bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum progesterone levels greater than 32.5 ng/ml on the day of embryo transfer are associated with lower live birth rate after artificial endometrial preparation: a prospective study
Authors: Alyasin Ashraf , Agha-Hosseini Marzieh , Kabirinasab Motahareh , Saeidi Hojatollah , Nashtaei Maryam Shabani 
Published: February 2021

Abstract
Background
Previous observational studies have highlighted the negative effects of serum hormone levels at the minimum threshold during frozen embryo transfer (FET) cycles. However, still the questions regarding the maximum threshold level, and the highest allowed dosage of hormonal medications remain unresolved. The present study was conducted to determine whether there is any relationship between the serum progesterone and estradiol levels on the day of ET, and live birth rate (LBR) in patients receiving HRT in FET cycles.

Methods
In this prospective cohort study, eligible women who were undergoing their first or second FET cycles with the top graded blastocyst stage embryos were included. All patients received the same HRT regimen. FET was scheduled 5 days after administration of the first dosage of progesterone. On the morning of ET, 4–6 h after the last dose of progesterone supplementation, the serum progesterone (P4, ng/ml) and estradiol (E2, pg/ml) levels were measured.

Results
Amongst the 258 eligible women that were evaluated, the overall LBR was 34.1 % (88/258). The serum P4 and E2 values were divided into four quartiles. The means of women’s age and BMI were similar between the four quartiles groups. Regarding both P4 and E2 values, it was found that the LBR was significantly lower in the highest quartile group (Q4) compared with the others, (P = 0.002 and P = 0.042, respectively). The analysis of the multivariable logistic regression showed that the serum level of P4 on ET day, was the only significant predictive variable for LBR. The ROC curve revealed a significant predictive value of serum P4 levels on the day of ET for LBR, with an AUC = 0.61 (95 % CI: 0.54–0.68, P = 0.002). The optimum level of serum P4, with 70 % sensitivity and 50 %specificity for LBR, was 32.5 ng/ml.

Conclusions
The present study suggests that a serum P4 value at the maximum threshold on the day of FET is associated with reduced LBR following blastocyst transfer. Therefore, measuring and monitoring of P4 levels during FET cycles might be necessary. However, the results regarding the necessity for the screening of serum E2 levels before ET, are still controversial, and further prospective studies are required.
Predictive factors of the general public’s willingness to be seen and seek treatment from a nurse practitioner in Australia: a cross-sectional national survey
Authors: Dwyer Trudy , Craswell Alison , Browne Matthew 
Published: February 2021

Abstract
Background
Health care delivery in Australia is experiencing challenges with services struggling to keep up with the increasing demands of an aging population, rising levels of chronic disease and limited funding for care. Where adjunct models of health care such as the Nurse Practitioner (NP) have the potential to address this gap, in Australia, they remain an underutilised service. Clarifying the nature of the consumers ‘willingness’ to be seen by NPs warrants further investigation.

Methods
Australia-wide, cross-sectional population-based survey was undertaken using computer-assisted telephone interviewing technique.

Results
While just over 53% of the general public participants (n = 1318) had heard of an NP, once they became aware of their scope of practice, the majority agreed or strongly agreed they were willing to be seen by an NP in the community (91.6%), the emergency department 88.2%), to manage chronic conditions (86%), to have scrips written and referrals made (85.3%), and if they did not have to wait so long to see a medical doctor (81%). Factors significantly predicting willingness were being: female, less than 65 years of age, native English speakers, or residents from town/regional and rural settings.

Conclusion
Despite limited awareness of the NP role, a large proportion of the Australian population, across different demographic groups, are willing to be seen and treated by an NP. Expansion of this role to support medical services in areas of need could improve healthcare delivery.
An analysis of the services provided by community health workers within an urban district in South Africa: a key contribution towards universal access to care
Authors: Thomas L. S. , Buch E. , Pillay Y. 
Published: February 2021

Abstract
Introduction
Community health worker teams are potential game-changers in ensuring access to care in vulnerable communities. Who are they? What do they actually do? Can they help South Africa realize universal health coverage? As the proactive arm of the health services, community health workers teams provide household and community education, early screening, tracing and referrals for a range of health and social services. There is little local or global evidence on the household services provided by such teams, beyond specific disease-oriented activities such as for HIV and TB. This paper seeks to address this gap.

Methods
Descriptive secondary data analysis of community health worker team activities in the Ekurhuleni health district, South Africa covering approximately 280,000 households with 1 million people.

Results
Study findings illustrated that community health workers in these teams provided early screening and referrals for pregnant women and children under five. They distributed condoms and chronic medication to homes. They screened and referred for hypertension, diabetes mellitus, HIV and TB. The teams also undertook defaulter and contact tracing, the majority of which was for HIV and TB clients. Psychosocial support provided was in the form of access to social grants, access to child and gender-based violence protection services, food parcels and other services.

Conclusion
Community health workers form the core of these teams and perform several health and psychosocial services in households and poor communities in South Africa, in addition to general health education. The teams studied provided a range of activities across many health conditions (mother and child related, HIV and TB, non-communicable diseases), as well as social services. These teams provided comprehensive care in a large-scale urban setting and can improve access to care.
Restoration of bilateral motor coordination from preserved agonist-antagonist coupling in amputation musculature
Authors: Shu Tony , Huang Shan Shan , Shallal Christopher , Herr Hugh M. 
Published: February 2021

AbstractBackgroundNeuroprosthetic devices controlled by persons with standard limb amputation often lack the dexterity of the physiological limb due to limitations of both the user’s ability to output accurate control signals and the control system’s ability to formulate dynamic trajectories from those signals. To restore full limb functionality to persons with amputation, it is necessary to first deduce and quantify the motor performance of the missing limbs, then meet these performance requirements through direct, volitional control of neuroprosthetic devices.MethodsWe develop a neuromuscular modeling and optimization paradigm for the agonist-antagonist myoneural interface, a novel tissue architecture and neural interface for the control of myoelectric prostheses, that enables it to generate virtual joint trajectories coordinated with an intact biological joint at full physiologically-relevant movement bandwidth. In this investigation, a baseline of performance is first established in a population of non-amputee control subjects ($$n = 8$$n=8). Then, a neuromuscular modeling and optimization technique is advanced that allows unilateral AMI amputation subjects ($$n = 5$$n=5) and standard amputation subjects ($$n = 4$$n=4) to generate virtual subtalar prosthetic joint kinematics using measured surface electromyography (sEMG) signals generated by musculature within the affected leg residuum.ResultsUsing their optimized neuromuscular subtalar models under blindfolded conditions with only proprioceptive feedback, AMI amputation subjects demonstrate bilateral subtalar coordination accuracy not significantly different from that of the non-amputee control group (Kolmogorov-Smirnov test,$$P \ge 0.052$$P≥0.052) while standard amputation subjects demonstrate significantly poorer performance (Kolmogorov-Smirnov test,$$P < 0.001$$P<0.001).ConclusionsThese results suggest that the absence of an intact biological joint does not necessarily remove the ability to produce neurophysical signals with sufficient information to reconstruct physiological movements. Further, the seamless manner in which virtual and intact biological joints are shown to coordinate reinforces the theory that desired movement trajectories are mentally formulated in an abstract task space which does not depend on physical limb configurations.
Immunostimulatory siRNA with a uridine bulge leads to potent inhibition of HBV and activation of innate immunity
Authors: Lan Tingyu , Wei Zhiqiang , He Yulin , Wan Song , Liu Li , Cheng Bin , Li Ruimin , Chen Hongxia , Liu Guohua , Meng Zhongji 
Published: February 2021

Abstract
Background
Hepatitis B virus (HBV) infection is difficult to cure. HBV-specific immune tolerance plays a key role in HBV persistence, and enhancing cellular and humoral immunity will improve the control of HBV infection. The purpose of the study was to explore the anti-HBV and immunostimulatory effects of msiRNAs that introduce unpaired uridine bulges in the passenger strand.

Methods
msiRNAs targeting the HBV S and X genes were designed and named msiHBs and msiHBx, respectively. HepG2 cells were cotransfected with siRNA or msiRNA and the HBV replication-competent plasmid pHY106-wta or pHY106-X15. HepG2.215 cells were transfected with siRNA or msiRNA. The levels of HBsAg, HBeAg, and the cytokines TNF-α, IFN-α, IFN-β, IL-1α, and IL-6 in the culture supernatant was detected by ELISA. The levels of intracellular HBV RNA, nuclear HBV replication intermediates, and HBV DNA in the supernatant were measured by quantitative RT-PCR and PCR. The levels of HBV replication intermediates were detected by Southern blotting. Peripheral blood mononuclear cells were transfected with siRNA or msiRNA, and the levels of secreted cytokines IFN-α and IFN-β were detected by ELISA. The bioactivity of type I interferons in the supernatants was detected by the virus protection assay.

Results
msiHBx treatment led to a significant decrease in HBsAg (to a negative level) and HBV DNA (95.5%) in the supernatant and intrahepatocellular HBV replication intermediates (89.8%) in HepG2 cells with transient HBV replication and in HepG2.2.15 cells. There was no significant difference between msiHBx and siHBx in terms of the reduction in HBV proteins and HBV replication (P > 0.05). Compared with siHBx, msiHBx treatment of HepG2 cells transfected with the HBV replication-competent plasmid led to a significant increase in the levels of the antiviral cytokines TNF-α (3.3-fold), IFN-α (1.4-fold), and IFN-β (2.5-fold) (P < 0.01), without upregulation of the proinflammatory cytokines IL-1α and IL-6. The virus protection assay results showed msiHBx-mediated type I interferons effectively protected L929 cells against ECMV infection.

Conclusions
msiHBx could effectively inhibit HBV expression and replication and induce an antiviral innate immune response without proinflammatory activation. The dual RNAi and immunostimulatory activity of msiRNAs may play an important role in the control of HBV infection.
Differential mitochondrial proteomic analysis of A549 cells infected with avian influenza virus subtypes H5 and H9
Authors: Yang Yuting , Zhang Yun , Yang Changcheng , Fang Fang , Wang Ying , Chang Haiyan , Chen Ze , Chen Ping 
Published: February 2021

Abstract
Background
Both the highly pathogenic avian influenza (HPAI) H5N1 and low pathogenic avian influenza (LPAI) H9N2 viruses have been reported to cross species barriers to infect humans. H5N1 viruses can cause severe damage and are associated with a high mortality rate, but H9N2 viruses do not cause such outcomes. Our purpose was to use proteomics technology to study the differential expression of mitochondrial-related proteins related to H5N1 and H9N2 virus infections.

Methods
According to the determined viral infection titer, A549 cells were infected with 1 multiplicity of infection virus, and the mitochondria were extracted after 24 h of incubation. The protein from lysed mitochondria was analyzed by the BCA method to determine the protein concentration, as well as SDS-PAGE (preliminary analysis), two-dimensional gel electrophoresis, and mass spectrometry. Differential protein spots were selected, and Western blotting was performed to verify the proteomics results. The identified proteins were subjected to GO analysis for subcellular localization, KEGG analysis for functional classification and signaling pathways assessment, and STRING analysis for functional protein association network construction.

Results
In the 2-D gel electrophoresis analysis, 227 protein spots were detected in the H5N1-infected group, and 169 protein spots were detected in the H9N2-infected group. Protein spots were further subjected to mass spectrometry identification and removal of redundancy, and 32 differentially expressed proteins were identified. Compared with the H9N2 group, the H5N1-infected group had 16 upregulated mitochondrial proteins and 16 downregulated proteins. The differential expression of 70-kDa heat shock protein analogs, short-chain enoyl-CoA hydratase, malate dehydrogenase, and ATP synthase was verified by Western blot, and the results were consistent with the proteomics findings. Functional analysis indicated that these differentially expressed proteins were primarily involved in apoptosis and metabolism.

Conclusions
Compared with their expression in the H9N2 group, the differential expression of eight mitochondrial proteins in the H5N1 group led to host T cell activation, antigen presentation, stress response, ATP synthesis and cell apoptosis reduction, leading to higher pathogenicity of H5N1 than H9N2.
Neurofibromin expression by normal salivary glands
Authors: Luna Eloá Borges , Montovani Pâmella Pinho , Rozza-de-Menezes Rafaela Elvira , Cunha Karin Soares 
Published: February 2021

AbstractIntroductionNeurofibromin, a protein encoded by theNF1gene, is mutated in neurofibromatosis 1, one of the most common genetic diseases. Oral manifestations are common and a high prevalence of hyposalivation was recently described in individuals with neurofibromatosis 1. Although neurofibromin is ubiquitously expressed, its expression levels vary depending on the tissue type and developmental stage of the organism. The role of neurofibromin in the development, morphology, and physiology of salivary glands is unknown and a detailed expression of neurofibromin in human normal salivary glands has never been investigated.AimTo investigate the expression levels and distribution of neurofibromin in acinar and ductal cells of major and minor salivary glands of adult individuals without NF1.Material and methodTen samples of morphologically normal major and minor salivary glands (three samples of each gland: parotid, submandibular and minor salivary; and one sample of sublingual gland) from individuals without neurofibromatosis 1 were selected to assess neurofibromin expression through immunohistochemistry. Immunoquantification was performed by a digital method.ResultsNeurofibromin was expressed in the cytoplasm of both serous and mucous acinar cells, as well as in ducts from all the samples of salivary glands. Staining intensity varied from mild to strong depending on the type of salivary gland and region (acini or ducts). Ducts had higher neurofibromin expression than acinar cells (p = 0.003). There was no statistical association between the expression of neurofibromin and the type of the salivary gland, considering acini (p = 0.09) or ducts (p = 0.50) of the four salivary glands (parotid, submandibular, minor salivary, and sublingual gland). Similar results were obtained comparing the acini (p = 0.35) and ducts (p = 0.50) of minor and major salivary glands. Besides, there was no correlation between the expression of neurofibromin and age (p = 0.08), and sex (p = 0.79) of the individuals, considering simultaneously the neurofibromin levels of acini and duct (n = 34).ConclusionNeurofibromin is expressed in the cytoplasm of serous and mucous acinar cells, and ductal cells of salivary glands, suggesting that this protein is important for salivary gland function.
Multi-modal imaging of high-risk ductal carcinoma in situ of the breast using C2Am: a targeted cell death imaging agent
Authors: Szucs Zoltan , Joseph James , Larkin Tim J. , Xie Bangwen , Bohndiek Sarah E. , Brindle Kevin M. , Neves André A. 
Published: February 2021

Abstract
Background
Ductal carcinoma in situ (DCIS) is a non-invasive form of early breast cancer, with a poorly understood natural history of invasive transformation. Necrosis is a well-recognized adverse prognostic feature of DCIS, and non-invasive detection of its presence and spatial extent could provide information not obtainable by biopsy. We describe here imaging of the distribution and extent of comedo-type necrosis in a model of human DCIS using C2Am, an imaging agent that binds to the phosphatidylserine exposed by necrotic cells.

Methods
We used an established xenograft model of human DCIS that mimics the histopathological features of the disease. Planar near-infrared and optoacoustic imaging, using fluorescently labeled C2Am, were used to image non-invasively the presence and extent of lesion necrosis.

Results
C2Am showed specific and sensitive binding to necrotic areas in DCIS tissue, detectable both in vivo and ex vivo. The imaging signal generated in vivo using near-infrared (NIR) fluorescence imaging was up to 6-fold higher in DCIS lesions than in surrounding fat pad or skin tissue. There was a correlation between the C2Am NIR fluorescence (Pearson R = 0.783, P = 0.0125) and optoacoustic signals (R > 0.875, P < 0.022) in the DCIS lesions in vivo and the corresponding levels of cell death detected histologically.

Conclusions
C2Am is a targeted multi-modal imaging agent that could complement current anatomical imaging methods for detecting DCIS. Imaging the presence and spatial extent of necrosis may give better prognostic information than that obtained by biopsy alone.
The colorectal cancer-associated faecal microbiome of developing countries resembles that of developed countries
Authors: Young Caroline , Wood Henry M. , Seshadri Ramakrishnan Ayloor , Van Nang Pham , Vaccaro Carlos , Melendez Luis Contreras , Bose Mayilvahanan , Van Doi Mai , Piñero Tamara Alejandra , Valladares Camilo Tapia , Arguero Julieta , Balaguer Alba Fuentes , Thompson Kelsey N. , Yan Yan , Huttenhower Curtis , Quirke Philip 
Published: February 2021

Abstract
Background
The incidence of colorectal cancer (CRC) is increasing in developing countries, yet limited research on the CRC- associated microbiota has been conducted in these areas, in part due to scarce resources, facilities, and the difficulty of fresh or frozen stool storage/transport. Here, we aimed (1) to establish a broad representation of diverse developing countries (Argentina, Chile, India, and Vietnam); (2) to validate a ‘resource-light’ sample-collection protocol translatable in these settings using guaiac faecal occult blood test (gFOBT) cards stored and, importantly, shipped internationally at room temperature; (3) to perform initial profiling of the collective CRC-associated microbiome of these developing countries; and (4) to compare this quantitatively with established CRC biomarkers from developed countries.

Methods
We assessed the effect of international storage and transport at room temperature by replicating gFOBT from five UK volunteers, storing two in the UK, and sending replicates to institutes in the four countries. Next, to determine the effect of prolonged UK storage, DNA extraction replicates for a subset of samples were performed up to 252 days apart. To profile the CRC-associated microbiome of developing countries, gFOBT were collected from 41 treatment-naïve CRC patients and 40 non-CRC controls from across the four institutes, and V4 16S rRNA gene sequencing was performed. Finally, we constructed a random forest (RF) model that was trained and tested against existing datasets from developed countries.

Results
The microbiome was stably assayed when samples were stored/transported at room temperature and after prolonged UK storage. Large-scale microbiome structure was separated by country and continent, with a smaller effect from CRC. Importantly, the RF model performed similarly to models trained using external datasets and identified similar taxa of importance (Parvimonas, Peptostreptococcus, Fusobacterium, Alistipes, and Escherichia).

Conclusions
This study demonstrates that gFOBT, stored and transported at room temperature, represents a suitable method of faecal sample collection for amplicon-based microbiome biomarkers in developing countries and suggests a CRC-faecal microbiome association that is consistent between developed and developing countries.
Novel DNA methylation signatures of tobacco smoking with trans-ethnic effects
Authors: Christiansen C. , Castillo-Fernandez J. E. , Domingo-Relloso A. , Zhao W. , El-Sayed Moustafa J. S. , Tsai P.-C. , Maddock J. , Haack K. , Cole S. A. , Kardia S. L. R. , Molokhia M. , Suderman M. , Power C. , Relton C. , Wong A. , Kuh D. , Goodman A. , Small K. S. , Smith J. A. , Tellez-Plaza M. , Navas-Acien A. , Ploubidis G. B. , Hardy R. , Bell J. T. 
Published: February 2021

Abstract
Background
Smoking remains one of the leading preventable causes of death. Smoking leaves a strong signature on the blood methylome as shown in multiple studies using the Infinium HumanMethylation450 BeadChip. Here, we explore novel blood methylation smoking signals on the Illumina MethylationEPIC BeadChip (EPIC) array, which also targets novel CpG-sites in enhancers.

Method
A smoking-methylation meta-analysis was carried out using EPIC DNA methylation profiles in 1407 blood samples from four UK population-based cohorts, including the MRC National Survey for Health and Development (NSHD) or 1946 British birth cohort, the National Child Development Study (NCDS) or 1958 birth cohort, the 1970 British Cohort Study (BCS70), and the TwinsUK cohort (TwinsUK). The overall discovery sample included 269 current, 497 former, and 643 never smokers. Replication was pursued in 3425 trans-ethnic samples, including 2325 American Indian individuals participating in the Strong Heart Study (SHS) in 1989–1991 and 1100 African-American participants in the Genetic Epidemiology Network of Arteriopathy Study (GENOA).

Results
Altogether 952 CpG-sites in 500 genes were differentially methylated between smokers and never smokers after Bonferroni correction. There were 526 novel smoking-associated CpG-sites only profiled by the EPIC array, of which 486 (92%) replicated in a meta-analysis of the American Indian and African-American samples. Novel CpG sites mapped both to genes containing previously identified smoking-methylation signals and to 80 novel genes not previously linked to smoking, with the strongest novel signal in SLAMF7. Comparison of former versus never smokers identified that 37 of these sites were persistently differentially methylated after cessation, where 16 represented novel signals only profiled by the EPIC array. We observed a depletion of smoking-associated signals in CpG islands and an enrichment in enhancer regions, consistent with previous results.

Conclusion
This study identified novel smoking-associated signals as possible biomarkers of exposure to smoking and may help improve our understanding of smoking-related disease risk.