bluuebunny/crossref_metadata_2025_split huggingface dataset:
The connected patient project: moving towards a population-based primary health care research registry
Authors: Coe Dorothy , Birt Angela , Forbes Gareth , Ling Jonathan , Foster Michael , Robson Stephen , McDonald Joe , Yiannakou Yan 
Published: May 2021

Abstract
Background
The NHS pledges to give all patients access to clinical research. In England, 32% of General Practices are research active and only 14% of patients engage in research. This project aimed to evaluate consent-for-contact and communication in primary care patients.

Methods
An explanatory mixed methods study of patients and staff within a single general practice. The study included all patients over the age of 18 years, and excluded those on the palliative care register and those unable to give informed consent. The questionnaire asked recipients to indicate their preferred contact method and data-sharing permissions with three organisations: NHS, Universities and Commercial Companies. Survey recipients and staff were invited to take part in a semi-structured interview. Interviews explored project acceptability, feasibility and reasoning behind choices made. Statistical data were triangulated with interview data.

Results
The target patient population was 4678, 24% (n = 1148) responded. Seven hundred and three gave permission for at least one of the organisations to contact them. Older people were more likely to respond than young people, (p < 0.001). There was a trend for more women than men to give permissions however, in the 70 years plus age group this was reversed. Short message service was the preferred method of communication (48% n = 330), but those aged 70 years and over, preferred letter (p = 0.001). Interviews suggested patients felt the project was primarily about improving communication and secondly access to research. Patients trusted the NHS and university researchers. Staff interviewees found the project was less onerous than expected. Barriers to wider rollout included workload and the fragmented nature of NHS digital systems.

Conclusions
A registry of patients was established; however, the response rate of 24% needs increasing before wider adoption. Health promotion and chronic disease-based research may recruit better when based in primary health care. Older demographics would be more likely to volunteer for research. NHS and academic researchers are trusted, commercial organisations less so. The move to digitalise communication methods has the potential to marginalise older women. Findings were used to drive forward two novel developments: a consent registry (Research+Me) and a federation-wide participant identification process.
The expression profiles and prognostic values of HSP70s in hepatocellular carcinoma
Authors: Wang Ben , Lan Tian , Xiao Han , Chen Zhong-Huo , Wei Chao , Chen Lei-Feng , Guan Jia-Fu , Yuan Rong-Fa , Yu Xin , Hu Zhi-Gang , Wu Hua-Jun , Dai Zhi , Wang Kai 
Published: May 2021

Abstract
Background
The HSP70 family of heat shock protein plays a critical role in protein synthesis and transport to maintain protein homeostasis. Several studies have indicated that HSP70s are related to the development and occurrence of various cancers.

Methods
The relationship between the overall survival rate of hepatocellular carcinoma patients and the expression of 14 HSP70s from multiple databases, such as TCGA, ONCOMINE, cBioPortal was investigated. Western Blot and PCR were used to evaluate HSPA4 and HSPA14 expressions in various HCC cells to identify suitable cell lines for further experiments .Wound-healing assays, Transwell assays and EdU assays were used to verify the effects of HSPA4 and HSPA14 on the function of hepatocellular carcinoma cells, and statistical analysis was performed.

Results
Hepatocellular carcinoma tissues significantly expressed the 14 HSP70s compared to the normal samples. Besides, the high HSPA1A, HSPA1B, HSPA4, HSPA5, HSPA8, HSPA13, and HSPA14 expressions were inversely associated with the overall survival rate of patients, tumor grade, and cancer stage. A PPI regulatory network was constructed using the 14 HSP70s proteins with HSPA5 and HSPA8 at the network center. Univariate and multivariate analyses showed that HSPA4 and HSPA14 could be independent risk factors for the prognosis of hepatocellular carcinoma patients. Cell experiments have also confirmed that reducing HSPA4 and HSPA14 expressions can inhibit the invasion, metastasis, and proliferation of hepatocellular carcinoma cells.

Conclusions
Therefore, the HSP70s significantly influence the occurrence and development of hepatocellular carcinoma. For instance, HSPA4 and HSPA14 can be novel therapeutic targets and prognostic biomarkers for hepatocellular carcinoma.
The application of drones for mosquito larval habitat identification in rural environments: a practical approach for malaria control?
Authors: Stanton Michelle C. , Kalonde Patrick , Zembere Kennedy , Hoek Spaans Remy , Jones Christopher M. 
Published: May 2021

Abstract
Background
Spatio-temporal trends in mosquito-borne diseases are driven by the locations and seasonality of larval habitat. One method of disease control is to decrease the mosquito population by modifying larval habitat, known as larval source management (LSM). In malaria control, LSM is currently considered impractical in rural areas due to perceived difficulties in identifying target areas. High resolution drone mapping is being considered as a practical solution to address this barrier. In this paper, the authors’ experiences of drone-led larval habitat identification in Malawi were used to assess the feasibility of this approach.

Methods
Drone mapping and larval surveys were conducted in Kasungu district, Malawi between 2018 and 2020. Water bodies and aquatic vegetation were identified in the imagery using manual methods and geographical object-based image analysis (GeoOBIA) and the performances of the classifications were compared. Further, observations were documented on the practical aspects of capturing drone imagery for informing malaria control including cost, time, computing, and skills requirements. Larval sampling sites were characterized by biotic factors visible in drone imagery and generalized linear mixed models were used to determine their association with larval presence.

Results
Imagery covering an area of 8.9 km2 across eight sites was captured. Larval habitat characteristics were successfully identified using GeoOBIA on images captured by a standard camera (median accuracy = 98%) with no notable improvement observed after incorporating data from a near-infrared sensor. This approach however required greater processing time and technical skills compared to manual identification. Larval samples captured from 326 sites confirmed that drone-captured characteristics, including aquatic vegetation presence and type, were significantly associated with larval presence.

Conclusions
This study demonstrates the potential for drone-acquired imagery to support mosquito larval habitat identification in rural, malaria-endemic areas, although technical challenges were identified which may hinder the scale up of this approach. Potential solutions have however been identified, including strengthening linkages with the flourishing drone industry in countries such as Malawi. Further consultations are therefore needed between experts in the fields of drones, image analysis and vector control are needed to develop more detailed guidance on how this technology can be most effectively exploited in malaria control.
Metformin reduces androgen receptor and upregulates homeobox A10 expression in uterine endometrium in women with polycystic ovary syndrome
Authors: Ohara Miki , Yoshida-Komiya Hiromi , Ono-Okutsu Miho , Yamaguchi-Ito Akiko , Takahashi Toshifumi , Fujimori Keiya 
Published: May 2021

Abstract
Background
Polycystic ovary syndrome (PCOS) causes anovulation and is associated with a reduced clinical pregnancy rate. Metformin, which is widely used for treating PCOS, can lead to successful pregnancy by restoring the ovulation cycle and possibly improving endometrial abnormality during the implantation period. However, the mechanism by which metformin improves endometrial abnormality remains unknown. Women with PCOS have an aberrant expression of steroid hormone receptors and homeobox A10 (HOXA10), which is essential for embryo implantation in the endometrium.

Methods
In this study, we examined whether metformin affects androgen receptor (AR) and HOXA10 expression in PCOS endometrium in vivo and in human endometrial cell lines in vitro. Expression of AR and HOXA10 was evaluated by immunohistochemistry, fluorescent immunocytochemistry, and western blot analysis.

Results
AR expression was localized in both epithelial and stromal cells; however, HOXA10 expression was limited to only stromal cells in this study. In women with PCOS, 3 months after metformin treatment, the expression of AR was reduced in epithelial and stromal cells in comparison to their levels before treatment. In contrast, HOXA10 expression in the stromal cells with metformin treatment increased in comparison to its level before treatment. Further, we showed that metformin counteracted the testosterone-induced AR expression in both Ishikawa cells and human endometrial stromal cells (HESCs); whereas, metformin partly restored the testosterone-reduced HOXA10 expression in HESCs in vitro.

Conclusions
Our results suggest that metformin may have a direct effect on the abnormal endometrial environment of androgen excess in women with PCOS.

Trial registration
The study was approved by the Ethical Committee of Fukushima Medical University (approval no. 504, approval date. July 6, 2006), and written informed consent was obtained from all patients. https://www.fmu.ac.jp/univ/sangaku/rinri.html
A Bayesian spatio-temporal analysis of mortality rates in Spain: application to the COVID-19 2020 outbreak
Authors: Saavedra Pedro , Santana Angelo , Bello Luis , Pacheco José-Miguel , Sanjuán Esther 
Published: May 2021

Abstract
Background
The number of deaths attributable to COVID-19 in Spain has been highly controversial since it is problematic to tell apart deaths having COVID as the main cause from those provoked by the aggravation by the viral infection of other underlying health problems. In addition, overburdening of health system led to an increase in mortality due to the scarcity of adequate medical care, at the same time confinement measures could have contributed to the decrease in mortality from certain causes. Our aim is to compare the number of deaths observed in 2020 with the projection for the same period obtained from a sequence of previous years. Thus, this computed mortality excess could be considered as the real impact of the COVID-19 on the mortality rates.

Methods
The population was split into four age groups, namely: (< 50; 50–64; 65–74; 75 and over). For each one, a projection of the death numbers for the year 2020, based on the interval 2008–2020, was estimated using a Bayesian spatio-temporal model. In each one, spatial, sex, and year effects were included. In addition, a specific effect of the year 2020 was added ("outbreak"). Finally, the excess deaths in year 2020 were estimated as the count of observed deaths minus those projected.

Results
The projected death number for 2020 was 426,970 people, the actual count being 499,104; thus, the total excess of deaths was 72,134. However, this increase was very unequally distributed over the Spanish regions.

Conclusion
Bayesian spatio-temporal models have proved to be a useful tool for estimating the impact of COVID-19 on mortality in Spain in 2020, making it possible to assess how the disease has affected different age groups accounting for effects of sex, spatial variation between regions and time trend over the last few years.
Exosomes contribution in COVID-19 patients’ treatment
Authors: Mazini Loubna , Rochette Luc , Malka Gabriel 
Published: May 2021

AbstractAdipose cell-free derivatives have been recently gaining attention as potential therapeutic agents for various human diseases. In this context, mesenchymal stromal/stem cells (MSCs), adipocyte mesenchymal stem cells (Ad-MSCs) and adipose-derived stem cells (ADSC) possessing potent immunomodulatory activities are proposed as a therapeutic option for the treatment of coronavirus disease 2019 (COVID-19). The COVID-19 represents a global concern of public health caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in which there is not actually any specific therapy. MSCs exert an immunomodulation effect due to the secretion of endogenous factors, such as vascular endothelial growth factor (VEGF), insulin growth factor (IGF), and nerve growth factor (NGF), transforming growth factor (TGF)-β and growth differentiation factor (GDF)-11. Recent reports are promising for further studies and clinical applications of ADSCs and Ad-MSCs in COVID-19 patients. Experimental and clinical studies are exploring the therapeutic potential of both MSCs and derived-exosomes in moderating the morbidity and mortality of COVID-19. In this field, more preclinical and clinical studies are warranted to find an effective treatment for the patients suffering from COVID-19 infection.
The “Intermediate” CD14 + CD16 + monocyte subpopulation plays a role in IVIG responsiveness of children with Kawasaki disease
Authors: Kim Yi Seul , Yang Hyun Jin , Kee Seung-Jung , Choi Insu , Ha Kisoo , Ki Katrina K , Jeong In Seok , Cho Hwa Jin 
Published: May 2021

Abstract
Background
Kawasaki disease (KD) is an acute, self-limited febrile illness of unknown cause. Intravenous immunoglobulin (IVIG)-resistance are related to greater risk for permanent cardiac complications. We aimed to determine the correlation between monocytes and the phenotype of KD in relation to IVIG responsiveness in children.

Materials and methods
The study cohort included 62 patients who were diagnosed with KD, 20 non febrile healthy controls (NFC), and 15 other febrile controls (OFC). In all enrolled patients, blood was taken at least 4 times and laboratory tests were performed. In addition, subtypes of monocytes were characterized via flow cytometry.

Results
The numbers of intermediate monocytes were significantly lower in IVIG-resistant group compared to IVIG-responsive group before IVIG infusion (p < 0.0001). After infusion, intermediate monocytes decreased in the responsive group, while a trend of increase was observed in the resistant group. Only intermediate monocytes were significant in logistic regression with adjusted OR of 0.001 and p value of 0.03.

Conclusions
CD14 + CD16 + intermediate monocyte may play an important role in IVIG responsiveness among KD children. Low starting levels of intermediate monocytes, followed by a dramatic increase post-IVIG infusion during acute phase of KD are associated with IVIG-resistance. Functional studies on intermediate monocyte may help to reveal the pathophysiology.
A missed opportunity: underutilization of inpatient behavioral health services to reduce injection drug use sequelae in Florida
Authors: Coye Austin E. , Jones Mackenzie T. , Bornstein Kasha J. , Tookes Hansel E. , St. Onge Joan E. 
Published: May 2021

Abstract
Background
People who inject drugs (PWID) suffer high morbidity and mortality from injection related infections (IRI). The inpatient setting is an ideal opportunity to treat underlying substance use disorder (SUD), but it is unclear how often this occurs.

Objectives
To quantify the utilization of behavioral health services for PWID during inpatient admissions for IRI.

Methods
Data for all hospital admissions in Florida in FY2017 were obtained from the Agency for Healthcare Administration. Hospitalization for IRI were obtained using a validated ICD-10 algorithm and treatment for substance use disorder was quantified using ICD-10-Procedure Coding System (ICD-10-PCS) codes.

Result
Among the 20,001 IRI admissions, there were 230 patients who received behavioral health services as defined by ICD-10-PCS SAT codes for treatment for SUD.

Conclusions
In a state with a large number of IRI, only a very small portion of admissions received behavioral health services. Increased efforts should be directed to studying referral patterns among physicians and other providers caring for this population and increasing utilization of behavioral health services.
Potential of biomarkers during pharmacological therapy setting for postmenopausal osteoporosis: a systematic review
Authors: Migliorini Filippo , Maffulli Nicola , Spiezia Filippo , Peretti Giuseppe Maria , Tingart Markus , Giorgino Riccardo 
Published: May 2021

Abstract
Background
Biochemical markers of bone turnover (BTMs), such as the bone alkaline phosphatase (bALP), procollagen type I N propeptide (PINP), serum cross-linked C-telopeptides of type I collagen (bCTx), and urinary cross-linked N-telopeptides of type I collagen (NTx), are used to manage therapy monitoring in osteoporotic patients. This systematic review analyzed the potential of these BMTs in predicting the clinical outcomes in terms of BMD, t-score, rate of fractures, and adverse events during the therapy setting in postmenopausal osteoporosis.

Methods
All randomized clinical trials (RCTs) reporting data on biomarkers for postmenopausal osteoporosis were accessed. Only articles reporting quantitative data on the level of biomarkers at baseline and on the outcomes of interest at the last follow-up were eligible.

Results
A total of 36,706 patients were retrieved. Greater values of bALP were associated with a greater rate of vertebral (P = 0.001) and non-vertebral fractures (P = 0.0001). Greater values of NTx at baseline were associated with a greater rate of adverse events at the last follow-up (P = 0.02). Greater values of CTx at baseline were associated with a greater rate of adverse events leading to discontinuation (P = 0.04), gastrointestinal adverse events (P = 0.0001), musculoskeletal adverse events (P = 0.04), and mortality (P = 0.04). Greater values of PINP at baseline were associated with greater rates of gastrointestinal adverse events (P = 0.02) at the last follow-up.

Conclusion
The present analysis supports the adoption of BMTs during pharmacological therapy setting of patients suffering from osteoporosis.

Level of evidence
I, systematic review of RCTs
Clinical, genetic and quality-of-life study of a cohort of adult patients with tuberous sclerosis
Authors: De Sautu De Borbón Elena Cristina , Guerra Vales Juan Manuel , Lumbreras Bermejo Carlos , Guerrero Ramos Felix , Buj Padilla María José , González de la Aleja Jesús , Morales Conejo Montserrat 
Published: May 2021

Abstract
Background and objective
Tuberous sclerosis (TS) is a condition whose manifestations in childhood have been extensively described, but whose presentation in adults is less well known. This study describes the clinical and genetic characteristics, therapeutic management and quality of life of a cohort of adult patients with TS. A comparative study of the characteristics of patients diagnosed in childhood and adulthood is also carried out.

Material and methods
This observational, retrospective, cross-sectional study included a large cohort of adult patients (≥ 16 years old) followed for 5 years in a specific rare diseases unit.

Results
Fifty-seven patients with a diagnosis of tuberous sclerosis were included, more than 50% of whom were diagnosed as adults. The mean age of the patients was 42 years (20–86). The central nervous system was the main area affected (97%), followed by the skin (80.7%) and kidneys (73%). The most frequent genetic alteration was a mutation in the TSC2 gene (47.7%). Among patients diagnosed in adulthood, there was less neurological involvement, with less frequency of epileptic seizures (30.8% vs 60.79% of patients diagnosed in childhood) and astrocytomas (3.8% vs 53.6%), less intellectual disability (11.5% vs 71.4%) and less expressiveness of the condition. 42% of patients were treated with mTOR pathway inhibitors, and presence of an angiomyolipoma was the main indication. In a quality-of-life analysis, the means of the summary indices were below the scores of the average Spanish population: (47.42 (SD ± 9.82) on the physical health scale, 45.61 (SD ± 7.99) on the mental health scale) versus 50 (SD ± 10) for the general population.

Conclusions
Up to 50% of adult patients with TS were diagnosed in adulthood, and the condition is less severe with less frequent epileptic seizures and intellectual disability. 42% require treatment with mTOR inhibitors, in most cases due to the presence of AMLs. The quality of life of adult patients with TS is diminished compared to the general population.
Impacts of allopolyploidization and structural variation on intraspecific diversification in Brassica rapa
Authors: Cai Xu , Chang Lichun , Zhang Tingting , Chen Haixu , Zhang Lei , Lin Runmao , Liang Jianli , Wu Jian , Freeling Michael , Wang Xiaowu 
Published: May 2021

AbstractBackgroundDespite the prevalence and recurrence of polyploidization in the speciation of flowering plants, its impacts on crop intraspecific genome diversification are largely unknown.Brassica rapais a mesopolyploid species that is domesticated into many subspecies with distinctive morphotypes.ResultsHerein, we report the consequences of the whole-genome triplication (WGT) on intraspecific diversification using a pan-genome analysis of 16 de novo assembled and two reported genomes. Among the genes that derive from WGT, 13.42% of polyploidy-derived genes accumulate more transposable elements and non-synonymous mutations than other genes during individual genome evolution. We denote such genes as being “flexible.” We construct theBrassica rapaancestral genome and observe the continuing influence of the dominant subgenome on intraspecific diversification inB. rapa. The gene flexibility is biased to the more fractionated subgenomes (MFs), in contrast to the more intact gene content of the dominant LF (least fractionated) subgenome. Furthermore, polyploidy-derived flexible syntenic genes are implicated in the response to stimulus and the phytohormone auxin; this may reflect adaptation to the environment. Using an integrated graph-based genome, we investigate the structural variation (SV) landscapes in 524B. rapagenomes. We observe that SVs track morphotype domestication. Four out of 266 candidate genes for Chinese cabbage domestication are speculated to be involved in the leafy head formation.ConclusionsThis pan-genome uncovers the possible contributions of allopolyploidization on intraspecific diversification and the possible and underexplored role of SVs in favorable trait domestication. Collectively, our work serves as a rich resource for genome-basedB. rapaimprovement.