prevalence among the homeless and slum dwellers compared to the general population may be due to constant movement of these people in the streets, a practice that could serve as a form of exercise for them. Intensive social support aimed at preventing and managing diabetes is crucial if we are to further reduce the incidence of diabetes in homeless people.
Keywords: Homeless, Diabetes mellitus, Hemoglobin A1c, Head porters