bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generic substitution for prescribed brand medicines in Ethiopia: knowledge, attitude and practice among pharmacy professionals in community drug retail outlets
Authors: Alemu Sintayehu , Tadesse Natnael , Mulugeta Tidenek , Assefa Desta 
Published: July 2022

Abstract
Background
Generic substitution is a good approach to reduce pharmaceutical expenses without compromising healthcare quality. Yet, the practice of generic substitution has been contentious due to concerns on quality and efficacy.

Objective
This study was aimed to assess knowledge, attitude and practice among pharmacy professionals toward generic substitution in community drug retail outlets in Jimma town, Southwest Ethiopia.

Methods
A descriptive cross-sectional study was conducted among pharmacy professionals working in community drug retail outlets. Data was collected using a self-administered questionnaire. Knowledge was tested using a 3-point response format consisting of “Yes,” “No” and “I am not sure.” Attitude was evaluated using the 5-point Likert scale ranging from 1(strong agreement) to 5 (strong disagreement). The practice was examined as never, seldom, sometimes, often, and always with scores ranging from 0 to 4. The influences of socio-demographic factors on knowledge, attitude, and practice were tested using the Mann–Whitney U and Kruskal–Wallis tests as appropriate. P ≤ 0.05 was considered statistically significant.

Results
The mean knowledge score of participants regarding generic medicines was 5.75 ± 1.79. Only 32 respondents (30.2%) of the participants were knowledgeable about the generic substitution. 54 (50.9%) of respondents had positive attitude toward generic substitution and 52 (49.1%) had practiced generic substitution. The year of experience had a significant effect on knowledge (X2 = 9.14, p = 0.01) and practice (X2 = 4.71, p = 0.03) of generic substitution.

Conclusions
Our study found that pharmacy professionals working in community drug retail outlets in Jimma town had lack of knowledge about generic substitution. Conversely, an enormous amount of participants had positive attitude toward generic substitution and nearly half of them had practiced generic substitution. The year of experience had a significant effect on knowledge and practice of generic substitution.
Prevalence of and factors associated with unintended pregnancies among sexually active undergraduates in mainland China
Authors: Yuan Yan , Ruan Fang , Liu Yusi , Wu Lei , Pan Mingliang , Ye Zijie , Zhao Youxiong , Lin Lu , Zhang Li , Liu Jiajun , Luo Dongsheng , Zhu Bangzheng , Liao Xinyu , Hong Mengsi , Wang Siyi , Chen Jilun , Li Zihao , Yang Gaoming , Jiang Hongfang , Fu Guochen , Wang Junfang 
Published: July 2022

Abstract
Background
Unintended pregnancies (UIP) among unmarried sexually active college students in mainland China have emerged as a major reproductive health issue with detrimental personal and socioeconomic consequences. This cross-sectional study aimed to determine the prevalence and factors associated with UIP among sexually active undergraduates in mainland China.

Methods
Between September 8, 2019 and January 17, 2020, a total of 48,660 participants were recruited across the Chinese mainland to complete the self-administered, structured, online questionnaire. This analysis was restricted to 6347 sexually experienced, never-married 15–26 year old undergraduates. Pearson’s Chi square tests and multivariate Logistic regression analyses were performed to identify sociodemographic, familial and individual variables associated with UIP.

Results
The overall prevalence of UIP was 17.7%. More specifically, 19.5% of male college students reported they had unintentionally gotten a partner pregnant, while 14.9% of female college students became unintentionally pregnant. Students who experienced UIP were more likely to belong to the older age group (23–26 years), live with only one parent or live without parents at home, report that their family members approve of premarital sex, initiate sexual activity younger than 14 years old and have casual sex partners. Furthermore, females with multiple partners and males who came from low- income households, experienced sexual abuse, perceived difficulties in acquiring condoms and did not know how to use condoms correctly were also at higher risk of experiencing an unintended pregnancy.

Conclusion
In order to prevent UIP, a comprehensive intervention measure should be taken to target older students and those engaging in risky sexual behaviors, work with young male students to improve condom use skills, improve the availability of free condoms, optimize the involvement of parents and other family members in their children’s sex education.
Prevalence and associated factors of sexual violence experienced by housemaids in Ethiopia: a systematic review and meta-analysis
Authors: Mekonnen Birye Dessalegn , Lakew Zemene Habtu , Melese Endalkachew Belayneh 
Published: July 2022

Abstract
Background
Housemaids often experience different types of sexual violence by different perpetrators. Sexual violence against housemaids remains usually concealed as victims cannot report such offenses. Except for fragmented studies with varying reports, there is no national prevalence studies conducted on sexual violence among housemaids in Ethiopia. Thus, this systematic review and meta-analysis aimed to determine the pooled prevalence and associated factors of sexual violence amongst housemaids in Ethiopia.

Methods
A systematic search of PubMed, Embase, Science Direct, HINARI, Scopus, Cochrane Library, and Google Scholar was conducted using relevant search terms. Data were extracted using the Joanna Briggs Institute (JBI) tool. The quality of all selected articles was evaluated using JBI critical appraisal checklist. Data analysis was performed using STATA Version 14 statistical software. Egger’s test and funnel plot were used to evaluate publication bias. Heterogeneity was assessed using Cochran’s chi-squared test and quantified by I2 values. A random-effects model was applied during meta-analysis if heterogeneity was exhibited; otherwise, a fixed-effects model was used.

Results
After reviewing 37,849 articles, 8 studies involving 3,324 housemaids were included for this systematic review and meta-analysis. The pooled prevalence of life time sexual violence among housemaids in Ethiopia was 46.26% (95% CI: 24.69, 67.84). The pooled prevalence was 55.43% (95% CI: 26.38, 84.47) for sexual harassment, 39.03% (95% CI: 14.55, 63.52) for attempted rape, and 18.85% (95% CI: 7.51, 30.19) for rape. Sexual violence is more likely among housemaid who previously lived rural residence (AOR = 2.25; 95% CI: 1.41, 3.60), drinks alcohol (AOR = 2.79 95% CI: 1.02, 4.56), and employer alcohol consumption (AOR = 6.01; 95% CI: 1.10, 32.96).

Conclusion
This study revealed that the prevalence of sexual violence against housemaids in Ethiopia is high. Of the forms of sexual violence against housemaids, sexual harassment is high. Male employers are the vast majority of perpetrators of their housemaids. Thus, concerned stakeholders should develop and implement interventions that could empower housemaids in their struggle toward the elimination of sexual violence, create awareness for men, control and monitor the implementation of legislation and policies, and prompt punishment of the perpetrators.
Systematic review and meta-analysis registration PROSPERO CRD42021160511.
Clinical profiles of treated and untreated adults with hypophosphatasia in the Global HPP Registry
Authors: Dahir Kathryn M. , Seefried Lothar , Kishnani Priya S. , Petryk Anna , Högler Wolfgang , Linglart Agnès , Martos-Moreno Gabriel Ángel , Ozono Keiichi , Fang Shona , Rockman-Greenberg Cheryl 
Published: July 2022

Abstract
Background
The clinical signs and symptoms of hypophosphatasia (HPP) can manifest during any stage of life. The age at which a patient’s symptoms are reported can impact access to targeted treatment with enzyme replacement therapy (asfotase alfa), as this treatment is indicated for patients with pediatric-onset HPP in most countries. As such, many patients reported to have adult-onset HPP typically do not receive treatment. Comparison of the disease in treated and untreated adult patients is confounded by the approved indication. To avoid this confounding factor, a comparison between baseline disease manifestations prominent among treated versus untreated adult patients was limited to those with pediatric-onset HPP using data collected from the Global HPP Registry. The hypothesis was that treated adults will have a greater disease burden at baseline than untreated adults. The analysis of disease manifestations in adults with adult-onset HPP was conducted separately.

Results
A total of 398 adults with HPP were included; 213 with pediatric-onset (114 treated, 99 untreated) and 141 with adult-onset HPP (2 treated and 139 untreated). The treated, pediatric-onset patients were more likely to have a history of pain (prevalence ratio [PR]: 1.3, 95% confidence interval [CI] 1.1, 1.4), skeletal (PR: 1.3, 95% CI 1.1, 1.6), constitutional/metabolic (PR: 1.7, 95% CI 1.3, 2.0), muscular (PR: 1.8, 95% CI 1.4, 2.1) and neurological (PR: 1.7, 95% CI 1.1, 2.3) manifestations of HPP, and also had poorer measures for health-related quality of life, pain, and disability compared with untreated pediatric-onset patients. In patients with adult-onset HPP, the most frequent signs and symptoms were chronic bone pain (52.5%), dental manifestations (42.6%), fatigue (23.4%), recurrent fractures or pseudofractures (22.0%), and generalized body pain (22.0%).

Conclusions
Along with the more classical skeletal signs and symptoms, pain, muscular, and constitutional/metabolic manifestations are common in adults with HPP, regardless of age of disease onset, highlighting a full spectrum of HPP manifestations.
Characterization of hearing-impairment in Generalized Arterial Calcification of Infancy (GACI)
Authors: Theng Elizabeth H. , Brewer Carmen C. , Oheim Ralf , Zalewski Christopher K. , King Kelly A. , Delsmann Maximillian M. , Rolvien Tim , Gafni Rachel I. , Braddock Demetrios T. , Jeffrey Kim H. , Ferreira Carlos R. 
Published: July 2022

Abstract
Background and importance
Hearing loss (HL) has been sporadically described, but not well characterized, in Generalized Arterial Calcification of Infancy (GACI), a rare disease in which pathological calcification typically presents in infancy.

Objectives
This study aims to describe the clinical audiologic and otologic features and potential etiology of hearing impairment in GACI and gain pathophysiological insight from a murine model of GACI.

Design
Cross-sectional cohort study of individuals with GACI. Murine ossicle micromorphology of the ENPP1asj/asj mutant compared to wild-type.

Setting
Clinical research hospital; basic science laboratory.

Participants
Nineteen individuals with GACI who met clinical, biochemical, and genetic criteria for diagnosis.

Main outcomes and measures
Clinical, biochemical, and radiologic features associated with hearing status.

Results
Pure-tone thresholds could be established in 15 (n = 30 ears) of the 19 patients who underwent audiological assessments. The prevalence of HL was 50% (15/30) of ears, with conductive HL in 80% and sensorineural HL in 20%. In terms of patients with HL (n = 8), seven patients had bilateral HL and one patient had unilateral HL. Degree of HL was mild to moderate for 87% of the 15 ears with hearing loss. Of those patients with sufficient pure-tone and middle ear function data, 80% (8/10) had audiometric configurations suggestive of ossicular chain dysfunction (OCD). Recurrent episodes of otitis media (ROM) requiring pressure-equalizing tube placement were common. In patients who underwent cranial CT, 54.5% (6/11) had auricular calcification. Quantitative backscattered electron imaging (qBEI) of murine ossicles supports an OCD component of auditory dysfunction in GACI, suggesting loss of ossicular osteocytes without initiation of bone remodeling.

Conclusions and relevance
Hearing loss is common in GACI; it is most often conductive, and mild to moderate in severity. The etiology of HL is likely multifactorial, involving dysfunction of the ossicular chain and/or recurrent otitis media. Clinically, this study highlights the importance of early audiologic and otologic evaluation in persons with GACI. Novel findings of high rates of OCD and ROM may inform management, and in cases of unclear HL etiology, dedicated temporal bone imaging should be considered.
Global epidemiology of amyloid light-chain amyloidosis
Authors: Kumar Nishant , Zhang Nicole J. , Cherepanov Dasha , Romanus Dorothy , Hughes Michael , Faller Douglas V. 
Published: July 2022

Abstract
Background
Amyloid light-chain (AL) amyloidosis is an ultra-rare disease associated with significant morbidity and mortality. Few studies have examined the global epidemiology of this condition.

Methods
This study estimated the diagnosed incidence and 1-year, 5-year, 10-year, and 20-year period prevalence of AL amyloidosis in 2018 for countries in and near Europe, and in the United States (US), Canada, Brazil, Japan, South Korea, Taiwan, and Russia. A systematic literature review (SLR) was conducted to identify country-specific, age- and gender-specific diagnosed incidence of AL amyloidosis and observed survival data-point inputs for an incidence-to-prevalence model. Extrapolations were used to estimate incidence and prevalence for countries without registry or published epidemiological data.

Results
Of 171 publications identified in the SLR, 10 records met the criteria for data extraction, and two records were included in the final incidence-to-prevalence model. In 2018, an estimated 74,000 AL amyloidosis cases worldwide were diagnosed during the preceding 20 years. The estimated incidence and 20-year prevalence rates were 10 and 51 cases per million population, respectively.

Conclusions
Orphan medicinal product designation criteria of the European Medicines Agency or Electronic Code of Federal Regulations indicate that a disease must not affect > 5 in 10,000 people across the European Union or affect < 200,000 people in the US. This study provides up-to-date epidemiological patterns of AL amyloidosis, which is vital for understanding the burden of the disease, increasing awareness, and to further research and treatment options.
A recurrent single-amino acid deletion (p.Glu500del) in the head domain of ß-cardiac myosin in two unrelated boys presenting with polyhydramnios, congenital axial stiffness and skeletal myopathy
Authors: Bader Ingrid , Freilinger M. , Landauer F. , Waldmüller S. , Mueller-Felber W. , Rauscher C. , Sperl W. , Bittner R. E. , Schmidt W. M. , Mayr J. A. 
Published: July 2022

Abstract
Background
Alterations in the MYH7 gene can cause cardiac and skeletal myopathies. MYH7-related skeletal myopathies are extremely rare, and the vast majority of causal variants in the MYH7 gene are predicted to alter the rod domain of the of ß-cardiac myosin molecule, resulting in distal muscle weakness as the predominant manifestation. Here we describe two unrelated patients harboring an in-frame deletion in the MYH7 gene that is predicted to result in deletion of a single amino acid (p.Glu500del) in the head domain of ß-cardiac myosin. Both patients display an unusual skeletal myopathy phenotype with congenital axial stiffness and muscular hypertonus, but no cardiac involvement.

Results
Clinical data, MRI results and histopathological data were collected retrospectively in two unrelated boys (9 and 3.5 years old). Exome sequencing uncovered the same 3-bp in-frame deletion in exon 15 (c.1498_1500delGAG) of the MYH7 gene of both patients, a mutation which deletes a highly conserved glutamate residue (p.Glu500del) in the relay loop of the head domain of the ß-cardiac myosin heavy chain. The mutation occurred de novo in one patient, whereas mosaicism was detected in blood of the father of the second patient. Both boys presented with an unusual phenotype of prenatal polyhydramnios, congenital axial stiffness and muscular hypertonus. In one patient the phenotype evolved into an axial/proximal skeletal myopathy without distal involvement or cardiomyopathy, whereas the other patient exhibited predominantly stiffness and respiratory involvement. We review and compare all patients described in the literature who possess a variant predicted to alter the p.Glu500 residue in the ß-cardiac myosin head domain, and we provide in-silico analyses of potential effects on polypeptide function.

Conclusion
The data presented here expand the phenotypic spectrum of mutations in the MYH7 gene and have implications for future diagnostics and therapeutic approaches.
Clinical and genetic spectrum of primary ciliary dyskinesia in Chinese patients: a systematic review
Authors: Peng Bo , Gao Yong-hua , Xie Jia-qi , He Xiao-wen , Wang Cong-cong , Xu Jin-fu , Zhang Guo-jun 
Published: July 2022

Abstract
Background
Primary ciliary dyskinesia (PCD) represents a highly heterogenous disorder with extensive clinical and genetic patterns among populations of different geographic location and ethnic origin. However, data about Chinese patients are limited. We aimed to summarize the clinical and genetic spectrum of Chinese PCD patients based on all available literatures.

Methods
We searched Embase, Pubmed, Web of Science and Chinese databases including CNKI, SinoMed and Wanfang from 1981 to 2021, to identify articles reporting patients with PCD in China, which had included information about transmission electron microscopy and/or genetic testing.

Results
A total of 244 Chinese PCD patients in 52 articles were included. Of these patients, the mean age was 13.1 years, and 55 patients (22.5%) were diagnosed with PCD after 18 years old. Compared with patients diagnosed with PCD in childhood or infancy, patients diagnosed with PCD in adulthood had a higher prevalence of chronic wet cough, sinusitis, Pseudomonas aeruginosa (PA) isolation and radiological bronchiectasis as well as worse lung function. 25 PCD-related genes were identified in 142 patients, and DNAH5, DNAH11, CCDC39 and CCDC40 were the most frequently detected mutations. More than half of genetic variants were loss-of-function mutations, and the majority of these variants were seen only once. Correlations between PCD phenotype, genotype and ciliary ultrastructure were also evidenced.

Conclusions
Diagnostic delay and under-recognition of PCD remain a big issue in China, which contributes to progressive lung disease and PA infection indicating worse outcome. Specialist equipment and expertise are urgently required to facilitate the early diagnosis and treatment of PCD.

Trial registry

PROSPERO; No.: CRD42021257804; URL:www.crd.york.ac.uk/prospero/
Neurodevelopmental outcome of Italian preterm ELBW infants: an eleven years single center cohort
Authors: Caporali Camilla , Longo Stefania , Tritto Giovanna , Perotti Gianfranco , Pisoni Camilla , Naboni Cecilia , Gardella Barbara , Spinillo Arsenio , Manzoni Federica , Ghirardello Stefano , Borgatti Renato , Orcesi Simona ,   ELBWI Neurodevelopmental Follow-up Study Group, Olivieri Ivana , La Piana Roberta , Tonduti Davide , Decio Alice , Ravelli Claudia , Olivotto Sara , Ariaudo Giada , Spairani Silvia , Figar Tiziana 
Published: July 2022

Abstract
Background
Preterm extremely low birth weight infants (ELBWi) are known to be at greater risk of developing neuropsychiatric diseases. Identifying early predictors of outcome is essential to refer patients for early intervention. Few studies have investigated neurodevelopmental outcomes in Italian ELBWi. This study aims to describe neurodevelopmental outcome at 24 months of corrected age in an eleven-year single-center cohort of Italian ELBWi and to identify early risk factors for adverse neurodevelopmental outcomes.

Methods
All infants born with birth weight < 1000 g and admitted to the Neonatal Intensive Care Unit of the “Fondazione IRCCS Policlinico San Matteo” hospital in Pavia, Italy, from Jan 1, 2005 to Dec 31, 2015 were eligible for inclusion. At 24 months, Griffiths’ Mental Developmental Scales Extended Revised (GMDS-ER) were administered. Neurodevelopmental outcome was classified as: normal, minor sequelae (minor neurological signs, General Quotient between 76 and 87), major sequelae (cerebral palsy; General Quotient ≤ 75; severe sensory impairment). Univariate and multivariate multinomial logistic regression models were performed to analyze the correlation between neonatal variables and neurodevelopmental outcome.

Results
176 ELBWi were enrolled (mean gestational age 26.52 weeks sd2.23; mean birthweight 777.45 g sd142.89). 67% showed a normal outcome at 24 months, 17% minor sequelae and 16% major sequelae (4.6% cerebral palsy on overall sample). The most frequent major sequela was cognitive impairment (8.52%).
In the entire sample the median score on the Hearing-Speech subscale was lower than the median scores recorded on the other subscales and showed a significantly weaker correlation to each of the other subscales of the GMDS-ER.
Severely abnormal cUS findings (RRR 10.22 p 0.043) and bronchopulmonary dysplasia (RRR 4.36 p 0.008) were independent risk factors for major sequelae and bronchopulmonary dysplasia for minor sequelae (RRR 3.00 p 0.018) on multivariate multinomial logistic regression.

Conclusions
This study showed an improvement in ELBWI survival rate without neurodevelopmental impairment at 24 months compared to previously reported international cohorts. Cognitive impairment was the most frequent major sequela. Median scores on GMDS-ER showed a peculiar developmental profile characterized by a selective deficit in the language domain. Severely abnormal cUS findings and bronchopulmonary dysplasia were confirmed as independent risk factors for major sequelae.
The potential roles of type I interferon activated neutrophils and neutrophil extracellular traps (NETs) in the pathogenesis of primary Sjögren’s syndrome
Authors: Peng Yu , Wu Xunyao , Zhang Shulan , Deng Chuiwen , Zhao Lidan , Wang Mu , Wu Qingjun , Yang Huaxia , Zhou Jiaxin , Peng Linyi , Luo Xuan , Chen Yingying , Wang Anqi , Xiao Qiufeng , Zhang Wen , Zhao Yan , Zeng Xiaofeng , Fei Yunyun 
Published: July 2022

Abstract
Objective
Neutrophils and aberrant NETosis have been implicated in the pathogenesis of diverse autoimmune diseases; however, their roles in primary Sjögren’s syndrome (pSS) remain unclear. We aimed to reveal the potential roles of neutrophils and neutrophil extracellular traps (NETs) in pSS.

Methods
pSS patients were enrolled and NETosis markers were measured in plasma and labial glands using ELISA and immunofluorescence. The gene signatures of neutrophils were assessed by RNA-Seq and RT-PCR. Reactive oxygen species (ROS), mitochondrial ROS (MitoSOX) production, and JC-1 were measured by flow cytometry.

Results
NETosis markers including cell-free DNA (cf-DNA) and myeloperoxidase (MPO) in plasma and labial glands from pSS patients were significantly higher than healthy controls (HCs) and were associated with disease activity. RNA sequencing and RT-qPCR revealed activated type I IFN signaling pathway and higher expression of genes related to type I interferon in pSS neutrophils. Further stimulating with IFN-α 2a in vitro significantly induced ROS production and JC-1 monomer percentage in pSS neutrophils.

Conclusions
Our data suggest the involvement of neutrophils and enhanced NETosis in pSS patients. Further mechanism study in vitro revealed that type I IFN activation in pSS neutrophils led to mitochondrial damage and related ROS production which finally result in the generation of NETs.