bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic analysis of field pennycress (Thlaspi arvense) provides insights into mechanisms of adaptation to high elevation
Authors: Geng Yupeng , Guan Yabin , Qiong La , Lu Shugang , An Miao , Crabbe M. James C. , Qi Ji , Zhao Fangqing , Qiao Qin , Zhang Ticao 
Published: July 2021

Abstract
Background
Understanding how organisms evolve and adapt to extreme habitats is of crucial importance in evolutionary ecology. Altitude gradients are an important determinant of the distribution pattern and range of organisms due to distinct climate conditions at different altitudes. High-altitude regions often provide extreme environments including low temperature and oxygen concentration, poor soil, and strong levels of ultraviolet radiation, leading to very few plant species being able to populate elevation ranges greater than 4000 m. Field pennycress (Thlaspi arvense) is a valuable oilseed crop and emerging model plant distributed across an elevation range of nearly 4500 m. Here, we generate an improved genome assembly to understand how this species adapts to such different environments.

Results
We sequenced and assembled de novo the chromosome-level pennycress genome of 527.3 Mb encoding 31,596 genes. Phylogenomic analyses based on 2495 single-copy genes revealed that pennycress is closely related to Eutrema salsugineum (estimated divergence 14.32–18.58 Mya), and both species form a sister clade to Schrenkiella parvula and genus Brassica. Field pennycress contains the highest percentage (70.19%) of transposable elements in all reported genomes of Brassicaceae, with the retrotransposon proliferation in the Middle Pleistocene being likely responsible for the expansion of genome size. Moreover, our analysis of 40 field pennycress samples in two high- and two low-elevation populations detected 1,256,971 high-quality single nucleotide polymorphisms. Using three complementary selection tests, we detected 130 candidate naturally selected genes in the Qinghai-Tibet Plateau (QTP) populations, some of which are involved in DNA repair and the ubiquitin system and potential candidates involved in high-altitude adaptation. Notably, we detected a single base mutation causing loss-of-function of the FLOWERING LOCUS C protein, responsible for the transition to early flowering in high-elevation populations.

Conclusions
Our results provide a genome-wide perspective of how plants adapt to distinct environmental conditions across extreme elevation differences and the potential for further follow-up research with extensive data from additional populations and species.
Prevalence of toxoplasmosis in semi-domesticated and pet cats within and around Bangkok, Thailand
Authors: Inpankaew Tawin , Sattasathuchana Panpicha , Kengradomkij Chanya , Thengchaisri Naris 
Published: July 2021

Abstract
Background
Toxoplasmosis is one of the most common parasitic zoonoses worldwide. Cats become infected after ingesting infected tissue cysts. The objective of the present study was to compare the prevalence of toxoplasmosis in pet cats and semi-domesticated cats in the Bangkok metropolitan region. A survey of Toxoplasma infection was conducted in 260 cats (median age [range]: 3 years [10 months–10 years]; 155 females and 105 males) by collecting blood samples from 130 client-owned pet cats and 130 semi-domesticated cats within and around Bangkok during 2016–2017 using indirect fluorescence antibody tests. An IgG antibody to Toxoplasma antigen ratio of ≥1:100 was considered positive for Toxoplasma infection.

Results
The overall prevalence of T. gondii in cats was 6.5% (17/260). The prevalence of T. gondii in semi-domesticated cats and pet cats was 11.5 and 1.5%, respectively. Semi-domesticated cats aged 1–5 years (14.9%) had a higher prevalence of infection than domesticated cats (1.3%, p = 0.002) of the same age. The odds (95% confidence interval [CI]) of having T. gondii infection in semi-domesticated cats were 8.34 (1.86–76.29, p = 0.0017) times higher than in pet cats. Interestingly, there was an association between T. gondii infection according to city ​region (p = 0.002). The odds (95% CI) of having T. gondii infection in cats living in the inner city were 4.96 (1.03–47.16, p = 0.023) times higher than cats living in the suburb and the vicinity.

Conclusions
The present study identified a higher prevalence of Toxoplasma infection in semi-domesticated cats compared with pet cats. The semi-domesticated cats could serve as a zoonotic reservoir. Public health regulations should be implemented to prevent toxoplasmosis spread.
Retinoblastoma genetics screening and clinical management
Authors: Gupta Himika , Malaichamy Sivasankar , Mallipatna Ashwin , Murugan Sakthivel , Jeyabalan Nallathambi , Suresh Babu Vishnu , Ghosh Anuprita , Ghosh Arkasubhra , Santhosh Sam , Seshagiri Somasekar , Ramprasad Vedam L. , Kumaramanickavel Govindasamy 
Published: July 2021

Abstract
Background
India accounts for 20% of the global retinoblastoma (RB) burden. However, the existing data on RB1 gene germline mutations and its influence on clinical decisions is minimally explored.

Methods
Fifty children with RB underwent complete clinical examination and appropriate multidisciplinary management. Screening of germline RB1 gene mutations was performed through next-generation sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA) analysis. The mutation and non-mutation groups were compared for clinical parameters especially severity, progression and recurrence.

Results
Twenty-nine patients had bilateral RB (BLRB) and 21 had unilateral RB (ULRB). The genetic analysis revealed 20 RB1 variations in 29 probands, inclusive of 3 novel mutations, known 16 mutations and heterozygous whole gene deletions. The mutation detection rate (MDR) was 86.2% in BLRB and 19% in ULRB. Associations of disease recurrence (p = 0.021), progression (p = 0.000) and higher percentage of optic nerve invasion, subretinal seeds and high-risk pathological factors were observed in the mutation group. Clinical management was influenced by the presence of germline mutations, particularly while deciding on enucleation, frequency of periodic follow up and radiotherapy.

Conclusions
We identified novel RB1 mutations, and our mutation detection rate was on par with the previous global studies. In our study, genetic results influenced clinical management and we suggest that it should be an essential and integral component of RB-care in India and elsewhere.
Effects of acuC on the growth development and spinosad biosynthesis of Saccharopolyspora spinosa
Authors: Liu Zhudong , Xiao Jie , Tang Jianli , Liu Yang , Shuai Ling , Cao Li , Xia Ziyuan , Ding Xuezhi , Rang Jie , Xia Liqiu 
Published: July 2021

Abstract
Background
Acetoin utilization protein (acuC) is a type I histone deacetylase which is highly conserved in bacteria. The acuC gene is related to the acetylation/deacetylation posttranslational modification (PTM) system in S. spinosa. Spinosyns, the secondary metabolites produced by Saccharopolyspora spinosa, are the active ingredients in a family of insect control agents. However, the specific functions and influences of acuC protein in S. spinosa are yet to be characterized.

Results
The knockout strain and overexpression strain were constructed separately with the shuttle vector pOJ260. The production of spinosyns A and D from S. spinosa-acuC were 105.02 mg/L and 20.63 mg/L, which were 1.82-fold and 1.63-fold higher than those of the wild-type strain (57.76 mg/L and 12.64 mg/L), respectively. The production of spinosyns A and D from S. spinosa-ΔacuC were 32.78 mg/L and 10.89 mg/L, respectively. The qRT-PCR results of three selected genes (bldD, ssgA and whiA) confirmed that the overexpression of acuC affected the capacities of mycelial differentiation and sporulation. Comparative proteomics analysis was performed on these strains to investigate the underlying mechanism leading to the enhancement of spinosad yield.

Conclusions
This study first systematically analysed the effects of overexpression acuC on the growth of S. spinosa and the production of spinosad. The results identify the differentially expressed proteins and provide evidences to understand the acetylation metabolic mechanisms which can lead to the increase of secondary metabolites.
Assessing the impact of the 2008 health reform in Ecuador on the performance of primary health care services: an interrupted time series analysis
Authors: Flores Jimenez Sergio E , San Sebastián Miguel 
Published: July 2021

Abstract
Background
In 2008, Ecuador started a national health reform based on the principles of Alma Ata to achieve Universal Health Coverage. While coverage indicators have increased, a systematic assessment of the impact of the reform on the delivery of health services at primary level is lacking. The aim of this study was to assess the impact of the 2008 health reform on the performance of primary health care services in Ecuador.

Methods
Ambulatory Care Sensitive Conditions (ACSC) are a subset of diseases where hospital admission is potentially avoidable by high quality well-functioning primary care. Thus, observing the behaviour of ACSC hospitalizations can serve as an indicator of how the primary health care level is performing. Crude and adjusted rates, stratified by sex, were calculated from ten selected ACSC hospitalization discharges during 22 years of data representing 11 years before and after the health reform. An interrupted time series analysis was then conducted by applying a negative binomial regression and adjusting for overdispersion and autocorrelation.

Results
Overall higher crude and adjusted rates for ACSC hospitalizations were observed in women compared to men; both increased gradually since the start of the observation, reaching a peak around 2010, and then started a downwards trend. In men, the incidence rate ratio increased significantly by 3 % per year during the period before the intervention. During the first year after intervention, an increase (13 %) was detected, and then a statistically significant 1 % decrease (IRR = 0.99; 95 % CI: 0.98, 0.99) was observed in the ACSC rate ratio per year in the period after the intervention. Similar trends and effect sizes were found for women.

Conclusions
The study revealed significant decreasing trends of the ACSC hospitalization rates in both sexes, indicating an improvement of the performance of the primary health care services following the 2008 national health reform. A continuous strengthening of the primary care model as well as a regular monitoring of ACSC hospitalization rates in the country is recommended. A health economic evaluation considering hospitalizations avoided and associated costs is also advisable.
Situational analysis and reflections on the introduction of advanced practice nurses in Brazilian primary healthcare
Authors: Magnago Carinne , Pierantoni Celia Regina 
Published: July 2021

Abstract
Background
The shortage of doctors and their unequal distribution serve as challenges to advancing primary healthcare (PHC) and achieving effective universal healthcare coverage in Brazil. In an effort to use nurses’ potential more efficiently, the country is investigating the introduction of the advanced practice nurse (APN) into PHC. This paper presents a situational analysis of the practices of Brazilian nurses based on the following components: regulation, practice, and education.

Methods
This is a national multi-method study with triangulated data from a documentary study, a scoping review, and an exploratory study. The regulation component involved the analysis of official normative documents on the regulation of nursing education and nurses’ scope of practice. The practice component aimed to identify the practices performed by nurses in Brazilian PHC based on primary studies. The education component intended to identify the practices taught in nursing training based on a survey and interviews with directors of undergraduate nursing programs.

Results
Federal legislation in Brazil authorizes nursing graduates to perform a set of advanced practices as part of the PHC nurse's daily routine. They can request and interpret complementary tests and prescribe medication. However, in the local context, municipalities define the scope of this assistance based on technical norms or nursing protocols. Furthermore, this study indicates that undergraduate nursing programs do not fully prepare students to adequately execute these tasks.

Conclusions
In the context of Brazilian PHC, advanced practices have already been implemented and respond to main healthcare demands. Therefore, it is unnecessary to introduce the APN as a new professional category. Upon detecting deficiencies in the training process, the current education model should undergo reforms that seek to incorporate the skills compatible with the regulated advanced practices and in-service training for practicing nurses. Regarding the introduction of APN along international lines, this article presents recommendations that may support the operationalization of a Brazilian APN model.
N6-Methyladenosine RNA modification in cerebrospinal fluid as a novel potential diagnostic biomarker for progressive multiple sclerosis
Authors: Ye Fei , Wang Tianzhu , Wu Xiaoxin , Liang Jie , Li Jiaoxing , Sheng Wenli 
Published: July 2021

Abstract
Background
Progressive multiple sclerosis (PMS) is an uncommon and severe subtype of MS that worsens gradually and leads to irreversible disabilities in young adults. Currently, there are no applicable or reliable biomarkers to distinguish PMS from relapsing–remitting multiple sclerosis (RRMS). Previous studies have demonstrated that dysfunction of N6-methyladenosine (m6A) RNA modification is relevant to many neurological disorders. Thus, the aim of this study was to explore the diagnostic biomarkers for PMS based on m6A regulatory genes in the cerebrospinal fluid (CSF).

Methods
Gene expression matrices were downloaded from the ArrayExpress database. Then, we identified differentially expressed m6A regulatory genes between MS and non-MS patients. MS clusters were identified by consensus clustering analysis. Next, we analyzed the correlation between clusters and clinical characteristics. The random forest (RF) algorithm was applied to select key m6A-related genes. The support vector machine (SVM) was then used to construct a diagnostic gene signature. Receiver operating characteristic (ROC) curves were plotted to evaluate the accuracy of the diagnostic model. In addition, CSF samples from MS and non-MS patients were collected and used for external validation, as evaluated by an m6A RNA Methylation Quantification Kit and by real-time quantitative polymerase chain reaction.

Results
The 13 central m6A RNA methylation regulators were all upregulated in MS patients when compared with non-MS patients. Consensus clustering analysis identified two clusters, both of which were significantly associated with MS subtypes. Next, we divided 61 MS patients into a training set (n = 41) and a test set (n = 20). The RF algorithm identified eight feature genes, and the SVM method was successfully applied to construct a diagnostic model. ROC curves revealed good performance. Finally, the analysis of 11 CSF samples demonstrated that RRMS samples exhibited significantly higher levels of m6A RNA methylation and higher gene expression levels of m6A-related genes than PMS samples.

Conclusions
The dynamic modification of m6A RNA methylation is involved in the progression of MS and could potentially represent a novel CSF biomarker for diagnosing MS and distinguishing PMS from RRMS in the early stages of the disease.
Persons living with HIV in sero-discordant partnerships experience improved HIV care engagement compared with persons living with HIV in sero-concordant partnerships: a cross-sectional analysis of four African countries
Authors: Reed Domonique M. , Esber Allahna L. , Crowell Trevor A. , Ganesan Kavitha , Kibuuka Hannah , Maswai Jonah , Owuoth John , Bahemana Emmanuel , Iroezindu Michael , Ake Julie A. , Polyak Christina S. ,   The AFRICOS Study Team
Published: July 2021

Abstract
Background
Persons living with HIV (PLWH) who are members of sero-discordant and sero-concordant relationships may experience psychological stressors or motivators that affect HIV care. We assessed the association between sero-discordance status, antiretroviral therapy (ART) uptake, and viral suppression in the African Cohort Study (AFRICOS).

Methods
AFRICOS enrolls PLWH and HIV-uninfected individuals at 12 sites in Uganda, Kenya, Tanzania, and Nigeria. At enrollment, we determined ART use through self-report. Viral suppression was defined as HIV RNA < 1000 copies/mL. We analyzed PLWH who were index participants within two types of sexual dyads: sero-discordant or sero-concordant. Binomial regression models were used to estimate prevalence ratios (PRs) and 95% confidence intervals (95% CIs) for factors associated with ART use and viral suppression at study enrollment.

Results
From January 2013 through March 2018, 223 index participants from sero-discordant dyads and 61 from sero-concordant dyads were enrolled. The majority of the indexes were aged 25–34 years (50.2%), female (53.4%), and married (96.5%). Sero-discordant indexes were more likely to disclose their status to partners compared with sero-concordant indexes (96.4% vs. 82.0%, p < 0.001). After adjustment, sero-discordant index participants were more likely to be on ART (aPR 2.8 [95% CI 1.1–6.8]), but no more likely to be virally suppressed. Results may be driven by unique psycho-social factors and global implementation of treatment as prevention.

Conclusions
PLWH in sero-discordant sexual partnerships demonstrated improved uptake of ART compared with those in sero-concordant partnerships. Interventions are needed to increase care engagement by individuals in sero-concordant relationships to improve HIV outcomes.
Lineage analysis of human papillomavirus type 39 in cervical samples of Iranian women
Authors: Hosseini Neda , Shoja Zabihollah , Arashkia Arash , Khodadadi Amir-Hossein , Jalilvand Somayeh 
Published: July 2021

AbstractBackgroundThe data with regards to the regional variants of distinct HPV types is of great value. Accordance with this, this study aimed to investigate the sequence variations of E6 gene and long control region of HPV 39 among normal, premalignant and malignant cervical samples in order to characterize the frequent HPV 39 variants circulating in Tehran, Iran.MethodsIn total, 70 cervical samples (45 normal, 16 premalignant, and 9 malignant samples) infected with HPV 39 were analyzed by nested-PCR and sequencing.ResultsOur results revealed that all samples belonged to A lineage. Almost all sequences (98.6%) were classified in A1 sublineage and only one sample (1.4%) was A2 sub lineage.ConclusionsOur findings showed that lineages A, sublineage A1, is dominant in Tehran, Iran. However, the small sample size was the most important limitations of this study. Further studies with larger sample size from different geographical regions of Iran are necessary to estimate the pathogenicity risk of HPV 39 variants in this population.
Evaluating risk detection methods to uncover ontogenic-mediated adverse drug effect mechanisms in children
Authors: Giangreco Nicholas P. , Tatonetti Nicholas P. 
Published: July 2021

AbstractBackgroundIdentifying adverse drugs effects (ADEs) in children, overall and within pediatric age groups, is essential for preventing disability and death from marketed drugs. At the same time, however, detection is challenging due to dynamic biological processes during growth and maturation, called ontogeny, that alter pharmacokinetics and pharmacodynamics. As a result, methodologies in pediatric drug safety have been limited to event surveillance and have not focused on investigating adverse event mechanisms. There is an opportunity to identify drug event patterns within observational databases for evaluating ontogenic-mediated adverse event mechanisms. The first step of which is to establish statistical models that can identify temporal trends of adverse effects across childhood.ResultsUsing simulation, we evaluated a population stratification method (the proportional reporting ratio or PRR) and a population modeling method (the generalized additive model or GAM) to identify and quantify ADE risk at varying reporting rates and dynamics. We found that GAMs showed improved performance over the PRR in detecting dynamic drug event reporting across child development stages. Moreover, GAMs exhibited normally distributed and robust ADE risk estimation at all development stages by sharing information across child development stages.ConclusionsOur study underscores the opportunity for using population modeling techniques, which leverage drug event reporting across development stages, as biologically-inspired detection methods for evaluating ontogenic mechanisms.
Tonsillectomy versus tonsillotomy for recurrent acute tonsillitis in children and adults (TOTO): study protocol for a randomized non-inferiority trial
Authors: Guntinas-Lichius Orlando , Geißler Katharina , Asendorf Thomas , Tostmann Ralf , Löhler Jan 
Published: July 2021

Abstract
Background
Tonsillectomy is one of the most frequently performed surgeries in children and young adults worldwide. For decades, tonsillectomy was the surgical treatment of choice for recurrent acute tonsillitis. Tonsillotomy was used in some countries as an alternative to tonsillectomy only for the treatment of obstructive sleep apnea in young children. In recent years, an increase of tonsillotomy also to treat recurrent acute tonsillitis can be observed. Therefore, the German Institute for Quality and Efficiency in Health Care (IQWiG) was commissioned by the Federal Joint Committee (G-BA) to investigate whether tonsillotomy offers advantages compared to tonsillectomy. The meta-analysis of the IQWiG including studies until 2016 revealed that the long-term benefits and harms of tonsillotomy compared to tonsillectomy are unclear. Consequently, the G-BA performed a European call for a clinical trial. A consortium of the German Professional Association of ENT-surgeons (BVHNO), the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery (DGHNO-KHC), and the Jena University Hospital were finally selected to perform the TOTO study.

Methods
TOTO is a multicenter, 1:1 two-arm, randomized non-blinded non-inferiority trial. Four hundred fifty-four patients ≥ 3 years of age will be randomly allocated to undergo either tonsillotomy or tonsillectomy as surgical treatment of recurrent acute tonsillitis. All participants will be followed up for a total of 24 months. The primary outcome is the number of sore throat days experienced over the 24-month follow-up.

Discussion
TOTO is designed to evaluate the effectiveness and efficiency of tonsillectomy versus tonsillectomy for the management of patients with recurrent acute tonsillitis. Tonsil disease and surgery have a major impact on preschool and school children as well as on economically active young adults, with individual and societal costs through loss of school visits, earnings, and productivity. If tonsillotomy is at least as effective as tonsillectomy but with reduced morbidity, this would reduce costs to the healthcare system and society.

Trial registration
German Clinical Trials Register DRKS00020823. Registered on 04 September 2020.