bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role and application of small extracellular vesicles in gastric cancer
Authors: Wu Hao , Fu Mengdi , Liu Jin , Chong Wei , Fang Zhen , Du Fengying , Liu Yang , Shang Liang , Li Leping 
Published: April 2021

AbstractGastric cancer (GC) is a common tumour that affects humans worldwide, is highly malignant and has a poor prognosis. Small extracellular vesicles (sEVs), especially exosomes, are nanoscale vesicles released by various cells that deliver bioactive molecules to recipient cells, affecting their biological characteristics, changing the tumour microenvironment and producing long-distance effects. In recent years, many studies have clarified the mechanisms by which sEVs function with regard to the initiation, progression, angiogenesis, metastasis and chemoresistance of GC. These molecules can function as mediators of cell-cell communication in the tumour microenvironment and might affect the efficacy of immunotherapy. Due to their unique physiochemical characteristics, sEVs show potential as effective antitumour vaccines as well as drug carriers. In this review, we summarize the roles of sEVs in GC and highlight the clinical application prospects in the future.
Nanomedicine-based technologies and novel biomarkers for the diagnosis and treatment of Alzheimer’s disease: from current to future challenges
Authors: Cano Amanda , Turowski Patric , Ettcheto Miren , Duskey Jason Thomas , Tosi Giovanni , Sánchez-López Elena , García Maria Luisa , Camins Antonio , Souto Eliana B. , Ruiz Agustín , Marquié Marta , Boada Mercè 
Published: April 2021

AbstractIncreasing life expectancy has led to an aging population, which has consequently increased the prevalence of dementia. Alzheimer's disease (AD), the most common form of dementia worldwide, is estimated to make up 50–80% of all cases. AD cases are expected to reach 131 million by 2050, and this increasing prevalence will critically burden economies and health systems in the next decades. There is currently no treatment that can stop or reverse disease progression. In addition, the late diagnosis of AD constitutes a major obstacle to effective disease management. Therefore, improved diagnostic tools and new treatments for AD are urgently needed. In this review, we investigate and describe both well-established and recently discovered AD biomarkers that could potentially be used to detect AD at early stages and allow the monitoring of disease progression. Proteins such as NfL, MMPs, p-tau217, YKL-40, SNAP-25, VCAM-1, and Ng / BACE are some of the most promising biomarkers because of their successful use as diagnostic tools. In addition, we explore the most recent molecular strategies for an AD therapeutic approach and nanomedicine-based technologies, used to both target drugs to the brain and serve as devices for tracking disease progression diagnostic biomarkers. State-of-the-art nanoparticles, such as polymeric, lipid, and metal-based, are being widely investigated for their potential to improve the effectiveness of both conventional drugs and novel compounds for treating AD. The most recent studies on these nanodevices are deeply explained and discussed in this review.Graphic Abstract
Research priority-setting for human, plant, and animal virology: an online experience for the Virology Institute of the Philippines
Authors: Sales Reneepearl Kim , Oraño Joseph , Estanislao Rafael Deo , Ballesteros Alfredo Jose , Gomez Ma. Ida Faye 
Published: April 2021

Abstract
Background
Viral pandemics have had catastrophic consequences on population health and economies. The Philippine government intends to establish the Virology Institute of the Philippines, one of the key areas of which will be virology research. This project aimed to develop the institute’s research agenda across the fields of human, plant, and animal virology.

Methodology
Key considerations for the prioritization methodology were (1) the imminent establishment of the Virology Institute of the Philippines, (2) mobility restrictions caused by the coronavirus disease 2019 (COVID-19) pandemic, (3) the timeline to develop the research agenda, and (4) the need to separate the research agenda for the three fields of human, plant, and animal virology. The process was fully conducted online in four steps: stakeholder identification, soliciting research priorities, generating initial research priorities, and final prioritization consultations conducted on Zoom Pro.

Results
Twenty-eight participants attended three online consultations between 21 and 27 July 2020 through Zoom Pro. Participants selected the research prioritization criteria and its weights, and used these to evaluate the research priorities. The final research agenda covers topics in epidemiology, diagnostics, surveillance, biosafety, and genomics.

Conclusion
This initiative resulted in the first research agenda for the Virology Institute of the Philippines across the three fields of human, plant, and animal virology. An expert-driven process which places a premium on consensus-building facilitated through online platforms was the most feasible approach to develop the research agenda. This process resulted in an agenda aligned with the mandates of national research councils but leaves gaps on areas such as emerging infectious diseases. Pre-COVID-19 literature expressed apprehensions on the online medium that weakens social ties necessary for consensus. Our experience with changing the mode of consensus-building shows that users will continually adapt to technology. Online tools are currently able to address the limitations of the virtual space.
Musculoskeletal ultrasound assessment in pediatric knee hypermobility: a case control study
Authors: Ballenger Laura R. , Moore-Clingenpeel Melissa , Oberle Edward J. 
Published: April 2021

Abstract
Background
While musculoskeletal ultrasound (MSUS) use in pediatric rheumatology is becoming more common, the majority of pediatric MSUS literature continues to focus on ultrasound findings in healthy children and juvenile idiopathic arthritis with little discussion of other musculoskeletal problems that may mimic arthritis such as joint hypermobility. Chronic joint pain related to hypermobility is a common referral to pediatric rheumatology clinics. Our aim is to describe the musculoskeletal ultrasound (MSUS) characteristics of the knee in a population with joint hypermobility and pain in comparison to control participants.

Methods
Participants were recruited into three groups for a case-control study. Case group participants had knee hypermobility and pain symptoms (H + P). Participants in one control group had knee hypermobility without pain symptoms (H-P), and participants in the other control group had no knee hypermobility or pain symptoms (NP). B-mode and Doppler MSUS images were obtained and scored for each knee. Descriptive statistics are used for demographic variables and MSUS findings. Regression analysis is used to evaluate risk of synovial effusion and higher synovial effusion/hypertrophy quantitative score.

Results
MSUS assessment was performed on 91 knees of 50 participants. H + P knees were more likely to have positive findings noted on MSUS (94% vs. 70% of H-P and 74% of NP knees, p = 0.043). Patellar tendon hyperemia was more common in H + P knees (52%, vs. 19% among H-P and 23% among NP, p = 0.025). Participants who reported taking scheduled non-steroidal anti-inflammatory drugs (NSAIDs) had an increased risk of synovial effusion (RR = 1.83, 95% CI = 1.07–2.30, p = 0.026) and a trend towards increased risk of a higher synovial effusion/hypertrophy quantitative score (RR = 1.77, 95% CI = 0.92–3.38, p = 0.086).

Conclusions
While positive MSUS findings were frequent in all participants, patellar tendon hyperemia was more frequent in participants with knee hypermobility and pain symptoms. Additionally, reported use of NSAIDs was associated with an increased risk of synovial effusion and higher synovial effusion/hypertrophy quantitative score. Further study should assess correlation between tendon abnormalities and degree of pain symptoms as well as the effect of NSAIDs on MSUS findings.
Women in larger bodies’ experiences with contraception: a scoping review
Authors: Boyce Tierney M. , Neiterman Elena 
Published: April 2021

Abstract
Background
As the prevalence of obesity increases and the age of onset decreases, more women of reproductive age will be living in larger bodies. Research on weight-related efficacy and safety has informed clinical guidelines for routine and emergency contraceptive use by women with a higher body mass index; however, patient perspectives are needed to understand women in larger bodies’ experiences with contraception and contraceptive care. This scoping review summarizes the literature on women in larger bodies’ experiences with contraception with the goal of gaining a better understanding of the nature of these experiences and identifying gaps in the existing research.

Methods
Following Arksey and O’Malley’s framework, a scoping review of the literature was conducted. Four databases (PubMed, PsycINFO, SCOPUS, and CINAHL) were searched for peer-reviewed, empirical articles published in English between 2010 and 2020, with a focus on North America, Europe, Australia, and New Zealand. Data were summarized by identifying key themes in the reviewed literature.

Results
Twenty-nine articles meeting the eligibility criteria were reviewed. The literature was predominantly quantitative (n = 27), with only one qualitative study and one systematic review, respectively. Five themes were identified, including (1) use of contraception among women in larger bodies; (2) knowledge, attitudes towards and beliefs about contraception; (3) contraceptive (dis)satisfaction among women in larger bodies; (4) contraceptive counseling; and (5) barriers to contraception. The findings revealed that women in larger bodies may have unmet contraceptive care needs. Despite many articles addressing the need to improve contraceptive counseling for women in larger bodies (n = 26), few explored how women felt about their care (n = 2). Finally, only two articles focused on emergency contraception, indicating a need for further research.

Conclusion
This scoping review emphasizes the pressing need for qualitative research to explore women in larger bodies’ experiences with routine and emergency contraception, as well as receiving contraceptive counseling and care. Future research exploring the lived experiences of women in larger bodies is necessary to better characterize their contraceptive needs and identify avenues to improve patient care.
Three-dimensional-printed porous implant combined with autograft reconstruction for giant cell tumor in proximal tibia
Authors: Zhang Yuqi , Lu Minxun , Min Li , Wang Jie , Wang Yitian , Luo Yi , Zhou Yong , Duan Hong , Tu Chongqi 
Published: April 2021

AbstractBackgroundThis study is to describe the design and surgical techniques of three- dimensional-printed porous implants for proximal giant cell tumors of bone and evaluate the short-term clinical outcomes.MethodsFrom December 2016 to April 2020, 8 patients with giant cell tumor of bone in the proximal tibia underwent intralesional curettage of the tumor and reconstruction with bone grafting and three-dimensional-printed porous implant. Detailed anatomy data were measured, including the size of lesion and thickness of the subchondral bone. Prostheses were custom-made for each patient by our team. All patients were evaluated regularly and short-term clinical outcomes were recorded.ResultsThe mean follow-up period was 26 months. According to the different defect sizes, the mean size of the plate and mean length of strut were 35 × 35 mm and 20 mm, respectively. The mean affected subchondral bone percentage was 31.5%. The average preoperative and postoperative thickness of the subchondral bone was 2.1 mm and 11.1 mm, respectively. There was no wound infection, skin necrosis, peroneal nerve injury, or other surgical related complications. No degeneration of the knee joint was found. Osseointegration was observed in all patients. The MSTS improved from an average of 12 preoperatively to 28 postoperatively.ConclusionThe application of three-dimensional-printed printed porous prosthesis combined autograft could supply enough mechanical support and enhance bone ingrowth. The design and operation management lead to satisfactory subchondral bone reconstruction.
Age of ovarian cancer diagnosis among BRIP1, RAD51C, and RAD51D mutation carriers identified through multi-gene panel testing
Authors: Cummings Shelly , Roman Susana San , Saam Jennifer , Bernhisel Ryan , Brown Krystal , Lancaster Johnathan M. , Usha Lydia 
Published: April 2021

Abstract
Background
Professional society guidelines recommend risk-reducing salpingo-oophorectomy (RRSO) for women with pathogenic variants (PVs) in ovarian cancer-risk genes. Personalization of that intervention is based on gene-specific phenotypes; however, the age of ovarian cancer diagnosis in women with PVs in moderate penetrance ovarian cancer-risk genes is not well characterized.
Women who had hereditary cancer panel testing from September 2013–May 2019 were included (N = 631,950). Clinical/demographic information was compared for women with a PV in BRIP1, RAD51C, or RAD51D versus in BRCA1 or BRCA2.

Results
PVs in BRIP1, RAD51C, or RAD51D were identified in 0.5% of all tested women but in 1.6% of women with a history of ovarian cancer (~ 3-fold increase). PVs in BRCA1 or BRCA2 were identified in 2.4% of all tested women but in 6.1% of women with a history of ovarian cancer (~ 2.5-fold increase). The proportion of women with a personal or family history of ovarian cancer was similar among women with a PV in BRIP1, RAD51C, RAD51D, BRCA1, or BRCA2. The median age at ovarian cancer diagnosis was 53 years for BRCA1, 59 years for BRCA2, 65 years for BRIP1, 62 years for RAD51C, and 57 years for RAD51D.

Conclusions
These data reinforce the importance of identifying PVs in moderate penetrance ovarian cancer-risk genes. The age at ovarian cancer diagnosis was older for women with PVs in BRIP1, RAD51C, or RAD51D, suggesting that it is safe to delay RRSO until age 45–50 in RAD51D PV carriers and possibly until age 50–55 in BRIP and RAD51C PV carriers.
Trajectories of depression in sepsis survivors: an observational cohort study
Authors: Boede Monique , Gensichen Jochen S. , Jackson James C. , Eißler Fiene , Lehmann Thomas , Schulz Sven , Petersen Juliana J. , Wolf Florian P. , Dreischulte Tobias , Schmidt Konrad F. R. 
Published: April 2021

Abstract
Background
Advances in critical care medicine have led to a growing number of critical illness survivors. A considerable part of them suffers from long-term sequelae, also known as post-intensive care syndrome. Among these, depressive symptoms are frequently observed. Depressive symptom trajectories and associated factors of critical illness survivors have rarely been investigated. Study objective was to explore and compare different trajectories of depressive symptoms in sepsis survivors over 1 year after discharge from ICU.

Methods
Data of a randomized controlled trial on long-term post-sepsis care were analyzed post hoc. Depressive symptoms were collected at 1, 6 and 12 months post-ICU discharge using the Major Depression Inventory (MDI), among others. Statistical analyses comprised descriptive analysis, univariate and multivariate, linear and logistic regression models and Growth Mixture Modeling.

Results
A total of 224 patients were included into this analysis. We identified three latent classes of depressive symptom trajectories: Over the course of 1 year, 152 patients recovered from mild symptoms, 27 patients showed severe persistent symptoms, and 45 patients recovered from severe symptoms. MDI sum scores significantly differed between the three classes of depressive symptom trajectories at 1 and 6 months after ICU discharge (p < 0.024 and p < 0.001, respectively). Compared with other classes, patients with the mild recovered trajectory showed lower levels of chronic pain (median sum score of 43.3 vs. 60.0/53.3 on the Graded Chronic Pain Scale, p < 0.010) and posttraumatic stress (4.6% with a sum score of ≥ 35 on the Posttraumatic Stress Scale 10 vs. 48.1%/33.3%, p < 0.003); and higher levels of health-related quality of life (HRQOL) using the Short Form-36 scale within 1 month after ICU discharge (p < 0.035).

Conclusions
In the first year after discharge from ICU, sepsis survivors showed three different trajectories of depressive symptoms. Course and severity of depressive symptoms were associated with chronic pain, posttraumatic stress and reduced HRQOL at discharge from ICU. Regular screening of sepsis survivors on symptoms of depression, chronic pain and posttraumatic stress within 1 year after ICU may be considered.
Trial registration ISRCTN, ISRCTN 61744782. Registered April 19, 2011—Retrospectively registered, http://www.isrctn.com/ISRCTN61744782.
Early assessment of shear wave elastography parameters foresees the response to neoadjuvant chemotherapy in patients with invasive breast cancer
Authors: Gu Juanjuan , Polley Eric C. , Denis Max , Carter Jodi M. , Pruthi Sandhya , Gregory Adriana V. , Boughey Judy C. , Fazzio Robert T. , Fatemi Mostafa , Alizad Azra 
Published: April 2021

Abstract
Background
Early prediction of tumor response to neoadjuvant chemotherapy (NACT) is crucial for optimal treatment and improved outcome in breast cancer patients. The purpose of this study is to investigate the role of shear wave elastography (SWE) for early assessment of response to NACT in patients with invasive breast cancer.

Methods
In a prospective study, 62 patients with biopsy-proven invasive breast cancer were enrolled. Three SWE studies were conducted on each patient: before, at mid-course, and after NACT but before surgery. A new parameter, mass characteristic frequency (fmass), along with SWE measurements and mass size was obtained from each SWE study visit. The clinical biomarkers were acquired from the pre-NACT core-needle biopsy. The efficacy of different models, generated with the leave-one-out cross-validation, in predicting response to NACT was shown by the area under the receiver operating characteristic curve and the corresponding sensitivity and specificity.

Results
A significant difference was found for SWE parameters measured before, at mid-course, and after NACT between the responders and non-responders. The combination of Emean2 and mass size (s2) gave an AUC of 0.75 (0.95 CI 0.62–0.88). For the ER+ tumors, the combination of Emean_ratio1, s1, and Ki-67 index gave an improved AUC of 0.84 (0.95 CI 0.65–0.96). For responders, fmass was significantly higher during the third visit.

Conclusions
Our study findings highlight the value of SWE estimation in the mid-course of NACT for the early prediction of treatment response. For ER+ tumors, the addition of Ki-67improves the predictive power of SWE. Moreover, fmass is presented as a new marker in predicting the endpoint of NACT in responders.
The impact of cell type and context-dependent regulatory variants on human immune traits
Authors: Mu Zepeng , Wei Wei , Fair Benjamin , Miao Jinlin , Zhu Ping , Li Yang I. 
Published: April 2021

Abstract
Background
The vast majority of trait-associated variants identified using genome-wide association studies (GWAS) are noncoding, and therefore assumed to impact gene regulation. However, the majority of trait-associated loci are unexplained by regulatory quantitative trait loci (QTLs).

Results
We perform a comprehensive characterization of the putative mechanisms by which GWAS loci impact human immune traits. By harmonizing four major immune QTL studies, we identify 26,271 expression QTLs (eQTLs) and 23,121 splicing QTLs (sQTLs) spanning 18 immune cell types. Our colocalization analyses between QTLs and trait-associated loci from 72 GWAS reveals that genetic effects on RNA expression and splicing in immune cells colocalize with 40.4% of GWAS loci for immune-related traits, in many cases increasing the fraction of colocalized loci by two fold compared to previous studies. Notably, we find that the largest contributors of this increase are splicing QTLs, which colocalize on average with 14% of all GWAS loci that do not colocalize with eQTLs. By contrast, we find that cell type-specific eQTLs, and eQTLs with small effect sizes contribute very few new colocalizations. To investigate the 60% of GWAS loci that remain unexplained, we collect H3K27ac CUT&Tag data from rheumatoid arthritis and healthy controls, and find large-scale differences between immune cells from the different disease contexts, including at regions overlapping unexplained GWAS loci.

Conclusion
Altogether, our work supports RNA splicing as an important mediator of genetic effects on immune traits, and suggests that we must expand our study of regulatory processes in disease contexts to improve functional interpretation of as yet unexplained GWAS loci.
Best practices on the differential expression analysis of multi-species RNA-seq
Authors: Chung Matthew , Bruno Vincent M. , Rasko David A. , Cuomo Christina A. , Muñoz José F. , Livny Jonathan , Shetty Amol C. , Mahurkar Anup , Dunning Hotopp Julie C. 
Published: April 2021

AbstractAdvances in transcriptome sequencing allow for simultaneous interrogation of differentially expressed genes from multiple species originating from a single RNA sample, termed dual or multi-species transcriptomics. Compared to single-species differential expression analysis, the design of multi-species differential expression experiments must account for the relative abundances of each organism of interest within the sample, often requiring enrichment methods and yielding differences in total read counts across samples. The analysis of multi-species transcriptomics datasets requires modifications to the alignment, quantification, and downstream analysis steps compared to the single-species analysis pipelines. We describe best practices for multi-species transcriptomics and differential gene expression.
PseudotimeDE: inference of differential gene expression along cell pseudotime with well-calibrated p-values from single-cell RNA sequencing data
Authors: Song Dongyuan , Li Jingyi Jessica 
Published: April 2021

AbstractTo investigate molecular mechanisms underlying cell state changes, a crucial analysis is to identify differentially expressed (DE) genes along the pseudotime inferred from single-cell RNA-sequencing data. However, existing methods do not account for pseudotime inference uncertainty, and they have either ill-posed p-values or restrictive models. Here we propose PseudotimeDE, a DE gene identification method that adapts to various pseudotime inference methods, accounts for pseudotime inference uncertainty, and outputs well-calibrated p-values. Comprehensive simulations and real-data applications verify that PseudotimeDE outperforms existing methods in false discovery rate control and power.
Next-generation microbiology: from comparative genomics to gene function
Authors: Kobras Carolin M. , Fenton Andrew K. , Sheppard Samuel K. 
Published: April 2021

AbstractMicrobiology is at a turning point in its 120-year history. Widespread next-generation sequencing has revealed genetic complexity among bacteria that could hardly have been imagined by pioneers such as Pasteur, Escherich and Koch. This data cascade brings enormous potential to improve our understanding of individual bacterial cells and the genetic basis of phenotype variation. However, this revolution in data science cannot replace established microbiology practices, presenting the challenge of how to integrate these new techniques. Contrasting comparative and functional genomic approaches, we evoke molecular microbiology theory and established practice to present a conceptual framework and practical roadmap for next-generation microbiology.