bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of a multi-level intervention on hookah smoking frequency and duration among Iranian adolescents and adults: an application of socio-ecological model
Authors: Aghdam Fatemeh Bakhtari , Alizadeh Nader , Nadrian Haidar , Augner Christoph , Mohammadpoorasl Asghar 
Published: January 2021

AbstractBackgroundThe present study aimed to investigate the effects of a multi-level intervention on hookah smoking frequency and duration among Iranian adolescents and adults.MethodsIn this study, two comparable cities in Iran were selected to participate in an intervention program based on a social-ecological model (SEM). In each city, 133 hookah smokers in coffee houses were selected. Environmental changes in coffee houses such as serving light foods and games were conducted. A virtual group named “no hookah” was established on the Telegram application to train participants in the intervention group. Messages, pictures, and short videos were sent to the participants through that virtual network. The frequency and duration of hookah consumption were assessed in both groups at baseline and after the intervention.ResultsThe frequency of hookah consumption decreased in 72.6% of participants in the intervention group (vs. 6.3% in the control group), and the duration of hookah consumption per session decreased in 39.5% of participants in the intervention group (vs. 5.5% in the control group).ConclusionsUsing multi-level interventions through a social-ecological model can reduce hookah consumption in adults.
Hotspots of female genital mutilation/cutting and associated factors among girls in Ethiopia: a spatial and multilevel analysis
Authors: Geremew Tesfahun Taddege , Azage Muluken , Mengesha Endalkachew Worku 
Published: January 2021

Abstract
Background
Female genital mutilation/cutting (FGM/C) is a harmful traditional practice that violates the human rights of girls and women. It is widely practiced mainly in Africa including Ethiopia. There are a number of studies on the prevalence of FGM/C in Ethiopia. However, little has been devoted to its spatial epidemiology and associated factors. Hence, this study aimed to explore the spatial pattern and factors affecting FGM/C among girls in Ethiopia.

Methods
A further analysis of the 2016 Ethiopia Demographic and Health Survey data was conducted, and a total of 6985 girls nested in 603 enumeration areas were included in this analysis. Global Moran’s I statistic was employed to test the spatial autocorrelation, and Getis-Ord Gi* as well as Kulldorff’s spatial scan statistics were used to detect spatial clusters of FGM/C. Multilevel logistic regression models were fitted to identify individual and community level factors affecting FGM/C.

Results
Spatial clustering of FGM/C was observed (Moran’s I = 0.31, p-value < 0.01), and eight significant clusters of FGM/C (hotspots) were detected. The most likely primary SaTScan cluster was detected in the neighborhood areas of Amhara, Afar, Tigray and Oromia regions (LLR = 279.0, p < 0.01), the secondary cluster in Tigray region (LLR = 67.3, p < 0.01), and the third cluster in Somali region (LLR = 55.5, P < 0.01). In the final best fit model, about 83% variation in the odds of FGM/C was attributed to both individual and community level factors. At individual level, older maternal age, higher number of living children, maternal circumcision, perceived beliefs as FGM/C are required by religion, and supporting the continuation of FGM/C practice were factors to increase the odds of FGM/C, whereas, secondary or higher maternal education, better household wealth, and regular media exposure were factors decreasing the odds of FGM/C. Place of residency, Region and Ethnicity were also among the community level factors associated with FGM/C.

Conclusions
In this study, spatial clustering of FGM/C among girls was observed in Ethiopia, and FGM/C hotspots were detected in Afar, Amhara, Tigray, Benishangul Gumuz, Oromia, SNNPR and Somali regions including Dire Dawa Town. Both individual and community level factors play a significant role in the practice of FGM/C. Hence, FGM/C hotspots require priority interventions, and it is also better if the targeted interventions consider both individual and community level factors.
Primary clear cell sarcoma of the femur: a unique case with RT-PCR and direct sequencing confirmation of EWSR1/ATF1 fusion gene
Authors: Kubota Yuta , Tanaka Kazuhiro , Hisaoka Masanori , Daa Tsutomu , Iwasaki Tatsuya , Kawano Masanori , Itonaga Ichiro , Tsumura Hiroshi 
Published: January 2021

AbstractBackgroundIt is very rare for clear cell sarcomas (CCS) to arise in the bone. During diagnosis, it is important to distinguish primary CCS of bone from bone metastasis of melanoma because this difference fundamentally changes the therapeutic options. Recently, characteristic fusion genes of CCS have been detected using reverse transcription polymerase chain reaction (RT-PCR) or direct sequencing which allowed to distinguish CCS from melanoma. However, there was no study applying these analyses with positive results. In this case, we describe the use of fusion gene analysis to diagnose a primary CCS of the bone.Case presentationA 36-year-old male presented with a four-months history of left knee pain. Magnetic resonance imaging showed a lesion in the left femoral medial epicondyle. Histological examination of the biopsy specimen revealed proliferating oval or rounded cells. These cells had clear cytoplasm arranged in fascicles or compact nests with frequent deposits of brown pigment. Furthermore, immunohistochemistry analysis revealed that tumor cells were positive for S-100 protein, HMB-45, Melan-A, and SOX10. It stained negative for CD34 and BRAF v600e. Conclusively, detection of theEWSR1/ATF1fusion gene using RT-PCR and direct sequencing confirmed that the lesion was a primary CCS of the bone. Wide-margin resection and reconstruction with a tumor endoprosthesis were performed.ConclusionsHerein, we diagnosed a rare case of primary CCS of the bone by detectingEWSR1/ATF1fusion gene using RT-PCR and direct sequencing. Since fluorescence-in situ hybridization (FISH) and RT-PCR could show false positive by mainly due to technical problems, it is better to perform direct sequencing to confidently diagnose the tumor as a primary CCS especially at very rare site such as bone.
Allergen fragrance molecules: a potential relief for COVID-19
Authors: Aydın Aslı Deniz , Altınel Faruk , Erdoğmuş Hüseyin , Son Çağdaş Devrim 
Published: January 2021

AbstractBackgroundThe latest coronavirus SARS-CoV-2, discovered in China and rapidly spread Worldwide. COVID-19 affected millions of people and killed hundreds of thousands worldwide. There are many ongoing studies investigating drug(s) suitable for preventing and/or treating this pandemic; however, there are no specific drugs or vaccines available to treat or prevent SARS-CoV-2 as of today.MethodsFifty-eight fragrance materials, which are classified as allergen fragrance molecules, were selected and used in this study. Docking simulations were carried out using four functional proteins; the Covid19 Main Protase (MPro), Receptor binding domain (RBD) of spike protein, Nucleocapsid, and host Bromodomain protein (BRD2), as target macromolecules. Three different software, AutoDock, AutoDock Vina (Vina), and Molegro Virtual Docker (MVD), running a total of four different docking protocol with optimized energy functions were used. Results were compared with the five molecules reported in the literature as potential drugs against COVID-19. Virtual screening was carried out using Vina, molecules satisfying our cut-off (− 6.5 kcal/mol) binding affinity was confirmed by MVD. Selected molecules were analyzed using the flexible docking protocol of Vina and AutoDock default settings.ResultsTen out of 58 allergen fragrance molecules were selected for further docking studies. MPro and BRD2 are potential targets for the tested allergen fragrance molecules, while RBD and Nucleocapsid showed weak binding energies. According to AutoDock results, three molecules, Benzyl Cinnamate, Dihydroambrettolide, and Galaxolide, had good binding affinities to BRD2. While Dihydroambrettolide and Galaxolide showed the potential to bind to MPro, Sclareol and Vertofix had the best calculated binding affinities to this target. When the flexible docking results analyzed, all the molecules tested had better calculated binding affinities as expected. Benzyl Benzoate and Benzyl Salicylate showed good binding affinities to BRD2. In the case of MPro, Sclareol had the lowest binding affinity among all the tested allergen fragrance molecules.ConclusionAllergen fragrance molecules are readily available, cost-efficient, and shown to be safe for human use. Results showed that several of these molecules had comparable binding affinities as the potential drug molecules reported in the literature to target proteins. Thus, these allergen molecules at correct doses could have significant health benefits.
“Brought to life through imagery” – animated graphic novels to promote empathic, patient-centred care in postgraduate medical learners
Authors: Sutherland Travis , Choi Dorothy , Yu Catherine 
Published: January 2021

Abstract
Background
Empathy levels decline through medical training. This has been associated with poor patient and physician outcomes, and strategies to combat this decline are increasingly recognized as critical aspects of medical education. The aim of this study was to qualitatively determine factors associated with empathy decline, and to assess the impact of a comics/graphic novel-based curriculum on enhancing empathy and a patient-centered approach to care in post-graduate medical learners.

Methods
Fourth and fifth year residents in the Adult and Pediatric Endocrinology and Metabolism Program at the University of Toronto were recruited from the 2017 cohort of the Empathy, Humanism & Comics course. Participants completed a 12-month curriculum, viewing a total of four animated graphic novels over six sessions. At the end of the course participants were interviewed either individually or in a focus group. A coding framework of emerging themes was developed based on consensus between the three authors using a qualitative descriptive approach and the constant-comparison method.

Results
Analysis of coded interview data revealed four themes. 1. The curriculum accurately reflected and addressed issues in real world medical practice; 2. The comics curriculum facilitated holistic development; 3. Participants appreciated the comics as an educational medium; 4. Participant feedback on the curriculum. The importance of empathy was noted, while participants acknowledged their own empathy decline and increased burnout. Stressors included increasing responsibility, long work hours, and competing work-life responsibilities. They felt the sessions developed resilience, an appreciation for the patient perspective, and communication skills. They appreciated the comics as a novel and engaging educational modality. Feedback on the effectiveness and relevancy of the curriculum was variable.

Conclusions
Residents appreciated sharing difficult experiences and seeking support. They acknowledged the curriculum as a commitment to wellness and felt it reduced burnout and improved empathy. The comics were viewed as an effective reminder of the patient perspective. Variable curriculum feedback highlights the challenge in designing a course for adult learners. Future investigations may include the development and incorporation of similar curricula in other post-graduate residency training programs.
Knowledge, attitudes, and understanding of probiotics among pediatricians in different regions of Saudi Arabia
Authors: Hasosah Mohammed , Qurashi Mansour , Balkhair Abdullah , Alzahrani Ziyad , Alabbasi Abdullah , Alzahrani Muhanad , Alnahdi Wejdan , Shafei Sohaib , Bafaqih Malak , Khan Muhammad 
Published: January 2021

Abstract
Background
Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit upon the host. Knowledge and attitudes of health professionals have been reported to be at a medium level for probiotics. The objective was to evaluate the knowledge and practice styles about probiotics among pediatricians working in different regions of Saudi Arabia.

Methods
This cross-sectional study was conducted at pediatric hospitals in Saudi Arabia. A national survey of 550 pediatric providers (PPs) was conducted between January and March 2020 anonymously on their knowledge and practice styles regarding probiotics, and it was completed by pediatric residents (PRs), pediatric specialist (PSs), pediatric consultants (PCs), and pediatric gastroenterologists (PGs).

Results
The survey had a response rate of 82%. Among the respondents, 57.7% were aware of the probiotic’s definition. There were significant differences in the percentage of participants who had little knowledge of probiotics (P < 0.05), with the highest being PRs and the lowest being PGs. The most common probiotic used by all participants was Lactobacillus acidophilus (63.3%), and Mycobacterium avium was prescribed the least often (8.6%). Most PRs and PSs correctly reported that probiotics reduce the risk of antibiotic-induced diarrhea (74.9 and 80.2%, respectively), but there were no significant differences among them.

Conclusions
Significant differences in knowledge and practice patterns exist for probiotics. Identification of knowledge gaps may be useful to develop educational materials to improve the proper definition, knowledge, and use of probiotics.
A multi-level hypoglycemia early alarm system based on sequence pattern mining
Authors: Yu Xia , Ma Ning , Yang Tao , Zhang Yawen , Miao Qing , Tao Junjun , Li Hongru , Li Yiming , Yang Yehong 
Published: January 2021

AbstractBackgroundEarly alarm of hypoglycemia, detection of asymptomatic hypoglycemia, and effective control of blood glucose fluctuation make a great contribution to diabetic treatment. In this study, we designed a multi-level hypoglycemia early alarm system to mine potential information in Continuous Glucose Monitoring (CGM) time series and improve the overall alarm performance for different clinical situations.MethodsThrough symbolizing the historical CGM records, the Prefix Span was adopted to obtain the early alarm/non-alarm frequent sequence libraries of hypoglycemia events. The longest common subsequence was used to remove the common frequent sequence for achieving the hypoglycemia early alarm in different clinical situations. Then, the frequent sequence pattern libraries with different risk thresholds were designed as the core module of the proposed multi-level hypoglycemia early alarm system.ResultsThe model was able to predict hypoglycemia events in the clinical dataset of level-I (sensitivity 85.90%, false-positive 23.86%, miss alarm rate 14.10%, average early alarm time 20.61 min), level-II (sensitivity 80.36%, false-positive 17.37%, miss alarm rate 19.63%, average early alarm time 27.66 min), and level-III (sensitivity 78.07%, false-positive 13.59%, miss alarm rate 21.93%, average early alarm time 33.80 min), respectively.ConclusionsThe proposed approach could effectively predict hypoglycemia events based on different risk thresholds to meet different prevention and treatment requirements. Moreover, the experimental results confirm the practicality and prospects of the proposed early alarm system, which reflects further significance in personalized medicine for hypoglycemia prevention.
DNA methyltransferase 3a mediates developmental thermal plasticity
Authors: Loughland Isabella , Little Alexander , Seebacher Frank 
Published: January 2021

AbstractBackgroundThermal plasticity is pivotal for evolution in changing climates and in mediating resilience to its potentially negative effects. The efficacy to respond to environmental change depends on underlying mechanisms. DNA methylation induced by DNA methyltransferase 3 enzymes in the germline or during early embryonic development may be correlated with responses to environmental change. This developmental plasticity can interact with reversible acclimation within adult organisms, which would increase the speed of response and could alleviate potential mismatches between parental or early embryonic environments and those experienced at later life stages. Our aim was to determine whether there is a causative relationship between DNMT3 enzyme and developmental thermal plasticity and whether either or both interact with short-term acclimation to alter fitness and thermal responses in zebrafish (Danio rerio).ResultsWe developed a novel DNMT3a knock-out model to show that sequential knock-out of DNA methyltransferase 3a isoforms (DNMT3aa−/−and DNMT3aa−/−ab−/−) additively decreased survival and increased deformities when cold developmental temperatures in zebrafish offspring mismatched warm temperatures experienced by parents. Interestingly, short-term cold acclimation of parents before breeding rescued DNMT3a knock-out offspring by restoring survival at cold temperatures. DNMT3a knock-out genotype interacted with developmental temperatures to modify thermal performance curves in offspring, where at least one DNMT3a isoform was necessary to buffer locomotion from increasing temperatures. The thermal sensitivity of citrate synthase activity, an indicator of mitochondrial density, was less severely affected by DNMT3a knock-out, but there was nonetheless a significant interaction between genotype and developmental temperatures.ConclusionsOur results show that DNMT3a regulates developmental thermal plasticity and that the phenotypic effects of different DNMT3a isoforms are additive. However, DNMT3a interacts with other mechanisms, such as histone (de)acetylation, induced during short-term acclimation to buffer phenotypes from environmental change. Interactions between these mechanisms make phenotypic compensation for climate change more efficient and make it less likely that thermal plasticity incurs a cost resulting from environmental mismatches.
Leopard-like retinopathy and severe early-onset portal hypertension expand the phenotype of KARS1-related syndrome: a case report
Authors: Peluso Francesca , Palazzo Viviana , Indolfi Giuseppe , Mari Francesco , Pasqualetti Roberta , Procopio Elena , Nesti Claudia , Guerrini Renzo , Santorelli Filippo , Giglio Sabrina 
Published: January 2021

Abstract
Background
Mutations in lysyl-tRNA synthetase (KARS1), an enzyme that charges tRNA with the amino acid lysine in both the cytoplasm and mitochondria, have been associated thus far with autosomal recessive Charcot–Marie–Tooth type CMTRIB, hearing loss type DFNB89, and mitochondrial encephalohepatopathy (MEH) featuring neurodevelopmental disorders with microcephaly, white matter changes, and cardiac and hepatic failure in less than 30 patients.

Case presentation
We report the clinical, biochemical and molecular findings of a 14-month-old girl with severe MEH compatible clinical features, profound sensorineural hearing loss, leopard spot retinopathy, pancytopenia, and advanced liver disease with portal hypertension leading to death at the age of 30 months.

Conclusions
Whole exome sequencing identified two rare variants in KARS1 gene. Our report expands the allelic and clinical features of tRNA synthase disorders. Moreover, with our report we confirm the usefulness of WES as first tier diagnostic method in infants with complex multisystem phenotypes.
Whole-exome sequencing identified a novel heterozygous mutation of SALL1 and a new homozygous mutation of PTPRQ in a Chinese family with Townes-Brocks syndrome and hearing loss
Authors: Yang Guangxian , Yin Yi , Tan Zhiping , Liu Jian , Deng Xicheng , Yang Yifeng 
Published: January 2021

Abstract
Background
Previous studies have revealed that mutations of Spalt Like Transcription Factor 1 (SALL1) are responsible for Townes-Brocks syndrome (TBS), a rare genetic disorder that is characterized by an imperforate anus, dysplastic ears, thumb malformations and other abnormalities, such as hearing loss, foot malformations, renal impairment with or without renal malformations, genitourinary malformations, and congenital heart disease. In addition, the protein tyrosine phosphatase receptor type Q (PTPRQ) gene has been identified in nonsyndromic hearing loss patients with autosomal recessive or autosomal dominant inherited patterns.

Methods
A Chinese family with TBS and hearing loss was enrolled in this study. The proband was a two-month-old girl who suffered from congenital anal atresia with rectal perineal fistula, ventricular septal defect, patent ductus arteriosus, pulmonary hypertension (PH), and finger deformities. The proband’s father also had external ear deformity with deafness, toe deformities and PH, although his anus was normal. Further investigation found that the proband’s mother presented nonsyndromic hearing loss, and the proband’s mother’s parents were consanguine married. Whole-exome sequencing and Sanger sequencing were applied to detect the genetic lesions of TBS and nonsyndromic hearing loss.

Results
Via whole-exome sequencing and Sanger sequencing of the proband and her mother, we identified a novel heterozygous mutation (ENST00000251020: c.1428_1429insT, p. K478QfsX38) of SALL1 in the proband and her father who presented TBS phenotypes, and we also detected a new homozygous mutation [ENST00000266688: c.1057_1057delC, p. L353SfsX8)] of PTPRQ in the proband’s mother and uncle, who suffered from nonsyndromic hearing loss. Both mutations were located in the conserved sites of the respective protein and were predicted to be deleterious by informatics analysis.

Conclusions
This study confirmed the diagnosis of TBS at the molecular level and expanded the spectrum of SALL1 mutations and PTPRQ mutations. Our study may contribute to the clinical management and genetic counselling of TBS and hearing loss.
Risk assessment in precapillary pulmonary hypertension: a comparative analysis
Authors: Sonnweber Thomas , Schneider Eva-Maria , Nairz Manfred , Theurl Igor , Weiss Günter , Tymoszuk Piotr , Löffler-Ragg Judith 
Published: January 2021

Abstract
Background
Risk stratification is essential to assess mortality risk and guide treatment in patients with precapillary pulmonary hypertension (PH). We herein compared the accuracy of different currently used PH risk stratification tools and evaluated the significance of particular risk parameters.

Methods
We conducted a retrospective longitudinal observational cohort study evaluating seven different risk assessment approaches according to the current PH guidelines. A comprehensive assessment including multi-parametric risk stratification was performed at baseline and 4 yearly follow-up time-points. Multi-step Cox hazard analysis was used to analyse and refine risk prediction.

Results
Various available risk models effectively predicted mortality in patients with precapillary pulmonary hypertension. Right-heart catheter parameters were not essential for risk prediction. Contrary, non-invasive follow-up re-evaluations significantly improved the accuracy of risk estimations. A lack of accuracy of various risk models was found in the intermediate- and high-risk classes. For these patients, an additional evaluation step including assessment of age and right atrium area improved risk prediction significantly.

Discussion
Currently used abbreviated versions of the ESC/ERS risk assessment tool, as well as the REVEAL 2.0 and REVEAL Lite 2 based risk stratification, lack accuracy to predict mortality in intermediate- and high-risk precapillary pulmonary hypertension patients. An expanded non-invasive evaluation improves mortality risk prediction in these individuals.