bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of novel genomic regions associated with nine mineral elements in Chinese winter wheat grain
Authors: Wang Wei , Guo Hong , Wu Chongning , Yu Hui , Li Xiaokang , Chen Guangfeng , Tian Jichun , Deng Zhiying 
Published: July 2021

Abstract
Background
Mineral elements are important for maintaining good human health besides heavy metals. Mining genes that control mineral elements are paramount for improving their accumulation in the wheat grain. Although previous studies have reported some loci for beneficial trace elements, they have mainly focused on Zn and Fe content. However, little information is available regarding the genetic loci differences in dissecting synchronous accumulation of multiple mineral elements in wheat grains, including beneficial and heavy elements. Therefore, a genome-wide association study (GWAS) was conducted on 205 wheat accessions with 24,355 single nucleotide polymorphisms (SNPs) to identify important loci and candidate genes for controlling Ca, Fe, Zn, Se, Cu, Mn, Cd, As, and Pb accumulation in wheat grains.

Results
A total of 101 marker-trait associations (MTAs) (P < 10–5) loci affecting the content of nine mineral elements was identified on chromosomes 1B, 1D, 2A, 2B, 3A, 3B, 3D, 4A, 4B, 5A, 5B, 5D, 6B, 7A, 7B, and 7D. Among these, 17 major MTAs loci for the nine mineral elements were located, and four MTAs loci (P < 10–5) were found on chromosomes 1B, 6B, 7B, and 7D. Eight multi-effect MTAs loci were detected that are responsible for the control of more than one trait, mainly distributed on chromosomes 3B, 7B, and 5A. Furthermore, sixteen candidate genes controlling Ca, Fe, Zn, Se, Cd, and Pb were predicted, whose functions were primarily related to ion binding, including metals, Fe, Ca, Cu, Mg, and Zn, ATP binding, ATPase activity, DNA binding, RNA binding, and protein kinase activity.

Conclusions
Our study indicated the existence of gene interactions among mineral elements based on multi-effect MTAs loci and candidate genes. Meanwhile this study provided new insights into the genetic control of mineral element concentrations, and the important loci and genes identified may contribute to the rapid development of beneficial mineral elements and a reduced content of harmful heavy metals in wheat grain.
Hyperimmune plasma in three immuno-deficient patients affected by non-severe, prolonged COVID-19: a single-center experience
Authors: Cusi Maria Grazia , Conticini Edoardo , Gandolfo Claudia , Anichini Gabriele , Savellini Gianni Gori , Valente Serafina , Franchi Federico , Scolletta Sabino , Percivalle Elena , Frediani Bruno 
Published: July 2021

Abstract
Background
Convalescent plasma (CP) and hyperimmune plasma (HP) are passive immunotherapies consisting in the infusion of plasma from recovered people into infected patients. Following pre-existing evidence in many other viral diseases, such as SARS, MERS and Ebola, CP and HP have also been proposed for the treatment of COVID-19. Nevertheless, due to the lack of large, well-designed, clinical trials, no clear-cut guidelines exist about what subtype of patient CP and HP should be administered to.

Case presentation
We have reported the cases of 3 patients, all immunosuppressed and affected by non-severe, prolonged COVID-19. They were treated with HP, whose neutralizing titer was higher than 1/80. The first patient was a 55-year-old male, who had undergone lung transplant. He was under therapy with Tacrolimus and developed non-neutralizing antibodies against SARS-CoV2. The second patient was a 77-year-old female, affected by follicular lymphoma. She had tested positive for SARS-CoV2 after 6 months. The third was a 60-year-old patient, affected by chronic leukemia. He did not develop antibodies after 2-month disease. All 3 patients received HP and had tested negative for SARS-CoV2 within 2 weeks.

Conclusion
Despite encouraging initial data, no strong evidence exist in support of CP and HP to treat COVID-19. In our experience, although limited due to the reduced number of patients, we found a good safety and efficacy of HP in 3 immuno-deficient subjects. Further data are needed in order to assess whether this subtype of patients may particularly benefit from passive immunization.
Implementation and effectiveness of an intensive education program on phosphate control among hemodialysis patients: a non-randomized, single-arm, single-center trial
Authors: Yin Jinmei , Yin Jun , Lian Rongli , Li Peiqiu , Zheng Jing 
Published: July 2021

AbstractBackgroundHyperphosphatemia is a common complication in patients on maintenance hemodialysis. Patients’ adherence to phosphorus control can be improved by consistent education. However, few studies have focused on the model construction and effects of health education on phosphate control for hemodialysis patients.ObjectiveTo develop an intensive education program focusing on phosphate control among hemodialysis patients and to analyze the effectiveness of this program.DesignA non-randomized, single-arm, single-center trial lasting for 6 months.SettingThis program was conducted in a hemodialysis center in a teaching hospital in Zhuhai, China.ParticipantsPatients on maintenance hemodialysis with hyperphosphatemia.MethodsAn intensive hyperphosphatemia control education program lasting for 6 months was conducted among 366 hemodialysis patients applying the First Principles of Instruction model, which focused on mastering four stages: (a) activation of prior experience, (b) demonstration of skills, (c) application of skills and (d) integration of these skills into real-world activities. The controlled percentage of serum phosphorus, knowledge of hyperphosphatemia, and adherence to phosphate binders before and after the education program were assessed.ResultsThe proportion of controlled serum phosphorus was significantly increased from 43.5 to 54.9% (P<0.001). The scores on the knowledge of phosphate control were improved significantly from 59.0 ± 18.9 to 80.6 ± 12.4 (P < 0.001). The proportion of high adherence to phosphate binders was increased dramatically from 21.9 to 44.5% (P < 0.001).ConclusionThe intensive education program can effectively improve serum phosphorus, knowledge of hyperphosphatemia, and adherence to phosphate binders among hemodialysis patients.Trial registrationChinese Clinical Trial Registry,ChiCTR2100042017. Retrospectively registered January 12th, 2021.
The perception of Italian pregnant women and new mothers about their psychological wellbeing, lifestyle, delivery, and neonatal management experience during the COVID-19 pandemic lockdown: a web-based survey
Authors: Stampini Viviana , Monzani Alice , Caristia Silvia , Ferrante Gianluigi , Gerbino Martina , De Pedrini Alberto , Amadori Roberta , Rabbone Ivana , Surico Daniela 
Published: July 2021

Abstract
Background
In response to the COVID-19 pandemic, drastic measures for social distancing have been introduced also in Italy, likely with a substantial impact in delicate conditions like pregnancy and puerperium. The study aimed to investigate the changes in lifestyle, access to health services, and mental wellbeing during the first Italian lockdown in a sample of Italian pregnant women and new mothers.

Methods
We carried out a web-based survey to evaluate how pregnant women and new mothers were coping with the lockdown. We collected data about healthy habits (physical exercise and dietary habits), access to health services (care access, delivery and obstetric care, neonatal care, and breastfeeding), and mental wellbeing (psychological well-being and emotive support). Descriptive analysis was performed for both groups of participants, whereas a Poisson analysis was used to measure the association between some structural variables (age, education, socio-economic data, partner support, contact, free time, previous children, and pregnancy trimester) and anxiety or depression, difficulties in healthy eating and reduction in physical activity after lockdown started. Chi2 and Adjusted Prevalence Ratios were estimated only for pregnant women.

Results
We included 739 respondents (response rate 85.8 %), 600 were pregnant (81.2 %), and 139 (18.8 %) had delivered during lockdown (new mothers). We found a high score for anxiety and depression in 62.8 % of pregnant women and 61.9 % of new mothers. During the lockdown, 61.8 % of pregnant women reduced their physical exercise, and 44.3 % reported eating in a healthier way. 94.0 % of new mothers reported to have breastfed their babies during the hospital stay. Regarding the perceived impact of restrictive measures on breastfeeding, no impact was reported by 56.1 % of new mothers, whereas a negative one by 36.7 %.

Conclusions
The high prevalence of anxiety and depressive symptoms in pregnant women and new mothers should be a public health issue. Clinicians might also recommend and encourage “home” physical exercise. On the other hand, about half of the sample improved their approach towards healthy eating and a very high breastfeeding rate was reported soon after birth: these data are an interesting starting point to develop new strategies for public health.
Selling cannabidiol products in Canada: A framing analysis of advertising claims by online retailers
Authors: Zenone Marco Antonio , Snyder Jeremy , Crooks Valorie 
Published: July 2021

Abstract
Background
In Canada, the legalization of cannabis has enabled cannabidiol (CBD) to become a popular commercial product, increasingly used for medical or therapeutic purposes. There are currently over one thousand CBD products available globally, ranging from oil extracts to CBD-infused beverages. Despite increased usage and availability, the evidence supporting the medical efficacy of CBD is limited. Anecdotal evidence suggests CBD sellers represent their products for medical use through direct medical claims or advice, which in Canada, is not allowed under the Cannabis Act without Health Canada approval. However, it is not clear the extent of sellers making health claims or other strategies used to promote medical usage of CBD. The objective of this study is to determine how CBD sellers advertise their products online to consumers.

Methods
The product descriptions of 2165 CBD products from 70 websites selling CBD products for human consumption in Canada were collected from January 14th, 2020 to February 2nd, 2020 using an automated website scraper tool. A framing analysis was used to determine how CBD sellers frame their products to prospective customers. The specific medical conditions CBD is represented to treat and product forms were tabulated.

Results
CBD products are framed to prospective customer through three distinct frames: a specific cure or treatment (n = 1153), a natural health product (n = 872), and a product used in certain ways to achieve particular results (n = 1388). Product descriptions contained medical or therapeutic claims for 171 medical conditions and ailments, with 53.3% of products containing at least one claim. The most prevalent claims found in product descriptions were the ability to treat or manage pain (n = 824), anxiety (n = 609), and inflammation (n = 545). Claims were found for treating or managing serious and-life-threatening illnesses such as multiple sclerosis (n = 210), arthritis (n = 179), cancer (n = 169), Crohn’s disease (n = 78), Parkinson’s disease (n = 59), and human immunodeficiency virus (HIV) (n = 54). CBD most often came in oil/tincture/concentrate form (n = 755), followed by edibles (n = 428), and vaporizer pen/cartridge/liquid products (n = 290).

Conclusion
The findings suggest CBD is represented as a medical option for numerous conditions and ailments. We recommend Health Canada to conduct a systematic audit of companies selling CBD for regulatory adherence.
Supporting the classification of patients in public hospitals in Chile by designing, deploying and validating a system based on natural language processing
Authors: Villena Fabián , Pérez Jorge , Lagos René , Dunstan Jocelyn 
Published: July 2021

Abstract
Background
In Chile, a patient needing a specialty consultation or surgery has to first be referred by a general practitioner, then placed on a waiting list. The Explicit Health Guarantees (GES in Spanish) ensures, by law, the maximum time to solve 85 health problems. Usually, a health professional manually verifies if each referral, written in natural language, corresponds or not to a GES-covered disease. An error in this classification is catastrophic for patients, as it puts them on a non-prioritized waiting list, characterized by prolonged waiting times.

Methods
To support the manual process, we developed and deployed a system that automatically classifies referrals as GES-covered or not using historical data. Our system is based on word embeddings specially trained for clinical text produced in Chile. We used a vector representation of the reason for referral and patient's age as features for training machine learning models using human-labeled historical data. We constructed a ground truth dataset combining classifications made by three healthcare experts, which was used to validate our results.

Results
The best performing model over ground truth reached an AUC score of 0.94, with a weighted F1-score of 0.85 (0.87 in precision and 0.86 in recall). During seven months of continuous and voluntary use, the system has amended 87 patient misclassifications.

Conclusion
This system is a result of a collaboration between technical and clinical experts, and the design of the classifier was custom-tailored for a hospital's clinical workflow, which encouraged the voluntary use of the platform. Our solution can be easily expanded across other hospitals since the registry is uniform in Chile.
Single-cell spatial transcriptomic analysis reveals common and divergent features of developing postnatal granule cerebellar cells and medulloblastoma
Authors: Luo Wenqin , Lin Guan Ning , Song Weichen , Zhang Yu , Lai Huadong , Zhang Man , Miao Juju , Cheng Xiaomu , Wang Yongjie , Li Wang , Wei Wenxiang , Gao Wei-Qiang , Yang Ru , Wang Jia 
Published: July 2021

Abstract
Background
Cerebellar neurogenesis involves the generation of large numbers of cerebellar granule neurons (GNs) throughout development of the cerebellum, a process that involves tight regulation of proliferation and differentiation of granule neuron progenitors (GNPs). A number of transcriptional regulators, including Math1, and the signaling molecules Wnt and Shh have been shown to have important roles in GNP proliferation and differentiation, and deregulation of granule cell development has been reported to be associated with the pathogenesis of medulloblastoma. While the progenitor/differentiation states of cerebellar granule cells have been broadly investigated, a more detailed association between developmental differentiation programs and spatial gene expression patterns, and how these lead to differential generation of distinct types of medulloblastoma remains poorly understood. Here, we provide a comparative single-cell spatial transcriptomics analysis to better understand the similarities and differences between developing granule and medulloblastoma cells.

Results
To acquire an enhanced understanding of the precise cellular states of developing cerebellar granule cells, we performed single-cell RNA sequencing of 24,919 murine cerebellar cells from granule neuron-specific reporter mice (Math1-GFP; Dcx-DsRed mice). Our single-cell analysis revealed that there are four major states of developing cerebellar granule cells, including two subsets of granule progenitors and two subsets of differentiating/differentiated granule neurons. Further spatial transcriptomics technology enabled visualization of their spatial locations in cerebellum. In addition, we performed single-cell RNA sequencing of 18,372 cells from Patched+/− mutant mice and found that the transformed granule cells in medulloblastoma closely resembled developing granule neurons of varying differentiation states. However, transformed granule neuron progenitors in medulloblastoma exhibit noticeably less tendency to differentiate compared with cells in normal development.

Conclusion
In sum, our study revealed the cellular and spatial organization of the detailed states of cerebellar granule cells and provided direct evidence for the similarities and discrepancies between normal cerebellar development and tumorigenesis.
Parental income gradients in adult health: a national cohort study
Authors: Evensen Miriam , Klitkou Søren Toksvig , Tollånes Mette C. , Øverland Simon , Lyngstad Torkild Hovde , Vollset Stein Emil , Kinge Jonas Minet 
Published: July 2021

Abstract
Background
Disparities in health by adult income are well documented, but we know less about the childhood origins of health inequalities, and it remains unclear how the shape of the gradient varies across health conditions. This study examined the association between parental income in childhood and several measures of morbidity in adulthood.

Methods
We used administrative data on seven complete Norwegian birth cohorts born in 1967–1973 (N = 429,886) to estimate the association between parental income from birth to age 18, obtained from tax records available from 1967, linked with administrative registries on health. Health measures, observed between ages 39 and 43, were taken from registry data on consultations at primary health care services based on diagnostic codes from the International Classification of Primary Care (ICPC-2) and hospitalizations and outpatient specialist consultations registered in the National Patient Registry (ICD-10).

Results
Low parental income during childhood was associated with a higher risk of being diagnosed with several chronic and pain-related disorders, as well as hospitalization, but not overall primary health care use. Absolute differences were largest for disorders related to musculoskeletal pain, injuries, and depression (7–9 percentage point difference). There were also differences for chronic disorders such as hypertension (8%, CI 7.9–8.5 versus 4%, CI 4.1–4.7) and diabetes (3.2%, CI 3.0–3.4 versus 1.4%, CI 1.2–1.6). There was no difference in consultations related to respiratory disorders (20.9%, CI 20.4–21.5 versus 19.7%, CI 19.2–20.3). Childhood characteristics (parental education, low birth weight, and parental marital status) and own adult characteristics (education and income) explained a large share of the association.

Conclusions
Children growing up at the bottom of the parental income distribution, compared to children in the top of the income distribution, had a two- to threefold increase in somatic and psychological disorders measured in adulthood. This shows that health inequalities by socioeconomic family background persist in a Scandinavian welfare-state context with universal access to health care.
Effectiveness of a combined transcranial direct current stimulation and virtual reality-based intervention on upper limb function in chronic individuals post-stroke with persistent severe hemiparesis: a randomized controlled trial
Authors: Llorens Roberto , Fuentes María Antonia , Borrego Adrián , Latorre Jorge , Alcañiz Mariano , Colomer Carolina , Noé Enrique 
Published: July 2021

AbstractBackgroundFunctional impairments derived from the non-use of severely affected upper limb after stroke have been proposed to be mitigated by action observation and imagination-based techniques, whose effectiveness is enhanced when combined with transcranial direct current stimulation (tDCS). Preliminary studies in mildly impaired individuals in the acute phase post-stroke show intensified effects when action is facilitated by tDCS and mediated by virtual reality (VR) but the effectiveness in cases of severe impairment and chronic stroke is unknown. This study investigated the effectiveness of a combined tDCS and VR-based intervention in the sensorimotor function of chronic individuals post-stroke with persistent severe hemiparesis compared to conventional physical therapy.MethodsTwenty-nine participants were randomized into an experimental group, who received 30 minutes of the combined tDCS and VR-based therapy and 30 minutes of conventional physical therapy, or a control group, who exclusively received conventional physical therapy focusing on passive and active assistive range of motion exercises. The sensorimotor function of all participants was assessed before and after 25 one-hour sessions, administered three to five times a week, using the upper extremity subscale of the Fugl-Meyer Assessment, the time and ability subscales of the Wolf Motor Function Test, and the Nottingham Sensory Assessment.ResultsA clinically meaningful improvement of the upper limb motor function was consistently revealed in all motor measures after the experimental intervention, but not after conventional physical therapy. Similar limited effects were detected in the sensory function in both groups.ConclusionThe combined tDCS and VR-based paradigm provided not only greater but also clinically meaningful improvement in the motor function (and similar sensory effects) in comparison to conventional physical therapy.
High Prevalence of Anal Oncogenic Human Papillomavirus Infection in Young Men Who Have Sex with Men Living in Bamako, Mali
Authors: Koyalta Donato , Mboumba Bouassa Ralph-Sydney , Maiga Almoustapha Issiaka , Balde Aliou , Bagendabanga Jules Bashi , Alinity Almahdy Ag , Veyer David , Péré Hélène , Bélec Laurent 
Published: July 2021

Abstract
Background
High-risk human papillomavirus (HR-HPV) anal infection is a major problem among men who have sex with men (MSM) living in sub-Saharan Africa. The prevalence of anal HR-HPV infection and associated risk factors were estimated in a cross-sectional study in MSM living in Bamako, Mali.

Methods
MSM consulting at sexual health center of the National NGO Soutoura, Bamako, were prospectively included. Sociodemographic and clinical-biological data were collected. HPV detection and genotyping were performed from anal swabs using multiplex real-time PCR. Risk factors associated with anal HPV infection were assessed by logistic regression analysis.

Results
Fifty MSM (mean age, 24.2 years; range, 18–35) of which 32.0% were infected with HIV-1, were prospectively included. The overall prevalence of anal HPV infection of any genotypes was 70.0% (35/50) with 80.0% (28/35) of swabs positive for HR-HPV. HR-HPV-58 was the most detected genotype [13/35 (37.1%)], followed by HR-HPV-16 and low-risk (LR)-HPV-6 [12/35 (34.2%)], LR-HPV-40 [10/35 (28.6%)], LR-HPV-11 [9/35 (25.7%)], HR-HPV-51 [8/35 (22.8%)], HR-HPV types 18 and 39 [7/35 (20.0%)] and LR-HPV-43 [6/35 (17.1%)]. HR-HPV-52 and LR-HPV-44 were detected in lower proportions [5/35 (14.3%) and 4/35 (11.4%), respectively]. LR-HPV-42, LR-HPV-54, HR-HPV-31 and HR-HPV-35 were detected in very low proportions [3/35 (8.5%)]. Multiple HR-HPV infections were diagnosed in one-third of anal samples [16/50 (32.0%)], including around half of HR-HPV-positive anal swabs [16/35 (45.7%)]. More than half [27/50 (54.0%)] swabs were infected by at least one of HPV genotypes targeted by Gardasil-9® vaccine, including a majority of vaccine HR-HPV [22/50 (44.0%)]. In multivariate analysis, participation to sex in group was associated with anal infection by multiple HPV (aOR: 4.5, 95% CI: 1.1–18.1%; P = 0.032), and HIV-1 infection was associated with anal shedding of multiple HR-HPV (aOR: 5.5, 95% CI: 1.3–24.5%; P = 0.024).

Conclusions
These observations indicate that the MSM community living in Bamako is at high-risk for HR-HPV anal infections, with a unique epidemiological HPV genotypes profile and high prevalence of anal HPV covered by the Gardasil-9® vaccine. Scaling up prevention strategies against HPV infection and related cancers adapted to this highly vulnerable MSM community should be urgently prioritized with innovative interventions.