bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum osteocalcin may serve as a predictor for the mortality in FOP patients aged ≤18 years at diagnosis
Authors: She Dunmin , Li Ran , Fang Ping , Zong Guannan , Xue Ying , Zhang Keqin 
Published: October 2019

Abstract
Background Fibrodysplasia ossificans progressive (FOP) is an ultra-rare genetic disorder characterized by extraskeletal heterotopic ossification. It is well recognized that FOP can lead to a devastating condition of disability. However, the mortality rate of FOP patients in China and risk factors for mortality are still largely unclear. Methods We conducted a retrospective research on a cohort of 65 cases of FOP patients in China from 2008 to 2018. We reviewed medical records of these FOP patients to retrieve information such as date of birth/death, gender, clinical features, genotypes and biochemical parameters and analyze the correlation of these parameters with the mortality. Results 92.3% (60/65 cases) patients were classic FOP patients, 3.1% (2/65 cases) were FOP-plus and 4.6% (3/65 cases) were FOP variants. 9 cases of this cohort were dead during the ten-year period, and the overall mortality rate was 13.8%. c.617G>A mutation was confirmed in all non-survivors. In FOP patients≤18 years at diagnosis, non-survivors demonstrated significantly lower blood osteocalcin and alkaline phosphatase levels compared with survivors ( P <0.05), and spearman correlation and logistic regression analysis indicated that serum osteocalcin and alkaline phosphatase levels were negatively correlated with the mortality. Furthermore, the receiver-operating characteristic curve analysis showed serum osteocalcin had the largest area under the curve of 0.855 among four biochemical parameters, and serum osteocalcin < 65.9 ng/ml displayed a good capacity to discriminate the non-survivors from survivors in FOP patients aged 18 years and younger at diagnosis.Conclusions Our findings showed that the mortality rate of FOP was 13.8% in China. Serum osteocalcin may serve as a clinical predictor for the mortality in FOP patients aged ≤18 years at diagnosis in China. 【 Key words 】Fibrodysplasia ossificans progressive (FOP); mortality; risk factors; osteocalcin
A novel individualized strategy for cryoballoon catheter ablation in patients with paroxysmal atrial fibrillation
Authors: Ding Jun , Xu Jing , Ma Wei , Chen Bingwei , Yang Peigen , Qi Yu , Sun Shan , Cheng Aijuan 
Published: October 2019

Abstract
Background : The optimal dosage for cryoablation of atrial fibrillation (Cryo-AF) is still unknown. To evaluate the efficacy of an individualized freeze duration, we compared the clinical outcome of patients treated with a time-to-pulmonary vein isolation (TT-PVI) or temperature-guided ablation protocol to the outcome of patients treated with a conventional ablation protocol.
Methods: A total of 164 consecutive patients were included in the study. One method employed was a conventional dosing protocol (at least 2 applications of 180 seconds each)(the Cryo-AF Conventional group n=84), and the second method had a shorter protocol that was based on the TT-PVI or achievement of -40°C within 60 seconds (the Cryo-AF Dosing group n=80).
Results: We treated 656 pulmonary veins (PVs) with 1420 cryotherapy applications. The mean number of applications per patient was 8.7±0.8, with no difference between groups (Cryo-AF Conventional , 8.7±0.8 versus Cryo-AF Dosing ,8.6±0.8; P =0.359). The Cryo-AF Dosing group required significantly less total cryotherapy application time (990.60±137.77versus 1501.58±89.60 seconds; P <0.001) and left atrial dwell time (69.91±6.91 versus 86.48±7.03 minutes; P <0.001) than the Cryo-AF Conventional group. Additionally, the Cryo-AF Dosing group required significantly less total procedure time (95.03±6.50 versus 112.43±7.11 minutes; P <0.001). We observed acute ATP-induced or spontaneous vein electric reconnections in 13 veins (1.98%) after 20 minutes. The reconnection rates between the Cryo-AF Conventional and Cryo-AF Dosing groups were similar in that 2.98% and 0.94% of the initially isolated veins were reconnected, respectively, ( P =0.061). There was no difference in the recurrence rate of free atrial arrhythmia after a 1-year follow-up, which were 78.75% in the Cryo-AF Dosing group versus 78.57% in the Cryo-AF Conventional group ( P =0.978).
Conclusion: A novel Cryo-AF dosing protocol guided by temperature or the TT-PVI can be used to individualize an ablation strategy. This new protocol can lead to a significant reduction in duration of the procedure, the cryoenergy dosage and the left atrial dwell time. The procedure had equal safety and similar acute and 1-year follow-up outcomes compared to the conventional approach.
Pilot test of an online training module on near-infrared spectroscopy monitoring (NIRS) for the randomised clinical trial SafeBoosC III
Authors: Hansen Mathias , Rasmussen Marie Isabel , Rubin Snorre , Pellicer Adelina , Cheng Guoqiang , Xu Xin , Zhaoqing Yin , Zoffman Vibeke , Greisen Gorm 
Published: October 2019

Abstract
Background SafeBoosC-III is an international randomised clinical trial, to evaluate the effect of treatment of extremely preterm infants during the first three days of life based on cerebral near-infrared spectroscopy monitoring (NIRS) versus treatment and monitoring as usual. To ensure high quality of the trial intervention as well as of patient care, we have developed a multilingual web-based training program, to train relevant staff and test their competence. As we enter an under-explored area of e-learning, we have conducted a pilot study on the first of the five modules comprising the web-based training program, to test the feasibility of developing such a program for an international trial with limited resources.Methods The module in this study focuses on the principles and practice of NIRS monitoring. The pedagogical idea was to integrate training and certification. One-hundred doctors and nurses from five Neonatal Intensive Care Units across China, Spain and Denmark were invited to participate in the piloting. Upon completion of the NIRS module, participants were invited to evaluate their experience by completing an online survey. Data from close-ended questions were analysed using descriptive statistics while data from open-ended questions underwent thematic analysis.Results In total, 81 of 100 invited staff members entered the training module and completed the online survey. The median time and the number of questions to pass the module was fifteen minutes and seven questions, respectively. Most staff found the academic level of the learning material and quiz appropriate (85% and 93% of all staff members, respectively), as well as agreeing that the module was relevant to prepare them to ‘use the NIRS device’ (90%). Thematic analysis revealed issues such as a discrepancy between learning material and quiz questions, lack of clarity and technical issues.Conclusion We provide evidence of the feasibility of developing a multilingual web-based training program for an international trial, despite challenges such as low budget, language barriers and possibly differences in the clinical training of staff. Exploring the integration of training and certification for international trials, the positive results of this study motivate further developments. Trial registration: ClinicalTrial.gov NCT03770741 (registered 10/12-2018), https://clinicaltrials.gov/ct2/show/NCT03770741?recrs=b&cond=cerebral+near+infrared+spectroscopy&rank=3
Determining the effects of exercise after smoking cessation therapy completion on continuous abstinence from smoking: Japanese study protocol
Authors: Ozaki Yuka , Komiyama Maki , Ueshima Kenji , Iso Hiroyasu , Sakata Satoko , Morino Ayumi , Takahara Mitsuyoshi , Noguchi Satoshi , Kuwabara Yoshihiro , Takahashi Yuko , Hasegawa Koji 
Published: October 2019

Abstract
Background: Despite a steady world-wide decline over recent decades, the smoking rates remain high in developed countries. In Japan, the smoking rate is 30% for men and 10% for women. Based on these rates, Japan's smoking population is estimated to be 18.8 million (14.06 million for men and 4.74 million for women). The rate of success for smoking cessation has recently improved due to the widespread availability of drug therapy; however, the success rate for quitting smoking one year after beginning therapy is only around 50%. Previous studies have demonstrated that exercise can relieve mental stress during continuous abstinence from smoking and curb smoking resumption. To date, no large-scale randomized controlled trials have examined the effects of exercise on smoking cessation. The present study aims to determine the effects of implementing an intervention in the form of exercise instruction after smoking cessation therapy completion on continuous abstinence from smoking.

Methods: This is a multicenter, prospective, parallel-group, randomized controlled trial in Japan.We will enroll 300 individuals visiting a smoking cessation clinic (over three months) who have abstained from smoking in the second month after their initial visit as potential participants. Participants will not habitually exercise and will consent to participate. Participants will be randomly assigned to the exercise intervention group or control group. The intervention group will receive instruction on exercises that can be incorporated into their daily lives. The control group will be followed during the standard smoking cessation support program. The primary endpoint will be the continuous abstinence rate, and secondary endpoints will be weight, blood pressure, exhaled carbon monoxide concentration, psychological state, and blood test results. These indices will be compared between the intervention and control groups, with follow-up periods of nine months for both groups.

Discussion: By examining the effects of exercise instruction after completion of a 12-week smoking cessation therapy, this study should yield quality information that can be used to develop protocols to improve the continuous abstinence rate and inhibit weight gain after smoking cessation therapy.
Diyaliz Hastalarında Sosyal Bütünleşme İhtiyacı
Authors: Oğuz Güner Yasemin 
Published: October 2019

Kronik
böbrek yetmezliği, hemodiyaliz , periton diyalizi ya da böbrek nakliyle
tedavisi yapılan hastalıklardan biridir. Diyaliz tedavisi, hastanın sağ kalımını
sağlasa da, yaşam kalitesi hala üzerinde çalışılması gereken sorunların başında
gelmektedir. Yaşam kalitesi kavramının içinde, fiziksel sağlık, ruh sağlığı,
bağımsızlık düzeyi, sosyal ilişkiler, yaşama ve sağlığa bakış açısı,
beklentiler ve alışkanlıklar yer
almaktadır. Kronik hastalıklarda birey yaşam boyu az yada çok hastalık
etkilerini yaşar. Bu gruptaki bireylerde, hastalığa bağlı günlük yaşam
aktiviteleri ve iyilik hali bozulması yaşam kalitesinin düşmesine neden olur.Bu
bağlamda yaşam kalitesini arttırmak için sadece medikal gelişmelerin yeterli
gelmediği, hastaların psikososyal desteğe de ihtiyaç duydukları bilinmektedir. Psikososyal
destek, bazı hastalıklar için uygulansa da çoğunlukla diğer kronik hastalıklarda
göz ardı edilmekte, medikal başarıya odaklanılmaktadır. Psikososyal destek için
ülkemizde multidisipliner ekibin içinde ihtiyaç duyulan meslek grupları henüz
yer almamaktadır. Yaşam kalitesinin hastalıkla ilişkili olarak azaldığı diyaliz
hastalarında, sosyal bütünleşme ihiyacını ortaya koymak amacıyla yapılan bu
çalışmada; sosyal etkileşimde bozulmayla başlayan yalnızlık, anksiyete ve
depresyon, tedaviye uyum güçlüğü ve intihara eğilim gibi önemli sorunlara neden
olduğu görülmüştür. Çalışmada son dönem böbrek yetmezliği olan hastalarda yaşam
kalitesini bozan başlıca sorunlar; İş ve eğitim engeli, sağlık giderleri, psikolojik
sorunlar, aile içi görev tanımındaki değişiklikler ve sosyal çevre sorunları altında
toplanıp, alan yazın taraması ile irdelenmiştir.
Non-invasive Biodiversified Sensors: A Modernized Screening Technology for Cancer
Authors: Takke Anjali , Shende Pravin 
Published: October 2019

Background:
Biological sensors revolutionize the method of diagnoses of diseases from early to final
stages using the biomarkers present in the body. Biosensors are advantageous due to the involvement of minimal
sample collection with improved specificity and sensitivity for the detection of biomarkers.

Methods:
Conventional biopsies restrict problems like patient non-compliance, cross-infection and high cost and to
overcome these issues biological samples like saliva, sweat, urine, tears and sputum progress into clinical and diagnostic
research for the development of non-invasive biosensors. This article covers various non-invasive measurements
of biological samples, optical-based, mass-based, wearable and smartphone-based biosensors for the detection
of cancer.

Results:
The demand for non-invasive, rapid and economic analysis techniques escalated due to the modernization
of the introduction of self-diagnostics and miniature forms of devices. Biosensors have high sensitivity and
specificity for whole cells, microorganisms, enzymes, antibodies, and genetic materials.

Conclusion:
Biosensors provide a reliable early diagnosis of cancer, which results in faster therapeutic outcomes
with in-depth fundamental understanding of the disease progression.
Amyloid-β Oligomers-induced Mitochondrial DNA Repair Impairment Contributes to Altered Human Neural Stem Cell Differentiation
Authors: Lu Jing , Li Yi , Mollinari Cristiana , Garaci Enrico , Merlo Daniela , Pei Gang 
Published: October 2019

Background:
Amyloid-β42 oligomers (Aβ42O), the proximate effectors of neurotoxicity observed
in Alzheimer’s disease (AD), can induce mitochondrial oxidative stress and impair mitochondrial
function besides causing mitochondrial DNA (mtDNA) damage. Aβ42O also regulate the proliferative
and differentiative properties of stem cells.

Objective:
We aimed to study whether Aβ42O-induced mtDNA damage is involved in the regulation of
stem cell differentiation.

Method:
Human iPSCs-derived neural stem cell (NSC) was applied to investigate the effect of Aβ42O on
reactive oxygen species (ROS) production and DNA damage using mitoSOX staining and long-range
PCR lesion assay, respectively. mtDNA repair activity was measured by non-homologous end joining
(NHEJ) in vitro assay using mitochondria isolates and the expression and localization of NHEJ components
were determined by Western blot and immunofluorescence assay. The expressions of Tuj-1 and
GFAP, detected by immunofluorescence and qPCR, respectively, were examined as an index of neurons
and astrocytes production.

Results:
We show that in NSC Aβ42O treatment induces ROS production and mtDNA damage and impairs
DNA end joining activity. NHEJ components, such as Ku70/80, DNA-PKcs, and XRCC4, are localized
in mitochondria and silencing of XRCC4 significantly exacerbates the effect of Aβ42O on
mtDNA integrity. On the contrary, pre-treatment with Phytic Acid (IP6), which specifically stimulates
DNA-PK-dependent end-joining, inhibits Aβ42O-induced mtDNA damage and neuronal differentiation
alteration.

Conclusion:
Aβ42O-induced mtDNA repair impairment may change cell fate thus shifting human NSC
differentiation toward an astrocytic lineage. Repair stimulation counteracts Aβ42O neurotoxicity, suggesting
mtDNA repair pathway as a potential target for the treatment of neurodegenerative disorders like
AD.
Alzheimer’s Disease and Retinal Degeneration: A Glimpse at Essential Trace Metals in Ocular Fluids and Tissues
Authors: Micera Alessandra , Bruno Luca , Cacciamani Andrea , Rongioletti Mauro , Squitti Rosanna 
Published: October 2019

Background:
Life expectancy is increasing all over the world, although neurodegenerative
disorders might drastically affect the individual activity of aged people. Of those, Alzheimer’s Disease
(AD) is one of the most social-cost age-linked diseases of industrialized countries. To date, retinal diseases
seem to be more common in the developing world and characterize principally aged people. Agerelated
Macular Degeneration (AMD) is a late-onset, neurodegenerative retinal disease that shares several
clinical and pathological features with AD, including stress stimuli such as oxidative stress, inflammation
and amyloid formations.

Method:
In both diseases, the detrimental intra/extra-cellular deposits have many similarities. Aging,
hypercholesterolemia, hypertension, obesity, arteriosclerosis and smoking are risk factors to develop
both diseases. Cellular aging routes have similar organelle and signaling patterns in retina and brain. The
possibility to find out new research strategies represent a step forward to disclose potential treatment for
both of them. Essential trace metals play critical roles in both physiological and pathological condition
of retina, optic nerve and brain, by influencing metabolic processes chiefly upon complex multifactorial
pathogenesis.

Conclusion:
Hence, this review addresses current knowledge about some up-to-date investigated essential
trace metals associated with AD and AMD. Changes in the levels of systemic and ocular fluid essential
metals might reflect the early stages of AMD, possibly disclosing neurodegeneration pathways
shared with AD, which might open to potential early detection.
Recursive Partitioning Analysis and Anti-Tubercular Screening of 3- Aminopyrazine-2-Carbohydrazide Derivatives
Authors: Miniyar Pankaj , Mahajan Anand , Anuse Dattatray , Kumar Ashish , Barmade Mahesh , Sarkar Dhiman , Arkile Manisha , Khedkar Vijay 
Published: October 2019

Background:
Treating tuberculosis is a challenge due to the development of drug
resistance. Hence, it is imperative to develop novel leads having high potency and efficacy to curb
drug resistance.

Methods:
The present research work is focused on microwave-assisted synthesis of novel twenty-six
3-amino-N’-benzylidenepyrazine-2-carbohydrazide derivatives (3a-z), where, lyophilization
technique was used for isolation of the major intermediate, 3-aminopyrazin-2-carbohydrazide. All
synthesized compounds were subjected for anti-tubercular screening against Mycobacterium
tuberculosis H37Ra by using XTT Reduction Menadione Assay (XRMA) protocol.

Results:
Out of 26 synthesized compounds, four N’-substitutedbenzaldehyde-3-amino-pyrazine-2-
carbohydrazide derivatives viz. 3i, 3j 3v and 3z showed significant activity against M. tuberculosis
H37Ra. The compounds 3i, 3j, 3v and 3z showed 99, 98, 92 and 87 % inhibition respectively as
compared to 94% inhibition shown by the standard drug rifampicin. The MIC and IC50 values were in
the range of 24.3-110 and 5.9-20.8 µg/ml respectively.

Conclusion:
A classification model called Recursive Partitioning (RP) based on binary Quantitative
Structure-Activity Relationship (QSAR) was derived for the establishment of structure-activity
relationship (SAR). The predictions derived on the basis of RP model were found to be in agreement
with anti-tubercular screening data.
Analysis of Organic Impurities of Besifloxacin Hydrochloride by High-Performance Liquid Chromatography with Isocratic and Gradient Elution
Authors: Manoel Joanna Wittckind , Alves Giordani Camila Ferrazza , Bueno Livia Maronesi , Campanharo Sarah Chagas , Sherman Schapoval Elfrides Eva , Garcia Cássia Virgínia , Steppe Martin , Volpato Nádia Maria 
Published: October 2019

Introduction:
Impurity analysis is an important step in the quality control of pharmaceutical
ingredients and the final product. Impurities can arise from drug synthesis or excipients and even at
small concentrations may affect product efficacy and safety. In this work, two methods using highperformance
liquid chromatography (HPLC) were developed and validated for the evaluation of besifloxacin
and its impurity synthesis, with isocratic elution and another with gradient elution.

Method:
The analysis by HPLC in isocratic elution mode was performed using a cyano column maintained
at 25 °C. The mobile phase was composed of 0.5% triethylamine (pH 3.0): acetonitrile (88:12
v/v) eluted at a flow rate of 1.0 mL/min with detection at 330 nm. The gradient elution method was
carried out with the same column and mobile phase components only modifying the rate between organic
and aqueous phase during analysis. The procedures have been validated according to internationally
accepted guidelines, observing results within acceptable limits.

Results:
The methods presented were found to be linear in the 140 to 260 μg/ mL range for besifloxacin
and 0.3 to 2.3 μg/ mL for an impurity named A. The limits of detection and quantification were,
respectively, 0.07 and 0.3 μg/ mL for impurity A, with a 20 μL injection volume. The precision
achieved for all analyses performed provided RSD inter-day equal to 6.47 and 6.36% for impurity A
with isocratic elution and gradient, respectively. The accuracy was higher than 99% and robustness
exhibited satisfactory results. In the isocratic method, an analysis time of 25 min and 15 min was obtained
for the gradient. For impurity A, the number of theoretical plates in the isocratic mode was about
5000 while in the gradient mode it was about 45000, hence, it made the column more efficient by
changing the mobile phase composition during elution. In besifloxacin raw material and in the pharmaceutical
product used in this study, other related impurities were present but impurity A was searched
for and not detected.

Conclusion:
The proposed methods can be applied for the quantitative determination of impurities in
the analysis of the besifloxacin raw material, as well as in ophthalmic suspension of the drug, considering
the quantitation limit.
Self-medication Pattern and Prevalence Among Iranian Medical Sciences Students
Authors: Niroomand Nastaran , Bayati Mohsen , Seif Mozhgan , Delavari Somayeh , Delavari Sajad 
Published: October 2019

Background:Self-medication could be risky behavior and has negative effects. While Over the Counter (OTC) drugs are available at drugstores, the behavior has become prevalent among the general population.Objective:This study aimed at surveying self-medication behavior among medical sciences students of Shiraz, Iran.Methods:A sample of 396 students from medical, paramedical, and health sciences disciplines were included in this cross-sectional study. They were asked to fill a questionnaire about their demographics and socioeconomic status, medication usage and self-medication in the last six months, information about the correct use of medication, and information about negative results of selfmedication. Data were analyzed using chi-square, t-test and logistic regression model using R statistical software.Results:Almost 72% of participants reported self-medication in the past sixth months. The main reasons included trust in their own diagnosis (59.9%), mildness of the disease (56.6%), and having previous experience about the disease (56%). Cough or cold (84.5%), headache (66.3%), and body pain (60.2%) were the most frequent diseases that led to self-medication. The majority of the participants (77.7%) reported they select their medicine on their own decision. Furthermore, self-medication was highly related to having medicine stock at home (OR=2.692), having less information about negative results of self-medication (OR=0.835), and more non-syllabus study time (OR=1.041).Conclusions:Although, medical science students have information about the treatment of illnesses, they should be more informed about negative results and side-effects of self-medication. They should also share their knowledge with society to decrease self-medication.